ABHD6 and MAGL control 2-AG levels in the PAG and allodynia in a CSD-induced periorbital model of headache.
2-AG
ABHD6
MAGL
PAG
endocannabinoid
migraine
Journal
Frontiers in pain research (Lausanne, Switzerland)
ISSN: 2673-561X
Titre abrégé: Front Pain Res (Lausanne)
Pays: Switzerland
ID NLM: 9918227269806676
Informations de publication
Date de publication:
2023
2023
Historique:
received:
21
02
2023
accepted:
05
05
2023
medline:
8
6
2023
pubmed:
8
6
2023
entrez:
8
6
2023
Statut:
epublish
Résumé
The high prevalence and severe symptoms of migraines in humans emphasizes the need to identify underlying mechanisms that can be targeted for therapeutic benefit. Clinical Endocannabinoid Deficiency (CED) posits that reduced endocannabinoid tone may contribute to migraine development and other neuropathic pain conditions. While strategies that increase levels of the endocannabinoid n-arachidonoylethanolamide have been tested, few studies have investigated targeting the levels of the more abundant endocannabinoid, 2-arachidonoylgycerol, as an effective migraine intervention. Cortical spreading depression was induced in female Sprague Dawley rats via KCl (potassium chloride) administration, followed by measures of endocannabinoid levels, enzyme activity, and neuroinflammatory markers. Efficacy of inhibiting 2-arachidonoylglycerol hydrolysis to mitigate periorbital allodynia was then tested using reversal and prevention paradigms. We discovered reduced 2-arachidonoylglycerol levels in the periaqueductal grey associated with increased hydrolysis following headache induction. Pharmacological inhibition of the 2-arachidonoylglycerol hydrolyzing enzymes, Our study unravels a mechanistic link between 2-arachidonoylglycerol hydrolysis activity in the periaqueductal grey in a preclinical, rat model of migraine. Thus, 2-arachidonoylglycerol hydrolysis inhibitors represent a potential new therapeutic avenue for the treatment of headache.
Identifiants
pubmed: 37287623
doi: 10.3389/fpain.2023.1171188
pmc: PMC10242073
doi:
Types de publication
Journal Article
Langues
eng
Pagination
1171188Subventions
Organisme : NINDS NIH HHS
ID : R01 NS126752
Pays : United States
Informations de copyright
© 2023 Liktor-Busa, Levine, Palomino, Singh, Wahl, Vanderah, Stella and Largent-Milnes.
Déclaration de conflit d'intérêts
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
Références
Eur Neuropsychopharmacol. 2015 Aug;25(8):1388-96
pubmed: 25910421
Int J Mol Sci. 2021 Aug 19;22(16):
pubmed: 34445635
Pain. 2004 Jul;110(1-2):419-26
pubmed: 15275794
Metabolomics. 2020 Oct 12;16(10):113
pubmed: 33044703
Life Sci. 1995;56(23-24):1941-7
pubmed: 7776817
Int J Mol Sci. 2018 Mar 13;19(3):
pubmed: 29533978
Cannabis Cannabinoid Res. 2022 Apr;7(2):188-198
pubmed: 34705543
Cephalalgia. 2018 Apr;38(4):626-638
pubmed: 28372497
Int J Mol Sci. 2021 Jan 26;22(3):
pubmed: 33530477
Br J Pharmacol. 2014 Mar;171(6):1379-91
pubmed: 24102242
Biol Sex Differ. 2021 Nov 8;12(1):60
pubmed: 34749819
J Neurosci. 2003 Feb 15;23(4):1398-405
pubmed: 12598628
eNeuro. 2018 Jul 16;5(4):
pubmed: 30073201
J Headache Pain. 2017 Dec;18(1):36
pubmed: 28321594
Life Sci. 2013 Mar 19;92(8-9):498-505
pubmed: 22749865
Front Pharmacol. 2018 Apr 24;9:420
pubmed: 29740328
Headache. 2021 Jan;61(1):60-68
pubmed: 33349955
Science. 2011 Nov 11;334(6057):809-13
pubmed: 22021672
J Headache Pain. 2021 Jun 10;22(1):55
pubmed: 34112082
Front Pharmacol. 2021 Jan 12;11:615028
pubmed: 33584293
Diabetes Obes Metab. 2017 Sep;19 Suppl 1:76-89
pubmed: 28880480
Trends Pharmacol Sci. 2019 Apr;40(4):267-277
pubmed: 30853109
Neurobiol Dis. 2014 Aug;68:200-14
pubmed: 24662368
Cephalalgia. 2018 May;38(6):1138-1147
pubmed: 28816506
Biol Psychiatry Cogn Neurosci Neuroimaging. 2021 Jun;6(6):607-615
pubmed: 32980261
Int J Mol Sci. 2020 Dec 22;22(1):
pubmed: 33375006
J Pharmacol Exp Ther. 2016 Apr;357(1):145-56
pubmed: 26791602
Neuropharmacology. 2017 Sep 15;124:105-120
pubmed: 28625720
Acta Pharm Sin B. 2020 Apr;10(4):582-602
pubmed: 32322464
Lancet Neurol. 2018 May;17(5):396-397
pubmed: 29550365
Headache. 2013 Mar;53(3):427-36
pubmed: 23470015
Ann Neurol. 2009 Feb;65(2):184-93
pubmed: 19259966
Prostaglandins Leukot Essent Fatty Acids. 2017 May;120:15-24
pubmed: 28515018
J Nucl Med. 2009 Nov;50(11):1904-11
pubmed: 19837755
J Cereb Blood Flow Metab. 2017 May;37(5):1735-1747
pubmed: 27381828
Int J Mol Sci. 2021 May 21;22(11):
pubmed: 34063947
Nature. 2014 May 15;509(7500):282-3
pubmed: 24834516
Cephalalgia. 2010 Jul;30(7):780-92
pubmed: 19740119
Pain. 2016 Apr;157(4):901-909
pubmed: 26683237