title: Ganglioside GM3 synthase depletion reverses neuropathic pain and small fiber neuropathy in diet-induced diabetic mice.
abstract: Small fiber neuropathy is a well-recognized complication of type 2 diabetes and has been shown to be responsible for both neuropathic pain and impaired wound healing. In previous studies, we have demonstrated that ganglioside GM3 depletion by knockdown of GM3 synthase fully reverses impaired wound healing in diabetic mice. However, the role of GM3 in neuropathic pain and small fiber neuropathy in diabetes is unknown.
  
  
  
  Determine whether GM3 depletion is able to reverse neuropathic pain and small fibers neuropathy and the mechanism of the reversal.
  
  
  
  We demonstrate that GM3 synthase knockout and the resultant GM3 depletion rescues the denervation in mouse footpad skin and fully reverses the neuropathic pain in diet-induced obese diabetic mice. In cultured dorsal root ganglia from diet-induced diabetic mice, GM3 depletion protects against increased intracellular calcium influx in vitro.
  
  
  
  These studies establish ganglioside GM3 as a new candidate responsible for neuropathic pain and small fiber neuropathy in diabetes. Moreover, these observations indicate that systemic or topically applied interventions aimed at depleting GM3 may improve both the painful neuropathy and the wound healing impairment in diabetes by protecting against nerve end terminal degeneration, providing a disease-modifying approach to this common, currently intractable medical issue.
authors: Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA d-menichella@northwestern.edu apaller@northwestern.edu.
authors: Daniela M
authors: DM
authors: Menichella
authors: Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
authors: Nirupa D
authors: ND
authors: Jayaraj
authors: Department of Dermatology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
authors: Heather M
authors: HM
authors: Wilson
authors: Department of Pharmacology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
authors: Dongjun
authors: D
authors: Ren
authors: Department of Dermatology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
authors: Kelsey
authors: K
authors: Flood
authors: Department of Dermatology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
authors: Xiao-Qi
authors: XQ
authors: Wang
authors: Department of Pharmacology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
authors: Andrew
authors: A
authors: Shum
authors: Department of Pharmacology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
authors: Richard J
authors: RJ
authors: Miller
authors: Department of Dermatology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
authors: Amy S
authors: AS
authors: Paller
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000235:genetics / Q000378:metabolism; D002478:Cells, Cultured; D003924:Diabetes Mellitus, Type 2 / Q000209:etiology / Q000473:pathology / Q000503:physiopathology*; D059305:Diet, High-Fat / Q000009:adverse effects; D004195:Disease Models, Animal; D005679:G(M3) Ganglioside / Q000378:metabolism; D005727:Ganglia, Spinal / Q000378:metabolism / Q000473:pathology; D007333:Insulin Resistance / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009474:Neurons / Q000378:metabolism; D010146:Pain / Q000209:etiology* / Q000235:genetics / Q000378:metabolism*; D010147:Pain Measurement; D010523:Peripheral Nervous System Diseases / Q000209:etiology* / Q000235:genetics / Q000378:metabolism*; D010812:Physical Stimulation / Q000009:adverse effects; D012584:Sciatic Nerve / Q000378:metabolism; D012799:Sialyltransferases / Q000172:deficiency* / Q000235:genetics; D012867:Skin / Q000294:innervation; D000071075:Small Fiber Neuropathy / Q000209:etiology* / Q000378:metabolism*
chemical_list: D001786:Blood Glucose; D005679:G(M3) Ganglioside; D012799:Sialyltransferases; C021343:haematoside synthetase
keywords: GM3 ganglioside; Neuropathic pain; diabetes; glucose intolerance; obesity; small fiber neuropathy