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 8^th 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.

In recent years, there has been a growing interest in the use of neuromodulation as an alternative treatment option for chronic pain. Neuromodulation techniques, such as spinal cord stimulation (SCS), dorsal root ganglion (DRG) stimulation, deep brain stimulation (DBS), and peripheral nerve stimulation, have shown promising results in the management of various chronic pain conditions and involve targeted modulation of neural activity to alleviate pain and restore functional capacity. The autonomic nervous system (ANS) plays a crucial role in the regulation of various bodily functions including pain perception. However, the effects of neuromodulation on the ANS in the context of chronic pain remain poorly understood. This systematic review aimed to comprehensively assess the existing literature about the effects of neuromodulation on the ANS in chronic pain settings. Searches were conducted using four electronic databases (PubMed, EMBASE, SCOPUS, and Web of Science). The study protocol was registered before initiation of the review process. The Office of Health Assessment and Translation (OHAT) Risk of Bias tool was used to evaluate risk of bias. A total of 43 studies were included, of which only one was an animal study. Several studies have reported more than one outcome parameter in the same population of chronic pain patients. Cardiovascular parameters were the most frequently used outcomes. More specifically, 18 outcome parameters were revealed to evaluate the function of the ANS, namely heart rate variability (n=17), arterial blood pressure (n=15), tissue oxygenation/perfusion (n=5), blood markers (n=6), multiunit postganglionic sympathetic nerve activity (n=4), skin temperature (n=3), skin conductance (n=3), cephalic autonomic symptoms (n=2), ventilatory frequency (n=2), vasomotor tone (n=1), baroreflex sensitivity (n=1), sympathetic innervation of the heart, neural activity of intrinsic cardiac neurons (n=1), vascular conductance (n=1), arterial diameter (n=1), blood pulse volume (n=1), and vagal efficiency (n=1). Most studies evaluated SCS (62.79%), followed by DBS (18.6%), peripheral nerve stimulation (9.3%), DRG stimulation (4.65%), and vagus nerve stimulation (4.65%). Overall, inconsistent results were revealed towards contribution of SCS, DBS, and peripheral nerve stimulation on ANS parameters. For DRG stimulation, included studies pointed towards a decrease in sympathetic activity. There are indications that neuromodulation alters the ANS, supported by high or moderate confidence in the body of evidence, however, heterogeneity in ANS outcome measures drives towards inconclusive results. Further research is warranted to elucidate the indirect or direct mechanisms of action on the ANS, with a potential benefit for optimisation of patient selection for these interventions. PROSPERO (CRD42021297287).

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. 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. 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. 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. The Clinicaltrials.gov registration number for the study is NCT03386058.

Aim: Chronic postsurgical pain (CPSP) is a common complication of surgery. This study was conducted to evaluate the efficacy and safety of paresthesia-free, 10-kHz spinal cord stimulation (SCS) as ...

Purpose: Spinal cord stimulation (SCS) using the Differential Target Multiplexed (DTM) waveform is an effective treatment for treating chronic neuropathic back and leg pain that is refractory to other interventions. The purpose of this research was to estimate the cost-effectiveness of this therapy in a population with Persistent Spinal Pain Syndrome Type 1 (PSPS T1) by updating an existing model with inputs from Belgian healthcare databases and Western European clinical data. Patients and Methods: A two-phase model was built using a 24-month decision tree followed by a 13-year Markov model. Model inputs were sourced from a recent European randomized controlled trial evaluating DTM-SCS for the treatment of PSPS T1, other published literature, and publicly available Belgian healthcare data. Costs and quality-adjusted life years (QALYs) were calculated using deterministic analysis. One-way sensitivity analyses were conducted to test the effect of individual model input parameters on results. Overall model uncertainty was tested using probabilistic sensitivity analysis. Results: The model estimated that DTM-SCS would be cost-effective versus conventional medical management (CMM) in 99.7% of 10,000 simulations, at an assumed willingness-to-pay threshold of € 30,000. DTM-SCS patients gained 1.29 QALYs compared to CMM patients, resulting in an incremental cost-effectiveness ratio (ICER) of € 11,518 and an incremental net benefit (INB) that became positive at year 5. The base-case results remained robust in scenario analyses, which found that medication use, utilities associated with suboptimal and optimal pain relief, and the time horizon were the largest drivers of uncertainty in the model. Conclusion: The results of the model suggest that DTM-SCS is likely to be a cost-effective treatment option for PSPS T1 compared to CMM for patients in the Belgian healthcare system. Plain Language Summary: Spinal cord stimulation (SCS) has been used for decades to help people manage chronic low-back pain when other conventional medical management (CMM) treatments do not provide adequate pain relief. In the last five years several clinical studies have evaluated the clinical outcomes of SCS among patients with Persistent Spinal Pain Syndrome (PSPS Type 1), also known as non-surgical refractory back pain (NSRBP) or patients without history of prior major back surgery. In this study, the researchers evaluated whether or not treatment with a novel form of SCS, called Differential Target Multiplexed SCS (DTM-SCS), is cost-effective compared to treatment with CMM alone, in a population of patients with pain classified as PSPS Type 1. Using cost information from the Belgian healthcare system and data about clinical outcomes from a randomized, controlled clinical trial, this study developed an economic model to estimate how much Belgian healthcare payers could expect to pay for the typical patient over 15 years of DTM-SCS treatment vs CMM alone. The results of the model showed that, on average, treatment with DTM-SCS gave patients with PSPS Type 1 more years of better health (called quality-adjusted life years, or QALYs) compared to CMM, even though DTM-SCS treatment costs more upfront. The extra cost was considered reasonable for the QALY benefit by European “willingness-to-pay” standards, and therefore the researchers concluded that DTM-SCS was more likely than not to be a cost-effective treatment for PSPS Type 1 in Belgium.