Percutaneous Peripheral Nerve Stimulation in the Non-opioid Management of Acute and Chronic Pain
Given their interests in effectively managing chronic and acute pain without opiates, the Department of Defense, the National Institutes of Health and the Veterans Administration have all recently provided grants to support research regarding the use of percutaneous Peripheral Nerve Stimulation (PNS). The most recent research funding has been directed toward the management of chronic and acute post-amputation pain, chronic low back pain and acute pain following total knee arthroplasty using PNS. An update on the outcomes of the research was recently
provided at the Military Health System Research Symposium (MHSRS), a venue for presenting new scientific knowledge resulting from military-unique research and development.
To date, these federally-funded grants and contracts, totaling $30M, have been awarded to research technology developed by SPR Therapeutics, Inc of Cleveland, OH and their SPRINT® PNS System, the only percutaneous PNS system FDA-cleared for the treatment of acute as well as chronic pain.
Although PNS was initially described as a treatment for pain in the late 1960’s, until recently it had required the neurosurgical implantation of a lead connected to an implanted battery-operated pulse generator under the belief that stimulation would be required indefinitely to provide pain relief. Due to invasiveness and cost, conventional PNS has been relegated to a treatment of last resort for chronic pain and not remotely considered as a treatment for acute pain.
The Sprint PNS system includes a wearable 1-ounce pulse generator connected to an implanted lead and controlled by a small hand-held Bluetooth® remote. The lead is constructed of a 100-micron helically wound wire that is placed under ultrasound guidance via a 20-gauge introducer approximately one centimeter remote to the targeted nerve. The lead is intended to remain implanted for up to 60 days after which it is withdrawn.
Chronic postoperative pain occurs in a substantial proportion of patients following many surgeries and can be as high as 80% in individuals following limb amputation. Research using the Sprint PNS System has demonstrated that peripheral nerve stimulation may be used effectively in the management of acute as well as chronic pain, and that stimulation for up to 60 days can provide significant and sustained relief.
PNS of the Femoral and Sciatic Nerves for Post-Amputation (Neuropathic) Pain
Percutaneous PNS for the treatment of chronic neuropathic post-amputation pain were presented at the MHSRS in August 2018. The findings in regard to residual and phantom limb pain at baseline and at lead withdrawal (EOT) are presented below. Seventy-five percent of subjects experienced highly clinically significant reductions (≥ 50%) overall in average post-amputation pain at EOT and 81% had highly clinically significant reductions (≥ 50%) overall in average post-amputation pain
interference at EOT.
One cohort of 12 subjects with post-amputation pain was followed for up to 12 months, and average pain was evaluated monthly. At EOT in the per protocol treatment group, 8 of 10 patients reported at least 50% reductions in pain. Four of the 5 responders who have reached the 12 month endpoint have reported >50% pain relief. Prospective follow-up is ongoing.
Preliminary findings from the first patient in a VA-funded trial evaluating PNS in the management of post-amputation pain were presented at the American Society of Regional Anesthesiologists in April 2018. According to clinicaltrials.gov, the Hunter Holmes McGuire Veteran Affairs Medical Center is evaluating percutaneous PNS in 16 patients with new nontraumatic transfemoral or transtibial amputation.
Patients are being randomized to either a treatment group, in which they undergo placement of PNS leads within 7 days of amputation surgery, or to a standard of care group. Patients in both groups are treated with standard pain therapies and evaluated weekly for 8 weeks, then at 3, 6, and 12 months postamputation. The principal investigator of this trial is Denise Lester, MD.
PNS of the Femoral and Sciatic Nerves for Post-TKA Pain At 1-month post-TKA 15 of 18 subjects (83%) implanted with PNS leads pre-operatively had mild and well-controlled pain (<4/10). At 3 months, 94% of subjects (17/18) had pain ≤ 2/10 and all subjects had pain <4/10. This compares very favorably versus historical controls in which persistent pain is typically
reported in ~20% or more of patients ≥3 months after TKA.
In regard to opioid cessation, 14/18 subjects (77%) ceased opioid use by 62 days following surgery and 16/18 (89%) had ceased opioid use by 3 months. This also compares favorably versus historical controls in which 25-40% of patients are still using opioids at 90 days (3 months) after TKA (Namba et al 2018; Goesling et al 2016; Hah et al 2014).
PNS of the Medial Branch for Low Back Pain Finally, significant results were also reported at the MHSRS in the use of PNS for the management of low back pain. In this application, PNS was delivered for up to 30 days resulting in 50% or greater pain relief in 6 of 9 patients. This relief endured in 80% of responders at 3 months post treatment and in 50% of responders at 12 months post-treatment.
Similar durable reductions in disability among responders were also
reported in which the average improvement in the Oswestry Disability
Index (ODI) was 32 points among responders at 12 months. To provide context relative to the thirty-two point reduction, the minimal clinically important difference (MCID) for the ODI is ten points. MCID are patient derived scores that reflect changes in a clinical intervention that are meaningful for the patient.
No lead infections, falls, motor block, or other serious devicerelated
adverse events (AE’s) have been reported in clinical studies. The most common adverse events have been skin irritation and erythema. More information may be found at the manufacturer’s website: https://www.sprtherapeutics.com/physicians/safety-information/
SPRINT system-related peer-reviewed publications and presentations
1. Yu, D.T., Chae, J., Walker, M.E., & Fang, Z. P. (2001). Percutaneous intramuscular neuromuscular electric stimulation for the treatment of shoulder subluxation and pain in patients with chronic hemiplegia: a pilot study. Archives of physical medicine and rehabilitation, 82(1), 20-25.
2. Chae, J., D. Yu, and M. Walker, Percutaneous, intramuscular neuromuscular electrical stimulation for the treatment of shoulder subluxation and pain in chronic hemiplegia: a case report. Am J Phys
Med Rehabil, 2001. 80(4): p. 296-301.
3. Yu, D.T., et al., Intramuscular neuromuscular electric stimulation for poststroke shoulder pain: a multicenter randomized clinical trial. Arch Phys Med Rehabil, 2004. 85(5): p. 695-704.
4. Renzenbrink, G.J. and I.J. MJ, Percutaneous neuromuscular electrical stimulation (P-NMES) for treating shoulder pain in chronic hemiplegia. Effects on shoulder pain and quality of life. Clin Rehabil, 2004. 18(4): p. 359-65.
5. Chae, J., David, T.Y., Walker, M.E., Kirsteins, A., Elovic, E.P., Flanagan, S.R., & Fang, Z.P. (2005) Intramuscular electrical stimulation for hemiplegic shoulder pain: a 12-month follow-up of a multiple-center, randomized clinical trial. American journal of physical medicine & rehabilitation,
6. Chae, J., et al., Intramuscular electrical stimulation for shoulder pain in hemiplegia: does time from stroke onset predict treatment success? Neurorehabil Neural Repair, 2007. 21(6): p. 561-7.
7. Wilson, R.D., et al., Single-lead percutaneous peripheral nerve stimulation for the treatment of hemiplegic shoulder pain: a case report. Arch Phys Med Rehabil, 2011. 92(5): p. 837-40.
8. Stolzenberg, D., G. Siu, and E. Cruz, Current and future interventions for glenohumeral subluxation in hemiplegia secondary to stroke. Top Stroke Rehabil, 2012. 19(5): p. 444-56.
9. Rauck, R.L., et al., Peripheral nerve stimulation for the treatment of post-amputation pain–a case report. Pain practice: the official journal of World Institute of Pain, 2012. 12(8): p. 649-55.
10. Chae, J., Wilson, R.D., Bennett, M.E., Lechman, T. E., & Stager, K.W. (2013). Single-lead percutaneous peripheral nerve stimulation for the treatment of hemiplegic shoulder pain: a case series. Pain practice, 13(1), 59-67.
11. Wilson, R.D., Gunzler, D.D., Bennett, M.E., & Chae, J. (2014). Peripheral nerve stimulation compared with usual care for pain relief of hemiplegic shoulder pain: a randomized controlled trial. American journal of physical medicine & rehabilitation/Association of Academic Physiatrists,
12. Wilson, R.D., Harris, M. A., Gunzler, D.D., Bennett, M.E., & Chae, J. (2014). Percutaneous peripheral nerve stimulation for chronic pain in subacromial impingement syndrome: a case series. Neuromodulation: Technology at the Neural Interface, 17(8), 771-776.
13. Rauck, R.L., Cohen, S.P., Gilmore, C.A., North, J.M., Kapural, L., Zang, R.H., & Boggs, J.W. (2014). Treatment of post-amputation pain with peripheral nerve stimulation. Neuromodulation: Technology at the Neural Interface, 17(2), 188-197.
14. Nguyen, V.Q., et al., Fully implantable peripheral nerve stimulation for the treatment of hemiplegic shoulder pain: a case report. Am J Phys Med Rehabil,2015. 94(2): p. 146-53.
15. Ilfeld, B.M., Grant, S.A., Gilmore, C.A., Chae, J., Wilson, R.D., Wongsarnpigoon, A., & Boggs, J.W. (2016). Neurostimulation for Postsurgical Analgesia: A Novel System Enabling Ultrasoundguided
Percutaneous Peripheral Nerve Stimulation. Pain Practice, 17(7), 892-901.
16. Ilfeld, B. M., et al., Infection Rates of Electrical Leads Used for Percutaneous Neurostimulation of the Peripheral Nervous System. Pain Pract. (2016)
17. Ilfeld, B.M. and S.A. Grant, Ultrasound-Guided Percutaneous Peripheral Nerve Stimulation for Postoperative Analgesia: Could Neurostimulation Replace Continuous Peripheral Nerve Blocks? Reg Anesth Pain Med, 2016.
18. Ilfeld, B.M., Gilmore, C.A., Grant, S.A., Bolognesi, M. P., Del Gaizo, D.J., Wongsarnpigoon, A., & Boggs, J.W. (2017). Ultrasound-guided percutaneous peripheral nerve stimulation for analgesia following total knee arthroplasty: a prospective feasibility study. Journal of orthopaedic surgery and research, 12(1), 4.
19. Kapural L, Gilmore CA, Chae J, et al. Percutaneous Peripheral Nerve Stimulation for the Treatment of Chronic Low Back Pain: Two Clinical Case Reports of Sustained Pain Relief. Pain Pract. 2017. doi: 10.1111/papr.12571
20. lIfeld, B. M., et al., Ultrasound-guided percutaneous peripheral nerve stimulation for analgesia following total knee arthroplasty Journal of Orthopaedic Surgery and Research (2017)
21. Staats, P. Neuromodulation as an Alternative to Opioid in the Evolving Health Care Crisis – A Supplement to Pain Medicine News (2017)
22. Gilmore C.A., Ilfeld B.M., Rosenow J.M., Li S., Desai M.J., Hunter C.W., Nader A., Mak J., Rauck, R.L., Kapural L., Crosby N.D., Boggs J.W. (2018). Percutaneous peripheral nerve stimulation (PNS) for the treatment of chronic neuropathic post-amputation pain: Initial results from a multicenter, randomized, placebo-controlled study. Napa Pain Conference.
23. Gilmore, C.A., Kapural, L, McGee, M.J., Boggs, J.W. (2018). Minimally invasive percutaneous peripheral nerve stimulation (PNS) reduces pain and disability in chronic low back pain. World Congress on Regional Anesthesia and Pain Medicine (ASRA), 2018.
24. Shellock, FG, Zare A, Ilfeld BM, Chae J, Strother, RB (2018).Vitro Magnetic Resonance Imaging Evaluation of Fragmented, Open-Coil, Percutaneous Peripheral Nerve Stimulation Leads. Neuromodulation
Volume 21, Issue 3, 276-283.
25. Ilfeld B.M., Ball S.T., Gabriel R.A., Sztain J.F., Monahan A.M., Abramson W.B., Khatibi B., Said E.T., Parekh J., Grant S.A., Wongsarnpigoon A., Boggs J.W. 2018. A Feasibility Study of Percutaneous Peripheral Nerve Stimulation for the Treatment of Postoperative Pain Following Total Knee
Arthroplasty. Neuromodulation 2018; E-pub ahead of print. DOI:10.1111/ner.12790
26. Ilfeld, Brian M., et al., Ultrasound-Guided Percutaneous Peripheral Nerve Stimulation: Neuromodulation of the Sciatic Nerve for Postoperative Analgesia Following Ambulatory Foot Surgery, a Proof-of-Concept Study. Regional Anesthesia and Pain Medicine 2018. 43(6): p. 580–589.
Source: SPR Therapeutics
507 East Jefferson Street
Brooksville, FL 34601
7341 Spring Hill Drive, #3138
Spring Hill, FL 34606-3138