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Genetic architecture of human pain perception

2007; Elsevier BV; Volume: 23; Issue: 12 Linguagem: Inglês

10.1016/j.tig.2007.09.004

1362-4555

Luda Diatchenko, Andrea G. Nackley, Inna E. Tchivileva, Svetlana A. Shabalina, William Maixner,

Hereditary Neurological Disorders

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. 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. Pain perception evoked by a stimulus that under normal conditions evokes non-painful sensations. A form of natural selection that maintains genetic variation at an individual locus. Unlike positive selection, balancing selection increases levels of nucleotide variation at linked sites. A variety of mechanisms can result in elevated levels of polymorphism including over-dominance (heterozygote advantage), frequency-dependent selection, and temporally or spatially variable selection. A phenotypic change in CNS pathways that leads to the augmentation of the processing of nociceptive stimuli. Medical conditions that occur with high frequencies with other medical conditions. This is a chronic musculoskeletal pain condition that is characterized by widespread pain throughout the body. It is associated with increased sensitivity to painful stimuli and psychologic distress. This condition has a prevalence of 3% in the US population and impacts female to males in a 3:1 ratio. A haploid genotype for multiple alleles at multiple linked loci that are transmitted together. Enhanced pain perception evoked by a stimulus that under normal conditions evokes painful sensations. A quantifiable phenotype that is a specific component or construct associated with a complex medical condition or syndrome. These are measurable traits or markers that contribute to the susceptibility or manifestation of a disorder or condition. The strength of association between alleles at two different markers (pairwise LD). Pain and pain behaviors evoked by the application of a brief noxious stimulus. Primary nerve fibers that respond to tissue injury or stimuli that are capable of evoking tissue injury. This is a common musculoskeletal pain condition associated with the temporomandibular joint and surrounding muscles of mastication. It is associated with increased sensitivity to painful stimuli and psychologic distress. This condition has a prevalence of 10% in the US population and impacts female to males in a 3:1 ratio.