Cannabinoid modulation of dynorphin A: correlation to cannabinoid-induced antinociception

Eur J Pharmacol. 1999 Aug 13;378(3):237-48. doi: 10.1016/s0014-2999(99)00479-3.

Abstract

Intrathecal administration of anandamide, delta9-tetrahydrocannabinol (THC) and (-)-3-[2-hydroxy-4-(1,1-dimethyheptyl)ptyl)phenyl]-4-(3-hydr oxypropyl)-cicloexan-1-ol (CP55,940) induced spinal antinociception accompanied by differential kappa-opioid receptor involvement and dynorphin A peptide release. Antinociception using the tail-flick test was induced by the classical cannabinoid THC and was blocked totally by 17,17'-bis(cyclopropylmethyl)-6',6,7,7'-tetrahydro-4,5,4'5'-diepoxy++ +-6,6'-(imino)[7,7'-bimorphinan]-3,3',14,14'-tetrol (norbinaltorphimine) indicating a significant and critical kappa-opioid receptor component. The endogenous cannabinoid, anandamide and the non-classical bicyclic cannabinoid, CP55,940, induced non-nor-BNI-sensitive effects. The N-piperidino-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-3-pyrazo le-carboxamide (SR141716A)-mediated attenuation of spinal antinociception imparted by the various cannabinoids indicates cannabinoid CB1 receptor involvement. THC-induced an enhancement of immunoreactive dynorphin A release which coincided with the onset, but not duration antinociception. The release of dynorphin A was also attenuated by SR141716A suggesting it is cannabinoid CB1 receptor-mediated. These data indicate a critical role for dynorphin A release in the initiation of the antinociceptive effects of the cannabinoids at the spinal level.

Publication types

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

MeSH terms

  • Analgesics / pharmacology
  • Animals
  • Cannabinoids / antagonists & inhibitors
  • Cannabinoids / pharmacology*
  • Cyclohexanols / pharmacology
  • Dimethyl Sulfoxide / pharmacology
  • Dronabinol / pharmacology
  • Dynorphins / cerebrospinal fluid
  • Dynorphins / drug effects*
  • Injections, Spinal
  • Male
  • Naltrexone / analogs & derivatives
  • Naltrexone / pharmacology
  • Narcotic Antagonists / pharmacology
  • Nociceptors / drug effects
  • Pain / prevention & control
  • Pain Measurement
  • Piperidines / pharmacology
  • Pyrazoles / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Rimonabant

Substances

  • Analgesics
  • Cannabinoids
  • Cyclohexanols
  • Narcotic Antagonists
  • Piperidines
  • Pyrazoles
  • norbinaltorphimine
  • Naltrexone
  • Dynorphins
  • Dronabinol
  • 3-(2-hydroxy-4-(1,1-dimethylheptyl)phenyl)-4-(3-hydroxypropyl)cyclohexanol
  • Rimonabant
  • Dimethyl Sulfoxide