Spinal analgesic action of endomorphins in acute, inflammatory and neuropathic pain in rats

We studied spinal analgesic and antiallodynic effects of endomorphin-1 and endomorphin-2 administered i.t. in comparison with Tyr-D-Ala-Gly-MePhe-Gly- ol (DAMGO) or morphine, during acute, inflammatory and neuropathic pain in rats chronically implanted with intrathecal cannulas. Endomorphin-1 and end omorphin-2 (2.5, 5, 10 mu g i.t.) increased the tail-flick latency and, to the lesser extent, the paw pressure latency. The range of potencies in both those models of acute pain was as follows: DAMGO > morphine= endomorphin-1 > endomorphin-2. In a model of inflammatory pain, the number of formalin-i nduced flinching episodes was decreased by endomorphin-1. The effect of end omorphin-2 was much less pronounced. Both DAMGO and morphine significantly inhibited the pain-related behavior evoked by formalin. In a neuropathic pa in model (sciatic nerve crushing in rats), endomorphin-1 and -2 (5 mu g i.t .) had a statistically significant effect on the tail-flick latency and on the cold-water tail flick latency. Morphine, 5 mu g, was found to be ineffe ctive. Endomorphin-1 and -2 (2.5 and 5 mu g i.t.) dose-dependently antagoni zed allodynia. Those effects of endomorphins were antagonized in acute (30 mu g), inflammatory (30 mu g) and neuropathic pain models (60 mu g) by cypr odime, a selective mu-opioid receptor antagonist. In conclusion, our result s show a strong analgesic action of endomorphins at the spinal cord level. The most interesting finding is a strong, stronger than in the case of morp hine, antiallodynic effect of endomorphins in rats subjected to sciatic ner ve crushing, which suggests a possible use of these compounds in a very dif ficult therapy of neuropathic pain. (C) 1999 Elsevier Science B.V. All righ ts reserved.