PROJECT: JTC2024 - Brain-Body: PainSociOT

Our overarching aim is to explore the bidirectional interplay between socio-emotional states and chronic pain and decipher the role of oxytocin (OT) in modulating this interplay. We plan to use state-of-the-art chemogenetic, optogenetic and electrophysiological techniques to probe the effect of various socio-emotional states and OT release in several stations of the brain's pain matrix. Moreover, using cutting-edge behavioral assays we will explore the effect of chronic pain on social behavior and vice versa and how these effects are modulated by OT. As a model for chronic pain in rodents we will use Spare Nerve Injury (SNI) in rats in all animal studies of the proposal. Finally, we plan to examine the link between human oxytocin genetic variants and pain. Impact: We will reveal precise mechanisms underlying the analgesic action of OT as well as its interplay on socio-emotional states in brain region-specific manner along the pain matrix. Furthermore, we aim to discover the link between OT signaling and chronic pain (e.g. oxytocin-pain polygenic score) in human patients and will test this in rodents using optimal OT analogues passing through the blood brain barrier, which can be further applied in clinic to treat chronic pain. Therefore, although our proposal uses mainly animal models, it carries translational value regarding the prospect of treating chronic pain and its psychiatric symptoms with a combination OT-related pharmacology and social behavior interventions.