Application of Nerve Stimulation: Current Status and Future Directions

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

Deadline for manuscript submissions: 15 December 2024 | Viewed by 13652

Special Issue Editors


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Guest Editor
Acupuncture & Meridian Science Research Center, Kyung Hee University, Seoul 02447, Republic of Korea
Interests: acupuncture; neuroimaging; neuromodulation; pain; placebo
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Guest Editor
Department of Physiology, Yonsei University College of Medicine, Seoul 03722, Republic of Korea
Interests: acupuncture; visceral organ; mechanical stimulation; mesolimbic dopamine system
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Neuromodulation is often employed to directly affect nerves, typically those in the peripheral nervous system. However, to develop more advanced approaches to precision treatment, understanding the interplay between nerves and organs is rather important. Within large densities of nerve terminals or receptive fields, acupuncture can stimulate myocutaneous nerve systems that overlap with neuromodulation techniques.

For an upcoming Special Issue in Brain Sciences, we invite researchers and practitioners to submit original research papers using a variety of techniques (such as neuroimaging, neurobiology, clinical trials, or machine learning), as well as review articles that will advance the ongoing efforts to gain new insights into peripheral nerve stimulation, including neuromodulation and acupuncture.

Dr. Younbyoung Chae
Dr. Hee Young Kim
Guest Editors

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Keywords

  • acupuncture
  • neuroanatomy
  • neuroimaging
  • neuromodulation
  • peripheral nervous system

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Published Papers (9 papers)

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Research

28 pages, 5532 KiB  
Article
Impact of Stimulation Duration in taVNS—Exploring Multiple Physiological and Cognitive Outcomes
by Till Bömmer, Luisa M. Schmidt, Katharina Meier, Julius Kricheldorff, Heiko Stecher, Christoph S. Herrmann, Christiane M. Thiel, Kathrin Janitzky and Karsten Witt
Brain Sci. 2024, 14(9), 875; https://doi.org/10.3390/brainsci14090875 - 29 Aug 2024
Viewed by 1078
Abstract
Transcutaneous auricular vagus nerve stimulation (taVNS) is a non-invasive neuromodulation technique that modulates the noradrenergic activity of the locus coeruleus (LC). Yet, there is still uncertainty about the most effective stimulation and reliable outcome parameters. In a double blind, sham-controlled study including a [...] Read more.
Transcutaneous auricular vagus nerve stimulation (taVNS) is a non-invasive neuromodulation technique that modulates the noradrenergic activity of the locus coeruleus (LC). Yet, there is still uncertainty about the most effective stimulation and reliable outcome parameters. In a double blind, sham-controlled study including a sample of healthy young individuals (N = 29), we compared a shorter (3.4 s) and a longer (30 s) stimulation duration and investigated the effects of taVNS (real vs. sham) on saliva samples (alpha amylase and cortisol concentration), pupil (pupillary light reflex and pupil size at rest) and EEG data (alpha and theta activity at rest, ERPs for No-Go signals), and cognitive tasks (Go/No-Go and Stop Signal Tasks). Salivary alpha amylase concentration was significantly increased in the real as compared to sham stimulation for the 30 s stimulation condition. In the 3.4 s stimulation condition, we found prolonged reaction times and increased error rates in the Go/No-Go task and increased maximum acceleration in the pupillary light reflex. For the other outcomes, no significant differences were found. Our results show that prolonged stimulation increases salivary alpha-amylase, which was expected from the functional properties of the LC. The finding of longer response times to short taVNS stimulation was not expected and cannot be explained by an increase in LC activity. We also discuss the difficulties in assessing pupil size as an expression of taVNS-mediated LC functional changes. Full article
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19 pages, 8695 KiB  
Article
Electroacupuncture Reduced Fibromyalgia-Pain-like Behavior through Inactivating Transient Receptor Potential V1 and Interleukin-17 in Intermittent Cold Stress Mice Model
by Yu-An Yeh, Hsien-Yin Liao, I-Han Hsiao, Hsin-Cheng Hsu and Yi-Wen Lin
Brain Sci. 2024, 14(9), 869; https://doi.org/10.3390/brainsci14090869 - 28 Aug 2024
Viewed by 1016
Abstract
Fibromyalgia (FM) is a widespread musculoskeletal pain associated with psychological disturbances, the etiopathogenesis of which is still not clear. One hypothesis implicates inflammatory cytokines in increasing central and peripheral sensitization along with neuroinflammation, leading to an elevation in pro-inflammatory cytokines, e.g., interleukin-17A (IL-17A), [...] Read more.
Fibromyalgia (FM) is a widespread musculoskeletal pain associated with psychological disturbances, the etiopathogenesis of which is still not clear. One hypothesis implicates inflammatory cytokines in increasing central and peripheral sensitization along with neuroinflammation, leading to an elevation in pro-inflammatory cytokines, e.g., interleukin-17A (IL-17A), enhanced in FM patients and animal models. The intermittent cold stress (ICS)-induced FM-like model in C57BL/6 mice has been developed since 2008 and proved to have features which mimic the clinical pattern in FM patients such as mechanical allodynia, hyperalgesia, and female predominance of pain. Electroacupuncture (EA) is an effective treatment for relieving pain in FM patients, but its mechanism is not totally clear. It was reported as attenuating pain-like behaviors in the ICS mice model through the transient receptor potential vanilloid 1 (TRPV1) pathway. Limited information indicates that TRPV1-positive neurons trigger IL-17A-mediated inflammation. Therefore, we hypothesized that the IL-17A would be inactivated by EA and TRPV1 deletion in the ICS-induced FM-like model in mice. We distributed mice into a control (CON) group, ICS-induced FM model (FM) group, FM model with EA treatment (EA) group, FM model with sham EA treatment (Sham) group, and TRPV1 gene deletion (Trpv1−/−) group. In the result, ICS-induced mechanical and thermal hyperalgesia increased pro-inflammatory cytokines including IL-6, IL-17, TNFα, and IFNγ in the plasma, as well as TRPV1, IL-17RA, pPI3K, pAkt, pERK, pp38, pJNK, and NF-κB in the somatosensory cortex (SSC) and cerebellum (CB) lobes V, VI, and VII. Moreover, EA and Trpv1−/− but not sham EA countered these effects significantly. The molecular mechanism may involve the pro-inflammatory cytokines, including IL-6, IL-17, TNFα, and IFNγ. IL-17A–IL-17RA play a crucial role in peripheral and central sensitization as well as neuroinflammation and cannot be activated without TRPV1 in the ICS mice model. EA alleviated FM-pain-like behaviors, possibly by abolishing the TRPV1- and IL-17A-related pathways. It suggests that EA is an effective and potential therapeutic strategy in FM. Full article
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9 pages, 956 KiB  
Article
Exploratory Study of Biomechanical Properties and Pain Sensitivity at Back-Shu Points
by Heeyoung Moon, Seoyoung Lee, Da-Eun Yoon, In-Seon Lee and Younbyoung Chae
Brain Sci. 2024, 14(8), 823; https://doi.org/10.3390/brainsci14080823 - 16 Aug 2024
Cited by 1 | Viewed by 854
Abstract
Objectives: Hypersensitive acupoints in specific body areas are associated with corresponding internal or visceral disorders. Back-shu points are clinically significant for the diagnosis of visceral organ disease, according to the biomechanical characteristics of the acupoints. In this study, we assessed the biomechanical characteristics [...] Read more.
Objectives: Hypersensitive acupoints in specific body areas are associated with corresponding internal or visceral disorders. Back-shu points are clinically significant for the diagnosis of visceral organ disease, according to the biomechanical characteristics of the acupoints. In this study, we assessed the biomechanical characteristics and pain sensitivities of five back-shu points linked to five visceral organs in healthy participants. Methods: The study included 48 volunteer participants. A myotonometry was used to assess muscle tone and muscle stiffness at five back-shu points associated with visceral organs. Pressure was monitored using a microcontroller and a force sensor. Pain sensitivity was assessed in response to deep pressure pain produced by a constant force. Results: Substantial differences in muscle tone and stiffness were observed at the five back-shu points; muscle tone was highest at BL15, whereas muscle tone and muscle stiffness were lowest at BL23. Moreover, pain sensitivity was significantly different among the acupoints; pain sensitivity was highest at BL23. There was a significant negative correlation between muscle tone and pain sensitivity. Conclusions: We found significant differences in muscle tone, muscle stiffness, and pain sensitivity among five back-shu points associated with visceral organs, which may be attributable to anatomical variations at each point. Our findings suggest that differences at back-shu points should be considered to ensure the accurate diagnosis of visceral disease. Full article
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11 pages, 2509 KiB  
Article
Transcutaneous Electrical Spinal Cord Stimulation Increased Target-Specific Muscle Strength and Locomotion in Chronic Spinal Cord Injury
by Niraj Singh Tharu, Arnold Yu Lok Wong and Yong-Ping Zheng
Brain Sci. 2024, 14(7), 640; https://doi.org/10.3390/brainsci14070640 - 26 Jun 2024
Viewed by 2049
Abstract
Background: The recovery of locomotion is greatly prioritized, and neuromodulation has been emerging as a promising approach in recent times. Study design: Single-subject research design. Settings: A laboratory at The Hong Kong Polytechnic University. Objectives: To investigate the effects of augmenting activity-based therapy [...] Read more.
Background: The recovery of locomotion is greatly prioritized, and neuromodulation has been emerging as a promising approach in recent times. Study design: Single-subject research design. Settings: A laboratory at The Hong Kong Polytechnic University. Objectives: To investigate the effects of augmenting activity-based therapy (ABT) to transcutaneous electrical spinal cord stimulation (TSCS) on enhancing specific lower limb muscle strength and improving locomotor ability in an individual with chronic incomplete spinal cord injury (iSCI). Methods: An individual with iSCI underwent two phases of treatment, ABT alone followed by combined ABT+TSCS, each for a period of 10 weeks. The TSCS stimulated T10-T11 and T12-L1 segments with a frequency of 30 Hz at an intensity between 105 mA and 130 mA. Manual muscle testing, 6 min walk test (6MWT), and surface electromyography (EMG) responses of specific lower limb muscles were measured. Additionally, spasticity and sensorimotor examinations were conducted every two weeks, while pain tolerance was recorded after each treatment session. Results: After the ABT+TSCS treatment, there was an increase in overall muscle strength grading (from 1.8 ± 0.3 to 2.2 ± 0.6 out of 5.0). The 6MWT showed a greater increase in walking distance (3.5 m to 10 m) after combined treatment than ABT alone. In addition, the EMG response of the anterior rectus femoris, biceps femoris, medial gastrocnemius, and tibialis anterior after ABT+TSCS increased more than after ABT alone. The spasticity grade was reduced (from 0.8 ± 0.7 to 0.5 ± 0.6) whereas the average lower limb motor score increased from 17 to 23 points. No adverse effects were reported. Conclusions: ABT+TSCS increased the target-specific lower limb muscle strength and walking ability more than ABT alone in an individual with chronic iSCI. Full article
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16 pages, 1220 KiB  
Article
Short-Term Therapeutic Effect of Repetitive Transcranial Magnetic Stimulations of Sleep Disorders in Parkinson’s Disease: A Randomized Clinical Trial (Pilot Study)
by Eman M. Khedr, Gellan K. Ahmed, Mohammad Ahmad Korayem, Sara Ahmed Salah Hussain Elamary, Maha M. El-kholy and Nourelhoda A. Haridy
Brain Sci. 2024, 14(6), 556; https://doi.org/10.3390/brainsci14060556 - 30 May 2024
Cited by 1 | Viewed by 977
Abstract
This study aimed to evaluate the efficacy of rTMS in treating sleep disorders in PD. It included 24 patients with PD who had sleep disorders. Group allocations (active or sham with a ratio of 2:1) were placed in serially numbered closed envelopes. Each [...] Read more.
This study aimed to evaluate the efficacy of rTMS in treating sleep disorders in PD. It included 24 patients with PD who had sleep disorders. Group allocations (active or sham with a ratio of 2:1) were placed in serially numbered closed envelopes. Each patient was evaluated with the following: MDS-UPDRS, Parkinson’s Disease Sleep Scale (PDSS), Beck Depression Inventory (BDI), and polysomnography (PSG) before and 10 days after the treatment sessions. Each session consisted of 10 trains, 20 Hz, 10 sec for each, over the parietal cortex (bilaterally). Scores of UPDRS, BDI, and PDSS improved significantly in the active group but not in the sham group. The PSG data showed that sleep onset and rapid eye movement (REM) latencies (min), REM duration, and time spent awake (both as %TST) were improved after rTMS in the active group compared with the sham group. The number of awakenings, the wake-after-sleep onset index, the arousal index, and periodic leg movements (PLMs) were all significantly reduced in the active group but not in the sham group. Ten sessions of 20 Hz rTMS over parietal cortexes improved sleep quality and PLMs in patients with PD. The improvement in PSG and PDSS were correlated with improvements in UPDRS and BDI scores. Full article
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21 pages, 27681 KiB  
Article
Acupuncture Extended the Thrombolysis Window by Suppressing Blood–Brain Barrier Disruption and Regulating Autophagy–Apoptosis Balance after Ischemic Stroke
by Zhihui Zhang, Tianliang Lu, Shanshan Li, Ruyu Zhao, Honglei Li, Xinchang Zhang, Yiyang Li, Yawen Xia and Guangxia Ni
Brain Sci. 2024, 14(4), 399; https://doi.org/10.3390/brainsci14040399 - 19 Apr 2024
Cited by 1 | Viewed by 1874
Abstract
Background: Ischemic stroke (IS) is one of the leading causes of death and disability worldwide. The narrow therapeutic window (within 4.5 h) and severe hemorrhagic potential limits therapeutic efficacy of recombinant tissue type plasminogen activator (rt-PA) intravenous thrombolysis for patients. Xingnao Kaiqiao (XNKQ) [...] Read more.
Background: Ischemic stroke (IS) is one of the leading causes of death and disability worldwide. The narrow therapeutic window (within 4.5 h) and severe hemorrhagic potential limits therapeutic efficacy of recombinant tissue type plasminogen activator (rt-PA) intravenous thrombolysis for patients. Xingnao Kaiqiao (XNKQ) acupuncture is an integral part of traditional Chinese medicine, specifically designed to address acute ischemic stroke by targeting key acupoints such as Shuigou (GV26) and Neiguan (PC6). In this study, we explored the therapeutic potential of XNKQ acupuncture in extending the time window for thrombolysis and interrogated the molecular mechanisms responsible for this effect. Methods: The effect of extending the thrombolysis window by acupuncture was evaluated via TTC staining, neuronal score evaluation, hemorrhagic transformation assay, and H&E staining. RNA sequencing (RNA-seq) technology was performed to identify the therapeutic targets and intervention mechanisms of acupuncture. Evans blue staining and transmission electron microscopy were used to assess blood–brain barrier (BBB) integrity. Immunofluorescence staining and co-immunoprecipitation were performed to evaluate the level of autophagy and apoptosis and validate their interactions with BBB endothelial cells. Results: Acupuncture alleviated infarction and neurological deficits and extended the thrombolysis window to 6 h. The RNA-seq revealed 16 potential therapeutic predictors for acupuncture intervention, which related to suppressing inflammation and restoring the function of BBB and blood vessels. Furthermore, acupuncture suppressed BBB leakage and preserved tight junction protein expression. The protective effect was associated with regulation of the autophagy–apoptosis balance in BBB endothelial cells. Acupuncture intervention dissociated the Beclin1/Bcl-2 complex, thereby promoting autophagy and reducing apoptosis. Conclusion: XNKQ acupuncture could serve as an adjunctive therapy for rt-PA thrombolysis, aiming to extend the therapeutic time window and mitigate ischemia–reperfusion injury. Acupuncture suppressed BBB disruption by regulating the autophagy–apoptosis balance, which in turn extended the therapeutic window of rt-PA in IS. These findings provide a rationale for further exploration of acupuncture as a complementary candidate co-administered with rt-PA. Full article
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14 pages, 3028 KiB  
Article
The Role of p38 Mitogen-Activated Protein Kinase-Mediated F-Actin in the Acupuncture-Induced Mitigation of Inflammatory Pain in Arthritic Rats
by Xu Zhou, Yu-Chen Zhang, Kai-Qiu Lu, Ran Xiao, Wen-Chao Tang and Fan Wang
Brain Sci. 2024, 14(4), 380; https://doi.org/10.3390/brainsci14040380 - 14 Apr 2024
Viewed by 1349
Abstract
The analgesic efficacy of acupuncture has been widely recognized. However, the mechanism by which manual acupuncture-generated mechanical stimuli translate into biological signals remains unclear. This study employed a CFA-induced inflammatory pain rat model. Acupuncture intervention was then performed following standardized procedures. Enzyme-linked immunosorbent [...] Read more.
The analgesic efficacy of acupuncture has been widely recognized. However, the mechanism by which manual acupuncture-generated mechanical stimuli translate into biological signals remains unclear. This study employed a CFA-induced inflammatory pain rat model. Acupuncture intervention was then performed following standardized procedures. Enzyme-linked immunosorbent assay (ELISA) assessed inflammatory cytokines levels, while immunofluorescence and qRT-PCR screened the level of p38 and F-actin expression in the ST36 acupoint area of rats. Results indicated increased inflammatory factors, including IL-1β and TNFα, with reduced paw withdrawal mechanical threshold (PWMT) and paw withdrawal thermal latency (PWTL) in CFA rats compared to unmodeled rats. After acupuncture intervention, the heightened expression level of F-actin and p38 mRNA and the phosphorylation of p38 in the acupoint area was observed alongside decreased inflammatory factors in diseased ankle joints. The application of lifting and thrusting manipulations further enhanced the effect of acupuncture, in which the molecular expression level of muscle and connective tissue increased most significantly, indicating that these two tissues play a major role in the transformation of acupuncture stimulation. Moreover, antagonizing p38 expression hindered acupuncture efficacy, supporting the hypothesis that p38 MAPK-mediated F-actin transduces mechanical signals generated by acupuncture and related manipulation into biological signals. Full article
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13 pages, 1615 KiB  
Article
Sensory Stimulation of the Triceps Surae Muscle Complex Modulates Spinal Reflex Responses—A Comparison between Tapotement Massage and Repetitive Peripheral Magnetic Stimulation (rPMS)
by Volker R. Zschorlich, Fengxue Qi, Jörg Schorer and Dirk Büsch
Brain Sci. 2024, 14(2), 119; https://doi.org/10.3390/brainsci14020119 - 24 Jan 2024
Cited by 1 | Viewed by 1683
Abstract
Background: The reduction of muscular hypertonia is important in the treatment of various diseases or rehabilitation. This study aims to test the efficacy of a 5 Hz mechanical muscle stimulation (tapotement massage) in comparison to a 5 Hz repetitive peripheral magnetic stimulation (rPMS) [...] Read more.
Background: The reduction of muscular hypertonia is important in the treatment of various diseases or rehabilitation. This study aims to test the efficacy of a 5 Hz mechanical muscle stimulation (tapotement massage) in comparison to a 5 Hz repetitive peripheral magnetic stimulation (rPMS) on the neuromuscular reflex response. Methods: In a randomized control trial, 15 healthy volunteers were administered with either 5 Hz rPMS, tapotement massage, or rPMS sham stimulation. The posterior tibial nerve was stimulated with rPMS and sham stimulation. The Achilles tendon was exposed to a mechanically applied high-amplitude 5 Hz repetitive tendon tapotement massage (rTTM). The tendon reflex (TR) was measured for the spinal response of the soleus muscle. Results: After rPMS, there was a reduction of the TR response (−9.8%, p ≤ 0.034) with no significant changes after sham stimulation. Likewise, TR decreased significantly (−17.4%, p ≤ 0.002) after Achilles tendon tapotement intervention. Conclusions: These findings support the hypothesis that both afferent 5 Hz sensory stimulations contributed to a modulation within the spinal and/or supraspinal circuits, which resulted in a reduction of the spinal reflex excitability. The effects could be beneficial for patients with muscle hypertonia and could improve the functional results of rehabilitation programs. Full article
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11 pages, 1169 KiB  
Article
Efficacy of Transcranial Direct Current Stimulation (tDCS) on Cognition, Anxiety, and Mobility in Community-Dwelling Older Individuals: A Controlled Clinical Trial
by Nathalia Oliveira Rodrigues, Anna Alice Vidal Bravalhieri, Tatiane Pereira de Moraes, Jorge Aparecido Barros, Juliana Hotta Ansai and Gustavo Christofoletti
Brain Sci. 2023, 13(12), 1614; https://doi.org/10.3390/brainsci13121614 - 21 Nov 2023
Cited by 3 | Viewed by 1681
Abstract
Transcranial direct current stimulation (tDCS) has gained popularity as a method of modulating cortical excitability in people with physical and mental disabilities. However, there is a lack of consensus on its effectiveness in older individuals. This study aimed to assess the efficacy of [...] Read more.
Transcranial direct current stimulation (tDCS) has gained popularity as a method of modulating cortical excitability in people with physical and mental disabilities. However, there is a lack of consensus on its effectiveness in older individuals. This study aimed to assess the efficacy of a 2-month tDCS program for improving physical and mental performance in community-dwelling older individuals. In this single-blinded, controlled clinical trial, forty-two participants were allocated to one of three groups: (1) the tDCS group, which received, twice a week, 20 min sessions of 2 mA electric current through electrodes placed on the dorsolateral prefrontal cortex; (2) the tDCS-placebo group, which underwent the same electrode placement as the tDCS group but without actual electric stimulation; and (3) the cognitive-control group, which completed crossword puzzles. Main outcome measures were cognition, mobility, and anxiety. Multivariate analyses of variance were employed. Significance was set at 5% (p < 0.05). Regarding the results, no significant benefits were observed in the tDCS group compared with the tDCS-placebo or cognitive-control groups for cognition (p = 0.557), mobility (p = 0.871), or anxiety (p = 0.356). Cognition exhibited positive oscillations during the assessments (main effect of time: p = 0.001). However, given that all groups showed similar variations in cognitive scores (main effect of group: p = 0.101; group × time effect: p = 0.557), it is more likely that the improvement reflects the learning response of the participants to the cognitive tests rather than the effect of tDCS. In conclusion, a 2-month tDCS program with two sessions per week appears to be ineffective in improving physical and mental performance in community-dwelling older individuals. Further studies are necessary to establish whether or not tDCS is effective in healthy older individuals. Full article
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