ANA-12靶向抑制BDNF/TrkB信号缓解奥沙利铂诱导化疗 大鼠的痛觉行为.

To investigate the effect and mechanism of ANA-12 on relieving oxaliplatin (OXA) induced neuropathic pain by targeting brain-derived neurotrophic factor (BDNF)/tyrosine kinase receptor B (TrkB) signaling in rats. Methods Eighteen male SD rats were randomly divided into 3 groups according to table of random number: the control group, the OXA treated group and the OXA + ANA-12 group (OXA+ANA-12), with 6 rats in each group. The OXA group and the OXA + ANA-12 group received an intraperitoneal injection of OXA (4 mg/kg for 5 days) to construct a chemotherapeutic pain model. After the model was successfully established, ANA-12 (20 g/L) was intrathecally administered in the OXA + ANA-12 group. After administration, pain behavior tests of rats in each group were performed, and changes in number of spontaneous flinches and mechanical pain threshold were recorded. The infiltration of spinal inflammatory cells and changes in expression level of interleukin (IL)-1β, tumor necrosis factor (TNF)-α, ionized calcium binding adapter molecule 1 (Iba1), BDNF, TrkB and nuclear factor kappa B (NF-κB) were detected by HE staining, immunofluorescence and Western blot assay. Results Compared with the control group, behavioral analysis showed that continuous injection of OXA significantly induced pain hyperalgesia and increased number of spontaneous flinches. Compared with the OXA group, intrathecal injection of ANA-12 significantly decreased the number of spontaneous flinches and increased mechanical pain threshold of rats. Morphological and protein expression analysis showed that OXA administration induced spinal inflammation, up-regulated BDNF/TrkB signaling and increased the expression levels of IL-1β, TNF-α, Iba1 and NF-κB compared with those of the control group. Compared with the OXA group, ANA-12 treatment significantly inhibited BDNF/ TrkB signaling and down-regulated the expression levels of IL-1β, TNF-α, Iba1 and NF-κB. Conclusion Intrathecal administration of ANA-12 inhibits spinal inflammation and relieves chemotherapy pain by blocking BDNF/TrkB signal. [ABSTRACT FROM AUTHOR]