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.
Wiesenfeld-Hallin
Z
Z
Department of Clinical Physiology, Karolinska Institute, Huddinge University Hospital, Sweden.
Xu
X J
XJ
Langel
U
U
Bedecs
K
K
Hökfelt
T
T
Bartfai
T
T
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