Neuromodulation: Overview

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.