The Mechanism of Allodynia and the Role of Opioids as Regulating Factors

长期的组织损伤或损伤通常会导致一种慢性状态，在这种状态下，无害的触觉刺激会引起疼痛；然而，痛觉异常发生的潜在机制尚不清楚，包括药物治疗在内的有效治疗疼痛的方法尚未建立。最近，鞘内注射一些神经递质受体的激动剂和拮抗剂可以引起小鼠和大鼠的痛觉异常。本研究通过鞘内注射包括嘌呤类或阿片类化合物拮抗剂和激动剂在内的多种药物来探讨小鼠痛觉异常的发生机制，发现三磷酸腺苷及其受体参与了痛觉异常的发生。苏拉明(5，10μg)和吡哆醇磷酸-6-偶氮苯基-2‘，4’-二磺酸(PPADS)可抑制前列腺素E_2(PG)E_2诱导的痛觉异常。PPADS不能阻断谷氨酸诱导的痛觉过敏。P2X受体激动剂α，β-亚甲基三磷酸腺苷可引起痛觉过敏。α，β受体拮抗剂Mk801和一氧化氮合酶抑制剂N^ω-硝基-L-精氨酸甲酯(N^NAME-NAME)可阻断PPADS引起的痛觉超敏。苏拉明在较高剂量(20~40μg)可引起痛觉过敏和痛觉过敏，其作用可被MK801和L所抑制。诺西汀1~500pg作用最强于50pg。吗啡10 ng可抑制伤害素引起的痛觉过敏，纳洛酮可逆转吗啡的抑制作用。PPADS不能阻断伤害素诱导的痛觉超敏反应。这些结果表明，脊髓中的ATP2X受体参与了触觉超感痛觉反应的调节。谷氨酸受体和一氧化氮系统在α，β-亚甲基-三磷酸腺苷和苏拉明所致痛觉过敏的发生发展中起重要作用。ATP可能介导PGE_2，但不能介导伤害素引起的痛觉超敏。

Prolonged tissue damage or injury often leads to a chronic state in which innocuous tactile stimuli evoked pain ; allodynia. However the underlying mechanisms for development of allodynia are not elucidated and the effective treatment for pain including drug therapy are yet established. Recently, intrathecal administration of a number of agonists and antagonists of neurotransmitter receptors have been shown to induce allodynia in mice and rats. The present study was performed to investigate the mechanism of allodynia by intrathecal administration of various drugs including antagonists and agonists of purinocetors or opioid and its related compounds in mice and found that ATP and its receptor are involved in the development of allodynia.Suramin (5, 10μg) and pyridoxalphosphate-6-azophenyl-2', 4'-disulfonic acid (PPADS), antagonists of P2X receptor, inhibited prostaglandin (PG) E_2-induced allodynia. PPADS did not block glutamate-induced allodynia. α, β-Methylene ATP, an agonist of P2X receptor, elicited allodynia. α, β-Methylene ATP-induced allodynia was blocked by co-administration of PPADS, Mk 801 an antagonist of NMDA receptor or N^ω-nitro-L-arginin methyl ester (L-NAME), an inhibitor of nitric monoxide synthetase. Suramin at higher doses (20〜40μg) induced allodynia and hyperalgesia, which was inhibited by MK 801 and L-NAME.Nociceptin 1〜500 pg with maximal effect at 50 pg produced allodynia. Nociceptin-induced allodynia was inhibited by 10 ng of morphine and the inhibitory effect of morphine was reversed by naloxon. Nociceptin-induced allodynia was not blocked by PPADS.These results suggest that ATP P2X receptors in the spinal cord are involved in the regulation of tactile allodynia. Glutamate receptor and nitric oxide systems play an important role in the development of allodynia produced by α, β-methylene ATP and suramin. ATP may mediate PGE_2 - but not nociceptin-induced allodynia.