Zhang Yu, Zhao Jun, Hu Nan, Wang Jing, Chen Xi, Wang Kaiyuan, Yin Yiqing
Key Laboratory of Cancer Prevention and Therapy, Department of Anesthesiology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin's Clinical Research Center for Cancer, Tianjin, China.
Department of Anesthesiology, Tianjin First Central Hospital, Nankai University, Tianjin, China.
Front Neurosci. 2023 Feb 2;17:1104862. doi: 10.3389/fnins.2023.1104862. eCollection 2023.
To observe the effects of intrathecal administration of motilin on pain behavior and expression of motilin (MTL)/motilin receptor (MTLR) in the spinal cord of a rat model of acute incisional pain.
An incisional pain model was established in rats using a unilateral plantar incision. The rats were also injected intrathecally with 1, 5, or 25 μg of motilin. The mechanical withdrawal threshold (MWT) and thermal withdrawal latency (TWL) were determined. MTL/MTLR expression in the spinal cord was detected by western blotting and immunofluorescence. The expression of MTL in the spinal cord, stomach, duodenum, and plasma was determined by enzyme-linked immunosorbent assay (ELISA).
Motilin/motilin receptor were detected in the spinal cord. Spinal cord MTL/MTLR expression peaks at 2 h after modeling ( < 0.05) and start to decrease at 24 h ( < 0.05) to almost reach baseline levels at 72 h. The changes in gastric, duodenal, plasma, and spinal cord motilin levels correlated with MWT and TWL (all > 0.82). The intrathecal injection of 1, 5, or 25 μg of motilin could increase the pain threshold of rats with incisional pain within 72 h in a dose-dependent manner.
This study showed for the first time that MTL/MTLR are expressed in rats' spinal dorsal horn. Acute pain increased MTL/MTLR expression in the spinal dorsal horn. Also, for the first time, this study showed that motilin intrathecal injection alleviates pain in rat models of acute incisional pain. These results suggest that MTL/MTLR could be a novel target for the management of acute pain.
观察鞘内注射胃动素对急性切口痛大鼠模型疼痛行为及脊髓中胃动素（MTL）/胃动素受体（MTLR）表达的影响。
采用单侧足底切口法建立大鼠切口痛模型。将大鼠鞘内注射1、5或25μg胃动素。测定机械缩足阈值（MWT）和热缩足潜伏期（TWL）。通过蛋白质免疫印迹法和免疫荧光法检测脊髓中MTL/MTLR的表达。采用酶联免疫吸附测定法（ELISA）测定脊髓、胃、十二指肠和血浆中MTL的表达。
在脊髓中检测到胃动素/胃动素受体。建模后2小时脊髓MTL/MTLR表达达到峰值（<0.05），24小时开始下降（<0.05），72小时几乎降至基线水平。胃、十二指肠、血浆和脊髓中胃动素水平的变化与MWT和TWL相关（均>0.82）。鞘内注射1、5或25μg胃动素可在72小时内以剂量依赖方式提高切口痛大鼠的痛阈。
本研究首次表明MTL/MTLR在大鼠脊髓背角表达。急性疼痛增加了脊髓背角MTL/MTLR的表达。此外，本研究首次表明鞘内注射胃动素可减轻急性切口痛大鼠模型的疼痛。这些结果表明MTL/MTLR可能是急性疼痛管理的新靶点。
