1. Developments in the Treatment of Chronic Pain

2. Agenda Welcome Types of pain Common chronic pain conditions
Introduction to Medtronic neurostimulation
Introduction to Medtronic intrathecal drug delivery
Patient selection
Neurostimulation clinical evidence
Intrathecal drug delivery clinical evidence
Role of interventional pain specialist
Case study

3. Welcome
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<Insert patient speaker(s) name(s), type of therapy>

4. Types of Pain

5. Types of Neuropathic Pain
Results from damage to nerves
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
Cole AJ. In Low Back Pain Handbook, 2nd ed. 2003; pg

6. Types of Nociceptive Pain
Results from damage to muscle, tissue, and organs
Cuts and bruises
Bone fractures
Burns
Mechanical low back pain
Most postsurgical pain

7. Combined Nociceptive and Neuropathic Pain
Failed back surgery syndrome (FBSS)*
Idiopathic chronic pain syndrome
Cancer pain
*Also referred to as “postsurgical chronic back pain”
Cole AJ. In Low Back Pain Handbook, 2nd ed. 2003; pg

8. Some Chronic Pain Conditions
Postsurgical chronic back pain or failed back
Radicular pain syndrome or radiculopathies
Fibromyalgia
Peripheral causalgia
Arachnoiditis
Complex regional pain syndrome

9. Rethinking the Pain Treatment Ladder
In contrast to earlier thinking on the order of treatments in the pain treatment continuum,1 it has been proposed that device therapies be considered at an earlier stage.2
1Krames ES. Intraspinal Opioid Therapy for Nonmalignant Pain: Current Practices and Clinical Guidelines. J Pain Symptom Manage 1996;11:
2Stamatos JM, et al. Live Your Life Pain Free, October Based on the interventional pain management experience of Dr. John Stamatos.

10. Introduction to Medtronic Neurostimulation

11. Neurostimulation Therapy
Delivers electrical signals to the epidural space
Inhibits pain signals before they reach the brain and replaces them with a tingling sensation that covers the specific areas where pain is felt
Indicated for management of chronic, intractable pain of the trunk and/or limbs, including unilateral or bilateral pain

12. Benefits of Neurostimulation
An effective method of pain control for many patients when used as directed
May reduce the need for pain medications
Less invasive than surgical alternatives
Reversible—can be discontinued or, if desired by the patient, surgically removed
Systems reprogrammable without surgery
Trial helps assess patient response
Patient control within preprogrammed limits
Kumar K, Taylor R, Jacques L, et al. Neurosurgery. 2008;63: 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:

13. Neurostimulation Trial
Neurostimulation therapy trial provides an opportunity to assess the effectiveness of neurostimulation without making a long-term commitment
Gauge patient response
Provide an adjustment period
Explore therapy parameters
Improve therapy cost-effectiveness
The goal is at least a 50% reduction in pain
Patient-specific goals may include less pain reduction but improved quality of life
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(3):

14. Neurostimulation Risks
The most frequently reported problems following the spinal cord stimulator implant surgery include:
infection,
lead movement,
pain at the implant site,
loss of therapy effect, and
therapy which did not meet the patient's expectations.
Some of the most severe reported problems following spinal cord simulator implant surgery include epidural hemorrhage, spinal fluid leakage, and paralysis.
For more details on risks/complications, refer to product package insert or visit

15. Neurostimulation Risks (cont.)
Information sources:
Medtronic Neurostimulation Therapy for Chronic Pain: Percutaneous Lead Implantation Guide. Minneapolis, MN: Medtronic, Inc.; 2008.
Medtronic Implantable Systems Performance Registry (ISPR) 2007 Annual Report: Protocol NSP Minneapolis, MN: Medtronic, Inc.; October 2, 2008.
Medtronic Neurostimulation Systems for Pain Therapy Brief Summary; Minneapolis, MN: Medtronic, Inc.; December 2004.

16. Introduction to Medtronic Intrathecal Drug Delivery (IDD)

17. Intrathecal Drug Delivery (IDD) Therapy
IDD therapy involves the delivery of pain medicine into the intrathecal space
The pump is connected to a thin, flexible catheter; both are implanted under the skin
Smaller doses of medication are needed for effective pain relief because drug is delivered directly to the pain receptors

18. Synchromed® II Drug Infusion System Indications
Chronic intrathecal infusion of preservative-free morphine sulfate sterile solution in the treatment of chronic intractable pain
Also indicated for chronic intrathecal infusion of preservative-free ziconotide sterile solution for the management of severe chronic pain

19. Approximate Equivalent Daily Doses of Morphine
Route of Administration
Relative Potency (mg)*
Oral
Intravenous
Epidural
Intrathecal
300
100 20 1
*Relative approximations based on clinical observations.
Lamer TJ. Treatment of cancer-related pain: when orally administered medications fail. Mayo Clin Proc. 1994;69:

20. Benefits of IDD Therapy
Pain relief for patients who have not received adequate relief with conventional therapies
May reduce adverse effects from oral opioids such as nausea, vomiting, sedation, and constipation
May decrease or eliminate use of oral analgesics
Increased ability to perform activities of daily living
Patient control of medication within physician-set limits
May be effective for patients who do not experience relief from neurostimulation therapy
Lamer TJ: Mayo Clin Proc. May 1994;69(5):
Paice JA. Intraspinal morphine for chronic pain: a retrospective, multicenter study. J Pain Symptom Manage. 1996;11:71-80.

21. IDD Trial
The purpose of the trial is to assess the efficacy and side effects of intrathecal morphine
Trialing methods include:
Continuous epidural
Continuous intrathecal
Bolus epidural
Bolus intrathecal
Patients who report at least 50% reduction in pain may be candidates for long-term therapy

22. IDD Therapy Risks
The most frequently reported problems following drug infusion system implant surgery include:
infection
spinal fluid leak
pump inversion
dislodged or blocked catheter
skin erosion
drug side effects
loss of therapy effect
therapy which did not meet the patient’s expectations
Other complications may occur, and may require surgery to correct.
Some of the most severe reported problems associated with intrathecal drug delivery therapy for chronic pain include inflammatory mass, spinal cord damage, meningitis, life threatening drug adverse effects due to over infusion as a result of programming or patient monitoring errors or device malfunction, and complications due to use of unapproved drugs and/or not using drugs in accordance with drug labeling.
For more details on risks/complications, refer to product package insert or visit

23. IDD Therapy Risks (cont.)
Information sources:
Medtronic Synchromed II Programmable Infusion System Clinical Reference Guide: Intrathecal Morphine for Pain Management. Minneapolis, MN: Medtronic, Inc.; May 2007.
Medtronic Implantable Systems Performance Registry (ISPR) 2007 Annual Report: Protocol NSP Minneapolis, MN: Medtronic, Inc.; October 2, 2008.
Synchromed II Drug Infusion System Brief Summary; Minneapolis, MN: Medtronic, Inc.; January 2008.
Coffey R. Mortality Associated with Intrathecal Opioid Drug Infusion to Treat Non-Cancer Pain: Risk Factors and Mitigation. Paper presented at the North American Neuromodulation Society 12th Annual Meeting; December 4-7, 2008; Las Vegas, NV.

24. Patient Selection

25. 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 Drug Infusion Systems.

26. Patient Selection Considerations
Patients who have neuropathic pain in a concordant anatomic distribution usually respond best to neurostimulation (NS) therapy.
Patients who have nociceptive pain in a concordant distribution usually respond best to intrathecal drug delivery (IDD).
Patients who do not respond well to NS may be candidates for IDD therapy.
Cole AJ. In Low Back Pain Handbook, 2nd ed. 2003; pg 362.

27. Patient Selection Checklist
Failure of oral/transdermal opiate use or intolerable side effects
More conservative therapies have failed
An observable pathology exists that is concordant with the pain complaint
Further surgical intervention is not indicated
No serious untreated drug habituation exists
Psychological evaluation and clearance for implantation has been obtained
No contraindications to implantation exist
Refer Patient for a Pain Therapy Trial
Cole AJ. In Low Back Pain Handbook, 2nd ed. 2003; pg 362.

28. Neurostimulation Clinical Evidence

29. Medtronic PROCESS Study Results
Primary outcome
Number of SCS + CMM patients with ≥ 50% leg pain relief (≥ 50% reduction in leg VAS) is:
at 6 months, 23 of 42 or 55%
at 12 months, 16 of 42 or 38%
at 24 months, 17 of 42 or 40%
Kumar K, Taylor R, Jacques L, et al. Neurosurgery. 2008;63:

30. Medtronic PROCESS Study Results
Secondary outcomes evaluated at 1, 3, 6, 9, 12, 18 and 24 months (24 month data presented)
Leg pain relief (leg VAS)
Leg: Significant improvement (p<0.0001)
Back pain relief (axial back VAS)
No significant difference
Quality of life (SF-36 and EQ-5D)
SF-36: significant improvement for 7 of 8 dimensions EQ-5D: significant improvement
Function (Oswestry Disability Index)
Significant improvement (p=0.0002)
Patient satisfaction
93% satisfied with treatment
Need for drug or nondrug therapy for pain
No clear pattern of change
Work status
Increased from 21% to 27%
Adverse events
See Adverse Events slide
Kumar K, Taylor R, Jacques L, et al. Neurosurgery. 2008;63:

31. Significant Improvement in Function
Key Findings: Significant improvement in function (Oswestry Disability Index) in SCS+CMM group over 24 months.
Kumar K, Taylor R, Jacques L, et al. Neurosurgery. 2008;63:

32. More Effective than Repeat Surgery
Key Findings:
Among patients available for long-term follow up, SCS was significantly more successful than reoperation: 9 (47%) of 19 patients randomized to SCS and 3 (12%) of 26 patients randomized to reoperation achieved at least 50% pain relief and were satisfied with treatment.
North RB, Kidd D, Shipley J, et al. Spinal cord stimulation versus reoperation for failed back surgery syndrome: a cost effectiveness and cost utility analysis based on a randomized, controlled trial. Neurosurg. 2007;61:

33. Efficacy of Spinal Cord Stimulation Neurostimulation Improves Quality of Life
Subjects were implanted with SCS over a period of 10 years at one pain center
Efficacy assessed after an average follow-up of almost four years
Van Buyten JP, Van Zundert J, Vueghes P, Vanduffel L. Efficacy of spinal cord stimulation: 10 years of experience in a pain centre in Belgium. Eur J Pain 2001;5: n=125 pain cases; P<0.01 for all activities

34. Intrathecal Drug Delivery Clinical Evidence

35. Decreased Use of Pain Medications
88.2% of patients were taking systemic opioids at baseline.
Key Findings:
At 6 months, 65% of patients decreased their use of systemic opioids from baseline.
At 12 months, 42% of patients decreased their usage compared with the 6-month follow-up.
Deer T, Chapple I, Classen A, et al. Intrathecal drug delivery for treatment of chronic low back pain: report from the National Outcomes Registry for Low Back Pain. Pain Med. 2004;5: n=136

36. Overall Global Pain Relief
Key Findings:
Overall pain relief of ≥ 50% was reported by 82% of patients (40 of 49).
Roberts LJ, Finch PM, Goucke CR, et al. Outcome of intrathecal opioids in chronic non-cancer pain. Eur J Pain. 2001;5: n=88

37. Role of Interventional Pain Specialist

38. Practice Management Collaboration

39. Interventional Pain Specialist Pain Management Approach
Recognizes unique benefits of technological advances and interventions
Communicates with all concerned parties to ensure best treatment possible
Develops follow-up plan once pain successfully treated
Collaborates with referring physician when treatment overlaps with general health care
Follows up with referring physician when pain is under better control

40. Interventional Pain Specialist Referral Considerations
Intractable pain
Intolerable side effects from systemic analgesics
Conservative therapies ineffective
Patient’s functional status declines
Uncomfortable prescribing or monitoring opioids

41. Case Study – Sample Referral Profile
Male, 45, office manager, no major psychosocial issues
One spine surgery to treat herniated disc
Referred from primary care physician to address axial back pain and secondary radicular pain that persists 6 months following anatomically corrective surgery
Average back pain score (VAS) of 80/100 with diminished functional capacity
Relief from physical rehabilitation therapy was not satisfactory
Unsuccessfully treated with neuropathic pain agents and two systemic opioids, patient experienced extreme sedation and constipation
Treated with nerve block series but relief was temporary

42. Device Therapy Referral Interventional Pain Specialist Role
Conduct a thorough patient history and physical exam
Develop an interventional pain treatment plan
Conduct a Medtronic pain therapy trial
Perform the Medtronic pain therapy implantation or refer after the trial
Develop a follow-up plan with the patient and primary/referring physician

43. Summary Patients should not have to wait for effective pain relief.
By partnering, we can help patients find the right pain treatment.
Together we can improve the quality of life for chronic pain patients.
Our decisions may change the course of a patient’s life.

44. SynchroMed® Infusion System Brief Summary
Product technical manuals and the appropriate drug labeling must be reviewed prior to use for detailed disclosure.
Indications: US: Chronic intraspinal (epidural and intrathecal) infusion of preservative-free morphine sulfate sterile solution in the treatment of chronic intractable pain, chronic intrathecal infusion of preservative-free ziconotide sterile solution for the management of severe chronic pain, and chronic intrathecal infusion of Lioresal® Intrathecal (baclofen injection) for the management of severe spasticity; chronic intravascular infusion of floxuridine (FUDR) or methotrexate for the treatment of primary or metastatic cancer. Outside of US: Chronic infusion of drugs or fluids tested as compatible and listed in the product labeling.
Contraindications: When infection is present; when the pump cannot be implanted 2.5 cm or less from the surface of the skin; when body size is not sufficient to accept pump bulk and weight; when contraindications exist relating to the drug; drugs with preservatives. Do not use the Personal Therapy Manager accessory to administer opioid to opioid-naïve patients or to administer ziconotide.
Warnings: Comply with all product instructions for initial preparation and filling, implantation, programming, refilling, and injecting into the catheter access port (CAP) of the pump. Failure to comply with all instructions can lead to technical errors or improper use of implanted infusion pumps and result in additional surgical procedures, a return of underlying symptoms, or a clinically significant or fatal drug under- or overdose. Refer to the appropriate drug labeling for specific under- or overdose symptoms and methods of management. Avoid using short wave (RF) diathermy within 30 cm of the pump or catheter. Diathermy may produce significant temperature rises in the area of the pump and continue to heat the tissue in a localized area. If overheated, the pump may over infuse the drug, potentially causing a drug overdose. Effects of other types of diathermy (microwave, ultrasonic, etc.) on the pump are unknown. An inflammatory mass that can result in serious neurological impairment, including paralysis, may occur at the tip of the implanted catheter. Clinicians should monitor patients on intraspinal therapy carefully for any new neurological signs or symptoms. For intraspinal therapy, use only preservative-free sterile solution indicated for intraspinal use. Use only Medtronic components indicated for use with this system. Failure to firmly secure connections can allow drug or cerebrospinal fluid (CSF) leakage into tissue and result in tissue damage or inadequate therapy. A postoperative priming bolus should not be programmed if the pump is a replacement and the catheter has not been aspirated.

45. SynchroMed® Infusion System Brief Summary continued
Refer to appropriate drug labeling for indications, contraindications, warnings, precautions, dosage and administration information, and screening procedures. Physicians must be familiar with the drug stability information in the technical manual and must understand the dose relationship to drug concentration and pump flow rate before prescribing pump infusion. Implantation and ongoing system management must be performed by individuals trained in the operation and handling of the infusion system.
Inform patients of the signs and symptoms of drug under- or overdose, appropriate drug warnings and precautions regarding drug interactions, potential side effects, and signs and symptoms that require medical attention. Instruct patients to notify their clinician of travel plans, to return for refills at prescribed times, avoid activities such as strenuous exercise or contact sports that jar, impact, twist, or stretch the body, to always carry their Medtronic device identification card, to avoid manipulating the pump through the skin, and to notify healthcare professionals of the implanted pump before medical tests/procedures. Patients must consult their physician before engaging in activities involving pressure or temperature changes (e.g., scuba diving, saunas, hot tubs, hyperbaric chambers, flights, skydiving, etc.) Inform patients that pump has an Elective Replacement Indicator (ERI) that sounds when the pump is nearing its end of service. When the alarm sounds, patients must contact their doctor to schedule pump replacement.
Precautions: The pump is ethylene oxide sterilized. Do not use if the product or package is damaged, the sterile seal is broken, or the “Use By” date has expired. Do not reuse or resterilize the pump; it is intended for “single use only.” Do not expose the pump to temperatures above 43°C or below 5°C. Consider use of peri- and post-operative antibiotics for pump implantation, for any subsequent surgical procedure, or if infection is present. For patients prone to CSF leaks, clinicians should consider special procedures, such as a blood patch. Follow instructions for emptying and filling the pump during a replacement or revisions that require removal of the pump from the pocket. Explant the pump postmortem if incineration is planned (to avoid explosion), or if local environmental regulations mandate removal. Return explanted devices to Medtronic for analysis and safe disposal. Do not implant a pump dropped onto a hard surface or showing signs of damage. Implant the pump less than 2.5 cm from the surface of the skin. Ensure pump ports will be easy to access after implant, that the catheter is not kinked and secured well away from pump ports before suturing. Keep the implant site clean, dry, and protected from pressure or irritation. If therapy is discontinued for an extended period of time, fill the reservoir with preservative-free saline in intraspinal applications or appropriate heparinized solution (if not contraindicated) in vascular applications.

46. SynchroMed® Infusion System Brief Summary continued
The magnetic field or telemetry signals produced by the programmer may cause sensing problems and inappropriate device responses with an implantable pacemaker and/or defibrillator. Electromagnetic interference (EMI) is an energy field generated by equipment found in the home, work, medical, or public environments. Most EMI normally encountered will not affect the operation of the pump. Exceptions include: injury resulting from heating of the pump which can damage surrounding tissue (diathermy, MRI), system damage which can require surgical replacement or result in loss/change in symptom control (defibrillation, electrocautery, high-output ultrasonics, radiation therapy), and operational changes to the pump causing the motor to stop, loss of therapy, return of underlying symptoms, and require confirmation of pump function (diathermy, high magnetic field devices, hyperbaric/hypobaric conditions, magnetic resonance imaging (MRI)). MRI will temporarily stop the pump motor’s rotor due to the magnetic field of the MRI scanner and suspend drug infusion during MRI exposure which will cause the pump alarm to sound. The pump should resume normal operation upon termination of MRI exposure. Prior to MRI, the physician should determine if the patient can safely be deprived of drug delivery. If not, alternative delivery methods for the drug can be utilized during the MRI scan. Prior to scheduling an MRI scan and upon its completion, pump status should be confirmed.
Adverse Events: Include, but are not limited to, cessation of therapy due to end of device service life or component failure, change in flow performance due to component failure, inability to program the device due to programmer failure, CAP component failure; inaccessible refill port due to inverted pump, pocket seroma, hematoma, erosion, infection, post-lumbar puncture (spinal headache), CSF leak, radiculitis, arachnoiditis, bleeding, spinal cord damage, meningitis (intrathecal applications), anesthesia complications, damage to the pump, catheter and catheter access system due to improper handling and filling before, during, or after implantation; change in catheter performance due to catheter kinking, disconnection, leakage, breakage, occlusion, dislodgement, migration, or catheter fibrosis; body rejection phenomena, surgical replacement of pump or catheter due to complications; local and systemic drug toxicity and related side effects, complications due to use of unapproved drugs and/or not using drugs in accordance with drug labeling, or inflammatory mass at the tip of the catheter.
USA Rx Only Rev 0209

47. Neurostimulation Systems for Pain Therapy Disclosure
Brief Summary: Product manuals must be reviewed prior to use for detailed disclosure.
Indications
Implantable neurostimulation systems - A Medtronic implantable neurostimulation system is indicated for spinal cord stimulation (SCS) system as an aid in the management of chronic, intractable pain of the trunk and/or limbs-including unilateral or bilateral pain associated with the following conditions:
Failed Back Syndrome (FBS) or low back syndrome or failed back
Radicular pain syndrome or radiculopathies resulting in pain secondary to FBS or herniated disk
Postlaminectomy pain
Multiple back operations
Unsuccessful disk surgery
Degenerative Disk Disease (DDD)/herniated disk pain refractory to conservative and surgical interventions
Peripheral causalgia
Epidural fibrosis
Arachnoiditis or lumbar adhesive arachnoiditis
Complex Regional Pain Syndrome (CRPS), Reflex Sympathetic Dystrophy (RSD), or causalgia
Contraindications
Diathermy - Do not use shortwave diathermy, microwave or therapeutic ultrasound diathermy (all now referred to as diathermy) on patients implanted with a neurostimulation system. Energy from diathermy can be transferred through the implanted system and cause tissue damage at the locations of the implanted electrodes, resulting in severe injury or death.
Warnings
Sources of strong electromagnetic interference (eg, defibrillation, diathermy, electrocautery, MRI, RF ablation, and therapeutic ultrasound) can interact with the neurostimulation system, resulting in serious patient injury or death. These and other sources of EMI can also result in system damage, operational changes to the neurostimulator or unexpected changes

48. Neurostimulation Systems for Pain Therapy Disclosure continued
in stimulation. Rupture or piercing of the neurostimulator can result in severe burns. An implanted cardiac device (eg, pacemaker, defibrillator) may damage a neurostimulator, and the electrical pulses from the neurostimulator may result in an inappropriate response of the cardiac device.
Precautions
The safety and effectiveness of this therapy has not been established for pediatric use (patients under the age of 18), pregnancy, unborn fetus, or delivery. Patients should be detoxified from narcotics prior to lead placement. Clinicians and patients should follow programming guidelines and precautions provided in product manuals. Patients should avoid activities that may put undue stress on the implanted neurostimulation system components. Patients should not scuba dive below 10 meters of water or enter hyperbaric chambers above 2.0 atmosphere absolute (ATA). Electromagnetic interference, postural changes, and other activities may cause shocking or jolting.
Adverse Events
Adverse events may include: undesirable change in stimulation described by some patients as uncomfortable, jolting or shocking; hematoma, epidural hemorrhage, paralysis, seroma, CSF leakage, infection, erosion, allergic response, hardware malfunction or migration, pain at implant site, loss of pain relief, chest wall stimulation, and surgical risks.
For further information, please call Medtronic at and/or consult Medtronic’s website at
USA Rx Only Rev 0209

49. Thank You