Potentiation of Amitriptyline Anti-Hyperalgesic-Like Action By Astroglial Connexin 43 Inhibition in Neuropathic Rats
| Autor: | Tiffany Jeanson, Pascal Ezan, Franck Mouthon, Michel Hamon, Damien Richard, Christian Giaume, Adeline Duchêne, Mathieu Charvériat, Sylvie Bourgoin, Christèle Picoli |
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| Přispěvatelé: | Centre interdisciplinaire de recherche en biologie (CIRB), Labex MemoLife, École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Collège de France (CdF (institution))-Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Theranexus [Lyon], Service de Pharmacologie Médicale [CHU Clermont-Ferrand], CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand, Institut de psychiatrie et neurosciences (U894 / UMS 1266), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Collège de France (CdF) - Institut National de la Santé et de la Recherche Médicale (INSERM) - Centre National de la Recherche Scientifique (CNRS), Service de Pharmacologie Médicale [Clermont-Ferrand], Centre de Psychiatrie et Neurosciences (CPN - U894), Institut National de la Santé et de la Recherche Médicale (INSERM) - Université Paris Descartes - Paris 5 (UPD5), École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS-PSL), Bourgoin-Hamon, Sylvie |
| Rok vydání: | 2016 |
| Předmět: |
Male
0301 basic medicine medicine.drug_class Amitriptyline Connexin Tricyclic antidepressant Pharmacology Article Rats Sprague-Dawley 03 medical and health sciences 0302 clinical medicine medicine Animals [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC] Neuroinflammation Multidisciplinary Mefloquine business.industry Gap Junctions Long-term potentiation Rats 3. Good health 030104 developmental biology Hyperalgesia Astrocytes Connexin 43 Neuropathic pain Neuralgia [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC] Sciatic nerve Sciatic Neuropathy business 030217 neurology & neurosurgery medicine.drug |
| Zdroj: | Scientific Reports Scientific Reports, Nature Publishing Group, 2016, 6, pp.38766-38766. ⟨10.1038/srep38766⟩ Scientific Reports, Nature Publishing Group, 2016, 6, pp.38766-38766. 〈10.1038/srep38766〉 Scientific Reports, 2016, 6, pp.38766-38766. ⟨10.1038/srep38766⟩ |
| ISSN: | 2045-2322 |
| DOI: | 10.1038/srep38766 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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