Document Detail


The neuropathy-protective agent acetyl-L-carnitine activates protein kinase C-gamma and MAPKs in a rat model of neuropathic pain.
MedLine Citation:
PMID:  19925851     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The gamma isoform of protein kinase C (PKCgamma) is an injury-activated intracellular modulator that boosts neuronal activity in algesic and neuroregenerative signalling pathways. Acetyl-L-carnitine (ALCAR), a physiological compound with role in bioenergetic functions, shows an antihyperalgesic effect and at the same time can exert neuroregenerative and neuroprotective effects. Aimed to explore the link between pain and neuroregeneration, the effect of ALCAR treatment (100 mg kg(-1) i.p. twice daily for 15 days) on PKCgamma and mitogen-activated protein kinases (MAPKs) expression has been evaluated in CCI (chronic constriction injury) rats. The sciatic nerve and the lumbar tract of the spinal cord were processed to evaluate the levels of the phosphorylated form of PKCgamma, ERK 1,2, SAP/JNK, p-38 and c-Jun; furthermore, the mRNA expression of the early genes c-Jun and c-Fos has been investigated. Fifteen days after injury, the analysis in the sciatic nerves highlighted a bilateral increase of the activated forms of PKCgamma, ERK 1,2 and SAP/JNK, whereas c-Jun showed an increase only ipsilaterally. ALCAR completely prevented mechanical hyperalgesia and provoked in the nerve a c-Jun increment only. In the lumbar tract of the spinal cord, higher levels of activated PKCgamma, ERK 1,2, p38, SAP/JNK and c-Jun proteins were detected in the ipsilateral side in respect of sham. ALCAR was able to stimulate this expression profile. At the transcriptional level c-Jun mRNA was increased in the ipsilateral side of spinal cord of CCI saline-treated rats, whereas c-Fos mRNA was unchanged. ALCAR had a stimulatory effect on both these early genes. These findings may represent a different approach in the study of the complex balance between pain and neuroregeneration and could constitute the basis for developing new disease modifying agents in the treatment of neuropathic pain.
Authors:
L Di Cesare Mannelli; C Ghelardini; A Toscano; A Pacini; A Bartolini
Publication Detail:
Type:  Journal Article     Date:  2009-11-17
Journal Detail:
Title:  Neuroscience     Volume:  165     ISSN:  1873-7544     ISO Abbreviation:  Neuroscience     Publication Date:  2010 Feb 
Date Detail:
Created Date:  2010-02-01     Completed Date:  2010-03-12     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7605074     Medline TA:  Neuroscience     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1345-52     Citation Subset:  IM    
Affiliation:
University of Florence, Department of Preclinical and Clinical Pharmacology, Florence, Italy. lorenzo.mannelli@unifi.it
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MeSH Terms
Descriptor/Qualifier:
Acetylcarnitine / pharmacology*
Animals
Disease Models, Animal
Enzyme Activation / drug effects
Functional Laterality
Hyperalgesia / drug therapy,  enzymology,  metabolism
Male
Mitogen-Activated Protein Kinases / metabolism*
Neuroprotective Agents / pharmacology*
Pain / drug therapy*,  enzymology,  metabolism
Protein Kinase C / metabolism*
Proto-Oncogene Proteins c-fos / metabolism
Proto-Oncogene Proteins c-jun / metabolism
RNA, Messenger / metabolism
Rats
Rats, Sprague-Dawley
Sciatic Nerve / drug effects,  enzymology,  metabolism
Sciatic Neuropathy / drug therapy*,  enzymology,  metabolism
Spinal Cord / drug effects,  enzymology,  metabolism
Chemical
Reg. No./Substance:
0/Neuroprotective Agents; 0/Proto-Oncogene Proteins c-fos; 0/Proto-Oncogene Proteins c-jun; 0/RNA, Messenger; 14992-62-2/Acetylcarnitine; EC 2.7.1.-/protein kinase C gamma; EC 2.7.11.13/Protein Kinase C; EC 2.7.11.24/Mitogen-Activated Protein Kinases

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


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