Journal of Pain Research (Jul 2020)
The Interaction Between Spinal PDGFRβ and μ Opioid Receptor in the Activation of Microglia in Morphine-Tolerant Rats
Abstract
Zheng Li, Xiaoqian Jia, Xiaoling Peng, Feng Gao Department of Anesthesiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of ChinaCorrespondence: Feng GaoDepartment of Anesthesiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Ave, Wuhan 430030, People’s Republic of ChinaEmail [email protected]: Opioid tolerance remains a challenging problem, which limits prolonged drug usage in clinics. Previous studies have shown a fundamental role of platelet-derived growth factor receptor β submit (PDGFRβ) in morphine tolerance. The aim of this study was to investigate the mechanisms of spinal PDGFRβ activation in morphine tolerance.Methods: Rats were treated with morphine for 7 days and the effect of drug was evaluated by tail-flick latency test. By using Western blot and real-time PCR, the interaction between μ opioid receptor (MOR) and PDGFRβ in microglia activation, as well as related signaling pathways during morphine tolerance were investigated.Results: Chronic PDGFRβ agonist could induce microglia activation in spinal cord and decrease the analgesic effect of morphine. PDGFRβ inhibitor suppressed microglia activation during the development of morphine tolerance. Furthermore, antagonizing MOR could effectively inhibit the phosphorylations of PDGFRβ and JNK. Blocking PDGFRβ had no influence on JNK signaling, while JNK inhibitor could decrease the phosphorylation of PDGFRβ.Conclusion: These results provide direct evidence that repeatedly activating MOR by morphine could induce the transactivation of PDGFRβ via JNK MAPK in spinal cord, which leads to microglia activation during the development of morphine tolerance.Keywords: mu opioid receptor, platelet-derived growth factor receptor β, microglia, JNK signaling, morphine tolerance
