Abstract:

Objective To investigate the role of cAMP/PKA signaling pathway in docetaxel（DTX）⁃ induced neuropathic pain. Methods The rat model of chemotherapy⁃induced neuropathic pain was constructed by injecting DTX via tail vein，and PKA inhibitor H⁃89 and PKA agonist SP⁃CAMP were used for intervention. The mechanical withdrawal threshold（MWT）and thermal withdrawal latency（MWT）were measured by behavioral test. The content of cAMP in dorsal root ganglion and the level of IL⁃1β，IL⁃6 and TNF⁃α in spinal cord was detected by ELISA. The expression of astrocyte activation marker GFAP in rat spinal cord was observed by Immunofluores⁃ cence. The protein expression of cAMP/PKA signaling pathway was detected by Western blot. Results Intervention with H⁃89 significantly increased the value of MWT and TWL in model rats（P < 0.05），but decreased the protein expression level of phospho⁃cAMP⁃response element binding protein（p⁃CREB）and PKAc，as well as the level of IL⁃1β，IL⁃6 and TNF⁃α and the mean fluorescence intensity of GFAP（P < 0.05），while SP⁃CAMP intervention showed the opposite effect，but both had no significant effect on the content of cAMP in the dorsal root ganglia （P > 0.05）. Conclusions Inhibition of cAMP/PKA signaling pathway can improve DTX⁃induced neuropathic pain in rats，and the mechanism may be related to inhibition of astrocyte activation and the reduction of inflammatory factor release

Key words:

cAMP/PKA signaling pathway, docetaxel, neuropathic pain, astrocyte ,