PMID- 29394316
OWN - NLM
STAT- MEDLINE
DCOM- 20190628
LR  - 20230815
IS  - 1460-2156 (Electronic)
IS  - 0006-8950 (Print)
IS  - 0006-8950 (Linking)
VI  - 141
IP  - 4
DP  - 2018 Apr 1
TI  - Brain-derived neurotrophic factor derived from sensory neurons plays a critical 
      role in chronic pain.
PG  - 1028-1039
LID - 10.1093/brain/awy009 [doi]
AB  - Many studies support the pro-nociceptive role of brain-derived neurotrophin 
      factor (BDNF) in pain processes in the peripheral and central nervous system. We 
      have previously shown that nociceptor-derived BDNF is involved in inflammatory 
      pain. Microglial-derived BDNF has also been shown to be involved in neuropathic 
      pain. However, the distinct contribution of primary afferent-derived BNDF to 
      chronic pain processing remains undetermined. In this study, we used Avil-CreERT2 
      mice to delete Bdnf from all adult peripheral sensory neurons. Conditional BDNF 
      knockouts were healthy with no sensory neuron loss. Behavioural assays and in 
      vivo electrophysiology indicated that spinal excitability was normal. Following 
      formalin inflammation or neuropathy with a modified Chung model, we observed 
      normal development of acute pain behaviour, but a deficit in second phase 
      formalin-induced nocifensive responses and a reversal of neuropathy-induced 
      mechanical hypersensitivity during the later chronic pain phase in conditional 
      BDNF knockout mice. In contrast, we observed normal development of acute and 
      chronic neuropathic pain in the Seltzer model, indicating differences in the 
      contribution of BDNF to distinct models of neuropathy. We further used a model of 
      hyperalgesic priming to examine the contribution of primary afferent-derived BDNF 
      in the transition from acute to chronic pain, and found that primed BDNF knockout 
      mice do not develop prolonged mechanical hypersensitivity to an inflammatory 
      insult. Our data suggest that BDNF derived from sensory neurons plays a critical 
      role in mediating the transition from acute to chronic pain.
FAU - Sikandar, Shafaq
AU  - Sikandar S
AD  - Molecular Nociception Group, Wolfson Institute for Biomedical Research, Division 
      of Medicine, University College London, Gower Street London WC1E 6BT, UK.
FAU - Minett, Michael S
AU  - Minett MS
AD  - Molecular Nociception Group, Wolfson Institute for Biomedical Research, Division 
      of Medicine, University College London, Gower Street London WC1E 6BT, UK.
FAU - Millet, Queensta
AU  - Millet Q
AD  - Molecular Nociception Group, Wolfson Institute for Biomedical Research, Division 
      of Medicine, University College London, Gower Street London WC1E 6BT, UK.
FAU - Santana-Varela, Sonia
AU  - Santana-Varela S
AD  - Molecular Nociception Group, Wolfson Institute for Biomedical Research, Division 
      of Medicine, University College London, Gower Street London WC1E 6BT, UK.
FAU - Lau, Joanne
AU  - Lau J
AD  - Molecular Nociception Group, Wolfson Institute for Biomedical Research, Division 
      of Medicine, University College London, Gower Street London WC1E 6BT, UK.
FAU - Wood, John N
AU  - Wood JN
AD  - Molecular Nociception Group, Wolfson Institute for Biomedical Research, Division 
      of Medicine, University College London, Gower Street London WC1E 6BT, UK.
FAU - Zhao, Jing
AU  - Zhao J
AD  - Molecular Nociception Group, Wolfson Institute for Biomedical Research, Division 
      of Medicine, University College London, Gower Street London WC1E 6BT, UK.
LA  - eng
GR  - 200183/Z/15/Z/WT_/Wellcome Trust/United Kingdom
GR  - G091905/MRC_/Medical Research Council/United Kingdom
GR  - 507928/ARC_/Arthritis Research UK/United Kingdom
GR  - 101054/Z/13/Z/WT_/Wellcome Trust/United Kingdom
GR  - WT_/Wellcome Trust/United Kingdom
GR  - 200183/Z/15/Z/WT_/Wellcome Trust/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Brain
JT  - Brain : a journal of neurology
JID - 0372537
RN  - 0 (Avil protein, mouse)
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Microfilament Proteins)
RN  - 1HG84L3525 (Formaldehyde)
RN  - 9000-07-1 (Carrageenan)
SB  - IM
MH  - Animals
MH  - Brain-Derived Neurotrophic Factor/genetics/*metabolism
MH  - Carrageenan/toxicity
MH  - Chronic Pain/chemically induced/*pathology
MH  - Disease Models, Animal
MH  - Female
MH  - Formaldehyde/toxicity
MH  - Ganglia, Spinal/*pathology
MH  - Hyperalgesia/etiology
MH  - Male
MH  - Mice
MH  - Mice, Transgenic
MH  - Microfilament Proteins/genetics/metabolism
MH  - Pain Measurement
MH  - Sensory Receptor Cells/*metabolism
PMC - PMC5888992
EDAT- 2018/02/03 06:00
MHDA- 2019/06/30 06:00
PMCR- 2018/01/30
CRDT- 2018/02/03 06:00
PHST- 2017/06/08 00:00 [received]
PHST- 2017/12/02 00:00 [accepted]
PHST- 2018/02/03 06:00 [pubmed]
PHST- 2019/06/30 06:00 [medline]
PHST- 2018/02/03 06:00 [entrez]
PHST- 2018/01/30 00:00 [pmc-release]
AID - 4831043 [pii]
AID - awy009 [pii]
AID - 10.1093/brain/awy009 [doi]
PST - ppublish
SO  - Brain. 2018 Apr 1;141(4):1028-1039. doi: 10.1093/brain/awy009.