The antinociceptive effect of Delta9-tetrahydrocannabinol in the arthritic rat

Eur J Pharmacol. 2004 Jun 16;493(1-3):65-74. doi: 10.1016/j.ejphar.2004.04.022.

Abstract

Our study addressed the hypothesis that spinal release of endogenous opioids underlies Delta9-tetrahydrocannabinol (Delta9-THC)-induced antinociception in Freund's adjuvant-induced arthritic and nonarthritic rats. The paw-pressure test was used to assess the antinociceptive effects of Delta9-THC versus those of morphine, and opioid and cannabinoid receptor-selective antagonists were used to characterize the involved receptors. Cerebrospinal fluid was collected after Delta9-THC injection (i.p.) for the measurement of endogenous opioid peptides. Our results indicate that morphine or Delta9-THC is equally potent and efficacious in both nonarthritic and arthritic rats. Delta9-THC-induced antinociception is attenuated by the kappa opioid receptor antagonist, nor-binaltorphimine, in arthritic rats only. Delta9-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 Delta9-THC induces antinociception by decreasing idyn A release.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Arthritis, Experimental / chemically induced
  • Arthritis, Experimental / physiopathology
  • Arthritis, Experimental / prevention & control*
  • Cannabinoid Receptor Antagonists
  • Dose-Response Relationship, Drug
  • Dronabinol / cerebrospinal fluid
  • Dronabinol / pharmacology*
  • Dronabinol / therapeutic use
  • Dynorphins / cerebrospinal fluid
  • Enkephalin, Leucine / cerebrospinal fluid
  • Enkephalin, Methionine / cerebrospinal fluid
  • Freund's Adjuvant / administration & dosage
  • Injections, Intradermal
  • Injections, Intraperitoneal
  • Male
  • Morphine / antagonists & inhibitors
  • Morphine / pharmacology
  • Mycobacterium / immunology
  • Naloxone / pharmacology
  • Naltrexone / analogs & derivatives*
  • Naltrexone / pharmacology
  • Narcotic Antagonists
  • Pain / drug therapy
  • Pain / physiopathology*
  • Pain Measurement / drug effects
  • Piperidines / pharmacology
  • Pyrazoles / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Receptor, Cannabinoid, CB1 / antagonists & inhibitors
  • Receptor, Cannabinoid, CB1 / therapeutic use
  • Receptors, Opioid / classification
  • Receptors, Opioid / therapeutic use
  • Rimonabant

Substances

  • Cannabinoid Receptor Antagonists
  • Narcotic Antagonists
  • Piperidines
  • Pyrazoles
  • Receptor, Cannabinoid, CB1
  • Receptors, Opioid
  • Naloxone
  • norbinaltorphimine
  • Enkephalin, Methionine
  • Enkephalin, Leucine
  • Naltrexone
  • Dynorphins
  • Morphine
  • Dronabinol
  • Freund's Adjuvant
  • naltrindole
  • Rimonabant