Block Sympathetically Dependent Hyperalgesia

Direct hyperalgesia induced by prostaglandin E, (PGE,) can be blocked by Nbut not 6or K-opioids. However, there is evidence that Kand &opioid receptors are located on sympathetic postganglionic neuron (SPGN) terminals, which mediate bradykinin (BK) hyperalgesia via SPGN-terminal-dependent production of PGE,. Therefore, we evaluated the antinociceptive effect of 6and K-opioids on BK hyperalgesia. We demonstrate that the mechanical hyperalgesia induced by intradermal injection of BK can be blocked by the K-opioid agonist trans-3,4-dichloro-Kmethyl-N[S-(-pyrolidinyl)cyclohexyl] benzeneacetamide (U50,488H) and by the &opioid agonist (o-Pen*+enkephalin (DPDPE), as well as the p-opioid agonist Tyr-o-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 Kand &opioid agonists result from actions upon SPGN terminals and that these effects are mediated by inhibitory G-proteins.