Buspirone attenuates neuropathic pain and related depression following sciatic nerve injury in mice: Role of opioid receptors.

Patients with neuropathic pain also experience depression. Although they are treated with various therapies, the effectiveness of these medications is unclear. In the present study, the effect of buspirone on allodynia and depressive-like behavior caused by chronic constriction injury (CCI) of the sciatic nerve, as well as the role of opioid pathways, was investigated. Our findings showed that acute and sub-chronic administration of buspirone (0.3-10mg/kg) attenuated the mechanical and cold allodynia induced by CCI. In addition, a moderate dose of buspirone (1mg/kg), but not a high dose (10mg/kg), reduced the depressive-like behavior induced by CCI. Furthermore, pretreatment with naloxone attenuated the effects of buspirone, whereas co-administration with an ineffective dose of morphine potentiated its action. Also, hippocampal μ-opioid receptor mRNA was decreased, whereas κ-opioid receptor mRNA was increased in CCI mice 14 days after surgery. However, repeated buspirone in CCI-mice mitigated the observed alteration in opioid receptors mRNA expression. In addition, unlike morphine, buspirone did not produce tolerance or withdrawal symptoms following repeated administration. Collectively, these data provide evidence that buspirone can effectively alleviate neuropathic pain and exerts antidepressant-like benefits, potentially through modulation of opioid receptors. Moreover, the effects of buspirone may also be associated with changes in mRNA expression of μ-and κ-opioid receptors in the hippocampus.