PMID- 22609428
OWN - NLM
STAT- MEDLINE
DCOM- 20121024
LR  - 20220408
IS  - 1872-6623 (Electronic)
IS  - 0304-3959 (Print)
IS  - 0304-3959 (Linking)
VI  - 153
IP  - 7
DP  - 2012 Jul
TI  - Functional interactions between NMDA receptors and TRPV1 in trigeminal sensory 
      neurons mediate mechanical hyperalgesia in the rat masseter muscle.
PG  - 1514-1524
LID - 10.1016/j.pain.2012.04.015 [doi]
AB  - The NMDA and TRPV1 receptors that are expressed in sensory neurons have been 
      independently demonstrated to play important roles in peripheral pain mechanisms. 
      In the present study, we investigated whether the 2 receptor-channel systems form 
      a functional complex that provides the basis for the development of mechanical 
      hyperalgesia. In the masseter muscle, direct application of NMDA induced a 
      time-dependent increase in mechanical sensitivity, which was significantly 
      blocked when the muscle was pretreated with a specific TRPV1 antagonist, AMG9810. 
      The NR1 subunit of the NMDA receptor and TRPV1 were coexpressed in 32% of 
      masseter afferents in trigeminal ganglia (TG). Furthermore, NR1 and NR2B formed 
      protein-protein complexes with TRPV1 in TG as demonstrated by 
      coimmunoprecipitation experiments. Calcium imaging analyses further corroborated 
      that NMDA and TRPV1 receptors functionally interact. In TG culture, application 
      of NMDA resulted in phosphorylation of serine, but not threonine or tyrosine, 
      residues of TRPV1 in a time course similar to that of the development of 
      NMDA-induced mechanical hyperalgesia. The NMDA-induced phosphorylation was 
      significantly attenuated by CaMKII and PKC inhibitors, but not by a PKA 
      inhibitor. Consistent with the biochemical data, the NMDA-induced mechanical 
      hyperalgesia was also effectively blocked when the muscle was pretreated with a 
      CaMKII or PKC inhibitor. Thus, NMDA receptors and TRPV1 functionally interact via 
      CaMKII and PKC signaling cascades and contribute to mechanical hyperalgesia. 
      These data offer novel mechanisms by which 2 ligand-gated channels in sensory 
      neurons interact and reinforce the notion that TRPV1 functions as a signal 
      integrator under pathological conditions.
CI  - Copyright (c) 2012 International Association for the Study of Pain. Published by 
      Elsevier B.V. All rights reserved.
FAU - Lee, Jongseok
AU  - Lee J
AD  - University of Maryland School of Dentistry, Department of Neural and Pain 
      Sciences, Program in Neuroscience, Baltimore, MA, USA Kyung Hee University, 
      School of Dentistry, Department of Oral Medicine, Seoul, Republic of Korea.
FAU - Saloman, Jami L
AU  - Saloman JL
FAU - Weiland, Gustave
AU  - Weiland G
FAU - Auh, Q-Schick
AU  - Auh QS
FAU - Chung, Man-Kyo
AU  - Chung MK
FAU - Ro, Jin Y
AU  - Ro JY
LA  - eng
GR  - R01 DE016062/DE/NIDCR NIH HHS/United States
GR  - R01 DE16062/DE/NIDCR NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20120519
PL  - United States
TA  - Pain
JT  - Pain
JID - 7508686
RN  - 0 (3-(4-t-butylphenyl)-N-(2,3-dihydrobenzo(b)(1,4)dioxin-6-yl)acrylamide)
RN  - 0 (Acrylamides)
RN  - 0 (Bridged Bicyclo Compounds, Heterocyclic)
RN  - 0 (Receptors, N-Methyl-D-Aspartate)
RN  - 0 (TRPV Cation Channels)
RN  - 0 (Trpv1 protein, rat)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - Acrylamides/pharmacology
MH  - Animals
MH  - Bridged Bicyclo Compounds, Heterocyclic/pharmacology
MH  - Calcium/metabolism
MH  - Hyperalgesia/*physiopathology
MH  - Male
MH  - Masseter Muscle/drug effects/*metabolism
MH  - Pain Measurement
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Receptors, N-Methyl-D-Aspartate/*metabolism
MH  - Sensory Receptor Cells/drug effects/*metabolism
MH  - Signal Transduction/drug effects/physiology
MH  - TRPV Cation Channels/antagonists & inhibitors/*metabolism
MH  - Trigeminal Ganglion/metabolism/physiopathology
PMC - PMC3377858
MID - NIHMS371598
EDAT- 2012/05/23 06:00
MHDA- 2012/10/25 06:00
PMCR- 2013/07/01
CRDT- 2012/05/22 06:00
PHST- 2011/12/22 00:00 [received]
PHST- 2012/03/07 00:00 [revised]
PHST- 2012/04/12 00:00 [accepted]
PHST- 2012/05/22 06:00 [entrez]
PHST- 2012/05/23 06:00 [pubmed]
PHST- 2012/10/25 06:00 [medline]
PHST- 2013/07/01 00:00 [pmc-release]
AID - 00006396-201207000-00026 [pii]
AID - 10.1016/j.pain.2012.04.015 [doi]
PST - ppublish
SO  - Pain. 2012 Jul;153(7):1514-1524. doi: 10.1016/j.pain.2012.04.015. Epub 2012 May 
      19.