Role of colchicine-induced microtubule depolymerization in hyperalgesia via TRPV4 in rats with chronic compression of the dorsal root ganglion

Abstract

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 Ca²⁺-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.

Keywords:

• Microtubule depolymerization
• Colchicine
• Transient receptor potential vanilloid 4
• Hyperalgesia
• CCD

This work is supported by the National Natural Science Foundation of China (grant No. 30872732). The technical assistance of the Cardiovascular Research Center of Qilu Hospital is gratefully acknowledged.