Dr. Pomberger’s Research

Beyond Opioids: Neural Circuits of Socially Induced Pain Relief

Abstract: Chronic pain affects more than 30% of people worldwide and is a leading cause of disability. Opioids carry serious risks of dependence and overdose and have driven a public-health crisis, while non-opioid analgesic strategies remain underdeveloped. Social context is one of the most powerful, underutilized levers in pain modulation: a supportive partner reduces pain intensity, opioid use, and negative affect. Yet the neural circuits that translate social signals into clinically meaningful pain relief are unknown. This proposal leverages a validated mouse model of socially induced analgesia, in which a complete Freund’s adjuvant (CFA)-injected bystander, after a brief interaction with a CFA + morphine partner, acquires durable, opioid-independent pain relief. We test the hypothesis that social analgesia is implemented by two dissociable circuits: a vlPAG–RVM descending arm suppressing the sensory component of pain via endogenous opioids, and a dorsal raphe (DRN) serotonergic arm projecting to the anterior cingulate (ACC) and nucleus accumbens (NAc) that suppresses the affective component. Aim 1 uses miniscope calcium imaging of projection-defined vlPAG–RVM, DRN–ACC, and DRN–NAc neurons during social analgesia. Aim 2 uses bidirectional optogenetics to test the necessity and sufficiency of vlPAG and vlPAG–RVM signaling for the sensory component. Aim 3 uses projection-specific manipulation of DRN–ACC and DRN–NAc 5-HT terminals in ePet-Cre mice to test their role in the affective component.

Relevance to anesthesiology: By dissociating the sensory and affective arms of social analgesia, this work identifies the affective dimension of pain as a serotonergically tractable target, providing rationale for non-opioid adjuncts (SSRIs, SNRIs, 5-HT2 compounds, MDMA-class agents) in multimodal perioperative care and a foundation for opioid-sparing strategies—directly aligned with the IARS mission to improve outcomes in anesthesia, perioperative care, and pain management.