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Different effects of opioid and cannabinoid receptor agonists on C-fiber-induced extracellular signal-regulated kinase activation in dorsal horn neurons in normal and spinal nerve-ligated rats.

Publication ,  Journal Article
Kawasaki, Y; Kohno, T; Ji, R-R
Published in: J Pharmacol Exp Ther
February 2006

Nerve injury results in neuropathic pain, a debilitating pain condition. Whereas cannabinoids are consistently shown to attenuate neuropathic pain, the efficacy of opioids is highly controversial. Molecular mechanisms underlying analgesic effects of opioids and cannabinoids are not fully understood. We have shown that the signaling molecule ERK (extracellular signal-regulated kinase) is activated by C-fiber stimulation in dorsal horn neurons and contributes to pain sensitization. In this study, we examined whether opioids and cannabinoids can affect C-fiber-induced ERK phosphorylation (pERK) in dorsal horn neurons in spinal cord slices from normal and spinal nerve-ligated rats. In normal control spinal slices, capsaicin induced a drastic pERK expression in superficial dorsal horn neurons, which was suppressed by morphine (10 microM), the selective mu-opioid receptor agonist DAMGO [[d-Ala2, N-Me-Phe4, Gly5-ol]-enkephalin (1 microM)], and the selective CB1 receptor ACEA agonist [arachidonyl-2'-chloroethylamide (5 microM)]. One week after spinal nerve ligation when neuropathic pain is fully developed, capsaicin induced less pERK expression in the injured L(5)-spinal segment. This pERK induction was not suppressed by morphine (10 microM) and DAMGO (1 microM) but was enhanced by high concentration of DAMGO (5 microM). In contrast, ACEA (10 microM) was still very effective in inhibiting capsaicin-induced pERK expression. In the adjacent L(4) spinal segment, both DAMGO and ACEA significantly suppressed pERK induction by capsaicin. These results indicate that, after nerve injury, opioids lose their capability to suppress C-fiber-induced spinal neuron activation in the injured L(5) but not in the intact L(4) spinal segment, whereas cannabinoids still maintain their efficacy.

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Published In

J Pharmacol Exp Ther

DOI

ISSN

0022-3565

Publication Date

February 2006

Volume

316

Issue

2

Start / End Page

601 / 607

Location

United States

Related Subject Headings

  • Spinal Nerves
  • Receptors, Opioid
  • Rats, Sprague-Dawley
  • Rats
  • Posterior Horn Cells
  • Phosphorylation
  • Pharmacology & Pharmacy
  • Morphine
  • Mononeuropathies
  • Male
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Kawasaki, Yasuhiko, Tatsuro Kohno, and Ru-Rong Ji. “Different effects of opioid and cannabinoid receptor agonists on C-fiber-induced extracellular signal-regulated kinase activation in dorsal horn neurons in normal and spinal nerve-ligated rats.J Pharmacol Exp Ther 316, no. 2 (February 2006): 601–7. https://doi.org/10.1124/jpet.105.093583.
Kawasaki, Yasuhiko, et al. “Different effects of opioid and cannabinoid receptor agonists on C-fiber-induced extracellular signal-regulated kinase activation in dorsal horn neurons in normal and spinal nerve-ligated rats.J Pharmacol Exp Ther, vol. 316, no. 2, Feb. 2006, pp. 601–07. Pubmed, doi:10.1124/jpet.105.093583.

Published In

J Pharmacol Exp Ther

DOI

ISSN

0022-3565

Publication Date

February 2006

Volume

316

Issue

2

Start / End Page

601 / 607

Location

United States

Related Subject Headings

  • Spinal Nerves
  • Receptors, Opioid
  • Rats, Sprague-Dawley
  • Rats
  • Posterior Horn Cells
  • Phosphorylation
  • Pharmacology & Pharmacy
  • Morphine
  • Mononeuropathies
  • Male