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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

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.

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

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.

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 patie

BACKGROUND Different waveforms of spinal cord stimulation (SCS) have now been evaluated for the management of painful diabetic neuropathy (PDN). However, no direct or indirect comparison between SCS waveforms has been performed to date. PURPOSE To conduct a systematic review and network meta-analysis to evaluate the effectiveness of SCS for PDN. DATA SOURCES MEDLINE, CENTRAL, Embase, and WikiStim were searched from inception until December 2021. STUDY SELECTION Randomized controlled trials (RCTs) of SCS for PDN were included. DATA EXTRACTION Pain intensity, proportion of patients achieving at least a 50% reduction in pain intensity, and health-related quality of life (HRQoL) data were extracted. DATA SYNTHESIS Significant reductions in pain intensity were observed for low-frequency SCS (LF-SCS) (mean difference [MD] 23.13 [95% CI 24.19 to 22.08], moderate certainty) and high-frequency SCS (HF-SCS) (MD25.20 [95% CI25.77 to24.63], moderate certainty) compared with conventional medical management (CMM) alone. There was a significantly greater reduction in pain intensity on HF-SCS compared with LF-SCS (MD 22.07 [95% CI 23.26 to 20.87], moderate certainty). Significant differences were observed for LF-SCS and HF-SCS compared with CMMfor the outcomes proportion of patients with at least 50% pain reduction and HRQoL (very low to moderate certainty). No significant differences were observed between LF-SCS and HF-SCS (very low to moderate certainty). LIMITATIONS Limited number of RCTs and no head-to-head RCTs conducted. CONCLUSIONS Our findings confirm the pain relief and HRQoL benefits of the addition of SCS to CMM for patients with PDN. However, in the absence of head-to-head RCT evidence, the relative benefits of HF-SCS compared with LF-SCS for patients with PDN remain uncertain.

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.