NAD+ metabolism in peripheral neuropathic pain

Abstract

Nicotinamide adenine dinucleotide (NAD⁺) is an omnipresent metabolite that participates in redox reactions. Multiple NAD⁺-consuming enzymes are implicated in numerous biological processes, including transcription, signaling, and cell survival. Multiple pieces of evidence have demonstrated that NAD⁺-consuming enzymes, including poly(ADP-ribose) polymerases (PARPs), sirtuins (SIRTs), and sterile alpha and TIR motif-containing 1 (SARM1), play major roles in peripheral neuropathic pain of various etiologies. These NAD⁺ consumers primarily participate in peripheral neuropathic pain via mechanisms such as mitochondrial dysfunction, oxidative stress, and inflammation. Furthermore, NAD⁺ synthase and nicotinamide phosphoribosyltransferase (NAMPT) have recently been found to contribute to the regulation of pain. Here, we review the evidence indicating the involvement of NAD⁺ metabolism in the pathological mechanisms of peripheral neuropathic pain. Advanced understanding of the molecular and cellular mechanisms associated with NAD⁺ in peripheral neuropathic pain will facilitate the development of novel treatment options for diverse types of peripheral neuropathic pain.

Keywords: Axonal degeneration; NAD(+) metabolism; NAD(+)-consuming enzymes; Neuropathic pain; Nicotinamide phosphoribosyltransferase; Peripheral neuropathy.