Role of colchicine-induced microtubule depolymerization in hyperalgesia via TRPV4 in rats with chronic compression of the dorsal root ganglion.
The aim of this study is to investigate the effect of microtubule depolymerization by colchicine on hyperalgesia mediated by transient receptor potential vanilloid 4 (TRPV4) in a neuropathic pain model of chronic compression of the dorsal root ganglion (DRG) (hereafter termed CCD) in rat. Intrathecal administration of microtubule-depolymerizing agent, colchicine, attenuated the activated effect of 4alpha-phorbol 12, 13-didecanoate (4alpha-PDD, TRPV4 specific agonist) on mechanical and thermal hyperalgesia in CCD rats. This observation is in agreement with our in vitro experiments with DRG cells that showed a significant attenuation of 4alpha-PDD-activated Ca(2+)-influx and substance P (SP) release with the colchicine treatment. We conclude that microtubule depolymerization by colchicine can regulate pain sensitivity by depressing the hyperalgesia mediated by TRPV4.
Liping
L
Ning
Chuanwei
C
Wang
Xiaohua
X
Fan
Xinli
X
Ding
Yonghui
Y
Wang
Yang
Y
Zhang
Jie
J
Wang
Shouwei
S
Yue
D000818:Animals; D002118:Calcium / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D003078:Colchicine / Q000494:pharmacology*; D005727:Ganglia, Spinal / Q000187:drug effects / Q000378:metabolism; D006358:Hot Temperature; D006930:Hyperalgesia / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism; D008297:Male; D008870:Microtubules / Q000187:drug effects* / Q000378:metabolism; D009408:Nerve Compression Syndromes / Q000150:complications / Q000188:drug therapy / Q000378:metabolism; D009437:Neuralgia / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism; D011843:Radiculopathy / Q000150:complications / Q000188:drug therapy / Q000378:metabolism; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D013373:Substance P / Q000378:metabolism; D050916:TRPV Cation Channels / Q000819:agonists / Q000378:metabolism*; D014110:Touch; D050257:Tubulin Modulators / Q000494:pharmacology*
D050916:TRPV Cation Channels; C486577:Trpv4 protein, rat; D050257:Tubulin Modulators; D013373:Substance P; D003078:Colchicine; D002118:Calcium
CCD; Colchicine,; Hyperalgesia,; Microtubule depolymerization,; Transient receptor potential vanilloid 4,