Galanin-mediated control of pain: enhanced role after nerve injury.
The endogenous inhibitory role of the neuropeptide galanin in pain transmission and spinal cord excitability was demonstrated by the use of a high-affinity galanin receptor antagonist, M-35 [galanin-(1-13)-bradykinin-(2-9)-amide]. M-35, which displaced 125I-labeled galanin from membranes of rat dorsal spinal cord with an IC50 of 0.3 nM, dose-dependently antagonized the effect of intrathecal galanin on the flexor reflex. M-35 potentiated the facilitation of the flexor reflex by conditioning stimulation of cutaneous unmyelinated afferents in rats with intact nerves and the potentiating effect of M-35 on the conditioning-stimulation-induced reflex facilitation of the cutaneous unmyelinated afferents was strongly enhanced after axotomy. These results demonstrate that endogenous galanin plays a tonic inhibitory role in the mediation of spinal cord excitability, and it is particularly noteworthy that this function of galanin is remarkably enhanced after peripheral nerve section.
Department of Clinical Physiology, Karolinska Institute, Huddinge University Hospital, Sweden.
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Wiesenfeld-Hallin
X J
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Xu
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Langel
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Bedecs
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Hökfelt
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Bartfai
D000818:Animals; D001920:Bradykinin / Q000031:analogs & derivatives* / Q000494:pharmacology; D002462:Cell Membrane / Q000378:metabolism; D003655:Decerebrate State; D005260:Female; D019004:Galanin; D007278:Injections, Spinal; D008297:Male; D009479:Neuropeptides / Q000502:physiology; D010146:Pain / Q000503:physiopathology*; D010446:Peptide Fragments / Q000494:pharmacology*; D010455:Peptides / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D044088:Receptors, Galanin; D011964:Receptors, Gastrointestinal Hormone / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D012018:Reflex / Q000187:drug effects; D012584:Sciatic Nerve / Q000293:injuries / Q000502:physiology*; D013116:Spinal Cord / Q000378:metabolism / Q000502:physiology
D009479:Neuropeptides; D010446:Peptide Fragments; D010455:Peptides; D044088:Receptors, Galanin; D011964:Receptors, Gastrointestinal Hormone; C074069:galanin-(1-13)-bradykinin-(2-9)-amide; D019004:Galanin; D001920:Bradykinin