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Electrical Stimuli (electrical + stimulus)
Selected AbstractsControl of the triceps surae during the postural sway of quiet standingACTA PHYSIOLOGICA, Issue 3 2007C. D. Tokuno Abstract Aim:, The present study investigated how the triceps surae are controlled at the spinal level during the naturally occurring postural sway of quiet standing. Methods:, Subjects stood on a force platform as electrical stimuli were applied to the posterior tibial nerve when the center of pressure (COP) was either 1.6 standard deviations anterior (COPant) or posterior (COPpost) to the mean baseline COP signal. Peak-to-peak amplitudes of the H-reflex and M-wave from the soleus (SOL) and medial gastrocnemius (MG) muscles were recorded to assess the efficacy of the Ia pathway. Results:, A significant increase in the Hmax : Mmax ratio for both the SOL (12 ± 6%) and MG (23 ± 6%) was observed during the COPant as compared to the COPpost condition. The source of the modulation between COP conditions cannot be determined from this study. However, the observed changes in the synaptic efficacy of the Ia pathway are unlikely to be simply a result of an altered level of background electromyographic activity in the triceps surae. This was indicated by the lack of differences observed in the Hmax : Mmax ratio when subjects stood without postural sway (via the use of a tilt table) at two levels of background activity. Conclusions:, It is suggested that the phase-dependent modulation of the triceps surae H-reflexes during the postural sway of quiet standing functions to maintain upright stance and may explain the results from previous studies, which, until now, had not taken the influence of postural sway on the H-reflex into consideration. [source] Focal Atrial Fibrillation: Experimental Evidence for a Pathophysiologic Role of the Autonomic Nervous SystemJOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY, Issue 5 2001PATRICK SCHAUERTE M.D. Focal AF and Autonomic Nerves.Introduction: Focal paroxysmal atrial fibrillation (AF) was shown recently to originate in the pulmonary veins (PVs) and superior vena cava (SVC). In the present study, we describe an animal model in which local high-frequency electrical stimulation produces focal atrial activation and AF/AT (atrial tachycardia) with electrogram characteristics consistent with clinical reports. Methods and Results: In 21 mongrel dogs, local high-frequency electrical stimulation was performed by delivering trains of electrical stimuli (200 Hz, impulse duration 0.1 msec) to the PVs/SVC during atrial refractoriness. Atrial premature depolarizations (APDs), AT, and AF occurred with increasing highfrequency electrical stimulation voltage. APD/AT/AF originated adjacent to the site of high-frequency electrical stimulation and were inducible in 12 of 12 dogs in the SVC and in 8 of 9 dogs in the left superior PV (left inferior PV: 7/8, right superior PV: 6/8; right inferior PV: 4/8). In the PVs, APDs occurred at 13 ± 8 V and AT/AF at 15 ± 9 V (P < 0.01; n = 25). In the SVC, APDs were elicited at 19 ± 6 V and AT/AF at 26 ± 6 V (P < 0.01; n = 12). High-frequency electrical stimulation led to local refractory period shortening in the PVs. The response to high-frequency electrical stimulation was blunted or prevented after beta-receptor blockade and abolished by atropine. In vitro, high-frequency electrical stimulation induced a heterogeneous response, with shortening of the action potential in some cells (from 89 ± 35 msec to 60 ± 22 msec; P < 0.001; n = 7) but lengthening of the action potential and development of early afterdepolarizations that triggered APD/AT in other cells. Action potential shortening was abolished by atropine. Conclusion: High-frequency electrical stimulation evokes rapid ectopic beats from the PV/SVC, which show variable degrees of conduction block to the atria and induce AF, resembling findings in patients with focal idiopathic paroxysmal AF. The occurrence of the arrhythmia in this animal model was likely due to alterations in local autonomic tone by high-frequency electrical stimulation. Further research is needed to prove absolutely that the observed effects of high-frequency electrical stimulation were caused by autonomic nerve stimulation. [source] Nerve growth factor-evoked nociceptor sensitization in pig skin in vivoJOURNAL OF NEUROSCIENCE RESEARCH, Issue 9 2010Roman Rukwied Abstract Peripheral sensitization of skin nociceptors by nerve growth factor (NGF) was explored in pig skin in vivo. As an objective output measure, the area of axon-reflex-mediated erythema was assessed upon mechanical, thermal, chemical, and electrical stimuli delivered at 1, 3, and 7 days after i.d. injection of 1 ,g NGF into the pig's back skin (n = 8). Pretreatment with NGF provoked a sensitization to mechanical (600 mN), thermal (10 sec 49°C) and chemical (15 ,l, pH 3) stimuli that lasted for 7 days. No sensitization, however, was found in response to weak mechanical (100 mN), weak thermal (10 sec 45°C), or electrical stimuli. Irrespective of the skin pretreatment (NGF or PBS vehicle control), the area of electrically induced erythema decreased upon repetition (days 1,7) by 70% (P < 0.05). Sensitization of sensory endings by NGF upon mechanical, heat, and chemical stimuli suggests recruitment of sensory transducer molecules [e.g., TRPV1, acid-sensing ion channels (ASICs)]. In contrast, the gradual decrease in electrically induced erythema over 7 days might be attributable to axonal desensitization and possibly activity-dependent down-regulation of sodium channels. Thus, long-lasting sensitization processes of nociceptor endings or axonal sodium channel desensitization mechanisms can be explored in the pig as a translational experimental animal model. © 2010 Wiley-Liss, Inc. [source] Effect of conditioning electrical stimuli on temporalis electromyographic activity during sleepJOURNAL OF ORAL REHABILITATION, Issue 3 2008F. JADIDI Summary, Inhibitory reflexes during voluntary contractions are well described; however, few studies have attempted to use such reflex-mechanisms to modulate electromyographic (EMG) activity in jaw-closing muscles during sleep. The aim was to apply a new intelligent biofeedback device (Grindcare®) using electrical pulses to inhibit EMG activity in the temporalis muscle during sleep. Fourteen volunteers participated who were aware of jaw-clenching activity as indicated by complaints from sleep partner, soreness or pain in the jaw-muscle upon awakening and tooth wear facets. The EMG activity was recorded from the temporalis muscle, online analysed and the frequency content determined using a signal recognition algorithm. Based on specific individual parameters for pattern recognition, an electrical square-wave pulse train, which was adjusted to a clear, but non-painful intensity (range 1,7 mA) was applied through the EMG electrodes, if jaw-clenching activity was detected. All volunteers had baseline EMG recordings for five to seven consecutive nights, followed by 3-weeks EMG recordings with the feedback turned on, 2 weeks without the feedback and finally 3 weeks with the biofeedback on. There were no session effects on the average duration of sleep hours (P = 0·626). The number of EMG episodes/hour sleep was significantly reduced during the two sessions with biofeedback (54 ± 14%; 55 ± 17%, P < 0·001) compared with baseline EMG activity and the session without biofeedback. The present study suggests that biofeedback with electrical pulses does not cause major disruption in sleep and is associated with pronounced reduction in temporalis EMG activity during sleep. [source] The effect of cutaneous input on intracortical inhibition in focal task-specific dystoniaMOVEMENT DISORDERS, Issue 9 2007Michelle N. McDonnell PhD Abstract In normal subjects short interval intracortical inhibition (SICI) is topographically modulated by cutaneous input, which may be important for focusing muscle activation during tasks. In patients with writer's cramp, a task-specific focal dystonia characterized by inappropriate and excessive muscle activation of the upper limb during certain motor tasks, intracortical inhibition is reduced at rest and lacks the normal topographically-specific modulation during motor tasks. In the present study we investigated whether cutaneous input modulated SICI in a group of patients with writer's cramp and a control group of subjects. Electromyographic recordings were made from the right first dorsal interosseous (FDI), abductor pollicis brevis (APB), and abductor digiti minimi (ADM) muscles. Brief electrical stimuli were applied to either digit II or digit V with ring electrodes. SICI was investigated using a paired transcranial magnetic stimulation paradigm employing interstimulus intervals of 1,15 ms. Cutaneous input from both digit II and digit V modulated motor evoked potentials and SICI in a topographically-specific manner in control subjects. In contrast, cutaneous input failed to modulate motor evoked potentials or SICI in the focal hand dystonia patients. These results provide further evidence of abnormal sensorimotor integration in focal hand dystonia. © 2007 Movement Disorder Society [source] Deficits of temporal discrimination in dystonia are independent from the spatial distance between the loci of tactile stimulationMOVEMENT DISORDERS, Issue 2 2002Michele Tinazzi MD Abstract To assess whether spatial variables influence deficits of temporal somesthetic discrimination in dystonic patients, 10 patients with idiopathic dystonia and 12 healthy controls were tested with pairs of non-noxious electrical stimuli separated by different time intervals. Stimuli were delivered: (1) to the pad of the index finger (same-point condition), (2) to the pad and to the base of the index finger (same-finger condition), and (3) to the pad of the index and ring fingers (different-finger condition). Subjects were asked to report whether they perceived single or double stimuli in the first condition and synchronous or asynchronous stimuli in the second and third conditions. Somesthetic temporal discrimination thresholds (STDTs) were obtained by computing the shortest time interval at which stimuli, applied to the left or the right hand, were perceived as separate in the first condition or asynchronous in the second and third conditions. STDTs were significantly higher in dystonic patients than controls in all three conditions. In both dystonia patients and controls, STDTs resulted highest in conditions whereby stimuli were maximally separated in space. Results extend current knowledge of deficits of somesthetic temporal discrimination in dystonia by showing that temporal deficits are not influenced by spatial variables. © 2002 Movement Disorder Society. [source] The inhibitory effect of a chewing task on a human jaw reflexMUSCLE AND NERVE, Issue 6 2010Pauline Maillou BDS Abstract This study was undertaken to investigate whether an inhibitory jaw reflex could be modulated by experimentally controlled conditions that mimicked symptoms of temporomandibular disorders. Reflecting on previous work, we anticipated that these conditions might suppress the reflex. Electromyographic recordings were made from a masseter muscle in 18 subjects, while electrical stimuli were applied to the upper lip. An inhibitory reflex wave (mean latency 47 ms) was identified and quantified. Immediately following an accelerated chewing task, which in most cases produced muscle fatigue and/or pain, the size of the reflex wave decreased significantly by about 30%. The suppression of inhibitory jaw reflexes by fatigue and pain may result in positive feedback, which may contribute to the symptoms of temporomandibular disorders. Future studies of temporomandibular disorder sufferers will help to determine whether such reflex changes reflect the underlying etiology and/or are a result of the temporomandibular disorder itself. Muscle Nerve, 2010 [source] Neurorehabilitation of Upper Extremities in Humans with Sensory-Motor ImpairmentNEUROMODULATION, Issue 1 2002Dejan B. Popovic PhD Abstract Today most clinical investigators agree that the common denominator for successful therapy in subjects after central nervous system (CNS) lesions is to induce concentrated, repetitive practice of the more affected limb as soon as possible after the onset of impairment. This paper reviews representative methods of neurorehabilitation such as constraining the less affected arm and using a robot to facilitate movement of the affected arm, and focuses on functional electrotherapy promoting the movement recovery. The functional electrical therapy (FET) encompasses three elements: 1) control of movements that are compromised because of the impairment, 2) enhanced exercise of paralyzed extremities, and 3) augmented activity of afferent neural pathway. Liberson et al. (1) first reported an important result of the FET; they applied a peroneal stimulator to enhance functionally essential ankle dorsiflexion during the swing phase of walking. Merletti et al. (2) described a similar electrotherapeutic effect for upper extremities; they applied a two-channel electronic stimulator and surface electrodes to augment elbow extension and finger extension during different reach and grasp activities. Both electrotherapies resulted in immediate and carry-over effects caused by systematic application of FET. In studies with subjects after a spinal cord lesion at the cervical level (chronic tetraplegia) (3,5) or stroke (6), it was shown that FET improves grasping and reaching by using the following outcome measures: the Upper Extremity Function Test (UEFT), coordination between elbow and shoulder movement, and the Functional Independence Measure (FIM). Externally applied electrical stimuli provided a strong central sensory input which could be responsible for the changes in the organization of impaired sensory-motor mechanisms. FET resulted in stronger muscles that were stimulated directly, as well as exercising other muscles. The ability to move paralyzed extremities also provided awareness (proprioception and visual feedback) of enhanced functional ability as being very beneficial for the recovery. FET contributed to the increased range of movement in the affected joints, increased speed of joint rotations, reduced spasticity, and improved functioning measured by the UEFT, the FIM and the Quadriplegia Index of Function (QIF). [source] Adenosine signalling at immature parallel fibre,Purkinje cell synapses in rat cerebellumTHE JOURNAL OF PHYSIOLOGY, Issue 18 2009Alison Atterbury The purine adenosine is an extracellular signalling molecule involved in a large number of physiological and pathological conditions throughout the mammalian brain. However little is known about how adenosine release and its subsequent clearance change during brain development. We have combined electrophysiology and microelectrode biosensor measurements to investigate the properties of adenosine signalling at early stages of cerebellar development, when parallel fibre,Purkinje cell synapses have recently been formed (postnatal days 9,12). At this stage of development, we could detect little or no inhibitory A1 receptor tone in basal conditions and during trains of stimuli. Addition of pharmacological agents, to inhibit adenosine clearance, had only minor effects on synaptic transmission suggesting that under basal conditions, the concentration of adenosine moving in and out of the extracellular space is small. Active adenosine release was stimulated with hypoxia and trains of electrical stimuli. Although hypoxia released significant concentrations of adenosine, the release was delayed and slow. No adenosine release could be detected following electrical stimulation in the molecular layer. In conclusion, at this stage of development, although adenosine receptors and the mechanisms of adenosine clearance are present there is very little adenosine release. [source] Auto-inhibition of rat parallel fibre,Purkinje cell synapses by activity-dependent adenosine releaseTHE JOURNAL OF PHYSIOLOGY, Issue 2 2007Mark J. Wall Adenosine is an important signalling molecule involved in a large number of physiological functions. In the brain these processes are as diverse as sleep, memory, locomotion and neuroprotection during episodes of ischaemia and hypoxia. Although the actions of adenosine, through cell surface G-protein-coupled receptors, are well characterized, in many cases the sources of adenosine and mechanisms of release have not been defined. Here we demonstrate the activity-dependent release of adenosine in the cerebellum using a combination of electrophysiology and biosensors. Short trains of electrical stimuli delivered to the molecular layer in vitro, release adenosine via a process that is both TTX and Ca2+ sensitive. As ATP release cannot be detected, adenosine must either be released directly or rapidly produced by highly localized and efficient extracellular ATP breakdown. Since adenosine release can be modulated by receptors that act on parallel fibre,Purkinje cell synapses, we suggest that the parallel fibres release adenosine. This activity-dependent adenosine release exerts feedback inhibition of parallel fibre,Purkinje cell transmission. Spike-mediated adenosine release from parallel fibres will thus powerfully regulate cerebellar circuit output. [source] After-effects of near-threshold stimulation in single human motor axonsTHE JOURNAL OF PHYSIOLOGY, Issue 3 2005Hugh Bostock Subthreshold electrical stimuli can generate a long-lasting increase in axonal excitability, superficially resembling the phase of superexcitability that follows a conditioning nerve impulse. This phenomenon of ,subthreshold superexcitability' has been investigated in single motor axons in six healthy human subjects, by tracking the excitability changes produced by conditioning stimuli of different amplitudes and waveforms. Near-threshold 1 ms stimuli caused a mean decrease in threshold at 5 ms of 22.1 ± 6.0% (mean ±s.d.) if excitation occurred, or 6.9 ± 2.6% if excitation did not occur. The subthreshold superexcitability was maximal at an interval of about 5 ms, and fell to zero at 30 ms. It appeared to be made up of two components: a passive component linearly related to conditioning stimulus amplitude, and a non-linear active component. The active component appeared when conditioning stimuli exceeded 60% of threshold, and accounted for a maximal threshold decrease of 2.6 ± 1.3%. The passive component was directly proportional to stimulus charge, when conditioning stimulus duration was varied between 0.2 and 2 ms, and could be eliminated by using triphasic stimuli with zero net charge. This change in stimulus waveform had little effect on the active component of subthreshold superexcitability or on the ,suprathreshold superexcitability' that followed excitation. It is concluded that subthreshold superexcitability in human motor axons is mainly due to the passive electrotonic effects of the stimulating current, but this is supplemented by an active component (about 12% of suprathreshold superexcitability), due to a local response of voltage-dependent sodium channels. [source] Evoked Human Oesophageal Hyperalgesia: A Potential Tool for Analgesic Evaluation?BASIC AND CLINICAL PHARMACOLOGY & TOXICOLOGY, Issue 2 2009Anne Estrup Olesen Therefore, in the development and testing of analgesics for the treatment of visceral pain, it is important to establish an experimental pain model of visceral hypersensitivity. Such a model will mimic the clinical situation to a higher degree than pain models where the receptors and peripheral afferents are briefly activated as with, for example, electrical, thermal, and mechanical stimulations. In this study, a model to evoke experimental hyperalgesia of the oesophagus with a combination of acid and capsaicin was introduced. The study was a randomised, double-blind, cross-over study. Fifteen healthy volunteers were included. Sensory assessments to mechanical, heat, and electrical stimulations were done in the distal oesophagus, before and after perfusion with a 200 ml solution of acid+capsaicin (180 ml HCL 0.1 M and 2 mg capsaicin in 20 ml solvent) or saline. Oesophageal pain assessment and referred pain areas were evaluated. There were reproducible pain assessments between repetitions within the same day and between days (all P > 0.05). Acid+capsaicin perfusion induced 56% reduction of the pain threshold to heat (P = 0.04), 19% reduction of the pain threshold to electrical stimuli (P < 0.001), 78% increase of the referred pain areas to mechanical stimulation (P < 0.001) and 52% increase of the referred pain areas to electrical stimulus (P = 0.045). All volunteers were sensitised to one or more modalities by acid+capsaicin. The model was able to evoke consistent hyperalgesia and may be useful in future pharmacological studies. [source] Regional variation in electrically-evoked contractions of rabbit isolated pulmonary arteryBRITISH JOURNAL OF PHARMACOLOGY, Issue 4 2002V Margaret Jackson Electrically-evoked contractions in different regions of the rabbit isolated pulmonary artery have been investigated using stimulation parameters generally assumed to stimulate nerves selectively. In extrapulmonary artery, trains of stimuli (10 Hz; pulse width 0.1 ms) evoked monophasic contractions. In contrast, a biphasic contraction was evoked in the intrapulmonary artery consisting of an initial fast component followed by a secondary very long-lasting component. The contraction in the extrapulmonary artery was prazosin-sensitive (1 ,M) whereas that in the intrapulmonary artery was prazosin-resistant. ,,,-Methylene ATP (1 ,M), atropine (1 ,M), losartan (1 ,M), BIBO3304 (1 nM) or nifedipine (1 ,M) had no effect on the biphasic contraction of the intrapulmonary artery. Bretylium (2 ,M) abolished the contraction of extrapulmonary artery but only partially inhibited the initial component in the intra region with no effect on the second component. Tetrodotoxin (0.3,1 ,M), abolished the contraction of extrapulmonary artery but only partially reduced the electrically-evoked contraction of intrapulmonary artery. Removal of the endothelium and application of sulphisoxazole (0.6,22 ,M) had no effect. Varying the resting tone on the arteries, or applying gadolinium, had no effect on contractions. Using confocal microscopy and calcium imaging, reproducible whole cell calcium transients were evoked in individual smooth muscle cells in intact preparations but only when direct muscle stimulation was used (pulse width of 5,10 ms). No detectable changes in calcium were elicited when brief pulse widths were used (0.1,2 ms). Together, these data suggest that noradrenaline is the neurotransmitter inducing contraction in extrapulmonary artery. Noradrenaline and sympathetic nerves appear to play a less important role in the intrapulmonary artery. The tetrodoxin-resistant component is not mediated by ATP, NPY, acetylcholine, angiotensins, ET-1, stretch-activation or Ca2+ influx through L-type Ca2+ channels. Smooth muscle cells do not appear to be damaged by the stimulation protocol. The mechanism underlying the long lasting contraction of intrapulmonary artery evoked by brief electrical stimuli remains to be elucidated. British Journal of Pharmacology (2002) 137, 488,496. doi:10.1038/sj.bjp.0704863 [source] Differences between the effects of three plasticity inducing protocols on the organization of the human motor cortexEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 3 2006Karin Rosenkranz Abstract Several experimental protocols induce lasting changes in the excitability of motor cortex. Some involve direct cortical stimulation, others activate the somatosensory system and some combine motor and sensory stimulation. The effects usually are measured as changes in amplitude of the motor-evoked-potential (MEP) or short-interval intracortical inhibition (SICI) elicited by a single or paired pulses of transcranial magnetic stimulation (TMS). Recent work has also tested sensorimotor organization within the motor cortex by recording MEPs and SICI during short periods of vibration applied to single intrinsic hand muscles. Here sensorimotor organization is focal: MEPs increase and SICI decreases in the vibrated muscle, whilst the opposite occurs in neighbouring muscles. In six volunteers we compared the after effects of three protocols that lead to lasting changes in cortical excitability: (i) paired associative stimulation (PAS) between a TMS pulse and an electrical stimulus to the median nerve; (ii) motor practice of rapid thumb abduction; and (iii) sensory input produced by semicontinuous muscle vibration, on MEPs and SICI at rest and on the sensorimotor organization. PAS increased MEP amplitudes, whereas vibration changed sensorimotor organization. Motor practice had a dual effect and increased MEPs as well as affecting sensorimotor organization. The implication is that different protocols target different sets of cortical circuits. We speculate that protocols that involve repeated activation of motor cortical output lead to lasting changes in efficacy of synaptic connections in output circuits, whereas protocols that emphasize sensory inputs affect the strength of sensory inputs to motor circuits. [source] Dopamine agonists restore cortical plasticity in patients with idiopathic restless legs syndrome,MOVEMENT DISORDERS, Issue 5 2009Vincenzo Rizzo MD Abstract In the present work, we aimed at assessing whether patients with idiopathic restless legs syndrome (RLS) showed alterations of sensory-motor plasticity, an indirect probe for motor learning, within the motor cortex (M1). Previous findings suggest that learning in human M1 occurs through LTP-like mechanisms. To test our hypothesis, we employed the paired associative stimulation (PAS) protocol by transcranial magnetic stimulation (TMS), which is able to induce LTP-like effects in the motor cortex of normal subjects. Twelve patients with idiopathic RLS and 10 age- and sex-matched control subjects were recruited. PAS protocol consisted of 0.05 Hz electrical median nerve stimulation (90 stimuli), paired with 0.05 Hz TMS (90 stimuli) over the hot spot for stimulating the abductor pollicis brevis (APB) muscle given 25 milliseconds after the onset of the electrical stimulus. Corticospinal excitability recorded in APB muscle, as indexed by MEP obtained after single stimulus, was tested before and up to 30 minutes after PAS protocol. Eight of 12 patients were studied before and after 4 weeks of dopaminergic treatment. PAS protocol increased significantly corticospinal excitability as long as 30 minutes in healthy subjects. On the contrary, PAS protocol did not change the amplitude of MEPs in patients with idiopathic RLS without treatment. PAS associative plasticity was restored after 4 weeks of dopaminergic treatment. Our data demonstrated that associative sensory-motor plasticity, an indirect probe for motor learning, is impaired in idiopathic RLS patients but may be reverted to normal after dopaminergic treatment. © 2008 Movement Disorder Society [source] Cannabinoid receptor 1 signalling dampens activity and mitochondrial transport in networks of enteric neuronesNEUROGASTROENTEROLOGY & MOTILITY, Issue 9 2009W. Boesmans Abstract, Cannabinoid (CB) receptors are expressed in the enteric nervous system (ENS) and CB1 receptor activity slows down motility and delays gastric emptying. This receptor system has become an important target for GI-related drug development such as in obesity treatment. The aim of the study was to investigate how CB1 ligands and antagonists affect ongoing activity in enteric neurone networks, modulate synaptic vesicle cycling and influence mitochondrial transport in nerve processes. Primary cultures of guinea-pig myenteric neurones were loaded with different fluorescent markers: Fluo-4 to measure network activity, FM1-43 to image synaptic vesicles and Mitotracker green to label mitochondria. Synaptic vesicle cluster density was assessed by immunohistochemistry and expression of CB1 receptors was confirmed by RT-PCR. Spontaneous network activity, displayed by both excitatory and inhibitory neurones, was significantly increased by CB1 receptor antagonists (AM-251 and SR141716), abolished by CB1 activation (methanandamide, mAEA) and reduced by two different inhibitors (arachidonylamide serotonin, AA-5HT and URB597) of fatty acid amide hydrolase. Antagonists reduced the number of synaptic vesicles that were recycled during an electrical stimulus. CB1 agonists (mAEA and WIN55,212) reduced and antagonists enhanced the fraction of transported mitochondria in enteric nerve fibres. We found immunohistochemical evidence for an enhancement of synaptophysin-positive release sites with SR141716, while WIN55,212 caused a reduction. The opposite effects of agonists and antagonists suggest that enteric nerve signalling is under the permanent control of CB1 receptor activity. Using inhibitors of the endocannabinoid degrading enzyme, we were able to show there is endogenous production of a CB ligand in the ENS. [source] Stimulation of the rat somatosensory cortex at different frequencies and pulse widthsNMR IN BIOMEDICINE, Issue 1 2006N. Van Camp Abstract Functional MRI (fMRI) during electrical somatosensory stimulation of the rat forepaw is a widely used model to investigate the functional organization of the somatosensory cortex or to study the underlying mechanisms of the blood oxygen level-dependent (BOLD) response. In reality, somatosensory stimuli have complex timing relationships and are of long duration. However, by default electrical sensory stimulation seems to be performed at an extremely short pulse width (0.3,ms). As the pulse duration may alter the neuronal response, our aim was to investigate the influence of a much longer stimulus pulse width (10,ms) using BOLD fMRI during electrical forepaw stimulation. The optimal neuronal response was investigated by varying the stimulus frequency at a fixed pulse duration (10,ms) and amplitude (1,mA). In a parallel experiment we measured the neuronal response directly by recording the somatosensory evoked potentials (SEPs). Quantification of the BOLD data revealed a shift in the optimal response frequencies to 8,10,Hz compared with 1,Hz at 0.3,ms. The amplitude of the recorded SEPs decreased with increasing stimulation frequency and did not display any correlation with the BOLD data. Nevertheless, the summated SEPs, which are a measure of the integrated neuronal activity as a function of time, displayed a similar response profile, with a similar maximum as observed by relative BOLD changes. This shift in optimal excitation frequencies might be related to the fact that an increased pulse width of an electrical stimulus alters the nature of the stimulation, generating also sensorimotor instead of merely somatosensory input. This may influence or alter the activated pathways, resulting in a shift in the optimal response profile. Copyright © 2006 John Wiley & Sons, Ltd. [source] Distraction produces an increase in pain-evoked anterior cingulate activityPSYCHOPHYSIOLOGY, Issue 4 2004Robert Dowman Abstract This study examined the effects of distraction on pain-evoked activity in the anterior cingulate cortex (ACC). Twenty-eight healthy adults were given painful electrical stimulation of the sural nerve during an attend condition, where they rated the subjective magnitude of each electrical stimulus, and during a distraction condition, where they performed an arithmetic distraction task. The magnitude of the pain-evoked ACC activity was estimated from the dipole source localization analysis of the somatosensory evoked potential. Subjective pain ratings were smaller and pain-evoked ACC activity was larger during the distraction condition than during the attend condition. Recent regional cerebral blood flow studies have also reported a distraction-related increase in pain-evoked ACC activity. Our results confirm these reports, and verify that the distraction effect specifically involves pain-evoked ACC activity. The cognitive demands of the distraction task present the possibility that the pain-evoked ACC activity might be involved, at least in part, in response competition and/or orienting attention toward painful stimuli. [source] Actions of R- and S-verapamil and nifedipine on rat vascular and intestinal smooth muscleAUTONOMIC & AUTACOID PHARMACOLOGY, Issue 3 2004L. Cleary Summary 1 We have investigated the actions of the calcium entry blockers nifedipine, R-verapamil and S-verapamil in rat aorta, colon and vas deferens. 2 In aorta and colon, these agents produced concentration-dependent relaxations of KCl (80 mm)-induced contractions. In both tissues, the order of potency was nifedipine > S-verapamil > R-verapamil. However, nifedipine showed selectivity for aorta (potency ratio, colon/aorta: 4.36), S-verapamil showed no selectivity (0.62), but R-verapamil showed selectivity for colon (0.19). 3 In prostatic portions of rat vas deferens, nifedipine (10 ,m) abolished the contraction to a single electrical stimulus, but R- and S-verapamil were without effect. In epididymal portions of rat vas deferens, R- and S-verapamil inhibited ,1 -adrenoceptor-mediated contractions to a single electrical stimulus at concentrations of 10 ,m and above. 4 In conclusion, R-verapamil may prove useful as an intestinal selective calcium entry blocker in the treatment of intestinal disease with a hypermotility component, e.g. irritable bowel syndrome. [source] Evoked Human Oesophageal Hyperalgesia: A Potential Tool for Analgesic Evaluation?BASIC AND CLINICAL PHARMACOLOGY & TOXICOLOGY, Issue 2 2009Anne Estrup Olesen Therefore, in the development and testing of analgesics for the treatment of visceral pain, it is important to establish an experimental pain model of visceral hypersensitivity. Such a model will mimic the clinical situation to a higher degree than pain models where the receptors and peripheral afferents are briefly activated as with, for example, electrical, thermal, and mechanical stimulations. In this study, a model to evoke experimental hyperalgesia of the oesophagus with a combination of acid and capsaicin was introduced. The study was a randomised, double-blind, cross-over study. Fifteen healthy volunteers were included. Sensory assessments to mechanical, heat, and electrical stimulations were done in the distal oesophagus, before and after perfusion with a 200 ml solution of acid+capsaicin (180 ml HCL 0.1 M and 2 mg capsaicin in 20 ml solvent) or saline. Oesophageal pain assessment and referred pain areas were evaluated. There were reproducible pain assessments between repetitions within the same day and between days (all P > 0.05). Acid+capsaicin perfusion induced 56% reduction of the pain threshold to heat (P = 0.04), 19% reduction of the pain threshold to electrical stimuli (P < 0.001), 78% increase of the referred pain areas to mechanical stimulation (P < 0.001) and 52% increase of the referred pain areas to electrical stimulus (P = 0.045). All volunteers were sensitised to one or more modalities by acid+capsaicin. The model was able to evoke consistent hyperalgesia and may be useful in future pharmacological studies. [source] Effects of excitatory and inhibitory neurotransmission on motor patterns of human sigmoid colon in vitroBRITISH JOURNAL OF PHARMACOLOGY, Issue 7 2008M Aulí Background and purpose: To characterize the in vitro motor patterns and the neurotransmitters released by enteric motor neurons (EMNs) in the human sigmoid colon. Experimental approach: Sigmoid circular strips were studied in organ baths. EMNs were stimulated by electrical field stimulation (EFS) and through nicotinic ACh receptors. Key results: Strips developed weak spontaneous rhythmic contractions (3.67±0.49 g, 2.54±0.15 min) unaffected by the neurotoxin tetrodotoxin (TTX; 1 ,M). EFS induced strong contractions during (on, 56%) or after electrical stimulus (off, 44%), both abolished by TTX. Nicotine (1,100 ,M) inhibited spontaneous contractions. Latency of off-contractions and nicotine responses were reduced by NG -nitro- L -arginine (1 mM) and blocked after further addition of apamin (1 ,M) or the P2Y1 receptor antagonist MRS 2179 (10 ,M) and were unaffected by the P2X antagonist NF279 (10 ,M) or ,-chymotrypsin (10 U mL,1). Amplitude of on- and off-contractions was reduced by atropine (1 ,M) and the selective NK2 receptor antagonist Bz-Ala-Ala-D-Trp-Phe-D-Pro-Pro-Nle-NH2 (1 ,M). MRS 2179 reduced the amplitude of EFS on- and off-contractions without altering direct muscular contractions induced by ACh (1 nM,1 mM) or substance P (1 nM,10 ,M). Conclusions and implications: Latency of EFS-induced off-contractions and inhibition of spontaneous motility by nicotine are caused by stimulation of inhibitory EMNs coreleasing NO and a purine acting at muscular P2Y1 receptors through apamin-sensitive K+ channels. EFS-induced on- and off-contractions are caused by stimulation of excitatory EMNs coreleasing ACh and tachykinins acting on muscular muscarinic and NK2 receptors. Prejunctional P2Y1 receptors might modulate the activity of excitatory EMNs. P2Y1 and NK2 receptors might be therapeutic targets for colonic motor disorders. British Journal of Pharmacology (2008) 155, 1043,1055; doi:10.1038/bjp.2008.332; published online 1 September 2008 [source] |