Neuropathic Pain: the Dysfunction of Drp1, Mitochondria, and ROS Homeostasis
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REVIEW ARTICLE
Neuropathic Pain: the Dysfunction of Drp1, Mitochondria, and ROS Homeostasis Chun-Qiu Dai 1 & Yu Guo 1 & Xue-Yan Chu 1 Received: 15 April 2020 / Revised: 9 July 2020 / Accepted: 13 July 2020 # Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract Neuropathic pain affects the physical and mental health status of patients. Due to its complex pathogenesis and the adverse reactions to medicines, its treatment remains challenging. Among all the etiologies, increasing evidence has pointed to mitochondrial dysfunction. Dynamin-related protein 1 (Drp1)–mediated mitochondrial fragmentation leads to excess ROS generation, which is implicated in the pathogenesis of neuropathic pain. However, the exact mechanism remains unclear. Studies aiming to clarify the possible pathway and relationship between Drp1, mitochondria, ROS, and neuropathic pain may identify a good treatment for neuropathic pain in the clinic. As shown in this review, dysfunction of Drp1 and ROS homeostasis plays essential roles in neuropathic pain. We summarized a Drp1-mitochondrial fission-ROS cycle that potentially functions in neuropathic pain and is regulated by posttranslational modifications and Ca2+. Additionally, we further enumerated six Drp1 inhibitors, including Mdivi-1, P110, Drp1 antisense oligodeoxynucleotides, hyperbaric oxygen, melatonin, and β-hydroxybutyrate, as potential treatments, with the aim of providing guidance for novel molecules to be used in the clinic. Keywords Neuropathic pain . Mitochondria . Drp1 . ROS . Fission
Introduction Neuropathic pain is a major public health problem (Geis et al. 2017). It affects the physical and mental health status of patients due to its complex pathogenesis and adverse reactions to medicine. The treatment of neuropathic pain remains challenging (Finnerup et al. 2015). To date, various medicines for neuropathic pain have only achieved a modest effect. Among all the etiologies, accumulating evidence has pointed to mitochondrial dysfunction. Many studies have revealed the relationship between neuropathic pain and mitochondrial dysfunction (Ferrari et al. 2011; Areti et al. 2016). Mitochondria are vital organelles in the central nervous system, particularly in neurons. Mitochondria will move along cytoskeletal tracks to the sites of a high energy demand and change their morphology through fusion and fission in response to cellular metabolic activity. Therefore, the balance of mitochondrial
* Xue-Yan Chu [email protected] 1
Third Medical District, Lintong Rehabilitation and Convalescent Centre, Xi’an 710600, People’s Republic of China
fission and fusion is very important for maintaining the number and function of mitochondria (Otera et al. 2013). Dynamin-related protein 1 (Drp1) is an ~ 80-kDa protein (monomer) that is widely expressed in the human brain, lung, heart, kidney, spleen, hepatocytes, and fibroblasts (Reddy et al. 2011). It has multiple roles in mediating mitochondriarelated physiological functions, including mitochondrial fission (Smirnova et al. 200
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