Kallenborn-Gerhardt Wiebke, Schröder Katrin, Schmidtko Achim
Institute of Pharmacology and Clinical Pharmacy, Goethe University Frankfurt, Max-von-Laue-Str. 9, 60438 Frankfurt, Germany.
Institute of Cardiovascular Physiology, Goethe University Frankfurt, 60590 Frankfurt, Germany.
Antioxidants (Basel). 2022 Jun 14;11(6):1162. doi: 10.3390/antiox11061162.
Inflammation or injury to the somatosensory nervous system may result in chronic pain conditions, which affect millions of people and often cause major health problems. Emerging lines of evidence indicate that reactive oxygen species (ROS), such as superoxide anion or hydrogen peroxide, are produced in the nociceptive system during chronic inflammatory and neuropathic pain and act as specific signaling molecules in pain processing. Among potential ROS sources in the somatosensory system are NADPH oxidases, a group of electron-transporting transmembrane enzymes whose sole function seems to be the generation of ROS. Interestingly, the expression and relevant function of the Nox family members Nox1, Nox2, and Nox4 in various cells of the nociceptive system have been demonstrated. Studies using knockout mice or specific knockdown of these isoforms indicate that Nox1, Nox2, and Nox4 specifically contribute to distinct signaling pathways in chronic inflammatory and/or neuropathic pain states. As selective Nox inhibitors are currently being developed and investigated in various physiological and pathophysiological settings, targeting Nox1, Nox2, and/or Nox4 could be a novel strategy for the treatment of chronic pain. Here, we summarize the distinct roles of Nox1, Nox2, and Nox4 in inflammatory and neuropathic processing and discuss the effectiveness of currently available Nox inhibitors in the treatment of chronic pain conditions.
躯体感觉神经系统的炎症或损伤可能导致慢性疼痛疾病，这类疾病影响着数百万人，并常常引发重大健康问题。新出现的证据表明，在慢性炎症性疼痛和神经性疼痛期间，伤害性感受系统会产生活性氧（ROS），如超氧阴离子或过氧化氢，它们在疼痛处理过程中充当特定的信号分子。躯体感觉系统中潜在的ROS来源包括NADPH氧化酶，这是一组电子传递跨膜酶，其唯一功能似乎就是产生活性氧。有趣的是，已经证实了Nox家族成员Nox1、Nox2和Nox4在伤害性感受系统的各种细胞中的表达及相关功能。使用基因敲除小鼠或特异性敲低这些异构体的研究表明，Nox1、Nox2和Nox4在慢性炎症性和/或神经性疼痛状态下特异性地参与不同的信号通路。由于目前正在开发选择性Nox抑制剂并在各种生理和病理生理环境中进行研究，靶向Nox1、Nox2和/或Nox4可能是治疗慢性疼痛的一种新策略。在此，我们总结了Nox1、Nox2和Nox4在炎症性和神经性疼痛处理中的不同作用，并讨论了目前可用的Nox抑制剂在治疗慢性疼痛疾病方面的有效性。
