Alpha-Lipoic Acid as an Antioxidant Strategy for Managing Neuropathic Pain

Abstract

Neuropathic pain (NP) is the most prevalent and debilitating form of chronic pain, caused by injuries or diseases of the somatosensory system. Since current first-line treatments only provide poor symptomatic relief, the search for new therapeutic strategies for managing NP is an active field of investigation. Multiple mechanisms contribute to the genesis and maintenance of NP, including damage caused by oxidative stress. The naturally occurring antioxidant alpha-lipoic acid (ALA) is a promising therapeutic agent for the management of NP. Several pre-clinical in vitro and in vivo studies as well as clinical trials demonstrate the analgesic potential of ALA in the management of NP. The beneficial biological activities of ALA are reflected in the various patents for the development of ALA-based innovative products. This review demonstrates the therapeutic potential of ALA in the management of NP by discussing its analgesic effects by multiple antioxidant mechanisms as well as the use of patented ALA-based products and how technological approaches have been applied to enhance ALA’s pharmacological properties.

Effects of Oral Alpha-Lipoic Acid Treatment on Diabetic Polyneuropathy: A Meta-Analysis and Systematic Review

“…Redox homeostasis is maintained with an endogenous defense system that involves enzymes such as superoxide dismutase, catalase, glutathione peroxidase, ascorbate, glutathione, flavonoids, tocopherol, carotenoid, and ubiquinol [ 31 ]. When ROS accumulate, endogenous molecules become insufficient for counteracting ROS, resulting in an increase in oxidative stress [ 33 ]. Oxidative stress has been reported to cause painful neuropathies, such as diabetic neuropathy, chemotherapy-induced neuropathy, peripheral-nerve-injury-induced neuropathic pain, and even poststroke neuropathic pain [ 33 ].…”

“…When ROS accumulate, endogenous molecules become insufficient for counteracting ROS, resulting in an increase in oxidative stress [ 33 ]. Oxidative stress has been reported to cause painful neuropathies, such as diabetic neuropathy, chemotherapy-induced neuropathy, peripheral-nerve-injury-induced neuropathic pain, and even poststroke neuropathic pain [ 33 ].…”

Novel Drug Targets and Emerging Pharmacotherapies in Neuropathic Pain

“…By influencing these processes, acetyl-L-carnitine may help to regulate pain signaling, repair damaged nerves, reduce oxidative stress and inflammation, and modulate abnormal neuronal activity associated with neuropathic pain [ 193 , 195 ]. Alpha–lipoic acid is an antioxidant that was previously studied for its neuroprotective and analgesic effects in suppressing neuropathic pain [ 196 ]. It is supposed to reduce oxidative stress and inflammation, thereby alleviating pain symptoms [ 196 ].…”

“…Alpha–lipoic acid is an antioxidant that was previously studied for its neuroprotective and analgesic effects in suppressing neuropathic pain [ 196 ]. It is supposed to reduce oxidative stress and inflammation, thereby alleviating pain symptoms [ 196 ]. Palmitoylethanolamide is an endogenous fatty acid that acts as a modulator of inflammation and pain [ 197 ].…”

Biological applications of lipoic acid-based polymers: an old material with new promise

“…Consequently, these have been extensively studied in biomedical applications, including protein modification, 25,26 tumor treatment, 27,28 biosensing, 29–31 and tissue scaffold 3D-printing. 32 Most reviews 33,34 have primarily focused on the properties and clinical applications of small-molecule LA, while limited attention is given to the synthesis strategies and biological applications of PLA-based systems. In this work, after fully considering the impact of specific structures on biological performances, we highlight the latest advancements of PLA in polymerization methods and biomedical applications, and the prospects for further development in the future (Scheme 1).…”