Subtype-Specific Roles of Anterior Cingulate Cortex Neurons in Pain-Induced Social Deficits in Mice.

Rationale: Pain is frequently accompanied by impairments in social behavior; however, the neural circuitry underlying pain-induced social deficits remains poorly understood. The aim of the present study was to delineate the distinct functional roles of γ-aminobutyric acid-releasing (GABAergic) neurons and calcium/calmodulin-dependent protein kinase II-positive (CaMKII Methods: Mouse models of inflammatory and neuropathic pain were employed. Optogenetic and chemogenetic approaches, combined with fiber photometry, were used to manipulate and monitor the activity of ACC neuronal subtypes. Social behaviors were assessed using the three-chamber social interaction test. Mechanical and thermal pain sensitivity were evaluated using von Frey filaments and the Hargreaves test, respectively. Results: Mice with chronic pain exhibited deficits in social preference and novelty. Conclusions: Distinct ACC neuronal subtypes differentially regulate pain and social behaviors, revealing a functional "conflict" within the ACC whereby modulation of a single neuronal population cannot simultaneously ameliorate both pain and social deficits. These results underscore the necessity of circuit- and subtype-specific intervention strategies to disentangle and therapeutically target pain-related social deficit.