Beta2-adrenoceptors are essential for desipramine, venlafaxine or reboxetine action in neuropathic pain.
Neuropathic pain is a disease caused by a lesion or dysfunction of the nervous system. Antidepressants or anticonvulsants are presently the best available treatments. The mechanism by which antidepressants relieve neuropathic pain remains poorly understood. Using pharmacological and transgenic approaches in mice, we evaluated adrenergic receptor (AR) implication in the action of the tricyclic antidepressant desipramine, the noradrenaline and serotonin reuptake inhibitor venlafaxine, and the noradrenaline reuptake inhibitor reboxetine. Neuropathy was induced by cuff insertion around the sciatic nerve. We showed that chronic antidepressant treatment suppressed cuff-induced allodynia in wild-type mice but not in beta(2)-AR deficient mice, and/or that this antiallodynic action was blocked by intraperitoneal or intrathecal injection of the beta(2)-AR antagonist ICI 118,551 but not by the alpha(2)-AR antagonist yohimbine. We also showed that the anticonvulsant gabapentin was still effective in beta(2)-AR deficient mice. Our results demonstrate that beta(2)-ARs are essential for the antiallodynic action of antidepressant drugs.
Yalcin
Ipek
I
Institut des Neurosciences Cellulaires et Intégratives, Centre National de Recherche Scientifique and Université de Strasbourg, Strasbourg, France.
Tessier
Luc-Henri
LH
Petit-Demoulière
Nathalie
N
Doridot
Stéphane
S
Hein
Lutz
L
Freund-Mercier
Marie-José
MJ
Barrot
Michel
M
D058669:Adrenergic alpha-2 Receptor Antagonists; D000317:Adrenergic alpha-Antagonists / Q000008:administration & dosage; D000319:Adrenergic beta-Antagonists / Q000008:administration & dosage; D000588:Amines / Q000627:therapeutic use; D000818:Animals; D000927:Anticonvulsants / Q000627:therapeutic use; D000928:Antidepressive Agents / Q000627:therapeutic use*; D003509:Cyclohexanecarboxylic Acids / Q000627:therapeutic use; D003511:Cyclohexanols / Q000627:therapeutic use*; D003891:Desipramine / Q000627:therapeutic use*; D000077206:Gabapentin; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009025:Morpholines / Q000627:therapeutic use*; D010146:Pain / Q000188:drug therapy* / Q000378:metabolism*; D017288:Pain Threshold / Q000187:drug effects / Q000502:physiology; D011412:Propanolamines / Q000008:administration & dosage; D000077593:Reboxetine; D018341:Receptors, Adrenergic, alpha-2 / Q000502:physiology; D018343:Receptors, Adrenergic, beta-2 / Q000235:genetics / Q000502:physiology*; D012584:Sciatic Nerve / Q000503:physiopathology; D000069470:Venlafaxine Hydrochloride; D015016:Yohimbine / Q000008:administration & dosage; D005680:gamma-Aminobutyric Acid / Q000627:therapeutic use
D058669:Adrenergic alpha-2 Receptor Antagonists; D000317:Adrenergic alpha-Antagonists; D000319:Adrenergic beta-Antagonists; D000588:Amines; D000927:Anticonvulsants; D000928:Antidepressive Agents; D003509:Cyclohexanecarboxylic Acids; D003511:Cyclohexanols; D009025:Morpholines; D011412:Propanolamines; D018341:Receptors, Adrenergic, alpha-2; D018343:Receptors, Adrenergic, beta-2; D015016:Yohimbine; C026777:ICI 118551; D005680:gamma-Aminobutyric Acid; D000077206:Gabapentin; D000069470:Venlafaxine Hydrochloride; D000077593:Reboxetine; D003891:Desipramine