Shad Benjamin Smith

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

A mouse model of chronic primary pain that integrates clinically relevant genetic vulnerability, stress, and minor injury.

Journal Article Sci Transl Med · April 10, 2024 Chronic primary pain conditions (CPPCs) affect over 100 million Americans, predominantly women. They remain ineffectively treated, in large part because of a lack of valid animal models with translational relevance. Here, we characterized a CPPC mouse mode ... Full text Link to item Cite

The Adaptive, Pain Sensitive, and Global Symptoms Clusters: Evidence from a Patient-Based Study.

Journal Article JDR Clin Trans Res · April 2024 OBJECTIVES: The largest epidemiologic study conducted about painful temporomandibular disorders (pTMDs) to date identified 3 clusters of individuals with similar symptoms-adaptive, pain sensitive, and global symptoms-which hold promise as a means of person ... Full text Open Access Link to item Cite

The Chronic Overlapping Pain Condition Screener.

Journal Article J Pain · January 2024 Ten Chronic Overlapping Pain Conditions (COPCs) are currently recognized by the National Institutes of Health Pain Consortium (eg, irritable bowel syndrome, chronic migraine headache, and chronic low back pain). These conditions affect millions of American ... Full text Link to item Cite

Clinical and biobehavioral phenotypic assessments and data harmonization for the RE-JOIN research consortium: Recommendations for common data element selection.

Journal Article Neurobiol Pain · 2024 BACKGROUND: The Restoring Joint Health and Function to Reduce Pain (RE-JOIN) Consortium is part of the Helping to End Addiction Long-term® (HEAL) Initiative. HEAL is an ambitious, NIH-wide initiative to speed scientific solutions to stem the national opioi ... Full text Link to item Cite

Applying the Rapid OPPERA Algorithm to Predict Persistent Pain Outcomes Among a Cohort of Women Undergoing Breast Cancer Surgery.

Journal Article J Pain · December 2022 Persistent postmastectomy pain after breast surgery is variable in duration and severity across patients, due in part to interindividual variability in pain processing. The Rapid OPPERA Algorithm (ROPA) empirically identified 3 clusters of patients with di ... 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

What Is My Patient's Pain Phenotype? An Exercise in Transferring Patient Clustering Solutions between Institutions and across Patient Samples

Conference JOURNAL OF PAIN · 2022 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

Discovery and fine-mapping of height loci via high-density imputation of GWASs in individuals of African ancestry.

Journal Article Am J Hum Genet · April 1, 2021 Although many loci have been associated with height in European ancestry populations, very few have been identified in African ancestry individuals. Furthermore, many of the known loci have yet to be generalized to and fine-mapped within a large-scale Afri ... 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

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

Clinical pain phenotyping for omics studies

Chapter · January 1, 2020 Pain is by definition a subjective experience that affects individuals in dramatically different ways. Individual variation across many domains of the pain experience, such as sensitivity to noxious stimuli and propensity to develop chronic pain, has been ... Full text 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

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

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

Discovery of Novel Mechanisms for Idiopathic Pain Disorders Through Genome Wide Approaches

Conference FASEB JOURNAL · 2019 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

Genomics of Cardiovascular Measures of Autonomic Tone.

Journal Article J Cardiovasc Pharmacol · March 2018 The autonomic nervous system exerts broad control over the involuntary functions of the human body through complex equilibrium between sympathetic and parasympathetic tone. Imbalance in this equilibrium is associated with a multitude of cardiovascular outc ... Full text Link to item Cite

Impact of human CA8 on thermal antinociception in relation to morphine equivalence in mice.

Journal Article Neuroreport · December 13, 2017 Recently, we showed that murine dorsal root ganglion (DRG) Car8 expression is a cis-regulated eQTL that determines analgesic responses. In this report, we show that transduction through sciatic nerve injection of DRG with human wild-type carbonic anhydrase ... 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

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

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

Evidence that Dry Eye Represents a Chronic Overlapping Pain Condition.

Journal Article Mol Pain · 2017 Recent data suggest that corneal somatosensory dysfunction may be the underlying cause of severe dry eye symptoms in the absence of ocular surface pathology seen in a subset of patients diagnosed with “dry eye syndrome.” This subset of patients tends to de ... 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

Overlapping Chronic Pain Conditions: Implications for Diagnosis and Classification.

Journal Article J Pain · September 2016 UNLABELLED: There is increasing recognition that many if not most common chronic pain conditions are heterogeneous with a high degree of overlap or coprevalence of other common pain conditions along with influences from biopsychosocial factors. At present, ... 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

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

MicroRNA expression profiles differentiate chronic pain condition subtypes.

Journal Article Transl Res · December 2015 Chronic pain is a significant health care problem, ineffectively treated because of its unclear etiology and heterogeneous clinical presentation. Emerging evidence demonstrates that microRNAs (miRNAs) regulate the expression of pain-relevant genes, yet lit ... 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

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

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

Progress and challenges in genome-wide association studies of pain

Chapter · June 1, 2015 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

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

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

Genome-Wide Association Study for Severe Radiographic Knee Osteoarthritis

Journal Article ARTHRITIS & RHEUMATOLOGY · October 1, 2014 Link to item Cite

FKBP5 Gene Is Associated With IBS Diagnosis

Conference GASTROENTEROLOGY · 2014 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

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

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

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

A meta-analysis identifies new loci associated with body mass index in individuals of African ancestry.

Journal Article Nat Genet · June 2013 Genome-wide association studies (GWAS) have identified 36 loci associated with body mass index (BMI), predominantly in populations of European ancestry. We conducted a meta-analysis to examine the association of >3.2 million SNPs with BMI in 39,144 men and ... 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

Preclinical episodes of orofacial pain symptoms and their association with health care behaviors in the OPPERA prospective cohort study.

Journal Article Pain · May 2013 The course of preclinical pain symptoms sheds light on the etiology and prognosis of chronic pain. We aimed to quantify rates of developing initial and recurrent symptoms of painful temporomandibular disorder (TMD) and to evaluate associations with health ... Full text Link to item Cite

Tactile system and nociception

Chapter · 2013 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

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

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

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

Pain sensitivity and vasopressin analgesia are mediated by a gene-sex-environment interaction.

Journal Article Nat Neurosci · October 23, 2011 Quantitative trait locus mapping of chemical/inflammatory pain in the mouse identified the Avpr1a gene, which encodes the vasopressin-1A receptor (V1AR), as being responsible for strain-dependent pain sensitivity to formalin and capsaicin. A genetic associ ... Full text Link to item Cite

Corrigenda

Journal Article Brain · July 1, 2011 Full text 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

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

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

Development of temporomandibular disorders is associated with greater bodily pain experience.

Journal Article Clin J Pain · February 2010 OBJECTIVES: The aim of this study is to examine the difference in the report of bodily pain experienced by patients who develop temporomandibular disorders (TMD) and by those who do not develop TMD over a 3-year observation period. METHODS: This is a 3-yea ... Full text Link to item Cite

Gnao1 (G alphaO protein) is a likely genetic contributor to variation in physical dependence on opioids in mice.

Journal Article Neuroscience · September 15, 2009 Chronic exposure to opioids leads to physical dependence, which manifests as the symptoms of drug withdrawal. Interindividual differences in withdrawal symptom severity are well known, and at least partially due to genetic variation. To identify genes cont ... Full text Link to item Cite

The beta3 subunit of the Na+,K+-ATPase mediates variable nociceptive sensitivity in the formalin test.

Journal Article Pain · August 2009 It is widely appreciated that there is significant inter-individual variability in pain sensitivity, yet only a handful of contributing genetic variants have been identified. Computational genetic mapping and quantitative trait locus analysis suggested tha ... Full text Link to item Cite

Quantitative trait locus and computational mapping identifies Kcnj9 (GIRK3) as a candidate gene affecting analgesia from multiple drug classes.

Journal Article Pharmacogenet Genomics · March 2008 AIMS: Interindividual differences in analgesic drug response complicate the clinical management of pain. We aimed to identify genetic factors responsible for variable sensitivity to analgesic drugs of disparate neurochemical classes. METHODS AND RESULTS: Q ... Full text Link to item Cite

Screening for pain phenotypes: analysis of three congenic mouse strains on a battery of nine nociceptive assays.

Journal Article Pain · December 15, 2006 In an attempt to identify new genes responsible for variability in pain sensitivity, we tested three congenic mouse strains--in which a small portion of the genome of the MOLF/Ei strain has been placed on a C57BL/6 genetic background--on a battery of nine ... Full text Link to item Cite

Influence of genotype, dose and sex on pruritogen-induced scratching behavior in the mouse.

Journal Article Pain · September 2006 Itch features considerable interindividual variability in humans, and initial studies using animal models have demonstrated a likely role of genetic factors in mediating such variability. In an attempt to systematically study genetic mediation of itch in t ... Full text Link to item Cite

Social modulation of pain as evidence for empathy in mice.

Journal Article Science · June 30, 2006 Empathy is thought to be unique to higher primates, possibly to humans alone. We report the modulation of pain sensitivity in mice produced solely by exposure to their cagemates, but not to strangers, in pain. Mice tested in dyads and given an identical no ... Full text Link to item Cite

Influence of nociception and stress-induced antinociception on genetic variation in isoflurane anesthetic potency among mouse strains.

Journal Article Anesthesiology · October 2005 BACKGROUND: Genetic background influences anesthetic potency to suppress motor response to noxious stimulation (minimum alveolar concentration [MAC]) as well as nociceptive sensitivity in unmedicated animals. However, the influence on MAC of baseline sensi ... Full text Link to item Cite

Variable sensitivity to noxious heat is mediated by differential expression of the CGRP gene.

Journal Article Proc Natl Acad Sci U S A · September 6, 2005 Heat sensitivity shows considerable functional variability in humans and laboratory animals, and is fundamental to inflammatory and possibly neuropathic pain. In the mouse, at least, much of this variability is genetic because inbred strains differ robustl ... Full text Link to item Cite

Melanocortin-1 receptor gene variants affect pain and mu-opioid analgesia in mice and humans.

Journal Article J Med Genet · July 2005 BACKGROUND: A recent genetic study in mice and humans revealed the modulatory effect of MC1R (melanocortin-1 receptor) gene variants on kappa-opioid receptor mediated analgesia. It is unclear whether this gene affects basal pain sensitivity or the efficacy ... Full text Link to item Cite

Paclitaxel-induced neuropathic hypersensitivity in mice: responses in 10 inbred mouse strains.

Conference Life Sci · April 9, 2004 Mechanical allodynia, or hypersensitivity to tactile stimuli, is a frequent clinical symptom of neuropathy. Large interindividual differences have been observed in neuropathic pain, both in susceptibility to its development and in its severity. Identificat ... Full text Link to item Cite

The heritability of antinociception: common pharmacogenetic mediation of five neurochemically distinct analgesics.

Journal Article J Pharmacol Exp Ther · February 2003 The heritability of nociception and antinociception has been well established in the mouse. The pharmacogenetics of morphine analgesia are fairly well characterized, but far less is known about other analgesics. The purpose of this work was to begin the sy ... Full text Link to item Cite