The influence of temporal summation on a C-fibre reflex in the rat: effects of lesions in the rostral ventromedial medulla (RVM)

In intact rats, an inhibitory mechanism counteracts the increase in excitability of a flexor reflex seen in spinal animals following high-intensity, repetitive stimulation of C-fibres. We tested the hypothesis that the rostral ventromedial medulla (RVM) is involved in these processes. Electromyographic responses elicited by electrical stimulation of the sural nerve, were recorded from the ipsilateral biceps femoris in halothane-anaesthetised, sham-operated or RVM-lesioned rats. There were no significant differences between the C-fibre reflexes in the two groups in terms of their thresholds, latencies, durations or mean recruitment curves. The excitability of the C-fibre reflex was tested following 20 s of high-intensity homotopic electrical conditioning stimuli at 1 Hz. During the conditioning period, the EMG responses first increased in both groups (the wind-up phenomenon), but then decreased in the sham-operated rats and plateaued in the RVM-lesioned rats. These effects were followed by inhibitions that were very much smaller in the RVM-lesioned rats, both in terms of their magnitudes and their durations. It is concluded that the RVM is involved in inhibitory feedback mechanisms elicited by temporal summation of C-fibre afferents that both counteract the wind-up phenomenon and trigger long periods of inhibition.     

Middle latency responses to electrical stimulation of the auditory nerve in unanaesthetized guinea pigs

Middle latency responses (MLR) to sinusoidal and pulsatile electrical stimulation (ES) of the cochlea and to acoustical stimulation (AS) were evaluated in awake guinea pigs with chronically implanted electrodes. The ear, which was later electrically stimulated, was deafened by local intracochlear application of gentamicin, the opposite ear was left intact. Waveforms and P1-P2 interpeak intervals of the electrically evoked MLR (ES-MLR) were similar to those evoked by acoustical stimulation of the intact ear (AS-MLR) and the latencies of the ES-MLR were shorter by about 1-3 ms. Thresholds of ES-MLR in the frequency range 0.5-32 kHz increased with increasing ES frequency (slope 3.2 dB/octave), thresholds were 3.5-9.5 dB lower for intracochlear than for extracochlear ES. Dynamic ranges for ES-MLR varied between 6-20 dB. MLR amplitude-intensity functions for ES were steeper (slope 2-12 microV/dB) than those for AS (slope 0.2-2 microV/dB). Maximal ES-MLR amplitudes exceeded usually 1.5-3 times the amplitudes of the acoustically evoked MLR. Both types of stimulations evoked larger MLR amplitudes to contralateral stimulation than to ipsilateral stimulation (average ratio = 4.1 +/- 2.2 for AS and 3.3 +/- 2.2 for ES). Because of the relatively long latency and therefore insensitivity to electrical artifact, the ES-MLR can be used for the evaluation of different strategies of the electrical stimulation of the cochlea in awake guinea pig.     

Brain stem auditory evoked potentials from bone stimulation in dogs

Brain stem auditory evoked potential (BAEP) testing with air-conducted click stimuli can be used to diagnose sensorineural deafness in dogs if conductive deafness can be ruled out. Detection of conductive deafness can be performed by recording BAEP elicited by a vibratory stimulus transducer placed against the skull. Air- and bone-conducted BAEP were compared in dogs, varying bone stimulator placement, click polarity, and stimulus intensity. Optimal bone stimulator placement was determined to be over the mastoid process, followed by the mandible and the zygomatic arch. Condensation polarity clicks gave responses preferable to those elicited by rarefaction or alternating polarity. Bone-conducted BAEP peak latencies were significantly longer than air-conducted latencies after correction of the latencies for the air conduction time accompanying air-conducted stimuli. Significant differences between stimulus modalities were not seen for BAEP peak amplitudes or interpeak latencies. Latency-intensity and amplitude-intensity regressions had similar effects for both modalities: latencies decreased and amplitudes increased as stimulus intensity increased.     

Neural mechanisms of the corneal blinking reflex in cats

Neural mechanisms of the blinking reflex elicited by corneal stimulation were analyzed with electrophysiological techniques in the encéphale isolé cat. (1) Mechanical and electrical stimulation elicited two successive responses of the electromyogram of the orbicularis oculi. Neuromuscular unit studies revealed that the same unit was excited twice and that the latencies of both responses corresponded well with the two EMG responses. (2) The late response was easily affected by anoxia and pentobarbital administration, and was also abolished with the slow-wave sleep stage. (3) Both responses were abolished by ipsilateral transection between the inferior colliculus and genu of the facial nerve. (4) Compared with the latencies of the EMG, the sum of the conduction times through the sensory trigeminal nucleus and the facial nucleus corresponded with the latency of the early response. The sum of the conduction times through the reticular formation, added to the former reflex arc, corresponded to the latency of the late response. (5) The reflex pathway of the early response is consistent with a three-neuron arc passing through the sensory trigeminal nucleus and the facial nucleus. The late response may employ a multisynaptic arc passing through the brain stem medial reticular formation between the sensory trigeminal nucleus and the facial nucleus.     

Intraoperative recording of the bulbocavernosus reflex

OBJECTIVE: To demonstrate the feasibility of intraoperative monitoring of the bulbocavernosus reflex (BCR) as an indicator of the functional integrity of sacral nervous structures to aid in preventing their intraoperative injury. METHODS: Intraoperative BCR was elicited by electrical stimulation of the dorsal penile/clitoral nerve in 119 patients anesthetized with propofol, fentanyl, and nitrous oxide, with short-acting relaxant. Thirty-eight patients underwent surgery without risk, whereas 81 underwent surgery with risk of damage to sacral structures. Different patterns of stimuli were applied through silver/silver chloride disc electrodes placed on the dorsal aspect of the penis in males and over the clitoris (cathode) and adjacent labia (anode) in females. Recordings were made from the anal sphincter using intramuscular wire electrodes introduced within a 27.5 gauge needle, with two electrodes each inserted in the right and left hemisphincter muscles. Preoperatively, some patients had minor urinary problems in controlling their sphincters. RESULTS: The BCR was reliably recorded without habituation under this anesthetic regime. Optimal stimulating parameters were found to be double pulses (0.5-ms duration), with an interstimulus interval of 3 ms, stimulating rate of 2.3 Hz, and intensity of 20 mA. With these parameters, it was possible to record the BCR intraoperatively in all patients. Isoflurane and nitrous oxide significantly suppressed the BCR, and muscle relaxant completely abolished it. CONCLUSION: We demonstrated that it is feasible, under certain anesthetic regimes, to intraoperatively monitor the BCR in both children and adults (24 d to 74 yr of age) who did not have significantly affected function in sacral nervous structures.     

A comparison of the electrophysiological effects of two organophosphates, mipafox and ecothiopate, on mouse limb muscles

Adult male albino mice were given single subcutaneous injections of either mipafox (110 mumol/kg) or ecothiopate (0.5 mumol/kg), two organophosphorus compounds (OPs). Acetylcholinesterase activity was measured in the soleus (slow-twitch) and extensor digitorum longus (EDL; fast-twitch) muscles. At 7 and 28 days after dosing, in vitro electrophysiological measurements were carried out in the soleus and EDL. Action potentials and end-plate potentials were evoked at 30 Hz and recorded intracellularly from single muscle fibers. The amplitudes, time course, and latencies of these potentials were measured and the variability (jitter) of latencies was calculated. Recordings after mipafox were also made with 3-Hz stimulation. Acetylcholinesterase activity was inhibited by mipafox (65% in the soleus; 76% in the EDL) and ecothiopate (59% in the soleus; 42% in the EDL). Mipafox and ecothiopate both increased postjunctional (muscle action potential) jitter in the soleus and EDL at 7 days after dosing. Organophosphates caused an increase in end-plate potential amplitudes in the soleus. Mipafox caused an increase in prejunctional (end-plate potential) jitter at 28 days after dosing in both muscles. A single dose of ecothiopate also caused an increase in prejunctional jitter at 28 days in the soleus. The OP-induced increase in jitter was different at different frequencies of stimulation. The results show that there are electrophysiological changes in both muscles after administration of organophosphorus compounds. The slow-twitch soleus appears more sensitive to prejunctional changes caused by OPs than the fast-twitch EDL.     

Early adverse experiences and the neurobiology of facial emotion processing.

To examine the neurobiological consequences of early institutionalization, the authors recorded event-related potentials (ERPs) from 3 groups of Romanian children--currently institutionalized, previously institutionalized but randomly assigned to foster care, and family-reared children--in response to pictures of happy, angry, fearful, and sad facial expressions of emotion. At 3 assessments (baseline, 30 months, and 42 months), institutionalized children showed markedly smaller amplitudes and longer latencies for the occipital components P1, N170, and P400 compared to family-reared children. By 42 months, ERP amplitudes and latencies of children placed in foster care were intermediate between the institutionalized and family-reared children, suggesting that foster care may be partially effective in ameliorating adverse neural changes caused by institutionalization. The age at which children were placed into foster care was unrelated to their ERP outcomes at 42 months. Facial emotion processing was similar in all 3 groups of children; specifically, fearful faces elicited larger amplitude and longer latency responses than happy faces for the frontocentral components P250 and Nc. These results have important implications for understanding of the role that experience plays in shaping the developing brain. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effect of prostaglandins and nitric oxide on basal blood flow and acetylcholine-induced vasodilation in rat diaphragmatic microcirculation

We compared the ability of 4 magnetic coils to activate peripheral nerves in healthy subjects. No differences in motor threshold intensities were found between the coils, but the intensities needed to elicit maximum compound muscle action potential (CMAP) amplitudes were different. For superficial nerves maximum CMAPs in comparison with electrical stimulation were usually but not always found. CMAPs were at their maximum only when the direction of induced current flowed from proximal to distal and when a certain part of the coil was over the nerve. Distal nerve stimulation was time consuming. Due to artifacts many stimuli were necessary and sometimes no maximum CMAP could be elicited. CMAPs were much less sensitive to position changes of the coil than to changes in an electrical stimulator. Small circular coils were superior to larger coils in terms of the lower intensities necessary to elicit maximum CMAPs, better focusing of the stimulus, and less artifacts. For deep nerves amplitudes were always submaximal. Coactivation of nearby nerves and underlying muscles was another main drawback especially at proximal sites and for coils of large diameter. Despite better focusing, double coils are less useful due to their great diameter. Magnetic stimulation cannot replace electrical neurography at the moment, even if different coils are used at different sites of stimulation.     

Electrical stimulation of the auditory nerve. I. Correlation of physiological responses with cochlear status

The purpose of the present study was to evaluate evoked potential and single fibre responses to biphasic current pulses in animals with varying degrees of cochlear pathology, and to correlate any differences in the physiological response with status of the auditory nerve. Six cats, whose cochleae ranged from normal to a severe neural loss (< 5% spiral ganglion survival), were used. Morphology of the electrically evoked auditory brainstem response (EABR) was similar across all animals, although electrophonic responses were only observed from the normal animal. In animals with extensive neural pathology, EABR thresholds were elevated and response amplitudes throughout the dynamic range were moderately reduced. Analysis of single VIIIth nerve fibre responses were based on 207 neurons. Spontaneous discharge rates among fibres depended on hearing status, with the majority of fibres recorded from deafened animals exhibiting little or no spontaneous activity. Electrical stimulation produced a monotonic increase in discharge rate, and a systematic reduction in response latency and temporal jitter as a function of stimulus intensity for all fibres examined. Short-duration current pulses elicited a highly synchronous response (latency < 0.7 ms), with a less well synchronized response sometimes present (0.7-1.1 ms). There were, however, a number of significant differences between responses from normal and deafened cochleae. Electrophonic activity was only present in recordings from the normal animal, while mean threshold, dynamic range and latency of the direct electrical response varied with cochlear pathology. Differences in the ability of fibres to follow high stimulation rates were also observed; while neurons from the normal cochlea were capable of 100% entrainment at high rates (600-800 pulses per second (pps)), fibres recorded from deafened animals were often not capable of such entrainment at rates above 400 pps. Finally, a number of fibres in deafened animals showed evidence of 'bursting', in which responses rapidly alternated between high entrainment and periods of complete inactivity. This bursting pattern was presumably associated with degenerating auditory nerve fibres, since it was not recorded from the normal animal. The present study has shown that the pathological response of the cochlea following a sensorineural hearing loss can lead to a number of significant changes in the patterns of neural activity evoked via electrical stimulation. Knowledge of the extent of these changes have important implications for the clinical application of cochlear implants.     

Neuromuscular inhibitory effects of propofol evaluated by cat's evoked EMG

Neuromuscular inhibitory effects of propofol were investigated in 7 cats using muscular compound action potential (mCAP) elicited from the gastrocnemius muscle by sciatic nerve stimulation. A rectangular pulse of supramaximal strength and duration of 0.2 msec was applied serially to the sciatic nerve at 0.1 Hz during the experiments, and mCAPs obtained from the gastrocnemius muscle were recorded. After obtaining a constant mCAP amplitude, a series of 8 consecutive mCAPs (M 1-8) evoked by repetitive stimulation at 100 Hz was recorded, and M 8/M 1 amplitude ratio (M 8 amplitude/M 1 amplitude.100%) was calculated as the control value. After control variables had been obtained, initial dose of 2.5 mg.kg-1 of propofol was administered intravenously followed by continuous infusion with incremental dosages of 10, 20, 50 and 100 mg.kg-1.hr-1 of each 30 minute duration. The effects on mCAPs evoked by single and 8 consecutive repetitive stimulation were observed in each period. The depression of single mCAP amplitudes and fading responses in the M 8/M 1 amplitude ratios were not observed at any infusion rate. Our results suggest that propofol has no influence on neuromuscular transmission in cats when administered intravenously at 10 times of human clinical infusion doses.     

Myogenic vestibular-evoked potentials in normal subjects: a comparison between responses obtained from sternomastoid and trapezius muscles

Brief intense clicks cause short latency microcontraction of cervical muscles. Several studies have supported the hypothesis that these microcontractions are of vestibular origin. Averaging these muscular responses enables us to obtain myogenic vestibular evoked potential (MVEP). The receptor of these responses is thought to be the saccule, afferent pathways being the vestibular nerve and efferent pathways the vestibulospinal tract. However, discrepancies are reported with regard to results obtained in healthy subjects: some authors obtained symmetrical response to monaural clicks whereas others obtained responses of greater amplitude on the muscle ispilateral to stimulation. These discrepancies may be due to the presence of different recording sites (inion, sternomastoid or trapezius muscles). The aim of this study was to clarify MVEP results in healthy subjects, using a simple non-traumatic method, and to compare the results obtained on sternomastoid (SM) and trapezius muscles (TRP). Sixteen normal hearing healthy subjects were involved. Latencies and amplitude of both SM and TRP muscle were reproducible in the same subject. Patterns of response were similar to those obtained in previous studies. Following binaural and monaural stimulations, latencies of MVEP were symmetrical on both muscles and amplitudes tended to be greater on muscles contralateral to stimulation, which conflicts with previous results in the literature. Whatever the type of stimulation, latencies of responses obtained on SM were significantly shorter (mean = -3.8 ms), and amplitudes lower (mean = -7.1 microV), than those obtained on TRP. Binaural stimulation resulted in responses of greater amplitude compared to monaural (mean = 0.45 microV). Given the intrasubject reproducibility of the responses, these methods allow MEVP to be recorded in a standardized and reproducible way.     

Biphasic modulation of spinal nociceptive transmission from the medullary raphe nuclei in the rat

The modulatory effects of electrical and chemical (glutamate) stimulation in the rostral ventromedial medulla (RVM) on spinal nociceptive transmission and a spinal nociceptive reflex were studied in rats. Electrical stimulation at a total 86 sites in the RVM in the medial raphe nuclei (n = 54) and adjacent gigantocellular areas (n = 32) produced biphasic (facilitatory and inhibitory, n = 43) or only inhibitory (n = 43) modulation of the tail-flick (TF) reflex. At these 43 biphasic sites in the RVM, facilitation of the TF reflex was produced at low intensities of stimulation (5-25 microA) and inhibition was produced at greater intensities of stimulation (50-200 microA). At 43 sites in the RVM, electrical stimulation only produced intensity-dependent inhibition of the TF reflex. Activation of cell bodies in the RVM by glutamate microinjection reproduced the biphasic modulatory effects of electrical stimulation. At biphasic sites previously characterized by electrical stimulation, glutamate at a low concentration (5 nmol) produced facilitation of the TF reflex; a greater concentration (50 nmol) only inhibited the TF reflex. In electrophysiological experiments, electrical stimulation at 62 sites in the RVM produced biphasic (n = 26), only inhibitory (n = 26), or only facilitatory (n = 10) modulation of responses of lumbar spinal dorsal horn neurons to noxious cutaneous thermal (50 degrees C) or mechanical (75.9 g) stimulation. Facilitatory effects were produced at lesser intensities of stimulation and inhibitory effects were produced at greater intensities of stimulation. The apparent latencies to stimulation-produced facilitation and inhibition, determined with the use of a cumulative sum method and bin-by-bin analysis of spinal neuron responses to noxious thermal stimulation of the skin, were 231 and 90 ms, respectively. The spinal pathways conveying descending facilitatory and inhibitory influences were found to be different. Descending facilitatory influences on the TF reflex were conveyed in ventral/ventrolateral funiculi, whereas inhibitory influences were conveyed in dorsolateral funiculi. The results indicate that descending inhibitory and facilitatory influences can be simultaneously engaged throughout the RVM, including nucleus raphe magnus, and that such influences are conveyed in different spinal funiculi.     

Vestibular-evoked electromyographic responses in soleus: a comparison between click and galvanic stimulation

The aim of this study was to demonstrate, if possible, vestibulospinal reflex responses in soleus using a stimulus known to be capable of exciting vestibular afferents, namely 100-dB (NHL) clicks. We were able to show short-latency electromyographic (EMG) responses after clicks in five of eight normal subjects, and then we compared these responses with those after transmastoid galvanic stimulation (12 normal subjects). Stimulation of the side towards which the head was rotated (i.e. the side facing backwards) with either clicks or the cathode (anode applied to the opposite side) gave an initial excitatory response in soleus, while click or cathodal stimulation of the opposite side (i.e. the side facing forwards) gave an initial inhibitory response. Onset latencies and modulation with changes in postural task were identical for both click- and galvanic-evoked responses. In addition, there was a significant correlation between the amplitudes of the responses in soleus after click and galvanic stimulation (R2=0.72). These similarities suggest that the earliest reflex responses in soleus after clicks and galvanic stimulation may be mediated by a common central pathway. In contrast, there was no correlation between the amplitudes of responses evoked by 100-dB clicks in soleus and those evoked by the same stimulus in the sternocleidomastoid. We conclude that vestibular activation by clicks can evoke reflex responses in lower-limb muscles and these responses have similar characteristics to the earliest responses evoked by galvanic vestibular stimulation.     

Effect of local standards on the implementation of national guidelines for asthma: primary care agreement with national asthma guidelines

In vivo electrophysiological assays in anesthetized rats have been used to compare the effects of the 5HT1B/1D receptor agonist, naratriptan, on central trigeminal nociceptive processing from dural and cutaneous inputs with its effects on nociceptive processing in the spinal cord. Naratriptan inhibited responses of single trigeminal neurons, to noxious electrical and mechanical stimulation of the dura and face, dose dependently by a maximum of 67+/-3% and 70+/-18%, respectively, at 3 mg kg(-1) i.v. In contrast, naratriptan did not affect spinal dorsal horn neuronal responses to noxious mechanical stimulation of the hind-paw. These findings suggest that 5HT1B/1D receptors have differential effects on nociceptive processing in the trigeminal versus spinal dorsal horns and provide a potential explanation for the lack of general analgesic effects of brain penetrant 5HT(1B/1D) agonist antimigraine drugs.     

Molecular mechanism of cell membrane lipids

The effects of nembutal and ketamine anesthesia on motor evoked potentials (MEPs) and spinal segment reflex (H-response, F and M waves) were investigated in rats by magnetic stimulation. These potentials were generated by magnetic stimulation of the motor cortex and the spinal cord (L4-L5). After application of nembutal, MEP and H-response decreased in amplitude, eventually disappearing. The amplitudes of F and M waves increased and persisted at the increased levels during anesthesia. The latencies of F and M waves were constant before and after anesthesia. Following ketamine administration, the threshold, latency and amplitude of the magnetically induced MEPs, and M, F and H responses were not influenced systematically. The results suggested that MEPs and H-response depression and/or disappearance due to synaptic site suppression after nembutal anesthesia, and the increase and persistence of increased F and M waves amplitudes were all due to the increasing motoneuron excitability, whereas ketamine did not affect synaptic sites subjected to magnetic stimulation.     

Effects of electric stimulation of the dentate nucleus of the cerebellum on neuronal activity of the centrum medianum of the optic thalamus

Electrical stimulation of the cerebellar dentate nucleus elicits in neurons of the center median responses with either constant or altering latencies. The constant latencies ranged from 2-3 to 8-12 msec. Responses with altering latencies were more numerous and had the latencies up to 20 msec. In both responses with early and late components were recorded as well. Dentate stimulations induced "periods of inhibition" in CM neurons with leading duration of 50-100 msec. Synchronization of the SM unit activity during low-frequency stimulation was also revealed, in many cases it was preceded by the "periods of inhibition". Activity of 49% of reactive neurons during 1, 7-12, and 70-100/sec stimulations was facilitated, 31% depressed, and 20% had a mixed type of responses: facilitation on one frequency and depression on another. Immediate cessation of the effects after termination of stimulations was observed in 34% of neurons, while tonic influences were manifest in 66%.     

The NSAID dexketoprofen trometamol is as potent as mu-opioids in the depression of wind-up and spinal cord nociceptive reflexes in normal rats

The aim of this study was to examine the potency of the antinociceptive effects of the non-steroidal antiinflammatory drug (NSAID), Dexketoprofen Trometamol (the active enantiomer of ketoprofen) on spinal cord nociceptive reflexes. These effects were compared with those of the mu-opioid receptor agonist fentanyl in normal animals. The experiments were performed in male Wistar rats anaesthetised with alpha-chloralose. The nociceptive reflexes were recorded as single motor units in peripheral muscles, activated by mechanical and electrical stimulation. Both dexketoprofen and fentanyl inhibited responses evoked by mechanical and electrical stimulation with doses in the same nanomolar range (dexketoprofen ID50s: 100 and 762 nmol kg-1 and fentanyl: 40 and 51 nmol kg-1, respectively). Dexketoprofen and fentanyl also significantly inhibited wind-up. Since fentanyl has been shown to be some 1000 times more potent than morphine in this type of experiments, we conclude that dexketoprofen has central analgesic actions in normal animals and depresses nociceptive responses with a potency similar to that of mu-opioid agonists.     

Normal Syk protein level but abnormal tyrosine phosphorylation in B-CLL cells

One characteristic of B cells that accumulate during chronic lymphocytic leukemia (CLL) is their highly heterogeneous functional responses to B cell receptor (BCR) stimulation. Leukemic B cells with very poor responses have defective rapid tyrosine phosphorylation of numerous substrates, especially phospholipase C (PLC)gamma, as well as a defective calcium elevation on BCR stimulation. This points to a defect in BCR-associated protein tyrosine kinase (PTK). We investigated whether a defect in Syk, a PTK that is pivotal in coupling BCR to downstream signaling events, could account for these alterations. Syk tyrosine phosphorylation triggered by BCR ligation was severely impaired in B-CLL cells with low calcium responses to anti-mu stimulation. Syk associations were also defective, as concomitant tyrosine phosphorylation of a Syk-associated 145 kDa protein comigrating with PLCgamma-2 was only detected in responding B-CLL cells. By contrast, we found similar expression of the kinase regardless of B-CLL cell responsiveness. These results are consistent with the possibility that very proximal BCR signaling elements in some B-CLL cells are unable to connect with downstream biochemical events dominated by tyrosine phosphorylation and the potential docking function of Syk PTK.     

Cortical excitability in patients with essential tremor

We used transcranial magnetic stimulation in 10 patients with essential tremor and 8 matched healthy subjects. A round stimulating coil was placed over the vertex and electromyographic activity was recorded from the first dorsal interosseous muscle. Paired transcranial stimuli were delivered at interstimulus intervals of 3, 5, 20, 100, 150, and 200 ms. The intensity of the conditioning stimulus was 80% of motor threshold at short and 150% at long interstimulus intervals (ISIs). We also measured the silent period obtained after a single magnetic pulse delivered at 150% of motor threshold during a submaximal muscle contraction. Patients and controls had similar motor threshold and similar latencies. Paired magnetic stimuli given at short and long ISIs at rest, and during a voluntary muscle contraction, elicited similar responses in both groups. The silent period evoked by transcranial magnetic stimulation had a similar duration in patients with ET and controls. In conclusion, these findings suggest that patients with essential tremor have normal cortical motor area excitability.