Abstract
Mitochondria are present at high concentration at the site of sensory transduction in the peripheral terminals of nociceptors. Because nerve growth factor (NGF), which induces nociceptor sensitization by acting on the high-affinity tropomyosin receptor kinase A (TrkA) receptor, also produces local recruitment of mitochondria in DRG neurons, we evaluated the role of mitochondria in NGF-induced mechanical hyperalgesia. Inhibition of 3 major mitochondrial functions-oxidation of nutrients, adenosine triphosphate (ATP) production, and generation of reactive oxygen species--markedly attenuated NGF-induced mechanical hyperalgesia in the rat. Disruption of microtubules, which are required for the trafficking and subcellular localization of mitochondria, also attenuated NGF-induced hyperalgesia. Our results suggest a contribution of mitochondrial localization and function to NGF-dependent pain syndromes.