PMID- 24103402
OWN - NLM
STAT- MEDLINE
DCOM- 20141006
LR  - 20211021
IS  - 1872-6623 (Electronic)
IS  - 0304-3959 (Print)
IS  - 0304-3959 (Linking)
VI  - 155
IP  - 2
DP  - 2014 Feb
TI  - Altered rate-dependent depression of the spinal H-reflex as an indicator of 
      spinal disinhibition in models of neuropathic pain.
PG  - 250-260
LID - 10.1016/j.pain.2013.10.001 [doi]
AB  - The unpredictable efficacy of current therapies for neuropathic pain may reflect 
      diverse etiological mechanisms operating between, and within, diseases. As 
      descriptions of pain rarely establish specific mechanisms, a tool that can 
      identify underlying causes of neuropathic pain would be useful in developing 
      patient-specific treatments. Rate-dependent depression (RDD), a measure of the 
      change in amplitude of the Hoffman reflex over consecutive stimulations, is 
      attenuated in diabetic rats that also exhibit impaired spinal gamma-aminobutyric acid 
      (GABA)A receptor function, reduced spinal potassium chloride co-transporter 
      (KCC2) expression, and indices of painful neuropathy. To investigate whether loss 
      of RDD is a reliable indicator of the contribution of spinal GABAergic 
      dysfunction to neuropathic pain, we assessed RDD, tactile allodynia, and 
      formalin-evoked hyperalgesia in 3 models: rats treated acutely with brain-derived 
      neurotrophic factor (BDNF), diabetic rats treated with the BDNF-sequestering 
      molecule tyrosine receptor kinase B/Fc (TrkB/Fc), and rats with 
      paclitaxel-induced neuropathy. Delivery of BDNF to the spinal cord of normal rats 
      produced RDD deficits and features of painful neuropathy associated with 
      disrupted GABAA receptor-mediated inhibitory function and reduced dorsal spinal 
      KCC2 expression. Treating diabetic rats with TrkB/Fc restored RDD and alleviated 
      indices of painful neuropathy. In paclitaxel-treated rats, RDD was not impaired 
      and behavioral indices of neuropathic pain were not associated with spinal 
      GABAergic dysfunction or reduced dorsal spinal KCC2 expression. Our data reveal 
      BDNF as part of the mechanism underlying spinal cord disinhibition caused by 
      altered GABAA receptor function in diabetic rats and suggest that RDD deficits 
      may be a useful indicator of neuropathic pain states associated with spinal 
      disinhibition, thereby revealing specific therapeutic targets.
CI  - Copyright (c) 2013 International Association for the Study of Pain. Published by 
      Elsevier B.V. All rights reserved.
FAU - Lee-Kubli, Corinne A G
AU  - Lee-Kubli CAG
AD  - Department of Pathology, University of California San Diego, La Jolla, CA 92093, 
      USA Graduate School of Biomedical Sciences, Sanford-Burnham Institute for Medical 
      Research, La Jolla, CA 92037, USA.
FAU - Calcutt, Nigel A
AU  - Calcutt NA
LA  - eng
GR  - R01 DK057629/DK/NIDDK NIH HHS/United States
GR  - DK57629/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20131005
PL  - United States
TA  - Pain
JT  - Pain
JID - 7508686
RN  - Neuropathy, Painful
SB  - IM
MH  - Animals
MH  - *Disease Models, Animal
MH  - Female
MH  - H-Reflex/*physiology
MH  - Long-Term Synaptic Depression/*physiology
MH  - Neural Inhibition/*physiology
MH  - Pain/diagnosis/*physiopathology
MH  - Pain Measurement/methods
MH  - Peripheral Nervous System Diseases/diagnosis/*physiopathology
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Spinal Cord/*physiology
PMC - PMC3946970
MID - NIHMS530543
OTO - NOTNLM
OT  - BDNF
OT  - Diabetic neuropathy
OT  - H-reflex
OT  - Pain
OT  - Spinal disinhibition
OT  - Taxol neuropathy
COIS- Neither author has any conflict of interest to declare.
EDAT- 2013/10/10 06:00
MHDA- 2014/10/07 06:00
PMCR- 2015/02/01
CRDT- 2013/10/10 06:00
PHST- 2012/06/19 00:00 [received]
PHST- 2013/10/01 00:00 [revised]
PHST- 2013/10/01 00:00 [accepted]
PHST- 2013/10/10 06:00 [entrez]
PHST- 2013/10/10 06:00 [pubmed]
PHST- 2014/10/07 06:00 [medline]
PHST- 2015/02/01 00:00 [pmc-release]
AID - 00006396-201402000-00008 [pii]
AID - 10.1016/j.pain.2013.10.001 [doi]
PST - ppublish
SO  - Pain. 2014 Feb;155(2):250-260. doi: 10.1016/j.pain.2013.10.001. Epub 2013 Oct 5.