Interstitial Cystitis and Chronic Pelvic Pain: Interstitial Cystitis and Chronic Pelvic Pain: Case report and search for reliefCase report and search for relief

Chad Baxter, MDChad Baxter, MDPelvic Medicine and Reconstructive SurgeryPelvic Medicine and Reconstructive Surgery

Department of UrologyDepartment of UrologyDavid Geffen School of Medicine at UCLADavid Geffen School of Medicine at UCLA

Los Angeles, CaliforniaLos Angeles, California

Case of Refractory ICCase of Refractory IC

43 year old woman with 4 year history of43 year old woman with 4 year history of……Urinary frequency every 20 Urinary frequency every 20 –– 30 minutes, q130 minutes, q1--2hrs at night2hrs at nightPain with increasingly full bladderPain with increasingly full bladderIntermittentIntermittent dyspareuniadyspareuniaNo anatomic abnormality (urethralNo anatomic abnormality (urethral diverticulumdiverticulum, pelvic organ, pelvic organ prolapseprolapse, , pelvic mass, etc.)pelvic mass, etc.)No history of infection (HPV, STD, UTI)No history of infection (HPV, STD, UTI)CystoscopicCystoscopic evaluation normalevaluation normalUrodynamicsUrodynamics reveal sensory urgency, low capacity, no suggestion of reveal sensory urgency, low capacity, no suggestion of neuropathologyneuropathology

Case Study: Refractory ICCase Study: Refractory IC

Symptoms not alleviated bySymptoms not alleviated by……Diet modificationDiet modificationFluid and caffeine restrictionFluid and caffeine restriction

Physical therapy with biofeedbackPhysical therapy with biofeedback

AnticholinergicAnticholinergic therapytherapyAmitriptyleneAmitriptylene,, gabapentingabapentin,, ElmironElmironIntravesicalIntravesical anestheticsanestheticsNarcoticsNarcotics

Intravesical BotoxIntravesical BotoxCystoscopyCystoscopy withwith hydrodistentionhydrodistention

Defining the target:Defining the target:

Interstitial Cystitis (IC) and Chronic Pelvic Pain (CPP) are pooInterstitial Cystitis (IC) and Chronic Pelvic Pain (CPP) are poorly defined rly defined conditionsconditionsEstimated prevalence of 0.5 to 1.0%Estimated prevalence of 0.5 to 1.0%

Typically present withTypically present with……Poorly localized, but generallyPoorly localized, but generally suprapubicsuprapubic painpainIncreased pain with bladder fillingIncreased pain with bladder fillingUrinary urgency, frequencyUrinary urgency, frequencyNo identifiable etiologyNo identifiable etiology

Refractory to treatments, includingRefractory to treatments, including cystectomycystectomy with urinary diversionwith urinary diversionSignificantly diminished quality of lifeSignificantly diminished quality of life

Etiologic TheoriesEtiologic Theories

Primary bladder injuryPrimary bladder injury

IncreasedIncreased urothelialurothelial permeabilitypermeability

Increased inflammatory mediatorsIncreased inflammatory mediators

UpregulationUpregulation of neural pain pathwayof neural pain pathway

Increased CNS sympathetic activityIncreased CNS sympathetic activity

DysregulationDysregulation of HPA axisof HPA axis

Persistent pain beyond presence of inciting agentPersistent pain beyond presence of inciting agent

Etiologic TheoriesEtiologic Theories

Normal afferent input to CNS, no bladder pathologyNormal afferent input to CNS, no bladder pathology

Primary sensitization of central pathwaysPrimary sensitization of central pathwaysEmotional distress, prior trauma, other medical disease, etc.Emotional distress, prior trauma, other medical disease, etc.Normal pelvic sensation misinterpreted asNormal pelvic sensation misinterpreted as aberrentaberrent and painful (and painful (allodyniaallodynia))Evidence for centralEvidence for central hyperresponsivenesshyperresponsiveness to visceral related threat in IC to visceral related threat in IC patients.patients.

TwissTwiss

C, Kilpatrick L,C, Kilpatrick L,

CraskeCraske

M, et al: Increased startle responses in interstitial cystitis:M, et al: Increased startle responses in interstitial cystitis:

evidence for centralevidence for central

hyperresponsivenesshyperresponsiveness

to visceral related threat. Jto visceral related threat. J

UrolUrol. 181(5):2127. 181(5):2127--3333

Creation of rat modelCreation of rat model

Water avoidance distressing of ratsWater avoidance distressing of ratsPre and postPre and post--distressdistress urodynamicsurodynamics

IncreasedIncreased micturitionmicturition frequencyfrequencyDecreased latency to voidDecreased latency to voidDecresedDecresed voided volumevoided volume

HistologyHistologyIncreased bladderIncreased bladder vascularityvascularity in stressed animalsin stressed animalsDecreased brainDecreased brain--derivedderived neurotrophicneurotrophic factor (BDNF) expressionfactor (BDNF) expression

This novel stress model is the first nonThis novel stress model is the first non--invasive method to stimulate urinary invasive method to stimulate urinary frequency and urgencyfrequency and urgency

InterventionIntervention

EtiologyEtiology remainesremaines elusive and interventions empiric and ineffectiveelusive and interventions empiric and ineffective

Similar to other chronic pain conditions, allopathic treatment tSimilar to other chronic pain conditions, allopathic treatment targets the endargets the end--organ andorgan and dysregulateddysregulated nervous systemnervous system

Patients remain dissatisfied with treatment and seek alternativePatients remain dissatisfied with treatment and seek alternativess

Physicians frustrated by lack of efficacious treatment, exhaustiPhysicians frustrated by lack of efficacious treatment, exhausting patient ng patient interactionsinteractions

PROCAIMPROCAIM

UCLA School of Public Health and UCLA Center forUCLA School of Public Health and UCLA Center for NeurovisceralNeurovisceral Sciences Sciences and Womenand Women’’s Health database: s Health database:

People Reported Outcomes of Complimentary, Alternative, and IntePeople Reported Outcomes of Complimentary, Alternative, and Integrative grative Medicine (PROCAIM)Medicine (PROCAIM)

Patient recruitmentPatient recruitmentAlternative care providersAlternative care providersInternet support groups and society webInternet support groups and society web--sitessitesCraigCraig’’s List, major newsprint outlets, etc.s List, major newsprint outlets, etc.

Access PROCAIM website, complete onAccess PROCAIM website, complete on--line validated questionnaires line validated questionnaires www.www.procaimprocaim.org.org

PROCAIM and IC/CPP PatientsPROCAIM and IC/CPP Patients

Invited to analyze 275 patients with IC/CPPInvited to analyze 275 patients with IC/CPPTreated byTreated by

Prescription, OTCPrescription, OTCAllopathicAllopathicReikiReikiYogaYogaFrequency SpecificFrequency Specific MicrocurrentMicrocurrentMassageMassagePTPT

ChiropracticChiropracticMeditationMeditationAcupunctureAcupunctureHerbalistHerbalistPsychologyPsychologyPsychiatryPsychiatryHomeopathyHomeopathyAyurvedicAyurvedic

PROCAIM and IC/CPP PatientsPROCAIM and IC/CPP Patients

Completed treatment history, Early Trauma Inventory at enrollmenCompleted treatment history, Early Trauma Inventory at enrollmentt

Completed validated surveys at enrollment and q3monthsCompleted validated surveys at enrollment and q3months……..Health Survey SFHealth Survey SF--3636Patient Health QuestionnairePatient Health QuestionnaireHospital Anxiety and DepressionHospital Anxiety and DepressionPerceived Stress ScalePerceived Stress ScaleCoping Strategies/Coping Strategies/CatastrophizingCatastrophizingBrief Pain InventoryBrief Pain Inventory

PROCAIM and IC/CPP PatientsPROCAIM and IC/CPP Patients

Enrollment and analysis ongoingEnrollment and analysis ongoingNo clear beneficial treatment for IC/CPPNo clear beneficial treatment for IC/CPPDatabase an inadequate tool for this analysisDatabase an inadequate tool for this analysis

Convenience sampleConvenience samplePatientPatient--reported diagnosesreported diagnosesNo confirmatory interaction with patientsNo confirmatory interaction with patientsNot significantly powered to answer questions of efficacyNot significantly powered to answer questions of efficacy

Despite limitationsDespite limitations……..Early trauma increases symptom severity and diminishes quality oEarly trauma increases symptom severity and diminishes quality of life in f life in IC and CPP patientsIC and CPP patients

Excellent medium for honing skills of statistical analysis!Excellent medium for honing skills of statistical analysis!

Case Study: Refractory ICCase Study: Refractory IC

NeuromodulationNeuromodulation (NMS) successfully used for chronic pain conditions(NMS) successfully used for chronic pain conditions……Migraines, back pain, idiopathic angina pectorisMigraines, back pain, idiopathic angina pectoris

NMS via 3rd sacral foramina (S3) efficacious for refractory urinNMS via 3rd sacral foramina (S3) efficacious for refractory urinary urgency ary urgency and refractory urinary retention (mechanism unknown)and refractory urinary retention (mechanism unknown)Surreptitiously found S3 NMS to ameliorate some IC/CPP symptomsSurreptitiously found S3 NMS to ameliorate some IC/CPP symptoms

Alo

KM,

Holsheimer

J (2002) New trends in

neuromodulation

for the management of

neuropathic

pain. Neurosurgery 50:690–703.

Whitmore KE, Payne CK,

Diokno

AC,

Lukban

JC (2003) Sacral

neuromodulation

in patients with interstitial cystitis: a

multicenterclinical trial.

Int Urogynecol

J Pelvic Floor

Dysfunct

14:305–308, discussion 308–309

Peters KM,

Konstandt

D (2004) Sacral

neuromodulation

decreases narcotic requirements in refractory interstitial cystitis. BJU

Int

93:777–779

Case Study: Refractory ICCase Study: Refractory IC

Traditional placement of unilateral NMS via S3 foramen.

Indicated for refractory urgency/frequency syndromes and idiopathic urinary retention.

Novel caudalNovel caudal

neuromodulationneuromodulation

technique for technique for IC/CPPIC/CPP

Devised method of NMS overlying S2-S4 nerve roots bilaterally.

Rationale:

Pain transmitted via multiple spinal levels

Pain transmitted viaunmyelinated C-fibers, exacerbated viaupregulation of these fibers.

Does not address additional recruitement of sympathetic fibers in chronic pain (e.g.hypogastric plexus)

Novel caudalNovel caudal

neuromodulationneuromodulation

technique for IC/CPPtechnique for IC/CPP

Rationale (continued)

Inability to capture dysfunctional pain foci in unilateral, focal therapy

Modulation of several spinal levels likely to more effectively captureabherrent signaling

Each lead independently programmable

Bilateral leads allows for crossover electrical fields, bipolar stimulation, or unilateral as desired

May expand and contract electrical field, decrease motor and sensory side effects

Still cannot capture hypogastric plexus

Early Outcomes of CaudalEarly Outcomes of Caudal

NeuromodulationNeuromodulation

23 consecutive patients (16 female, 7 male)23 consecutive patients (16 female, 7 male)Average f/u 15 months (6 to 32)Average f/u 15 months (6 to 32)Average age 46.3Average age 46.3All refractory cases, exhausted pain All refractory cases, exhausted pain management servicesmanagement services57% on daily narcotics57% on daily narcotics

Zabihi

N,

Mourtzinos

A, Maher M,

Raz

S, Rodriguez R: Short-term results of bilateral S2-S4 sacral

neuromodulation

for treatment of refractory interstitial cystitis, painful bladder syndrome, and chronic pelvic pain. Int.

Urogyn. J (2008) 19: 553-557

Early Outcomes of CaudalEarly Outcomes of Caudal

NeuromodulationNeuromodulation

Validated outcomes questionnaires:

IC Symptom Index (ICSI)

IC Problem Index (ICPI)

Urogenital Distress Inventory (UCI-6)

RAND Health Survey SF-36

Visual analog pain scale

Improved 35% (p=0.005)

Improved 38% (p=0.007)

Improved 26% (p=0.05)

No significant change

Improved 40% (p=0.04)

Early Outcomes of CaudalEarly Outcomes of Caudal

NeuromodulationNeuromodulation

5 of 23 devices removed5 of 23 devices removed1 for infection1 for infection4 for loss of efficacy4 for loss of efficacy

Significant, durable effect in 18 of 23 (78%) and all off of narSignificant, durable effect in 18 of 23 (78%) and all off of narcoticscotics

Now performed more than 75 caudal NMS proceduresNow performed more than 75 caudal NMS procedures

Preparing longPreparing long--term f/u to assess efficacy, durability, plasticity of term f/u to assess efficacy, durability, plasticity of neural response, etc.neural response, etc.

Case of Refractory ICCase of Refractory IC

43 year old woman with 4 year history of43 year old woman with 4 year history of……Urinary frequency was every 20 Urinary frequency was every 20 –– 30 minutes, now q330 minutes, now q3--4 hours4 hoursResolution of pain with bladder fillingResolution of pain with bladder fillingRequired postRequired post--operative reoperative re--programming 3 timesprogramming 3 timesWill require battery change in approximately 6Will require battery change in approximately 6--8 years (outpatient surgery)8 years (outpatient surgery)

Future of CaudalFuture of Caudal

NeuromodulationNeuromodulation

Randomize to unilateral v. bilateral stimulationRandomize to unilateral v. bilateral stimulationRandomize to intermittent or continuousRandomize to intermittent or continuous stimstim..Obtain postoperative videoObtain postoperative video urodynamicsurodynamics ($)($)

Thank youThank you

Chad Baxter, MDChad Baxter, MDPelvic Medicine and Reconstructive SurgeryPelvic Medicine and Reconstructive Surgery

Department of UrologyDepartment of UrologyDavid Geffen School of Medicine at UCLADavid Geffen School of Medicine at UCLA

Los Angeles, CaliforniaLos Angeles, California