The Role of Mitochondrial Dysfunction, Reactive Oxygen Species, and Oxidative Stress in the Progression of Neuropathic Pain and Neuronal Damage

Abstract

Neuropathic pain, a chronic condition resulting from injury or dysfunction in the somatosensory nervous system, is characterized by complex pathological processes, including mitochondrial dysfunction, elevated production of reactive oxygen species (ROS), and oxidative stress. Mitochondria play a crucial role in maintaining cellular energy homeostasis and regulating apoptosis. However, in the context of nerve injury, mitochondrial function is often compromised, leading to an overproduction of ROS, which can damage cellular components and disrupt redox balance. The accumulation of ROS, in turn, activates signaling pathways that contribute to neuroinflammation, neuronal hyperexcitability, and synaptic plasticity—key factors in the persistence of chronic pain. Oxidative stress, a state in which the production of ROS exceeds the capacity of cellular antioxidant defenses, exacerbates mitochondrial damage and contributes to neuronal injury and degeneration. This review explores the interplay between mitochondrial dysfunction, ROS, and oxidative stress in the pathophysiology of neuropathic pain. We highlight the molecular mechanisms underlying these processes, including the role of NADPH oxidase, calcium dysregulation, and the activation of pro-inflammatory pathways such as NF-$\kappa$B and MAPK. Additionally, we discuss potential therapeutic strategies aimed at targeting mitochondrial health and reducing oxidative stress to alleviate neuropathic pain. By understanding the intricate role of mitochondrial dysfunction and oxidative stress, new avenues for treatment can be developed to protect neurons and improve pain outcomes for patients suffering from neuropathic conditions.