PMID- 28621704
OWN - NLM
STAT- MEDLINE
DCOM- 20180502
LR  - 20210113
IS  - 1872-6623 (Electronic)
IS  - 0304-3959 (Linking)
VI  - 158
IP  - 9
DP  - 2017 Sep
TI  - Sensitization of TRPV1 and TRPA1 via peripheral mGluR5 signaling contributes to 
      thermal and mechanical hypersensitivity.
PG  - 1754-1764
LID - 10.1097/j.pain.0000000000000973 [doi]
AB  - Peripheral tissue inflammation or injury causes glutamate release from 
      nociceptive axons, keratinocytes, and Schwann cells, resulting in thermal 
      hypersensitivity. However, the detailed molecular mechanisms underlying 
      glutamate-induced thermal hypersensitivity are unknown. The aim of this study was 
      to clarify the involvement of peripheral transient receptor potential (TRP) TRP 
      vanilloid 1 (TRPV1), TRP ankyrin 1 (TRPA1), and protein kinase C epsilon (PKCepsilon) 
      in glutamate-induced pain hypersensitivity. The amount of glutamate in the facial 
      tissue was significantly increased 3 days after facial Complete Freund's adjuvant 
      injection. The head-withdrawal reflex threshold to heat, cold, or mechanical 
      stimulation was significantly decreased on day 7 after continuous glutamate or 
      metabotropic glutamate receptor 5 (mGluR5) agonist (CHPG) injection into the 
      facial skin compared with vehicle-injected rats, and glutamate-induced 
      hypersensitivity was significantly recovered by mGluR5 antagonist MTEP, TRPA1 
      antagonist HC-030031, TRPV1 antagonist SB366791, or PKCepsilon translocation inhibitor 
      administration into the facial skin. TRPV1 and TRPA1 were expressed in 
      mGluR5-immunoreactive (IR) trigeminal ganglion (TG) neurons innervating the 
      facial skin, and mGluR5-IR TG neurons expressed PKCepsilon. There was no significant 
      difference in the number of GluR5-IR TG neurons among glutamate-injected, 
      saline-injected, and naive rats, whereas that of TRPV1- or TRPA1-IR TG neurons 
      was significantly increased 7 days after continuous glutamate injection into the 
      facial skin compared with vehicle injection. PKCepsilon phosphorylation in TG was 
      significantly enhanced following glutamate injection into the facial skin. 
      Moreover, neuronal activity of TG neurons was significantly increased following 
      facial glutamate treatment. The present findings suggest that sensitization of 
      TRPA1 and/or TRPV1 through mGluR5 signaling via PKCepsilon is involved in facial 
      thermal and mechanical hypersensitivity.
FAU - Honda, Kuniya
AU  - Honda K
AD  - Departments of Physiology.
AD  - Oral and Maxillofacial Surgery.
FAU - Shinoda, Masamichi
AU  - Shinoda M
AD  - Departments of Physiology.
FAU - Kondo, Masahiro
AU  - Kondo M
AD  - Departments of Physiology.
FAU - Shimizu, Kohei
AU  - Shimizu K
AD  - Endodontics, and.
FAU - Yonemoto, Hisashi
AU  - Yonemoto H
AD  - Departments of Physiology.
FAU - Otsuki, Katsuhiko
AU  - Otsuki K
AD  - Departments of Physiology.
FAU - Akasaka, Ryuta
AU  - Akasaka R
AD  - Clinical Medicine, Nihon University School of Dentistry, Tokyo, Japan.
FAU - Furukawa, Akihiko
AU  - Furukawa A
AD  - Clinical Medicine, Nihon University School of Dentistry, Tokyo, Japan.
FAU - Iwata, Koichi
AU  - Iwata K
AD  - Departments of Physiology.
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Pain
JT  - Pain
JID - 7508686
RN  - 0 
      (2-(1,3-dimethyl-2,6-dioxo-1,2,3,6-tetrahydro-7H-purin-7-yl)-N-(4-isopropylphenyl)acetamide)
RN  - 0 (2-chloro-5-hydroxyphenylglycine)
RN  - 0 (3-((2-methyl-1,3-thiazol-4-yl)ethynyl)pyridine)
RN  - 0 (Acetanilides)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Phenylacetates)
RN  - 0 (Purines)
RN  - 0 (Pyridines)
RN  - 0 (Receptor, Metabotropic Glutamate 5)
RN  - 0 (TRPA1 Cation Channel)
RN  - 0 (TRPV Cation Channels)
RN  - 0 (Thiazoles)
RN  - 0 (Trpa1 protein, rat)
RN  - 0 (Trpv1 protein, rat)
RN  - 3KX376GY7L (Glutamic Acid)
RN  - 9007-81-2 (Freund's Adjuvant)
RN  - TE7660XO1C (Glycine)
SB  - IM
MH  - Acetanilides/pharmacology
MH  - Animals
MH  - Disease Models, Animal
MH  - Enzyme Inhibitors/pharmacology
MH  - Freund's Adjuvant/toxicity
MH  - Glutamic Acid/metabolism/toxicity
MH  - Glycine/analogs & derivatives/pharmacology
MH  - Hyperalgesia/etiology/*metabolism
MH  - Male
MH  - Neurons/drug effects/physiology
MH  - Pain/chemically induced/complications
MH  - Pain Threshold/drug effects/*physiology
MH  - Phenylacetates/pharmacology
MH  - Physical Stimulation/adverse effects
MH  - Purines/pharmacology
MH  - Pyridines/pharmacology
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Receptor, Metabotropic Glutamate 5/*metabolism
MH  - Signal Transduction/*physiology
MH  - Skin/innervation
MH  - TRPA1 Cation Channel/antagonists & inhibitors/*metabolism
MH  - TRPV Cation Channels/antagonists & inhibitors/*metabolism
MH  - Thiazoles/pharmacology
MH  - Trigeminal Ganglion/cytology
EDAT- 2017/06/18 06:00
MHDA- 2018/05/03 06:00
CRDT- 2017/06/17 06:00
PHST- 2017/06/18 06:00 [pubmed]
PHST- 2018/05/03 06:00 [medline]
PHST- 2017/06/17 06:00 [entrez]
AID - 00006396-201709000-00015 [pii]
AID - 10.1097/j.pain.0000000000000973 [doi]
PST - ppublish
SO  - Pain. 2017 Sep;158(9):1754-1764. doi: 10.1097/j.pain.0000000000000973.