Expression of endomcrphine along pain puthuay in experimental peripmend neuropathy in rat

大鼠实验性周围神经病变中内啡肽沿痛觉的表达

• 批准号: 10671412
• 负责人: SHIBATA Masahiko
• 金额: $ 2.11万
• 依托单位: Osaka University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1998
• 资助国家: 日本
• 起止时间: 1998 至 1999
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10671412/
• 关键词: neuropathic pain; rat; lithium; nerve stimulation; halothane; 痛み; ノチセプチン; 神経因性疼病; endomorphin

After peripheral nerve injury, patients sometimes suffer from refractory pain, such as post herpetic neuralgia and causalgia Non-steroidal anti-inflammatory drugs or opioid are not effective for such condition. We, using sciatic nerve injury model in rat, showed that electro-convulsive treatment and intrathecal administration of lithium are effective for pain after nerve injury. These studies suggest that central nervotus system relating affective component can be a primary target for treating neuropathic pain.At first stage in this study, we planned to investigate about change of endomorphine and nociceptinalong pain transmitting tract by using immuno-cytochemistry technique because we speculated that poor effect of opioid for neuropathic pain might be due to changes in these opioid system. However antibody for endomorphine and nociceptin did not work well, so, we changed the protocol of this study. In this study we investigated about mechanism of lithium on pain relieving effect after nerve injury by co-administrating myo-inositol. Intrathecal co-administration of myo-inositol reversed the effect of lithitum on pain after nerve injury, which suggests that second messenger system had important role for lithium effect on pain after nerve injury. We also examined whether repetitive stimulation to injured nerve under halothane anesthesia could relieve pain after nerve injury. We also showed that repetitive stimulation to injured nerve under halothane anesthesia could relieve pain after nerve injury, suggesting long term depression may contribute for pain relief after nerve injury. These results encourage the new therapetttic approach for neuropathic pain.

周围神经损伤后，患者有时会出现顽固性疼痛，如带状疱疹后神经痛和灼痛性疼痛，非类固醇抗炎药或阿片类药物对此类情况无效。我们利用大鼠坐骨神经损伤模型，证明电惊厥治疗和鞘内注射锂盐对神经损伤后的疼痛是有效的。这些研究表明，与情感成分相关的中枢神经系统可能是治疗神经病理性疼痛的主要靶点。在本研究的第一阶段，我们计划利用免疫细胞化学技术研究内吗啡和伤害素在疼痛传递通路上的变化，因为我们推测阿片类药物对神经病理性疼痛的疗效较差可能是由于这些阿片系统的改变。然而，抗内吗啡和伤害素的抗体效果不佳，因此，我们改变了本研究的方案。本研究通过联合应用肌醇来探讨锂对神经损伤后疼痛的缓解作用机制。鞘内联合应用肌醇可逆转石膏对神经损伤后疼痛的影响，提示第二信使系统在锂对神经损伤后疼痛的作用中起重要作用。我们还观察了在氟烷麻醉下对损伤神经进行重复刺激是否能减轻神经损伤后的疼痛。在氟烷麻醉下对受损神经进行重复刺激可以减轻神经损伤后的疼痛，提示长期抑郁可能有助于神经损伤后疼痛的缓解。这些结果鼓励了治疗神经病理性疼痛的新疗法。

项目成果

T Shimizu: "Intrathecal lithium roduces neuropathic pain responses in a rat model of peripheral neuropathy"Pain. 85. 59-64 (2000)

T Shimizu：“鞘内锂在周围神经病变大鼠模型中产生神经性疼痛反应”疼痛。

T Inoue: "ラットにおける末梢神経損瘍後の疼痛過敏行動に対する経皮的末梢神経刺激療法の効果"麻酔. 13. 171 (1999)

T Inoue：“经皮周围神经刺激疗法对大鼠周围神经损伤后疼痛超敏行为的影响”麻醉，13. 171 (1999)。

柴田政彦: "痛みの診療"克誠堂出版. 337 (2000)

柴田正彦：《疼痛的医学治疗》Kuseido Publishing 337（2000）。

T Shimizu: "Intrathecal lithium reduces neuropathic pain responses in a rat model of peripheral nearopathy"Anesthesidogy. 91. A857 (1999)

T Shimizu：“鞘内锂可减少周围性近病大鼠模型中的神经性疼痛反应”麻醉学。

T.Shimizu et al.: "Intrathecal lithium reduces neuropcithic pain responses in a rat model of poripheral neuropathy"Pain. 85. 59-64 (2000)

T.Shimizu 等人：“鞘内锂可减少周围神经病变大鼠模型中的神经原性疼痛反应”疼痛。