Journal
NEUROBIOLOGY OF DISEASE
Volume 60, Issue -, Pages 39-50Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.nbd.2013.08.012
Keywords
Allodynia; Antidepressant; Adrenoceptor; Cytokine; Dorsal root ganglia; Satellite; Neuropathy; Noradrenergic; Pain; TNF alpha
Categories
Funding
- Centre National de la Recherche Scientifique [UPR3212]
- University of Strasbourg
- Neurex
- Neurex fellowship
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Neuropathic pain is pain arising as a direct consequence of a lesion or disease affecting the somatosensory system. It is usually chronic and challenging to treat. Some antidepressants are first-line pharmacological treatments for neuropathic pain. The noradrenaline that is recruited by the action of the antidepressants on reuptake transporters has been proposed to act through beta 2-adrenoceptors (beta 2-ARs) to lead to the observed therapeutic effect. However, the complex downstream mechanism mediating this action remained to be identified. In this study, we demonstrate in a mouse model of neuropathic pain that an antidepressant's effect on neuropathic allodynia involves the peripheral nervous system and the inhibition of cytokine tumor necrosis factor a (TNF alpha) production. The antiallodynic action of nortriptyline is indeed lost after peripheral sympathectomy, but not after lesion of central descending noradrenergic pathways. More particularly, we report that antidepressant-recruited noradrenaline acts, within dorsal root ganglia, on beta 2-ARs expressed by non-neuronal satellite cells. This stimulation of beta 2-ARs decreases the neuropathy-induced production of membrane-bound TNFa, resulting in relief of neuropathic allodynia. This indirect anti-TNF alpha action was observed with the tricyclic antidepressant nortriptyline, the selective serotonin and noradrenaline reuptake inhibitor venlafaxine and the beta 2-AR agonist terbutaline. Our data revealed an original therapeutic mechanism that may open novel research avenues for the management of painful peripheral neuropathies. (C) 2013 Elsevier Inc. All rights reserved.
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