Neuroinflammation, oxidative stress and their interplay in neuropathic pain: Focus on specialized pro-resolving mediators and NADPH oxidase inhibitors as potential therapeutic strategies

Abstract

Neuropathic pain (NP) is a chronic condition that results from a lesion or disease of the nervous system, greatly impacting patients' quality of life. Current pharmacotherapy options deliver inadequate and/or insufficient responses and thus a significant unmet clinical need remains for alternative treatments in NP. Neuroinflammation, oxidative stress and their reciprocal relationship are critically involved in NP pathophysiology. In this context, new pharmacological approaches, aiming at enhancing the resolution phase of inflammation and/or restoring redox balance by targeting specific reactive oxygen species (ROS) sources, are emerging as potential therapeutic strategies for NP, with improved efficacy and safety profiles. Several reports have demonstrated that administration of exogenous specialized pro-resolving mediators (SPMs) ameliorates NP pathophysiology. Likewise, deletion or inhibition of the ROS-generating enzyme NADPH oxidase (NOX), particularly its isoforms 2 and 4, results in beneficial effects in NP models. Notably, SPMs also modulate oxidative stress and NOX also regulates neuroinflammation. By targeting neuroinflammatory and oxidative pathways, both SPMs analogues and isoform-specific NOX inhibitors are promising therapeutic strategies for NP.

Keywords: Isoform-specific NADPH oxidase inhibitors; Neuroinflammation; Neuropathic pain; Oxidative stress; Specialized pro-resolving mediators.