ArticleScientific reports2016
Potentiation of Amitriptyline Anti-Hyperalgesic-Like Action By Astroglial Connexin 43 Inhibition in Neuropathic Rats.
Article in Scientific reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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14 citing papers in PubMed, 31 citations in OpenAlex.
- Inhibition of sodium-calcium exchanger by tricyclic antidepressants.Frontiers in pharmacology · 2026Article
- The Double-Edged Effect of Connexins and Pannexins of Glial Cells in Central and Peripheral Nervous System After Nerve Injury.Molecular neurobiology · 2025Review
- Spinal astrocytes involved in the pathogenesis and treatment of neuropathic pain.Frontiers in cellular neuroscience · 2025Review
- Spreading depolarization suppression from inter-astrocytic gap junction blockade assessed with multimodal imaging and a novel wavefront detection scheme.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2024Article
- Mechanism of connexin channel inhibition by mefloquine and 2-aminoethoxydiphenyl borate.PloS one · 2024Article
- Modeling and Targeting Neuroglial Interactions with Human Pluripotent Stem Cell Models.International journal of molecular sciences · 2022Review
- The Role of Neuro-Immune Interactions in Chronic Pain: Implications for Clinical Practice.Journal of pain research · 2022Review
- Examination and characterisation of the effect of amitriptyline therapy for chronic neuropathic pain on neuropeptide and proteomic constituents of human cerebrospinal fluid.Brain, behavior, & immunity - health · 2021Article
- Pharmaco-fUS for Characterizing Drugs for Alzheimer's Disease - The Case of THN201, a Drug Combination of Donepezil Plus Mefloquine.Frontiers in neuroscience · 2020Article
- Efficacy of THN201, a Combination of Donepezil and Mefloquine, to Reverse Neurocognitive Deficits in Alzheimer's Disease.Frontiers in neuroscience · 2020Article
- A New Tool for In Vivo Study of Astrocyte Connexin 43 in Brain.Scientific reports · 2019Article
- Therapeutic strategies targeting connexins.Nature reviews. Drug discovery · 2018Review
- Cortico-Amygdala-Striatal Activation by Modafinil/Flecainide Combination.The international journal of neuropsychopharmacology · 2018Article
- Connexin-Dependent Neuroglial Networking as a New Therapeutic Target.Frontiers in cellular neuroscience · 2017Review
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Authors and funding
10 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
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.
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