PMID- 24388921
OWN - NLM
STAT- MEDLINE
DCOM- 20140919
LR  - 20220311
IS  - 1873-7544 (Electronic)
IS  - 0306-4522 (Linking)
VI  - 261
DP  - 2014 Mar 7
TI  - Inflammation enhanced brain-derived neurotrophic factor-induced suppression of 
      the voltage-gated potassium currents in small-diameter trigeminal ganglion 
      neurons projecting to the trigeminal nucleus interpolaris/caudalis transition 
      zone.
PG  - 223-31
LID - S0306-4522(13)01073-7 [pii]
LID - 10.1016/j.neuroscience.2013.12.048 [doi]
AB  - We recently indicated that brain-derived neurotrophic factor (BDNF) enhances the 
      excitability of small-diameter trigeminal ganglion (TRG) neurons projecting onto 
      the trigeminal nucleus interpolaris/caudalis (Vi/Vc) transition zone via a 
      paracrine mechanism following masetter muscle (MM) inflammation. The present 
      study investigated whether modulation of voltage-gated potassium (K) channels by 
      BDNF contributes to this hyperexcitability effect. To induce inflammation we 
      injected complete Freund's adjuvant (CFA) into the MM. The escape threshold from 
      mechanical stimulation applied to skin above the inflamed MM was significantly 
      lower than in naive rats. TRG neurons innervating the site of inflammation were 
      subsequently identified by fluorogold (FG) labeling, and microbeads (MB) were 
      used to label neurons projecting specifically to the Vi/Vc region. BDNF 
      significantly decreased the total, transient (IA), and sustained (IK) currents in 
      FG-/MB-labeled small-diameter TRG neurons under voltage-clamp conditions in naive 
      and inflamed rats. The magnitude of inhibition of IA and IK currents by BDNF in 
      FG-/MB-labeled TRG neurons was significantly greater in inflamed rats than in 
      naive rats, and BDNF inhibited IA to a significantly greater extent than IK. 
      Furthermore, co-administration of K252a, a tyrosine kinase inhibitor, abolished 
      the suppression of IA and IK currents by BDNF. These results suggested that the 
      inhibitory effects of BDNF on IA and IK currents in small-diameter TRG neurons 
      projecting onto the Vi/Vc potentiate neuronal excitability, and in turn, 
      contribute to MM inflammatory hyperalgesia. These findings support the 
      development of voltage-gated K(+) channel openers and tyrosine kinase inhibitors 
      as potential therapeutic agents for the treatment of trigeminal inflammatory 
      hyperalgesia.
CI  - Copyright (c) 2014 IBRO. Published by Elsevier Ltd. All rights reserved.
FAU - Takeda, M
AU  - Takeda M
AD  - Department of Physiology, School of Life Dentistry at Tokyo, Nippon Dental 
      University, 1-9-20, Fujimi-cho, Chiyoda-ku, Tokyo 102-8159, Japan. Electronic 
      address: m-takeda@tokyo.ndu.ac.jp.
FAU - Takahashi, M
AU  - Takahashi M
AD  - Department of Physiology, School of Life Dentistry at Tokyo, Nippon Dental 
      University, 1-9-20, Fujimi-cho, Chiyoda-ku, Tokyo 102-8159, Japan.
FAU - Matsumoto, S
AU  - Matsumoto S
AD  - Department of Physiology, School of Life Dentistry at Tokyo, Nippon Dental 
      University, 1-9-20, Fujimi-cho, Chiyoda-ku, Tokyo 102-8159, Japan.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140103
PL  - United States
TA  - Neuroscience
JT  - Neuroscience
JID - 7605074
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Carbazoles)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Indole Alkaloids)
RN  - 0 (Potassium Channels, Voltage-Gated)
RN  - 9007-81-2 (Freund's Adjuvant)
RN  - 97161-97-2 (staurosporine aglycone)
RN  - RWP5GA015D (Potassium)
SB  - IM
MH  - Animals
MH  - Brain-Derived Neurotrophic Factor/*metabolism
MH  - Carbazoles/pharmacology
MH  - Enzyme Inhibitors/pharmacology
MH  - Freund's Adjuvant
MH  - Hyperalgesia/metabolism
MH  - Indole Alkaloids/pharmacology
MH  - Inflammation/*metabolism
MH  - Male
MH  - Masseter Muscle/innervation/metabolism
MH  - Membrane Potentials/drug effects/physiology
MH  - Neurons/drug effects/*metabolism
MH  - Potassium/metabolism
MH  - Potassium Channels, Voltage-Gated/*metabolism
MH  - Rats
MH  - Rats, Wistar
MH  - Touch
MH  - Trigeminal Ganglion/drug effects/*metabolism
OTO - NOTNLM
OT  - BDNF
OT  - hyperalgesia
OT  - inflammation
OT  - trigeminal ganglion
OT  - trkB
OT  - voltage-gated K(+) currents
EDAT- 2014/01/07 06:00
MHDA- 2014/09/23 06:00
CRDT- 2014/01/07 06:00
PHST- 2013/11/07 00:00 [received]
PHST- 2013/12/12 00:00 [revised]
PHST- 2013/12/20 00:00 [accepted]
PHST- 2014/01/07 06:00 [entrez]
PHST- 2014/01/07 06:00 [pubmed]
PHST- 2014/09/23 06:00 [medline]
AID - S0306-4522(13)01073-7 [pii]
AID - 10.1016/j.neuroscience.2013.12.048 [doi]
PST - ppublish
SO  - Neuroscience. 2014 Mar 7;261:223-31. doi: 10.1016/j.neuroscience.2013.12.048. 
      Epub 2014 Jan 3.