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 central nervous system dynamics, stress responsiveness and inflammatory state. As a complex trait, it is expected to have a polygenic nature shaped by environmental pressures. Here we discuss what is known about these contributing genetic variants, including recent discoveries that show a crucial role of voltage-gated sodium channel Nav1.7 in pain perception and how we can advance our understanding of the pain genetic network. We propose how both rare deleterious genetic variants and common genetic polymorphisms are mediators of human pain perception and clinical pain phenotypes.
"cluster headache, post-traumatic headache, post-herpetic neuralgia ) (Cairns, 2007). Genetic variants and polymorphisms as well as environmental factors have been shown to affect the susceptibility to different pain conditions (Diatchenko et al., 2007). Still, pain symptoms in women with IBS, TMD, and migraine fluctuate with the menstrual cycle (Houghton et al., 2002; Johannes et al., 1995; LeResche et al., 2003) and increased estrogen levels also correlate with a higher risk of chronic lower back pain (Wijnhoven et al., 2006) and temporomandibular disorders (LeResche et al., 1997). "
[Show abstract][Hide abstract] ABSTRACT: Gonadal hormones not only play a pivotal role in reproductive behavior and sexual differentiation, they also contribute to thermoregulation, feeding, memory, neuronal survival, and the perception of somatosensory stimuli. Numerous studies on both animals and human subjects have also demonstrated the potential effects of gonadal hormones, such as estrogens, on pain transmission. These effects most likely involve multiple neuroanatomical circuits as well as diverse neurochemical systems and they therefore need to be evaluated specifically to determine the localization and intrinsic characteristics of the neurons engaged. The aim of this review is to summarize the morphological as well as biochemical evidence in support for gonadal hormone modulation of nociceptive processing, with particular focus on estrogens and spinal cord mechanisms.
Frontiers in Neuroendocrinology 06/2013; 34(4). DOI:10.1016/j.yfrne.2013.06.001 · 7.04 Impact Factor
"It is likely that pain perception is under the control of a number of different interacting genetic and environmental influences . Despite minimising the number of non-genetic confounders by carrying out these analyses in healthy volunteers, the data presented in this paper demonstrate that there remain a number of other factors which are likely to significantly contribute to variability in pain sensitivity. "
[Show abstract][Hide abstract] ABSTRACT: Background
Pain tolerance is subject to considerable inter-individual variation, which may be influenced by a number of genetic and non-genetic factors. The mu, delta and kappa opioid receptors play a role in pain perception and are thought to mediate different pain modalities. The aim of this study was to explore associations between pain thresholds and gender and genetic variants in the three opioid receptor genes (OPRM, OPRD and OPRK). Experimental multi-modal pain data from previously published studies carried out in healthy Caucasian volunteers were used in order to limit the number of confounders to the study outcome. Data on thermal skin pain (n=36), muscle pressure pain (n=31) and mechanical visceral pain (n=50)) tolerance thresholds were included.
Nineteen genetic polymorphisms were included in linear regression modeling. Males were found to tolerate higher thermal and muscle pressure pain than females (p=0.003 and 0.02). Thirty four percent of variability in thermal skin pain was accounted for by a model consisting of OPRK rs6473799 and gender. This finding was just outside significance when correction for multiple testing was applied. Variability in muscle pressure pain tolerance was associated with OPRK rs7016778 and rs7824175. These SNPs accounted for 43% of variability in muscle pressure pain sensitivity and these findings remained significant after adjustment for multiple testing. No association was found with mechanical visceral pain.
This is a preliminary and hypothesis generating study due to the relatively small study size. However, significant association between the opioid receptor genes and experimental pain sensitivity supports the influence of genetic variability in pain perception. These findings may be used to generate hypotheses for testing in larger clinical trials of patients with painful conditions.
"Contrary to data derived from familial pain syndromes, results from genetic association studies are more applicable to the general population and, in the case of GWASs, should be able to give rise to the discovery of completely new targets. Many putative 'pain genes' have indeed been genetically linked to various chronic pain conditions [17,18,41], but study results have proven difficult to replicate and consequently are yet to have real impact on treatment approaches. Of a wide range of candidates, three have received particular attention from researchers and can be used to illustrate the contradictory nature of the findings in the field: GCH1, which encodes GTP cyclohydrolase; COMT, an enzyme that eliminates catecholamines; and OPRM1, the μ-opioid receptor gene. "
[Show abstract][Hide abstract] ABSTRACT: Chronic pain affects approximately one in five adults, resulting in a greatly reduced quality of life and a higher risk of developing co-morbidities such as depression. Available treatments often provide inadequate pain relief, but it is hoped that through deeper understanding of the molecular mechanisms underlying chronic pain states we can discover new and improved therapies. Although genetic research has flourished over the past decade and has identified many key genes in pain processing, the budding field of epigenetics promises to provide new insights and a more dynamic view of pain regulation. This review gives an overview of basic mechanisms and current therapies to treat pain, and discusses the clinical and preclinical evidence for the contribution of genetic and epigenetic factors, with a focus on how this knowledge can affect drug development.
Genome Medicine 02/2013; 5(2):12. DOI:10.1186/gm416 · 5.34 Impact Factor
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