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BackgroundPrimary nocturnal enuresis (PNE) is defined as recurrent voiding of urine into bed or clothing, causing distress or impairment in social, academic, or other critical areas. Despite neuroimaging data and brain models, targeted therapeutic approaches are lacking. Magnetic stimulation, including transcranial and direct sacral stimulation, could be a potential treatment for nocturnal enuresis. Results40 patients with PNE were recruited and randomly distributed into 2 groups. Group (I): 22 patients received real magnetic stimulation (transcranial and direct sacral root stimulation) and Group (II): 18 patients received sham stimulation as a control group. Patients were evaluated before, immediately after the sessions, 1 and 3 months after sessions, assessing frequency of wet nights, quality of life according to International Consultation on Incontinence Questionnaire–Lower Urinary Tract Symptom Quality of Life (ICIQ–LUTS qol) score and motor threshold (MT) as a measure for brain excitability and neuronal integrity. There was a substantial reduction in the frequency of wet nights per week for the treatment group compared to the control group, with a significant difference observed after 1 month (P value 0.086) and 3 months (P value < 0.001). MT assessment showed alterations in cortical excitability, with a significant difference observed at dates 2, 3 (P value 0.044, < 0.001). The clinical improvement was associated with correlated improvement in the quality of life, although it was not significantly observed immediately after the sessions. The International Children’s Continence Society (ICCS) criteria response rate showed a higher response rate for the real stimulation with no significant adverse effects. ConclusionsThe research highlights the effectiveness and safety of using both transcranial and sacral magnetic stimulation in treating pediatric patients with PMNE. To maximize therapeutic success in this patient population, more research is required to clarify the mechanisms of action and improve therapy regimens.

Spinal cord injury (SCI) results in severe autonomic dysfunction, across cardiovascular, bladder, bowel and sexual domains, negatively affecting quality of life. Recently, there has been growing interest in the application of spinal cord stimulation (SCS) to restore or modulate autonomic functions in people with SCI. This review systematically evaluated the evidence for spinal cord and/or root stimulation, delivered via epidural (eSCS), transcutaneous (tSCS) spinal cord stimulation, or sacral (posterior) anterior root stimulation (SARS/SPARS) - in managing autonomic dysfunction after SCI. A systematic search of OVID Medline, OVID Embase, and Web of Science, was completed in September 2024. Eligible studies included adults with SCI (≥18 years old) receiving eSCS, tSCS, or SARS, reporting at least one quantitative autonomic outcome measure. Extracted data were synthesised by autonomic domain (cardiovascular, urinary, bowel, sexual), intervention type (eSCS, tSCS, or SARS) and duration of stimulation (acute vs. chronic). Fifty-seven articles were identified, evaluating eSCS (30 studies,  = 151), tSCS (10 studies,  = 48), and SARS (17 studies,  = 1,249) effects on cardiovascular (22 studies), bladder (23 studies), bowel (14 studies), and sexual function (13 studies). Acute application of eSCS or tSCS consistently elevated blood pressure and mitigated orthostatic hypotension, with variable effects on suppressing autonomic dysreflexia. Acute application of eSCS, tSCS or SPARS, improved bladder capacity and voiding efficiency, although not consistently and often outcomes did not reach clinically acceptable levels. eSCS, tSCS and SARS consistently reduced bowel management times. In most participants, erections could be achieved or were improved with eSCS or SARS. Chronic interventions, particularly SARS with dorsal root deafferentation, produced long term bladder and bowel improvements, whereas chronic eSCS and tSCS evidence was limited. Stimulation was most often applied to lumbosacral segments (L1-S1) at 30-60 Hz, although some studies used systematic mapping approaches. Electrical stimulation of the spinal cord and/or nerve roots is a promising method for modulating or restoring autonomic function after SCI. However, current evidence is based on small cohort or case studies, or retrospective reporting. Larger controlled studies are recommended to establish efficacy and long-term safety, and further mechanistic investigations are required. https://www.crd.york.ac.uk/PROSPERO/view/CRD420250621447, identifier PROSPERO (CRD420250621447).

Implantable sacral anterior root stimulators enable bladder emptying after spinal cord injury but do not prevent reflex incontinence. A closed-loop neuroprosthesis that detects and inhibits reflex bladder contractions could address this, but first, reliable detection of bladder fullness from the sacral roots. Further, the distribution of afferent bladder activity between sacral roots, and the relationship between efferent and afferent activity within each root, remains unclear and must be clarified to guide implant design. Electrode books were implanted on the S1-S3 extra-dural sacral roots bilaterally in six terminally anesthetized sheep. Afferent electroneurogram (ENG) was recorded concurrently from all implanted roots during filling cystometries and correlated with bladder pressure. Each root was individually electrically stimulated and the bladder pressure response recorded. Post-mortem morphometric analysis determined fiber size distribution in each root. Overall, S2 ENG activity showed the highest correlation with bladder pressure, and electrical stimulation of S2 and S3 produced the greatest increases in bladder pressure. Fiber size distribution did not correlate with either ENG activity or bladder pressure response. Significant variation was identified between individual sheep, but notably, in four of six sheep, a single sacral root had both the highest ENG correlation to bladder pressure and the greatest bladder response to stimulation. This study demonstrates reliable recording of bladder afferents from sacral roots using clinically applicable electrodes. It provides the first systematic recording of bladder ENG concurrently across three pairs of sacral roots in multiple animals, and the first characterization of signal distribution between roots. Significant individual variation is identified, impacting the design of future implantable sacral neuroprostheses for bladder control.

Abstract Objective The dorsal root ganglion (DRG) is a novel target for neuromodulation, and DRG stimulation is proving to be a viable option in the treatment of chronic intractable neuropathic pain. Although the overall principle of conventional spinal cord stimulation (SCS) and DRG stimulation—in which an electric field is applied to a neural target with the intent of affecting neural pathways to decrease pain perception—is similar, there are significant differences in the anatomy and physiology of the DRG that make it an ideal target for neuromodulation and may account for the superior outcomes observed in the treatment of certain chronic neuropathic pain states. This review highlights the anatomy of the DRG, its function in maintaining homeostasis and its role in neuropathic pain, and the unique value of DRG as a target in neuromodulation for pain. Methods A narrative literature review was performed. Results Overall, the DRG is a critical structure in sensory transduction and modulation, including pain transmission and the maintenance of persistent neuropathic pain states. Unique characteristics including selective somatic organization, specialized membrane characteristics, and accessible and consistent location make the DRG an ideal target for neuromodulation. Because DRG stimulation directly recruits the somata of primary sensory neurons and harnesses the filtering capacity of the pseudounipolar neural architecture, it is differentiated from SCS, peripheral nerve stimulation, and other neuromodulation options. Conclusions There are several advantages to targeting the DRG, including lower energy usage, more focused and posture-independent stimulation, reduced paresthesia, and improved clinical outcomes.

Background Radical resection of spinal cord lipomas reduces the rate of re-tethering. Current conventional neurophysiological mapping techniques are not able to differentiate between crucial motor nerve roots and sensory roots. Enhanced differentiation could contribute to complete resection. We present our experience with a double-train paradigm to differentiate between motor and sensory roots. Methods In children undergoing spinal cord lipoma resection, the double-train mapping paradigm was used with an inter-train interval of 60 ms. Given the longer recovery time due to the H-reflex, a single muscle response was presumed to be elicited from a sensory root, and a double muscle response from a motor root. The primary endpoint was postoperative neurological outcome and bladder function at discharge. Results We included 8 children undergoing 10 lipoma resections between 2016 and 2023. Double-train mapping was used in all cases. Motor and sensory roots were clearly differentiated in 6 cases and altered the course of surgery in 4 cases. Post-surgery, no sensory and motor function worsened within 3 months. Bladder function was stable in six and improved in two children. In two patients, bladder function worsened slightly at 3 months and 6 months, at which point one patient was re-operated on for re-tethering. Conclusion Intraoperative mapping with the double-train paradigm reliably differentiated between motor and sensory nerve roots. Informing the surgeon on the specific function of a tethering root may help to maximize resection without risking major neurological deficits.

The recent interest in targeting the dorsal root ganglion (DRG) has led to the development of new techniques of electrode placement. In this article, we describe a new \"Transgrade\" approach to the DRG, accessing the contralateral interlaminar space and steering the lead out the opposite foramen. The purpose of this study was to evaluate the Transgrade technique to the DRG in the management of focal neuropathic pain, predominately complex regional pain syndrome in terms of efficacy and safety. A retrospective, observational review of all patients selected for DRG stimulation using the Transgrade technique to the DRG. Pain Management and Neuromodulation Centre, Guys and St. Thomas NHS Foundation Trust, London, United Kingdom. Data were taken from a hospital password-protected database. All patients were contacted by telephone for Numeric Rating Scale (NRS-11) score, Patient Global Impression of Change (PGIC) score, and complications. A patient responder was defined as having a PGIC score of 6 or 7, and a 2-point reduction from baseline NRS-11. A total of 39 patients (46% women) with a mean age of 46 years (± 2) underwent a trial of DRG stimulation that resulted in an implantation rate of 82% (32 of 39). The responder rates, according to NRS-11 and PGIC results, were 87% (28 of 32) at 6 weeks and 66% (21 of 32) at a mean of 18 months (± 1.8) follow-up. Pocket pain was the most common complication, occurring in 7 of 32 (22%) patients, and the lead migration rate was 3 out of 57 leads placed (5.2%). A burst protocol was the favored method of stimulation in the majority of patients, 25 of 32 (78%). Retrospective nature of design, small sample size. The Transgrade technique of placing DRG leads offers an alternative method that is safe and effective. New methods of stimulation to the DRG offer more choice and potentially better efficacy for patients with chronic neuropathic pain. Neuromodulation, dorsal root ganglion, neuropathic pain, complex regional pain syndrome, spinal cord stimulation, chronic pain, implantable neurostimulators, spinal nerve root stimulation.

Percutaneous spinal stimulation is a promising new technique for understanding human spinal reflexes and for evaluating the pathophysiology of motor roots. Previous studies have generally stimulated the T11/T12 or T12/L1 vertebral junctions, sites that overlie the lumbosacral enlargement. The present study sought to determine the best location for targeting sensory and motor roots during sitting. We used paired stimuli, 50 ms apart, to distinguish the contribution of the reflex and motor components which make up the root evoked potential. This assumed that post-stimulation attenuation, primarily through homosynaptic depression, would abolish the second potential if it was trans-synaptic in origin. Conversely, successive responses would be unchanged if motor roots were being stimulated. Here, we show that sensory root reflexes were optimally elicited with percutaneous stimulation over the L1–L3 vertebrae. However, the optimal position varied between subjects and depended on the target muscle being studied. A collision test showed that the reflex recorded in pre-tibial flexors was low in amplitude and was prone to crosstalk from neighbouring muscles. In contrast to the reflex response, direct motor root activation was optimal with stimulation over the more caudal L5–S1 vertebrae. The present results support the utility of paired stimulation for evaluating the topographical recruitment of sensory and motor roots to human leg muscles.

Current agricultural practices rely heavily on synthetic fertilizers, which not only consume a lot of energy but also disrupt the ecological balance. The overuse of synthetic fertilizers has led to soil degradation. In a more sustainable approach, alternative methods based on biological interactions, such as plant growth-promoting bacteria (PGPRs), are being explored. PGPRs, which include both symbiotic and free-living bacteria, form mutualistic relationships with plants by enhancing nutrient availability, producing growth regulators, and regulating stress responses. This study investigated the potential of Sphingomonas sediminicola Dae20, an α-Proteobacteria species commonly found in the rhizosphere, as a beneficial PGPR. We observed that S. sediminicola Dae20 stimulated the root system and growth of three different plant species in the Brassicaceae family, including Arabidopsis thaliana, mustard, and rapeseed. The bacterium produced auxin, nitric oxide, siderophores and showed ACC deaminase activity. In addition to activating an auxin response in the plant, S. sediminicola Dae20 exhibited the ability to modulate other plant hormones, such as abscisic acid, jasmonic acid and salicylic acid, which are critical for plant development and defense responses. This study highlights the multifunctional properties of S. sediminicola Dae20 as a promising PGPR and underscores the importance of identifying effective and versatile beneficial bacteria to improve plant nutrition and promote sustainable agricultural practices.

BACKGROUND: Postherpetic neuralgia (PHN) is a common complication after herpes zoster infection. While conventional dorsal column temporary spinal cord stimulation (tSCS) has been shown as an effective treatment option for this pain condition, recent data suggests ipsilateral temporary spinal nerve root stimulation (tSNRS) as a safe alternative for treating PHN. However, there is no direct clinical comparison between the newer tSNRS and the traditional tSCS. OBJECTIVES: The current retrospective study aimed to describe the technical factors and the therapeutic efficacy of tSNR for patients with unilateral PHN and to compare these parameters with those treated with tSCS. STUDY DESIGN: Retrospective cohort study. SETTING: Single-center study in a large academic hospital. METHODS: One hundred sixty patients with unilateral PHN who underwent 7-14 days of tSCS (n = 109) or tSNRS (n = 51) treatment were included. Technical factors between the 2 groups, such as procedure time, radiation dosage, number of electrodes used, number of stimulation parameter adjustments, and average cost, were compared. Treatment efficacy, measured by analgesic coverage, pain visual analog scale (VAS), total analgesic agent consumption, Pittsburgh sleep quality index (PSQI), and physical and mental quality of life, were also compared between the 2 groups at baseline, post-procedure, and 3 months after stimulation treatment. RESULTS: Patients who underwent tSNRS reported significant improvement in pain level, sleep quality, and overall quality of life immediately postprocedure and during the follow-up period. This therapeutic effect was comparable to the tSCS group. Moreover, tSNRS achieved this therapeutic effect with a fewer number of implanted electrodes and stimulation adjustments than tSCS. The precision and consistency of the tSNRS technique were associated with a significant overall lower cost, a shorter procedure time, and less intraoperative radiation exposure in the tSNRS group than in those who received tSCS. LIMITATIONS: The current retrospective cohort study was limited by its relatively short follow-up period. Also, the selection of stimulation techniques was not randomized. CONCLUSIONS: While tSNRS provides similar therapeutic efficacy compared to tSCS for patients with unilateral PHN; it offers several technical advantages. These advantages include shorter procedure time, less radiation exposure, fewer implanted electrodes, more effective stimulation, and lower overall cost.

Purpose Intracellular Ca 2+ imaging is a valuable tool for studying neuronal activity; however, its application in the spinal cord of mature animals remains underdeveloped. This study aimed to establish an intracellular Ca 2+ imaging method in adult rat spinal cord slices without complex genetic modifications and characterize primary afferent-evoked intracellular Ca 2+ responses in spinal dorsal horn neurons. Methods L5 lumbar spinal cord slices from adult rats were stained with a Ca 2+ indicator. The relationship between intracellular Ca 2+ signals and electrophysiological responses induced by dorsal root stimulation was examined. Additionally, the effects of analgesics, anesthetics, and hyperalgesics on the Ca 2+ responses were analyzed. Results Monophasic intracellular Ca 2+ responses were observed with A-fiber intensity stimulation, while biphasic responses were noted with C-fiber intensity stimulation. These responses were not photobleached after repeated measurements (n = 12). The rising phase of Ca 2+ responses coincided with action potential generation, whereas the falling phase did not. Dorsal root stimulation-induced Ca 2+ responses were significantly suppressed by morphine (10 μM, 43.9 ± 4.9% of control, n = 8) but not by remimazolam (10 μM, 98.0 ± 2.0% of control, n = 8). Conversely, bicuculline (40 μM, 288.4 ± 48.4% of control, n = 10) and high concentrations of tranexamic acid (3, 10 mM, 132.6 ± 19.9%, 152.6 ± 25.3%, respectively, n = 8) significantly enhanced Ca 2 ⁺ responses. Conclusion This is a simple and effective approach to examining the effects of drugs that target the spinal cord and investigating nociceptive transmission and modulation mechanisms in the spinal dorsal horn.