1. PERIPHERAL NERVE FIELD STIMULATION: MIRAGE OR REALITY? Dr Paul Verrills Interventional Pain Physician MBBS FAFMM MPainMed FIPP Metro Spinal Clinic, Australia

2. Disclosures  Royalties: NIL  Shareholder for Clinical Intelligence Pty Ltd  Teaching – Consultant (adhoc peer-peer)  Nevro Corporation  St. Jude Medical  Medtronic  Arthrocare  Mundipharma  Spinal Modulation  Boston Scientific

3. Peripheral Nerve field Stimulation  subcutaneous implantation of percutaneous leads in the painful areas  electrical field around the activated bipoles  field of paresthesia within the peripheral distribution of pain

4. Peripheral Nerve field Stimulation Theory behind Neuromodulation:  stimulation of large myelinated fibres closes the gate (via spinal cord)  putative inhibitory neurotransmitters thought to be released during large myelinated nerve fibre stimulation include:  gamma-aminobutyric acid (GABA)  adenosine

5. Peripheral Nerve field Stimulation  Scientific challenges:  exact mechanism of producing pain relief is poorly understood  lack of prospective randomized clinical studies  no unifying protocol for implantation  confusion in regards to Indications for the PNfS  lack of scientific data on:  adequate lead depth of implant  adequate parameters for implant  stimulation modalities

6. Metro Spinal Clinic PNfS lead depth study (2011)  observational study (n = 28)  low-back, n = 19 (17 subcutaneous and 2 iliac crest nerve stimulation)  occipital nerve stimulation, n = 9  influence of (1) electrode depth and (2) electrode configuration on sensation perception

7. Metro Spinal Clinic PNfS lead depth study (2011) 1.Abejón D., Deer T., Verrills P. 2011. Subcutaneous Stimulation: How to Assess Optimal Implantation Depth. Neuromodulation 2011; e-pub ahead of print. DOI: 10.1111/j.1525-1403.2011.00357 2.McRoberts WP., Cairns K. 2010. A Retrospective Study Evaluating the Effects of Electrode Depth and Spacing for Peripheral Nerve Field Stimulation in Patients with Back Pain. North American Neuromodulation Society Meeting, Las Vegas. Poster Presentation. References

8. Metro Spinal Clinic PNfS lead depth study (2011)  Electrode depths were measured using the 'pin-drop- technique’.

9. Programming combinations used in the study

10. Distribution of lead depth in PNfS: ONS vs PNLI

11. Lead depth Correlates with Perception Threshold Pearson Correlation = 0.348, p≤0.001 n= 459 data points from 27 patients (head and low back subcutaneous) with 18 different stimulation configurations (27 points missing) = data obtained from McRoberts et al. Similar trends were observed between the two studies.

12. Lead depth studies Across three separate studies using three different depth measurement methods, low back subcutaneous paresthesia was observed at an average lead depth of 9.2 - 10.5mm.

13. Paresthesia Descriptions Paresthesia descriptions were classified into 5 groups based on cutaneous fibre type

14. Distribution of categorised sensations at maximum discomfort

15. Distribution of categorised sensations at 70% usage range

16. Distributions of sensations at maximum discomfort amplitude The LBP and ONS groups have similar distributions. Major sensations experienced are tingling, vibration, pinch, and stabbing.

17. Low back PNfS has higher perception thresholds than ONS Head (ONS) n = 8 Low Back n = 13

18. Study summary 1.Implant depth of 10~12 mm from the surface can maximise the target sensation (Aβ_FA) of PNfS effective pain relief. 2.Cathodal threshold is lower than anodal one (as in Spinal cord Stimulation (SCS)).  However, it is likely that anodes reach threshold within the normal usage range of current in PNfS. 3.In PNFS both cathodes and anodes may be used to target the stimulation location. =

19. PNfS 200 cases study  IRB approved  Prospective observational study over 2 years +  203 patients with intractable pain  Key pain regions:  Occipital / craniofacial  Thoracic  Abdominal / groin  Low back

20. PNfS 200 cases  Outcomes:  Average pain (11 - point NPRS / VAS scale)  Percentage pain relief (%)  Oswestry Disability Index (ODI)  Analgesic medication use  Changes to paid employment (if applicable)  Patient satisfaction with the treatment  Adverse events monitored

21. Results: occipital - craniofacial n = 63 an average pain reduction of 4.9 ± 0.32, on an 11-point scale was reported (***p≤0.0001, Wilcoxon Mann-Whitney U-test) ***

22. Results: thoracic n = 17 an average pain reduction of 5.3 ± 0.56, on an 11-point scale was reported (***p≤0.0001, Wilcoxon Mann-Whitney U-test) ***

23. Results: abdominal / groin n = 15 an average pain reduction of 5.8 ± 0.52, on an 11-point scale was reported (***p≤0.0001, Wilcoxon Mann-Whitney U-test) ***

24. Results: low back n = 108 an average pain reduction of 4.1 ± 0.26, on an 11-point scale was reported (***p≤0.0001, Wilcoxon Mann-Whitney U-test) ***

25. Results: occipital / craniofacial 66% of patients reported good (>50%) to excellent (>75%) pain relief

26. Results: thoracic 82% of patients reported good (>50%) to excellent (>75%) pain relief

27. Results: abdominal / groin 87% of patients reported good (>50%) to excellent (>75%) pain relief

28. Results: low back 68% of patients reported good (>50%) to excellent (>75%) pain relief

29. Results: combined areas combined regions PNfS, n = 203 an average pain reduction of 4.3 ± 2.5, on an 11-point scale was reported (**p≤0.00, Wilcoxon Mann-Whitney U-test) **

30. Results: combined areas 73% of patients reported good (>50%) to excellent (>75%) pain relief

31. Does the pain relief last post-implant?

32. Sustained pain relief: combined areas Pain relief achieved shortly after implantation was sustained for greater than 12 months

33. Sustained pain relief: combined areas Pain relief achieved shortly after implantation was sustained for greater than 12 months

34. Sustained pain relief: combined areas Pain relief achieved shortly after implantation was sustained for greater than 12 months

35. Results: combined areas 74% of patients reduced their analgesic use reduction in analgesics correlated with improved pain relief (next slide)

36. Results: combined areas Pain Relief correlates with Decreased Analgesic Use Pearson’s Correlation, r = 0.704; p ≤ 0.0001

37. Results: combined areas *

38. 48% of patients below the age of 60 years increased their capacity for paid employment.

39. Complications and adverse events OUTCOMES Complication No. of patients Reposition / Re-implant / Replace Explant 2007200820092010201120072008200920102011 Hardware erosion 1013111111 Lead Infection 211 Leads too superficial 51211 Hardware migration 51121 IPG pain 211 Implant rejection 211 TOTAL COMPLICATIONS 20072008200920102011 36575 26 patients total (12.8% of all cases)

40. Patient satisfaction (≥ 12 months) Overall, 85% of patients were satisfied with their outcome

41. Summary  Science behind PNfS  Underlying Issues of PNfS therapy  Clinical data for key pain areas  Combined clinical data for 203 PNfS patients

42. Conclusions  PNFS therapy for intractable chronic pain conditions:  Safe  Effective  PNFS has the potential to fundamentally change the way we think about pain management

43. Conclusions Peripheral Nerve field Stimulation