Document Detail


Intrathecal substance P-induced thermal hyperalgesia and spinal release of prostaglandin E2 and amino acids.
MedLine Citation:
PMID:  10077333     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Substance P is an important neuromediator in spinal synaptic transmission, particularly in processing nociceptive afferent information. The effects of substance P are mediated by activation of the neurokinin 1 receptor. Evidence has suggested that excitatory amino acids such as glutamate, and prostaglandins including prostaglandin E2 are involved in the enhanced spinal excitability and hyperalgesia produced by spinal substance P. In the present study, we have demonstrated that intrathecal injection of substance P (20 nmol) in rats chronically implanted with intrathecal dialysis catheters induced a decrease in thermal paw withdrawal latency (before: 10.4+/-0.3 s; after 7.6+/-0.6 s), which was accompanied by an increase in prostaglandin E2 (362+/-37% of baseline), glutamate (267+/-84%) and taurine (279+/-57%), but not glycine, glutamine, serine or asparagine. Intrathecal injection of artificial cerebrospinal fluid had no effect upon the behavior or release. Substance P-induced thermal hyperalgesia and prostaglandin E2 release were significantly attenuated by a selective neurokinin 1 receptor antagonist RP67580, but not by an enantiomer RP68651. However, substance P-induced release of glutamate and taurine was not reduced by treatment with RP67580. SR140333, another neurokinin 1 receptor antagonist, displayed the same effects as RP67580 (i.e. block of thermal hyperalgesia and prostaglandin E2 release, but not release of amino acids). These results provide direct evidence suggesting that the spinal substance P-induced thermal hyperalgesia is mediated by an increase in spinal prostaglandin E2 via activation of the neurokinin 1 receptor. These findings define an important linkage between small afferents, sensory neurotransmitter release and spinal prostanoids in the cascade of spinally-mediated hyperalgesia. The evoked release of glutamate is apparently not a result of activation of neurokinin 1 receptors. Accordingly, consistent with other pharmacological data, acute spinal glutamate release does not contribute to the hyperalgesia induced by activation of spinal neurokinin 1 receptors.
Authors:
X Y Hua; P Chen; M Marsala; T L Yaksh
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Neuroscience     Volume:  89     ISSN:  0306-4522     ISO Abbreviation:  Neuroscience     Publication Date:  1999 Mar 
Date Detail:
Created Date:  1999-05-07     Completed Date:  1999-05-07     Revised Date:  2013-06-05    
Medline Journal Info:
Nlm Unique ID:  7605074     Medline TA:  Neuroscience     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  525-34     Citation Subset:  IM    
Affiliation:
Department of Anesthesiology, University of California, San Diego, La Jolla 92093-0818, USA.
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MeSH Terms
Descriptor/Qualifier:
Amino Acids / metabolism*
Analgesics / pharmacology
Animals
Dinoprostone / metabolism*
Hot Temperature*
Hyperalgesia / chemically induced*
Indoles / pharmacology
Injections, Spinal
Isoindoles
Male
Piperidines / pharmacology
Quinuclidines / pharmacology
Rats
Rats, Inbred Strains
Receptors, Neurokinin-1 / antagonists & inhibitors
Spinal Cord / drug effects,  metabolism*
Substance P / administration & dosage*,  pharmacology
Grant Support
ID/Acronym/Agency:
NS16541/NS/NINDS NIH HHS; R29 HL50403/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Amino Acids; 0/Analgesics; 0/Indoles; 0/Isoindoles; 0/Piperidines; 0/Quinuclidines; 0/Receptors, Neurokinin-1; 135911-02-3/7,7-diphenyl-2-(1-imino-2-(2-methoxyphenyl)ethyl)perhydroisoindol-4-one; 153050-21-6/SR 140333; 33507-63-0/Substance P; 363-24-6/Dinoprostone

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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