A5048597717- Pain Mechanisms and Treatments
- Pain Management and Opioid Use
- Hemoglobinopathies and Related Disorders
- Pain Management and Placebo Effect
- Musculoskeletal pain and rehabilitation
- Neuropeptides and Animal Physiology
- Pediatric Pain Management Techniques
- Anesthesia and Pain Management
- Ion channel regulation and function
- Spine and Intervertebral Disc Pathology
- Pharmacology and Obesity Treatment
- Receptor Mechanisms and Signaling
- Iron Metabolism and Disorders
- Pharmacological Effects and Toxicity Studies
- Diet and metabolism studies
- Botulinum Toxin and Related Neurological Disorders
- Cancer, Stress, Anesthesia, and Immune Response
- Metabolism and Genetic Disorders
- Complementary and Alternative Medicine Studies
- Neurobiology and Insect Physiology Research
- Hereditary Neurological Disorders
- Stress Responses and Cortisol
- Cancer Treatment and Pharmacology
- Cannabis and Cannabinoid Research
- Nicotinic Acetylcholine Receptors Study
National Institutes of Health
2007-2024
National Center for Complementary and Integrative Health
2018-2024
University of Pittsburgh
2010-2020
Foundation for Physical Medicine and Rehabilitation
2020
Shirley Ryan AbilityLab
2020
Brigham and Women's Hospital
2020
Office of the Director
2017-2019
McGill University
2014-2018
Center for Drug Evaluation and Research
2015-2017
Ospedale di Parma
2016
Pain sensitivity varies substantially among humans. A significant part of the human population develops chronic pain conditions that are characterized by heightened sensitivity. We identified three genetic variants (haplotypes) gene encoding catecholamine- O -methyltransferase (COMT) we designated as low (LPS), average (APS) and high (HPS). show these haplotypes encompass 96% population, five combinations strongly associated ( P =0.0004) with variation in to experimental pain. The presence...
Variations in the gene encoding catechol-O-methyltransferase (COMT) are linked to individual differences pain sensitivity. A single nucleotide polymorphism (SNP) codon 158 (val(158)met), which affects COMT protein stability, has been associated with human experience of pain. We recently demonstrated that three common haplotypes, affect efficiency translation, strongly a global measure sensitivity derived from individuals' responses noxious thermal, ischemic, and pressure stimuli. Specific...
The gene SCN9A is responsible for three human pain disorders. Nonsense mutations cause a complete absence of pain, whereas activating severe episodic in paroxysmal extreme disorder and primary erythermalgia. This led us to investigate whether single nucleotide polymorphisms (SNPs) were associated with differing perception the general population. We first genotyped 27 SNPs 578 individuals radiographic diagnosis osteoarthritis score assessment. A significant association was found between SNP...
Not all patients with nerve injury develop neuropathic pain. The extent of damage and age at the time are two few risk factors identified to date. In addition, preclinical studies show that pain variance is heritable. To define such further, we performed a large-scale gene profiling experiment which plotted global expression changes in rat dorsal root ganglion three peripheral models. This resulted discovery potassium channel alpha subunit KCNS1, involved neuronal excitability,...
Psychological characteristics potentially may be a cause or consequence of temporomandibular disorder (TMD). We hypothesized that psychological associated with pain sensitivity would influence risk first-onset TMD, but the effect could attributed to variation in gene encoding catechol- O-methyltransferase (COMT). undertook prospective cohort study healthy female volunteers aged 18–34 yrs. At baseline, participants were genotyped, they completed questionnaires, and underwent quantitative...
Abstract Adrenergic receptor β 2 (ADRB2) is a primary target for epinephrine. It plays critical role in mediating physiological and psychological responses to environmental stressors. Thus, functional genetic variants of ADRB2 will be associated with complex array phenotypes. These should also interact factors such as physical or emotional stress produce phenotype vulnerable pathological states. In this study, we determined whether common contribute the development chronic pain condition...
The μ-opioid receptor (OPRM1) is the principal target for both endogenous and exogenous opioid analgesics. There are substantial individual differences in human responses to painful stimuli opiate drugs that attributed genetic variations OPRM1. In searching new functional variants, we employed comparative genome analysis obtained evidence existence of an expanded OPRM1 gene locus with promoters, alternative exons regulatory elements. Examination polymorphisms within identified strong...
Persistent postmastectomy pain (PPMP) is a major individual and public health problem. Increasingly, psychosocial factors such as anxiety catastrophizing are being revealed crucial contributors to differences in processing outcomes. Furthermore, patients' responses standardized quantitative sensory testing (QST) may aid the discernment of who at risk for acute chronic after surgery. However, characterization variables that differentiate those with PPMP from whose postoperative resolves...
Background Preclinical studies suggest that opioids may promote tumor growth. Genetic polymorphisms have been shown to affect opioid receptor function and modify the clinical effects of morphine. In this study we assessed association between six common in μ-opioid gene, including well known A118G polymorphism, breast cancer survival. Methods A total 2,039 women ages 23-74 yr (38% African-American, 62% European-American, 55% postmenopausal) diagnosed with 1993-2001 were followed through 2006....
Nociception is protective and prevents tissue damage but can also facilitate chronic pain. Whether a general principle governs these two types of pain unknown. Here, we show that both basal mechanical neuropathic are controlled by the microRNA-183 (miR-183) cluster in mice. This single controls more than 80% pain-regulated genes scales sensitivity allodynia regulating auxiliary voltage-gated calcium channel subunits α2δ-1 α2δ-2. Basal nociceptors, involves TrkB+ light-touch mechanoreceptors....
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 mechanical allodynia, prominent symptom of chronic pain. identified levels Chrna6, which encodes the α6 subunit nicotinic acetylcholine receptor (nAChR), as associated with allodynia. confirmed importance α6* (α6-containing) nAChRs by analyzing both gain- loss-of-function...
Pain in patients with chronic pancreatitis (CP) remains the primary clinical complaint and source of poor quality life. However, clear guidance on evaluation treatment is lacking.
Available evidence indicates voltage-gated Na+ channels (VGSCs) in peripheral sensory neurons are essential for the pain and hypersensitivity associated with tissue injury. However, our understanding of biophysical pharmacological properties is largely based on study heterologous systems or rodent tissue, despite that both expression species differences influence these properties. Therefore, we sought to determine extent which VGSCs were comparable rat human neurons. Whole cell patch clamp...
Rheumatoid arthritis-associated joint pain is frequently observed independent of disease activity, suggesting unidentified mechanisms. We demonstrate that antibodies binding to cartilage, specific for collagen type II (CII) or cartilage oligomeric matrix protein (COMP), elicit mechanical hypersensitivity in mice, uncoupled from visual, histological and molecular indications inflammation. Cartilage antibody-induced pain-like behavior does not depend on complement activation inflammation, but...
The effects of COMT genetic polymorphism on pain and analgesia are modality – selective gender dependent, in both mouse humanPlease approve Summary as edited. enzyme catechol-O-methyltransferase (COMT) metabolizes catecholamine neurotransmitters involved a number physiological functions, including perception. Both human genes possess functional polymorphisms contributing to interindividual variability phenotypes such sensitivity noxious stimuli, severity clinical pain, response treatment. In...
•Significant numbers of patients still suffer from significant acute pain, despite the advent modern multimodal analgesic strategies.•Mismanaged pain has a broad societal impact, as may progress to chronic pain.•An taxonomy provides much needed standardization clinical diagnostic criteria which benefits care, research, education, and public policy.•For purposes present taxonomy, is considered last up 7 days with prolongation 30 being common.•Current understanding mechanisms poorly...