Upregulation of the oxytocin receptor in dorsal root ganglion mediated peripheral analgesia of oxytocin in chemotherapy-induced peripheral neuropathic pain

Abstract

Background: Currently, chemotherapy-induced peripheral neuropathic pain (CIPNP) has no effective treatment. Oxytocin (OXT) and the oxytocin receptor (OXTR) play roles in central analgesia. However, the expression and role of OXTR in the peripheral nervous system in CIPNP remain unclear. Here, we studied the peripheral analgesic profiles of OXTR and related mechanisms in CIPNP pain models.Methods: The chemotherapeutic agent paclitaxel (PTX) was used to establish CIPNP. qRT-PCR, fluorescent in situ hybridization, western blotting, and immunocytochemistry were used to observe the properties of OXTR expression in dorsal root ganglion (DRG). The analgesic effects were assessed by the hot plate and the Von Frey tests. The whole-cell patch-clamp was performed to record the effects of the OXTR activation on the excitability of DRG neurons and the excitatory transmissions from the primary afferents to the spinal cord.Results: The expression of OXTR in DRG neurons was boosted significantly after PTX treatment, which is rarely expressed in the vehicle group without sex difference. The activation of OXTR exhibited analgesic effects and decreased the excitability of DRG neurons. Additionally, the OXTR activation impaired the voltage-gated sodium current through the PLC/PKC pathway. Oxytocin also suppressed the excitatory transmission in the spinal dorsal horn and the excitatory inputs from the primary afferents in PTX-treated mice.Conclusions: Paclitaxel upregulates the expression of OXTR in DRG neurons. This upregulation leads to effective analgesic effects of peripheral oxytocin which is mediated by the reduction of the excitability of DRG neurons and the excitatory transmission in the spinal dorsal horn. Our results suggested that OXTR on peripheral sensory neurons can be utilized to relieve CIPNP.