Testosterone signaling pathways for reducing neuropathic pain in a rat model of spinothalamic tract lesion

Objective(s): Most individuals who suffer from spinal cord injury (SCI) experience neuropathic pain, which currently has no effective treatment. In this study, we examined how testosterone affects neuropathic pain resulting from SCI. Materials and Methods: We administered three different doses of testosterone (4, 8, 16 mg/kg, intraperitoneal) to male rats after an electrolytic lesion of the spinothalamic tract. We then conducted behavioral tests, including open field and von Frey tests, within 28 days post-SCI. On day 28 after SCI, we analyzed spinal tissue using western blot to measure the levels of ionized calcium binding adaptor molecule 1 (Iba1), glial fibrillary acidic protein (GFAP), phospho-extracellular signal-regulated kinase (p-ERK1/2), and p-P38 at the injury site. Results: The results showed that testosterone significantly improved both motor activity and mechanical allodynia compared to the SCI-only group. Testosterone also inhibited microglia and astrocyte activation. Furthermore, testosterone significantly decreased p-P38 and p-ERK levels.  Conclusion: The findings indicate that testosterone may alleviate SCI-induced neuropathic pain by inhibiting the activation of astrocytes and microglia, as well as suppressing MAPK signaling pathways.