I.Y. and N.C.-J. equally contributed to this work.
β2-adrenoceptors are critical for antidepressant treatment of neuropathic pain†
Article first published online: 3 MAR 2009
Copyright © 2009 American Neurological Association
Annals of Neurology
Volume 65, Issue 2, pages 218–225, February 2009
How to Cite
Yalcin, I., Choucair-Jaafar, N., Benbouzid, M., Tessier, L.-H., Muller, A., Hein, L., Freund-Mercier, M.-J. and Barrot, M. (2009), β2-adrenoceptors are critical for antidepressant treatment of neuropathic pain. Ann Neurol., 65: 218–225. doi: 10.1002/ana.21542
Potential conflict of interest: Nothing to report.
- Issue published online: 3 MAR 2009
- Article first published online: 3 MAR 2009
- Manuscript Accepted: 5 SEP 2008
- Manuscript Revised: 11 AUG 2008
- Manuscript Received: 26 FEB 2008
- Centre National de la Recherche Scientifique and the Université Louis Pastéur. Grant Number: UMR7168
- Région Alsace
- Conectus grant
- CNRS postdoctoral position
- Alsace Région postdoctoral contract
- M. Benhouzid was supported Présidence fellowship from the Universite' Louis Pasteur.
Tricyclic antidepressants (TCAs) are one of the first-line pharmacological treatments against neuropathic pain. TCAs increase the extracellular concentrations of noradrenaline and serotonin by blocking the reuptake transporters of these amines. However, the precise downstream mechanism leading to the therapeutic action remains identified. In this work, we evaluated the role of adrenergic receptors (ARs) in the action of TCAs.
We used pharmacological and genetic approaches in mice to study the role of ARs in the antiallodynic action of the TCA nortriptyline. Peripheral neuropathy was induced by the insertion of a polyethylene cuff around the main branch of the sciatic nerve. The specific role of β2-AR was evaluated by studying β2-AR−/− mice. We used von Frey filaments to assess mechanical allodynia.
The antiallodynic action of nortriptyline was not affected by cotreatment with the α2-AR antagonist yohimbine, the β1-AR antagonists atenolol or metoprolol, or the β3-AR antagonist SR 59230A. On the contrary, the β-AR antagonists propranolol or sotalol, the β1/β2-AR antagonists alprenolol or pindolol, or the specific β2-AR antagonist ICI 118,551 blocked the action of nortriptyline. The effect of nortriptyline was also totally absent in β2-AR–deficient mice.
Stimulation of β2-AR is necessary for nortriptyline to exert its antiallodynic action against neuropathic pain. These findings provide new insight into the mechanism by which antidepressants alleviate neuropathic pain. Our results also raise the question of a potential incompatibility between β-blockers that affect β2-AR and antidepressant drugs in patients treated for neuropathic pain. Ann Neurol 2009;65:218–225