Scholars@Duke
Luda Diatchenko

Luda Diatchenko

Adjunct Professor in the Department of Anesthesiology
Anesthesiology
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Selected Publications

Statistical modeling of acute and chronic pain patient-reported outcomes obtained from ecological momentary assessment.

Journal Article Pain · September 1, 2024 Ecological momentary assessment (EMA) allows for the collection of participant-reported outcomes (PROs), including pain, in the normal environment at high resolution and with reduced recall bias. Ecological momentary assessment is an important component in ... Full text Link to item Cite

Genome-wide association studies with experimental validation identify a protective role for B lymphocytes against chronic post-surgical pain.

Journal Article Br J Anaesth · August 2024 BACKGROUND: Chronic post-surgical pain (CPSP) significantly impacts patients' recovery and quality of life. Although environmental risk factors are well-established, genetic risk remains less understood. METHODS: A meta-analysis of genome-wide association ... Full text Link to item Cite

Sex differences in mechanisms of pain hypersensitivity.

Journal Article Neurosci Biobehav Rev · August 2024 The introduction of sex-as-a-biological-variable policies at funding agencies around the world has led to an explosion of very recent observations of sex differences in the biology underlying pain. This review considers evidence of sexually dimorphic mecha ... Full text Link to item Cite

Trajectories of pain and depressive symptoms among people living with low back pain during the COVID-19 pandemic: a 24-month longitudinal study

Journal Article Pain Reports · May 31, 2024 Introduction: We explored trajectories of pain intensity and depressive symptoms over the first 24 months of the pandemic in people with low back pain. Methods: This longitudinal study was conducted alongside the Quebec Low Back Pain Study. Starting in Apr ... Full text Cite

Whole-genome methylation profiling reveals regions associated with painful temporomandibular disorders and active recovery processes.

Journal Article Pain · May 1, 2024 Temporomandibular disorders (TMDs), collectively representing one of the most common chronic pain conditions, have a substantial genetic component, but genetic variation alone has not fully explained the heritability of TMD risk. Reasoning that the unexpla ... 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

Characterization of Common Genetic Variants in P2RX7 and Their Contribution to Chronic Pain Conditions.

Journal Article J Pain · February 2024 The adenosine triphosphate (ATP)-gated channel P2X7 is encoded by a gene enriched for common nonsynonymous variants. Many of these variants have functional cellular effects, and some have been implicated in chronic pain. In this study, we first systematica ... Full text Link to item Cite

Prospective Blood Transcriptomics Study in a Motor Vehicle Collision Cohort Identified a Protective Function of the SAMD15 Gene Against Chronic Pain.

Journal Article J Pain · September 2023 Traumatic brain injuries following motor vehicle collisions (MVCs) are ubiquitous. Surprisingly, there are no correlates between concussion impact force and long-term pain outcomes. To study the molecular underpinnings of chronic pain after MVC, we assembl ... Full text Link to item Cite

Rare variant analyses in large-scale cohorts identified SLC13A1 associated with chronic pain.

Journal Article Pain · August 1, 2023 Chronic pain is a prevalent disease with increasing clinical challenges. Genome-wide association studies in chronic pain patients have identified hundreds of common pathogenic variants, yet they only explained a portion of individual variance of chronic pa ... Full text Link to item Cite

Fibromyalgia patients with elevated levels of anti-satellite glia cell immunoglobulin G antibodies present with more severe symptoms.

Journal Article Pain · August 1, 2023 Transferring fibromyalgia patient immunoglobulin G (IgG) to mice induces pain-like behaviour, and fibromyalgia IgG binds mouse and human satellite glia cells (SGCs). These findings suggest that autoantibodies could be part of fibromyalgia pathology. Howeve ... 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

Genetic risk factors for chronic postsurgical pain in children: A narrative review.

Journal Article Eur J Anaesthesiol · July 1, 2023 Genetic risk factors for chronic postsurgical pain in adults have been established, but little is known whether the same associations exist in children. It is even less clear how much influence single nucleotide polymorphisms can exert on the phenotypic ex ... Full text Link to item Cite

A prognostic risk score for development and spread of chronic pain.

Journal Article Nat Med · July 2023 Chronic pain is a complex condition influenced by a combination of biological, psychological and social factors. Using data from the UK Biobank (n = 493,211), we showed that pain spreads from proximal to distal sites and developed a biopsychosocial model t ... Full text Link to item Cite

Optimizing and Accelerating the Development of Precision Pain Treatments for Chronic Pain: IMMPACT Review and Recommendations.

Journal Article J Pain · February 2023 Large variability in the individual response to even the most-efficacious pain treatments is observed clinically, which has led to calls for a more personalized, tailored approach to treating patients with pain (ie, "precision pain medicine"). Precision pa ... Full text Link to item Cite

Helminth-induced reprogramming of the stem cell compartment inhibits type 2 immunity.

Journal Article J Exp Med · September 5, 2022 Enteric helminths form intimate physical connections with the intestinal epithelium, yet their ability to directly alter epithelial stem cell fate has not been resolved. Here we demonstrate that infection of mice with the parasite Heligmosomoides polygyrus ... Full text Link to item Cite

Sodium-calcium exchanger-3 regulates pain "wind-up": From human psychophysics to spinal mechanisms.

Journal Article Neuron · August 17, 2022 Repeated application of noxious stimuli leads to a progressively increased pain perception; this temporal summation is enhanced in and predictive of clinical pain disorders. Its electrophysiological correlate is "wind-up," in which dorsal horn spinal neuro ... Full text Link to item Cite

Unbiased immune profiling reveals a natural killer cell-peripheral nerve axis in fibromyalgia.

Journal Article Pain · July 1, 2022 The pathophysiology of fibromyalgia syndrome (FMS) remains elusive, leading to a lack of objective diagnostic criteria and targeted treatment. We globally evaluated immune system changes in FMS by conducting multiparametric flow cytometry analyses of perip ... Full text Link to item Cite

Statistical modeling of acute and chronic pain patient-reported outcomes obtained from ecological momentary assessment.

Journal Article Pain · September 1, 2024 Ecological momentary assessment (EMA) allows for the collection of participant-reported outcomes (PROs), including pain, in the normal environment at high resolution and with reduced recall bias. Ecological momentary assessment is an important component in ... Full text Link to item Cite

Genome-wide association studies with experimental validation identify a protective role for B lymphocytes against chronic post-surgical pain.

Journal Article Br J Anaesth · August 2024 BACKGROUND: Chronic post-surgical pain (CPSP) significantly impacts patients' recovery and quality of life. Although environmental risk factors are well-established, genetic risk remains less understood. METHODS: A meta-analysis of genome-wide association ... Full text Link to item Cite

Sex differences in mechanisms of pain hypersensitivity.

Journal Article Neurosci Biobehav Rev · August 2024 The introduction of sex-as-a-biological-variable policies at funding agencies around the world has led to an explosion of very recent observations of sex differences in the biology underlying pain. This review considers evidence of sexually dimorphic mecha ... Full text Link to item Cite

Trajectories of pain and depressive symptoms among people living with low back pain during the COVID-19 pandemic: a 24-month longitudinal study

Journal Article Pain Reports · May 31, 2024 Introduction: We explored trajectories of pain intensity and depressive symptoms over the first 24 months of the pandemic in people with low back pain. Methods: This longitudinal study was conducted alongside the Quebec Low Back Pain Study. Starting in Apr ... Full text Cite

Whole-genome methylation profiling reveals regions associated with painful temporomandibular disorders and active recovery processes.

Journal Article Pain · May 1, 2024 Temporomandibular disorders (TMDs), collectively representing one of the most common chronic pain conditions, have a substantial genetic component, but genetic variation alone has not fully explained the heritability of TMD risk. Reasoning that the unexpla ... 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

Characterization of Common Genetic Variants in P2RX7 and Their Contribution to Chronic Pain Conditions.

Journal Article J Pain · February 2024 The adenosine triphosphate (ATP)-gated channel P2X7 is encoded by a gene enriched for common nonsynonymous variants. Many of these variants have functional cellular effects, and some have been implicated in chronic pain. In this study, we first systematica ... Full text Link to item Cite

Prospective Blood Transcriptomics Study in a Motor Vehicle Collision Cohort Identified a Protective Function of the SAMD15 Gene Against Chronic Pain.

Journal Article J Pain · September 2023 Traumatic brain injuries following motor vehicle collisions (MVCs) are ubiquitous. Surprisingly, there are no correlates between concussion impact force and long-term pain outcomes. To study the molecular underpinnings of chronic pain after MVC, we assembl ... Full text Link to item Cite

Rare variant analyses in large-scale cohorts identified SLC13A1 associated with chronic pain.

Journal Article Pain · August 1, 2023 Chronic pain is a prevalent disease with increasing clinical challenges. Genome-wide association studies in chronic pain patients have identified hundreds of common pathogenic variants, yet they only explained a portion of individual variance of chronic pa ... Full text Link to item Cite

Fibromyalgia patients with elevated levels of anti-satellite glia cell immunoglobulin G antibodies present with more severe symptoms.

Journal Article Pain · August 1, 2023 Transferring fibromyalgia patient immunoglobulin G (IgG) to mice induces pain-like behaviour, and fibromyalgia IgG binds mouse and human satellite glia cells (SGCs). These findings suggest that autoantibodies could be part of fibromyalgia pathology. Howeve ... 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

Genetic risk factors for chronic postsurgical pain in children: A narrative review.

Journal Article Eur J Anaesthesiol · July 1, 2023 Genetic risk factors for chronic postsurgical pain in adults have been established, but little is known whether the same associations exist in children. It is even less clear how much influence single nucleotide polymorphisms can exert on the phenotypic ex ... Full text Link to item Cite

A prognostic risk score for development and spread of chronic pain.

Journal Article Nat Med · July 2023 Chronic pain is a complex condition influenced by a combination of biological, psychological and social factors. Using data from the UK Biobank (n = 493,211), we showed that pain spreads from proximal to distal sites and developed a biopsychosocial model t ... Full text Link to item Cite

Optimizing and Accelerating the Development of Precision Pain Treatments for Chronic Pain: IMMPACT Review and Recommendations.

Journal Article J Pain · February 2023 Large variability in the individual response to even the most-efficacious pain treatments is observed clinically, which has led to calls for a more personalized, tailored approach to treating patients with pain (ie, "precision pain medicine"). Precision pa ... Full text Link to item Cite

Helminth-induced reprogramming of the stem cell compartment inhibits type 2 immunity.

Journal Article J Exp Med · September 5, 2022 Enteric helminths form intimate physical connections with the intestinal epithelium, yet their ability to directly alter epithelial stem cell fate has not been resolved. Here we demonstrate that infection of mice with the parasite Heligmosomoides polygyrus ... Full text Link to item Cite

Sodium-calcium exchanger-3 regulates pain "wind-up": From human psychophysics to spinal mechanisms.

Journal Article Neuron · August 17, 2022 Repeated application of noxious stimuli leads to a progressively increased pain perception; this temporal summation is enhanced in and predictive of clinical pain disorders. Its electrophysiological correlate is "wind-up," in which dorsal horn spinal neuro ... Full text Link to item Cite

Unbiased immune profiling reveals a natural killer cell-peripheral nerve axis in fibromyalgia.

Journal Article Pain · July 1, 2022 The pathophysiology of fibromyalgia syndrome (FMS) remains elusive, leading to a lack of objective diagnostic criteria and targeted treatment. We globally evaluated immune system changes in FMS by conducting multiparametric flow cytometry analyses of perip ... Full text Link to item Cite

Microglia-mediated degradation of perineuronal nets promotes pain.

Journal Article Science · July 2022 Activation of microglia in the spinal cord dorsal horn after peripheral nerve injury contributes to the development of pain hypersensitivity. How activated microglia selectively enhance the activity of spinal nociceptive circuits is not well understood. We ... Full text Link to item Cite

A graph-embedded topic model enables characterization of diverse pain phenotypes among UK biobank individuals.

Journal Article iScience · June 17, 2022 Large biobank repositories of clinical conditions and medications data open opportunities to investigate the phenotypic disease network. We present a graph embedded topic model (GETM). We integrate existing biomedical knowledge graph information in the for ... Full text Link to item Cite

Identifying genetic determinants of inflammatory pain in mice using a large-scale gene-targeted screen.

Journal Article Pain · June 1, 2022 Identifying the genetic determinants of pain is a scientific imperative given the magnitude of the global health burden that pain causes. Here, we report a genetic screen for nociception, performed under the auspices of the International Mouse Phenotyping ... Full text Link to item Cite

Acute inflammatory response via neutrophil activation protects against the development of chronic pain.

Journal Article Sci Transl Med · May 11, 2022 The transition from acute to chronic pain is critically important but not well understood. Here, we investigated the pathophysiological mechanisms underlying the transition from acute to chronic low back pain (LBP) and performed transcriptome-wide analysis ... Full text Link to item Cite

Genome-wide analysis identifies impaired axonogenesis in chronic overlapping pain conditions.

Journal Article Brain · April 29, 2022 Chronic pain is often present at more than one anatomical location, leading to chronic overlapping pain conditions. Whether chronic overlapping pain conditions represent a distinct pathophysiology from the occurrence of pain at only one site is unknown. Us ... Full text Link to item Cite

Long-term male-specific chronic pain via telomere- and p53‑mediated spinal cord cellular senescence.

Journal Article J Clin Invest · April 15, 2022 Mice with experimental nerve damage can display long‑lasting neuropathic pain behavior. We show here that 4 months and later after nerve injury, male but not female mice displayed telomere length (TL) reduction and p53‑mediated cellular senescence in the s ... Full text Link to item Cite

Modeling Secondary Phenotypes Conditional on Genotypes in Case–Control Studies

Journal Article Stats · March 1, 2022 Traditional case–control genetic association studies examine relationships between case–control status and one or more covariates. It is becoming increasingly common to study secondary phenotypes and their association with the original covariates. The Orof ... Full text Cite

Single-cell RNA sequencing reveals time- and sex-specific responses of mouse spinal cord microglia to peripheral nerve injury and links ApoE to chronic pain.

Journal Article Nat Commun · February 11, 2022 Activation of microglia in the spinal cord following peripheral nerve injury is critical for the development of long-lasting pain hypersensitivity. However, it remains unclear whether distinct microglia subpopulations or states contribute to different stag ... Full text Link to item Cite

Brain-specific genes contribute to chronic but not to acute back pain.

Journal Article Pain Rep · 2022 INTRODUCTION: Back pain is the leading cause of disability worldwide. Although most back pain cases are acute, 20% of acute pain patients experience chronic back pain symptoms. It is unclear whether acute pain and chronic pain have similar or distinct unde ... Full text Link to item Cite

Alternative Splicing of Opioid Receptor Genes Shows a Conserved Pattern for 6TM Receptor Variants.

Journal Article Cell Mol Neurobiol · July 2021 The opioid receptor (OPR) family comprises the mu-, delta-, and kappa-opioid, and nociceptin receptors that belong to the superfamily of 7-transmembrane spanning G protein-coupled receptors (GPCRs). The mu-opioid receptor is the main target for clinically ... 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

Phenotypic profile clustering pragmatically identifies diagnostically and mechanistically informative subgroups of chronic pain patients.

Journal Article Pain · May 1, 2021 Traditional classification and prognostic approaches for chronic pain conditions focus primarily on anatomically based clinical characteristics not based on underlying biopsychosocial factors contributing to perception of clinical pain and future pain traj ... Full text Open Access Link to item Cite

Sex- and age-specific genetic analysis of chronic back pain.

Journal Article Pain · April 1, 2021 Sex differences for chronic back pain (cBP) have been reported, with females usually exhibiting greater morbidity, severity, and poorer response to treatment. Genetic factors acting in an age-specific manner have been implicated but never comprehensively e ... Full text Link to item Cite

Multi-ethnic GWAS and meta-analysis of sleep quality identify MPP6 as a novel gene that functions in sleep center neurons.

Journal Article Sleep · March 12, 2021 Poor sleep quality can have harmful health consequences. Although many aspects of sleep are heritable, the understandings of genetic factors involved in its physiology remain limited. Here, we performed a genome-wide association study (GWAS) using the Pitt ... Full text Open Access Link to item Cite

Single cell transcriptomics of primate sensory neurons identifies cell types associated with chronic pain.

Journal Article Nat Commun · March 8, 2021 Distinct types of dorsal root ganglion sensory neurons may have unique contributions to chronic pain. Identification of primate sensory neuron types is critical for understanding the cellular origin and heritability of chronic pain. However, molecular insi ... Full text Link to item Cite

Mast cell stabilizer ketotifen fumarate reverses inflammatory but not neuropathic-induced mechanical pain in mice.

Journal Article Pain Rep · 2021 INTRODUCTION: Mast cell (MC) activation could establish a positive feedback loop that perpetuates inflammation and maintains pain. Stabilizing MCs with ketotifen fumarate (KF) may disrupt this loop and relieve pain. OBJECTIVE: We aimed to test the effect o ... Full text Link to item Cite

A genetic polymorphism that is associated with mitochondrial energy metabolism increases risk of fibromyalgia.

Journal Article Pain · December 2020 Alterations in cellular energy metabolism have been implicated in chronic pain, suggesting a role for mitochondrial DNA. Previous studies reported associations of a limited number of mitochondrial DNA polymorphisms with specific pain conditions. In this st ... Full text Open Access Link to item Cite

Reversion mutation of cDNA CA8-204 minigene construct produces a truncated functional peptide that regulates calcium release in vitro and produces profound analgesia in vivo.

Journal Article Mamm Genome · December 2020 Intracellular calcium is critical in orchestrating neuronal excitability and analgesia. Carbonic anhydrase-8 (CA8) regulates intracellular calcium signaling through allosteric inhibition of neuronal inositol trisphosphate receptor 1 (ITPR1) to produce prof ... Full text Link to item Cite

Detangling red hair from pain: phenotype-specific contributions from different genetic variants in melanocortin-1 receptor.

Journal Article Pain · May 2020 Genetic variation in melanocortin-1 receptor (MC1R) has a known role in red hair. Studies on responses to noxious stimuli in red-haired individuals have also been conducted, with mixed findings. To investigate a possible divergence between variants respons ... Full text Link to item Cite

The dichotomous role of epiregulin in pain.

Journal Article Pain · May 2020 It has recently been shown that epidermal growth factor receptor (EGFR) contributes to the pathogenesis of pain. We scanned genetic markers within genes coding for receptors of the EGFR family (EGFR, ERBB2, ERBB3, and ERBB4) and their ligands (AREG, BTC, E ... Full text Link to item Cite

The geriatric pain experience in mice: intact cutaneous thresholds but altered responses to tonic and chronic pain.

Journal Article Neurobiol Aging · May 2020 Older individuals have an elevated risk for chronic pain as half of all individuals over 65 years old have at least one chronic pain condition. Unfortunately, relevant assessment tools and recommendations for chronic pain management targeting older adults ... Full text Link to item Cite

A functional polymorphism in the ATP-Binding Cassette B1 transporter predicts pharmacologic response to combination of nortriptyline and morphine in neuropathic pain patients.

Journal Article Pain · March 2020 Many genetic markers have been associated with variations in treatment response to analgesics, but none have been assessed in the context of combination therapies. In this study, the treatment effects of nortriptyline and morphine were tested for an associ ... Full text Link to item Cite

NK cell recruitment limits tissue damage during an enteric helminth infection.

Journal Article Mucosal Immunol · March 2020 Parasitic helminths cause significant damage as they migrate through host tissues to complete their life cycle. While chronic helminth infections are characterized by a well-described Type 2 immune response, the early, tissue-invasive stages are not well u ... Full text Link to item Cite

Premorbid and concurrent predictors of TMD onset and persistence.

Journal Article Eur J Pain · January 2020 BACKGROUND: Multiple risk factors predict temporomandibular disorders (TMD) onset, but temporal changes in risk factors and their contribution to risk of TMD have not been evaluated. The study aims were to (a) describe changes occurring in premorbid TMD ri ... Full text Link to item Cite

The Quebec Low Back Pain Study: a protocol for an innovative 2-tier provincial cohort.

Journal Article Pain Rep · 2020 INTRODUCTION: The neurobiological mechanisms underlying recovery from or persistence of low back pain (LBP) remain misunderstood, limiting progress toward effective management. We have developed an innovative two-tier design to study the transition from ac ... 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

Cartilage-binding antibodies induce pain through immune complex-mediated activation of neurons.

Journal Article J Exp Med · August 5, 2019 Rheumatoid arthritis-associated joint pain is frequently observed independent of disease activity, suggesting unidentified pain mechanisms. We demonstrate that antibodies binding to cartilage, specific for collagen type II (CII) or cartilage oligomeric mat ... Full text Link to item Cite

A functional substitution in the L-aromatic amino acid decarboxylase enzyme worsens somatic symptoms via a serotonergic pathway.

Journal Article Ann Neurol · August 2019 OBJECTIVE: Heightened somatic symptoms are reported by a wide range of patients with chronic pain and have been associated with emotional distress and physical dysfunction. Despite their clinical significance, molecular mechanisms leading to their manifest ... Full text Link to item Cite

Clinical predictors of persistent temporomandibular disorder in people with first-onset temporomandibular disorder: A prospective case-control study.

Journal Article J Am Dent Assoc · July 2019 BACKGROUND: When patients first develop a painful temporomandibular disorder (TMD) and seek care, 1 priority for clinicians is to assess prognosis. The authors aimed to develop a predictive model by using biopsychosocial measures from the Diagnostic Criter ... Full text Link to item Cite

A study in scarlet: MC1R as the main predictor of red hair and exemplar of the flip-flop effect.

Journal Article Hum Mol Genet · June 15, 2019 Genetic variation in melanocortin-1 receptor (MC1R) is a known contributor to disease-free red hair in humans. Three loss-of-function single-nucleotide variants (rs1805007, rs1805008 and rs1805009) have been established as strongly correlated with red hair ... Full text Link to item Cite

Profound analgesia is associated with a truncated peptide resulting from tissue specific alternative splicing of DRG CA8-204 regulated by an exon-level cis-eQTL.

Journal Article PLoS Genet · June 2019 Carbonic anhydrase-8 (CA8) is an intracellular protein that functions as an allosteric inhibitor of inositol trisphosphate receptor-1 (ITPR1) critical to intracellular Ca++ release, synaptic functions and neuronal excitability. We showed previously that mu ... Full text Link to item Cite

Alternative Splicing of the Delta-Opioid Receptor Gene Suggests Existence of New Functional Isoforms.

Journal Article Mol Neurobiol · April 2019 The delta-opioid receptor (DOPr) participates in mediating the effects of opioid analgesics. However, no selective agonists have entered clinical care despite potential to ameliorate many neurological and psychiatric disorders. In an effort to address the ... Full text Link to item Cite

Genetic pathway analysis reveals a major role for extracellular matrix organization in inflammatory and neuropathic pain.

Journal Article Pain · April 2019 Chronic pain is a debilitating and poorly treated condition whose underlying mechanisms are poorly understood. Nerve injury and inflammation cause alterations in gene expression in tissues associated with pain processing, supporting molecular and cellular ... Full text Link to item Cite

The Role of Tobacco Smoking in the Transition from Acute to Chronic Pain

Conference Journal of Pain · April 1, 2019 Tobacco smoking is highly prevalent among patients with chronic pain. The prevalence of smoking has been found to range between 30-60% among patients with chronic pain, and to be approximately 15% in the general population. To date, however, the degree to ... Full text Cite

CACNG2 polymorphisms associate with chronic pain after mastectomy.

Journal Article Pain · March 2019 Chronic postmastectomy pain (PMP) imposes a major burden on the quality of life of the ever-increasing number of long-term survivors of breast cancer. An earlier report by Nissenbaum et al. claimed that particular polymorphisms in the gene CACNG2 are assoc ... Full text Link to item Cite

Genome-wide association reveals contribution of MRAS to painful temporomandibular disorder in males.

Journal Article Pain · March 2019 Painful temporomandibular disorders (TMDs) are the leading cause of chronic orofacial pain, but its underlying molecular mechanisms remain obscure. Although many environmental factors have been associated with higher risk of developing painful TMD, family ... Full text Open Access Link to item Cite

Disentangling the genetics of lean mass.

Journal Article Am J Clin Nutr · February 1, 2019 BACKGROUND: Lean body mass (LM) plays an important role in mobility and metabolic function. We previously identified five loci associated with LM adjusted for fat mass in kilograms. Such an adjustment may reduce the power to identify genetic signals having ... Full text Link to item Cite

Anatomical selectivity in overlap of chronic facial and bodily pain.

Journal Article Pain Rep · 2019 BACKGROUND: Chronic facial pain often overlaps with pain experienced elsewhere in the body, although previous studies have focused on a few, selected pain conditions when assessing the degree of overlap. AIM: To quantify the degree of overlap between facia ... Full text Link to item Cite

Low back pain.

Chapter · December 13, 2018 Low back pain affects individuals of all ages and is a leading contributor to disease burden worldwide. Despite advancements in assessment and treatment methods, the management of low back pain remains a challenge for researchers and clinicians alike. One ... Full text Link to item Cite

Human carbonic anhydrase-8 AAV8 gene therapy inhibits nerve growth factor signaling producing prolonged analgesia and anti-hyperalgesia in mice.

Journal Article Gene Ther · July 2018 Carbonic anhydrase-8 (Car8; murine gene symbol) is an allosteric inhibitor of inositol trisphosphate receptor-1 (ITPR1), which regulates neuronal intracellular calcium release. We previously reported that wild-type Car8 overexpression corrects the baseline ... Full text Link to item Cite

The human pain genetics database: an interview with Luda Diatchenko.

Journal Article Pain Manag · July 1, 2018 Luda Diatchenko, MD, PhD is a Canada Excellence Research Chair in Human Pain Genetics, Professor, Faculty of Medicine, Department of Anesthesia and Faculty of Dentistry at McGill University, Alan Edwards Centre for Research on Pain. She earned her MD and P ... Full text Link to item Cite

Human pain genetics database: a resource dedicated to human pain genetics research.

Journal Article Pain · April 2018 The Human Pain Genetics Database (HPGDB) is a comprehensive variant-focused inventory of genetic contributors to human pain. After curation, the HPGDB currently includes 294 studies reporting associations between 434 distinct genetic variants and various p ... Full text Link to item Cite

Genetic studies of human neuropathic pain conditions: a review.

Journal Article Pain · March 2018 Numerous studies have shown associations between genetic variants and neuropathic pain disorders. Rare monogenic disorders are caused by mutations of substantial effect size in a single gene, whereas common disorders are likely to have a contribution from ... Full text Link to item Cite

The more you test, the more you find: The smallest P-values become increasingly enriched with real findings as more tests are conducted.

Journal Article Genet Epidemiol · December 2017 The increasing accessibility of data to researchers makes it possible to conduct massive amounts of statistical testing. Rather than follow specific scientific hypotheses with statistical analysis, researchers can now test many possible relationships and l ... Full text Link to item Cite

Erratum: Large meta-analysis of genome-wide association studies identifies five loci for lean body mass.

Journal Article Nat Commun · November 7, 2017 A correction to this article has been published and is linked from the HTML version of this article. ... Full text Open Access Link to item Cite

T-Cell Mediation of Pregnancy Analgesia Affecting Chronic Pain in Mice.

Journal Article J Neurosci · October 11, 2017 It has been reported consistently that many female chronic pain sufferers have an attenuation of symptoms during pregnancy. Rats display increased pain tolerance during pregnancy due to an increase in opioid receptors in the spinal cord. Past studies did n ... Full text Link to item Cite

Car8 dorsal root ganglion expression and genetic regulation of analgesic responses are associated with a cis-eQTL in mice.

Journal Article Mamm Genome · October 2017 Carbonic anhydrase-8 (Car8 mouse gene symbol) is devoid of enzymatic activity, but instead functions as an allosteric inhibitor of inositol trisphosphate receptor-1 (ITPR1) to regulate this intracellular calcium release channel important in synaptic functi ... Full text Link to item Cite

Epiregulin and EGFR interactions are involved in pain processing.

Journal Article J Clin Invest · September 1, 2017 The EGFR belongs to the well-studied ErbB family of receptor tyrosine kinases. EGFR is activated by numerous endogenous ligands that promote cellular growth, proliferation, and tissue regeneration. In the present study, we have demonstrated a role for EGFR ... Full text Link to item Cite

Large meta-analysis of genome-wide association studies identifies five loci for lean body mass.

Journal Article Nat Commun · July 19, 2017 Lean body mass, consisting mostly of skeletal muscle, is important for healthy aging. We performed a genome-wide association study for whole body (20 cohorts of European ancestry with n = 38,292) and appendicular (arms and legs) lean body mass (n = 28,330) ... Full text Link to item Cite

miR-183 cluster scales mechanical pain sensitivity by regulating basal and neuropathic pain genes.

Journal Article Science · June 16, 2017 Nociception is protective and prevents tissue damage but can also facilitate chronic pain. Whether a general principle governs these two types of pain is unknown. Here, we show that both basal mechanical and neuropathic pain are controlled by the microRNA- ... Full text Link to item Cite

N6-methyladenosine alters RNA structure to regulate binding of a low-complexity protein.

Journal Article Nucleic Acids Res · June 2, 2017 N6-methyladenosine (m6A) is the most abundant internal modification in eukaryotic messenger RNA (mRNA), and affects almost every stage of the mRNA life cycle. The YTH-domain proteins can specifically recognize m6A modification to control mRNA maturation, t ... Full text Link to item Cite

Effect of Human Genetic Variability on Gene Expression in Dorsal Root Ganglia and Association with Pain Phenotypes.

Journal Article Cell Rep · May 30, 2017 Dorsal root ganglia (DRG) relay sensory information to the brain, giving rise to the perception of pain, disorders of which are prevalent and burdensome. Here, we mapped expression quantitative trait loci (eQTLs) in a collection of human DRGs. DRG eQTLs we ... Full text Link to item Cite

GWAS Identifies New Loci for Painful Temporomandibular Disorder: Hispanic Community Health Study/Study of Latinos.

Journal Article J Dent Res · March 2017 Temporomandibular disorder (TMD) is a musculoskeletal condition characterized by pain and reduced function in the temporomandibular joint and/or associated masticatory musculature. Prevalence in the United States is 5% and twice as high among women as men. ... Full text Open Access Link to item Cite

Genetic variant rs3750625 in the 3'UTR of ADRA2A affects stress-dependent acute pain severity after trauma and alters a microRNA-34a regulatory site.

Journal Article Pain · February 2017 α2A adrenergic receptor (α2A-AR) activation has been shown in animal models to play an important role in regulating the balance of acute pain inhibition vs facilitation after both physical and psychological stress. To our knowledge, the influence of geneti ... Full text Open Access Link to item Cite

Genotypic data in relational databases: Efficient storage and rapid retrieval

Conference Lecture Notes in Computer Science (including subseries Lecture Notes in Artificial Intelligence and Lecture Notes in Bioinformatics) · January 1, 2017 As technologies to produce genotypic data have become less expensive, the widths and depths of such data have sharply increased. Relational databases have performed poorly in this domain. Data storage and retrieval is now mostly conducted by highly coupled ... Full text Cite

Post-concussion symptoms and chronic pain after mild traumatic brain injury are modulated by multiple locus effect in the BDNF gene through the expression of antisense: A pilot prospective control study.

Journal Article Can J Pain · 2017 Background: Mild traumatic brain injury (mTBI) often results in post-concussion symptoms, chronic pain, and sleepiness. Genetic factors are thought to play an important role in poor prognosis. Aims: The aims of this study are to (1) document the prevalence ... Full text Link to item Cite

Genetic predictors of human chronic pain conditions.

Journal Article Neuroscience · December 3, 2016 Chronic pain conditions are multifactorial disorders with a high frequency in the population. Their pathophysiology is often unclear, and treatment is inefficient. During the last 20years, genetic linkage analysis and association studies have made consider ... Full text Link to item Cite

Painful Temporomandibular Disorder: Decade of Discovery from OPPERA Studies.

Journal Article J Dent Res · September 2016 In 2006, the OPPERA project (Orofacial Pain: Prospective Evaluation and Risk Assessment) set out to identify risk factors for development of painful temporomandibular disorder (TMD). A decade later, this review summarizes its key findings. At 4 US study si ... Full text Link to item Cite

Agonist-dependence of functional properties for common nonsynonymous variants of human transient receptor potential vanilloid 1.

Journal Article Pain · July 2016 Transient receptor potential vanilloid 1 (TRPV1) is a polymodal receptor activated by capsaicin, heat, and acid, which plays critical roles in thermosensation and pain. In addition, TRPV1 also contributes to multiple pathophysiological states in respirator ... Full text Link to item Cite

Identification of clusters of individuals relevant to temporomandibular disorders and other chronic pain conditions: the OPPERA study.

Journal Article Pain · June 2016 The classification of most chronic pain disorders gives emphasis to anatomical location of the pain to distinguish one disorder from the other (eg, back pain vs temporomandibular disorder [TMD]) or to define subtypes (eg, TMD myalgia vs arthralgia). Howeve ... Full text Link to item Cite

Human Genetic Variability Contributes to Postoperative Morphine Consumption.

Journal Article J Pain · May 2016 UNLABELLED: High interindividual variability in postoperative opioid consumption is related to genetic and environmental factors. We tested the association between morphine consumption, postoperative pain, and single nucleotide polymorphisms (SNPs) within ... Full text Link to item Cite

Modification of COMT-dependent pain sensitivity by psychological stress and sex.

Journal Article Pain · April 2016 Catecholamine-O-methyltransferase (COMT) is a polymorphic gene whose variants affect enzymatic activity and pain sensitivity via adrenergic pathways. Although COMT represents one of the most studied genes in human pain genetics, findings regarding its asso ... Full text Link to item Cite

N(6)-Methyladenosine Modification in a Long Noncoding RNA Hairpin Predisposes Its Conformation to Protein Binding.

Journal Article J Mol Biol · February 27, 2016 N(6)-Methyladenosine (m(6)A) is a reversible and abundant internal modification of messenger RNA (mRNA) and long noncoding RNA (lncRNA) with roles in RNA processing, transport, and stability. Although m(6)A does not preclude Watson-Crick base pairing, the ... Full text Link to item Cite

Structural and functional interactions between six-transmembrane μ-opioid receptors and β2-adrenoreceptors modulate opioid signaling.

Journal Article Sci Rep · December 11, 2015 The primary molecular target for clinically used opioids is the μ-opioid receptor (MOR). Besides the major seven-transmembrane (7TM) receptors, the MOR gene codes for alternatively spliced six-transmembrane (6TM) isoforms, the biological and clinical signi ... Full text Link to item Cite

Differences in the Antinociceptive Effects and Binding Properties of Propranolol and Bupranolol Enantiomers.

Journal Article J Pain · December 2015 UNLABELLED: Recent efforts have suggested that the β-adrenergic receptor (β-AR) system may be a novel and viable therapeutic target for pain reduction; however, most of the work to date has focused on the β(2)-adrenergic receptor (AR). Here, we compared th ... Full text Link to item Cite

Dual allosteric modulation of opioid antinociceptive potency by α2A-adrenoceptors.

Journal Article Neuropharmacology · December 2015 Opioid and α2-adrenoceptor (AR) agonists are analgesic when administered in the spinal cord and show a clinically beneficial synergistic interaction when co-administered. However, α2-AR antagonists can also inhibit opioid antinociception, suggesting a comp ... Full text Link to item Cite

Quantitative H2S-mediated protein sulfhydration reveals metabolic reprogramming during the integrated stress response.

Journal Article Elife · November 23, 2015 The sulfhydration of cysteine residues in proteins is an important mechanism involved in diverse biological processes. We have developed a proteomics approach to quantitatively profile the changes of sulfhydrated cysteines in biological systems. Bioinforma ... Full text Link to item Cite

Genome-wide association meta-analyses to identify common genetic variants associated with hallux valgus in Caucasian and African Americans.

Journal Article J Med Genet · November 2015 OBJECTIVE: Hallux valgus (HV) affects ∼36% of Caucasian adults. Although considered highly heritable, the underlying genetic determinants are unclear. We conducted the first genome-wide association study (GWAS) aimed to identify genetic variants associated ... Full text Link to item Cite

Neuropathic pain phenotyping by international consensus (NeuroPPIC) for genetic studies: a NeuPSIG systematic review, Delphi survey, and expert panel recommendations.

Journal Article Pain · November 2015 For genetic research to contribute more fully to furthering our knowledge of neuropathic pain, we require an agreed, valid, and feasible approach to phenotyping, to allow collaboration and replication in samples of sufficient size. Results from genetic stu ... Full text Link to item Cite

COMT gene locus: new functional variants.

Journal Article Pain · October 2015 Catechol-O-methyltransferase (COMT) metabolizes catecholaminergic neurotransmitters. Numerous studies have linked COMT to pivotal brain functions such as mood, cognition, response to stress, and pain. Both nociception and risk of clinical pain have been as ... Full text Link to item Cite

μ-Opioid receptor 6-transmembrane isoform: A potential therapeutic target for new effective opioids.

Journal Article Prog Neuropsychopharmacol Biol Psychiatry · October 1, 2015 The μ-opioid receptor (MOR) is the primary target for opioid analgesics. MOR induces analgesia through the inhibition of second messenger pathways and the modulation of ion channels activity. Nevertheless, cellular excitation has also been demonstrated, an ... Full text Link to item Cite

Molecular genetic mechanisms of allelic specific regulation of murine Comt expression.

Journal Article Pain · October 2015 A functional allele of the mouse catechol-O-methyltransferase (Comt) gene is defined by the insertion of a B2 short interspersed repeat element in its 3'-untranslated region (UTR). This allele has been associated with a number of phenotypes, such as pain a ... Full text Link to item Cite

COMT Diplotype Amplifies Effect of Stress on Risk of Temporomandibular Pain.

Journal Article J Dent Res · September 2015 When measured once, psychological stress predicts development of painful temporomandibular disorder (TMD). However, a single measurement fails to characterize the dynamic nature of stress over time. Moreover, effects of stress on pain likely vary according ... Full text Link to item Cite

OPRM1 receptor as new biomarker to help the prediction of post mastectomy pain and recurrence in breast cancer.

Journal Article Minerva Anestesiol · August 2015 Breast cancer is the most common type of cancer among women worldwide. Short-term postsurgical recovery is complicated by many factors, including imbalanced inflammatory and immune response, acute pain associated with functional impairment, and chronic pos ... Link to item Cite

Genetic risk factors for orofacial pain: Insights from human experimental studies

Chapter · June 1, 2015 This chapter takes, as a starting point, the clinically well-known notion that symptoms of chronic orofacial pain are highly variable from patient to patient and that using these symptoms to guide pain treatment is not enough to manage patients successfull ... Cite

The nicotinic α6 subunit gene determines variability in chronic pain sensitivity via cross-inhibition of P2X2/3 receptors.

Journal Article Sci Transl Med · May 13, 2015 Chronic pain is a highly prevalent and poorly managed human health problem. We used microarray-based expression genomics in 25 inbred mouse strains to identify dorsal root ganglion (DRG)-expressed genetic contributors to mechanical allodynia, a prominent s ... Full text Link to item Cite

Subgrouping of low back pain patients for targeting treatments: evidence from genetic, psychological, and activity-related behavioral approaches.

Journal Article Clin J Pain · February 2015 INTRODUCTION: Many patients with low back pain (LBP) are treated in a similar manner as if they were a homogenous group. However, scientific evidence is available that pain is a complex perceptual experience influenced by a wide range of genetic, psycholog ... Full text Link to item Cite

Carbonic anhydrase-8 regulates inflammatory pain by inhibiting the ITPR1-cytosolic free calcium pathway.

Journal Article PLoS One · 2015 Calcium dysregulation is causally linked with various forms of neuropathology including seizure disorders, multiple sclerosis, Huntington's disease, Alzheimer's, spinal cerebellar ataxia (SCA) and chronic pain. Carbonic anhydrase-8 (Car8) is an allosteric ... Full text Link to item Cite

Differential Regulation of 6- and 7-Transmembrane Helix Variants of μ-Opioid Receptor in Response to Morphine Stimulation.

Journal Article PLoS One · 2015 The pharmacological effect of opioids originates, at the cellular level, by their interaction with the μ-opioid receptor (mOR) resulting in the regulation of voltage-gated Ca2+ channels and inwardly rectifying K+ channels that ultimately modulate the synap ... Full text Link to item Cite

Epistasis between polymorphisms in COMT, ESR1, and GCH1 influences COMT enzyme activity and pain.

Journal Article Pain · November 2014 Abnormalities in the enzymatic activity of catechol-O-methyltransferase (COMT) contribute to chronic pain conditions, such as temporomandibular disorders (TMD). Thus, we sought to determine the effects of polymorphisms in COMT and functionally related pain ... Full text Link to item Cite

Complex multilocus effects of catechol-O-methyltransferase haplotypes predict pain and pain interference 6 weeks after motor vehicle collision.

Journal Article Neuromolecular Med · March 2014 Catechol-O-methyltransferase, encoded by COMT gene, is the primary enzyme that metabolizes catecholamines. COMT haplotypes have been associated with vulnerability to persistent non-traumatic pain. In this prospective observational study, we investigated th ... Full text Link to item Cite

Differential expression of the alternatively spliced OPRM1 isoform μ-opioid receptor-1K in HIV-infected individuals.

Journal Article AIDS · January 2, 2014 OBJECTIVE: We previously examined the expression of specific C-terminal μ-opioid receptor (MOR) splice variants in human central nervous system cell types and HIV-infected brain tissue from individuals with neurocognitive impairment ± HIV encephalitis (HIV ... Full text Link to item Cite

Genetic variants associated with development of TMD and its intermediate phenotypes: the genetic architecture of TMD in the OPPERA prospective cohort study.

Journal Article J Pain · December 2013 UNLABELLED: Genetic risk factors are believed to combine with environmental exposures and contribute to the risk of developing temporomandibular disorder (TMD). In this prospective cohort study, 2,737 people without TMD were assessed for common genetic var ... Full text Link to item Cite

Summary of findings from the OPPERA prospective cohort study of incidence of first-onset temporomandibular disorder: implications and future directions.

Journal Article J Pain · December 2013 UNLABELLED: Papers in this issue investigate when and how putative risk factors influence development of first-onset, painful temporomandibular disorder (TMD). The results represent first findings from the Orofacial Pain: Prospective Evaluation and Risk As ... Full text Link to item Cite

Clinical orofacial characteristics associated with risk of first-onset TMD: the OPPERA prospective cohort study.

Journal Article J Pain · December 2013 UNLABELLED: Case-control studies have documented clinical manifestations of chronic temporomandibular disorder (TMD), whereas clinical predictors of TMD development are largely unknown. We evaluated 41 clinical orofacial characteristics thought to predict ... Full text Link to item Cite

Study protocol, sample characteristics, and loss to follow-up: the OPPERA prospective cohort study.

Journal Article J Pain · December 2013 UNLABELLED: When studying incidence of pain conditions such as temporomandibular disorder (TMD), repeated monitoring is needed in prospective cohort studies. However, monitoring methods usually have limitations and, over a period of years, some loss to fol ... Full text Link to item Cite

Psychological factors associated with development of TMD: the OPPERA prospective cohort study.

Journal Article J Pain · December 2013 UNLABELLED: Case-control studies have consistently associated psychological factors with chronic pain in general and with temporomandibular disorder (TMD) specifically. However, only a handful of prospective studies have explored whether preexisting psycho ... Full text Link to item Cite

Multivariable modeling of phenotypic risk factors for first-onset TMD: the OPPERA prospective cohort study.

Journal Article J Pain · December 2013 UNLABELLED: Incidence of temporomandibular disorder (TMD) was predicted with multivariable models that used putative risk factors collected from initially TMD-free individuals in the Orofacial Pain: Prospective Evaluation and Risk Assessment (OPPERA) study ... Full text Link to item Cite

Pain sensitivity and autonomic factors associated with development of TMD: the OPPERA prospective cohort study.

Journal Article J Pain · December 2013 UNLABELLED: Multiple studies report that individuals with chronic temporomandibular disorder (TMD) have enhanced sensitivity to experimental pain. Additionally, chronic TMD cases show altered autonomic function, including elevated heart rate and reduced he ... Full text Link to item Cite

Signs and symptoms of first-onset TMD and sociodemographic predictors of its development: the OPPERA prospective cohort study.

Journal Article J Pain · December 2013 UNLABELLED: Although cross-sectional studies of temporomandibular disorder (TMD) often report elevated prevalence in young women, they do not address the risk of its development. Here we evaluate sociodemographic predictors of TMD incidence in a community- ... Full text Link to item Cite

Translating Genetic Knowledge into Clinical Practice for Musculoskeletal Pain Conditions

Chapter · November 25, 2013 This chapter focuses on the genetic factors that contribute to chronic low back pain (LBP), chronic widespread pain (CWP), fibromyalgia (FM), and painful temporomandibular joint disorders (TMD), which collectively represent a set of pain conditions that ar ... Full text Cite

Pain Genetics: Basic to Translational Science

Book · November 25, 2013 Pain Genetics: Basic to Translational Science is a timely synthesis of the key areas of research informing our understanding of the genetic basis of pain. The book opens with foundational information on basic genetic mechanisms underlying pain perception a ... Full text Cite

Discovering Multilocus Associations with Complex Pain Phenotypes

Chapter · November 25, 2013 This chapter covers statistical complexity in pain genetics. It discusses the analysis of the multiple genetic markers within one gene locus. The choice of the best analysis between these markers and phenotype depends on the relationships between these mar ... Full text Cite

Facial pain with localized and widespread manifestations: separate pathways of vulnerability.

Journal Article Pain · November 2013 Human association studies of common genetic polymorphisms have identified many loci that are associated with risk of complex diseases, although individual loci typically have small effects. However, by envisaging genetic associations in terms of cellular p ... Full text Link to item Cite

Multisystem dysregulation in painful temporomandibular disorders.

Journal Article J Pain · September 2013 UNLABELLED: Multiple physiological and psychological regulatory domains may contribute to the pathophysiology of pain in temporomandibular disorder (TMD) and other bodily pain conditions. The purpose of this study was to evaluate the relationship between m ... Full text Link to item Cite

Pain modality- and sex-specific effects of COMT genetic functional variants.

Journal Article Pain · August 2013 The enzyme catechol-O-methyltransferase (COMT) metabolizes catecholamine neurotransmitters involved in a number of physiological functions, including pain perception. Both human and mouse COMT genes possess functional polymorphisms contributing to interind ... Full text Link to item Cite

Polymorphisms in the glucocorticoid receptor co-chaperone FKBP5 predict persistent musculoskeletal pain after traumatic stress exposure.

Journal Article Pain · August 2013 Individual vulnerability factors influencing the function of the hypothalamic-pituitary-adrenal axis may contribute to the risk of the development of persistent musculoskeletal pain after traumatic stress exposure. The objective of the study was to evaluat ... Full text Link to item Cite

Sleep apnea symptoms and risk of temporomandibular disorder: OPPERA cohort.

Journal Article J Dent Res · July 2013 The authors tested the hypothesis that obstructive sleep apnea (OSA) signs/symptoms are associated with the occurrence of temporomandibular disorder (TMD), using the OPPERA prospective cohort study of adults aged 18 to 44 years at enrollment (n = 2,604) an ... Full text Link to item Cite

The phenotypic and genetic signatures of common musculoskeletal pain conditions.

Journal Article Nat Rev Rheumatol · June 2013 Musculoskeletal pain conditions, such as fibromyalgia and low back pain, tend to coexist in affected individuals and are characterized by a report of pain greater than expected based on the results of a standard physical evaluation. The pathophysiology of ... Full text Link to item Cite

Relationship between temporomandibular disorders, widespread palpation tenderness, and multiple pain conditions: a case-control study.

Journal Article J Pain · October 2012 UNLABELLED: The multiple bodily pain conditions in temporomandibular disorders (TMD) have been associated with generalized alterations in pain processing. The purpose of this study was to examine the relationship between the presence of widespread body pal ... Full text Link to item Cite

Janus molecule I: dichotomous effects of COMT in neuropathic vs nociceptive pain modalities.

Journal Article CNS Neurol Disord Drug Targets · May 2012 The enzyme catechol-O-methyltransferase (COMT) has been shown to play a critical role in pain perception by regulating levels of epinephrine (Epi) and norepinephrine (NE). Although the key contribution of catecholamines to the perception of pain has been r ... Full text Link to item Cite

Serotonin-induced hypersensitivity via inhibition of catechol O-methyltransferase activity.

Journal Article Mol Pain · April 13, 2012 The subcutaneous and systemic injection of serotonin reduces cutaneous and visceral pain thresholds and increases responses to noxious stimuli. Different subtypes of 5-hydroxytryptamine (5-HT) receptors are suggested to be associated with different types o ... Full text Link to item Cite

Genetically determined P2X7 receptor pore formation regulates variability in chronic pain sensitivity.

Journal Article Nat Med · March 25, 2012 Chronic pain is highly variable between individuals, as is the response to analgesics. Although much of the variability in chronic pain and analgesic response is heritable, an understanding of the genetic determinants underlying this variability is rudimen ... Full text Link to item Cite

Large candidate gene association study reveals genetic risk factors and therapeutic targets for fibromyalgia.

Journal Article Arthritis Rheum · February 2012 OBJECTIVE: Fibromyalgia (FM) represents a complex disorder that is characterized by widespread pain and tenderness and is frequently accompanied by additional somatic and cognitive/affective symptoms. Genetic risk factors are known to contribute to the eti ... Full text Link to item Cite

Excess risk of temporomandibular disorder associated with cigarette smoking in young adults.

Journal Article J Pain · January 2012 UNLABELLED: Evidence suggests that the effect of cigarette smoking on chronic pain is stronger in younger than older adults. This case-control study investigated whether age modified an effect of smoking on temporomandibular disorder (TMD) in 299 females a ... Full text Link to item Cite

Construction of a global pain systems network highlights phospholipid signaling as a regulator of heat nociception.

Journal Article PLoS Genet · 2012 The ability to perceive noxious stimuli is critical for an animal's survival in the face of environmental danger, and thus pain perception is likely to be under stringent evolutionary pressure. Using a neuronal-specific RNAi knock-down strategy in adult Dr ... Full text Link to item Cite

Catechol-O-methyltransferase genotype predicts pain severity in hospitalized burn patients.

Journal Article J Burn Care Res · 2012 Increasing evidence suggests that stress system activation after burn injury may contribute to burn-related pain. If this is the case, then genetic variations influencing the function of important stress system components, such as the enzyme catechol-O-met ... Full text Link to item Cite

Cytokine biomarkers and chronic pain: association of genes, transcription, and circulating proteins with temporomandibular disorders and widespread palpation tenderness.

Journal Article Pain · December 2011 For reasons unknown, temporomandibular disorder (TMD) can manifest as localized pain or in conjunction with widespread pain. We evaluated relationships between cytokines and TMD without or with widespread palpation tenderness (TMD-WPT or TMD+WPT, respectiv ... Full text Link to item Cite

Relax, you won't feel the pain.

Journal Article Nat Neurosci · November 23, 2011 Full text Link to item Cite

Elucidation of mu-Opioid Gene Structure: How Genetics Can Help Predict Responses to Opioids.

Journal Article Eur J Pain Suppl · November 11, 2011 Opioid drugs are among the most commonly used and effective human analgesics. To date, the clinical benefits of opioid analgesics have not been fully realized due to substantial individual variations in the responses to opioids, insufficient drug dosing, a ... Full text Link to item Cite

Structural basis for μ-opioid receptor binding and activation.

Journal Article Structure · November 9, 2011 Opioids that stimulate the μ-opioid receptor (MOR1) are the most frequently prescribed and effective analgesics. Here we present a structural model of MOR1. Molecular dynamics simulations show a ligand-dependent increase in the conformational flexibility o ... Full text Link to item Cite

Potential genetic risk factors for chronic TMD: genetic associations from the OPPERA case control study.

Journal Article J Pain · November 2011 UNLABELLED: Genetic factors play a role in the etiology of persistent pain conditions, putatively by modulating underlying processes such as nociceptive sensitivity, psychological well-being, inflammation, and autonomic response. However, to date, only a f ... Full text Link to item Cite

Potential autonomic risk factors for chronic TMD: descriptive data and empirically identified domains from the OPPERA case-control study.

Journal Article J Pain · November 2011 UNLABELLED: Several case-control studies have been conducted that examine the association between autonomic variables and persistent pain conditions; however, there is a surprising dearth of published studies in this area that have focused on temporomandib ... Full text Link to item Cite

Study methods, recruitment, sociodemographic findings, and demographic representativeness in the OPPERA study.

Journal Article J Pain · November 2011 UNLABELLED: This paper describes methods used in the project "Orofacial Pain Prospective Evaluation and Risk Assessment" (OPPERA) and evaluates sociodemographic characteristics associated with temporomandibular disorders (TMD) in the OPPERA case-control st ... Full text Link to item Cite

Disruptive mRNA folding increases translational efficiency of catechol-O-methyltransferase variant.

Journal Article Nucleic Acids Res · August 2011 Catechol-O-methyltransferase (COMT) is a major enzyme controlling catecholamine levels that plays a central role in cognition, affective mood and pain perception. There are three common COMT haplotypes in the human population reported to have functional ef ... Full text Link to item Cite

Catechol O-methyltransferase haplotype predicts immediate musculoskeletal neck pain and psychological symptoms after motor vehicle collision.

Journal Article J Pain · January 2011 UNLABELLED: Genetic variations in the catechol-O-methyltransferase (COMT) gene have been associated with experimental pain and risk of chronic pain development, but no studies have examined genetic predictors of neck pain intensity and other patient charac ... Full text Link to item Cite

Structural mechanism of S-adenosyl methionine binding to catechol O-methyltransferase.

Journal Article PLoS One · 2011 Methyltransferases possess a homologous domain that requires both a divalent metal cation and S-adenosyl-L-methionine (SAM) to catalyze its reactions. The kinetics of several methyltransferases has been well characterized; however, the details regarding th ... Full text Link to item Cite

A genome-wide Drosophila screen for heat nociception identifies α2δ3 as an evolutionarily conserved pain gene.

Journal Article Cell · November 12, 2010 Worldwide, acute, and chronic pain affects 20% of the adult population and represents an enormous financial and emotional burden. Using genome-wide neuronal-specific RNAi knockdown in Drosophila, we report a global screen for an innate behavior and identif ... Full text Link to item Cite

Comt1 genotype and expression predicts anxiety and nociceptive sensitivity in inbred strains of mice.

Journal Article Genes Brain Behav · November 2010 Catechol-O-methyltransferase (COMT) is a ubiquitously expressed enzyme that maintains basic biologic functions by inactivating catechol substrates. In humans, polymorphic variance at the COMT locus has been associated with modulation of pain sensitivity an ... Full text Link to item Cite

Multiple chronic pain states are associated with a common amino acid-changing allele in KCNS1.

Journal Article Brain · September 2010 Not all patients with nerve injury develop neuropathic pain. The extent of nerve damage and age at the time of injury are two of the few risk factors identified to date. In addition, preclinical studies show that neuropathic pain variance is heritable. To ... Full text Link to item Cite

A novel alternatively spliced isoform of the mu-opioid receptor: functional antagonism.

Journal Article Mol Pain · June 2, 2010 BACKGROUND: Opioids are the most widely used analgesics for the treatment of clinical pain. They produce their therapeutic effects by binding to mu-opioid receptors (MORs), which are 7 transmembrane domain (7TM) G-protein-coupled receptors (GPCRs), and inh ... Full text Link to item Cite

Effect of catechol-O-methyltransferase polymorphism on response to propranolol therapy in chronic musculoskeletal pain: a randomized, double-blind, placebo-controlled, crossover pilot study.

Journal Article Pharmacogenet Genomics · April 2010 INTRODUCTION: Three common haplotypes in the gene encoding catechol-O-methyltransferase (COMT) have been associated with pain modulation and the risk of developing chronic musculoskeletal pain, namely temporomandibular disorder (TMD). Haplotypes coding for ... Full text Link to item Cite

Pain perception is altered by a nucleotide polymorphism in SCN9A.

Journal Article Proc Natl Acad Sci U S A · March 16, 2010 The gene SCN9A is responsible for three human pain disorders. Nonsense mutations cause a complete absence of pain, whereas activating mutations cause severe episodic pain in paroxysmal extreme pain disorder and primary erythermalgia. This led us to investi ... Full text Link to item Cite

Assessing potential functionality of catechol-O-methyltransferase (COMT) polymorphisms associated with pain sensitivity and temporomandibular joint disorders.

Journal Article Methods Mol Biol · 2010 Catechol-O-methyltransferase (COMT) is an enzyme that plays a key role in the modulation of catechol-dependent functions such as cognition, cardiovascular function, and pain processing. Recently, our group demonstrated that three common haplotypes of the h ... Full text Link to item Cite

Molecular assays for characterization of alternatively spliced isoforms of the u opioid receptor (MOR).

Journal Article Methods Mol Biol · 2010 Mu-opioid receptor (MOR) belongs to a family of heptahelical G-protein-coupled receptors (GPCRs). Studies in humans and rodents demonstrated that the OPRM1 gene coding for MOR undergoes extensive alternative splicing afforded by the genetic complexity of O ... Full text Link to item Cite

Signaling pathways mediating beta3-adrenergic receptor-induced production of interleukin-6 in adipocytes.

Journal Article Mol Immunol · July 2009 The beta(3)-adrenergic receptor (beta(3)AR) is an essential regulator of metabolic and endocrine functions. A major cellular and clinically significant consequence of beta(3)AR activation is the substantial elevation in interleukin-6 (IL-6) levels. Althoug ... Full text Link to item Cite

Characterization of NF-kB-mediated inhibition of catechol-O-methyltransferase.

Journal Article Mol Pain · March 16, 2009 BACKGROUND: Catechol-O-methyltransferase (COMT), an enzyme that metabolizes catecholamines, has recently been implicated in the modulation of pain. Specifically, low COMT activity is associated with heightened pain perception and development of musculoskel ... Full text Link to item Cite

Expansion of the human mu-opioid receptor gene architecture: novel functional variants.

Journal Article Hum Mol Genet · March 15, 2009 The mu-opioid receptor (OPRM1) is the principal receptor target for both endogenous and exogenous opioid analgesics. There are substantial individual differences in human responses to painful stimuli and to opiate drugs that are attributed to genetic varia ... Full text Link to item Cite

Low enzymatic activity haplotypes of the human catechol-O-methyltransferase gene: enrichment for marker SNPs.

Journal Article PLoS One · 2009 Catechol-O-methyltransferase (COMT) is an enzyme that plays a key role in the modulation of catechol-dependent functions such as cognition, cardiovascular function, and pain processing. Three common haplotypes of the human COMT gene, divergent in two synon ... Full text Link to item Cite

Haplotype associations with quantitative traits in the presence of complex multilocus and heterogeneous effects.

Journal Article Genet Epidemiol · January 2009 In genetic mapping of complex traits, scored haplotypes are likely to represent only a subset of all causal polymorphisms. At the extreme of this scenario, observed polymorphisms are not themselves functional, and only linked to causal ones via linkage dis ... Full text Link to item Cite

Orthodontic Treatment, Genetic Factors and Risk of Temporomandibular Disorder.

Journal Article Semin Orthod · June 2008 Traditionally, four groups of factors have been identified in the etiology of temporomandibular disorder (TMD): anatomical variation in the masticatory system; psychosocial characteristics; pain in other body regions; and demographics. Orthodontic treatmen ... Full text Link to item Cite

Homogeneous reporter system enables quantitative functional assessment of multiple transcription factors.

Journal Article Nat Methods · March 2008 We developed a high-content reporter system that allows quantitative assessment of activities of multiple transcription factors (TFs) in a eukaryotic cell. The system comprises a library of reporter constructs that are evaluated according to their transcri ... Full text Link to item Cite

Genetic architecture of human pain perception.

Journal Article Trends Genet · December 2007 Pain is emotionally detrimental and consciously avoided; however, it is absolutely crucial for our survival. Pain perception is one of the most complicated measurable traits because it is an aggregate of several phenotypes associated with peripheral and ce ... Full text Link to item Cite

Influence of psychological factors on risk of temporomandibular disorders.

Journal Article J Dent Res · November 2007 Psychological characteristics potentially may be a cause or consequence of temporomandibular disorder (TMD). We hypothesized that psychological characteristics associated with pain sensitivity would influence risk of first-onset TMD, but the effect could b ... Full text Link to item Cite

Catechol-O-methyltransferase inhibition increases pain sensitivity through activation of both beta2- and beta3-adrenergic receptors.

Journal Article Pain · April 2007 Catechol-O-methyltransferase (COMT), an enzyme that metabolizes catecholamines, has recently been implicated in the modulation of pain. Our group demonstrated that human genetic variants of COMT are predictive for the development of Temporomandibular Joint ... Full text Link to item Cite

Beta2 adrenergic receptor activation stimulates pro-inflammatory cytokine production in macrophages via PKA- and NF-kappaB-independent mechanisms.

Journal Article Cell Signal · February 2007 Activation of the beta(2) adrenergic receptor (beta(2)AR) located on macrophages has been reported to possess anti-inflammatory properties, inhibiting nuclear factor kappaB (NF-kappaB) activation and cytokine production induced by pro-inflammatory stimuli. ... Full text Link to item Cite

Human catechol-O-methyltransferase haplotypes modulate protein expression by altering mRNA secondary structure.

Journal Article Science · December 22, 2006 Catechol-O-methyltransferase (COMT) is a key regulator of pain perception, cognitive function, and affective mood. Three common haplotypes of the human COMT gene, divergent in two synonymous and one nonsynonymous position, code for differences in COMT enzy ... Full text Link to item Cite

Catechol-O-methyltransferase gene polymorphisms are associated with multiple pain-evoking stimuli.

Journal Article Pain · December 5, 2006 Variations in the gene encoding catechol-O-methyltransferase (COMT) are linked to individual differences in pain sensitivity. A single nucleotide polymorphism (SNP) in codon 158 (val(158)met), which affects COMT protein stability, has been associated with ... Full text Link to item Cite

GTP cyclohydrolase and tetrahydrobiopterin regulate pain sensitivity and persistence.

Journal Article Nat Med · November 2006 We report that GTP cyclohydrolase (GCH1), the rate-limiting enzyme for tetrahydrobiopterin (BH4) synthesis, is a key modulator of peripheral neuropathic and inflammatory pain. BH4 is an essential cofactor for catecholamine, serotonin and nitric oxide produ ... Full text Link to item Cite

Three major haplotypes of the beta2 adrenergic receptor define psychological profile, blood pressure, and the risk for development of a common musculoskeletal pain disorder.

Journal Article Am J Med Genet B Neuropsychiatr Genet · July 5, 2006 Adrenergic receptor beta(2) (ADRB2) is a primary target for epinephrine. It plays a critical role in mediating physiological and psychological responses to environmental stressors. Thus, functional genetic variants of ADRB2 will be associated with a comple ... Full text Link to item Cite

Identification of novel mediators of NF-kappaB through genome-wide survey of monocyte adherence-induced genes.

Journal Article J Leukoc Biol · December 2005 The transcription factor nuclear factor (NF)-kappaB controls the expression of genes involved in inflammation, cell proliferation, apoptosis, and differentiation. Impaired regulation of NF-kappaB has been associated with many diseases; thus, there is signi ... Full text Link to item Cite

Genetic basis for individual variations in pain perception and the development of a chronic pain condition.

Journal Article Hum Mol Genet · January 1, 2005 Pain sensitivity varies substantially among humans. A significant part of the human population develops chronic pain conditions that are characterized by heightened pain sensitivity. We identified three genetic variants (haplotypes) of the gene encoding ca ... Full text Link to item Cite

Gene expression analysis of purified hematopoietic stem cells and committed progenitors.

Journal Article Blood · July 1, 2003 Lifelong self-renewal is a unique property of somatic stem cells. Recently, several primitive multipotent yet committed (non-self-renewing) hematopoietic progenitor populations were identified in mouse bone marrow. We have characterized the expression of 1 ... Full text Link to item Cite

Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.

Journal Article Proc Natl Acad Sci U S A · December 24, 2002 The National Institutes of Health Mammalian Gene Collection (MGC) Program is a multiinstitutional effort to identify and sequence a cDNA clone containing a complete ORF for each human and mouse gene. ESTs were generated from libraries enriched for full-len ... Full text Link to item Cite

Subtractive cloning: new genes for studying inflammatory disorders.

Journal Article Ann Periodontol · December 2002 Understanding of the biology of interaction between pathogens and host is the central question in studying inflammatory disorders. Subtractive DNA cloning is one of the most efficient and comprehensive methods available for identifying eukaryotic genes reg ... Full text Link to item Cite

Caveolin-1 is down-regulated in human ovarian carcinoma and acts as a candidate tumor suppressor gene.

Journal Article Am J Pathol · November 2001 To identify novel markers differentially expressed in ovarian cancer versus normal ovary, we hybridized microarrays with cDNAs derived from normal human ovaries and advanced stage ovarian carcinomas. This analysis revealed down-regulation of the caveolin-1 ... Full text Link to item Cite

Generation of full-length cDNA libraries enriched for differentially expressed genes for functional genomics.

Journal Article Biotechniques · March 2001 Here, we describe the application of a RecA-based cloning technology to generate full-length cDNA libraries enriched for genes that are differentially expressed between tumor and normal tissue samples. First, we show that the RecA-based method can be used ... Full text Link to item Cite

Use of SMART-generated cDNA for gene expression studies in multiple human tumors.

Journal Article Biotechniques · January 2001 We demonstrate here that SMART PCR-amplified cDNAs arrayed on a nylon membrane are suitable for high-throughput tissue expression profiling when starting biological materials are limited. We show that SMART cDNA accurately reflects gene expression patterns ... Full text Link to item Cite

Structure and regulation of the mouse ing1 gene. Three alternative transcripts encode two phd finger proteins that have opposite effects on p53 function.

Journal Article J Biol Chem · November 5, 1999 The human ING1 gene encodes nuclear protein p33(ING1), previously shown to cooperate with p53 in cell growth control (Garkavtsev, I., Grigorian, I. A., Ossovskaya, V. S., Chernov, M. V., Chumakov, P. M., and Gudkov, A. V. (1998) Nature 391, 295-298). p33(I ... Full text Link to item Cite

Amplification of cDNA ends based on template-switching effect and step-out PCR.

Journal Article Nucleic Acids Res · March 15, 1999 A new method for amplifying cDNA ends is described which requires only first-strand cDNA synthesis and a single PCR to generate a correct product with very low or no background. The method can be successfully applied to total RNA as well as poly A+ RNA. Th ... Full text Link to item Cite

Suppression subtractive hybridization: a versatile method for identifying differentially expressed genes.

Journal Article Methods Enzymol · 1999 A new and highly effective method, termed suppression subtractive hybridization (SSH), has been developed for the generation of subtracted cDNA libraries. It is based primarily on a technique called suppression PCR, and combines normalization and subtracti ... Full text Link to item Cite

PCR-based subtractive hybridization and differences in gene content among strains of Helicobacter pylori.

Journal Article Proc Natl Acad Sci U S A · October 27, 1998 Genes that are characteristic of only certain strains of a bacterial species can be of great biologic interest. Here we describe a PCR-based subtractive hybridization method for efficiently detecting such DNAs and apply it to the gastric pathogen Helicobac ... Full text Link to item Cite

Stress-induced secretion of growth inhibitors: a novel tumor suppressor function of p53.

Journal Article Oncogene · September 3, 1998 p53 tumor suppressor gene controls cell response to a variety of stresses inducing growth arrest or apoptosis in damaged cells. It largely determines the sensitivity of tumor and normal cells to radiation and chemotherapy, and, therefore, defines both the ... Full text Link to item Cite

Differential screening of a subtracted cDNA library: a method to search for genes preferentially expressed in multiple tissues.

Journal Article Biotechniques · December 1997 We have developed a new strategy for differential screening of genes that are expressed in two or more tissues, and have used it to identify genes that are preferentially expressed in both testis and ovary. In this approach, testis-specific cDNAs were firs ... Full text Link to item Cite

Construction of cDNA libraries from small amounts of total RNA using the suppression PCR effect.

Journal Article Biochem Biophys Res Commun · January 13, 1997 Here we describe a method for preparing high-quality cDNA libraries from total RNA. By this method, double-stranded (ds) cDNA ligated with a specially designed ds adaptor is amplified by PCR using a modified T-primer and another primer corresponding to the ... Full text Link to item Cite

Suppression subtractive hybridization: A new method for cDNA subtraction of differentially expressed genes

Journal Article FASEB Journal · December 1, 1996 A new and highly effective method, termed Suppression Subtractive Hybridization (SSH), has been developed for cDNA subtraction of differentially expressed genes, including the generation of subtracted cDNA libraries. It is based primarily on a recently des ... Cite

CAPswitch based PCR technology for full-length cDNA library construction from small amount of RNA

Journal Article FASEB Journal · December 1, 1996 We describe a CAPswitch based PCR cDNA library construction method. In this method, a modified oligo(dT) primer is used to prime the first-strand reaction, and a CAPswitch oligonucleotide serves as a short, extended template at the 5' mRNA end for reverse ... Cite

Equalizing cDNA subtraction based on selective suppression of polymerase chain reaction: cloning of Jurkat cell transcripts induced by phytohemaglutinin and phorbol 12-myristate 13-acetate.

Journal Article Anal Biochem · August 15, 1996 The major drawback of subtractive cDNA libraries is that the original disproportion in concentrations of different types of transcripts is preserved. This usually makes the isolation of specific rare transcripts extremely difficult. To overcome this diffic ... Full text Link to item Cite

Suppression subtractive hybridization: a method for generating differentially regulated or tissue-specific cDNA probes and libraries.

Journal Article Proc Natl Acad Sci U S A · June 11, 1996 A new and highly effective method, termed suppression subtractive hybridization (SSH), has been developed for the generation of subtracted cDNA libraries. It is based primarily on a recently described technique called suppression PCR and combines normaliza ... Full text Link to item Cite