Modulations in high-density EEG during the suppression of phantom-limb pain with neurostimulation in upper limb amputees.

Phantom limb pain (PLP) is a distressing and persistent sensation that occurs after the amputation of a limb. While medication-based treatments have limitations and adverse effects, neurostimulation is a promising alternative approach whose mechanism of action needs research, including electroencephalographic (EEG) recordings for the assessment of cortical manifestation of PLP relieving effects. Here we collected and analyzed high-density EEG data in 3 patients (P01, P02, and P03). Peripheral nerve stimulation suppressed PLP in P01 but was ineffective in P02. In contrast, transcutaneous electrical nerve stimulation was effective in P02. In P03, spinal cord stimulation was used to suppress PLP. Changes in EEG oscillatory components were analyzed using spectral analysis and Petrosian fractal dimension. With these methods, changes in EEG spatio-spectral components were found in the theta, alpha, and beta bands in all patients, with these effects being specific to each individual. The changes in the EEG patterns were found for both the periods when PLP level was stationary and the periods when PLP was gradually changing after neurostimulation was turned on or off. Overall, our findings align with the proposed roles of brain rhythms in thalamocortical dysrhythmia or disruption of cortical excitation and inhibition which has been linked to neuropathic pain. The individual differences in the observed effects could be related to the specifics of each patient's treatment and the unique spectral characteristics in each of them. These findings pave the way to the closed-loop systems for PLP management where neurostimulation parameters are adjusted based on EEG-derived markers.

Focused ultrasound excites action potentials in mammalian peripheral neurons in part through the mechanically gated ion channel PIEZO2.

Neurons of the peripheral nervous system (PNS) are tasked with diverse roles, from encoding touch, pain, and itch to interoceptive control of inflammation and organ physiology. Thus, technologies that allow precise control of peripheral nerve activity have the potential to regulate a wide range of biological processes. Noninvasive modulation of neuronal activity is an important translational application of focused ultrasound (FUS). Recent studies have identified effective strategies to modulate brain circuits; however, reliable parameters to control the activity of the PNS are lacking. To develop robust noninvasive technologies for peripheral nerve modulation, we employed targeted FUS stimulation and electrophysiology in mouse ex vivo skin-saphenous nerve preparations to record the activity of individual mechanosensory neurons. Parameter space exploration showed that stimulating neuronal receptive fields with high-intensity, millisecond FUS pulses reliably and repeatedly evoked one-to-one action potentials in all peripheral neurons recorded. Interestingly, when neurons were classified based on neurophysiological properties, we identified a discrete range of FUS parameters capable of exciting all neuronal classes, including myelinated A fibers and unmyelinated C fibers. Peripheral neurons were excited by FUS stimulation targeted to either cutaneous receptive fields or peripheral nerves, a key finding that increases the therapeutic range of FUS-based peripheral neuromodulation. FUS elicited action potentials with millisecond latencies compared with electrical stimulation, suggesting ion channel­mediated mechanisms. Indeed, FUS thresholds were elevated in neurons lacking the mechanically gated channel PIEZO2. Together, these results demonstrate that transcutaneous FUS drives peripheral nerve activity by engaging intrinsic mechanotransduction mechanisms in neurons [B. U. Hoffman, PhD thesis, (2019)].

Motor point stimulation activates fewer Ia-sensory nerves than peripheral nerve stimulation in human soleus muscle.

Peripheral nerve stimulation (PNS) and motor point stimulation (MPS) are noninvasive techniques used to induce muscle contraction, aiding motor function restoration in individuals with neurological disorders. Understanding sensory inputs from PNS and MPS is crucial for facilitating neuroplasticity and restoring impaired motor function. Although previous studies suggest that MPS could induce Ia-sensory inputs less than PNS, experimental evidence supporting this claim is insufficient. Here, we implemented a conditioning paradigm combining transcutaneous spinal cord stimulation (tSCS) with PNS or MPS to investigate their Ia-sensory inputs. This paradigm induces postactivation depression of spinal reflexes associated with transient decreases in neurotransmitter release from Ia-afferent terminals, allowing us to examine the Ia-sensory input amount from PNS and MPS based on the depression degree. We hypothesized that MPS would induce less postactivation depression than PNS. Thirteen individuals underwent MPS and PNS on the soleus muscle as conditioning stimuli, with tSCS applied to the skin between the spinous processes (L1-L2) as test stimuli. PNS- and MPS-conditioned spinal reflexes were recorded at five interstimulus intervals (ISIs) and four intensities. Results revealed that all PNS conditioning showed significant decreases in spinal reflex amplitudes, indicating postactivation depression. Furthermore, PNS conditioning exhibited greater depression for shorter ISIs and higher conditioning intensities. In contrast, MPS conditioning demonstrated intensity-dependent depression, but without all-conditioning depression and clear ISI dependency as seen in PNS conditioning. In addition, PNS induced significantly greater depression than MPS across most conditions. Our findings provide experimental evidence supporting the conclusion that MPS activates Ia-sensory nerves less than PNS.NEW & NOTEWORTHY Peripheral nerve stimulation (PNS) and motor point stimulation (MPS) induce neuroplasticity, but differences in their effects on Ia-sensory inputs are unclear. We investigated their Ia-sensory inputs using a conditioning paradigm with spinal reflexes. Results showed that PNS conditioning significantly inhibited spinal reflexes than MPS conditioning, indicating greater postactivation depression due to Ia-sensory nerve activation. These findings provide experimental evidence that MPS activates Ia-sensory nerves to a lesser extent than PNS, enhancing our understanding of neuroplasticity.

Effects of auricular vagus nerve stimulation and electrical earlobe stimulation on motor-evoked potential changes induced by paired associative stimulation.

Paired associative stimulation (PAS) is a combination of transcranial magnetic stimulation (TMS) and peripheral nerve stimulation (PNS). PAS can induce long-term potentiation (LTP)-like plasticity in humans, manifested as motor-evoked potential (MEP) enhancement. We have developed a variant of PAS ("high-PAS"), which consists of high-frequency PNS and high-intensity TMS and targets spinal plasticity and promotes rehabilitation after spinal cord injury (SCI). Vagus nerve stimulation (VNS) promotes LTP-like plasticity and enhances recovery in SCI and stroke in humans and animals when combined with repetitive motor training. We combined high-PAS with simultaneous noninvasive transcutaneous auricular VNS (aVNS) to determine if aVNS enhances the extent of PAS-induced MEP amplitude increase. Sixteen healthy participants were stimulated for 20 min in four different sessions (PAS, PAS + aVNS, PAS + shamVNS, and aVNS) in a randomized single-blind setup. MEPs were measured before, immediately after, and at 30, 60, and 90 min post-stimulation. Stimulation protocols with PAS significantly potentiated MEPs (p = 0.005) when compared with aVNS (p = 0.642). Although not significant, MEP enhancement observed after PAS (43.5%) is further increased by aVNS (49.7%) and electrical earlobe stimulation (63.9%). Our aVNS setup failed to significantly enhance the effect of PAS, but sham VNS revealed a trend towards enhanced plasticity. Optimization of auricular VNS stimulation setup is required for possible tests of patients with SCI.

Short-latency afferent inhibition is reduced in people with multiple sclerosis during fatiguing muscle contractions.

Understanding how inhibitory pathways influence motor cortical activity during fatiguing contractions may provide valuable insight into mechanisms associated with multiple sclerosis (MS) muscle activation. Short-latency afferent inhibition (SAI) reflects inhibitory interactions between the somatosensory cortex and the motor cortex, and although SAI is typically reduced with MS, it is unknown how SAI is regulated during exercise-induced fatigue. The current study examined how SAI modulates motor evoked potentials (MEPs) during fatiguing contractions. Fourteen people with relapsing-remitting MS (39 ± 6 years, nine female) and 10 healthy individuals (36 ± 6 years, six female) participated. SAI was induced by stimulation of the median nerve that was paired with TMS over the motor representation of the abductor pollicis brevis. A contraction protocol was employed that depressed force generating capacity using a sustained 3-min 15% MVC, immediately followed by a low-intensity (15% MVC) intermittent contraction protocol so that MEP and SAI could be measured during the rest phases of each duty cycle. Similar force, electromyography and MEP responses were observed between groups. However, the MS group had significantly reduced SAI during the contraction protocol compared to the healthy control group (p < .001). Despite the MS group reporting greater scores on the Fatigue Severity Scale and Modified Fatigue Impact Scale, these scales did not correlate with inhibitory measures. As there were no between-group differences in SSEPs, MS-related SAI differences during the fatiguing contractions were most likely associated with disease-related changes in central integration.

Experimental validation of a PNS-optimized whole-body gradient coil.

PURPOSE: Peripheral nerve stimulation (PNS) limits the usability of state-of-the-art whole-body and head-only MRI gradient coils. We used detailed electromagnetic and neurodynamic modeling to set an explicit PNS constraint during the design of a whole-body gradient coil and constructed it to compare the predicted and experimentally measured PNS thresholds to those of a matched design without PNS constraints. METHODS: We designed, constructed, and tested two actively shielded whole-body Y-axis gradient coil winding patterns: YG1 is a conventional symmetric design without PNS-optimization, whereas YG2's design used an additional constraint on the allowable PNS threshold in the head-imaging landmark, yielding an asymmetric winding pattern. We measured PNS thresholds in 18 healthy subjects at five landmark positions (head, cardiac, abdominal, pelvic, and knee). RESULTS: The PNS-optimized design YG2 achieved 46% higher average experimental thresholds for a head-imaging landmark than YG1 while incurring a 15% inductance penalty. For cardiac, pelvic, and knee imaging landmarks, the PNS thresholds increased between +22% and +35%. For abdominal imaging, PNS thresholds did not change significantly between YG1 and YG2 (-3.6%). The agreement between predicted and experimental PNS thresholds was within 11.4% normalized root mean square error for both coils and all landmarks. The PNS model also produced plausible predictions of the stimulation sites when compared to the sites of perception reported by the subjects. CONCLUSION: The PNS-optimization improved the PNS thresholds for the target scan landmark as well as most other studied landmarks, potentially yielding a significant improvement in image encoding performance that can be safely used in humans.

Minimizing electric fields and increasing peripheral nerve stimulation thresholds using a body gradient array coil.

PURPOSE: To demonstrate the performance of gradient array coils in minimizing switched-gradient-induced electric fields (E-fields) and improving peripheral nerve stimulation (PNS) thresholds while generating gradient fields with adjustable linearity across customizable regions of linearity (ROLs). METHODS: A body gradient array coil is used to reduce the induced E-fields on the surface of a body model by modulating applied currents. This is achieved by performing an optimization problem with the peak E-field as the objective function and current amplitudes as unknown variables. Coil dimensions and winding patterns are fixed throughout the optimization, whereas other engineering metrics remain adjustable. Various scenarios are explored by manipulating adjustable parameters. RESULTS: The array design consistently yields lower E-fields and higher PNS thresholds across all scenarios compared with a conventional coil. When the gradient array coil generates target gradient fields within a 44-cm-diameter spherical ROL, the maximum E-field is reduced by 10%, 18%, and 61% for the X, Y, and Z gradients, respectively. Transitioning to a smaller ROL (24 cm) and relaxing the gradient linearity error results in further E-field reductions. In oblique gradients, the array coil demonstrates the most substantial reduction of 40% in the Z-Y direction. Among the investigated scenarios, the most significant increase of 4.3-fold is observed in the PNS thresholds. CONCLUSION: Our study demonstrated that gradient array coils offer a promising pathway toward achieving high-performance gradient coils regarding gradient strength, slew rate, and PNS thresholds, especially in scenarios in which linear magnetic fields are required within specific target regions.

Blood flow effects of percutaneous peripheral nerve stimulation. A blinded, randomized clinical trial.

BACKGROUND: The vasculature function is mainly regulated by the autonomic nervous system. Importantly, the sensory-motor nervous system also innervates peripheral vessels and has the capacity to modulate vascular tone. Here we investigated the effects of electrical stimulation of a mixed nerve trunk on blood flow in deep arteries and muscle perfusion. Our hypothesis is that stimulation of a mixed nerve can modify blood flow. METHODS: Twenty-nine healthy participants were included into a randomized-crossover and blinded clinical trial. Each subject received a placebo and two percutaneous peripheral nerve stimulation (pPNS) protocols on the median nerve: Pain Threshold continuous Low Frequency (PT-cLF) and Sensory Threshold burst High Frequency (ST-bHF). Blood flow was then assessed bilaterally using Power Doppler Ultrasonography at the main arteries of the arm, and blood perfusion at the forearm muscles. Afterwards, blood flow was quantified using a semi-automatized software, freely shared here. RESULTS: Placebo, consisting in needle insertion, produced an immediate and generalized reduction on peak systolic velocity in all arteries. Although nerve stimulation produced mainly no effects, some significant differences were found: both protocols increased the relative perfusion area of the forearm muscles, the ST-bHF protocol prevented the reduction in peak systolic velocity and TAMEAN of the radial artery produced by the control protocol and PT-cLF produced a TAMEAN reduction of the ulnar artery. CONCLUSIONS: Therefore, the arterial blood flow in the arm is mainly impervious to the electrical stimulation of the median nerve, composed by autonomic and sensory-motor axons, although it produces mild modifications in the forearm muscles perfusion.

Ischemic preconditioning increases spinal excitability and voluntary activation during maximal plantar flexion contractions in men.

The enigmatic benefits of acute limb ischemic preconditioning (IP) in enhancing muscle force and exercise performance have intrigued researchers. This study sought to unravel the underlying mechanisms, focusing on increased neural drive and the role of spinal excitability while excluding peripheral factors. Soleus Hoffmann (H)-reflex /M-wave recruitment curves and unpotentiated supramaximal responses were recorded before and after IP or a low-pressure control intervention. Subsequently, the twitch interpolation technique was applied during maximal voluntary contractions to assess conventional parameters of neural output. Following IP, there was an increase in both maximum normalized force and voluntary activation (VA) for the plantar flexor group, with negligible peripheral alterations. Greater benefits were observed in participants with lower VA levels. Despite greater H-reflex gains, soleus volitional (V)-wave and sEMG amplitudes remained unchanged. In conclusion, IP improves muscle force via enhanced neural drive to the muscles. This effect appears associated, at least in part, to reduced presynaptic inhibition and/or increased motoneuron excitability. Furthermore, the magnitude of the benefit is inversely proportional to the skeletal muscle's functional reserve, making it particularly noticeable in under-recruited muscles. These findings have implications for the strategic application of the IP procedure across diverse populations.

Peripheral Nerve Stimulation in Postoperative Analgesia: A Narrative Review.

PURPOSE OF REVIEW: Recent research has shown the effectiveness of peripheral nerve stimulators (PNS) in managing chronic pain conditions. Ongoing studies aim to explore its potential application in treating acute postoperative pain states. The purpose of this systematic review is to assess the role of PNS in providing relief for postoperative pain. RECENT FINDINGS: Clinical studies investigating the use of peripheral nerve stimulators (PNS) for analgesia following various surgeries, such as total knee arthroplasty, anterior cruciate ligament repair, ankle arthroplasty, rotator cuff repair, hallux valgus correction, and extremity amputation, have shown promising results. Lead placement locations include the brachial plexus, sciatic, femoral, tibial, genicular, perineal, sural, radial, median, and ulnar nerves. These studies consistently report clinically significant reductions in pain scores, and some even indicate a decrease in opioid consumption following PNS for postoperative pain. PNS involves the subcutaneous placement of electrode leads to target peripheral nerve(s) followed by delivery of an electric current via an external pulse generator. While the precise mechanism is not fully understood, the theory posits that PNS modulates electrical stimulation, hindering the signaling of nociceptive pain. PNS presents itself as an alternative to opioid therapy, holding promise to address the opioid epidemic by offering a nonpharmacologic approach for both acute and chronic pain states.

Literature Review: Mechanism, Indications, and Clinical Efficacy of Peripheral Nerve Stimulators in Lower Extremity Pain.

PURPOSE OF REVIEW: Lower extremity pain is deemed by Center for Disease Control and Prevention (CDC) to be a significant source of chronic pain in adults. If not appropriately managed, patients are subjected to risks of prolonged musculoskeletal dysfunction, disruption to quality of life, and elevated healthcare expenditures. Peripheral nerve stimulation (PNS) has shown great potential in recent years demonstrating efficacy in multiple diagnoses ranging from acute post-surgical pain to complex regional pain syndrome (CRPS). This study seeks to delineate efficacy of peripheral neuromodulation in the context of chronic lower extremity pain. RECENT FINDINGS: Prevailing clinical studies demonstrate evidence levels ranging from II to V (Oxford Centre of Level of Evidence) in lower limb PNS, attaining positive outcomes in pain scores, opioid use, and quality of life measures. Nerves most frequently targeted are the sciatic and femoral nerves with post-amputation pain and CRPS most commonly investigated for efficacy. PNS is a promising therapeutic modality demonstrated to be effective for a variety of nociceptive and neuropathic pain conditions in the lower extremity. PNS offers chronic pain physicians a powerful tool in the multi-modal management of lower limb chronic pain.

Peripheral Nerve Stimulation for Pain Management: A Survey of Clinical Practice Patterns.

BACKGROUND: Clinical interest in and utilization of peripheral nerve stimulation (PNS) for treating chronic pain has significantly increased in recent years owing to its potential for providing analgesia and improved function and quality of life in comparison with pharmacologic treatments. However, the relative infancy of PNS-specific systems and limited clinical practice guidance likely contribute to significant variation in PNS utilization patterns. OBJECTIVES: We sought to conduct a survey study to characterize PNS-specific clinical practices and propose the next steps in standardizing key practices for PNS utilization. MATERIALS AND METHODS: A 19-question survey exploring PNS-relevant clinical parameters was disseminated online to pain physicians in practice. Descriptive statistics were used to summarize results. RESULTS: A total of 94 responses were collected. Regarding patient selection, most practitioners would apply PNS to treat nociceptive pain from major joint osteoarthritis (77.7%) and chronic low back pain (64.9%), but not for axial neck pain (50.0%). In contrast, most would apply PNS to treat neuropathic pain from peripheral neuralgia (94.7%), pericranial neuralgia (77.7%), and cancer-related neuropathic pain (64.9%). In treating complex regional pain syndrome, most practitioners would apply PNS before all other forms of neuraxial neuromodulation (>50% for each form). Similarly, for treating nonsurgical low back pain, most would apply PNS before neuraxial neuromodulation (>50% for each form) but not before radiofrequency ablation (19.2%). Most routinely performed nerve blocks before PNS, mainly to confirm anatomical coverage (84.0%), and regarded a 50% to 75% interquartile range as the minimum analgesic benefit required before proceeding with PNS. Regarding nerve target selection for treating complex regional pain syndrome of the wrist/hand or ankle/foot, or knee osteoarthritis, we observed a very wide variance of PNS target locations and discrete nerves. Regarding "minor" adverse events, most reported not changing PNS utilization on encountering skin/soft tissue reactions (85.1%), minor infections (76.6%), or lead migration/loss of efficacy (50.0%). In comparison, most reported reducing PNS utilization on encountering skin erosion (58.5%), major infections (58.5%), or lead fractures (41.5%). CONCLUSIONS: There is significant practice variation regarding the utilization of PNS across numerous key clinical considerations. Future research that explores the reasons driving these differences might help optimize patient selection, target selection, periprocedural management, and ultimately outcomes.

Randomized Placebo-Controlled Trial of 60-Day Percutaneous Peripheral Nerve Stimulation Treatment Indicates Relief of Persistent Postoperative Pain, and Improved Function After Knee Replacement.

OBJECTIVES: Total knee arthroplasty (TKA) is an effective surgery for end-stage knee osteoarthritis, but chronic postoperative pain and reduced function affect up to 20% of patients who undergo such surgery. There are limited treatment options, but percutaneous peripheral nerve stimulation (PNS) is a promising nonopioid treatment option for chronic, persistent postoperative pain. The objective of the present study was to evaluate the effect of a 60-day percutaneous PNS treatment in a multicenter, randomized, double-blind, placebo-controlled trial for treating persistent postoperative pain after TKA. MATERIALS AND METHODS: Patients with postoperative pain after knee replacement were screened for this postmarket, institutional review board-approved, prospectively registered (NCT04341948) trial. Subjects were randomized to receive either active PNS or placebo (sham) stimulation. Subjects and a designated evaluator were blinded to group assignments. Subjects in both groups underwent ultrasound-guided placement of percutaneous fine-wire coiled leads targeting the femoral and sciatic nerves on the leg with postoperative pain. Leads were indwelling for eight weeks, and the primary efficacy outcome compared the proportion of subjects in each group reporting ≥50% reduction in average pain relative to baseline during weeks five to eight. Functional outcomes (6-minute walk test; 6MWT and Western Ontario and McMaster Universities Osteoarthritis Index) and quality of life (Patient Global Impression of Change) also were evaluated at end of treatment (EOT). RESULTS: A greater proportion of subjects in the PNS groups (60%; 12/20) than in the placebo (sham) group (24%; 5/21) responded with ≥50% pain relief relative to baseline (p = 0.028) during the primary endpoint (weeks 5-8). Subjects in the PNS group also walked a significantly greater distance at EOT than did those in the placebo (sham) group (6MWT; +47% vs -9% change from baseline; p = 0.048, n = 18 vs n = 20 completed the test, respectively). Prospective follow-up to 12 months is ongoing. CONCLUSIONS: This study provides evidence that percutaneous PNS decreases persistent pain, which leads to improved functional outcomes after TKA at EOT.

Ultrasound-Guided Percutaneous Peripheral Nerve Stimulation of C2 Dorsal Root Ganglion for the Treatment of Refractory Atypical Facial Pain: A Technical Report and Case Series.

BACKGROUND: Chronic craniofacial pain can be difficult to manage clinically. This technical report documents the peripheral nerve stimulation of the C2 dorsal root ganglion as an effective modality to treat refractory atypical facial pain. MATERIALS AND METHODS: In this case series, three patients with chronic refractory atypical facial pain and p >50% pain relief following diagnostic C2 dorsal root ganglion blockade underwent ultrasound-guided percutaneous placement of a peripheral nerve stimulator adjacent to the C2 dorsal root ganglion. Patients were then observed clinically and monitored for improvement in symptoms and adverse events. RESULTS: Three patients underwent peripheral nerve stimulator placement. At follow-up, there were no reported adverse events, and all patients reported satisfactory improvement in pain. CONCLUSION: The neuromodulation of C2 dorsal root ganglion via ultrasound-guided percutaneously implanted peripheral nerve stimulator is a novel and potentially effective approach for the management of chronic refractory craniofacial pain.

Use of Temporary Percutaneous Peripheral Nerve Stimulation in an Oncologic Population: A Retrospective Review.

OBJECTIVES: Patients with an underlying cancer diagnosis may experience pain from many sources. Temporary, percutaneous peripheral nerve stimulation (PNS) is a minimally invasive procedure that can control pain in those who have failed conservative management. The purpose of this retrospective review is to show the use of PNS in managing pain in the oncologic setting. MATERIALS AND METHODS: Temporary, percutaneous PNS was placed under fluoroscopic or ultrasound guidance for 15 patients at a cancer pain facility. Cases were grouped by subtypes of cancer pain (ie, tumor-related, treatment-related, cancer-associated conditions, and cancer-independent). Before PNS, patients were refractory to medical management or previous interventional treatments. Patients were observed with routine clinic visits to monitor pain levels via visual analog scale (VAS) and quality-of-life measures. PNS was removed after the indicated 60-day treatment period. RESULTS: This retrospective review presents ten successful cases of oncologic-related pain treated with PNS. Patients with subtypes of pain that were tumor related, from cancer-associated conditions, and cancer independent all experienced a similar degree of pain relief. However, patients with cancer-treatment-related pain experienced the least analgesia from PNS. We also present six cases in which PNS did not provide adequate pain relief. CONCLUSION: PNS is an emerging technology in neuromodulation that may be useful in managing pain, especially in the oncologic population. Patients with cancer-related and non-cancer-related pain localized to a specific nerve distribution should be considered appropriate candidates for PNS. Further research is needed to optimize patient selection and indications for PNS in the population with cancer.

Peripheral Nerve Stimulation With a High-Frequency Electromagnetic Coupled Powered Implanted Receiver at the Posterior Tibial Nerve for the Treatment of Chronic Pain in the Foot.

INTRODUCTION: Peripheral neuropathy has several causes, with diabetes being the most common. Conservative management may fail to control pain. Our study aimed at evaluating the use of peripheral nerve stimulation of the posterior tibial nerve for treating peripheral neuropathy. MATERIALS AND METHODS: This was an observational study of 15 patients who received peripheral nerve stimulation at the posterior tibial nerve to treat peripheral neuropathy. Outcomes measured were improvement of pain scores and Patient Global Impression of Change (PGIC) at 12 months compared with before the implant. RESULTS: Mean pain scores with the verbal rating scale were 3 ± 1.8 at >12 months compared with 8.6 ± 1.2 at baseline, a reduction of 65% (p < 0.001). Median satisfaction with the PGIC at >12 months was 7 of 7, with most subjects reporting a 6 (better) or a 7 (a great deal better). CONCLUSION: Peripheral nerve stimulation of the posterior tibial nerve can be a safe and effective modality for treating chronic pain symptoms related to peripheral neuropathy of the foot.

Case Series of Multicontact Peripheral Nerve Stimulation in the Transversus Abdominis Plane for Chronic Abdominal Wall Pain.

OBJECTIVES: Managing abdominal pain can be difficult. This is due to the nonspecific nature of the pain, the multiple etiologies, and the different mechanisms underlying this type of pain. Abdominal wall pain in particular poses its own challenges. Traditionally, chronic abdominal wall pain has been managed with nonopioid analgesics, and in severe cases, opioid therapy has been considered. For patients with chronic abdominal wall pain refractory to medication management, peripheral nerve blocks and spinal cord stimulation also have been trialed with some success. In this study, we present a case series in patients with chronic abdominal wall pain who were treated with a multicontact peripheral nerve stimulation (PNS) system in the transversus abdominis plane (TAP). MATERIALS AND METHODS: This was a single-center, retrospective case series. Data were included from adults with chronic abdominal wall pain whose symptoms were refractory to standard medical management and who underwent a multicontact PNS system placement in the TAP. RESULTS: Four patients met the inclusion criteria. All four patients underwent a multicontact PNS trial lead placement in the TAP. One patient reported no benefit from the trial. The remaining three patients underwent a permanent multicontact PNS system placement in the TAP. CONCLUSIONS: In patients with chronic abdominal wall pain whose symptoms are refractory to conservative medical management, PNS may be an alternative treatment option. As the use of PNS for chronic abdominal wall pain and other fascial planes continues to develop, additional research is necessary to determine optimal placements and specific stimulation parameters.

A Review of the Factors and Outcomes of Institutional Interdisciplinary Neuromodulation Committees: A Multicenter Experience.

INTRODUCTION: Neuromodulation represents one of the more advanced tools in the armamentarium of pain physicians. To optimize neuromodulation patient selection and management, an institutional interdisciplinary neuromodulation committee was created at each of two academic medical centers (University of California Davis [UCD] and Stanford University). The committee aims to collaboratively optimize neuromodulation candidates, to assess and minimize medical and psychologic risks, and to select the best device given a patient's pain condition. In this study, we present the methods and outcome data of the Neuromodulation Committee at the two institutions. MATERIALS AND METHODS: After institutional review board approval, we included all adult patients who were evaluated by the Neuromodulation Committee between 2017 and 2020 at two academic pain clinics. Patients with insufficient data were excluded from the study. A retrospective chart review was completed on 385 UCD and Stanford University patient committee reviews. Data collected from the chart review included demographics (age, sex), committee meeting results (proceed with trial/implant or decline), trial success, and implant rate. RESULTS: Of the 385 patients screened, the committees recommended proceeding with an implantable device (peripheral and neuraxial) in 337 patients (87.5%). Of the 278 patients recommended for neuraxial neuromodulation, 131 underwent trials with percutaneous leads (47.1%). Trials were successful (causing a ≥50% reduction in self-reported pain or improved function) in 108 patients (82.4%). The institutions completed 87 implants of 131 trials, representing a trial-to-permanent ratio of 66.4%. CONCLUSIONS: The Neuromodulation Committee aims to identify optimal patients for neuromodulation, address procedural challenges, decrease adverse events, provide educational context for trainees, and improve patient-related outcomes. Patients who were recommended for neuromodulation and subsequently underwent intervention had high trial success rates for dorsal root ganglion stimulation and spinal cord stimulation. The findings indicate that such an approach can lead to neuromodulation success, especially at academic centers, by combining the expertise of both medical and psychologic professionals.

Five-Year Longitudinal Follow-Up of Restorative Neurostimulation Shows Durability of Effectiveness in Patients With Refractory Chronic Low Back Pain Associated With Multifidus Muscle Dysfunction.

BACKGROUND: Adults with refractory, mechanical chronic low back pain associated with impaired neuromuscular control of the lumbar multifidus muscle have few treatment options that provide long-term clinical benefit. This study hypothesized that restorative neurostimulation, a rehabilitative treatment that activates the lumbar multifidus muscles to overcome underlying dysfunction, is safe and provides relevant and durable clinical benefit to patients with this specific etiology. MATERIALS AND METHODS: In this prospective five-year longitudinal follow-up of the ReActiv8-B pivotal trial, participants (N = 204) had activity-limiting, moderate-to-severe, refractory, mechanical chronic low back pain, a positive prone instability test result indicating impaired multifidus muscle control, and no indications for spine surgery. Low back pain intensity (10-cm visual analog scale [VAS]), disability (Oswestry Disability Index), and quality of life (EuroQol's "EQ-5D-5L" index) were compared with baseline and following the intent-to-treat principle, with a supporting mixed-effects model for repeated measures that accounted for missing data. RESULTS: At five years (n = 126), low back pain VAS had improved from 7.3 to 2.4 cm (-4.9; 95% CI, -5.3 to -4.5 cm; p < 0.0001), and 71.8% of participants had a reduction of ≥50%. The Oswestry Disability Index improved from 39.1 to 16.5 (-22.7; 95% CI, -25.4 to -20.8; p < 0.0001), and 61.1% of participants had reduction of ≥20 points. The EQ-5D-5L index improved from 0.585 to 0.807 (0.231; 95% CI, 0.195-0.267; p < 0.0001). Although the mixed-effects model attenuated completed-case results, conclusions and statistical significance were maintained. Of 52 subjects who were on opioids at baseline and had a five-year visit, 46% discontinued, and 23% decreased intake. The safety profile compared favorably with neurostimulator treatments for other types of back pain. No lead migrations were observed. CONCLUSION: Over a five-year period, restorative neurostimulation provided clinically substantial and durable benefits with a favorable safety profile in patients with refractory chronic low back pain associated with multifidus muscle dysfunction. CLINICAL TRIAL REGISTRATION: The Clinicaltrials.gov registration number for the study is NCT02577354; registration date: October 15, 2016; principal investigator: Christopher Gilligan, MD, Brigham and Women's Hospital, Boston, MA, USA. The study was conducted in Australia (Broadmeadow, New South Wales; Noosa Heads, Queensland; Welland, South Australia; Clayton, Victoria), Belgium (Sint-Niklaas; Wilrijk), The Netherlands (Rotterdam), UK (Leeds, London, Middlesbrough), and USA (La Jolla, CA; Santa Monica, CA; Aurora, CO; Carmel, IN; Indianapolis, IN; Kansas City, KS; Boston, MA; Royal Oak, MI; Durham, NC; Winston-Salem, NC; Cleveland, OH; Providence, RI; Spartanburg, SC; Spokane, WA; Charleston, WV).

Long-Term Treatment of Chronic Postamputation Pain With Bioelectric Nerve Block: Twelve-Month Results of the Randomized, Double-Blinded, Cross-Over QUEST Study.

OBJECTIVE: The multicenter, randomized, double-blinded, active-sham controlled trial (high-freQUEncy nerve block for poST amputation pain [QUEST]) was conducted to show the safety and efficacy of a novel, peripherally placed high-frequency nerve block (HFNB) system in treating chronic postamputation pain (PAP) in patients with lower limb amputations. The primary outcomes from QUEST were reported previously. This study presents the long-term, single-cross-over, secondary outcomes of on-demand HFNB treatment for chronic PAP. MATERIALS AND METHODS: After the three-month randomized period, subjects in the active-sham group were crossed over to receive therapy for 12 months. Subjects self-administered HFNB therapy as needed and reported their pain (numerical rating scale [NRS]; range, 1-10) before and 30 and 120 minutes after each treatment. Pain medication use was reported throughout the study. Pain-days per week and quality of life (QOL) were assessed using the Brief Pain Inventory (BPI). Adverse events (AEs) were recorded for all subjects implanted for 12 months. RESULTS: Of 180 subjects implanted in QUEST, 164 (91%) were included in the cross-over period, and 146 (82%) completed follow-up. By month 12, average NRS pain in the combined cohort was reduced by 2.3 ± 2.2 points (95% CI, 1.7-2.8; p < 0.0001) 30 minutes after treatment and 2.9 ± 2.4 points (95% CI, 2.2-3.6; p < 0.0001) 120 minutes after treatment. Mean pain-days per week were significantly reduced (-3.5 ± 2.7 days; p < 0.001), and subject daily opioid use was reduced by 6.7 ± 29.0 morphine equivalent dose from baseline to month 12 (p = 0.013). Mean BPI-interference scores (QOL) improved by 2.7 ± 2.7 points from baseline (p < 0.001). The incidence of nonserious AEs and serious AEs was 72% (130/180) and 42% (76/180), respectively; serious device-related AEs occurred in 15 of 180 subjects (8%). CONCLUSION: Overall, HFNB delivered directly to the damaged peripheral nerve provided sustained, on-demand relief of acute PAP exacerbations, reduced opioid utilization, and improved QOL for patients with lower limb amputations with chronic PAP.