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PubMedDate not supplied

[Tibial neuromodulation in the treatment of neurogenic detrusor hyperactivity in patients with Parkinson's disease].

Twenty nine patients with neurogenic detrusor overactivity due to Parkinson's disease have undergone percutaneous tibial neuromodulation. The treatment consisted of percutaneous insertion of a 34-gauge solid stainless steel needle at a point of 5 cm cephald from the medial malleolus. The patients were treated weekly for 30 minutes. A subjective effect was assessed using a dairy and I-PSS score. Objective results were evaluated by cystometry. We observed a decrease in the average voiding frequency, number of leakage episodes after 12 sessions and 6 months of the tibial neuromodulation. An over 50% symptomatic improvement was achieved in 26 of 29 patients including 6 patients who were refractory to anticholinergic agents and 9 men with benign prostatic hyperplasia. Tibial neuromodulation is an effective treatment in patients with neurogenic detrusor overactivity due to Parkinson's disease.

Aged↗

PubMed1996

Differential distribution of functional receptors for neuromodulators evoking short-term heterosynaptic plasticity in Aplysia sensory neurons.

Synaptic transmission and excitability in Aplysia sensory neurons (SNs) are bidirectionally modulated by 5-HT and FMRFamide. To explore the regional distribution of different functional receptors that modulate SN properties, we examined changes in synaptic efficacy and excitability with brief focal applications of the neuromodulators to different regions of SNs that have established connections with motor cell L7 in culture. Short-term changes in synaptic efficacy were evoked only when 5-HT or FMRFamide was applied to regions with SN varicosities along the surface of L7 axons. Applications to adjacent SN neurites with few varicosities in contact with L7 axons failed to evoke a significant change in synaptic efficacy. The distribution of functional receptors mediating changes in excitability differed for 5-HT and FMRFamide. Whereas excitability increases were evoked only when 5-HT was applied to SN cell bodies, excitability decreases in SNs were evoked only when FMRFamide was applied to regions along the L7 axon with SN varicosities. Without the target cell, cell bodies of SNs expressed both 5-HT and FMRFamide receptors that modulate excitability. These results indicate that functional G-protein-coupled receptors for two neuromodulators are distributed differentially along the surface of a presynaptic neuron that forms chemical connections in vitro. This differential distribution of receptors on the presynaptic neuron is regulated by a target and does not require the physical presence of neurons that release the neuromodulators.

Animals↗

PubMed2026

Neuromodulation for Subjective Tinnitus: A Systematic Review and Meta-Analysis of Randomized Trials.

OBJECTIVE: To evaluate the effectiveness and safety of neuromodulation and bimodal stimulation for chronic subjective tinnitus in randomized controlled trials (RCTs). DATA SOURCES: PubMed/MEDLINE, Web of Science, and EMBASE (January 2015-December 2025) searched per PRISMA 2020. REVIEW METHODS: Adult RCTs (≥ 18 years) with chronic subjective tinnitus (> 3 months) assessing validated outcomes (THI, TFI, TQ) for neuromodulation/bimodal interventions vs. sham/controls. Two-stage screening, Cochrane RoB-2 risk-of-bias assessment. Random-effects meta-analyses (REML) were performed when ≥ 3 comparable trials were available; effects reported as standardized mean differences (SMD) with 95% CIs. Main Outcomes and measures included change in tinnitus severity (THI/TFI/TQ) while secondary outcomes included loudness (VAS/NRS), durability, and adverse events. RESULTS: Twenty-six RCTs (n = 1576) met criteria: tES (11; n = 372), rTMS (8; n = 432), acoustic coordinated reset (1; n = 100), vagus nerve stimulation (2; n = 90), and bimodal stimulation (4; n = 582). Meta-analysis showed a nonsignificant pooled effect for tDCS (SMD -0.36; 95% CI -0.75 to 0.02; I 2 = 51%) and rTMS (SMD -0.15; 95% CI -0.37 to 0.07; I 2 = 0%). Single-trial evidence for coordinated reset showed no advantage over broadband noise. VNS demonstrated modest benefits with safety concerns limited to implanted approaches. Bimodal stimulation yielded consistent, clinically meaningful reductions (often ≥ 10-20 points on THI/TFI), with durability up to 12 months. Adverse events were mild/transient across noninvasive modalities. CONCLUSIONS: Noninvasive neuromodulation appears safe with average benefits; among modalities, bimodal stimulation shows the most consistent and durable clinical improvements. Standardized, adequately powered RCTs with harmonized protocols and long-term follow-up are needed to refine targets and dosing.

Humans↗

PubMed2026

Efficacy of targeted neuromodulation treatments: a clinical report.

BACKGROUND: Peripheral neuropathy is a debilitating condition characterized by chronic pain, numbness, tingling, burning, and tightness/swelling. Conventional therapies often focus on symptom management, and some patients experience chronic and refractory symptoms. RESEARCH DESIGN AND METHODS: This retrospective clinical analysis evaluated the clinical outcomes of neuromodulation neuropathy treatment using the NeuroGen-Series device in patients with diabetic peripheral neuropathy (DPN) or idiopathic peripheral neuropathy (IPN). 9,805 unique patients who underwent 133,741 treatments between 18 August 2017, and 23 July 2024, were analyzed. Patients were divided into treatment completers (≥24 sessions) and noncompleters (<24 sessions). Paired t-tests confirmed statistically significant reductions in pre- and post-treatment symptom scores (p < 0.001). RESULTS: Among completers, symptom severity decreased by an average of 46.2%. Tingling and pain showed the greatest improvement, while tightness/swelling and numbness showed the least reduction. 64% of patients reported improvement after one session, and 84% reported improvement after 24 sessions. Nonresponders accounted for 5.8% of patients overall. Younger patients and those with higher initial symptom severity were more likely to discontinue treatment. CONCLUSIONS: Overall, neuromodulation treatment resulted in statistically significant reductions in symptom severity, though nonresponders and high attrition rate highlight the need for individualized treatment strategies and further investigation.

Humans↗

PubMed2005

Effect of sacral neuromodulation on the rectum.

BACKGROUND: Sacral neuromodulation (SNM) is a new treatment for faecal incontinence. At present the exact underlying mechanism is still unclear. Modulation of the sacral reflex arcs might have an effect on rectal sensitivity, wall tension and compliance. METHODS: Fifteen consecutive patients with faecal incontinence who qualified for SNM underwent barostat measurements before and during neuromodulation. An 'infinitely' compliant plastic bag with a volume of 600 ml was placed in the rectum and connected to a computer-controlled barostat system. An isobaric phasic distension protocol was used. Patients were asked to report rectal filling sensations: first sensation (FS), earliest urge to defaecate (EUD) and an irresistible, painful urge to defaecate (maximum tolerated volume; MTV). Rectal wall tension and compliance were calculated. RESULTS: During isobaric phasic distension each patient experienced all rectal filling sensations at the time of stimulation. Median volume thresholds decreased significantly during stimulation, from 98.1 to 44.2 ml for FS (P = 0.003), from 132.3 to 82.8 ml for EUD (P = 0.001) and from 205.8 to 162.8 ml for MTV (P = 0.002). Pressure thresholds tended to be lower for all filling sensations, but only that to evoke MTV was reduced significantly by stimulation (37.3 versus 30.3 mmHg; P = 0.005). Median rectal wall tension for all filling sensations decreased significantly with stimulation. There was no significant difference between compliance before and during stimulation. CONCLUSION: SNM affects rectal sensory perception, but further research is required to clarify the mechanism.

Adult↗

PubMed2004

Characterization of retinoic acid neuromodulation in the carp retina.

Visual sensation in vertebrates starts with the isomerization of 11-cis retinaldehyde into all-trans retinaldehyde. Aldehyde dehydrogenases, present in the pigment epithelium and some retinal cells, convert all-trans retinaldehyde into all-trans retinoic acid (at-RA). Evidence in the retina and the hippocampus has accumulated, showing that at-RA, besides being a morphogenetic factor, also acts as a neuromodulator. In mature retina, at-RA affects visual processing by acting on gap junctional conductances and the synaptic transfer between photoreceptors and horizontal cells. We present evidence supporting a neuromodulatory role of at-RA in the carp retina. High performance liquid chromatography (HPLC) measurements and an RA bioassay indicate a light dependency of at-RA formation, which can explain the observed effects of at-RA on spinule formation at horizontal cell dendrites in this retina. Furthermore, inhibiting endogenous metabolism and catabolism of at-RA affects formation and persistence of spinules in a way, supporting a direct involvement of at-RA in this light-dependent mechanism of synaptic plasticity. The action of at-RA, however, seems independent of the dopaminergic system, known for its light-signaling role in the retina, because at-RA effects on spinule formation persisted in retina depleted of dopaminergic neurons or in the presence of haloperidol. Together, these data indicate that at-RA acts effectively as a direct neuromodulator in carp retina, transmitting information about ambient light conditions to the neuronal retina.

Animals↗

PubMed2005

Sacral neuromodulation in lower urinary tract dysfunction.

Vesico-urethral dysfunction is a major problem in daily medical practice due to its psychological disturbances, its social costs and its high impact on quality of life. Recently, sacral neuromodulation, namely the electrical stimulation of the sacral nerves, appears to have become an alternative for radical bladder surgery particularly in cases of idiopathic bladder overactivity. The mechanism of action is only partially understood but it seems to involve a modulation in the spinal cord due to stimulation of inhibitory interneurons. Temporary sacral nerve stimulation is the first step. It comprises the temporary application of neuromodulation as a diagnostic test to determine the best location for the implant and to control the integrity of the sacral root. If test stimulation is successful, a permanent device is implanted. This procedure is safe in experienced hands. So-called idiopathic bladder overactivity still the major indication for this technique. Patients not likely to benefit from the procedure were those with complete or almost complete spinal lesions, but incomplete spinal lesions seemed to be a potential indication. This technique is now also indicated in the case of idiopathic chronic retention and chronic pelvic pain syndrome. When selection is performed, more than three-quarters of the patients showed a clinically significant response with 50% or more reduction in the frequency of incontinent episodes, but the results vary according to the author's mode of evaluation. From the economic point of view, the initial investment in the device is amortized in the mid-term by savings related to lower urinary tract dysfunction. Finally, this technique requires an attentive follow-up and adjustments to the electric parameters so as to optimize the equilibrium between the neurological systems.

Afferent Pathways↗

PubMed1979

Neurotransmitters and neuromodulators and their mediation by cyclic nucleotides.

An effort has been made here to devise criteria allowing discrimination between neurotransmitters, modulators and mediators. However, after consideration of several technical pitfalls in studies of these criteria, and examination of the properties of two examples of neuroactive agents (norepinephrine and endorphins) often referred to as "modulators", it is still difficult to classify these agents in all cases. Thus, in most central targets where NE-fibers are known to terminate, the synaptic actions of NE appear to have properties of both a neuromodulator and a neurotransmitter. Although much more research needs to be pursued, the opioid peptides may be neuromodulators for some neurons (spinal cord neurons) and neurotransmitters for others (myenteric plexus and spinal cord neurons). It may be that classification of such peptide agonists will need to be done on a cell-by-cell basis, with the endogenous peptides subserving a multi-faceted role in central and peripheral neuronal communication. As more and more endogenous ligands and transmitter-like substances are extracted from brain, it begins to appear that the language of neuronal communication is much richer than originally imagined from responses of spinal neurons to the fast-acting classical neurotransmitters. Indeed, it may evolve that the "deviant" forms of communication or transmission are more the rule than the exception. In the final analysis, each neurotransmitter may possess its own "fingerprint" of holistic actions attesting to the unique individuality of neuron types and their neurotransmitters. Such individualities might be expected to accomplish more sophisticated integrative operations, and hence behaviors, than could simple rapid "yes" or "no" messages.

Acetylcholine↗

PubMed1988

Inhibitory neuromodulators do not alter the course of experimental hepatic encephalopathy.

The neuromodulators, adenosine, serotonin, and glycine, did not alter the course of hepatic encephalopathy (HE) that followed a portacaval shunt and hepatic artery ligation in rats. The substances were instilled into the brain ventricle through an intraventricular cannula in doses that affect other aspects of behavior in the normal rat (adenosine, suppression of food intake; serotonin, loss of muscle strength and ataxia; glycine, leaning and circling). A subconvulsive dose of the glycine antagonist, strychnine, also had no effect on the course of HE. A large dose of the adenosine antagonist, caffeine, had a depressive rather than excitatory effect and shortened the time taken to induction of coma. These studies and a similar previous one with gamma-aminobutyric acid (GABA) suggest that the inhibitory neuromodulators do not have a prominent role in the pathogenesis of hepatic coma.

Adenosine↗

PubMed2006

Effects of sacral neuromodulation on female sexual function.

The aim of this prospective study was to determine if sacral neuromodulation has an effect on the patient's subsequent sexual function. Sexually active patients that underwent an Interstim Sacroneuromodulator implantation (Medtronic, Minneapolis, MN) for control of bladder symptoms were enrolled. A Female Sexual Function Index (FSFI) was completed before surgery and at a mean of 5.7 months postoperatively. Eleven subjects proceeded to permanent implantation, seven of these were sexually active before and after placement. Three subjects (43%) felt the device impacted on their sexual function in a positive way (1) by decreasing urgency and (2) by increasing desire. Overall sexual frequency increased significantly after the surgery (p=0.047). There were also significant increases in the FSFI total (p=0.002), and domain scores for desire (p=0.004), lubrication (p=0.005), orgasm (p=0.043), satisfaction (p=0.007), and pain (p=0.015). There was no correlation between patient report of urinary symptom improvement and FSFI scores. In conclusion, sacral neuromodulation may improve sexual frequency and sexual function scores in subjects with urgency frequency and urge incontinence.

Adult↗

PubMed1998

Clinical results of sacral neuromodulation for chronic voiding dysfunction using unilateral sacral foramen electrodes.

The aim of this study was to determine the long-term clinical efficacy and complications of neuromodulation with a unilateral sacral foramen electrode in 36 patients with chronic voiding dysfunction. Following a positive effect of a percutaneous nerve evaluation test, patients underwent open surgery. A permanent electrode was implanted in 24 patients with urge incontinence, in 6 with urgency-frequency syndrome, and in 6 with nonobstructive urinary retention. After an average follow-up period of 37.8 months, 19 patients (52.8%) continue to benefit from the neuromodulation with a significant improvement of symptoms and urodynamic parameters. The median duration of the therapeutic effect for the total study population was longer than 60 months. No significant difference in the median duration of therapeutic effect with regard to sex, the type of voiding disorder, or the implant pulse generator was found. However, in patients with previous psychological disorders the median duration of therapeutic effect was only 12 months (P = 0.008). Complications were mild. In the group of patients in whom the therapeutic effect remains, 37 reoperations have had to be performed. We conclude that although reoperations were needed to overcome technical problems, patients can achieve lasting symptomatic improvement. Since technical changes in the equipment have reduced the number of complications, even better results can be expected in terms of the reoperation rate.

Adult↗

PubMed2001

Influence of exercise on serotonergic neuromodulation in the brain.

Implications of exercise on serotonergic neuromodulation in the brain have been investigated in two studies. Acute paroxetine (selective serotonin (5-HT) reuptake inhibitor) administration to endurance athletes, who performed a cycle ergometer test to exhaustion at moderate intensity, reduced time to exhaustion and post exercise cognitive performance in comparison to trials with placebo or BCAA administration. Furthermore, during a 3-week moderate endurance training of sedentary males basaline values of Bmax of 5-HT transporters (5-HTT) and 5-HT2A receptors (5-HT(2A)R) on isolated platelet membranes increased while plasma prolactin (PRL) concentrations decreased as well as mood and physical efficiency improved. In contrast, after an excessive training program over four weeks, well-trained endurance athletes showed no change of Bmax of 5-HTT, but a decline of 5-HT(2A)R density and an increase in basal plasma PRL concentration. Mood was impaired and central fatigue increased. Thus, the impact of exercise on 5-HT neurotransmission may depend on training state of athletes and extent of exertion. The theoretical background of the implication of exercise and the effect of long lasting exhaustive exercise in athletes on mental and physical efficiency or central fatigue are evaluated. The significance of the primary disturbance of central neuromodulation and dysfunction of 5-HTT, 5-HT receptor subtypes and the phosphoinositol signal transduction as well as the limited modulation capacity of the 5-HT system in overstrain are also addressed.

Adult↗

PubMed2004

Sacral neuromodulation in patients with fecal incontinence: a single-center study.

PURPOSE: Fecal incontinence is a psychologically devastating and socially incapacitating condition. Conventional treatment is likely to improve continence in many patients; however, there remains a group with persisting symptoms who are not amenable for a simple surgical repair. We evaluated the effect of sacral neuromodulation in patients with structurally intact sphincters after failure of conventional treatment. METHODS: Patients aged 18 to 75 years were evaluated. Incontinence was defined as involuntary loss of stool at least once per week, which was objectified by completion of a three-week bowel-habits diary during ambulatory electrode stimulation at the S3 or S4 foramen. Patients were qualified for permanent stimulation when showing a reduction of at least 50 percent in incontinence episodes or days. RESULTS: Seventy-five patients (66 females; mean age, 52 (range, 26-75) years) were treated. Three patients had partial spinal cord injury, two patients a previous low-anterior resection, and nine patients had a previous sphincter repair. Evaluation after trial screening showed that 62 patients (83 percent) had improved continence. Median incontinence episodes per week decreased from 7.5 to 0.67 (P < 0.01), median incontinence days per week from 4 to 0.5 (P < 0.01). The symptomatic response stayed unchanged after implantation of a permanent electrode and pacemaker in 50 patients. After a median follow-up of 12 months, this effect could be sustained in 48 patients. Anal manometry during stimulation showed no increase of sphincter pressures. CONCLUSIONS: Sacral neuromodulation is a feasible treatment option for fecal incontinence in patients with structurally intact sphincters.

Adult↗

PubMed2003

Update on sacral neuromodulation: indications and outcomes.

Tanagho and Schmidt first introduced sacral nerve neuromodulation in 1981. Since then, it has become increasingly popular and the indications for this procedure are growing. The purpose of this article is to discuss the established indications for sacral nerve stimulation (SNS). The outcomes of the most recent studies and trials dealing with SNS are presented. An overview of the most recent techniques used for neuromodulation is detailed.

Adult↗

PubMed1995

Neuromodulation and cortical function: modeling the physiological basis of behavior.

Neuromodulators including acetylcholine, norepinephrine, serotonin, dopamine and a range of peptides alter the processing characteristics of cortical networks through effects on excitatory and inhibitory synaptic transmission, on the adaptation of cortical pyramidal cells, on membrane potential, on the rate of synaptic modification, and on other cortical parameters. Computational models of self-organization and associative memory function in cortical structures such as the hippocampus, piriform cortex and neocortex provide a theoretical framework in which the role of these neuromodulatory effects can be analyzed. Neuromodulators such as acetylcholine and norepinephrine appear to enhance the influence of synapses from afferent fibers arising outside the cortex relative to the synapses of intrinsic and association fibers arising from other cortical pyramidal cells. This provides a continuum between a predominant influence of external stimulation to a predominant influence of internal recall (extrinsic vs. intrinsic). Modulatory influence along this continuum may underlie effects described in terms of learning and memory, signal to noise ratio, and attention.

Acetylcholine↗

PubMed1992

Gonadotropin-releasing hormone (GnRH) cells of the terminal nerve as a model neuromodulator system.

Modulation of ionic channel properties by neurotransmitters and hormones is called neuromodulation and may be the basis for many long-lasting changes in animal behavior, e.g. changes in the arousal or motivational states. Gonadotropin-releasing hormone (GnRH), originally identified as a hypophysiotropic hormone, is now believed to act also as a neuromodulator. From studies of electrical activities and morphology of terminal nerve cells (major source of GnRH) of a fish brain, a general hypothesis regarding modulator neurons is proposed; modulator neurons have endogenous oscillatory activities which vary according to the animal's hormonal or environmental conditions. These modulator neurons, in turn, regulate neuronal excitabilities in a wide variety of brain regions simultaneously via multiple axonal branches.

Animals↗

PubMed2004

Novelty stress and reproductive state alters responsiveness to sensory stimuli and 5-HT neuromodulation in crayfish.

Sensory stimuli can produce varied responses depending on the physiological state of an animal. Stressors and reproductive stage can result in altered biochemical status that changes the responsiveness of an animal to hormones and neuromodulators, which affects whole animal behavior in relation to sensory stimuli. Crayfish serve as a model for examining the effects of neuromodulators at the neuromuscular junctions (NMJs) and for alterations in stereotypic behaviors for particular stimuli. Thus, we used crayfish to examine the effect of novelty stressors in males and the effect of being gravid in female crayfish to exogenous application of serotonin (5-HT). The responsiveness of neuromuscular junctions to 5-HT revealed that stressed as well as gravid crayfish have a reduced response to 5-HT at NMJs. The stressed crayfish were not fatigued since the basal synaptic responses are large and still showed a pronounced response to 5-HT. Using intact animals to examine a tail flip behavior, we showed that the rate of habituation in tail flipping to a strong repetitive stimulus on the telson is reduced in stressed males. Gravid females show no tail flipping behavior upon telson stimulation.

Animals↗

PubMed2006

Measuring dopamine neuromodulation in the thalamus: using [F-18]fallypride PET to study dopamine release during a spatial attention task.

We used the highly selective D2/D3 dopamine PET radioligand [F-18]fallypride to demonstrate that cognitive task induced dopamine release can be measured in the extrastriatal region of the thalamus, a region containing 10-fold fewer D2 dopamine receptors than the striatum. Human studies were acquired on 8 healthy volunteers using a single [F-18]fallypride injection PET imaging session. A spatial attention task, previously demonstrated to increase FDG uptake in the thalamus, was initiated following a period of radioligand uptake. Thalamic dopamine release was statistically tested by measuring time-dependent alterations in the kinetics (focusing on specific binding) of the [F-18]fallypride using the linearized extension of the simplified reference region model. Voxel-based analysis of the dynamic PET data sets revealed a high correlation (r = 0.86, P = 0.0067) between spatial attention task performance and thalamic dopamine release. Various aspects of the kinetic model were analyzed to address concerns such as blood flow artifacts and model bias, as well as issues with task timing and regional variations in D2/D3 receptor density. In addition to the thalamus, measurement of dopamine neuromodulation using [F-18]fallypride and a single injection PET protocol can be extended to other extrastriatal regions of the brain, such as the amygdala, hippocampus, and regions of the temporal cortex. However, issues of task timing and detection sensitivity will vary depending on regional D2/D3 dopamine receptor density. Measurements of extrastriatal dopamine neuromodulation hold great promise to further our understanding of extrastriatal dopamine involvement in normal cognition and neuropsychiatric pathology.

Adult↗