PMID- 29503395
OWN - NLM
STAT- MEDLINE
DCOM- 20181011
LR  - 20181011
IS  - 1880-4926 (Electronic)
IS  - 1343-4934 (Linking)
VI  - 60
IP  - 1
DP  - 2018 Mar 24
TI  - Inhibition of 2-arachydonoylgycerol degradation attenuates orofacial neuropathic 
      pain in trigeminal nerve-injured mice.
PG  - 37-44
LID - 10.2334/josnusd.17-0005 [doi]
AB  - Current therapeutics are not effective for orofacial neuropathic pain, and better 
      options are needed. The present study used inferior orbital nerve (ION)-injured 
      mice to investigate the effect of inhibiting monoacylglycerol lipase (MAGL), an 
      enzyme that degrades the major endocannabinoid 2-arachydonoylgycerol (2-AG) in 
      orofacial neuropathic pain. The head-withdrawal threshold to mechanical 
      stimulation of the whisker pad was reduced on days 3, 5, and 7 after ION injury. 
      Injection of JZL184, a selective inhibitor of MAGL, on day 7 after ION injury 
      attenuated the reduction in head-withdrawal threshold at 2 h after 
      administration. Moreover, the numbers of MAGL-immunoreactive neurons in the 
      trigeminal subnucleus caudalis (Vc) and upper cervical spinal cord (C1-C2) were 
      significantly greater in ION-injured mice than in sham-operated mice but were 
      reduced after administration of JZL184. The increase in MAGL immunoreactivity 
      suggests that increased 2-AG production is followed by rapid enzymatic 
      degradation of 2-AG. JZL184 inhibited this degradation and thus increased 2-AG 
      concentration in the brain, particularly in the Vc and C1-C2 regions, thus 
      attenuating pain. Our findings suggest that inhibition of 2-AG degradation by 
      MAGL inhibitors is a promising therapeutic option for treatment of orofacial 
      neuropathic pain.
FAU - Kamimura, Rantaro
AU  - Kamimura R
AD  - Division of Orthodontics, Department of Oral Biological Science,Niigata 
      University Graduate School of Medical and Dental Sciences.
FAU - Hossain, Mohammad Z
AU  - Hossain MZ
AD  - Department of Oral Physiology, School of Dentistry, Matsumoto Dental University.
FAU - Unno, Shumpei
AU  - Unno S
AD  - Department of Oral Physiology, School of Dentistry, Matsumoto Dental University.
FAU - Ando, Hiroshi
AU  - Ando H
AD  - Department of Biology, Institute for Oral Science, Matsumoto Dental University.
FAU - Masuda, Yuji
AU  - Masuda Y
AD  - Institute for Oral Science, Matsumoto Dental University.
FAU - Takahashi, Kojiro
AU  - Takahashi K
AD  - Division of Orthodontics, Department of Oral Biological Science,Niigata 
      University Graduate School of Medical and Dental Sciences.
FAU - Otake, Masanori
AU  - Otake M
AD  - Division of Orthodontics, Department of Oral Biological Science,Niigata 
      University Graduate School of Medical and Dental Sciences.
FAU - Saito, Isao
AU  - Saito I
AD  - Division of Orthodontics, Department of Oral Biological Science,Niigata 
      University Graduate School of Medical and Dental Sciences.
FAU - Kitagawa, Junichi
AU  - Kitagawa J
AD  - Department of Oral Physiology, School of Dentistry, Matsumoto Dental University.
LA  - eng
PT  - Journal Article
DEP - 20180302
PL  - Japan
TA  - J Oral Sci
JT  - Journal of oral science
JID - 9808942
RN  - 0 (Arachidonic Acids)
RN  - 0 (Benzodioxoles)
RN  - 0 (Endocannabinoids)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Glycerides)
RN  - 0 (JZL 184)
RN  - 0 (Piperidines)
RN  - 8D239QDW64 (glyceryl 2-arachidonate)
RN  - EC 3.1.1.23 (Monoacylglycerol Lipases)
SB  - IM
MH  - Animals
MH  - Arachidonic Acids/*antagonists & inhibitors/metabolism
MH  - Behavior, Animal
MH  - Benzodioxoles/pharmacology
MH  - Endocannabinoids/*antagonists & inhibitors/metabolism
MH  - Enzyme Inhibitors/pharmacology
MH  - Facial Pain/etiology/*prevention & control
MH  - Glycerides/*antagonists & inhibitors/metabolism
MH  - Male
MH  - Mice, Inbred C57BL
MH  - Monoacylglycerol Lipases/antagonists & inhibitors/metabolism
MH  - Neuralgia/etiology/*prevention & control
MH  - Piperidines/pharmacology
MH  - Trigeminal Nerve Injuries/*complications
OTO - NOTNLM
OT  - 2-arachydonoylglycerol (2-AG)
OT  - JZL184
OT  - monoacylglycerol lipase (MAGL)
OT  - orofacial neuropathic pain
EDAT- 2018/03/06 06:00
MHDA- 2018/10/12 06:00
CRDT- 2018/03/06 06:00
PHST- 2018/03/06 06:00 [pubmed]
PHST- 2018/10/12 06:00 [medline]
PHST- 2018/03/06 06:00 [entrez]
AID - 10.2334/josnusd.17-0005 [doi]
PST - ppublish
SO  - J Oral Sci. 2018 Mar 24;60(1):37-44. doi: 10.2334/josnusd.17-0005. Epub 2018 Mar 
      2.