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

Rationale: ) neurons in the anterior cingulate cortex (ACC) in mediating pain-induced social deficits. 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: ) neurons regulating both pain and pain-induced social preference deficits, and somatostatin-positive (SST⁺) neurons selectively mediating pain-induced social novelty deficits. These findings indicate that ACC neuronal subtypes exert complementary yet specialized roles in the comorbidity of pain and social deficits. 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.