Effects of colchicine-induced microtubule depolymerization on TRPV4 in rats with chronic compression of the dorsal root ganglion

Neurosci Lett. 2013 Feb 8;534:344-50. doi: 10.1016/j.neulet.2012.12.003. Epub 2012 Dec 20.

Abstract

The aim of this study was to investigate the effect of colchicine-induced microtubule depolymerization on allodynia in rats with chronic compression of the dorsal root ganglion (DRG) (CCD) and the effect of colchicine on transient receptor potential vanilloid 4 (TRPV4). Intrathecal administration of the anti-microtubule agent, colchicine, resulted in a dose-dependent and partial reduction in CCD-induced mechanical and thermal allodynia. The reduction of allodynia was associated with significant and dose-dependent decreases in the levels of both TRPV4 mRNA and protein expression in CCD rats. In addition, colchicine resulted in reduction and advance of TRPV4 currents in both DRG neurons and HEK293-TRPV4 cells. The current-voltage (IV) relation in HEK293-TRPV4 cells that were exposed to colchicine displayed a typical outward rectification characteristic of TRPV4 with the reversal potential shifted toward a more positive voltage. In conclusion, intrathecal administration of colchicine attenuated allodynia and TRPV4 contributed to the colchicine-induced attenuation of allodynia in CCD rats.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line
  • Cell Survival
  • Chronic Disease
  • Colchicine / pharmacology*
  • Ganglia, Spinal / metabolism*
  • Ganglia, Spinal / pathology
  • Humans
  • Hyperalgesia / etiology
  • Hyperalgesia / physiopathology
  • Microtubules / drug effects*
  • Microtubules / ultrastructure
  • Neuralgia / etiology
  • Neuralgia / metabolism*
  • Neuralgia / physiopathology
  • Patch-Clamp Techniques
  • Posterior Horn Cells / drug effects
  • Posterior Horn Cells / physiology
  • Radiculopathy / complications
  • Rats
  • TRPV Cation Channels / metabolism*
  • Tubulin Modulators / pharmacology*

Substances

  • TRPV Cation Channels
  • Trpv4 protein, rat
  • Tubulin Modulators
  • Colchicine