Satkeviciute Ieva, Goodwin George, Bove Geoffrey M, Dilley Andrew
Brighton and Sussex Medical School, University of Sussex , Brighton , United Kingdom.
University of New England, Biddeford, Maine.
J Neurophysiol. 2018 May 1;119(5):1993-2000. doi: 10.1152/jn.00882.2017. Epub 2018 Feb 21.
Local nerve inflammation (neuritis) leads to ongoing activity and axonal mechanical sensitivity (AMS) along intact nociceptor axons and disrupts axonal transport. This phenomenon forms the most feasible cause of radiating pain, such as sciatica. We have previously shown that axonal transport disruption without inflammation or degeneration also leads to AMS but does not cause ongoing activity at the time point when AMS occurs, despite causing cutaneous hypersensitivity. However, there have been no systematic studies of ongoing activity during neuritis or noninflammatory axonal transport disruption. In this study, we present the time course of ongoing activity from primary sensory neurons following neuritis and vinblastine-induced axonal transport disruption. Whereas 24% of C/slow Aδ-fiber neurons had ongoing activity during neuritis, few (<10%) A- and C-fiber neurons showed ongoing activity 1-15 days following vinblastine treatment. In contrast, AMS increased transiently at the vinblastine treatment site, peaking on days 4-5 (28% of C/slow Aδ-fiber neurons) and resolved by day 15. Conduction velocities were slowed in all groups. In summary, the disruption of axonal transport without inflammation does not lead to ongoing activity in sensory neurons, including nociceptors, but does cause a rapid and transient development of AMS. Because it is proposed that AMS underlies mechanically induced radiating pain, and a transient disruption of axonal transport (as previously reported) leads to transient AMS, it follows that processes that disrupt axonal transport, such as neuritis, must persist to maintain AMS and the associated symptoms. NEW & NOTEWORTHY Many patients with radiating pain lack signs of nerve injury on clinical examination but may have neuritis, which disrupts axonal transport. We have shown that axonal transport disruption does not induce ongoing activity in primary sensory neurons but does cause transient axonal mechanical sensitivity. The present data complete a profile of key axonal sensitivities following axonal transport disruption. Collectively, this profile supports that an active peripheral process is necessary for maintained axonal sensitivities.
局部神经炎症（神经炎）会导致完整的伤害感受器轴突持续活动和轴突机械敏感性（AMS），并扰乱轴突运输。这种现象构成了放射性疼痛（如坐骨神经痛）最可能的原因。我们之前已经表明，在没有炎症或变性的情况下，轴突运输中断也会导致AMS，但在AMS出现的时间点并不会引起持续活动，尽管会导致皮肤超敏反应。然而，尚未有对神经炎或非炎性轴突运输中断期间持续活动的系统性研究。在本研究中，我们呈现了神经炎和长春碱诱导的轴突运输中断后初级感觉神经元持续活动的时间进程。在神经炎期间，24%的C/慢Aδ纤维神经元有持续活动，而在长春碱治疗后1 - 15天，很少有（<10%）A纤维和C纤维神经元表现出持续活动。相比之下，在长春碱治疗部位，AMS短暂增加，在第4 - 5天达到峰值（28%的C/慢Aδ纤维神经元），并在第15天恢复。所有组的传导速度均减慢。总之，无炎症的轴突运输中断不会导致感觉神经元（包括伤害感受器）的持续活动，但会导致AMS迅速且短暂地发展。因为有人提出AMS是机械性诱导的放射性疼痛的基础，并且轴突运输的短暂中断（如先前报道）会导致短暂的AMS，所以可以推断，扰乱轴突运输的过程（如神经炎）必须持续存在才能维持AMS及相关症状。新发现与值得注意的是许多患有放射性疼痛的患者在临床检查中没有神经损伤的迹象，但可能患有神经炎，这会扰乱轴突运输。我们已经表明，轴突运输中断不会在初级感觉神经元中诱导持续活动，但会导致短暂的轴突机械敏感性。目前的数据完善了轴突运输中断后关键轴突敏感性的概况。总体而言，这一概况支持了活跃的外周过程对于维持轴突敏感性是必要的。
