Endogenous analgesia, dependence, and latent pain sensitization.
Endogenous analgesia, dependence, and latent pain sensitization.
复制标题
DOI：
10.1007/7854_2014_351
复制
发表时间：
2014
影响因子：
--
通讯作者：
Corder, Gregory
中科院分区：
文献类型：
--
作者：
Taylor, Bradley K;Corder, Gregory
μ-阿片受体（M0 R）的内源性激活提供急性疼痛的缓解。最近的研究已经确定，组织炎症产生潜伏性疼痛敏感化（LS），其被脊髓莫尔信号传导掩盖数月，甚至在从损伤中完全恢复并重新建立正常疼痛阈值之后。用莫尔反向激动剂中断恢复疼痛并沉淀身体戒断的细胞、躯体和令人厌恶的体征;这种现象需要N-甲基-D-天冬氨酸受体介导的钙敏感腺苷酸环化酶1型（AC 1）的激活。在这篇综述中，我们提出了一个新的概念模型的过渡，从急性到慢性疼痛，LS和内源性镇痛之间的微妙平衡的基础上，疼痛的组织损伤后发展。首先，损伤激活疼痛通路。第二，当脊髓试图控制疼痛时，它建立了莫尔组成性活性（MORCA）。第三，随着时间的推移，身体变得依赖于MORCA，这矛盾地使疼痛通路敏感。应激或损伤使对伤害性感受处理的相反抑制和兴奋影响升级，这是内源性阿片张力增加的病理结果。疼痛引发MORCA，疼痛引发脆弱性，恶性循环。最终的结果是一种无声的潜伏状态，其特征是对疼痛传递的两种相反的兴奋和抑制影响的升级：AC 1介导的LS（维持加速器）和MORCA介导的疼痛抑制（维持制动器）。这提出了前景，即MORCA镇痛和潜在的NMDAR-AC 1介导的疼痛敏化之间的对立稳态相互作用产生了发展慢性疼痛的持久脆弱性。因此，慢性疼痛综合征可能是由于脊髓MORs的组成性信号传导失败和内源性镇痛控制丧失所致。未来研究的总体长期治疗目标是通过以下任一方式缓解慢性疼痛：a）促进内源性阿片类镇痛，从而将LS限制在缓解状态内;或B）完全消除LS。
Endogenous activation of μ-opioid receptors (MORs) provides relief from acute pain. Recent studies have established that tissue inflammation produces latent pain sensitization (LS) that is masked by spinal MOR signaling for months, even after complete recovery from injury and re-establishment of normal pain thresholds. Disruption with MOR inverse agonists reinstates pain and precipitates cellular, somatic and aversive signs of physical withdrawal; this phenomenon requires N-methyl-D-aspartate receptor-mediated activation of calcium-sensitive adenylyl cyclase type 1 (AC1). In this review, we present a new conceptual model of the transition from acute to chronic pain, based on the delicate balance between LS and endogenous analgesia that develops after painful tissue injury. First, injury activates pain pathways. Second, the spinal cord establishes MOR constitutive activity (MORCA) as it attempts to control pain. Third, over time, the body becomes dependent on MORCA, which paradoxically sensitizes pain pathways. Stress or injury escalates opposing inhibitory and excitatory influences on nociceptive processing as a pathological consequence of increased endogenous opioid tone. Pain begets MORCA begets pain vulnerability in a vicious cycle. The final result is a silent insidious state characterized by the escalation of two opposing excitatory and inhibitory influences on pain transmission: LS mediated by AC1 (which maintains accelerator), and pain inhibition mediated by MORCA (which maintains the brake). This raises the prospect that opposing homeostatic interactions between MORCA analgesia and latent NMDAR–AC1-mediated pain sensitization create a lasting vulnerability to develop chronic pain. Thus, chronic pain syndromes may result from a failure in constitutive signaling of spinal MORs and a loss of endogenous analgesic control. An overarching long-term therapeutic goal of future research is to alleviate chronic pain by either: a) facilitating endogenous opioid analgesia, thus restricting LS within a state of remission; or b) extinguishing LS altogether.