Temporary Peripheral Nerve Stimulation as Treatment for Chronic Pain.

INTRODUCTION: Chronic pain is a growing problem across the world, and in the midst of an opioid epidemic, it is imperative that alternative treatment measures are identified to help alleviate the pain experienced by these patients. Chronic pain greatly affects ones quality of life and many patients do not experience adequate relief with conventional treatment measures. The purpose of this retrospective analysis is to assess the efficacy of peripheral nerve stimulation (PNS) therapy in adult patients suffering from chronic pain refractory to conventional treatment measures who underwent therapy on various anatomical locations. METHODS: This retrospective analysis consisted of data collected from electronic health records for n = 89 patients who underwent PNS therapy. Data collected relates to patient age, sex, weight, height, body mass index (BMI), diagnosis, targeted nerves, follow-up encounters, pain scores from before and after PNS therapy, and duration of improvement. Statistical analysis used SPSS software, version 26 (IBM), using a paired t test to assess significance between pre and post PNS therapy pain scores. P values were significant if found to be ≤ 0.05. Further analysis assessed the correlation between age and BMI with visual analog scale (VAS) pain improvement and subjective percentage pain relief. RESULTS: The mean pre-operative (pre-op) pain score before PNS therapy was 6.36 (standard deviation (SD) = 2.18, SEM = 0.23) and the mean post-operative (post-op) pain score after PNS therapy was 4.19 (SD = 2.70, SEM = 0.29). The mean patient-reported percent improvement in pain following PNS therapy was 49.04% (SD = 34.79). The improvement in pain scores between pre-op and post-op was statistically significant (M = 2.17, SD = 2.82, SEM = 0.30, t(88) = 7.26, p < .001), 95% confidence interval (CI) [1.57, 2.76]. The mean duration of improvement for patients was 123 days after therapy initiation (min = 6, max = 683, SD = 126). CONCLUSIONS: This study demonstrated the potential role for PNS therapy in improving patient-reported pain levels for various neuropathies, targeting various nerves. With PNS therapy's use as a chronic pain treatment and available research being limited, further study needs to be done on the efficacy of PNS therapy for pain management and complications associated with PNS device placements at various locations.

Case report: Peripheral nerve stimulation relieves post-traumatic trigeminal neuropathic pain and secondary hemifacial dystonia.

Post-traumatic trigeminal neuropathic pain (PTNP) combined with secondary dystonia are rare sequelae of orofacial injury and often do not respond to conservative treatment. The consensus on treatment for both symptoms is yet to be standardized. This study reports the case of a 57-year-old male patient with left orbital trauma who developed PTNP immediately after the injury and secondary hemifacial dystonia 7 months thereafter. To treat his neuropathic pain, we performed peripheral nerve stimulation (PNS) using a percutaneously implanted electrode to the ipsilateral supraorbital notch along the brow arch, which instantly resolved the patient's pain and dystonia. PTNP was relieved in a satisfactory manner until 18 months after the surgery, despite a gradual recurrence of the dystonia since 6 months after the surgery. To the best of our knowledge, this is the first reported case of PNS used for the treatment of PTNP combined with dystonia. This case report highlights the potential benefits of PNS in relieving neuropathic pain and dystonia and discusses the underlying therapeutic mechanism. Moreover, this study suggests that secondary dystonia occurs due to the uncoordinated integration of afferent sensory and efferent motor information. The findings of the present study indicate that PNS should be considered for patients with PTNP following the failure of conservative treatment. Secondary hemifacial dystonia may benefit from PNS upon further research and long-term assessment.

Electrical stimulation for the treatment of spinal cord injuries: A review of the cellular and molecular mechanisms that drive functional improvements.

Spinal cord injury (SCI) is a devastating condition that causes severe loss of motor, sensory and autonomic functions. Additionally, many individuals experience chronic neuropathic pain that is often refractory to interventions. While treatment options to improve outcomes for individuals with SCI remain limited, significant research efforts in the field of electrical stimulation have made promising advancements. Epidural electrical stimulation, peripheral nerve stimulation, and functional electrical stimulation have shown promising improvements for individuals with SCI, ranging from complete weight-bearing locomotion to the recovery of sexual function. Despite this, there is a paucity of mechanistic understanding, limiting our ability to optimize stimulation devices and parameters, or utilize combinatorial treatments to maximize efficacy. This review provides a background into SCI pathophysiology and electrical stimulation methods, before exploring cellular and molecular mechanisms suggested in the literature. We highlight several key mechanisms that contribute to functional improvements from electrical stimulation, identify gaps in current knowledge and highlight potential research avenues for future studies.

Neurosurgical Treatment of Pain.

The aim of this review is to draw attention to neurosurgical approaches for treating chronic and opioid-resistant pain. In a first chapter, an up-to-date overview of the main pathophysiological mechanisms of pain has been carried out, with special emphasis on the details in which the surgical treatment is based. In a second part, the principal indications and results of different surgical approaches are reviewed. Cordotomy, Myelotomy, DREZ lesions, Trigeminal Nucleotomy, Mesencephalotomy, and Cingulotomy are revisited. Ablative procedures have a limited role in the management of chronic non-cancer pain, but they continues to help patients with refractory cancer-related pain. Another ablation lesion has been named and excluded, due to lack of current relevance. Peripheral Nerve, Spine Cord, and the principal possibilities of Deep Brain and Motor Cortex Stimulation are also revisited. Regarding electrical neuromodulation, patient selection remains a challenge.

Magneto-stimulation limits in medical imaging applications with rapid field dynamics.

Objective.The goal of this work is to extend previous peripheral nerve stimulation (PNS) studies to scenarios relevant to magnetic particle imaging (MPI) and low-field magnetic resonance imaging (MRI), where field dynamics can evolve at kilo-hertz frequencies.Approach.We have constructed an apparatus for PNS threshold determination on a subject's limb, capable of narrow and broad-band magnetic stimulation with pulse characteristic times down to 40µs.Main result.From a first set of measurements on 51 volunteers, we conclude that the PNS dependence on pulse frequency/rise-time is compatible with traditional stimulation models where nervous responses are characterized by a rheobase and a chronaxie. Additionally, we have extended pulse length studies to these fast timescales and confirm thresholds increase significantly as trains transition from tens to a few pulses. We also look at the influence of field spatial distribution on PNS effects, and find that thresholds are higher in an approximately linearly inhomogeneous field (relevant to MRI) than in a rather homogeneous distribution (as in MPI).Significance.PNS constrains the clinical performance of MRI and MPI systems. Extensive magneto-stimulation studies have been carried out recently in the field of MPI, where typical operation frequencies range from single to tens of kilo-hertz. However, PNS literature is scarce for MRI in this fast regime, relevant to small (low inductance) dedicated MRI setups, and where the resonant character of MPI coils prevents studies of broad-band stimulation pulses. This work advances in this direction.

Peripherical Electrical Stimulation for Parkinsonian Tremor: A Systematic Review.

Parkinsonian tremor is one of the most common motor disorders in patients with Parkinson's disease (PD). Compared to oral medications and brain surgery, electrical stimulation approaches have emerged as effective and non-invasive methods for tremor reduction. The pathophysiology, detection and interventions of tremors have been introduced, however, a systematic review of peripherical electrical stimulation approaches, methodologies, experimental design and clinical outcomes for PD tremor suppression is still missing. Therefore, in this paper, we summarized recent studies on electrical stimulation for tremor suppression in PD patients and discussed stimulation protocols and effectiveness of different types of electrical stimulation approaches in detail. Twenty out of 528 papers published from 2010 to 2021 July were reviewed. The results show that electrical stimulation is an efficient intervention for tremor suppression. The methods fall into three main categories according to the mechanisms: namely functional electrical stimulation (FES), sensory electrical stimulation (SES) and transcutaneous electrical nerve stimulation (TENS). The outcomes of tremor suppression were varied due to various stimulation approaches, electrode locations and stimulation parameters. The FES method performed the best in tremor attenuation where the efficiency depends mainly by the control strategy and accuracy of tremor detection. However, the mechanism underlying tremor suppression with SES and TENS, is not well-known. Current electrical stimulation approaches may only work for a number of patients. The potential mechanism of tremor suppression still needs to be further explored.

Case report: Use of peripheral nerve stimulation for treatment of pain from vertebral plana fracture.

Vertebral plana fractures are a severe form of compression fractures that can cause significant morbidity due to incapacitating pain. Due to the flattening of the vertebrae in a plana fracture, accessing the vertebral body transpedicularly can be difficult, making traditional vertebral augmentation treatment dangerous. These injuries also typically occur in elderly patients with contraindications to invasive procedures. Peripheral nerve stimulation is a relatively new and minimally invasive treatment that uses electrical stimulation to inhibit pain signals from reaching the somatosensory cortex. Our case describes an 80 Year old female with multiple comorbidities and refractory pain due to a vertebral planar fracture successfully treated with a 60 day course of peripheral nerve stimulation as evidenced by over 50% reduction in symptoms and discontinuation of opioid pain medication use.

The Immediate and Short-Term Effects of Transcutaneous Spinal Cord Stimulation and Peripheral Nerve Stimulation on Corticospinal Excitability.

Rehabilitative interventions involving electrical stimulation show promise for neuroplastic recovery in people living with Spinal Cord Injury (SCI). However, the understanding of how stimulation interacts with descending and spinal excitability remain unclear. In this study we compared the immediate and short-term (within a few minutes) effects of pairing Transcranial Magnetic Stimulation (TMS) with transcutaneous Spinal Cord stimulation (tSCS) and Peripheral Nerve Stimulation (PNS) on Corticospinal excitability in healthy subjects. Three separate experimental conditions were assessed. In Experiment I, paired associative stimulation (PAS) was applied, involving repeated pairing of single pulses of TMS and tSCS, either arriving simultaneously at the spinal motoneurones (PAS0ms) or slightly delayed (PAS5ms). Corticospinal and spinal excitability, and motor performance, were assessed before and after the PAS interventions in 24 subjects. Experiment II compared the immediate effects of tSCS and PNS on corticospinal excitability in 20 subjects. Experiment III compared the immediate effects of tSCS with tSCS delivered at the same stimulation amplitude but modulated with a carrier frequency (in the kHz range) on corticospinal excitability in 10 subjects. Electromyography (EMG) electrodes were placed over the Tibialis Anterior (TA) soleus (SOL) and vastus medialis (VM) muscles and stimulation electrodes (cathodes) were placed on the lumbar spine (tSCS) and lateral to the popliteal fossa (PNS). TMS over the primary motor cortex (M1) was paired with tSCS or PNS to produce Motor Evoked Potentials (MEPs) in the TA and SOL muscles. Simultaneous delivery of repetitive PAS (PAS0ms) increased corticospinal excitability and H-reflex amplitude at least 5 min after the intervention, and dorsiflexion force was increased in a force-matching task. When comparing effects on descending excitability between tSCS and PNS, a subsequent facilitation in MEPs was observed following tSCS at 30-50 ms which was not present following PNS. To a lesser extent this facilitatory effect was also observed with HF- tSCS at subthreshold currents. Here we have shown that repeated pairing of TMS and tSCS can increase corticospinal excitability when timed to arrive simultaneously at the alpha-motoneurone and can influence functional motor output. These results may be useful in optimizing stimulation parameters for neuroplasticity in people living with SCI.

Treatment of chronic axial back pain with 60-day percutaneous medial branch PNS: Primary end point results from a prospective, multicenter study.

BACKGROUND: The objective of this prospective, multicenter study is to characterize responses to percutaneous medial branch peripheral nerve stimulation (PNS) to determine if results from earlier, smaller single-center studies and reports were generalizable when performed at a larger number and wider variety of centers in patients recalcitrant to nonsurgical treatments. MATERIALS & METHODS: Participants with chronic axial low back pain (LBP) were implanted with percutaneous PNS leads targeting the lumbar medial branch nerves for up to 60 days, after which the leads were removed. Participants were followed long-term for 12 months after the 2-month PNS treatment. Data collection is complete for visits through end of treatment with PNS (primary end point) and 6 months after lead removal (8 months after start of treatment), with some participant follow-up visits thereafter in progress. RESULTS: Clinically and statistically significant reductions in pain intensity, disability, and pain interference were reported by a majority of participants. Seventy-three percent of participants were successes for the primary end point, reporting clinically significant (≥30%) reductions in back pain intensity after the 2-month percutaneous PNS treatment (n = 54/74). Whereas prospective follow-up is ongoing, among those who had already completed the long-term follow-up visits (n = 51), reductions in pain intensity, disability, and pain interference were sustained in a majority of participants through 14 months after the start of treatment. CONCLUSION: Given the minimally invasive, nondestructive nature of percutaneous PNS and the significant benefits experienced by participants who were recalcitrant to nonsurgical treatments, percutaneous PNS may provide a promising first-line neurostimulation treatment option for patients with chronic axial back pain.

Anatomical measurements correlate with individual magnetostimulation thresholds for kHz-range homogeneous magnetic fields.

PURPOSE: Magnetostimulation, also known as peripheral nerve stimulation (PNS), is the dominant safety constraint in magnetic resonance imaging (MRI) for the gradient magnetic fields that operate around 0.1-1 kHz, and for the homogeneous drive field in magnetic particle imaging (MPI) that operates around 10-150 kHz. Previous studies did not report correlations between anatomical measures and magnetostimulation thresholds for the gradient magnetic fields in MRI. In contrast, a strong linear correlation was shown between the thresholds and the inverse of body part size in MPI. Yet, the effects of other anatomical measures on the thresholds for the drive field remain unexplored. Here, we investigate the effects of fat percentage on magnetostimulation thresholds for kHz-range homogeneous magnetic fields such as the drive field in MPI, with the ultimate goal of predicting subject-specific thresholds based on simple anatomical measures. METHODS: Human subject experiments were performed on the upper arms of 10 healthy male subjects (age: 26 ± 2 yr) to determine magnetostimulation thresholds. Experiments were repeated three times for each subject, with brief resting periods between repetitions. Using a solenoidal magnetostimulation coil, a homogeneous magnetic field at 25 kHz with 100 ms pulse duration was applied at 4-s intervals, while the subject reported stimulation via a mouse click. To determine the thresholds, individual subject responses were fitted to a cumulative distribution function modeled by a sigmoid curve. Next, anatomical images of the upper arms of the subjects were acquired on a 3 T MRI scanner. A two-point Dixon method was used to obtain separate images of water and fat tissues, from which several anatomical measures were derived: the effective outer radius of the upper arm, the effective inner radius (i.e., the muscle radius), and fat percentage. Pearson's correlation coefficient was used to assess the relationship between the threshold and anatomical measures. This statistical analysis was repeated after factoring out the expected effects of body part size. An updated model for threshold prediction is provided, where in addition to scaling in proportion with the inverse of the outer radius, the threshold has an affine dependence on fat percentage. RESULTS: A strong linear correlation (r = 0.783, P < 0.008) was found between magnetostimulation threshold and fat percentage, and the correlation became stronger after factoring out the effects of outer radius (r = 0.839, P < 0.003). While considering body part size alone did not explain any significant variance in measured thresholds (P > 0.398), the updated model that also incorporates fat percentage yielded substantially improved threshold predictions with R 2  = 0.654 (P < 0.001). CONCLUSIONS: This work shows for the first time that fat percentage strongly correlates with magnetostimulation thresholds for kHz-range homogenous magnetic fields such as the drive field in MPI, and that the correlations get even stronger after factoring out the effects of body part size. These results have important practical implications for predicting subject-specific thresholds, which in turn can increase the performance of the drive field and improve image quality while remaining within the safety limits.

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

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.