脊髓中的小胶质细胞脑源性神经营养因子、PI3K 和 p-ERK 被背根神经节的脉冲射频抑制，以缓解大鼠 SNI 诱导的神经性疼痛。
Microglial BDNF, PI3K, and p-ERK in the Spinal Cord Are Suppressed by Pulsed Radiofrequency on Dorsal Root Ganglion to Ease SNI-Induced Neuropathic Pain in Rats.
机构信息
Department of Pain Management, Fujian Provincial Hospital, Fujian Key Laboratory of Geriatrics, Provincial Clinic College of Fujian Medical University, Fuzhou, Fujian, China.
出版信息
Pain Res Manag. 2019 Apr 28;2019:5948686. doi: 10.1155/2019/5948686. eCollection 2019.
BACKGROUND
Pulsed radiofrequency (PRF) on the dorsal root ganglion (DRG) has been applied to alleviate neuropathic pain effectively, yet the mechanisms underlying pain reduction owing to this treatment are not clarified completely. The activated microglia, brain-derived neurotrophic factor (BDNF), phosphatidylinositol 3-kinase (PI3K), and phosphorylated extracellular signal-regulated kinase (p-ERK) in the spinal cord were demonstrated to be involved in developing neuropathic pain. Also, it has been just known that PRF on DRG inhibits the microglial activation in nerve injury rats. Here, we aim to investigate whether PRF treatment could regulate the levels of BDNF, PI3K, and p-ERK in the spinal cord of rats with spared nerve injury (SNI) via suppressing the spinal microglia activation to ease neuropathic pain.
METHODS
The rats with SNI were intrathecally treated with minocycline (specific microglia inhibitor) or same volume of dimethyl sulfoxide once daily, beginning from 1 h before nerve transection to 7 days. PRF was applied adjacent to the L-L DRG of rats with SNI at 45 V for 6 min on the seventh postoperative day, whereas the free-PRF rats were treated without PRF. The withdrawal thresholds were studied, and the spinal levels of ionized calcium-binding adapter molecule 1 (Iba1), BDNF, PI3K, and p-ERK were calculated by western blot analysis, reverse transcription-polymerase chain reaction, and immunofluorescence.
RESULTS
The paw withdrawal mechanical threshold and paw withdrawal thermal latency decreased in the ipsilateral hind paws after SNI, and the spinal levels of Iba1, BDNF, PI3K, and p-ERK increased on day 21 after SNI compared with baseline ( < 0.01). An intrathecal injection of minocycline led to the reversal of SNI-induced allodynia and increase in levels of Iba1, BDNF, PI3K, and p-ERK. Withdrawal thresholds recovered partially after a single PRF treatment for 14 days, and SNI-induced microglia hyperactivity, BDNF upregulation, and PI3K and ERK phosphorylation in the spinal cord reduced on D14 due to the PRF procedure.
CONCLUSION
Microglial BDNF, PI3K, and p-ERK in the spinal cord are suppressed by the therapy of PRF on DRG to ease SNI-induced neuropathic pain in rats.
背景
背根神经节（DRG）的脉冲射频（PRF）已被应用于有效缓解神经性疼痛，但这种治疗方法减轻疼痛的机制尚不完全清楚。脊髓中激活的小胶质细胞、脑源性神经营养因子（BDNF）、磷酸肌醇 3-激酶（PI3K）和磷酸化细胞外信号调节激酶（p-ERK）被证明与神经性疼痛的发展有关。此外，我们刚刚知道，DRG 上的 PRF 可抑制神经损伤大鼠的小胶质细胞激活。在这里，我们旨在通过抑制脊髓小胶质细胞激活来缓解神经病理性疼痛，研究 PRF 治疗是否可以通过抑制脊髓小胶质细胞激活来调节 spared 神经损伤（SNI）大鼠脊髓中的 BDNF、PI3K 和 p-ERK 水平。
方法
SNI 大鼠鞘内给予米诺环素（特异性小胶质细胞抑制剂）或等体积二甲基亚砜，每天一次，从神经切断前 1 小时开始至 7 天。在第 7 天术后，将 PRF 施加于 SNI 大鼠的 L-L DRG 旁，电压为 45V，持续 6 分钟，而自由 PRF 大鼠则不接受 PRF 治疗。通过测定机械缩足阈值和热缩足潜伏期来研究疼痛，通过 Western blot 分析、逆转录聚合酶链反应和免疫荧光测定来计算离子钙结合接头分子 1（Iba1）、BDNF、PI3K 和 p-ERK 的脊髓水平。
结果
SNI 后，对侧后爪的机械缩足阈值和热缩足潜伏期降低，与基线相比，SNI 后 21 天脊髓中 Iba1、BDNF、PI3K 和 p-ERK 的水平升高（<0.01）。鞘内注射米诺环素导致 SNI 诱导的痛觉过敏逆转，并增加 Iba1、BDNF、PI3K 和 p-ERK 的水平。单次 PRF 治疗 14 天后，部分恢复了缩足阈值，并且由于 PRF 程序，DRG 上的 PRF 治疗减轻了 SNI 诱导的脊髓小胶质细胞过度活跃、BDNF 上调以及 PI3K 和 ERK 磷酸化。
结论
DRG 上的 PRF 治疗通过抑制脊髓中小胶质细胞的 BDNF、PI3K 和 p-ERK 来减轻大鼠 SNI 诱导的神经性疼痛。
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