PMID- 22137657
OWN - NLM
STAT- MEDLINE
DCOM- 20120910
LR  - 20191114
IS  - 1872-6240 (Electronic)
IS  - 0006-8993 (Linking)
VI  - 1432
DP  - 2012 Jan 13
TI  - Involvement of the long-chain fatty acid receptor GPR40 as a novel pain 
      regulatory system.
PG  - 74-83
LID - 10.1016/j.brainres.2011.11.012 [doi]
AB  - G-protein receptor (GPR) 40 is known to be activated by docosahexaenoic acid 
      (DHA). However, reports studying the role and functions (including pain 
      regulation) of GPR40 in the brain are lacking. We investigated the involvement of 
      GPR40 in the brain on DHA-induced antinociceptive effects. Expression of GPR40 
      protein was observed in the olfactory bulb, striatum, hippocampus, midbrain, 
      hypothalamus, medulla oblongata, cerebellum and cerebral cortex in the brain as 
      well as the spinal cord, whereas GPR120 protein expression in these areas was not 
      observed. Intracerebroventricular (i.c.v.), but not intrathecal (i.t.) injection 
      of DHA (25 and 50mug/mouse) and GW9508 (a GPR40- and GPR120-selective agonist; 0.1 
      and 1.0mug/mouse) significantly reduced formalin-induced pain behavior. These 
      effects were inhibited by pretreatment with the mu opioid receptor antagonist 
      beta-funaltrexamine (beta-FNA), naltrindole (delta opioid receptor antagonist) and 
      anti-beta-endorphin antiserum. The kappa opioid receptor antagonist norbinaltorphimine 
      (nor-BNI) did not affect the antinociception of DHA or GW9508. Furthermore, the 
      immunoreactivity of beta-endorphin in the hypothalamus increased at 10 and 20min 
      after i.c.v. injection of DHA and GW9508. These findings suggest that DHA-induced 
      antinociception via beta-endorphin release may be mediated (at least in part) 
      through GPR40 signaling in the supraspinal area, and may provide valuable 
      information on a novel therapeutic approach for pain control.
CI  - Copyright (c) 2011 Elsevier B.V. All rights reserved.
FAU - Nakamoto, Kazuo
AU  - Nakamoto K
AD  - Department of Clinical Pharmacy, Kobe Gakuin University, School of Pharmaceutical 
      Sciences, 1-1-3 Minatojima, Chuo-ku, Kobe 650-8586, Japan.
FAU - Nishinaka, Takashi
AU  - Nishinaka T
FAU - Matsumoto, Kengo
AU  - Matsumoto K
FAU - Kasuya, Fumiyo
AU  - Kasuya F
FAU - Mankura, Mitsumasa
AU  - Mankura M
FAU - Koyama, Yutaka
AU  - Koyama Y
FAU - Tokuyama, Shogo
AU  - Tokuyama S
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20111111
PL  - Netherlands
TA  - Brain Res
JT  - Brain research
JID - 0045503
RN  - 0 (Analgesics)
RN  - 0 (Ffar1 protein, mouse)
RN  - 0 (GW9508)
RN  - 0 (Methylamines)
RN  - 0 (Narcotic Antagonists)
RN  - 0 (Propionates)
RN  - 0 (Receptors, G-Protein-Coupled)
RN  - 0 (Receptors, Opioid)
RN  - 25167-62-8 (Docosahexaenoic Acids)
RN  - 60617-12-1 (beta-Endorphin)
SB  - IM
MH  - Analgesics/*pharmacology
MH  - Animals
MH  - Brain/metabolism/*physiology
MH  - Docosahexaenoic Acids/*physiology
MH  - Drug Synergism
MH  - Hypothalamus/drug effects/metabolism
MH  - Injections, Intraventricular/methods
MH  - Male
MH  - Methylamines/pharmacology
MH  - Mice
MH  - Narcotic Antagonists/pharmacology
MH  - Pain Management/*methods
MH  - Pain Measurement
MH  - Propionates/pharmacology
MH  - Receptors, G-Protein-Coupled/*physiology
MH  - Receptors, Opioid/drug effects/physiology
MH  - beta-Endorphin/physiology
EDAT- 2011/12/06 06:00
MHDA- 2012/09/11 06:00
CRDT- 2011/12/06 06:00
PHST- 2011/08/22 00:00 [received]
PHST- 2011/10/18 00:00 [revised]
PHST- 2011/11/04 00:00 [accepted]
PHST- 2011/12/06 06:00 [entrez]
PHST- 2011/12/06 06:00 [pubmed]
PHST- 2012/09/11 06:00 [medline]
AID - S0006-8993(11)02039-7 [pii]
AID - 10.1016/j.brainres.2011.11.012 [doi]
PST - ppublish
SO  - Brain Res. 2012 Jan 13;1432:74-83. doi: 10.1016/j.brainres.2011.11.012. Epub 2011 
      Nov 11.