SEX-DEPENDENT EFFECTS OF EARLY LIFE ADVERSITY AND NEUROPATHIC PAIN ON ANXIETY-RELATED BEHAVIOR IN MICE

Early life adversity increases vulnerability to anxiety disorders and chronic pain, yet how these factors interact across behavioral domains and sexes remains unclear. Here, we investigated the combined effects of early social isolation and neuropathic pain on pain sensitivity, anxiety-like behavior, social interaction, and alcohol intake in mice.
Male and female mice were exposed to early social isolation from PND 21, followed by spared nerve injury or sham surgery in adulthood. Mechanical sensitivity was assessed longitudinally using the von Frey test. Anxiety-like behavior was evaluated with the Open-Field, Light–Dark Box, and Novelty Suppressed Feeding Test. Social behavior was measured using social interaction and three-chamber tests, while alcohol intake was assessed with a two-bottle choice paradigm.
SNI induced a robust mechanical hypersensitivity that was not further exacerbated by early social isolation. Open Field and Light–Dark Box performance revealed no significant group differences in either sex. In contrast, the NSFT uncovered a sex-specific effect: females exposed to early social isolation, both with and without neuropathic pain, showed a significantly increased latency to feed, indicating enhanced anxiety-like behavior. Social interaction and social novelty preference were largely preserved across groups, with only subtle alterations observed in isolated females following SNI. Alcohol intake assessment is ongoing.
Overall, these findings demonstrate that early life adversity selectively affects anxiety-related behavior in a sex-dependent manner, while pain hypersensitivity remains largely independent of early social experience. This highlights the importance of sex-specific vulnerability and task sensitivity when modeling the long-term consequences of early adversity and chronic pain.