Role of JNK isoforms in the development of neuropathic pain following sciatic nerve transection in the mouse.

Détails

Ressource 1Télécharger: BIB_DBDB5C1D0726.P001.pdf (1664.81 [Ko])
Etat: Public
Version: de l'auteur
ID Serval
serval:BIB_DBDB5C1D0726
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Role of JNK isoforms in the development of neuropathic pain following sciatic nerve transection in the mouse.
Périodique
Molecular Pain
Auteur(s)
Manassero G., Repetto I.E., Cobianchi S., Valsecchi V., Bonny C., Rossi F., Vercelli A.
ISSN
1744-8069 (Electronic)
ISSN-L
1744-8069
Statut éditorial
Publié
Date de publication
2012
Volume
8
Numéro
1
Pages
39
Langue
anglais
Notes
Publication types: Journal ArticlePublication Status: epublish. Authors' contributions: GM designed, performed the experiments and wrote the manuscripttogether with AV. IR performed part of the experiments. SC contributed to behavioral tests and statistical analysis. VV contributed to the RT-PCR. CBcontributed to design of experimentation and of drug administration. AV and FR supervised the experiments. All authors read and approved the finalmanuscript.
Résumé
ABSTRACT:
BACKGROUND: Current tools for analgesia are often only partially successful, thus investigations of new targets for pain therapy stimulate great interest. Consequent to peripheral nerve injury, c-Jun N-terminal kinase (JNK) activity in cells of the dorsal root ganglia (DRGs) and spinal cord is involved in triggering neuropathic pain. However, the relative contribution of distinct JNK isoforms is unclear. Using knockout mice for single isoforms, and blockade of JNK activity by a peptide inhibitor, we have used behavioral tests to analyze the contribution of JNK in the development of neuropathic pain after unilateral sciatic nerve transection. In addition, immunohistochemical labelling for the growth associated protein (GAP)-43 and Calcitonin Gene Related Peptide (CGRP) in DRGs was used to relate injury related compensatory growth to altered sensory function.
RESULTS: Peripheral nerve injury produced pain-related behavior on the ipsilateral hindpaw, accompanied by an increase in the percentage of GAP43-immunoreactive (IR) neurons and a decrease in the percentage of CGRP-IR neurons in the lumbar DRGs. The JNK inhibitor, D-JNKI-1, successfully modulated the effects of the sciatic nerve transection. The onset of neuropathic pain was not prevented by the deletion of a single JNK isoform, leading us to conclude that all JNK isoforms collectively contribute to maintain neuropathy. Autotomy behavior, typically induced by sciatic nerve axotomy, was absent in both the JNK1 and JNK3 knockout mice.
CONCLUSIONS: JNK signaling plays an important role in regulating pain threshold: the inhibition of all of the JNK isoforms prevents the onset of neuropathic pain, while the deletion of a single splice JNK isoform mitigates established sensory abnormalities. JNK inactivation also has an effect on axonal sprouting following peripheral nerve injury.
Pubmed
Web of science
Open Access
Oui
Création de la notice
04/10/2012 17:17
Dernière modification de la notice
20/08/2019 16:00
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