The specific antagonistic effect of intrathecal spantide II on substance P- and C-fiber conditioning stimulation-induced facilitation of the nociceptive flexor reflex in rat.
The effect of intrathecally (i.t.) applied tachykinin antagonist D-NicLys1, 3-Pal3, D-Cl2Phe5, Asn6, D-Trp7.9, Nle11-substance P (SP), spantide II, on the nociceptive flexor reflex was studied in decerebrate, spinalized, unanaesthetized rats over the dose range of 10 ng-10 micrograms. I.t. spantide II usually caused weak facilitation of the flexor reflex, especially at lower doses (10-100 ng) and at higher doses (1-10 micrograms) it sometimes depressed the reflex. Pre-treatment with spantide II (1, 3 or 10 micrograms) effectively antagonized the facilitatory effect of 10 ng i.t. SP on the flexor reflex for about 30 min. The facilitation of the reflex induced by i.t. administration of other neuropeptides present in primary afferents, somatostatin (SOM), vasoactive intestinal peptide (VIP), calcitonin gene-related peptide (CGRP) and galanin (GAL), was not influenced by spantide II. This non-toxic antagonist also effectively blocked facilitation of the flexor reflex induced by C-fiber conditioning stimulation of the sural nerve. The present results indicate that spantide II is an effective and specific tachykinin antagonist in the spinal cord. Furthermore, C-fiber stimulation facilitates the nociceptive flexor reflex through a mechanism involving the release of SP from the central terminals of primary afferents.
Wiesenfeld-Hallin
Z
Z
Department of Clinical Physiology, Karolinska Institute, Huddinge University Hospital, Sweden.
Xu
X J
XJ
Håkanson
R
R
Feng
D M
DM
Folkers
K
K
D000595:Amino Acid Sequence; D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D003214:Conditioning, Classical / Q000187:drug effects* / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004558:Electric Stimulation; D005260:Female; D007278:Injections, Spinal; D008297:Male; D008969:Molecular Sequence Data; D009412:Nerve Fibers / Q000187:drug effects*; D009479:Neuropeptides / Q000494:pharmacology; D010146:Pain / Q000503:physiopathology*; D051381:Rats; D011919:Rats, Inbred Strains; D013373:Substance P / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors* / Q000494:pharmacology
D000700:Analgesics; D009479:Neuropeptides; C065446:spantide II; D013373:Substance P