The GLP-1 receptor herbal agonist morroniside attenuates neuropathic pain via spinal microglial expression of IL-10 and β-endorphin.

Objectives: To assess the protective effect of the glucagon-like peptide-1 receptor (GLP-1R) agonist morroniside against neuropathic pain and its downstream mechanisms of activating microglial GLP-1R/interleukin-10 (IL-10)/β-endorphin antinociceptive pathway.

Methods: Spinal nerve ligation-induced neuropathic pain rats were intrathecally injected with morroniside, with mechanical paw withdrawal threshold being assessed. The expression of spinal and cultured microglia IL-10 and β-endorphin were detected with qRT-PCR. Key findings: Morroniside alleviated mechanical allodynia in neuropathic rats, which was blocked by inhibiting or depleting microglia. In addition, neutralizing spinal IL-10 or β-endorphin with specialized antibodies or blocking the μ-opioid receptor was able to fully reverse the morroniside-induced mechanical antiallodynia. Morroniside treatment stimulated the gene expression of IL-10 and β-endorphin in the spinal lumbar enlargements of neuropathic rats as well as in primary cultured microglia. Furthermore, pretreatment with the IL-10 antibody blocked morroniside-stimulated β-endorphin expression in the spinal cords of neuropathic rats and cultured primary microglia, whereas the β-endorphin antibody failed to affect morroniside-stimulated gene expression of IL-10.

Conclusions: These results reveal that morroniside produces therapeutic effects in neuropathy through spinal microglial expression of IL-10 and subsequent β-endorphin after activation of GLP-1R.