Tuina Manipulation Alleviates Neuropathic Pain in Cervical Spondylotic Radiculopathy via PPARγ/Nrf2/HO-1 Pathway-Mediated Microglial Polarization Modulation

Background Neuropathic pain in cervical spondylotic radiculopathy (CSR) is closely associated with spinal microglial activation and neuroinflammation. Tuina manipulation is clinically effective for CSR, but its antinociceptive mechanisms remain unclear. This study investigated whether tuina alleviates neuropathic pain in CSR rats via PPARγ/Nrf2/HO-1 pathway-mediated microglial modulation. Methods A CSR neuropathic pain model was established in rats and divided into Control, Model, TN, MI, and TN + MI groups. Mechanical withdrawal threshold (PWMT) and paw withdrawal thermal latency (PWTL) were used to assess pain hypersensitivity. ELISA determined IL-10, TGF-β, and TNF-α levels in the ipsilateral dorsal horn. Microglial activation was evaluated by CD11b immunofluorescence. Western blotting and qRT-PCR were performed to detect PPARγ, Nrf2, and HO-1 protein and mRNA expression. Results Compared with the Control group, Model rats showed decreased PWMT and PWTL, reduced IL-10 and TGF-β, elevated TNF-α, enhanced CD11b intensity, and down-regulated PPARγ, Nrf2, and HO-1 at both protein and mRNA levels (all P < 0.01). TN and MI each significantly improved pain behaviors, partially restored IL-10 and TGF-β, reduced TNF-α, attenuated CD11b expression, and upregulated PPARγ/Nrf2/HO-1 versus the Model group (P < 0.05). TN + MI produced more pronounced effects on all behavioral, inflammatory, and molecular indices (P < 0.01), approaching Control values. Conclusion Tuina manipulation significantly alleviates mechanical and thermal hyperalgesia in CSR rats, likely by inhibiting microglial activation and shifting toward an anti-inflammatory phenotype through activation of the PPARγ/Nrf2/HO-1 pathway. When combined with microglial modulation, Tuina produces more pronounced antinociceptive and neuroprotective effects.