The superoxide scavenger tempol attenuates DNA oxidative injury and spontaneous pain-like behavior in chronic post-cast pain model rats
The superoxide scavenger tempol attenuates DNA oxidative injury and spontaneous pain-like behavior in chronic post-cast pain model rats
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DOI：
10.1016/j.bbrc.2020.09.044
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发表时间：
2020-12-17
影响因子：
3.1
通讯作者：
Naito，Munekazu
中科院分区：
文献类型：
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作者：
Ohmichi，Yusuke;Ohmichi，Mika;Naito，Munekazu
由于身体废用而发生的剧烈疼痛的机制，如I型复杂区域疼痛综合征，迄今尚未阐明。因此，为了研究这种机制，我们开发了一种称为慢性石膏后疼痛（CPCP）模型的模型。固定肢体产生的氧化应激相关因子可能是由于身体废用而引起的伤害性信号的触发器。在我们以前的研究结果的基础上，我们推测，氧化应激相关的因素在固定后肢也可能是触发器的伤害性信号，由于物理废用。在这项研究中，我们的目的是澄清是否氧化应激相关因子参与诱导伤害性信号。通过8-羟基-2 ′-脱氧鸟苷（DNA中氧化损伤的标志物）的免疫染色来评估比目鱼肌（慢缩纤维）和腓肠肌（快缩纤维）肌肉中氧化损伤的时间过程。我们还研究了超氧化物清除剂tempol对DNA氧化损伤、自发性疼痛相关行为（舔和/或咬和退缩）以及脊髓背角神经元（c-Fos）激活的影响。全身管理tempol石膏拆除前衰减固定骨骼肌DNA的氧化损伤，抑制自发性疼痛相关的行为，并抑制脊髓背角神经元的激活。我们认为，在固定骨骼肌石膏拆除后产生的超氧化物是触发伤害性信号的外周因素之一。
The mechanism of severe pain occurring because of physical disuse, such as complex regional pain syndrome Type I, has not been elucidated so far. Therefore, to investigate this mechanism, we have developed a model called a chronic post-cast pain (CPCP) model. Oxidative stress-related factors generated in a fixed limb may be triggers for nociceptive signals due to physical disuse. On the basis of the results of our previous studies, we speculated that oxidative stress-related factors in immobilized hind limbs may also be triggers of nociceptive signals due to physical disuse. In this study, we aimed to clarify whether an oxidative stress-related factor is involved in the induction of nociceptive signals. The time course of oxidative damage in the soleus (slow-twitch fiber) and gastrocnemius (fast-twitch fiber) muscles was evaluated by immunostaining of 8-hydroxy-2′-deoxyguanosine (a marker of oxidative damage in DNA). We also investigated the effects of tempol, a scavenger of superoxide, on oxidative damage in DNA, spontaneous pain-related behaviors (licking and/or biting and flinching), and the activation of spinal dorsal horn neurons (c-Fos). Systemic administration of tempol before cast removal attenuated oxidative damage to DNA in immobilized skeletal muscles, suppressed spontaneous pain-related behavior, and suppressed the activation of spinal dorsal horn neurons. We suggest that superoxide generated in immobilized skeletal muscles after cast removal is one of the peripheral factors that trigger nociceptive signals.