From antidepressant drugs to beta-mimetics: preclinical insights on potential new treatments for neuropathic pain.
The market for pain treatment is a major segment of nervous system pathologies. Despite this dynamism, the management of some pain conditions remains a clinical challenge. Neuropathic pain arises as a direct consequence of a lesion or disease affecting the somatosensory system. It is generally a chronic and disabling condition which is difficult to treat. Antidepressant drugs are recommended as one of the first line treatments, but they display noticeable side effects and are not effective on all patients. Using a murine model of neuropathy, we demonstrated that the stimulation of beta2-adrenergic receptors (beta2-AR) is not only necessary for antidepressant drugs to exert their antiallodynic action but that it is in fact sufficient to alleviate neuropathic allodynia. Chronic, but not acute, treatment with beta-mimetics such as terbutaline, salbutamol, fenoterol, salmeterol, ritodrine, isoprenaline (isoproterenol), metaproterenol (orciprenaline), procaterol, formoterol, clenbuterol or bambuterol, relieves allodynia. Agonists of beta2-ARs, and more generally any molecule stimulating beta2-ARs such as beta-mimetics, are thus proposed as potential new treatments for neuropathic pain. Clinical studies are now in preparation to confirm this potential in patients with neuropathic pain. This article reviews the findings leading to propose beta-mimetics for neuropathic pain treatment and other recent patents on the topic.
Barrot
Michel
M
Institute of Cellular and Integrative Neurosciences, Centre National de la Recherche Scientifique, Strasbourg, France. mbarrot@neurochem.u-strasbg.fr
Yalcin
Ipek
I
Choucair-Jaafar
Nada
N
Benbouzid
Malika
M
Freund-Mercier
Marie-José
MJ
D058666:Adrenergic beta-2 Receptor Agonists; D000318:Adrenergic beta-Agonists / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D009437:Neuralgia / Q000188:drug therapy*; D018343:Receptors, Adrenergic, beta-2 / Q000502:physiology; D020886:Somatosensory Disorders / Q000188:drug therapy
D058666:Adrenergic beta-2 Receptor Agonists; D000318:Adrenergic beta-Agonists; D000928:Antidepressive Agents; D018343:Receptors, Adrenergic, beta-2