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Upregulation of spinal cannabinoid-1-receptors following nerve injury enhances the effects of Win 55,212-2 on neuropathic pain behaviors in rats.

Publication ,  Journal Article
Lim, G; Sung, B; Ji, R-R; Mao, J
Published in: Pain
September 2003

Exogenous cannabinoids are effective in attenuating neuropathic pain behaviors induced by peripheral nerve injury, but the mechanisms of their effectiveness remain unclear. Here we examined the expression of spinal cannabinoid-1-receptors (CB1Rs) following chronic constriction sciatic nerve injury (CCI) and its relation to the effects of a CBR agonist (Win 55,212-2) on neuropathic pain in rats. CCI induced a time-dependent upregulation of spinal CB1Rs primarily within the ipsilateral superficial spinal cord dorsal horn as revealed by both Western blot and immunohistochemistry. This CCI-induced CB1R upregulation was at least in part mediated through tyrosine kinase receptors (Trk), because intrathecal treatment with the Trk inhibitor K252a (1 microg) for postoperative days 1-6 significantly reduced the CB1R upregulation in CCI rats. At the intracellular level, the mitogen-activated protein kinase (ERK-MAPK) inhibitor PD98059 (1 microg) prevented, while the protein kinase C inhibitor chelerythrine (10 microg) partially reduced, the CCI-induced CB1R upregulation when each agent was administered intrathecally for postoperative days 1-6. Importantly, the CCI-induced upregulation of spinal CB1Rs enhanced the effects of Win 55,212-2 on both thermal hyperalgesia and mechanical allodynia, since inhibition of the CB1R upregulation by PD98059 resulted in a significant reduction of the effects of Win 55,212-2 in CCI rats. These results indicate that upregulation of spinal CB1Rs following peripheral nerve injury may contribute to the therapeutic effects of exogenous cannabinoids on neuropathic pain.

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Published In

Pain

DOI

ISSN

0304-3959

Publication Date

September 2003

Volume

105

Issue

1-2

Start / End Page

275 / 283

Location

United States

Related Subject Headings

  • Wounds and Injuries
  • Up-Regulation
  • Time Factors
  • Spinal Cord
  • Sciatic Nerve
  • Receptors, Drug
  • Receptors, Cannabinoid
  • Receptor Protein-Tyrosine Kinases
  • Rats, Sprague-Dawley
  • Rats
 

Citation

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Lim, G., Sung, B., Ji, R.-R., & Mao, J. (2003). Upregulation of spinal cannabinoid-1-receptors following nerve injury enhances the effects of Win 55,212-2 on neuropathic pain behaviors in rats. Pain, 105(1–2), 275–283. https://doi.org/10.1016/s0304-3959(03)00242-2
Lim, Grewo, Backil Sung, Ru-Rong Ji, and Jianren Mao. “Upregulation of spinal cannabinoid-1-receptors following nerve injury enhances the effects of Win 55,212-2 on neuropathic pain behaviors in rats.Pain 105, no. 1–2 (September 2003): 275–83. https://doi.org/10.1016/s0304-3959(03)00242-2.
Lim, Grewo, et al. “Upregulation of spinal cannabinoid-1-receptors following nerve injury enhances the effects of Win 55,212-2 on neuropathic pain behaviors in rats.Pain, vol. 105, no. 1–2, Sept. 2003, pp. 275–83. Pubmed, doi:10.1016/s0304-3959(03)00242-2.
Journal cover image

Published In

Pain

DOI

ISSN

0304-3959

Publication Date

September 2003

Volume

105

Issue

1-2

Start / End Page

275 / 283

Location

United States

Related Subject Headings

  • Wounds and Injuries
  • Up-Regulation
  • Time Factors
  • Spinal Cord
  • Sciatic Nerve
  • Receptors, Drug
  • Receptors, Cannabinoid
  • Receptor Protein-Tyrosine Kinases
  • Rats, Sprague-Dawley
  • Rats