Abstract: Abstract：Objective: In this study, we examined the hypothesis that chronic constrictive injury (CCI) of the sciatic nerve could promote spinal cord release of TNF-α and produce allodynia via the p38 MAPK pathway. Methods: SD rats were divided into five groups: 1) control rats, 2) sham surgery rats, 3) CCI surgery rats without treatment, 4) CCI surgery rats with saline treatment, and 5) CCI surgery rats with the p38 inhibitor SB203580 treatment. In treatment groups, saline or SB203580 was given intrathecally starting 1 day before or 1 day or 7 days after CCI. All rats were killed at different times after surgery to examine p38 activity and TNF-α levels in the spinal cord by Western blot analysis or immunohistochemistry. Mechanical allodynia was tested by a series of von Frey hairs 3, 7, and 14 days after surgery. Results p-p38was significantly increased at 3, 7, and 14 days after CCI surgery compared with time-matched shams (P <0.05). Peripheral nerve injury induced mechanical allodynia and enhanced spinal concentrations of TNF-α (P<0.05). Pretreatment or early treatment with SB203580 inhibited p38 activity, resulting in reduction of TNF-α synthesis and attenuation of mechanical allodynia (P< 0.05). Conclusion: p38 activation is one aspect of the signaling cascade that culminates in TNF-α synthesis and contributes to mechanical allodynia after peripheral nerve injury.

Key words: Neuropathic Pain, p38MAPK, TNF-α, Spinal