[Roles of TRPA1 in Painful Dysesthesia].

This study assessed the roles of transient receptor potential ankyrin 1 (TRPA1) in dysesthesia by utilizing three animal models of dysesthesia characterized by reductions in blood flow to the skin: a transient hindlimb ischemia/reperfusion model, characterized by spontaneous licking and tactile hypoesthesia of the ischemic hindpaw; a streptozotocin-induced diabetic neuropathy model in mice, characterized by cold hypersensitivity, which is likely parallel to the reduced skin blood flow of the hindpaw; and a hindlimb ischemia model. TRPA1 inhibition or deficiency blocked spontaneous licking in the transient hindlimb ischemia/reperfusion model and cold hypersensitivity in the diabetic mouse model mice. Consistent with these results, the nocifensive behaviors induced by intraplantar injection of a TRPA1 agonist were enhanced in the diabetic neuropathy and hindlimb ischemia models. Hypoxia enhanced H2O2-induced TRPA1 responses in human TRPA1-expressing cells and cultured mouse dorsal root ganglion neurons, with this hypoxia-induced TRPA1 sensitization to H2O2 being associated with hypoxia-induced inhibition of the hydroxylation of prolyl hydroxylases. These results suggest that dysesthesia following blood flow reduction is caused by the activation of TRPA1 sensitized by hypoxia and that hypoxia-induced TRPA1 sensitization plays a pivotal role in painful dysesthesia induced by peripheral blood flow reduction. PMID: 31902877 [PubMed - in process]
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - Category: Drugs & Pharmacology Authors: Tags: Yakugaku Zasshi Source Type: research