1. MHNI Patient Selection Strategies Research Studies and Others Joel R Saper, MD, FACP,FAAN Founder/Director, Michigan Head Pain and Neurological Institute Ann Arbor, Mi Clinical Professor of Neurology, MSU NANS, 2012

2. MHNI “It not so much what’s done to the head but to whose head it’s done”! Saper, 1992

7. Procedure Success and Adequate Reimbursement Depend on Fulfillment of Key Clinical Outcomes: Sustained reduction of pain Improved Function Overall cost reduction(utilization) Achieving value in the delivery of the care

8. Among the requirements… Achieve sustained benefit IDing proper diagnosis and symptom complex in moderately refractory patients, at a time and evolution of the illness that assures reversibility! Surgical/Procedural competence Selecting patients without barriers or conflicts to acknowledging improvement

9. Some Barriers and Confounding Features Wrong Diagnosis Inadequate science/ the illness trumps the knowledge Long duration opioid dependency Mod./severe psychological disturbance Patient commitment to disability: “I want to feel better but not get better” Enrolling “Nothing has ever worked at all” patients Absence of objective/genetic markers Others

11. SYNDROME OF MEDICATION OVERUSE HEADACHE Characteristics of Rebound Headache Occurs in patients with pre-existing HA Regular intake, more than 2-3d/wk, for months A self-sustaining rhythm of predictable, reliable & escalating HA frequency & med. use Refractory to otherwise appropriate symptomatic & preventive treatments Med withdrawal results in escalation of HA Saper JR. 1983,1992,1999

13. Opioids and the Brain Review of literature Opioids can cause receptor hypersensivity, opioid induced hyperalgesia (Mao et al,2002) Glutamate induced apototic cell death(Mao.2002) Induce CGRP increase in dorsal horn( Meng and Porecca, 2004) Morphine activates glia and increases pro- inflammatory cytokines(Watkins, 2002) Pro-nociceptive cholecystokinin (CCK) is upregulated in the rostral ventromedial medulla (RVM) during persistent opioid exposure CCK activates descending RVM pain facilitation, enhancing pain transmission and hyperalgesia (Ossipov,2004)

14. Opioids and the Brain Review of Literature Long-lasting receptor change after initial exposure to morphine(Lim,et al,Mao, 2005) Numerous endocrine disturbances Age dependant tolerance: exceptional receptor sensitivity and tolerance in adolescents(Buntin- Mushok, 2005) Opioid induced MOH more likely to be unrelieved following D/C than with triptans and ergots(Lake 2005; others) Prevents response to parenteral NSAIDS (Jakubowski,et al 2005)

15. MHNI In HA patients, at least, opioids induce progression of pathology and refractoriness to appropriate treatment

16. MHNI Many use drugs to have a life; others to hide from life!

17. PSYCHOBIOLOGY OF PAIN Psychological variables modulate PAG and nociceptive neurons in dorsal horn (Fields, 1997) –Bidirectional control over pain transmission (somatosensory, cortical, limbic via PAG, engaged by psychological factors) –Physiological mechanisms convert psychological distress to painful symptomatology (Fields, 1997) –Limbic enhanced pain via neuroplasticity mechanisms(Rome,2002)

18. PSYCHOBIOLOGY OF PAIN Psychological variables modulate PAG and nociceptive neurons in dorsal horn (Fields, 1997) –Bidirectional control over pain transmission (somatosensory, cortical, limbic via PAG, engaged by psychological factors) –Physiological mechanisms convert psychological distress to painful symptomatology (Fields, 1997) –Limbic enhanced pain via neuroplastic mechanisms(Rome,2002) –Stress evokes proinflammatory cytokines (Watkins, 2005)

19. Pain Has Power Pain communicates Pain can control others Pain can instill guilt Pain prevents abandonment Pain protects Pain and disability pay $ And it cannot be proven or disproved

20. The Troubled Patient Must be Recognized and Confronted Early Overt drug misuse/ addictive disease Severe anxiety / depression/ somatization “Pain Theater” starring the Drama Queen/King and cast of supporting enablers and sympathizers Missed visits Lost/ “ran short” of scripts Noncompliance Anger Family dysfunction Usually Axis ll, Cluster B

21. How can some patients say they are better? Disability lost Performance expectations: job, family, marital No more opioids Relinquishing special status/protections/reduced expectations Some spouses/relatives are only attentive when partner is ill Chronic impairment and disability, role reversals and drug dependency may lock even motivated people into a sick role

22. MHNI Some patients become “illness locked”!

23. MHNI Some patients cannot/won’t get better! They are not good procedural candidates!

24. MHNI The Goal: Choose patients for studies and interventional treatment that can and will benefit and report benefit if therapy is effective!

25. Recommendations for Study/Intv Patients 1 Chronic pain/disability lasting no more than 2-4 years (avoid “locked in” patients) Use of opioids limited, compliant, and relatively short term (use state to state drug monitoring programs) No evidence of Axis II, cluster B psych illness (borderline, narcissistic, sociopathic) Absence of severe Axis I disorders: anxiety, depression, OCD, Bipolar D or somatizational conditions Absence of multiple chronic pain disorders MHNI

26. Recommendations for Study/Intv. Patients 2 Previous non-pain procedures (dental, GYN, etc.) without notable sequelae Motivated to regain functional status and recovery Willingness to give up opioids Hasn’t failed ALL therapies: some at least modest elements of improvement along the way. NO end stage “failed everything” patients Supportive, reasonably healthy, family relationships with collateral support Avoid patients critical of or sued doc(s) AVOID the HARDCORE, ENTRENCHED PAIN PATIENT MHNI

27. Patient Selection Profile Motivated, compliant pts, free of long term permanent disability, opioid dependency or severe polypharmacy/recreational drug use Absence of multiple chronic pain conditions and /or more than 5 or more years of persistent, unrelenting pain Absence of multiple adverse responses to previous interventional or surgical treatments Adequate support relationships Have pattern of at least some, even if modest, benefit from one or more past or current therapies, ideally other than opioids Pts motivated to be rehabilitated to functional improvement

28. Methods Entry criteria must include “failure certain” or clinically confounding exclusions,PMP screens Well chosen, strategically designed end points Well designed psych screening tools/battery;experienced/ ”street smart” pain psychologist Accurate drug use, treatment path, and functional history/ obtaining collateral info from other docs Experienced consultants to review study/treatment eligibility Develop genetic therapeutic response markers Screen out likely placebo responders(Rezai) MHNI

29. Going Forward and Secure and Responsible Coverage Improved product and lead design and implanting techniques Well targeted, carefully screened, and selected study population, with strategic psych and behavioral profile assessments Exclude opioid dependent and “barrier ridden” patients Robust, well considered end points Longer trial duration Creative and effective blinding techniques and design Convincing outcome data MHNI

30. A Patient Selection Quiz Dr Rezai, what do you think?

31. MHNI The patient was narcotized, pasteurized, analyzed, surgerized, anesthetized, hypnotized, herbalized, pulverized, paralyzed(Botox), magnetized, homogenized and vibratized---- and still has pain. Saper,2000

32. “Shove your behavior contract up your a--, Doctor!”

33. “I want my Demerol”

34. “You’re calling me a drug addict, aren’t you? I said want my Demerol!”

35. MHNI “My Oxy fell down the toilet”

36. “My dog ate my narcotics” (but not her ibuprofen )

37. Doc: “What about the ibuprofen?” Pt: “No!”

38. Dogs that love opioids… OxyCollie OxyRetriever PercoSpanial VicoCocker Morphi-Yorkie

39. Dogs That Treat Misuse DetoxerBoxer

40. MHNI A 39 y/o F. with intractable LBP, has Borderline PD, Bipolar disorder, takes 860mg/day of Oxycontin,,and has sued her last interventionalist for neglect and abandonment. Offers to endow a university chair in your name with a $10M grant.

41. MHNI “How did that cocaine get in my urine, Doc?”

42. MHNI Doc: “Nurse Ratshitt, did you put cocaine in Herbie’s urine?!!!!”

43. MHNI “My pain is no better, but I need more Oxycontin because it makes ME feel better.”

44. MHNI “Let’s face it, I like the buzz!” --a headache patient on Actiq

45. MHNI “Let’s face it, it takes 30 seconds to say yes, but 30 minutes to say no!” Dr Howard Heit, 2004

46. MHNI “Sometimes the best medicine is to stop taking something” Ashleigh Brilliant

47. MHNI “Treating pain is a thinking sport” Dr Jeff Okeson, 2003

48. MHNI “Treating some borderline patients is a blood sport! Saper, 2006

49. “What do you mean I have a borderline personality? I’ve never even been to Mexico!” --a perplexed borderline patient

50. MHNI “Justice will be served only when the last lawyer on earth has been strangled with the intestines of the last politician”! George Bernard Shaw