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-1β (IL-1β),
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-1β
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.