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Characterizing the Mechanical Properties of Ectopic Axonal Receptive Fields in Inflamed Nerves and Following Axonal Transport Disruption.
Neuroscience ( IF 2.9 ) Pub Date : 2019-12-23 , DOI: 10.1016/j.neuroscience.2019.11.042
George Goodwin 1 , Geoffrey M Bove 2 , Bryony Dayment 1 , Andrew Dilley 1
Affiliation  

Radiating pain is a significant feature of chronic musculoskeletal pain conditions such as radiculopathies, repetitive motion disorders and whiplash associated disorders. It is reported to be caused by the development of mechanically-sensitive ectopic receptive fields along intact nociceptor axons at sites of peripheral neuroinflammation (neuritis). Since inflammation disrupts axonal transport, we have hypothesised that anterogradely-transported mechanically sensitive ion channels accumulate at the site of disruption, which leads to axonal mechanical sensitivity (AMS). In this study, we have characterised the mechanical properties of the ectopic axonal receptive fields in the rat and have examined the contribution of mechanically sensitive ion channels to the development of AMS following neuritis and vinblastine-induced axonal transport disruption. In both models, there was a positive force-discharge relationship and mechanical thresholds were low (∼9 mN/mm2). All responses were attenuated by Ruthenium Red and FM1-43, which block mechanically sensitive ion channels. In both models, the transport of TRPV1 and TRPA1 was disrupted, and intraneural injection of agonists of these channels caused responses in neurons with AMS following neuritis but not vinblastine treatment. In summary, these data support a role for mechanically sensitive ion channels in the development of AMS.

中文翻译:

表征发炎神经中异位轴突感受野的机械特性和轴突运输中断。

放射痛是慢性肌肉骨骼疼痛疾病的一个重要特征,例如神经根病、重复性运动障碍和挥鞭相关疾病。据报道,这是由于在周围神经炎症(神经炎)部位沿完整的伤害感受器轴突发展出机械敏感的异位感受野所致。由于炎症破坏了轴突运输,我们假设顺行运输的机械敏感离子通道在破坏部位积聚,从而导致轴突机械敏感性 (AMS)。在这项研究中,我们描述了大鼠异位轴突感受野的机械特性,并研究了机械敏感离子通道对神经炎和长春碱诱导的轴突运输中断后 AMS 发展的贡献。在这两种模型中,存在正的力-放电关系,并且机械阈值较低(~9 mN/mm2)。所有反应都被钌红和 FM1-43 减弱,它们阻断了机械敏感的离子通道。在这两种模型中,TRPV1 和 TRPA1 的运输都被破坏了,神经内注射这些通道的激动剂会在神经炎后引起 AMS 神经元的反应,而不是长春碱治疗。总之,这些数据支持机械敏感离子通道在 AMS 发展中的作用。这些通道的激动剂的神经内注射引起神经炎后 AMS 神经元的反应,而不是长春碱治疗。总之,这些数据支持机械敏感离子通道在 AMS 发展中的作用。这些通道的激动剂的神经内注射引起神经炎后 AMS 神经元的反应,而不是长春碱治疗。总之,这些数据支持机械敏感离子通道在 AMS 发展中的作用。
更新日期:2019-12-23
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