Department of Orthopedics, The Affiliated Hospital of Qingdao University, Qingdao 266003, China.
Department of Orthopedics, The Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, China.
Mediators Inflamm. 2023 Jul 10;2023:9151967. doi: 10.1155/2023/9151967. eCollection 2023.
There is no effective treatment for peripheral nerve injury-induced chronic neuropathic pain (NP), which profoundly impacts the quality of life of those affected. Transmembraneprotein100 (TMEM100) is considered to be a pain regulatory protein and is expressed in the dorsal root ganglion (DRG) of rats. However, the mechanism of pain regulation and the expression of TMEM100 following various peripheral nerve injuries are unclear. In this study, we constructed two pain models of peripheral nerve injury: tibial nerve injury (TNI) and chronic constriction injury (CCI). This study found that the Paw Withdrawal Mechanical Threshold (PWMT) and Paw Withdraw Thermal Latency (PWTL) of the rats in the two pain models decreased significantly, and the expression of TMEM100 in the DRG of two groups also decreased significantly. Furthermore, the decrease in the CCI group was more obvious than in the TNI group. There was no significant statistical significance ( > 0.05). We constructed an adeno-associated virus 6 (AAV6) vector expressing recombinant fluorescent TMEM100 protein and injected it into the sciatic nerve (SN) of two pain models: CCI and TNI. PWMT and PWTL were significantly increased in the two groups, along with the expression of TMEM100 in the spinal cord and DRG. It also significantly inhibited the activation of microglia, astrocytes, and several inflammatory mediators (TNF- , IL-1 , and IL-6). In summary, the results of this study suggested that TMEM100 might be a promising molecular strategy for the treatment of NP, and its anti-inflammatory effects might play an important role in pain relief.
目前，外周神经损伤引起的慢性神经性疼痛（NP）尚无有效治疗方法，严重影响患者的生活质量。跨膜蛋白 100（TMEM100）被认为是一种疼痛调节蛋白，在大鼠背根神经节（DRG）中表达。然而，TMEM100 在外周神经损伤后的疼痛调节机制及其表达尚不清楚。在本研究中，我们构建了两种外周神经损伤疼痛模型：胫神经损伤（TNI）和慢性缩窄性损伤（CCI）。研究发现，两种疼痛模型大鼠的足底机械缩足阈值（PWMT）和足底热缩足潜伏期（PWTL）均明显降低，两组大鼠 DRG 中 TMEM100 的表达也明显降低。此外，CCI 组的下降比 TNI 组更明显。两组间差异无统计学意义（>0.05）。我们构建了表达重组荧光 TMEM100 蛋白的腺相关病毒 6（AAV6）载体，并将其注入两种疼痛模型的坐骨神经（SN）：CCI 和 TNI。两组 PWMT 和 PWTL 均明显升高，脊髓和 DRG 中 TMEM100 的表达也明显升高。它还显著抑制小胶质细胞、星形胶质细胞和几种炎症介质（TNF- 、IL-1 和 IL-6）的激活。综上所述，本研究结果表明，TMEM100 可能是治疗 NP 的一种有前途的分子策略，其抗炎作用可能在缓解疼痛中发挥重要作用。
