beta(2)-adrenoceptors are critical for antidepressant treatment of neuropathic pain
| Autor: | Michel Barrot, Ipek Yalcin, Lutz Hein, Luc-Henri Tessier, Malika Benbouzid, Marie-José Freund-Mercier, André Muller, Nada Choucair-Jaafar |
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| Přispěvatelé: | Institut des Neurosciences Cellulaires et Intégratives (INCI), Université Louis Pasteur - Strasbourg I-Centre National de la Recherche Scientifique (CNRS) |
| Rok vydání: | 2009 |
| Předmět: |
Male
Time Factors Adrenergic beta-Antagonists Propranolol Pharmacology Antidepressive Agents Tricyclic Motor Activity chemistry.chemical_compound Mice Sciatica Adrenergic beta-2 Receptor Antagonists medicine Animals Pindolol Adrenergic alpha-Antagonists Pain Measurement Mice Knockout Adrenergic Uptake Inhibitors business.industry Atenolol Mice Inbred C57BL Disease Models Animal Neurology chemistry Hyperalgesia Neuropathic pain Antidepressant Alprenolol [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC] Neurology (clinical) Nortriptyline Receptors Adrenergic beta-2 medicine.symptom business medicine.drug |
| Zdroj: | Annals of Neurology Annals of Neurology, Wiley, 2009, 65, pp.218-225. ⟨10.1002/ana.21542⟩ |
| ISSN: | 1531-8249 0364-5134 |
| DOI: | 10.1002/ana.21542⟩ |
| Popis: | Objective 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. Methods 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 beta(2)-AR was evaluated by studying beta(2)-AR(-/-) mice. We used von Frey filaments to assess mechanical allodynia. Results The antiallodynic action of nortriptyline was not affected by cotreatment with the alpha(2)-AR antagonist yohimbine, the beta(1)-AR antagonists atenolol or metoprolol, or the beta(3)-AR antagonist SR 59230A. On the contrary, the beta-AR antagonists propranolol or sotalol, the beta(1)/beta(2)-AR antagonists alprenolol or pindolol, or the specific beta(2)-AR antagonist ICI 118,551 blocked the action of nortriptyline. The effect of nortriptyline was also totally absent in beta(2)-AR-deficient mice. Interpretation Stimulation of beta(2)-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 beta-blockers that affect beta(2)-AR and antidepressant drugs in patients treated for neuropathic pain. |
| Databáze: | OpenAIRE |
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