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

TL;DR

A new rat model mimics chronic pelvic pain and depression, offering insights into pain mechanisms and treatment development.

Contribution

A pharmacological rat model captures recurrent pelvic pain and comorbid depression, with novel insights into BDNF and serotonin dysregulation.

Findings

The model shows sustained writhing responses and reduced pain thresholds, indicating hyperalgesia.

Depression-like behaviors were observed with increased immobility and reduced sucrose preference.

Metabolomic changes in amino acid and arachidonic acid pathways were identified in serum.

Abstract

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.

•Pharmacological rat model shows recurrent pelvic pain with hyperalgesia and depression•Peripheral BDNF and 5-HT dysregulation may underlie pain-depression comorbidity•Serum metabolomics reveal altered amino acid and lipid metabolism in chronic pain•This model provides a translational platform for chronic pelvic pain research

Pharmacological rat model shows recurrent pelvic pain with hyperalgesia and depression

Peripheral BDNF and 5-HT dysregulation may underlie pain-depression comorbidity

Serum metabolomics reveal altered amino acid and lipid metabolism in chronic pain

This model provides a translational platform for chronic pelvic pain research

Neuroscience; Behavioral neuroscience; Molecular biology; Omics

Figures