K- and δ-opioids block sympathetically dependent hyperalgesia

Abstract

Direct hyperalgesia induced by prostaglandin E2 (PGE2) can be blocked by μ but not δ or x-opioids. However, there is evidence that k- and δ-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 δ and 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-N-methyl-N[2-(-pyrolidinyl)cyclohexyl] benzeneacetamide (U50,488H) and by the δ-opioid agonist D-Pen 2,5)-enkephalin (DPDPE), as well as the μ-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 k- and δ-opioid agonists result from actions upon SPGN terminals and that these effects are mediated by inhibitory G-proteins.