Diacylglycerol lipase beta inhibition reverses nociceptive behaviour in mouse models of inflammatory and neuropathic pain
dc.contributor.author | Wilkerson, Jenny L. | |
dc.contributor.author | Ghosh, Sudeshna | |
dc.contributor.author | Mason, Brittany L. | |
dc.contributor.author | Crowe, Molly S. | |
dc.contributor.author | Hsu, Kulung | |
dc.contributor.author | Wise, Laura E. | |
dc.contributor.author | Kinsey, Steven G. | |
dc.contributor.author | Damaj, Mohamad Imad | |
dc.contributor.author | Cravatt, Benjamin F. | |
dc.contributor.author | Lichtman, Aron H. | |
dc.contributor.buuauthor | Baǧdaş, Deniz | |
dc.contributor.department | Uludağ Üniversitesi/Tıp Fakültesi/Deney Hayvanları Yetiştirme ve Araştırma Merkezi. | tr_TR |
dc.contributor.scopusid | 15062425700 | tr_TR |
dc.date.accessioned | 2022-10-12T08:08:39Z | |
dc.date.available | 2022-10-12T08:08:39Z | |
dc.date.issued | 2016-02-16 | |
dc.description.abstract | Background and PurposeInhibition of diacylglycerol lipase (DGL) prevents LPS-induced pro-inflammatory responses in mouse peritoneal macrophages. Thus, the present study tested whether DGL inhibition reverses allodynic responses of mice in the LPS model of inflammatory pain, as well as in neuropathic pain models. Experimental ApproachInitial experiments examined the cellular expression of DGL and inflammatory mediators within the LPS-injected paw pad. DAGL- (-/-) mice or wild-type mice treated with the DGL inhibitor KT109 were assessed in the LPS model of inflammatory pain. Additional studies examined the locus of action for KT109-induced antinociception, its efficacy in chronic constrictive injury (CCI) of sciatic nerve and chemotherapy-induced neuropathic pain (CINP) models. Key ResultsIntraplantar LPS evoked mechanical allodynia that was associated with increased expression of DGL, which was co-localized with increased TNF- and prostaglandins in paws. DAGL- (-/-) mice or KT109-treated wild-type mice displayed reductions in LPS-induced allodynia. Repeated KT109 administration prevented the expression of LPS-induced allodynia, without evidence of tolerance. Intraplantar injection of KT109 into the LPS-treated paw, but not the contralateral paw, reversed the allodynic responses. However, i.c.v. or i.t. administration of KT109 did not alter LPS-induced allodynia. Finally, KT109 also reversed allodynia in the CCI and CINP models and lacked discernible side effects (e.g. gross motor deficits, anxiogenic behaviour or gastric ulcers). Conclusions and ImplicationsThese findings suggest that local inhibition of DGL at the site of inflammation represents a novel avenue to treat pathological pain, with no apparent untoward side effects. | en_US |
dc.description.sponsorship | United States Department of Health & Human Services - DA009789 - DA017259 - DA032933 - DA033934-01A1 DA035864 - DA038493-01A1 | en_US |
dc.description.sponsorship | National Institutes of Health (NIH) - USA | en_US |
dc.description.sponsorship | NIH-NINDS Center core grant - 5P30NS047463 | en_US |
dc.description.sponsorship | United States Department of Health & Human Services | en_US |
dc.description.sponsorship | National Institutes of Health (NIH) - USA - P30NS047463 | en_US |
dc.description.sponsorship | NIH National Institute of Neurological Disorders & Stroke (NINDS) | en_US |
dc.description.sponsorship | United States Department of Health & Human Services | en_US |
dc.description.sponsorship | National Institutes of Health (NIH) - USA - R01DA032933 - K99DA035864 - P01DA017259 - P01DA009789 - F32DA038493 - R00DA035864 - P30DA033934 | en_US |
dc.description.sponsorship | NIH National Institute on Drug Abuse (NIDA) | en_US |
dc.description.sponsorship | European Commission | en_US |
dc.identifier.citation | Wilkerson, J. L. vd. (2016). "Diacylglycerol lipase beta inhibition reverses nociceptive behaviour in mouse models of inflammatory and neuropathic pain". British Journal of Pharmacology, 173(10), Special Issue, 1678-1692. | en_US |
dc.identifier.endpage | 1692 | tr_TR |
dc.identifier.issn | 0007-1188 | |
dc.identifier.issn | 1476-5381 | |
dc.identifier.issue | 10, Special Issue | en_US |
dc.identifier.pubmed | 26915789 | tr_TR |
dc.identifier.scopus | 2-s2.0-84962634946 | tr_TR |
dc.identifier.startpage | 1678 | tr_TR |
dc.identifier.uri | https://doi.org/10.1111/bph.13469 | |
dc.identifier.uri | https://bpspubs.onlinelibrary.wiley.com/doi/10.1111/bph.13469 | |
dc.identifier.uri | http://hdl.handle.net/11452/29061 | |
dc.identifier.volume | 173 | tr_TR |
dc.identifier.wos | 000374976000010 | tr_TR |
dc.indexed.pubmed | PubMed | en_US |
dc.indexed.scopus | Scopus | en_US |
dc.indexed.wos | SCIE | en_US |
dc.language.iso | en | en_US |
dc.publisher | Wiley | en_US |
dc.relation.collaboration | Yurt dışı | tr_TR |
dc.relation.collaboration | Sanayi | tr_TR |
dc.relation.journal | British Journal of Pharmacology | en_US |
dc.relation.publicationcategory | Makale - Uluslararası Hakemli Dergi | tr_TR |
dc.rights | info:eu-repo/semantics/openAccess | en_US |
dc.subject | Pharmacology & pharmacy | en_US |
dc.subject | Monoacylglycerol lipase | en_US |
dc.subject | Endogenous cannabinoids | en_US |
dc.subject | Cell-differentiation | en_US |
dc.subject | Concise guide | en_US |
dc.subject | Alpha | en_US |
dc.subject | Pharmacology | en_US |
dc.subject | Responses | en_US |
dc.subject | Blockade | en_US |
dc.subject | Agonist | en_US |
dc.subject | System | en_US |
dc.subject.emtree | Diacylglycerol lipase beta | en_US |
dc.subject.emtree | Diclofenac | en_US |
dc.subject.emtree | Esterase | en_US |
dc.subject.emtree | Esterase inhibitor | en_US |
dc.subject.emtree | Kt 195 | en_US |
dc.subject.emtree | Lipopolysaccharide | en_US |
dc.subject.emtree | Prostaglandin E2 | en_US |
dc.subject.emtree | Tumor necrosis factor alpha | en_US |
dc.subject.emtree | Unclassified drug | en_US |
dc.subject.emtree | [4 [(1,1' biphenyl) 4 yl] 1h 1,2,3 triazol 1 yl](2 benzylpiperidin 1 yl)methanone | en_US |
dc.subject.emtree | Diacylglycerol lipase beta | en_US |
dc.subject.emtree | Mouse | en_US |
dc.subject.emtree | Enzyme inhibitor | en_US |
dc.subject.emtree | Lipopolysaccharide | en_US |
dc.subject.emtree | Lipoprotein lipase | en_US |
dc.subject.emtree | Adult | en_US |
dc.subject.emtree | Allodynia | en_US |
dc.subject.emtree | Analgesic activity | en_US |
dc.subject.emtree | Animal experiment | en_US |
dc.subject.emtree | Animal model | en_US |
dc.subject.emtree | Animal tissue | en_US |
dc.subject.emtree | Antinociception | en_US |
dc.subject.emtree | Anxiety | en_US |
dc.subject.emtree | Article | en_US |
dc.subject.emtree | Controlled study | en_US |
dc.subject.emtree | Drug efficacy | en_US |
dc.subject.emtree | Enzyme inhibition | en_US |
dc.subject.emtree | Hyperalgesia | en_US |
dc.subject.emtree | Inflammatory pain | en_US |
dc.subject.emtree | Male | en_US |
dc.subject.emtree | Motor dysfunction | en_US |
dc.subject.emtree | Mouse | en_US |
dc.subject.emtree | Neuropathic pain | en_US |
dc.subject.emtree | Nonhuman | en_US |
dc.subject.emtree | Priority journal | en_US |
dc.subject.emtree | Protein expression | en_US |
dc.subject.emtree | Sciatic nerve injury | en_US |
dc.subject.emtree | Stomach hemorrhage | en_US |
dc.subject.emtree | Stomach ulcer | en_US |
dc.subject.emtree | Animal | en_US |
dc.subject.emtree | Antagonists and inhibitors | en_US |
dc.subject.emtree | C57BL mouse | en_US |
dc.subject.emtree | Chemistry | en_US |
dc.subject.emtree | Deficiency | en_US |
dc.subject.emtree | Disease model | en_US |
dc.subject.emtree | Dose response | en_US |
dc.subject.emtree | Drug effects | en_US |
dc.subject.emtree | Inflammation | en_US |
dc.subject.emtree | Knockout mouse | en_US |
dc.subject.emtree | Metabolism | en_US |
dc.subject.emtree | Neuralgia | en_US |
dc.subject.emtree | Nociception | en_US |
dc.subject.emtree | Structure activity relation | en_US |
dc.subject.mesh | Animals | en_US |
dc.subject.mesh | Disease models, animal | en_US |
dc.subject.mesh | Dose-response relationship, drug | en_US |
dc.subject.mesh | Enzyme inhibitors | en_US |
dc.subject.mesh | Inflammation | en_US |
dc.subject.mesh | Lipopolysaccharides | en_US |
dc.subject.mesh | Lipoprotein lipase | en_US |
dc.subject.mesh | Male | en_US |
dc.subject.mesh | Mice | en_US |
dc.subject.mesh | Mice, inbred C57BL | en_US |
dc.subject.mesh | Mice, knockout | en_US |
dc.subject.mesh | Neuralgia | en_US |
dc.subject.mesh | Nociception | en_US |
dc.subject.mesh | Structure-activity relationship | en_US |
dc.subject.scopus | Acylglycerol Lipase; Fatty-Acid Amide Hydrolase; Animals | en_US |
dc.subject.wos | Pharmacology & pharmacy | en_US |
dc.title | Diacylglycerol lipase beta inhibition reverses nociceptive behaviour in mouse models of inflammatory and neuropathic pain | en_US |
dc.type | Article | |
dc.wos.quartile | Q1 | en_US |