Olgart L
Institutionen för fysiologi och farmakologi, Karolinska Institutet, Stockholm.
Nord Med. 1998 Jan;113(1):6-12.
Increased pain fibre activity in response to tissue injury results in changes in gene expression and prolonged changes in nerves and their environment. The resulting hyperalgesia and prolonged spontaneous pain are due both to increased sensitivity of peripheral nociceptors (primary hyperalgesia) and to faciliated spinal cord transmission (secondary hyperalgesia, receptive field expansion and allodynia). Hyperexcitability of dorsal horn neurones is first triggered by increased neuronal barrage into the central nervous system ("wind-up"), and later by retrograde chemical influences from the peripheral inflammation (central sensitisation). Central transmission and hyperexcitability are mediated by excitatory amino acids (aspartate and glutamate) and by tachykinins (substance P). Normally, the net effect of the activity in a complex network of inhibitory neurones in the spinal cord ("gate control"), driven by descending projections from brain stem sites, is to dampen and counteract the spinal cord hyperexcitability produced by tissue or nerve injury. Thus, peripherally evoked pain impulses pass through a filtering process involving gamma-aminobutyric acid, glycine and enkephalins. The activity of these substances in the spinal cord usually attenuates and limits the duration of pain. In the case of persistent pain, there is evidence of pathological reduction of the supraspinal net inhibitory actions in combination with ectopic afferent input in damaged nerves. Hence, the pathology of chronic pain (neuropathic pain) differs from that of nociceptive pain and conventional pharmacological treatment of chronic central pain is usually less successful than treatment of inflammation-related pain. The many newly discovered mechanisms for the transmission and modulation of pain impulses are characterised by complex activity-dependent plasticity, which means that therapeutic strategies for persistent pain must be adapted to changing targets--either at the site of injury or at other sites in the central nervous system.
对组织损伤做出反应时，疼痛纤维活动增加会导致基因表达变化以及神经及其周围环境的长期改变。由此产生的痛觉过敏和持续的自发痛，既归因于外周伤害感受器敏感性增加（原发性痛觉过敏），也归因于脊髓传递的易化（继发性痛觉过敏、感受野扩大和痛觉过敏）。背角神经元的兴奋性过高首先由进入中枢神经系统的神经元冲动增加（“wind-up”）引发，随后由外周炎症的逆行化学影响（中枢敏化）引发。中枢传递和兴奋性过高由兴奋性氨基酸（天冬氨酸和谷氨酸）以及速激肽（P物质）介导。正常情况下，由脑干部位下行投射驱动的脊髓抑制性神经元复杂网络（“闸门控制”）活动的净效应，是抑制和抵消由组织或神经损伤产生的脊髓兴奋性过高。因此，外周诱发的疼痛冲动会经过一个涉及γ-氨基丁酸、甘氨酸和脑啡肽的过滤过程。这些物质在脊髓中的活动通常会减弱并限制疼痛持续时间。在持续性疼痛的情况下，有证据表明脊髓上网络抑制作用的病理性降低，同时受损神经中存在异位传入输入。因此，慢性疼痛（神经性疼痛）的病理与伤害性疼痛不同，慢性中枢性疼痛的传统药物治疗通常不如炎症相关疼痛的治疗成功。许多新发现的疼痛冲动传递和调制机制具有复杂的活动依赖性可塑性，这意味着持续性疼痛的治疗策略必须适应不断变化的靶点——无论是在损伤部位还是中枢神经系统的其他部位。
