疼痛基础研究（中青年优秀论文评奖）

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1、疼痛基础研究(中青年优秀论文评奖)延髓5•轻色胺能下行易化作用参与大鼠骨癌痛形成的机制研究刘希江卜慧莲柯昌斌曹菲杨辉高峰□□玉科°华中科技大学同济医学院附属同济医院麻醉学教研室，武汉，430030【摘要】目的探讨延髓5■疑色胺能下行易化作用参与大鼠骨癌痛形成的机制。方法构建大鼠骨癌痛模型，采用高效液相色谱和免疫组化法检测脊髓背角5■轻色胺(5-HT)的表达。延髓头端腹内侧区(RVM)立体定位注射色氨酸疑化酶(Tph)抑制剂对氯苯丙氨酸(PCPA)选择性下调脊髓背角5・HT含量,并检测其镇痛效果。RVM区注射p38MAPK抑制剂SB203580并检测其对Tph蛋口表达的影响及脊髓背角5-

2、HT含量变化。釆用基因芯片检测骨癌痛大鼠脊髓所冇5-HT受体表达的变化。结果骨癌痛大鼠脊髓背角5-HT含量显著升高，并与机械痛阈呈负相关。RVM区注射PCPA和SB203580均可逆转RVM区Tph和脊髓背角5-HT的高表达，并产生镇痛作用。基因芯片结果显示脊髓5・HT受体屮起易化疼痛和抑制疼痛的受体均表达增高，但起易化疼痛作用的受体表达高于起抑制疼痛作用的受体。结论延髓5■疑色胺能下行易化作用参与了大鼠骨癌痛的形成，其机制与5-HT卜•行投射增多和脊髓5-HT受体向易化疼痛的方向偏移有关。【关键词】骨肿瘤；疼痛；脊髓；延髓；血清索；基因芯片CTF1—1mopwNoom.os.c7so

3、-ii.<_>MechanismsofthefacilitatoryroleofdescendingserotoninfromtherostralventromedialmedullainaratmodelofcancerinducedbonepainLIUXi-jiang,BUHui-lian,KEChang-bin,CAOFei,YANGHui,GAOFengand刘希江，Email:xijiang_liu@163.com;Tel:15871716812基金项目：国家自然科器基金资助项目（30901396、81070890）A通讯作者：田玉科，E-mail:yktian@tjh.t

4、jmu.edu.cnTIANYu-keDepartmentofAnesthesiology,TongjiHospitalofTongjiMedicalCollege,HuazhongUniversityofScienceandTechnology,Wuhan430030,ChinaCorrespondingauthor:TIANYu-kc,E-mail:yktian@1jh.tjmu.cdu.cn【Abstract]ObjectiveToinvestigatemechanismsofthefacilitatoryroleofdescendingserotoninfromtherostr

5、alventromedialmedullainaratmodelofcancerinducedbonepain.MethodsConstructingaratmodelofcancerinducedbonepain,highpcrfonnanccliquidchromatographyandimmunohistochemistrywereusedtoassay5-hydroxytryptamine(5-HT)contentsinspinalcorddorsalhorns・Thetryptophanhydroxylase(Tph)inhibitorpara-chlorophenylala

6、nine(PCPA)wasstereotaxiclyinjectedintorostralventromedialmedulla(RVM)toselectivelydepletethe5-HTinspinalcorddorsalhornsanditsanalgesicefftetwasassayed・p38MAPKinhibitorSB203580wasinjectedintoRVManditsinfluenceontheexpressionofRVMTphandspinalcorddorsalhorn5-HTwasdetected.The5-HTreceptorsgeneexpres

7、sionprofilesinthespinalcordofcancerinducedbonepainratsareanalyzedusingmicroarray.Results5-HTcontentinspinalcorddorsalhornincancerinducedbonepaingroupwassignificantlyincreasedfromthe7thto21stdayaftersurgery(P<0.05).5-HTconten