title: Mitochondrial and bioenergetic dysfunction in trauma-induced painful peripheral neuropathy.
abstract: BACKGROUND
  Mitochondrial dysfunction is observed in various neuropathic pain phenotypes, such as chemotherapy induced neuropathy, diabetic neuropathy, HIV-associated neuropathy, and in Charcot-Marie-Tooth neuropathy. To investigate whether mitochondrial dysfunction is present in trauma-induced painful mononeuropathy, a time-course of mitochondrial function and bioenergetics was characterized in the mouse partial sciatic nerve ligation model.
  
  
  RESULTS
  Traumatic nerve injury induces increased metabolic indices of the nerve, resulting in increased oxygen consumption and increased glycolysis. Increased metabolic needs of the nerve are concomitant with bioenergetic and mitochondrial dysfunction. Mitochondrial dysfunction is characterized by reduced ATP synthase activity, reduced electron transport chain activity, and increased futile proton cycling. Bioenergetic dysfunction is characterized by reduced glycolytic reserve, reduced glycolytic capacity, and increased non-glycolytic acidification.
  
  
  CONCLUSIONS
  Traumatic peripheral nerve injury induces persistent mitochondrial and bioenergetic dysfunction which implies that pharmacological agents which seek to normalize mitochondrial and bioenergetic dysfunction could be expected to be beneficial for pain treatment. Increases in both glycolytic acidification and non-glycolytic acidification suggest that pH sensitive drugs which preferentially act on acidic tissue will have the ability to preferential act on injured nerves without affecting healthy tissues.
authors.affiliation: Neurology and Neurosurgery, McGill University, Montreal, QC, H3A 2B4, Canada. tony.lim@mail.mcgill.ca.|Alan Edwards Centre for Research on Pain, McGill University, 740 Docteur Penfield Ave, Suite 3200, Montreal, QC, H3A 0G1, Canada. tony.lim@mail.mcgill.ca.
authors.forename: Tony K Y
authors.initials: TK
authors.lastname: Lim
authors.affiliation: Neurology and Neurosurgery, McGill University, Montreal, QC, H3A 2B4, Canada. malena.rone@mail.mcgill.ca.
authors.forename: Malena B
authors.initials: MB
authors.lastname: Rone
authors.affiliation: Alan Edwards Centre for Research on Pain, McGill University, 740 Docteur Penfield Ave, Suite 3200, Montreal, QC, H3A 0G1, Canada. seunghwan.lee@mail.mcgill.ca.|Faculty of Dentistry, McGill University, Montreal, QC, H3A 0C7, Canada. seunghwan.lee@mail.mcgill.ca.
authors.forename: Seunghwan
authors.initials: S
authors.lastname: Lee
authors.affiliation: Neurology and Neurosurgery, McGill University, Montreal, QC, H3A 2B4, Canada. jack.antel@mcgill.ca.
authors.forename: Jack P
authors.initials: JP
authors.lastname: Antel
authors.affiliation: Neurology and Neurosurgery, McGill University, Montreal, QC, H3A 2B4, Canada. ji.zhang@mcgill.ca.|Alan Edwards Centre for Research on Pain, McGill University, 740 Docteur Penfield Ave, Suite 3200, Montreal, QC, H3A 0G1, Canada. ji.zhang@mcgill.ca.|Faculty of Dentistry, McGill University, Montreal, QC, H3A 0C7, Canada. ji.zhang@mcgill.ca.
authors.forename: Ji
authors.initials: J
authors.lastname: Zhang
mesh_terms: D000143:Acids / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D019069:Cell Respiration; D004734:Energy Metabolism; D005110:Extracellular Space / Q000378:metabolism; D006019:Glycolysis; D008026:Ligation; D008297:Male; D008810:Mice, Inbred C57BL; D008928:Mitochondria / Q000378:metabolism*; D009437:Neuralgia / Q000209:etiology* / Q000378:metabolism*; D010101:Oxygen Consumption; D011522:Protons; D012584:Sciatic Nerve / Q000293:injuries / Q000378:metabolism / Q000473:pathology; D014947:Wounds and Injuries / Q000150:complications* / Q000378:metabolism*
chemical_list: D000143:Acids; D011522:Protons; D000255:Adenosine Triphosphate