ANA- 12 inhibits spinal inflammation and alleviates acute and chronic pain in rats by targeted blocking of BDNF/TrkB signaling].

J Zhao, H Yang, Z Wang, H Zhu, M Xie

Nan fang yi ke da xue xue bao = Journal of Southern Medical University 2022 Feb 20

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To investigate the inhibitory effect of ANA-12 that blocks brain-derived neurotrophic factor (BDNF)/ tropomyosin receptor kinase B (TrkB) signaling on inflammatory pain in rats and explore the underlying mechanism. Forty-two adult SD rats were randomized into BDNF-induced acute pain group (n=24) and CFA-induced chronic pain group. The former group were randomly divided into 4 subgroups, including a control group, ANA-12 treatment group, BDNF treatment group, and BDNF+ANA-12 treatment group; the latter group were subgrouped into control group, CFA treatment group (CFA) and CFA + ANA-12 treatment group. The effects of ANA-12 treatment on pain behaviors of the rats with BDNF-induced acute pain and CFA-induced chronic inflammatory pain were observed. Western blotting was used to examine TrkB signaling and expressions of microglia marker protein Iba1 and TNF-α in the spinal cord of the rats. BDNF injection into the subarachnoid space significantly increased the number of spontaneous paw withdrawal of the rats (P < 0.05), which was obviously reduced by ANA-12 treatment (P < 0.05). The rats with intraplantar injection of CFA, showed significantly increased ipsilateral mechanical stimulation sensitivity (P < 0.05), and ANA-12 treatment obviously increased the ipsilateral foot withdrawal threshold (P < 0.05). Treatment with either BDNF or CFA significantly increased the phosphorylation level of TrkB (Y705) in the spinal cord of the rats (P < 0.05), which was significantly lowered by ANA-12 treatment (P < 0.05). Treatment with BDNF and CFA both significantly up-regulated the expressions of Iba1 and TNF-α in the spinal cord (P < 0.05), but ANA-12 significantly reduced their expression levels (P < 0.05). ANA-12 can reduce spinal cord inflammation and relieve acute and chronic pain in rats by targeted blocking of BDNF/TrkB signaling.

Citation

J Zhao, H Yang, Z Wang, H Zhu, M Xie. ANA- 12 inhibits spinal inflammation and alleviates acute and chronic pain in rats by targeted blocking of BDNF/TrkB signaling]. Nan fang yi ke da xue xue bao = Journal of Southern Medical University. 2022 Feb 20;42(2):232-237