Cortical representation of first and second pain sensation in humans

Single painful stimuli evoke two successive and qualitatively distinct sensations referred to as first and second pain sensation. Peripherally, the neural basis of this phenomenon is a dual pathway for pain with Aδ and C fibers mediating first and second pain, respectively. Yet, the differential cortical correlates of both sensations are largely unknown. We therefore used magnetoencephalography to record and directly compare first and second pain-related cortical responses to cutaneous laser stimuli in humans. Our results show that brief painful stimuli evoke sustained cortical activity corresponding to sustained pain perception comprising early first pain-related and late second pain-related components. Cortical activity was located in primary (S1) and secondary (S2) somatosensory cortices and anterior cingulate cortex. Time courses of activations disclosed that first pain was particularly related to activation of S1 whereas second pain was closely related to anterior cingulate cortex activation. Both sensations were associated with S2 activation. These results correspond to the different perceptual characteristics of both sensations and probably reflect different biological functions of first and second pain. First pain signals threat and provides precise sensory information for an immediate withdrawal, whereas second pain attracts longer-lasting attention and motivates behavioral responses to limit further injury and optimize recovery.

单次伤害性刺激可诱发两种相继出现且性质迥异的感觉，即第一痛觉与第二痛觉。从外周机制来看，该现象的神经基础为疼痛的双通路传导：Aδ纤维与C类纤维分别介导第一痛觉与第二痛觉。然而，目前学界对这两种痛觉对应的差异化皮层表征仍知之甚少。为此，我们采用脑磁图（magnetoencephalography）技术，记录并直接对比了人体接受皮肤激光刺激时，与第一、第二痛觉相关的皮层反应。研究结果显示，短暂的伤害性刺激可诱发持续的皮层活动，该活动对应持续的痛觉感知，包含早期的第一痛觉相关成分与晚期的第二痛觉相关成分。上述皮层活动主要定位于初级躯体感觉皮层（S1）、次级躯体感觉皮层（S2）以及前扣带回皮层（anterior cingulate cortex）。激活时序分析显示，第一痛觉尤其与S1的激活相关，而第二痛觉则与前扣带回皮层的激活紧密关联；两种痛觉均与S2的激活存在关联。上述研究结果契合两种痛觉各自的感知特性，或也反映了第一与第二痛觉的不同生物学功能：第一痛觉可传递威胁信号，并为即刻的撤离行为提供精准的感觉信息；而第二痛觉则能引发更持久的注意力，并驱动行为反应以限制进一步损伤、优化恢复过程。