Inhibition of 2-arachydonoylgycerol degradation attenuates orofacial neuropathic pain in trigeminal nerve-injured mice
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- Kamimura Rantaro
- Division of Orthodontics, Department of Oral Biological Science,Niigata University Graduate School of Medical and Dental Sciences
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- Hossain Mohammad Z.
- Department of Oral Physiology, School of Dentistry, Matsumoto Dental University
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- Unno Shumpei
- Department of Oral Physiology, School of Dentistry, Matsumoto Dental University
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- Ando Hiroshi
- Department of Biology, Institute for Oral Science, Matsumoto Dental University
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- Masuda Yuji
- Institute for Oral Science, Matsumoto Dental University
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- Takahashi Kojiro
- Division of Orthodontics, Department of Oral Biological Science,Niigata University Graduate School of Medical and Dental Sciences
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- Otake Masanori
- Division of Orthodontics, Department of Oral Biological Science,Niigata University Graduate School of Medical and Dental Sciences
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- Saito Isao
- Division of Orthodontics, Department of Oral Biological Science,Niigata University Graduate School of Medical and Dental Sciences
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- Kitagawa Junichi
- Department of Oral Physiology, School of Dentistry, Matsumoto Dental University
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Abstract
<p>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.</p>
Journal
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- Journal of Oral Science
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Journal of Oral Science 60 (1), 37-44, 2018
Nihon University School of Dentistry