Andrographolide Inhibits Mechanical and Thermal Hyperalgesia in a Rat Model of HIV-Induced Neuropathic Pain.

Aim: In this study, we investigated whether andrographolide (Andro) can alleviate neuropathic pain induced by HIV gp120 plus ddC treatment and the mechanism of its action. Methods: The paw withdrawal threshold and the paw withdrawal latency were observed to assess pain behaviors in all groups of the rats, including control group, control combined with Andro treatment group, sham group, gp120 combined with ddC treatment group, gp120 plus ddC combined with A438079 treatment group, and gp120 plus ddC combined with Andro treatment by intrathecally injecting at a dose of 25 µg/20 µl group. The protein expression levels of the P2X7 receptor, tumor necrosis factor-α-receptor (TNFα-R), interleukin-1ß (IL-1ß), IL-10, phospho-extracellular regulated protein kinases (ERK) (p-ERK) in the L4-L6 dorsal root ganglia (DRG) were measured by western blotting. Real-time quantitative polymerase chain reaction was used to test the mRNA expression level of the P2X7 receptor. Double-labeling immunofluorescence was used to identify the co-localization of the P2X7 receptor with glial fibrillary acidic protein (GFAP) in DRG. Molecular docking was performed to identify whether the Andro interacted perfectly with the rat P2X7 (rP2X7) receptor. Results: Andro attenuated the mechanical and thermal hyperalgesia in gp120+ddC-treated rats and down-regulated the P2X7 receptor mRNA and protein expression in the L4-L6 DRGs of gp120+ddC-treated rats. Additionally, Andro simultaneously decreased the expression of TNFα-R and IL-1ß protein, increased the expression of IL-10 protein in L4-L6 DRGs, and inhibited the activation of ERK signaling pathways. Moreover, Andro decreased the co-expression of GFAP and the P2X7 receptor in the SGCs of L4-L6 DRG on 14th day after surgery. Conclusion: Andro decreased the hyperalgesia induced by gp120 plus ddC.