Scholars@Duke
Yong Chen

Yong Chen

Associate Professor in Neurology
Neurology, Translational Brain Sciences
yong.chen@duke.edu
Box 2900 Med Ctr, Durham, NC 27710
251 Bryan Res Bldg, Durham, NC 27710

Selected Publications

Neuronal Mechanisms of Psoriatic Itch: Role of IL-17R/ERK/TRPV4 Signaling Pathway.

Journal Article J Invest Dermatol · November 2025 Itch represents a major disease burden of psoriasis. Despite recent clinical studies showing the effectiveness of IL-17- and IL-17R-blocking antibodies in alleviating psoriatic itch, significant questions remain unanswered. Specifically, the crucial cellul ... Full text Link to item Cite

Preclinical perspectives on disorders of the temporomandibular joint: Tracing the past, navigating the present, and shaping the future.

Journal Article J Pain · November 2025 Temporomandibular disorders (TMDs) are complex conditions characterized by orofacial pain and dysfunction, affecting a significant portion of the population. TMDs may involve joint and/or muscle pain, dysfunction (e.g., noise, limited or altered jaw moveme ... Full text Open Access Link to item Cite

Chondrocyte-specific knockout of Piezo1 and Piezo2 protects against post-traumatic osteoarthritis structural damage and pain in mice.

Journal Article Arthritis Res Ther · July 19, 2025 BACKGROUND: Osteoarthritis (OA) is a debilitating joint disease characterized by cartilage degeneration, synovial inflammation, and bone remodeling, with limited therapeutic options targeting the underlying pathophysiology. Mechanosensitive ion channels Pi ... Full text Open Access Link to item Cite

Sensory Neuron-TRPV4 Modulates Temporomandibular Disorder Pain Via CGRP in Mice.

Journal Article J Pain · May 2023 Temporomandibular disorder (TMD) pain that involves inflammation and injury in the temporomandibular joint (TMJ) and/or masticatory muscle is the most common form of orofacial pain. We recently found that transient receptor potential vanilloid-4 (TRPV4) in ... Full text Open Access Link to item Cite

TMEM100, a regulator of TRPV1-TRPA1 interaction, contributes to temporomandibular disorder pain.

Journal Article Front Mol Neurosci · 2023 There is an unmet need to identify new therapeutic targets for temporomandibular disorder (TMD) pain because current treatments are limited and unsatisfactory. TMEM100, a two-transmembrane protein, was recently identified as a regulator to weaken the TRPA1 ... Full text Open Access Link to item Cite

Silencing of TRPV4-expressing sensory neurons attenuates temporomandibular disorders pain.

Journal Article Mol Pain · 2023 Identification of potential therapeutic targets is needed for temporomandibular disorders (TMD) pain, the most common form of orofacial pain, because current treatments lack efficacy. Considering TMD pain is critically mediated by the trigeminal ganglion ( ... Full text Open Access Link to item Cite

Functional coupling between TRPV4 channel and TMEM16F modulates human trophoblast fusion.

Journal Article Elife · June 7, 2022 TMEM16F, a Ca2+-activated phospholipid scramblase (CaPLSase), is critical for placental trophoblast syncytialization, HIV infection, and SARS-CoV2-mediated syncytialization, however, how TMEM16F is activated during cell fusion is unclear. Here, using troph ... Full text Open Access Link to item Cite

Spinal cord dorsal horn sensory gate in preclinical models of chemotherapy-induced painful neuropathy and contact dermatitis chronic itch becomes less leaky with Kcc2 gene expression-enhancing treatments.

Journal Article Front Mol Neurosci · 2022 Low intraneuronal chloride in spinal cord dorsal horn (SCDH) pain relay neurons is of critical relevance for physiological transmission of primary sensory afferents because low intraneuronal chloride dictates GABA-ergic and glycin-ergic neurotransmission t ... Full text Open Access Link to item Cite

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

Journal Article Nat Commun · October 27, 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 Link to item 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

Emerging Role of Transient Receptor Potential Vanilloid 4 (TRPV4) Ion Channel in Acute and Chronic Itch.

Journal Article Int J Mol Sci · July 15, 2021 Itch is a clinical problem that leaves many sufferers insufficiently treated, with over 20 million cases in the United States. This is due to incomplete understanding of its molecular, cellular, and cell-to-cell signaling mechanisms. Transient receptor pot ... 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

Transient Receptor Potential (TRP) Ion Channels in Orofacial Pain.

Journal Article Mol Neurobiol · June 2021 Orofacial pain, including temporomandibular joint disorders pain, trigeminal neuralgia, dental pain, and debilitating headaches, affects millions of Americans each year with significant population health impact. Despite the existence of a large body of inf ... Full text Link to item Cite

Inflammatory signaling sensitizes Piezo1 mechanotransduction in articular chondrocytes as a pathogenic feed-forward mechanism in osteoarthritis.

Journal Article Proc Natl Acad Sci U S A · March 30, 2021 Osteoarthritis (OA) is a painful and debilitating condition of synovial joints without any disease-modifying therapies [A. M. Valdes, T. D. Spector, Nat. Rev. Rheumatol. 7, 23-32 (2011)]. We previously identified mechanosensitive PIEZO channels, PIEZO1 and ... Full text Open Access Link to item Cite

General anesthetics activate a potent central pain-suppression circuit in the amygdala.

Journal Article Nat Neurosci · July 2020 General anesthesia (GA) can produce analgesia (loss of pain) independent of inducing loss of consciousness, but the underlying mechanisms remain unclear. We hypothesized that GA suppresses pain in part by activating supraspinal analgesic circuits. We disco ... Full text Open Access Link to item Cite

The multifunctional peptide DN-9 produced peripherally acting antinociception in inflammatory and neuropathic pain via μ- and κ-opioid receptors.

Journal Article Br J Pharmacol · January 2020 BACKGROUND AND PURPOSE: Considerable effort has recently been directed at developing multifunctional opioid drugs to minimize the unwanted side effects of opioid analgesics. We have developed a novel multifunctional opioid agonist, DN-9. Here, we studied t ... Full text Link to item Cite

Preemptive intrathecal administration of endomorphins relieves inflammatory pain in male mice via inhibition of p38 MAPK signaling and regulation of inflammatory cytokines.

Journal Article J Neuroinflammation · November 15, 2018 BACKGROUND: Preemptive administration of analgesic drugs reduces perceived pain and prolongs duration of antinociceptive action. Whereas several lines of evidence suggest that endomorphins, the endogenous mu-opioid agonists, attenuate acute and chronic pai ... Full text Open Access Link to item Cite

Regulation of Pain and Itch by TRP Channels.

Journal Article Neurosci Bull · February 2018 Nociception is an important physiological process that detects harmful signals and results in pain perception. In this review, we discuss important experimental evidence involving some TRP ion channels as molecular sensors of chemical, thermal, and mechani ... Full text Link to item Cite

A craniofacial-specific monosynaptic circuit enables heightened affective pain.

Journal Article Nat Neurosci · December 2017 Humans often rank craniofacial pain as more severe than body pain. Evidence suggests that a stimulus of the same intensity induces stronger pain in the face than in the body. However, the underlying neural circuitry for the differential processing of facia ... Full text Open Access Link to item Cite

TRPV4 Moves toward Center-Fold in Rosacea Pathogenesis.

Journal Article J Invest Dermatol · April 2017 Mascarenhas et al. report that TRPV4 expression is upregulated in mast cells in response to the proteolytic cathelicidin fragment LL37 in a murine rosacea model and that TRPV4 loss of function attenuates mast cell degranulation. These findings render TRPV4 ... Full text Link to item Cite

Small molecule dual-inhibitors of TRPV4 and TRPA1 for attenuation of inflammation and pain.

Journal Article Sci Rep · June 1, 2016 TRPV4 ion channels represent osmo-mechano-TRP channels with pleiotropic function and wide-spread expression. One of the critical functions of TRPV4 in this spectrum is its involvement in pain and inflammation. However, few small-molecule inhibitors of TRPV ... Full text Open Access Link to item Cite

Transient Receptor Potential Vanilloid 4 Ion Channel Functions as a Pruriceptor in Epidermal Keratinocytes to Evoke Histaminergic Itch.

Journal Article J Biol Chem · May 6, 2016 TRPV4 ion channels function in epidermal keratinocytes and in innervating sensory neurons; however, the contribution of the channel in either cell to neurosensory function remains to be elucidated. We recently reported TRPV4 as a critical component of the ... Full text Open Access Link to item Cite

Lack of evidence for ectopic sprouting of genetically labeled Aβ touch afferents in inflammatory and neuropathic trigeminal pain.

Journal Article Mol Pain · April 10, 2015 BACKGROUND: Mechanical and in particular tactile allodynia is a hallmark of chronic pain in which innocuous touch becomes painful. Previous cholera toxin B (CTB)-based neural tracing experiments and electrophysiology studies had suggested that aberrant axo ... Full text Open Access Link to item Cite

TRPV4 is necessary for trigeminal irritant pain and functions as a cellular formalin receptor.

Journal Article Pain · December 2014 Detection of external irritants by head nociceptor neurons has deep evolutionary roots. Irritant-induced aversive behavior is a popular pain model in laboratory animals. It is used widely in the formalin model, where formaldehyde is injected into the roden ... Full text Open Access Link to item Cite

Synergy between Piezo1 and Piezo2 channels confers high-strain mechanosensitivity to articular cartilage.

Journal Article Proc Natl Acad Sci U S A · November 25, 2014 Diarthrodial joints are essential for load bearing and locomotion. Physiologically, articular cartilage sustains millions of cycles of mechanical loading. Chondrocytes, the cells in cartilage, regulate their metabolic activities in response to mechanical l ... Full text Open Access Link to item Cite

UVB radiation generates sunburn pain and affects skin by activating epidermal TRPV4 ion channels and triggering endothelin-1 signaling.

Journal Article Proc Natl Acad Sci U S A · August 20, 2013 At our body surface, the epidermis absorbs UV radiation. UV overexposure leads to sunburn with tissue injury and pain. To understand how, we focus on TRPV4, a nonselective cation channel highly expressed in epithelial skin cells and known to function in se ... Full text Open Access Link to item Cite

Temporomandibular joint pain: a critical role for Trpv4 in the trigeminal ganglion.

Journal Article Pain · August 2013 Temporomandibular joint disorder (TMJD) is known for its mastication-associated pain. TMJD is medically relevant because of its prevalence, severity, chronicity, the therapy-refractoriness of its pain, and its largely elusive pathogenesis. Against this bac ... Full text Open Access Link to item Cite

5-Hydroxyindolacetic Acid (5-HIAA), a Main Metabolite of Serotonin, is Responsible for Complete Freund's Adjuvant-Induced Thermal Hyperalgesia in Mice

Journal Article Molecular Pain · January 1, 2011 Background:The role of serotonin (5-hydroxytrptamine, 5-HT) in the modulation of pain has been widely studied. Previous work led to the hypothesis that 5-hydroxyindolacetic acid (5-HIAA), a main metabolite of sero ... Full text Open Access Cite

Nitric Oxide Synthase Modulates CFA-Induced Thermal Hyperalgesia through Cytokine Regulation in Mice

Journal Article Molecular Pain · January 1, 2010 Background: Although it has been largely demonstrated that nitric oxide synthase (NOS), a key enzyme for nitric oxide (NO) production, modulates inflammatory pain, the molecular mechanisms underlying these effects ... Full text Cite

The role of mitogen-activated protein kinase (MAPK) in morphine tolerance and dependence.

Journal Article Mol Neurobiol · October 2009 Despite the existence of a large body of information on the subject, the mechanisms of morphine tolerance and dependence are not yet fully understood. There is substantial evidence indicating that mitogen-activated protein kinase (MAPK), a family including ... Full text Open Access Link to item Cite

Reduced thermal hyperalgesia and enhanced peripheral nerve injury after hind paw inflammation in mice lacking the serotonin‐transporter

Journal Article European Journal of Pain · August 2008 AbstractMice lacking the serotonin‐transporter (5‐HTT‐/‐ mice) develop reduced thermal hyperalgesia after nerve injury, concomitant with reduced serotonin (5‐HT) levels in nervous tissue. Here we investigated pain behaviour ... Full text Open Access Cite

Activation of TRPV1 Contributes to Morphine Tolerance: Involvement of the Mitogen-Activated Protein Kinase Signaling Pathway

Journal Article The Journal of Neuroscience · May 28, 2008 Tolerance to the analgesic effects of opioids occurs after their chronic administration, a pharmacological phenomenon that has been associated with the development of abnormal pain sensitivity such as hyperalgesia. In the present study, we investig ... Full text Open Access Cite

Differences in inflammatory pain in nNOS‐, iNOS‐ and eNOS‐deficient mice

Journal Article European Journal of Pain · October 2007 AbstractTo assess the relative importance of the isoforms of nitric oxide synthase (NOS) in inflammatory pain, we directly compared pain behaviour and paw thickness after intraplantar injection of complete Freund's adjuvant ... Full text Open Access Cite

Activation of the nociceptin opioid system in rat sensory neurons produces antinociceptive effects in inflammatory pain: Involvement of inflammatory mediators

Journal Article Journal of Neuroscience Research · May 15, 2007 AbstractDespite a large body of literature on the nociceptin (NC) opioid system in pain modulation, the mechanism of action of NC remains largely unexplored. Here, we investigated the role and mode of action of the spinal N ... Full text Open Access Cite

Nociceptin and its receptor in rat dorsal root ganglion neurons in neuropathic and inflammatory pain models: implications on pain processing

Journal Article Journal of the Peripheral Nervous System · September 2006 Abstract Nociceptin (NC), by activating its receptor, the opioid receptor‐like 1 (ORL1) receptor, exerts an effect on a number of functions in the nervous system including locomotion, learning and memory, and processing of pa ... Full text Open Access Cite

Effects of [Nphe1]nociceptin(1-13)NH2, [Phe1(CH2-NH)Gly2]nociceptin(1- 13)NH2, and nocistatin on nociceptin inhibited constrictions of guinea pig isolated bronchus.

Journal Article Protein Pept Lett · 2006 Electric field stimulation (EFS) causes excitatory non adrenergic-non cholinergic (eNANC) and cholinergic constrictions in the guinea pig isolated bronchus, the activation of eNANC and cholinergic nerves respectively. We investigated the effects of [Nphe1] ... Full text Link to item Cite

Study in vitro and in vivo of nociceptin/orphanin FQ(1-13)NH2 analogues substituting N-Me-Gly for Gly2 or Gly3.

Journal Article Peptides · August 2004 In the present study, two analogues containing N-Me-Gly (Sarcosine, Sar) were synthesized to further investigate the structural-activity relationships of orphanin FQ/nociceptin (OFQ/NC, NC). The replacement of Gly(2) or Gly(3) with Sar increased the flexib ... Full text Open Access Link to item Cite

Effects of nocistatin and nocistatin (10-17) on nociceptin in antagonizing endomorphin-1 and endomorphin-2 analgesia in mice

Journal Article Yaoxue Xuebao · November 1, 2002 AIM: To investigate the effects of nocistatin and nocistatin (10-17) on nociceptin in antagonizing endomorphin-1 or endomorphin-2 analgesia in mice. METHODS: Nocistatin and nocistatin (10-17) were synthesized by solid-phase peptide synthesis method. The mo ... Open Access Cite

Effects of nociceptin (13-17) in pain modulation at supraspinal level in mice.

Journal Article Neurosci Lett · October 11, 2002 This work was designed to observe the effects of nociceptin(13-17), one of the main metabolites of nociceptin (also termed orphanin FQ), in pain modulation at supraspinal level in mice. Intracerebroventricular (i.c.v.) administration of nociceptin/orphanin ... Full text Open Access Link to item Cite

[Nphe1]nociceptin(1-13)-NH2 antagonizes nociceptin-induced hypotension, bradycardia, and hindquarters vasodilation in the anesthetized rat.

Journal Article Can J Physiol Pharmacol · January 2002 The purpose of this study was to investigate the effects of [Nphe1]nociceptin(1-13)-NH2 on nociceptin-induced decreases in mean arterial pressure (MAP), heart rate (HR), and hindquarters vascular bed resistance (HVBR) of the anesthetized rat. The results s ... Full text Link to item Cite

The effects of the synthetic nocistatin on blood vessel activities

Journal Article Chinese Science Bulletin · January 1, 2001 Nocistatin was synthesized by the solid-phase peptide synthesis method. Its effects on rat systemic arterial pressure; rat hindquarter vascular bed resistance; tension of rabbit pectoral, abdominal, femoral aorta muscle strips without endothelium; and noci ... Full text Open Access Cite