PMID- 29408929
OWN - NLM
STAT- MEDLINE
DCOM- 20180402
LR  - 20220408
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 13
IP  - 2
DP  - 2018
TI  - Cytokine-mediated inflammation mediates painful neuropathy from metabolic 
      syndrome.
PG  - e0192333
LID - 10.1371/journal.pone.0192333 [doi]
LID - e0192333
AB  - Painful neuropathy (PN) is a prevalent condition in patients with metabolic 
      syndrome (MetS). However, the pathogenic mechanisms of metabolic 
      syndrome-associated painful neuropathy (MetSPN) remain unclear. In the current 
      study, high-fat-fed mice (HF mice) were used to study MetSPN. HF mice developed 
      MetS phenotypes, including increased body weight, elevated plasma cholesterol 
      levels, and insulin resistance in comparison with control-fat-fed (CF) mice. 
      Subsequently, HF mice developed mechanical allodynia and thermal hyperalgesia in 
      hind paws after 8 wk of diet treatment. These pain behaviors coincided with 
      increased densities of nociceptive epidermal nerve fibers and inflammatory cells 
      such as Langerhans cells and macrophages in hind paw skin. To study the effect of 
      MetS on profiles of cytokine expression in HF mice, we used a multiplex cytokine 
      assay to study the protein expression of 12 pro-inflammatory and 
      anti-inflammatory cytokines in dorsal root ganglion and serum samples. This 
      method detected the elevated levels of proinflammatory cytokines, including tumor 
      necrosis factor (TNF)-alpha, and interleukin (IL)-6, IL-1beta as well as reduced 
      anti-inflammatory IL-10 in lumbar dorsal root ganglia (LDRG) of HF mice. 
      Intraperitoneal administration of IL-10 reduced the upregulation of 
      pro-inflammatory cytokines and alleviated pain behaviors in HF mice without 
      affecting MetS phenotypes. Our findings suggested targeting HF-induced cytokine 
      dysregulation could be an effective strategy for treating MetSPN.
FAU - Zhang, Can
AU  - Zhang C
AD  - Genetics and Aging Research Unit, MassGeneral Institute for Neurodegenerative 
      Disease, Department of Neurology, Massachusetts General Hospital, Boston, 
      Massachusetts, United States of America.
FAU - Ward, Joseph
AU  - Ward J
AD  - Genetics and Aging Research Unit, MassGeneral Institute for Neurodegenerative 
      Disease, Department of Neurology, Massachusetts General Hospital, Boston, 
      Massachusetts, United States of America.
FAU - Dauch, Jacqueline R
AU  - Dauch JR
AD  - Department of Neurology, University of Michigan Medical Center, Ann Arbor, 
      Michigan, United States of America.
FAU - Tanzi, Rudolph E
AU  - Tanzi RE
AD  - Genetics and Aging Research Unit, MassGeneral Institute for Neurodegenerative 
      Disease, Department of Neurology, Massachusetts General Hospital, Boston, 
      Massachusetts, United States of America.
FAU - Cheng, Hsinlin T
AU  - Cheng HT
AUID- ORCID: 0000-0002-6309-7298
AD  - Genetics and Aging Research Unit, MassGeneral Institute for Neurodegenerative 
      Disease, Department of Neurology, Massachusetts General Hospital, Boston, 
      Massachusetts, United States of America.
LA  - eng
GR  - K08 NS061039/NS/NINDS NIH HHS/United States
GR  - 1K08NS061039/NH/NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20180206
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Cytokines)
RN  - 0 (Inflammation Mediators)
RN  - 0 (Insulin)
RN  - Neuropathy, Painful
SB  - IM
MH  - Animals
MH  - Cytokines/*physiology
MH  - Diet, High-Fat
MH  - Hypercholesterolemia/physiopathology
MH  - Inflammation Mediators/*physiology
MH  - Insulin/blood
MH  - Male
MH  - Metabolic Syndrome/*physiopathology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Pain/*physiopathology
MH  - Peripheral Nervous System Diseases/*physiopathology
MH  - Real-Time Polymerase Chain Reaction
MH  - Weight Gain
PMC - PMC5800683
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2018/02/07 06:00
MHDA- 2018/04/03 06:00
PMCR- 2018/02/06
CRDT- 2018/02/07 06:00
PHST- 2017/05/12 00:00 [received]
PHST- 2017/12/29 00:00 [accepted]
PHST- 2018/02/07 06:00 [entrez]
PHST- 2018/02/07 06:00 [pubmed]
PHST- 2018/04/03 06:00 [medline]
PHST- 2018/02/06 00:00 [pmc-release]
AID - PONE-D-17-18377 [pii]
AID - 10.1371/journal.pone.0192333 [doi]
PST - epublish
SO  - PLoS One. 2018 Feb 6;13(2):e0192333. doi: 10.1371/journal.pone.0192333. 
      eCollection 2018.