Granulocyte Colony-Stimulating Factor Inhibits Pontine Astrogliosis and Induces Sciatic Remyelination In a Neuropathic Rat Model: Roles Of GFAP, PCNA And S100

Purpose: Neuropathic pain is characterized by poor treatment response. While previous studies on granulocyte colony-stimulating factor (GCSF) have primarily explored its effects on peripheral nerves, recent evidence suggests the central nervous system, particularly the brainstem pons, plays a crucial role in neuropathic pain modulation. This study investigated the effects of GCSF on the pons and sciatic nerve to alleviate neuropathic pain. Methods: Four groups of rats were created: the normal control, sham group, neuropathic group induced by chronic constriction injury of the sciatic nerve (CCI), and the GCSF-treated group received 50 μg/kg of GCSF subcutaneously starting on the 7th day of CCI for 5 consecutive days. Experimental testing for heat hyperalgesia, mechanical allodynia and mechanical hyperalgesia was performed. Immunohistochemical analyses were conducted to evaluate the central (pons) expression of glial fibrillary acidic protein (GFAP), proliferating cell nuclear antigen (PCNA), and S100 protein in the peripheral (sciatic nerve) tissues. Results: GCSF significantly alleviated heat hyperalgesia, mechanical allodynia, and mechanical hyperalgesia in CCI rats. In the pons, GCSF reduced GFAP expression, indicating inhibition of astrogliosis, and enhanced PCNA expression, suggesting promotion of neurogenesis. In the sciatic nerve, S100 expression was markedly elevated, implying enhanced remyelination. Conclusion: GCSF alleviates neuropathic pain not only by modulating peripheral nerve repair but also by inhibiting pontine astrogliosis and promoting central neuronal regeneration. These findings suggest GCSF may be a promising therapeutic agent for central and peripheral components of neuropathic pain.