Kappa- and delta-opioids block sympathetically dependent hyperalgesia.
Direct hyperalgesia induced by prostaglandin E2 (PGE2) can be blocked by mu- but not delta- or kappa-opioids. However, there is evidence that kappa- and delta-opioid receptors are located on sympathetic postganglionic neuron (SPGN) terminals, which mediate bradykinin (BK) hyperalgesia via SPGN-terminal-dependent production of PGE2. Therefore, we evaluated the antinociceptive effect of delta- and kappa-opioids on BK hyperalgesia. We demonstrate that the mechanical hyperalgesia induced by intradermal injection of BK can be blocked by the kappa-opioid agonist trans-3,4-dichloro-N-methyl-N[2-(-pyrrolidinyl)cyclo-hexyl] benzeneacetamide (U50,488H) and by the delta-opioid agonist (D-Pen2,5)-enkephalin (DPDPE), as well as the mu-opioid agonist Tyr-D-Ala-Gly-NMe-Phe-Gly-ol(DAMGO). Pertussis toxin prevented the inhibition of BK-induced hyperalgesia by U50,488H, DPDPE, or DAMGO. We conclude that the observed peripheral analgesic effects of kappa- and delta-opioid agonists result from actions upon SPGN terminals and that these effects are mediated by inhibitory G-proteins.
Taiwo
Y O
YO
Department of Anatomy, University of California, San Francisco 94143-0724.
Levine
J D
JD
D000818:Animals; D001920:Bradykinin / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004723:Endorphins / Q000494:pharmacology* / Q000502:physiology; D006930:Hyperalgesia / Q000139:chemically induced / Q000503:physiopathology*; D008297:Male; D009270:Naloxone / Q000494:pharmacology; D009619:Nociceptors / Q000187:drug effects; D037342:Pertussis Toxin; D051381:Rats; D011919:Rats, Inbred Strains; D012684:Sensory Thresholds / Q000187:drug effects; D013564:Sympathetic Nervous System / Q000503:physiopathology*; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D004723:Endorphins; D010566:Virulence Factors, Bordetella; D009270:Naloxone; D037342:Pertussis Toxin; D001920:Bradykinin