Exercise training modulates glutamic acid decarboxylase-65/67 expression through TrkB signaling to ameliorate neuropathic pain in rats with spinal cord injury
Exercise training modulates glutamic acid decarboxylase-65/67 expression through TrkB signaling to ameliorate neuropathic pain in rats with spinal cord injury
复制标题
运动训练通过 TrkB 信号调节谷氨酸脱羧酶 65/67 表达，改善脊髓损伤大鼠的神经病理性疼痛
DOI：
10.1177/1744806920924511
复制
发表时间：
2020-05-01
期刊：
影响因子：
3.3
通讯作者：
Wu, Qinfeng
中科院分区：
文献类型：
--
作者：
Li, Xiangzhe;Wang, Qinghua;Wu, Qinfeng
神经性疼痛是脊髓损伤后最常见的并发症之一。脊髓损伤后，远端脊髓内γ氨基丁酸合成减少是神经性疼痛的主要原因之一。本研究的主要研究问题是，运动训练是否通过原肌球蛋白相关激酶B信号传导促进脊髓远端γ氨基丁酸合成的关键酶谷氨酸脱羧酶-65和谷氨酸脱羧酶-67的表达，其合成有助于缓解脊髓损伤后神经性疼痛。进行动物实验，将所有大鼠分为Sham组、SCI/PBS组、SCI- tt /PBS组、SCI/原肌球蛋白相关激酶B- igg组、SCI- tt /原肌球蛋白相关激酶B- igg组，制作T10挫伤性脊髓损伤模型，并用原肌球蛋白相关激酶B- igg阻断原肌球蛋白相关激酶B的活化。机械戒断阈值和热戒断潜伏期用于评估疼痛相关行为。Western blot检测脊髓远端脑源性神经营养因子、原肌球蛋白相关激酶B、CREB、p-REB、谷氨酸脱羧酶-65、谷氨酸脱羧酶-67的表达。免疫组化分析脊髓背角远端CREB、p-CREB、谷氨酸脱羧酶-65、谷氨酸脱羧酶-67的分布。结果表明，运动训练可显著减轻脊髓损伤后机械性异常痛和热痛觉过敏，增加脊髓远端脑源性神经营养因子、原肌球蛋白相关激酶B、CREB、p-CREB、谷氨酸脱羧酶-65和谷氨酸脱羧酶-67的合成。原肌球蛋白相关激酶B信号被阻断后，运动训练的镇痛作用被抑制，SCI-TT/原肌球蛋白相关激酶B- igg组脊髓远端CREB、p-CREB、谷氨酸脱羧酶-65、谷氨酸脱羧酶-67的合成也较SCI-TT/PBS组明显减少。本研究表明，运动训练可通过原肌球蛋白相关激酶B信号通路增加脊髓背角内谷氨酸脱羧酶-65和谷氨酸脱羧酶-67的表达，该机制可能在缓解不完全性脊髓损伤大鼠神经性疼痛中发挥重要作用。
Neuropathic pain is one of the most frequently stated complications after spinal cord injury. In post-spinal cord injury, the decrease of gamma aminobutyric acid synthesis within the distal spinal cord is one of the main causes of neuropathic pain. The predominant research question of this study was whether exercise training may promote the expression of glutamic acid decarboxylase-65 and glutamic acid decarboxylase-67, which are key enzymes of gamma aminobutyric acid synthesis, within the distal spinal cord through tropomyosin-related kinase B signaling, as its synthesis assists to relieve neuropathic pain after spinal cord injury. Animal experiment was conducted, and all rats were allocated into five groups: Sham group, SCI/PBS group, SCI-TT/PBS group, SCI/tropomyosin-related kinase B-IgG group, and SCI-TT/tropomyosin-related kinase B-IgG group, and then T10 contusion SCI model was performed as well as the tropomyosin-related kinase B-IgG was used to block the tropomyosin-related kinase B activation. Mechanical withdrawal thresholds and thermal withdrawal latencies were used for assessing pain-related behaviors. Western blot analysis was used to detect the expression of brain-derived neurotrophic factor, tropomyosin-related kinase B, CREB, p-REB, glutamic acid decarboxylase-65, and glutamic acid decarboxylase-67 within the distal spinal cord. Immunohistochemistry was used to analyze the distribution of CREB, p-CREB, glutamic acid decarboxylase-65, and glutamic acid decarboxylase-67 within the distal spinal cord dorsal horn. The results showed that exercise training could significantly mitigate the mechanical allodynia and thermal hyperalgesia in post-spinal cord injury and increase the synthesis of brain-derived neurotrophic factor, tropomyosin-related kinase B, CREB, p-CREB, glutamic acid decarboxylase-65, and glutamic acid decarboxylase-67 within the distal spinal cord. After the tropomyosin-related kinase B signaling was blocked, the analgesic effect of exercise training was inhibited, and in the SCI-TT/tropomyosin-related kinase B-IgG group, the synthesis of CREB, p-CREB, glutamic acid decarboxylase-65, and glutamic acid decarboxylase-67 within the distal spinal cord were also significantly reduced compared with the SCI-TT/PBS group. This study shows that exercise training may increase the glutamic acid decarboxylase-65 and glutamic acid decarboxylase-67 expression within the spinal cord dorsal horn through the tropomyosin-related kinase B signaling, and this mechanism may play a vital role in relieving the neuropathic pain of rats caused by incomplete SCI.