Article

Genetic architecture of human pain perception.

Center for Neurosensory Disorders, University of North Carolina, 2190 Old Dental Building, Chapel Hill, NC 27599, USA.
Trends in Genetics (Impact Factor: 11.6). 01/2008; 23(12):605-13. DOI: 10.1016/j.tig.2007.09.004
Source: PubMed

ABSTRACT 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.

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    • "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). "
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    • "It is well known that the degree of chronic pain differs considerably among individuals with seemingly similar types of injuries. It is also well established that there is wide variability in threshold sensitivity and tolerance level to noxious stimulation among human populations, which cannot be fully explained by environmental and cultural causes (Mogil, 1999; Diatchenko et al., 2007). Ample evidence demonstrates that this is also the case in a range of experimental pain models, including neuropathic pain models (Devor and Raber, 1990; Lacroix-Fralish et al., 2006b; Costigan et al., 2010). "
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    • "Rodent and human studies suggest that neuropathic pain susceptibility is genetically linked (Diatchenko et al., 2007; Lacroix-Fralish and Mogil, 2009; Costigan et al., 2009b). We used a convergent experimental approach that implicates KCNS1 as a gene marking the risk of developing neuropathic pain. "
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