Afferent Impulses Research Articles

The involvement of cutaneous receptors in the biological effects of electromagnetic millimeter waves

The involvement of peripheral nerve terminations in the mechanisms of action of electromagnetic millimeter waves (mmW) was assessed. It is currently thought that mmW could be used in noninvasive complementary therapy because of their analgesic effect. However, the mechanisms of their antinociceptive effect and non-ionizing radiation are the subjects of controversy. The mechanisms of interaction of mmW and the cutaneous tissue have not been elucidated. We observed mast cell degranulation at the place of mmW action, a decrease of chronaxie and Turck reflex time, an increase in the number of afferent impulses after sciatic nerve at stimulation, as well as an increase electrocardiogram R-R interval of isolated frog heart after application of mmW. Based on these investigations, we propose that electromagnetic waves of millimeter length modify, through indirect mechanisms, the excitability and reactivity of peripheral nerve terminations.

Sensory nerves and pancreatitis.

Sensory nerves are a kind of nerve that conduct afferent impulses from the periphery receptors to the central nervous system (CNS) and are able to release neuromediators from the activated peripheral endings. Sensory nerves are particularly important for microcirculatory response, and stimulation of pancreatic sensory nerves releases a variety of neuropeptides such as substance P (SP), calcitonin gene-related peptide (CGRP), etc., leading to neurogenic inflammation characterized as the local vasodilatation and plasma extravasation. Deactivation of sensory nerves often leads to the disturbances of pancreatic microcirculation. Pancreatitis is a common digestive disease that can lead to severe complications and even death if it goes untreated. Experimental studies in animals and tissue analysis in patients with pancreatitis have shown significant changes in sensory nerves supplying the pancreatic gland. Thus making clear the whole mechanism of pancreatitis is essential to treat and cure it. Sensory nerves may have a close correlation with the development of pancreatitis, and knowing more about the role of sensory nerve in pancreatitis is important for the treatment for pancreatitis. This review is aimed to summarize the relationship between sensory nerves and pancreatitis.

Involvement of Hippocampal Inputs and Intrinsic Circuit in the Acquisition of Context and Cues During Classical Conditioning in Behaving Rabbits

Learning-related changes in strength in selected hippocampal synapses have been described recently. However, information is scarce regarding the spatial-temporal sequence of changes in synaptic weights taking place during the acquisition of a classical conditioning task and the contribution of both context (environmental details) and cues (conditioned and unconditioned stimuli: CS, US) to those activity-dependent changes. We recorded in rabbits the monosynaptic field excitatory postsynaptic potentials (fEPSPs) evoked at 6 different hippocampal synapses during the acquisition and extinction of a classical eyeblink conditioning using trace or delay paradigms, as well as during pseudoconditioning and in the absence of CS and US presentations (context). Context and pseudoconditioning training evoked early, lasting changes in synaptic strength in perforant pathway synapses in dentate gyrus (PP-DG), and hippocampal CA3 (PP-CA3) and CA1 (PP-CA1) areas. Pseudoconditioning also evoked early, nonlasting changes in strength within the intrinsic hippocampal circuit (CA3-CA1 and CA3-cCA1 synapses). In contrast, during both trace and delay training sessions, synaptic changes in strength were mostly noticed within the intrinsic hippocampal circuit (DG-CA3, CA3-CA1, CA3-cCA1). The response of hippocampal synapses to afferent impulses seems to be modulated by both context and cues during associative learning in behaving rabbits.

Oxidative Stress and Neuronal NOS Activity: Putative Determinants of Rapid Blood Pressure Increase After Renal Denervation in Anesthetized Rats

Long-term effects of renal denervation (DNX) commonly include a decrease in blood pressure (BP), observed in both normotensive animals and various models of hypertension. On the other hand, short term BP responses vary. We examined how post-DNX increase in BP observed in this study depends on baseline metabolic and functional status of animals, with a special interest for the role of oxidative stress. Anesthetized Wistar rats on standard (STD), low-sodium (LS) or high-sodium (HS) diet were used, untreated or pre-treated with tempol, a superoxide scavenger, or N(omega)-propyl-L-arginine (L-NPA), an inhibitor of neuronal NOS (nNOS). Early BP and renal hemodynamic responses were examined to right- and then left-side DNX performed using an own relatively non-invasive technique. Left kidney cortical, outer- and inner-medullary blood flows (CBF, OMBF, IMBF) were continuously recorded as laser-Doppler fluxes. Sequential denervations significantly increased BP to final 19 %, 12 %, and 6 % above control level in HS, LS, and STD groups, respectively. CBF, a measure of total renal perfusion, increased in LS and STD but not in HS rats. Tempol pretreatment prevented the post-denervation BP increase on each diet. Selective inhibition of nNOS prevented BP increase in STD and HS groups, a modest increase persisted in LS rats. We propose that enhanced afferent impulsation from intrarenal chemoreceptors related to oxidative stress in the kidney was the background for acute BP increase after DNX. The response was triggered by a release of brain sympatho-excitatory centers from inhibition by renal afferents, this was followed by widespread sympathetic cardiovascular stimulation.

Cardiorespiratory coupling of sympathetic outflow in humans: a comparison of respiratory and cardiac modulation of sympathetic nerve activity to skin and muscle

What is the central question of this study?Muscle sympathetic nerve activity (MSNA) is well known to be modulated by the arterial baroreceptors and respiration, but what are the magnitudes of cardiac and respiratory modulation of skin sympathetic nerve activity (SSNA), which primarily subserves thermoregulation?What is the main finding and what is its importance?Using direct microelectrode recordings of MSNA and SSNA in awake humans, we show that the magnitude of respiratory modulation of SSNA is identical to that of MSNA, the primary difference between the two sources of sympathetic outflow being the greater cardiac modulation of MSNA. This emphasises the role of the baroreceptors in entraining sympathetic outflow to muscle. It is well known that microelectrode recordings of skin sympathetic nerve activity (SSNA) in awake human subjects reveal spontaneous bursts of activity with no overt modulation by changes in blood pressure or respiration, in contrast to the clear cardiac and respiratory modulation of muscle sympathetic nerve activity (MSNA). However, cross-correlation analysis has revealed that, like individual muscle vasoconstrictor neurones, the firing of individual cutaneous vasoconstrictor neurones is temporally coupled to both the cardiac and respiratory rhythms during cold-induced cutaneous vasoconstriction, and the same is true of single sudomotor neurones during heat-induced sweating. Here, we used cross-correlation analysis to determine whether SSNA exhibits cardiac and respiratory modulation in thermoneutral conditions and to compare respiratory and cardiac modulation of SSNA with that of MSNA. Oligounitary recordings of spontaneous SSNA (n = 20) and MSNA (n = 18) were obtained during quiet, unrestrained breathing. Respiration was recorded by a strain-gauge transducer around the chest and ECG recorded by surface electrodes. Respiratory and cardiac modulation of SSNA and MSNA were quantified by fitting polynomial equations to the cross-correlation histograms constructed between the sympathetic spikes and respiration or ECG. The amplitude of the respiratory modulation (52.5 ± 3.4%) of SSNA was not significantly different from the amplitude of the cardiac modulation (46.6 ± 3.2%). Both were comparable to the respiratory modulation of MSNA (47.7 ± 4.2%), while cardiac modulation of MSNA was significantly higher (89.8 ± 1.5%). We conclude that SSNA and MSNA share similar levels of respiratory modulation, the primary difference between the two sources of sympathetic outflow being the marked cardiac modulation of MSNA provided by the baroreceptors.

Identity of endogenous NMDAR glycine site agonist in amygdala is determined by synaptic activity level

Mechanisms of NMDA receptor-dependent synaptic plasticity contribute to the acquisition and retention of conditioned fear memory. However, synaptic rules which may determine the extent of NMDA receptor activation in the amygdala, a key structure implicated in fear learning, remain unknown. Here we show that the identity of the NMDAR glycine site agonist at synapses in the lateral nucleus of the amygdala may depend on the level of synaptic activation. Tonic activation of NMDARs at synapses in the amygdala under low-activity conditions is supported by ambient D-serine, whereas glycine may be released from astrocytes in response to afferent impulses. The release of glycine may decode the increases in afferent activity levels into enhanced NMDAR-mediated synaptic events, serving an essential function in the induction of NMDAR-dependent long-term potentiation in fear conditioning pathways.

Bradykinin 2 receptor blockade attenuates the responses of group III afferents to contraction in decerebrate cats

Exercise‐induced stimulation of group III and IV muscle afferents raises blood pressure, heart rate, and ventilation. Bradykinin has been shown to stimulate and sensitize group III and IV afferents, but the effect of bradykinin 2 (B2) receptor blockade on the responses of group III afferents during exercise was unknown. Using decerebrate cats, we examined the effect of carotid arterial injections of the B2 receptor antagonist, HOE‐140 (40 μg/kg) on the responses of group III afferents (conduction velocity range: 2.8 – 26.2 m/s; mean: 16.1 ± 2.3 m/s) to both 45 second intermittent and static contraction. Before HOE‐140, static contraction increased the impulse activity of ten group III afferents from 0.3 ± 0.1 imp/s at rest to 6.7 ± 3.0 imp/s during contraction (p<0.05). After HOE‐140, impulse activity went from 0.7 ± 0.3 imp/s at rest to 2.9 ± 1.2 imp/s during contraction (p>;0.05). There was a similar trend during intermittent contraction. Before HOE‐140, intermittent contraction increased the activity of seven group III afferents from 0.2 ± 0.04 imp/s at rest to 9.1 ± 5.2 imp/s during contraction (p>;0.05). After HOE‐140, impulse activity increased from 0.5 ± 0.2 imp/s at rest to 4.0 ± 2.3 imp/s during contraction (p>;0.05). Our data suggests B2 receptors contribute to group III afferent impulse activity during exercise.

How olfaction disorders can cause depression? The role of habenular degeneration

The removal of bilateral olfactory bulbs (OBs) can result in serious behavioral, neurochemical, neuroendocrine, and neuroimmune alterations in depressed patients. However, there is little information on how olfactory bulbectomy (OBX) leads to depression. Habenular nuclei and their connections are important in the regulation of psychomotor and psychosocial behaviors through afferent impulses of the olfactory system. Therefore, we investigated whether OB lesions lead to habenular degeneration. We used a sample of 50 rats (25 female and 25 male) for this study. Of these rats, five male and five female rats were taken as the control group. The remaining 40 rats (20 male and 20 female rats) constituted the study group, and frontal burr holes were performed at the OB level on these rats. OB cauterization was applied to 10 male and 10 female rats (n=10, 10; study group 1), mechanical OBX was applied to five male and five female rats (n=5, 5; study group 2), and no procedure was performed on the remaining 10 rats (n=5, 5). The psychomotor movements; pregnancy rates; and sexual, feeding, maternal, social, and grooming behaviors for both study groups were observed daily for 3 months. Their OBs, olfactory cortices, and habenular complexes were examined using stereological methods. All of the animals in the study groups, especially in the cauterization group, demonstrated anorexia, nutritional disorders, weight loss, psychomotor retardation, sexual aversion, decreased grooming behavior, and reduced social interaction similar to depression symptoms. As compared to the control group, the pregnancy rates, number of offspring per mother rat, and birth weights in the study groups were lower, whereas the number of stillbirths was higher. Gross anatomical examinations revealed that the OBs of all of the animals in the study groups were atrophied. Histopathological examinations detected prominent neuronal loss due to apoptosis in the habenular structures in the study groups. We detected a relationship between a decreased healthy neuronal density of the habenula and depressive symptomatology in rats with OBX. We suggest that olfaction disorders might cause neuropsychiatric disorders by affecting neuronal degeneration in habenular nuclei.

Failure of action potential propagation in sensory neurons: mechanisms and loss of afferent filtering in C-type units after painful nerve injury.

The T-junction of sensory neurons in the dorsal root ganglion (DRG) is a potential impediment to action potential (AP) propagation towards the CNS. Using intracellular recordings from rat DRG neuronal somata during stimulation of the dorsal root, we determined that the maximal rate at which all of 20 APs in a train could successfully transit the T-junction (following frequency) was lowest in C-type units, followed by A-type units with inflected descending limbs of the AP, and highest in A-type units without inflections. In C-type units, following frequency was slower than the rate at which AP trains could be produced in either dorsal root axonal segments or in the soma alone, indicating that the T-junction is a site that acts as a low-pass filter for AP propagation. Following frequency was slower for a train of 20 APs than for two, indicating that a cumulative process leads to propagation failure. Propagation failure was accompanied by diminished somatic membrane input resistance, and was enhanced when Ca(2+)-sensitive K(+) currents were augmented or when Ca(2+)-sensitive Cl(-) currents were blocked. After peripheral nerve injury, following frequencies were increased in axotomized C-type neurons and decreased in axotomized non-inflected A-type neurons. These findings reveal that the T-junction in sensory neurons is a regulator of afferent impulse traffic. Diminished filtering of AP trains at the T-junction of C-type neurons with axotomized peripheral processes could enhance the transmission of activity that is ectopically triggered in a neuroma or the neuronal soma, possibly contributing to pain generation.

抗グリシン受容体抗体関連疾患の臨床スペクトラム

Anti-glycine receptor (anti-GlyR) antibodies were first reported in 2008 in a case of progressive encephalomyelitis with myoclonus and rigidity (PERM), which is a variant of stiff-person syndrome (SPS). After that, the antibodies have been studied extensively. At least 40 patients have been reported or presented until May 2013. We reviewed 28 patients (median age 47 years, range 1 to 75 years), whose clinical data are available. Seventeen patients (60%) were male. We classified clinical phenotype into PERM (17), classic SPS (5), variant SPS (5), and others (1: progressive optic atrophy). Nine patients (32%) had ant-GAD antibodies. Accompanied diseases included thyroiditis (5), diabetes mellitus (3), thymoma (3), and Addison's disease (2). Twenty-one patients (75%) treated with immunotherapy or thymectomy improved, but two of six patients without immunotherapy died or developed cardiac arrest. The clinical features suggested that antibody-mediated inhibition of the GlyR on the brainstem nuclei or spinal inhibitory interneurons may cause continuous firing of α motor neurons and paroxysmal excessive response to a variety of afferent impulses, leading to increased stiffness, brainstem signs, trismus, myoclonus, painful spasms or hyperekplexia. Phenotype associated with the anti-GlyR antibodies may be broader than previously thought, but among those PERM is the most common phenotype.

Aetiology and Pathogenesis of Trigeminal Neuralgia: a Comprehensive Review

ABSTRACTObjectivesThe aim of present paper was to discuss issues related to trigeminal neuralgia with strong emphasis on the aetiology and pathogenesis of this problem.Material and MethodsAn electronic search of 5 databases (1965 - Oct 2012) and a hand search of peer-reviewed journals for relevant articles were performed. In addition, experience acquired from treating 3263 patients in the Department of Maxillofacial Surgery, Lithuanian University of Health Sciences, were also summarized.ResultsGenerally, aetiological factors can be classified into 3 most popular theories that were based on: 1) Related to other disease, 2) Direct injury to the trigeminal nerve, and 3) Propagates the polyetiologic origin of the disease. In addition, two pathogenesis mechanisms of trigeminal neuralgia were proposed. First: the peripheral pathogenetic mechanism that is often induced by progressive dystrophy around the peripheral branches of the trigeminal nerve. Second, central pathogenetic mechanism which often triggered by peripheral pathogen that causes long-lasting afferent impulsation and the formation of a stable pathologic paroxysmal type irritation focus on the central nerve system (CNS).ConclusionsPatients with susceptive trigeminal neuralgia should be examined carefully by specialists who have expertise in assessing and diagnosing of possible pathological processes and be able to eliminate the contributing factors so the trigeminal neuralgia can be properly managed.

Scalp-Recorded Evoked Potentials as a Marker for Afferent Nerve Impulse in Clinical Vagus Nerve Stimulation

BackgroundVagus nerve stimulation (VNS) is a palliative treatment for drug resistant epilepsy for which the efficacy and safety are well established. Accumulating evidence suggests that ascending vagal signals modulate abnormal cortical excitability via various pathways. However, there is no direct evidence for an ascending conduction of neural impulses in a clinical case of VNS. ObjectiveWe recorded and analyzed the short-latency components of the vagus nerve (VN) evoked potential (EP) from the viewpoint of determining whether or not it is a marker for the ascending neural conduction. MethodsEPs within 20 ms were prospectively recorded simultaneously from a surgical wound in the neck and at multiple scalp sites during implantation surgery in 25 patients with drug-resistant epilepsy. Electrical stimulation was delivered using the clinical VNS Therapy system. A recording was made before and after a muscle relaxant was administered, when changing the rostrocaudal position of stimulation, or when stimulating the ansa cervicalis instead of the VN. ResultsThe short-latency components consisted of four peaks. The early component around 3 ms, which was most prominent in A1–Cz, remained unchanged after muscle relaxation while the later peaks disappeared. Rostral transition of the stimulation resulted in an earlier shift of the early component. The estimated conduction velocity was 27.4 ± 10.2 m/s. Stimulation of the ansa cervicalis induced no EP. ConclusionsThe early component was regarded as directly resulting from ascending neural conduction of A fibers of the VN, probably originating around the jugular foramen. Recording of VN-EP might document the cause of treatment failure in some patients.

Endocannabinoid modulation of jejunal afferent responses to LPS

Endocannabinoids influence immune function and nociceptive signaling. This study examines cannabinoid modulation of sensory signaling from the GI tract following an acute inflammatory response triggered by systemic administration of bacterial lipopolysaccharide (LPS). A segment of proximal jejunum was intubated, to measure intraluminal pressure, in anesthetized rats. Afferent impulse traffic was recorded from a single isolated paravascular nerve bundle supplying the jejunal loop. Drugs and LPS were administered intravenously and changes in afferent firing were determined. The non-selective cannabinoid agonist, WIN55,212-2 (1 mg kg(-1) i.v.) and the anandamide transport inhibitor, VDM11 (1 mg kg(-1) i.v.) but not the fatty acid amide hydrolase (FAAH) inhibitor, URB597 (0.3 mg kg(-1)) caused a significant increase in afferent activity. The WIN55,212-2-induced afferent response was mediated by activation of CB(1) receptors whereas the VDM11 response was mediated by both CB(1) and CB(2) receptor mechanisms. LPS (10 mg kg(-1)) evoked an increase in afferent activity which was significantly reduced in the presence of WIN55,212-2 and VDM11 but not URB597. The inhibitory effect of WIN55,212-2 was prevented by CB(1) but not CB(2) receptor antagonism. In contrast, the inhibitory effect of VDM11 remained unaltered after CB(1) or CB(2) receptor blockade. Endocannabinoids play a role in modulating afferent signaling and may represent a target for the treatment of visceral hypersensitivity. In contrast to the effects of blocking endocannabinoid uptake (VDM11), inhibiting breakdown of endocannabinoids (URB597) had no effect on baseline or LPS induced afferent firing. Therefore, uptake of cannabinoids rather than breakdown via FAAH terminates their action in the GI tract.

How the Dream of an “Artificial Heart” Was Realized in Japan

How the Dream of an “Artificial Heart” Was Realized in Japan

A muscle spindle abnormity in one laryngeal muscle would be sufficient to cause stuttering

Muscle spindles are increasingly recognized as playing a pivotal role in the cause of dystonia. This development and own laryngeal observations that support the idea of causally “well-intentioned” stuttering motivated us to present the following hypothesis: stuttering events compensate for a sensory problem that arises when the abductor/adductor ratio of afferent impulse rates from the posterior cricoarytenoid and lateral cricoarytenoid muscle spindles is abnormally reduced and processed for the occasional determination of the vocal fold position. This hypothesis implies that functional and structural brain abnormalities might be interpreted as secondary compensatory reactions. Verification of this hypothesis (using technologies such as microneurography, dissection and muscle afferent block) is important because its confirmation could relink dystonia and stuttering research, change the direction of stuttering therapy and destigmatize stuttering radically.

IMMUNOCYTOCHEMICAL CHARACTERIZATION H2S-POSITIVE NEURONS IN THE NUCLEI OF BULBAR CARDIOVASCULAR CENTER IN THE DEVELOPMENT OF RENOVASCULAR HYPERTENSION

Immunocytochemical method in Wistar rats in 6 nuclei of the medulla oblongata, related to the cardiovascular center, identified nerve cells (H2S-neurons) with a positive reaction to cystathionine beta-synthase (CBS)--an enzyme involved in the synthesis of hydrogen sulfide in the brain. Found that in rats with renovascular hypertension only after 6 weeks of hypertension in the neurons of the reticular nuclei observed a significant reduction of CBS, while the number of H2S-positive cells in this period does not change significantly. Only at week 12 renovascular hypertension notes marked reduction in the proportion of positive H2S-neurons in the reticular nuclei of most of the medial zone, although further reduction in the intensity of the enzymatic reaction in the neurons were observed. Between 14-16 weeks of hypertension to further reduce the proportion of neurons and H2S-content of the enzyme is not observed. In a single nucleus and reticular lateral nucleus, which receive afferent impulses in the development of renovascular hypertension specify the minimum change of the indicators.

Role of Cardiac Reflexes in the Control of Heart Rate

Role of Cardiac Reflexes in the Control of Heart Rate

Gillies lift induced Asystole!

The oculocardiac reflex occurring after orbital surgical procedures is a well recognised peri operative complication which has been well reported in the literature. In this reflex the ophthalmic branch of trigeminal nerve transmits the afferent impulse to the sensory nucleus of trigeminal nerve (V) in the brain stem via the gasserion ganglion. The efferent arc involves the motor nucleus of the vagus nerve through short internuntial fibres in the brain stem, stimulation of which is responsible for the bradycardia.

Understanding mechanisms and documenting plausibility of palliative interventions for dyspnea

To review the mechanisms for the perception of dyspnea and to consider the plausibility of interventions that palliate dyspnea after optimal treatment of the underlying disease. Activation of sensory receptors by blood gas abnormalities, mechanical respiratory loads, and hyperinflation provides afferent information to the central nervous system for integration and processing. It has been proposed that a discriminative pathway processes afferent impulses to the somatosensory cortex that reflects the intensity of dyspnea, whereas an affective pathway projects afferent impulses to structures of the limbic system that reflects the unpleasantness of dyspnea. In one study, patients with chronic obstructive pulmonary disease reported consistently higher ratings of breathlessness after administration of naloxone, an opioid receptor antagonist, compared with physiological saline during high-intensity treadmill exercise. This finding supports the role of endogenous opioids in modulating dyspnea. Nebulized furosemide, anti-inflammatory therapy, and chest wall vibration are potential approaches for modulating lung and chest wall receptors to relieve dyspnea. Targets for palliating dyspnea in patients with advanced disease include sensory receptors within the lung/chest wall and the central nervous system. The opioid system plays an important role in palliating dyspnea. Both endogenous (β-endorphins) and exogenous (morphine) opioids modulate breathlessness.

21. Phantom Pain

Phantom pain is pain caused by elimination or interruption of sensory nerve impulses by destroying or injuring the sensory nerve fibers after amputation or deafferentation. The reported incidence of phantom limb pain after trauma, injury or peripheral vascular diseases is 60% to 80%. Over half the patients with phantom pain have stump pain as well. Phantom pain can also occur in other parts of the body; it has been described after mastectomies and enucleation of the eye. Most patients with phantom pain have intermittent pain, with intervals that range from 1 day to several weeks. Even intervals of over a year have been reported. The pain often presents itself in the form of attacks that vary in duration from a few seconds to minutes or hours. In most cases, the pain is experienced distally in the missing limb, in places with the most extensive innervation density and cortical representation. Although there are still many questions as to the underlying mechanisms, peripheral as well as central neuronal mechanisms seem to be involved. Conservative therapy consists of drug treatment with amitriptyline, tramadol, carbamazepine, ketamine, or morphine. Based on the available evidence some effect may be expected from drug treatment. When conservative treatment fails, pulsed radiofrequency treatment of the stump neuroma or of the spinal ganglion (DRG) or spinal cord stimulation could be considered (evidence score 0). These treatments should only be applied in a study design.