Expression of beta(2)-adrenoceptors (beta(2)-ARs) within the nociceptive system suggested their potential implication in nociception and
pain. Recently, we demonstrated that these receptors are essential for
neuropathic pain treatment by
antidepressant drugs. The aim of the present study was to investigate whether the stimulation of beta(2)-ARs could in fact be adequate to alleviate neuropathic
allodynia. Neuropathy was induced in mice by sciatic nerve cuffing. We demonstrate that chronic but not acute stimulation of beta(2)-ARs with agonists such as
clenbuterol,
formoterol,
metaproterenol and
procaterol suppressed neuropathic
allodynia. By using a pharmacological approach with the beta(2)-AR antagonist
ICI 118,551 or a transgenic approach with mice deficient for beta(2)-ARs, we confirmed that the antiallodynic effect of these agonists was specifically related to their action on beta(2)-ARs. We also showed that chronic treatment with the beta(1)-AR agonist
xamoterol or with the beta(3)-AR agonist
BRL 37344 had no effect on neuropathic
allodynia. Chronic stimulation of beta(2)-ARs, but not beta(1)- or beta(3)-ARs, by specific agonists is thus able to alleviate neuropathic
allodynia. This action of beta(2)-AR agonists might implicate the endogenous
opioid system; indeed chronic
clenbuterol effect can be acutely blocked by the
delta-opioid receptor antagonist
naltrindole. Present results show that beta(2)-ARs are not only essential for the antiallodynic action of
antidepressant drugs on sustained
neuropathic pain, but also that the stimulation of these receptors is sufficient to relieve neuropathic
allodynia in a murine model. Our data suggest that beta(2)-AR agonists may potentially offer an alternative
therapy to
antidepressant drugs for the chronic treatment of
neuropathic pain.