Rauck Chronic Pain

8/7/2019 Rauck Chronic Pain

1/23

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


2/23

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


3/23

Full Disclosure

Research funding: Medtronic, Boston Scientific

Consultant: Elan, Boston Scientific, Medtronic

Speaker: Elan, Boston Scientific


4/23

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


5/23

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


6/23


7/23

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


8/23

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


9/23

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


10/23

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.


11/23

Axial Back Pain: Momentary

p


12/23

Radicular Pain: Momentary

p


13/23

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


14/23


15/23

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


16/23

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


17/23

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


18/23

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


19/23

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


20/23

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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Rauck Chronic Pain

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