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Brain Sciences
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Neuromodulation for Pain Management: Evidence of Safety and Efficacy
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Neuromodulation for Pain Management: Evidence of Safety and Efficacy

A special issue of Brain Sciences (ISSN 2076-3425). This special issue belongs to the section "Sensory and Motor Neuroscience".

Deadline for manuscript submissions: 15 December 2025 | Viewed by 1833

Special Issue Editors

Dr. Andrés Molero-Chamizo

E-Mail Website
Guest Editor
Department of Clinical and Experimental Psychology, University of Huelva, 21071 Huelva, Spain
Interests: cognitive neuroscience; neural systems; neuromodulation; neuroplasticity; non-invasive brain stimulation
Special Issues, Collections and Topics in MDPI journals
Dr. Rafael Tomás Andújar-Barroso

E-Mail Website
Guest Editor
Department of Clinical and Experimental Psychology, University of Huelva, 21071 Huelva, Spain
Interests: clinical psychology; health psychology; medical psychology; neuropsychology; neuroscience

Special Issue Information

Dear Colleagues,

Pain management is a complex process that requires different therapeutic approaches. Chronic pain in certain medical conditions is particularly difficult to resolve, and some patients are refractory to available pharmacological and interventional treatments. Neuromodulation is a research and interventional method aimed to modulate nervous system activity and regulate potentially altered processes in different neurological and psychiatric conditions. The effectivity of neuromodulation is being investigated in multiple pathologies associated with chronic pain, such as migraine, rheumatic pain, fibromyalgia, neuropathies, epilepsy, myalgic encephalomyelitis, post-stroke pain, etc., and recent non-invasive brain and spinal cord stimulation procedures provide clinical effects comparable to approved invasive or surgical methods, but in a safer and more tolerable way. In this Special Issue, recent advances in the treatment of pain via invasive and non-invasive neuromodulation, including vagal, brain, and spinal stimulation, both magnetic and electric, are collected, with a focus on those critical factors determining the effectiveness and safety of current protocols used in pain management. Basic research and clinical trial papers on neuromodulation and pain are welcome in this Special Issue, as well as comprehensive and systematic reviews providing significant insights on this topic.

Dr. Andrés Molero-Chamizo
Dr. Rafael Tomás Andújar-Barroso
Guest Editors

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Keywords

  • chronic pain
  • clinical neurostimulation
  • invasive neuromodulation
  • neurostimulation-induced plasticity
  • non-invasive neuromodulation
  • pain management
  • transcranial electric stimulation
  • transcranial magnetic stimulation

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Published Papers (4 papers)

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Research

13 pages, 986 KiB  
Article
Uncomfortable Paresthesia and Dysesthesia Following Tonic Spinal Cord Stimulator Implantation
by Zubin Sethi, Tabish Aijaz, Alvaro Ortega-Camacho, Ned F. Nasr and Nebojsa Nick Knezevic
Brain Sci. 2025, 15(6), 616; https://doi.org/10.3390/brainsci15060616 - 7 Jun 2025
Viewed by 209
Abstract
Background/Objectives: To determine the incidence of and risk factors for uncomfortable paresthesia and/or dysesthesia after tonic percutaneous spinal cord stimulator implantation. Methods: A retrospective analysis was conducted on the prospectively collected data of patients that had permanent percutaneous tonic spinal cord [...] Read more.
Background/Objectives: To determine the incidence of and risk factors for uncomfortable paresthesia and/or dysesthesia after tonic percutaneous spinal cord stimulator implantation. Methods: A retrospective analysis was conducted on the prospectively collected data of patients that had permanent percutaneous tonic spinal cord stimulators implanted. Our primary objective was to assess the prevalence of complications over a period of 24 months after the implantation of this device. Results: The mean post-implantation follow-up time was 27.3 months. The mean pain score before spinal cord stimulator implantation was 8.05, which was reduced to 3.6 after 24 months. The most common complications in our study sample were the need for revision and the development of unpleasant paresthesia, which were reported by 34.95% and 27.86% of patients, respectively. There was no association between paresthesia and age, sex, or body mass index (BMI). The only risk factor of statistical significance was current tobacco use (p = 0.001). Conclusions: The development of uncomfortable paresthesia after SCS is associated with considerable morbidity, particularly the explantation of SCS, despite adequate pain relief. Focusing on strategies, such as appropriate waveform selection, might reduce the incidence of uncomfortable paresthesia requiring revision or explantation. Current tobacco use appears to be a significant risk factor for the development of unpleasant paresthesia/dysesthesia when compared with non-tobacco and former tobacco users after tonic percutaneous spinal cord stimulator implantation. Full article
(This article belongs to the Special Issue Neuromodulation for Pain Management: Evidence of Safety and Efficacy)
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11 pages, 475 KiB  
Article
Predictive Factors of Successful Spinal Cord Stimulation in Patients with Chronic Pain: A Retrospective Cohort Study
by Yongjae Yoo, Hyungsang Roh, Jee Youn Moon, Eun Joo Choi, Francis Sahngun Nahm and Pyung Bok Lee
Brain Sci. 2025, 15(6), 614; https://doi.org/10.3390/brainsci15060614 - 6 Jun 2025
Viewed by 141
Abstract
Background: Spinal cord stimulation (SCS) is applied for managing chronic intractable pain, but the factors predicting its effectiveness have not been extensively researched. Our study aimed to identify clinical variables that can predict the outcome of SCS. Methods: The electronic medical records of [...] Read more.
Background: Spinal cord stimulation (SCS) is applied for managing chronic intractable pain, but the factors predicting its effectiveness have not been extensively researched. Our study aimed to identify clinical variables that can predict the outcome of SCS. Methods: The electronic medical records of patients who received SCS for chronic intractable pain at two large tertiary teaching institutions in South Korea from 2008 to 2022 were reviewed. A successful outcome was characterized by attaining at least a 50% reduction in pain on the numerical rating scale (NRS) assessed at 6 months. Multivariable analysis was used to investigate the correlation between outcomes of SCS and clinical variables. Results: Of the 213 patients, 108 (50.7%) experienced successful outcomes at 6 months after SCS implantation. At 6 months, both the positive and negative outcome groups had significantly lower NRS pain scores than at baseline. Multivariable analysis revealed that male gender (p = 0.023) was an independent predictor of positive SCS outcomes; conversely, longer pain duration (p = 0.011) was a negative predictor. No significant adverse events associated with SCS were observed throughout the six-month follow-up duration. Conclusions: SCS could be an effective treatment for chronic intractable pain, including complex regional pain syndrome (CRPS) and persistent spinal pain syndrome (PSPS). More successful outcomes may be expected in male patients with a shorter duration of pain. Additional research is required to enhance patient selection processes and to identify clinical characteristics that contribute to improved long-term outcomes. Full article
(This article belongs to the Special Issue Neuromodulation for Pain Management: Evidence of Safety and Efficacy)
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12 pages, 824 KiB  
Article
Evaluating Repetitive Transcranial Magnetic Stimulation for Refractory Chronic Cluster Headache Prevention: Insights from a Randomized Crossover Pilot Trial
by Leonardo Portocarrero-Sánchez, Cristian Rizea, Exuperio Díez-Tejedor, Moisés León-Ruiz and Javier Díaz-de-Terán
Brain Sci. 2025, 15(6), 554; https://doi.org/10.3390/brainsci15060554 - 23 May 2025
Viewed by 421
Abstract
Background/Objectives: Cluster headache (CH) is a debilitating primary headache disorder characterized by severe unilateral pain attacks. Chronic CH (CCH) poses significant treatment challenges, especially in refractory cases. Neuromodulation, including repetitive transcranial magnetic stimulation (rTMS), offers a potential alternative; however, evidence for its [...] Read more.
Background/Objectives: Cluster headache (CH) is a debilitating primary headache disorder characterized by severe unilateral pain attacks. Chronic CH (CCH) poses significant treatment challenges, especially in refractory cases. Neuromodulation, including repetitive transcranial magnetic stimulation (rTMS), offers a potential alternative; however, evidence for its efficacy in CCH is lacking. Methods: A randomized, double-blind, placebo-controlled, crossover pilot study was conducted. Eligibility criteria included patients with refractory CCH (rCCH), who were then randomized to receive two treatment sequences: A, rTMS followed by sham stimulation, or B, sham followed by rTMS, separated by a one-month washout, with a follow-up period of 3 months. The primary endpoint was to analyze efficacy by assessing the change in the number of attacks per week (APW). Secondary endpoints included treatment tolerability and changes in intensity, duration, and use of rescue medication. The trial was registered with ClinicalTrials.gov (NCT06917144). Results: Eight patients were enrolled and randomized with a 50% probability of assignment to either treatment arm. Despite this, five patients were allocated to sequence A and three to sequence B. Three patients completed the entire study; five received treatment with rTMS and six with sham. The APW change during rTMS showed a change of (mean ± SD) +2.2 (10.8) attacks per week (p = 0.672). Two patients achieved complete remission during the rTMS phase, though symptoms returned by the washout period. In comparison with sham, the difference was also not statistically significant. No significant changes were observed in secondary endpoints. Side effects (two cases) were mild and transient. Conclusions: This pilot study suggests that rTMS may provide clinical benefits for rCCH in selected cases, though its effects seem transient. Adherence to treatment remains a critical challenge. Full article
(This article belongs to the Special Issue Neuromodulation for Pain Management: Evidence of Safety and Efficacy)
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12 pages, 319 KiB  
Article
Superficial Neuromodulation in Dysautonomia in Women with Post-COVID-19 Condition: A Pilot Study
by Alberto Melián-Ortíz, Eduardo Zurdo-Sayalero, Sara Perpiñá-Martínez, Antonio Delgado-Lacosta, Carmen Jiménez-Antona, Josué Fernández-Carnero and Sofía Laguarta-Val
Brain Sci. 2025, 15(5), 510; https://doi.org/10.3390/brainsci15050510 - 16 May 2025
Viewed by 342
Abstract
Post-COVID-19 condition involves persistent symptoms after acute infection, often linked to dysautonomia, which affects heart rate variability, pain perception, fatigue, and sleep. Superficial neuromodulation has been proposed as a treatment. Objective: To assess the effects of superficial neuromodulation on symptoms, sleep quality, and [...] Read more.
Post-COVID-19 condition involves persistent symptoms after acute infection, often linked to dysautonomia, which affects heart rate variability, pain perception, fatigue, and sleep. Superficial neuromodulation has been proposed as a treatment. Objective: To assess the effects of superficial neuromodulation on symptoms, sleep quality, and autonomic function in post-COVID-19 condition patients. Methods: A pilot study was conducted based on a triple-blind randomized controlled trial methodology involving 16 female participants. The experimental group received neuromodulation, while the control group used a placebo device. The intervention spanned 15 sessions over two months. Primary outcomes included heart rate variability, pain threshold, cortisol levels, fatigue, sleep quality, and quality of life, analyzed using repeated-measures ANOVA. Results: Both groups improved over time. Heart rate variability (SDNN) increased in the experimental group (30.42 to 39.11 ms) but decreased in controls (31.88 to 28.73 ms) (p < 0.05). Pain threshold at C5–C6 improved in the experimental group (2.1 to 3.5 kg/cm2) but remained stable in controls (p = 0.032). Fatigue decreased significantly in both groups (p = 0.002). Sleep quality improved, with Pittsburgh Sleep Quality Index scores decreasing similarly in both groups. Cortisol levels increased, with a non-significant trend favoring controls. Conclusions: While improvements were seen, both groups benefited, suggesting a possible placebo effect. Superficial neuromodulation appears safe, but further studies with larger samples are needed to confirm efficacy. Full article
(This article belongs to the Special Issue Neuromodulation for Pain Management: Evidence of Safety and Efficacy)
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