Pain Genes 英文参考文献.docVIP

Review PainGenes TomFoulkes1,JohnN.Wood2* 1Department of Stem Cell Biology and Developmental Genetics, National Institute for Medical Research, London, United Kingdom, 2Molecular Nociception Group, UniversityCollegeLondon,London,UnitedKingdom ThePainSystem Abstract:Pain,whichafflictsupto20%ofthepopulation at any time, provides both a massive therapeutic challenge and a route to understanding mechanisms in the nervous system. Specialised sensory neurons (noci- ceptors) signal the existence of tissue damage to the central nervous system (CNS), where pain is represented in a complex matrix involving many CNS structures. Geneticapproachestoinvestigatingpainpathwaysusing modelorganismshaveidentifiedthemolecularnatureof the transducers, regulatory mechanisms involved in changing neuronal activity, as well as the critical role of immune system cells in driving pain pathways. In man, mappingofhumanpainmutantsaswellastwinstudies and association studies of altered pain behaviour have identifiedimportantregulatorsofthepainsystem.Inturn, new drug targets for chronic pain treatment have been validated in transgenic mouse studies. Thus, genetic studies of pain pathways have complemented the traditionalneuroscienceapproachesofelectrophysiology and pharmacology to give us fresh insights into the molecularbasisofpainperception. Figure 1 summarises the basic wiring and defined genes involvedinthepainsystem.Unlikeothersensorymodalities,such asvision,hearing,andsmell,thebrainregionsassociatedwithpain perception are complex and have been best described as a pain matrix[3].Giventheuncertaintyaboutcentralrepresentationof painsensation,itisnotsurprisingthatmostresearchactivityhas focused on genes expressed by specialised peripheral sensory neurons essential for pain. The mechanisms by which noxious stimuliactivatesensoryneuronsaresummarisedinBox1.Spinal cordplasticityanddescendingcircuitsthatregulatenoxiousinput tothethalamusandhigherbraincentreshavebeenexaminedin detailatthesyst