Differential release of substance P and somatostatin in the rat spinal cord in response to noxious cold and heat; effect of dynorphin A(1-17).
Dynorphin A(1-17), the proposed endogenous ligand for the kappa receptor, has been reported to demonstrate no antinociceptive activity when tested in analgesic assays involving noxious (heat (e.g., tail-flick and hot-plate assays). By using a rat tail-flick analgesic assay that utilizes extreme cold as its noxious stimulus (an ethylene glycol-water mixture maintained at -10 degrees C), we have recently reported a dose-related and naloxone-reversible antinociceptive effect for i.c.v. administered dynorphin A(1-17). To elucidate the biochemical mechanism of this antinociception, we designed a push-pull perfusion system which would allow us to measure changes in neuropeptide release in the spinal cord during exposure to noxious heat or cold. Male Sprague-Dawley rats were implanted surgically with two lengths of PE-10 tubing inserted into the spinal subarachnoid space via the cisterna magna, with the push cannula at the level of T-1, and the pull cannula at the rostral edge of the lumbar enlargement. At the time of testing, samples of cerebrospinal fluid were collected both in the presence and absence of a noxious stimulus. Substance P (SP) and somatostatin (SST) levels were measured by radioimmunoassay. Exposing the animal's tail to the noxious cold (30 sec/min for 20 min) resulted in a significant elevation in SP release (69% above base-line levels), but no change in the level of SST release. Conversely, exposure to noxious heat (50 degrees C, 20 sec/min for 20 min) produced a significant increase in SST release (56% above base line), but no change in the level of SP release.(ABSTRACT TRUNCATED AT 250 WORDS)
Temple University School of Medicine, Department of Pharmacology, Phildelphia, Pennsylvania.
P J
PJ
Tiseo
M W
MW
Adler
L Y
LY
Liu-Chen
D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D000818:Animals; D003080:Cold Temperature; D004399:Dynorphins / Q000494:pharmacology*; D006358:Hot Temperature; D008297:Male; D009270:Naloxone / Q000494:pharmacology; D010146:Pain / Q000503:physiopathology*; D011759:Pyrrolidines / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013004:Somatostatin / Q000378:metabolism*; D013116:Spinal Cord / Q000187:drug effects* / Q000378:metabolism; D013373:Substance P / Q000378:metabolism*
D011759:Pyrrolidines; D013373:Substance P; D009270:Naloxone; D013004:Somatostatin; D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D004399:Dynorphins