Neuromodulation: Journals & articles

Abstract
Background and aims: Percutaneous electrical nerve field stimulation (PENFS) is a minimally invasive, nonpharmacologic approach to treat children with functional abdominal pain disorders (FAPD). Allodynia refers to pain from a stimulus that does not usually provoke pain. We aimed to characterize auricular allodynia during PENFS and associate it with outcomes.

Materials and methods: We conducted a retrospective cohort study reviewing charts of patients who underwent PENFS for an FAPD. We included demographic data, medical history, and validated questionnaire responses. Allodynia was noted through physician notes of localized ear pain, soreness, or tenderness. Baseline clinical scores and PENFS outcomes were compared in patients with and without allodynia.

Results: Of 219 patients with FAPD (mean age 16.2 ± 2.7 years), 79% were female, and 87% were Caucasian; 28% of patients experienced allodynia with no significant demographic differences. The most common gastrointestinal symptoms were abdominal pain (100%) and nausea (70%), and the most common FAPD diagnoses included irritable bowel syndrome (58%) and functional dyspepsia (54%). Of the 93 total visits with allodynia, 44% of the visits had patients report allodynia once and 34% twice. Common interventions included placing
Conclusion: Allodynia in patients with FAPD who underwent PENFS had worse clinical outcomes. Excitation thresholds of rapidly conducting Aβ fibers in the ear are lower than those of nociceptive slowly conducting Aδ and C fibers. Patients with allodynia may require adjustment of nerve fiber stimulation to improve outcomes.

Abstract
Temporal summation of second pain (TSSP) is a phenomenon that has clinical relevance but insights into its functioning are limited. Lately, 'affective touch' (AT) has been shown to have pain relieving properties but only one study has investigated its effects on TSSP and the neural underpinnings of such interaction are unknown. In the present EEG study, thirty-six healthy participants went through three conditions where a TSSP protocol was applied in concomitance with no touch (NoT), discriminative touch (DT) and AT. A fourth no-pain no-touch condition acted as a baseline. Measures of attention during the four conditions and of pleasantness during the touch conditions were also recorded. Pain ratings were significantly lower only during the AT condition. The neural response during NoT, compared to the baseline, brought about a temporal decrease in power at delta and theta frequencies and a fronto-central increase mainly in the alpha rhythm. Adding AT to TSSP yielded, compared to NoT, a decrease in delta, theta and beta bands in midline regions at both central (Cz) and parietal (Pz) and also of gamma at Pz. Notably, DT was not associated with significant changes compared to pain alone (NoT), but a specific marked difference was found between AT and DT with the former showing a significant decrease in beta frequencies localized at Pz. While TSSP seems to be characterized by a modulation mostly of the lower frequencies, adding AT to TSSP brings a clear depression of all the major frequency bands. Additionally, the parietal beta reduction may be a biomarker of AT. Future studies can examine if such brain response can help finding a suitable intervention for TSSP-related chronic pain conditions. PERSPECTIVE: This study consolidates the idea that AT can lower pain in a TSSP paradigm and shows what are the brain (EEG) responses associated with both TSSP and TSSP modulation by AT. Given that TSSP is linked to central sensitization and that it can be used as an experimental model for chronic pain, our results pave the way for further studies into the neural mechanisms of AT-led analgesia, which can lead to future effective treatments.

Abstract
Objectives: Restorative neurostimulation for multifidus muscle is a novel therapy for chronic low back pain (CLBP). Optimal outcomes require interdisciplinary follow-up. We describe a clinical care pathway (CPW) for this therapy and report patient compliance, clinical outcomes, and patient satisfaction with the CPW.

Materials and methods: This study aimed to develop, at a single center, a CPW with derivation, practical basis, description, and evolution. Included in the study were audits of 1) patient compliance with attendance over 24 months, 2) medical and paramedical attendance at the clinic, 3) clinical outcomes in terms of reductions in both patient and cohort disability (Oswestry Disability Index, ODI) and CLBP numeric rating score (NRS), and 4) adverse events; and a prospective cross-sectional survey of patient satisfaction with the CPW.

Results: A CPW that involved both preoperative and postoperative education and integrated interdisciplinary care was developed and incorporated into the clinical service with a dedicated clinic. In the two years under study, 172 patients attended the education session, and 92 proceeded to restorative neurostimulation for multifidus muscle therapy; 15 patients who had this therapy before the CPW also were incorporated into the CPW. Patient compliance with the pathway was 88% (95% CI 79%-94%) at 12 months. Attendance at the dedicated CPW clinic by the various subspeciality clinicians ranged between 74% and 100%. There were serial reductions in both ODI (38.9 [95% CI 35.9-41.9] to 24.7 (95% CI 21.1-28.3) and CLBP NRS (6.3 [95% CI 6.0-6.7] to 3.3 (95% 2.7-3.9) after 12 months; 76 of the 99 patients assessable (77%: 95% CI 67%-85%) had a minimally important clinical difference reduction in either ODI or pain NRS, whereas eight were unassessable. Patient satisfaction with the CPW was very high (mean 26.9; median 27, maximum 28).

Conclusions: The CPW facilitated clinical management and optimized outcomes in patients having restorative neurostimulation. Its design and delivery were very well accepted by patients.

Keywords: Clinical care pathway; clinical outcomes; low back pain; patient satisfaction; restorative neurostimulation.

Abstract
Background and objective: Non-invasive neuromodulation techniques (NIN), such as transcranial Direct Current Stimulation (tDCS) and repetitive Transcranial Magnetic Stimulation (rTMS), have been extensively researched for their potential to alleviate pain by reversing neuroplastic changes associated with neuropathic pain (NP), a prevalent and complex condition. However, treating NP remains challenging due to the numerous variables involved, such as different techniques, dosages and aetiologies. It is necessary to provide insights for clinicians and public healthcare managers to support clinical decision-making. This umbrella review aims to consolidate existing evidence on the effectiveness of various NIN in managing chronic NP.

Databases and data treatment: A systematic search was conducted in the PubMed/MEDLINE database, including meta-analyses of controlled trials comparing NIN techniques with sham interventions for NP treatment. The quality of included studies was assessed using the AMSTAR-2 tool and the GRADE system, with effect sizes adjusted to the standard mean difference (SMD).

Results: The review included 22 meta-analyses comprising 8151 participants from 214 controlled trials. The most investigated NIN techniques were tDCS and rTMS, with primary targets being the motor cortex and dorsolateral prefrontal cortex. The findings suggest that excitatory protocols, particularly high-frequency rTMS and anodal tDCS, are effective in reducing pain intensity in individuals with NP. However, the overall quality of evidence was rated low, primarily due to heterogeneity among studies and small sample sizes.

Conclusion: NIN techniques show promise in managing NP, with potential benefits in pain reduction. However, further high-quality research is needed to establish optimal protocols and long-term effects.

Significance statement: This paper consolidates the evidence regarding non-invasive neuromodulation for the treatment of neuropathic pain, including differentiating the most effective techniques based on the aetiology of pain, and provides clinicians with easy access to this critical information. It also highlights key aspects that require further research in the field of non-invasive neuromodulation and neuropathic pain.

Abstract
Objectives: Spinal cord stimulation (SCS) is a therapeutic option for those with chronic pain due to persistent spinal pain syndrome (PSPS). Current literature suggests a higher rate of SCS explant in female patients, but evidence regarding sex differences in the rates of receiving SCS therapy is limited. We do not know whether there is a disparity between female and male patients who receive SCS therapy. The objectives of this retrospective analysis were to determine whether there is a sex-based disparity in SCS therapy and SCS explants between female and male patients for the treatment of PSPS.

Materials and methods: This retrospective study included medical record data from TriNetX US collaborative research network (TriNetX, Inc, Cambridge, MA), which included 61 large US healthcare organizations. Patients with a diagnosis of PSPS were identified. From the PSPS cohort, those who received SCS therapy (leads and/or generator) were included for the primary outcome, which was to compare the rates of SCS therapy in women and men, and those who received SCS explants were included for the secondary outcome. Propensity matched scoring was used to ensure comparability of cohorts.

Results: The propensity-score matched sample included 87,681 female and 87,681 male patients for analysis, with SCS therapy being provided to 6782 women (risk of 7.735%) and 6783 men (risk of 7.736%), with a risk difference of -0.001%, 95% CI (-0.251%, 0.249%), z = -0.009, p = 0.9929. Within the same propensity-score matched sample, SCS explant occurred in 2999 women (risk of 3.420%) and 2608 men (risk of 2.974%). The risk difference was 0.446%, 95% CI (0.281%, 0.611%), z = 5.307, p < 0.0001.

Conclusions: Our retrospective analysis shows that there is not a difference in the rates of SCS therapy between a matched sample of women and men with PSPS, and a small difference in rates of SCS explants between women and men.

Abstract
Introduction: Chronic pelvic pain (CPP) is a multifaceted condition that poses significant challenges in clinical management owing to its complex and varied pathophysiology, including neuropathic, somatic, visceral, and musculoskeletal components. Endometriosis is frequently associated with CPP, necessitating a comprehensive, multimodal treatment strategy. This approach typically includes physical and behavioral therapy, pharmacologic interventions, surgical management of endometriosis, and various pain-modulating procedures. Neuromodulation, particularly spinal cord stimulation (SCS), has been used in refractory cases; however, its use is often met with limited success and a notable rate of explants. This case series presents nine patients with intractable CPP secondary to endometriosis, unresponsive to conventional treatments, who were treated with dorsal root ganglion stimulation (DRG-S).

Materials and methods: Between 2022 and 2023, ten patients with severe CPP secondary to endometriosis, unresponsive to various multimodal treatments-including previous interventional pain procedures, gynecologic surgery, and in some cases, SCS-were recruited for this prospective study. Of these, nine patients underwent permanent DRG-S, with bilateral L1 and S2 DRG-S leads placed (four leads per patient). Patients were assessed for pain intensity using the visual analog scale (VAS), narcotic consumption, and quality of life (QoL) using the 12-item short-form (SF-12) survey, with a 12-month follow-up period. Nonparametric statistical analyses were conducted using SPSS.

Results: One patient was excluded from the study owing to a lack of pain relief during the DRG-S trial. The remaining nine patients underwent permanent bilateral L1 and S2 DRG-S placement. Significant improvement in pain scores was observed and sustained throughout the follow-up period (VAS 9 ± 1.5-2 ± 2.0; p = 0.003), along with a marked reduction in opioid consumption, with four patients becoming completely free of narcotics (p = 0.046). SF-12 physical scores improved by 60.2 ± 7.8 (p = 0.006), and SF-12 mental scores improved by 45.9 ± 2.76 (p = 0.01).

Conclusion: Bilateral L1 and S2 DRG-S yielded robust and sustained outcomes, including significant improvements in pain scores, reduced narcotic consumption, and enhanced QoL over a 12-month follow-up period.

Abstract
Objectives: Cancer pain is among the most prevalent and challenging symptoms in cancer care, with up to 95% of patients with late-stage cancer experiencing moderate-to-severe pain. Conventional pharmacologic treatments, including opioids, carry risks, and patients' conditions may be refractory to medical management or have contraindications. Neurostimulation techniques, such as spinal cord stimulation (SCS), dorsal root ganglion stimulation (DRGS), and peripheral nerve stimulation (PNS), have shown promise in treating treatment-induced cancer pain. However, a comprehensive review focusing on these techniques for cancer-induced pain alone is necessary.

Materials and methods: A comprehensive literature review was conducted using Medline, Embase, and Cochrane Library data bases, focusing on studies from 2000 onward. Inclusion criteria included interventional and observational studies reporting on SCS, DRGS, and PNS in cancer-induced pain. Studies addressing treatment-induced pain, systematic reviews, meta-analyses, and non-English studies were excluded. Data were extracted and evaluated using the Grades of Recommendation, Assessment, Development, and Evaluation system.

Results: The search yielded 831 references, with 24 studies meeting the inclusion criteria. Sixteen studies focused on SCS, seven on PNS, and two cases on DRGS. SCS showed significant pain reduction, with an average decrease in numeric rating scale (NRS) scores from 8.0 to 2.2 over an average 8.4-month follow-up period. PNS also indicated substantial pain relief, with NRS scores decreasing from 8.29 to 3.04 over an average 5.2-month follow-up period. DRGS, although less studied, showed a reduction in NRS scores from 6.0 to 1.0 over an average 6.0-month follow-up period. SCS was associated with a significant reduction in opioid use, with average reported morphine equivalent daily dose (MEDD) change from 1152.2 mg to 739.7 mg over an average 5.0-month period, whereas PNS and DRGS had limited impact on opioid consumption, with no reported MEDD change.

Conclusions: Our scoping review synthesizes evidence on neurostimulation interventions for treating cancer-induced pain. Current evidence suggests that interventions such as SCS, DRGS, and PNS may provide clinically meaningful pain relief in patients with cancer-induced pain. Several studies also reported improvements in functionality and quality of life. However, the level of evidence is limited owing to the lack of prospective comparative studies, clinical and methodologic heterogeneity, and small sample sizes.

Abstract
Objectives: This systematic review compares the long-term efficacy of cylindrical-lead spinal cord stimulation (CL-SCS) vs paddle-lead spinal cord stimulation (Paddle-SCS) for chronic pain management.

Materials and methods: We included prospective and retrospective studies with at least ten patients reporting on the efficacy of either lead type. Primary outcomes were pain score reduction (measured by the visual analog scale [VAS] and numeric rating scale [NRS]) and 50% pain relief after at least 12 months. Secondary outcomes included functional disability and complications, such as lead migration and infection rates. Meta-analyses compared effect sizes, while meta-regression and subgroup analyses addressed heterogeneity.

Results: A total of 96 studies, comprising 7726 patients, met the inclusion criteria. Paddle-SCS demonstrated superior pain reduction, with a standardized mean difference (SMD) of 5.37 (95% CI [5.35, 5.38]) compared with CL-SCS, which had an SMD of 4.09 (95% CI [4.08, 4.10]) on the VAS. However, CL-SCS outperformed Paddle-SCS on the NRS, with SMDs of 4.39 vs 2.35, respectively. For 50% pain relief, Paddle-SCS had a success rate of 41.4%, as opposed to 35.4% for CL-SCS. Paddle-SCS showed a lower migration rate (4.3% vs 7.2% for CL-SCS) but higher infection rates (5.0% vs 3.3%).

Conclusions: Paddle-SCS offers superior pain reduction (as measured by the VAS) and a lower migration rate, but a higher infection risk compared with CL-SCS. CL-SCS showed better outcomes as measured by the NRS. The choice between Paddle-SCS and CL-SCS should be individualized according to patient-specific factors and treatment goals. Further research with rigorous study designs is needed to provide clearer comparisons between these interventions.

Abstract
Background: This study assessed the effect of expectation of analgesia on conditioned pain modulation (CPM) in healthy participants stratified into inhibitors and non-inhibitors.

Methods: A parallel CPM protocol was assessed on 21 women and 22 men across two sessions: baseline and expectation of analgesia, which was induced by a standardized audiovisual suggestion. The CPM assessment involved two different test stimuli (TS): mechanically controlled palpation and the pressure pain threshold, applied to two different regions: anterior temporalis and thenar eminence of the hand. The conditioning stimulus (CS) involved immersing the non-dominant forearm in cold water. The order of the TS and regions was randomized for each participant. The CPM protocol was performed three times, with a 1-min interval between TS/region sequences. After a 20-min rest, the CPM assessment was repeated (two blocks in total). The standard error of measurement (SEM) was computed to identify inhibitors (inhibitory responses) and non-inhibitors (including non-inhibitors and facilitatory responses). Cochran's Q, ANOVA and ANCOVA were applied to the data (p < 0.05).

Results: There was a significant decrease in the proportion of non-inhibitors during the expectation of analgesia session (32.6%-44.2%) when compared with the baseline session (51.2%-72.1%). The non-inhibitors exhibited a lower inhibitory CPM magnitude than the inhibitors only in block 1 of the baseline session. The expectation of analgesia resulted in an increased magnitude of the inhibitory CPM solely in non-inhibitors.

Conclusion: Expectation of analgesia can increase the inhibitory response of the CPM beyond the measurement error in healthy participants with a baseline non-inhibitory profile.

Significance: Several studies have investigated whether cognitive modulation can alter the magnitude of the inhibitory response of conditioned pain modulation (CPM), yet some gaps remain. This study accounted for measurement error to accurately determine changes in CPM influenced by expectation of analgesia.

Abstract
Objectives: This study aimed to investigate the analgesic effects of H-coil repetitive transcranial magnetic stimulation (rTMS) primarily targeting the hand area of the primary motor cortex (M1) in patients with peripheral neuropathic pain. Given that the H-coil has a wider reach than conventional coils, there is a possibility that targeting the hand motor cortex also may stimulate prefrontal areas. Thus, we also aimed to examine whether rTMS with an M1 target could produce effects on psychologic outcomes.

Materials and methods: In total, 17 patients were randomly assigned to receive active or sham H-coil rTMS in a counterbalanced order. After a nine-week washout period, they crossed over to either active or sham rTMS, according to a double-blind crossover design. Each treatment period consisted of five daily rTMS sessions and a one- and three-week follow-up visit. The primary outcome was average usual pain intensity. Secondary outcomes included pain unpleasantness, dynamic and static mechanical allodynia, anxiety and depression, sleep, pain catastrophizing, function, and patients' impression of change. Effects of rTMS were investigated using linear mixed model analyses.

Results: We found two significant interactions between treatment and time, indicating that active H-coil rTMS induced significant analgesic effects (t [134] = -2.18; p = .03; d = -0.10) and significant reductions in anxiety and depression compared with sham stimulation over the treatment course (t [73] = -2.14; p = .04; d = -0.09). The analgesic effect occurred two weeks after the treatment, and the effect on anxiety and depression occurred three weeks after treatment. No other significant interactions were found for the secondary variables.

Conclusions: Five days of H-coil rTMS targeting the hand area of M1 induced statistically significant effects on pain intensity. Moreover, rTMS improved symptoms of anxiety and depression, possibly because of the wide and deep reach of the H-coil.

Clinical trial registration: The Clinicaltrials.gov registration number for the study is NCT05488808.

Keywords: Anxiety; H-coil; depression; neuropathic pain; rTMS.

Abstract
Introduction: Standard anterograde placement of a surgical paddle lead (SPL) for spinal cord stimulation (SCS) can be challenging in patients with scarring from prior spine surgery, instrumentation obstructing the targeted level, or severe stenosis below the targeted level. One potential alternative is retrograde (caudal) insertion by performing laminotomies cephalad to the targeted levels. The literature is limited to only a small number of individual cases describing this technique. In this report, the authors present their experience over the last ten years of the retrograde insertion of SPLs for SCS.

Materials and methods: This is a retrospective study of 298 consecutive surgical paddle implants performed by a single neurosurgeon from 2013 to 2023 in an academic medical center.

Results: A total of 26 patients underwent retrograde insertion of SPLs. The average patient age was 61 years, with women comprising 58% of cases. Three different manufacturers were used. The retrograde approach was planned before surgery in 96% of cases. The indications for the retrograde approach were 1) scarring from current or prior SCS leads placed from below in the standard anterograde fashion (46%); 2) scarring from prior extensive spine surgery and/or instrumentation (42%); 3) anatomical considerations of scoliosis and stenosis below the targeted levels or the requirement of high cervical stimulation (8%); or 4) intraoperative decision due to extensive scarring during planned anterograde placement (4%). The targeted spinal regions were thoracic (88%) or cervical (12%). There was one case of lead migration that required revision surgery. There were no paddle-lead fractures or deep surgical site infections.

Conclusions: The retrograde insertion of SPLs is a low-risk and feasible procedure that can be performed with minimal risk of lead migration, fracture, or deep surgical site infection. The retrograde strategy can be used in SPL trials or permanent placements.

Abstract
Objectives: Spinal cord stimulation (SCS) therapy is an effective treatment for chronic pain, particularly in conditions such as postlaminectomy syndrome and complex regional pain syndrome (CRPS). Rare case reports described significant weight loss in patients who underwent dorsal column SCS therapy for chronic pain. Recently, neuromodulation for obesity has become a novel field for research. We aimed to investigate weight trends among patients treated with SCS for chronic pain.

Materials and methods: We conducted a retrospective chart review in 342 patients treated with SCS or dorsal root ganglion stimulators at our institution between 2010 and 2023. Patients had their weight recorded before SCS implantation and at least once within 12 months after surgery. We also conducted interviews with 28 patients who experienced significant weight loss or had revision procedures owing to weight loss.

Results: We found that 105 of 342 patients (30.7%) experienced weight loss of ≥5% within a year of implantation, and 32 of 105 (30.5%, 9.4% of all patients) experienced weight loss of ≥ 10%. A multivariate regression analysis revealed a modest increase in the likelihood of weight loss among patients with CRPS (odds ratio [OR] = 1.17, 95% CI [1.04, 1.30], p = 0.007) and in those who achieved pain relief after implantation (OR = 1.22, 95% CI [1.05,1.40], p = 0.008). Of the 28 patients with significant weight loss who were interviewed, 12 (43%) could not explain the reasons for their weight loss, whereas eight (29%) reported decreased appetite. Leads placed at higher thoracic levels were associated with increased rates of weight loss (37.2% at T6-T8 and 22.3% at T8-T10; p = 0.038).

Conclusions: Our findings suggest that SCS therapy may affect weight in patients with chronic pain. Further studies are needed to investigate the potential role of SCS in weight modulation.

Abstract
Objectives: Raynaud's phenomenon (RP) is a vascular disorder characterized by episodic peripheral artery vasospasms, resulting in paleness, cyanosis, and/or erythema. There are few reports, mostly case reports, on the benefits of spinal cord stimulation (SCS) for the treatment of RP. However, there is a lack of objective evidence on SCS-induced modulation of the sympathetic system (eg, vasodilation) in this condition. We hypothesize that evoked compound action potential-controlled closed-loop SCS may relieve pain, reduce the severity and frequency of Raynaud attacks, and improve peripheral blood flow.

Materials and methods: This prospective, observational, single-center pilot study aimed to evaluate the effectiveness of SCS in treating primary and secondary RP. Patient outcomes such as pain, Raynaud severity/condition score, Cochin Hand Function Scale, Scleroderma Health Assessment Questionnaire RP visual analog scale, EQ-5D-5L, Patient Global Impression of Change, blood flow assessments, and neurophysiological measurements were collected at baseline, trial end, one month, three months, and six months.

Results: Ten patients were successfully enrolled in the study and underwent epidural electrode placement for SCS. SCS resulted in a significant improvement in the severity of RP attacks (severity difference from baseline at trial end: -1.8, 95% CI, -3.1 to -0.5; p = 0.01; at one month: -2.1; 95% CI, -3.4 to -0.8; p = 0.004; at three months: -2.9; 95% CI, -4.2 to -1.6; p = 0.0002) and Raynaud condition score (difference from baseline at trial end: -2.1; 95% CI, -3.3 to -0.9; p = 0.002; at one month: -2.2; 95% CI, -3.4 to -1.0; p = 0.002; at three months: -3.3; 95% CI, -4.6 to -2.1; p = 0.00002; at six months: -4.1; 95% CI, -5.4 to -2.8; p = 0.0000008), and an objective reduction in peripheral occlusion and ulceration. While one of the combined primary end points was successfully achieved in terms of severity at the three-month follow-up, it is worth noting that the primary end point related to frequency improvement was not met during the same time frame.

Conclusions: This pilot study offers evidence linking SCS with the activation of large, myelinated fibers within the dorsal column in patients with RP. This activation is associated with improvement in the number of patient-related outcomes and enhanced peripheral circulation.

Abstract
Objectives: The aim of this study was to evaluate the effectiveness and safety of a novel subperception spinal cord stimulation (SCS) waveform paradigm designed to target the dorsal horn dendrites for treating chronic neuropathic low back pain (LBP). The final 12-month results are reported here.

Materials and methods: Twenty-seven participants were implanted with a commercial SCS system. Devices were programmed to deliver the waveform (frequency 100 Hz, pulse width 1000 μsec, T9-T10 disk bipole) at decreasing stimulation perception threshold amplitudes (80%, 60%, then 40%) over a 14-week period. Participants were blinded to the program settings. Participants then received their preferred program for further evaluation at 26 and 52 weeks after activation. Outcome measures included back pain score (visual analogue scale [VAS]), Brief Pain Inventory (BPI), EuroQol 5-Dimension 5-Level (EQ-5D-5L), 36-Item Short Form Health Survey (SF-36), treatment satisfaction, and clinician global impression of change (CGIC).

Results: At 52 weeks (n = 24), the responder rate (≥50% pain relief) was 65.6%, and the high-responder rate (≥80% pain relief) was 56.5%. The mean change from baseline in pain VAS was -43.94 mm (95% CI -57.89, -30.00; p < 0.001) and mean pain relief was 64.69% ± 39.43%. BPI and SF-36 scores remained significantly improved (p ≤ 0.001). EQ-5D-5L index and EuroQoL-VAS further improved, and 87.0% of participants met the minimum clinically important difference for the EQ-5D-5L index. Treatment satisfaction was 83%, and 91% of participants had a CGIC rating of "much improved" or above. No serious study-related adverse events were reported.

Conclusions: The 12-month trial results show sustained improvements in pain, quality of life, and health-related outcomes. This novel subperception dorsal horn dendrite SCS approach seems a safe and promising treatment option for patients with chronic neuropathic LBP. The open-source availability of this waveform on commercial SCS platforms allows widespread patient access. Further evaluation seems warranted.

Abstract
Objectives: The aim of this systematic review and meta-analysis was to evaluate the effectiveness of the percutaneous electrical stimulation in the modulation of pain and its implication in the function of patients with a painful knee condition.

Methods: A search was conducted from database inception to September 2023 across PubMed, Web of Science and Scopus databases. Randomized controlled trials were included. Two reviewers performed independent data extraction and methodologic quality assessment of the studies. Study quality was assessed using the PEDro scale and the risk of bias was evaluated with the Cochrane Assessment tool.

Results: Eight studies were included. A significant statistical effect was found (P<0.001) for reducing pain and improving function after treatment. Additionally, a significant statistical effect was presented for reducing pain (P=0.009) and improving function (P<0.001) after follow-up. The risk of bias was low.

Conclusion: This review showed a positive effect of applying the percutaneous electrical stimulation reducing pain and improving function in adults with a painful knee.

Abstract
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.

Abstract
Background: Chronic pancreatic pain is one of the most severe causes of visceral pain, and treatment response is often limited. Neurostimulation techniques have been investigated for chronic pain syndromes once there are pathophysiological reasons to believe that these methods activate descending pain inhibitory systems. Considering this, we designed this systematic literature review to investigate the evidence on neuromodulation techniques as a treatment for chronic pancreatic pain.

Materials and methods: We performed a literature search using the databases MEDLINE, Cochrane Central Register of Controlled Trials (CENTRAL), and Embase until April 2024. The included studies used neurostimulation techniques in participants with chronic pancreatic pain and reported pain-related outcomes, with a focus on pain scales and opioid intake. Two reviewers screened and extracted data, and a third reviewer resolved discrepancies. We assessed the risk of bias using the Jadad scale. The authors then grouped the findings by the target of the neurostimulation, cortex, spinal cord, or peripheral nerves; described the findings qualitatively in the results section, including qualitative data reported by the articles; and calculated effect sizes of pain-related outcomes.

Results: A total of 22 studies were included (7 randomized clinical trials [RCTs], 14 case series, and 1 survey), including a total of 257 clinical trial participants. The two outcomes most commonly reported were pain, measured by the visual analogue scale (VAS), numeric rating scale (NRS), and pressure pain threshold scores, and opioid intake. Two RCTs investigated repetitive transcranial magnetic stimulation (rTMS), showing a reduction of 36% (±16) (d = 2.25; 95% CI, 0.66-3.83) and 27.2% (±24.5%) (d = 2.594; 95% CI, 1.303-3.885) in VAS pain scale. In another clinical trial, transcranial direct-current stimulation (tDCS) and transcranial pulsed current stimulation were not observed to effect a significant reduction in VAS pain (χ2 = 5.87; p = 0.12). However, a complete remission was reported in one tDCS case. Spinal cord stimulation (SCS) and dorsal root ganglion stimulation were performed in a survey and 11 case series, showing major pain decrease and diminished opioid use in 90% of participants after successful implantation; most studies had follow-up periods of months to years. Two noninvasive vagal nerve stimulation (VNS) RCTs showed no significant pain reduction in pain thresholds or VAS (d = 0.916; 95% CI, -0.005 to 1.838; and d = 0.17; -0.86 to 1.20; p = 0.72; respectively). Splanchnic nerve stimulation in one case report showed complete pain reduction accompanied by discontinuation of oral morphine and fentanyl lozenges and a 95% decrease in fentanyl patch use. Two RCTs investigated transcutaneous electrical nerve stimulation (TENS). One found a significant pain reduction effect with the NRS (d = 1.481; 95% CI, 1.82-1.143), and decreased opioid use, while the other RCT did not show significant benefit. Additionally, one case report with TENS showed pain improvement that was not quantitatively measured.

Discussion: The neuromodulation techniques of rTMS and SCS showed the most consistent potential as a treatment method for chronic pancreatic pain. However, the studies have notable limitations, and SCS has had no clinical trials. For VNS, we have two RCTs that showed a non-statistically significant improvement; we believe that both studies had a lack of power issue and suggest a gap in the literature for new RCTs exploring this modality. Additionally, tDCS and TENS showed mixed results. Another important insight was that opioid intake decrease is a common trend among most studies included and that adverse effects were rarely reported. To further elucidate the potential of these neurostimulation techniques, we suggest the development of new clinical trials with larger samples and adequate sham controls.

Abstract
Introduction: During the last decade, the complementary value of real-world data (through registries or medical records) and data from randomized clinical trials has been recognized as increasingly important. In the field of neuromodulation, only a few industry-independent nationwide neuromodulation registries are available. The interest in creating a European registry has increased but without a successful result. The goal of this online survey is to gain further insights into the need for and burden of a European registry for neuromodulation.

Materials and methods: An online survey was developed and distributed during the 3rd Joint Congress of the International Neuromodulation Society European Chapters in September 2023 (Hamburg, Germany). Healthcare professionals were asked to indicate the need for a European registry, the items that should be collected, and the restrictions to access of a European registry.

Results: In total, 125 respondents opened the link to the survey, of whom 104 completed (at least partly) the survey. Of the 104 responses, 91% indicated that there is a need for a European registry, whereas 6% indicated there is no need. The main reasons for establishing a registry on a European level were the possibility of collecting real-world evidence (84%), the potential to collect big data from European patients (82%), to evaluate safety in neuromodulation (70%), and the possibility of reporting yearly on European activity in neuromodulation (51%). Indications for neuromodulation, patient characteristics, and follow-up assessments were most often stated as items that should be collected. Access should not only be granted to implanters but also to nurses, the assessment team, and other physicians, as agreed on by 64%, 52%, and 51%, respectively.

Discussion: More than 90% of the respondents believed that a European registry for neuromodulation is needed, mainly to obtain real-world (big) data about the effectiveness and safety of this therapy. This survey clearly pointed to the need for a European registry for which it seems key to ensure financial and logistical support, in addition to in-depth legal guidance in developing this registry.

Abstract
Objectives: Non-malignant chronic pain is a clinical challenge because pharmacological treatment often fails to relieve pain. Transcranial direct current stimulation (tDCS) is a treatment that could have the potential for pain relief and improvement in quality of life. However, there is a lack of clinical trials evaluating the effects of tDCS on the pain system. The aim of the present study was to evaluate the effect of 5 days of anodal tDCS treatment on the pain system in chronic non-malignant pain patients using quantitative sensory testing (QST) and quality of life questionnaires: (1) Brief Pain Inventory-short form (BPI-sf), (2) European Organization for Research and Treatment of Life Questionnaire (EORTC-C30), and (3) Hospital Anxiety Depression Scale (HADS).

Methods: Eleven non-malignant chronic pain patients (51±13.6 years old, 5M) participated in the study. Anodal tDCS was applied for five consecutive days, followed by sham stimulation after a washout period of at least two weeks. Pressure pain thresholds (PPT) and pain tolerance thresholds (PTT) were assessed in different body regions on days 1 and 5.

Results: Anodal tDCS appeared to maintain PTT at C5 (clavicle) on day 5, but sham stimulation decreased PTT (P=0.007). Additionally, anodal tDCS increased PTT compared to sham at day 5 at Th10 ventral dermatomes (P=0.014). Both anodal and sham tDCS decreased the BPI-sf total and interference scores, and the EORTC-C30 fatigue score, but no interaction effect was observed.

Discussion: This study adds to the evidence in the literature that tDCS may be a potential therapeutic tool for the management of non-malignant chronic pain.

Abstract
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.

Abstract
Background: Fibromyalgia pain and related symptoms are poorly managed by approved pharmacological and alternative interventions. This trial aimed to evaluate the effects of the EXOPULSE Mollii Suit-a multisite transcutaneous electrical nerve stimulation device-on fibromyalgia pain, fatigue, affective symptoms, disease impact, and quality of life.

Methods: Adult patients with fibromyalgia were enrolled. Phase 1 implied a randomized, sham-controlled, cross-over, double-blind trial, applying daily 1 h sessions of active or sham intervention, over 2 weeks (2-week washout). In the open-label phase 2, all patients received daily active intervention for 4 weeks. Comparisons on pain, fatigue, disease impact, affective symptoms, quality of life, clinical impression, and comfort ratings were performed using Friedman, Wilcoxon signed rank, and Chi2 tests.

Results: Thirty-three patients completed the study (93.9% female, mean age: 51.3 years). Pain (primary endpoint assessed via a visual analog scale) was significantly reduced after the active (pre-active: 6.9 ± 1.4, post-active: 5.9 ± 1.8, pre-sham: 6.8 ± 1.4, post-sham: 6.6 ± 1.5) versus the sham intervention (X2 = 10.60, p = 0.014). This was also the case of other secondary endpoints (i.e., fatigue, anxiety, and disease impact), except depression and quality of life. The Clinical Global Impression of Change (CGI-C) was significantly different between the active and sham intervention periods (X2 p = 0.035), and the different proportions of categories were as follows: 'worsening' (sham: 18.2% vs. active: 0.0%), 'improvement' (sham: 48.5% vs. active 63.6%) or 'no change (sham: 33.3% vs. active 36.4%) respectively. After phase 2, significant positive effects were observed for most of the outcomes, and 78.8% of patients reported improvement according to CGI-C.

Conclusions: This study suggests the clinical benefits of the EXOPULSE Mollii Suit in alleviating pain and fibromyalgia-related fatigue, emotional symptoms, and disease impact. It is worth noting that the study has several limitations related to the low number of participants, the short-term analysis of effects in the first blinded and controlled phase, and the open-label nature of phase 2. Future studies with a larger cohort and longer protocol treatment are needed, to further confirm the current results, and evaluate the long-term effects of this technique.

Significance: Patients with fibromyalgia suffer from pain as well as fatigue, sleep impairment, emotional disturbances, and altered quality of life. Transcutaneous electrical nerve stimulation might help manage those symptoms, but the available systems are limited by the fact that they could be applied at best over two sites. This randomized controlled study is the first to apply a multi-site transcutaneous electrical nerve stimulation device, the EXOPULSE Mollii Suit, with significant effects on fibromyalgia pain and related symptoms.

Abstract
Objectives: Neuromodulation is an effective treatment for chronic pain; however, socioeconomic differences may influence decision-making to initiate this therapy. This review investigated potential differences in accessibility of neuromodulation for patients with chronic pain due to socioeconomic determinants.

Materials and methods: Four electronic databases were used for this systematic review: MEDLINE, Embase, Scopus, and Web of Science. Risk of bias was assessed using the modified version of the Downs and Black checklist. The study protocol was prospectively registered on PROSPERO (CRD42023426035).

Results: The initial database search identified a total of 1118 unique studies, of which 36 were eventually included in the systematic review. Of the 36 included studies, six studies reported on education, 24 on employment status, ten on insurance, five on household income, and three on miscellaneous topics. Neuromodulation seems accessible for patients with different education levels and different types of insurance. Additionally, it is not restricted to patients who are (un)employed. When comparing patients who initiated neuromodulation with those who did not, a significantly higher number of patients in the top quartile for education were found in the group without neuromodulation. Regarding insurance, inconclusive evidence was found.

Conclusions: Although neuromodulation was accessible for patients with varying levels of socioeconomic determinants, disparities were noted. When comparing the socioeconomic profiles of patients who receive neuromodulation and those who do not, education levels differ. Health-related inequality should be carefully monitored in chronic pain management with neuromodulation to ensure that potential disparities do not increase.

Abstract
Objectives: Spinal cord stimulation (SCS) has been challenged by the lack of neurophysiologic data to guide therapy optimization. Current SCS programming by trial-and-error results in suboptimal and variable therapeutic effects. A novel system with a physiologic closed-loop feedback mechanism using evoked-compound action potentials enables the optimization of physiologic neural dose by consistently and accurately activating spinal cord fibers. We aimed to identify neurophysiologic dose metrics and their ranges that resulted in clinically meaningful treatment responses.

Materials and methods: Subjects from 3 clinical studies (n = 180) with baseline back and leg pain ≥60 mm visual analog scale and physical function in the severe to crippled category were included. Maximal analgesic effect (MAE) was operationally defined as the greatest percent reduction in pain intensity or as the greatest cumulative responder score (minimal clinically important differences [MCIDs]) obtained within the first 3 months of SCS implant. The physiologic metrics that produced the MAE were analyzed.

Results: We showed that a neural dose regimen with a high neural dose accuracy of 2.8μV and dose ratio of 1.4 resulted in a profound clinical benefit to chronic pain patients (MAE of 79 ± 1% for pain reduction and 12.5 ± 0.4 MCIDs). No differences were observed for MAE or neurophysiological dose metrics between the trial phase and post-implant MAE visit.

Conclusion: For the first time, an evidence-based neural dose regimen is available for a neurostimulation intervention as a starting point to enable optimization of clinical benefit, monitoring of adherence, and management of the therapy.

Abstract
Introduction: Spinal cord stimulation (SCS) is a well-established treatment for chronic pain and is supported by numerous studies. However, some recent articles have questioned its efficacy. This article examines a cohort of >1800 patients with SCS from the UK and Ireland National Neuromodulation Registry. It is intended to provide a "real-world" assessment of efficacy and compare its effects with other procedures performed for painful indications.

Materials and methods: Quality of life (QoL) data (EuroQoL five-level [EQ5D]) and demographic data were extracted from the National Neuromodulation Registry for all patients (N = 1811) who underwent SCS for chronic pain in 27 centers in the UK between February 2018 and July 2022. These were compared with data from the published literature for other commonly performed elective surgical procedures.

Results: The EQ5D utility index increased by a mean of 0.202 in the 1236 patients with paired pre- and postoperative utility scores. The median utility was 0.263 (interquartile range [IQR] = 0.384; n = 1811) preoperatively, whereas at six months after the operation, it was 0.550 (IQR = 0.396; n = 1025), p < 0.0001, Wilcoxon rank sum test. The median utility score at 12 months postoperation was 0.548 (IQR = 0.417; n = 970). There was no difference in utility scores at six months and 12 months after implantation (p = 0.15, Wilcoxon rank sum test). There was a significant improvement in QoL in all five domains of the five-level EQ5D tool at six months after baseline (p < 0.01, for all subcategories), and this was sustained at one year after implantation. The baseline utility was lower than in patients who underwent elective surgery for other painful conditions, and the absolute (and proportionate) increase in utility produced by SCS was greater than that achieved with most other interventions.

Conclusions: SCS increases the QoL in patients requiring surgery for pain. Similar results were seen regardless of SCS indication. When comparing analogous data bases, SCS produces a greater percentage improvement in EQ5D utility than do many other elective surgical procedures for painful conditions, including spinal surgery and some joint replacements.

Abstract
Spinal cord stimulation (SCS) is an effective modality for pain treatment, yet its underlying mechanisms remain elusive. Neurokinin 1 receptor-positive (NK1R+) neurons in spinal lamina I play a pivotal role in pain transmission. To enhance our mechanistic understanding of SCS-induced analgesia, we investigated how different SCS paradigms modulate the activation of NK1R+ neurons, by developing NK1R-Cre;GCaMP6s transgenic mice and using in vivo calcium imaging of superficial NK1R+ neurons under anesthesia (1.5% isoflurane). Neurokinin 1 receptor-positive neurons in the lumbar spinal cord (L4-5) showed a greater activation by electrical test stimulation (TS, 3.0 mA, 1 Hz) at the hindpaw at 2 weeks after tibia-sparing nerve injury (SNI-t) than in naïve mice. Spinal cord stimulation was then delivered through a bipolar plate electrode placed epidurally at L1-2 level. The short-term 50-Hz high-intensity SCS (80% motor threshold [MoT], 10 minutes) induced robust and prolonged inhibition of NK1R+ neuronal responses to TS in both naïve and SNI-t mice. The 30-minute 50-Hz and 900-Hz SCS applied at moderate intensity (50% MoT) also significantly inhibited neuronal responses in SNI-t mice. However, at low intensity (20% MoT), the 30-minute 900-Hz SCS only induced persistent neuronal inhibition in naïve mice, but not in SNI-t mice. In conclusion, both 10-minute high-intensity SCS and 30-minute SCS at moderate intensity inhibit the activation of superficial NK1R+ neurons, potentially attenuating spinal nociceptive transmission. Furthermore, in vivo calcium imaging of NK1R+ neurons provides a new approach for exploring the spinal neuronal mechanisms of pain inhibition by neuromodulation pain therapies.

Abstract
Objectives: This prospective, open-label, single-arm, multicenter study evaluated the use of differential target multiplexed (DTM) spinal cord stimulation (SCS) therapy for chronic upper limb pain (ULP).

Materials and methods: A total of 58 candidates for SCS who had chronic ULP were enrolled at 11 sites in the USA. The safety and effectiveness of DTM SCS for treating chronic intractable ULP were evaluated over 12 months. The primary end point was the percentage of responders (≥50% ULP relief versus baseline) to treatment at three months after device activation. This study also evaluated the extent of disability, patient satisfaction, and patient global impression of change with DTM SCS therapy.

Results: The mean baseline pain score (10-cm visual analog scale [VAS-10]) for ULP was 7.2 cm, with a mean age of 56 years and mean ULP duration of ten years; 47 subjects were assessed at the primary end point. The percentage of ULP responders was 92% at three months, which was consistent at six (91%) and 12 months (86%). Significant ULP relief (81% reduction in VAS-10) was observed at the primary end point and sustained throughout the study duration. Significant improvements in disability in addition to high levels (>95%) of satisfaction and feelings of improvement were reported. Frequency of study-related anticipated adverse events was in line with expectations of SCS therapy.

Conclusion: In this patient population with difficult-to-treat conditions with limited clinical evidence of the effectiveness of SCS, subjects reported significant reduction in chronic ULP in response to treatment with DTM SCS.

Abstract
Purpose of review: Neuromodulation approaches have been a part of a revolution in migraine therapies with multiple devices approved or in development. These devices vary in the nerve(s) being targeted, implantable versus noninvasive form factors as well as their effectiveness for acute pain reduction or migraine prevention. This review will summarize these recent advancements and approaches that are being developed which build upon prior work and improved technology that may help enhance the effectiveness as well as the patient experience.

Recent findings: Both noninvasive and implantable devices primarily targeting cranial nerves have shown the ability to help alleviate migraine symptoms. Multiple prospective and retrospective studies have demonstrated clinically meaningful reductions in headache intensity with noninvasive approaches, while prevention of migraine demonstrates more modest effects. Implantable neuromodulation technologies focusing on occipital and supraorbital stimulation have shown promise in migraine/headache prevention in chronic migraine patients, but there is a need for improvements in technology to address key needs for surgical approaches.

Summary: Electrical neuromodulation approaches in the treatment of migraine is undergoing a transformation towards improved outcomes with better technologies that may suit various patient needs on a more individualized basis.

Abstract
Introduction: One of the most common questions patients ask when they are contemplating deep brain stimulation (DBS) is how long it will last. To guide physicians in answering this query, we performed a scoping review to assess the current state of the literature and to identify the gaps that need to be addressed.

Materials and methods: The authors performed a MEDLINE search inclusive of articles from January 1987 (advent of DBS literature) to June 2023 including human and modeling studies written in English. For longevity of therapy data, only studies with a mean follow-up of ≥three years were included. Using the Rayyan platform, two reviewers (JP and RM) performed a title screen. Of the 734 articles, 205 were selected by title screen and 109 from abstract review. Ultimately, a total of 122 articles were reviewed. The research questions we explored were 1) how long can the different components of the DBS system maintain functionality? and 2) how long can DBS remain efficacious in treating Parkinson's disease (PD), essential tremor (ET), dystonia, and other disorders?

Results: We showed that patients with PD, ET, and dystonia maintain a considerable long-term benefit in motor scores seven to ten years after implant, although the percentage improvement decreases over time. Stimulation off scores in PD and ET show worsening, consistent with disease progression. Battery life varies by the disease treated and the programming settings used. There remains a paucity of literature after ten years, and the impact of new device technology has not been classified to date.

Conclusion: We reviewed existing data on DBS longevity. Overall, outcomes data after ten years of therapy are substantially limited in the current literature. We recommend that physicians who have data for patients with DBS exceeding this duration publish their results.

Abstract
Background: Spinal cord stimulation (SCS) has been reported to cause substantial pain relief and improved quality of life (QoL) in patients with persistent spinal pain syndrome (PSPS). Despite implantable pulse generator (IPG)-related inconveniences such as pain, shame, and discomfort affecting QoL and patient satisfaction, these are often neglected. Hence, the current study aims to determine the associations between patient satisfaction, IPG-related inconveniences, and preoperative counseling in a homogeneous group of patients with PSPS receiving SCS with IPG implantation in the gluteal or abdominal area.

Materials and methods: Retrospective data on sample characteristics were gathered from the EPIC (electronic health record software) digital patient data base. Prospective data on patient satisfaction were obtained with a questionnaire that covered various topics such as shame, pain, disturbances in daily/intense activities, night rest and/or sleep, discomfort caused by clothing, and preoperative counseling. The exact location of the IPG and its scar were determined with photo analysis. Thereafter, the site of IPG placement was classified into separate quadrants within the gluteal and abdominal area. Patient satisfaction was defined as accepting the current location of the IPG without having the wish to undergo revision surgery.

Results: In total, 81 participants (50.9 ± 10 years) were included in this analysis, with patient satisfaction observed in 61 patients (75.3%). Among satisfied patients, more extensive preoperative counseling concerning IPG pain and discomfort was reported compared with patients who were not satisfied (p < 0.001). When comparing the two groups, significant differences were found in shame (8/81, 9.9%), IPG site pain (21/81, 25.9%), disturbance of activities (42/81, 51.9%), and clothing-related discomfort (42/81, 51.9%).

Conclusions: On the basis of the current results, shared decision-making and comprehensive preoperative provision of information are recommended to optimize patient satisfaction regarding IPG pain, discomfort, and inconveniences. Although many patients experience these disadvantages despite successful SCS for pain related to PSPS, most of them accept this if they have received adequate preoperative information about expectations.

Abstract
Objectives: Chronic pain poses a significant health challenge worldwide and is associated with both disability and reduced quality of life. Sleep disturbances are reported in 67% to 88% of patients with chronic pain. Pain and sleep affect each other reciprocally; we aimed to study this bidirectional relationship in patients treated with spinal cord stimulation (SCS) for chronic pain. Specifically, we investigated whether sleep improves after treatment with SCS and whether this improvement may be mediated by pain reduction.

Materials and methods: An observational cohort study was conducted in patients with chronic neuropathic pain treated with SCS at a single neurosurgical department in Denmark. Outcomes were assessed preoperatively and at three, six, and 12 months postoperatively, and thereafter annually. Primary outcomes were pain intensity (numeric rating scale) and insomnia at first follow-up (Insomnia Severity Index). The association between sleep and pain was investigated using linear regression and mediation analysis.

Results: Forty-three patients were included in the study. The mean insomnia score was reduced by 25% from 18.1 (SD 6.0) to 13.5 (SD 6.6) (p = 0.0001). Pain intensity was reduced 38% from 7.4 (SD 1.6) to 4.6 (SD 2.1) at the first follow-up (p ≤ 0.0001). Changes in pain and changes in insomnia scores were significantly but weakly associated (regression coefficient = 1.3, 95% CI [0.3; 2.2], p = 0.008, r2 = 15.7%); and changes in pain score were not found to mediate changes in sleep score (β = -0.02, 95% CI [-0.15; 0.11], p = 0.76).

Conclusions: We found that patients treated with SCS showed significant improvements in both insomnia and pain intensity at first follow-up. Improvements in insomnia and pain intensity were significantly but weakly associated, and improvements in pain intensity score did not mediate improvements in insomnia score. Thus, improvements in self-reported insomnia in patients treated with SCS for chronic pain may predominantly be caused by other factors than reduced pain intensity.

Keywords: Chronic pain; insomnia; pain management; sleep; spinal cord stimulation.

Abstract
Background: Adverse effects of opioids could prolong the duration of stay in the post-anaesthesia care unit (PACU). This study aimed to assess time in the PACU and the pain-relieving effect of high-frequency, high-intensity transcutaneous electrical nerve stimulation (HFHI TENS) versus standard treatment with intravenous (IV) opioids.

Methods: Patients undergoing laparoscopic cholecystectomy at two Swedish hospitals were invited to participate. Patients reporting postoperative pain intensity ≥3 according to the Numeric Rating Scale (NRS) in the PACU were randomized to receive standard treatment with IV opioids or HFHI TENS, administered with an intensity of 40-60 mA for 1 min, repeated once if insufficient pain relief. If NRS remained ≥3 after two TENS stimulation the patients received IV opioids.

Results: In total, 163 patients were randomized to receive HFHI TENS (n = 85) or IV opioids (n = 78). There was no difference between the HFHI TENS group versus the opioid group regarding time in the PACU (138 min [SD 69] vs. 142 min [SD 95], mean difference -4.42 [95% CI-30:22], p = 0.74), time to pain relief NRS < 3 (median 10 min) and pain intensity at PACU discharge (NRS 1.7 [SD 1.45] vs. 1.6 [SD 1.20], p = 0.58). In the HFHI TENS group, 39 patients (46%) needed additional treatment with IV opioids. Mean opioid consumption was significantly lower in the HFHI TENS group than in the opioid group (4.5 vs. 11.0 morphine equivalents; p < 0.001).

Conclusions: HFHI TENS may be an opioid-sparing alternative for postoperative pain relief.

Significance statement: In this multicentre, RCT time in the PACU and the pain-relieving effect of HFHI TENS was compared to standard treatment with IV opioids. There were no differences between the groups regarding time in the PACU, time to pain relief and side effects but opioid consumption in the HFHI TENS group was significantly lower. Both groups reported high satisfaction with pain treatment and care. In summary, HFHI TENS should be considered a safe, fast-onsetting, opioid-sparing option for postoperative pain relief.

Abstract
Introduction: The International Neuromodulation Society convened a multispecialty group of physicians based on expertise and international representation to establish evidence-based guidance on the mitigation of neuromodulation complications. This Neurostimulation Appropriateness Consensus Committee (NACC)® project intends to update evidence-based guidance and offer expert opinion that will improve efficacy and safety.

Materials and methods: Authors were chosen on the basis of their clinical expertise, familiarity with the peer-reviewed literature, research productivity, and contributions to the neuromodulation literature. Section leaders supervised literature searches of MEDLINE, BioMed Central, Current Contents Connect, Embase, International Pharmaceutical Abstracts, Web of Science, Google Scholar, and PubMed from 2017 (when NACC last published guidelines) to October 2023. Identified studies were graded using the United States Preventive Services Task Force criteria for evidence and certainty of net benefit. Recommendations are based on the strength of evidence or consensus when evidence was scant.

Results: The NACC examined the published literature and established evidence- and consensus-based recommendations to guide best practices. Additional guidance will occur as new evidence is developed in future iterations of this process.

Conclusions: The NACC recommends best practices regarding the mitigation of complications associated with neurostimulation to improve safety and efficacy. The evidence- and consensus-based recommendations should be used as a guide to assist decision-making when clinically appropriate.

Abstract
Objective: Advancements in deep brain stimulation (DBS) devices provide a unique opportunity to record local field potentials longitudinally to improve the efficacy of treatment for intractable facial pain. We aimed to identify potential electrophysiological biomarkers of pain in the ventral posteromedial nucleus (VPM) of the thalamus and periaqueductal gray (PAG) using a long-term sensing DBS system.

Materials and methods: We analyzed power spectra of ambulatory pain-related events from one patient implanted with a long-term sensing generator, representing different pain intensities (pain >7, pain >9) and pain qualities (no pain, burning, stabbing, and shocking pain). Power spectra were parametrized to separate oscillatory and aperiodic features and compared across the different pain states.

Results: Overall, 96 events were marked during a 16-month follow-up. Parameterization of spectra revealed a total of 62 oscillatory peaks with most in the VPM (77.4%). The pain-free condition did not show any oscillations. In contrast, β peaks were observed in the VPM during all episodes (100%) associated with pain >9, 56% of episodes with pain >7, and 50% of burning pain events (center frequencies: 28.4 Hz, 17.8 Hz, and 20.7 Hz, respectively). Episodes of pain >9 indicated the highest relative β band power in the VPM and decreased aperiodic exponents (denoting the slope of the power spectra) in both the VPM and PAG.

Conclusions: For this patient, an increase in β band activity in the sensory thalamus was associated with severe facial pain, opening the possibility for closed-loop DBS in facial pain.

Abstract
Objectives: Different types of spinal cord stimulation (SCS) have now been evaluated for the management of chronic non-surgical refractory back pain (NSRBP). A direct comparison between the different types of SCS or between closed-loop SCS with conventional medical management (CMM) for patients with NSRBP has not been previously conducted, and therefore, their relative effectiveness and cost-effectiveness remain unknown. The aim of this study was to perform a systematic review, network meta-analysis (NMA) and economic evaluation of closed-loop SCS compared with fixed-output SCS and CMM for patients with NSRBP.

Methods: Databases were searched to 8th September 2023. Randomised controlled trials of SCS for NSRBP were included. Results of studies were combined using fixed-effect NMA models. A cost-utility analysis was performed from the perspective of the UK National Health Service with results reported as incremental cost per quality-adjusted life-year (QALY).

Results: Closed-loop SCS resulted in statistically and clinically significant reductions in pain intensity (mean difference [MD] 32.72 [95% CrI 15.69-49.78]) and improvements in secondary outcomes compared to fixed-output SCS at 6-months follow-up. Compared to CMM, both closed-loop and fixed-output SCS result in statistically and clinically significant reductions in pain intensity (closed-loop SCS vs. CMM MD 101.58 [95% CrI 83.73-119.48]; fixed-output SCS versus CMM MD 68.86 [95% CrI 63.43-74.31]) and improvements in secondary outcomes. Cost-utility analysis shows that closed-loop SCS dominates fixed-output SCS and CMM, and fixed-output SCS also dominates CMM.

Discussion: Current evidence shows that closed-loop and fixed-output SCS provide more benefits and are cost-saving compared to CMM for patients with NSRBP.

Abstract
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.

Keywords: Chronic pain; neurostimulation; percutaneous peripheral nerve stimulation; peripheral nerve stimulation; total knee arthroplasty.

Abstract
Objectives: Quantitative sensory testing (QST) has been used for decades to study sensory abnormalities in multiple conditions in which the somatosensory system is compromised, including pain. It is commonly used in pharmacologic studies on chronic pain but less so in conjunction with neuromodulation. This review aims to assess the utility of QST in spinal cord stimulation (SCS) protocols.

Materials and methods: For this narrative review, we searched PubMed for records of studies in which sensory testing has been performed as part of a clinical study on SCS from 1975 onward until October 2023. We focused on studies in which QST has been used to explore the effect of SCS on neuropathic, neuropathic-like, or mixed pain.

Results: Our search identified 22 useful studies, all small and exploratory, using heterogeneous methods. Four studies used the full battery of validated German Research Network on Neuropathic Pain QST. There is emerging evidence that assessment dynamic mechanical allodynia (eight studies), and mechanical/thermal temporal summation of pain (eight studies) may have a role in quantifying the response to various SCS waveforms. There also were sporadic reports of improvement of sensory deficits in a proportion of patients with neuropathic pain that warrant further study.

Conclusions: We recommend the adoption of QST into future clinical research protocols, using either the full QST protocol or a less time-demanding short-form QST.

Abstract
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.

Abstract
Background: Percutaneous stellate ganglion block (PSGB) through single bolus injection and thoracic epidural anaesthesia (TEA) have been proposed for the acute management of refractory ventricular arrhythmias (VAs). However, data on continuous PSGB (C-PSGB) are scant.

Aims: To report our dual-center experience with C-PSGB and to perform a systematic review on C-PSGB and TEA.

Methods: Consecutive patients receiving C-PSGB at 2 centers were enrolled. The systematic literature review follows the latest PRISMA criteria.

Results: Our case series (26 patients, 88% male, 60±16 years, all with advanced structural heart disease, LVEF 23±11%, 32 C-PSGB performed, median duration 3 days) shows that C-PSGB is feasible and safe and leads to complete VAs suppression in 59% and to overall clinical benefit in 94% of cases. Overall, 61 patients received 68 C-PSGB and 22 TEA, with complete VAs suppression in 63% of C-PSGBs (61% of patients). Most TEA procedures (55%) were performed on intubated patients, as opposed to 28% C-PSGBs (p=0.02); 52% of patients were on full anticoagulation at C-PSGB, none at TEA (p<0.001). Ropivacaine and lidocaine were the most used drugs for C-PSGB, and the available data support a starting dose of 12 mg/h and 100 mg/h, respectively. No major complications occurred, yet TEA discontinuation rate due to side-effects was higher than C-PSGB (18% versus 1%, p=0.01).

Conclusions: C-PSGB seems feasible, safe, and effective for the acute management of refractory VAs. The antiarrhythmic effect may be accomplished with less concerns for concomitant anticoagulation compared to TEA, and with a lower side-effects related discontinuation rate.

Abstract
Introduction: DeRidder burst spinal cord stimulation (SCS) has shown superior relief from overall pain to traditional tonic neurostimulation therapies and a reduction in back and leg pain. However, nearly 80% of patients have two or more noncontiguous pain areas. This affects the ability to effectively program stimulation and deliver long-term efficacy of the therapy. Multiple DeRidder burst region programming is an option to treat multisite pain by interleaving stimulation at multiple areas along the spinal cord. Previous intraoperative neuromonitoring studies have shown that DeRidder burst stimulation provides broader myotomal coverage at a lower recruitment threshold. The goal of this study is to correlate intraoperative electromyogram (EMG) threshold and postsynaptic excitability with postoperative paresthesia thresholds and optimal burst stimulation programming.

Materials and methods: Neuromonitoring was performed during permanent implant of SCS leads in ten patients diagnosed with chronic intractable back and/or leg pain. Each patient underwent the surgical placement of a Penta Paddle electrode through laminectomy at the T8-T11 spinal levels. Subdermal electrode needles were placed into lower extremity muscle groups, in addition to the rectus abdominis muscles, for EMG recording. Evoked responses were compared across multiple trials of burst stimulation in which the number of independent burst areas was varied. After intraoperative data collection, all patients were programmed with single- and multiarea DeRidder burst. Intermittent dosing was delivered at 30:90, 120:360, 120:720, and 120:1440 (seconds ON/OFF) intervals. Numerical rating scale (NRS) and Patient Global Impression of Change scores were evaluated at one, two, three, four, and six months after permanent implant.

Results: The thresholds for EMG recruitment after DeRidder burst differed across all patients owing to anatomical and physiological variations. After a 30-second dose of stimulation, the average decrease in thresholds was 1.25 mA for two-area and 0.9 mA for four-area DeRidder burst. Furthermore, a 30-second dose of multisite DeRidder burst produced a 0.25 mA reduction in the postoperative paresthesia thresholds. Across all patients, the baseline NRS score was 6.5 ± 0.5, and the NRS score after single or multiarea DeRidder burst therapy was 2.87 ± 1.50. Eight of ten patients reported a ≥50% decrease in their pain scores through the six-month follow-up visit. Pain outcomes using intermittent multiarea stimulation with longer OFF times (120:360, 120:720, 120:1440) were comparable to those using single-area DeRidder burst at 30:90 up to six months after implant with patient preference being two-area DeRidder burst.

Conclusions: This study aims to evaluate the use of intraoperative neuromonitoring to optimize stimulation programming for multisite pain and correlate it with postoperative programming and efficacy. These results suggest that multisite programming can be used to further customize DeRidder burst stimulation to each individual patient and improve outcomes and quality of life for patients receiving SCS therapy for multisite pain.

Abstract
Dorsal root ganglion stimulation (DRG-S) is a relatively new neuromodulation technique that has shown promising results in the treatment of chronic pain conditions. We present a case of a difficult lead extraction during the explantation of a DRG-S device. The lead was unable to be removed despite multiple attempts until a sheath and stylet were used to facilitate extraction. As DRG-S utilization becomes more widespread, DRG-S device explantation will inevitably become more common. The technique described in this report may be beneficial in certain cases of difficult DRG-S lead extraction.

Abstract
Background: Moral philosophy and psychology have sought to define the nature of right and wrong, and good and evil. The industrial turn of the twentieth century fostered increasingly technological approaches that conjoined philosophy to psychology, and psychology to the natural sciences. Thus, moral philosophy and psychology became ever more vested to investigations of the anatomic structures and physiologic processes involved in cognition, emotion and behavior--ultimately falling under the rubric of the neurosciences. Since 2002, neuroscientific studies of moral thought, emotions and behaviors have become known as--and a part of--the relatively new discipline of neuroethics. Herein we present Part 2 of a bibliography of neuroethics from 2002-2013 addressing the "neuroscience of ethics"--studies of putative neural substrates and mechanisms involved in cognitive, emotional and behavioral processes of morality and ethics.

Methods: A systematic survey of the neuroethics literature was undertaken. Bibliographic searches were performed by accessing 11 databases, 8 literature depositories, and 4 individual journal searches, and employed indexing language for National Library of Medicine (NLM) Medical Subject Heading databases. All bibliographic searches were conducted using the RefWorks citation management program.

Results: This bibliography lists 397 articles, 65 books, and 52 book chapters that present (1) empirical/experimental studies, overviews, and reviews of neural substrates and mechanisms involved in morality and ethics, and/or (2) reflections upon such studies and their implications. These works present resources offering iterative descriptions, definitions and criticisms of neural processes involved in moral cognition and behaviors, and also provide a historical view of this field, and insights to its developing canon.

Abstract
Advances in neurotechnology will raise new ethical dilemmas, to which scientists and the rest of society must respond. Here I present a "toolbox" of concepts to help us analyze these issues and communicate with each other about them across differences of ethical intuition.

Abstract
The requirement that doctors obtain valid consent from patients before providing medical treatment has long been ingrained in both legal doctrine and medical ethics. We summarize the foundations of the informed consent doctrine and discuss the recent evolution in thinking about consent and medical decision making. We show how consent has evolved from physicians merely providing patients information to shared decision making between patients and physicians. We then address three specific examples of situations common in neurological practice that pose challenges in obtaining valid consent: the administration of intravenous tPA following ischemic stroke, consideration of carotid endarterectomy for carotid artery stenosis, and implementation of do-not-resuscitate orders.

The journal Pain Medicine published a supplement in 2019 on the theme of Neuromodulation in relation to the spine and nervous system.

Anaesthesia is the official journal of the Association of Anaesthetists of Great Britain and Ireland and is international in scope and comprehensive in coverage. It publishes original, peer-reviewed articles on all aspects of general and regional anaesthesia, intensive care and pain therapy, including research on equipment.

Published monthly by the International Anesthesia Research Society (IARS) and includes peer-reviewed, original clinical and research articles, providing practicing physicians, researchers and allied medical personnel in anaesthesiology and related fields with a wealth of information to keep them up-to-date with the latest issues and advances in the field.

Anesthesiology is the official Journal of the American Society of Anesthesiologists. The Journal published its first issue in July 1940. The Journal receives nearly 1500 manuscript submissions per year, and publishes almost 4000 pages (about 3,000,000 words) of peer-reviewed material annually. Over 50% of the submissions and more than 6000 of its subscribers are from outside the United States, making it a major international publication.

A well-established journal in the field of behavioural and cognitive neuroscience, Behavioral and Brain Functions welcomes manuscripts which provide insight into the neurobiological mechanisms underlying behaviour and brain function, or dysfunction. The journal gives priority to manuscripts that combine both neurobiology and behaviour in a non-clinical manner.

Founded in 1923, the British Journal of Anaesthesia (BJA) remains the oldest and largest independent journal of anaesthesia. The journal strives to support research and discovery in the field by publishing the best original articles in all branches of Anaesthesia.

Brain Sciences (ISSN 2076-3425) is a peer-reviewed scientific journal that publishes original articles, critical reviews, research notes and short communications in the areas of cognitive neuroscience, developmental neuroscience, molecular and cellular neuroscience, neural engineering, neuroimaging, neurolinguistics, clinical neuroscience, systems neuroscience, and theoretical and computational neuroscience.

The scope of Brain Stimulation extends across the entire field of brain stimulation, including noninvasive and invasive techniques and technologies that alter brain function through the use of electrical, magnetic, radiowave, or focally targeted pharmacologic stimulation. This includes investigations that study the effects of brain stimulation on basic processes, such as gene expression and other aspects of molecular biology, neurochemical regulation, functional brain activity, sensorimotor function, and cognitive and affective processes at the systems level.

Child Neurology Open (CNO) is an interdisciplinary, peer-reviewed, open access forum for the most current information from clinical and investigative studies in the wide field of clinical pediatric neuroscience. Published articles come from a variety of disciplines, including child neurology, pediatric neurosurgery, pediatric neuroradiology, child and adolescent psychiatry, pediatric neuropsychology, developmental and behavioral pediatrics, and developmental neurobiology. Following careful peer review of submitted material, subsequent acceptance results in very rapid online publication and indexing in the major scientific publication databases.

The Clinical Journal of Pain explores all aspects of pain and its effective treatment, bringing you the insights of leading anesthesiologists, surgeons, internists, neurologists, orthopedists, psychiatrists and psychologists, clinical pharmacologists, and physical and rehabilitation therapists.

A multi-disciplinary, international journal that aims to be a global forum on all aspects of pain research and pain management. The journal publishes clinical and basic science research papers relevant to all aspects of pain and its management.

Frontiers in Neuroscience is a leading journal in its field, publishing rigorously peer-reviewed research across a wide spectrum of specialties and disciplines.

Human Brain Mapping publishes peer-reviewed basic, clinical, technical, and theoretical research in the interdisciplinary and rapidly expanding field of human brain mapping.

Interdisciplinary Neurosurgery: Advanced Techniques and Case Management is an open access journal, devoted to the publication of manuscripts of original work and review articles in the field of interdisciplinary neurosurgery, promoting excellence and advances in complex neurosurgical situations pioneering neurosurgical techniques , including case series and technical notes.

The Journal of Neurorestoratology is an international, peer-reviewed, open access journal focusing on original experimental and clinical research, methodological advances, neurorestorative mechanisms’ exploring, and expert reviews in the field of Neurorestoratology. Clinical studies on geriatric, pediatric, hereditary and traumatic disorders in central nervous system are of particular interest. And welcome neurorestorative strategies' exploring, which involve cell therapy, tissue engineering or bioengineering, neuromodulation by electro-magnetic stimulation, neural prostheses or brain-machine interface, pharmacotherapy or chemical therapies, neurorestorative surgery, active rehabilitation training, others, and combinations of these strategies.

Neurobiology of Pain is an international journal for the publication of basic and translational research on the mechanisms of acute and chronic pain. It focuses on experimental studies of pain mechanisms at every level from molecular and cellular to brain imaging and behavioural.

Neuroethics is a forum for interdisciplinary studies in neuroethics and related issues in the sciences of the mind. The focus is on ethical issues posed by new technologies developed via neuroscience, such as psycho-pharmaceuticals and other ways of intervening in the mind and the practice of neuroscience itself. This important publication covers the dual areas of neuroethics: the ethics of neuroscience and the neuroscience of ethics. It offers comprehensive bibliographies, reviews of significant literature, information on activities including partial proceedings of selected meetings, and an opinions section for reader commentaries.

NeuroImage: Clinical, a journal of diseases, disorders and syndromes involving the Nervous System, provides a vehicle for communicating important advances in the study of abnormal structure-function relationships of the human nervous system based on imaging.

Neurological Sciences and Neurophysiology is the double blind peer-reviewed, open access, online only, international publication organ of Turkish Society of Clinical Neurophysiology EEG-EMG. The journal is a quarterly publication, published in March, June, September and December and the publication language of the journal is English. Neurological Sciences and Neurophysiology aims to contribute to the international literature by publishing original clinical and experimental research articles, review articles, and letters to the editor on all fields of neurological sciences and especially in neurophysiology. The journal is directed at an audience of physicians and scientists of Neurology, Neurosurgery, Psychiatry, Neurophysiology, Neuropathology, Neuroradiology.

In recognition of the belief that the future for dissemination of scientific and medical research lies in open access on-line journals, Neurology International has been developed as a forum for the free and open international exchange of progress in the clinical neurosciences. By adhering to standards for high quality and ethics, Neurology International offers a unique service to the world's medical community. The international board of editors for the journal are committed to promoting scientific advancement and excellence for the benefit of all, in all aspects of neurology, as well as diagnosis and treatment of stroke, Alzheimer disease, epilepsy, Parkinson disease, multiple sclerosis, and other disorders of the brain and nervous system.

Neurology Research International is a peer-reviewed, Open Access journal that publishes original research articles, review articles, and clinical studies focusing on diseases of the nervous system, as well as normal neurological functioning. The journal will consider basic, translational, and clinical research, including animal models and clinical trials.

Neuromodulation: Technology at the Neural Interface is the preeminent journal in the area of neuromodulation, providing our readership with the state of the art clinical, translational and basic science research in our field and representing the needs of the broad neuromodulation community. For clinicians, engineers, scientists and members of the biotechnology industry alike, Neuromodulation provides timely and rigorously peer reviewed articles on the technology, science and clinical application of devices that interface with the nervous system to treat disease and improve function. Neuromodulation covers an ever expanding field including pain, headache, movement disorders, spasticity, paralysis, psychiatric disorders, epilepsy, sensory deprivation, gastric dysfunction, obesity and incontinence.

The mission of Neuronal Signaling is to provide an interdisciplinary home for neuroscientific disciplines covering all aspects of in vitro and in vivo signaling from cell to brain in health and disease. Relevant topics range from signaling pathways involved in nervous system development and normal physiology through to neurodegenerative, neurological and psychiatric disorders and other pathologies.

PAIN® is the official publication of the International Association for the Study of Pain® (IASP®). PAIN® publishes original research on the nature, mechanisms, and treatment of pain and provides a multidisciplinary forum for the dissemination of research in the basic and clinical sciences.

Pain Medicine is dedicated to pain clinicians, educators, and researchers with an interest in pain from various medical specialties and related health disciplines. The journal reflects the rapid growth in pain science and practice, as well as the field's need for policy, ethical, and forensic commentary on pain and its management. It promotes the visibility and development of pain medicine as a worldwide interdisciplinary medical specialty within a collaborative, multidisciplinary pain field.

A peer-reviewed, multi-disciplinary journal written by and directed to an audience of interventional pain physicians, clinicians and basic scientists with an interest in interventional pain management and pain medicine.

Pain Practice, the official journal of the World Institute of Pain, publishes international multidisciplinary articles on pain and analgesia that provide its readership with up-to-date research, evaluation methods, and techniques for pain management.

World Neurosurgery: X offers authors with high-quality research who want to publish in a gold open access journal the opportunity to make their work immediately, permanently, and freely accessible.