Morphine and endomorphin-1 differently influence pronociceptin/orphanin FQ system in neuropathic rats.
In the present study, we investigated the influence of intrathecal (i.t.) administration of morphine and endomorphin-1 on the level of pronociceptin/orphanin FQ and opioid receptor-like 1 (ORL1) receptor mRNAs in the lumbar part of the spinal cord in the rat model of neuropathic pain. The ligation of the sciatic nerve did not change the levels of pronociceptin/orphanin FQ and ORL1 receptor mRNAs in laminae I-VI of the dorsal horn when measured by in situ hybridisation 2 and 7 days after the nerve injury, but ORL1 receptor mRNA level in the ventral horn was significantly increased. Two micro-opioid receptor agonists, morphine and endomorphin-1, whose effectiveness in neuropathic pain is different, also disparately influenced nociceptin/orphanin FQ system in this pain model, inasmuch as an increase in pronociceptin/orphanin FQ and ORL1 receptor mRNAs was observed in laminae I-VI after morphine administration (5 microg i.t.) but not after endomorphin-1 treatment (5 microg i.t.). Moreover, the injection of ORL1 receptor antagonists (PhePsi; 30 microg i.t.) before morphine potentiated the effect of morphine in neuropathic pain model. Therefore, the activation of the endogenous nociceptin/orphanin FQ system, which is known to exhibit antiopioidergic activity, apart from its analgesic action, could be the reason for lower responsiveness to morphine in neuropathic pain.
Mika
Joanna
J
Department of Molecular Neuroscience, Institute of Anatomy and Cell Biology, Philipps University, 35033 Marburg, Germany.
Schäfer
Martin K H
MK
Obara
Ilona
I
Weihe
Eberhard
E
Przewlocka
Barbara
B
D000818:Animals; D008297:Male; D009020:Morphine / Q000494:pharmacology* / Q000627:therapeutic use; D009842:Oligopeptides / Q000494:pharmacology* / Q000627:therapeutic use; D011498:Protein Precursors / Q000096:biosynthesis* / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D011957:Receptors, Opioid / Q000096:biosynthesis* / Q000235:genetics; D020426:Sciatic Neuropathy / Q000188:drug therapy / Q000378:metabolism*
D009842:Oligopeptides; D011498:Protein Precursors; D012333:RNA, Messenger; D011957:Receptors, Opioid; C105293:endomorphin 1; C119224:pronociceptin; D009020:Morphine