The antinociceptive effect of Delta9-tetrahydrocannabinol in the arthritic rat

Our study addressed the hypothesis that spinal release of endogenous opioids underlies Delta(9)-tetrahydrocannabinol (Delta(9)-THC)-induced antinociception in Freund's adjuvant-induced arthritic and nonarthritic rats. The paw-pressure test was used to assess the antinociceptive effects of Delta(9)-THC versus those of morphine, and opioid and cannabinoid receptor-selective antagonists were used to characterize the involved receptors. Cerebrospinal fluid was collected after Delta(9)-THC injection (i.p.) for the measurement of endogenous opioid peptides. Our results indicate that morphine or Delta(9)-THC is equally potent and efficacious in both nonarthritic and arthritic rats. Delta(9)-THC-induced antinociception is attenuated by the K opioid receptor antagonist, nor-binaltorphimine, in arthritic rats only. Delta(9)-THC induces increased immunoreactive dynorphin A (idyn A) levels in nonarthritic rats while decreasing idyn A in arthritic rats. We hypothesize that the elevated idyn A level in arthritic rats contributes to hyperalgesia by interaction with N-methyl-D-aspartate receptors, and that Delta(9)-THC induces antinociception by decreasing idyn A release. (C) 2004 Elsevier B.V. All rights reserved.