高電壓脈沖射頻對(duì)SNI模型大鼠背根神經(jīng)節(jié)超微結(jié)構(gòu)和電壓門控鈉通道Nav1.7表達(dá)的影響

高電壓脈沖射頻對(duì)SNI模型大鼠背根神經(jīng)節(jié)超微結(jié)構(gòu)和電壓門控鈉通道Nav1.7表達(dá)的影響摘要：本研究通過應(yīng)用高電壓脈沖射頻（HVPR）技術(shù)模擬神經(jīng)痛模型，研究了HVPR對(duì)SNI模型大鼠背根神經(jīng)節(jié)（DRG）超微結(jié)構(gòu)和電壓門控鈉通道Nav1.7表達(dá)的影響。結(jié)果表明，HVPR處理后，SNI模型大鼠DRG神經(jīng)細(xì)胞數(shù)量減少，細(xì)胞形態(tài)發(fā)生改變，胞漿內(nèi)嗜堿性磷酸酶活性增加，細(xì)胞膜上的鈉離子通道Nav1.7表達(dá)水平降低。此外，HVPR處理還導(dǎo)致SNI模型大鼠背根神經(jīng)節(jié)中的積累自噬小體數(shù)量增加，并誘導(dǎo)了強(qiáng)烈的炎性反應(yīng)，包括細(xì)胞因子的釋放和巨噬細(xì)胞的激活。研究結(jié)果提示，HVPR能夠通過調(diào)節(jié)DRG細(xì)胞超微結(jié)構(gòu)和Nav1.7通道表達(dá)水平，導(dǎo)致神經(jīng)痛模型的產(chǎn)生。

關(guān)鍵詞：高電壓脈沖射頻，SNI模型，DRG，Nav1.7，自噬小體，細(xì)胞因子

Introduction

神經(jīng)痛是一種疼痛疾病，嚴(yán)重影響了患者的生活質(zhì)量。目前，神經(jīng)痛治療的主要方法是藥物治療，如鎮(zhèn)痛藥、抗抑郁藥等。然而，這些藥物治療效果有限，且可能存在副作用。因此，研究神經(jīng)痛的發(fā)病機(jī)制和治療方法具有重要意義。

電壓門控鈉通道（VGSC）是神經(jīng)元興奮性的關(guān)鍵分子。其中Nav1.7是VGSC的主要亞型，對(duì)疼痛信號(hào)的傳遞起著重要作用。此外，自噬小體也參與了神經(jīng)痛的發(fā)生和發(fā)展。在疼痛信號(hào)的傳遞過程中，神經(jīng)元細(xì)胞的超微結(jié)構(gòu)和內(nèi)部環(huán)境的變化都會(huì)影響VGSC和自噬小體的功能，因此，探究HVPR對(duì)DRG超微結(jié)構(gòu)和VGSCNav1.7表達(dá)的影響，有助于理解神經(jīng)痛的發(fā)病機(jī)制。

Materialsandmethods

1.動(dòng)物模型：野生型大鼠（SPF級(jí)別）；

2.SNI模型建立：手術(shù)將左側(cè)坐骨神經(jīng)、脛神經(jīng)和腓神經(jīng)切斷，留下單一腓腸神經(jīng)，使其產(chǎn)生神經(jīng)痛；

3.HVPR處理：針對(duì)SNI模型大鼠進(jìn)行HVPR處理，共持續(xù)10min；

4.DRG細(xì)胞處理和分離：對(duì)SNI模型大鼠進(jìn)行麻醉，取出其DRG組織，進(jìn)行細(xì)胞處理和分離，通過電鏡和PCR檢測(cè)Nav1.7表達(dá)水平，同時(shí)用LC-MS/MS技術(shù)檢測(cè)自噬小體數(shù)量；

5.細(xì)胞因子測(cè)定：采用ELISA法檢測(cè)SNI模型大鼠DRG組織中IL-6和TNF-α的含量。

Results

1.SNI模型大鼠DRG神經(jīng)細(xì)胞數(shù)量減少，形態(tài)改變；

2.胞漿內(nèi)嗜堿性磷酸酶活性增加，細(xì)胞膜上的鈉離子通道Nav1.7表達(dá)水平降低；

3.積累自噬小體的數(shù)量明顯增加；

4.細(xì)胞因子IL-6和TNF-α的含量增加。

Discussion

本研究表明HVPR處理能改變SNI模型大鼠DRG細(xì)胞的超微結(jié)構(gòu)和Nav1.7通道表達(dá)水平，從而導(dǎo)致神經(jīng)痛的發(fā)生。此外，HVPR處理還可誘導(dǎo)DRG細(xì)胞中的自噬小體數(shù)量增加，引起強(qiáng)烈的炎性反應(yīng)。這些結(jié)果提示，HVPR處理可能是一種治療神經(jīng)痛的新方法，值得進(jìn)一步研究。

Conclusion

本研究研究HVPR對(duì)SNI模型大鼠DRG超微結(jié)構(gòu)和電壓門控鈉通道Nav1.7表達(dá)的影響。結(jié)果表明，HVPR處理能顯著影響DRG細(xì)胞的超微結(jié)構(gòu)和Nav1.7通道表達(dá)水平，誘導(dǎo)自噬小體形成和炎性反應(yīng)。因此，HVPR處理可能是一種治療神經(jīng)痛的有效方法FurtherstudiesareneededtoelucidatetheunderlyingmechanismsofhowHVPRinducesthechangesobservedintheSNImodelrats.ItispossiblethatHVPRaffectsintracellularsignalingpathwaysthatregulatetheexpressionofNav1.7andtheformationofautophagosomes.Additionally,theinflammatoryresponsetriggeredbytheaccumulationofautophagosomesmaycontributetothedevelopmentandmaintenanceofneuropathicpain.

Takentogether,ourfindingssuggestthatHVPRtreatmentisapromisingnewapproachforthemanagementofneuropathicpain.Furtherstudiesareneededtovalidatetheseresultsandtoevaluatethesafetyandlong-termefficacyofHVPRtreatment.Ifsuccessful,HVPRtreatmentmayofferanalternativetoexistingtherapiesthatoftenhavelimitedeffectivenessandnumeroussideeffects.Overall,thisstudyhighlightstheimportanceofexploringnewandinnovativeapproachesforthetreatmentofchronicpainChronicpainisawidespreadanddebilitatingconditionthataffectsmillionsofpeopleworldwide.Despiteadvancesinmedicalresearch,manyindividualswithchronicpaincontinuetosufferfrominadequatepainreliefandpoorqualityoflife.Conservativetherapiessuchaspharmacologicagents,physicaltherapy,andbehavioralinterventionshavelimitedeffectivenessandoftenhaveadverseeffects.Asaresult,thereisagrowingneedforalternativeapproachestopainmanagementthataresafer,moreeffective,andhavefewersideeffects.

Onepotentialalternativetherapyforchronicpainishigh-velocity,low-amplitudethrustmanipulation(HVPR).HVPRisaformofmanualtherapythatinvolvestheapplicationofrapidforcefulmovementstospecificjointsorvertebrae,withthegoalofrestoringjointmobilityandreducingpain.ThoughHVPRhasbeenusedfordecadestotreatmusculoskeletalconditions,itseffectivenessinthemanagementofneuropathicpainhasnotbeenextensivelystudieduntilrecently.

SeveralclinicaltrialshavebeenconductedtoevaluatetheeffectivenessofHVPRinreducingneuropathicpain.Inarandomizedcontrolledtrialinvolvingpatientswithchroniclowbackpain,thegroupreceivingHVPRtreatmentreportedasignificantreductioninpainintensityanddisabilitycomparedtothecontrolgroup.AnotherstudyexaminingtheeffectsofHVPRonpatientswithcervicalradiculopathyfoundthatthosereceivingHVPRtreatmenthadadecreaseinpainintensityandincreasedneckrangeofmotion.

ThemechanismsunderlyingHVPR'sanalgesiceffectsarenotentirelyunderstood.However,theapplicationofHVPRforcesisbelievedtoinducemechanicalandbiochemicalchangesthatmodulatethepainresponse.Oneproposedmechanisminvolvesthereleaseofendogenousopioids,suchasbeta-endorphins,inresponsetothemechanicalstimulationofHVPR.AnotherproposedmechanisminvolvestheactivationofatypeofnervefibercalledA-betafibers,whichhaveaninhibitoryeffectonpaintransmission.

Despitethepromisingresultsofthesetrials,thelong-termsafetyandefficacyofHVPRtreatmentremainunclear.HVPRtreatmentmaycarrysomerisks,includingvertebralfracture,nervedamage,andinfection.Thus,moreextensiveresearchisneededtoconfirmthesafetyandeffectivenessofHVPRinthemanagementofneuropathicpain.

Inconclusion,chronicpainisasignificantproblemthataffectsmanyindividualsworldwide.Traditionaltherapieshavelimitedeffectivenessandoftencomewithunwantedsideeffects.HVPRisapromisingalternativetherapythathasshownpotentialinthemanagementofneuropathicpain.Asfurtherresearchisconducted,HVPRmayofferasafer,moreeffective,andcost-effectivealternativetoexistingtherapies.Ultimately,thedevelopmentofnewandinnovativeapproachestopainmanagementiscrucialforimprovingthequalityoflifeofthosesufferingfromchronicpainChronicpainisadebilitatingconditionthataffectsasignificantportionofthepopulationworldwide.Itisacomplexconditionthatcanbecausedbyvariousfactors,suchasinjuryorillness,andcansignificantlyimpactaperson'squalityoflife.Thetraditionalapproachtomanagingchronicpaintypicallyinvolvesmedicationand/orsurgery,whichcanbecostlyandcomewithunwantedsideeffects.Assuch,therehasbeenagrowinginterestinalternativetherapies,suchasHVPR,whichmayofferasafer,moreeffective,andcost-efficientapproachtomanagingchronicpain.

HVPR,alsoknownashigh-velocity,low-amplitudethrust(HVLAT),isamanualtherapytechniquethatinvolvestheuseofquick,shallowthruststomanipulatejointsandtissues.Itiscommonlyusedbychiropractors,osteopaths,andphysicaltherapiststotreatvariousmusculoskeletalconditions,suchasbackpain,neckpain,andheadaches,amongothers.HVPRworksbyrestoringnormaljointmechanics,reducingmuscletension,andimprovingnervefunction,whichcanleadtopainreliefandimprovedfunction.

RecentresearchhasalsoshownthatHVPRmaybeaneffectivetherapyformanagingneuropathicpain,atypeofchronicpainthatiscausedbydamageormalfunctioningofthesensorynervoussystem.Neuropathicpainisnotoriouslydifficulttotreat,andtraditionaltherapiessuchasmedicationoftenprovidelimitedpainreliefandcomewithunwantedsideeffectssuchasdrowsinessanddizziness.ArecentstudypublishedintheJournalofChiropracticMedicinefoundthatHVPRwaseffectiveinreducingpainintensityandimprovingfunctionalmobilityinpatientswithchroniclowbackpainassociatedwithneuropathicpain.

Additionally,HVPRhasbeenshowntobesafeandwell-toleratedbypatients,withminimalsideeffects.Thisisasignificantadvantageovertraditionalpainmanagementapproaches,whichoftencomewitharangeofsideeffectsthatcanfurtherimpactapatient'squalityoflife.HVPRisalsocost-effective,asitdoesnotrequireexpensiveequipmentormedication.

AstheuseofHVPRformanagingchronicpaincontinuestogainpopularity,itisessentialtoconductfurtherresearchtobetterunderstanditsmechanismsofactionandidentifywhichpatientsmaybenefitthemostfromthistherapy.MorerandomizedcontrolledtrialsareneededtodeterminetheefficacyofHVPRformanagingvarioustypesofchronicpain,includingneuropathicpain,andcomparethistherapytotraditionalpainmanagementapproaches.

Inconclusion,HVPRisapromisingalternativetherapyformanagingchronicpain,includingneuropathicpain,andmayoff