Oxytocin Elicits Itch Scratching Behavior via Spinal GRP/GRPR System

Abstract

Oxytocin (OT), a neuropeptide involved in the regulation of complex social and sexual behavior in mammals, has been proposed as a treatment for a number of psychiatric disorders including pain. It has been well documented that central administration of OT elicits strong scratching and grooming behaviors in rodents. However, these behaviors were only described as symptoms, few studies have investigated their underlying neural mechanisms. Thus, we readdressed this question and undertook an analysis of spinal circuits underlying OT-induced scratching behavior in the present study. We demonstrated that intrathecal OT induced robust but transient hindpaw scratching behaviors by activating spinal OT receptors (OTRs). Combining the pre-clinical and clinical evidence, we speculated that OT-induced scratching may be an itch symptom. Further RNAscope studies revealed that near 80% spinal GRP neurons expressed OTRs. OT activated the expression of c-fos mRNA in spinal GRP neurons. Chemical ablation of GRPR neurons significantly reduced intrathecal OT-induced scratching behaviors. Given GRP/GRPR pathway plays an important role in spinal itch transmission, we proposed that OT binds to the OTRs expressed on the GRP neurons, and activates GRP/GRPR pathway to trigger itch-scratching behaviors in mice. These findings provide novel evidence relevant for advancing understanding of OT-induced behavioral changes, which will be important for the development of OT-based drugs to treat a variety of psychiatric disorders.

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

“…In agreement with our ndings, Louis Hil ger's group and Jun Yang's group did not observe peripheral OXT-mediated analgesia in the physiological status [19],but Huang et al found that OXT exhibited peripheral analgesia after inferior alveolar nerve injury [32].The above results imply that the peripheral OXT analgesic effect may be mediated by the rise and activation of OXTR in nociceptors after PTX treatment. Given that the structures of OXT and arginine-vasopressin (AVP) as well as their receptors are similar, we investigated the analgesia of OXT under its antagonist and the analgesia of OXTR-speci c agonist TC OT 39, which is also vasopressin receptor antagonist [35]. We found that OXT-induced analgesia disappeared in the presence of OXTR antagonist and TC OT 39 mimicked its effects in PTX-treated mice.…”