Hypoxia-induced sensitisation of TRPA1 in painful dysesthesia evoked by transient hindlimb ischemia/reperfusion in mice

• DOI: 10.1038/srep23261
• Publication Date: 2016-03-17T10:03:13Z
• Authors: Kanako So; Yuna Tei; Meng Zhao; Takahito Miyake; Haruka Hiyama; Hisashi Shirakawa; Satoshi Imai; Yasuo Mori; Takayuki Nakagawa; Kazuo Matsubara; Shuji Kaneko
• Keywords: Hindlimb; Licking; Dorsal root ganglion; Hypoxia; Capsazepine

Abstract Dysesthesia is an unpleasant abnormal sensation, which often accompanied by peripheral neuropathy or vascular impairment. Here, we examined the roles of transient receptor potential ankyrin 1 (TRPA1) in dysesthesia-like behaviours elicited hindlimb ischemia (15–60 min) tightly compressing and reperfusion releasing ligature. The paw-withdrawal responses to tactile stimulation were reduced during lasted for a while after reperfusion. Hindlimb ischemia/reperfusion spontaneous licking ischemic hindpaw that peaked within 10 min. was inhibited reactive oxygen species (ROS) scavengers, TRPA1 antagonist, deficiency, but not TRPV1 deficiency. In human TRPA1-expressing cells as well cultured mouse dorsal root ganglion neurons, H 2 O -evoked response significantly increased pretreatment with hypoxia (80 mmHg) 30 This hypoxia-induced sensitisation overexpressing catalytically-inactive mutant prolyl hydroxylase (PHD) proline resistant PHDs. Consistent these results, PHD inhibitor nocifensive through activation. Our results suggest ischemia/reperfusion-evoked licking, i.e. painful dysesthesia, caused ROS-evoked activation sensitised inhibiting PHD-mediated hydroxylation residue TRPA1.