The Analgesic and Antidepressant Role of Oxytocin‐Containing Neurons in the Hypothalamic Paraventricular Nucleus in Mice With Spared Nerve Injury

Abstract Neuropathic pain is the debilitating chronic pain frequently comorbid with anxiety and depression. The mechanism and treatment strategy of neuropathic pain are to be elucidated. Oxytocin (OXT)‐containing neurons (simplified as OXT neurons) in the hypothalamic paraventricular nucleus (PVN) have been highlighted recently in the field of pain regulation and social function. But so far, the adaptive change and endogenous function of the neurons in neuropathic pain remain unclear. By immunofluorescent staining, we investigated the changes in FOSB expression in OXT neurons in the PVN with the development of neuropathic pain induced by spared nerve injury (SNI). The effect of neuronal activation on pain, as well as comorbid anxiety and depression, was subsequently assessed by chemogenetic manipulation. FOSB expression in the OXT neurons was significantly increased at 1 day and then gradually decreased at 7, 28, and 49 days after SNI. Activation of OXT neurons in the PVN by the OXT promoter‐directed hM3Dq virus or by the Cre‐loxP system in OXT‐Cre mice significantly improved the mechanical pain, cold pain, and depressive‐like behaviors in male and female mice, but exerted weak anxiolytic effects in female mice. These results demonstrate the altered activational status and the analgesic/antidepressant role of the OXT neurons in the PVN, thus providing a cellular‐based strategy for the comprehensive treatment of neuropathic pain.