The Effect of Various Spinal Neurostimulation Paradigms on the Supraspinal Somatosensory Evoked Response: A Systematic Review.

INTRODUCTION: Spinal neurostimulation is a therapy for otherwise intractable chronic pain. Spinal neurostimulation includes stimulation of the spinal cord (SCS), dorsal root ganglion (DRGS), and dorsal root entry zone (DREZS). New paresthesia-free neurostimulation paradigms may rely on different mechanisms of action from those of conventional tonic neurostimulation. The aim of this systematic review is to assess the existing knowledge on the effect of spinal neurostimulation on somatosensory processing in patients with chronic pain. We therefore reviewed the existing literature on the effect of various spinal neurostimulation paradigms on the supraspinal somatosensory evoked response (SER). MATERIALS AND METHODS: Multiple scientific data bases were searched for studies that assessed the effect of spinal neurostimulation on the supraspinal SER, evoked by painful or nonpainful peripheral stimuli in patients with chronic pain. We found 205 studies, of which 24 were included. Demographic data, study design, and study outcome were extracted. RESULTS: Of the 24 included studies, 23 used electroencephalography to assess the SER; one study used magnetoencephalography. Fifteen studies evaluated tonic SCS; six studies (also) evaluated paresthesia-free paradigms; three studies evaluated the effect of tonic DRGS or DREZS. Sixteen studies used nonpainful stimuli to elicit the SER, 14 observed a decreased SER amplitude. Ten studies used painful stimuli to elicit the SER, yielding mixed results. DISCUSSION: The included studies suggest that both paresthesia-based and paresthesia-free spinal neurostimulation paradigms can decrease (part of) the SER elicited by a nonpainful peripheral stimulus. The observed SER amplitude reduction likely is the effect of various spinal and supraspinal mechanisms of spinal neurostimulation that also contribute to pain relief. CONCLUSIONS: Spinal neurostimulation modulates the processing of a peripherally applied nonpainful stimulus. For painful stimuli, the results are not conclusive. It is not yet clear whether paresthesia-free neurostimulation affects the SER differently from paresthesia-based neurostimulation.

Examining the Duration of Carryover Effect in Patients With Chronic Pain Treated With Spinal Cord Stimulation (EChO Study): An Open, Interventional, Investigator-Initiated, International Multicenter Study.

OBJECTIVES: Spinal cord stimulation (SCS) is a surgical treatment for severe, chronic, neuropathic pain. It is based on one to two lead(s) implanted in the epidural space, stimulating the dorsal column. It has long been assumed that when deactivating SCS, there is a variable interval before the patient perceives the return of the pain, a phenomenon often termed echo or carryover effect. Although the carryover effect has been problematized as a source of error in crossover studies, no experimental investigation of the effect has been published. This open, prospective, international multicenter study aimed to systematically document, quantify, and investigate the carryover effect in SCS. MATERIALS AND METHODS: Eligible patients with a beneficial effect from their SCS treatment were instructed to deactivate their SCS device in a home setting and to reactivate it when their pain returned. The primary outcome was duration of carryover time defined as the time interval from deactivation to reactivation. Central clinical parameters (age, sex, indication for SCS, SCS treatment details, pain score) were registered and correlated with carryover time using nonparametric tests (Mann-Whitney/Kruskal-Wallis) for categorical data and linear regression for continuous data. RESULTS: In total, 158 patients were included in the analyses. A median carryover time of five hours was found (interquartile range 2.5;21 hours). Back pain as primary indication for SCS, high-frequency stimulation, and higher pain score at the time of deactivation were correlated with longer carryover time. CONCLUSIONS: This study confirms the existence of the carryover effect and indicates a remarkably high degree of interindividual variation. The results suggest that the magnitude of carryover may be correlated to the nature of the pain condition and possibly stimulation paradigms. CLINICAL TRIAL REGISTRATION: The Clinicaltrials.gov registration number for the study is NCT03386058.

Intermittent versus continuous esketamine infusions for long-term pain modulation in complex regional pain syndrome: protocol of a randomized controlled non-inferiority study (KetCRPS-2).

BACKGROUND: Complex regional pain syndrome (CRPS) is a chronic pain condition of an extremity. While achieving pain relief in CRPS is challenging, esketamine infusions can accomplish pain relief for several weeks post-infusion in a subgroup of CRPS patients. Unfortunately, CRPS esketamine protocols are very heterogeneous in advice on dosage, administration and treatment setting. Currently, no trials are available that study differences between intermittent and continuous esketamine infusions for CRPS. With the current situation of bed shortages, it is difficult to admit patients for several consecutive days for inpatient esketamine treatments. In this study, we investigate whether 6 intermittent outpatient esketamine treatments are not inferior to a continuous 6-day inpatient esketamine treatment in establishing pain relief. In addition, several secondary study parameters will be assessed in order to investigate mechanisms responsible for pain relief by esketamine infusions. Furthermore, the cost-effectiveness will be analyzed. METHODS: In this RCT, the primary objective is to demonstrate that an intermittent esketamine dosing regimen is non-inferior to a continuous esketamine dosing regimen at 3 months follow-up. We will include 60 adult CRPS patients. The inpatient treatment group receives a continuous intravenous esketamine infusion for 6 consecutive days. The outpatient treatment group receives a 6-hour intravenous esketamine infusion every 2 weeks for 3 months. Esketamine dose will be individually tailored and is started at 0.05 mg/kg/h and can be increased to a maximum of 0.2 mg/kg/h. Each patient will be followed for 6 months. The primary study parameter is perceived pain intensity, measured by an 11-point Numerical Rating Scale. Secondary study parameters are conditioned pain modulation, quantitative sensory testing, adverse events, thermography, blood inflammatory parameter, questionnaires about functionality, quality of life and mood and costs per patient. DISCUSSION: If our study reveals non-inferiority between intermittent and continuous esketamine infusions, these findings can be beneficial to increase the availability and flexibility of esketamine infusions through outpatient treatments. Furthermore, the costs of outpatient esketamine infusions could be lower than inpatient esketamine infusions. In addition, secondary parameters may predict response to esketamine treatment. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT05212571 , date of registration 01-28-2022. PROTOCOL VERSION: Version 3, February 2022.

A Review of Effects of Spinal Cord Stimulation on Spectral Features in Resting-State Electroencephalography.

BACKGROUND: Spinal cord stimulation (SCS) is an effective therapy for patients with refractory chronic pain syndromes. Although studies have shown that SCS has both spinal and supraspinal effects, the current understanding of cortical effects is still limited. Neuroimaging techniques, such as magnetoencephalography (MEG) and electroencephalography (EEG), combined here as M/EEG, can reveal modulations in ongoing resting-state cortical activity. We aim to provide an overview of available literature on resting-state M/EEG in patients with chronic pain who have been treated with SCS. MATERIALS AND METHODS: We searched multiple online data bases for studies on SCS, chronic pain, and resting-state M/EEG. Primary outcome measures were changes in spectral features, combined with brain regions in which these changes occurred. RESULTS: We included eight studies reporting various SCS paradigms (tonic, burst, high-dose, and high-frequency stimulation) and revealing heterogeneity in outcome parameters. We summarized changes in cortical activity in various frequency bands: theta (4-7 Hz), alpha (7-12 Hz), beta (13-30 Hz), and gamma (30-44 Hz). In multiple studies, the somatosensory cortex showed modulation of cortical activity under tonic, burst, and high-frequency stimulation. Changes in connectivity were found in the dorsal anterior cingulate cortex, dorsolateral prefrontal cortex, and parahippocampus. CONCLUSIONS: The large heterogeneity observed in outcome measures is probably caused by the large variety in study designs, stimulation paradigms, and spectral features studied. Paresthesia-free paradigms have been compared with tonic stimulation in multiple studies. These studies suggest modulation of medial, lateral, and descending pathways for paresthesia-free stimulation, whereas tonic stimulation predominantly modulates lateral and descending pathways. Moreover, multiple studies have reported an increased alpha peak frequency, increased alpha power, and/or decreased theta power when SCS was compared with baseline, indicating modulation of thalamocortical pathways. Further studies with well-defined groups of responders and nonresponders to SCS are recommended to independently study the cortical effects of pain relief and SCS.

Heterogeneous Cortical Effects of Spinal Cord Stimulation.

OBJECTIVES: The understanding of the cortical effects of spinal cord stimulation (SCS) remains limited. Multiple studies have investigated the effects of SCS in resting-state electroencephalography. However, owing to the large variation in reported outcomes, we aimed to describe the differential cortical responses between two types of SCS and between responders and nonresponders using magnetoencephalography (MEG). MATERIALS AND METHODS: We conducted 5-minute resting-state MEG recordings in 25 patients with chronic pain with active SCS in three sessions, each after a one-week exposure to tonic, burst, or sham SCS. We extracted six spectral features from the measured neurophysiological signals: the alpha peak frequency; alpha power ratio (power 7-9 Hz/power 9-11 Hz); and average power in the theta (4-7.5 Hz), alpha (8-12.5 Hz), beta (13-30 Hz), and low-gamma (30.5-60 Hz) frequency bands. We compared these features (using nonparametric permutation t-tests) for MEG sensor and cortical map effects across stimulation paradigms, between participants who reported low (< 5, responders) vs high (≥ 5, nonresponders) pain scores, and in three representative participants. RESULTS: We found statistically significant (p < 0.05, false discovery rate corrected) increased MEG sensor signal power below 3 Hz in response to burst SCS compared with tonic and sham SCS. We did not find statistically significant differences (all p > 0.05) between the power spectra of responders and nonresponders. Our data did not show statistically significant differences in the spectral features of interest among the three stimulation paradigms or between responders and nonresponders. These results were confirmed by the MEG cortical maps. However, we did identify certain trends in the MEG source maps for all comparisons and several features, with substantial variation across participants. CONCLUSIONS: The considerable variation in cortical responses to the various SCS treatment options necessitates studies with sample sizes larger than commonly reported in the field and more personalized treatment plans. Studies with a finer stratification between responders and nonresponders are required to advance the knowledge on SCS treatment effects.

Allodynia, Hyperalgesia, (Quantitative) Sensory Testing and Conditioned Pain Modulation in Patients With Complex Regional Pain Syndrome Before and After Spinal Cord Stimulation Therapy.

OBJECTIVES: Complex regional pain syndrome (CRPS) is a chronic debilitating disease characterized by sensory abnormalities. Spinal cord stimulation (SCS) is an effective therapy for CRPS, but few studies have investigated the effects of SCS therapy on sensory characteristics. Therefore, this study investigated the effect of SCS on allodynia, hyperalgesia, electrical quantitative sensory testing (QST) parameters, and conditioned pain modulation (CPM) effect. MATERIALS AND METHODS: This study is part of a multicenter randomized controlled trial (ISRCTN 36655259). Patients with CRPS in one extremity and eligible for SCS were included. The outcome parameters allodynia (symptom and sign), hyperalgesia (symptom), sensory thresholds with QST, CPM effect, and pain scores were tested before and after three months of SCS (40-Hz tonic SCS). Both the CRPS-affected extremity and the contralateral, clinically unaffected extremity were used to test three sensory thresholds with electrical QST: current perception threshold (CPT), pain perception threshold (PPT), and pain tolerance threshold (PTT). The PTT also was used as a test stimulus for the CPM paradigm both before and after the conditioning ice-water test. Nonparametric testing was used for all statistical analyses. RESULTS: In total, 31 patients were included for analysis. Pain, allodynia (sign and symptom), and hyperalgesia (symptom) were all significantly reduced after SCS therapy. On the unaffected side, none of the QST thresholds (CPT, PPT, and PTT) was significantly altered after SCS therapy. However, the CPT on the CRPS-affected side was significantly increased after SCS therapy. A CPM effect was present both before and after SCS. CONCLUSIONS: Standard 40-Hz tonic SCS significantly reduces pain, hyperalgesia, and allodynia in patients with CRPS. These findings suggest that SCS therapy should not be withheld from patients who suffer from allodynia and hyperalgesia, which contradicts previous findings derived from retrospective analysis and animal research. ISRCTN Registry: The ISRCTN registration number for the study is ISRCTN 36655259.

Electrical neurostimulation for the treatment of chronic pruritus: A systematic review.

Approximately one fifth of the world population experiences continuous itch for 6 weeks or more during their life, that is chronic itch. It is diverse in its aetiologies, and it is notoriously hard to treat. Because itch and pain have largely overlapping pathophysiology and the demonstrated efficacy of neurostimulation in treatment of selected chronic pain conditions, we conducted a systematic review to investigate whether neurostimulation could be an effective treatment for chronic itch. We identified two randomized controlled trials and 17 open label studies or case reports investigating various neurostimulation modalities for the treatment of refractory itch of various aetiologies. Transcutaneous electrical nerve stimulation (TENS) was the most investigated modality (n = 17), and in the largest number of conditions. Other modalities were cutaneous field stimulation (n = 2), painscrambler (n = 1), transcranial direct current stimulation (n = 1) and peripheral nerve field stimulation (n = 1). Atopic dermatitis was the most studied condition (n = 5). Despite the large heterogeneity in used stimulation paradigms and outcome parameters, all studies reported a positive effect of at least one neurostimulation modality. Our review indicates that electrical neurostimulation could be considered for the treatment of refractory chronic itch of selected aetiologies, such as atopic dermatitis or burn pruritus. However, better understanding of the mechanisms of action of the neurostimulation modalities and regimens in various pruritic conditions is necessary.

How to Identify Responders and Nonresponders to Dorsal Root Ganglion-Stimulation Aimed at Eliciting Motor Responses in Chronic Spinal Cord Injury: Post Hoc Clinical and Neurophysiological Tests in a Case Series of Five Patients.

OBJECTIVE: While integrity of spinal pathways below injury is generally thought to be an important factor in the success-rate of neuromodulation strategies for spinal cord injury (SCI), it is still unclear how the integrity of these pathways conveying the effects of stimulation should be assessed. In one of our institutional case series of five patients receiving dorsal root ganglion (DRG)-stimulation for elicitation of immediate motor response in motor complete SCI, only two out of five patients presented as responders, showing immediate muscle activation upon DRG-stimulation. The current study focuses on post hoc clinical-neurophysiological tests performed within this patient series to illustrate their use for prediction of spinal pathway integrity, and presumably, responder-status. MATERIALS AND METHODS: In a series of three nonresponders and two responders (all male, American Spinal Injury Association [ASIA] impairment scale [AIS] A/B), a test-battery consisting of questionnaires, clinical measurements, as well as a series of neurophysiological measurements was performed less than eight months after participation in the initial study. RESULTS: Nonresponders presented with a complete absence of spasticity and absence of leg reflexes. Additionally, nonresponders presented with close to no compound muscle action potentials (CMAPs) or Hofmann(H)-reflexes. In contrast, both responders presented with clear spasticity, elicitable leg reflexes, CMAPs, H-reflexes, and sensory nerve action potentials, although not always consistent for all tested muscles. CONCLUSIONS: Post hoc neurophysiological measurements were limited in clearly separating responders from nonresponders. Clinically, complete absence of spasticity-related complaints in the nonresponders was a distinguishing factor between responders and nonresponders in this case series, which mimics prior reports of epidural electrical stimulation, potentially illustrating similarities in mechanisms of action between the two techniques. However, the problem remains that explicit use and report of preinclusion clinical-neurophysiological measurements is missing in SCI literature. Identifying proper ways to assess these criteria might therefore be unnecessarily difficult, especially for nonestablished neuromodulation techniques.

Effect of intravenous low-dose S-ketamine on pain in patients with Complex Regional Pain Syndrome: A retrospective cohort study.

OBJECTIVE: The objective of this study was to assess the effectiveness of a low-dose intravenous S-ketamine treatment on refractory pain in patients with Complex Regional Pain Syndrome (CRPS). METHODS: In this retrospective study, patients with CRPS who received intravenous S-ketamine from March 2010 to April 2019 were included. According to our inpatient protocol, S-ketamine dose was increased until pain reduction was achieved or side effects were observed. Maximum dose was 14 mg/h and treatment duration was 7 days. Primary outcome parameters were pain scores (Numeric Rating Scale) at baseline (T0), end of infusion (T1), and approximately 4 weeks postinfusion (T2). Patients were categorized as responder/nonresponder at T1 and T2. Patients were considered a responder in case there was pain score reduction of greater than or equal to 2 points or if treatment was reported as successful. RESULTS: Forty-eight patients were included. Mean disease duration was 5 years (interquartile range [IQR] = 6 years). Median pain score significantly decreased from 8 (IQR = 2) at T0 to 6 (IQR = 4) at T1 (p < 0.001). At T1, 62% of the patients were responders. At T2, 48% of the patients remained a responder. A significant proportion of the responders at T1 turned into nonresponders at T2 (p = 0.03). CONCLUSION: In a group of patients with CRPS with refractory pain, low-dose intravenous S-ketamine treatment resulted in effective pain relief during infusion. Although a significant proportion of initial responders became nonresponders at follow-up, half of the patients were still a responder at ~ 4 weeks postinfusion. Further research is needed to investigate mechanisms responsible for pain relief by S-ketamine infusions and to ascertain possible predictors of response to the treatment.

Quality of life increases in patients with painful diabetic neuropathy following treatment with spinal cord stimulation.

PURPOSE: This study aims to explore the changes in pain intensity and quality of life (QoL) experienced by patients with painful diabetic neuropathy (PDN) treated with spinal cord stimulation (SCS) and conventional medical practice (CMP). METHODS: Patient-reported pain intensity and QoL data were obtained from participants in an international multicentre randomised controlled trial comparing SCS versus CMP. Data were collected at randomisation and 6 month follow up by means of a visual analogue scale for pain intensity, the EuroQoL Visual Analogue Scale (EQ VAS) and the EuroQol EQ-5D index. Quality-adjusted life years (QALYs) were calculated for each treatment using the 'area under the curve' method. Differences in QALYs were calculated after adjusting for between-treatment imbalances in baseline QoL. RESULTS: At 6 months, patients allocated to SCS reported larger reductions in pain intensity and improvements in QoL measured by the EQ-5D utility score and EQ VAS as compared to those allocated to CMP. Initial calculations of QALYs for the SCS and CMP groups suggested no statistical differences between the groups. Adjusting for imbalances in baseline EQ-5D scores showed SCS to be associated with significantly higher QALYs compared to CMP. CONCLUSIONS: SCS resulted in significant improvement in pain intensity and QoL in patients with PDN, offering further support for SCS as an effective treatment for patients suffering from PDN. From a methodological point of view, different results would have been obtained if QALY calculations were not adjusted for baseline EQ-5D scores, highlighting the need to account for imbalances in baseline QoL.

Effect of Burst Stimulation Evaluated in Patients Familiar With Spinal Cord Stimulation.

OBJECTIVE: Spinal cord stimulation (SCS) is used for treating intractable neuropathic pain. It has been suggested that burst SCS (five pulses at 500 Hz, delivered 40 times per second) suppresses neuropathic pain at least as well as conventional tonic SCS, but without evoking paraesthesia. The efficacy of paraesthesia-free high and low amplitude burst SCS for the treatment of neuropathic pain in patients who are already familiar with tonic SCS was evaluated. MATERIALS AND METHODS: Forty patients receiving conventional (30-120 Hz) tonic SCS for at least six months were included. All patients received high and low amplitude burst SCS, for a two-week period in a double blind randomized crossover design, with a two-week period of tonic stimulation in between. The average visual analogue scale (VAS) scores for pain during the last three days of each stimulation period were evaluated as well as quality of life (QoL) scores, and patient's preferences. RESULTS: Average VAS score for pain were lower during high (40, p = 0.013) and low amplitude burst stimulation (42, p = 0.053) compared with tonic stimulation (52). QoL scores did not differ significantly. At the individual level 58% of the patients experienced significant additional pain reduction (>30% decrease in VAS for pain) during high and/or low amplitude burst stimulation. Eleven patients preferred tonic stimulation, fifteen high, and fourteen low amplitude burst stimulation. CONCLUSION: Burst stimulation is in general more effective than tonic stimulation. Individual patients can highly benefit from burst stimulation; however, the therapeutic range of burst stimulation amplitudes requires individual assessment.

Masking the Auditory Evoked Potential in TMS-EEG: A Comparison of Various Methods.

There is growing interest in combining transcranial magnetic stimulation (TMS) with electroencephalography (EEG). Because TMS pulses are accompanied by a clicking sound, it is very likely that part of the response in the EEG consists of an auditory evoked potential (AEP). Different methods have been applied to mask the sound of TMS. However, it is unclear which masking method is most effective in reducing the AEP. In this study we explore the presumed contribution of the AEP to the response and evaluate different ways to mask the TMS clicking sound. Twelve healthy subjects and one completely deaf subject participated in this study. Eight different masking conditions were evaluated in nine hearing subjects. The amplitude of the N100-P180 complex was compared between the different masking conditions. We were not able to completely suppress the N100-P180 when the coil was placed on top of the head. Using an earmuff or exposing the subjects to white or adapted noise caused a small but significant reduction in N100-P180 amplitude, but the largest reduction was achieved when combining a layer of foam, placed between coil and head, with white or adapted noise. The deaf subject also showed a N100-P180 complex. We conclude that both the TMS clicking sound and cortical activation by the magnetic pulse contribute to the N100-P180 amplitude.

Is preoperative pain duration important in spinal cord stimulation? A comparison between tonic and burst stimulation.

OBJECTIVE: Conflicting data have been published as to whether the success rate of spinal cord stimulation (SCS) is inversely proportional to the time interval from the initial onset of symptoms to implantation. Recently, a new stimulation design called burst stimulation has been developed that seems to exert its effect by modulating both the medial and lateral pain pathways and has a better effect than tonic stimulation on global pain, back pain, and limb pain. MATERIALS AND METHODS: We analyzed the effect of preoperative pain duration on the degree of pain suppression by both tonic and burst stimulation in a group of patients (n = 49) who underwent both tonic and burst SCS. RESULTS: Using Pearson correlation analysis and controlling for age and duration of SCS, no correlation could be found between the preoperative pain duration and the success of SCS, either for tonic or for burst SCS, as defined by a numeric rating scale for pain. Using a different analysis method, dividing patients into groups according to preoperative pain duration, the same absence of influence was found. Pain was better suppressed by burst stimulation than tonic stimulation, irrespective of the preoperative pain duration. CONCLUSIONS: These results suggest that the duration of pain is not an exclusion criterion for SCS and that similar success rates can be obtained for longstanding pain and pain of more recent onset.

Burst spinal cord stimulation evaluated in patients with failed back surgery syndrome and painful diabetic neuropathy.

OBJECTIVE: Spinal cord stimulation (SCS) is used for treating intractable neuropathic pain. Generally, it induces paresthesia in the area covered by SCS. Burst SCS was introduced as a new stimulation paradigm with good pain relief without causing paresthesia. Good results have been obtained in patients who were naive to SCS. In this study we assess the effectiveness of burst stimulation in three groups of chronic pain patients who are already familiar with SCS and the accompanying paresthesia. METHODS: Forty-eight patients with at least six months of conventional, tonic stimulation tested burst stimulation for a period of two weeks. They were classified in three different groups: a cross-section of our population with painful diabetic neuropathy (PDN), a cross-section of our population with failed back surgery syndrome (FBSS), and FBSS patients who over time had become poor responders (PR) to SCS. Visual analog scale scores for pain were assessed prior to implantation, with tonic stimulation, and after two weeks of burst stimulation. RESULTS: Burst stimulation reduced pain significantly for almost all patients. When compared with tonic stimulation, burst stimulation led to a significant additional pain reduction of on average 44% in patients with PDN (p < 0.001) and 28% in patients with FBSS (p < 0.01). Patients from the PR group benefitted less from burst stimulation on average. In addition, burst stimulation caused little or no paresthesia whereas tonic stimulation did induce paresthesia. Most patients preferred burst stimulation, but several preferred tonic stimulation because the paresthesia assured them that the SCS was working. CONCLUSION: About 60% of the patients with tonic SCS experienced further pain reduction upon application of burst stimulation.

A multidisciplinary approach on music induced-analgesia differentiated by socio-cultural background in healthy volunteers (MOSART): A cross-over randomized controlled trial protocol.

Background: Integrating music into pain treatment demonstrates significant benefits, effectively reducing subjective pain levels and perioperative opioid requirements. Currently, the relationship between the impact of specific types of music and listeners' socio-cultural background is still unclear. This is especially relevant given that sociological research indicates that these factors can have a notable influence on music preference and perception. Current evidence suggests that individuals who choose their own music may experience greater benefits. However, additional research is needed to comprehensively grasp whether the effect of (preferred) music on pain endurance remains consistent across different socio-cultural backgrounds. Methods: In this study, a collaborative effort between medical and sociological researchers aims to investigate music-induced analgesia differentiated by socio-cultural background in healthy volunteers. Participants (n = 84) will listen to self-, and researcher-chosen music and a podcast as a control condition in a cross-over study design. The primary outcome of this study is pain endurance measured by electric stimuli of increasing intensity. Detailed sociological validated questionnaires will be utilized. Considering the notable influence of educational level on music taste formation found in previous research and its crucial role as a source of socio-cultural differentiation, participants will be stratified based on their level of education. Discussion: This experimental study represents one of the first efforts to gain a socio-culturally differentiated understanding of the therapeutic potential of music. Consequently, this could pave the way to purposefully and inclusively implement personalized music in healthcare settings.

Neurophysiological oscillatory markers of hypoalgesia in conditioned pain modulation.

Introduction: Conditioned pain modulation (CPM) is an experimental procedure that consists of an ongoing noxious stimulus attenuating the pain perception caused by another noxious stimulus. A combination of the CPM paradigm with concurrent electrophysiological recordings can establish whether an association exists between experimentally modified pain perception and modulations of neural oscillations. Objectives: We aimed to characterize how CPM modifies pain perception and underlying neural oscillations. We also interrogated whether these perceptual and/or neurophysiological effects are distinct in patients affected by chronic pain. Methods: We presented noxious electrical stimuli to the right ankle before, during, and after CPM induced by an ice pack placed on the left forearm. Seventeen patients with chronic pain and 17 control participants rated the electrical pain in each experimental condition. We used magnetoencephalography to examine the anatomy-specific effects of CPM on the neural oscillatory responses to the electrical pain. Results: Regardless of the participant groups, CPM induced a reduction in subjective pain ratings and neural responses (beta-band [15-35 Hz] oscillations in the sensorimotor cortex) to electrical pain. Conclusion: Our findings of pain-induced beta-band activity may be associated with top-down modulations of pain, as reported in other perceptual modalities. Therefore, the reduced beta-band responses during CPM may indicate changes in top-down pain modulations.

Spinal cord stimulation with hybrid lead relieves pain in low back and legs.

OBJECTIVE: The failed back surgery syndrome (FBSS) is the most common chronic pain syndrome. Whereas it is relatively easy to achieve pain relief in the lower limbs of FBSS patients with spinal cord stimulation (SCS), it is difficult to manage low back pain with SCS. The performance of a paddle-shaped SCS lead that can be inserted surgically as well as percutaneously (a hybrid lead) was evaluated in a prospective study on the relief of low back pain and leg pain in patients with FBSS. MATERIALS AND METHODS: Patients with FBSS being eligible for SCS were enrolled in the study, and a hybrid lead was placed surgically. Outcome measures included pain scores for low back and leg pain assessed by visual analog scale (VAS), pain medication, and patient satisfaction. These scores were assessed before and at regular intervals after implantation. RESULTS: It was shown that a single hybrid lead, generally positioned over the physiological midline of the spinal cord, is capable of alleviating both low back and leg pain in patients with FBSS. Forty-five subjects were eligible for SCS and received trial stimulation. Forty-two of them had a successful trial period and were converted to a permanent system. Their average VAS score at baseline was 8.0 for lower limb pain and 7.5 for low back pain. After six months of SCS, these average VAS scores were reduced to 3.2 and 3.5, respectively, and also pain medication was reduced significantly. CONCLUSION: SCS with a hybrid lead in subjects with FBSS is safe, and causes significant pain relief in both the low back and the lower limbs.

Neural and behavioral correlates of human pain avoidance in participants with and without episodic migraine.

ABSTRACT: The innate motivation to avoid pain can be disrupted when individuals experience uncontrollable stress, such as pain. This can lead to maladaptive behaviors, including passivity, and negative affect. Despite its importance, motivational aspects of pain avoidance are understudied in humans and their neural mechanisms vastly unknown. Rodent models suggest an important role of the periaqueductal gray, but it is unknown whether it subserves a similar role in humans. Furthermore, it is unclear whether pain avoidance is associated with individual differences in pain coping. Using functional magnetic resonance imaging, networks underlying pain avoidance behavior were examined in 32 participants with and without episodic migraine. Pain avoidance behavior was assessed using an adaptation of the incentive delay task. In each trial of the task, participants tried to avoid a painful stimulus and receive a nonpainful one instead while the difficulty to succeed varied across trials (3 difficulty levels: safe, easy, and difficult). After unsuccessful pain avoidance on the preceding trial, participants showed reduced pain avoidance behavior, especially in the difficult condition. This reduction in behavior was associated with higher helplessness scores only in participants with migraine. Higher helplessness in participants with migraine was further correlated with a stronger decrease in activation of cortical areas associated with motor behavior, attention, and memory after unsuccessful pain avoidance. Of these areas, specifically posterior parietal cortex activation predicted individual's pain avoidance behavior on the next trial. The results link individual pain coping capacity to patterns of neural activation associated with altered pain avoidance in patients with migraine.