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Chronic Pain and
Neuromodulation
Pain Fellowship Director, WakeForest University Health Sciences,
1986-2011President, Carolinas Pain Institute,2004-2011
CEO, Center for Clinical Research,1988-2011
President-elect, World Institute of
Pain, 2011-13
Founder, Sceptor Pain Foundation
Chief Editor, Pain Pathways
Richard L. Rauck MD
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Chronic Pain and Neuromodulation
Richard L. Rauck MD
Director, Carolinas Pain Institute
Wake Forest University Medical Center
Center for Clinical Research
Winston Salem, North Carolina
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Full Disclosure
Research funding: Medtronic, Boston Scientific
Consultant: Elan, Boston Scientific, Medtronic
Speaker: Elan, Boston Scientific
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Interventional Pain Management for
Therapeutic Benefit Neurodestruction
Radiofrequency
facet denervation Cryoanalgesia
peripheral nerve
Chemical
celiac plexus block Disc manipulation
Percutaneous discectomy
Intradiscal electrocautery
nucleoplasty
Neuromodulatory
Electrical
spinal cord stimulation peripheral nerve
stimulation
Intrathecal/epiduralmedication
internal pump subcutaneous port
externalized catheters
osmotic pumps
xenographic transplants
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Safety and Efficacy of Spinal Cord
Stimulation for the Treatment of Chronic
Pain: A 20 Year Literature Review
68 studies and 3679 patients
Positive long-term effect in:
Refractory angina pain (11 studies) Severe ischemic limb pain secondary to vascular
disease (13 studies)
Peripheral neuropathic pain
Complex regional pain syndrome (12 studies) Chronic low back pain (16 studies)
Studies were RCTs, prospective w/o controls, orretrospective
Cameron, 2004, J Neurosurgery
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Spinal Cord Stimulation for Chronic Pain of
Spinal Origin: A Valuable Long-Term Solution
Review article
North prospective trial: 50 patients selected for
repeat laminectomy Crossover allowed at 6 months
10/15 surgery patients crossed over to SCS
2/12 SCS patients crossed over to surgery
90% of patients at 3 years demonstrated SCS to bemore effective than re-operation
Those randomized to re-operation used significantlymore opioid analgesics (p
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Spinal Cord Stimulation in Chronic Pain:
A Review of the Evidence Success with FBSS is 50-60% but cannot be
advocated for all patients with this condition
Better evidence exists for Neuropathic pain Complex regional pain syndromes
Angina pectoris
Critical limb ischemia Lack of high quality evidence relating to SCS
secondary to difficulty performing RCTs
Carter, ML. Anaesth Intensive Care 2004
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Benchmark Study: Methods
Study Purpose: to assess the acute and chronic effectiveness of the spinalcord stimulation in subjects with Failed Back Surgery Syndrome and associatedlow back pain.
Methods: 259 subjects with FBSS, a primary complaint of axial low back pain,who had failed conservative therapy were implanted with 1 or 2 percutaneous
leads and external trial stimulator for 5-10 days. Subjects who reported significant pain reduction from baseline and were
considered appropriate clinical candidates were considered successful trials.
Outcome Measures: Pain, disability, quality of life, medical satisfaction,healthcare utilization and other measures were assessed at baseline and at 3, 6, &12 months
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Benchmark Study: Results
Subjects demonstrated high trial success rate of 76.1% (172) with 92.4%(159) conversion rate to permanent implants.
Reasons for withdrawal included patient choice, lack of insurance, andlost to follow up.
Subjects reported 40% average decrease in self reported pain rating
Preliminary data suggest that long termreduction maintained and consistent withthat observed during trial phase.
Long term data will be reported when allsubjects have completed 12 month followup later this year.
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Axial Back Pain: Momentary
p
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Radicular Pain: Momentary
p
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If you had to spend the rest of your life with the
symptoms you have right now, how satisfied would
you be with your medical outcome?
p
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Mechanism of Action (MOA)
Calcium entering through
presynaptic calcium
channels trigger calcium-
dependent transmitterrelease
Results in animals suggest
that PRIALT binding to
N-type calcium channelsblocks excitatory
neurotransmitter release;
the MOA has not been
established in humans
Ziconotide
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Change in VASPI Score
Primary efficacy variable
was mean % change in
VASPI score from baseline
to day 21
Patients who did not have a
VASPI score recorded days
17-23, inclusive, were
assigned 0% improvement
12.0
5.0
0
5
10
15
20
PRIALT
(n=112)
Placebo
(n=108)
Mean%C
hangein
VASPI
p=0.04
Mean % Change in VASPI Scores
from Baseline to Day 21
Rauck, et al, JPSM, 2005
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Current Topics with Ziconotide
Narrow therapeutic window
Start low (.5-1.2 mcg/day) and titrate slowly
Increase by 1.2 mcg/day no more than 1 time/week
Peptide that is unstable in combination withmorphine secondary to oxidative degradation
Appears stable with clonidine, bupivicaine, baclofenand hydromorphone and off-label combinations in use
Tolerance has not been reported
Respiratory depression not a problem
No withdrawal problems with acute cessation
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Status of Intrathecal Gabapentin
Drug is currently in early investigational stage of
human development No human administration to date via implantable device
Spinal neurotoxicity trials are ongoing
Use outside an investigational trial design could
be potentially very dangerous
Medico-legal risk to physician
Drug development if complication occurred
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CSF & Plasma Pharmacokinetics
Observed and Fitted Lumbar CSF and Plasma
0 24 48 72 96 120 144 1681
10
100
1000
10000
100000
1000000
CSF Observed
CSF Fitted
Plasma Fitted
Plasma Observed
Time (hr)
Concentrat
ion
(ug/L)
Increasing CSF & plasma levels as infusion rate/dose was escalated
Steady-state levels determined with linear pharmacokinetics
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Phase II/III Program
120 patients with indication for intrathecal therapy
Chronic pain below the neck
No previous intrathecal experience
Intrathecal pump implanted
No intrathecal trial
2 fixed doses versus placebo
Look at maximally tolerated dose versus minimallyeffective dose
Primary endpoint: VAS reduction at 4 weeks
Open label extension trial with dose ranging allowed
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Summary
Trend is away from anatomic (neurodestruction)
to physiologic and pharmacologic
(neuromodulation) alterations
Thalamus and somatosensory cortex have been
difficult to modulate except with systemic agents
Spinal cord technology present for significantphysiologic/pharmacologic alterations
Periphery: peripheral modulation of nociceptive
pathways in a site specific mechanism is evolving
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