Percutaneous Peripheral Nerve Stimulation for Pain Reduction and Improvements in Functional Outcomes in Chronic Low Back Pain

Abstract

Chronic low back pain represents one of the most common sources of disability and a significant healthcare burden for the U.S. military. Present treatments for chronic back pain are often ineffective, poorly tolerated, invasive, destructive, and/or associated with complications and lead to the progression to invasive surgical procedures. There have been multiple calls for the development of a minimally invasive system that is effective without the risks or complications of existing surgical therapies, which could prevent the need for surgery and the recurrence of pain. The goal of this study was to evaluate a novel, minimally invasive approach using a percutaneous peripheral nerve stimulation (PNS) system designed to provide pain relief without surgery, to reduce complications, and provide a less-invasive treatment option. In nine subjects, percutaneous PNS improved participants’ function, as evidenced by clinically and statistically significant reductions in pain, disability, and pain interference. Subjects also experienced reductions in opioid and non-opioid analgesic medication usage and reported improvements in quality of life with treatment. There were no serious or unanticipated adverse events. These results demonstrate the potential of percutaneous PNS as a non-surgical therapy to treat chronic back pain without opioids.

Low back pain, Percutaneous peripheral nerve stimulation (PNS), chronic pain, disability

INTRODUCTION

Chronic musculoskeletal disorders are a major problem in the U.S. military population and represent a significant burden on the U.S. military as a significant source of disability, lost work time, outpatient visits or hospitalization, and decreased military readiness. In particular, chronic low back pain (LBP) is the most common musculoskeletal disorder and is challenging to treat. Disabling chronic LBP significantly decreases military readiness and carries the highest risk of permanent disability.¹ Back-related musculoskeletal disorders have the greatest 5-year cumulative risk of disability in the military and chronic LBP is extremely prevalent among military personnel and highest in occupations requiring heavy physical demands (e.g., infantrymen and wheeled vehicle drivers).^1–3 Pain attributed to musculoskeletal overuse injuries in the military has a cumulative incidence as high as 51% (e.g., during military training). In Operation Enduring Freedom and Operation Iraqi Freedom (OIF), back pain was the leading cause for non-battle injury medical evacuations and responsible for a low rate of return to duty.¹ Further, back pain is the most commonly reported problem among Veterans, in both those who have been operationally deployed and those who have not.⁴

Present non-opioid treatments for chronic back pain are often ineffective, poorly tolerated, invasive, destructive, and/or associated with complications. The inadequacy of existing therapies for back pain may result in prolonged use of opioids or progression to highly invasive surgical procedures, which are often associated with significant risk of complications and may limit a Service members’ ability to return to active duty at full capacity. Injured Service members with significant pain in OIF experienced poor outcomes and low return-to-duty rates despite treatment with a wide range of non-opioid modalities.

Peripheral nerve stimulation (PNS) is a promising non-opioid treatment for pain, but the use of conventional PNS systems is limited by invasiveness and complications (e.g., hardware complications, lead migration). A novel PNS system with has been designed to enable percutaneous delivery of therapy without surgery while reducing complications, providing a less-invasive treatment option to restore function by reducing pain and disability. The PNS system uses a unique lead with a coiled, fine wire design intended to reduce lead migration and has been shown previously to have a low risk of infection. The goal of the current study was to demonstrate the effectiveness of PNS to reduce pain and improve function in patients with LBP.

METHODS

A case-series study was conducted to evaluate percutaneous PNS in nine civilians with chronic LBP confined to the lumbar region. Subjects were enrolled under an FDA investigational device exemption-approved and institutional review board (IRB, Quorum IRB, Seattle, WA)-approved study. Written informed consent was obtained from each individual prior to participation. At the time of subject participation, the device was investigational; however the SPRINT PNS System has since received FDA 510(k) clearance and is indicated for up to 60 days in the back and/or extremities for: (i) Symptomatic relief of chronic, intractable pain, post-surgical and post-traumatic acute pain; (ii) Symptomatic relief of post-traumatic pain; and (iii) Symptomatic relief of post-operative pain.

Individuals with a history of chronic LBP, long-term pain confined to the lumbar region (i.e., pain lasting ≥3 months not radiating to the lower extremities) underwent a baseline exam to determine eligibility and must have had at least 1 month of stable medication history. Eligible subjects recorded their average pain every day in a diary on a 0–10 numeric rating scale (Question #5 of the validated Brief Pain Inventory Short Form; BPI-5). To enroll, subjects must have had a baseline pain ≥4 (BPI-5). Exclusion criteria included serious underlying causes of LBP, history of significant trauma to the low back, prior lumbar surgery, injections within 3 months of baseline or radiofrequency ablation within 6 months of baseline (e.g., which could damage nerves and limit efficacy of PNS), pending litigation or secondary gain issues, allergy to adhesives, an implanted neurostimulator or pacemaker/defibrillator, or score >20 on the Beck Depression Inventory (BDI-II). The use of previous LBP therapies was collected for analysis, but was not required for enrollment.

Following the 1-week baseline period, subjects underwent bilateral lead placement to target nerves innervating the paraspinal muscles in the low back (one subject with unilateral pain received unilateral PNS). Twenty-gauge introducers, each preloaded with a percutaneous lead (MicroLead™, SPR Therapeutics, Cleveland, OH, Fig. 1), were inserted, one on each side of the spinous process in the center of the subject’s region of greatest pain with the subject in prone position under sterile conditions. The percutaneous leads were deployed ~1–2 cm posterior to the lamina to target the medial branch of the dorsal primary ramus (~4–5 cm under the skin). Lead placement was guided using ultrasound and known anatomical landmarks (e.g., spinous process, transverse process, paraspinal muscles, etc.). Electrical stimulation was applied to target the medial branch of the dorsal ramus after the branch exits the intervertebral foramen prior to innervation of the multifidus and facet joints. Successful lead placement relative to the nerve target was confirmed by the ability to selectively evoke comfortable contractions of the lumbar multifidus, which was confirmed with ultrasound⁵ and patient-reported sensations. Following the procedure, the introducer needles were removed and the percutaneous fine-wire leads remained in place for the duration of the therapy (1 month). The leads were connected to small body-worn stimulators (SPRINT PNS System^®, SPR Therapeutics, Cleveland, OH, USA).

FIGURE 1.

Percutaneous lead used for PNS. Flexible, fine wire coiled lead (MicroLead, SPR Therapeutics, Cleveland, OH, USA) used for PNS for chronic back pain. Lead is shown preloaded into needle introducer, with inset showing details of electrode and coiled lead structure.

Stimulation was programmed to selectively stimulate the medial branch of the dorsal ramus and each subject was provided with a customized range of intensities to produce comfortable sensations. Subjects were instructed to use stimulation therapy for 6 hours per day for the duration of the 1-month treatment period. Subjects were encouraged to continue with their normal routine and activities of daily living, but were not allowed to engage in any other treatments for LBP apart from their baseline medications. Subjects recorded daily pain levels and analgesic medication consumption in weekly diaries and returned to the clinic once per week during the therapy period for assessment of pain, disability, and adverse events. At the end of treatment (EOT), stimulation was discontinued and leads were withdrawn using gentle traction. Subjects completed follow-up visits up to 7 months after start of treatment (See Fig. 2 for timeline of subject participation). Additional functional outcomes were evaluated using validated questionnaires of disability (Oswestry Disability Index, ODI)⁶, pain interference (BPI-9)⁷, and patient global impression of change (PGIC), assessed at baseline and throughout the follow-up period.

FIGURE 2.

Timeline of subject participation. Subjects were consented and enrolled in the case-series study following completion of a baseline diary. Subjects received one month of percutaneous PNS. Leads were removed at the end of treatment (1 month) and subjects completed long-term follow-up visits (up to 7 months after start of treatment).

RESULTS

Nine subjects with chronic pain confined to the lower back met the inclusion and exclusion criteria, were enrolled, and received the percutaneous PNS therapy. Baseline characteristics of the enrolled subjects are shown in Table I. On average, subjects reported chronic LBP lasting 10 years, despite use of several previous therapies for back pain (i.e., opioid analgesic medications, non-opioid analgesic medications, physical therapy, corticosteroid injections). Percutaneous leads were placed in each subject without complications, as outlined in the Methods. Subjects reported that stimulation produced comfortable sensations (e.g., described as comfortable, pulsing, vibrating, tingling, and/or tapping) in the region of their LBP. Weekly inspections of the lead exit sites, queries for changes in sensation, and evaluation of stimulation thresholds for comfortable muscle activation were used to confirm correct lead positioning. At the EOT, stimulation was discontinued and the leads were removed without discomfort or complication. The only adverse events related to the device or procedure were mild skin irritation in two subjects, which were resolved by providing latex-free dressings.

TABLE I.

Baseline Characteristics and Results for All Subjects

Age, years (n)	53.3 (9)
BMI (n)	29.5 (9)
Sex, n (%)
Male	1 (11%)
Female	8 (89%)
Race, n (%)
Caucasian	8 (89%)
African American	1 (11%)
Employment status, n (%)
Currently working	5 (56%)
Retired (not due to health)	2 (22%)
Disabled	2 (22%)
Duration of back pain, years (n)	10.0
Average Pain Intensity (BPI-5), mean (n)
Baseline	5.7 (9)
1 month (End of Treatment with PNS)	2.2 (9)
4 months	2.3 (5)
7 months	4.1 (5)
Oswestry Disability Index (ODI), mean (n)
Baseline	32.9 (9)
1 month (End of Treatment with PNS)	18.5 (9)
4 months	19.4 (5)
7 months	26.1 (5)
Pain Interference (BPI-9), mean (n)
Baseline	5.1 (8)
1 month (End of Treatment with PNS)	2.2 (8)
4 months	2.9 (4)
7 months	5.1 (4)

Following 1 month of treatment with percutaneous PNS, a majority of subjects (67%, n = 6/9) experienced highly clinically significant (≥50%) reductions in average back pain intensity (Brief Pain Inventory short form, question #5, BPI-5) compared to baseline (average 80% reduction among responders). Across all subjects, the mean reduction in average pain intensity with treatment was 59% (results for all subjects listed in Table I). There was a statistically significant effect of treatment on the average back pain intensity score (n = 9, ANOVA, p < 0.0084) and post-hoc analysis with Tukey–Kramer tests revealed that average pain intensity was statistically significantly reduced at end of treatment (p < 0.0096) and 4 months after start of treatment (p < 0.0382) compared to baseline. Further, a majority of subjects completing the long-term follow-up visits continued to experience clinically significant (≥30%) reductions in average back pain intensity at four months (80%, n = 4/5, average 84% reduction among responders) and seven months (60%, n = 3/5, average 57% reduction among responders) after start of treatment (Fig. 3). A majority of subjects (56%) also experienced highly clinically significant (≥50%) reductions in worst pain intensity (BPI-3) with treatment (83% average reduction in worst pain among responders).

FIGURE 3.

Pain intensity over time with PNS among responders. A majority of subjects (67%, n = 6/9) experienced highly clinically significant reductions in average pain intensity (Brief Pain Inventory Short Form, Question #5, BPI-5) with percutaneous PNS compared to baseline. Clinically significant reductions in pain intensity were sustained long-term (up to 7 months after start of treatment) in a majority of patients.

Reductions in pain intensity reported by these subjects were also accompanied by substantial reductions in analgesic medication usage with percutaneous PNS treatment that continued long-term. Subjects substantially reduced non-opioid analgesic medication usage (avg. 76% reduction non-opioids, n = 6) and opioid analgesic medication usage (100% reduction, n = 1 taking opioids at baseline), compared to baseline, which continued long-term. Overall, 83% of subjects (n = 5/6 taking analgesic medications) reported greater than 50% reductions in total analgesic medication usage (including both opioids and non-opioids).

In addition to clinically significant reductions in pain and analgesic medication usage, subjects also experienced clinically significant improvements in functional outcomes, such as disability and pain interference on activities of daily living and other secondary outcomes. A majority of subjects (67%, n = 6/9) experienced clinically significant improvements (≥10-pt) in function as measured using the validated Oswestry Disability Index (ODI, average 22.9-point reduction among responders).⁶ Reductions in disability were sustained long-term and are shown in Figure 4. Subjects also experienced clinically significant reductions in pain interference, as measured using the validated Brief Pain Inventory, Question #9, which assesses how much pain has interfered with seven daily activities, including general activity, walking, work, mood, enjoyment of life, relations with others, and sleep. A majority of subjects (75%, n = 6/8) experienced clinically significant reductions in pain interference with treatment compared to baseline (average 75% reduction among responders). Reductions in pain interference continued long-term among responders, as shown in Figure 5. Patient global impression of change (PGIC) in quality of life after treatment was found to be on average “much improved” with treatment, and a majority of subjects (60%) reported improvement 7 months after start of treatment.

FIGURE 4.

Disability over time with PNS among responders. A majority of subjects (67%, n = 6/9) experienced clinically significant (>10 points) reductions in disability (Oswestry Disability Index, ODI) with percutaneous PNS compared to baseline. Reductions in disability were sustained long-term.

FIGURE 5.

Pain Interference over time with PNS among responders. A majority of subjects (75%, n = 6/8) experienced clinically significant reductions in pain interference (Brief Pain Inventory, Question #9, BPI-9) with percutaneous PNS compared to baseline. Reductions in pain interference were sustained long-term.

DISCUSSION

The results of this case-series study demonstrate the potential utility of this innovative approach, suggesting that percutaneous PNS targeting the medial branch of the dorsal ramus can provide sustained improvements in pain and functional outcomes. The use of percutaneous PNS may also reduce or eliminate the need for analgesics in individuals with chronic LBP.

In this study, selective activation of the medial branch of the dorsal ramus with percutaneous PNS was evidenced by multifidus contractions visualized with ultrasound, and patient-reported sensations. This 1-month stimulation therapy produced clinically significant reductions in average back pain intensity at the end of treatment, which were sustained long-term. Therefore, this study reveals the potential to use percutaneous PNS to produce long-term (7 or more months) improvements in pain.

Improvements in functional outcomes were also seen in these subjects. A majority of subjects experienced clinically significant reductions in disability (ODI) and the interference of pain on activities of daily living and physical functioning (BPI-9).⁷ The meaningful improvements in assessments of physical functioning (i.e., ODI, BPI-9) were substantiated by the improvements reported by subjects’ response for PGIC in quality of life, indicating that this minimally invasive therapy has potential to significantly impact functional outcomes, in addition to pain.

Additional evidence of the long-term impact on pain produced by this percutaneous PNS therapy can be found in the reduction of analgesic medication usage by all subjects taking analgesic medications at baseline. More than 83% of subjects experienced at least 50% reduction in opioid and non-opioid analgesic medication usage, which continued long-term. These results demonstrate the feasibility of this percutaneous PNS therapy as an alternative to analgesic medications, which could significantly reduce opioid and non-opioid consumption. Further, by reducing pain and improving functional outcomes, PNS may also reduce the need for or progression to use of destructive or irreversible therapies (e.g., lumbar radiofrequency ablation, which destroys signal transduction in nerves that are reversibly activated with PNS and spinal fusion).

These results are consistent with the previous studies of percutaneous PNS across several pain conditions (e.g., chronic shoulder pain, neuropathic pain in amputees, post-surgical knee pain, back pain), in which clinically significant pain relief was sustained long-term.^8–12 In several of these previous studies, subject-reported improvements in functional outcomes and increased activity levels were sustained long-term.⁸ One proposed mechanism that may be responsible for the prolonged analgesic effects following percutaneous PNS is the modulation of central sensitization.¹³ Specifically, afferent signals from muscle spindle activation generated by percutaneous PNS of efferent nerve fibers may cause the normalization or partial reversal of membrane excitability and synaptic efficacy of neurons and circuits in nociceptive pathways. Such a mechanism may explain not only the pain reduction during treatment but also the maintenance of this analgesic effect and improvements in function long-term.¹⁴

Therefore, percutaneous PNS provides an effective neurostimulation therapy for the treatment of LBP. Typically, traditional neurostimulation has required permanent neurosurgical placement of electrodes in intimate proximity to the targeted peripheral nerve and continuous stimulation to provide lasting pain relief. Further, PNS applications in the low back have been plagued by high rates of adverse events, highlighting the value of a minimally invasive, percutaneous PNS system (SPRINT PNS System, SPR Therapeutics), which was specifically developed for use as a percutaneous therapy and has an excellent safety profile and fewer complications than other permanently implanted neurostimulation systems.^15–18 Limitations of this small sample feasibility study will be addressed in future multicenter trials, which will further explore the extent to which this method of percutaneous PNS can reduce pain and improve function in individuals, including Service members and Veterans, with chronic LBP. Additionally, future trials are expected to further differentiate the characteristics of responders and non-responders to PNS, as well as explore the effects of longer durations of PNS therapy. The present findings from this case series suggest that this percutaneous PNS therapy offers significant advantages with the potential to reduce pain and improve functional outcomes long-term.

CONCLUSION

This case-series study demonstrates the potential to use PNS as a rehabilitative therapy to provide prolonged pain relief and improvements in function and readiness for military service members, Veterans, and other military health system beneficiaries with chronic LBP and disability. This study is consistent with previous trials of percutaneous PNS in post-amputation pain and chronic shoulder pain, which demonstrated clinically significant reductions in pain and improvements in functional outcomes. Together, these studies indicate the potential for percutaneous PNS to reduce pain and opioid use while improving function (i.e., improvements in the ability to complete daily activities or occupational tasks) in areas highly relevant to the military. This approach has the potential to be adapted to relieve chronic pain and restore function across a wide range of musculoskeletal injuries.

Previous Presentation

Presented as an oral presentation at the 2017 Military Health System Research Symposium

Funding

SPR Therapeutics, Inc. This supplement was sponsored by the Office of the Secretary of Defense for Health Affairs.

Acknowledgments

The authors thank the staff at the Center for Clinical Research for the referral, recruitment, and care of all subjects participating in this study.