Multiunit Discharges Research Articles

The Isolated Mouse Jejunal Afferent Nerve Assay as a Tool to Assess the Effect of Botulinum Neurotoxins in Visceral Nociception.

For the past two decades, botulinum neurotoxin A (BoNT/A) has been described as a strong candidate in the treatment of pain. With the production of modified toxins and the potential new applications at the visceral level, there is a real need for tools allowing the assessment of these compounds. In this study, we evaluated the jejunal mesenteric afferent nerve assay to investigate BoNT/A effects on visceral nociception. This ex vivo model allowed the continuous recording of neuronal activity in response to various stimuli. BoNT/A was applied intraluminally during three successive distensions, and the jejunum was distended every 15 min for 3 h. Finally, samples were exposed to external capsaicin. BoNT/A intoxication was validated at the molecular level with the presence of cleaved synaptosomal-associated protein of 25 (SNAP25) in nerve terminals in the mucosa and musculosa layers 3 h after treatment. BoNT/A had a progressive inhibitory effect on multiunit discharge frequency induced by jejunal distension, with a significant decrease from 1 h after application without change in jejunal compliance. The capsaicin-induced discharge was also affected by the toxin. This assay allowed the description of an inhibitory effect of BoNT/A on afferent nerve activity in response to distension and capsaicin, suggesting BoNT/A could alleviate visceral nociception.

Delta-Frequency Augmentation and Synchronization in Seizure Discharges and Telencephalic Transmission.

SummaryEpileptic seizures constitute a common neurological disease primarily diagnosed by characteristic rhythms or waves in the local field potentials (LFPs) of cerebral cortices or electroencephalograms. With a basolateral amygdala (BLA) kindling model, we found that the dominant frequency of BLA oscillations is in the delta range (1–5 Hz) in both normal and seizure conditions. Multi-unit discharges are increased with higher seizure staging but remain phase-locked to the delta waves in LFPs. Also, the change in synchrony precedes and outlasts the changes in discharging units as well as behavioral seizures. One short train of stimuli readily drives the pyramidal-inhibitory neuronal networks in BLA slices into prolonged reverberating activities, where the burst and interburst intervals may concurrently set a “natural wavelength” for delta frequencies. Seizures thus could be viewed as erroneous temporospatial continuums to normal oscillations in a system with a built-in synchronizing and resonating nature for information relay.

A discriminative feature set in the fast phase of spikes for sorting oligo-unit discharges of arterial baroreceptors

Abstract The present study was aimed to establish a simple and robust protocol that was more suitable for sorting discharges of the arterial baroreceptor. Oligo-unit (≤ 5) baroreceptor discharges were recorded in vitro from fine filaments of the rabbit carotid sinus nerve. Different time windows, covering the fast phase only or both the fast and slow phases of the spike were used to extract spike event data for sorting. Three measurements focusing on the fast phase of spikes—the maximum slope in the ascending limb from the half amplitude to the peak, the peak amplitude, and the width of the spike at the half amplitude—were selected as a feature set. The performance of this measurement-based analysis with subsequent K-means algorithm (MBAKM) in sorting oligo-unit discharges was compared with the performance of principal component analysis followed by K-means (PCAKM) and template matching (TM). The present study proved that: (1) MBAKM was more discriminative with less intervention than PCAKM and TM in determining the number of clusters and cluster attributions of spikes; (2) there was a higher consistency (larger intersection set) among the three algorithms with narrow windows of 0.45–0.65 ms than with 1.45 ms window. This study suggested that discriminative features were embodied in the fast phase of spikes and the oligo-unit discharges of baroreceptors could be sorted more robustly and accurately with less intervention by MBAKM than by PCAKM and TM. MBAKM with narrow time window would be promising in further studying baroreceptors and multiunit discharges from other neural structures.

Electrophysiological study on sensory nerve activity from the submandibular salivary gland in rats

To evaluate the role of afferent information from the salivary gland, we analyzed the neural activity of the sensory nerve innervating the submandibular gland in anesthetized rats. The sensory nerves running through the parasympathetic nerve supply responded to mechanical pressure applied to the surface of the main duct and the body of the gland, whilst those in the sympathetic nerve supply responded only to the body of the gland. The sensory nerves in the sympathetic and parasympathetic nerve routes responded to pressure in the duct system produced by a retrograde injection of saline into the main duct. The threshold pressure for production of afferent discharges was higher than the maximum secretory pressure evoked by electrical stimulation of the parasympathetic secretory nerve. The retrograde ductal injection of drugs related to the inflammatory process (capsaicin and bradykinin) evoked intense multi-unit discharges in the sensory nerves of both routes. The sensory nerve in the sympathetic route was responsive to ligation of the artery to the gland. These results suggest that sensory nerves in the sympathetic and parasympathetic routes mainly conduct noxious information, and that those in the sympathetic route are responsive to ischemia and may control blood flow of the gland.

In Vitro Characterization of the Electrophysiological Properties of Colonic Afferent Fibers in Rats.

Dysfunction of the colonic sensory nerves has been implicated in the pathophysiology of several common conditions, including functional and inflammatory bowel diseases and diabetes. Here, we describe a protocol for the in vitro characterization of the electrophysiological properties of colonic afferents in rats. The colorectum, with the intact pelvic ganglion (PG) attached, is removed from the rat; superfused with carbogenated Krebs solution in the recording chamber; and cannulated at the oral and anal ends to allow for distension. A fine nerve bundle emanating from the PG is identified, and the multiunit afferent nerve activity is recorded using a suction electrode. Distension of the colonic segment elicits gradual increases in multiunit discharge. A principal component analysis is conducted to differentiate the low-threshold, the high-threshold, and the wide-dynamic range afferent fibers. Chemical sensitivity of colonic afferents can be studied through the bath or intraluminal administration of test compounds. This protocol can be modified for application to other species, such as mice and guinea pigs, and to study the differences in the electrophysiological properties of thoracolumbar/hypogastric and lumbosacral/pelvic afferents of the descending colon in normal and pathological conditions.

Pathologic electrographic changes after experimental traumatic brain injury.

To investigate possible electroencephalography (EEG) correlates of epileptogenesis after traumatic brain injury (TBI) using the fluid percussion model. Experiments were conducted on adult 2- to 4-month-old male Sprague-Dawley rats. Two groups of animals were studied: (1) the TBI group with depth and screw electrodes implanted immediately after the fluid percussion injury (FPI) procedure, and (2) a naive age-matched control group with the same electrode implantation montage. Pairs of tungsten microelectrodes (50 μm outer diameter) and screw electrodes were implanted in neocortex inside the TBI core, areas adjacent to TBI, and remote areas. EEG activity, recorded on the day of FPI, and continuously for 2 weeks, was analyzed for possible electrographic biomarkers of epileptogenesis. Video-EEG monitoring was also performed continuously in the TBI group to capture electrographic and behavioral seizures until the caps came off (28-189 days), and for 1 week, at 2, 3, and 6 months of age, in the control group. Pathologic high-frequency oscillations (pHFOs) with a central frequency between 100 and 600 Hz, were recorded from microelectrodes, beginning during the first two post-FPI weeks, in 7 of 12 animals in the TBI group (58%) and never in the controls. pHFOs only occurred in cortical areas within or adjacent to the TBI core. These were associated with synchronous multiunit discharges and popSpikes, duration 15-40 msec. Repetitive pHFOs and EEG spikes (rHFOSs) formed paroxysmal activity, with a unique arcuate pattern, in the frequency band 10-16 Hz in the same areas as isolated pHFOs, and these events were also recorded by screw electrodes. Although loss of caps prevented long-term recordings from all rats, pHFOs and rHFOSs occurred during the first 2 weeks in all four animals that later developed seizures, and none of the rats without these events developed late seizures. pHFOs, similar to those associated with epileptogenesis in the status rat model of epilepsy, may also reflect epileptogenesis after FPI. rHFOSs could be noninvasive biomarkers of epileptogenesis.

The gut microbiome restores intrinsic and extrinsic nerve function in germ‐free mice accompanied by changes in calbindin

The microbiome is essential for normal myenteric intrinsic primary afferent neuron (IPAN) excitability. These neurons control gut motility and modulate gut-brain signaling by exciting extrinsic afferent fibers innervating the enteric nervous system via an IPAN to extrinsic fiber sensory synapse. We investigated effects of germ-free (GF) status and conventionalization on extrinsic sensory fiber discharge in the mesenteric nerve bundle and IPAN electrophysiology, and compared these findings with those from specific pathogen-free (SPF) mice. As we have previously shown that the IPAN calcium-dependent slow afterhyperpolarization (sAHP) is enhanced in GF mice, we also examined the expression of the calcium-binding protein calbindin in these neurons in these different animal groups. IPAN sAHP and mesenteric nerve multiunit discharge were recorded using ex vivo jejunal gut segments from SPF, GF, or conventionalized (CONV) mice. IPANs were excited by adding 5 μM TRAM-34 to the serosal superfusate. We probed for calbindin expression using immunohistochemical techniques. SPF mice had a 21% increase in mesenteric nerve multiunit firing rate and CONV mice a 41% increase when IPANs were excited by TRAM-34. For GF mice, this increase was barely detectable (2%). TRAM-34 changed sAHP area under the curve by -77 for SPF, +3 for GF, or -54% for CONV animals. Calbindin-immunopositive neurons per myenteric ganglion were 36% in SPF, 24% in GF, and 52% in CONV animals. The intact microbiome is essential for normal intrinsic and extrinsic nerve function and gut-brain signaling.

Salicylate-induced auditory perceptual disorders and plastic changes in nonclassical auditory centers in rats.

Previous studies have shown that sodium salicylate (SS) activates not only central auditory structures, but also nonauditory regions associated with emotion and memory. To identify electrophysiological changes in the nonauditory regions, we recorded sound-evoked local field potentials and multiunit discharges from the striatum, amygdala, hippocampus, and cingulate cortex after SS-treatment. The SS-treatment produced behavioral evidence of tinnitus and hyperacusis. Physiologically, the treatment significantly enhanced sound-evoked neural activity in the striatum, amygdala, and hippocampus, but not in the cingulate. The enhanced sound evoked response could be linked to the hyperacusis-like behavior. Further analysis showed that the enhancement of sound-evoked activity occurred predominantly at the midfrequencies, likely reflecting shifts of neurons towards the midfrequency range after SS-treatment as observed in our previous studies in the auditory cortex and amygdala. The increased number of midfrequency neurons would lead to a relative higher number of total spontaneous discharges in the midfrequency region, even though the mean discharge rate of each neuron may not increase. The tonotopical overactivity in the midfrequency region in quiet may potentially lead to tonal sensation of midfrequency (the tinnitus). The neural changes in the amygdala and hippocampus may also contribute to the negative effect that patients associate with their tinnitus.

Psychoactive bacteriaLactobacillus rhamnosus(JB-1) elicits rapid frequency facilitation in vagal afferents

Mounting evidence supports the influence of the gut microbiome on the local enteric nervous system and its effects on brain chemistry and relevant behavior. Vagal afferents are involved in some of these effects. We previously showed that ingestion of the probiotic bacterium Lactobacillus rhamnosus (JB-1) caused extensive neurochemical changes in the brain and behavior that were abrogated by prior vagotomy. Because information can be transmitted to the brain via primary afferents encoded as neuronal spike trains, our goal was to record those induced by JB-1 in vagal afferents in the mesenteric nerve bundle and thus determine the nature of the signals sent to the brain. Male Swiss Webster mice jejunal segments were cannulated ex vivo, and serosal and luminal compartments were perfused separately. Bacteria were added intraluminally. We found no evidence for translocation of labeled bacteria across the epithelium during the experiment. We recorded extracellular multi- and single-unit neuronal activity with glass suction pipettes. Within minutes of application, JB-1 increased the constitutive single- and multiunit firing rate of the mesenteric nerve bundle, but Lactobacillus salivarius (a negative control) or media alone were ineffective. JB-1 significantly augmented multiunit discharge responses to an intraluminal distension pressure of 31 hPa. Prior subdiaphragmatic vagotomy abolished all of the JB-1-evoked effects. This detailed exploration of the neuronal spike firing that encodes behavioral signaling to the brain may be useful to identify effective psychoactive bacteria and thereby offer an alternative new perspective in the field of psychiatry and comorbid conditions.

Can cortical spreading depression activate central trigeminovascular neurons without peripheral input? Pitfalls of a new concept

Can cortical spreading depression activate central trigeminovascular neurons without peripheral input? Pitfalls of a new concept

Gamma-Band Activation Predicts Both Associative Memory and Cortical Plasticity

Gamma-band oscillations are a ubiquitous phenomenon in the nervous system and have been implicated in multiple aspects of cognition. In particular, the strength of gamma oscillations at the time a stimulus is encoded predicts its subsequent retrieval, suggesting that gamma may reflect enhanced mnemonic processing. Likewise, activity in the gamma-band can modulate plasticity in vitro. However, it is unclear whether experience-dependent plasticity in vivo is also related to gamma-band activation. The aim of the present study was to determine whether gamma activation in primary auditory cortex modulates both the associative memory for an auditory stimulus during classical conditioning and its accompanying specific receptive field plasticity. Rats received multiple daily sessions of single tone/shock trace and two-tone discrimination conditioning, during which local field potentials and multiunit discharges were recorded from chronically implanted electrodes. We found that the strength of tone-induced gamma predicted the acquisition of associative memory 24 h later and ceased to predict subsequent performance once asymptote was reached. Gamma activation also predicted receptive field plasticity that specifically enhanced representation of the signal tone. This concordance provides a long-sought link between gamma oscillations, cortical plasticity, and the formation of new memories.

Effect of sleep deprivation on multi-unit discharge activity of basal forebrain

The basal forebrain (BF) is an important wakefulness/arousal-promoting structure involved in homeostatic responses to sleep deprivation (SD). However, the effects of SD and subsequent sleep recovery on the BF discharge have not been investigated. Multi-unit BF activity was recorded on freely moving rats during 8 h of baseline (BL) and, on the following day, during 4 h of SD by gentle handling followed by 4 h of recovery. The effect of SD on the waking discharge was evaluated during the last 10 min of each hour when attentive waking was induced. The wakefulness level was defined based on the ratio between theta and delta electroencephalogram (EEG) powers, and epochs with ratios >or=1 but <2 (T/D-1) and >or=2 but <4 (T/D-2) were analysed separately. During T/D-1 wakefulness, the BF multi-unit discharge rate increased significantly during the second and third hours of SD and decreased during the third hour of recovery when compared with corresponding hours of BL. Non-rapid eye movement sleep discharge rate during recovery decreased significantly in the second and third versus the first and last hours. The results suggest that maintenance of the level of vigilance necessary for adequate performance during SD requires increased activation of BF neurones when compared with the BL, whereas the same level of vigilance after several hours of recovery can be maintained with lesser activation of BF neurones.

A novel suction electrode recording technique for monitoring circadian rhythms in single and multiunit discharge from brain slices

The study of spontaneous neuronal discharge for several days in vitro poses substantial technical difficulties not readily addressed by existing methodologies. Here we describe a novel method for recording bioelectrical signals from brain slices, using media-filled, glass micropipettes stabilized at the recording interface by negative pressure. Such electrodes are durable, economical and easily constructed using standard laboratory equipment. Through these suction electrodes, we monitored ∼24 h oscillations in spontaneous single and multiunit discharge from acutely prepared adult mouse suprachiasmatic nuclei (SCN) slices for up to 4 days in vitro, with very high success rates. Neuronal oscillations exhibited all the characteristics previously determined in SCN recordings using other techniques. Importantly, our electrode assembly enables SCN activity in acutely prepared brain slices to be monitored for substantially longer than with other methodologies. In summary, our data suggest that suction electrodes are likely to provide a favorable alternative to existing methods for recording long-term neuronal activity from brain slices.

Recording of Neural Activity From Goat Cervical Facet Joint Capsule Using Custom-Designed Miniature Electrodes

To establish a methodology for the neurophysiologic study of mechanoreceptors in the cervical facet joint capsule. To test a custom designed miniature dual bipolar electrode for recording the neural activity in cervical dorsal roots. To determine if the neural activity from different receptors in the capsule can be differentiated using this methodology. Injury to cervical facet joint capsules has been regarded as an important source of whiplash pain, but no neurophysiologic study has been performed to demonstrate or characterize sensory nerve function in the capsule. Nineteen goats weighing 34 to 55 kg were used under general anesthesia. A C4-C6 laminectomy was performed to expose the C6 nerve root. Custom designed miniature dual bipolar electrodes were used to record neural activity in the left C6 branches. Electrical and mechanical stimuli were used to evoke receptor activity in the dorsal aspect of the C5/6 capsule. Conduction velocities (CVs) of evoked units were determined by electrical stimulation and dual-bipolar-electrode recording methods. The units were classified based on their CVs. The waveform of each classified unit was saved as a template for later single unit discharge search among multiunit discharges during the stretch of the capsule. The C5/6 facet joint with capsule was pulled by a computer-controlled actuator instrumented with a load cell at a rate of 0.5 mm per second. The evoked neural activity and load were recorded, digitized, and analyzed to determine CV, discharge rate, and response to the stretch. Miniature bipolar electrodes recorded the neural activity in both channels, with single unit CVs being measured. There was no discernible motion between the electrode and dorsal root when the capsule was pulled. Both local compression and stretch on capsule evoked multiunit discharges. A-beta, A-delta, and C-fiber units were found among these multiunit discharges. The rate of single unit and multiunit discharges increased during capsule stretch in the physiologic range and afterdischarges occurred beyond the physiologic range. The novel miniature electrodes not requiring a micromanipulator made it feasible and reliable to record neural activity from short cervical spinal roots. Waveforms of different units could be identified, making it possible to study sensory functions of the facet joint capsule. A-beta, A-delta, and C-fiber units were found responding to mechanical stimuli, indicating that facet joint capsule has functional proprioceptors and nociceptors.

Vagal-Evoked Activity in the Parafascicular Nucleus of the Primate Thalamus

The physiological effects of ascending vagal afferent activity in the primate forebrain have not been established, and because vagus nerve stimulation (VNS) is useful clinically for treatment of epilepsy and depression, these actions need to be identified. We used a roving microelectrode to record vagal-evoked potentials in the thalamus of the macaque monkey. In addition to the anticipated activation in the gustatory/visceral thalamic relay nucleus, we found an unexpectedly larger and earlier response focus with multi-unit discharges in the adjacent parafascicular nucleus. These data reveal a potent vagal input to this intralaminar nucleus, which is normally considered to be involved in motor control. This finding indicates that a role for this vagal activation site in the anti-epileptic effects of VNS needs to be considered.

Sympathetic Neural Activation in Nondiabetic Metabolic Syndrome and Its Further Augmentation by Hypertension

Hypertension is a major cardiovascular risk factor in the metabolic syndrome (MS) in which the presence of insulin resistance, glucose intolerance, abnormal lipoprotein metabolism, and central obesity all confer an increased risk. Because essential hypertension (EHT), insulinemia, and visceral fat are associated with sympathetic hyperactivity, which is itself known to increase cardiovascular risk, the aim of this study was to see if MS is a state of sympathetic nerve hyperactivity and if the additional presence of EHT intensifies this hyperactivity. In 69 closely matched subjects, comprising hypertensive MS (MS+EHT, 18), normotensive MS (MS-EHT, 17), hypertensives without MS (EHT, 16), and normotensive controls without MS (NC, 18), we measured resting muscle sympathetic nerve activity (MSNA) as assessed from multiunit discharges and from single units with defined vasoconstrictor properties (s-MSNA). The s-MSNA in MS+EHT (76+/-3.1 impulses/100 beats) was greater (at least P<0.01) than in MS-EHT (62+/-3.2 impulses/100 beats) and in EHT (60+/-2.3 impulses/100 beats), and all these were significantly greater (at least P<0.01) than in NC (46+/-2.7 impulse/100 beats). The multi-unit MSNA followed a similar trend. These findings suggest that MS is a state of sympathetic nerve hyperactivity and that the additional presence of hypertension further intensifies this hyperactivity. The degree of sympathetic hyperactivity seen in this study could be argued at least partly to contribute to the higher cardiovascular risk and metabolic abnormalities seen in MS+EHT patients.

Sympathetic neural hyperactivity and its normalization following unstable angina and acute myocardial infarction.

Impaired autonomic function occurs after AMI (acute myocardial infarction) and UA (unstable angina), which may be important prognostically. However, the pattern of sympathetic nerve hyperactivity has been investigated only after AMI. We aimed to quantify central sympathetic output to the periphery in patients with UA, investigate its progress over time relative to that after uncomplicated AMI and to explore the mechanisms involved. Muscle sympathetic nerve activity (MSNA) assessed from multiunit discharges and from single units (s-MSNA) was obtained in matched patients with UA ( n =9), AMI ( n =14) and stable CAD (coronary artery disease, n =11), patients with chest pain in which AMI was excluded (NMI, n =9) and normal controls (NCs, n =14). Measurements were obtained 2-4 days after UA or AMI, and repeated at 3 monthly intervals until they returned to normal levels. The respective MSNA and s-MSNA early after UA (72+/-4.0 bursts/100 beats and 78+/-4.2 impulses/100 beats respectively) were less than those after AMI (83+/-4.4 bursts/100 beats and 93+/-5.5 impulses/100 beats respectively). Relative to the control groups of NCs (51+/-2.7 bursts/100 beats and 58+/-3.4 impulses/100 beats respectively) and patients with CAD (54+/-3.7 bursts/100 beats and 58+/-3.9 impulses/100 beats respectively) and NMI (52+/-4.5 bursts/100 beats and 59+/-4.9 impulses/100 beats respectively), values returned to normal after 6 months in UA (55+/-5.0 bursts/100 beats and 62+/-5.5 impulses/100 beats respectively) and 9 months after AMI (60+/-3.8 bursts/100 beats and 66+/-4.2 impulses/100 beats respectively). In conclusion, both UA and AMI result in sympathetic hyper-activity, although this is of smaller magnitude in UA and is less protracted than in AMI. It is suggested that this hyperactivity is related to the degree of left ventricular dysfunction and reflexes.

Interplay between local GABAergic interneurons and relay neurons generates gamma oscillations in the rat olfactory bulb.

Olfactory stimuli have been known for a long time to elicit oscillations in olfactory brain areas. In the olfactory bulb (OB), odors trigger synchronous oscillatory activity that is believed to arise from the coherent and rhythmic discharges of large numbers of neurons. These oscillations are known to take part in encoding of sensory information before their transfer to higher subcortical and cortical areas. To characterize the cellular mechanisms underlying gamma (30-80 Hz) local field potential (LFP) oscillations, we simultaneously recorded multiunit discharges, intracellular responses, and LFP in rat OB slices. We showed that a single and brief electrical stimulation of olfactory nerve elicited LFP oscillations in the mitral cell body layer lasting >1 sec. Both action potentials and subthreshold oscillations of mitral/tufted cells, the bulbar output neurons, were precisely synchronized with LFP oscillations. This synchronization arises from the interaction between output neurons and granule cells, the main population of local circuit inhibitory interneurons, through dendrodendritic synapses. Interestingly enough, the synchronization exerted by reciprocal synaptic interactions did not require action potentials initiated in granule cell somata. Finally, local application of a GABA(A) receptor antagonist at the mitral cell and external plexiform layers confirmed the exclusive role of the granule cell reciprocal synapses in generating the evoked oscillations. We concluded that interneurons located in the granule cell layer generate synaptic activity capable of synchronizing activity of output neurons by interacting with both their subthreshold and spiking activity.

Relationship of neurovascular compression to central sympathetic discharge and essential hypertension

ObjectivesWe planned to examine the relationship between neurovascular compression (NVC) of the rostral ventrolateral medulla (RVLM) and the magnitude of central sympathetic hyperactivity in normal subjects and in patients with untreated and uncomplicated essential hypertension (EHT). BackgroundPreviously it has not been possible to establish a definitive relationship between EHT and NVC of the RVLM, a location containing efferent sympathetic vasoconstrictor neurons. Furthermore, the relationship between NVC and magnitude of sympathetic nerve hyperactivity has not been adequately examined, despite the knowledge that hyperactivity varies according to EHT severity. MethodsIn 83 subjects, we used magnetic resonance imaging to detect NVC and, independently, peroneal microneurography to quantify muscle sympathetic nerve activity (MSNA), expressed as the mean frequency of multi-unit discharge (m-MSNA) and of single units (s-MSNA). Subjects were classified according to arterial pressure values into groups with normal (NT) (n = 24) or high-normal (HN) (n = 14) arterial pressure and mild (EHT-1) (n = 26) or severe (EHT-2/3) (n = 19) EHT. ResultsA significantly greater sympathetic activity was found in 23 subjects with NVC, compared with 60 subjects without NVC. The prevalence of NVC and the magnitude of sympathetic hyperactivity were greater in the EHT-1 group (p < 0.05) than in the other three groups. There was no significant difference in confounding variables between the groups. Although increased sympathetic activity was strongly predictive of NVC, this was not significantly related to baroreceptor sensitivity controlling the pulse interval (cardiac baroreceptor reflex sensitivity). ConclusionsNeurovascular compression of the RVLM may cause central sympathetic activation in normal and hypertensive populations and therefore has significant implications regarding the pathogenesis of EHT.

Relationship between central sympathetic activity and stages of human hypertension

Background The magnitude of sympathetic hyperactivity in essential hypertension (EHT) varies with its severity and complications. There are no data on sympathetic nerve activity in borderline (BHT) or white-coat hypertension (WHT) relative to the various stages of EHT, despite suggestions that both lead to established EHT and organ damage through sympathetic mechanisms. We planned to determine the magnitude of sympathetic nerve activity in patients with BHT and WHT in relation to normality and various stages of sustained EHT. Methods We examined 90 untreated subjects comprising matched groups with BHT ( n = 13), WHT ( n = 12), Sixth Report of the Joint National Committee on the Prevention, Detection, Evaluation, and Treatment of High Blood Pressure EHT stage 1 (EHT-1 n = 12), EHT stages 2 and 3 (EHT-2/3 n = 14), high–normal pressure (HN n = 14), and normal pressure (NT n = 13), as well as a group with EHT complicated by left ventricular hypertrophy (EHT+LVH n = 12). We quantified muscle sympathetic nerve activity as the mean frequency of multiunit discharge (MSNA) and that of single-units (s-MSNA). Results We found a greater (at least P < .01) mean central sympathetic frequency in BHT (75 ± 5.8 impulses/100 beats), EHT-1 (76 ± 4.0 impulses/100 beats), and EHT+LVH (79 ± 4.3 impulses/100 beats) than in EHT-2/3 (57 ± 3.1 impulses/100 beats), WHT (52 ± 3.6 impulses/100 beats), HN (42 ± 3.9 impulses/100 beats), and NT (33 ± 3.6 impulses/100 beats). BHT hyperactivity was closer to that of EHT, whereas WHT was closer to NT. Conclusions Central sympathetic activity was greatest in BHT, early stage, and complicated EHT, and as such is likely to play an integral role in the development of hypertension and its complications. Sympathetic hyperactivity occurs in WHT, but to a lesser extent than in BHT.