4.7 Article

Sciatic nerve block downregulates the BDNF pathway to alleviate the neonatal incision-induced exaggeration of incisional pain via decreasing microglial activation

期刊

BRAIN BEHAVIOR AND IMMUNITY
卷 105, 期 -, 页码 204-224

出版社

ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbi.2022.07.010

关键词

Sciatic nerve block; Microglia; Incisional pain; Neonate; Brain-derived neurotrophic factor (BDNF); Src homology-2 domain-containing protein; tyrosine phosphatase-2 (SHP2); GluA1

资金

  1. National Natural Science Foundation of China [81500942]
  2. Beijing Talents Fund [2015000021469G204]
  3. Scientific Research Cultivation Fund of Capital Medical Uni-versity [PYZ19030]

向作者/读者索取更多资源

Sciatic nerve block can alleviate pain hypersensitivity and microglial activation in rats subjected to neonatal and adult incision. Decreased activation of spinal microglia contributes to the beneficial effects of sciatic nerve block on the exaggerated incisional pain induced by neonatal incision.
Sciatic nerve block is under investigation as a possible therapeutic strategy for neonatal injury-induced exag-geration of pain responses to reinjury. Spinal microglial priming, brain-derived neurotrophic factor (BDNF) and Src homology-2 domain-containing protein tyrosine phosphatase-2 (SHP2) participate in exaggerated incisional pain induced by neonatal incision. However, effects of sciatic nerve block on exacerbated incisional pain and underlying mechanisms remain unclear. Here, we demonstrated that sciatic nerve block alleviates pain hyper-sensitivity and microglial activation in rats subjected to neonatal incision and adult incision (nIN-IN). Chemo-genetic activation or inhibition of spinal microglia attenuates or mimics effects of sciatic nerve block on pain hypersensitivity, respectively. Moreover, alpha-amino-3-hydroxy- 5-methy-4-isoxazole propionate (AMPA) receptor subunit GluA1 contributes to the exaggeration of incisional pain. The inhibition of BDNF or SHP2 blocks upregulations of downstream molecules in nIN-IN rats. Knockdown of SHP2 attenuates the increase of GluA1 induced by injection of BDNF in adult rats with only neonatal incision. The inhibition of microglia or ablation of microglial BDNF attenuates upregulations of SHP2 and GluA1. Additionally, sciatic nerve block downregulates the expression of these three molecules. Upregulation of BDNF, SHP2 or AMPA receptor attenuates sciatic nerve block-induced reductions of downstream molecules and pain hypersensitivity. Microglial activation abrogates reductions of these three molecules induced by sciatic nerve block. These results suggest that decreased acti-vation of spinal microglia contributes to beneficial effects of sciatic nerve block on the neonatal incision-induced exaggeration of incisional pain via downregulating BDNF/SHP2/GluA1-containing AMPA receptor signaling. Thus, sciatic nerve block may be a promising therapy.

作者

我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。

评论

主要评分

4.7
评分不足

次要评分

新颖性
-
重要性
-
科学严谨性
-
评价这篇论文

推荐

暂无数据
暂无数据