Quick Search:

uzh logo
Browse by:
bullet
bullet
bullet
bullet

Zurich Open Repository and Archive 

Permanent URL to this publication: http://dx.doi.org/10.5167/uzh-4722

Muth-Selbach, U; Dybek, E; Kollosche, K; Stegmann, J U; Holthusen, H; Lipfert, P; Zeilhofer, H U (2004). The spinal antinociceptive effect of nocistatin in neuropathic rats is blocked by D-serine. Anesthesiology, 101(3):753-758.

[img]PDF - Registered users only
1289Kb

Abstract

BACKGROUND: The neuropeptide nocistatin (NST) has been implicated in the modulation of nociceptive responses in the spinal cord. Depending on the dose, both pronociceptive and antinociceptive effects have repeatedly been reported. The pronociceptive effect is most likely attributable to inhibition of synaptic glycine and gamma-aminobutyric acid release and a subsequent reduction in the activation of inhibitory glycine and gamma-aminobutyric acid receptors, but the mechanisms of its antinociceptive action have hitherto remained elusive. It has recently been demonstrated that synaptically released glycine contributes to N-methyl-D-aspartate receptor activation. The authors therefore investigated whether a reduction in glycine release might also account for the antinociceptive action of NST in neuropathic rats. METHODS: The authors analyzed the effects of spinally applied NST in the chronic constriction injury model of neuropathic pain. NST was injected intrathecally from nanomolar to picomolar doses and its effects on thermal paw withdrawal latencies were monitored. Furthermore, we tested whether D-serine (100 microg per rat), a full agonist at the glycine binding site of the N-methyl-D-aspartate receptor, would interfere with the effects of NST. RESULTS: At high doses (10 nmol/rat), intrathecally injected NST was pronociceptive, whereas lower doses (1 pmol/rat) elicited antinociception. The antinociceptive, but not the pronociceptive, action was occluded by intrathecal pretreatment with D-serine. L-serine, which does not bind to N-methyl-D-aspartate receptors, affected neither the pronociceptive nor the antinociceptive effect. CONCLUSIONS: These results demonstrate that NST produces a biphasic dose-dependent effect on neuropathic pain. The spinal antinociception by NST is most likely attributable to inhibition of glycine-dependent N-methyl-D-aspartate receptor activation.

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Institute of Pharmacology and Toxicology
DDC:570 Life sciences; biology
610 Medicine & health
Language:English
Date:September 2004
Deposited On:27 Mar 2009 12:15
Last Modified:27 Nov 2013 17:28
Publisher:Lippincott Wiliams & Wilkins
ISSN:0003-3022
Publisher DOI:10.1097/00000542-200409000-00025
Official URL:http://journals.lww.com/anesthesiology/pages/articleviewer.aspx?year=2004&issue=09000&article=00025&type=abstract
PubMed ID:15329601
Citations:Web of Science®. Times Cited: 18
Google Scholar™

Users (please log in): suggest update or correction for this item

Repository Staff Only: item control page