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Neuromodulation
Kinds of Neuromodulation Selected AbstractsNeuromodulation for the treatment of urinary incontinenceINTERNATIONAL JOURNAL OF UROLOGY, Issue 8 2008Tomonori Yamanishi Abstract: Neuromodulation has been reported to be effective for the treatment of stress and urgency urinary incontinence. The cure and improvement rates of pelvic floor neuromodulation in urinary incontinence are 30,50% and 60,90%, respectively. In clinical practice, vaginal, anal and surface electrodes are used for external, short-term stimulation, and sacral nerve stimulation for internal, chronic (long-term) stimulation. The effectiveness of neuromodulation has been verified in a randomized, placebo-controlled study. However, the superiority to other conservative treatments, such as pelvic floor muscle training has not been confirmed. A long-term effect has also been reported. In conclusion, pelvic floor exercise with adjunctive neuromodulation is the mainstay of conservative management for the treatment of stress incontinence. For urgency and mixed stress plus urgency incontinence, neuromodulation may therefore be the treatment of choice as an alternative to drug therapy. [source] The Politics of Neuromodulation in the USA: Spinal Cord Stimulation and the Washington State Department of Labor and IndustryNEUROMODULATION, Issue 4 2010PhD Editor-in-Chief, Robert M. Levy MD First page of article [source] Ethical Issues in NeuromodulationNEUROMODULATION, Issue 3 2010PhD Editor-in-Chief, Robert M. Levy MD First page of article [source] The Future of NeuromodulationNEUROMODULATION, Issue 2 2010Ph.D. Editor-in-Chief, Robert M. Levy M.D. No abstract is available for this article. [source] "On the Shoulders of Giants": A History of the Understandings of Pain, Leading to the Understandings of NeuromodulationNEUROMODULATION, Issue 2 2009Thomas Keller MD ABSTRACT The history of the use of electrical stimulation for pain is a cavalcade of research and innovation of many great scholars, scientists, and physicians over centuries that continues up to the present day. The legacy of this philosophy, research, and innovation is the field of neuromodulation for pain control. Today, patients with chronic pain from damage to the nervous system and chronic pain of the extremities, the axial low back, and neck, the face, and the viscera, all derive benefit from these early pioneers that have led to the expanding field of neuromodulation ... "on the shoulders of giants." We present here a history of the understandings of pain from the ancients to the present, which has led to our understandings of the use of electricity to cure disease and release patients from their suffering, generating the new, exciting, and expanding field of neuromodulation. [source] Evidence-Based Medicine and NeuromodulationNEUROMODULATION, Issue 3 2008John D. Loeser MD ABSTRACT Evidence-based medicine is gaining increasing penetrance in the United States. Neuromodulation providers need to know how to use this resource and how to get what we do appropriately evaluated and included in structured reviews and meta-analyses. Randomized clinical trials are not the only form of evidence for patient care activities; other, equally valid strategies are available and should be used for interventions that may preclude blinding and randomization. Those who determine payment are going to use evidence-based medicine to make decisions that may not be in the best interests of our patients or our profession. [source] Physicians, Industry, and Science: Moving Forward as Neuromodulation MaturesNEUROMODULATION, Issue 3 2007Timothy R. Deer MD [source] The "New Look and Feel" of NeuromodulationNEUROMODULATION, Issue 1 2007Elliot Krames MD [source] Neuromodulation in Epilepsy and in Chronic PainNEUROMODULATION, Issue 2 2006Belgium, Ghent, Third Meeting of the Benelux Neuromodulation Society Chapter of the International Neuromodulation Society November 1 [source] Neuromodulation by Means of Electrical Brain StimulationNEUROMODULATION, Issue 2 2004Article first published online: 22 MAR 200 [source] Measuring the sensations of urge and bladder filling during cystometry in urge incontinence and the effects of neuromodulationNEUROUROLOGY AND URODYNAMICS, Issue 1 2003Sarah Oliver Abstract Aims: As urge and urgency contribute greatly to a patient's symptoms, it follows that sensory evaluation combined with noninvasive neuromodulation during urodynamics may provide new criteria for improving patient selection for an implantable stimulator. The purpose of this research was to develop and validate an objective measure of bladder sensations during filling cystometry and then to apply this technique to evaluate the effects of neuromodulation on the sensations of urge measured in this way. Methods: In study 1 a new patient-activated keypad device was tested during urodynamics to measure bladder sensations according to a 0,4 scale and validated by using a technique adapted from a standard psychophysical sensory threshold testing method. In study 2 the effects of pudendal afferent nerve stimulation on measured sensations of urge were assessed during cystometry with patients as their own controls. Forty-three patients diagnosed with idiopathic detrusor instability were studied; 10 participated in study 1 and 35 in study 2. Results: The new device gave reliable and repeatable measures of sensations with statistically significant differences in bladder volume at each of the urge levels tested (Wilcoxon matched pairs test). Neuromodulation suppressed urinary urge in 89% of the 35 patients. This effect was associated with a statistically significant increase in bladder volume at all urge levels. Conclusions: A new patient operated key-pad device provided a reliably objective measure of sensations of urge during urodynamics without the need for prompting. Neuromodulation using noninvasive pudendal afferent stimulation suppressed these sensations whilst increasing bladder volume. Neurourol. Urodynam. 22:7,16, 2003. © 2003 Wiley-Liss, Inc. [source] Estimation of endogenous adenosine activity at adenosine receptors in guinea-pig ileum using a new pharmacological methodACTA PHYSIOLOGICA, Issue 2 2010K. F. Nilsson Abstract Aim:, Adenosine modulates neurotransmission and in the intestine adenosine is continuously released both from nerves and from smooth muscle. The main effect is modulation of contractile activity by inhibition of neurotransmitter release and by direct smooth muscle relaxation. Estimation of adenosine concentration at the receptors is difficult due to metabolic inactivation. We hypothesized that endogenous adenosine concentrations can be calculated by using adenosine receptor antagonist and agonist and dose ratio (DR) equations. Methods:, Plexus-containing guinea-pig ileum longitudinal smooth muscle preparations were made to contract intermittently by electrical field stimulation in organ baths. Schild plot regressions were constructed with 2-chloroadenosine (agonist) and 8-(p -sulfophenyl)theophylline (8-PST; antagonist). In separate experiments the reversing or enhancing effect of 8-PST and the inhibiting effect of 2-chloroadenosine (CADO) were analysed in the absence or presence of an adenosine uptake inhibitor (dilazep), and nucleoside overflow was measured by HPLC. Results:, Using the obtained DR, baseline adenosine concentration was calculated to 28 nm expressed as CADO activity, which increased dose dependently after addition of 10,6 m dilazep to 150 nm (P < 0.05). HPLC measurements yielded a lower fractional increment (80%) in adenosine during dilazep, than found in the pharmacological determination (440%). Conclusion:, Endogenous adenosine is an important modulator of intestinal neuro-effector activity, operating in the linear part of the dose,response curve. Other adenosine-like agonists might contribute to neuromodulation and the derived formulas can be used to calculate endogenous agonist activity, which is markedly affected by nucleoside uptake inhibition. The method described should be suitable for other endogenous signalling molecules in many biological systems. [source] Astrocytic calcium signals induced by neuromodulators via functional metabotropic receptors in the ventral respiratory group of neonatal miceGLIA, Issue 8 2009Kai Härtel Abstract A controlled, periodic exchange of air between lungs and atmosphere requires a neuronal rhythm generated by a network of neurons in the ventral respiratory group (VRG) of the brainstem. Glial cells, e.g. astrocytes, have been shown to be supportive in stabilizing this neuronal activity in the central nervous system during development. In addition, a variety of neuromodulators including serotonin (5-HT), Substance P (SP), and thyrotropin-releasing hormone (TRH) stimulate respiratory neurons directly. If astrocytes in the VRG, like their neuronal neighbors, are also directly stimulated by neuromodulators, they might indirectly affect the respiratory neurons and consequently the respiratory rhythm. In the present study, we provide support for this concept by demonstrating expression of NK1-R, TRH-R, and 5-HT2 -R in astrocytes of the VRG with immunohistochemistry. Additionally, we showed that the external application of the neuromodulators 5-HT, SP, and TRH activate calcium transients in VRG astrocytes. Consequently, we postulate that in the VRG of the neonatal mouse, neuromodulation by SP, TRH, and serotonin also involves astrocytic calcium signaling. © 2008 Wiley-Liss, Inc. [source] The G51S purine nucleoside phosphorylase polymorphism is associated with cognitive decline in Alzheimer's disease patientsHUMAN PSYCHOPHARMACOLOGY: CLINICAL AND EXPERIMENTAL, Issue 2 2007Emanuela Tumini Abstract Alzheimer's disease (AD) is a polygenic and multifactorial complex disease, whose etiopathology is still unclear, however several genetic factors have shown to increase the risk of developing the disease. Purine nucleotides and nucleosides play an important role in the brain. Besides their role in neurotransmission and neuromodulation, they are involved in trophic factor release, apoptosis, and inflammatory responses. These mediators may also have a pivotal role in the control of neurodegenerative processes associated with AD. In this report the distribution of the exonic G/A single nucleotide polymorphism (SNP) in purine nucleoside phosphorylase (PNP) gene, resulting in the amino acid substitution serine to glycine at position 51 (G51S), was investigated in a large population of AD patients (n,=,321) and non-demented control (n,=,208). The PNP polymorphism distribution was not different between patients and controls. The polymorphism distribution was also analyzed in AD patients stratified according to differential progressive rate of cognitive decline during a 2-year follow-up. An increased representation of the PNP AA genotype was observed in AD patients with fast cognitive deterioration in comparison with that from patients with slow deterioration rate. Our findings suggest that the G51S PNP polymorphism is associated with a faster rate of cognitive decline in AD patients, highlighting the important role of purine metabolism in the progression of this neurodegenerative disorder. Copyright © 2007 John Wiley & Sons, Ltd. [source] Neuromodulation for the treatment of urinary incontinenceINTERNATIONAL JOURNAL OF UROLOGY, Issue 8 2008Tomonori Yamanishi Abstract: Neuromodulation has been reported to be effective for the treatment of stress and urgency urinary incontinence. The cure and improvement rates of pelvic floor neuromodulation in urinary incontinence are 30,50% and 60,90%, respectively. In clinical practice, vaginal, anal and surface electrodes are used for external, short-term stimulation, and sacral nerve stimulation for internal, chronic (long-term) stimulation. The effectiveness of neuromodulation has been verified in a randomized, placebo-controlled study. However, the superiority to other conservative treatments, such as pelvic floor muscle training has not been confirmed. A long-term effect has also been reported. In conclusion, pelvic floor exercise with adjunctive neuromodulation is the mainstay of conservative management for the treatment of stress incontinence. For urgency and mixed stress plus urgency incontinence, neuromodulation may therefore be the treatment of choice as an alternative to drug therapy. [source] TYRA-2 (F01E11.5): a Caenorhabditis elegans tyramine receptor expressed in the MC and NSM pharyngeal neuronsJOURNAL OF NEUROCHEMISTRY, Issue 1 2005Elizabeth Rex Abstract Tyramine appears to regulate key processes in nematodes, such as pharyngeal pumping, and more complex behaviors, such as foraging. Recently, a Caenorhabditis elegans tyramine receptor, SER-2, was identified that is involved in the TA-dependent regulation of these processes. In the present study, we have identified a second C. elegans gene, tyra-2 (F01E11.5) that encodes a tyramine receptor. This is the first identification of multiple tyramine receptor genes in any invertebrate. Membranes from COS-7 cells expressing TYRA-2 bind [3H]tyramine with high affinity with a Kd of 20 ± 5 nm. Other physiologically relevant biogenic amines, such as octopamine and dopamine, inhibit [3H]tyramine binding with much lower affinity (Kis of 1.55 ± 0.5 and 1.78 ± 0.6 ,m, respectively), supporting the identification of TYRA-2 as a tyramine receptor. Indeed, tyramine also dramatically increases GTP,S binding to membranes from cells expressing TYRA-2 (EC50 of 50 ± 13 nm) and the TA-dependent GTP,S binding is PTX-sensitive suggesting that TYRA-2 may couple to G,i/o. Based on fluorescence from tyra::gfp fusion constructs, TYRA-2 expression appears to be exclusively neuronal in the MC and NSM pharyngeal neurons, the AS family of amphid neurons and neurons in the nerve ring, body and tail. Taken together, these results suggest that TYRA-2 encodes a second G,i/o -coupled tyramine receptor and suggests that TA-dependent neuromodulation may be mediated by multiple receptors and more complex than previously appreciated. [source] Chronic bilateral subthalamic deep brain stimulation in a patient with homozygous deletion in the Parkin geneMOVEMENT DISORDERS, Issue 12 2004Marianna Capecci MD Abstract Chronic subthalamic nucleus deep brain stimulation (STN-DBS) is an efficacious treatment for idiopathic Parkinson's disease (PD) that cannot be further improved by medical therapy. We present a case of an individual with juvenile parkinsonism caused by homozygous deletion of exon 3 in the parkin gene with disabling long-term side-effects from levodopa who underwent bilateral STN neuromodulation. Parkin-linked parkinsonism may show clinical features different from sporadic PD, yet it shares levodopa responsiveness. Because levodopa responsiveness is a predictor of STN-DBS efficacy, we argued that this kind of surgical approach might be efficacious in hereditary parkin-linked juvenile parkinsonism. We evaluated clinical and functional assessment before and 12 months after surgery. The results showed that the Unified Parkinson Disease Rating Scales Motor score improved by 84% in our patient, the levodopa equivalent daily dose medication (LEDD) was reduced by 66%, and, finally, disabling and severe dyskinesias disappeared. © 2004 Movement Disorder Society [source] "On the Shoulders of Giants": A History of the Understandings of Pain, Leading to the Understandings of NeuromodulationNEUROMODULATION, Issue 2 2009Thomas Keller MD ABSTRACT The history of the use of electrical stimulation for pain is a cavalcade of research and innovation of many great scholars, scientists, and physicians over centuries that continues up to the present day. The legacy of this philosophy, research, and innovation is the field of neuromodulation for pain control. Today, patients with chronic pain from damage to the nervous system and chronic pain of the extremities, the axial low back, and neck, the face, and the viscera, all derive benefit from these early pioneers that have led to the expanding field of neuromodulation ... "on the shoulders of giants." We present here a history of the understandings of pain from the ancients to the present, which has led to our understandings of the use of electricity to cure disease and release patients from their suffering, generating the new, exciting, and expanding field of neuromodulation. [source] Unilateral versus bilateral stage I neuromodulator lead placement for the treatment of refractory voiding dysfunctionNEUROUROLOGY AND URODYNAMICS, Issue 8 2008Khanh Pham Abstract Aims To determine if bilateral S3 lead placement during the stage I trial period improves the "success" rate for advancing to stage II (permanent) sacral neuromodulator placement. Methods A retrospective chart review of 124 (20 male and 104 female) patients undergoing stage I sacral neuromodulation (InterStim®, Medtronic, Minneapolis, Minnesota) implantation for the treatment of refractory voiding dysfunction was performed. Patients were divided into two cohorts based on unilateral versus bilateral stage I lead placement in the S3 foramina. Both groups were then evaluated and compared with regards to overall "success", defined as progression from stage I to stage II placement. Results Fifty-five (44%) patients underwent unilateral stage I lead placement and 69 (56%) received bilateral S3 leads. Successful stage I trials were reported in 32/55 (58%) and 53/69 (76%) of unilateral and bilateral cohorts, respectively (P,=,0.03). Five wound infections were reported,2 (3.6%) following unilateral and 3 (4.3%) after bilateral stage I lead placement. No other complications were encountered. Conclusions Bilateral stage I neuromodulation trial provides a significantly higher rate of improvement in refractory voiding symptoms to allow for the progress to stage II implantation. Neurourol. Urodynam. 27:779,781, 2008, © 2008 Wiley-Liss, Inc. [source] Management of refractory urinary urge incontinence following urogynecological surgery with sacral neuromodulation,,NEUROUROLOGY AND URODYNAMICS, Issue 1 2007Jonathan S. Starkman Abstract Aims We sought to explore our patient outcomes utilizing sacral neuromodulation in the management of refractory urinary urge incontinence following urogynecological surgical procedures. Methods A total of 25 women with urinary urge incontinence following urogynecological surgery were selected for SNS therapy and retrospectively analyzed. All patients completed a comprehensive urological evaluation. Clinical data was recorded to determine outcomes and identify parameters that would be predictive of response to neuromodulation. Outcomes were determined via subjective patient questionnaire and graded as follows: significant response (,80% improvement), moderate response (,50% and <80% improvement), and poor response (<50% response). Results Nineteen patients had a previous pubovaginal sling (10 with concomitant pelvic prolapse repair), 3 a previous retropubic suspension, and 3 a transperitoneal vesicovaginal fistula repair. Urethrolysis was performed in 4 patients to alleviate bladder outlet obstruction prior to sacral neuromodulation. Mean patient age was 59.8 years and length of follow-up was 7.2 months. Twenty-two women (88%) had the IPG placed during a Stage 2 procedure. Twenty patients maintained at least a 50% improvement in clinical symptoms at last follow-up and 6 patients were continent. Overall, the number of pads/day improved from 4.2 to 1.1 (P,<,0.001). There were no significant differences in response to neuromodulation based upon age, duration of symptoms, type of surgery, or urodynamic parameters. Conclusion Sacral neuromodulation appears to be an effective therapy in patients with refractory urge incontinence following urogynecological surgery. Larger prospective studies with longer follow-up are needed to assess the durability of this therapeutic modality. Neurourol. Urodynam. © 2006 Wiley-Liss, Inc. [source] External anal sphincter responses after S3 spinal root surface electrical stimulationNEUROUROLOGY AND URODYNAMICS, Issue 7 2006Giuseppe Pelliccioni Abstract Aims The aim of this study is to present the normative data of direct and reflex motor anal sphincter responses, simultaneously evoked by S3 surface electrical stimulation. By this method, it is possible to test the functional integrity of the nervous pathways activated during sacral neuromodulation (SNM). Methods Twenty healthy subjects were studied. Motor-evoked potentials (MEPs) were recorded by concentric needle electrode from external anal sphincter (EAS). Electrical stimulation was applied by means of a bipolar surface electrode over the S3 right or left sacral foramina. Results Direct (R1) and reflex responses (R2 and R3) were found at latencies of 6.98, 25.12, and 50.31 msec, respectively. The two first responses were recorded in all the cases; the last response is steadily recorded in 17 out of 20 subjects. Conclusions Our data can serve as reference values for future study in patients with pelvic floor dysfunction. EAS responses following S3 percutaneous electrical stimulation can represent a useful aid in the selection of candidates to SNM. Neurourol. Urodynam. 25:788,791, 2006. © 2006 Wiley-Liss, Inc. [source] A new minimally invasive procedure for pudendal nerve stimulation to treat neurogenic bladder: Description of the method and preliminary dataNEUROUROLOGY AND URODYNAMICS, Issue 4 2005Michele Spinelli Pudendal nerve stimulation has beneficial effects on numerous pelvic floor function impairments such as urinary and/or fecal incontinence, retention, and constipation. In preceding literature the implant technique required a fairly complex and invasive surgery, although recent advances with percutaneous placement of the lead through an introducer have made the procedure much less invasive. We performed staged procedure similar to that of sacral neuromodulation (SNM) to place tined lead near the pudendal nerve, using neurophysiological guidance that allowed accurate pudendal nerve stimulation through either perineal or posterior approach. We have named this approach chronic pudendal nerve stimulation (CPNS). Methods Fifteen neurogenic patients (eight male, seven female) with symptoms of urge incontinence due to neurogenic overactive bladder underwent CPNS. All patients had complete neurophysiological and urodynamic evaluation at baseline and follow-up and were asked to complete voiding and bowel diary for 7 days. Results During screening, average number of incontinent episodes per day decreased from 7,±,3.3 to 2.6,±,3.3 (P,<,0.02, paired t -test). Eight patients became continent, two improved by more than 88% (from 9 to 1 daily incontinence episode) and two patients reduced the number of incontinence episodes by 50%. The implantable pulse generator (IPG) was subsequently implanted in those 12 patients. Three patients without improvement did not continue to second stage. In implanted patients with 6 months follow-up, urodynamic evaluation showed an objective improvement in the maximum cystometric capacity which increased from 153.3,±,49.9 to 331.4,±,110.7 ml (P,<,0.01, paired t -test). The maximum pressure decreased from 66,±,24.3 to 36.8,±,35.9 cmH2O (P,=,0.059, paired t -test). Eight patients reported significant improvement in bowel function. Conclusion Chronic pundedal nerve stimulation is feasible. Neurophysiological guidance is mandatory to place the lead near the pudendal nerve either using perineal or posterior approach. Further studies must be carried out to identify the best stimulation parameters and to verify the long term results. Neurourol. Urodynam. 24:305,309, 2005. © 2005 Wiley-Liss, Inc. [source] Measuring the sensations of urge and bladder filling during cystometry in urge incontinence and the effects of neuromodulationNEUROUROLOGY AND URODYNAMICS, Issue 1 2003Sarah Oliver Abstract Aims: As urge and urgency contribute greatly to a patient's symptoms, it follows that sensory evaluation combined with noninvasive neuromodulation during urodynamics may provide new criteria for improving patient selection for an implantable stimulator. The purpose of this research was to develop and validate an objective measure of bladder sensations during filling cystometry and then to apply this technique to evaluate the effects of neuromodulation on the sensations of urge measured in this way. Methods: In study 1 a new patient-activated keypad device was tested during urodynamics to measure bladder sensations according to a 0,4 scale and validated by using a technique adapted from a standard psychophysical sensory threshold testing method. In study 2 the effects of pudendal afferent nerve stimulation on measured sensations of urge were assessed during cystometry with patients as their own controls. Forty-three patients diagnosed with idiopathic detrusor instability were studied; 10 participated in study 1 and 35 in study 2. Results: The new device gave reliable and repeatable measures of sensations with statistically significant differences in bladder volume at each of the urge levels tested (Wilcoxon matched pairs test). Neuromodulation suppressed urinary urge in 89% of the 35 patients. This effect was associated with a statistically significant increase in bladder volume at all urge levels. Conclusions: A new patient operated key-pad device provided a reliably objective measure of sensations of urge during urodynamics without the need for prompting. Neuromodulation using noninvasive pudendal afferent stimulation suppressed these sensations whilst increasing bladder volume. Neurourol. Urodynam. 22:7,16, 2003. © 2003 Wiley-Liss, Inc. [source] D2 receptors receive paracrine neurotransmission and are consistently targeted to a subset of synaptic structures in an identified neuron of the crustacean stomatogastric nervous systemTHE JOURNAL OF COMPARATIVE NEUROLOGY, Issue 3 2010Max F. Oginsky Dopamine (DA) modulates motor systems in phyla as diverse as nematodes and arthropods up through chordates. A comparison of dopaminergic systems across a broad phylogenetic range should reveal shared organizing principles. The pyloric network, located in the stomatogastric ganglion (STG), is an important model for neuromodulation of motor networks. The effects of DA on this network have been well characterized at the circuit and cellular levels in the spiny lobster, Panulirus interruptus. Here we provide the first data about the physical organization of the DA signaling system in the STG and the function of D2 receptors in pyloric neurons. Previous studies showed that DA altered intrinsic firing properties and synaptic output in the pyloric dilator (PD) neuron, in part by reducing calcium currents and increasing outward potassium currents. We performed single cell reverse transcriptase-polymerase chain reaction (RT-PCR) experiments to show that PD neurons exclusively expressed a type 2 (D2,Pan) DA receptor. This was confirmed by using confocal microscopy in conjunction with immunohistochemistry (IHC) on STG wholemount preparations containing dye-filled PD neurons. Immunogold electron microscopy showed that surface receptors were concentrated in fine neurites/terminal swellings and vesicle-laden varicosities in the synaptic neuropil. Double-label IHC experiments with tyrosine hydroxylase antiserum suggested that the D2,Pan receptors received volume neurotransmissions. Receptors were further mapped onto three-dimensional models of PD neurons built from Neurolucida tracings of confocal stacks from the IHC experiments. The data showed that D2,Pan receptors were selectively targeted to approximately 40% of synaptic structures in any given PD neuron, and were nonuniformly distributed among neurites. J. Comp. Neurol. 518:255,276, 2010. © 2009 Wiley-Liss, Inc. [source] Modulation and function of the autaptic connections of layer V fast spiking interneurons in the rat neocortexTHE JOURNAL OF PHYSIOLOGY, Issue 12 2010William M. Connelly Neocortical fast-spiking (FS) basket cells form dense autaptic connections that provide inhibitory GABAergic feedback after each action potential. It has been suggested that these autaptic connections are used because synaptic communication is sensitive to neuromodulation, unlike the voltage-sensitive potassium channels in FS cells. Here we show that layer V FS interneurons form autaptic connections that are largely perisomatic, and without perturbing intracellular Cl, homeostasis, that perisomatic GABAergic currents have a reversal potential of ,78 ± 4 mV. Using variance,mean analysis, we demonstrate that autaptic connections have a mean of 14 release sites (range 4,26) with a quantal amplitude of 101 ± 16 pA and a probability of release of 0.64 (Vcommand=,70 mV, [Ca2+]o= 2 mm, [Mg2+]o= 1 mm). We found that autaptic GABA release is sensitive to GABAB and muscarinic acetylcholine receptors, but not a range of other classical neuromodulators. Our results indicate that GABA transporters do not regulate FS interneuron autapses, yet autaptically released GABA does not act at GABAB or extrasynaptic GABAA receptors. This research confirms that the autaptic connections of FS cells are indeed susceptible to modulation, though only via specific GABAergic and cholinergic mechanisms. [source] Active properties of motoneurone dendrites: diffuse descending neuromodulation, focused local inhibitionTHE JOURNAL OF PHYSIOLOGY, Issue 5 2008C. J. Heckman The dendrites of spinal motoneurones are highly active, generating a strong persistent inward current (PIC) that has an enormous impact on processing of synaptic input. The PIC is subject to regulation by descending neuromodulatory systems releasing the monoamines serotonin and noradrenaline. At high monoaminergic drive levels, the PIC dominates synaptic integration, generating an intrinsic dendritic current that is as much as 5-fold larger than the current entering via synapses. Without the PIC, motoneurone excitability is very low. Presumably, this descending control of the synaptic integration via the PIC is used to adjust the excitability (gain) of motoneurones for different motor tasks. A problem with this gain control is that monoaminergic input to the cord is very diffuse, affecting many motor pools simultaneously, probably including both agonists and antagonists. The PIC is, however, exquisitely sensitive to the reciprocal inhibition mediated by length sensitive muscle spindle Ia afferents and Ia interneurones. Reciprocal inhibition is tightly focused, shared only between strict mechanical antagonists, and thus can act to ,sculpt' specific movement patterns out of a background of diffuse neuromodulation. Thus it is likely that motoneurone gain is set by the interaction between diffuse descending neuromodulation and specific and focused local synaptic inhibitory circuits. [source] Potentiation of mouse vagal afferent mechanosensitivity by ionotropic and metabotropic glutamate receptorsTHE JOURNAL OF PHYSIOLOGY, Issue 1 2006James A. Slattery Glutamate acts at central synapses via ionotropic (iGluR , NMDA, AMPA and kainate) and metabotropic glutamate receptors (mGluRs). Group I mGluRs are excitatory whilst group II and III are inhibitory. Inhibitory mGluRs also modulate peripherally the mechanosensitivity of gastro-oesophageal vagal afferents. Here we determined the potential of excitatory GluRs to play an opposing role in modulating vagal afferent mechanosensitivity, and investigated expression of receptor subunit mRNA within the nodose ganglion. The responses of mouse gastro-oesophageal vagal afferents to graded mechanical stimuli were investigated before and during application of selective GluR ligands to their peripheral endings. Two types of vagal afferents were tested: tension receptors, which respond to circumferential tension, and mucosal receptors, which respond only to mucosal stroking. The selective iGluR agonists NMDA and AMPA concentration-dependently potentiated afferent responses. Their corresponding antagonists AP-5 and NBQX alone attenuated mechanosensory responses as did the non-selective antagonist kynurenate. The kainate selective agonist SYM-2081 had minor effects on mechanosensitivity, and the antagonist UBP 302 was ineffective. The mGluR5 antagonist MTEP concentration-dependently inhibited mechanosensitivity. Efficacy of agonists and antagonists differed on mucosal and tension receptors. We conclude that excitatory modulation of afferent mechanosensitivity occurs mainly via NMDA, AMPA and mGlu5 receptors, and the role of each differs according to afferent subtypes. PCR data indicated that all NMDA, kainate and AMPA receptor subunits plus mGluR5 are expressed, and are therefore candidates for the neuromodulation we observed. [source] Expression of the PACAP-immunoreactivity in the Lymphoid Organs of the DuckANATOMIA, HISTOLOGIA, EMBRYOLOGIA, Issue 2005C. Squillacioti Introduction:, The interactions occurring between nervous and immune systems are well documented. These interactions involve several types of chemical messengers including hormones, cytokines, classic neurotransmitters and neuropeptides. It has been observed that the lymphoid organs receive a dense peptidergic innervation and immune cells produce neuropeptides. Neuropeptides, in turn, are involved in the regulation of the inflammatory processes and in the maturation of the lymphoid organs. Several studies have demonstrated that the immunomodulatory neuropeptides and their receptors are expressed in the thymus and bursa of fabricius. PACAP is a glucagon/VIP/secretin family peptide. It was originally isolated from the ovine hypothalamus and then it was found in the autonomic nervous system. PACAP is involved in the regulation of the hypothalamic-pituitary function, neurotransmission and neuromodulation. In the immune system, PACAP is expressed in lymphoid tissues of the rat and in the lymphocytes of the duck GALT. PACAP, therefore, could be a messenger of the dialogue between nervous and immune system. It may have a role in the regulation of the inflammatory processes by stimulating histamine and serotonin and modulating the production of the cytokines in immune cells. Methods:, Immunohistochemistry on paraffin-embedded sections of thymus and bursa of fabricius of the duck of different ages by using an antibody anti-PACAP38. Results and Discussion:, In the thymus, PACAP-immunoreactivity was found in lymphoid cells and, with a lesser extent, in epithelial reticular cells. The immunoreactive lymphocytes were primarily observed in the interlobular septa in close vicinity to the interlobular veins. The number of positive lymphocytes increased with ageing. In the bursa of fabricius, PACAP-IR was found in nerve fibres and in a few lymphoid cells. These results suggest that PACAP could play a role in the maturation and involution of these organs and in the immune functions. [source] Early sacral neuromodulation prevents urinary incontinence after complete spinal cord injuryANNALS OF NEUROLOGY, Issue 1 2010Karl-Dietrich Sievert MD Background The study aim was to investigate potential influences on human nerves and pelvic organs through early implantation of bilateral sacral nerve modulators (SNMs) in complete spinal cord injury (SCI) patients during the acute bladder-areflexia phase. Methods Ten patients with neurologically-confirmed complete spinal cord lesions (SCLs) were provided with bilateral SNMs during the phase of atonic-detrusor muscle. Modulation was achieved by two electrodes implanted into each S3 -foramen. Six patients declined and served as controls. The mean follow-up was 26.2 months. Results Videourodynamics (VU) confirmed detrusor acontractility, resulting in urinary continence as well as significant reductions in urinary tract infections (UTIs). Bowel movements did not require oral laxatives; additional preprogrammed parameters achieved erections for intercourse. Interpretation Early SNM implantation in SCI patients may revolutionize neurogenic lower urinary tract (LUT) dysfunction management; it prevented detrusor overactivity and urinary incontinence, ensured normal bladder capacity, reduced UTI rates, and improved bowel and erectile functionality without nerve damage. Conclusion Future SCI investigations will be conducted to evaluate the potential benefits of even earlier SNM placement to progressively enhance pelvic organ functionality. This new approach may provide important clues required for assessing whether neuronal information is passed through the sympathetic trunk ganglion to the brain after complete SCI. Further investigations are needed to determine if functional magnetic resonance imaging (fMRI) might be helpful for analyzing changes in brain function in patients with SNMs and those taking antimuscarinics. ANN NEUROL 2010;67:74,84 [source] The role of neuromodulation in the management of urinary urge incontinenceBJU INTERNATIONAL, Issue 7 2004P. Abrams First page of article [source] |