PDGFR-α Mediated the Neuroinflammation and Autophagy via the JAK2/STAT3 Signaling Pathway Contributing to Depression-Like Behaviors in Myofascial Pain Syndrome Rats

Depression often occurs in patients with additional co-morbidities, particularly in cases of chronic pain. Currently, there is a lack of research on the molecular mechanisms of depression under chronic pain conditions and suitable animal models. Due to the contradiction exhibited by platelet-derived growth factor receptor (PDGF/PDGFR) in neuroprotection, further investigation is required. In the present study, we investigated the roles of PDGFR-alpha in the hippocampus based on rat models of chronic pain (myofascial pain syndrome, MPS) that exhibited depressive phenotypes. The depression-like phenotypes were assessed by the sucrose preference test, forced swimming test, tail suspension test, and the levels of BDNF and 5HT1AR. Electron microscopic analysis and altered expression of autophagy-related proteins revealed reduced autophagy levels in the hippocampus of MPS rats. Phosphorylation PDGFR-alpha was significantly upregulated in the MPS rat model of depression, as well as the levels of inflammatory factors and p-JAK2/p-STAT3. Treatment with inhibitors of PDGFR-alpha or JAK2/STAT3 alleviated depressive behaviors, Nissl bodies staining, increased the protein levels of BDNF and 5HT1AR, and decreased the levels of inflammatory factors in MPS rats. Additionally, it restored autophagy levels. These results indicate that PDGFR-alpha induces neuroinflammation, altered autophagy, and depressive behavior, potentially mediated by the JAK2/STAT3 signaling pathway in MPS rats. PDGFR-alpha may thus represent a promising therapeutic target for the treatment of this type of depression.