Document Detail


Inhibition of neuropathic pain by a potent disintegrin--triflavin.
MedLine Citation:
PMID:  15364408     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Injury to peripheral nerves may result in severe and intractable neuropathic pain. Many efforts have been focused on the elucidation of the mechanisms of neuropathic pain. It was found here that integrin plays an important role in the induction of neuropathic pain and treatment of disintegrin is able to attenuate neuropathic pain. The rats were induced hyperalgesia by tightly ligating the L5 spinal nerve and cut just distal to the ligature on one side. Mechanical and thermal stimuli were applied in the middle dermatome of the hind paw. Epidural administration of triflavin (TFV), an arginine-glycine-aspartic acid (RGD) containing disintegrin, inhibited hyperalgesia induced by either mechanical or thermal stimulation. Immunohistochemistry showed that the sprouting of sympathetic nerves into DRG by neuropathic surgery was markedly inhibited by TFV. Beta 1 integrin mRNA of L5 DRG increased immediately 1 day after tight ligation and cut of L5 spinal nerve. However, beta 1 integrin mRNA in uninjured L4 DRG increased later on Day 3 after surgery. On the other hand, alpha-CGRP precursor mRNA decreased in ipsilateral L5 DRG but increased in L4 DRG after neuropathic surgery. Immunohistochemistry shows that beta 3 integrins of L5 as well as L4 increased in response to neuropathic surgery and administration of triflavin antagonized the increasing action. These results suggest that there is interaction between injured and uninjured neurons and the induction of neuropathic pain is related to neuronal sprouting. Disintegrin is able to inhibit neuronal sprouting and the induction of hyperalgesia induced by peripheral nerve injury and may thus be a new category of drugs to be developed for the treatment of neuropathic pain.
Authors:
Wen-Mei Fu; Tung-Kai Chang; Wei-Zen Sun; Qing-Dong Ling; Hui-Chin Peng; Houng-Chi Liou; Dah-Yuu Lu; Tur-Fu Huang
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Neuroscience letters     Volume:  368     ISSN:  0304-3940     ISO Abbreviation:  Neurosci. Lett.     Publication Date:  2004 Sep 
Date Detail:
Created Date:  2004-09-14     Completed Date:  2005-01-31     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  7600130     Medline TA:  Neurosci Lett     Country:  Ireland    
Other Details:
Languages:  eng     Pagination:  263-8     Citation Subset:  IM    
Affiliation:
Department of Pharmacology, College of Medicine, National Taiwan University, No. 1, Sec. 1, Jen-Ai Road, Taipei, Taiwan, ROC. wenmei@ha.mc.ntu.edu.tw
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MeSH Terms
Descriptor/Qualifier:
Animals
Crotalid Venoms / pharmacology,  therapeutic use*
Disintegrins / pharmacology,  therapeutic use*
Integrins / biosynthesis,  physiology
Pain / metabolism,  prevention & control*
Pain Measurement / drug effects,  methods
Peptides / pharmacology,  therapeutic use*
Rats
Rats, Sprague-Dawley
Spinal Nerves / drug effects,  injuries,  metabolism
Chemical
Reg. No./Substance:
0/Crotalid Venoms; 0/Disintegrins; 0/Integrins; 0/Peptides; 133247-60-6/triflavin

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


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