The aqueous extract of Armadillidium vulgare Latreille alleviates neuropathic pain via inhibiting neuron-astrocyte crosstalk mediated by the IL-12-IFN-γ-IFNGR-CXCL10 pathway.

Abstract

Ethnopharmacological relevance: Armadillidium vulgare Latreille (AV), the dried body of pillbug, was originally described in Shennong's Classic of Materia Medica. As a common analgesic in animal-based traditional Chinese medicine, it is mainly used to relieve pain, promoting diuresis, relieving fatigue and so on. Our work demonstrated that AV could alleviate various types of acute and chronic pain including neuropathic pain (NP). And transcriptome sequencing analysis revealed that AV could suppress CXCL10 to alleviate NP, however, the upstream mechanisms governing CXCL10 synthesis remain vague.

Aim of the study: The research's goal was to identify the mechanism via which AV regulates CXCL10 to ameliorate NP.

Materials and methods: Chronic constriction injury (CCI) to the sciatic nerve was used to induce the NP model 14 days following surgery. To identify cell signaling pathways, various approaches were used, including transcriptome sequencing, western blotting, immunofluorescence, as well as ELISA. The in vitro assay involved the cultivation of neuron PC12 cells and astrocyte C6 cells.

Results: Both in vivo and in vitro results demonstrated that IL-12/IL-18 enhanced IFN-γ production in spinal neurons, which acted on IFN-γ receptors on neurons and astrocytes to upregulate CXCL10 expression in these cells, illustrating the pivotal role of IL-12 in the crosstalk between neurons and astrocytes. The role of IL-12 in pain regulation was elucidated for the first time within the nervous system. Additionally, its synergistic interaction with IL-18 on the downstream IFN-γ-CXCL10 pathway dramatically altered the activation of neurons and astrocytes. And AV could suppress CXCL10 to alleviate NP by mediating the IL-12-IFN-γ-IFNGR signaling pathway.

Conclusions: We explored a new target for NP by regulating neuron-astrocyte crosstalk and provided a theoretical basis for AV in clinical use.