title: Mitochondrial dependence of nerve growth factor-induced mechanical hyperalgesia.
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.
authors.affiliation: Department of Oral and Maxillofacial Surgery, University of California, San Francisco, CA, USA Division of Neuroscience, University of California, San Francisco, CA, USA Department of Medicine, University of California, San Francisco, CA, USA.
authors.forename: Carissa
authors.initials: C
authors.lastname: Chu
authors.forename: Emma
authors.initials: E
authors.lastname: Levine
authors.forename: Robert W
authors.initials: RW
authors.lastname: Gear
authors.forename: Oliver
authors.initials: O
authors.lastname: Bogen
authors.forename: Jon D
authors.initials: JD
authors.lastname: Levine
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D000977:Antiparasitic Agents / Q000627:therapeutic use; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006930:Hyperalgesia / Q000139:chemically induced* / Q000188:drug therapy / Q000473:pathology*; D008297:Male; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D020932:Nerve Growth Factor / Q000009:adverse effects*; D009840:Oligomycins / Q000494:pharmacology; D010147:Pain Measurement; D017288:Pain Threshold / Q000187:drug effects / Q000523:psychology*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000977:Antiparasitic Agents; D004791:Enzyme Inhibitors; D009840:Oligomycins; D020932:Nerve Growth Factor; D000111:Acetylcysteine