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

长期的组织损伤或损伤常常导致一种慢性状态，在这种状态下，无害的触觉刺激引起疼痛；异常性疼痛。然而，异常性疼痛发生的潜在机制尚不清楚，包括药物治疗在内的有效治疗方法尚未建立。最近，鞘内注射一些神经递质受体激动剂和拮抗剂已被证明可诱导小鼠和大鼠的异常性疼痛。本研究通过对小鼠鞘内给予嘌呤受体拮抗剂、激动剂或阿片类药物及其相关化合物等多种药物，探讨异位性痛的发生机制，发现ATP及其受体参与异位性痛的发生。P2X受体拮抗剂sulamin （5,10 μg）和pyridoxal磷酸-6-偶氮苯基-2′，4′-二磺酸（PPADS）抑制前列腺素（PG） e_2诱导的异常性疼痛。PPADS不能阻断谷氨酸诱导的异常性疼痛。α， β-亚甲基ATP，一种P2X受体激动剂，引起异常性疼痛。α， β-亚甲基atp诱导的异位性疼痛可通过PPADS、NMDA受体拮抗剂Mk 801或一氧化氮合成酶抑制剂N^ω-硝基- l -精氨酸甲酯（L-NAME）共同阻断。大剂量苏拉明（20 ~ 40μg）可引起痛觉异常和痛觉过敏，MK 801和L-NAME可抑制该反应。痛觉肽1 ~ 500pg， 50pg时效果最大。10 ng吗啡可抑制痛觉西肽引起的异常痛觉，纳洛酮可逆转吗啡的抑制作用。痛觉西肽诱导的异常痛觉不被PPADS阻断。这些结果表明，脊髓ATP P2X受体参与了触觉异常性痛的调节。谷氨酸受体和一氧化氮系统在α、β-亚甲基ATP和苏拉明引起的异位性疼痛的发展中起重要作用。ATP可介导PGE_2 -，但不能介导痛觉肽诱导的异常性疼痛。

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.