Abstract
BackgroundC-fibers express transient receptor potential (TRP) channels. These high-voltage gated channels function as integrators of different physical stresses (e.g. heat, protons, ATP). Additionally channel activation can be induced by capsaicin. Topically applied, capsaicin elicits burning pain, heat and mechanical hyperalgesia and serves as a human surrogate model for pain. It was suggested that the TRPV1-variant rs8065080 (1911A>G) plays a pivotal role in patients with neuropathic pain syndromes. We investigated the effect of this TRPV1-SNP on thermal sensitivity and superficial skin perfusion in 25 healthy subjects.Methods and findingsNine subjects being homozygous TRPV1 wild type (AA), 8 heterozygous (AG) and 8 homozygous variant (GG) carriers were selected out of a pool of genotyped healthy individuals. Under physiological conditions (no capsaicin application), there was no statistical significant difference in thermal thresholds or skin perfusion between carriers of different TRPV1 1199A>G genotypes. However, intra-individual calculations (Δ% pre vs. post capsaicin) revealed (1) less warm-detection in AA/AG (-82.1%) compared to GG (-13.1%) and (2) a gain of heat pain sensitivity in AA/AG (+22.2%) compared to GG carriers (+15.6%) after adjustment for perfusion measurements ((1)p = 0.009, (2)p = 0.021).ConclusionPresence of homozygous variant TRPV1 genotype (GG) demonstrated less capsaicin-induced warm hypoesthesia in warm-detection and less capsaicin-induced heat pain sensitivity suggesting an altered channel function. This demonstrates not only the functional influence of TRPV1 rs8065080 polymorphism itself; it further more underpins the relevance of genotyping-based approaches in both patients and surrogate models of neuropathic pain in healthy volunteers.
Highlights
Transient receptor potential (TRP) channels are high-threshold voltage-gated cation channels expressed on small diameter afferent nerves
Protein expression analysis showed an increase of TRPV1 in damaged nerve fibers and corresponding dorsal root ganglia (DRG) and in adjacent non-damaged afferents of partially damaged nerves [6,7,8]
Among the rs8065080 (1911A>G) variant, which we explore in the presented study other single nucleotide polymorphisms (SNPs) have been identified to play a role in human pain perception
Summary
Transient receptor potential (TRP) channels are high-threshold voltage-gated cation channels expressed on small diameter afferent nerves. They serve as integrators of different physical stressors transducing these into electrical impulses [1]. Several findings suggested that TRPV1 plays a role in neuropathic pain syndromes [4]. These are defined as chronic pain directly caused by a lesion or disease of the somatosensory system [5]. C-fibers express transient receptor potential (TRP) channels These high-voltage gated channels function as integrators of different physical stresses (e.g. heat, protons, ATP). We investigated the effect of this TRPV1-SNP on thermal sensitivity and superficial skin perfusion in 25 healthy subjects
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