Department of Neuroscience II, Research Institute of Environmental Medicine, Nagoya University, Nagoya, Japan.
Department of Neural Regulation, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Eur J Pain. 2019 Nov;23(10):1801-1813. doi: 10.1002/ejp.1454. Epub 2019 Aug 5.
Delayed onset muscle soreness (DOMS) is characterized by mechanical hyperalgesia after lengthening contractions (LC). It is relatively common and causes disturbance for many people who require continuous exercise, yet its molecular and peripheral neural mechanisms are poorly understood.
We examined whether muscular myelinated Aδ-fibres, in addition to unmyelinated C-fibres, are involved in LC-induced mechanical hypersensitivity, and whether acid-sensing ion channel (ASIC)-3 expressed in thin-fibre afferents contributes to this type of pain using a rat model of DOMS. The peripheral contribution of ASIC3 was investigated using single-fibre electrophysiological recordings in extensor digitorum longus muscle-peroneal nerve preparations in vitro.
Behavioural tests demonstrated a significant decrease of the muscular mechanical withdrawal threshold following LC to ankle extensor muscles, and it was improved by intramuscular injection of APETx2 (2.2 μM), a selective blocker of ASIC3. The lower concentration of APETx2 (0.22 µM) and its vehicle had no effect on the threshold. Intramuscular injection of APETx2 (2.2 μM) in naïve rats without LC did not affect the withdrawal threshold. In the ankle extensor muscles that underwent LC one day before the electrophysiological recordings, the mechanical response of Aδ- and C-fibres was significantly facilitated (i.e. decreased response threshold and increased magnitude of the response). The facilitated mechanical response of the Aδ- and C-fibres was significantly suppressed by selective blockade of ASIC3 with APETx2, but not by its vehicle.
These results clearly indicate that ASIC3 contributes to the augmented mechanical response of muscle thin-fibre receptors in delayed onset muscular mechanical hypersensitivity after LC.
Here, we show that not only C- but also Aδ-fibre nociceptors in the muscle are involved in mechanical hypersensitivity after lengthening contractions, and that acid-sensing ion channel (ASIC)-3 expressed in the thin-fibre nociceptors is responsible for the mechanical hypersensitivity. ASIC3 might be a novel pharmacological target for pain after exercise.
延迟性肌肉酸痛（DOMS）的特征是牵张收缩（LC）后出现机械性痛觉过敏。它在许多需要持续运动的人中相对常见，并引起困扰，但它的分子和周围神经机制还了解甚少。
我们研究了肌内有髓 Aδ-纤维，除无髓 C-纤维外，是否参与 LC 引起的机械性敏感性，以及在 DOMS 大鼠模型中，表达在细纤维传入中的酸感应离子通道（ASIC）-3 是否有助于这种类型的疼痛。ASIC3 的外周贡献通过体外伸趾长肌-腓神经制备中的单纤维电生理记录进行研究。
行为测试表明，LC 后踝关节伸肌的肌肉机械撤回阈值显著降低，肌肉内注射 ASIC3 选择性阻滞剂 APETx2（2.2 μM）可改善该阈值。较低浓度的 APETx2（0.22 μM）及其载体对阈值没有影响。LC 前一天进行 LC 的大鼠肌肉内注射 APETx2（2.2 μM）而不影响撤回阈值。在进行电生理记录前一天进行 LC 的踝关节伸肌中，Aδ-和 C-纤维的机械反应明显得到促进（即反应阈值降低，反应幅度增加）。ASIC3 的选择性阻滞剂 APETx2 显著抑制 Aδ-和 C-纤维的机械反应，但载体无作用。
这些结果清楚地表明，ASIC3 有助于 LC 后延迟性肌肉机械性敏感性中肌肉细纤维受体的增强机械反应。
在这里，我们表明，在 LC 后，不仅 C-纤维，而且 Aδ-纤维在肌肉中的伤害感受器也参与机械性敏感性，并且在细纤维伤害感受器中表达的酸感应离子通道（ASIC）-3 负责机械性敏感性。ASIC3 可能是运动后疼痛的新的药理学靶点。
