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Dorsal Root Ganglion Stimulation: Anatomy, Physiology, and Potential for Therapeutic Targeting in Chronic Pain

Dorsal Root Ganglion Stimulation: Anatomy, Physiology, and Potential for Therapeutic Targeting in Chronic Pain

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axonexitsthesomaanddividestoformtwobranches,oneofwhichtravelsto

theperipheryandtheothertothespinalcord.Positionedbetweenthedistaland

proximal axons is the T junction. Studies have shown very little variability in

DRGpositionamonghealthyindividuals.

•Thesomaoftheprimarysensoryneuronsarehousedinthedorsalroot

ganglion.Therecanbeupto15,000primarysensoryneuronsomahousedina

singleDRGdependinguponspinallevel(Figure73-1).



Figure73-1.IllustrationofprimarysensoryneuroncellbodieswithintheDRG.

•ThesomawithintheDRGcanbelargeandstretchesfromdistaltissue

structurestothespinemeansitcanbemetersinlength.

•Therelativesizeofthesomacomparedtotheaxonisverysmall.

•Sincemuchofthecell’sproteinsynthesisoccursinthesoma,themetabolic



demandsonthisstructureareveryhigh.

•TheDRGistypicallylocatedintheforaminalspacebetweenthemedialand

lateraledgesofthepedicles(Figure73-2).



Figure73-2.LumbarDRGsfromcoronalMIPimaging.Thepediclesaredark

(whiteP)andtheDRGsareindicatedbythewhitearrows.Noticetherelatively



uniformpositionoftheDRGsrelativetothepedicles.Thevastmajorityof

DRGsfromhealthyvolunteersliebetweenthemedialandlateralbordersofthe

pedicles.(ReproducedwithpermissionfromShenJ,WangHY,ChenJY,Liang

BL.AJNRAmJNeuroradiol.2006Nov-Dec;27(10):2098-103.)

•ThereisslightvariabilityinDRGsizeasDRGslocatedmorecaudaltendto

belarger.

•Sensoryaxonsmaintainafairlyconsistentanatomicaldistributionasthey

traveltothespinalcord.

•Thereisanorganizedandconvergentdistributionofcellularfibersthat

eventuallysynapseinthedorsalhorn.

The vascular structure of the DRG provides the metabolic intermediates to

supporttherelativelyhighmetabolicdemandsofthecellsintheganglion.This

vascularstructuredoesnotcreateaclassicbloodbrainbarrierduetotheporous

nature of the structure. To this extent, the ganglion is exposed to blood-borne

stimuliandmayprovidesomesortofchemosensoryfunction.



PHYSIOLOGYOFTHEDRG

ThephysiologyofthecellsoftheDRGisthoughttobefairlystagnant.Inrecent

years, we have realized that neurons in many different regions of the nervous

systemaresomeofthemostplasticcellsinthebody.Theprimaryfunctionof

theprimarysensoryneuronistoconductactionpotentialsfromtheperipheryto

thecentralnervoussystem,therebygeneratingspecificsensations.

•Actionpotentialsoriginatingfromtheperipherymaynotnecessarilyinvade

themembraneofthesoma,suggestingthattheTjunctionmayactasafilter.

•Thisallowsactionpotentialstobypassthesomaresultinginrapidconduction

ofactionpotentialsfromtheperipherytothespinalcord.

•TheafferentimpulsescanoriginatefromtheDRG,suggestingthattheDRG

maybeanadditionalsourceofsensoryinput.

•Theneuroncontainsanexcitablemembranethatallowsthepassageof

selectedioniccurrentsinaspecificsequencetogenerateactionpotential.

•Disruptionsofthesecurrentswillnotallowthemembranetobesufficiently

excitableoritmaybehyperexcitablewherebysensationsareexperiencedin

theabsenceofadirectstimulus.

•ThechangescontributingtothehyperexcitabilityofDRGneuronsareoneof



themajorcausesofchronicneuropathicpain.

Animal models have demonstrated that primary sensory neurons exhibit a

number of pathophysiologic changes that may contribute to a hyperexcitable

state in chronic pain. Both genetic and proteonomic changes that alter the

electrophysiologicalmembranepropertiesoftheDRGcellshavebeenobserved

(Figure73-3). For example, reduced action potential thresholds, reduced Ca2+

conductance,sodiumchannelfunctionalalterations,andalteredgeneexpression

havebeenobserved.Furthermore,spontaneousactionpotentialsgeneratedinthe

DRG cell body have been reported. These changes have been correlated with

behavioral changes that mimic chronic pain states such as hyperalgesia and

allodynia, suggesting a relationship between the pathophysiological alterations

andthedevelopmentofpain.



Figure73-3.SchematicoutliningthepathophysiologicalchangestotheDRG

contributingtoitshyperexcitablestate.(A)Normalsensorypathwayand(B)

depictionofanalteredsensorypathwaywherebytheprimarysensoryneurons

arehyperexcitable,leadingtothegenerationofneuropathicpain.



CLINICALTARGETINGOFTHEDRG



Clinically,theanatomyandphysiologyoftheDRGmakeitanopportunisticarea

tomodulatenociceptiveorpaintransmittingneurons.Avarietyofsurgicaland

nonsurgical techniques have targeted the DRG with varying levels of success.

The therapeutic success of this procedure varies and the long-term clinical

efficacyremainsunclear.

•Dorsalrootentryzonelesioningandganglionectomyareusedtodenervate

selecteddermatomesinindividualswithchronicpainconditions.

•Thelimitedsuccessofsurgicalproceduresandtheoccurrenceof

deafferentationsyndromesprecludedtheirultimateutilityandcontinueduse.

•Radiofrequency(RF)targetingoftheDRGisalessinvasivetechniqueandis

usedinaclinicalsetting.

•RFcanbeeitherdestructive(continuousRF)ornondestructive(pulsed-RF).

ConventionalRFiscontroversialintheDRGandhasbeenusedmore

commonlywithdenervationofthespinaljoints.

The DRG is a robust neural structure that can withstand thermal insult and

remain robust. The amount of energy that is delivered to the DRG in

radiofrequency-based techniques is immense. Yet, very low rates of serious

sensory or motor complications arising from this energy delivery have been

reported.



NeuroaugmentationofDRG

Limited published data have shown that neural stimulation of the DRG may

provide pain relief. Unfortunately, design limitations of current spinal cord

stimulatorsystemsprecludetheabilitytoadequatelystudythepotentialroleof

DRG stimulation in the treatment of chronic pain. New systems are currently

being developed to address this potentially useful stimulation therapy. These

systems consist of novel leads and epidural delivery systems to aid in the

placementofleadsnearthetargetDRGs(Figure73-4).Morespecifically,anew

systemthathasbeendevelopedtostimulatetheDRGinthetreatmentofchronic,

intractablepainutilizesaslightlydifferentleadanddeliverysystemdesignedto

navigate toward the lateral epidural space and near or about the dorsal root

ganglion(Figure73-5).



Figure73-4.Spinalmodulationleadanddeliverysystemforplacementof

speciallydesignedleadsforDRGstimulation.Theleadishousedwithinasheath

thatprovidesprotectionandstabilityforepiduralleadplacement.Theleadcan

bedeployedfromthedistalendofthesheathtoeffectivelyplacethelead

contactsneartheDRGforstimulation.



Figure73-5.Schematicviewoftheproceduretoplaceproprietaryleadsfor

dorsalrootganglion(DRG)stimulation.(A)Epiduralaccessisobtainedusinga

lossofresistancetechnique;(B)theleadanddeliverysheathisthenfedthrough

thedeliveryneedle,afterwhich;(C)theleadissteeredthroughtheepidural

spacetowardtheDRG;(D)finalplacementofupto4leadsfortherapydelivery.

•Asmall,flexibleleadcontainedwithinasheathcomponentthatprovidesa

lead-sheathdeliverycombinationsteeringtothelateralepiduralspace.

•Eventually,theleaddeployedinsuchmannersothatleadcontactscan

providestimulationtherapy.

•OncetheleadsarepositionedneartheDRG,stimulationcanbetailoredvia

pulsegeneratorprogramming.



•Similartootherprogrammablestimulators,contactsareselectedasanodesor

cathodesandstimulationpulse-wavesareadjusted(pulsewaveheight,width,

andfrequency)tobestcapturethepainfulanatomies.

•Paresthesiasaredevelopedandsteeredtowardthepainfulareas.

•Patientscanthencontrolthestimulationtherapywithawirelessprogrammer.

•Leadplacementcanvaryfrompatienttopatientdependinguponseveral

factorsincludingdifferencesinspinalanatomy,anddesiredleadlocation.

Figure 73-6 depicts flexible epidural needle placement techniques to

effectively deliver stimulation leads to the desired DRG. Both ipsilateral and

contralateralleadplacementtechniquesarepossibletoadjacentspinallevelsor

levelsmultiplesegmentsawayfromtheepiduralaccesspoint.Trialprocedures

are completed similar to other neurostimulator systems to gauge the level of

therapysuccesspriortofullyimplantingtheneurostimulatorsystem.Procedural

and postprocedural care is similar to standards typically utilized for fully

implantable neurostimulator systems. Adverse event rates are low and

comparabletosimilartechnologies.



Figure73-6.Finalleadplacementsinanterior-posterior(AP;panelA)and

lateral(LAT;panelB)views.PanelA:Notethedifferentialepiduralneedle

placementapproachestoaccommodatevaryingleaddeliverytechniques

requirements.Bothcontralateralandipsilateralneedletrajectoriescanbeusedto

deliveryleadsoneormorelevelsawayfromtheepiduralaccesspoint.PanelB:

LATviewshowingdorsalleadplacementwithintheforamen.



PATIENTSELECTION

DRGstimulationcouldpotentiallyaidinthetreatmentofanumberof chronic



painconditionssuchas:

•Discogenicspinepain

•Postherpeticneuralgia

•Chronicfootpain

TheseconditionshavebeentreatedusingDRGstimulationandtherearelikely

a number of other indications that would benefit from this therapy, including

CRPS and FBSS. The ideal patient characteristics for this type of therapy are

outlinedbelow(Table73-1).

TABLE73-1.SummaryofIdealPatientCharacteristicsforDRG

Stimulation

Idealpatientcharacteristics

Chronicneuropathicpainrefractorytoconservativetherapy

Radicularsymptoms

CandidatefortraditionalSCStherapy

Peripheralneuropathy

Postsurgicalneuralgias

CRPS

Peripheralvasculardiseaseconditions



ACaseReport

AuthorshaveperformedacaseoftrialDRGstimulationona69-year-oldman

withahistoryofneuropathyandbilateralcausalgiainhisshinsandfeet.Hehad

experienced pain for over 9 years at the time of treatment and had failed a

numberofothertherapies,includingspinalcordstimulation.

•TwoleadswereplacedusingapercutaneousapproachattheleftL4andL5

DRGsandconnectedtoanexternalneurostimulator(SpinalModulation,Inc,

MenloPark,CA).

•Following3daysoftrialstimulation,thepatientexperiencedan80%

reductioninoverallpainanda70%reductioninpainintheleftfoot.

•Heratedhisoverallimprovementas7outof10.

ThiscasesuggeststhatDRGstimulationmaysucceedintreatingpaindueto

CRPSofthefooteveninpatientsforwhomspinalcordstimulationhasfailed.



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Dorsal Root Ganglion Stimulation: Anatomy, Physiology, and Potential for Therapeutic Targeting in Chronic Pain

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