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Papers of the Week

Papers: 4 Nov 2023 - 10 Nov 2023

2023 Oct 31

Cell Rep Med


Editor's Pick

Inflammation-induced mitochondrial and metabolic disturbances in sensory neurons control the switch from acute to chronic pain.


Willemen HLDM, Santos Ribeiro PS, Broeks M, Meijer N, Versteeg S, Tiggeler A, de Boer TP, Małecki JM, Falnes PØ, Jans J, Eijkelkamp N


Pain often persists in patients with an inflammatory disease, even when inflammation has subsided. The molecular mechanisms leading to this failure in pain resolution and the transition to chronic pain are poorly understood. Mitochondrial dysfunction in sensory neurons links to chronic pain, but its role in resolution of inflammatory pain is unclear. Transient inflammation causes neuronal plasticity, called hyperalgesic priming, which impairs resolution of pain induced by a subsequent inflammatory stimulus. We identify that hyperalgesic priming in mice increases the expression of a mitochondrial protein (ATPSc-KMT) and causes mitochondrial and metabolic disturbances in sensory neurons. Inhibition of mitochondrial respiration, knockdown of ATPSCKMT expression, or supplementation of the affected metabolite is sufficient to restore resolution of inflammatory pain and prevents chronic pain development. Thus, inflammation-induced mitochondrial-dependent disturbances in sensory neurons predispose to a failure in resolution of inflammatory pain and development of chronic pain.