The antinociceptive effect of Delta9-tetrahydrocannabinol in the arthritic rat.
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.
Cox
Melinda L
ML
Virginia Commonwealth University, Department of Pharmacology and Toxicology, Medical College of Virginia, P.O. Box 980613, MCV Station, Richmond, VA 23298-0613, USA.
Welch
Sandra P
SP
D000818:Animals; D001169:Arthritis, Experimental / Q000139:chemically induced / Q000503:physiopathology / Q000517:prevention & control*; D063387:Cannabinoid Receptor Antagonists; D004305:Dose-Response Relationship, Drug; D013759:Dronabinol / Q000134:cerebrospinal fluid / Q000494:pharmacology* / Q000627:therapeutic use; D004399:Dynorphins / Q000134:cerebrospinal fluid; D004743:Enkephalin, Leucine / Q000134:cerebrospinal fluid; D004744:Enkephalin, Methionine / Q000134:cerebrospinal fluid; D005620:Freund's Adjuvant / Q000008:administration & dosage; D007271:Injections, Intradermal; D007274:Injections, Intraperitoneal; D008297:Male; D009020:Morphine / Q000037:antagonists & inhibitors / Q000494:pharmacology; D009161:Mycobacterium / Q000276:immunology; D009270:Naloxone / Q000494:pharmacology; D009271:Naltrexone / Q000031:analogs & derivatives* / Q000494:pharmacology; D009292:Narcotic Antagonists; D010146:Pain / Q000188:drug therapy / Q000503:physiopathology*; D010147:Pain Measurement / Q000187:drug effects; D010880:Piperidines / Q000494:pharmacology; D011720:Pyrazoles / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D043884:Receptor, Cannabinoid, CB1 / Q000037:antagonists & inhibitors / Q000627:therapeutic use; D011957:Receptors, Opioid / Q000145:classification / Q000627:therapeutic use; D000077285:Rimonabant
D063387:Cannabinoid Receptor Antagonists; D009292:Narcotic Antagonists; D010880:Piperidines; D011720:Pyrazoles; D043884:Receptor, Cannabinoid, CB1; D011957:Receptors, Opioid; D009270:Naloxone; C051844:norbinaltorphimine; D004744:Enkephalin, Methionine; D004743:Enkephalin, Leucine; D009271:Naltrexone; D004399:Dynorphins; D009020:Morphine; D013759:Dronabinol; D005620:Freund's Adjuvant; C055382:naltrindole; D000077285:Rimonabant