Neuropathic pain (NP), is a chronic pain resulting from nerve injury, with limited treatment options. Teneligliptin (TEN) is a dipeptidyl peptidase-4 inhibitor (DPP-4i) approved to treat type 2 diabetes. DPP-4is prevent the degradation of the incretin hormone glucagon-like peptide 1 (GLP-1) and prolong its circulation. Apart from glycemic control, GLP-1 is known to have antinociceptive and anti-inflammatory effects. Herein, we investigated the antinociceptive properties of TEN on acute pain, and partial sciatic nerve transection (PSNT)-induced NP in Wistar rats. Seven days post PSNT, allodynia and hyperalgesia were confirmed as NP, and intrathecal (i.t) catheters were implanted and connected to an osmotic pump for the vehicle (1 μL/h) or TEN (5 μg/1 μL/h) or TEN (5 μg) + GLP-1R antagonist Exendin-3 (9–39) amide (EXE) 0.1 μg/1 μL/h infusion. The tail-flick response, mechanical allodynia, and thermal hyperalgesia were measured for 7 more days. On day 14, the dorsal horn was harvested and used for Western blotting and immunofluorescence assays. The results showed that TEN had mild antinociceptive effects against acute pain but remarkable analgesic effects against NP. Furthermore, co-infusion of GLP-1R antagonist EXE with TEN partially reversed allodynia but not tail-flick latency. Immunofluorescence examination of the spinal cord revealed that TEN decreased the immunoreactivity of glial fibrillary acidic protein (GFAP). Taken together, our findings suggest that TEN is efficient in attenuation of PSNT-induced NP. Hence, the pleiotropic effects of TEN open a new avenue for NP management.

中文翻译：

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特力列汀在部分坐骨神经横断引起的神经病理性疼痛大鼠模型中发挥镇痛作用

神经性疼痛 (NP) 是由神经损伤引起的慢性疼痛，治疗选择有限。Teneligliptin (TEN) 是一种二肽基肽酶-4 抑制剂 (DPP-4i)，被批准用于治疗 2 型糖尿病。DPP-4 可防止肠促胰岛素激素胰高血糖素样肽 1 (GLP-1) 降解并延长其循环。除了血糖控制之外，已知 GLP-1 具有镇痛和抗炎作用。在此，我们研究了 TEN 对Wistar 中急性疼痛和部分坐骨神经横断 (PSNT) 诱导的 NP 的镇痛特性老鼠。PSNT 后 7 天，异常性疼痛和痛觉过敏被确认为 NP，鞘内 (it) 导管被植入并连接到用于载体 (1 μL/h) 或 TEN (5 μg/1 μL/h) 或 TEN ( 5 μg) + GLP-1R 拮抗剂 Exendin-3 (9–39) 酰胺 (EXE) 0.1 μg/1 μL/h 输注。连续 7 天测量甩尾反应、机械异常性疼痛和热痛觉过敏。在第 14 天，收获背角并用于蛋白质印迹和免疫荧光测定。结果表明，TEN对急性疼痛具有轻微的镇痛作用，但对NP具有显着的镇痛作用。此外，GLP-1R 拮抗剂 EXE 与 TEN 的共同输注部分逆转了异常性疼痛，但不能逆转甩尾潜伏期。脊髓的免疫荧光检查显示 TEN 降低了胶质纤维酸性蛋白 (GFAP) 的免疫反应性。总之，我们的研究结果表明 TEN 在减弱 PSNT 诱导的 NP 方面是有效的。因此，TEN 的多效性为 NP 管理开辟了一条新途径。