NAD metabolism in peripheral neuropathic pain.

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.