Nicotinamide Riboside Improves Inflammation-Induced Chronic Pain | Preclinical Findings

Synopsis

Many patients continue to feel pain even after inflammation has healed, but the reason has been unclear. This study found that mitochondrial dysfunction in sensory neurons—the nerve cells that detect pain—drives the transition from temporary to chronic pain. In mice, brief inflammation caused long-lasting changes, called hyperalgesic priming, making neurons more sensitive to future pain. This was linked to increased ATPSc-KMT and disrupted metabolism, including lower levels of NAD+ precursors like nicotinamide riboside (NR). Giving NR to primed mice restored NAD+ levels and helped resolve PGE2-induced pain, while it had no effect in non-primed mice. Blocking mitochondrial respiration, reducing ATPSc-KMT, or restoring metabolism also reversed priming and prevented chronic pain. These findings suggest inflammation-induced mitochondrial changes “lock” neurons into a pain-sensitive state and that targeting metabolism and NAD+ pathways may offer new treatments.

Journal

Cell Reports Medicine