Mitochondrial Dysfunction as a Driver of Chronic Pain: New Insights and Therapeutic Prospects
Pharmacol Res. 2026 Mar 21:108170. doi: 10.1016/j.phrs.2026.108170. Online ahead of print.
ABSTRACT
Chronic pain is a significant global health burden often resistant to conventional analgesics. Evidence implicates that mitochondrial dysfunction is not only a cellular consequence of injury, but also a fundamental driver of pain chronification. This review synthesizes current insights into how mitochondrial impairment contributes to pain chronification across diverse pathological contexts. Bioenergetic failure marked by ATP depletion and electron transport chain defects plays a central role. This energy crisis converges with oxidative stress, calcium overload, and neuroinflammation to promote neuronal hyperexcitability. Meanwhile, impaired mitophagy, suppressed biogenesis, and abnormal dynamics all contribute to the disrupted mitochondrial quality control, which further perpetuates cellular stress. Crucially, the efficacy of multiple mitochondria-targeted therapeutic strategies was summarized in this review. Despite gaps in current research, we emphasize that developments in biomarker and exploration of neuro-glial immune interactions could advance mitochondria-based precision medicine for pain management.
PMID:41871674 | DOI:10.1016/j.phrs.2026.108170