Mechanisms of pain in arthritis
Mechanisms of pain in arthritis
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DOI：
10.1111/j.1749-6632.2002.tb04234.x
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发表时间：
2002-01-01
期刊：
影响因子：
--
通讯作者：
Von Banchet, GS
中科院分区：
文献类型：
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作者：
Schaible, HG;Ebersberger, A;Von Banchet, GS
关节炎症引起外周敏化（伤害性初级传入神经元的敏感性增加）和中枢敏化（伤害性神经元在中枢神经系统中的过度兴奋）。敏化过程被认为是关节炎疼痛的基础，关节炎疼痛表现为自发性疼痛（休息时的关节）和痛觉过敏（对有害刺激的疼痛反应增强和对正常无痛刺激的疼痛）。敏化还促进传出神经元过程，神经系统通过传出神经元过程影响炎症过程。外周敏化是由缓激肽、前列腺素、神经肽和细胞因子等炎症介质的作用产生的，这些介质激活神经纤维中相应的受体。此外，受体（例如缓激肽和神经激肽 1 受体）的表达在炎症过程中上调。脊髓神经元过度兴奋的发展是由构成和调节神经元突触激活的各种发射器/受体系统产生的。关键递质是谷氨酸，可激活脊髓神经元上的 N-甲基-D-天冬氨酸 (NMDA) 和非 NMDA 受体。阻断这些受体可以防止和减少中枢敏化。兴奋性神经肽（P物质和降钙素基因相关肽）进一步中枢敏化。具有复杂作用的介质（例如前列腺素 E-2）也可以促进中枢敏化。脊髓 PGE(2) 与初级传入神经元突触前末端的受体结合（从而影响突触释放），并与突触后脊髓神经元上的受体结合。向脊髓表面施用PGE(2)会产生类似于周围炎症的脊髓神经元反应性变化，并且向脊髓施用脊髓吲哚美辛可显着减弱过度兴奋的发展。
Inflammation in the joint causes peripheral sensitization (increase of sensitivity of nociceptive primary afferent neurons) and central sensitization (hyperexcitability of nociceptive neuro is in the central nervous system). The processes of sensitization are thought to be the basis of arthritic pain that appears as spontaneous pain (joints at rest) and hyperalgesia (augmented pain response on noxious stimulation and pain on normally nonpainful stimulation). Sensitization also facilitates efferent neuronal processes through which the nervous system influences the inflammatory process. Peripheral sensitization is produced by the action of inflammatory mediators such as bradykinin, prostaglandins, neuropeptides, and cytokines which activate corresponding receptors in proportions of nerve fibers. In addition, the expression of receptors, for example, bradykinin and neurokinin 1 receptors, is upregulated during inflammation. The development of hyperexcitability of spinal cord neurons is produced by various transmitter/receptor systems that constitute and modulate synaptic activation of the neurons. The key transmitter is glutamate that activates N-methyl-D-aspartate (NMDA) and non-NMDA receptors on spinal cord neurons. Blockade of these receptors prevents and reduces central sensitization. Excitatory neuropeptides (substance P and calcitonin gene-related peptide) further central sensitization. Central sensitization also is facilitated by mediators that have complex actions (e.g., prostaglandin E-2). Spinal PGE(2) binds to receptors at presynaptic endings of primary afferent neurons (thus influencing synaptic release) and to receptors on postsynaptic spinal cord neurons. The administration of PGE(2) to the spinal cord surface produces changes of responsiveness of spinal neurons similar to peripheral inflammation, and spinal indomethacin to the spinal cord attenuates development of hyperexcitability significantly.