FIGURE 11.

Schematic diagram depicting the role of bile acids in SNI‐induced neuropathic pain. (1) SNI induced multiple changes in the spinal dorsal horn, including decreased levels of bile acids, upregulated expression of TGR5/FXR, activated microglia/astrocytes and phosphorylated ERK in neurons, and downregulated expression of GABA_A receptor δ subunit. All these changes contributed to the maintenance of neuropathic pain. (2) Intrathecal injection of TGR5 or an FXR agonist alleviated neuropathic pain (pain relieved) by decreasing microglial and astrocyte activation and ERK phosphorylation in the spinal dorsal horn. (3) Effect of TGR5 or the FXR agonist on inhibition of glial cells and ERK pathway was abolished by bicuculline. Therefore, pain was aggravated.