Program in Neurobiology and FM Kirby Neurobiology Center, Children's Hospital Boston, Department of Neurobiology, Harvard Medical School, Boston, MA, USA.
Pain. 2011 Mar;152(3 Suppl):S2-S15. doi: 10.1016/j.pain.2010.09.030. Epub 2010 Oct 18.
Nociceptor inputs can trigger a prolonged but reversible increase in the excitability and synaptic efficacy of neurons in central nociceptive pathways, the phenomenon of central sensitization. Central sensitization manifests as pain hypersensitivity, particularly dynamic tactile allodynia, secondary punctate or pressure hyperalgesia, aftersensations, and enhanced temporal summation. It can be readily and rapidly elicited in human volunteers by diverse experimental noxious conditioning stimuli to skin, muscles or viscera, and in addition to producing pain hypersensitivity, results in secondary changes in brain activity that can be detected by electrophysiological or imaging techniques. Studies in clinical cohorts reveal changes in pain sensitivity that have been interpreted as revealing an important contribution of central sensitization to the pain phenotype in patients with fibromyalgia, osteoarthritis, musculoskeletal disorders with generalized pain hypersensitivity, headache, temporomandibular joint disorders, dental pain, neuropathic pain, visceral pain hypersensitivity disorders and post-surgical pain. The comorbidity of those pain hypersensitivity syndromes that present in the absence of inflammation or a neural lesion, their similar pattern of clinical presentation and response to centrally acting analgesics, may reflect a commonality of central sensitization to their pathophysiology. An important question that still needs to be determined is whether there are individuals with a higher inherited propensity for developing central sensitization than others, and if so, whether this conveys an increased risk in both developing conditions with pain hypersensitivity, and their chronification. Diagnostic criteria to establish the presence of central sensitization in patients will greatly assist the phenotyping of patients for choosing treatments that produce analgesia by normalizing hyperexcitable central neural activity. We have certainly come a long way since the first discovery of activity-dependent synaptic plasticity in the spinal cord and the revelation that it occurs and produces pain hypersensitivity in patients. Nevertheless, discovering the genetic and environmental contributors to and objective biomarkers of central sensitization will be highly beneficial, as will additional treatment options to prevent or reduce this prevalent and promiscuous form of pain plasticity.
伤害感受器的输入可触发中枢伤害感受通路上神经元的兴奋性和突触效能的延长但可逆转的增加，即中枢敏化现象。中枢敏化表现为痛觉过敏，特别是动态触觉超敏，继发点状或压力痛觉过敏、后感觉和时间总和增强。通过对皮肤、肌肉或内脏的各种实验性伤害性条件刺激，可在人类志愿者中轻易且快速地诱发这种现象，除了产生痛觉过敏外，还导致大脑活动的继发性变化，这些变化可以通过电生理或成像技术检测到。临床队列研究揭示了痛觉敏感性的变化，这些变化被解释为表明中枢敏化对纤维肌痛、骨关节炎、全身性痛觉过敏的肌肉骨骼疾病、头痛、颞下颌关节紊乱、牙痛、神经病理性疼痛、内脏痛觉过敏障碍和术后疼痛患者疼痛表型的重要贡献。那些在没有炎症或神经损伤的情况下出现的痛觉过敏综合征的共病，以及它们类似的临床表现模式和对中枢作用镇痛药的反应，可能反映了它们的病理生理学的中枢敏化的共同性。仍需要确定的一个重要问题是，是否存在比其他人更易发生中枢敏化的个体，如果是这样，这是否会增加发展为痛觉过敏的条件的风险，以及它们的慢性化。在患者中建立中枢敏化存在的诊断标准将极大地有助于对患者进行表型分析，以选择通过使过度兴奋的中枢神经活动正常化来产生镇痛作用的治疗方法。自从首次发现脊髓中的活动依赖性突触可塑性，以及揭示其在患者中发生并产生痛觉过敏以来，我们已经取得了很大的进展。然而，发现中枢敏化的遗传和环境因素以及客观生物标志物，以及预防或减少这种普遍存在且混杂的疼痛可塑性的额外治疗选择，将是非常有益的。
