Spinal antinociception by morphine in rats is antagonised by galanin receptor antagonists.
Galanin, a 29 amino acid peptide, has been reported to possess antinociceptive properties at the spinal site and to potentiate opioid-induced antinociception. Our aim was to investigate whether also endogenous galanin interacts with an exogenously administered opioid, morphine, in the rat spinal cord. This question was investigated by use of the recently developed galanin receptor antagonists galantide [M-15, galanin-(1-13)-substance P-(5-11) amide] and M-35 [galanin-(1-13)-bradykinin-(2-9) amide]. Nociception was assessed in the rat tail-flick test using radiant heat and the rat Randall-Selitto model of inflammatory pain using vocalization as the nociceptive criterion. Intrathecal (i.t.) injections were performed in rats under either anaesthesia. Morphine was administered either i.t. or intraperitoneally (i.p.), and the antagonists were injected i.t. [125I]Galanin binding experiments were performed on crude synaptosomal membranes of the rat spinal cord. In the rat tail-flick test, i.t. injection of 3 micrograms morphine evoked antinociception of about 75% of the maximal possible effect (% MPE). Co-injection of either 2 micrograms galantide or 2 micrograms M-35 with morphine almost completely abolished the antinociceptive effect of morphine. I.p. injection of 2.15 mg/kg morphine elicited about 80% MPE when given 10 min prior to i.t. saline injection. Injection of the antagonists instead of saline antagonised the antinociceptive effect of morphine partially thus showing the spinal proportion of the overall antinociceptive effect. In the rat Randall-Selitto test, 3 micrograms morphine, injected i.t., produced antinociception of almost 100% MPE.(ABSTRACT TRUNCATED AT 250 WORDS)
Reimann
W
W
Abteilung Pharmakologie, Grünenthal GmbH, Aachen, Germany.
Englberger
W
W
Friderichs
E
E
Selve
N
N
Wilffert
B
B
D000818:Animals; D001665:Binding Sites; D001920:Bradykinin / Q000031:analogs & derivatives / Q000494:pharmacology; D019004:Galanin / Q000031:analogs & derivatives; D007278:Injections, Spinal; D008297:Male; D009020:Morphine / Q000037:antagonists & inhibitors*; D010146:Pain / Q000517:prevention & control*; D010446:Peptide Fragments / Q000494:pharmacology; D010455:Peptides / Q000378:metabolism / Q000494:pharmacology* / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D044088:Receptors, Galanin; D011964:Receptors, Gastrointestinal Hormone / Q000037:antagonists & inhibitors*; D013116:Spinal Cord / Q000187:drug effects* / Q000378:metabolism; D013373:Substance P / Q000031:analogs & derivatives*; D013570:Synaptic Membranes / Q000378:metabolism
D010446:Peptide Fragments; D010455:Peptides; D044088:Receptors, Galanin; D011964:Receptors, Gastrointestinal Hormone; C074975:galantide; C074069:galanin-(1-13)-bradykinin-(2-9)-amide; D013373:Substance P; D009020:Morphine; D019004:Galanin; D001920:Bradykinin