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

Abstract

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 endomorphin-2 (2.5, 5, 10 microg 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-induced flinching episodes was decreased by endomorphin-1. The effect of endomorphin-2 was much less pronounced. Both DAMGO and morphine significantly inhibited the pain-related behavior evoked by formalin. In a neuropathic pain model (sciatic nerve crushing in rats), endomorphin-1 and -2 (5 microg i.t.) had a statistically significant effect on the tail-flick latency and on the cold-water tail flick latency. Morphine, 5 microg, was found to be ineffective. Endomorphin-1 and -2 (2.5 and 5 microg i.t.) dose-dependently antagonized allodynia. Those effects of endomorphins were antagonized in acute (30 microg), inflammatory (30 microg) and neuropathic pain models (60 microg) by cyprodime, a selective mu-opioid receptor antagonist. In conclusion, our results 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 morphine, antiallodynic effect of endomorphins in rats subjected to sciatic nerve crushing, which suggests a possible use of these compounds in a very difficult therapy of neuropathic pain.

• Authors: B Przewłocka, J Mika, D Labuz, G Toth, R Przewłocki
• Journal: European journal of pharmacology (Eur J Pharmacol) Vol. 367 Issue 2-3 Pg. 189-96 (Feb 19 1999) ISSN: 0014-2999 [Print] Netherlands
• PMID: 10078992 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Analgesics, Opioid
• Enkephalins
• Enkephalin, Ala(2)-MePhe(4)-Gly(5)-
• Morphine

Topics

• Acute Disease
• Analgesics, Opioid (pharmacology)
• Animals
• Enkephalin, Ala(2)-MePhe(4)-Gly(5)-
• Enkephalins (pharmacology)
• Inflammation (drug therapy)
• Injections, Spinal
• Male
• Morphine (pharmacology)
• Pain (drug therapy)
• Rats
• Spinal Cord (drug effects)