1. Patient selection for the treatment of chronic visceral pain syndromes using SCS: Angina, Abdominal and Pelvic Leonardo Kapural, MD, PhD Carolinas Pain Institute and Center for Clinical Research Professor of Anesthesiology, Wake Forest University School of Medicine

2. Disclosure Consultant to Boston Scientific Consultant to St Jude Medical

3. Patient Selection Failed appropriate conservative therapies Pain intractable to less complex, less invasive therapies, including conventional opioid therapy or intolerable side effects Definable cause for his or her pain Psychological stability of the patient Assessing patient's potential to respond to SCS No surgically correctable pathology underlying symptoms Risks of surgery to outweigh potential benefit

4. Best practice tips Psychological evaluation for implantable devices Interdisciplinary Committee for Implantable devices Family support Prolonged trial Functional Capacity Measurement

5. Abdominal pain: Patient selection and Implantation

6. Studies-case series: Mesenteric Ischemia (Ceballos et al, 2000) Irritable Bowel Syndrome (Krames, 2005) Epigastric abdominal pain (Khan, 2005) Gastroparesis (Tiede et al., 2006) Pelvic visceral pain (Kapural et al., 2006) Familial Mediterranean fever (Kapur et al, 2006) Non-alcoholic pancreatitis (Kapural, 2008)

7. Retrospective study –SCS for abdominal visceral pain (Kapural et al., Pain Medicine, 2010) 35 patients; Age 17-87 12 man; 23 women Chronic abdominal pain duration from 1-25 years Location: 1. epigastric 2. RUQ 3. LUQ Aching, burning, stabbing, sharp Chronic pancreatitis, Abdominal adhesions, Gastroparesis, Mesenteric Ischemia, Post-gastric bypass chronic pain

8. Retrospective study (Kapural et al., Pain Medicine, 2010) h/o depression 18 patients h/o alcohol abuse 7 Psych evaluation and IDC passed Differential block visceral (3 mixed visceral/central) Splanchnic or hypogastric block (50-100% pain relief)

9. Abdominal pain of unclear source Physical examination, history, location and referral pattern Differential retrograde epidural block (if confirmed visceral pain) GI functional and cause-specific studies Celiac or/and splanchnic nerve block Splanch nic RF SCS trial SCS Algorithm Kapural, 2010

10. Potential diagnostic value Ad and C fibers:ratio 1:10 in viscera as opposed to 1:2 in cutaneous afferents Visceral nociceptives extensive overlap among receptive fields Majority of patients of unexplained abdominal pain may have non- visceral chronic pain (4/22 had a positive visceral response to DDNB) despite a pre-DDNB diagnosis of chronic pancreatitis Attempt to diagnose visceral origin of pain- could dictate further treatment plans Janig W, Morrison JF: Functional properties of spinal visceral afferents supplying abdominal and pelvic organs, with special emphasis on visceral nociception. Prog.Brain Res. 1986; 67: 87-114 Cervero F: Visceral versus somatic pain: similarities and differences. Dig.Dis. 2009; 27 Suppl 1: 3-10 Cervero F: Sensory innervation of the viscera: peripheral basis of visceral pain. Physiol Rev. 1994; 74: 95-138 Conwell DL, Vargo JJ, Zuccaro G, Dews TE, Mekhail N, Scheman J, Walsh RM, Grundfest-Broniatowski SF, Dumot JA, Shay SS: Role of differential neuroaxial blockade in the evaluation and management of pain in chronic pancreatitis. Am.J.Gastroenterol. 2001; 96: 431-6

11. Retrograde phase of DENB LA through an epidural catheter to achieve surgical anesthesia in the dermatomal distribution that overlaps the patient’s site of pain visceral or non-visceral significance of abolishment of visceral pain that outlasts the duration of LA block is important in establishing the diagnosis of chronic abdominal pains of unclear origin

12. DENB for unclear source of abdominal pain Out of 402 differential NB, 367 complete data Age 47.3 (median 48) 201 women, 166 men 6.6 years of pain (SD 5) 36 % epigastric; 33 % diffuse VAS 6.7 (SD 1.7) 52.5 mg MSO4 (SD 75) 24 % diagnosis of depression 4.4% h/o drug abuse 8% alcohol abuse

13. DENB for unclear source of abdominal pain Number of other pain locations: 1 other site-81 patient 2 other sites- 44 patients 3 other sites 12 patients 4 other sites 2 patients 5 other sites 2 patients 32% on antidepressants 26% on membrane stabilizers

14. DENB for unclear source of abdominal pain Most frequent dermatomal level of pain T7 Most frequent catheter placement T9-10 71%-3-chloroprocaine; rest lidocaine 19 patients-no level, technical difficulties 21 patients-first placebo response 12 patients (out of 241)-second placebo response 94 patients-majority of the pain still present with bilateral T4 block 23 patients residual pain (<50%) after bilateral T4 block 126 considered visceral

15. DENB for unclear source of abdominal pain If visceral on DENB? If good predictive value for splanchnic/celiac blocks/and/or SCS

16. Initial Evaluation for SCS (237 patients) 96 Patients: Differential Retrograde Epidural block 101 Patients: Referred to Psych Rehab Program and/or Detox 19 Patients: referred to GI/ Colorectal Surgery/ GYN/ Neurology 11 Patients: other Pain Management Center Care 59 Patients: Predominantly Visceral 16 Patients: Somatosensory2 Patients: Placebo responders not to return 19 Patients: Central/ or Psychogenic or Malingering Interdisciplinary Committee for Implantable Devices 40 Patients: Yes 5 Patients: Psychological Care 41 Patients: Proceed to Trial 46 Patients: Psychological Evaluation for Implantable Devices 4 Patients: lost to follow-up5 Patients: Negative Response/ <50% or no pain improvement 48 Patients: Positive/ >50% response to Celiac/Splanchnic 57 Patients Celiac/ Splanchnic2 patients lost to follow-up 1 Patient: No 35 Patients: SCS Trial Approved by Insurance Providers 2 patients lost to follow-up 5 Patients: Denied by Insurance Providers 30 Patients: Successful Trial 5 Patients: Unsuccessful trial 28 Patients: Successfully Implanted2 Patients: Postponed

17. Lead placement Entry point T10-11 or higher Tip placed at T5 or lower We regularly achieve paresthesias over the painful areas Midline placement (Kapural et al., Pain Medicine, 2010)

18. Trial success (Kapural et al., Pain Medicine, 2010)

19. Pain relief (Kapural et al., Pain Medicine, in press) One lost to follow-up after the implant 3 patients not completed one year follow-up 3 infections 1 explant dissatisfied with treatment 1 lead migration

20. Opioid use (Morphine equivalents)

21. Survey (Kapural et al., Pain Medicine, 2010) Patients 16-85 years of age; 47.3 years (median 47) identifiable causes: chronic pancreatitis (23), post-surgical intraabdominal adhesions (20), gastroparesis (9) post-surgical-following: cholecystectomy, bowel resection, gastric bypass, endometriosis-related surgical procedures and Nissen’s 9 patients: no cause could be determined Celiac plexus blocks, opoids, anticonvulsants, antidepressants, multiple explorative surgeries 76 case reports-23 responding physicians: 6 incompletely filled-excluded; 70 reported Characteristics: burning and aching then throbbing, stabbing, cramping, dull and sharp Most frequent areas epigastric and periumbilical

22. Survey (Kapural et al., Pain Medicine, 2010) Conservative: most of the patients opioids membrane stabilizers, antidepressants Interventions: sympathetic blocks prevailed (only 53%) pancreatic resection, ileostomy closures, ERCP, gastric pacemakers (5 patients) and multiple laparoscopic adhesiolysis 62 out of 70 psychological evaluation Only 24 out of 70 (34%) evaluated by multidisciplinary committee for appropriateness of implantable devices

23. Pelvic pain: Patient selection

24. Patient selection Early h/o physical and/or sexual abuse and victimization relevant in painful disorders (Schofferman et al., 1992; McMahon et al. 1997) Depression and anxiety or common psychological co-morbidities are associated with pain and disability (Covington et al., 2005). Schofferman, J., Anderson, D., Hines, R. et al. (1992) Childhood psychological trauma correlates with unsuccessful lumbar spine surgery. Spine 17 (6, Suppl.): S1380-S1384. McMahon, M.J., Gatchel, R.J., Polatin, P.B. and Mayer, T.J. (1997) Early childhood abuse in chronic spinal disorder patients: A major barrier to treatment success. Spine 22: 2408-24. Covington, E.C., Gallagher, R.M. and Doleys, D.M. (2005) The association between chronic pain and mood and anxiety disorders. Pain Medicine News, Oct: 1-7.

25. Patient selection Pre-SCS evaluation – Beck Depression Inventory – Pain Questionnaire such as MPQ – QOL Instrument SF 36 – Pain Map and Diary – “It is important to remember that many of these scales are self-administered and represent the patient’s perception, which may or may not reflect reality.” (Doleys et al, 2007) – Doleys, D.M. and Kraus, T.J. (2007) Trialing for intrathecal therapy: comments and considerations. Practical Pain Manag. 7 (5): 48-9.

26. Patient and physician expectations Physician expectations- impact outcomes (Graz et al., 2005) Positive outcomes from “sham” surgeries (Flum, 2006) Possible solution: different practitioners in patient selection, pre-implant trial, and post-implant management dependent, obsessive, and suggestible the patient, the greater effect expectations are likely to have. Internet, patient testimonials, public media Graz, B., Wietisbach, V., Porchet, F. and Vader, J.P. (2005) Prognosis or “curabo effect?” Physician prediction and patients outcome of surgery fir low back pain and sciatica. Spine 30: 1448-52. Flum, D.R. (2006) Interpreting surgical trials with subjective outcomes: avoiding UnSPORTsmanlike conduct. JAMA 296: 2483-5.

27. SCS for visceral pelvic pain Kapural et al, Pain Medicine 2006 severe visceral pelvic pains Treated for an average of 14.8 years (from 4 to 38) series of hypogastric blocks (in average 5.3) All received SCS systems with two leads implanted Pain Disability Index (PDI) questionnaires before the implant and recently following implant Opioid use calculated as MSO4 milligram equivalents.

28. Retrograde or anterograde implantation Anterograde: Posterior pelvic wall, post-hysterectomy, visceral pelvic adhesions; endometriosis remission with persistent visceral pain Retrograde: interstitial cystitis, pelvic floor issues

29. Patient selection: SCS for Intractable Angina

30. Indications: severe angina despite optimum medical and surgical treatment angina pectoris in syndrome X (angina pectoris, normal coronary arteriograms, objective signs of myocardial ischemia) patients with angina and no prognostic benefit from coronary bypass current reversible myocardial ischemia in good psychological condition cognitive dysfunction or somatization disorder should be excluded Eliasson T, Augustinsson LE, Mannheimer C: Spinal cord stimulation in severe angina pectoris: presentation of current studies, indications and clinical experience. Pain 1996,65:169–179. Jessurun GA, TenVaarwerk IA, DeJongste MJ, et al.: Sequelae of spinal cord stimulation for refractory angina pectoris. Reliability and safety profi le of long-term clinical application. Coron Artery Dis 1997, 8:33–38. Mannheimer C, Eliasson T, Andersson B, et al.: Effects of spinal cord stimulation in angina pectoris induced bypacing and possible mechanisms of action. BMJ 1993, 307:477–480.

31. General characteristics: small group of patients with angina refractory to all treatments- including revascularization Usually are classified under the NYHA (New York Heart Association) functional class 3-4 and have angina at rest or with minimal exertion (Murphy& Giles, 1987; Augustinsson et al, 1989; Sanderson et al,1994; Andersen et al1994; DeJongste et al 1994; Mannheimer el al,1998; Hautvast et al 1998; Bagger, et al, 1998)

32. Krames, 2005

33. Angina Trial Implanted electrode or electrodes between C7-T2 ascertaining concordant paresthesia Implant if: intensity of episodes are decreased by 50% exercise tolerance increases by 50% time interval between anginal episodes increases significantly SCS system use: continuously or to turn stimulation on when anginal episode begins

34. What is different when stimulating for angina Collaboration with cardiac team if implantation is proper Cardiologist-blood pressure control, ejection fraction, and ability to tolerate SCS Clearance for procedure and anesthetic Ongoing anticoagulation- aspirin, warfarin, antiplatelet drugs- clearance Clopidogrel-discontinued10 days before implant and remain discontinued until trial end Inpatient using heparin infusion, discontinuing 6 hours before, restarting 6 hours after Deer T. Current Pain and Headache Reports 2009, 13:18–23

35. In conclusion: Proper patient selection-better outcome Appropriate trial required Psychological evaluation for implantable devices Interdisciplinary committee for implantable devices Collaboration and consultation with referring physician Continued exchange of information on implantation techniques

36. Thank you lkapural@wfubmc.edu