A dual noradrenergic mechanism for the relief of neuropathic allodynia by the antidepressant drugs duloxetine and amitriptyline
Send a publication request

Publication request

Thank you for your interest in our product range and your request for this publication, which will be sent to you if the research team and the journal allow it. Our commercial team will contact you as soon as possible.

- Categories : Neuropathic pain , Pain , Publications - ID: 1066

M Kremer, I Yalcin, Y Goumon, X Wurtz, L Nexon et al

Centre National de la Recherche Scientifique, Université de Strasbourg, Institut des Neurosciences Cellulaires et Intégratives, Strasbourg, France.

Journal of Neuroscience

Beside depression, antidepressant drugs are also a first-line treatment for neuropathic pain, which is consecutive to a lesion or pathology of the nervous system. Despite a widespread use of these drugs, the mechanism underlying their therapeutic action in this pain context remains partly elusive. The present study combined data collected in male and female mice from a model of neuropathic pain and data from the clinics to understand how antidepressant drugs act. We showed two distinct mechanisms by which the selective inhibitor of serotonin and noradrenaline reuptake duloxetine and the tricyclic antidepressant amitriptyline relieved neuropathic allodynia. One of these mechanisms is acute, central, and requiring descending noradrenergic inhibitory controls and _2A adrenoceptors, as well as the mu and delta opioid receptors. The second mechanism is delayed, peripheral and requires noradrenaline from peripheral sympathetic endings and _2 adrenoceptors, as well as the delta opioid receptors. We then conducted a transcriptomic analysis in dorsal root ganglia which suggested that the peripheral component of duloxetine action involves the inhibition of neuroimmune mechanisms accompanying nerve injury, including the downregulation of the TNF_-NF_B signaling pathway. Accordingly, immunotherapies against either TNF_ or TLR2 provided allodynia relief. We also compared duloxetine plasma levels in the animal model and in patients and we observed that patients drug concentrations are compatible with those measured in animals under chronic treatment involving the peripheral mechanism. Our study highlights a peripheral neuroimmune component of antidepressant drugs that is relevant to their delayed therapeutic action against neuropathic pain.

BIOSEB Instruments Used:
Von Frey Filaments (Bio-VF-M)

Related products

Share this content