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Chronic and interventional pain
Pain intensity and opioid consumption after temporary and permanent peripheral nerve stimulation: a 2-year multicenter analysis
  1. Tyler West1,
  2. Nasir Hussain2,
  3. Anuj Bhatia3,
  4. Mariam ElSaban1,
  5. Anthony E Kilgore4,
  6. Marilly Palettas5,
  7. Mahmoud Abdel-Rasoul5,
  8. Saba Javed6 and
  9. Ryan S D'Souza1
  1. 1Department of Anesthesiology and Perioperative Medicine, Mayo Clinic, Rochester, Minnesota, USA
  2. 2Department of Anesthesiology, The Ohio State University Wexner Medical Center, Columbus, Ohio, USA
  3. 3Anesthesia and Pain Medicine, University of Toronto Health Policy Management and Evaluation, Toronto, Ontario, Canada
  4. 4Physical Medicine & Rehabilitation, Mayo Clinic, Rochester, Minnesota, USA
  5. 5Center for Biostatistics, The Ohio State University Wexner Medical Center, Columbus, Ohio, USA
  6. 6Department of Pain Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
  1. Correspondence to Dr Ryan S D'Souza, Department of Anesthesiology and Perioperative Medicine, Mayo Clinic, Rochester, MN 55905, USA; DSouza.Ryan{at}mayo.edu

Abstract

Objective Peripheral nerve stimulation (PNS) is an emerging neuromodulation modality, yet there remains limited data highlighting its long-term effectiveness. The objective of this study was to report real-world data on pain intensity and opioid consumption after temporary and permanent PNS for chronic pain up to 24 months postimplantation.

Methods A retrospective study was conducted on all patients who received PNS implants at a multi-centered enterprise between January 1, 2014 and February 24, 2022. The two co-primary outcomes were: (1) change in pain intensity (11-point Numerical Rating Scale) from baseline to 12 months postimplant; and (2) comparison of the change in pain intensity between temporary and permanent PNS cohorts 12 months postimplant.

Results 126 patients were included in this analysis. Pain intensity significantly decreased 12 months postimplant in the overall cohort (mean difference (MD) −3.0 (95% CI −3.5 to −2.4), p<0.0001). No significant difference in this reduction was identified between temporary and permanent PNS cohorts (MD 0.0 (95% CI −1.1 to 1.0), p=1.00) 12 months postimplantation. Pain intensity significantly decreased in the overall, temporary, and permanent cohorts at all secondary time points (3, 6, and 24 months). No change in daily opioid consumption was observed at 6 and 12 months postimplant in the overall cohort.

Conclusion This study found that both temporary and permanent PNS may be effective for reducing pain intensity in patients with chronic pain up to 24 months postimplantation, although no changes in opioid consumption were observed. The decrease in pain intensity was comparable between patients receiving temporary versus permanent implants, highlighting that temporary PNS may achieve long-lasting clinical benefits. However, given the substantial loss to follow-up, further large-scale studies are needed to solidify conclusions about the efficacy of PNS.

  • Neuromodulation
  • CHRONIC PAIN
  • Peripheral Nerve Injuries
  • Pain Management

Data availability statement

All data relevant to the study are included in the article or uploaded as supplementary information.

http://creativecommons.org/licenses/by-nc/4.0/

This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, an indication of whether changes were made, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.

https://doi.org/10.1136/rapm-2024-105704

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    WHAT IS ALREADY KNOWN ON THIS TOPIC

    • Both temporary and permanent peripheral nerve stimulation (PNS) implants may provide pain relief for various chronic pain indications up to 12 months postimplantation.

    WHAT THIS STUDY ADDS

    • Both temporary and permanent PNS implantation were associated with a statistically and clinically significant decrease in pain scores up to 24 months postimplantation. There was no difference in pain scores 12 months postimplantation between temporary and permanent PNS cohorts, suggesting that temporary PNS implants may provide continued relief after implant removal.

    HOW THIS STUDY MIGHT AFFECT RESEARCH, PRACTICE OR POLICY

    • Clinicians may offer temporary and permanent PNS as long-term pain management options with relief potentially lasting up to 24 months postimplantation, although there remains uncertainty in this finding due to a high study drop-out rate and lack of decrease in opioid utilization postimplantation. Future well-powered prospective trials are warranted to confirm improvement in pain scores, as well as analyze other outcomes in opioid consumption, functionality, and emotional function.

    Introduction

    Peripheral nerve stimulation (PNS) is an emerging and increasingly common treatment modality for acute and chronic pain refractory to conventional medical management. Currently, there are several indications approved by the Food and Drug Administration for its use, including chronic intractable acute or chronic pain of the head, neck, trunk, and limbs1–12; however, the therapy has also been used off-label for facial pain.13 Similar to spinal cord stimulation (SCS), PNS is thought to act through “gate-control” by selectively activating Aβ fibers which subsequently inhibits Aδ/C fibers, thereby modulating afferent pain signals.10 14

    Despite PNS being available for decades since its inception in 1966, there are few large-scale studies that have investigated its long-term analgesic effectiveness.15 Further, there are limited comparative data on the different types of PNS implants, such as temporary and permanent systems. Patients often undergo temporary PNS implantation as a trial and then receive a permanent implant if the temporary implant is effective. Some studies have found that there may be a “carryover” effect where pain relief is maintained for a period after lead removal in temporary PNS systems, potentially leading to long-term pain relief.6 16 Despite the literature showing that temporary implants can result in pain relief after lead removal, there are no studies comparing the durability of outcomes from temporary and permanent PNS systems.

    The objective of this study was to determine the short-term and long-term effectiveness up to 24 months of temporary and permanent PNS implants for various chronic pain conditions. Primary outcomes included: (1) the change in pain intensity 12 months after PNS implantation compared with baseline, and (2) the difference in pain intensity 12 months after PNS implantation in temporary versus permanent PNS implant cohorts. Our hypothesis was that pain intensity would decrease at 12 months postimplantation compared with baseline, and that there would be no difference in pain intensity between temporary and permanent PNS cohorts, suggesting a carryover effect of temporary implants after lead removal.6 16 To the authors’ best knowledge, there are no 24-month follow-up data comparing temporary and permanent PNS in the literature.

    Methods

    Study design

    The protocol was developed a priori without registration, with no protocol deviations except for the addition of a mixed-effect regression analysis and post-hoc subgroup analysis based on the type of pain (neuropathic vs non-neuropathic) and presence of chronic pain outside the distribution of PNS implantation versus focal pain. A retrospective chart review was conducted on all patients who received PNS implants for chronic pain conditions at the Mayo Clinic Enterprise (Mayo Clinic, Rochester, Minnesota; Mayo Clinic, Phoenix, Arizona; Mayo Clinic, Jacksonville, Florida; satellite Mayo Clinic Healthcare systems) between January 01, 2014 and February 24, 2022. This study started on February 24, 2023 so all implants would have at least 12 months of follow-up data. We excluded patients who declined authorization for research review, for which data on reasons for exclusion were not available as Mayo Clinic has an opt-out policy for patient outcome research.

    Implant procedure

    Seven pain physicians with experience in PNS implantation implanted the devices during the period of this study. The overall steps of PNS implantation including positioning and sterility were similar between providers and implant location. The majority of included patients received a preimplant diagnostic block and were offered PNS due to an at least 50% improvement in pain intensity. The decision to place a temporary versus permanent PNS implant was based on many factors, which included patient preference to try temporary PNS prior to a permanent implant, provider preference to use a temporary implant as a trial prior to permanent implantation, and increased difficulty in explanting permanent PNS devices. Temporary implants were removed after a 60-day stimulation period.

    For temporary PNS implants, test stimulation was delivered with a percutaneous sleeve with a stimulating probe inside. After skin localization, the needle was driven by ultrasound guidance to the target location, 0.5–1 cm from the nerve of interest. Once the position was confirmed, stimulation was performed until comfortable sensations were produced in the distribution of the patient’s chronic pain, with repositioning of the probe as necessary. Once the probe was in an optimal location, it was removed from the sleeve. Next, an introducer containing the lead was inserted into the percutaneous sleeve. The lead was then connected to the stimulator and stimulation parameters were tested again, adjusting intensity until the desired response was obtained. The introducer and sleeve were then withdrawn, after which the lead was deployed and secured with surgical glue. Stimulation was again delivered to confirm the lead did not migrate with removal of the introducer. For permanent PNS implants, the lead was tunneled towards the direction of the planned generator location.

    Data collection

    Two reviewers (ME and AEK) accessed patient medical records, including standardized pain nurse follow-up surveys, provider office notes, and operative reports. Data were independently extracted for baseline characteristics including sex, age at the time of implantation, body mass index (BMI), smoking status, comorbidities (anxiety, depression, diabetes, fibromyalgia), indication for PNS implantation, target of PNS leads, worker’s compensation utilization, completion of a preimplantation diagnostic block, baseline pain scores, preimplantation opioid use, preimplantation neuropathic medication use, and postimplantation outcomes of interest. Any discrepancies between reviewers were discussed with the corresponding author (RSD).

    Primary and secondary outcomes

    We elected to have two co-primary outcomes for this study. One primary outcome was the interval change in pain intensity (0–10 Numerical Rating Scale (NRS)) from baseline to 12 months after PNS implantation. Data from standardized PNS follow-up nursing questionnaires sent through the patient portal or completed in the office were used first if available. Otherwise, NRS pain scores from office visit notes closest to the follow-up time points were recorded. The second primary outcome was the comparison of change in pain intensity from baseline to 12 months postimplantation between temporary and permanent PNS implants. Secondary outcomes included: (1) change in pain intensity from baseline to other time points after implantation (3, 6, 24 months), (2) difference in pain intensity between temporary and permanent implant cohorts at other time points postimplantation (3, 6, 24 months), (3) daily opioid utilization at 6 and 12 months postimplantation compared with baseline, and (4) change in cumulative opioid consumption from baseline to 6 and 12 months after PNS implantation in oral morphine equivalents (OME). Opioid utilization at 24 months was not analyzed due to the significant lack of follow-up opioid utilization data. Only patients who were using opioids at baseline, 6 months, or 12 months after PNS implantation were included in the analysis of opioid consumption. When analyzing cumulative opioid consumption, all patients who were on opioids at any follow-up time point were included at each time point that prescription data were available. For example, if a patient was not using opioids at baseline or at 6 months postimplantation but was started on opioids 12 months postimplantation, they were included in the OME utilization analysis at all time points with zero OME/day recorded at baseline and 6-month follow-up. Opioid consumption was assessed as a binary variable (yes/no) as well as a continuous variable (OME in mg/day).

    The baseline time point was set at the date of the first temporary/permanent implant if a patient had multiple temporary/permanent PNS implants. If a patient had both temporary and permanent implants, the baseline time point was set at the date of the first permanent implant. Outcomes were analyzed in aggregate for all PNS implants and then separately for temporary and permanent PNS implants. For opioid consumption, OME utilization was recorded based on provider notes that explicitly stated the name of the opioid, dose, and frequency of intake. If this was not available, the medication prescription, patient questionnaires, or Prescription Drug Monitoring Program (PDMP) queries were used to identify OME utilization. PDMP access is a built-in application of the Mayo Clinic electronic medical record. We manually converted the reported opioid dose to the respective OME by using the Mayo Opioid Online Converter tool (https://kmt-prod-opioidui.mayo.edu/%23/converter; accessed February 2023). In the protocol for this study, the authors had planned to also abstract physical functionality metrics at baseline and at follow-up time points. However, physical functionality metrics were not reliably documented in the clinical records and therefore this outcome was unable to be analyzed.

    Statistical analysis

    Patient demographic and clinical characteristics were summarized overall and by the two implant groups using appropriate descriptive statistics. Means with SD were used to summarize continuous variables while frequencies and proportions were used to summarize categorical variables. Comparisons between the temporary and permanent PNS implant groups included patient demographics, comorbidities, analgesic use, indication, preimplant block, PNS targets, and baseline pain scores. Categorical variables were compared between groups using either a χ2 test or a Fisher’s exact test, and continuous variables were compared using an analysis of variance F-test. The two co-primary outcomes of change in pain intensity (11-point NRS) from baseline to 12 months postimplant and the comparison of the change in pain intensity between temporary and permanent PNS cohorts 12 months postimplant were presented as mean differences (MDs) and 95% CIs. Mixed-effects linear regression models were used to evaluate change in pain scores from baseline to 12 months postimplant as well as evaluate differences between temporary and permanent implant groups over time. The decision to conduct a mixed-effects linear regression model was severalfold, including the model’s ability to accommodate missing values or dropouts in longitudinal datasets, no requirement to have the same number of observations per participant, and flexibility in specifying the covariance structure among repeated measures.17 Group and time were included as fixed effects in the model, and patients were included as a random effect to account for the correlation between repeated measures on the same patient. Compound symmetry was used as the covariance structure in the model given there was no correlation among repeated measure observations when evaluating the residual plots. Secondary outcomes which included changes in pain intensity at other timepoints (3, 6, and 24 months) as well as changes in daily opioid consumption over time were evaluated using the same mixed-effects regression models outlined for the primary analysis. The minimal clinically important difference (MCID) threshold for change in pain intensity was defined as a change of 2.0 on an 11-point NRS scale.18 Based on prior literature, the MCID for OME utilization was a change of 23 OME.19 Statistical analyses and plots were performed using SAS V.9.4 (SAS Institute, Cary, North Carolina, USA).

    Post-hoc analysis

    Patients were divided into those who had neuropathic pain as an indication of PNS implantation and those who had non-neuropathic pain as an indication of PNS implantation. Additionally, patients were divided into those who had chronic pain at other sites outside of the distribution of PNS implantation and those who had chronic pain only in the distribution of PNS implantation. Mixed-effects linear regression models as described previously were used to compare NRS pain intensity scores and OME utilization over time between these subgroups.

    Results

    Baseline characteristics

    This retrospective chart review was comprised 126 unique patients who underwent 158 separate PNS procedures (figure 1). Baseline characteristics are reported in table 1.

    Figure 1
    Figure 1

    Consort diagram showing patient population at each study time point (baseline, 3-, 6-, 12-, 24-month follow-up).

    View this table:
    Table 1

    Baseline characteristics of overall, temporary implant, and permanent implant cohorts

    The mean age of this population was 55.9±17.6 years. 59 (46.8%) patients were male and the average BMI was 29.2±6.5 kg/m2. 75 patients (59.5%) had never smoked tobacco, 31 (24.6%) were former smokers, and 20 (15.9%) were current smokers at the time of implantation. Eight patients (6.3%) reimbursed medical expenses for PNS implantation using worker’s compensation. 38 patients (30.2%) had a medical history of anxiety, 47 (37.3%) had depression, 16 (12.7%) had diabetes, and four (3.2%) had fibromyalgia. 44 patients (34.9%) used opioids and 80 (63.5%) used neuropathic medications prior to implantation. 120 patients (95.2%) received a preimplantation diagnostic block. The baseline pain score for all included patients was 7.7±1.51.

    69 patients (54.8%) received only temporary PNS implants while 57 (45.2%) received a permanent PNS implant. 18 patients underwent permanent PNS implantation after trying a temporary PNS implant first. Three patients underwent placement of multiple permanent implants during the course of the study period, one receiving a more distal implant 1 year after the first in the same distribution due to decreased coverage and two receiving bilateral implants (ulnar nerves within 1 month of each other and intercostal nerves 1 year apart). Seven patients in the temporary implant group underwent multiple temporary implants during the course of the study. Five of these patients underwent re-implantation within 1–2 months of their first temporary implant (two patients for loss of efficacy, two for lead fracture, and one for lead migration). The last two patients underwent additional temporary implantation for loss of efficacy at 6 and 12 months from first implant. The most common indications for PNS implantation were neuralgia in a peripheral distribution (92 patients, 73.0%), meralgia paresthetica (11 patients, 8.7%), and occipital neuralgia (eight patients, 6.3%). The most common targets for PNS implantation were the ulnar nerve (14 patients, 9.4%), sural nerve (13 patients, 8.7%), and the lateral femoral cutaneous nerve (12 patients, 8.1%) (online supplemental table 1).

    Supplemental material

    The permanent implant group had a significantly higher number of patients with fibromyalgia (four in permanent implant group vs zero in temporary implant group, p=0.04) and a significantly higher percentage of patients who underwent a preimplant diagnostic nerve block (100% in the permanent PNS group vs 91.3% in the temporary PNS group, p=0.03). There was a significant difference in the indication for PNS implantation (p=0.04), however, no significant differences were seen in pairwise comparisons of individual indications given that with eight comparisons, significance was set at α=0.0063 per the Bonferroni correction (online supplemental table 2). PNS indications of neuralgia in a peripheral distribution and axial low back pain both had p values of 0.01 when comparing temporary and permanent implant groups. There was no significant difference in nerve target or other baseline characteristics between the temporary and permanent PNS groups.

    Primary outcomes

    Figure 2 and table 2 show the mixed-effects regression model-based pain scores and MDs at baseline and at follow-up time points after implantation in the overall, temporary PNS, and permanent PNS cohorts.

    Figure 2
    Figure 2

    Mixed-effects linear regression model pain intensity scores (Numerical Rating Scale 11-point scale) of overall, temporary, and permanent implant cohorts at baseline in addition to 3, 6, and 12 months postimplantation. Error bars represent 95% CI.

    View this table:
    Table 2

    Mixed-effects linear regression model pain intensity scores and mean differences from baseline in the overall, temporary, and permanent implant cohorts

    Compared with baseline, there was a significant reduction in interval pain intensity at 12 months postimplant in the overall (MD −3.0 (95% CI −3.5 to −2.4), p<0.0001), temporary PNS (MD −3.0 (95% CI −3.9 to −2.2), p<0.0001), and permanent PNS cohorts (MD −3.0 (95% CI −3.7 to −2.3, p<0.0001). The MD values for all three comparisons surpassed the MCID threshold for pain intensity (ie, 2.0 on a 0–10 pain NRS).18 There was no difference in the change in interval pain intensity at 12 months postimplant between the temporary and permanent PNS cohorts (MD 0.0 (95% CI −1.1 to 1.0), p=1.00).

    Secondary outcomes

    Change in pain intensity at 3, 6, and 24 months postimplantation with comparison of temporary and permanent implant groups

    Compared with baseline, there was a significant reduction in pain intensity in the overall, temporary PNS, and permanent PNS cohorts at all other follow-up time points (3, 6, and 24 months; table 2). The MD values for these comparisons surpassed the MCID threshold for pain intensity (ie, 2.0 on a 0–10 pain NRS).18 There was no difference seen in pain intensity between temporary and permanent PNS cohorts at all time points (table 2).

    Opioid utilization and change at 6 and 12 months postimplantation

    When opioid use was analyzed as a binary categorical variable, there was no difference in the percentage of participants taking opioids at 6 months compared with baseline in the overall cohort (28.8% vs 34.9%, p=0.18), temporary PNS cohort (31.9% vs 37.7%, p=0.33), and permanent PNS cohort (25.0% vs 31.6%, p=0.34) (online supplemental table 3). Similarly, there was no difference in this outcome at 12 months compared to baseline in the overall cohort (28.0% vs 34.9%, p=0.19), temporary PNS cohort (32.3% vs 37.7%, p=0.39), and permanent PNS cohort (22.6% vs 31.6%, p=0.32).

    When opioid use was analyzed in terms of the amount consumed on a daily basis (OME, mg/day), there was no change in OME utilization at 6 months compared with baseline in the overall (MD −2.1 (95% CI −8.6 to 4.5), p=0.97), temporary (MD –3.7 (95% CI −33.0 to 25.7), p=1.00), and permanent PNS cohorts (MD –9.4 (95% CI −44.6 to 25.7), p=0.99) (table 3). Similarly, there was no change in this outcome at 12 months compared with baseline in the overall (MD –1.2 (95% CI −8.0 to 5.6), p=1.00), temporary (MD –4.1 (95% CI −34.0 to 25.8), p=1.00), and permanent PNS cohorts (MD –7.2 (95% CI −44.0 to 29.6), p=1.00). There were no differences between OME utilization in the temporary versus permanent implant cohorts at baseline, 6 months, and 12 months postimplant (table 3).

    View this table:
    Table 3

    Mean oral morphine equivalent (OME) utilization in overall, temporary implant, and permanent implant cohorts in patients who were using opioids at any time point during study

    Complications and adverse events

    Overall, 56 complications were reported in 158 (35.44%) PNS implant procedures (online supplemental table 4). The most common complication was skin reactions or irritation, which occurred with 22 implants (13.92%). Lead fractures occurred in 15 implants (9.49%), 14 of which occurred with temporary PNS implants. The lead fracture rate was significantly higher in the temporary PNS cohort compared with the permanent PNS cohort (14.29% vs 1.67%, p=0.01). The majority of lead fractures were noted or occurred during removal of the lead after the trial period, without a loss of efficacy. Other less frequent complications included lead migration in 11 implants (6.96%), worsening pain after implantation in four implants (2.53%), and site infections in three implants (1.90%). One patient had a seroma at the implantation site in the permanent implant group (1.67%).

    Post-hoc analysis

    43 patients (34.1%) had a history of chronic pain at sites other than in the distribution of stimulation (eg, metastatic cancer, chronic neck pain with PNS implantation in the lower extremity). When comparing patients who had chronic pain at a site other than that addressed by PNS and patients with chronic pain primarily in the distribution of stimulation, there was no difference in pain intensity scores or daily OME utilization at any follow-up time point (online supplemental tables 5 and 6). 116 patients (92.1%) had neuropathic indications for PNS while 10 patients (7.9%) had non-neuropathic indications for PNS. When comparing patients with neuropathic indications and patients with non-neuropathic indications for PNS, there was no difference in pain intensity scores or daily OME utilization at any follow-up time point (online supplemental tables 7 and 8).

    Discussion

    In this 2-year multicenter longitudinal retrospective cohort study, we observed significant reductions in pain intensity up to 24 months after temporary and permanent PNS implantation. This highlights that both temporary and permanent PNS implants may be effective and durable treatment modalities for chronic pain. While improvement in pain intensity is shown, the significant patient loss to follow-up, potential adverse events (eg, lead fracture), and lack of change in opioid utilization over time make it difficult to ensure that the benefits of PNS implantation outweigh the risks. Prospective, long-term trials are needed to provide further evidence of the long-term effectiveness of PNS.

    An important finding in this study is that temporary PNS implants may result in durable pain relief extending beyond the removal of the temporary lead. Despite being explanted after 60 days, temporary PNS led to reductions in pain intensity for up to 24 months. This prolonged relief is concordant with the published literature highlighting the durability of temporary PNS implants.6 16 The exact mechanism of PNS, as with SCS and other forms of neuromodulation, is unknown, however, the “gate control theory” is the leading concept on what provides the immediate therapeutic effect of neuromodulation.10 14 In contrast, prolonged relief after temporary PNS removal is thought to be due to long-term modulation and inhibition of central neuroplasticity.16 20 21 As described in the prospective trial on temporary PNS in treatment of postamputation pain by Gilmore et al, PNS not only may stimulate A-beta afferent fibers as described by the gate control theory, but it may also stimulate efferent nerve fibers resulting in muscle activation.6 This activation may generate proprioceptive afferent signals, impacting the excitability of neurons in the pain pathway. During the temporary PNS trial, this decreased neuronal excitability may reset the cycle of central sensitization, partially explaining long-term relief after implant removal.6 16 22 23 This carryover effect has not been observed in the same capacity in SCS patients. A study by Meier et al found that in patients who were experiencing benefit from their SCS treatment, their pain returned to baseline in a median of 5 hours after the device was turned off.24 The carryover effect in our PNS study may be longer due to regular close follow-ups for reprogramming visits to ensure capture in anticipation of temporary implant removal. It is also possible that a portion of patients in this study had pain that improved by the natural course of their disease process, resulting in a perceived carryover effect.

    Though we did not find a change in opioid use after PNS implantation, the favorable improvement in pain intensity scores highlights that PNS may be beneficial for chronic pain. A possible reason why this discrepancy in opioid consumption may exist is that approximately one-third of patients included in this study had chronic pain outside of the distribution of PNS coverage. While our implants were typically placed in areas of the greatest pain or areas amenable to PNS therapy, there was still likely a component of chronic pain originating from other regions of the body for which opioids were used. Pain scores specifically in the distribution of PNS implantation were recorded in follow-up questionnaires or during office visits. However, in the post-hoc analysis, when patients were separated by those who had a history of chronic pain at a site other than that targeted by PNS and those who primarily had chronic pain in the distribution of stimulation, there was no difference in OME utilization at 12 months. The majority (65%) of the included patients were not on any opioids at baseline for chronic pain, therefore making it challenging to identify a significant change in opioid consumption.

    Notable differences were observed when comparing outcomes between temporary and permanent PNS cohorts. There was a significant difference in PNS indication between temporary and permanent implant groups, however, there were no significant differences found in pairwise comparisons per the Bonferroni correction. Additionally, the rate of lead fracture was significantly higher in the temporary implant group compared with the permanent implant group, potentially reflecting limitations in hardware design. However, nearly all of the lead fractures in the temporary implants were discovered during scheduled lead removal without an apparent loss of effectiveness during the implant period. Temporary PNS implants have been shown to have anywhere from a 3% to 21% incidence of lead fracture seen at the time of removal.25–28 The manufacturer of the temporary leads that we used developed a new lead design in September 2022, after the period of our study, with lead structural integrity being one of the main factors addressed. Retained tip fragments of the leads used in this study are MR Conditional (1.5-Tesla static magnetic field, maximum spatial field gradient of 2000 gauss/cm, and maximum MR system reported whole body averaged specific absorption rate of 2 W/kg).

    This study has several strengths. First, the study provides a real-world analysis of a large sample size with over 100 unique patients and over 150 individual implants, which is lacking in the current literature on PNS. Additionally, this analysis includes outcome data up to 24 months after implantation in both temporary and permanent implant populations, which to the authors’ best knowledge has not been previously reported. The present study also analyzes multiple relevant outcomes besides pain intensity, including opioid consumption and adverse events.

    This study also has notable limitations. First, this is a retrospective study, which decreases the standardization of reported outcomes and introduces reporting bias. Second, given the non-randomized non-placebo-controlled study design, our results could represent the natural improvement of the pain process or from other therapies that may not have been accounted for in the chart review. Third, physical functionality metrics were unable to be analyzed due to the lack of standardized recording of this outcome in the electronic medical record. Also, clinical heterogeneity is observed in this study with different clinical indications for PNS implantation, different implanting physicians, and different baseline characteristics. Additionally, we allowed patients who received multiple permanent or temporary implants to be included, which potentially could affect outcome data since the baseline time point was set at the timing of the first implant. However, only two patients in the permanent implant group and two patients in the temporary implant group had implants placed greater than 6 months apart. Therefore, we do not believe that this significantly affected our results. Finally, we do note a high dropout rate of participants with unavailable data at longer time points. It is possible patients with suboptimal outcomes did not return for follow-ups resulting in a reporting bias. The substantial loss to follow-up in addition to the insignificant change in opioid utilization makes it difficult to truly determine the long-term effectiveness of PNS, particularly at the 24-month time point. However, by using a mixed effects regression model we believe that our analysis is appropriate for the available data.

    There are future opportunities in PNS research. Larger prospective, placebo-controlled trials are warranted to provide high-quality evidence of the long-term efficacy of PNS implants. As government and commercial payers become stricter on approving reimbursement for interventional pain procedures, it is imperative that high-quality research on PNS therapy is conducted and published.

    Conclusion

    This retrospective multicenter analysis highlights that both temporary and permanent PNS implants may be effective for chronic pain refractory to conventional medical management for upwards of 24 months. Further, this improvement in pain appears to be clinically meaningful for patients in the short-term and long-term. The main limitation of this study is the substantial loss to follow-up, particularly at the 24-month time point. Therefore, until more long-term data from large-scale prospective studies are completed, physicians need to remain cautious when describing the durability of PNS treatment to patients, particularly regarding temporary implants.

    Data availability statement

    All data relevant to the study are included in the article or uploaded as supplementary information.

    Ethics statements

    Patient consent for publication

    Ethics approval

    This study involves human participants but the study protocol was approved by the Mayo Clinic Institutional Review Board, who assigned it exempt status (IRB#:23-012089) and waived the need for consent exempted this study. Participants gave informed consent to participate in the study before taking part.

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    Footnotes

    • X @DrAnujBhatia

    • Contributors TW, NH, AB, ME, AEK, MP, MA-R, SJ, and RSD contributed to the data acquisition, data analysis, table and figure generation, manuscript drafts and revisions, and final approval of the manuscript. RSD is the guarantor.

    • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

    • Competing interests AB has received consultancy fees from Medtronic and Bioventus. His institution has also received funding for studies to track outcomes of neuromodulation therapies from Medtronic. RSD has received investigator-initiated grant funding paid to his institution from Nevro Corp and Saol Therapeutics.

    • Provenance and peer review Not commissioned; externally peer reviewed.

    • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.