Evidence Based for Failed

Back Syndrome
•Chair, Department of Pain Medicine,
Mayo Clinic Florida
• Assistant Professor, Department of
Anesthesia, Mayo Clinic Florida
• Co-Chair, Essential Tools AAPM
• Interests:
• International Chronic Pain
Management
• SCS
• Intrathecal Pump
• RFD, Cooled RFD, Pulsed RF
Salim M. Ghazi, MD • Cancer Pain
• Contact:
Ghazi.Salim@mayo.edu
NEUROMODULATION EVIDENCE
IN NEUROPATHIC PAIN

SALIM M GHAZI MD
S.P.I.N.E
BEIRUT 2010
Jacksonville
Orlando to
Jacksonville
140 miles

Orlando
 DISCLOSURES

Financial Off-Label
Disclosures Discussion
1.Use of spinal
stimulation electrodes
and generators for
peripheral nerve
stimulation
NONE 2. Spinal stimulation
systems for visceral
pain, ischemic pain,
and miscellaneous
pain syndromes
 Pain Definitions
• The IASP defines pain as “an unpleasant
sensory and emotional experience associated
with actual or perceived tissue damage or
described in terms of such damage”1

• Pain can be classified according to primary

etiology2
• Neuropathic
• Nociceptive
• Mixed neuropathic and nociceptive

• All types of pain can also be classified by

duration3
• Acute: less than 6 weeks
1
• Sub-acute: between 6 weeks and 3 months
Merskey H, Bogduk N, eds. Classification of Chronic Pain, 2nd Ed. IASP Press Seattle, 1994
2
3
• Handbook,
Cole AJ. In Low Back Pain Chronic: lasting
2nd ed. 2003; pg
Koes BW, et al. Br Med J. 2006;332:1430-1434
361-374 > 3-6 months
 What is Neuropathic Pain?

 The International Association for the Study of Pain

(IASP) definition of neuropathic pain:
 “Pain initiated or caused by a primary lesion or
dysfunction in the peripheral or central nervous system”.

 Neuropathic pain must involve the somatosensory

pathways with damage to small fibers in peripheral
nerves or to the spino-thalamo-cortical system in
the central nervous system.

10
 What is neuropathic Pain?

 Caused by damage to the nervous system

 Described as “burning”, “shooting” or “tingling” sensations
1
 A common problem with an estimated prevalence of 1.5%
2,3
 Causes major disability and significantly reduces quality of life
1
 The burden on patients and healthcare systems is substantial
1
 Patients consume a high level of healthcare resources
4
 Associated with a 3-fold increase in healthcare costs

1. Taylor RS. Pain Practice 2006

2. Meyer-Rosberg K, et al. Eur J Pain 2001
3. Kemler MA, et al. New Eng J Med 2000
4. Berger A, et al. J Pain 2004
11
 Types of Neuropathic Pain
• Direct nerve root injury: radiculopathy
• Battered root syndrome
• Perineural fibrosis
• Intrafascicular fibrosis
• Adhesive arachnoiditis
• Peripheral deafferentation
• Phantom limb pain
• Sympathetic-mediated pain syndrome
• Herpetic neuralgia
• Diabetic polyneuropathy
• Central deafferentation-thalamic stroke
nd
Cole AJ. In Low Back Pain Handbook, 2 ed. 2003; pg 361-374
 Actual treatment of NP

 Pharmacotherapy is currently the mainstay of treatment and is

routinely used in all patients with neuropathic pain
 However, not all drugs are suitable for all patients at all stages of their
disease

 Less than 50% of patients achieve greater than 50% relief of

6,7
neuropathic pain with pharmacotherapy
 Many patients experience intolerable side effects (eg: sedation, cognitive
impairment, somnolence, nausea, constipation)

 One-third of patients with chronic pain are currently not being

5
treated at all 5. Breivik H, et al. Eur J Pain 2006
6. Eisenberg E. JAMA 2005
7. Finnerup NB et al. Pain 2005

13
Pharmacologic Management of Neuropathic Pain

Pain 2007;132:237-251
 Pharmacologic Management of Neuropathic Pain:
Evidence-based Recommendations
Pain 2007;132:237-251

Conclusion: “Existing pharmacologic

treatments for NP pain are limited, with
no more than 40-60% of patients
obtaining partial relief of their pain.”
 NEUROMODULATION

• ELECTRICAL = NEUROSTIMULATION
• CHEMICAL: INTRATHECAL DRUG
DELIVERY
• OPIOIDS
• NON-OPIOIDS
 Spinal Cord Stimulation
Introduced in the late 1960s by Melzack and Wall

• What is Neurostimulation?
• A technique that alleviates pain by sending
electrical impulses via implanted leads to
the spinal cord
 The impulses activate pain-inhibiting neuronal
circuits in the dorsal horn and induce a tingling
sensation (paresthesiae) that masks the
sensations of pain

• What is the goal of Neurostimulation?

• To obtain more than 80% coverage of the
painful areas with paresthesiae, so that at
least a 50% reduction in pain can be 17
maintained at one year follow-up
 Gate Control Theory

• When sensory impulses are greater than pain

impulses
• “Gate” in the spinal cord closes preventing the pain
signal from reaching the brain

C FIBER
Sensory INHIBITORY
INTERNEURON

Gate

Pain PROJECTION
AaAb FIBERS
NEURON
 Gate Theory and SCS
SCS system implanted near dorsal column
stimulates the pain-inhibiting nerve fibers masking
painful sensation with a tingling sensation
(paresthesia)

C FIBER
Sensory
SCS INHIBITORY
INTERNEURON

Gate

Pain AaAb FIBERS

PROJECTION
NEURON
 History of Neurostimulation
• 1967-1ST Technical report for back/limb pain
• 1970s-Equipment limitations/ open surgery
• 1975-76-percutaneous technique introduced
• 1980s-Equipment advances-mainstream therapy
(Medtronic)
• 1987-First SCS trial for angina
• 1990s-Three major vendors
• 1990s-Multiple leads/multiple
programs/expanded indications.
• 20,000-30,000 pts/yr worldwide.
 Indications

• Back Pain
• Failed Back Syndrome

• CRPS 1 & 2

• Radiculopathy – non operative

• Peripheral vascular disease

• Post Herpetic Neuralgia

• Ischemic Heart Disease

• Arachnoiditis

• Others eg: Sacral, peripheral

22
 Pain Indications for Stimulation

• Intractable neuropathic pain

• Any body region: Head-to-Toe

• Properly screened patient

 Outcomes of SCS

In the treatment of neuropathic pain:

• Pharmacological management: 50% of
patients achieve adequate pain relief
• SCS: 65% of medically refractory patients
achieve at least 50% pain relief sustained
long-term 1

1 Taylor et al (2005)

27
 Neurostimulation: Reduction in Pain

Reference # of Patients Mean Results

Follow up
North 171 7 years 52% with > 50% relief
Pain, 1993
Turner 39 study meta analysis 16 months 59% with > 50% relief
Neurosurgery, 1995
De la Porte 64 4 years 55% good to excellent
relief
Pain, 1993
Segal 24 19 months 78% good to very good
effect
Neurol Research, 1991
Kumar 111 5.6 years 59% good to excellent
results
Surg Neurol, 1991
Burchiel 70 Multi-center 1 year 55% with > 50% relief
Spine, 1996

28
 Reduction in Analgesic Consumption

# of Mean
Reference Patients Follow-up Results

Ohnmeiss 40 2 years 66% decreased eliminated

Spine, 1996 narcotics
North 171 7 years 58% reduced/eliminated
Neurosurgery, 1995 analgesics
De La Porte 64 4 years 90% reduced medication
Pain, 1993
Kumar 111 5.6 years 59% satisfactory relief
Surg Neurol, 1991
Racz 26 1.8 years 81% reduced/eliminated
Spine, 1989 narcotics
Segal 24 19 months 59% satisfactory relief

29
Treatment of Chronic Pain with Spinal Cord Stimulation
versus Alternative Therapies: Cost-effectiveness
Analysis.

CONCLUSION:
SCS is cost-effective in the long term, despite the
initial high costs of the implantable devices.

Kumar, Krishna F.R.C.S.(C), F.A.C.S.; Malik, Samaad M.D., B.Sc.; Demeria,

Denny M.D. July 2002

30
 SCS for Chronic Pain-22 Year Experience

• 452 patients treated with SCS over 22 yrs

• 220 patients with “FBSS”
-Mean f/u duration-97 months
-f/u by ‘disinterested’ 3rd party
• 132/220 pts. with greater than 50% pain relief
(65%)
• Other notables:
-9/9 angina patients had relief
-4/19 PHN patients had relief
• Kumar, et al. Neurosurgery 2006;58:481-496
 SCS vs Repeat Surgery for Chronic Back Pain

• 45 patients w persistent pain after L-spine

Surgery
• RCT w crossover
• Success: >50% pain relief, patient satisfaction,
crossover
• 9/19 SCS vs 3/26 Surgery successful outcome
(p<0.01)
• 6/14 re-operations that crossed to SCS were
successful (vs 0/4 SCS to Surgery)
North et.al. Neurosurgery 2005;56:98-107
 Spinal Stimulation (SCS) vs Conventional Medical Management
(CMM) for Neuropathic Pain…in Patients with Failed Back surgery
Syndrome

• RCT-100 patients w FBSS (neuropathic radicular pain)

• SCS+CMM vs CMM
• 48% of SCS and 4% of CMM achieved primary
outcome of > 50% pain relief
• SCS group also had
-improved Q.O.L.
-improved functional measures
-greater treatment satisfaction
Kumar K. et al. Pain 2007;132:179-188
 Spine Surgery and Post –Procedure Pain

• Incidence of persistent or recurrent pain after

lumbar surgery-10-40%
• Success rate of 2nd operation is 10-30%
• Fusion/Instrumentation-Increased frequency
of FBSS ( Donor site 15%, pseudoarthrosis
15%, instrument failure 7%, nerve injury 3%,
etc)
• Surgery/Fusion rate has increased by nearly
100% since 1996. >500,000 per year.
Deyo, et al. NEJM 350:722-726,2004
North, et al. Neurosurgery 56:89-107;2005
 SCS for Angina/Chest pain
Randomized Trial-104 patients, SCS vs CABG
 SCS in Severe Angina Pectoris-A Systematic Review
Borjesson M, et al. Pain 2008;140:501-508

• Evaluated 43 Clinical Trials

• 8 medium to high quality studies
• “Strong Evidence” that SCS gives rise to
symptomatic benefits…
-decreased anginal attacks
-decreased NTG, analgesic use
• “Strong evidence that SCS can improve the
functional status of these patients…”
-improved exercise treadmill time
-increased walking distance w/o angina
 PNS for Neuropathic Pain-Outcomes

• 6 clinical trials, 202 patients (no RCTs)

• Average success rate-60% of patients

with greater than 50% improvement

Cruccu G, et al. Guideline on Neurostimulation

Therapy for Neuropathic Pain. Eur J Neurol
2007;14:952-970
 MOTOR CORTEX STIMULATION
Mayo Clinic experience – 22 patients
• Results
• 90% effective for neuropathic
trigeminal pain, anesthesia
dolorosa, and ophthalmic post-
herpetic neuralgia

• 75% excellent results for thalamic

pain
 MCS-Indications and Outcomes

• Indications
-Post-stroke pain (thalamic pain)
-anesthesia dolorosa (surgery, trauma)
-postherpetic neuralgia

• Results
-No large scale series and/or RCTs
-multiple clinical series since 1993: 40-75% of patients with
> 50% pain relief
-Largest series;29/38(76%) of patients improved
Neurosurgical Focus 2006;21:1-4
 Indications for Neurostimulation and
Intrathecal Drug Delivery Therapy

Cole AJ. In Low Back Pain Handbook, 2nd ed. 2003; pg 362. Refer to full prescribing information for Medtronic
Neurostimulation Systems and Synchromed® II and Isomed® Drug Infusion Systems
 CONCLUSION

• NEUROPATHIC PAIN IS DIFFICULT

TO TREAT
• MULTIDISCIPLINARY APPROACH
NEEDED
• CONSERVATIOVE APPROACH
SHOULD BE INITIATED FIRST:
• MEDICATIONS
• APPROPRIATE PT
• INJECTIONS
AND IF NOT HELPFUL OR SHORT-
LIVED:

• NEURO-STIMULATION
 QUESTIONS?

• Ghazi.salim@mayo.edu
14. Struijk JJ, Holsheimer J, Spincemaille GHJ, Gielen FLH, Hoekema R.
Theoretical performance and clinical evaluation of transverse tripolar spinal
cord stimulation. IEEE Trans Rehabil Eng 1998;6(3):277–85
15. Taylor RS, Taylor RJ, Van Buyten J-P, et al. The cost effectiveness of spinal
cord stimulation in the treatment of pain: A systematic review of the literature. J
Pain Symptom Manage 2004;27:370–8.
16. Yearwood TL. Tripolar neurostimulator array in the cervical epidural space for
the treatment of bilateral lower extremity pain [Abstract]. Neuromodulation
2006;9(1):18–9.
17. SCS for Non-reconstructable Chronic Critical Leg Ischemia- SCS vs Standard
Conservative Treatment
Cochrane Database of Systematic Reviews, (Feb 2008)
18. Ambrosini, A. (2007). "Occipital nerve stimulation for intractable cluster
headache." Lancet 369(9567): 1063-5.
19. Amin, S., A. Buvanendran, et al. (2008). "Peripheral nerve stimulator for the
treatment of supraorbital neuralgia: a retrospective case series." Cephalalgia
28(4): 355-9.
20. Bartsch, T. and P. J. Goadsby (2002). "Stimulation of the greater occipital nerve
induces increased central excitability of dural afferent input." Brain 125(Pt 7):
1496-509
 Bibliography

1. Bennett DS, Aló KM, Oakley J, Feler CA. Spinal cord stimulation for
Complex Regional Pain Syndrome I (RSD). A retrospective multicenter
experience from 1995–1998 of 101 patients. Neuromodulation
1999;2(3):202–10.
2. Burchiel KJ, Anderson VC, Brown FD, et al. Prospective, multicenter study
of spinal cord stimulation for relief of chronic back and extremity pain.
Spine 1996;21(23):2786–94.
3. Grabow TS, Tella PK, Raja SN. Spinal cord stimulation for complex regional
pain syndrome.
: An evidence-based medicine review of the literature. Clin J Pain
2003;19(6):371–83
4. Harke H, Gretenkort P, Ladleif HU, Koester P, Rahman S. Spinal cord
stimulation in postherpetic neuralgia and in acute herpes zoster pain.
Anesth Analg 2002;94(3):694–700.
5. Holsheimer J, Khan YN, Raza SS, Khan EA. Effects of electrode positioning
on perception threshold and paresthesia coverage in spinal cord
stimulation. Neuromodulation 2007;10(1):34–41.
6. Holsheimer J, Wesselink WA. Optimum electrode geometry for spinal cord
stimulation: The narrow bipole and tripole. Med Biol Eng Comput
1997;35(5):493–7
7. Kemler MA, Barendse GA, van Kleef M, et al. Spinal cord stimulation in patients
with chronic reflex sympathetic dystrophy. N Engl J Med 2000;343(9):618–24.
8. Kemler MA, De Vet HC, Barendse GA, Van Den Wildenberg FA, Van Kleef M. The
effect of spinal cord stimulation in patients with chronic reflex sympathetic
dystrophy: Two years' follow-up of the randomized controlled trial. Ann Neurol
2004;55(1):13–8.
9. Kim SH, Tasker RR, Oh MY. Spinal cord stimulation for nonspecific limb pain
versus neuropathic pain and spontaneous versus evoked pain. Neurosurgery
2001;48(5):1056–64
10. Kumar K, Buchser E, Linderoth B, Meglio M, Van Buyten J-P. Avoiding
complications from spinal cord stimulation: Practical recommendations from an
international panel of experts. Neuromodulation 2007;10(1):24–33.
11. Kumar K, Toth C, Nath RK. Spinal cord stimulation for chronic pain in
peripheral neuropathy. Surg Neurol 1996;46(4):363–9.
12. Oakley J, Varga C, Krames E, Bradley K. Real-time paresthesia steering using
continuous electric field adjustment. Part I: Intraoperative performance.
Neuromodulation 2004;7(3):157–67
13. Slavin KV, Burchiel KJ, Anderson VC, Cooke B. Efficacy of transverse tripolar
stimulation for relief of chronic low back pain: Results of a single center.
Stereotact Funct Neurosurg 1999;73(1-4):126–30.
21. Burns, B., L. Watkins, et al. (2007). "Treatment of medically intractable cluster
headache by occipital nerve stimulation: long-term follow-up of eight patients."
Lancet 369(9567): 1099-106.
22. Busch, V., W. Jakob, et al. (2006). "Functional connectivity between trigeminal
and occipital nerves revealed by occipital nerve blockade and nociceptive blink
reflexes." Cephalalgia 26(1): 50-5.
23. Goadsby, P. J. (2007). "Neurostimulation in primary headache syndromes."
Expert Rev Neurother 7(12): 1785-9.
24. Goadsby, P. J., T. Bartsch, et al. (2008). "Occipital nerve stimulation for
headache: mechanisms and efficacy." Headache 48(2): 313-8.
25. Leone, M., A. Franzini, et al. (2007). "Stimulation of occipital nerve for drug-
resistant chronic cluster headache." Lancet Neurol 6(4): 289-91.
26. Magis, D., M. Allena, et al. (2007). "Occipital nerve stimulation for drug-resistant
chronic cluster headache: a prospective pilot study." Lancet Neurol 6(4): 314-
21.
27. Melvin, E. A., Jr., F. R. Jordan, et al. (2007). "Using peripheral stimulation to
reduce the pain of C2-mediated occipital headaches: a preliminary report." Pain
Physician 10(3): 453-60.
28. Slavin, K. V., H. Nersesyan, et al. (2006). "Peripheral neurostimulation for
treatment of intractable occipital neuralgia." Neurosurgery 58(1): 112-9;
discussion 112-9.
29. Hornberger, J., K. Kumar, et al. (2008). "Rechargeable Spinal Cord Stimulation
Versus Nonrechargeable System for Patients With Failed Back Surgery
Syndrome: A Cost-Consequences Analysis." Clin J Pain 24(3): 244-252.
30. Andrell, P., O. Ekre, et al. (2003). "Cost-effectiveness of spinal cord stimulation
versus coronary artery bypass grafting in patients with severe angina pectoris--
long-term results from the ESBY study." Cardiology 99(1): 20-4.
31. Buchser, E., A. Durrer, et al. (2006). "Spinal cord stimulation for the
management of refractory angina pectoris." J Pain Symptom Manage 31(4
Suppl): S36-42.
32. Chua, R. and A. Keogh (2005). "Spinal cord stimulation significantly improves
refractory angina pectoris-a local experience spinal cord stimulation in
refractory angina." Heart Lung Circ 14(1): 3-7.
33. Di Pede, F., G. A. Lanza, et al. (2003). "Immediate and long-term clinical
outcome after spinal cord stimulation for refractory stable angina pectoris." Am
J Cardiol 91(8): 951-5.
34. Eddicks, S., K. Maier-Hauff, et al. (2007). "Thoracic spinal cord stimulation
improves functional status and relieves symptoms in patients with refractory
angina pectoris: the first placebo-controlled randomised study." Heart 93(5):
585-90.
35. Lanza, G. A., A. Sestito, et al. (2005). "Effect of spinal cord stimulation on
spontaneous and stress-induced angina and 'ischemia-like' ST-segment
depression in patients with cardiac syndrome X." Eur Heart J 26(10): 983-9.
36. Lapenna, E., D. Rapati, et al. (2006). "Spinal cord stimulation for patients with
refractory angina and previous coronary surgery." Ann Thorac Surg 82(5): 1704-
8.
37. Yu, W., F. Maru, et al. (2004). "Spinal cord stimulation for refractory angina
pectoris: a retrospective analysis of efficacy and cost-benefit." Coron Artery Dis
15(1): 31-7.
38. Borjesson M. et al. “Spinal cord stimulation in severe angina pectoris-A
systematic review …” (2008) Pain 140;501-508
 Male, 45, office manager, no major
psychosocial issue

One spine surgery to treat herniated

disc
• Referred from primary care physician
to address axial back pain and
secondary radicular pain that
persists six months following
anatomically corrective surgery
• Average back pain score (VAS) of
80/100 with diminished functional
capacity