High-intensity interval training relieves osteoarthritis-induced neuropathic pain through promoting the polarization of M1 to M2 in microglia via the Jak2/Stat3 pathway in rats

Abstract

Objective: Osteoarthritis (OA)-induced neuropathic pain is closely related to microglial polarization in the central nervous system. This study aimed to determine whether high-intensity interval training (HIIT) could relieve neuropathic pain and promote the polarization of M1 to M2 in microglia through the Jak2/Stat3 pathway in OA rats. Methods: Wistar rats received intra-articular injection of monosodium iodoacetate for an OA model. After four weeks, moderate-intensity continuous training (MICT) or HIIT was conducted consecutively for six weeks. Pain threshold was measured by the von Frey test. The degree of cartilage damage was analyzed by magnetic resonance imaging and safranin-O staining. Tmem119, substance P (SP), Vglut2, c-Fos, and IL6 were detected by immunofluorescence. The CD68 and CD163 were analyzed by flow cytometry. The proteomics sequencing and quantitative real-time polymerase chain reaction analyzed the differences in protein and mRNA expression levels between MICT and HIIT groups. Intraperitoneal injection of C-A1 activated the Jak2/Stat3 pathway in OA rats, followed by HIIT treatment, and pain neurotransmitters were detected by Western blotting. Results: The pain threshold was significantly decreased from third weeks to tenth weeks in OA rats. HIIT treatment promoted the polarization of M1 to M2 in microglia and down-regulated Tmem119, SP, Vglut2, c-Fos, and IL6. Moreover, HIIT suppressed Jak2 and Stat3 expression levels when compared with MICT rats. The pain threshold and pain neurotransmitters were lower in C-A1+HIIT rats than in C-A1 rats. Conclusions: HIIT relieves OA-induced neuropathic pain and promotes the polarization of M1 to M2 in microglia through the Jak2/Stat3 pathway.