1. Influence of Different Lengths of Stimulation on the Effectiveness of SQS in a Rodent Model of Neuropathic Pain Presented by Louis Vera-Portocarrero, Medtronic Neurostimulation Research Co-Authors: Toni Cordero 1, Paul Wacnik 1, Lisa Johanek 1, Tina Billstrom 2, Kim Swearingen 2 1 Medtronic Neurostimulation Research 2 Medtronic Physiological Research Laboratories

2. Disclosure The authors are employees of Medtronic, Inc. This presentation and associated abstract discuss uses that the U.S. Food and Drug Administration has not approved for Medtronic Implantable Neurostimulation Systems.

3. Background SQS (subcutaneous electrical stimulation) is a technique that targets the peripheral nervous system. Parameters used for SQS vary and there is little understanding of optimal parameters. Using a recently developed rodent model, we have begun a systematic investigation of parameters to help inform future pre-clinical studies examining mechanisms of SQS.

4. Background: SQS Model Development Lead placement Proximal end for connection to ENS L. Vera-Portocarrero; NANS 2010, INS 2011 Stim day 1 2 3 4 Anesthetized 20 min SQS Awake 20 min SQS

5. Background: SQS compared to TENS TENS was not effective in reducing hypersensitivity. SQS reduced hypersensitivity in the neuropathic pain model. The effect reached a peak at day 5, suggesting that the effects of SQS could be cumulative over time. Vera-Portocarrero et al., submitted to Neuromodulation

6. Hypothesis, Design and Outcome Measures Hypothesis: Longer lengths of stimulation yield greater effectiveness. Design: Stimulation lengths were 30, 60 and 120 minutes applied to awake rodents. Tester was blind to the frequency of SCS (0Hz or 60 Hz). Amplitude was 80-90% of motor threshold with 250  sec pulse width. Outcome measures: Allodynia, measured by von Frey filaments Number of responders The criteria for a responder was a return to at least 50% value of their pre-injury baseline.

7. Pre-Injury Testing SNI surgery and SQS lead implantation 7 days Testing and stim Day 3 Day 1 Day 2 Day 4Day 5 Methods Spared Nerve Injury stim Testing and stim stim Testing and stim Decosterd and Woolf, 2000

8. Results

9. Stimulation lengthCarry-over effect & duration # of responders 30 minutesYes, 3 Hours6/8 60 minutesYes, 24 hours6/8 120 minutesNo5/8 Results

10. Conclusions SQS was effective while stimulation was turned ON. SQS administered at a specific amplitude (80 – 90% MT) for 30 and 60 minutes produced a carry-over effect while 120 minutes did not. –Preliminary study; replication is necessary –If the phenomenon is real, neuromodulatory mechanisms could be investigated The results of this study set the stage for future studies examining other parameters (amplitude, frequency, pulse widths).