Potentiation of Amitriptyline Anti-Hyperalgesic-Like Action By Astroglial Connexin 43 Inhibition in Neuropathic Rats - CNRS - Centre national de la recherche scientifique Accéder directement au contenu
Article Dans Une Revue Scientific Reports Année : 2016

Potentiation of Amitriptyline Anti-Hyperalgesic-Like Action By Astroglial Connexin 43 Inhibition in Neuropathic Rats

Résumé

Antidepressants, prescribed as first line treatment of neuropathic pain, have a limited efficacy and poorly tolerated side effects. Because recent studies pointed out the implication of astroglial connexins (Cx) in both neuropathic pain and antidepressive treatment, we investigated whether their blockade by mefloquine could modulate the action of the tricyclic antidepressant amitriptyline. Using primary cultures, we found that both mefloquine and amitriptyline inhibited Cx43-containing gap junctions, and that the drug combination acted synergically. We then investigated whether mefloquine could enhance amitriptyline efficacy in a preclinical model of neuropathic pain. Sprague-Dawley rats that underwent chronic unilateral constriction injury (CCI) to the sciatic nerve (SN) were treated with either amitriptyline, mefloquine or the combination of both drugs. Whereas acute treatments were ineffective, chronic administration of amitriptyline reduced CCI-SN-induced hyperalgesia-like behavior, and this effect was markedly enhanced by co-administration of mefloquine, which was inactive on its own. No pharmacokinetic interactions between both drugs were observed and CCI-SN-induced neuroinflammatory and glial activation markers remained unaffected by these treatments in dorsal root ganglia and spinal cord. Mechanisms downstream of CCI-SN-induced neuroinflammation and glial activation might therefore be targeted. Connexin inhibition in astroglia could represent a promising approach towards improving neuropathic pain therapy by antidepressants.
Fichier principal
Vignette du fichier
Jeanson et al 2016.pdf (1.23 Mo) Télécharger le fichier
Origine : Publication financée par une institution

Dates et versions

inserm-01472405 , version 1 (20-02-2017)

Identifiants

Citer

Tiffany Jeanson, Adeline Duchêne, Damien Richard Richard, Sylvie Bourgoin, Christèle Picoli, et al.. Potentiation of Amitriptyline Anti-Hyperalgesic-Like Action By Astroglial Connexin 43 Inhibition in Neuropathic Rats. Scientific Reports, 2016, 6, pp.38766 - 38766. ⟨10.1038/srep38766⟩. ⟨inserm-01472405⟩
99 Consultations
209 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More