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dc.contributor.authorDrissi, Ichrak
dc.contributor.authorWoods, William Aidan
dc.contributor.authorWoods, Christopher Geoffrey
dc.date.accessioned2020-02-27T00:30:16Z
dc.date.available2020-02-27T00:30:16Z
dc.date.issued2020-05-15
dc.identifier.issn0007-1420
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/302789
dc.description.abstractINTRODUCTION OR BACKGROUND: Congenital insensitivity to pain (CIP) is caused by extremely rare Mendelian genetic disorders. CIP individuals demonstrate the unexpectedly severe consequences of painlessness. Although only a small number of causative conditions and genes are known, most have led to profound insights into human nociception. CIP gene discovery is catalyzing the manufacture of completely new classes of analgesics, and these are needed as alternatives to synthetic highly potent opioids. SOURCES OF DATA: Pubmed.gov peer-reviewed journal articles and reviews. AREAS OF AGREEMENT: The importance of nerve growth factor-tropomyosin receptor kinase A (NGF-TRKA) signalling for nociceptor genesis and subsequent pain sensing.New analgesics can be generated from knowledge of the NGF-TRKA nociceptor pathway.Increased susceptibility to Staphylococcus aureus infection is a consequence of deficient NGF-TRKA signalling.Mutations in the voltage-gated sodium channels SCN9A and SCN11A can cause congenital painlessness, and in contradistinction, other mutations can cause episodic neuropathic pain. SCN9A/Nav1.7 is an analgesic target. SCN11A/Nav1.9 is unlikely to be an analgesic target.There are further Mendelian causes of painlessness to be discovered. AREAS OF CONTROVERSY: Which NGF-TRKA intracellular signalling pathways operate in nociceptor development and which in post-natal pain sensing?Why have no clinically effective Nav1.7 antagonist been generated? SCN9A-CIP causes analgesia, at least in part, through endogenous opioids.Why do all CIP phenotypes involve a complete loss of all types of nociception? AREAS TIMELY FOR DEVELOPING RESEARCH: PRDM12 as an analgesic target.Discovery of the function and analgesic potential of new CIP genes.Can NGF-TRKA be used in the treatment of S. aureus?
dc.description.sponsorshipWellcome Trust Cambridge NIHR Biomedical Research Centre
dc.format.mediumPrint
dc.languageeng
dc.publisherOxford University Press (OUP)
dc.rightsAll rights reserved
dc.subjectHumans
dc.subjectPain Insensitivity, Congenital
dc.subjectNerve Tissue Proteins
dc.subjectSignal Transduction
dc.subjectDrug Discovery
dc.subjectNociception
dc.subjectPharmacogenomic Testing
dc.titleUnderstanding the genetic basis of congenital insensitivity to pain.
dc.typeArticle
prism.endingPage78
prism.issueIdentifier1
prism.publicationDate2020
prism.publicationNameBr Med Bull
prism.startingPage65
prism.volume133
dc.identifier.doi10.17863/CAM.49864
dcterms.dateAccepted2020-01-31
rioxxterms.versionofrecord10.1093/bmb/ldaa003
rioxxterms.versionAM
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserved
rioxxterms.licenseref.startdate2020-05
dc.contributor.orcidDrissi, Ichrak [0000-0003-1438-9646]
dc.contributor.orcidWoods, Geoff [0000-0002-8077-2101]
dc.identifier.eissn1471-8391
rioxxterms.typeJournal Article/Review
pubs.funder-project-idCambridge University Hospitals NHS Foundation Trust (CUH) (3819-1415-50)
pubs.funder-project-idBiotechnology and Biological Sciences Research Council (BB/N504142/1)
pubs.funder-project-idWellcome Trust (via University College London (UCL)) (532344)
cam.issuedOnline2020-03-27
cam.orpheus.successWed Apr 15 08:35:13 BST 2020 - Embargo updated
cam.orpheus.counter1
rioxxterms.freetoread.startdate2021-03-27


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