DRG Stimulation: Evolution or Revolution in Neurostimulation?...Comparison of DRG vs Tonic Lower...

DRG Stimulation: Evolution or

Revolution in Neurostimulation?

Joseph Melrose MDColumbia University Medical Center

Fellow, Pain Medicine

Michael Weinberger MDColumbia University Medical Center

Associate Professor of AnesthesiologyDirector, Pain Management Center

Chief, Division of Pain Medicine

Introduction: What is Neurostimulation?

The use of pulsed electrical energy to control pain

At the beginning it included things like:

1882: The “Faradic Electrifier,” Late 1800s: The Gaiffe

TENS unit

1919: The Electreat

Eventually included:

Peripheral nerve and deep brain stimulators, TENS units

Traditional (Tonic) Spinal Cord Stimulator (SCS), High-frequency (HF) SCS, Burst SCS and Dorsal Root Ganglion Stimulators (DRG)

How Does it Work?

Conventional/tonic SCS:

1965: Gate Control theory

Mid 1960s: Peripheral nerve stimulators

1972: Dorsal column neurostimulators were first marketed to neurosurgeons in the United States

Favorably alters the local neurochemistry →suppresses the hyperexcitability of wide dynamic range interneurons

Activation of supraspinal circuitry

Restoration of a favorable oxygen supply and demand balance

Programming – SCS/DRG

Amplitude

Intensity/strength of each individual pulse

Controlled by voltage (V) or current (ohms)

Pulse width

Duration of a pulse (msec)

Rate (frequency)

Pulses per second (Hz).

Electrode selection

Complex topic for Tonic, less complex for HF

2015 Burst FDA Approval:

2015 HF FDA Approval:

2016 DRG FDA Approval:

How Do the High-Density Patterns Work?

HF

Multiple hypotheses

Burst

1970s – BURST TENS existed.

Was applied more for nociceptive pain types.

Was developed to mimic nature

Additionally, works on the medial spinothalamic pathway

DRG

Works on the DRG (first-order sensory neuron)

Major Studies 2008: PROCESS Study (18)

2010: Burst SCS: Toward Paresthesia-Free Pain Suppression (19)

2013: Burst SCS for Limb and Back Pain (15)

2015: Tonic versus Burst SCS: Amount of Responders and Amount of pain Suppression (14).

2015: Tonic versus HF SCS: Response to HF in Tonic Non-responders (10)

July 2016: SENZA-RCT 24mos follow-up (7)

March 2017: Burst or HF (10 kHz) SCS in FBSS Patients With Predominant Back Pain: One Year Comparative Data. (5)

Apr. 2017: ACCURATE Trial (2)

Sept. 2017: SUNBURST Trial (17)

PROCESS Study (18) Prospective, Multicenter RCT

Compared Tonic SCS + Conventional Medical Management (CMM) and CMM alone

FBSS over 24 months

Tonic SCS + CMM (52 assigned → 42 @24mos)

Primary Outcome: >50% leg pain relief

48% of Tonic SCS subjects [using SCS as final therapy]

Secondary Outcomes at 2 years:

No statistically significant improvement in back pain relief

Improved health-related QOL, and functional capacity over CMM only.

Conclusions:

Tonic SCS were effective for neuropathic radicular pain

Are they only effective for neuropathic radicular pain?

2008

Burst SCS: Toward Paresthesia-Free Pain Suppression (19)

SCS electrodes implanted for neuropathic pain in 12 patients via laminectomy

During external stimulation, the patients received BOTH:

TONIC

VAS

t = 0

Axial: 4.42 (improvement of 1.83)

Limb: 3.13 (improvement of 4.41)

Paresthesias: 92% - relatively stable at 1 year.

Compared to Tonic: ↓Paresthesias, ↑Analgesia (including axial pain), Better Sensory and Affective scores on McGill Short Form.

The effects were sustained.

BURST

VAS

t = 0

Axial: 1 (improvement of 5.25)

Limb: 0.25 (improvement of 7.29)

t >1 year (average follow-up 20.5mos)

Axial: (improvement of 3.7)

Limb: (improvement of 5.15)

Paresthesias: 17% - relatively stable

2010

Burst for Limb & Back Pain (15)

Randomized, placebo-controlled trial comparing burst (x1 week), tonic (x1 week) and placebo (x1 week)

15 consecutive pts. Primarily FBSS. Paddles placed via laminectomy.

Primary Outcomes:

Burst

%Improvement of VAS Overall: 55%

%Improvement of VAS Back: 51%

%Improvement of VAS Limb: 53%

Secondary outcomes

Pain Vigilance Questionnaire and Awareness Questionnaire

Burst improved attention to pain and pain changes. Tonic and placebo worsened these measurements.

Encephalogram:

Burst stimulation activates the dorsal anterior cingulate and right dorsolateral prefrontal cortex more than tonic stimulation

Placebo

%Improvement of VAS Overall: 10.9%

%Improvement of VAS Back: 18.9%

%Improvement of VAS Limb: 11.7%

Tonic

%Improvement of VAS Overall: 30.9%

%Improvement of VAS Back: 30.3%

%Improvement of VAS Limb: 51.5%

2013

Tonic vs Burst: Responders & Suppression (14)

2 centers (1 Belgium, 1 Netherlands), Retrospective, 102 pts.

All neuropathic pain – mostly related to FBSS or DMPN

1st group = Tonic failures (24), 2nd group = Tonic responders (78)

Switched them all to Burst

Overall NRS: Baseline 7.8 → Tonic 4.9 → Burst 3.2

Tonic SCS Failures

62.5% responded to Burst → 43% pain suppression

Tonic SCS Responders

50.6% suppression w/ Tonic → 73.63% suppression with Burst

94.87% had a better effect on burst suppression

Conclusions:

If a pt failed Tonic, there’s a good chance they might stillrespond to burst

2015

Tonic vs HF: Responders & Suppression (10)

Prospective RCT

22 (primarily FBSS) non-responders to Tonic

Randomized to 1kHz stim (HF) or Tonic for 3 weeks →1 week washout → switched to the other programming for 3 weeks.

Results

95% (21) improved with HF (average NPRS reduction = 2.41)

41% (9) improved with Tonic (average NPRS reduction = 0.32)

Conclusions:

If a pt failed Tonic, there’s a good chance they might stillrespond to HF

2015

SENZA Trial (7) Prospective RCT w/ 24-month follow-up.

Comparison of HF and Tonic SCS

For chronic BACK and LEG pain

Pre-trial VAS >5 for both back and leg pain

Assigned randomly (1:1) to receive:

HF (101→trial→90)

Tonic (97→trial→81)

Responder rate (defined as >50% back pain reduction from baseline):

July2016

3 months:

HF

84.5% for back pain

83.1% for leg pain

Tonic

43.8% for back pain

55.5% for leg pain

24-months

HF

76.5% for back pain

72.9% for leg pain

Tonic

49.3% for back pain

49.3% for leg pain

SENZA Trial (7) – Cont’d Also, less disability and increased satisfaction with HF

Conclusion:

Long-term superiority of HF to Tonic

No Paresthesias

Worked for back pain & leg pain

July2016

HF vs Burst (5) Prospective, single-center

Comparison of Burst and HF – f/up 3-14mos

FBSS w/ >/=70% back pain +/- leg pain

Assigned in alternating non-randomized fashion (1:1) to receive:

HF (8→trial→6) – Percutaneous leads

Burst (8→trial→8) – Paddle leads via laminectomy

March2017

VAS-Leg

HF

VAS-leg not reported

Increased 18% from baseline

Burst

VAS-leg 3.6 to 1.5

Decreased 50.2% from baseline

VAS-Back (***)

HF

8 (+/-0.63) to 3.5 (+/-3.27)

Burst

8 (+/-0.76) to 1 (+/-1.41)

*** = NOT statistically significant!

PSQI (***)

Baseline: 93% had PSQI score >5 (poor sleep quality)

HF

50% PSQI <5

Burst

88% PSQI <5

BDI (***)

Baseline –100% had moderate depression (BDI 20-29)

HF

33% had improvement from moderate to minimal.

Burst

75% had improvement from moderate to minimal.

HF vs Burst (5) - Cont’d Conclusions:

Burst (*w/ paddle leads) and HF (*w/ percutaneous leads) are effective with a slight superiority for subjects using burst (*w/ paddle leads) in a small sample study in patients w/ FBSS

Statistically significant:

Burst > HF reduction in leg pain

Non-statistically significant

Burst > HF

Reduction in back pain

Improvement in depression

Improvement in sleep

Burst may be more stable with time (paddle leads?) – although SENZA-RCT seems to indicate that HF is also stable with time

March2017

ACCURATE Trial (2) Prospective, multicenter, randomized comparative

effectiveness trial over 12 mos

Comparison of DRG vs Tonic

Lower extremity CRPS 1 or 2

Assigned randomly (1:1) to receive:

DRG (73→trial→61)

Tonic (73→trial→54)

April2017

Responder rate (>50% pain reduction

3 months

DRG – 81.2%

Tonic – 55.7%

12 months

DRG – 74.2%

Tonic – 53.0%

DRG

Greater improvements in quality of life

Greater improvements in psychological disposition.

Less postural variation in paresthesia,

Reduced extraneous stimulation in nonpainful areas

ACCURATE Trial (2) – Cont’d April2017 Paresthesias

3mos

DRG: 15.3% (Just in their pain site: 84.7%)

Tonic: 35.2% (Just in their pain site: 64.8%)

12mos

DRG 5.5% (Just in their pain site: 94.5%)

Tonic 38.8% (Just in their pain site: 61.2%)

No difference in device-related and serious adverse events

Conclusions

More targeted therapy (if they have paresthesias – likely just at the pain site)

Greater improvement in QOL, psychological disposition

SUNBURST trial (17) Prospective, randomized multicenter study.

Successful tonic trial → 100 subjects were randomized to Burst or Tonic for the first 12 weeks, and then the other stimulation mode for the next 12 weeks.

Subjects then used their choice of Burst or Tonic and were followed for one year.

70.8% preferred Burst over Tonic (p < 0.001).

Preference was sustained through one year:

68.2% preferred burst

23.9% preferred tonic

8.0% had no preference.

Conclusions: 23.9% preferred Tonic (because of paresthesias?)

Sept.2017

Advantages:

More stable with time than HF (2017 HF vs Burst)

Contradicted by 2016 SENZA-RCT

Likely better for nociceptive pain than tonic and possibly HF (2017 HF vs Burst)

Contradicted for HF comparison by 2016 SENZA-RCT

Subparesthetic (compared to Tonic)

~17% with paresthesias

Some pts like paresthesias (more versatility in reprogramming with burst)

Paddle and percutaneous leads are available

Improved mood and sleep (vs HF and possibly DRG)

Not statistically significant but there is a physiologic mechanism for it

Limitations:

More paresthesias than HF (17% paresthesias vs none)

Higher amplitude signal required than DRG

High current demand.

Presumably:

More positional variations in stimulation than DRG

Burst – Advantages vs Limitations

Advantages:

Seems to be stable with time (SENZA Trial)

Works well for nociceptive and neuropathic pain (SENZA Trial)

No paresthesias

Limitations:

Very limited programming

Higher amplitude signal required than DRG

Very high current demand – need rechargeable pulse generators; May need daily recharging.

No paddle lead available

Trend towards less improvement in mood/sleep (than Burst)

Presumably:

More positional variations in stimulation than DRG

HF – Advantages vs Limitations

Advantages:

Theoretically could be more effective in historically challenging pain targets (w/ Tonic) such as the foot or chest wall

Dorsal CSF diameter is largest at T5. Spinal nerves at the end of the spinal cordfloat freely with the CSF.

Whereas HF and Burst (like Tonic) theoretically may be ineffective

Much more likely to report paresthesias just in their painful site

Less energy requirements

Less postural instability

Limited mobility of the DRG relative to the spinal cord, ↓CSF volume at the DRG

Limitations

1 lead per 1 Dorsal Root Ganglion limits the applicability

5%-15% paresthesias (ACCURATE Trial)

No paddle leads

No strong evidence that it covers nociceptive pain

Longer procedure (107mins vs 76mins – ACCURATE Trial), more leads

More non-serious procedure-related AEs in the DRG arm (46% vs 26% - statistically significant)

Significantly more fluoroscopy time

DRG – Advantages vs Limitations

Conclusions at this Point?

Burst and HF are superior to Tonic

And if tonic fails it’s reasonable to try Burst or HF

DRG is superior to Tonic for neuropathic pain that covers a limited number of dermatomes

Burst and HF cover nociceptive pain well (better than Tonic)

Some patients like paresthesias

Other Factors in Choosing Neurostimulation Features of the battery/energy usage?

Chargeable vs rechargeable?

How often do you have to recharge?

MRI-safe?

Do you need paddle leads?

Any additional features?

Activity tracker

Support staff

Quality of the reps

Size of the implantable

The Future

More head-to-head studies

Efficacy in different neuropathic and nociceptive conditions

Efficacy in different regions of the body

What factors predict who will respond better to HF vs Burst vs DRG or even tonic?

Better programming

Cost-effectiveness

Mechanisms of action – not well understood

References – Page 11. Efficacious Dorsal Root Ganglion Stimulation for Painful Small Fiber Neuropathy: A Case Report. Maino P, Koetsier E, Kaelin-

Lang A, Gobbi C, Perez R. Pain Physician. 2017 Mar;20(3):E459-E463.

2. Dorsal root ganglion stimulation yielded higher treatment success rate for complex regional pain syndrome and causalgia at 3 and 12 months: a randomized comparative trial. Deer TR, Levy RM, Kramer J, Poree L, Amirdelfan K, Grigsby E, Staats P, Burton AW, Burgher AH, Obray J, Scowcroft J, Golovac S, Kapural L, Paicius R, Kim C, Pope J, Yearwood T, Samuel S, McRoberts WP, Cassim H, Netherton M, Miller N, Schaufele M, Tavel E, Davis T, Davis K, Johnson L, Mekhail N. Pain. 2017 Apr;158(4):669-681.

3. Dorsal root ganglion stimulation approval by the Food and Drug Administration: advice on evolving the process. Deer TR, Pope JE. Expert Rev Neurother. 2016 Oct;16(10):1123-5. doi: 10.1080/14737175.2016.1206817. Epub 2016 Jul 25.

4. Dorsal Root Ganglion (DRG) Stimulation in the Treatment of Phantom Limb Pain (PLP). Eldabe S, Burger K, Moser H, Klase D, Schu S, Wahlstedt A, Vanderick B, Francois E, Kramer J, Subbaroyan J. Neuromodulation. 2015 Oct;18(7):610-6; discussion 616-7. doi: 10.1111/ner.12338. Epub 2015 Aug 13.

5. Burst or High-Frequency (10 kHz) Spinal Cord Stimulation in Failed Back Surgery Syndrome Patients With Predominant Back Pain: One Year Comparative Data. Muhammad S, Roeske S, Chaudhry SR, Kinfe TM. Neuromodulation. 2017 Oct;20(7):661-667. doi: 10.1111/ner.12611. Epub 2017 May 24.

6. Conventional and Novel Spinal Stimulation Algorithms: Hypothetical Mechanisms of Action and Comments on Outcomes. Linderoth B, Foreman RD. Neuromodulation. 2017 Aug;20(6):525-533. doi: 10.1111/ner.12624. Epub 2017 May 31. Review.

7. Comparison of 10-kHz High-Frequency and Traditional Low-Frequency Spinal Cord Stimulation for the Treatment of Chronic Back and Leg Pain: 24-Month Results From a Multicenter, Randomized, Controlled Pivotal Trial. Kapural L, Yu C, Doust MW, Gliner BE, Vallejo R, Sitzman BT, Amirdelfan K, Morgan DM, Yearwood TL, Bundschu R, Yang T, Benyamin R, Burgher AH. Neurosurgery. 2016 Nov;79(5):667-677.

8. New modalities of neurostimulation: high frequency and dorsal root ganglion. Roy LA, Gunasingha RM, Rauck R. Curr Opin Anaesthesiol. 2016 Oct;29(5):590-5.

9. High-Frequency Stimulation of Dorsal Column Axons: Potential Underlying Mechanism of Paresthesia-Free Neuropathic Pain Relief. Arle JE, Mei L, Carlson KW, Shils JL. Neuromodulation. 2016 Jun;19(4):385-97. doi: 10.1111/ner.12436. Epub 2016 May 4.

10. Clinical Outcomes of 1 kHz Subperception Spinal Cord Stimulation in Implanted Patients With Failed Paresthesia-Based Stimulation: Results of a Prospective Randomized Controlled Trial. North JM, Hong KJ, Cho PY. Neuromodulation. 2016 Oct;19(7):731-737. doi: 10.1111/ner.12441. Epub 2016 May 17.

11. Burst and Tonic Spinal Cord Stimulation: Different and Common Brain Mechanisms. De Ridder D, Vanneste S. Neuromodulation. 2016 Jan;19(1):47-59. doi: 10.1111/ner.12368. Epub 2015 Nov 20.

References – Page 212. Comparison of 10-kHz High-Frequency and Traditional Low-Frequency Spinal Cord Stimulation for the Treatment of Chronic

Back and Leg Pain: 24-Month Results From a Multicenter, Randomized, Controlled Pivotal Trial. Kapural L, Yu C, Doust MW, Gliner BE, Vallejo R, Sitzman BT, Amirdelfan K, Morgan DM, Yearwood TL, Bundschu R, Yang T, Benyamin R, Burgher AH. Neurosurgery. 2016 Nov;79(5):667-677.

13. Neurostimulation for the treatment of axial back pain: a review of mechanisms, techniques, outcomes, and future advances. Deer T, Pope J, Hayek S, Narouze S, Patil P, Foreman R, Sharan A, Levy R. Neuromodulation. 2014 Oct;17 Suppl 2:52-68. doi: 10.1111/j.1525-1403.2012.00530.x. Review.

14. A 2-center comparative study on tonic versus burst spinal cord stimulation: amount of responders and amount of pain suppression. De Ridder D, Lenders MW, De Vos CC, Dijkstra-Scholten C, Wolters R, Vancamp T, Van Looy P, Van Havenbergh T, Vanneste S. Clin J Pain. 2015 May;31(5):433-7

15. Burst spinal cord stimulation for limb and back pain. De Ridder D, Plazier M, Kamerling N, Menovsky T, Vanneste S. World Neurosurg. 2013 Nov;80(5):642-649.e1. doi: 10.1016/j.wneu.2013.01.040. Epub 2013 Jan 12.

16. Mechanisms and models of spinal cord stimulation for the treatment of neuropathic pain. Zhang TC, Janik JJ, Grill WM. Brain Res. 2014 Jun 20;1569:19-31. doi: 10.1016/j.brainres.2014.04.039. Epub 2014 May 4. Review.

17. Success Using Neuromodulation With BURST (SUNBURST) Study: Results From a Prospective, Randomized Controlled Trial Using a Novel Burst Waveform. Deer T, Slavin KV, Amirdelfan K, North RB, Burton AW, Yearwood TL, Tavel E, Staats P, Falowski S, Pope J, Justiz R, Fabi AY, Taghva A, Paicius R, Houden T, Wilson D. Neuromodulation. 2017 Sep 29. doi: 10.1111/ner.12698.

18. Spinal Cord Stimulation vs. Conventional Medical Management: A Prospective, Randomized, Controlled, Multicenter Study of Patients with Failed Back Surgery Syndrome (PROCESS Study). Kumar K, North R, Taylor R, Sculpher M, Van den Abeele C, Gehring M, Jacques L, Eldabe S, Meglio M, Molet J, Thomson S, O'Callaghan J, Eisenberg E, Milbouw G, Fortini G, Richardson J,Buchser E, Tracey S, Reny P, Brookes M, Sabene S, Cano P, Banks C, Pengelly L, Adler R, Leruth S, Kelly C, Jacobs M. Neuromodulation. 2005 Oct;8(4):213-8

19. Burst spinal cord stimulation: toward paresthesia-free pain suppression. De Ridder D, Vanneste S, Plazier M, van der Loo E, Menovsky T. Neurosurgery. 2010 May;66(5):986-90

References – Pictures/Diagrams/Tables

Pictures 1,2,3,4 from

http://www.burtonreport.com/infspine/nshistneurostimparti.htm

Picture 5 and 11 from

http://acupunturacontemporanea.blogspot.com/2007/11/eletroanalgesia.html

Picture 6,7,8,9,12 adapted from:

Conventional and Novel Spinal Stimulation Algorithms: Hypothetical Mechanisms of Action and Comments on Outcomes. Linderoth B, Foreman RD. Neuromodulation. 2017 Aug;20(6):525-533. doi: 10.1111/ner.12624. Epub 2017 May 31. Review.

DRGTarget for Neurostimulation

DRG contain cell bodies of primary sensory neurons

DRG Type A- touch, proprioception, vibration

large

DRG Type B – nociception

small

Participate in signaling process

sense and manufacture molecules

modulate sensory processing

The Dorsal Root Ganglion in Chronic Pain and as a Target for Neuromodulation: A Review

Neuromodulation: Technology at the Neural Interface29 OCT 2014 DOI: 10.1111/ner.12247http://onlinelibrary.wiley.com/doi/10.1111/ner.12247/full#ner12247-fig-0001

DRG Anatomy

Sensory root connect to cell bodies via T junction

DRG sits in neural foramen

Surrounded by Glial Cells

Neurons in DRG have receptors for neurotransmitters

DRG Anatomy

Surrounded by Satellite Glial Cells

Receptors to various neuroactive chemicals

e.g. bradykinin, ATP, cytokines

Respond to environmental change

Probable participation in signal processing and transmission in DRG

? Role in neuropathic pain

morphological and biochemical change after nerve injury

DRG and Neuropathic Pain

Injured DRG neurons may become hyperexcitable

Injured Peripheral afferent fibers can lead to hyperexcitability in axotomized DRG neurons

With injured PAF electrical impulses may originate in DRG and can be blocked with lidocaine

Na channels

Neuropathic Pain may involve not just PAF injury but involvement of SGC, Schwann cells, spinal microglia, peripheral immune system

Ectopic DRG firing may lead too central sensitization and allodynia

DRG and Gene Expression

Up regulation of neuropeptides, receptors, ion channels, signal transduction molecules, synaptic vesicle protein etc seen in DRG after peripheral nerve injury consistent with changes in gene expression in animal model.

May alter function of cell body

May play role in development of neuropathic pain

DRG and Ion Channels

DRG express several Sodium Channels

Channels may change expression and gating properties after PAF injury. May lead to spontaneous activity and burst firing, the electrical signature of neuropathic pain

Suggested that electrical stimulation may alter sodium channel gene expression. ? Return to normal


Potassium Channels

PAF injury can lead to reduction in K channel subunit expression in DRG neurons, probable role in hyperexcitability


Calcium

Increased Ca currents in periphery may lower nociceptive threshold

PAF injury may lead to decrease in Ca currents in primary afferents

Inflammation may alter Ca channels in DRG (rat model)

Electrical stimulation of DRG may modify burst and tonic activity in pseudopolar cells

Electrical field stimulation of DRG increases Ca influx and reduces multiple action potential frequency and conduction velocity; neuronal excitability

Role of DRG in Pain

DRG not a passive conduit for afferent transmission

Cellular changes can occur in DRG with PAF injury

Electrical Stimulation of DRG

Possible impact of stimulation on growth factors in DRG which can impact the development of neuropathic pain

Also stimulation may impact immune system response to PAF injury and therefore development of chronic pain

Stimulation may lead to modification of tonic and bursting neurons in DRG which may be abnormal with PAF injury

Hypothesized Mechanisms of Action of Dorsal Root Ganglion Stimulation Modification of growth factor release Release of abnormal growth

factors and inhibition of normally produced growth factors within the DRG resulting from PAF injury may be modified by direct or indirect electrical stimulation of the DRG, resulting in a decrease in chronic pain.

Reversal of cytokine release We have seen that PAF fiber injury leads to activation of microglia within the DRG, which, in turn, leads to a cytokine cascade. This cytokine cascade leads to inflammation and neuropathic pain. Electrical stimulation of the DRG reverses activation of microglia within the DRG, thereby reversing the abnormal cytokine cascade that leads to the development of neuropathic pain.

Downstream and upstream effects It is proposed that electrical stimulation of the DRG results in chronic pain relief through its downstream effects of vasodilation and stabilizing the sensitized peripheral nociceptors and its upstream effects of deactivating sensitized wide-dynamic-range neurons within the spinal cord and turning off brain centers that are turned on by PAF injury and inflammation.

Hypothesized Mechanisms of Action of Dorsal Root Ganglion Stimulation Rectification of electrical activity patterns It

is proposed that electrical stimulation of the DRG may alter abnormal patterns of electrical activity of DRG neurons resulting from PAF injury, thereby decreasing chronic pain.

Reversal of genetic changes It is proposed that electrical stimulation of the DRG reverses nonphysiological early and late genetic changes that result from PAF injury.

Hypothesized Mechanisms of Action of Dorsal Root Ganglion Stimulation Down-regulation of abnormal ion channels and restitution of

normal ion flux We have also seen that there are changes to Na+, K+, and Ca++ ion channels and ion current flux resulting from injury and inflammation that lead to increased excitability of the periphery, the DRG, and the spinal cord. We have also seen that electrical stimulation has effects on the immune system, Ca++ currents, and Na+ channels. Therefore, it is proposed that electrical stimulation of the DRG reverses the production of abnormal Na+, K+, and Ca++ channels and reverses abnormal flux of Ca++ ions.

Filtering of electrical impulses The T-junction of the DRG neuron can either act as an impediment to electrical impulses from the nociceptor to the dorsal root entry zone, participate in the propagation of the electrical pulse, or act as a low-pass filter to electrical information from the periphery.

DRG StimulationAnimal

Ganglionic Field Stimulation to rat DRGs

Measured by action potential #, conduction velocity, AP propagation failure measured pre and post GFS

GFS reduced neuronal excitability demonstrated with reduction in # neurons which could generate AP or multiple AP and a reduction in conduction velocity

Koopmeiners et al Neuromodulation 2013

DRG StimulationClinical

Deer et all 2013

N = 10

Trunk and limb pain

Trial DRG stimulation

f/u 3 to 7 days

Pain reduction, improvement, medication use, adverse effects

A Prospective Study of Dorsal Root Ganglion Stimulation for the Relief of Chronic Pain

Neuromodulation: Technology at the Neural InterfaceVolume 16, Issue 1, pages 67-72, 14 DEC 2012 DOI: 10.1111/ner.12013http://onlinelibrary.wiley.com/doi/10.1111/ner.12013/full#ner12013-fig-0001


Results

average 70% reduction in VAS

8/9 patients >30% pain reduction

7/9 reduced pain medication

No adverse effects

A Multicenter, Prospective Trial to Assess the Safety and Performance of the Spinal Modulation Dorsal Root Ganglion Neurostimulator System in the Treatment of Chronic Pain

Liem et al 2013 Neuromodulation

N = 32

6 month f/u

pain rating reduced by 58%

50% or greater pain reduction

57% back pain, 70% leg, 89% foot

Discontinuation of DRG stimulation led to return of pain

Parethesia did not change with change in position


Neuromodulation: Technology at the Neural InterfaceVolume 16, Issue 5, pages 471-482, 13 MAY 2013 DOI: 10.1111/ner.12072http://onlinelibrary.wiley.com/doi/10.1111/ner.12072/full#ner12072-fig-0001

One-Year Outcomes of Spinal Cord Stimulation of the Dorsal Root Ganglion in the Treatment of Chronic Neuropathic PainAuthors

Liong Liem MD et al 21 August 2014

N = 51

76.5% good outcome with average pain relief 74%

Nonresponders average pain relief 5%

One-Year Outcomes of Spinal Cord Stimulation of the Dorsal Root Ganglion in the Treatment of Chronic Neuropathic Pain

Neuromodulation: Technology at the Neural Interface21 AUG 2014 DOI: 10.1111/ner.12228http://onlinelibrary.wiley.com/doi/10.1111/ner.12228/full#ner12228-fig-0002

One-Year Outcomes of Spinal Cord Stimulation of the Dorsal Root Ganglion in the Treatment of Chronic Neuropathic PainAuthors

Liong Liem MD et al 21 August 2014

Adverse Events

N = 86

Temporary motor stimulation n = 12

CSF leak, headache n = 7, infection n = 7

Lead revision 4

Explants 7

Questions ?

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