SOCIAL EXPOSURE TO CHRONIC NEUROPATHIC PAIN INDUCES SEX-DEPENDENT BEHAVIORAL AND PHYSIOLOGICAL RESPONSES IN RATS

This study investigated sex-dependent behavioral, nociceptive, endocrine, and cardiovascular responses in rats cohabiting with a conspecific experiencing chronic constriction injury (CCI). Male and female Wistar rats (n = 5–11/group; CEUA n^o 22/2023) were housed in same-sex pairs for 28 days after weaning (PND21). After 13 days, baseline nociceptive thresholds were assessed using the electronic von Frey test. On day 14, one animal per pair underwent sciatic nerve constriction or sham surgery (demonstrator), while the paired rat remained unmanipulated (observer). On day 28, nociception was assessed in both demonstrator and observer animals, and anxiety-like and locomotor behaviors were evaluated in observers. Femoral artery cannulation was performed on day 29. On day 30, baseline and restraint reactivity of mean arterial pressure (MAP), heart rate (HR), tail skin temperature and circulating corticosterone were assessed. CCI induced mechanical pain hypersensitivity in demonstrator and observer rats of both sexes. Behavioral analyses revealed increased anxiety-like behavior in observers and sex-dependent alterations in open-field exploration, particularly in females. Observers of both sexes exhibited reduced body weight gain. Cardiovascular assessment showed increased baseline MAP in observers of both sexes, whereas HR exhibited sex-dependent modulation, with enhanced baseline values and attenuated restraint-induced tachycardic response in females. Baseline corticosterone levels were unchanged; however, restraint stress elicited an augmented corticosterone response in observers, particularly in females. Baseline tail skin temperature was reduced only in CCI males. These findings indicate that social exposure to chronic pain acts as a persistent stressor, eliciting sex-dependent multisystem dysfunctions.