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dc.contributor.authorMadasu, Manish K.
dc.contributor.authorOkine, Bright N.
dc.contributor.authorOlango, Weredeselam M.
dc.contributor.authorRea, Kieran
dc.contributor.authorLenihan, Róisín
dc.contributor.authorRoche, Michelle
dc.contributor.authorFinn, David P.
dc.date.accessioned2019-04-02T13:12:30Z
dc.date.available2019-04-02T13:12:30Z
dc.date.issued2016-08-09
dc.identifier.citationMadasu, Manish K., Okine, Bright N., Olango, Weredeselam M., Rea, Kieran, Lenihan, Róisín, Roche, Michelle, et al. (2016). Genotype-dependent responsivity to inflammatory pain: A role for TRPV1 in the periaqueductal grey. Pharmacological Research, 113, 44-54., doi: 10.1016/j.phrs.2016.08.011en_IE
dc.identifier.issn1096-1186
dc.identifier.urihttp://hdl.handle.net/10379/15087
dc.description.abstractNegative affective state has a significant impact on pain, and genetic background is an important moderating influence on this interaction. The Wistar-Kyoto (WKY) inbred rat strain exhibits a stress-hyperresponsive, anxiety/depressive-like phenotype and also displays a hyperalgesic response to noxious stimuli. Transient receptor potential subfamily V member 1 (TRPV1) within the midbrain periaqueductal grey (PAG) plays a key role in regulating both aversive and nociceptive behaviour. In the present study, we investigated the role of TRPV1 in the sub-columns of the PAG in formalin-evoked nociceptive behaviour in WKY versus Sprague-Dawley (SD) rats. TRPV1 mRNA expression was significantly lower in the dorsolateral (DL) PAG and higher in the lateral (L) PAG of WKY rats, compared with SD counterparts. There were no significant differences in TRPV1 mRNA expression in the ventrolateral (VL) PAG between the two strains. TRPV1 mRNA expression significantly decreased in the DLPAG and increased in the VLPAG of SD, but not WKY rats upon intra-plantar formalin administration. Intra-DLPAG administration of either the TRPV1 agonist capsaicin, or the TRPV1 antagonist 5'-lodoresiniferatoxin (5'-IRTX), significantly increased formalin-evoked nociceptive behaviour in SD rats, but not in WKY rats. The effects of capsaicin were likely due to TRPV1 desensitisation, given their similarity to the effects of 5'-IRTX. Intra-VLPAG administration of capsaicin or 5'-IRTX reduced nociceptive behaviour in a moderate and transient manner in SD rats, and similar effects were seen with 5'-IRTX in WKY rats. Intra-LPAG administration of 5'-IRTX reduced nociceptive behaviour in a moderate and transient manner in SD rats, but not in WKY rats. These results indicate that modulation of inflammatory pain by TRPV1 in the PAG occurs in a sub-column-specific manner. The data also provide evidence for differences in the expression of TRPV1, and differences in the effects of pharmacological modulation of TRPV1 in specific PAG sub-columns, between WKY and SD rats, suggesting that TRPV1 expression and/or functionality in the PAG plays a role in hyper-responsivity to noxious stimuli in a genetic background prone to negative affect. (C) 2016 Elsevier Ltd. All rights reserved.en_IE
dc.description.sponsorshipThis work was funded by grants from Science Foundation Ireland (10/IN.1/B2976), the Irish Research Council, and a PhD scholarship from the College of Science, National University of Ireland Galway.en_IE
dc.formatapplication/pdfen_IE
dc.language.isoenen_IE
dc.publisherElsevieren_IE
dc.relation.ispartofPharmacological research : the official journal of the Italian Pharmacological Societyen
dc.subjectTRPV1en_IE
dc.subjectPainen_IE
dc.subjectNegative affective stateen_IE
dc.subjectPeriaqueductal greyen_IE
dc.subjectCapsaicinen_IE
dc.subjectRaten_IE
dc.subjectROSTRAL VENTROMEDIAL MEDULLAen_IE
dc.subjectVANILLOID TYPE-1 RECEPTORSen_IE
dc.subjectN-ARACHIDONOYL-SEROTONINen_IE
dc.subjectROOT GANGLION NEURONSen_IE
dc.subjectCAPSAICIN RECEPTORen_IE
dc.subjectWKY RATSen_IE
dc.subjectCOLUMNAR ORGANIZATIONen_IE
dc.subjectEMOTIONAL EXPRESSIONen_IE
dc.subjectCELL-ACTIVITYen_IE
dc.subjectGRAY REGIONen_IE
dc.titleGenotype-dependent responsivity to inflammatory pain: A role for TRPV1 in the periaqueductal greyen_IE
dc.typeArticleen_IE
dc.date.updated2019-03-28T05:24:36Z
dc.identifier.doi10.1016/j.Phrs.2016.08.011
dc.local.publishedsourcehttps://doi.org/10.1016/j.phrs.2016.08.011en_IE
dc.description.peer-reviewedpeer-reviewed
dc.contributor.funderScience Foundation Irelanden_IE
dc.contributor.funderIrish Research Councilen_IE
dc.contributor.funderCollege of Science, National University of Ireland, Galwayen_IE
dc.internal.rssid11841545
dc.local.contactDavid Finn, Dept. Of Pharmacology &, Therapeutics, Nui, Galway. 5280 Email: david.finn@nuigalway.ie
dc.local.copyrightcheckedYes
dc.local.versionACCEPTED
dcterms.projectinfo:eu-repo/grantAgreement/SFI/SFI Principal Investigator Programme (PI)/10/IN.1/B2976/IE/The role of the endocannabinoid system in anxiety-induced modulation of pain: sites and mechanisms of action/en_IE
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