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Functional blockage of the cannabinoid receptor type 1 evokes a kappa‐opiate‐dependent analgesia
Author(s) -
SáezCassanelli José L.,
Fontanella German H.,
DelgadoGarcía José M.,
Carrión Ángel M.
Publication year - 2007
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2007.05000.x
Subject(s) - dynorphin , nociception , endocannabinoid system , cannabinoid , opioid , cannabinoid receptor , pharmacology , medicine , hypoalgesia , naltrexone , spinal cord , opioid receptor , κ opioid receptor , nociceptor , antagonist , endogenous opioid , noxious stimulus , morphine , anesthesia , receptor , hyperalgesia , opioid peptide , psychiatry
Progress in the control and treatment of pain may be facilitated by a better understanding of mechanisms underlying nociceptive processing. Cannabinoids and opioids are endogenous modulator of pain sensation, but therapies based in these compounds are not completely exploited because of their side effects. To test the role of cannabinoid receptor type 1 (CB1‐R) inhibition in nociception, we performed a subchronic administration of the CB1‐R antagonist N ‐(piperidin‐1‐yl)‐5‐(4‐iodophenyl)‐1‐(2,4‐dichlorophenyl)‐4‐methyl‐1H‐pyrazole‐3‐carboxamide (AM281) in mice. This treatment provoked analgesia in peripheral thermal and visceral models of pain. Analysis of genes encoded for the opioid system in the spinal cord showed an increase in the expression of genes encoded for the κ‐opioid system in AM281‐injected mice compared with vehicle‐injected ones. Furthermore, systemic administration of nor‐binaltorphimine, a κ‐opioid receptor antagonist, blocked AM281‐induced analgesia. Finally, c‐fos expression in the dorsal spinal cord and higher centers of pain processing after noxious stimulation were significantly lower in AM281‐injected mice than in vehicle‐injected animals, indicating that dynorphin could block nociceptive information transmission at the spinal cord level. These results indicate the existence of a cross‐talk between opioid and cannabinoid systems in nociception. Furthermore, the results suggest that CB1‐R antagonists could be useful as a new therapeutic approach for pain relief.