THE CRISIS OF PAIN IN AMERICA

Our Role in the Management of Chronic Pain

Disclosures

Speaker/consultant for St. Jude’s; also receiving research grants

Speaker/stock holder for Insys Therapeutics

Speaker/consultant for Central Avenue Pharmacy

Confidential. For

Internal Use Only.

Do Not Distribute

Objectives

Understand the impact that pain, specifically chronic pain, has on our society

Discuss pharmacological approach to pain management

Review neuromodulation as it pertains to interventional pain management

Determine when interventional approaches to pain management are appropriate

Discuss surgical implants for pain management

BURDEN OF CHRONIC PAIN IN THE UNITED STATES

Affects 100 million Americans (more than heart disease, cancer and diabetes combined)1

Costs society up to $635 billion annually1

Associated with 40 million doctor visits annually2

Results in 515 million lost workdays annually2

40% of all work absences are related to low back pain3

4

1. Institute of Medicine. Relieving pain in America: A blueprint for transforming prevention, care, education, and research. 2011.

2. Rich SJ. Adv Stud Pharm. 2009;6(4):115-119.3. Manchikanti L, et al. Pain Physician. 2009;12:699-802.

CHRONIC PAIN IS AMONG THE TOP COSTLY CONDITIONS IN THE UNITED STATES

5

Chronic pain

Heart disease

Cancer Diabetes Obesity$0

$100

$200

$300

$400

$500

$600

$700

Co

st in

bill

ion

s o

f d

olla

rs (

20

10

)

1. Institute of Medicine. Relieving pain in America: A blueprint for transforming prevention, care, education, and research. 2011.

2. Wang Y, et al. Obesity 2008;16(10):2323-2330.

$635billion

$309billion $243

billion $188billion $151

billion

1 1

1 1 2

National Health Care Costs in the United States

The National Health Expenditure reached $2.5 trillion in 2009 and is expected to reach $4.5 trillion in 20191

6

1. Centers for Medicare and Medicaid Services. National Health Expenditure Projections 2009-2019. Accessed April 23, 2014.

2. Orszag PR, Emanuel EJ. N Engl J Med. 2010;363;7:601-603.

2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015 2016 2017 2018 2019$1.0

$2.0

$3.0

$4.0

$5.0

$U

S b

illi

on

s

The Affordable Care Act includes measures to reduce waste in health care spending, including Medicare and Medicaid fraud and abuse, resulting in an

anticipated savings of $7 billion over 10 years2

Complications and Comorbidities Associated With Chronic Pain

7

1. Institute of Medicine. Relieving pain in America: A blueprint for transforming prevention, care, education, and research. 2011.

2. Reid KJ, et al. Curr Med Res Opin. 2011;27:449-62.3. Miller LR, Cano A. J Pain. 2009; 10(6):619-627.4. Tang NKY, et al. Psych Med. 2006;36:575-586.5. Bruehl S, et al. Clin J Pain. 2005;21(2):147-153.6. Tang NKY, et al. J Sleep Res. 2007;16:85-1695.7. Sullivan MD, et al. Pain. 2010;150(2):332-339.

8. Behavioral Health Coordinating Committee Prescription Drug Abuse Subcommittee. Addressing prescription drug abuse in the United States: current activities and future opportunities. Accessed June 4, 2014..

9. Strine TW, Hootman JM. Arthritis Rhem. 2007;57(4):656-665.

In addition to the significant economic burden1 and negativeimpact on quality of life,2 untreated chronic pain is associated

with physical and psychological complications3-6

Depression3 35% of chronic pain patientsvs 4.6% of the general study population

Suicide4

Suicide ideationlifetime prevalence in

chronic pain patients, ~20%vs 13.5% in the general population

Suicide attemptslifetime prevalence in

chronic pain patients, 5-14%vs 4.6% of the general population

Hypertension5 39% of chronic pain patientsvs 21% of the general population

Insomnia6 53% of chronic pain patientsvs 3% of pain-free controls

Overweight/obese9 62.7% of patients with low back/neck painvs 56.5% of the general population

Opioid misuse/abuse7,8 20-24% of chronic pain patientsvs 3.8% of the general population

THE BENEFITS OF SENDING PATIENTS TOPAIN SPECIALISTS

8

Establish accurate diagnosis

Improve patient care1

Increase activity levels2

Improve functional life activities2

Reduce disability, return patients back to work2

Decrease overutilization of opioids2

Reduce emotional distress, such as depression and anxiety2

Decrease the use of medical resources2

Goals of Pain Physicians Treating Chronic Pain

Chronic back, neck, shoulder, trunk, and limb pain

Neuropathic pain

Post-surgical pain syndromes

Failed back surgery syndrome

Arthritis

Degenerative disc disease

Complex regional pain

Cancer pain

Types of Pain Treated by Pain Physicians

1. Davies HTO, et al. J R Soc Med. 1994;87(7):382-385.2. Clark TS. BUMC Proceedings. 2000;13:240-243.

US-2001416 A EN (06/14)

CONFIDENTIAL – For Internal Use Only. Do Not Distribute

A Changing Paradigm for the Management of Chronic Pain The historical approach to chronic pain treatment involves sequential testing of multiple analgesics,

with interventional therapies (eg, spinal cord stimulation) as “last resort”1

In a new, simplified, patient-centric approach, interventional therapies are earlier in the treatment continuum2

1. Kaplan R. J Support Oncol. 2010;8:62-63.2. Poree L, et al. Neuromodulation. 2013;16(2):125-141.

New Approach to Chronic Pain Treatment

Conservative Care (Step 1)

Physical therapy

OTC pain medications

Psychological therapy

NSAIDs

Injection therapies†

Low dose opioids

TENS

Neurolysis

Thermal procedures

Chronic opioid maintenance

Intrathecal therapy

Surgical intervention

Neuroablation

Spinal cord stimulation

Less Conservative - Moderate Care (Step 2)

Aggressive Care(Step 3)

Conservative Care (Step 1)

Physical therapy

OTC pain medications

Psychological therapy

NSAIDs

Injection therapies

Low-dose opioids

TENS

Spinal cord stimulation

Neurolysis

Thermal procedures

Chronic opioid maintenance

Intrathecal therapy

Surgical intervention

Neuroablation

Less Conservative -Moderate Care (Step 2)

Aggressive Care(Step 3)

9

MORTALITY AND COSTS RELATED TO OPIOID MISUSE AND OVERDOSE IN THE UNITED STATES

The percentage of drug overdose deaths related to opioids doubled from 1999 to 20101

Opioid overdose is responsible for more than 16,000 deaths annually1

Non-medical opioid use is associated with $75.2 billion in insurance costs per year2

10

Rate of Opioid Overdose Deaths (per 100,000)1

1. Behavioral Health Coordinating Committee Prescription Drug Abuse Subcommittee. Addressing prescription drug abuse in the United States: current activities and future opportunities. Accessed June 4, 2014.

2. Coalition Against Insurance Fraud. Prescription for peril: how insurance fraud finances theft and abuse of addictive prescription drugs. Accessed April 22, 2014.

6

5

4

3

2

1

02009 2010

Ra

te

Year

20082006 2007200520042002 2003200120001999

http://www.cdc.gov/homeandrecreationalsafety/overdose/hhs_rx_abuse.html

RISKS ASSOCIATED WITH OPIOID THERAPY

11

1. Behavioral Health Coordinating Committee PrescriptionDrug Abuse Subcommittee. Addressing prescription drug abuse in the United States: current activities and future opportunities. Accessed June 4, 2014.

2. Coalition Against Insurance Fraud. Prescription for peril: how insurance fraud finances theft and abuse of addictive prescription drugs. Accessed April 22, 2014.

3. Kalso E , et al. Pain. 2004;112:372-80.4. Colameco S, Coren JS. J Am Osteopath Assoc. 2009;109:20-24.

5. Ballantyne JC. South Med J. 2006;99:1245-1255.6. Walker JM, et al. J Clin Sleep Med. 2007;3(5):455-461.7. Taylor RS, et al. Spine. 2005;30(1):152-160.8. Frey ME, et al. Pain Physician. 2009;12:379-397.

Overdose-related deaths1 16,651 deaths/year

Non-medical use rate1 3.8% of the US population

Insurance costs of non-medical use2 $72.5 billion/year

Constipation/bowel dysfunction3 ~41% of chronic opioid users

Endocrine effects (opioid-induced androgen deficiency4)

Affects ~5 million men taking opioids for chronic pain in the US

Immunologic challenges5 May be associated with immunosuppression

Ataxic breathing during sleep6 ~70% of chronic opioid users

Long-Term Pain Affects Most of Your Patients (Peter D. Hart Research Associates) 3 out of 4 Americans have experienced chronic or

recurring pain or have a family member who has experienced such pain

Almost 62% of pain sufferers have had their pain for a year or more

A majority of adults (57%) have experienced chronic or recurring pain, including 54% of adults aged 18–34

Types and Definitions of Pain Acute pain

Accompanies tissue injury or pathology Comes on quickly and lasts a short time Varies in severity and intensity

Chronic pain Continues a month or more beyond usual recovery

period Goes on for months or years due to a chronic

condition Difficult to define onset

Types and Definitions of Pain Nociceptive pain

Caused by irritation to special nerve endings (nociceptors)

Can be dull or sharp Can be mild or severe

Neuropathic pain Caused by a malfunction of the nervous system The result of injury, disease, or trauma Can be sharp, intense, and constant Can be dull, aching, and throbbing

Failed Back Surgery Syndrome Back and/or leg pain that recurs or persists following

seemingly successful back surgery Surgical goals not met Patient goals not met

Diabetic Peripheral Neuropathy (Belgrade) Simultaneous decreased sensation in the distal

extremities in patients with diabetes Manifested by loss of sharp vs. light touch discrimination,

numbness, and tingling in combination with burning pain

Intrathecal Pump as a therapy for chronic, intractable pain.

Significant decrease in oral opioid need. Trial can be single injection or epidural catheter. Combination of local anesthetics, alpha-blockade, and/or

opioids create synergistic effects. New medications (ie. ziconitide – calcium channel

blocker) create new opportunities and abilities to control chronic pain.

Pump can be accessed easily and effectively programmed to control pain medication in microliters.

SCS as an Advanced Treatment for Pain

History of Neurostimulation (Glindenberg) One of the earliest uses of electricity in medicine was for

pain relief. Around 15 A.D., Scribonius reported that a torpedo fish

could be used to apply an electrical charge to patients to relieve pain.

Courtesy of Dr. Thomas Simopolous, Boston, MA

Neuromodulation Devices (Electrical Stimulators and Drug Pumps)

Allow the delivery of very small, precise doses of electricity

or drugs directly to targeted nerve sites.

What is Spinal Cord Stimulation (SCS)?

Tenets of SCS Comprehensive trial Customizable system components Optimized efficiency in programs and design Team approach to patient care

SCS Phases Trial period Permanent implant

Advantage of an SCS Trial One big advantage of SCS over other pain management

therapies is that it can be tested on patients before an SCS device is permanently implanted

The trial gives the pain management physician important information for determining which of the two SCS systems, conventional or rechargeable, is appropriate for a specific patient

About the SCS Trial A short outpatient procedure during which the physician

places one or more leads in the space over the spinal cord

The patient is generally awake during the procedure so that he or she can provide feedback to the physician regarding exact placement

A lead connects to a device that can be worn on a belt. The device will contain a variety of programs

About the Trial System

Trial Lead

Trial Cable

Trial

Generator/Programmer

Lengths of Trials Short-term trials

1 to 3 days 3 to 5 days

Long-term trials 7 to 10 days

Trial Diary Can be used as a guide to determine the device type and

the parameters that were favored during the trial Helps patients get involved in their therapy

Patient/Device Criteria

Conventional IPG Rechargeable IPG

Power requirements Low to moderate Moderate to high

Frequency requirements Low Low to moderate

Disease state Stable Likely to progress

Coverage needs(contacts/leads)

8 contacts on1 or 2 leads

8 or 16 contacts on1-4 leads

Compliance(motivation and ability)

Requires very littleinteraction

High—due torecharging protocol

Competence(physical or mental)

Appropriate for all levels Higher level required

Skin sensitivity Patients with highsensitivity

Patients with moderateto low sensitivity

Implant size Moderate to large sizes Small to moderate size

Implant longevity 2-7 years 5-10 years

Patient interface Easier to use Requires management

Lead Family

The 5-Column Paddle Lead Designed to provide greater lateral electrode coverage and

nerve fiber selectivity Provides five columns of the smallest electrodes on the market,

for greater specificity and programming flexibility

Lateral Electrode Coverage

40% of patients have a spinal cord 1-2 mm off midline (Holsheimer)

*Approx. 4.5 mm 2 mm2 mm

*At T9

8.5 mm of lateral electrode coverage needed

Improved Lateral Current Steering

Actual Clinical Results Certain programming configurations on the 5-column paddle lead may be able to isolate paresthesia within the dermatome itself. (Feler)

The diagrams above depict actual patient-reported stimulation effects with a 5-column paddle lead.

SCS Studies

Author No. Patients Follow-Up Results

Kumar 410 8 years 74% had ≥50% relief

North 19 3 years 47% had ≥50% relief

Barolat 41 1 year 50%-65% had good/excel. relief

Van Buyten 123 3 years 68% had good/excel. relief

Alò 80 30 months (2.5 years) Mean pain scores declined from 8.2 at baseline to 4.8

Cameron 747 up to 59 mos. 62% had ≥50% relief or significant reduction in pain scores

Reduction in pain

SCS Studies

Reduction in medication

Author No. Patients Follow-Up Results

North 19 3 years 50% reduced their med use

Van Buyten 123 3 years as a group reduced the medication use by >50%

Cameron 766 up to 84 mos. 45% reduced their med use

Taylor 681 n/a 53% no longer needed analgesics

SCS Studies

Improvement in daily activities

Author No. Patients Follow-Up Results

Barolat 41

1 year As a group, significant improvements infunction and mobility

North 19 3 years As a group, improvements in a range ofactivities

SCS Studies

Return to work

Author No. Patients Follow-Up Results

Van Buyten 123 3 years 31% returned to work

Taylor 1133 n/a 40% returned to work

Dario 23 3 years 35% returned to work

Spinal Cord Stimulation (SCS)

SCS can be used to manage neuropathic pain that arises from: CRPS (Complex Regional Pain Syndromes I and II)

Peripheral neuropathy (Diabetic, Post-Chemo, Idiopathic)

SCS can be used in the treatment of pain, numbness, and circulatory deficits with associated small-fiber peripheral neuropathy (SFPN)—with or without a diagnosis of diabetes mellitus (DM).

Twenty-five percent of Americans are either diabetic or pre-diabetic (20 million and 60 million, respectively). SFPN is a significant comorbid process, with onset of DM occurring at a mean of 5 years after diagnosis of SFPN, with a range of 3 months to 20 years. This suggests patients may have SFPN in the absence of diagnosed DM. SCS treatment have been shown to be successful in providing >70% pain relief in over 80% of patients with pain attributable to SFPN. 52% reported significant reduction in medication usage. 90% of patients had reversal of sensory loss. Whether this is permanent or is due to continuous SCS in unclear. Trophic change improvement with increased circulation associated with SCS has also been well documented. However, to our current knowledge, reversal of sensory loss in SFPN patients from SCS has not been well-studied.

Ischemic/Neuropathic Limb Pain Primary erythromelalgia or Mitchell’s disease is a rare neurovascular

condition causing severe neuropathic pain. Often times, treatment for this rare condition is difficult, and can involve neuropathic pain medications, sodium channel blockers, lumbar sympathetic blocks, and spinal interventions. Although peripheral neuropathy has been well studied and treated with spinal cord stimulation, using it for treatment of erythromelalgia is novel.

Now… For the FUN STUFF!!!

OFF-LABEL USE of theSpinal Cord Stimulator

Intractable, chronic, tension/cluster/ migraine/sinus headaches / Occipital Neuralgia/ Temporal Arteritis

Chronic headache disorders are among the most debilitating medical conditions worldwide with an estimated prevalence of 47% of all adults having suffered at least one episode of headache in the past 12 months. 10% of people are affected by migraine alone. Up to 4% of the entire world’s adult population suffer from headaches for 15 days each month! (Data from the WHO, updated October, 2012: http://www.who.int/mediacentre/factsheets/fs277/en/)

These headache states are often refractory to conventional drug therapy. An emerging treatment for these patients in whom medical management is insufficient is the implantation of subcutaneous electrodes.

Sacral nerve stimulation can be a successful treatment for chronic Pelvic, Perineal, Rectal, Post-Radiation Prostitis pain. In addition, it is a viable therapeutic option for patients with pelvic pain that have failed spinal cord stimulation trials with lead placement in the thoracic epidural space.

Angina Pectoris / Thoracic Chest Wall Pain

MORE off-label use of the SCS:

• Trigeminal Neuralgia/Facial Pain/TMJ Syndrome

• Post-Herpetic Neuralgia (PHN)• Neck/thoracic pain with/without

cervical/thoracic radiculopathy• Phantom limb pain• Hyperhidrosis• Neurogenic Bladder

Chronic Abdominal Pain / Irritable Bowel SyndromeIrritable bowel syndrome (IBS) is a disorder that leads to debilitating symptoms including abdominal pain and cramping and changes in bowel movements affecting approximately 1 in 6 people. As causes for this condition continue to evolve, studies have linked visceral hypersensitivity and spinal nociceptor hyper excitability between the gastrointestinal system and nervous system.

The technical goals of electrical stimulation for pain management have been to mask the perception of pain with stimulation-induced paresthesia by disrupting pain signaling to the brain as well as determining what drugs can be co-administered to enhance analgesia. A more recent focus has been the optimization of electrical parameters for treating neuropathic pain. Few studies have examined the modulatory effect of an electrical field applied near the spinal cord on gene expression. More recently, studies are showing that SCS has the ability to modulate both pro- and anti-inflammatory gene expression, particularly in interleukin-1ß (IL-1ß), interleukin-10 (IL-10), IL-6, and the glia activation marker GFAP, with increasing current. This fosters a better understanding of the mechanism behind SCS-induced analgesia.

Future of Neuromodulation:

Dorsal Root Ganglion Stimulation Vagus Nerve Stimulation (for Epilepsy… or… ??

Weightloss??) Burst waveform stimulation High frequency stimulation

BONUS STIM???!!!

References

Aló K, Yland M, Charnov, J, Redko V. Multiple program spinal cord stimulation in the treatment of chronic pain: follow-up of multiple program SCS. Neuromodulation. 1999;2(4):266 272.

Arnst, C. Conquering pain: new discoveries and treatments offer hope. Business Week. Available at:

http://www.businessweek.com/1999/99_09/b3618001.htm. Accessed January 11, 2009.

Barolat G, Oakley JC, Law JD, North RB, Ketick B, Sharan A. Epidural Spinal Cord Stimulation with a Multiple Electrode Paddle Lead is Effective in Treating Intractable Low Back Pain. Neuromodulation. 2001;4:59-66.

Belgrade, Miles J; Cole, B. Eliot; McCarberg, Bill H. McLean, Michael J. Diabetic Peripheral Neuropathic Pain: Case Studies. April 2006;81(4l,suppl):S26-S32.

Cameron T. Safety and Efficacy of Spinal Cord Stimulation for the Treatment of Chronic Pain: A 20-Year Literature Review. J Neurosurg Spine. 2004;100(3):254-267.

Dario A, Fortini G, Bertollo D, Bacuzzi A, Grizzetti C, Cuffari S. Treatment of Failed Back Surgery Syndrome. Neuromodulation. 2001;4:105-110.

Gildenberg PL. History of electrical neuromodulation for chronic pain. Pain Medicine. 2006;7(S1):S7-S13

Kumar K, Hunter G Demeria D. Spinal Cord Stimulation in Treatment of Chronic Benign Pain: Challenges in Treatment Planning and Present status, a 22-Year Experience. Neurosurgery. 2006;58:481-496.

References

Feler C, Garber J. Selective dermatome activation using a novel five-column spinal cord stimulation paddle lead: a case series. Poster presented at: Annual meeting of the North American Neuromodulation Society; December 3-5, 2009, Las Vegas, NV.

Hill, Catherine L., Gill, Tiffany K., Menz Hylton B., Taylor, Anne W. Journal of Foot and Ankle Research. 2008, 1:2doi:10.1186/1757-1146-1-2.

Holsheimer J, den Boer JA, Struijk JJ, Rozeboom AR. MR assessment of the normal position of the spinal cord in the spinal canal. AJNR Am J Neuroradiol. 1994;15(5):951-959

Mironer E, Bernstein C, Ghodsi A, et al. Evidence for long-term efficacy of SCS in patients with FBSS or CRPS I or II. Poster presented at: North American Neuromodulation Society; December 3-6, 2009; Las Vegas, Nevada.

Nicosia, Mareesa. Chronic pain sufferers hit hard by the spiraling economy. The Saratogian. May 3, 2009. Available at: http://www.saratogian.com/articles/2009/05/03/news/doc49fd09f938b25829273434.prt. Accessed on January 11, 2010.

North RB, Kidd DH, Farrokhi F,Piantadosi SA. Spinal Cord Stimulation versus Repeated Lumbosacral Spine Surgery for Chronic Pain: a Randomized Controlled Trial in Patients with Failed Back Surgery Syndrome. Pain. 2007;132:179-188.

Pain Management. Drug War Facts. Available at: http://www.drugwarfacts.org/cms/node/59. Accessed on: January 11, 2009.

Pain Surveys. American Pain Foundation. Available at: http://www.painfoundation.org/newsroom/reporter-resources/pain-surveys.html. Accessed on: January 11, 2009.

Peter D. Hart Research Associates. Americans talk about pain: a survey among adults nationwide. August 2003. Available at: http://www.researchamerica.org/uploads/poll2003pain.pdf. Accessed January 19, 2010.

References

Taylor RS, Van Buyten JP, Buchser E. Spinal Cord Stimulation for Chronic Back and Leg Pain and Failed Back Surgery Syndrome: A Systematic Review and Analysis of Prognostic Factors. Spine. 2005;30:152-160.

Van Buyten JP,Van Zundert J,Vueghs P, Vanduffel L. Efficacy of Spinal Cord Stimulation : 10 Years of Experience in a Pain Centre in Belgium. Eur J Pain. 2001;5:299-307.

Zeigler, Dan MD Treatment of Diabetic Neuropathy and Neuropathic Pain. Diabetes Care. Feb 2008;Volume 31, Supplement 2, pg S255.

THANK YOU FOR YOUR TIME

The EndQuestions?

54