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 Cordero1, Paul Wacnik1, Lisa Johanek1, Tina Billstrom2, Kim Swearingen2

1Medtronic Neurostimulation Research 2Medtronic Physiological Research

Laboratories

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.

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.

Background: SQS Model Development

0

5

10

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20

0 Hz (n=10)4 Hz (n=8)60 Hz (n=8)100 Hz (n=6)

BAS Bas1 Stim1 Bas2 Stim2 Bas3 Stim3 Bas4 Stim4

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With

dra

wal

Th

resh

old

(g

)0

5

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20 0 Hz (n=10)4 Hz (n=8)60 Hz (n=8)100 Hz (n=6)

BAS Bas1 Stim1 Bas2 Stim2 Bas3 Stim3 Bas4 Stim4

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With

dra

wal

Th

resh

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Lead placement

Proximal end for connection to ENS

L. Vera-Portocarrero; NANS 2010, INS 2011

Stim day 1 2 3 4

0

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Mechanical (n=12)Thermal (n=12)

BAS 1 3 8 10 13 15 17

Days after implant

With

draw

al T

hres

hold

(g)

Latency (seconds)

1 3 8 10 15 170

2

4

6 n=12

Days after implant

MT

(vol

ts)

Anesthetized 20 min SQS

Awake 20 min SQS

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

Pre-stim 1 2 3 4 50

20

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100TENSSQSSham TENSSham SQS

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Mechanical

Days of testing

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ry B

asel

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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 msec 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.

Pre-InjuryTesting SNI surgery and

SQS lead implantation

7 days

Testingand stim

Day 3Day 1 Day 2 Day 4 Day 5

MethodsSpared Nerve Injury

stim Testingand stim

stim Testingand stim

Decosterd and Woolf, 2000

Results

30 minutes of Stimulation

Wit

hd

raw

al T

hre

sho

ld (

g)

BAS 0 0.5 1 2 3 240

5

10

15

20 60 Hz0 Hz

Hours after end of Stim

+ ++

+ + Pre-injury BAS

Stimulation length Carry-over effect & duration

# of responders

30 minutes Yes, 3 Hours 6/8

60 minutes Yes, 24 hours 6/8

120 minutes No 5/8

Results1 hour of stimulation

Wit

hd

raw

al T

hre

sho

ld (

g)

BAS 0 1 2 3 240

5

10

15

20 60 Hz0 Hz

Hours after end of Stim

++

+

++

+

STIMON

Pre-injury BAS

2 hours of stimulation

Wit

hd

raw

al T

hre

sho

ld (

g)

BAS 0 1 2 3 240

5

10

15

2060 Hz0 Hz

Hours after end of Stim

+

STIMON

Pre-injury BAS

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).