Antinociceptive effect of intrathecal administration of hypotaurine in rat models of inflammatory and neuropathic pain
Antinociceptive effect of intrathecal administration of hypotaurine in rat models of inflammatory and neuropathic pain
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DOI：
10.1007/s00726-011-1094-9
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发表时间：
2012-07-01
期刊：
影响因子：
3.5
通讯作者：
Sata, Takeyoshi
中科院分区：
文献类型：
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作者：
Hara, Koji;Nakamura, Motohiro;Sata, Takeyoshi
次牛磺酸是星形胶质细胞半胱氨酸生物合成牛磺酸的中间产物。尽管亚牛磺酸具有抗氧化剂和有机渗透调节剂的功能，但它在中枢神经系统中的生理作用尚不清楚。这项研究使用行为学评估来确定亚牛磺酸是否影响急性、炎症性和神经病理性疼痛的伤害性传递。对雄性SD大鼠进行甩尾、爪压和福尔马林实验，观察鞘内注射亚牛磺酸(100、200、400、600 mg)对热、机械和化学伤害性感觉的影响。采用大鼠坐骨神经慢性压迫性损伤(CCI)模型，采用电子von Frey试验和足底试验评价其对神经病理性疼痛的影响。为了确定哪条神经递质通路(S)参与下牛磺酸的作用，在本研究中，我们观察了脊髓痛处理受体拮抗剂如何改变600mU g下牛磺酸的作用。为了探索亚牛磺酸是否影响运动能力，进行了旋转棒测试。次牛磺酸对脊髓的热、机械和化学伤害性感受有抗伤害性作用。在CCI大鼠，次牛磺酸可减轻机械性痛觉过敏和热痛觉过敏。鞘内注射士的宁(一种甘氨酸受体拮抗剂)可完全逆转这些效应。相反，亚牛磺酸不会影响运动能力。这项研究表明，鞘内注射亚牛磺酸可以抑制急性、炎症和神经病理性疼痛。次牛磺酸可能通过激活脊髓中的甘氨酸能神经元，从生理上调节伤害性信息的传递，有望成为治疗各种疼痛状态的候选药物。
Hypotaurine is an intermediate in taurine biosynthesis from cysteine in astrocytes. Although hypotaurine functions as an antioxidant and organic osmolyte, its physiological role in the central nervous system remains unclear. This study used behavioral assessments to determine whether hypotaurine influenced nociceptive transmission in acute, inflammatory, and neuropathic pain. The tail flick, paw pressure, and formalin tests were performed in male Sprague-Dawley rats to examine the effects of the intrathecal administration of hypotaurine (100, 200, 400, 600 mu g) on thermal, mechanical, and chemical nociception. Chronic constriction injury (CCI) to the sciatic nerve was induced in the rats, and the electronic von Frey test and plantar test were performed to assess the effects on neuropathic pain. To determine which neurotransmitter pathway(s) was involved in the action of hypotaurine, in this study, we examined how the antagonists of spinal pain processing receptors altered the effect of 600 mu g hypotaurine. To explore whether hypotaurine affected motor performance, the Rotarod test was conducted. Hypotaurine had antinociceptive effects on thermal, mechanical, and chemical nociception in the spinal cord. In CCI rats, hypotaurine alleviated mechanical allodynia and thermal hyperalgesia. These effects were reversed completely by pretreatment with an intrathecal injection of strychnine, a glycine receptor antagonist. Conversely, hypotaurine did not affect motor performance. This study demonstrated that intrathecal hypotaurine suppressed acute, inflammatory, and neuropathic pain. Hypotaurine may regulate nociceptive transmission physiologically by activating glycinergic neurons in the spinal cord, and it is a promising candidate for treating various pain states.