Membrane cholesterol depletion as a trigger of Nav1.9 channel-mediated inflammatory pain.

ABSTRACT: Cholesterol is a major lipid component of the mammalian plasma membrane. While much is known about its metabolism, its transport, and its role in atherosclerotic vascular disease, less is known about its role in neuronal pathophysiology. This study reveals an unexpected function of cholesterol in controlling pain transmission. We show that inflammation lowers cholesterol content in skin tissue and sensory DRG culture. Pharmacological depletion of cellular cholesterol entails sensitization of nociceptive neurons and promotes mechanical and thermal hyperalgesia through the activation of voltage-gated Nav1.9 channels. Inflammatory mediators enhance the production of reactive oxygen species and induce partitioning of Nav1.9 channels from cholesterol-rich lipid rafts to cholesterol-poor non-raf

SUBMITTER: Amsalem M 

PROVIDER: S-EPMC5897772 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature