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Ru-Rong Ji

Distinguished Professor of Anesthesiology, in the School of Medicine
Anesthesiology

Selected Publications


Satellite glial GPR37L1 and its ligand maresin 1 regulate potassium channel signaling and pain homeostasis.

Journal Article J Clin Invest · March 26, 2024 G protein-coupled receptor 37-like 1 (GPR37L1) is an orphan GPCR with largely unknown functions. Here, we report that Gpr37l1/GRP37L1 ranks among the most highly expressed GPCR transcripts in mouse and human dorsal root ganglia (DRGs) and is selectively ex ... Full text Link to item Cite

MicroRNA let-7b enhances spinal cord nociceptive synaptic transmission and induces acute and persistent pain through neuronal and microglial signaling.

Journal Article Pain · March 6, 2024 Secreted microRNAs (miRNAs) have been detected in various body fluids including the cerebrospinal fluid, yet their direct role in regulating synaptic transmission remains uncertain. We found that intrathecal injection of low dose of let-7b (1 μg) induced s ... Full text Link to item Cite

Microglial STING activation alleviates nerve injury-induced neuropathic pain in male but not female mice.

Journal Article Brain Behav Immun · March 2024 Microglia, resident immune cells in the central nervous system, play a role in neuroinflammation and the development of neuropathic pain. We found that the stimulator of interferon genes (STING) is predominantly expressed in spinal microglia and upregulate ... Full text Link to item Cite

Recurrent infections drive persistent bladder dysfunction and pain via sensory nerve sprouting and mast cell activity.

Journal Article Sci Immunol · March 2024 Urinary tract infections (UTIs) account for almost 25% of infections in women. Many are recurrent (rUTI), with patients frequently experiencing chronic pelvic pain and urinary frequency despite clearance of bacteriuria after antibiotics. To elucidate the b ... Full text Link to item Cite

Microglial Refinement of A-Fiber Projections in the Postnatal Spinal Cord Dorsal Horn Is Required for Normal Maturation of Dynamic Touch.

Journal Article J Neurosci · January 10, 2024 Sensory systems are shaped in postnatal life by the refinement of synaptic connectivity. In the dorsal horn of the spinal cord, somatosensory circuits undergo postnatal activity-dependent reorganization, including the refinement of primary afferent A-fiber ... Full text Link to item Cite

Pain management by chemogenetic control of sensory neurons.

Journal Article Cell Rep Med · December 19, 2023 In this study, Perez-Sanchez et al.1 developed a chemogenetic method aimed at alleviating pain in mouse models while dampening excitability in human sensory neurons. This analgesic effect was attained through the introduction of human α7 nicotinic acetylch ... Full text Link to item Cite

Satellite glial GPR37L1 regulates maresin and potassium channel signaling for pain control.

Journal Article bioRxiv · December 5, 2023 G protein coupled receptor 37-like 1 (GPR37L1) is an orphan GPCR and its function remains largely unknown. Here we report that GPR37L1 transcript is highly expressed compared to all known GPCRs in mouse and human dorsal root ganglia (DRGs) and selectively ... Full text Link to item Cite

Inflammatory changes in the plasma and cerebrospinal fluid of patients with persistent pain and postpartum depression after elective Cesarean delivery: an exploratory prospective cohort study.

Journal Article Can J Anaesth · December 2023 PURPOSE: Severe acute pain after Cesarean delivery increases the risk of developing persistent pain (~20% incidence) and postpartum depression (PPD) (~15% incidence). Both conditions contribute to maternal morbidity and mortality, yet early risk stratifica ... Full text Link to item Cite

Macrophages and microglia in inflammation and neuroinflammation underlying different pain states.

Journal Article Med Rev (2021) · October 2023 Pain is a main symptom in inflammation, and inflammation induces pain via inflammatory mediators acting on nociceptive neurons. Macrophages and microglia are distinct cell types, representing immune cells and glial cells, respectively, but they share simil ... Full text Link to item Cite

PD-L1/PD-1 checkpoint pathway regulates hippocampal neuronal excitability and learning and memory behavior.

Journal Article Neuron · September 6, 2023 Programmed death protein 1 (PD-1) and its ligand PD-L1 constitute an immune checkpoint pathway. We report that neuronal PD-1 signaling regulates learning/memory in health and disease. Mice lacking PD-1 (encoded by Pdcd1) exhibit enhanced long-term potentia ... Full text Link to item Cite

Immunotherapies in chronic pain through modulation of neuroimmune interactions.

Journal Article Pharmacol Ther · August 2023 It is generally believed that immune activation can elicit pain through production of inflammatory mediators that can activate nociceptive sensory neurons. Emerging evidence suggests that immune activation may also contribute to the resolution of pain by p ... Full text Link to item Cite

Intrathecal administration of conditioned serum from different species resolves Chemotherapy-Induced neuropathic pain in mice via secretory exosomes.

Journal Article Brain Behav Immun · July 2023 Chemotherapy-induced peripheral neuropathy (CIPN) is the most prevalent neurological complication of chemotherapy for cancer, and has limited effective treatment options. Autologous conditioned serum (ACS) is an effective biologic therapy used by intra-art ... Full text Link to item Cite

Novel proresolving lipid mediator mimetic 3-oxa-PD1n-3 docosapentaenoic acid reduces acute and chronic itch by modulating excitatory and inhibitory synaptic transmission and astroglial secretion of lipocalin-2 in mice.

Journal Article Pain · June 1, 2023 Specialized proresolving mediators (SPMs) have demonstrated potent analgesic actions in animal models of pathological pain. The actions of SPMs in acute and chronic itch are currently unknown. Recently, n-3 docosapentaenoic acid (DPA) was found to be a sub ... Full text Link to item Cite

The Similar and Distinct Roles of Satellite Glial Cells and Spinal Astrocytes in Neuropathic Pain.

Journal Article Cells · March 22, 2023 Preclinical studies have identified glial cells as pivotal players in the genesis and maintenance of neuropathic pain after nerve injury associated with diabetes, chemotherapy, major surgeries, and virus infections. Satellite glial cells (SGCs) in the dors ... Full text Link to item Cite

A mast cell-thermoregulatory neuron circuit axis regulates hypothermia in anaphylaxis.

Journal Article Sci Immunol · March 17, 2023 IgE-mediated anaphylaxis is an acute life-threatening systemic reaction to allergens, including certain foods and venoms. Anaphylaxis is triggered when blood-borne allergens activate IgE-bound perivascular mast cells (MCs) throughout the body, causing an e ... Full text Link to item Cite

Mechanisms and treatments of neuropathic itch in a mouse model of lymphoma.

Journal Article J Clin Invest · February 15, 2023 Our understanding of neuropathic itch is limited due to a lack of relevant animal models. Patients with cutaneous T cell lymphoma (CTCL) experience severe itching. Here, we characterize a mouse model of chronic itch with remarkable lymphoma growth, immune ... Full text Link to item Cite

Piezo2 mediates visceral mechanosensation: A new therapeutic target for gut pain?

Journal Article Neuron · February 15, 2023 Mechanical distension/stretch in the colon provokes visceral hypersensitivity and pain. In this issue of Neuron, Xie et al. report that mechanosensitive Piezo2 channels, expressed by TRPV1-lineage nociceptors, are involved in visceral mechanical nociceptio ... Full text Link to item Cite

Specialized Pro-Resolving Mediators as Resolution Pharmacology for the Control of Pain and Itch.

Journal Article Annu Rev Pharmacol Toxicol · January 20, 2023 Specialized pro-resolving mediators (SPMs), including resolvins, protectins, and maresins, are endogenous lipid mediators that are synthesized from omega-3 polyunsaturated fatty acids during the acute phase or resolution phase of inflammation. Synthetic SP ... Full text Link to item Cite

SHANK3 in vagal sensory neurons regulates body temperature, systemic inflammation, and sepsis.

Journal Article Front Immunol · 2023 Excessive inflammation has been implicated in autism spectrum disorder (ASD), but the underlying mechanisms have not been fully studied. SHANK3 is a synaptic scaffolding protein and mutations of SHANK3 are involved in ASD. Shank3 expression in dorsal root ... Full text Link to item Cite

Satellite glial GPR37L1 and its ligand maresin 1 regulate potassium channel signaling and pain homeostasis.

Journal Article J Clin Invest · March 26, 2024 G protein-coupled receptor 37-like 1 (GPR37L1) is an orphan GPCR with largely unknown functions. Here, we report that Gpr37l1/GRP37L1 ranks among the most highly expressed GPCR transcripts in mouse and human dorsal root ganglia (DRGs) and is selectively ex ... Full text Link to item Cite

MicroRNA let-7b enhances spinal cord nociceptive synaptic transmission and induces acute and persistent pain through neuronal and microglial signaling.

Journal Article Pain · March 6, 2024 Secreted microRNAs (miRNAs) have been detected in various body fluids including the cerebrospinal fluid, yet their direct role in regulating synaptic transmission remains uncertain. We found that intrathecal injection of low dose of let-7b (1 μg) induced s ... Full text Link to item Cite

Microglial STING activation alleviates nerve injury-induced neuropathic pain in male but not female mice.

Journal Article Brain Behav Immun · March 2024 Microglia, resident immune cells in the central nervous system, play a role in neuroinflammation and the development of neuropathic pain. We found that the stimulator of interferon genes (STING) is predominantly expressed in spinal microglia and upregulate ... Full text Link to item Cite

Recurrent infections drive persistent bladder dysfunction and pain via sensory nerve sprouting and mast cell activity.

Journal Article Sci Immunol · March 2024 Urinary tract infections (UTIs) account for almost 25% of infections in women. Many are recurrent (rUTI), with patients frequently experiencing chronic pelvic pain and urinary frequency despite clearance of bacteriuria after antibiotics. To elucidate the b ... Full text Link to item Cite

Microglial Refinement of A-Fiber Projections in the Postnatal Spinal Cord Dorsal Horn Is Required for Normal Maturation of Dynamic Touch.

Journal Article J Neurosci · January 10, 2024 Sensory systems are shaped in postnatal life by the refinement of synaptic connectivity. In the dorsal horn of the spinal cord, somatosensory circuits undergo postnatal activity-dependent reorganization, including the refinement of primary afferent A-fiber ... Full text Link to item Cite

Pain management by chemogenetic control of sensory neurons.

Journal Article Cell Rep Med · December 19, 2023 In this study, Perez-Sanchez et al.1 developed a chemogenetic method aimed at alleviating pain in mouse models while dampening excitability in human sensory neurons. This analgesic effect was attained through the introduction of human α7 nicotinic acetylch ... Full text Link to item Cite

Satellite glial GPR37L1 regulates maresin and potassium channel signaling for pain control.

Journal Article bioRxiv · December 5, 2023 G protein coupled receptor 37-like 1 (GPR37L1) is an orphan GPCR and its function remains largely unknown. Here we report that GPR37L1 transcript is highly expressed compared to all known GPCRs in mouse and human dorsal root ganglia (DRGs) and selectively ... Full text Link to item Cite

Inflammatory changes in the plasma and cerebrospinal fluid of patients with persistent pain and postpartum depression after elective Cesarean delivery: an exploratory prospective cohort study.

Journal Article Can J Anaesth · December 2023 PURPOSE: Severe acute pain after Cesarean delivery increases the risk of developing persistent pain (~20% incidence) and postpartum depression (PPD) (~15% incidence). Both conditions contribute to maternal morbidity and mortality, yet early risk stratifica ... Full text Link to item Cite

Macrophages and microglia in inflammation and neuroinflammation underlying different pain states.

Journal Article Med Rev (2021) · October 2023 Pain is a main symptom in inflammation, and inflammation induces pain via inflammatory mediators acting on nociceptive neurons. Macrophages and microglia are distinct cell types, representing immune cells and glial cells, respectively, but they share simil ... Full text Link to item Cite

PD-L1/PD-1 checkpoint pathway regulates hippocampal neuronal excitability and learning and memory behavior.

Journal Article Neuron · September 6, 2023 Programmed death protein 1 (PD-1) and its ligand PD-L1 constitute an immune checkpoint pathway. We report that neuronal PD-1 signaling regulates learning/memory in health and disease. Mice lacking PD-1 (encoded by Pdcd1) exhibit enhanced long-term potentia ... Full text Link to item Cite

Immunotherapies in chronic pain through modulation of neuroimmune interactions.

Journal Article Pharmacol Ther · August 2023 It is generally believed that immune activation can elicit pain through production of inflammatory mediators that can activate nociceptive sensory neurons. Emerging evidence suggests that immune activation may also contribute to the resolution of pain by p ... Full text Link to item Cite

Intrathecal administration of conditioned serum from different species resolves Chemotherapy-Induced neuropathic pain in mice via secretory exosomes.

Journal Article Brain Behav Immun · July 2023 Chemotherapy-induced peripheral neuropathy (CIPN) is the most prevalent neurological complication of chemotherapy for cancer, and has limited effective treatment options. Autologous conditioned serum (ACS) is an effective biologic therapy used by intra-art ... Full text Link to item Cite

Novel proresolving lipid mediator mimetic 3-oxa-PD1n-3 docosapentaenoic acid reduces acute and chronic itch by modulating excitatory and inhibitory synaptic transmission and astroglial secretion of lipocalin-2 in mice.

Journal Article Pain · June 1, 2023 Specialized proresolving mediators (SPMs) have demonstrated potent analgesic actions in animal models of pathological pain. The actions of SPMs in acute and chronic itch are currently unknown. Recently, n-3 docosapentaenoic acid (DPA) was found to be a sub ... Full text Link to item Cite

The Similar and Distinct Roles of Satellite Glial Cells and Spinal Astrocytes in Neuropathic Pain.

Journal Article Cells · March 22, 2023 Preclinical studies have identified glial cells as pivotal players in the genesis and maintenance of neuropathic pain after nerve injury associated with diabetes, chemotherapy, major surgeries, and virus infections. Satellite glial cells (SGCs) in the dors ... Full text Link to item Cite

A mast cell-thermoregulatory neuron circuit axis regulates hypothermia in anaphylaxis.

Journal Article Sci Immunol · March 17, 2023 IgE-mediated anaphylaxis is an acute life-threatening systemic reaction to allergens, including certain foods and venoms. Anaphylaxis is triggered when blood-borne allergens activate IgE-bound perivascular mast cells (MCs) throughout the body, causing an e ... Full text Link to item Cite

Mechanisms and treatments of neuropathic itch in a mouse model of lymphoma.

Journal Article J Clin Invest · February 15, 2023 Our understanding of neuropathic itch is limited due to a lack of relevant animal models. Patients with cutaneous T cell lymphoma (CTCL) experience severe itching. Here, we characterize a mouse model of chronic itch with remarkable lymphoma growth, immune ... Full text Link to item Cite

Piezo2 mediates visceral mechanosensation: A new therapeutic target for gut pain?

Journal Article Neuron · February 15, 2023 Mechanical distension/stretch in the colon provokes visceral hypersensitivity and pain. In this issue of Neuron, Xie et al. report that mechanosensitive Piezo2 channels, expressed by TRPV1-lineage nociceptors, are involved in visceral mechanical nociceptio ... Full text Link to item Cite

Specialized Pro-Resolving Mediators as Resolution Pharmacology for the Control of Pain and Itch.

Journal Article Annu Rev Pharmacol Toxicol · January 20, 2023 Specialized pro-resolving mediators (SPMs), including resolvins, protectins, and maresins, are endogenous lipid mediators that are synthesized from omega-3 polyunsaturated fatty acids during the acute phase or resolution phase of inflammation. Synthetic SP ... Full text Link to item Cite

SHANK3 in vagal sensory neurons regulates body temperature, systemic inflammation, and sepsis.

Journal Article Front Immunol · 2023 Excessive inflammation has been implicated in autism spectrum disorder (ASD), but the underlying mechanisms have not been fully studied. SHANK3 is a synaptic scaffolding protein and mutations of SHANK3 are involved in ASD. Shank3 expression in dorsal root ... Full text Link to item Cite

Targeting dorsal root ganglia and primary sensory neurons for the treatment of chronic pain: an update.

Journal Article Expert Opin Ther Targets · 2023 INTRODUCTION: Current treatments for chronic pain are inadequate. Here, we provide an update on the new therapeutic strategies that target dorsal root ganglia (DRGs) in the peripheral nervous system for a better and safer treatment of chronic pain. AREAS C ... Full text Link to item Cite

Neuroimmune Interactions in Acute and Chronic Itch

Chapter · January 1, 2023 Itch is a sensory experience of the skin that is familiar to all humans. Recent studies have established that the immune system and central and peripheral nervous systems engage in extensive interactions termed “crosstalk,” which gives rise to both acute a ... Full text Cite

Neuroimmune Interactions in Pain: Mechanisms and Therapeutics

Book · January 1, 2023 As lifespans increase, more people around the world find themselves victims of chronic pain. In spite of this, treatment options continue to be severely limited. Anti-inflammatory drugs can only do so much, while painkillers like opioids have led to crippl ... Full text Cite

Mechanisms-Based Pain Therapies

Chapter · January 1, 2023 Chronic pain is a prevalent disease with high impact on public health and individual’s quality of life. Understanding the complex mechanisms and causes of pain is crucial for precise diagnosis, adequate management, and better patient outcomes. As we deepen ... Full text Cite

Animal Models of Pain and Anti-inflammatory Treatments

Chapter · January 1, 2023 Animal models are critical to the field of pain research, both for the study of mechanisms and the testing of novel therapeutics. Unfortunately, many findings that appear promising in animals fail to translate to human disease, underscoring the criticality ... Full text Cite

Inflammation and Pain

Chapter · January 1, 2023 Inflammation is the body’s natural response to injury or the infiltration of a foreign substance. The process is defined by five cardinal signs: redness, heat, swelling, loss of function, and pain. Because of its relationship with pain and injury, various ... Full text Cite

Immune and Glial Cells in Pain and Their Interactions with Nociceptive Neurons

Chapter · January 1, 2023 While pain is sensed and conducted by neurons, including primary sensory neurons (nociceptors) and spinal cord pain transmission neurons, mounting evidence suggests that non-neuronal cells such as immune cells and glial cells in the peripheral nervous syst ... Full text Cite

Sex Differences in Pain with Emphasis on Neuroimmune Interactions

Chapter · January 1, 2023 To date, the mechanisms underlying how neuroimmune interactions contribute to sex dimorphism of chronic pain remain elusive. Although women suffer from chronic pain at greater rates than men, the current mechanistic understanding of chronic pain has been p ... Full text Cite

Exercise and Diet in the Control of Inflammation and Pain

Chapter · January 1, 2023 Lifestyle choices, such as exercise and diet, can play significant roles in mediating inflammation and consequently, pain. Functional medicine is an emerging medical specialty that focuses on lifestyle influences, genetics, and the environment to determine ... Full text Cite

Inflammatory Mediators, Nociceptors, and Their Interactions in Pain

Chapter · January 1, 2023 Inflammation produces pro-inflammatory mediators for the induction of pain. These mediators include inflammatory cytokines and chemokines, lipids, and microRNAs. These inflammatory mediators bind respective receptors on nociceptor terminals and cell bodies ... Full text Cite

Immunotherapy and Pain

Chapter · January 1, 2023 Immunotherapy was initially developed as a method to treat cancer through the use of the host’s immune system. Now, immunotherapy is used as a treatment for a wide variety of diseases. The connection between the nervous system and the immune system in chro ... Full text Cite

Preface

Journal Article Neuroimmune Interactions in Pain: Mechanisms and Therapeutics · January 1, 2023 Cite

Hevin/Sparcl1 drives pathological pain through spinal cord astrocyte and NMDA receptor signaling.

Journal Article JCI insight · December 2022 High endothelial venule protein/SPARC-like 1 (hevin/Sparcl1) is an astrocyte-secreted protein that regulates synapse formation in the brain. Here we show that astrocytic hevin signaling plays a critical role in maintaining chronic pain. Compared with WT mi ... Full text Open Access Cite

Inflammation and Infection in Pain and the Role of GPR37.

Journal Article Int J Mol Sci · November 20, 2022 Inflammation is known to cause pain, and pain is of one of the cardinal signs of inflammation. Mounting evidence suggests that acute inflammation also resolves pain through specialized pro-resolving mediators (SPMs) and macrophage signaling. GPR37 is expre ... Full text Link to item Cite

Emerging Roles of Type-I Interferons in Neuroinflammation, Neurological Diseases, and Long-Haul COVID.

Journal Article Int J Mol Sci · November 19, 2022 Interferons (IFNs) are pleiotropic cytokines originally identified for their antiviral activity. IFN-α and IFN-β are both type I IFNs that have been used to treat neurological diseases such as multiple sclerosis. Microglia, astrocytes, as well as neurons i ... Full text Link to item Cite

In vivo single microglial cell isolation after intracerebral hemorrhage in mice.

Journal Article Neurosci Lett · September 14, 2022 Failure to translate promising potential therapeutics for intracerebral hemorrhage (ICH) partially results from limited understanding of cellular mechanisms underlying brain injury and repair. Understanding neural repair mechanisms after brain injury requi ... Full text Link to item Cite

Skin Injury Activates a Rapid TRPV1-Dependent Antiviral Protein Response.

Journal Article J Invest Dermatol · August 2022 The skin serves as the interface between the body and the environment and plays a fundamental role in innate antimicrobial host immunity. Antiviral proteins (AVPs) are part of the innate host defense system and provide protection against viral pathogens. H ... Full text Link to item Cite

Interleukin-6 signaling mediates cartilage degradation and pain in posttraumatic osteoarthritis in a sex-specific manner.

Journal Article Sci Signal · July 26, 2022 Osteoarthritis (OA) and posttraumatic OA (PTOA) are caused by an imbalance in catabolic and anabolic processes in articular cartilage and proinflammatory changes throughout the joint, leading to joint degeneration and pain. We examined whether interleukin- ... Full text Link to item Cite

Repurposing cancer drugs identifies kenpaullone which ameliorates pathologic pain in preclinical models via normalization of inhibitory neurotransmission.

Journal Article Nature communications · October 2021 Inhibitory GABA-ergic neurotransmission is fundamental for the adult vertebrate central nervous system and requires low chloride concentration in neurons, maintained by KCC2, a neuroprotective ion transporter that extrudes intracellular neuronal chloride. ... Full text Cite

IL-23/IL-17A/TRPV1 axis produces mechanical pain via macrophage-sensory neuron crosstalk in female mice.

Journal Article Neuron · September 1, 2021 Although sex dimorphism is increasingly recognized as an important factor in pain, female-specific pain signaling is not well studied. Here we report that administration of IL-23 produces mechanical pain (mechanical allodynia) in female but not male mice, ... Full text Link to item Cite

HepaCAM controls astrocyte self-organization and coupling.

Journal Article Neuron · August 4, 2021 Astrocytes extensively infiltrate the neuropil to regulate critical aspects of synaptic development and function. This process is regulated by transcellular interactions between astrocytes and neurons via cell adhesion molecules. How astrocytes coordinate ... Full text Link to item Cite

Emerging Role of PD-1 in the Central Nervous System and Brain Diseases.

Journal Article Neurosci Bull · August 2021 Programmed cell death protein 1 (PD-1) is an immune checkpoint modulator and a major target of immunotherapy as anti-PD-1 monoclonal antibodies have demonstrated remarkable efficacy in cancer treatment. Accumulating evidence suggests an important role of P ... Full text Link to item Cite

STING suppresses bone cancer pain via immune and neuronal modulation.

Journal Article Nat Commun · July 27, 2021 Patients with advanced stage cancers frequently suffer from severe pain as a result of bone metastasis and bone destruction, for which there is no efficacious treatment. Here, using multiple mouse models of bone cancer, we report that agonists of the immun ... Full text Link to item Cite

Identification and characterization of novel candidate compounds targeting 6- and 7-transmembrane μ-opioid receptor isoforms.

Journal Article Br J Pharmacol · July 2021 BACKGROUND AND PURPOSE: The μ-opioid receptor (μ receptor) is the primary target for opioid analgesics. The 7-transmembrane (TM) and 6TM μ receptor isoforms mediate inhibitory and excitatory cellular effects. Here, we developed compounds selective for 6TM- ... Full text Link to item Cite

Epithelia-Sensory Neuron Cross Talk Underlies Cholestatic Itch Induced by Lysophosphatidylcholine.

Journal Article Gastroenterology · July 2021 BACKGROUND & AIMS: Limited understanding of pruritus mechanisms in cholestatic liver diseases hinders development of antipruritic treatments. Previous studies implicated lysophosphatidic acid (LPA) as a potential mediator of cholestatic pruritus. METHODS: ... Full text Link to item Cite

A Role for Protease Activated Receptor Type 3 (PAR3) in Nociception Demonstrated Through Development of a Novel Peptide Agonist.

Journal Article J Pain · June 2021 The protease activated receptor (PAR) family is a group of G-protein coupled receptors (GPCRs) activated by proteolytic cleavage of the extracellular domain. PARs are expressed in a variety of cell types with crucial roles in homeostasis, immune responses, ... Full text Link to item Cite

A new synthetic protectin D1 analog 3-oxa-PD1n-3 DPA reduces neuropathic pain and chronic itch in mice.

Journal Article Org Biomol Chem · March 28, 2021 The resolution of inflammation is a biosynthetically active process controlled by the interplay between oxygenated polyunsaturated mediators and G-protein coupled receptor-signaling pathways. These enzymatically oxygenated polyunsaturated fatty acids belon ... Full text Link to item Cite

Activation of GPR37 in macrophages confers protection against infection-induced sepsis and pain-like behaviour in mice.

Journal Article Nat Commun · March 17, 2021 GPR37 was discovered more than two decades ago, but its biological functions remain poorly understood. Here we report a protective role of GPR37 in multiple models of infection and sepsis. Mice lacking Gpr37 exhibited increased death and/or hypothermia fol ... Full text Link to item Cite

Dectin-1 limits autoimmune neuroinflammation and promotes myeloid cell-astrocyte crosstalk via Card9-independent expression of Oncostatin M.

Journal Article Immunity · March 9, 2021 Pathologic roles of innate immunity in neurologic disorders are well described, but their beneficial aspects are less understood. Dectin-1, a C-type lectin receptor (CLR), is largely known to induce inflammation. Here, we report that Dectin-1 limited exper ... Full text Link to item Cite

Central opioid receptors mediate morphine-induced itch and chronic itch via disinhibition.

Journal Article Brain · March 3, 2021 Opioids such as morphine are mainstay treatments for clinical pain conditions. Itch is a common side effect of opioids, particularly as a result of epidural or intrathecal administration. Recent progress has advanced our understanding of itch circuits in t ... Full text Link to item Cite

STING controls nociception via type I interferon signalling in sensory neurons.

Journal Article Nature · March 2021 The innate immune regulator STING is a critical sensor of self- and pathogen-derived DNA. DNA sensing by STING leads to the induction of type-I interferons (IFN-I) and other cytokines, which promote immune-cell-mediated eradication of pathogens and neoplas ... Full text Link to item Cite

Degradable polymeric vehicles for postoperative pain management.

Journal Article Nat Commun · March 1, 2021 Effective control of pain management has the potential to significantly decrease the need for prescription opioids following a surgical procedure. While extended release products for pain management are available commercially, the implementation of a devic ... Full text Link to item Cite

Controlled release of etoricoxib from poly(ester urea) films for post-operative pain management.

Journal Article J Control Release · January 10, 2021 Medical prescriptions for the alleviation of post-surgical pain are the most abundant source of opioids in circulation. As a systemic drug delivery source, opioids leave patients at high risk for side effects after being dosed. Given the significant rate o ... Full text Link to item Cite

Reciprocal interactions between osteoclasts and nociceptive sensory neurons in bone cancer pain.

Journal Article Pain Rep · 2021 Many common cancers such as breast, prostate, and lung cancer metastasize to bones at advanced stages, producing severe pain and functional impairment. At present, the current pharmacotherapies available for bone cancer pain are insufficient to provide saf ... Full text Link to item Cite

STING suppresses cancer pain via immune and neuronal modulation

Journal Article · 2021 Agonists of the innate immune regulator stimulator of interferon genes (STING) have shown great efficacy in promoting antitumor immunity in preclinical models, leading to their exploration in cancer immunotherapy trials. Patients with advanced stage cancer ... Full text Cite

Spinal Cord Stimulation Attenuates Mechanical Allodynia and Increases Central Resolvin D1 Levels in Rats With Spared Nerve Injury.

Journal Article Front Physiol · 2021 Mounting evidence from animal models of inflammatory and neuropathic pain suggests that inflammation regulates the resolution of pain by producing specialized pro-resolving mediators (SPMs), such as resolvin D1 (RvD1). However, it remains unclear how SPMs ... Full text Link to item Cite

Interferons in Pain and Infections: Emerging Roles in Neuro-Immune and Neuro-Glial Interactions.

Journal Article Front Immunol · 2021 Interferons (IFNs) are cytokines that possess antiviral, antiproliferative, and immunomodulatory actions. IFN-α and IFN-β are two major family members of type-I IFNs and are used to treat diseases, including hepatitis and multiple sclerosis. Emerging evide ... Full text Link to item Cite

Cancer-specific type-I interferon receptor signaling promotes cancer stemness and effector CD8+ T-cell exhaustion.

Journal Article Oncoimmunology · 2021 Type-I interferon (IFN-I) signaling is critical to maintaining antigen-presenting cell function for anti-tumor immunity. However, recent studies have suggested that IFN-I signaling may also contribute to more aggressive phenotypes, raising the possibility ... Full text Link to item Cite

IL-23 Enhances C-Fiber-Mediated and Blue Light-Induced Spontaneous Pain in Female Mice.

Journal Article Front Immunol · 2021 The incidence of chronic pain is especially high in women, but the underlying mechanisms remain poorly understood. Interleukin-23 (IL-23) is a pro-inflammatory cytokine and contributes to inflammatory diseases (e.g., arthritis and psoriasis) through dendri ... Full text Link to item Cite

Lysophospholipids Contribute to Oxaliplatin-Induced Acute Peripheral Pain.

Journal Article J Neurosci · December 2, 2020 Oxaliplatin, a platinum-based chemotherapeutic drug, which is used as first-line treatment for some types of colorectal carcinoma, causes peripheral neuropathic pain in patients. In addition, an acute peripheral pain syndrome develop in almost 90% of patie ... Full text Link to item Cite

PD-1 Regulates GABAergic Neurotransmission and GABA-Mediated Analgesia and Anesthesia.

Journal Article iScience · October 23, 2020 The immune checkpoint inhibitor programmed cell death protein 1 (PD-1) plays a critical role in immune regulation. Recent studies have demonstrated functional PD-1 expression in peripheral sensory neurons, which contributes to neuronal excitability, pain, ... Full text Link to item Cite

How Do Sensory Neurons Sense Danger Signals?

Journal Article Trends Neurosci · October 2020 Sensory neurons are activated by physical and chemical stimuli, eliciting sensations such as temperature, touch, pain, and itch. From an evolutionary perspective, sensing danger is essential for organismal survival. Upon infection and injury, immune cells ... Full text Link to item Cite

Computer-aided Discovery of a New Nav1.7 Inhibitor for Treatment of Pain and Itch.

Journal Article Anesthesiology · September 2020 BACKGROUND: Voltage-gated sodium channel Nav1.7 has been validated as a perspective target for selective inhibitors with analgesic and anti-itch activity. The objective of this study was to discover new candidate compounds with Nav1.7 inhibitor properties. ... Full text Link to item Cite

Computer-aided Discovery of a New Nav1.7 Inhibitor for Treatment of Pain and Itch.

Journal Article Anesthesiology · September 1, 2020 BACKGROUND: Voltage-gated sodium channel Nav1.7 has been validated as a perspective target for selective inhibitors with analgesic and anti-itch activity. The objective of this study was to discover new candidate compounds with Nav1.7 inhibitor properties. ... Full text Link to item Cite

PD-1 blockade inhibits osteoclast formation and murine bone cancer pain.

Journal Article J Clin Invest · July 1, 2020 Emerging immune therapy, such as with the anti-programmed cell death-1 (anti-PD-1) monoclonal antibody nivolumab, has shown efficacy in tumor suppression. Patients with terminal cancer suffer from cancer pain as a result of bone metastasis and bone destruc ... Full text Link to item Cite

Neuromodulation, Specialized Proresolving Mediators, and Resolution of Pain.

Journal Article Neurotherapeutics · July 2020 The current crises in opioid abuse and chronic pain call for the development of nonopioid and nonpharmacological therapeutics for pain relief. Neuromodulation-based approaches, such as spinal cord stimulation, dorsal root ganglion simulation, and nerve sti ... Full text Link to item Cite

Central Nervous System Targets: Glial Cell Mechanisms in Chronic Pain.

Journal Article Neurotherapeutics · July 2020 Interactions between central glial cells and neurons in the pain circuitry are critical contributors to the pathogenesis of chronic pain. In the central nervous system (CNS), two major glial cell types predominate: astrocytes and microglia. Injuries or pat ... Full text Link to item Cite

Regulation of pain by neuro-immune interactions between macrophages and nociceptor sensory neurons.

Journal Article Curr Opin Neurobiol · June 2020 Inflammation is the body's protective reaction to injury and infection. Pain is a hallmark of inflammation and can be either protective or detrimental during acute or chronic phase. Macrophages play a chief role in the pathogenesis of pain and have bilater ... Full text Link to item Cite

Dectin-1 limits central nervous system autoimmunity through a non-canonical pathway

Conference · May 8, 2020 ABSTRACTPathologic roles for innate immunity in neurologic disorders are well-described, but protective aspects of the immune response are less understood. Dectin-1, a C-type lectin receptor (CLR), is largely known to induc ... Full text Cite

Neuroimmune modulation of pain and regenerative pain medicine.

Journal Article J Clin Invest · May 1, 2020 Regenerative pain medicine, which seeks to harness the body's own reparative capacity, is rapidly emerging as a field within pain medicine and orthopedics. It is increasingly appreciated that common analgesic mechanisms for these treatments depend on neuro ... Full text Link to item Cite

Periostin Activation of Integrin Receptors on Sensory Neurons Induces Allergic Itch.

Journal Article Cell Rep · April 7, 2020 Chronic allergic itch is a common symptom affecting millions of people and animals, but its pathogenesis is not fully explained. Herein, we show that periostin, abundantly expressed in the skin of patients with atopic dermatitis (AD), induces itch in mice, ... Full text Link to item Cite

Structural Insights into Electrophile Irritant Sensing by the Human TRPA1 Channel.

Journal Article Neuron · March 4, 2020 Transient receptor potential channel subfamily A member 1 (TRPA1) is a Ca2+-permeable cation channel that serves as one of the primary sensors of environmental irritants and noxious substances. Many TRPA1 agonists are electrophiles that are recognized by T ... Full text Link to item Cite

Anti-PD-1 treatment impairs opioid antinociception in rodents and nonhuman primates.

Journal Article Sci Transl Med · February 19, 2020 Emerging immunotherapies with monoclonal antibodies against programmed cell death protein-1 (PD-1) have shown success in treating cancers. However, PD-1 signaling in neurons is largely unknown. We recently reported that dorsal root ganglion (DRG) primary s ... Full text Link to item Cite

Astrocytes in chronic pain and itch.

Journal Article Nat Rev Neurosci · November 2019 Astrocytes are critical for maintaining the homeostasis of the CNS. Increasing evidence suggests that a number of neurological and neuropsychiatric disorders, including chronic pain, may result from astrocyte 'gliopathy'. Indeed, in recent years there has ... Full text Link to item Cite

Stabilization of μ-opioid receptor facilitates its cellular translocation and signaling.

Journal Article Proteins · October 2019 The G protein-coupled μ-opioid receptor (μ-OR) mediates the majority of analgesia effects for morphine and other pain relievers. Despite extensive studies of its structure and activation mechanisms, the inherently low maturation efficiency of μ-OR represen ... Full text Link to item Cite

Scratching after Stroking and Poking: A Spinal Circuit Underlying Mechanical Itch.

Journal Article Neuron · September 25, 2019 Mechanical itch is a desire to scratch due to light mechanical stimuli. In this issue of Neuron, Pan et al. (2019) identify a feedforward inhibition circuit in the spinal cord dorsal horn that processes mechanical itch as well as spontaneous itch. ... Full text Link to item Cite

Macrophage Toll-like Receptor 9 Contributes to Chemotherapy-Induced Neuropathic Pain in Male Mice.

Journal Article J Neurosci · August 28, 2019 Chemotherapy-induced peripheral neuropathy (CIPN) remains a pressing clinical problem; however, our understanding of sexual dimorphism in CIPN remains unclear. Emerging studies indicate a sex-dimorphic role of Toll-like receptor 4 (TLR4) in driving neuropa ... Full text Link to item Cite

Functional selection of protease inhibitory antibodies.

Journal Article Proc Natl Acad Sci U S A · August 13, 2019 Critical for diverse biological processes, proteases represent one of the largest families of pharmaceutical targets. To inhibit pathogenic proteases with desired selectivity, monoclonal antibodies (mAbs) hold great promise as research tools and therapeuti ... Full text Link to item Cite

Is Optogenetic Activation of Vglut1-Positive Aβ Low-Threshold Mechanoreceptors Sufficient to Induce Tactile Allodynia in Mice after Nerve Injury?

Journal Article J Neurosci · July 31, 2019 Mechanical allodynia is a cardinal feature of pathological pain. Recent work has demonstrated the necessity of Aβ-low-threshold mechanoreceptors (Aβ-LTMRs) for mechanical allodynia-like behaviors in mice, but it remains unclear whether these neurons are su ... Full text Link to item Cite

Contribution of Baroreceptor Function to Pain Perception and Perioperative Outcomes.

Journal Article Anesthesiology · April 2019 Baroreceptors are mechanosensitive elements of the peripheral nervous system that maintain homeostasis by coordinating physiologic responses to external and internal stimuli. While it is recognized that carotid and cardiopulmonary baroreceptor reflexes mod ... Full text Link to item Cite

Author Correction: PD-L1 inhibits acute and chronic pain by suppressing nociceptive neuron activity via PD-1.

Journal Article Nat Neurosci · March 2019 In the version of this article initially published, what was originally described as 'conditioned place preference' in a two-chamber mouse experiment could be better described as 'conditioned place avoidance'. ... Full text Link to item Cite

Roles of inflammation, neurogenic inflammation, and neuroinflammation in pain.

Journal Article J Anesth · February 2019 Inflammation is the body's response to injury and infection, involving a complex biological response of the somatosensory, immune, autonomic, and vascular systems. Inflammatory mediators such as prostaglandin, proinflammatory cytokines, and chemokines indu ... Full text Link to item Cite

The role of Nav1.7 and methylglyoxal-mediated activation of TRPA1 in itch and hypoalgesia in a murine model of type 1 diabetes.

Journal Article Theranostics · 2019 Methylglyoxal (MGO), an endogenous reactive carbonyl compound, plays a key role in the pathogenesis of diabetic neuropathy. The aim of this study is to investigate the role of MGO in diabetic itch and hypoalgesia, two common symptoms associated with diabet ... Full text Link to item Cite

Resolvin D5 Inhibits Neuropathic and Inflammatory Pain in Male But Not Female Mice: Distinct Actions of D-Series Resolvins in Chemotherapy-Induced Peripheral Neuropathy.

Journal Article Front Pharmacol · 2019 Earlier studies have demonstrated that essential fatty acid-derived specialized pro-resolving mediators (SPMs) promote the resolution of inflammation and pain. However, the potential analgesic actions of SPMs in chemotherapy-induced peripheral neuropathy ( ... Full text Open Access Link to item Cite

Microglia in Pain: Detrimental and Protective Roles in Pathogenesis and Resolution of Pain.

Journal Article Neuron · December 19, 2018 The previous decade has seen a rapid increase in microglial studies on pain, with a unique focus on microgliosis in the spinal cord after nerve injury and neuropathic pain. Numerous signaling molecules are altered in microglia and contribute to the pathoge ... Full text Link to item Cite

miRNA-711 Binds and Activates TRPA1 Extracellularly to Evoke Acute and Chronic Pruritus.

Journal Article Neuron · August 8, 2018 Increasing evidence suggests that extracellular miRNAs may serve as biomarkers of diseases, but the physiological relevance of extracellular miRNA is unclear. We find that intradermal cheek injection of miR-711 induces TRPA1-depedent itch (scratching) with ... Full text Link to item Cite

Intrathecal administration of antisense oligonucleotide against p38α but not p38β MAP kinase isoform reduces neuropathic and postoperative pain and TLR4-induced pain in male mice.

Journal Article Brain Behav Immun · August 2018 p38 mitogen-activated protein kinase (MAPK) consists of two major isoforms: p38α and p38β; however, it remains unclear which isoform is more important for chronic pain development. Recently, we developed potent, long-lasting, and p38 MAPK subtype-specific ... Full text Link to item Cite

Neuroinflammation and Central Sensitization in Chronic and Widespread Pain.

Journal Article Anesthesiology · August 2018 Chronic pain is maintained in part by central sensitization, a phenomenon of synaptic plasticity, and increased neuronal responsiveness in central pain pathways after painful insults. Accumulating evidence suggests that central sensitization is also driven ... Full text Link to item Cite

GPR37 regulates macrophage phagocytosis and resolution of inflammatory pain.

Journal Article J Clin Invest · August 1, 2018 The mechanisms of pain induction by inflammation have been extensively studied. However, the mechanisms of pain resolution are not fully understood. Here, we report that GPR37, expressed by macrophages (MΦs) but not microglia, contributes to the resolution ... Full text Link to item Cite

Transition to chronic pain: opportunities for novel therapeutics.

Journal Article Nat Rev Neurosci · July 2018 Although chronic pain is one of the most important medical problems facing society, there has been very limited progress in the development of novel therapies for this condition. Here, we discuss high-impact research priorities to reduce the number of peop ... Full text Link to item Cite

Transcriptional Profiling of Somatostatin Interneurons in the Spinal Dorsal Horn.

Journal Article Sci Rep · May 1, 2018 The spinal dorsal horn (SDH) is comprised of distinct neuronal populations that process different somatosensory modalities. Somatostatin (SST)-expressing interneurons in the SDH have been implicated specifically in mediating mechanical pain. Identifying th ... Full text Link to item Cite

Spinal CCL2 Promotes Central Sensitization, Long-Term Potentiation, and Inflammatory Pain via CCR2: Further Insights into Molecular, Synaptic, and Cellular Mechanisms.

Journal Article Neurosci Bull · February 2018 Mounting evidence supports an important role of chemokines, produced by spinal cord astrocytes, in promoting central sensitization and chronic pain. In particular, CCL2 (C-C motif chemokine ligand 2) has been shown to enhance N-methyl-D-aspartate (NMDA)-in ... Full text Link to item Cite

TNF-α/TNFR1 Signaling is Required for the Full Expression of Acute and Chronic Itch in Mice via Peripheral and Central Mechanisms.

Journal Article Neurosci Bull · February 2018 Increasing evidence suggests that cytokines and chemokines play crucial roles in chronic itch. In the present study, we evaluated the roles of tumor necrosis factor-alpha (TNF-α) and its receptors TNF receptor subtype-1 (TNFR1) and TNFR2 in acute and chron ... Full text Link to item Cite

Expression and Role of Voltage-Gated Sodium Channels in Human Dorsal Root Ganglion Neurons with Special Focus on Nav1.7, Species Differences, and Regulation by Paclitaxel.

Journal Article Neurosci Bull · February 2018 Voltage-gated sodium channels (Navs) play an important role in human pain sensation. However, the expression and role of Nav subtypes in native human sensory neurons are unclear. To address this issue, we obtained human dorsal root ganglion (hDRG) tissues ... Full text Link to item Cite

Sex-Dependent Glial Signaling in Pathological Pain: Distinct Roles of Spinal Microglia and Astrocytes.

Journal Article Neurosci Bull · February 2018 Increasing evidence suggests that spinal microglia regulate pathological pain in males. In this study, we investigated the effects of several microglial and astroglial modulators on inflammatory and neuropathic pain following intrathecal injection in male ... Full text Link to item Cite

Differential Inhibition of Nav1.7 and Neuropathic Pain by Hybridoma-Produced and Recombinant Monoclonal Antibodies that Target Nav1.7 : Differential activities of Nav1.7-targeting monoclonal antibodies.

Journal Article Neurosci Bull · February 2018 The voltage-gated Na+ channel subtype Nav1.7 is important for pain and itch in rodents and humans. We previously showed that a Nav1.7-targeting monoclonal antibody (SVmab) reduces Na+ currents and pain and itch responses in mice. Here, we investigated whet ... Full text Link to item Cite

Distinct Analgesic Actions of DHA and DHA-Derived Specialized Pro-Resolving Mediators on Post-operative Pain After Bone Fracture in Mice.

Journal Article Front Pharmacol · 2018 Mechanisms of pain resolution are largely unclear. Increasing evidence suggests that specialized pro-resolving mediators (SPMs), derived from fish oil docosahexaenoic acid (DHA), promote the resolution of acute inflammation and potently inhibit inflammator ... Full text Link to item Cite

Astrocytic neuroligins control astrocyte morphogenesis and synaptogenesis.

Journal Article Nature · November 8, 2017 Astrocytes are complex glial cells with numerous fine cellular processes that infiltrate the neuropil and interact with synapses. The mechanisms that control the establishment of astrocyte morphology are unknown, and it is unclear whether impairing astrocy ... Full text Link to item Cite

Deficiency of Shank2 causes mania-like behavior that responds to mood stabilizers.

Journal Article JCI insight · October 2017 Genetic defects in the synaptic scaffolding protein gene, SHANK2, are linked to a variety of neuropsychiatric disorders, including autism spectrum disorders, schizophrenia, intellectual disability, and bipolar disorder, but the molecular mechanisms underly ... Full text Cite

Gene Expression Profiling of Cutaneous Injured and Non-Injured Nociceptors in SNI Animal Model of Neuropathic Pain.

Journal Article Sci Rep · August 24, 2017 Nociceptors are a particular subtype of dorsal root ganglion (DRG) neurons that detect noxious stimuli and elicit pain. Although recent efforts have been made to reveal the molecular profile of nociceptors in normal conditions, little is known about how th ... Full text Link to item Cite

Targeting dorsal root ganglia and primary sensory neurons for the treatment of chronic pain.

Journal Article Expert Opin Ther Targets · July 2017 Currently the treatment of chronic pain is inadequate and compromised by debilitating central nervous system side effects. Here we discuss new therapeutic strategies that target dorsal root ganglia (DRGs) in the peripheral nervous system for a better and s ... Full text Link to item Cite

PD-L1 inhibits acute and chronic pain by suppressing nociceptive neuron activity via PD-1.

Journal Article Nat Neurosci · July 2017 Programmed cell death ligand-1 (PD-L1) is typically produced by cancer cells and suppresses immunity through the receptor PD-1 expressed on T cells. However, the role of PD-L1 and PD-1 in regulating pain and neuronal function is unclear. Here we report tha ... Full text Link to item Cite

Neuroinflammation, Bone Marrow Stem Cells, and Chronic Pain.

Journal Article Front Immunol · 2017 Current treatments for chronic pain, such as inflammatory pain, neuropathic pain, and cancer pain are insufficient and cause severe side effects. Mounting evidence suggests that neuroinflammation in the peripheral and central nervous system (PNS and CNS) p ... Full text Link to item Cite

SHANK3 Deficiency Impairs Heat Hyperalgesia and TRPV1 Signaling in Primary Sensory Neurons.

Journal Article Neuron · December 21, 2016 Abnormal pain sensitivity is commonly associated with autism spectrum disorders (ASDs) and affects the life quality of ASD individuals. SHANK3 deficiency was implicated in ASD and pain dysregulation. Here, we report functional expression of SHANK3 in mouse ... Full text Open Access Link to item Cite

Pain regulation by non-neuronal cells and inflammation.

Journal Article Science · November 4, 2016 Acute pain is protective and a cardinal feature of inflammation. Chronic pain after arthritis, nerve injury, cancer, and chemotherapy is associated with chronic neuroinflammation, a local inflammation in the peripheral or central nervous system. Accumulati ... Full text Open Access Link to item Cite

Targeting CYP2J to reduce paclitaxel-induced peripheral neuropathic pain.

Journal Article Proc Natl Acad Sci U S A · November 1, 2016 Chemotherapy-induced peripheral neuropathic pain (CIPNP) is a severe dose- and therapy-limiting side effect of widely used cytostatics that is particularly difficult to treat. Here, we report increased expression of the cytochrome-P450-epoxygenase CYP2J6 a ... Full text Open Access Link to item Cite

Interferon alpha inhibits spinal cord synaptic and nociceptive transmission via neuronal-glial interactions.

Journal Article Sci Rep · September 27, 2016 It is well known that interferons (IFNs), such as type-I IFN (IFN-α) and type-II IFN (IFN-γ) are produced by immune cells to elicit antiviral effects. IFNs are also produced by glial cells in the CNS to regulate brain functions. As a proinflammatory cytoki ... Full text Open Access Link to item Cite

Microglial Signaling in Chronic Pain with a Special Focus on Caspase 6, p38 MAP Kinase, and Sex Dependence.

Journal Article J Dent Res · September 2016 Microglia are the resident immune cells in the spinal cord and brain. Mounting evidence suggests that activation of microglia plays an important role in the pathogenesis of chronic pain, including chronic orofacial pain. In particular, microglia contribute ... Full text Link to item Cite

β-arrestin-2 regulates NMDA receptor function in spinal lamina II neurons and duration of persistent pain.

Journal Article Nat Commun · August 19, 2016 Mechanisms of acute pain transition to chronic pain are not fully understood. Here we demonstrate an active role of β-arrestin 2 (Arrb2) in regulating spinal cord NMDA receptor (NMDAR) function and the duration of pain. Intrathecal injection of the mu-opio ... Full text Open Access Link to item Cite

Spinal inhibition of p38 MAP kinase reduces inflammatory and neuropathic pain in male but not female mice: Sex-dependent microglial signaling in the spinal cord.

Journal Article Brain Behav Immun · July 2016 Previous studies have shown that activation of p38 mitogen-activating kinase (MAPK) in spinal microglia participates in the generation of inflammatory and neuropathic pain in various rodent models. However, these studies focused on male mice to avoid confo ... Full text Link to item Cite

TLR signaling adaptor protein MyD88 in primary sensory neurons contributes to persistent inflammatory and neuropathic pain and neuroinflammation.

Journal Article Sci Rep · June 17, 2016 Increasing evidence suggests that neuro-immune and neuro-glial interactions are critically involved in chronic pain sensitization. It is well studied how immune/glial mediators sensitize pain, but how sensory neurons control neuroinflammation remains uncle ... Full text Link to item Cite

Lipoxin A4 inhibits microglial activation and reduces neuroinflammation and neuropathic pain after spinal cord hemisection.

Journal Article J Neuroinflammation · April 8, 2016 BACKGROUND: Spinal cord injury (SCI) is a severe neurological disorder with many disabling consequences, including persistent neuropathic pain, which develops in about 40 % of SCI patients and is induced and sustained by excessive and uncontrolled spinal n ... Full text Link to item Cite

Toll-like receptor 4 contributes to chronic itch, alloknesis, and spinal astrocyte activation in male mice.

Journal Article Pain · April 2016 Increasing evidence suggests that Toll-like receptor 4 (TLR4) contributes importantly to spinal cord glial activation and chronic pain sensitization; however, its unique role in acute and chronic itch is unclear. In this study, we investigated the involvem ... Full text Link to item Cite

CXCL13 drives spinal astrocyte activation and neuropathic pain via CXCR5.

Journal Article J Clin Invest · February 2016 Recent studies have implicated chemokines in microglial activation and pathogenesis of neuropathic pain. C-X-C motif chemokine 13 (CXCL13) is a B lymphocyte chemoattractant that activates CXCR5. Using the spinal nerve ligation (SNL) model of neuropathic pa ... Full text Link to item Cite

Astrocytes Assemble Thalamocortical Synapses by Bridging NRX1α and NL1 via Hevin.

Journal Article Cell · January 14, 2016 Proper establishment of synapses is critical for constructing functional circuits. Interactions between presynaptic neurexins and postsynaptic neuroligins coordinate the formation of synaptic adhesions. An isoform code determines the direct interactions of ... Full text Link to item Cite

Neuroimmune interactions in itch: Do chronic itch, chronic pain, and chronic cough share similar mechanisms?

Journal Article Pulm Pharmacol Ther · December 2015 Itch and pain are closely related but also clearly distinct sensations. Pain is known to suppress itch, while analgesics such as morphine can provoke itch. However, in pathological and chronic conditions, pain and itch also have similarities. Dysfunction o ... Full text Link to item Cite

Inhibition of mechanical allodynia in neuropathic pain by TLR5-mediated A-fiber blockade.

Journal Article Nat Med · November 2015 Mechanical allodynia, induced by normally innocuous low-threshold mechanical stimulation, represents a cardinal feature of neuropathic pain. Blockade or ablation of high-threshold, small-diameter unmyelinated group C nerve fibers (C-fibers) has limited eff ... Full text Link to item Cite

Intrathecal bone marrow stromal cells inhibit neuropathic pain via TGF-β secretion.

Journal Article J Clin Invest · August 3, 2015 Neuropathic pain remains a pressing clinical problem. Here, we demonstrate that a local, intrathecal (i.t.) injection of bone marrow stromal cells (BMSCs) following lumbar puncture alleviates early- and late-phase neuropathic pain symptoms, such as allodyn ... Full text Open Access Link to item Cite

Different immune cells mediate mechanical pain hypersensitivity in male and female mice.

Journal Article Nat Neurosci · August 2015 A large and rapidly increasing body of evidence indicates that microglia-to-neuron signaling is essential for chronic pain hypersensitivity. Using multiple approaches, we found that microglia are not required for mechanical pain hypersensitivity in female ... Full text Link to item Cite

Spinal sensory projection neuron responses to spinal cord stimulation are mediated by circuits beyond gate control.

Journal Article J Neurophysiol · July 2015 Spinal cord stimulation (SCS) is a therapy used to treat intractable pain with a putative mechanism of action based on the Gate Control Theory. We hypothesized that sensory projection neuron responses to SCS would follow a single stereotyped response curve ... Full text Link to item Cite

Delayed activation of spinal microglia contributes to the maintenance of bone cancer pain in female Wistar rats via P2X7 receptor and IL-18.

Journal Article J Neurosci · May 20, 2015 Accumulating evidence suggests that activation of spinal microglia contributes to the development of inflammatory and neuropathic pain. However, the role of spinal microglia in the maintenance of chronic pain remains controversial. Bone cancer pain shares ... Full text Link to item Cite

Evidence for brain glial activation in chronic pain patients.

Journal Article Brain · March 2015 Although substantial evidence has established that microglia and astrocytes play a key role in the establishment and maintenance of persistent pain in animal models, the role of glial cells in human pain disorders remains unknown. Here, using the novel tec ... Full text Link to item Cite

Neuropathic pain is constitutively suppressed in early life by anti-inflammatory neuroimmune regulation.

Journal Article J Neurosci · January 14, 2015 Peripheral nerve injury can trigger neuropathic pain in adults but not in infants; indeed, for unknown reasons, neuropathic pain is rare before adolescence. We show here that the absence of neuropathic pain response in infant male rats and mice following n ... Full text Link to item Cite

Itch control by Toll-like receptors.

Journal Article Handb Exp Pharmacol · 2015 Toll-like receptors (TLRs) are cellular sensors designed to recognize molecular danger signals associated with exogenous or endogenous threats. Their activation leads to initiation of the host's immune responses in order to remove or contain the danger. Ho ... Full text Link to item Cite

TRAF6 upregulation in spinal astrocytes maintains neuropathic pain by integrating TNF-α and IL-1β signaling.

Journal Article Pain · December 2014 The proinflammatory cytokines tumor necrosis factor (TNF) α and interleukin (IL) 1β have been strongly implicated in the pathogenesis of neuropathic pain, but the intracellular signaling of these cytokines in glial cells is not fully understood. TNF recept ... Full text Link to item Cite

Chemokine CXCL1 enhances inflammatory pain and increases NMDA receptor activity and COX-2 expression in spinal cord neurons via activation of CXCR2.

Journal Article Exp Neurol · November 2014 Recent studies have shown that CXCL1 upregulation in spinal astrocytes is involved in the maintenance of neuropathic pain. However, whether and how CXCL1 regulates inflammatory pain remains unknown. Here we show that intraplantar injection of CFA increased ... Full text Link to item Cite

Connexin-43 induces chemokine release from spinal cord astrocytes to maintain late-phase neuropathic pain in mice.

Journal Article Brain · August 2014 Accumulating evidence suggests that spinal cord astrocytes play an important role in neuropathic pain sensitization by releasing astrocytic mediators (e.g. cytokines, chemokines and growth factors). However, it remains unclear how astrocytes control the re ... Full text Link to item Cite

Emerging targets in neuroinflammation-driven chronic pain.

Journal Article Nat Rev Drug Discov · July 2014 Current analgesics predominately modulate pain transduction and transmission in neurons and have limited success in controlling disease progression. Accumulating evidence suggests that neuroinflammation, which is characterized by infiltration of immune cel ... Full text Link to item Cite

Development of a membrane-anchored chemerin receptor agonist as a novel modulator of allergic airway inflammation and neuropathic pain.

Journal Article J Biol Chem · May 9, 2014 The chemerin receptor (CMKLR1) is a G protein-coupled receptor found on select immune, epithelial, and dorsal root ganglion/spinal cord neuronal cells. CMKLR1 is primarily coupled to the inhibitory G protein, Gαi, and has been shown to modulate the resolut ... Full text Link to item Cite

Extracellular microRNAs activate nociceptor neurons to elicit pain via TLR7 and TRPA1.

Journal Article Neuron · April 2, 2014 Intracellular microRNAs (miRNAs) are key regulators of gene expression. The role of extracellular miRNAs in neuronal activation and sensory behaviors are unknown. Here we report an unconventional role of extracellular miRNAs for rapid excitation of nocicep ... Full text Link to item Cite

Extracellular caspase-6 drives murine inflammatory pain via microglial TNF-α secretion.

Journal Article J Clin Invest · March 2014 Increasing evidence indicates that the pathogenesis of neuropathic pain is mediated through spinal cord microglia activation. The intracellular protease caspase-6 (CASP6) is known to regulate neuronal apoptosis and axonal degeneration; however, the contrib ... Full text Link to item Cite

Protection of neuropathic pain by pro-resolution lipid mediators

Conference JOURNAL OF NEUROIMMUNE PHARMACOLOGY · March 1, 2014 Link to item Cite

Toll-Like Receptors and Itch

Chapter · January 1, 2014 TLRs are also found to be expressed by various cell types in the central nervous system (CNS) and peripheral nervous system (PNS), such as microglia, astrocytes, oligodendrocytes, Schwann cells, and neurons (Okun et al. 2011; Buchanan et al. 2010; Lehnardt ... Full text Cite

Glia and pain: is chronic pain a gliopathy?

Journal Article Pain · December 2013 Activation of glial cells and neuro-glial interactions are emerging as key mechanisms underlying chronic pain. Accumulating evidence has implicated 3 types of glial cells in the development and maintenance of chronic pain: microglia and astrocytes of the c ... Full text Link to item Cite

New insights into the mechanisms of itch: are pain and itch controlled by distinct mechanisms?

Journal Article Pflugers Arch · December 2013 Itch and pain are closely related but distinct sensations. They share largely overlapping mediators and receptors, and itch-responding neurons are also sensitive to pain stimuli. Itch-mediating primary sensory neurons are equipped with distinct receptors a ... Full text Link to item Cite

Tissue plasminogen activator contributes to morphine tolerance and induces mechanical allodynia via astrocytic IL-1β and ERK signaling in the spinal cord of mice.

Journal Article Neuroscience · September 5, 2013 Accumulating evidence indicates that activation of spinal cord astrocytes contributes importantly to nerve injury and inflammation-induced persistent pain and chronic opioid-induced antinociceptive tolerance. Phosphorylation of extracellular signal-regulat ... Full text Link to item Cite

A feed-forward spinal cord glycinergic neural circuit gates mechanical allodynia.

Journal Article J Clin Invest · September 2013 Neuropathic pain is characterized by mechanical allodynia induced by low-threshold myelinated Aβ-fiber activation. The original gate theory of pain proposes that inhibitory interneurons in the lamina II of the spinal dorsal horn (DH) act as "gate control" ... Full text Link to item Cite

Loss of NR1 subunit of NMDARs in primary sensory neurons leads to hyperexcitability and pain hypersensitivity: involvement of Ca(2+)-activated small conductance potassium channels.

Journal Article J Neurosci · August 14, 2013 It is well established that activation of NMDARs plays an essential role in spinal cord synaptic plasticity (i.e., central sensitization) and pain hypersensitivity after tissue injury. Despite prominent expression of NMDARs in DRG primary sensory neurons, ... Full text Link to item Cite

Resolvin E1 inhibits neuropathic pain and spinal cord microglial activation following peripheral nerve injury.

Journal Article J Neuroimmune Pharmacol · March 2013 Accumulating evidence indicates that activation of spinal cord microglia plays an important role in the genesis of neuropathic pain. Resolvin E1 (E1) is derived from omega-3 polyunsaturated fatty acid and exhibits potent anti-inflammatory, pro-resolution, ... Full text Link to item Cite

The Qualitative Hyperalgesia Profile: A New Metric to Assess Chronic Post-Thoracotomy Pain.

Journal Article Open Pain J · 2013 Thoracotomy often results in chronic pain, characterized by resting pain and elevated mechano-sensitivity. This paper defines complex behavioral responses to tactile stimulation in rats after thoracotomy, shown to be reversibly relieved by systemic morphin ... Full text Link to item Cite

Microglia and spinal cord synaptic plasticity in persistent pain.

Journal Article Neural Plast · 2013 Microglia are regarded as macrophages in the central nervous system (CNS) and play an important role in neuroinflammation in the CNS. Microglial activation has been strongly implicated in neurodegeneration in the brain. Increasing evidence also suggests an ... Full text Link to item Cite

Astrocytic CX43 hemichannels and gap junctions play a crucial role in development of chronic neuropathic pain following spinal cord injury.

Journal Article Glia · November 2012 Chronic neuropathic pain is a frequent consequence of spinal cord injury (SCI). Yet despite recent advances, upstream releasing mechanisms and effective therapeutic options remain elusive. Previous studies have demonstrated that SCI results in excessive AT ... Full text Link to item Cite

TLR3 deficiency impairs spinal cord synaptic transmission, central sensitization, and pruritus in mice.

Journal Article J Clin Invest · June 2012 Itch, also known as pruritus, is a common, intractable symptom of several skin diseases, such as atopic dermatitis and xerosis. TLRs mediate innate immunity and regulate neuropathic pain, but their roles in pruritus are elusive. Here, we report that scratc ... Full text Link to item Cite

5,6-EET is released upon neuronal activity and induces mechanical pain hypersensitivity via TRPA1 on central afferent terminals.

Journal Article J Neurosci · May 2, 2012 Epoxyeicosatrienoic acids (EETs) are cytochrome P450-epoxygenase-derived metabolites of arachidonic acid that act as endogenous signaling molecules in multiple biological systems. Here we have investigated the specific contribution of 5,6-EET to transient ... Full text Link to item Cite

Short small-interfering RNAs produce interferon-α-mediated analgesia.

Journal Article Br J Anaesth · April 2012 BACKGROUND: There is increasing interest in RNA interference in pain research using the intrathecal route to deliver small-interfering RNA (siRNA). An interferon (IFN) response is a common side-effect of siRNA. However, the IFN response in the spinal cord ... Full text Link to item Cite

Emerging role of Toll-like receptors in the control of pain and itch.

Journal Article Neurosci Bull · April 2012 Toll-like receptors (TLRs) are germline-encoded pattern-recognition receptors that initiate innate immune responses by recognizing molecular structures shared by a wide range of pathogens, known as pathogen-associated molecular patterns (PAMPs). After tiss ... Full text Link to item Cite

Oxidative stress induces itch via activation of transient receptor potential subtype ankyrin 1 in mice.

Journal Article Neurosci Bull · April 2012 OBJECTIVE: To investigate the role of oxidative stress in itch-indicative scratching behavior in mice, and furthermore, to define the cellular and molecular mechanisms underlying oxidative stress-mediated itch. METHODS: Scratching behavior was induced by i ... Full text Link to item Cite

Macrophage proresolving mediator maresin 1 stimulates tissue regeneration and controls pain.

Journal Article FASEB J · April 2012 Self-resolving inflammatory exudates and lipid mediator metabolomics recently uncovered a new family of potent anti-inflammatory and proresolving mediators biosynthesized by macrophages (MΦs), denoted maresins. Here we determined that maresin 1 (MaR1) prod ... Full text Link to item Cite

Acute morphine induces matrix metalloproteinase-9 up-regulation in primary sensory neurons to mask opioid-induced analgesia in mice.

Journal Article Mol Pain · March 25, 2012 BACKGROUND: Despite decades of intense research efforts, actions of acute opioids are not fully understood. Increasing evidence suggests that in addition to well-documented antinociceptive effects opioids also produce paradoxical hyperalgesic and excitator ... Full text Link to item Cite

Acute morphine activates satellite glial cells and up-regulates IL-1β in dorsal root ganglia in mice via matrix metalloprotease-9.

Journal Article Mol Pain · March 22, 2012 BACKGROUND: Activation of spinal cord glial cells such as microglia and astrocytes has been shown to regulate chronic opioid-induced antinociceptive tolerance and hyperalgesia, due to spinal up-regulation of the proinflammatory cytokines such as interleuki ... Full text Link to item Cite

Resolvin D2 is a potent endogenous inhibitor for transient receptor potential subtype V1/A1, inflammatory pain, and spinal cord synaptic plasticity in mice: distinct roles of resolvin D1, D2, and E1.

Journal Article J Neurosci · December 14, 2011 Inflammatory pain such as arthritic pain is typically treated with opioids and cyclo-oxygenase-2 inhibitors with well known side effects. Transient receptor potential subtype vanilloid 1 (TRPV1) and TRP ankyryn 1 (TRPA1) contribute importantly to the genes ... Full text Link to item Cite

Emerging roles of resolvins in the resolution of inflammation and pain.

Journal Article Trends Neurosci · November 2011 Resolvins, including D and E series resolvins, are endogenous lipid mediators generated during the resolution phase of acute inflammation from the omega-3 polyunsaturated fatty acids docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA). Resolvins hav ... Full text Link to item Cite

Resolving TRPV1- and TNF-α-mediated spinal cord synaptic plasticity and inflammatory pain with neuroprotectin D1.

Journal Article J Neurosci · October 19, 2011 Mechanisms of inflammatory pain are not fully understood. We investigated the role of TRPV1 (transient receptor potential subtype V1) and TNF-α, two critical mediators for inflammatory pain, in regulating spinal cord synaptic transmission. We found in mice ... Full text Link to item Cite

Resolvins are potent analgesics for arthritic pain.

Journal Article Br J Pharmacol · September 2011 Arthritis-associated inflammatory pain represents a serious medical problem worldwide. Current treatments for arthritic pain are not very effective and cause unwanted side effects. Resolvins, including the resolvin D and resolvin E series, are a family of ... Full text Link to item Cite

Microglia: a promising target for treating neuropathic and postoperative pain, and morphine tolerance.

Journal Article J Formos Med Assoc · August 2011 Management of chronic pain, such as nerve-injury-induced neuropathic pain associated with diabetic neuropathy, viral infection, and cancer, is a real clinical challenge. Major surgeries, such as breast and thoracic surgery, leg amputation, and coronary art ... Full text Link to item Cite

Suppression of inflammatory and neuropathic pain by uncoupling CRMP-2 from the presynaptic Ca²⁺ channel complex.

Journal Article Nat Med · June 5, 2011 The use of N-type voltage-gated calcium channel (CaV2.2) blockers to treat pain is limited by many physiological side effects. Here we report that inflammatory and neuropathic hypersensitivity can be suppressed by inhibiting the binding of collapsin respon ... Full text Link to item Cite

JAK-STAT3 pathway regulates spinal astrocyte proliferation and neuropathic pain maintenance in rats.

Journal Article Brain · April 2011 Neuropathic pain, a debilitating pain condition, is a common consequence of damage to the nervous system. Optimal treatment of neuropathic pain is a major clinical challenge because the underlying mechanisms remain unclear and currently available treatment ... Full text Link to item Cite

TNF-α contributes to spinal cord synaptic plasticity and inflammatory pain: distinct role of TNF receptor subtypes 1 and 2.

Journal Article Pain · February 2011 Tumor necrosis factor-alpha (TNF-α) is a key proinflammatory cytokine. It is generally believed that TNF-α exerts its effects primarily via TNF receptor subtype-1 (TNFR1). We investigated the distinct roles of TNFR1 and TNFR2 in spinal cord synaptic transm ... Full text Link to item Cite

Perioperative nerve blockade: clues from the bench.

Journal Article Anesthesiol Res Pract · 2011 Peripheral and neuraxial nerve blockades are widely used in the perioperative period. Their values to diminish acute postoperative pain are established but other important outcomes such as chronic postoperative pain, or newly, cancer recurrence, or infecti ... Full text Link to item Cite

Toll-like receptor 7 mediates pruritus.

Journal Article Nat Neurosci · December 2010 Toll-like receptors are typically expressed in immune cells to regulate innate immunity. We found that functional Toll-like receptor 7 (TLR7) was expressed in C-fiber primary sensory neurons and was important for inducing itch (pruritus), but was not neces ... Full text Link to item Cite

Spinal injection of TNF-α-activated astrocytes produces persistent pain symptom mechanical allodynia by releasing monocyte chemoattractant protein-1.

Journal Article Glia · November 15, 2010 Accumulating evidence suggests that spinal astrocytes play an important role in the genesis of persistent pain, by increasing the activity of spinal cord nociceptive neurons, i.e., central sensitization. However, direct evidence of whether activation of as ... Full text Link to item Cite

VGLUT2-dependent glutamate release from nociceptors is required to sense pain and suppress itch.

Journal Article Neuron · November 4, 2010 Itch can be suppressed by painful stimuli, but the underlying neural basis is unknown. We generated conditional null mice in which vesicular glutamate transporter type 2 (VGLUT2)-dependent synaptic glutamate release from mainly Nav1.8-expressing nociceptor ... Full text Link to item Cite

Light touch induces ERK activation in superficial dorsal horn neurons after inflammation: involvement of spinal astrocytes and JNK signaling in touch-evoked central sensitization and mechanical allodynia.

Journal Article J Neurochem · October 2010 Activation of extracellular signal-regulated kinase (ERK) in spinal cord neurons could serve as a marker for sensitization of dorsal horn neurons in persistent pain. ERK is normally activated by high-threshold noxious stimuli. We investigated how low-thres ... Full text Link to item Cite

Glial cells and chronic pain.

Journal Article Neuroscientist · October 2010 Over the past few years, the control of pain exerted by glial cells has emerged as a promising target against pathological pain. Indeed, changes in glial phenotypes have been reported throughout the entire nociceptive pathway, from peripheral nerves to hig ... Full text Link to item Cite

Targeting astrocyte signaling for chronic pain.

Journal Article Neurotherapeutics · October 2010 Clinical management of chronic pain after nerve injury (neuropathic pain) and tumor invasion (cancer pain) is a real challenge due to our limited understanding of the cellular mechanisms that initiate and maintain chronic pain. It has been increasingly rec ... Full text Link to item Cite

Resolvins RvE1 and RvD1 attenuate inflammatory pain via central and peripheral actions.

Journal Article Nat Med · May 2010 Inflammatory pain, such as arthritis pain, is a growing health problem. Inflammatory pain is generally treated with opioids and cyclooxygenase (COX) inhibitors, but both are limited by side effects. Recently, resolvins, a unique family of lipid mediators, ... Full text Link to item Cite

Treating triple-negative breast cancer by a combination of rapamycin and cyclophosphamide: an in vivo bioluminescence imaging study.

Journal Article Eur J Cancer · April 2010 Rapamycin, a mammalian target of rapamycin (mTOR) inhibitor, has been shown to inhibit the growth of oestrogen positive breast cancer. However, triple-negative (TN) breast cancer is resistant to rapamycin treatment in vitro. We set to test a combination tr ... Full text Link to item Cite

Chemokines, neuronal-glial interactions, and central processing of neuropathic pain.

Journal Article Pharmacol Ther · April 2010 Millions of people worldwide suffer from neuropathic pain as a result of damage to or dysfunction of the nervous system under various disease conditions. Development of effective therapeutic strategies requires a better understanding of molecular and cellu ... Full text Link to item Cite

The c-Jun N-terminal kinase 1 (JNK1) in spinal astrocytes is required for the maintenance of bilateral mechanical allodynia under a persistent inflammatory pain condition.

Journal Article Pain · February 2010 Peripheral inflammation induces persistent central sensitization characterized by mechanical allodynia and heat hyperalgesia that are mediated by distinct mechanisms. Compared to well-demonstrated mechanisms of heat hyperalgesia, mechanisms underlying the ... Full text Link to item Cite

Large A-fiber activity is required for microglial proliferation and p38 MAPK activation in the spinal cord: different effects of resiniferatoxin and bupivacaine on spinal microglial changes after spared nerve injury.

Journal Article Mol Pain · September 22, 2009 BACKGROUND: After peripheral nerve injury, spontaneous ectopic activity arising from the peripheral axons plays an important role in inducing central sensitization and neuropathic pain. Recent evidence indicates that activation of spinal cord microglia als ... Full text Link to item Cite

Selective inhibition of JNK with a peptide inhibitor attenuates pain hypersensitivity and tumor growth in a mouse skin cancer pain model.

Journal Article Exp Neurol · September 2009 Cancer pain significantly affects the quality of cancer patients, and current treatments for this pain are limited. C-Jun N-terminal kinase (JNK) has been implicated in tumor growth and neuropathic pain sensitization. We investigated the role of JNK in can ... Full text Link to item Cite

Matrix metalloprotease regulation of neuropathic pain.

Journal Article Trends Pharmacol Sci · July 2009 Neuropathic pain affects millions of people globally and could be a disease on its own right. Current treatments focus on blocking neurotransmission and have resulted in limited success. Recent progress points to an important role of neuroinflammation in t ... Full text Link to item Cite

Organization of intralaminar and translaminar neuronal connectivity in the superficial spinal dorsal horn.

Journal Article J Neurosci · April 22, 2009 The spinal dorsal horn exhibits a high degree of intrinsic connectivity that is critical to its role in the processing of nociceptive information. To examine the spatial organization of this intrinsic connectivity, we used laser-scanning photostimulation i ... Full text Link to item Cite

JNK-induced MCP-1 production in spinal cord astrocytes contributes to central sensitization and neuropathic pain.

Journal Article J Neurosci · April 1, 2009 Our previous study showed that activation of c-jun-N-terminal kinase (JNK) in spinal astrocytes plays an important role in neuropathic pain sensitization. We further investigated how JNK regulates neuropathic pain. In cultured astrocytes, tumor necrosis fa ... Full text Link to item Cite

MAP kinase and pain.

Journal Article Brain Res Rev · April 2009 Mitogen-activated protein kinases (MAPKs) are important for intracellular signal transduction and play critical roles in regulating neural plasticity and inflammatory responses. The MAPK family consists of three major members: extracellular signal-regulate ... Full text Link to item Cite

Activation of extracellular signal-regulated kinase in the anterior cingulate cortex contributes to the induction and expression of affective pain.

Journal Article J Neurosci · March 11, 2009 The anterior cingulate cortex (ACC) is implicated in the affective response to noxious stimuli. However, little is known about the molecular mechanisms involved. The present study demonstrated that extracellular signal-regulated kinase (ERK) activation in ... Full text Link to item Cite

MAP kinase and cell signaling in DRG neurons and spinal microglia in neuropathic pain

Journal Article · January 1, 2009 Nerve injury is known to produce neuropathic pain by inducing changes not only in neurons such as primary sensory neurons in the dorsal root ganglion (DRG), but also in non-neuronal cells such as microglia in the spinal cord. Increasing evidence suggests t ... Full text Cite

Activation of p38 mitogen-activated protein kinase in spinal microglia contributes to incision-induced mechanical allodynia.

Journal Article Anesthesiology · January 2009 BACKGROUND: Recent studies have implicated the activation of stress-activated mitogen-activated protein kinase (MAPK) p38 in spinal microglial cells for development of neuropathic and inflammatory pain. The aim of the present study was to investigate wheth ... Full text Link to item Cite

Pain and Plasticity

Journal Article · January 1, 2009 Under normal conditions, pain is acute and protective, manifested as responsiveness to noxious stimuli. However, after tissue or nerve injury, pain becomes pathological and chronic, with increased responsiveness to noxious stimuli and even becoming respons ... Full text Cite

Nociceptors are interleukin-1beta sensors.

Journal Article J Neurosci · December 24, 2008 A cardinal feature of inflammation is heightened pain sensitivity at the site of the inflamed tissue. This results from the local release by immune and injured cells of nociceptor sensitizers, including prostaglandin E(2), bradykinin, and nerve growth fact ... Full text Link to item Cite

Intracellular signaling in primary sensory neurons and persistent pain.

Journal Article Neurochem Res · October 2008 During evolution, living organisms develop a specialized apparatus called nociceptors to sense their environment and avoid hazardous situations. Intense stimulation of high threshold C- and Adelta-fibers of nociceptive primary sensory neurons will elicit p ... Full text Link to item Cite

Use of bulleyaconitine A as an adjuvant for prolonged cutaneous analgesia in the rat.

Journal Article Anesth Analg · October 2008 BACKGROUND: Bulleyaconitine A (BLA) is an analgesic and antiinflammatory drug isolated from Aconitum plants. BLA has several potential targets, including voltage-gated Na+ channels. We tested whether BLA elicited long-lasting cutaneous analgesia, when co-i ... Full text Link to item Cite

Activation of JNK pathway in persistent pain.

Journal Article Neurosci Lett · June 6, 2008 The c-Jun N-terminal kinase (JNK) is a stress-activated member of MAP kinase family. JNK activation has been strongly implicated in inflammatory responses, neurodegeneration, and apoptosis. Recent evidence shows that JNK pathway is also transiently activat ... Full text Link to item Cite

Cytokine mechanisms of central sensitization: distinct and overlapping role of interleukin-1beta, interleukin-6, and tumor necrosis factor-alpha in regulating synaptic and neuronal activity in the superficial spinal cord.

Journal Article J Neurosci · May 14, 2008 Central sensitization, increased sensitivity in spinal cord dorsal horn neurons after injuries, plays an essential role in the induction and maintenance of chronic pain. However, synaptic mechanisms underlying central sensitization are incompletely known. ... Full text Link to item Cite

Endogenous tumor necrosis factor alpha (TNFalpha) requires TNF receptor type 2 to generate heat hyperalgesia in a mouse cancer model.

Journal Article J Neurosci · May 7, 2008 To provide a tool to investigate the mechanisms inducing and maintaining cancer-related pain and hyperalgesia, a soft tissue tumor/metastasis model was developed that is applicable in C57BL/6J wild-type and transgenic mice. We show that the experimental tu ... Full text Link to item Cite

Bradykinin enhances AMPA and NMDA receptor activity in spinal cord dorsal horn neurons by activating multiple kinases to produce pain hypersensitivity.

Journal Article J Neurosci · April 23, 2008 Bradykinin potentiates synaptic glutamate release and action in the spinal cord via presynaptic and postsynaptic B(2) receptors, contributing thereby to activity-dependent central sensitization and pain hypersensitivity (Wang et al., 2005). We have now exa ... Full text Link to item Cite

Distinct roles of matrix metalloproteases in the early- and late-phase development of neuropathic pain.

Journal Article Nat Med · March 2008 Treatment of neuropathic pain, triggered by multiple insults to the nervous system, is a clinical challenge because the underlying mechanisms of neuropathic pain development remain poorly understood. Most treatments do not differentiate between different p ... Full text Link to item Cite

Transcriptional and functional profiles of voltage-gated Na(+) channels in injured and non-injured DRG neurons in the SNI model of neuropathic pain.

Journal Article Mol Cell Neurosci · February 2008 Changes in expression and function of voltage-gated sodium channels (VGSC) in dorsal root ganglion (DRG) neurons may play a major role in the genesis of peripheral hyperexcitability that occurs in neuropathic pain. We present here the first description of ... Full text Link to item Cite

p38 MAPK, microglial signaling, and neuropathic pain.

Journal Article Mol Pain · November 1, 2007 Accumulating evidence over last several years indicates an important role of microglial cells in the pathogenesis of neuropathic pain. Signal transduction in microglia under chronic pain states has begun to be revealed. We will review the evidence that p38 ... Full text Link to item Cite

Neurokinin-1 receptor enhances TRPV1 activity in primary sensory neurons via PKCepsilon: a novel pathway for heat hyperalgesia.

Journal Article J Neurosci · October 31, 2007 The neuropeptide substance P (SP) is expressed in unmyelinated primary sensory neurons and represents the best known "pain" neurotransmitter. It is generally believed that SP regulates pain transmission and sensitization by acting on neurokinin-1 receptor ... Full text Link to item Cite

Do glial cells control pain?

Journal Article Neuron Glia Biol · August 2007 Management of chronic pain is a real challenge, and current treatments that focus on blocking neurotransmission in the pain pathway have resulted in limited success. Activation of glial cells has been widely implicated in neuroinflammation in the CNS, lead ... Full text Link to item Cite

Nerve conduction blockade in the sciatic nerve prevents but does not reverse the activation of p38 mitogen-activated protein kinase in spinal microglia in the rat spared nerve injury model.

Journal Article Anesthesiology · August 2007 BACKGROUND: Current evidence indicates that p38 mitogen-activated protein kinase activation in spinal microglia contributes to the development of neuropathic pain. However, how nerve injury activates p38 in spinal microglia is incompletely unknown. Nerve i ... Full text Link to item Cite

Role of the CX3CR1/p38 MAPK pathway in spinal microglia for the development of neuropathic pain following nerve injury-induced cleavage of fractalkine.

Journal Article Brain Behav Immun · July 2007 Accumulating evidence suggests that microglial cells in the spinal cord play an important role in the development of neuropathic pain. However, it remains largely unknown how glia interact with neurons in the spinal cord after peripheral nerve injury. Rece ... Full text Link to item Cite

Differential wiring of local excitatory and inhibitory synaptic inputs to islet cells in rat spinal lamina II demonstrated by laser scanning photostimulation.

Journal Article J Physiol · May 1, 2007 The substantia gelatinosa (lamina II) of the spinal dorsal horn contains inhibitory and excitatory interneurons that are thought to play a critical role in the modulation of nociception. However, the organization of the intrinsic circuitry within lamina II ... Full text Link to item Cite

Protein kinases as potential targets for the treatment of pathological pain.

Journal Article Handb Exp Pharmacol · 2007 Pathological pain or clinical pain refers to tissue injury-induced inflammatory pain and nerve injury-induced neuropathic pain and is often chronic. Pathological pain is an expression of neural plasticity that occurs both in the peripheral nervous system ( ... Full text Link to item Cite

Possible role of spinal astrocytes in maintaining chronic pain sensitization: review of current evidence with focus on bFGF/JNK pathway.

Journal Article Neuron Glia Biol · November 2006 Although pain is regarded traditionally as neuronally mediated, recent progress shows an important role of spinal glial cells in persistent pain sensitization. Mounting evidence has implicated spinal microglia in the development of chronic pain (e.g. neuro ... Full text Link to item Cite

Induction of CB1 cannabinoid receptor by inflammation in primary afferent neurons facilitates antihyperalgesic effect of peripheral CB1 agonist.

Journal Article Pain · September 2006 Cannabinoids act on various regions in the nervous system to modulate neuronal activity including nociception. Here, we investigated CB1 receptor expression in primary afferent neurons in the dorsal root ganglion (DRG) and the efficacy of a local (intrapla ... Full text Link to item Cite

Effects of bupivacaine and tetrodotoxin on carrageenan-induced hind paw inflammation in rats (Part 2): cytokines and p38 mitogen-activated protein kinases in dorsal root ganglia and spinal cord.

Journal Article Anesthesiology · July 2006 BACKGROUND: The authors previously showed that bupivacaine and tetrodotoxin via contralateral or ipsilateral sciatic block, but not systemically, attenuate local edema and hyperalgesia induced by carrageenan hind paw injection in rats. Bupivacaine, by all ... Full text Link to item Cite

Neural-glial interaction in the spinal cord for the development and maintenance of nerve injury-induced neuropathic pain

Journal Article Drug Development Research · April 1, 2006 Damage to the nervous system often results in neuropathic pain. Current treatment for this disabling state is unsuccessful due to our incomplete understanding of cellular mechanisms causing this pain. Although glial cells were largely ignored in most textb ... Full text Cite

A peptide c-Jun N-terminal kinase (JNK) inhibitor blocks mechanical allodynia after spinal nerve ligation: respective roles of JNK activation in primary sensory neurons and spinal astrocytes for neuropathic pain development and maintenance.

Journal Article J Neurosci · March 29, 2006 Optimal management of neuropathic pain is a major clinical challenge. We investigated the involvement of c-Jun N-terminal kinase (JNK) in neuropathic pain produced by spinal nerve ligation (SNL) (L5). SNL induced a slow (>3 d) and persistent (>21 d) activa ... Full text Link to item Cite

Is endogenous D-serine in the rostral anterior cingulate cortex necessary for pain-related negative affect?

Journal Article J Neurochem · March 2006 Functional activation of NMDA receptors requires co-activation of glutamate- and glycine-binding sites. D-serine is considered to be an endogenous ligand for the glycine site of NMDA receptors. Using a combination of a rat formalin-induced conditioned plac ... Full text Link to item Cite

Different effects of opioid and cannabinoid receptor agonists on C-fiber-induced extracellular signal-regulated kinase activation in dorsal horn neurons in normal and spinal nerve-ligated rats.

Journal Article J Pharmacol Exp Ther · February 2006 Nerve injury results in neuropathic pain, a debilitating pain condition. Whereas cannabinoids are consistently shown to attenuate neuropathic pain, the efficacy of opioids is highly controversial. Molecular mechanisms underlying analgesic effects of opioid ... Full text Link to item Cite

Emotional distress and related memory of pain: A neurobiological review

Journal Article Neuroscience Bulletin · December 1, 2005 The pain experience includes a sensory-discriminative and an emotional-affective component. The sensory dimension describes the quality, intensity, and spatio-temporal characteristics of the sensation. The affective dimension refers to the unpleasantness o ... Cite

The role of MAP kinase cascades in cell signaling, neural plasticity and pain facilitation

Journal Article Neuroscience Bulletin · December 1, 2005 Pathological pain, normally referring to tissue injury-induced inflammatory pain and nerve injury-induced neuropathic pain, is an expression of neural plasticity. Injuries and intense noxious stimuli result in pain hypersensitivity, which is contributed by ... Cite

Upregulation of the voltage-gated sodium channel beta2 subunit in neuropathic pain models: characterization of expression in injured and non-injured primary sensory neurons.

Journal Article J Neurosci · November 23, 2005 The development of abnormal primary sensory neuron excitability and neuropathic pain symptoms after peripheral nerve injury is associated with altered expression of voltage-gated sodium channels (VGSCs) and a modification of sodium currents. To investigate ... Full text Link to item Cite

Peripheral axonal injury results in reduced mu opioid receptor pre- and post-synaptic action in the spinal cord.

Journal Article Pain · September 2005 In both the spared nerve injury (SNI) and spinal nerve ligation (SNL) rat peripheral neuropathic pain models the presynaptic inhibitory effect of the mu opioid receptor (MOR) agonist (DAMGO) on primary afferent-evoked excitatory postsynaptic currents (EPSC ... Full text Link to item Cite

Bradykinin produces pain hypersensitivity by potentiating spinal cord glutamatergic synaptic transmission.

Journal Article J Neurosci · August 31, 2005 Bradykinin, an inflammatory mediator, sensitizes nociceptor peripheral terminals reducing pain threshold. We now show that the B2 kinin receptor is expressed in rat dorsal horn neurons and that bradykinin, a B2-specific agonist, augments AMPA- and NMDA-ind ... Full text Link to item Cite

ERK is sequentially activated in neurons, microglia, and astrocytes by spinal nerve ligation and contributes to mechanical allodynia in this neuropathic pain model.

Journal Article Pain · March 2005 Activation of extracellular signal-regulated kinase (ERK), a mitogen activated-protein kinase (MAPK), in dorsal horn neurons contributes to inflammatory pain by transcription-dependent and -independent means. We have now investigated if ERK is activated in ... Full text Link to item Cite

Phosphatidylinositol 3-kinase activates ERK in primary sensory neurons and mediates inflammatory heat hyperalgesia through TRPV1 sensitization.

Journal Article J Neurosci · September 22, 2004 Although the PI3K (phosphatidylinositol 3-kinase) pathway typically regulates cell growth and survival, increasing evidence indicates the involvement of this pathway in neural plasticity. It is unknown whether the PI3K pathway can mediate pain hypersensiti ... Full text Link to item Cite

Ionotropic and metabotropic receptors, protein kinase A, protein kinase C, and Src contribute to C-fiber-induced ERK activation and cAMP response element-binding protein phosphorylation in dorsal horn neurons, leading to central sensitization.

Journal Article J Neurosci · September 22, 2004 Molecular mechanisms underlying C-fiber stimulation-induced ERK (extracellular signal-regulated kinase) activation in dorsal horn neurons and its contribution to central sensitization have been investigated. In adult rat spinal slice preparations, activati ... Full text Link to item Cite

Cell signaling and the genesis of neuropathic pain.

Journal Article Sci STKE · September 21, 2004 Damage to the nervous system can cause neuropathic pain, which is in general poorly treated and involves mechanisms that are incompletely known. Currently available animal models for neuropathic pain mainly involve partial injury of peripheral nerves. Mult ... Full text Link to item Cite

Peripheral and central mechanisms of inflammatory pain, with emphasis on MAP kinases.

Journal Article Curr Drug Targets Inflamm Allergy · September 2004 Tissue injury is associated with inflammation and produces inflammatory pain. In animal models, inflammatory pain is normally produced by injection of irritative chemicals into the hindpaw or joint of animal. Inflammatory pain manifests as an expression of ... Full text Link to item Cite

Peripheral noxious stimulation induces phosphorylation of the NMDA receptor NR1 subunit at the PKC-dependent site, serine-896, in spinal cord dorsal horn neurons.

Journal Article Eur J Neurosci · July 2004 The N-methyl-D-aspartate receptor (NMDAR) contributes to central sensitization in the spinal cord and the generation of pain hypersensitivity. NMDAR function is modulated by post-translational modifications including phosphorylation, and this is proposed t ... Full text Link to item Cite

DRAGON: a member of the repulsive guidance molecule-related family of neuronal- and muscle-expressed membrane proteins is regulated by DRG11 and has neuronal adhesive properties.

Journal Article J Neurosci · February 25, 2004 DRG11, a transcription factor expressed in embryonic dorsal root ganglion (DRG) and dorsal horn neurons, has a role in the development of sensory circuits. We have used a genomic binding strategy to screen for the promoter region of genes regulated by DRG1 ... Full text Link to item Cite

Mitogen-activated protein kinases as potential targets for pain killers.

Journal Article Curr Opin Investig Drugs · January 2004 Pathological pain, such as inflammatory and neuropathic pain, is an expression of neural plasticity. Mitogen-activated protein kinases (MAPKs) play an important role in neural plasticity via post-translational, translational and transcriptional regulation. ... Link to item Cite

Central sensitization and LTP: do pain and memory share similar mechanisms?

Journal Article Trends Neurosci · December 2003 Synaptic plasticity is fundamental to many neurobiological functions, including memory and pain. Central sensitization refers to the increased synaptic efficacy established in somatosensory neurons in the dorsal horn of the spinal cord following intense pe ... Full text Link to item Cite

Removal of GABAergic inhibition facilitates polysynaptic A fiber-mediated excitatory transmission to the superficial spinal dorsal horn.

Journal Article Mol Cell Neurosci · November 2003 Primary afferent A-fiber stimulation normally evokes fast mono- or polysynaptic EPSCs of short duration. However, in the presence of the GABA(A) receptor antagonist bicuculline, repetitive, long lasting, polysynaptic EPSCs can be observed following the ini ... Full text Link to item Cite

Disruption of ErbB receptor signaling in adult non-myelinating Schwann cells causes progressive sensory loss.

Journal Article Nat Neurosci · November 2003 Here we studied the role of signaling through ErbB-family receptors in interactions between unmyelinated axons and non-myelinating Schwann cells in adult nerves. We generated transgenic mice that postnatally express a dominant-negative ErbB receptor in non ... Full text Link to item Cite

Upregulation of spinal cannabinoid-1-receptors following nerve injury enhances the effects of Win 55,212-2 on neuropathic pain behaviors in rats.

Journal Article Pain · September 2003 Exogenous cannabinoids are effective in attenuating neuropathic pain behaviors induced by peripheral nerve injury, but the mechanisms of their effectiveness remain unclear. Here we examined the expression of spinal cannabinoid-1-receptors (CB1Rs) following ... Full text Link to item Cite

p38 mitogen-activated protein kinase is activated after a spinal nerve ligation in spinal cord microglia and dorsal root ganglion neurons and contributes to the generation of neuropathic pain.

Journal Article J Neurosci · May 15, 2003 The possible involvement of p38 mitogen-activated protein kinase activation in spinal cord and dorsal root ganglion (DRG) cells in the development of peripheral neuropathic pain has been explored. Ligation of the L5 spinal nerve (SNL) on one side in adult ... Full text Link to item Cite

p38 MAPK activation by NGF in primary sensory neurons after inflammation increases TRPV1 levels and maintains heat hyperalgesia.

Journal Article Neuron · September 26, 2002 Peripheral inflammation induces p38 MAPK activation in the soma of C fiber nociceptors in the dorsal root ganglion (DRG) after 24 hr. Inflammation also increases protein, but not mRNA levels, of the heat-gated ion channel TRPV1 (VR1) in these cells, which ... Full text Link to item Cite

Chronic morphine induces downregulation of spinal glutamate transporters: implications in morphine tolerance and abnormal pain sensitivity.

Journal Article J Neurosci · September 15, 2002 Tolerance to the analgesic effects of an opioid occurs after its chronic administration, a pharmacological phenomenon that has been associated with the development of abnormal pain sensitivity such as hyperalgesia. In the present study, we examined the rol ... Full text Link to item Cite

Neuronal apoptosis associated with morphine tolerance: evidence for an opioid-induced neurotoxic mechanism.

Journal Article J Neurosci · September 1, 2002 Tolerance to the analgesic effect of an opioid is a pharmacological phenomenon that occurs after its prolonged administration. Activation of the NMDA receptor (NMDAR) has been implicated in the cellular mechanisms of opioid tolerance. However, activation o ... Full text Link to item Cite

The pattern of expression of the voltage-gated sodium channels Na(v)1.8 and Na(v)1.9 does not change in uninjured primary sensory neurons in experimental neuropathic pain models.

Journal Article Pain · April 2002 A spared nerve injury of the sciatic nerve (SNI) or a segmental lesion of the L5 and L6 spinal nerves (SNL) lead to behavioral signs of neuropathic pain in the territory innervated by adjacent uninjured nerve fibers, while a chronic constriction injury (CC ... Full text Link to item Cite

ERK MAP kinase activation in superficial spinal cord neurons induces prodynorphin and NK-1 upregulation and contributes to persistent inflammatory pain hypersensitivity.

Journal Article J Neurosci · January 15, 2002 Activation of ERK (extracellular signal-regulated kinase) MAP (mitogen-activated protein) kinase in dorsal horn neurons of the spinal cord by peripheral noxious stimulation contributes to short-term pain hypersensitivity. We investigated ERK activation by ... Full text Link to item Cite

beta-Endorphin-containing memory-cells and mu-opioid receptors undergo transport to peripheral inflamed tissue.

Journal Article J Neuroimmunol · April 2, 2001 Immunocyte-derived beta-endorphin can activate peripheral opioid receptors on sensory neurons to inhibit pain within inflamed tissue. This study examined mu-opioid receptors (MOR) on sensory nerves and beta-endorphin (END) in activated/memory CD4(+) cells ... Full text Link to item Cite

Neuronal plasticity and signal transduction in nociceptive neurons: implications for the initiation and maintenance of pathological pain.

Journal Article Neurobiol Dis · February 2001 Pathological pain, consisting of tissue injury-induced inflammatory and nerve injury-induced neuropathic pain, is an expression of neuronal plasticity. One component of this is that the afferent input generated by injury and intense noxious stimuli trigger ... Full text Link to item Cite

Nociceptive-specific activation of ERK in spinal neurons contributes to pain hypersensitivity.

Journal Article Nat Neurosci · December 1999 We investigated the involvement of extracellular signal-regulated protein kinases (ERK) within spinal neurons in producing pain hypersensitivity. Within a minute of an intense noxious peripheral or C-fiber electrical stimulus, many phosphoERK-positive neur ... Full text Link to item Cite

Neurotrophins: peripherally and centrally acting modulators of tactile stimulus-induced inflammatory pain hypersensitivity.

Journal Article Proc Natl Acad Sci U S A · August 3, 1999 Brain-derived neurotrophic factor (BDNF) is expressed in nociceptive sensory neurons and transported anterogradely to the dorsal horn of the spinal cord where it is located in dense core vesicles in C-fiber terminals. Peripheral inflammation substantially ... Full text Link to item Cite

Repetitive transcranial magnetic stimulation activates specific regions in rat brain.

Journal Article Proc Natl Acad Sci U S A · December 22, 1998 Repetitive transcranial magnetic stimulation (rTMS) is a noninvasive technique to induce electric currents in the brain. Although rTMS is being evaluated as a possible alternative to electroconvulsive therapy for the treatment of refractory depression, lit ... Full text Link to item Cite

Specific agrin isoforms induce cAMP response element binding protein phosphorylation in hippocampal neurons.

Journal Article J Neurosci · December 1, 1998 The synaptic basal lamina protein agrin is essential for the formation of neuromuscular junctions. Agrin mediates the postsynaptic clustering of acetylcholine receptors and regulates transcription in muscles. Agrin expression is not restricted to motor neu ... Full text Link to item Cite

The effect of intrathecal neuropeptide Y on the flexor reflex in rats after carrageenan-induced inflammation.

Journal Article Neuropeptides · October 1998 We examined the effects of intrathecal (i.t.) administration of neuropeptide Y (NPY) on the excitability of the flexor reflex in normal rats and 24 h after inflammation induced by subcutaneous carrageenan. In normal rats, i.t. NPY at low doses (10 and 100 ... Full text Link to item Cite

Phosphorylation of transcription factor CREB in rat spinal cord after formalin-induced hyperalgesia: relationship to c-fos induction.

Journal Article J Neurosci · March 1, 1997 The involvement of cAMP-responsive element-binding protein (CREB) signaling in tissue injury-induced inflammation and hyperalgesia has been characterized by measuring phosphorylation of CREB at serine-133 (CREB Ser133) using a specific antibody. In the uns ... Full text Link to item Cite

aFGF, bFGF and NGF differentially regulate neuropeptide expression in dorsal root ganglia after axotomy and induce autotomy.

Journal Article Regul Pept · October 22, 1996 Using immunohistochemistry and in situ hybridization the in vivo effects of acidic and basic fibroblast growth factor (aFGF, bFGF), and of nerve growth factor (NGF) on the expression of galanin, neuropeptide Y (NPY) and substance P in axotomized dorsal roo ... Full text Link to item Cite

Expression of peptides, nitric oxide synthase and NPY receptor in trigeminal and nodose ganglia after nerve lesions.

Journal Article Exp Brain Res · October 1996 Using immunohistochemistry and in situ hybridization, the expression of galanin (GAL)/galanin message associated peptide (GMAP)-, neuropeptide Y (NPY)-, vasoactive intestinal polypeptide (VIP)/peptide histidine isoleucine (PHI)- and nitric oxide synthase ( ... Full text Link to item Cite

Ca2+/calmodulin-dependent protein kinase type IV in dorsal root ganglion: colocalization with peptides, axonal transport and effect of axotomy.

Journal Article Brain Res · May 20, 1996 Using the indirect immunofluorescence technique, the distribution of Ca2+/calmodulin-dependent protein kinase IV (CaM kinase IV) was studied in dorsal root ganglia (DRGs) and the sciatic nerve under normal circumstances and after axotomy and nerve ligation ... Full text Link to item Cite

Expression of pituitary adenylate cyclase-activating polypeptide in dorsal root ganglia following axotomy: time course and coexistence.

Journal Article Brain Res · December 24, 1995 Pituitary adenylate cyclase-activating polypeptide (PACAP) has recently been demonstrated in sensory neurons. In the present study on rat 17.5% of all neurons, mainly of small size, contained PACAP in normal dorsal root ganglia (DRGs). Transection of the s ... Full text Link to item Cite

Expression of mu-, delta-, and kappa-opioid receptor-like immunoreactivities in rat dorsal root ganglia after carrageenan-induced inflammation.

Journal Article J Neurosci · December 1995 Recently, antisera that recognize unique epitopes of the cloned mu-, delta-, and kappa-opioid, receptors (MOR, DOR, KOR, respectively) have been developed. In the present study MOR-, DOR-, and KOR-like immunoreactivities (LIs) were examined in rat dorsal r ... Full text Link to item Cite

Prominent expression of bFGF in dorsal root ganglia after axotomy.

Journal Article Eur J Neurosci · December 1, 1995 Using quantitative in situ hybridization and immunohistochemistry the expression of acidic and basic fibroblast growth factors (aFGF, bFGF) in dorsal root ganglia (DRGs) was examined. Around 5% of the small neurons expressed bFGF mRNA in normal DRGs. Nerve ... Full text Link to item Cite

Effect of administration of high dose intrathecal clonidine or morphine prior to sciatic nerve section on c-Fos expression in rat lumbar spinal cord.

Journal Article Neuroscience · October 1995 The effects of moderate and high intrathecal doses of clonidine, an alpha 2 adrenoceptor agonist, or a high dose of morphine on sciatic nerve section-induced expression of c-Fos-like immunoreactivity was studied in laminae I and II of the dorsal horn and l ... Full text Link to item Cite

Central and peripheral expression of galanin in response to inflammation.

Journal Article Neuroscience · September 1995 Using in situ hybridization, immunohistochemistry and receptor binding methodology, the galanin messenger RNA levels, galanin binding and galanin-like immunoreactivity were examined in rats injected with carrageenan into the left hindpaw. Three days after ... Full text Link to item Cite

Fibroblast growth factors regulate calcitonin gene-related peptide mRNA expression in rat motoneurons after lesion and in culture.

Journal Article Eur J Neurosci · August 1, 1995 In this study, we have investigated the effect of fibroblast growth factors (bFGF and FGF-5) and brain derived neurotrophic factor (BDNF) on the expression of calcitonin gene-related peptide (CGRP) in rat motoneurons in vivo and in vitro. Following sciatic ... Full text Link to item Cite

Effect of growth factors on substance P mRNA expression in axotomized dorsal root ganglia.

Journal Article Neuroreport · June 19, 1995 The effects of NGF, BDNF, NT-3, BDNF plus NT-3 and LIF on substance P (SP) mRNA levels were analysed in axotomized dorsal root ganglia (DRGs) in vivo by quantitative in situ hybridization. The growth factors were applied on to the transected sciatic nerve. ... Full text Link to item Cite

Neuropeptide Y and galanin binding sites in rat and monkey lumbar dorsal root ganglia and spinal cord and effect of peripheral axotomy.

Journal Article Eur J Neurosci · March 1, 1995 Using monoiodinated peptide YY (PYY) and galanin as radioligands, and neuropeptide Y (NPY) fragments, the distribution of NPY binding sites and its subtypes Y1 and Y2, and of galanin binding sites, was investigated in rat and monkey lumbar (L) 4 and L5 dor ... Full text Link to item Cite

Galanin antisense oligonucleotides reduce galanin levels in dorsal root ganglia and induce autotomy in rats after axotomy.

Journal Article Proc Natl Acad Sci U S A · December 20, 1994 Antisense (AS) oligonucleotides (ONs) to galanin (GAL) were applied to the proximal end of a transected sciatic nerve, allowing their cellular uptake and transport into injured axons. GAL expression in dorsal root ganglia and self-mutilation behavior (auto ... Full text Link to item Cite

Expression of neuropeptide Y and neuropeptide Y (Y1) receptor mRNA in rat spinal cord and dorsal root ganglia following peripheral tissue inflammation.

Journal Article J Neurosci · November 1994 By using in situ hybridization histochemistry and immunohistochemistry, neuropeptide Y (NPY) and NPY (Y1) receptor mRNA as well as NPY-like immunoreactivity were examined in the lumbar spinal cord (L4-L5) and in dorsal root ganglia (DRG, L5) in rats inject ... Full text Link to item Cite

Increased expression of galanin in the rat superior cervical ganglion after pre- and postganglionic nerve lesions.

Journal Article Exp Neurol · May 1994 Using immunohistochemistry the expression of galanin (GAL) and galanin message-associated peptide (GMAP) in the superior cervical ganglion (SCG) was investigated 2, 4, 7, and 14 days after unilateral transection of the cervical sympathetic trunk (decentral ... Full text Link to item Cite

Topical capsaicin treatment suppresses formalin-induced fos expression in rat spinal cord.

Journal Article Zhongguo Yao Li Xue Bao · January 1994 Capsaicin (Cap) is a pharmacological tool to inactivate nociceptive afferents. The present study was undertaken to investigate the effects of topical application of Cap to sciatic nerve on the formalin-induced expression of proto-oncogene proteins c-fos in ... Link to item Cite

Expression of preprodynorphin and preproenkephalin mRNA in nucleus tractus solitarii of rats subjected to endotoxin (and effect of naltrexone on the expression)

Journal Article Chinese Journal of Physiological Sciences · December 1, 1993 Previous studies have shown that opioid peptides in the central nervous system are involved in the pathogenesis of endotoxic shock in the rat. In the present study in situ hybridization technique was used to examine the expression of mRNA coding for prepro ... Cite

Induction of c-fos expression in the rostral medulla of rats following electroacupuncture stimulation.

Journal Article Int J Neurosci · October 1993 The present study was designed to examine the induction of c-fos mRNA and Fos-like protein in the rostral medulla of awake rats following electroacupuncture (EA) stimulation, using in situ hybridization and immunohistochemical method. Rats were subjected t ... Full text Link to item Cite

[Electroacupuncture enhances enkephalin mRNA expression in the spinal cord and medulla, an in situ hybridization study].

Journal Article Sheng Li Xue Bao · August 1993 Previous studies in this laboratory have shown that electroacupuncture (EA) accelerated the release of enkephalin in the spinal cord. The present study was undertaken to investigate the effect of EA stimulation on the expression of preproenkephalin (PPE) m ... Link to item Cite

[Induction of Fos-like protein in the rat spinal cord following electroacupuncture stimulation].

Journal Article Sheng Li Xue Bao · August 1992 The expression of the c-fos proto-oncogene has been regarded as a marker for noxious stimulation. We now report that electroacupuncture (EA) stimulation (100 Hz, 0.3 ms, 1-2-3 mA, 30 min) delivered into the acupoint Sanyinjiao (SP6) could also induce the c ... Link to item Cite

[Proto-oncogene and pain modulation].

Journal Article Sheng Li Ke Xue Jin Zhan · October 1991 Link to item Cite