Intranasal oxytocin alleviates postsurgical pain and comorbid anxiety in mice: Participation of BK(Ca) channels in the hippocampus.

The affective dimension in postsurgical pain is still poorly understood. Since neuropeptide oxytocin (OXT) has been implicated in a broad spectrum of pain and negative emotion, we investigated the potential therapeutic effect of intranasal OXT on postsurgical pain and associated anxiety in a mice model of plantar incision. The role of large conductance Ca(2+)-activated K(+) (BK(Ca)) channels was explored by using behavioral pharmacology experiments. We reported that plantar incision in mice induced anxiety-like behaviors and mechanical pain hypersensitivity, with a concurrent decrease of the oxytocin receptor (OTR) in the hippocampus. The immunofluorescence staining showed that the OTR were enriched in pyramidal neurons in CA3 subregion of hippocampus and which were highly co-expressed with the BK(Ca) channels in CA3 subregion. Intranasal OXT significantly ameliorated this postsurgical pain and associated anxiety in a dose-dependent manner, while Intra-CA3 microinjection of OTR antagonist atosiban or the BK(Ca) channel blocker paxilline reduced the effect of OXT in incisional mice. Moreover, intra-CA3 microinjection of BK(Ca) channel opener NS1619 produced a similar effect on postsurgical pain and associated anxiety-like behaviors as those observed following intranasal OXT administration. Conversely, intra-CA3 microinjection of BK(Ca) channel blocker paxilline in normal mice was sufficient to evoke mechanical pain hypersensitivity. Taken together, our data suggested that intranasal OXT administration exerted analgesic and anxiolytic effects in incisional mice by opening BK(Ca) channels in the CA3 subregion of hippocampus.