This research investigated the potential therapeutic role of α-(phenylselanyl) acetophenone (PSAP) in the comorbidity of chronic pain and depression triggered by partial sciatic nerve ligation (PSNL). Male Swiss mice underwent PSNL surgery, and after a four-week period, they received either PSAP (1–50 mg/kg, administered intragastrically) or imipramine (IMI) (50 mg/kg) 30 minutes prior to behavioral assessments. Both PSAP and IMI effectively alleviated PSNL-induced hypersensitivity to pain and depressive-like symptoms, as demonstrated in forced swim and allodynia tests. Additionally, PSAP counteracted the elevated levels of lipid peroxidation and reactive oxygen species observed in the cortex and hippocampus following PSNL. These neuroprotective effects appear to be linked to PSAP’s anti-inflammatory properties, as it downregulated the expression of pro-inflammatory markers such as NF-κB p65, TNF-α, and IDO mRNA in the affected brain regions. Furthermore, PSAP restored hippocampal BDNF mRNA levels, which had been diminished by nerve injury. Since inflammation is a common pathway in both chronic pain and depression, the findings indicate that PSAP holds promise as a treatment for this comorbid condition. • PSAP alleviates pain hypersensitivity and depressive-like symptoms in PSNL mice • PSAP reduces cortical and hippocampal lipid peroxidation and ROS levels • PSAP downregulates NF-κB, TNF-α, and IDO mRNA expression • PSAP restores hippocampal BDNF mRNA diminished by sciatic nerve injury • Findings support PSAP as a candidate therapy for pain–depression comorbidity
Sousa et al. (Sun,) studied this question.