Antinociceptive effect of continuous intrathecal administration of endomorphin-1.
Endomorphin-1 is a novel endogenous opioid peptide with high affinity and selectivity for the mu-opioid receptor. Earlier results have shown that it causes antinociception in different pain tests, but its effect is short-lasting. The purpose of the present study was to investigate the antinociceptive potency of continuously administered endomorphin-1 on carrageenan-induced thermal hyperalgesia by means of a paw withdrawal test in awake rats. The possible interaction between endomorphin-1 and the C-terminal octapeptide of the novel endogenous peptide nocistatin (bPNP-3-8P) was examined in the same experimental set-up. Continuous administration of endomorphin-1 (0.1, 0.3, 1 or 2 microg/min for 60 min) did not influence the paw withdrawal latencies of the normal paws. On the inflamed side, endomorphin-1 dose-dependently decreased the thermal hyperalgesia during continuous administration. The cessation of administration resulted in a gradual decrease in the antinociceptive effect of endomorphin-1. bPNP-3-8P (0.003-30 microg, administered cumulatively) significantly decreased the heat hyperalgesia at higher doses (3 and 30 microg). Continuous administration of bPNP-3-8P (0.03, 0.1 and 1 microg/min) did not potentiate the antinociceptive effect of endomorphin-1; instead, it even shortened the duration of its effect. The results demonstrate that continuous administration of endomorphin-1 is an effective method of inhibiting thermal hyperalgesia in rats. Furthermore, the fragment bPNP-3-8P itself has low antinociceptive potency and does not potentiate the antinociceptive effect of endomorphin-1 under these circumstances.
Csullog
Emese
E
Department of Physiology, Faculty of Medicine, University of Szeged, P.O. Box 427, H-6701 Szeged, Hungary Department of Anesthesiology and Intensive Care, Faculty of Medicine, University of Szeged, Szeged, Hungary Isotope Laboratory of Biological Research Center of the Hungarian Academy of Sciences, Szeged, Hungary Department of Physical Therapy, Faculty of Health Science, University of Szeged, Szeged, Hungary.
Joo
Gabriella
G
Toth
Geza
G
Dobos
Ildiko
I
Benedek
György
G
Horvath
Gyöngyi
G
D000700:Analgesics / Q000008:administration & dosage*; D000701:Analgesics, Opioid / Q000008:administration & dosage*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D006930:Hyperalgesia / Q000188:drug therapy; D007278:Injections, Spinal / Q000379:methods; D008297:Male; D009842:Oligopeptides / Q000008:administration & dosage*; D010147:Pain Measurement / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D011930:Reaction Time / Q000187:drug effects; D013997:Time Factors
D000700:Analgesics; D000701:Analgesics, Opioid; D009842:Oligopeptides; C105293:endomorphin 1