A pharmacological rat model of recurrent pelvic pain exhibiting hyperalgesia and depression-like behaviors.

Primary dysmenorrhea (PDM) involves recurrent pelvic pain (RPP), alongside menstruation and psychological comorbidity, yet existing models inadequately capture its recurrent nature. In this study, we established a pharmacologically induced rat model of RPP, using estradiol benzoate and oxytocin over six 4-day cycles. The RPP model produced robust and sustained writhing responses, with writhing latency dropping from 30 to 4 min (p < 0.001) and scores rising to 88.30 (p = 0.002), alongside persistent hyperalgesia (reduced mechanical and thermal thresholds, p < 0.05). Depression-like behaviors were observed as longer immobility time (p = 0.032) and decreased sucrose preference (p = 0.012). Reduced serotonin with brain-derived neurotrophic factor (BDNF) overexpression was identified in the dorsal root ganglia and serum, along with metabolomic dysregulation of amino acid and arachidonic acid pathways. While not replicating full human PDM pathophysiology, this model captures core features of RPP and affective comorbidity, providing a translational platform for mechanistic and therapeutic research.