The Journal of neuroscience : the official journal of the Society for Neuroscience
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The selective mu-opioid agonist, D-Ala2,N-Me-Phe4,Gly5-ol-enkephalin (DAMGO), or the selective A1-adenosine agonist N6-cyclopentyladenosine (CPA), when coinjected intradermally with prostaglandin E2 (PGE2), dose-dependently inhibited PGE2-induced mechanical hyperalgesia in the rat hindpaw, as determined by the Randall-Selitto paw-withdrawal test. Repeated (hourly x 3) intradermal injections of DAMGO or CPA produced tolerance to the antinociceptive effect of a fourth injection 1 hr later. Furthermore, repeated (hourly x 3) intradermal injections of DAMGO produced cross-tolerance to the antinociceptive effect of CPA, and repeated (hourly x 3) intradermal injection of CPA produced cross-tolerance to the antinociceptive effect of DAMGO. ⋯ Furthermore, naloxone elicited a cross-withdrawal hyperalgesia response in CPA-tolerant paws. Similarly, the A1-adenosine antagonist 1,3-dipropyl-8-(2-amino-4- chlorophenyl)-xanthine (PACPX), which had no effect on paw-withdrawal threshold in normal paws, elicited a withdrawal hyperalgesia response in CPA-tolerant paws and cross-withdrawal hyperalgesia responses in DAMGO-tolerant paws. These cross-dependence and cross-withdrawal responses suggest that the development of dependence to mu-opioid and A1-adenosine agonists involves changes in the same second messenger system downstream to both mu-opioid and A1-adenosine receptor activation.
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Recently, antisera that recognize unique epitopes of the cloned mu-, delta-, and kappa-opioid, receptors (MOR, DOR, KOR, respectively) have been developed. In the present study MOR-, DOR-, and KOR-like immunoreactivities (LIs) were examined in rat dorsal root ganglia (DRGs, L4-5) after injection of carrageenan (CAR) into the hindpaw. In normal control rats 20.9%, 13.5%, and 9% of the DRG neurons contained MOR-, DOR-, KOR-LI, respectively. ⋯ However, DOR-LI accumulation was stronger than that of MOR- and KOR-LIs. Taken together, these results suggest that all three opioid receptors are involved in the response to inflammation and that they may play different roles in this pathological state. The coexistence of MOR, DOR, and KOR in at least some primary sensory neurons provides a substrate for functional interactions between these receptors.