Transient Receptor Potential Channel Polymorphisms Are Associated with the Somatosensory Function in Neuropathic Pain Patients

Abstract

Transient receptor potential channels are important mediators of thermal and mechanical stimuli and play an important role in neuropathic pain. The contribution of hereditary variants in the genes of transient receptor potential channels to neuropathic pain is unknown. We investigated the frequency of transient receptor potential ankyrin 1, transient receptor potential melastin 8 and transient receptor potential vanilloid 1 single nucleotide polymorphisms and their impact on somatosensory abnormalities in neuropathic pain patients. Within the German Research Network on Neuropathic Pain (Deutscher Forscbungsverbund Neuropathischer Schmerz) 371 neuropathic pain patients were phenotypically characterized using standardized quantitative sensory testing. Pyrosequencing was employed to determine a total of eleven single nucleotide polymorphisms in transient receptor potential channel genes of the neuropathic pain patients and a cohort of 253 German healthy volunteers. Associations of quantitative sensory testing parameters and single nucleotide polymorphisms between and within groups and subgroups, based on sensory phenotypes, were analyzed. Single nucleotide polymorphisms frequencies did not differ between both the cohorts. However, in neuropathic pain patients transient receptor potential ankyrin 1 710G>A (rs920829, E179K) was associated with the presence of paradoxical heat sensation (p = 0.03), and transient receptor potential vanilloid 1 1911A>G (rs8065080, I585V) with cold hypoalgesia (p = 0.0035). Two main subgroups characterized by preserved (1) and impaired (2) sensory function were identified. In subgroup 1 transient receptor potential vanilloid 1 1911A>G led to significantly less heat hyperalgesia, pinprick hyperalgesia and mechanical hypaesthesia (p = 0.006, p = 0.005 and p<0.001) and transient receptor potential vanilloid 1 1103C>G (rs222747, M315I) to cold hypaesthesia (p = 0.002), but there was absence of associations in subgroup 2. In this study we found no evidence that genetic variants of transient receptor potential channels are involved in the expression of neuropathic pain, but transient receptor potential channel polymorphisms contributed significantly to the somatosensory abnormalities of neuropathic pain patients.

Unravelling the Mystery of Capsaicin: A Tool to Understand and Treat Pain

“…I315M was associated with cold hypoesthesia (Binder et al, 2011). Although they found no evidence that TRP genetic variants are associated specifically with the prevalence of neuropathic pain, the polymorphisms contributed significantly to the somatosensory abnormalities that are experienced by patients with neuropathic pain (Binder et al, 2011).…”

“…Although they found no evidence that TRP genetic variants are associated specifically with the prevalence of neuropathic pain, the polymorphisms contributed significantly to the somatosensory abnormalities that are experienced by patients with neuropathic pain (Binder et al, 2011). Further investigation into TRPV1 SNPs and neuropathic pain conditions may be useful, but these very recent studies show that variations in TRPV1 can explain some of the CAPSAICIN: TO UNDERSTAND AND TREAT PAIN variability in pain seen in patients with pathophysiological conditions.…”

Genetic variants affecting human TRPA1 or TRPM8 structure can be classified in vitro as ‘well expressed’, ‘poorly expressed’ or ‘salvageable’

“…Data for estimates of IC 50 from treatments performed in triplicate on three separate occasions and include + − S.D. The AMTB IC 50 value for non-mutated information regarding gene sequence variation, suggest that further screening of the properties of variants may aid implementation of targeted clinical studies [3][4][5][6][7][8][9].…”

Differential Expression and Functionality of TRPA1 Protein Genetic Variants in Conditions of Thermal Stimulation

“…Our work highlights some functional consequences of naturally occurring genetic TRPA1 variants. Some evidence for modulation of human pain behavior by genetic variants in the TRPA1 gene has been published previously (5,11,12,22). Recently, we observed that the change of a glutamate residue to lysine at TRP peptide position 179 (E179K) diminished occurrence of PHS in patients suffering from neuropathic pain (12).…”

“…They described a N855S gain-of-function mutation in the S4 transmembrane segment of TRPA1, which resulted in increased activation of the ion channel by noxious cold temperature underlining the contribution of genetics in pain plasticity (11). Recently, we identified the nonsynonymous genetic variant E179K (rs920829) of the human TRPA1 gene to be associated with the occurrence of paradoxical heat sensation (PHS) 2 in neuropathic pain patients (12). PHS is defined as a burning heat sensation when a noxious cold stimulus is applied.…”