Pain Mechanisms Lab, Department of Anesthesiology, Wake Forest School of Medicine, Winston-Salem, NC, United States.
Pain. 2020 May;161(5):960-969. doi: 10.1097/j.pain.0000000000001782.
Pain alters cognitive performance through centrally mediated effects in the brain. In this study, we hypothesized that persistent activation of peripheral nociceptors after injury would lead to the development of a chronic pain state that impairs attention-related behavior and results in changes in peripheral neuron phenotypes. Attentional performance was measured in rats using the 5-choice serial reaction time titration variant to determine the initial impact of partial L5 spinal nerve ligation and the effect of persistent nociceptor activation on the resolution of injury. The changes in peripheral neuronal sensibilities and phenotypes were determined in sensory afferents using electrophysiologic signatures and receptive field properties from dorsal root ganglion recordings. Partial spinal nerve injury impaired attentional performance, and this was further impaired in a graded fashion by nociceptive input through an engineered surface. Impairment in attention persisted for only up to 4 days initially, followed by a second phase 7 to 10 weeks after injury in animals exposed to nociceptive input. In animals with prolonged impairment in behavior, the mechanonociceptors displayed a persistent hypersensitivity marked by decreased threshold, increased activity to a given stimulus, and spontaneous activity. Nerve injury disrupts attentional performance acutely and is worsened with peripheral mechanonociceptor activation. Acute impairment resolves, but persistent nociceptive activation produces re-emergence of impairment in the attention-related task associated with electrophysiological abnormalities in peripheral nociceptors. This is consistent with the development of a chronic pain state marked by cognitive impairment and related to persistently abnormal peripheral input.
疼痛通过大脑中枢介导的效应改变认知表现。在这项研究中，我们假设损伤后外周伤害感受器的持续激活会导致慢性疼痛状态的发展，从而损害与注意力相关的行为，并导致外周神经元表型的变化。使用 5 选择序列反应时间滴定变体在大鼠中测量注意力表现，以确定部分 L5 脊神经结扎的初始影响以及持续伤害感受器激活对损伤解决的影响。使用电生理特征和背根神经节记录的感受野特性，在感觉传入中确定外周神经元敏感性和表型的变化。部分脊髓神经损伤会损害注意力表现，而通过工程表面施加的伤害性输入会以分级的方式进一步损害注意力表现。最初，注意力损伤仅持续长达 4 天，然后在受伤后 7 至 10 周，暴露于伤害性输入的动物会出现第二阶段。在行为持续受损的动物中，机械伤害感受器表现出持久的超敏反应，表现为阈值降低、对给定刺激的活性增加和自发性活性增加。神经损伤会急性损害注意力表现，并随着外周机械伤害感受器的激活而恶化。急性损伤会得到解决，但持续的伤害性激活会导致与外周伤害感受器异常传入相关的注意力相关任务再次出现损伤。这与认知功能障碍和持续异常外周输入相关的慢性疼痛状态的发展一致。
