Spinal dorsal horn IGF1 mediates the preventive effect of electroacupuncture on cisplatin-induced peripheral neuropathy via neuronal IGF1R in mice
Abstract
Background: Our previous study demonstrated that neuronal G protein-coupled receptor kinase (GRK2) upregulation alleviated chemotherapy-induced peripheral neuropathy (CIPN) in mice, which was characterized by numbness and pain in distal hind limbs. The neuronal GRK2 was identified as a mediator of electroacupuncture (EA) effects on CIPN. Given that spinal insulin-like growth factor 1 (IGF1), a known inducer of GRK2 in the peripheral neurons, decreases after oxaliplatin treatment in mice, this study is designed to investigate whether spinal IGF1 contributes to EA-mediated prevention of cisplatin-induced peripheral neuropathy via neuronal IGF1 receptor (IGF1R).
Methods: A total of 133 male C57BL/6 J mice were included in this study and randomly assigned to different experimental groups. The level of Igf1 mRNA was detected by Real-time PCR, the p-IGF1R protein level by Western blot, after EA treatment in cisplatin-treated mice. The cellular distribution of p-IGF1R in the spinal dorsal horn was observed by immunofluorescent staining. To study the role of neuronal IGF1R in EA preventing cisplatin-induced mechanical allodynia, sensory deficit, and microglia activation and neuroinflammation in the spinal cord of mice, the neuronal IGF1R was downregulated by intraspinal injection of an AAV vector delivering IGF1R shRNA with hSyn promotor (AAV-shIGF1R). Finally, the regulatory effect of EA on spinal GRK2 was assessed by Western blot in AAV-shIGF1R mice.
Results: Cisplatin treatment…
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