Relief of fecal incontinence by sacral nerve stimulation linked to focal brain activation

DEFF Research Database (Denmark)

Lundby, Lilli; Møller, Arne; Buntzen, Steen

2011-01-01

This study aimed to test the hypothesis that sacral nerve stimulation affects afferent vagal projections to the central nervous system associated with frontal cortex activation in patients with fecal incontinence.......This study aimed to test the hypothesis that sacral nerve stimulation affects afferent vagal projections to the central nervous system associated with frontal cortex activation in patients with fecal incontinence....

Differential roles of stretch-sensitive pelvic nerve afferents innervating mouse distal colon and rectum

OpenAIRE

Feng, Bin; Brumovsky, Pablo R.; Gebhart, Gerald F.

2010-01-01

Information about colorectal distension (i.e., colorectal dilation by increased intraluminal pressure) is primarily encoded by stretch-sensitive colorectal afferents in the pelvic nerve (PN). Despite anatomic differences between rectum and distal colon, little is known about the functional roles of colonic vs. rectal afferents in the PN pathway or the quantitative nature of mechanosensory encoding. We utilized an in vitro mouse colorectum-PN preparation to investigate pressure-encoding charac...

Mechanoreceptor afferent activity compared with receptor field dimensions and pressure changes in feline urinary bladder.

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Downie, J W; Armour, J A

1992-11-01

The relationship between vesical mechanoreceptor field dimensions and afferent nerve activity recorded in pelvic plexus nerve filaments was examined in chloralose-anesthetized cats. Orthogonal receptor field dimensions were monitored with piezoelectric ultrasonic crystals. Reflexly generated bladder contractile activity made measurements difficult, therefore data were collected from cats subjected to actual sacral rhizotomy. Afferent activity was episodic and was initiated at different pressure and receptor field dimension thresholds. Maximum afferent activity did not correlate with maximum volume or pressure. Furthermore, activity was not linearly related to intravesical pressure, receptor field dimensions, or calculated wall tension. Pressure-length hysteresis of the receptor fields occurred. The responses of identified afferent units and their associated receptor field dimensions to brief contractions elicited by the ganglion stimulant 1,1-dimethyl-4-phenylpiperazinium iodide (2.5-20 micrograms i.a.), studied under constant volume or constant pressure conditions, are compatible with bladder mechanoreceptors behaving as tension receptors. Because activity generated by bladder mechanoreceptors did not correlate in a simple fashion with intravesical pressure or receptor field dimensions, it is concluded that such receptors are influenced by the viscoelastic properties of the bladder wall. Furthermore, as a result of the heterogeneity of the bladder wall, receptor field tension appears to offer a more precise relationship with the activity of bladder wall mechanoreceptors than does intravesical pressure.

elPBN neurons regulate rVLM activity through elPBN-rVLM projections during activation of cardiac sympathetic afferent nerves

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Longhurst, John C.; Tjen-A-Looi, Stephanie C.; Fu, Liang-Wu

2016-01-01

The external lateral parabrachial nucleus (elPBN) within the pons and rostral ventrolateral medulla (rVLM) contributes to central processing of excitatory cardiovascular reflexes during stimulation of cardiac sympathetic afferent nerves (CSAN). However, the importance of elPBN cardiovascular neurons in regulation of rVLM activity during CSAN activation remains unclear. We hypothesized that CSAN stimulation excites the elPBN cardiovascular neurons and, in turn, increases rVLM activity through elPBN-rVLM projections. Compared with controls, in rats subjected to microinjection of retrograde tracer into the rVLM, the numbers of elPBN neurons double-labeled with c-Fos (an immediate early gene) and the tracer were increased after CSAN stimulation (P < 0.05). The majority of these elPBN neurons contain vesicular glutamate transporter 3. In cats, epicardial bradykinin and electrical stimulation of CSAN increased the activity of elPBN cardiovascular neurons, which was attenuated (n = 6, P < 0.05) after blockade of glutamate receptors with iontophoresis of kynurenic acid (Kyn, 25 mM). In separate cats, microinjection of Kyn (1.25 nmol/50 nl) into the elPBN reduced rVLM activity evoked by both bradykinin and electrical stimulation (n = 5, P < 0.05). Excitation of the elPBN with microinjection of dl-homocysteic acid (2 nmol/50 nl) significantly increased basal and CSAN-evoked rVLM activity. However, the enhanced rVLM activity induced by dl-homocysteic acid injected into the elPBN was reversed following iontophoresis of Kyn into the rVLM (n = 7, P < 0.05). These data suggest that cardiac sympathetic afferent stimulation activates cardiovascular neurons in the elPBN and rVLM sequentially through a monosynaptic (glutamatergic) excitatory elPBN-rVLM pathway. PMID:27225950

Inhibition of Parkinsonian tremor with cutaneous afferent evoked by transcutaneous electrical nerve stimulation.

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Hao, Man-Zhao; Xu, Shao-Qin; Hu, Zi-Xiang; Xu, Fu-Liang; Niu, Chuan-Xin M; Xiao, Qin; Lan, Ning

2017-07-14

Recent study suggests that tremor signals are transmitted by way of multi-synaptic corticospinal pathway. Neurophysiological studies have also demonstrated that cutaneous afferents exert potent inhibition to descending motor commands by way of spinal interneurons. We hypothesize in this study that cutaneous afferents could also affect the transmission of tremor signals, thus, inhibit tremor in patients with PD. We tested this hypothesis by activating cutaneous afferents in the dorsal hand skin innervated by superficial radial nerve using transcutaneous electrical nerve stimulation (TENS). Eight patients with PD having tremor dominant symptom were recruited to participate in this study using a consistent experimental protocol for tremor inhibition. Resting tremor and electromyogram (EMG) of muscles in the upper extremity of these subjects with PD were recorded, while surface stimulation was applied to the dorsal skin of the hand. Fifteen seconds of data were recorded for 5 s prior to, during and post stimulation. Power spectrum densities (PSDs) of tremor and EMG signals were computed for each data segment. The peak values of PSDs in three data segments were compared to detect evidence of tremor inhibition. At stimulation intensity from 1.5 to 1.75 times of radiating sensation threshold, apparent suppressions of tremor at wrist, forearm and upper arm and in the EMGs were observed immediately at the onset of stimulation. After termination of stimulation, tremor and rhythmic EMG bursts reemerged gradually. Statistical analysis of peak spectral amplitudes showed a significant difference in joint tremors and EMGs during and prior to stimulation in all 8 subjects with PD. The average percentage of suppression was 61.56% in tremor across all joints of all subjects, and 47.97% in EMG of all muscles. The suppression appeared to occur mainly in distal joints and muscles. There was a slight, but inconsistent effect on tremor frequency in the 8 patients with PD tested. Our

elPBN neurons regulate rVLM activity through elPBN-rVLM projections during activation of cardiac sympathetic afferent nerves.

Science.gov (United States)

Guo, Zhi-Ling; Longhurst, John C; Tjen-A-Looi, Stephanie C; Fu, Liang-Wu

2016-08-01

The external lateral parabrachial nucleus (elPBN) within the pons and rostral ventrolateral medulla (rVLM) contributes to central processing of excitatory cardiovascular reflexes during stimulation of cardiac sympathetic afferent nerves (CSAN). However, the importance of elPBN cardiovascular neurons in regulation of rVLM activity during CSAN activation remains unclear. We hypothesized that CSAN stimulation excites the elPBN cardiovascular neurons and, in turn, increases rVLM activity through elPBN-rVLM projections. Compared with controls, in rats subjected to microinjection of retrograde tracer into the rVLM, the numbers of elPBN neurons double-labeled with c-Fos (an immediate early gene) and the tracer were increased after CSAN stimulation (P neurons contain vesicular glutamate transporter 3. In cats, epicardial bradykinin and electrical stimulation of CSAN increased the activity of elPBN cardiovascular neurons, which was attenuated (n = 6, P neurons in the elPBN and rVLM sequentially through a monosynaptic (glutamatergic) excitatory elPBN-rVLM pathway. Copyright © 2016 the American Physiological Society.

Electrophysiological study in the infraorbital nerve of the rat: Spontaneous and evoked activity

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AlbarracIn, A L [Catedra de Neurociencias, Facultad de Medicina, Universidad Nacional de Tucuman, Av. Roca 2200, PC 4000 (Argentina); Farfan, F D [Departamento de BioingenierIa, FACET, Universidad Nacional de Tucuman, INSIBIO - CONICET, CC 327, PC 4000 (Argentina); Felice, C J [Departamento de BioingenierIa, FACET, Universidad Nacional de Tucuman, INSIBIO - CONICET, CC 327, PC 4000 (Argentina)

2007-11-15

In this work we present some studies in the afferent nerve of the rat vibrissae. Studies on spontaneous activity (SA) in this sensorial system are of long data. Nevertheless, SA recordings in the nerve of a single vibrissa have not been made until present. In this work, we use an algorithm based on signal decomposition with Continuous Wavelet Transform (CWT) to analyse the discharges of two nerves. The action potentials of both nerves were detected and the firing rates were calculated. These results suggest that the firing rate of one vibrissa innervation is low considering that this nerve contains hundred of fibers. In addition, we present preliminary studies suggesting important effects of the hair shaft length in the afferent discharge during the vibrissae movements. The experiments consisted in recording the nerve activity after the vibrissae were sectioned at two different levels. The results showed important differences in the signal energy contents. It suggests that the hair shaft length would produce a differential activation of the mechanoreceptors located in the vibrissae follicle.

Electrophysiological study in the infraorbital nerve of the rat: Spontaneous and evoked activity

International Nuclear Information System (INIS)

AlbarracIn, A L; Farfan, F D; Felice, C J

2007-01-01

In this work we present some studies in the afferent nerve of the rat vibrissae. Studies on spontaneous activity (SA) in this sensorial system are of long data. Nevertheless, SA recordings in the nerve of a single vibrissa have not been made until present. In this work, we use an algorithm based on signal decomposition with Continuous Wavelet Transform (CWT) to analyse the discharges of two nerves. The action potentials of both nerves were detected and the firing rates were calculated. These results suggest that the firing rate of one vibrissa innervation is low considering that this nerve contains hundred of fibers. In addition, we present preliminary studies suggesting important effects of the hair shaft length in the afferent discharge during the vibrissae movements. The experiments consisted in recording the nerve activity after the vibrissae were sectioned at two different levels. The results showed important differences in the signal energy contents. It suggests that the hair shaft length would produce a differential activation of the mechanoreceptors located in the vibrissae follicle

Histological identification of phrenic afferent projections to the spinal cord.

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Nair, Jayakrishnan; Bezdudnaya, Tatiana; Zholudeva, Lyandysha V; Detloff, Megan R; Reier, Paul J; Lane, Michael A; Fuller, David D

2017-02-01

Limited data are available regarding the spinal projections of afferent fibers in the phrenic nerve. We describe a method that robustly labels phrenic afferent spinal projections in adult rats. The proximal end of the cut phrenic nerve was secured in a microtube filled with a transganglionic tracer (cholera toxin β-subunit, CT-β, or Cascade Blue) and tissues harvested 96-h later. Robust CT-β labeling occurred in C3-C5 dorsal root ganglia cell bodies and phrenic afferent projections were identified in the mid-cervical dorsal horn (laminae I-III), intermediate grey matter (laminae IV, VII) and near the central canal (laminae X). Afferent fiber labeling was reduced or absent when CT-β was delivered to the intrapleural space or directly to the hemidiaphragm. Soaking the phrenic nerve with Cascade Blue also produced robust labeling of mid-cervical dorsal root ganglia cells bodies, and primary afferent fibers were observed in spinal grey matter and dorsal white matter. Our results show that the 'nerve soak' method effectively labels both phrenic motoneurons and phrenic afferent projections, and show that primary afferents project throughout the ipsilateral mid-cervical gray matter. Copyright © 2016. Published by Elsevier B.V.

Inhibition of muscle spindle afferent activity during masseter muscle fatigue in the rat.

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Brunetti, Orazio; Della Torre, Giovannella; Lucchi, Maria Luisa; Chiocchetti, Roberto; Bortolami, Ruggero; Pettorossi, Vito Enrico

2003-09-01

The influence of muscle fatigue on the jaw-closing muscle spindle activity has been investigated by analyzing: (1) the field potentials evoked in the trigeminal motor nucleus (Vmot) by trigeminal mesencephalic nucleus (Vmes) stimulation, (2) the orthodromic and antidromic responses evoked in the Vmes by stimulation of the peripheral and central axons of the muscle proprioceptive afferents, and (3) the extracellular unitary discharge of masseter muscle spindles recorded in the Vmes. The masseter muscle was fatigued by prolonged tetanic masseter nerve electrical stimulation. Pre- and postsynaptic components of the potentials evoked in the Vmot showed a significant reduction in amplitude following muscle fatigue. Orthodromic and antidromic potentials recorded in the Vmes also showed a similar amplitude decrease. Furthermore, muscle fatigue caused a decrease of the discharge frequency of masseter muscle spindle afferents in most of the examined units. The inhibition of the potential amplitude and discharge frequency was strictly correlated with the extent of muscle fatigue and was mediated by the group III and IV afferent muscle fibers activated by fatigue. In fact, the inhibitory effect was abolished by capsaicin injection in the masseter muscle that provokes selective degeneration of small afferent muscle fibers containing neurokinins. We concluded that fatigue signals originating from the muscle and traveling through capsaicin-sensitive fibers are able to diminish the proprioceptive input by a central presynaptic influence. In the second part of the study, we examined the central projection of the masseter small afferents sensitive to capsaicin at the electron-microscopic level. Fiber degeneration was induced by injecting capsaicin into the masseter muscle. Degenerating terminals were found on the soma and stem process in Vmes and on the dendritic tree of neurons in Vmot. This suggests that small muscle afferents may influence the muscle spindle activity through

Peripheral afferent mechanisms underlying acupuncture inhibition of cocaine behavioral effects in rats.

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Seol Ah Kim

Full Text Available Administration of cocaine increases locomotor activity by enhancing dopamine transmission. To explore the peripheral mechanisms underlying acupuncture treatment for drug addiction, we developed a novel mechanical acupuncture instrument (MAI for objective mechanical stimulation. The aim of this study was to evaluate whether acupuncture inhibition of cocaine-induced locomotor activity is mediated through specific peripheral nerves, the afferents from superficial or deep tissues, or specific groups of nerve fibers. Mechanical stimulation of acupuncture point HT7 with MAI suppressed cocaine-induced locomotor activity in a stimulus time-dependent manner, which was blocked by severing the ulnar nerve or by local anesthesia. Suppression of cocaine-induced locomotor activity was elicited after HT7 stimulation at frequencies of either 50 (for Meissner corpuscles or 200 (for Pacinian corpuscles Hz and was not affected by block of C/Aδ-fibers in the ulnar nerve with resiniferatoxin, nor generated by direct stimulation of C/Aδ-fiber afferents with capsaicin. These findings suggest that HT7 inhibition of cocaine-induced locomotor activity is mediated by A-fiber activation of ulnar nerve that originates in superficial and deep tissue.

Fatigue-induced changes in group IV muscle afferent activity: differences between high- and low-frequency electrically induced fatigues.

Science.gov (United States)

Darques, J L; Jammes, Y

1997-03-07

Recordings of group IV afferent activity of tibialis anterior muscle were performed in paralysed rabbits during runs of electrically induced fatigue produced by direct muscle stimulation at a high (100 Hz, high-frequency fatigue HFF) or a low rate (10 Hz, low-frequency fatigue LFF). In addition to analysis of afferent nerve action potentials, muscle force and compound muscle action potentials (M waves) elicited by direct muscle stimulation with single shocks were recorded. Changes in M wave configuration were used as an index of the altered propagation of membrane potentials and the associated efflux of potassium from muscle fibers. The data show that increased group IV afferent activity occurred during LFF as well as HFF trials and developed parallel with force failure. Enhanced afferent activity was significantly higher during LFF (maximal delta f(impulses) = 249 +/- 35%) than HFF (147 +/- 45%). No correlation was obtained between the responses of group IV afferents to LFF or to pressure exerted on tibialis anterior muscle. On the other hand, decreased M wave amplitude was minimal with LFF while it was pronounced with HFF. Close correlations were found between fatigue-induced activation of group IV afferents and decreases in force or M wave amplitude, but their strength was significantly higher with LFF compared to HFF. Thus, electrically induced fatigue activates group IV muscle afferents with a prominent effect of low-frequency stimulation. The mechanism of muscle afferent stimulation does not seem to be due to the sole increase in extracellular potassium concentration, but also by the efflux of muscle metabolites, present during fatiguing contractions at low rate of stimulation.

Peripheral axotomy of the rat mandibular trigeminal nerve leads to an increase in VIP and decrease of other primary afferent neuropeptides in the spinal trigeminal nucleus.

Science.gov (United States)

Atkinson, M E; Shehab, S A

1986-12-01

In the vasoactive intestinal polypeptide (VIP)-rich lumbosacral spinal cord, VIP increases at the expense of other neuropeptides after primary sensory nerve axotomy. This study was undertaken to ascertain whether similar changes occur in peripherally axotomised cranial sensory nerves. VIP immunoreactivity increased in the terminal region of the mandibular nerve in the trigeminal nucleus caudalis following unilateral section of the sensory root of the mandibular trigeminal nerve at the foramen orale. Other primary afferent neuropeptides (substance P, cholecystokinin and somatostatin) were depleted and fluoride-resistant acid phosphatase activity was abolished in the same circumscribed areas of the nucleus caudalis. The rise in VIP and depletion of other markers began 4 days postoperatively and was maximal by 10 days, these levels remaining unchanged up to 1 year postoperatively. VIP-immunoreactive cell bodies were absent from trigeminal ganglia from the unoperated side but small and medium cells stained intensely in the ganglia of the operated side after axotomy. These observations indicate that increase of VIP in sensory nerve terminals is a general phenomenon occurring in both cranial and spinal sensory terminal areas. The intense VIP immunoreactivity in axotomised trigeminal ganglia suggests that the increased levels of VIP in the nucleus caudalis are of peripheral origin, indicating a change in expression of neuropeptides within primary afferent neurons following peripheral axotomy.

Modulation of jaw muscle spindle afferent activity following intramuscular injections with hypertonic saline.

Science.gov (United States)

Ro, J Y; Capra, N F

2001-05-01

Transient noxious chemical stimulation of small diameter muscle afferents modulates jaw movement-related responses of caudal brainstem neurons. While it is likely that the effect is mediated from the spindle afferents in the mesencephalic nucleus (Vmes) via the caudally projecting Probst's tract, the mechanisms of pain induced modulations of jaw muscle spindle afferents is not known. In the present study, we tested the hypothesis that jaw muscle nociceptors gain access to muscle spindle afferents in the same muscle via central mechanisms and alter their sensitivity. Thirty-five neurons recorded from the Vmes were characterized as muscle spindle afferents based on their responses to passive jaw movements, muscle palpation, and electrical stimulation of the masseter nerve. Each cell was tested by injecting a small volume (250 microl) of either 5% hypertonic and/or isotonic saline into the receptor-bearing muscle. Twenty-nine units were tested with 5% hypertonic saline, of which 79% (23/29) showed significant modulation of mean firing rates (MFRs) during one or more phases of ramp-and-hold movements. Among the muscle spindle primary-like units (n = 12), MFRs of 4 units were facilitated, five reduced, two showed mixed responses and one unchanged. In secondary-like units (n = 17), MFRs of 9 were facilitated, three reduced and five unchanged. Thirteen units were tested with isotonic saline, of which 77% showed no significant changes of MFRs. Further analysis revealed that the hypertonic saline not only affected the overall output of muscle spindle afferents, but also increased the variability of firing and altered the relationship between afferent signal and muscle length. These results demonstrated that activation of muscle nociceptors significantly affects proprioceptive properties of jaw muscle spindles via central neural mechanisms. The changes can have deleterious effects on oral motor function as well as kinesthetic sensibility.

GABA in Paraventricular Nucleus Regulates Adipose Afferent Reflex in Rats.

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Lei Ding

Full Text Available Chemical stimulation of white adipose tissue (WAT induces adipose afferent reflex (AAR, and thereby causes a general sympathetic activation. Paraventricular nucleus (PVN is important in control of sympathetic outflow. This study was designed to investigate the role of γ-aminobutyric acid (GABA in PVN in regulating the AAR.Experiments were carried out in anesthetized rats. Renal sympathetic nerve activity (RSNA and mean arterial pressure (MAP were continuously recorded. AAR was evaluated by the RSNA and MAP responses to electrical stimulation of the right epididymal WAT (eWAT afferent nerve. Electrical stimulation of eWAT afferent nerve increase RSNA. Bilateral microinjection of the GABAA receptor agonist isoguvacine or the GABAB receptor agonist baclofen attenuated the AAR. The effect of isoguvacine on the AAR was greater than that of baclofen. The GABAA receptor antagonist gabazine enhanced the AAR, while the GABAB receptor antagonist CGP-35348 had no significant effect on the AAR. Bilateral PVN microinjection of vigabatrin, a selective GABA-transaminase inhibitor, to increase endogenous GABA levels in the PVN abolished the AAR. The inhibitory effect of vigabatrin on the AAR was attenuated by the pretreatment with gabazine or CGP-35348. Pretreatment with combined gabazine and CGP-35348 abolished the effects of vigabatrin.Activation of GABAA or GABAB receptors in the PVN inhibits the AAR. Blockade of GABAA receptors in the PVN enhances the AAR. Endogenous GABA in the PVN plays an important role in regulating the AAR.

Theobromine inhibits sensory nerve activation and cough.

Science.gov (United States)

Usmani, Omar S; Belvisi, Maria G; Patel, Hema J; Crispino, Natascia; Birrell, Mark A; Korbonits, Márta; Korbonits, Dezso; Barnes, Peter J

2005-02-01

Cough is a common and protective reflex, but persistent coughing is debilitating and impairs quality of life. Antitussive treatment using opioids is limited by unacceptable side effects, and there is a great need for more effective remedies. The present study demonstrates that theobromine, a methylxanthine derivative present in cocoa, effectively inhibits citric acid-induced cough in guinea-pigs in vivo. Furthermore, in a randomized, double-blind, placebo-controlled study in man, theobromine suppresses capsaicin-induced cough with no adverse effects. We also demonstrate that theobromine directly inhibits capsaicin-induced sensory nerve depolarization of guinea-pig and human vagus nerve suggestive of an inhibitory effect on afferent nerve activation. These data indicate the actions of theobromine appear to be peripherally mediated. We conclude theobromine is a novel and promising treatment, which may form the basis for a new class of antitussive drugs.

Limb venous distension evokes sympathetic activation via stimulation of the limb afferents in humans

Science.gov (United States)

Cui, Jian; McQuillan, Patrick M.; Blaha, Cheryl; Kunselman, Allen R.

2012-01-01

We have recently shown that a saline infusion in the veins of an arterially occluded human forearm evokes a systemic response with increases in muscle sympathetic nerve activity (MSNA) and blood pressure. In this report, we examined whether this response was a reflex that was due to venous distension. Blood pressure (Finometer), heart rate, and MSNA (microneurography) were assessed in 14 young healthy subjects. In the saline trial (n = 14), 5% forearm volume normal saline was infused in an arterially occluded arm. To block afferents in the limb, 90 mg of lidocaine were added to the same volume of saline in six subjects during a separate visit. To examine whether interstitial perfusion of normal saline alone induced the responses, the same volume of albumin solution (5% concentration) was infused in 11 subjects in separate studies. Lidocaine abolished the MSNA and blood pressure responses seen with saline infusion. Moreover, compared with the saline infusion, an albumin infusion induced a larger (MSNA: Δ14.3 ± 2.7 vs. Δ8.5 ± 1.3 bursts/min, P blood pressure responses. These data suggest that venous distension activates afferent nerves and evokes a powerful systemic sympathoexcitatory reflex. We posit that the venous distension plays an important role in evoking the autonomic adjustments seen with postural stress in human subjects. PMID:22707559

Immunomodulation of afferent neurons in guinea-pig isolated airway.

Science.gov (United States)

Riccio, M M; Myers, A C; Undem, B J

1996-03-01

1. The trachea, larynx and main bronchi with the right vagus nerve and nodose ganglion were isolated from guinea-pigs passively immunized 24 h previously with serum containing anti-ovalbumin antibody. 2. The airways were placed in one compartment of a Perspex chamber for recording of isometric tension while the nodose ganglion and attached vagus nerve were pulled into another compartment. Action potentials arriving from single airway afferent nerve endings were monitored extracellularly using a glass microelectrode positioned near neuronal cell bodies in the ganglion. Mechanosensitivity of the nerve endings was quantified using calibrated von Frey filaments immediately before and after exposure to antigen (10 micrograms ml-1 ovalbumin). 3. Ten endings responded to the force exerted by the lowest filament (0.078 mN) and were not further investigated. In airways from thirteen immunized guinea-pigs, the mechanical sensitivity of A delta afferent fibres (conduction velocity = 4.3 +/- 0.6 m s-1) was enhanced 4.1 +/- 0.9-fold following airway exposure to antigen (P action potential generation except in one instance when the receptive field was located over the smooth muscle. This ending also responded to methacholine suggesting that spatial changes in the receptive field, induced by muscle contraction, were responsible for the activation. 5. The mediators responsible for these effects are unknown, although histamine, prostaglandins, leukotrienes and tachykinins do not appear to be essential. The increase in mechanical responsiveness was not associated with the smooth muscle contraction since leukotriene C4, histamine and tachykinins, which all caused a similar contraction to antigen, did not affect mechanical thresholds. Moreover, the antigen-induced increases in excitability persisted beyond the duration of the smooth muscle contraction. 6. These results demonstrate that antigen-antibody-mediated inflammatory processes may enhance the excitability of vagal afferent

Afferent fibers and sensory ganglion cells within the oculomotor nerve in some mammals and man. II. Electrophysiological investigations.

Science.gov (United States)

Manni, E; Bortolami, R; Pettorossi, V E; Lucchi, M L; Callegari, E

1978-01-01

The main aim of the present study was to localize with electrophysiological techniques the central projections and terminations of the aberrant trigeminal fibres contained in the oculomotor nerve of the lamb. After severing a trigeminal root, single-shock electrical stimulation of the trigeminal axons present in the central stump of the ipsilateral oculomotor nerve evoked field potentials in the area of, i) the subnucleus gelatinosus of the nucleus caudalis trigemini at the level of C1-C2; ii) the main sensory trigeminal nucleus; iii) the descending trigeminal nucleus and tract; iv) the adjacent reticular formation. Units whose discharge rate was influenced by such a stimulation were also found in the same territories. These regions actually exhibited degenerations after cutting an oculomotor nerve. We conclude, therefore, that the trigeminal fibres which leave the Vth nerve at the level of the cavernous sinus and enter the brain stem through the IIIrd nerve, end in the same structures which receive the terminations of the afferent fibres entering the brain stem through the sensory trigeminal root.

TRPM8 mechanism of autonomic nerve response to cold in respiratory airway

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Wang Cong-Yi

2008-06-01

Full Text Available Abstract Breathing cold air without proper temperature exchange can induce strong respiratory autonomic responses including cough, airway constriction and mucosal secretion, and can exacerbate existing asthma conditions and even directly trigger an asthma attack. Vagal afferent fiber is thought to be involved in the cold-induced respiratory responses through autonomic nerve reflex. However, molecular mechanisms by which vagal afferent fibers are excited by cold remain unknown. Using retrograde labeling, immunostaining, calcium imaging, and electrophysiological recordings, here we show that a subpopulation of airway vagal afferent nerves express TRPM8 receptors and that activation of TRPM8 receptors by cold excites these airway autonomic nerves. Thus activation of TRPM8 receptors may provoke autonomic nerve reflex to increase airway resistance. This putative autonomic response may be associated with cold-induced exacerbation of asthma and other pulmonary disorders, making TRPM8 receptors a possible target for prevention of cold-associated respiratory disorders.

[Myofibroblasts and afferent signalling in the urinary bladder. A concept].

Science.gov (United States)

Neuhaus, J; Scholler, U; Freick, K; Schwalenberg, T; Heinrich, M; Horn, L C; Stolzenburg, J U

2008-09-01

Afferent signal transduction in the urinary bladder is still not clearly understood. An increasing body of evidence supports the view of complex interactions between urothelium, suburothelial myofibroblasts, and sensory nerves. Bladder tissue from tumour patients was used in this study. Methods included confocal immunofluorescence, polymerase chain reaction, calcium imaging, and fluorescence recovery after photobleaching (FRAP).Myofibroblasts express muscarinic and purinergic receptors. They show constitutive spontaneous activity in calcium imaging, which completely depends on extracellular calcium. Stimulation with carbachol and ATP-evoked intracellular calcium transients also depend on extracellular calcium. The intensive coupling between the cells is significantly diminished by incubation with TGF-beta 1. Myofibroblasts form an important cellular element within the afferent signalling of the urinary bladder. They possess all features required to take part in the complex interactions with urothelial cells and sensory nerves. Modulation of their function by cytokines may provide a pathomechanism for bladder dysfunction.

Ablation of capsaicin sensitive afferent nerves impairs defence but not rapid repair of rat gastric mucosa.

Science.gov (United States)

Pabst, M A; Schöninkle, E; Holzer, P

1993-07-01

Capsaicin sensitive afferent neurones have previously been reported to play a part in gastric mucosal protection. The aim of this study was to investigate whether these nociceptive neurones strengthen mucosal defence against injury or promote rapid repair of the damaged mucosa, or both. This hypothesis was examined in anaesthetised rats whose stomachs were perfused with ethanol (25 or 50% in saline, wt/wt) for 30 minutes. The gastric mucosa was inspected 0 and 180 minutes after ethanol had been given at the macroscopic, light, and scanning electron microscopic level. Rapid repair of the ethanol injured gastric mucosa (reduction of deep injury, partial re-epithelialisation of the denuded surface) took place in rats anaesthetised with phenobarbital, but not in those anaesthetised with urethane. Afferent nerve ablation as a result of treating rats with a neurotoxic dose of capsaicin before the experiment significantly aggravated ethanol induced damage as shown by an increase in the area and depth of mucosal erosions. Rapid repair of the injured mucosa, however, as seen in rats anesthetised with phenobarbital 180 minutes after ethanol was given, was similar in capsaicin and vehicle pretreated animals. Ablation of capsaicin sensitive afferent neurones was verified by a depletion of calcitonin gene related peptide from the gastric corpus wall. These findings indicate that nociceptive neurones control mechanisms of defence against acute injury but are not required for rapid repair of injured mucosa.

Tonic aortic depressor nerve stimulation does not impede baroreflex dynamic characteristics concomitantly mediated by the stimulated nerve.

Science.gov (United States)

Kawada, Toru; Turner, Michael J; Shimizu, Shuji; Kamiya, Atsunori; Shishido, Toshiaki; Sugimachi, Masaru

2018-03-01

Although electrical activation of the carotid sinus baroreflex (baroreflex activation therapy) is being explored as a device therapy for resistant hypertension, possible effects on baroreflex dynamic characteristics of interaction between electrical stimulation and pressure inputs are not fully elucidated. To examine whether the electrical stimulation of the baroreceptor afferent nerve impedes normal short-term arterial pressure (AP) regulation mediated by the stimulated nerve, we electrically stimulated the right aortic depressor nerve (ADN) while estimating the baroreflex dynamic characteristics by imposing pressure inputs to the isolated baroreceptor region of the right ADN in nine anesthetized rats. A Gaussian white noise signal with a mean of 120 mmHg and standard deviation of 20 mmHg was used for the pressure perturbation. A tonic ADN stimulation (2 or 5 Hz, 10 V, 0.1-ms pulse width) decreased mean sympathetic nerve activity (367.0 ± 70.9 vs. 247.3 ± 47.2 arbitrary units, P ADN stimulation did not affect the slope of dynamic gain in the neural arc transfer function from pressure perturbation to sympathetic nerve activity (16.9 ± 1.0 vs. 14.7 ± 1.6 dB/decade, not significant). These results indicate that electrical stimulation of the baroreceptor afferent nerve does not significantly impede the dynamic characteristics of the arterial baroreflex concomitantly mediated by the stimulated nerve. Short-term AP regulation by the arterial baroreflex may be preserved during the baroreflex activation therapy.

Effect of superficial radial nerve stimulation on the activity of nigro-striatal dopaminergic neurons in the cat: role of cutaneous sensory input

International Nuclear Information System (INIS)

Nieoullon, A.; Dusticier, N.

1982-01-01

The release of 3 H-dopamine (DA) continuously synthesized from 3 H-thyrosine was measured in the caudate nucleus (CN) and in the substantia nigra (SN) in both sides of the brain during electrical stimulation of the superficial radial nerve in cats lightly anaesthetized with halothane. Use of appropriate electrophysiologically controlled stimulation led to selective activation of low threshold afferent fibers whereas high stimulation activated all cutaneous afferents. Results showed that low threshold fiber activation induced a decreased dopaminergic activity in CN contralateral to nerve stimulation and a concomitant increase in dopaminergic activity on the ipsilateral side. Stimulation of group I and threshold stimulation of group II afferent fibers induced changes in the release of 3 H-DA mainly on the contralateral CN and SN and in the ipsilateral CN. High stimulation was followed by a general increase of the neurotransmitter release in the four structures. This shows that the nigro-striatal dopaminergic neurons are mainly-if not exclusively-controlled by cutaneous sensory inputs. This control, non-specific when high threshold cutaneous fibers are also activated. Such activations could contribute to restablish sufficient release of DA when the dopaminergic function is impaired as in Parkinson's disease. (Author)

Effect of superficial radial nerve stimulation on the activity of nigro-striatal dopaminergic neurons in the cat: role of cutaneous sensory input

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Nieoullon, A; Dusticier, N [Centre National de la Recherche Scientifique, 13 - Marseille (France). Inst. de Neurophysiologie et Psychophysiologie

1982-01-01

The release of /sup 3/H-dopamine (DA) continuously synthesized from /sup 3/H-thyrosine was measured in the caudate nucleus (CN) and in the substantia nigra (SN) in both sides of the brain during electrical stimulation of the superficial radial nerve in cats lightly anaesthetized with halothane. Use of appropriate electrophysiologically controlled stimulation led to selective activation of low threshold afferent fibers whereas high stimulation activated all cutaneous afferents. Results showed that low threshold fiber activation induced a decreased dopaminergic activity in CN contralateral to nerve stimulation and a concomitant increase in dopaminergic activity on the ipsilateral side. Stimulation of group I and threshold stimulation of group II afferent fibers induced changes in the release of /sup 3/H-DA mainly on the contralateral CN and SN and in the ipsilateral CN. High stimulation was followed by a general increase of the neurotransmitter release in the four structures. This shows that the nigro-striatal dopaminergic neurons are mainly-if not exclusively-controlled by cutaneous sensory inputs. This control, non-specific when high threshold cutaneous fibers are also activated. Such activations could contribute to reestablish sufficient release of DA when the dopaminergic function is impaired as in Parkinson's disease.

Merkel cells transduce and encode tactile stimuli to drive Aβ-afferent impulses

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Ikeda, Ryo; Cha, Myeounghoon; Ling, Jennifer; Jia, Zhanfeng; Coyle, Dennis; Gu, Jianguo G.

2014-01-01

SUMMARY Sensory systems for detecting tactile stimuli have evolved from touch-sensing nerves in invertebrates to complicated tactile end-organs in mammals. Merkel discs are tactile end-organs consisting of Merkel cells and Aβ-afferent nerve endings, and are localized in fingertips, whisker hair follicles and other touch-sensitive spots. Merkel discs transduce touch into slowly adapting impulses to enable tactile discrimination, but their transduction and encoding mechanisms remain unknown. Using rat whisker hair follicles, we show that Merkel cells rather than Aβ-afferent nerve endings are primary sites of tactile transduction, and identify the Piezo2 ion channel as the Merkel cell mechanical transducer. Piezo2 transduces tactile stimuli into Ca2+-action potentials in Merkel cells, which drive Aβ-afferent nerve endings to fire slowly adapting impulses. We further demonstrate that Piezo2 and Ca2+-action potentials in Merkel cells are required for behavioral tactile responses. Our findings provide insights into how tactile end-organs function and have clinical implications for tactile dysfunctions. PMID:24746027

Patterns of motor activity in the isolated nerve cord of the octopus arm.

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Gutfreund, Yoram; Matzner, Henry; Flash, Tamar; Hochner, Binyamin

2006-12-01

The extremely flexible octopus arm provides a unique opportunity for studying movement control in a highly redundant motor system. We describe a novel preparation that allows analysis of the peripheral nervous system of the octopus arm and its interaction with the muscular and mechanosensory elements of the arm's intrinsic muscular system. First we examined the synaptic responses in muscle fibers to identify the motor pathways from the axial nerve cord of the arm to the surrounding musculature. We show that the motor axons project to the muscles via nerve roots originating laterally from the arm nerve cord. The motor field of each nerve is limited to the region where the nerve enters the arm musculature. The same roots also carry afferent mechanosensory information from the intrinsic muscle to the axial nerve cord. Next, we characterized the pattern of activity generated in the dorsal roots by electrically stimulating the axial nerve cord. The evoked activity, although far reaching and long lasting, cannot alone account for the arm extension movements generated by similar electrical stimulation. The mismatch between patterns of activity in the isolated cord and in an intact arm may stem from the involvement of mechanosensory feedback in natural arm extension.

Hericium erinaceus (Bull.: Fr.) Pers., a medicinal mushroom, activates peripheral nerve regeneration.

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Wong, Kah-Hui; Kanagasabapathy, Gowri; Naidu, Murali; David, Pamela; Sabaratnam, Vikineswary

2016-10-01

To study the ability of aqueous extract of Hericium erinaceus mushroom in the treatment of nerve injury following peroneal nerve crush in Sprague-Dawley rats. Aqueous extract of Hericium erinaceus was given by daily oral administration following peroneal nerve crush injury in Sprague-Dawley rats. The expression of protein kinase B (Akt) and mitogen-activated protein kinase (MAPK) signaling pathways; and c-Jun and c-Fos genes were studied in dorsal root ganglia (DRG) whereas the activity of protein synthesis was assessed in peroneal nerves by immunohistochemical method. Peripheral nerve injury leads to changes at the axonal site of injury and remotely located DRG containing cell bodies of sensory afferent neurons. Immunofluorescence studies showed that DRG neurons ipsilateral to the crush injury in rats of treated groups expressed higher immunoreactivities for Akt, MAPK, c-Jun and c-Fos as compared with negative control group (P <0.05). The intensity of nuclear ribonucleoprotein in the distal segments of crushed nerves of treated groups was significantly higher than in the negative control group (P <0.05). H. erinaceus is capable of promoting peripheral nerve regeneration after injury. Potential signaling pathways include Akt, MAPK, c-Jun, and c-Fos, and protein synthesis have been shown to be involved in its action.

Chronic implantation of cuff electrodes on the pelvic nerve in rats is well tolerated and does not compromise afferent or efferent fibre functionality

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Crook, J. J.; Brouillard, C. B. J.; Irazoqui, P. P.; Lovick, T. A.

2018-04-01

Objective. Neuromodulation of autonomic nerve activity to regulate physiological processes is an emerging field. Vagal stimulation has received most attention whereas the potential of modulate visceral function by targeting autonomic nerves within the abdominal cavity remains under-exploited. Surgery to locate intra-abdominal targets is inherently more stressful than for peripheral nerves. Electrode leads risk becoming entrapped by intestines and loss of functionality in the nerve-target organ connection could result from electrode migration or twisting. Since nociceptor afferents are intermingled with similar-sized visceral autonomic fibres, stimulation may induce pain. In anaesthetised rats high frequency stimulation of the pelvic nerve can suppress urinary voiding but it is not known how conscious animals would react to this procedure. Our objective therefore was to determine how rats tolerated chronic implantation of cuff electrodes on the pelvic nerve, whether nerve stimulation would be aversive and whether nerve-bladder functionality would be compromised. Approach. We carried out a preliminary de-risking study to investigate how conscious rats tolerated chronic implantation of electrodes on the pelvic nerve, their responsiveness to intermittent high frequency stimulation and whether functionality of the nerve-bladder connection became compromised. Main results. Implantation of cuff electrodes was well-tolerated. The normal diurnal pattern of urinary voiding was not disrupted. Pelvic nerve stimulation (up to 4 mA, 3 kHz) for 30 min periods evoked mild alerting at stimulus onset but no signs of pain. Stimulation evoked a modest (nerve temperature but the functional integrity of the nerve-bladder connection, reflected by contraction of the detrusor muscle in response to 10 Hz nerve stimulation, was not compromised. Significance. Chronic implantation of cuff electrodes on the pelvic nerve was found to be a well-tolerated procedure in rats and high frequency

Capsaicin-sensitive intestinal mucosal afferent mechanism and body fat distribution.

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Leung, Felix W

2008-07-04

This report summarizes clinical and experimental data in support of the hypothesis that capsaicin-sensitive intestinal mucosal afferent mechanism plays a role in regulating body fat distribution. Epidemiological data have revealed that the consumption of foods containing capsaicin is associated with a lower prevalence of obesity. Rural Thai people consume diets containing 0.014% capsaicin. Rodents fed a diet containing 0.014% capsaicin showed no change in caloric intake but a significant 24% and 29% reduction in the visceral (peri-renal) fat weight. Increase in intestinal blood flow facilitates nutrient energy absorption and decrease in adipose tissue blood flow facilitates storage of nutrient energy in adipose tissue. Stimulation of intestinal mucosal afferent nerves increases intestinal blood flow, but decreases visceral (mesenteric) adipost tissue blood flow. In in vitro cell studies capsaicin has a direct effect on adipocytes. Intravenous capsaicin produces measurable plasma level and subcutaneous capsaicin retards accumulation of adipose tissue. The data on a direct effect of oral capsaicin on adipose tissue at remote sites, however, are conflicting. Capsaicin absorbed from the gut lumen is almost completely metabolized before reaching the general circulation. Oral capsaicin significantly increases transient receptor potential vanilloid type-1 (TRPV1) channel expression as well as TRPV1 messenger ribonucleic acid (mRNA) in visceral adipose tissue. In TRPV1 knockout mice on a high fat diet the body weight was not significantly different in the absence or presence of oral capsaicin. In rodent experiments, daily intragastric administration of capsaicin for two weeks led to defunctionalization of intestinal mucosal afferent nerves, manifested by loss of acute mucosal capsaicin-induced effects; but not the corneal afferent nerves, with preservation of the paw wiping reflex of the eye exposed briefly to dilute capsaicin. The latter indicated the absence of an oral

The morphological substrate for Renal Denervation: Nerve distribution patterns and parasympathetic nerves. A post-mortem histological study.

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van Amsterdam, Wouter A C; Blankestijn, Peter J; Goldschmeding, Roel; Bleys, Ronald L A W

2016-03-01

Renal Denervation as a possible treatment for hypertension has been studied extensively, but knowledge on the distribution of nerves surrounding the renal artery is still incomplete. While sympathetic and sensory nerves have been demonstrated, there is no mention of the presence of parasympathetic nerve fibers. To provide a description of the distribution patterns of the renal nerves in man, and, in addition, provide a detailed representation of the relative contribution of the sympathetic, parasympathetic and afferent divisions of the autonomic nervous system. Renal arteries of human cadavers were each divided into four longitudinal segments and immunohistochemically stained with specific markers for afferent, parasympathetic and sympathetic nerves. Nerve fibers were semi-automatically quantified by computerized image analysis, and expressed as cross-sectional area relative to the distance to the lumen. A total of 3372 nerve segments were identified in 8 arteries of 7 cadavers. Sympathetic, parasympathetic and afferent nerves contributed for 73.5% (95% CI: 65.4-81.5%), 17.9% (10.7-25.1%) and 8.7% (5.0-12.3%) of the total cross-sectional nerve area, respectively. Nerves are closer to the lumen in more distal segments and larger bundles that presumably innervate the kidney lie at 1-3.5mm distance from the lumen. The tissue-penetration depth of the ablation required to destroy 50% of the nerve fibers is 2.37 mm in the proximal segment and 1.78 mm in the most distal segments. Sympathetic, parasympathetic and afferent nerves exist in the vicinity of the renal artery. The results warrant further investigation of the role of the parasympathetic nervous system on renal physiology, and may contribute to refinement of the procedure by focusing the ablation on the most distal segment. Copyright © 2015 Elsevier GmbH. All rights reserved.

Cervical vagus nerve stimulation augments spontaneous discharge in second- and higher-order sensory neurons in the rat nucleus of the solitary tract.

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Beaumont, Eric; Campbell, Regenia P; Andresen, Michael C; Scofield, Stephanie; Singh, Krishna; Libbus, Imad; KenKnight, Bruce H; Snyder, Logan; Cantrell, Nathan

2017-08-01

Vagus nerve stimulation (VNS) currently treats patients with drug-resistant epilepsy, depression, and heart failure. The mild intensities used in chronic VNS suggest that primary visceral afferents and central nervous system activation are involved. Here, we measured the activity of neurons in the nucleus of the solitary tract (NTS) in anesthetized rats using clinically styled VNS. Our chief findings indicate that VNS at threshold bradycardic intensity activated NTS neuron discharge in one-third of NTS neurons. This VNS directly activated only myelinated vagal afferents projecting to second-order NTS neurons. Most VNS-induced activity in NTS, however, was unsynchronized to vagal stimuli. Thus, VNS activated unsynchronized activity in NTS neurons that were second order to vagal afferent C-fibers as well as higher-order NTS neurons only polysynaptically activated by the vagus. Overall, cardiovascular-sensitive and -insensitive NTS neurons were similarly activated by VNS: 3/4 neurons with monosynaptic vagal A-fiber afferents, 6/42 neurons with monosynaptic vagal C-fiber afferents, and 16/21 polysynaptic NTS neurons. Provocatively, vagal A-fibers indirectly activated C-fiber neurons during VNS. Elevated spontaneous spiking was quantitatively much higher than synchronized activity and extended well into the periods of nonstimulation. Surprisingly, many polysynaptic NTS neurons responded to half the bradycardic intensity used in clinical studies, indicating that a subset of myelinated vagal afferents is sufficient to evoke VNS indirect activation. Our study uncovered a myelinated vagal afferent drive that indirectly activates NTS neurons and thus central pathways beyond NTS and support reconsideration of brain contributions of vagal afferents underpinning of therapeutic impacts. NEW & NOTEWORTHY Acute vagus nerve stimulation elevated activity in neurons located in the medial nucleus of the solitary tract. Such stimuli directly activated only myelinated vagal afferents

Central projections and entries of capsaicin-sensitive muscle afferents.

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Della Torre, G; Lucchi, M L; Brunetti, O; Pettorossi, V E; Clavenzani, P; Bortolami, R

1996-03-25

The entry pathway and central distribution of A delta and C muscle afferents within the central nervous system (CNS) were investigated by combining electron microscopy and electrophysiological analysis after intramuscular injection of capsaicin. The drug was injected into the rat lateral gastrocnemius (LG) and extraocular (EO) muscles. The compound action potentials of LG nerve and the evoked field potentials recorded in semilunar ganglion showed an immediate and permanent reduction in A delta and C components. The morphological data revealed degenerating unmyelinated axons and terminals in the inner sublamina II and in the border of laminae I-II of the dorsal horn at L4-L5 and C1-C2 (subnucleus caudalis trigemini) spinal cord segments. Most degenerating terminals were the central bouton (C) of type I and II synaptic glomeruli. Furthermore, degenerating peripheral axonal endings (V2) presynaptic to normal C were found. Since V2 were previously found degenerated after cutting the oculomotor nerve (ON) or L4 ventral root, we conclude that some A delta and C afferents from LG and EO muscles entering the CNS by ON or ventral roots make axoaxonic synapses on other primary afferents to promote an afferent control of sensory input.

Spinal cord stimulation paresthesia and activity of primary afferents.

Science.gov (United States)

North, Richard B; Streelman, Karen; Rowland, Lance; Foreman, P Jay

2012-10-01

A patient with failed back surgery syndrome reported paresthesia in his hands and arms during a spinal cord stimulation (SCS) screening trial with a low thoracic electrode. The patient's severe thoracic stenosis necessitated general anesthesia for simultaneous decompressive laminectomy and SCS implantation for chronic use. Use of general anesthesia gave the authors the opportunity to characterize the patient's unusual distribution of paresthesia. During SCS implantation, they recorded SCS-evoked antidromic potentials at physiologically relevant amplitudes in the legs to guide electrode placement and in the arms as controls. Stimulation of the dorsal columns at T-8 evoked potentials in the legs (common peroneal nerves) and at similar thresholds, consistent with the sensation of paresthesia in the arms, in the right ulnar nerve. The authors' electrophysiological observations support observations by neuroanatomical specialists that primary afferents can descend several (in this case, at least 8) vertebral segments in the spinal cord before synapsing or ascending. This report thus confirms a physiological basis for unusual paresthesia distribution associated with thoracic SCS.

Gait phase detection from sciatic nerve recordings in functional electrical stimulation systems for foot drop correction

International Nuclear Information System (INIS)

Chu, Jun-Uk; Song, Kang-Il; Han, Sungmin; Suh, Jun-Kyo Francis; Choi, Kuiwon; Youn, Inchan; Lee, Soo Hyun; Kang, Ji Yoon; Hwang, Dosik

2013-01-01

Cutaneous afferent activities recorded by a nerve cuff electrode have been used to detect the stance phase in a functional electrical stimulation system for foot drop correction. However, the implantation procedure was difficult, as the cuff electrode had to be located on the distal branches of a multi-fascicular nerve to exclude muscle afferent and efferent activities. This paper proposes a new gait phase detection scheme that can be applied to a proximal nerve root that includes cutaneous afferent fibers as well as muscle afferent and efferent fibers. To test the feasibility of this scheme, electroneurogram (ENG) signals were measured from the rat sciatic nerve during treadmill walking at several speeds, and the signal properties of the sciatic nerve were analyzed for a comparison with kinematic data from the ankle joint. On the basis of these experiments, a wavelet packet transform was tested to define a feature vector from the sciatic ENG signals according to the gait phases. We also propose a Gaussian mixture model (GMM) classifier and investigate whether it could be used successfully to discriminate feature vectors into the stance and swing phases. In spite of no significant differences in the rectified bin-integrated values between the stance and swing phases, the sciatic ENG signals could be reliably classified using the proposed wavelet packet transform and GMM classification methods. (paper)

Afferent control of central pattern generators: experimental analysis of locomotion in the decerebrate cat.

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Baev, K V; Esipenko, V B; Shimansky YuP

1991-01-01

Changes in the motor activity of the spinal locomotor generator evoked by tonic and phasic peripheral afferent signals during fictitious locomotion of both slow and fast rhythms were analysed in the cat. The tonic afferent inflow was conditioned by the position of the hindlimb. The phasic afferent signals were imitated by electrical stimulation of hindlimb nerves. The correlation between the kinematics of hindlimb locomotor movement and sensory inflow was investigated during actual locomotion. Reliable correlations between motor activity parameters during fictitious locomotion were revealed in cases of both slow and fast "locomotor" rhythms. The main difference between these cases was that correlations "duration-intensity" were positive in the first and negative in the second case. The functional role of "locomotor" pattern dependence on tonic sensory inflow consisted of providing stability for planting the hindlimb on the ground. For any investigated afferent input the phase moments in the "locomotor" cycle were found, in which an afferent signal caused no rearrangement in locomotor generator activity. These moments corresponded to the transitions between "flexion" and "extension" phases and to the bursts of integral afferent activity observed during real locomotion. The data obtained are compared with the results previously described for the scratching generator. The character of changes in "locomotor" activity in response to tonic and phasic sensory signals was similar to that of such changes in "scratching" rhythm in the case of fast "locomotion". Intensification of the "flexion" phase caused by phasic high-intensity stimulation of cutaneous afferents during low "locomotor" rhythm was changed to inhibition (such as observed during "scratching") when this rhythm was fast. It is concluded that the main regularities of peripheral afferent control for both the locomotor and scratching generators are the same. Moreover, these central pattern generators are just

Afferent activity to necklace glomeruli is dependent on external stimuli

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Munger Steven D

2009-03-01

Full Text Available Abstract Background The main olfactory epithelium (MOE is a complex organ containing several functionally distinct subpopulations of sensory neurons. One such subpopulation is distinguished by its expression of the guanylyl cyclase GC-D. The axons of GC-D-expressing (GC-D+ neurons innervate 9–15 "necklace" glomeruli encircling the caudal main olfactory bulb (MOB. Chemosensory stimuli for GC-D+ neurons include two natriuretic peptides, uroguanylin and guanylin, and CO2. However, the biologically-relevant source of these chemostimuli is unclear: uroguanylin is both excreted in urine, a rich source of olfactory stimuli for rodents, and expressed in human nasal epithelium; CO2 is present in both inspired and expired air. Findings To determine whether the principal source of chemostimuli for GC-D+ neurons is external or internal to the nose, we assessed the consequences of removing external chemostimuli for afferent activity to the necklace glomeruli. To do so, we performed unilateral naris occlusions in Gucy2d-Mapt-lacZ +/- mice [which express a β-galactosidase (β-gal reporter specifically in GC-D+ neurons] followed by immunohistochemistry for β-gal and a glomerular marker of afferent activity, tyrosine hydroxylase (TH. We observed a dramatic decrease in TH immunostaining, consistent with reduced or absent afferent activity, in both necklace and non-necklace glomeruli ipsilateral to the occluded naris. Conclusion Like other MOB glomeruli, necklace glomeruli exhibit a large decrease in afferent activity upon removal of external stimuli. Thus, we conclude that activity in GC-D+ neurons, which specifically innervate necklace glomeruli, is not dependent on internal stimuli. Instead, GC-D+ neurons, like other OSNs in the MOE, primarily sense the external world.

Cortical Presynaptic Control of Dorsal Horn C–Afferents in the Rat

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Martínez-Lorenzana, Guadalupe; Condés-Lara, Miguel; Rojas-Piloni, Gerardo

2013-01-01

Lamina 5 sensorimotor cortex pyramidal neurons project to the spinal cord, participating in the modulation of several modalities of information transmission. A well-studied mechanism by which the corticospinal projection modulates sensory information is primary afferent depolarization, which has been characterized in fast muscular and cutaneous, but not in slow-conducting nociceptive skin afferents. Here we investigated whether the inhibition of nociceptive sensory information, produced by activation of the sensorimotor cortex, involves a direct presynaptic modulation of C primary afferents. In anaesthetized male Wistar rats, we analyzed the effects of sensorimotor cortex activation on post tetanic potentiation (PTP) and the paired pulse ratio (PPR) of dorsal horn field potentials evoked by C–fiber stimulation in the sural (SU) and sciatic (SC) nerves. We also explored the time course of the excitability changes in nociceptive afferents produced by cortical stimulation. We observed that the development of PTP was completely blocked when C-fiber tetanic stimulation was paired with cortex stimulation. In addition, sensorimotor cortex activation by topical administration of bicuculline (BIC) produced a reduction in the amplitude of C–fiber responses, as well as an increase in the PPR. Furthermore, increases in the intraspinal excitability of slow-conducting fiber terminals, produced by sensorimotor cortex stimulation, were indicative of primary afferent depolarization. Topical administration of BIC in the spinal cord blocked the inhibition of C–fiber neuronal responses produced by cortical stimulation. Dorsal horn neurons responding to sensorimotor cortex stimulation also exhibited a peripheral receptive field and responded to stimulation of fast cutaneous myelinated fibers. Our results suggest that corticospinal inhibition of nociceptive responses is due in part to a modulation of the excitability of primary C–fibers by means of GABAergic inhibitory

One-tone suppression in the frog auditory nerve

DEFF Research Database (Denmark)

Christensen-Dalsgaard, J; Jørgensen, M B

1996-01-01

Sixty-seven fibers of a sample of 401 in the auditory nerve of grassfrogs (Rana temporaria) showed one-tone suppression, i.e., their spontaneous activity was suppressed by tones. All fibers were afferents from the amphibian papilla with best frequencies between 100 and 400 Hz. Best suppression...

Chicken (Gallus domesticus) inner ear afferents

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Hara, H.; Chen, X.; Hartsfield, J. F.; Hara, J.; Martin, D.; Fermin, C. D.

1998-01-01

Neurons from the vestibular (VG) and the statoacoustic (SAG) ganglion of the chick (Gallus domesticus) were evaluated histologically and morphometrically. Embryos at stages 34 (E8 days), 39 (E13 days) and 44 (E18 days) were sacrificed and temporal bones microdissected. Specimens were embedded in JB-4 methacrylate plastic, and stained with a mixture of 0.2% toluidine blue (TB) and 0.1% basic Fuschin in 25% ethanol or with a mixture of 2% TB and 1% paraphenylenediamine (PDA) for axon and myelin measurement study. Images of the VIIIth nerve were produced by a V150 (R) color imaging system and the contour of 200-300 neuronal bodies (perikarya) was traced directly on a video screen with a mouse in real time. The cross-sectional area of VG perikarya was 67.29 micrometers2 at stage 34 (E8), 128.46 micrometers2 at stage 39 (E13) and 275.85 micrometers2 at stage 44 (E18). The cross-sectional area of SAG perikarya was 62.44 micrometers2 at stage 34 (E8), 102.05 micrometers2 at stage 39 (E13) and 165.02 micrometers2 at stage 44 (E18). A significant cross-sectional area increase of the VG perikarya between stage 39 (E13) and stage 44 (E18) was determined. We randomly measured the cross-sectional area of myelin and axoplasm of hatchling afferent nerves, and found a correspondence between axoplasmic and myelin cross-sectional area in the utricular, saccular and semicircular canal nerve branches of the nerve. The results suggest that the period between stage 34 (E8) and 39 (E13) is a critical period for afferent neuronal development. Physiological and behavioral vestibular properties of developing and maturing hatchlings may change accordingly. The results compliment previous work by other investigators and provide valuable anatomical measures useful to correlate physiological data obtained from stimulation of the whole nerve or its parts.

Neuronal thresholds and choice-related activity of otolith afferent fibers during heading perception.

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Yu, Xiong-jie; Dickman, J David; DeAngelis, Gregory C; Angelaki, Dora E

2015-05-19

How activity of sensory neurons leads to perceptual decisions remains a challenge to understand. Correlations between choices and single neuron firing rates have been found early in vestibular processing, in the brainstem and cerebellum. To investigate the origins of choice-related activity, we have recorded from otolith afferent fibers while animals performed a fine heading discrimination task. We find that afferent fibers have similar discrimination thresholds as central cells, and the most sensitive fibers have thresholds that are only twofold or threefold greater than perceptual thresholds. Unlike brainstem and cerebellar nuclei neurons, spike counts from afferent fibers do not exhibit trial-by-trial correlations with perceptual decisions. This finding may reflect the fact that otolith afferent responses are poorly suited for driving heading perception because they fail to discriminate self-motion from changes in orientation relative to gravity. Alternatively, if choice probabilities reflect top-down inference signals, they are not relayed to the vestibular periphery.

Does metabosensitive afferent fibers activity differ from slow- and fast-twitch muscles?

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Caron, Guillaume; Decherchi, Patrick; Marqueste, Tanguy

2015-09-01

This study was designed to investigate the metabosensitive afferent response evoked by electrically induced fatigue (EIF), lactic acid (LA) and potassium chloride (KCl) in three muscle types. We recorded the activity of groups III-IV afferents originating from soleus, gastrocnemius and tibialis anterior muscles. Our data showed a same pattern of response in the three muscles after chemical injections, i.e., a bell curve with maximal discharge rate at 1 mM for LA injections and a linear relationship between KCl concentrations and the afferent discharge rate. Furthermore, a stronger response was recorded after EIF in the gastrocnemius muscle compared to the two other muscles. The change in afferent discharge after 1 mM LA injection was higher for the gastrocnemius muscle compared to the response obtained with the corresponding concentration applied in the two other muscles, whereas changes to KCl injections did not dramatically differ between the three muscles. We conclude that anatomical (mass, phenotype, vascularization, receptor and afferent density…) and functional (flexor vs. extensor) differences between muscles could explain the amplitude of these responses.

Novel Neurostimulation of Autonomic Pelvic Nerves Overcomes Bladder-Sphincter Dyssynergia

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Peh, Wendy Yen Xian; Mogan, Roshini; Thow, Xin Yuan; Chua, Soo Min; Rusly, Astrid; Thakor, Nitish V.; Yen, Shih-Cheng

2018-01-01

The disruption of coordination between smooth muscle contraction in the bladder and the relaxation of the external urethral sphincter (EUS) striated muscle is a common issue in dysfunctional bladders. It is a significant challenge to overcome for neuromodulation approaches to restore bladder control. Bladder-sphincter dyssynergia leads to undesirably high bladder pressures, and poor voiding outcomes, which can pose life-threatening secondary complications. Mixed pelvic nerves are potential peripheral targets for stimulation to treat dysfunctional bladders, but typical electrical stimulation of pelvic nerves activates both the parasympathetic efferent pathway to excite the bladder, as well as the sensory afferent pathway that causes unwanted sphincter contractions. Thus, a novel pelvic nerve stimulation paradigm is required. In anesthetized female rats, we combined a low frequency (10 Hz) stimulation to evoke bladder contraction, and a more proximal 20 kHz stimulation of the pelvic nerve to block afferent activation, in order to produce micturition with reduced bladder-sphincter dyssynergia. Increasing the phase width of low frequency stimulation from 150 to 300 μs alone was able to improve voiding outcome significantly. However, low frequency stimulation of pelvic nerves alone evoked short latency (19.9–20.5 ms) dyssynergic EUS responses, which were abolished with a non-reversible proximal central pelvic nerve cut. We demonstrated that a proximal 20 kHz stimulation of pelvic nerves generated brief onset effects at lower current amplitudes, and was able to either partially or fully block the short latency EUS responses depending on the ratio of the blocking to stimulation current. Our results indicate that ratios >10 increased the efficacy of blocking EUS contractions. Importantly, we also demonstrated for the first time that this combined low and high frequency stimulation approach produced graded control of the bladder, while reversibly blocking afferent

Anatomy and physiology of phrenic afferent neurons.

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Nair, Jayakrishnan; Streeter, Kristi A; Turner, Sara M F; Sunshine, Michael D; Bolser, Donald C; Fox, Emily J; Davenport, Paul W; Fuller, David D

2017-12-01

Large-diameter myelinated phrenic afferents discharge in phase with diaphragm contraction, and smaller diameter fibers discharge across the respiratory cycle. In this article, we review the phrenic afferent literature and highlight areas in need of further study. We conclude that 1 ) activation of both myelinated and nonmyelinated phrenic sensory afferents can influence respiratory motor output on a breath-by-breath basis; 2 ) the relative impact of phrenic afferents substantially increases with diaphragm work and fatigue; 3 ) activation of phrenic afferents has a powerful impact on sympathetic motor outflow, and 4 ) phrenic afferents contribute to diaphragm somatosensation and the conscious perception of breathing. Much remains to be learned regarding the spinal and supraspinal distribution and synaptic contacts of myelinated and nonmyelinated phrenic afferents. Similarly, very little is known regarding the potential role of phrenic afferent neurons in triggering or modulating expression of respiratory neuroplasticity. Copyright © 2017 the American Physiological Society.

Withdrawal and restoration of central vagal afferents within the dorsal vagal complex following subdiaphragmatic vagotomy.

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Peters, James H; Gallaher, Zachary R; Ryu, Vitaly; Czaja, Krzysztof

2013-10-15

Vagotomy, a severing of the peripheral axons of the vagus nerve, has been extensively utilized to determine the role of vagal afferents in viscerosensory signaling. Vagotomy is also an unavoidable component of some bariatric surgeries. Although it is known that peripheral axons of the vagus nerve degenerate and then regenerate to a limited extent following vagotomy, very little is known about the response of central vagal afferents in the dorsal vagal complex to this type of damage. We tested the hypothesis that vagotomy results in the transient withdrawal of central vagal afferent terminals from their primary central target, the nucleus of the solitary tract (NTS). Sprague-Dawley rats underwent bilateral subdiaphragmatic vagotomy and were sacrificed 10, 30, or 60 days later. Plastic changes in vagal afferent fibers and synapses were investigated at the morphological and functional levels by using a combination of an anterograde tracer, synapse-specific markers, and patch-clamp electrophysiology in horizontal brain sections. Morphological data revealed that numbers of vagal afferent fibers and synapses in the NTS were significantly reduced 10 days following vagotomy and were restored to control levels by 30 days and 60 days, respectively. Electrophysiology revealed transient decreases in spontaneous glutamate release, glutamate release probability, and the number of primary afferent inputs. Our results demonstrate that subdiaphragmatic vagotomy triggers transient withdrawal and remodeling of central vagal afferent terminals in the NTS. The observed vagotomy-induced plasticity within this key feeding center of the brain may be partially responsible for the response of bariatric patients following gastric bypass surgery. Copyright © 2013 Wiley Periodicals, Inc.

Afferent Innervation, Muscle Spindles, and Contractures Following Neonatal Brachial Plexus Injury in a Mouse Model.

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Nikolaou, Sia; Hu, Liangjun; Cornwall, Roger

2015-10-01

We used an established mouse model of elbow flexion contracture after neonatal brachial plexus injury (NBPI) to test the hypothesis that preservation of afferent innervation protects against contractures and is associated with preservation of muscle spindles and ErbB signaling. A model of preganglionic C5 through C7 NBPI was first tested in mice with fluorescent axons using confocal imaging to confirm preserved afferent innervation of spindles despite motor end plate denervation. Preganglionic and postganglionic injuries were then created in wild-type mice. Four weeks later, we assessed total and afferent denervation of the elbow flexors by musculocutaneous nerve immunohistochemistry. Biceps muscle volume and cross-sectional area were measured by micro computed tomography. An observer who was blinded to the study protocol measured elbow flexion contractures. Biceps spindle and muscle fiber morphology and ErbB signaling pathway activity were assessed histologically and immunohistochemically. Preganglionic and postganglionic injuries caused similar total denervation and biceps muscle atrophy. However, after preganglionic injuries, afferent innervation was partially preserved and elbow flexion contractures were significantly less severe. Spindles degenerated after postganglionic injury but were preserved after preganglionic injury. ErbB signaling was inactivated in denervated spindles after postganglionic injury but ErbB signaling activity was preserved in spindles after preganglionic injury with retained afferent innervation. Preganglionic and postganglionic injuries were associated with upregulation of ErbB signaling in extrafusal muscle fibers. Contractures after NBPI are associated with muscle spindle degeneration and loss of spindle ErbB signaling activity. Preservation of afferent innervation maintained spindle development and ErbB signaling activity, and protected against contractures. Pharmacologic modulation of ErbB signaling, which is being investigated as a

Muscle afferent receptors engaged in augmented sympathetic responsiveness in peripheral artery disease

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Jianhua eLi

2012-07-01

Full Text Available The exercise pressor reflex (EPR is a neural control mechanism responsible for the cardiovascular responses to exercise. As exercise is initiated, thin fiber muscle afferent nerves are activated by mechanical and metabolic stimuli arising in the contracting muscles. This leads to reflex increases in arterial blood pressure and heart rate primarily through activation of sympathetic nerve activity (SNA. Studies of humans and animals have indicated that the EPR is exaggerated in a number of cardiovascular diseases. For the last several years, studies have specifically employed a rodent model to examine the mechanisms at receptor and cellular levels by which responses of SNA and blood pressure to static exercise are heightened in peripheral artery disease (PAD, one of the most common cardiovascular disorders. A rat model of this disease has well been established. Specifically, femoral artery occlusion is used to study intermittent claudication that is observed in human PAD. The receptors on thin fiber muscle afferents that are engaged in this disease include transient receptor potential vanilloid type 1 (TRPV1, purinergic P2X and acid sensing ion channel (ASIC. The role played by nerve growth factor (NGF in regulating those sensory receptors in the processing of amplified EPR was also investigated. The purpose of this review is to focus on a theme namely that PAD accentuates autonomic reflex responses to exercise and further address regulatory mechanisms leading to abnormal sympathetic responsiveness. This review will present some of recent results in regard with several receptors in muscle sensory neurons in contribution to augmented autonomic reflex responses in PAD. Review of the findings from recent studies would lead to a better understanding in integrated processing of sympathetic nervous system in PAD.

Device-based approaches for renal nerve ablation for hypertension and beyond

OpenAIRE

Alicia Ann Thorp; Markus Peter Schlaich; Markus Peter Schlaich

2015-01-01

Animal and human studies have demonstrated that chronic activation of renal sympathetic nerves is critical in the pathogenesis and perpetuation of treatment-resistant hypertension. Bilateral renal denervation has emerged as a safe and effective, non-pharmacological treatment for resistant hypertension that involves the selective ablation of efferent and afferent renal nerves to lower blood pressure. However, the most recent and largest randomized controlled trial failed to confirm the primacy...

Pulmonary Stress Induced by Hyperthermia: Role of Airway Sensory Nerves

Science.gov (United States)

2016-01-01

Myers AC, Kajekar R, Undem BJ. Allergic inflammation-induced neuropeptide production in rapidly adapting afferent nerves in guinea pig airways. Am J...induced neuro- peptide production in rapidly adapting afferent nerves in guinea pig airways. Am. J. Physiol. Lung Cell. Mol. Physiol. 282, L775–L781...co-localization of transient receptor po- tential vanilloid (trpv)1 and sensory neuropeptides in the guinea - pig respiratory system. Neuroscience

Selective stimulation of sacral nerve roots for bladder control: a study by computer modeling

NARCIS (Netherlands)

Rijkhoff, N. J.; Holsheimer, J.; Koldewijn, E. L.; Struijk, J. J.; van Kerrebroeck, P. E.; Debruyne, F. M.; Wijkstra, H.

1994-01-01

The aim of this study was to investigate theoretically the conditions for the activation of the detrusor muscle without activation of the urethral sphincter and afferent fibers, when stimulating the related sacral roots. Therefore, the sensitivity of excitation and blocking thresholds of nerve

Vagus nerve is involved in the changes in body temperature induced by intragastric administration of 1,8-cineole via TRPM8 in mice.

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Urata, Tomomi; Mori, Noriyuki; Fukuwatari, Tsutomu

2017-05-22

Transient Receptor Potential Melastatin 8 (TRPM8) is a cold receptor activated by mild cold temperature (<28°C). TRPM8 expressed in cutaneous sensory nerves is involved in cold sensation and thermoregulation. TRPM8 mRNA is detected in various tissues, including the gastrointestinal mucosa, and in the vagal afferent nerve. The relationship between vagal afferent nerve-specific expression of TRPM8 and thermoregulation remains unclear. In this study, we aimed to investigate whether TRPM8 expression in the vagal afferent nerve is involved in autonomic thermoregulation. We found that intragastric administration of 1,8-cineole, a TRPM8 agonist, increased intrascapular brown adipose tissue and colonic temperatures, and M8-B-treatment (TRPM8 antagonist) inhibited these responses. Intravenous administration of 1,8-cineole also showed similar effects. In vagotomized mice, the responses induced by intragastric administration of 1,8-cineole were attenuated. These results suggest that TRPM8 expressed in tissues apart from cutaneous sensory nerves are involved in autonomic thermoregulation response. Copyright © 2017 Elsevier B.V. All rights reserved.

Psychoactive bacteria Lactobacillus rhamnosus (JB-1) elicits rapid frequency facilitation in vagal afferents.

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Perez-Burgos, Azucena; Wang, Bingxian; Mao, Yu-Kang; Mistry, Bhavik; McVey Neufeld, Karen-Anne; Bienenstock, John; Kunze, Wolfgang

2013-01-15

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.

Function and morphology correlates of rectal nerve mechanoreceptors innervating the guinea pig internal anal sphincter.

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Lynn, P A; Brookes, S J H

2011-01-01

Mechanoreceptors to the internal anal sphincter (IAS) contribute to continence and normal defecation, yet relatively little is known about their function or morphology. We investigated the function and structure of mechanoreceptors to the guinea pig IAS. Extracellular recordings from rectal nerve branches to the IAS in vitro, combined with anterograde labeling of recorded nerve trunks, were used to characterize extrinsic afferent nerve endings activated by circumferential distension. Slowly adapting, stretch-sensitive afferents were recorded in rectal nerves to the IAS. Ten of 11 were silent under basal conditions and responded to circumferential stretch in a saturating linear manner. Rectal nerve afferents responded to compression with von Frey hairs with low thresholds (0.3-0.5 mN) and 3.4 ± 0.5 discrete, elongated mechanosensitive fields of innervation aligned parallel to circular muscle bundles (length = 62 ± 16 mm, n = 10). Anterogradely labeled rectal nerve axons typically passed through sparse irregular myenteric ganglia adjacent to the IAS, before ending in extensive varicose arrays within the circular muscle and, to a lesser extent, the longitudinal muscle overlying the IAS. Few (8%) IAS myenteric ganglia contained intraganglionic laminar endings. In eight preparations, mechanotransduction sites were mapped in combination with successful anterograde fills. Mechanotransduction sites were strongly associated with extensive fine varicose arrays within the circular muscle (P IAS are likely to correspond to extensive fine varicose arrays within the circular muscle. © 2010 Blackwell Publishing Ltd.

Abdominal and internal intercostal motoneurones are strong synergists for expiration but are not synergists for Group I monosynaptic afferent inputs

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Ford, Tim W; Meehan, Claire Francesca; Kirkwood, Peter

2014-01-01

, 9 being in Group B Dist motoneurones. The complete absence of heteronymous monosynaptic Group I reflex excitation between muscles that are synergistically activated in expiration leads us to conclude that such connections from muscle spindle afferents of the thoracic nerves have little role...... in controlling expiratory movements but, where present, support other motor acts....

Bradykinin Contributes to Sympathetic and Pressor Responses Evoked by Activation of Skeletal Muscle Afferents P2X in Heart Failure

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Jihong Xing

2016-11-01

Full Text Available Background/Aims: Published data suggest that purinergic P2X receptors of muscle afferent nerves contribute to the enhanced sympathetic nervous activity (SNA and blood pressure (BP responses during static exercise in heart failure (HF. In this study, we examined engagement of bradykinin (BK in regulating responses of SNA and BP evoked by P2X stimulation in rats with HF. We further examined cellular mechanisms responsible for BK. We hypothesized that BK potentiates P2X currents of muscle dorsal root ganglion (DRG neurons, and this effect is greater in HF due to upregulation of BK kinin B2 and P2X3 receptor. As a result, BK amplifies muscle afferents P2X-mediated SNA and BP responses. Methods: Renal SNA and BP responses were recorded in control rats and rats with HF. Western Blot analysis and patch-clamp methods were employed to examine the receptor expression and function of DRG neurons involved in the effects of BK. Results: BK injected into the arterial blood supply of the hindlimb muscles heightened the reflex SNA and BP responses induced by P2X activation with α,β-methylene ATP to a greater degree in HF rats. In addition, HF upregulated the protein expression of kinin B2 and P2X3 in DRG and the prior application of BK increased the magnitude of α,β-methylene ATP-induced currents in muscle DRG neurons from HF rats. Conclusion: BK plays a facilitating role in modulating muscle afferent P2X-engaged reflex sympathetic and pressor responses. In HF, P2X responsivness is augmented due to increases in expression of kinin B2 and P2X3 receptors and P2X current activity.

Cholecystokinin enhances visceral pain-related affective memory via vagal afferent pathway in rats

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Cao Bing

2012-06-01

Full Text Available Abstract Background Pain contains both sensory and affective dimensions. Using a rodent visceral pain assay that combines the colorectal distension (CRD model with the conditioned place avoidance (CPA paradigms, we measured a learned behavior that directly reflects the affective component of visceral pain, and showed that perigenual anterior cingulate cortex (pACC activation is critical for memory processing involved in long-term visceral affective state and prediction of aversive stimuli by contextual cue. Progress has been made and suggested that activation of vagal afferents plays a role in the behavioral control nociception and memory storage processes. In human patients, electrical vagus nerve stimulation enhanced retention of verbal learning performance. Cholecystokinin-octapeptide (CCK, which is a gastrointestinal hormone released during feeding, has been shown to enhance memory retention. Mice access to food immediately after training session enhanced memory retention. It has been well demonstrated that CCK acting on vagal afferent fibers mediates various physiological functions. We hypothesize that CCK activation of vagal afferent enhances visceral pain-related affective memory. Results In the presented study, infusion of CCK-8 at physiological concentration combining with conditional training significantly increased the CRD-induced CPA scores, and enhanced the pain affective memory retention. In contrast, CCK had no effect on CPA induced by non-nociceptive aversive stimulus (U69,593. The physiological implications were further strengthened by the similar effects observed in the rats with duodenal infusion of 5% peptone, which has been shown to induce increases in plasma CCK levels. CCK-8 receptor antagonist CR-1409 or perivagal application of capsaicin abolished the effect of CCK on aversive visceral pain memory, which was consistent with the notion that vagal afferent modulates affective aspects of visceral pain. CCK does not change

Cholecystokinin enhances visceral pain-related affective memory via vagal afferent pathway in rats.

Science.gov (United States)

Cao, Bing; Zhang, Xu; Yan, Ni; Chen, Shengliang; Li, Ying

2012-06-09

Pain contains both sensory and affective dimensions. Using a rodent visceral pain assay that combines the colorectal distension (CRD) model with the conditioned place avoidance (CPA) paradigms, we measured a learned behavior that directly reflects the affective component of visceral pain, and showed that perigenual anterior cingulate cortex (pACC) activation is critical for memory processing involved in long-term visceral affective state and prediction of aversive stimuli by contextual cue. Progress has been made and suggested that activation of vagal afferents plays a role in the behavioral control nociception and memory storage processes.In human patients, electrical vagus nerve stimulation enhanced retention of verbal learning performance. Cholecystokinin-octapeptide (CCK), which is a gastrointestinal hormone released during feeding, has been shown to enhance memory retention. Mice access to food immediately after training session enhanced memory retention. It has been well demonstrated that CCK acting on vagal afferent fibers mediates various physiological functions. We hypothesize that CCK activation of vagal afferent enhances visceral pain-related affective memory. In the presented study, infusion of CCK-8 at physiological concentration combining with conditional training significantly increased the CRD-induced CPA scores, and enhanced the pain affective memory retention. In contrast, CCK had no effect on CPA induced by non-nociceptive aversive stimulus (U69,593). The physiological implications were further strengthened by the similar effects observed in the rats with duodenal infusion of 5% peptone, which has been shown to induce increases in plasma CCK levels. CCK-8 receptor antagonist CR-1409 or perivagal application of capsaicin abolished the effect of CCK on aversive visceral pain memory, which was consistent with the notion that vagal afferent modulates affective aspects of visceral pain. CCK does not change the nociceptive response (visceral pain

Immobilization induces changes in presynaptic control of group Ia afferents in healthy humans

DEFF Research Database (Denmark)

Jensen, Jesper Lundbye; Nielsen, Jens Bo

2008-01-01

immobilized the left foot and ankle joint for 2 weeks in 12 able-bodied subjects. Disynaptic reciprocal inhibition of soleus (SOL) motoneurones and presynaptic control of SOL group Ia afferents was measured before and after the immobilization as well as following 2 weeks of recovery. Following immobilization...... maximal voluntary plantar- and dorsiflexion torque (MVC) was significantly reduced and the maximal SOL H-reflex amplitude increased with no changes in Mmax. Decreased presynaptic inhibition of the Ia afferents likely contributed to the increase of the H-reflex size, since we observed a significant...... decrease in the long-latency depression of the SOL H-reflex evoked by peroneal nerve stimulation (D2 inhibition) and an increase in the size of the monosynaptic Ia facilitation of the SOL H-reflex evoked by femoral nerve stimulation. These two measures provide independent evidence of changes in presynaptic...

Brain imaging signatures of the relationship between epidermal nerve fibers and heat pain perception.

Science.gov (United States)

Tseng, Ming-Tsung; Kong, Yazhuo; Chiang, Ming-Chang; Chao, Chi-Chao; Tseng, Wen-Yih I; Hsieh, Sung-Tsang

2015-11-15

Although the small-diameter primary afferent fibers in the skin promptly respond to nociceptive stimuli and convey sensory inputs to the central nervous system, the neural signatures that underpin the relationship between cutaneous afferent fibers and pain perception remain elusive. We combined skin biopsy at the lateral aspect of the distal leg, which is used to quantify cutaneous afferent fibers, with fMRI, which is used to assess brain responses and functional connectivity, to investigate the relationship between cutaneous sensory nerves and the corresponding pain perception in the brain after applying heat pain stimulation to the dorsum of the right foot in healthy subjects. During painful stimulation, the degree of cutaneous innervation, as measured by epidermal nerve fiber density, was correlated with individual blood oxygen level-dependent (BOLD) signals of the posterior insular cortex and of the thalamus, periaqueductal gray, and rostral ventromedial medulla. Pain perception was associated with the activation of the anterior insular cortex and with the functional connectivity from the anterior insular cortex to the primary somatosensory cortex during painful stimulation. Most importantly, both epidermal nerve fiber density and activity in the posterior insular cortex showed a positive correlation with the strength of coupling under pain between the anterior insular cortex and the primary somatosensory cortex. Thus, our findings support the notion that the neural circuitry subserving pain perception interacts with the cerebral correlates of peripheral nociceptive fibers, which implicates an indirect role for skin nerves in human pain perception. Copyright © 2015 Elsevier Inc. All rights reserved.

Anatomy and physiology of the afferent visual system.

Science.gov (United States)

Prasad, Sashank; Galetta, Steven L

2011-01-01

The efficient organization of the human afferent visual system meets enormous computational challenges. Once visual information is received by the eye, the signal is relayed by the retina, optic nerve, chiasm, tracts, lateral geniculate nucleus, and optic radiations to the striate cortex and extrastriate association cortices for final visual processing. At each stage, the functional organization of these circuits is derived from their anatomical and structural relationships. In the retina, photoreceptors convert photons of light to an electrochemical signal that is relayed to retinal ganglion cells. Ganglion cell axons course through the optic nerve, and their partial decussation in the chiasm brings together corresponding inputs from each eye. Some inputs follow pathways to mediate pupil light reflexes and circadian rhythms. However, the majority of inputs arrive at the lateral geniculate nucleus, which relays visual information via second-order neurons that course through the optic radiations to arrive in striate cortex. Feedback mechanisms from higher cortical areas shape the neuronal responses in early visual areas, supporting coherent visual perception. Detailed knowledge of the anatomy of the afferent visual system, in combination with skilled examination, allows precise localization of neuropathological processes and guides effective diagnosis and management of neuro-ophthalmic disorders. Copyright © 2011 Elsevier B.V. All rights reserved.

Sensory and motor innervation of the crural diaphragm by the vagus nerves.

Science.gov (United States)

Young, Richard L; Page, Amanda J; Cooper, Nicole J; Frisby, Claudine L; Blackshaw, L Ashley

2010-03-01

During gastroesophageal reflux, transient lower esophageal sphincter relaxation and crural diaphragm (CD) inhibition occur concomitantly. Modifying vagus nerve control of transient lower esophageal sphincter relaxation is a major focus of development of therapeutics for gastroesophageal reflux disease, but neural mechanisms that coordinate the CD are poorly understood. Nerve tracing and immunolabeling were used to assess innervation of the diaphragm and lower esophageal sphincter in ferrets. Mechanosensory responses of vagal afferents in the CD and electromyography responses of the CD were recorded in novel in vitro preparations and in vivo. Retrograde tracing revealed a unique population of vagal CD sensory neurons in nodose ganglia and CD motor neurons in brainstem vagal nuclei. Anterograde tracing revealed specialized vagal endings in the CD and phrenoesophageal ligament-sites of vagal afferent mechanosensitivity recorded in vitro. Spontaneous electromyography activity persisted in the CD following bilateral phrenicotomy in vivo, while vagus nerve stimulation evoked electromyography responses in the CD in vitro and in vivo. We conclude that vagal sensory and motor neurons functionally innervate the CD and phrenoesophageal ligament. CD vagal afferents show mechanosensitivity to distortion of the gastroesophageal junction, while vagal motor neurons innervate both CD and distal esophagus and may represent a common substrate for motor control of the reflux barrier. Copyright 2010 AGA Institute. Published by Elsevier Inc. All rights reserved.

Persistent pain after spinal cord injury is maintained by primary afferent activity.

Science.gov (United States)

Yang, Qing; Wu, Zizhen; Hadden, Julia K; Odem, Max A; Zuo, Yan; Crook, Robyn J; Frost, Jeffrey A; Walters, Edgar T

2014-08-06

Chronic pain caused by insults to the CNS (central neuropathic pain) is widely assumed to be maintained exclusively by central mechanisms. However, chronic hyperexcitablility occurs in primary nociceptors after spinal cord injury (SCI), suggesting that SCI pain also depends upon continuing activity of peripheral sensory neurons. The present study in rats (Rattus norvegicus) found persistent upregulation after SCI of protein, but not mRNA, for a voltage-gated Na(+) channel, Nav1.8, that is expressed almost exclusively in primary afferent neurons. Selectively knocking down Nav1.8 after SCI suppressed spontaneous activity in dissociated dorsal root ganglion neurons, reversed hypersensitivity of hindlimb withdrawal reflexes, and reduced ongoing pain assessed by a conditioned place preference test. These results show that activity in primary afferent neurons contributes to ongoing SCI pain. Copyright © 2014 the authors 0270-6474/14/3410765-05$15.00/0.

Device-based approaches for renal nerve ablation for hypertension and beyond

Directory of Open Access Journals (Sweden)

Alicia Ann Thorp

2015-07-01

Full Text Available Animal and human studies have demonstrated that chronic activation of renal sympathetic nerves is critical in the pathogenesis and perpetuation of treatment-resistant hypertension. Bilateral renal denervation has emerged as a safe and effective, non-pharmacological treatment for resistant hypertension that involves the selective ablation of efferent and afferent renal nerves to lower blood pressure. However, the most recent and largest randomized controlled trial failed to confirm the primacy of renal denervation over a sham procedure, prompting widespread re-evaluation of the therapy’s efficacy. Disrupting renal afferent sympathetic signalling to the hypothalamus with renal denervation lowers central sympathetic tone, which has the potential to confer additional clinical benefits beyond blood pressure control. Specifically, there has been substantial interest in the use of renal denervation as either a primary or adjunct therapy in pathological conditions characterized by central sympathetic over-activity such as renal disease, heart failure and metabolic-associated disorders. Recent findings from pre-clinical and proof-of–concept studies appear promising with renal denervation shown to confer cardiovascular and metabolic benefits, largely independent of changes in blood pressure. This review explores the pathological rationale for targeting sympathetic renal nerves for blood pressure control. Latest developments in renal nerve ablation modalities designed to improve procedural success are discussed along with prospective findings on the efficacy of renal denervation to lower blood pressure in treatment-resistant hypertensive patients. Preliminary evidence in support of renal denervation as a possible therapeutic option in disease states characterized by central sympathetic over-activity is also presented.

Tumors of the optic nerve

DEFF Research Database (Denmark)

Lindegaard, Jens; Heegaard, Steffen

2009-01-01

A variety of lesions may involve the optic nerve. Mainly, these lesions are inflammatory or vascular lesions that rarely necessitate surgery but may induce significant visual morbidity. Orbital tumors may induce proptosis, visual loss, relative afferent pupillary defect, disc edema and optic...... atrophy, but less than one-tenth of these tumors are confined to the optic nerve or its sheaths. No signs or symptoms are pathognomonic for tumors of the optic nerve. The tumors of the optic nerve may originate from the optic nerve itself (primary tumors) as a proliferation of cells normally present...... in the nerve (e.g., astrocytes and meningothelial cells). The optic nerve may also be invaded from tumors originating elsewhere (secondary tumors), invading the nerve from adjacent structures (e.g., choroidal melanoma and retinoblastoma) or from distant sites (e.g., lymphocytic infiltration and distant...

Modulation of the masseteric reflex by gastric vagal afferents.

Science.gov (United States)

Pettorossi, V E

1983-04-01

Several investigations have shown that the vagal nerve can affect the reflex responses of the masticatory muscles acting at level either of trigeminal motoneurons or of the mesencephalic trigeminal nucleus (MTN). The present experiments have been devoted to establish the origin of the vagal afferent fibres involved in modulating the masseteric reflex. In particular, the gastric vagal afferents were taken into consideration and selective stimulations of such fibres were performed in rabbit. Conditioning electrical stimulation of truncus vagalis ventralis (TVV) reduced the excitability of the MTN cells as shown by a decrease of the antidromic response recorded from the semilunar ganglion and elicited by MTN single-shock electrical stimulation. Sympathetic and cardiovascular influences were not involved in these responses. Mechanical stimulation of gastric receptors, by means of gastric distension, clearly diminished the amplitude of twitch tension of masseteric reflex and inhibited the discharge frequency of proprioceptive MTN units. The effect was phasic and depended upon the velocity of distension. Thus the sensory volleys originating from rapid adapting receptors reach the brain stem through vagal afferents and by means of a polysynaptic connection inhibits the masseteric reflex at level of MTN cells.

The crosstalk between the kidney and the central nervous system: the role of renal nerves in blood pressure regulation.

Science.gov (United States)

Nishi, Erika E; Bergamaschi, Cássia T; Campos, Ruy R

2015-04-20

What is the topic of this review? This review describes the role of renal nerves as the key carrier of signals from the kidneys to the CNS and vice versa; the brain and kidneys communicate through this carrier to maintain homeostasis in the body. What advances does it highlight? Whether renal or autonomic dysfunction is the predominant contributor to systemic hypertension is still debated. In this review, we focus on the role of the renal nerves in a model of renovascular hypertension. The sympathetic nervous system influences the renal regulation of arterial pressure and body fluid composition. Anatomical and physiological evidence has shown that sympathetic nerves mediate changes in urinary sodium and water excretion by regulating the renal tubular water and sodium reabsorption throughout the nephron, changes in the renal blood flow and the glomerular filtration rate by regulating the constriction of renal vasculature, and changes in the activity of the renin-angiotensin system by regulating the renin release from juxtaglomerular cells. Additionally, renal sensory afferent fibres project to the autonomic central nuclei that regulate blood pressure. Hence, renal nerves play a key role in the crosstalk between the kidneys and the CNS to maintain homeostasis in the body. Therefore, the increased sympathetic nerve activity to the kidney and the renal afferent nerve activity to the CNS may contribute to the outcome of diseases, such as hypertension. © 2014 The Authors. Experimental Physiology © 2014 The Physiological Society.

Imaging of the facial nerve

Energy Technology Data Exchange (ETDEWEB)

Veillon, F. [Service de Radiologie I, Hopital de Hautepierre, 67098 Strasbourg Cedex (France)], E-mail: Francis.Veillon@chru-strasbourg.fr; Ramos-Taboada, L.; Abu-Eid, M. [Service de Radiologie I, Hopital de Hautepierre, 67098 Strasbourg Cedex (France); Charpiot, A. [Service d' ORL, Hopital de Hautepierre, 67098 Strasbourg Cedex (France); Riehm, S. [Service de Radiologie I, Hopital de Hautepierre, 67098 Strasbourg Cedex (France)

2010-05-15

The facial nerve is responsible for the motor innervation of the face. It has a visceral motor function (lacrimal, submandibular, sublingual glands and secretion of the nose); it conveys a great part of the taste fibers, participates to the general sensory of the auricle (skin of the concha) and the wall of the external auditory meatus. The facial mimic, production of tears, nasal flow and salivation all depend on the facial nerve. In order to image the facial nerve it is mandatory to be knowledgeable about its normal anatomy including the course of its efferent and afferent fibers and about relevant technical considerations regarding CT and MR to be able to achieve high-resolution images of the nerve.

Functional recovery of anterior semicircular canal afferents following hair cell regeneration in birds

Science.gov (United States)

Boyle, Richard; Highstein, Stephen M.; Carey, John P.; Xu, Jinping

2002-01-01

Streptomycin sulfate (1.2 g/kg i.m.) was administered for 5 consecutive days to 5-7-day-old white Leghorn chicks; this causes damage to semicircular canal hair cells that ultimately regenerate to reform the sensory epithelium. During the recovery period, electrophysiological recordings were taken sequentially from anterior semicircular canal primary afferents using an indentation stimulus of the canal that has been shown to mimic rotational stimulation. Chicks were assigned to an early (14-18 days; n = 8), intermediate (28-34 days; n = 5), and late (38-58 days; n = 4) period based on days after treatment. Seven untreated chicks, 15-67 days old, provided control data. An absence of background and indent-induced discharge was the prominent feature of afferents in the early period: only "silent" afferents were encountered in 5/8 experiments. In several of these chicks, fascicles of afferent fibers were seen extending up to the epithelium that was void of hair cells, and intra- and extracellular biocytin labeling revealed afferent processes penetrating into the supporting cell layer of the crista. In 3/8 chicks 74 afferents could be characterized, and they significantly differed from controls (n = 130) by having a lower discharge rate and a negligible response to canal stimulation. In the intermediate period there was considerable variability in discharge properties of 121 afferents, but as a whole the number of "silent" fibers in the canal nerve diminished, the background rate increased, and a response to canal stimulation detected. Individually biocytin-labeled afferents had normal-appearing terminal specializations in the sensory epithelium by 28 days poststreptomycin. In the late period, afferents (n = 58) remained significantly different from controls in background discharge properties and response gain. The evidence suggests that a considerable amount of variability exists between chicks in the return of vestibular afferent function following ototoxic injury and

Vagus Nerve as Modulator of the Brain–Gut Axis in Psychiatric and Inflammatory Disorders

Directory of Open Access Journals (Sweden)

Sigrid Breit

2018-03-01

Full Text Available The vagus nerve represents the main component of the parasympathetic nervous system, which oversees a vast array of crucial bodily functions, including control of mood, immune response, digestion, and heart rate. It establishes one of the connections between the brain and the gastrointestinal tract and sends information about the state of the inner organs to the brain via afferent fibers. In this review article, we discuss various functions of the vagus nerve which make it an attractive target in treating psychiatric and gastrointestinal disorders. There is preliminary evidence that vagus nerve stimulation is a promising add-on treatment for treatment-refractory depression, posttraumatic stress disorder, and inflammatory bowel disease. Treatments that target the vagus nerve increase the vagal tone and inhibit cytokine production. Both are important mechanism of resiliency. The stimulation of vagal afferent fibers in the gut influences monoaminergic brain systems in the brain stem that play crucial roles in major psychiatric conditions, such as mood and anxiety disorders. In line, there is preliminary evidence for gut bacteria to have beneficial effect on mood and anxiety, partly by affecting the activity of the vagus nerve. Since, the vagal tone is correlated with capacity to regulate stress responses and can be influenced by breathing, its increase through meditation and yoga likely contribute to resilience and the mitigation of mood and anxiety symptoms.

Presence and Absence of Muscle Contraction Elicited by Peripheral Nerve Electrical Stimulation Differentially Modulate Primary Motor Cortex Excitability

Science.gov (United States)

Sasaki, Ryoki; Kotan, Shinichi; Nakagawa, Masaki; Miyaguchi, Shota; Kojima, Sho; Saito, Kei; Inukai, Yasuto; Onishi, Hideaki

2017-01-01

Modulation of cortical excitability by sensory inputs is a critical component of sensorimotor integration. Sensory afferents, including muscle and joint afferents, to somatosensory cortex (S1) modulate primary motor cortex (M1) excitability, but the effects of muscle and joint afferents specifically activated by muscle contraction are unknown. We compared motor evoked potentials (MEPs) following median nerve stimulation (MNS) above and below the contraction threshold based on the persistence of M-waves. Peripheral nerve electrical stimulation (PES) conditions, including right MNS at the wrist at 110% motor threshold (MT; 110% MNS condition), right MNS at the index finger (sensory digit nerve stimulation [DNS]) with stimulus intensity approximately 110% MNS (DNS condition), and right MNS at the wrist at 90% MT (90% MNS condition) were applied. PES was administered in a 4 s ON and 6 s OFF cycle for 20 min at 30 Hz. In Experiment 1 (n = 15), MEPs were recorded from the right abductor pollicis brevis (APB) before (baseline) and after PES. In Experiment 2 (n = 15), M- and F-waves were recorded from the right APB. Stimulation at 110% MNS at the wrist evoking muscle contraction increased MEP amplitudes after PES compared with those at baseline, whereas DNS at the index finger and 90% MNS at the wrist not evoking muscle contraction decreased MEP amplitudes after PES. M- and F-waves, which reflect spinal cord or muscular and neuromuscular junctions, did not change following PES. These results suggest that muscle contraction and concomitant muscle/joint afferent inputs specifically enhance M1 excitability. PMID:28392766

Tuning of spinal networks to frequency components of spike trains in individual afferents.

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Koerber, H R; Seymour, A W; Mendell, L M

1991-10-01

Cord dorsum potentials (CDPs) evoked by primary afferent fiber stimulation reflect the response of postsynaptic dorsal horn neurons. The properties of these CDPs have been shown to vary in accordance with the type of primary afferent fiber stimulated. The purpose of the present study was to determine the relationships between frequency modulation of the afferent input trains, the amplitude modulation of the evoked CDPs, and the type of primary afferent stimulated. The somata of individual primary afferent fibers were impaled in the L7 dorsal root ganglion of alpha-chloralose-anesthetized cats. Action potentials (APs) were evoked in single identified afferents via the intracellular microelectrode while simultaneously recording the response of dorsal horn neurons as CDPs, or activity of individual target interneurons recorded extracellularly or intracellularly. APs were evoked in afferents using temporal patterns identical to the responses of selected afferents to natural stimulation of their receptive fields. Two such physiologically realistic trains, one recorded from a hair follicle and the other from a slowly adapting type 1 receptor, were chosen as standard test trains. Modulation of CDP amplitude in response to this frequency-modulated afferent activity varied according to the type of peripheral mechanoreceptor innervated. Dorsal horn networks driven by A beta afferents innervating hair follicles, rapidly adapting pad (Krause end bulb), and field receptors seemed "tuned" to amplify the onset of activity in single afferents. Networks driven by afferents innervating down hair follicles and pacinian corpuscles required more high-frequency activity to elicit their peak response. Dorsal horn networks driven by afferents innervating slowly adapting receptors including high-threshold mechanoreceptors exhibited some sensitivity to the instantaneous frequency, but in general they reproduced the activity in the afferent fiber much more faithfully. Responses of

Physiological recruitment of motor units by high-frequency electrical stimulation of afferent pathways.

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Dideriksen, Jakob L; Muceli, Silvia; Dosen, Strahinja; Laine, Christopher M; Farina, Dario

2015-02-01

Neuromuscular electrical stimulation (NMES) is commonly used in rehabilitation, but electrically evoked muscle activation is in several ways different from voluntary muscle contractions. These differences lead to challenges in the use of NMES for restoring muscle function. We investigated the use of low-current, high-frequency nerve stimulation to activate the muscle via the spinal motoneuron (MN) pool to achieve more natural activation patterns. Using a novel stimulation protocol, the H-reflex responses to individual stimuli in a train of stimulation pulses at 100 Hz were reliably estimated with surface EMG during low-level contractions. Furthermore, single motor unit recruitment by afferent stimulation was analyzed with intramuscular EMG. The results showed that substantially elevated H-reflex responses were obtained during 100-Hz stimulation with respect to a lower stimulation frequency. Furthermore, motor unit recruitment using 100-Hz stimulation was not fully synchronized, as it occurs in classic NMES, and the discharge rates differed among motor units because each unit was activated only after a specific number of stimuli. The most likely mechanism behind these observations is the temporal summation of subthreshold excitatory postsynaptic potentials from Ia fibers to the MNs. These findings and their interpretation were also verified by a realistic simulation model of afferent stimulation of a MN population. These results suggest that the proposed stimulation strategy may allow generation of considerable levels of muscle activation by motor unit recruitment that resembles the physiological conditions. Copyright © 2015 the American Physiological Society.

Electrophysiological characterization of texture information slip-resistance dependent in the rat vibrissal nerve

Directory of Open Access Journals (Sweden)

Albarracín Ana L

2011-04-01

Full Text Available Abstract Background Studies in tactile discrimination agree that rats are able to learn a rough-smooth discrimination task by actively touching (whisking objects with their vibrissae. In particular, we focus on recent evidence of how neurons at different levels of the sensory pathway carry information about tactile stimuli. Here, we analyzed the multifiber afferent discharge of one vibrissal nerve during active whisking. Vibrissae movements were induced by electrical stimulation of motor branches of the facial nerve. We used sandpapers of different grain size as roughness discrimination surfaces and we also consider the change of vibrissal slip-resistance as a way to improve tactile information acquisition. The amplitude of afferent activity was analyzed according to its Root Mean Square value (RMS. The comparisons among experimental situation were quantified by using the information theory. Results We found that the change of the vibrissal slip-resistance is a way to improve the roughness discrimination of surfaces. As roughness increased, the RMS values also increased in almost all cases. In addition, we observed a better discrimination performance in the retraction phase (maximum amount of information. Conclusions The evidence of amplitude changes due to roughness surfaces and slip-resistance levels allows to speculate that texture information is slip-resistance dependent at peripheral level.

Presynaptic control of group Ia afferents in relation to acquisition of a visuo-motor skill in healthy humans

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Perez, Monica A.; Lungholt, Bjarke K.S.; Nielsen, Jens Bo

2005-01-01

Sensory information continuously converges on the spinal cord during a variety of motor behaviours. Here, we examined presynaptic control of group Ia afferents in relation to acquisition of a novel motor skill. We tested whether repetition of two motor tasks with different degrees of difficulty......, a novel visuo-motor task involving the ankle muscles, and a control task involving simple voluntary ankle movements, would induce changes in the size of the soleus H-reflex. The slope of the H-reflex recruitment curve and the H-max/M-max ratio were depressed after repetition of the visuo-motor skill task...... of the monosynaptic Ia facilitation of the soleus H-reflex evoked by femoral nerve stimulation. The D1 inhibition was increased and the femoral nerve facilitation was decreased following the visuo-motor skill task, suggesting an increase in presynaptic inhibition of Ia afferents. No changes were observed...

Regulating cough through modulation of sensory nerve function in the airways.

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Spina, D; Page, C P

2013-10-01

Whilst local anaesthetics when applied directly to laryngeal nerves or topically to the lung can suppress cough, their chronic use is constrained because of dose limiting side effects. However, the effectiveness of local anaesthetics suggests that selectivity targeting nerves in the airway may provide novel approaches for the treatment of cough in the future. There is a considerable wealth of evidence showing that there are different afferent nerve subtypes in the airways. Traditionally C-fibres have been the focus of much research in the cough field since the stimulation of these afferents by capsaicin is able to elicit cough in guinea-pigs and in man, and drugs targeting various proteins expressed in these nerves (e.g. mu-opioid, NOP1, TRPV1, sodium channels) have been shown to be anti-tussive in preclinical models of cough. However, interest in Aδ fibres has increased recently in light of the discovery of a specific cough receptor in the guinea-pig that is provoked by citric acid and punctate stimulation, but not capsaicin and which has been anatomically linked to Aδ fibres. There is also some evidence that as a result of inflammation in the airways, Aδ fibres can begin to express neuropeptides and TRPV1 receptors so that they can become responsive to endogenous activators of this ion channel and to irritants like capsaicin. Consequently, there is considerable interest in targeting either one or both afferent nerve types for the treatment of chronic cough. However, to date the translation of preclinical studies into man has largely been disappointing and certainly there is a need for better preclinical models in this field. There also remain many challenges to overcome at a clinical level, such as what patient group(s) should be used to assess anti-tussive drugs and whether the use of irritants that induce cough in healthy volunteers (such as citric acid or capsaicin) is of any value in the assessment of novel anti-tussive drugs. The development of several

Anatomic assessment of sympathetic peri-arterial renal nerves in man.

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Sakakura, Kenichi; Ladich, Elena; Cheng, Qi; Otsuka, Fumiyuki; Yahagi, Kazuyuki; Fowler, David R; Kolodgie, Frank D; Virmani, Renu; Joner, Michael

2014-08-19

Although renal sympathetic denervation therapy has shown promising results in patients with resistant hypertension, the human anatomy of peri-arterial renal nerves is poorly understood. The aim of our study was to investigate the anatomic distribution of peri-arterial sympathetic nerves around human renal arteries. Bilateral renal arteries were collected from human autopsy subjects, and peri-arterial renal nerve anatomy was examined by using morphometric software. The ratio of afferent to efferent nerve fibers was investigated by dual immunofluorescence staining using antibodies targeted for anti-tyrosine hydroxylase and anti-calcitonin gene-related peptide. A total of 10,329 nerves were identified from 20 (12 hypertensive and 8 nonhypertensive) patients. The mean individual number of nerves in the proximal and middle segments was similar (39.6 ± 16.7 per section and 39.9 ± 1 3.9 per section), whereas the distal segment showed fewer nerves (33.6 ± 13.1 per section) (p = 0.01). Mean subject-specific nerve distance to arterial lumen was greatest in proximal segments (3.40 ± 0.78 mm), followed by middle segments (3.10 ± 0.69 mm), and least in distal segments (2.60 ± 0.77 mm) (p renal sympathetic nerve fibers is lower in distal segments and dorsal locations. There is a clear predominance of efferent nerve fibers, with decreasing prevalence of afferent nerves from proximal to distal peri-arterial and renal parenchyma. Understanding these anatomic patterns is important for refinement of renal denervation procedures. Copyright © 2014 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Detection thresholds of macaque otolith afferents.

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Yu, Xiong-Jie; Dickman, J David; Angelaki, Dora E

2012-06-13

The vestibular system is our sixth sense and is important for spatial perception functions, yet the sensory detection and discrimination properties of vestibular neurons remain relatively unexplored. Here we have used signal detection theory to measure detection thresholds of otolith afferents using 1 Hz linear accelerations delivered along three cardinal axes. Direction detection thresholds were measured by comparing mean firing rates centered on response peak and trough (full-cycle thresholds) or by comparing peak/trough firing rates with spontaneous activity (half-cycle thresholds). Thresholds were similar for utricular and saccular afferents, as well as for lateral, fore/aft, and vertical motion directions. When computed along the preferred direction, full-cycle direction detection thresholds were 7.54 and 3.01 cm/s(2) for regular and irregular firing otolith afferents, respectively. Half-cycle thresholds were approximately double, with excitatory thresholds being half as large as inhibitory thresholds. The variability in threshold among afferents was directly related to neuronal gain and did not depend on spike count variance. The exact threshold values depended on both the time window used for spike count analysis and the filtering method used to calculate mean firing rate, although differences between regular and irregular afferent thresholds were independent of analysis parameters. The fact that minimum thresholds measured in macaque otolith afferents are of the same order of magnitude as human behavioral thresholds suggests that the vestibular periphery might determine the limit on our ability to detect or discriminate small differences in head movement, with little noise added during downstream processing.

Functionality of the baroreceptor nerves in heart rate regulation

DEFF Research Database (Denmark)

Ottesen, Johnny T.; Olufsen, Mette

2011-01-01

are a consequence of the memory encapsulated by the models, and the nonlinearity gives rise to sigmoidal response curves. The nonlinear afferent baroreceptor models are coupled with an effector model, and the coupled model has been used to predict baroreceptor feedback regulation of heart rate during postural...... change from sitting to standing and during head-up tilt. The efferent model couples the afferent nerve paths to the sympathetic and parasympathetic outflow, and subsequently predicts the build up of an action potential at the sinus knot of the heart. In this paper, we analyze the nonlinear afferent model...... and show that the coupled model is able to predict heart rate regulation using blood pressure data as an input...

The role of capsaicin-sensitive muscle afferents in fatigue-induced modulation of the monosynaptic reflex in the rat.

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Pettorossi, V E; Della Torre, G; Bortolami, R; Brunetti, O

1999-03-01

1. The role of group III and IV afferent fibres of the lateral gastrocnemious muscle (LG) in modulating the homonymous monosynaptic reflex was investigated during muscle fatigue in spinalized rats. 2. Muscle fatigue was induced by a series of increasing tetanic electrical stimuli (85 Hz, 600 ms) delivered to the LG muscle nerve. Series consisted of increasing train numbers from 1 to 60. 3. Potentials from the spinal cord LG motor pool and from the ventral root were recorded in response to proprioceptive afferent stimulation and analysed before and during tetanic muscle activations. Both the pre- and postsynaptic waves showed an initial enhancement and, after a '12-train' series, an increasing inhibition. 4. The enhancement of the responses to muscle fatiguing stimulation disappeared after L3-L6 dorsal root section, while a partial reflex inhibition was still present. Conversely, after section of the corresponding ventral root, there was only a reduction in the inhibitory effect. 5. The monosynaptic reflex was also studied in animals in which a large number of group III and IV muscle afferents were eliminated by injecting capsaicin (10 mM) into the LG muscle. As a result of capsaicin treatment, the fatigue-induced inhibition of the pre- and postsynaptic waves disappeared, while the response enhancement remained. 6. We concluded that the monosynaptic reflex inhibition, but not the enhancement, was mediated by those group III and IV muscle afferents that are sensitive to the toxic action of capsaicin. The afferents that are responsible for the response enhancement enter the spinal cord through the dorsal root, while those responsible for the inhibition enter the spinal cord through both the ventral and dorsal roots.

Rimonabant induced anorexia in rodents is not mediated by vagal or sympathetic gut afferents

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Madsen, Andreas Nygaard; Jelsing, Jacob; van de Wall, Esther H E M

2009-01-01

The selective CB1 receptor antagonist rimonabant is a novel weight control agent. Although CB1 receptors and binding sites are present in both the rodent central and peripheral nervous systems, including the afferent vagus nerve, the role of gut afferents in mediating anorexia following CB1R...... blockade is still debated. In the present study we examined rimonabant-induced anorexia in male C57BL/6J mice with subdiaphragmatic vagotomy (VGX) as well as in male Sprague-Dawley rats subjected to either subdiaphragmatic vagal deafferentation (SDA) alone or in combination with a complete celiac...... system, are required for rimonabant to inhibit food intake leading to the hypothesis that centrally located CB1 receptors are the prime mediators of rimonabant-induced anorexia....

Device-based approaches for renal nerve ablation for hypertension and beyond

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Thorp, Alicia A.; Schlaich, Markus P.

2015-01-01

Animal and human studies have demonstrated that chronic activation of renal sympathetic nerves is critical in the pathogenesis and perpetuation of treatment-resistant hypertension. Bilateral renal denervation has emerged as a safe and effective, non-pharmacological treatment for resistant hypertension that involves the selective ablation of efferent and afferent renal nerves to lower blood pressure. However, the most recent and largest randomized controlled trial failed to confirm the primacy of renal denervation over a sham procedure, prompting widespread re-evaluation of the therapy's efficacy. Disrupting renal afferent sympathetic signaling to the hypothalamus with renal denervation lowers central sympathetic tone, which has the potential to confer additional clinical benefits beyond blood pressure control. Specifically, there has been substantial interest in the use of renal denervation as either a primary or adjunct therapy in pathological conditions characterized by central sympathetic overactivity such as renal disease, heart failure and metabolic-associated disorders. Recent findings from pre-clinical and proof-of-concept studies appear promising with renal denervation shown to confer cardiovascular and metabolic benefits, largely independent of changes in blood pressure. This review explores the pathological rationale for targeting sympathetic renal nerves for blood pressure control. Latest developments in renal nerve ablation modalities designed to improve procedural success are discussed along with prospective findings on the efficacy of renal denervation to lower blood pressure in treatment-resistant hypertensive patients. Preliminary evidence in support of renal denervation as a possible therapeutic option in disease states characterized by central sympathetic overactivity is also presented. PMID:26217232

Device-based approaches for renal nerve ablation for hypertension and beyond.

Science.gov (United States)

Thorp, Alicia A; Schlaich, Markus P

2015-01-01

Animal and human studies have demonstrated that chronic activation of renal sympathetic nerves is critical in the pathogenesis and perpetuation of treatment-resistant hypertension. Bilateral renal denervation has emerged as a safe and effective, non-pharmacological treatment for resistant hypertension that involves the selective ablation of efferent and afferent renal nerves to lower blood pressure. However, the most recent and largest randomized controlled trial failed to confirm the primacy of renal denervation over a sham procedure, prompting widespread re-evaluation of the therapy's efficacy. Disrupting renal afferent sympathetic signaling to the hypothalamus with renal denervation lowers central sympathetic tone, which has the potential to confer additional clinical benefits beyond blood pressure control. Specifically, there has been substantial interest in the use of renal denervation as either a primary or adjunct therapy in pathological conditions characterized by central sympathetic overactivity such as renal disease, heart failure and metabolic-associated disorders. Recent findings from pre-clinical and proof-of-concept studies appear promising with renal denervation shown to confer cardiovascular and metabolic benefits, largely independent of changes in blood pressure. This review explores the pathological rationale for targeting sympathetic renal nerves for blood pressure control. Latest developments in renal nerve ablation modalities designed to improve procedural success are discussed along with prospective findings on the efficacy of renal denervation to lower blood pressure in treatment-resistant hypertensive patients. Preliminary evidence in support of renal denervation as a possible therapeutic option in disease states characterized by central sympathetic overactivity is also presented.

Quantitative assessment of integrated phrenic nerve activity.

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Nichols, Nicole L; Mitchell, Gordon S

2016-06-01

Integrated electrical activity in the phrenic nerve is commonly used to assess within-animal changes in phrenic motor output. Because of concerns regarding the consistency of nerve recordings, activity is most often expressed as a percent change from baseline values. However, absolute values of nerve activity are necessary to assess the impact of neural injury or disease on phrenic motor output. To date, no systematic evaluations of the repeatability/reliability have been made among animals when phrenic recordings are performed by an experienced investigator using standardized methods. We performed a meta-analysis of studies reporting integrated phrenic nerve activity in many rat groups by the same experienced investigator; comparisons were made during baseline and maximal chemoreceptor stimulation in 14 wild-type Harlan and 14 Taconic Sprague Dawley groups, and in 3 pre-symptomatic and 11 end-stage SOD1(G93A) Taconic rat groups (an ALS model). Meta-analysis results indicate: (1) consistent measurements of integrated phrenic activity in each sub-strain of wild-type rats; (2) with bilateral nerve recordings, left-to-right integrated phrenic activity ratios are ∼1.0; and (3) consistently reduced activity in end-stage SOD1(G93A) rats. Thus, with appropriate precautions, integrated phrenic nerve activity enables robust, quantitative comparisons among nerves or experimental groups, including differences caused by neuromuscular disease. Copyright © 2015 Elsevier B.V. All rights reserved.

Cerebro-afferent vessel and pupillary basal diameter variation induced by stomatognathic trigeminal proprioception: a case report.

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De Cicco, Vincenzo

2012-09-03

A patient affected by asymmetric hemodynamics of cerebro-afferent vessels underwent duplex color scanner investigations in occlusal proprioceptive un- and rebalance conditions. Pupillometric video-oculographic examinations were performed in order to spot connected trigeminal proprioceptive motor patterns able to interfere on sympathetic autonomic activity. The aim of this case report is to verify if involuntary jaw closing during swallowing, executed in unbalance and rebalance myoelectric activity, would be able to modify cerebral hemodynamics. A 56-year-old Caucasian Italian woman affected by asymmetric blood flow of cerebro-afferent vessels underwent an electromyographic investigation of her occlusal muscles in order to assess their occlusal functional balance. The extreme asymmetry of myoelectric activity in dental occlusion evidenced by electromyographic values suggested the rebalancing of the functions of occlusal muscles through concurrent transcutaneous stimulation of the trigeminal nerve supra- and submandibular motor branches. The above-mentioned method allowed the detection of a symmetric craniomandibular muscular relation that can be kept constant through the use of a cusp bite modeled on the inferior dental arch: called orthotic-syntropic bite for its peculiar use of electrostimulation. A few days later, the patient underwent a duplex color scanner investigation and pupillometric video-oculographic examinations in occlusal unbalance and rebalance conditions. A comparative data analysis showed that an unbalanced dental occlusal function may represent an interferential pattern on cerebral hemodynamics velocity and pupillometric evaluations have proved useful both in the analysis of locus coeruleus functional modalities and as a diagnostic tool in the assessment of pathologies involving locus coeruleus and autonomic systems. The inclusion of myoelectric masseter examinations can be useful in patients with asymmetric hemodynamics of cerebro-afferent

Afferent connections of nervus facialis and nervus glossopharyngeus in the pigeon (Columba livia) and their role in feeding behavior.

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Dubbeldam, J L

1984-01-01

The afferent connections of the facial nerve and glossopharyngeal nerve in the pigeon have been studied with the Fink-Heimer I method after ganglion lesions. The nucleus ventrolateralis anterior of the solitary complex and an indistinct cell group S VII medial to the nucleus interpolaris of the descending trigeminal tract are the terminal fields for facial afferents. The n. ventrolateralis anterior also receives an important projection from the distal glossopharyngeal ganglion. Other projection areas of this ganglion are the n. presulcalis , n. centralis anterior, n. intermedius anterior and the parasolitary nucleus. Both ganglia have only ipsilateral projections. A lesion in the jugular ganglion complex causes degeneration throughout the ipsilateral solitary complex, in the contralateral n. commissuralis and n. centralis posterior and in the n. cuneatus externus. The lack of a substantial contribution to the trigeminal system is ascribed to the absence of mechanoreceptors in the tongue. The implications for the organization of neuronal pathways related to the feeding behavior are discussed.

Afferent control of central pattern generators: experimental analysis of scratching in the decerebrate cat.

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Baev, K V; Esipenko, V B; Shimansky, Y P

1991-01-01

Systematic quantitative analysis of changes in the spinal scratching generator motor activity evoked by tonic and phasic peripheral afferent signals during "fictitious" scratching was carried out in the cat. Correlations between the kinematics of hindlimb scratching movement, sensory inflow, and primary afferent depolarization were investigated. Reliable correlations between the parameters of generator motor activity during fictitious scratching were revealed: they depended on tonic peripheral afferent inflow. The functional role of these dependencies consists of providing stability for aiming the hindlimb to the itch site. It was shown that scratching generator reaction to a phasic sensory signal depended significantly on afferent input, signal intensity, and its arrival phase in the cycle of motor activity. Phase correction of "scratching" rhythm was performed by inhibition of the current stage of "scratching" cycle, the inhibition magnitude depending on the intensity of a sensory signal run along high threshold afferent fibers. The moments in the scratching cycle, in which the afferent signal caused no rearrangement in scratching generator activity, were discovered for all investigated afferent inputs. These moments corresponded to the transitions from one scratching cycle phase to another. Integral afferent activity was distributed unevenly in the cycle during real scratching. The main part of it was observed just in that scratching cycle part which included the above mentioned no rearrangement phase points. The data obtained allowed us to conclude that the scratching generator should be considered as a working program for the motor optimal control system containing the intrinsic model of the controlled object dynamics (e.g. hindlimb scratching movement dynamics), which produces an inner analog of peripheral flow. This inner flow interacts with peripheral afferent inflow just as one of the latter components. Centrally originated modulation of primary afferent

Nerve-muscle activation by rotating permanent magnet configurations.

Science.gov (United States)

Watterson, Peter A; Nicholson, Graham M

2016-04-01

The standard method of magnetic nerve activation using pulses of high current in coils has drawbacks of high cost, high electrical power (of order 1 kW), and limited repetition rate without liquid cooling. Here we report a new technique for nerve activation using high speed rotation of permanent magnet configurations, generating a sustained sinusoidal electric field using very low power (of order 10 W). A high ratio of the electric field gradient divided by frequency is shown to be the key indicator for nerve activation at high frequencies. Activation of the cane toad sciatic nerve and attached gastrocnemius muscle was observed at frequencies as low as 180 Hz for activation of the muscle directly and 230 Hz for curved nerves, but probably not in straight sections of nerve. These results, employing the first prototype device, suggest the opportunity for a new class of small low-cost magnetic nerve and/or muscle stimulators. Conventional pulsed current systems for magnetic neurostimulation are large and expensive and have limited repetition rate because of overheating. Here we report a new technique for nerve activation, namely high-speed rotation of a configuration of permanent magnets. Analytical solutions of the cable equation are derived for the oscillating electric field generated, which has amplitude proportional to the rotation speed. The prototype device built comprised a configuration of two cylindrical magnets with antiparallel magnetisations, made to rotate by interaction between the magnets' own magnetic field and three-phase currents in coils mounted on one side of the device. The electric field in a rectangular bath placed on top of the device was both numerically evaluated and measured. The ratio of the electric field gradient on frequency was approximately 1 V m(-2) Hz(-1) near the device. An exploratory series of physiological tests was conducted on the sciatic nerve and attached gastrocnemius muscle of the cane toad (Bufo marinus). Activation was

C-tactile afferent stimulating touch carries a positive affective value.

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Pawling, Ralph; Cannon, Peter R; McGlone, Francis P; Walker, Susannah C

2017-01-01

The rewarding sensation of touch in affiliative interactions is hypothesized to be underpinned by a specialized system of nerve fibers called C-Tactile afferents (CTs), which respond optimally to slowly moving, gentle touch, typical of a caress. However, empirical evidence to support the theory that CTs encode socially relevant, rewarding tactile information in humans is currently limited. While in healthy participants, touch applied at CT optimal velocities (1-10cm/sec) is reliably rated as subjectively pleasant, neuronopathy patients lacking large myelinated afferents, but with intact C-fibres, report that the conscious sensation elicited by stimulation of CTs is rather vague. Given this weak perceptual impact the value of self-report measures for assessing the specific affective value of CT activating touch appears limited. Therefore, we combined subjective ratings of touch pleasantness with implicit measures of affective state (facial electromyography) and autonomic arousal (heart rate) to determine whether CT activation carries a positive affective value. We recorded the activity of two key emotion-relevant facial muscle sites (zygomaticus major-smile muscle, positive affect & corrugator supercilii-frown muscle, negative affect) while participants evaluated the pleasantness of experimenter administered stroking touch, delivered using a soft brush, at two velocities (CT optimal 3cm/sec & CT non-optimal 30cm/sec), on two skin sites (CT innervated forearm & non-CT innervated palm). On both sites, 3cm/sec stroking touch was rated as more pleasant and produced greater heart rate deceleration than 30cm/sec stimulation. However, neither self-report ratings nor heart rate responses discriminated stimulation on the CT innervated arm from stroking of the non-CT innervated palm. In contrast, significantly greater activation of the zygomaticus major (smiling muscle) was seen specifically to CT optimal, 3cm/sec, stroking on the forearm in comparison to all other stimuli

C-tactile afferent stimulating touch carries a positive affective value.

Directory of Open Access Journals (Sweden)

Ralph Pawling

Full Text Available The rewarding sensation of touch in affiliative interactions is hypothesized to be underpinned by a specialized system of nerve fibers called C-Tactile afferents (CTs, which respond optimally to slowly moving, gentle touch, typical of a caress. However, empirical evidence to support the theory that CTs encode socially relevant, rewarding tactile information in humans is currently limited. While in healthy participants, touch applied at CT optimal velocities (1-10cm/sec is reliably rated as subjectively pleasant, neuronopathy patients lacking large myelinated afferents, but with intact C-fibres, report that the conscious sensation elicited by stimulation of CTs is rather vague. Given this weak perceptual impact the value of self-report measures for assessing the specific affective value of CT activating touch appears limited. Therefore, we combined subjective ratings of touch pleasantness with implicit measures of affective state (facial electromyography and autonomic arousal (heart rate to determine whether CT activation carries a positive affective value. We recorded the activity of two key emotion-relevant facial muscle sites (zygomaticus major-smile muscle, positive affect & corrugator supercilii-frown muscle, negative affect while participants evaluated the pleasantness of experimenter administered stroking touch, delivered using a soft brush, at two velocities (CT optimal 3cm/sec & CT non-optimal 30cm/sec, on two skin sites (CT innervated forearm & non-CT innervated palm. On both sites, 3cm/sec stroking touch was rated as more pleasant and produced greater heart rate deceleration than 30cm/sec stimulation. However, neither self-report ratings nor heart rate responses discriminated stimulation on the CT innervated arm from stroking of the non-CT innervated palm. In contrast, significantly greater activation of the zygomaticus major (smiling muscle was seen specifically to CT optimal, 3cm/sec, stroking on the forearm in comparison to all

Convergence of cranial visceral afferents within the solitary tract nucleus.

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McDougall, Stuart J; Peters, James H; Andresen, Michael C

2009-10-14

Primary afferent axons within the solitary tract (ST) relay homeostatic information via glutamatergic synapses directly to second-order neurons within the nucleus of the solitary tract (NTS). These primary afferents arise from multiple organ systems and relay multiple sensory modalities. How this compact network organizes the flow of primary afferent information will shape central homeostatic control. To assess afferent convergence and divergence, we recorded ST-evoked synaptic responses in pairs of medial NTS neurons in horizontal brainstem slices. ST shocks activated EPSCs along monosynaptic or polysynaptic pathways. Gradations in shock intensity discriminated multiple inputs and stimulus recruitment profiles indicated that each EPSC was unitary. In 24 pairs, 75% were second-order neurons with 64% receiving one direct ST input with the remainder receiving additional convergent ST afferent inputs (22% two; 14% three monosynaptic ST-EPSCs). Some (34%) second-order neurons received polysynaptic EPSCs. Neurons receiving only higher-order inputs were uncommon (13%). Most ST-EPSCs were completely independent, but 4 EPSCs of a total of 81 had equal thresholds, highly correlated latencies, and synchronized synaptic failures consistent with divergence from a single source ST axon or from a common interneuron producing a pair of polysynaptic EPSCs. We conclude that ST afferent inputs are remarkably independent with little evidence of substantial shared information. Individual cells receive highly focused information from the viscera. Thus, afferent excitation of second-order NTS neurons is generally dominated by single visceral afferents and therefore focused on a single afferent modality and/or organ region.

Evaluation of dermal myelinated nerve fibers in diabetes mellitus

Science.gov (United States)

Peltier, Amanda C.; Myers, M. Iliza; Artibee, Kay J.; Hamilton, Audra D.; Yan, Qing; Guo, Jiasong; Shi, Yaping; Wang, Lily; Li, Jun

2013-01-01

Skin biopsies have primarily been used to study the non-myelinated nerve fibers of the epidermis in a variety of neuropathies. In the present study, we have expanded the skin biopsy technique to glabrous, non-hairy skin to evaluate myelinated nerve fibers in the most highly prevalent peripheral nerve disease, diabetic polyneuropathy (DPN). Twenty patients with DPN (Type I, n=9; Type II, n=11) and sixteen age-matched healthy controls (ages 29–73) underwent skin biopsy of the index finger, nerve conduction studies, and composite neuropathy scoring. In patients with DPN, we found a statistically significant reduction of both mechanoreceptive Meissner corpuscles (MC) and their afferent myelinated nerve fibers (p=0.01). This myelinated nerve fiber loss was correlated with the decreased amplitudes of sensory/motor responses in nerve conduction studies. This study supports the utilization of skin biopsy to quantitatively evaluate axonal loss of myelinated nerve fibers in patients with DPN. PMID:23781963

Transcutaneous vagus nerve stimulation (tVNS) enhances divergent thinking.

Science.gov (United States)

Colzato, Lorenza S; Ritter, Simone M; Steenbergen, Laura

2018-03-01

Creativity is one of the most important cognitive skills in our complex and fast-changing world. Previous correlative evidence showed that gamma-aminobutyric acid (GABA) is involved in divergent but not convergent thinking. In the current study, a placebo/sham-controlled, randomized between-group design was used to test a causal relation between vagus nerve and creativity. We employed transcutaneous vagus nerve stimulation (tVNS), a novel non-invasive brain stimulation technique to stimulate afferent fibers of the vagus nerve and speculated to increase GABA levels, in 80 healthy young volunteers. Creative performance was assessed in terms of divergent thinking (Alternate Uses Task) and convergent thinking tasks (Remote Associates Test, Creative Problem Solving Task, Idea Selection Task). Results demonstrate active tVNS, compared to sham stimulation, enhanced divergent thinking. Bayesian analysis reported the data to be inconclusive regarding a possible effect of tVNS on convergent thinking. Therefore, our findings corroborate the idea that the vagus nerve is causally involved in creative performance. Even thought we did not directly measure GABA levels, our results suggest that GABA (likely to be increased in active tVNS condition) supports the ability to select among competing options in high selection demand (divergent thinking) but not in low selection demand (convergent thinking). Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

Combined genetic and pharmacological inhibition of TRPV1 and P2X3 attenuates colorectal hypersensitivity and afferent sensitization

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Kiyatkin, Michael E.; Feng, Bin; Schwartz, Erica S.

2013-01-01

The ligand-gated channels transient receptor potential vanilloid 1 (TRPV1) and P2X3 have been reported to facilitate colorectal afferent neuron sensitization, thus contributing to organ hypersensitivity and pain. In the present study, we hypothesized that TRPV1 and P2X3 cooperate to modulate colorectal nociception and afferent sensitivity. To test this hypothesis, we employed TRPV1-P2X3 double knockout (TPDKO) mice and channel-selective pharmacological antagonists and evaluated combined channel contributions to behavioral responses to colorectal distension (CRD) and afferent fiber responses to colorectal stretch. Baseline responses to CRD were unexpectedly greater in TPDKO compared with control mice, but zymosan-produced CRD hypersensitivity was absent in TPDKO mice. Relative to control mice, proportions of mechanosensitive and -insensitive pelvic nerve afferent classes were not different in TPDKO mice. Responses of mucosal and serosal class afferents to mechanical probing were unaffected, whereas responses of muscular (but not muscular/mucosal) afferents to stretch were significantly attenuated in TPDKO mice; sensitization of both muscular and muscular/mucosal afferents by inflammatory soup was also significantly attenuated. In pharmacological studies, the TRPV1 antagonist A889425 and P2X3 antagonist TNP-ATP, alone and in combination, applied onto stretch-sensitive afferent endings attenuated responses to stretch; combined antagonism produced greater attenuation. In the aggregate, these observations suggest that 1) genetic manipulation of TRPV1 and P2X3 leads to reduction in colorectal mechanosensation peripherally and compensatory changes and/or disinhibition of other channels centrally, 2) combined pharmacological antagonism produces more robust attenuation of mechanosensation peripherally than does antagonism of either channel alone, and 3) the relative importance of these channels appears to be enhanced in colorectal hypersensitivity. PMID:23989007

Contributions of central command and muscle feedback to sympathetic nerve activity in contracting human skeletal muscle

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Daniel eBoulton

2016-05-01

Full Text Available During voluntary contractions, muscle sympathetic nerve activity (MSNA to contracting muscles increases in proportion to force but the underlying mechanisms are not clear. To shed light on these mechanisms, particularly the influences of central command and muscle afferent feedback, the present study tested the hypothesis that MSNA is greater during voluntary compared with electrically-evoked contractions. Seven male subjects performed a series of 1-minute isometric dorsiflexion contractions (left leg separated by 2-minute rest periods, alternating between voluntary and electrically-evoked contractions at similar forces (5-10 % of maximum. MSNA was recorded continuously (microneurography from the left peroneal nerve and quantified from cardiac-synchronised, negative-going spikes in the neurogram. Compared with pre-contraction values, MSNA increased by 51 ± 34 % (P 0.05. MSNA analysed at 15-s intervals revealed that this effect of voluntary contraction appeared 15-30 s after contraction onset (P < 0.01, remained elevated until the end of contraction, and disappeared within 15 s after contraction. These findings suggest that central command, and not feedback from contracting muscle, is the primary mechanism responsible for the increase in MSNA to contracting muscle. The time-course of MSNA suggests that there is a longer delay in the onset of this effect compared with its cessation after contraction.

Capsaicin-sensitive muscle afferents modulate the monosynaptic reflex in response to muscle ischemia and fatigue in the rat.

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Della Torre, G; Brunetti, O; Pettorossi, V E

2002-01-01

The role of muscle ischemia and fatigue in modulating the monosynaptic reflex was investigated in decerebrate and spinalized rats. Field potentials and fast motoneuron single units in the lateral gastrocnemious (LG) motor pool were evoked by dorsal root stimulation. Muscle ischemia was induced by occluding the LG vascular supply and muscle fatigue by prolonged tetanic electrical stimulation of the LG motor nerve. Under muscle ischemia the monosynaptic reflex was facilitated since the size of the early and late waves of the field potential and the excitability of the motoneuron units increased. This effect was abolished after L3-L6 dorsal rhizotomy, but it was unaffected after L3-L6 ventral rhizotomy. By contrast, the monosynaptic reflex was inhibited by muscle fatiguing stimulation, and this effect did not fully depend on the integrity of the dorsal root. However, when ischemia was combined with repetitive tetanic muscle stimulation the inhibitory effect of fatigue was significantly enhanced. Both the ischemia and fatigue effects were abolished by capsaicin injected into the LG muscle at a dose that blocked a large number of group III and IV muscle afferents. We concluded that muscle ischemia and fatigue activate different groups of muscle afferents that are both sensitive to capsaicin, but enter the spinal cord through different roots. They are responsible for opposite effects, when given separately: facilitation during ischemia and inhibition during fatigue; however, in combination, ischemia enhances the responsiveness of the afferent fibres to fatigue.

Identification of the visceral pain pathway activated by noxious colorectal distension in mice

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Melinda eKyloh

2011-02-01

Full Text Available In patients with irritable bowel syndrome (IBS, visceral pain is evoked more readily following distension of the colorectum. However, the identity of extrinsic afferent nerve pathway that detects and transmits visceral pain from the colorectum to the spinal cord is unclear. In this study, we identified which extrinsic nerve pathway(s underlies nociception from the colorectum to the spinal cord of rodents. Electromyogram (EMG recordings were made from the transverse oblique abdominal muscles in anesthetized wild type (C57BL/6 mice and acute noxious intraluminal distension (100-120 mmHg applied to the terminal 15mm of rectum to activate visceromotor responses (VMRs. Cutting the lumbar colonic nerves in vivo had no detectable effect on the VMRs evoked by colorectal distension. Lesioning right or left hypogastric nerves also failed to reduce VMRs. However, lesioning left and right branches of the rectal nerves completely abolished the VMRs, regardless of whether the lumbar colonic or hypogastric nerves were severed. Electrical stimulation applied to either the lumbar colonic or hypogastric nerves in vivo, failed to elicit a VMR. In contrast, electrical stimulation (2-5Hz, 0.4ms, 60V applied to the rectum reliably elicited VMRs, which were abolished by selective lesioning of the rectal nerves. DiI retrograde labelling from the colorectum labelled sensory neurons only in dorsal root ganglia (DRG of the lumbosacral region of the spinal cord. In contrast, injection of DiI into the mid to proximal colon labelled sensory neurons in DRG primarily of the lower thoracic level (T8-L4 of the spinal cord. The visceral pain pathway activated by acute noxious distension of the terminal 15 mm of mouse rectum is transmitted predominantly, if not solely, through rectal/pelvic afferent nerve fibres to the spinal cord. The sensory neurons of this spinal afferent pathway lie in the lumbosacral region of the spinal cord, primarily at the level of S2 and S3.

Liver afferents contribute to water drinking-induced sympathetic activation in human subjects: a clinical trial.

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Marcus May

Full Text Available Water drinking acutely increases sympathetic activity in human subjects. In animals, the response appears to be mediated through transient receptor potential channel TRPV4 activation on osmosensitive hepatic spinal afferents, described as osmopressor response. We hypothesized that hepatic denervation attenuates water drinking-induced sympathetic activation. We studied 20 liver transplant recipients (44±2.6 years, 1.2±0.1 years post transplant as model of hepatic denervation and 20 kidney transplant recipients (43±2.6 years, 0.8±0.1 years post transplant as immunosuppressive drug matched control group. Before and after 500 ml water ingestion, we obtained venous blood samples for catecholamine analysis. We also monitored brachial and finger blood pressure, ECG, and thoracic bioimpedance. Plasma norepinephrine concentration had changed by 0.01±0.07 nmol/l in liver and by 0.21±0.07 nmol/l in kidney transplant recipients (p<0.05 between groups after 30-40 minutes of water drinking. While blood pressure and systemic vascular resistance increased in both groups, the responses tended to be attenuated in liver transplant recipients. Our findings support the idea that osmosensitive hepatic afferents are involved in water drinking-induced sympathetic activation in human subjects.ClinicalTrials.gov NCT01237431.

Liver Afferents Contribute to Water Drinking-Induced Sympathetic Activation in Human Subjects: A Clinical Trial

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May, Marcus; Gueler, Faikah; Barg-Hock, Hannelore; Heiringhoff, Karl-Heinz; Engeli, Stefan; Heusser, Karsten; Diedrich, André; Brandt, André; Strassburg, Christian P.; Tank, Jens; Sweep, Fred C. G. J.; Jordan, Jens

2011-01-01

Water drinking acutely increases sympathetic activity in human subjects. In animals, the response appears to be mediated through transient receptor potential channel TRPV4 activation on osmosensitive hepatic spinal afferents, described as osmopressor response. We hypothesized that hepatic denervation attenuates water drinking-induced sympathetic activation. We studied 20 liver transplant recipients (44±2.6 years, 1.2±0.1 years post transplant) as model of hepatic denervation and 20 kidney transplant recipients (43±2.6 years, 0.8±0.1 years post transplant) as immunosuppressive drug matched control group. Before and after 500 ml water ingestion, we obtained venous blood samples for catecholamine analysis. We also monitored brachial and finger blood pressure, ECG, and thoracic bioimpedance. Plasma norepinephrine concentration had changed by 0.01±0.07 nmol/l in liver and by 0.21±0.07 nmol/l in kidney transplant recipients (pwater drinking. While blood pressure and systemic vascular resistance increased in both groups, the responses tended to be attenuated in liver transplant recipients. Our findings support the idea that osmosensitive hepatic afferents are involved in water drinking-induced sympathetic activation in human subjects. Trial Registration ClinicalTrials.gov NCT01237431 PMID:22016786

Lung vagal afferent activity in rats with bleomycin-induced lung fibrosis.

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Schelegle, E S; Walby, W F; Mansoor, J K; Chen, A T

2001-05-01

Bleomycin treatment in rats results in pulmonary fibrosis that is characterized by a rapid shallow breathing pattern, a decrease in quasi-static lung compliance and a blunting of the Hering-Breuer Inflation Reflex. We examined the impulse activity of pulmonary vagal afferents in anesthetized, mechanically ventilated rats with bleomycin-induced lung fibrosis during the ventilator cycle and static lung inflations/deflations and following the injection of capsaicin into the right atrium. Bleomycin enhanced volume sensitivity of slowly adapting stretch receptors (SARs), while it blunted the sensitivity of these receptors to increasing transpulmonary pressure. Bleomycin treatment increased the inspiratory activity, while it decreased the expiratory activity of rapidly adapting stretch receptors (RARs). Pulmonary C-fiber impulse activity did not appear to be affected by bleomycin treatment. We conclude that the fibrosis-related shift in discharge profile and enhanced volume sensitivity of SARs combined with the increased inspiratory activity of RARs contributes to the observed rapid shallow breathing of bleomycin-induced lung fibrosis.

Stimulation of renal afferent fibers leads to activation of catecholaminergic and non-catecholaminergic neurons in the medulla oblongata.

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Nishi, Erika E; Martins, Beatriz S; Milanez, Maycon I O; Lopes, Nathalia R; de Melo, Jose F; Pontes, Roberto B; Girardi, Adriana C; Campos, Ruy R; Bergamaschi, Cássia T

2017-05-01

Presympathetic neurons in the rostral ventrolateral medulla (RVLM) including the adrenergic cell groups play a major role in the modulation of several reflexes required for the control of sympathetic vasomotor tone and blood pressure (BP). Moreover, sympathetic vasomotor drive to the kidneys influence natriuresis and diuresis by inhibiting the cAMP/PKA pathway and redistributing the Na + /H + exchanger isoform 3 (NHE3) to the body of the microvilli in the proximal tubules. In this study we aimed to evaluate the effects of renal afferents stimulation on (1) the neurochemical phenotype of Fos expressing neurons in the medulla oblongata and (2) the level of abundance and phosphorylation of NHE3 in the renal cortex. We found that electrical stimulation of renal afferents increased heart rate and BP transiently and caused activation of tyrosine hydroxylase (TH)-containing neurons in the RVLM and non-TH neurons in the NTS. Additionally, activation of the inhibitory renorenal reflex over a 30-min period resulted in increased natriuresis and diuresis associated with increased phosphorylation of NHE3 at serine 552, a surrogate for reduced activity of this exchanger, in the contralateral kidney. This effect was not dependent of BP changes considering that no effects on natriuresis or diuresis were found in the ipsilateral-stimulated kidney. Therefore, our data show that renal afferents leads to activation of catecholaminergic and non-catecholaminergic neurons in the medulla oblongata. When renorenal reflex is induced, NHE3 exchanger activity appears to be decreased, resulting in decreased sodium and water reabsorption in the contralateral kidney. Copyright © 2017 Elsevier B.V. All rights reserved.

Afferent Pathway-Mediated Effect of α1 Adrenergic Antagonist, Tamsulosin, on the Neurogenic Bladder After Spinal Cord Injury.

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Han, Jin-Hee; Kim, Sung-Eun; Ko, Il-Gyu; Kim, Jayoung; Kim, Khae Hawn

2017-09-01

The functions of the lower urinary tract (LUT), such as voiding and storing urine, are dependent on complex central neural networks located in the brain, spinal cord, and peripheral ganglia. Thus, the functions of the LUT are susceptible to various neurologic disorders including spinal cord injury (SCI). SCI at the cervical or thoracic levels disrupts voluntary control of voiding and the normal reflex pathways coordinating bladder and sphincter functions. In this context, it is noteworthy that α1-adrenoceptor blockers have been reported to relieve voiding symptoms and storage symptoms in elderly men with benign prostatic hyperplasia (BPH). Tamsulosin, an α1-adrenoceptor blocker, is also considered the most effective regimen for patients with LUT symptoms such as BPH and overactive bladder (OAB). In the present study, the effects of tamsulosin on the expression of c-Fos, nerve growth factor (NGF), and nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-d) in the afferent micturition areas, including the pontine micturition center (PMC), the ventrolateral periaqueductal gray matter (vlPAG), and the spinal cord (L5), of rats with an SCI were investigated. SCI was found to remarkably upregulate the expression of c-Fos, NGF, and NADPH-d in the afferent pathway of micturition, the dorsal horn of L5, the vlPAG, and the PMC, resulting in the symptoms of OAB. In contrast, tamsulosin treatment significantly suppressed these neural activities and the production of nitric oxide in the afferent pathways of micturition, and consequently, attenuated the symptoms of OAB. Based on these results, tamsulosin, an α1-adrenoceptor antagonist, could be used to attenuate bladder dysfunction following SCI. However, further studies are needed to elucidate the exact mechanism and effects of tamsulosin on the afferent pathways of micturition.

The projection and synaptic organisation of NTS afferent connections with presympathetic neurons, GABA and nNOS neurons in the paraventricular nucleus of the hypothalamus

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Affleck, V.S.; Coote, J.H.; Pyner, S.

2012-01-01

Elevated sympathetic nerve activity, strongly associated with cardiovascular disease, is partly generated from the presympathetic neurons of the paraventricular nucleus of the hypothalamus (PVN). The PVN-presympathetic neurons regulating cardiac and vasomotor sympathetic activity receive information about cardiovascular status from receptors in the heart and circulation. These receptors signal changes via afferent neurons terminating in the nucleus tractus solitarius (NTS), some of which may result in excitation or inhibition of PVN-presympathetic neurons. Understanding the anatomy and neurochemistry of NTS afferent connections within the PVN could provide important clues to the impairment in homeostasis cardiovascular control associated with disease. Transynaptic labelling has shown the presence of neuronal nitric oxide synthase (nNOS)-containing neurons and GABA interneurons that terminate on presympathetic PVN neurons any of which may be the target for NTS afferents. So far NTS connections to these diverse neuronal pools have not been demonstrated and were investigated in this study. Anterograde (biotin dextran amine – BDA) labelling of the ascending projection from the NTS and retrograde (fluorogold – FG or cholera toxin B subunit – CTB) labelling of PVN presympathetic neurons combined with immunohistochemistry for GABA and nNOS was used to identify the terminal neuronal targets of the ascending projection from the NTS. It was shown that NTS afferent terminals are apposed to either PVN-GABA interneurons or to nitric oxide producing neurons or even directly to presympathetic neurons. Furthermore, there was evidence that some NTS axons were positive for vesicular glutamate transporter 2 (vGLUT2). The data provide an anatomical basis for the different functions of cardiovascular receptors that mediate their actions via the NTS–PVN pathways. PMID:22698695

The expression profile of acid-sensing ion channel (ASIC) subunits ASIC1a, ASIC1b, ASIC2a, ASIC2b, and ASIC3 in the esophageal vagal afferent nerve subtypes.

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Dusenkova, Svetlana; Ru, Fei; Surdenikova, Lenka; Nassenstein, Christina; Hatok, Jozef; Dusenka, Robert; Banovcin, Peter; Kliment, Jan; Tatar, Milos; Kollarik, Marian

2014-11-01

Acid-sensing ion channels (ASICs) have been implicated in esophageal acid sensing and mechanotransduction. However, insufficient knowledge of ASIC subunit expression profile in esophageal afferent nerves hampers the understanding of their role. This knowledge is essential because ASIC subunits form heteromultimeric channels with distinct functional properties. We hypothesized that the esophageal putative nociceptive C-fiber nerves (transient receptor potential vanilloid 1, TRPV1-positive) express multiple ASIC subunits and that the ASIC expression profile differs between the nodose TRPV1-positive subtype developmentally derived from placodes and the jugular TRPV1-positive subtype derived from neural crest. We performed single cell RT-PCR on the vagal afferent neurons retrogradely labeled from the esophagus. In the guinea pig, nearly all (90%-95%) nodose and jugular esophageal TRPV1-positive neurons expressed ASICs, most often in a combination (65-75%). ASIC1, ASIC2, and ASIC3 were expressed in 65-75%, 55-70%, and 70%, respectively, of both nodose and jugular TRPV1-positive neurons. The ASIC1 splice variants ASIC1a and ASIC1b and the ASIC2 splice variant ASIC2b were similarly expressed in both nodose and jugular TRPV1-positive neurons. However, ASIC2a was found exclusively in the nodose neurons. In contrast to guinea pig, ASIC3 was almost absent from the mouse vagal esophageal TRPV1-positive neurons. However, ASIC3 was similarly expressed in the nonnociceptive TRPV1-negative (tension mechanoreceptors) neurons in both species. We conclude that the majority of esophageal vagal nociceptive neurons express multiple ASIC subunits. The placode-derived nodose neurons selectively express ASIC2a, known to substantially reduce acid sensitivity of ASIC heteromultimers. ASIC3 is expressed in the guinea pig but not in the mouse vagal esophageal TRPV1-positive neurons, indicating species differences in ASIC expression. Copyright © 2014 the American Physiological Society.

Comparison of Transcutaneous Electrical Nerve Stimulation and Cryotherapy for Increasing Quadriceps Activation in Patients With Knee Pathologies.

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Gabler, Conrad M; Lepley, Adam S; Uhl, Tim L; Mattacola, Carl G

2016-08-01

Proper neuromuscular activation of the quadriceps muscle is essential for maintaining quadriceps (quad) strength and lower-extremity function. Quad activation (QA) failure is a common characteristic observed in patients with knee pathologies, defined as an inability to voluntarily activate the entire alpha-motor-neuron pool innervating the quad. One of the more popular techniques used to assess QA is the superimposed burst (SIB) technique, a force-based technique that uses a supramaximal, percutaneous electrical stimulation to activate all of the motor units in the quad during a maximal, voluntary isometric contraction. Central activation ratio (CAR) is the formula used to calculate QA level (CAR = voluntary force/SIB force) with the SIB technique. People who can voluntarily activate 95% or more (CAR = 0.95-1.0) of their motor units are defined as being fully activated. Therapeutic exercises aimed at improving quad strength in patients with knee pathologies are limited in their effectiveness due to a failure to fully activate the muscle. Within the past decade, several disinhibitory interventions have been introduced to treat QA failure in patients with knee pathologies. Transcutaneous electrical nerve stimulation (TENS) and cryotherapy are sensory-targeted modalities traditionally used to treat pain, but they have been shown to be 2 of the most successful treatments for increasing QA levels in patients with QA failure. Both modalities are hypothesized to positively affect voluntary QA by disinhibiting the motor-neuron pool of the quad. In essence, these modalities provide excitatory afferent stimuli to the spinal cord, which thereby overrides the inhibitory afferent signaling that arises from the involved joint. However, it remains unknown whether 1 is more effective than the other for restoring QA levels in patients with knee pathologies. By knowing the capabilities of each disinhibitory modality, clinicians can tailor treatments based on the rehabilitation goals

Experimental study of vascularized nerve graft: evaluation of nerve regeneration using choline acetyltransferase activity.

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Iwai, M; Tamai, S; Yajima, H; Kawanishi, K

2001-01-01

A comparative study of nerve regeneration was performed on vascularized nerve graft (VNG) and free nerve graft (FNG) in Fischer strain rats. A segment of the sciatic nerve with vascular pedicle of the femoral artery and vein was harvested from syngeneic donor rat for the VNG group and the sciatic nerve in the same length without vascular pedicle was harvested for the FNG group. They were transplanted to a nerve defect in the sciatic nerve of syngeneic recipient rats. At 2, 4, 6, 8, 12, 16, and 24 weeks after operation, the sciatic nerves were biopsied and processed for evaluation of choline acetyltransferase (CAT) activity, histological studies, and measurement of wet weight of the muscle innervated by the sciatic nerve. Electrophysiological evaluation of the grafted nerve was also performed before sacrifice. The average CAT activity in the distal to the distal suture site was 383 cpm in VNG and 361 cpm in FNG at 2 weeks; 6,189 cpm in VNG and 2,264 cpm in FNG at 4 weeks; and 11,299 cpm in VNG and 9,424 cpm in FNG at 6 weeks postoperatively. The value of the VNG group was statistically higher than that of the FNG group at 4 weeks postoperatively. Electrophysiological and histological findings also suggested that nerve regeneration in the VNG group was superior to that in the FNG group during the same period. However, there was no significant difference between the two groups after 6 weeks postoperatively in any of the evaluations. The CAT measurement was useful in the experiments, because it was highly sensitive and reproducible. Copyright 2001 Wiley-Liss, Inc.

Effects of capsaicin in the motor nerve.

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Pettorossi, V E; Bortolami, R; Della Torre, G; Brunetti, O

1994-08-01

The injection of capsaicin into the lateral gastrocnemius (LG) muscle of the rat induced an immediate and sustained reduction in the A delta and C components of the compound action potential (CAP) of the LG motor nerve. Conversely, the drug did not immediately affect the CAP wave belonging to fast-conducting fibers or the motor responses to LG nerve stimulation. It seems that capsaicin only affects the group III and IV afferents of LG nerve. However, a week after the injection the capsaicin also altered the motor responses, as shown by the threshold enhancement and amplitude reduction of the muscle twitch and by the decrease of the A alpha-beta CAP components. This late motor impairment was attributed to a central depression following a reduction of capsaicin-sensitive neuron input into the CNS. However, this motor effect was transient since the LG nerve regained the preinjection excitability level in a week and the muscle twitch amplitude reached the control value in a month.

Expression of phosphorylated cAMP response element binding protein (p-CREB) in bladder afferent pathways in VIP-/- mice with cyclophosphamide (CYP)-induced cystitis

DEFF Research Database (Denmark)

Jensen, Dorthe G; Studeny, Simon; May, Victor

2008-01-01

The expression of phosphorylated cAMP response element binding protein (p-CREB) in dorsal root ganglia (DRG) with and without cyclophosphamide (CYP)-induced cystitis (150 mg/kg, i.p; 48 h) was determined in VIP(-/-) and wild-type (WT) mice. p-CREB immunoreactivity (IR) was determined in bladder...... (Fast blue) afferent cells. Nerve growth factor (NGF) bladder content was determined by enzyme-linked immunosorbent assays. Basal expression of p-CREB-IR in DRG of VIP(-/-) mice was (p DRG compared to WT mice. CYP treatment in WT mice increased (p ...-CREB-IR in L1, L2, L5-S1 DRG. CYP treatment in VIP(-/-) mice (p DRG compared to WT with CYP. In WT mice, bladder afferent cells (20-38%) in DRG expressed p-CREB-IR under basal conditions. With CYP, p-CREB-IR increased in bladder afferent cells (60...

Duodenal activation of cAMP-dependent protein kinase induces vagal afferent firing and lowers glucose production in rats.

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Rasmussen, Brittany A; Breen, Danna M; Luo, Ping; Cheung, Grace W C; Yang, Clair S; Sun, Biying; Kokorovic, Andrea; Rong, Weifang; Lam, Tony K T

2012-04-01

The duodenum senses nutrients to maintain energy and glucose homeostasis, but little is known about the signaling and neuronal mechanisms involved. We tested whether duodenal activation of adenosine 3',5'-cyclic monophosphate (cAMP)-dependent protein kinase A (PKA) is sufficient and necessary for cholecystokinin (CCK) signaling to trigger vagal afferent firing and regulate glucose production. In rats, we selectively activated duodenal PKA and evaluated changes in glucose kinetics during the pancreatic (basal insulin) pancreatic clamps and vagal afferent firing. The requirement of duodenal PKA signaling in glucose regulation was evaluated by inhibiting duodenal activation of PKA in the presence of infusion of the intraduodenal PKA agonist (Sp-cAMPS) or CCK1 receptor agonist (CCK-8). We also assessed the involvement of a neuronal network and the metabolic impact of duodenal PKA activation in rats placed on high-fat diets. Intraduodenal infusion of Sp-cAMPS activated duodenal PKA and lowered glucose production, in association with increased vagal afferent firing in control rats. The metabolic and neuronal effects of duodenal Sp-cAMPS were negated by coinfusion with either the PKA inhibitor H89 or Rp-CAMPS. The metabolic effect was also negated by coinfusion with tetracaine, molecular and pharmacologic inhibition of NR1-containing N-methyl-d-aspartate (NMDA) receptors within the dorsal vagal complex, or hepatic vagotomy in rats. Inhibition of duodenal PKA blocked the ability of duodenal CCK-8 to reduce glucose production in control rats, whereas duodenal Sp-cAMPS bypassed duodenal CCK resistance and activated duodenal PKA and lowered glucose production in rats on high-fat diets. We identified a neural glucoregulatory function of duodenal PKA signaling. Copyright © 2012 AGA Institute. Published by Elsevier Inc. All rights reserved.

Cooling reduces the cutaneous afferent firing response to vibratory stimuli in glabrous skin of the human foot sole.

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Lowrey, Catherine R; Strzalkowski, Nicholas D J; Bent, Leah R

2013-02-01

Skin on the foot sole plays an important role in postural control. Cooling the skin of the foot is often used to induce anesthesia to determine the role of skin in motor and balance control. The effect of cooling on the four classes of mechanoreceptor in the skin is largely unknown, and thus the aim of the present study was to characterize the effects of cooling on individual skin receptors in the foot sole. Such insight will better isolate individual receptor contributions to balance control. Using microneurography, we recorded 39 single nerve afferents innervating mechanoreceptors in the skin of the foot sole in humans. Afferents were identified as fast-adapting (FA) or slowly adapting (SA) type I or II (FA I n = 16, FA II n = 7, SA I n = 6, SA II n = 11). Receptor response to vibration was compared before and after cooling of the receptive field (2-20 min). Overall, firing response was abolished in 30% of all receptors, and this was equally distributed across receptor type (P = 0.69). Longer cooling times were more likely to reduce firing response below 50% of baseline; however, some afferent responses were abolished with shorter cooling times (2-5 min). Skin temperature was not a reliable indicator of the level of receptor activation and often became uncoupled from receptor response levels, suggesting caution in the use of this parameter as an indicator of anesthesia. When cooled, receptors preferentially coded lower frequencies in response to vibration. In response to a sustained indentation, SA receptors responded more like FA receptors, primarily coding "on-off" events.

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

Science.gov (United States)

Gemes, Geza; Koopmeiners, Andrew; Rigaud, Marcel; Lirk, Philipp; Sapunar, Damir; Bangaru, Madhavi Latha; Vilceanu, Daniel; Garrison, Sheldon R; Ljubkovic, Marko; Mueller, Samantha J; Stucky, Cheryl L; Hogan, Quinn H

2013-02-15

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.

Influence of ventilation and hypocapnia on sympathetic nerve responses to hypoxia in normal humans.

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Somers, V K; Mark, A L; Zavala, D C; Abboud, F M

1989-11-01

The sympathetic response to hypoxia depends on the interaction between chemoreceptor stimulation (CRS) and the associated hyperventilation. We studied this interaction by measuring sympathetic nerve activity (SNA) to muscle in 13 normal subjects, while breathing room air, 14% O2, 10% O2, and 10% O2 with added CO2 to maintain isocapnia. Minute ventilation (VE) and blood pressure (BP) increased significantly more during isocapnic hypoxia (IHO) than hypocapnic hypoxia (HHO). In contrast, SNA increased more during HHO [40 +/- 10% (SE)] than during IHO (25 +/- 19%, P less than 0.05). To determine the reason for the lesser increase in SNA with IHO, 11 subjects underwent voluntary apnea during HHO and IHO. Apnea potentiated the SNA responses to IHO more than to HHO. SNA responses to IHO were 17 +/- 7% during breathing and 173 +/- 47% during apnea whereas SNA responses to HHO were 35 +/- 8% during breathing and 126 +/- 28% during apnea. During ventilation, the sympathoexcitation of IHO (compared with HHO) is suppressed, possibly for two reasons: 1) because of the inhibitory influence of activation of pulmonary afferents as a result of a greater increase in VE, and 2) because of the inhibitory influence of baroreceptor activation due to a greater rise in BP. Thus in humans, the ventilatory response to chemoreceptor stimulation predominates and restrains the sympathetic response. The SNA response to chemoreceptor stimulation represents the net effect of the excitatory influence of the chemoreflex and the inhibitory influence of pulmonary afferents and baroreceptor afferents.

Transient receptor potential A1 channel contributes to activation of the muscle reflex.

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Koba, Satoshi; Hayes, Shawn G; Sinoway, Lawrence I

2011-01-01

This study was undertaken to elucidate the role played by transient receptor potential A1 channels (TRPA1) in activating the muscle reflex, a sympathoexcitatory drive originating in contracting muscle. First, we tested the hypothesis that stimulation of the TRPA1 located on muscle afferents reflexly increases sympathetic nerve activity. In decerebrate rats, allyl isothiocyanate, a TRPA1 agonist, was injected intra-arterially into the hindlimb muscle circulation. This led to a 33% increase in renal sympathetic nerve activity (RSNA). The effect of allyl isothiocyanate was a reflex because the response was prevented by sectioning the sciatic nerve. Second, we tested the hypothesis that blockade of TRPA1 reduces RSNA response to contraction. Thirty-second continuous static contraction of the hindlimb muscles, induced by electrical stimulation of the peripheral cut ends of L(4) and L(5) ventral roots, increased RSNA and blood pressure. The integrated RSNA during contraction was reduced by HC-030031, a TRPA1 antagonist, injected intra-arterially (163 ± 24 vs. 95 ± 21 arbitrary units, before vs. after HC-030031, P reflex. Increases in RSNA in response to injection into the muscle circulation of arachidonic acid, bradykinin, and diprotonated phosphate, which are metabolic by-products of contraction and stimulants of muscle afferents during contraction, were reduced by HC-030031. These observations suggest that the TRPA1 located on muscle afferents is part of the muscle reflex and further support the notion that arachidonic acid metabolites, bradykinin, and diprotonated phosphate are candidates for endogenous agonists of TRPA1.

Excitatory and inhibitory synaptic mechanisms at the first stage of integration in the electroreception system of the shark

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Rotem, Naama; Sestieri, Emanuel; Hounsgaard, Jørn Dybkjær

2014-01-01

High impulse rate in afferent nerves is a common feature in many sensory systems that serve to accommodate a wide dynamic range. However, the first stage of integration should be endowed with specific properties that enable efficient handling of the incoming information. In elasmobranches...... of this afferent pathway. We found that stimulating the afferent nerve activates a mixture of excitatory and inhibitory synapses mediated by AMPA-like and GABAA receptors, respectively. The excitatory synapses that are extremely efficient in activating the postsynaptic neurons display unusual voltage dependence......, enabling them to operate as a current source. The inhibitory input is powerful enough to completely eliminate the excitatory action of the afferent nerve but is ineffective regarding other excitatory inputs. These observations can be explained by the location and efficiency of the synapses. We conclude...

Perceptual consequences of disrupted auditory nerve activity.

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Zeng, Fan-Gang; Kong, Ying-Yee; Michalewski, Henry J; Starr, Arnold

2005-06-01

Perceptual consequences of disrupted auditory nerve activity were systematically studied in 21 subjects who had been clinically diagnosed with auditory neuropathy (AN), a recently defined disorder characterized by normal outer hair cell function but disrupted auditory nerve function. Neurological and electrophysical evidence suggests that disrupted auditory nerve activity is due to desynchronized or reduced neural activity or both. Psychophysical measures showed that the disrupted neural activity has minimal effects on intensity-related perception, such as loudness discrimination, pitch discrimination at high frequencies, and sound localization using interaural level differences. In contrast, the disrupted neural activity significantly impairs timing related perception, such as pitch discrimination at low frequencies, temporal integration, gap detection, temporal modulation detection, backward and forward masking, signal detection in noise, binaural beats, and sound localization using interaural time differences. These perceptual consequences are the opposite of what is typically observed in cochlear-impaired subjects who have impaired intensity perception but relatively normal temporal processing after taking their impaired intensity perception into account. These differences in perceptual consequences between auditory neuropathy and cochlear damage suggest the use of different neural codes in auditory perception: a suboptimal spike count code for intensity processing, a synchronized spike code for temporal processing, and a duplex code for frequency processing. We also proposed two underlying physiological models based on desynchronized and reduced discharge in the auditory nerve to successfully account for the observed neurological and behavioral data. These methods and measures cannot differentiate between these two AN models, but future studies using electric stimulation of the auditory nerve via a cochlear implant might. These results not only show the unique

Mast Cells and Nerve Signal Conduction in Acupuncture

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Na Yin

2018-01-01

Full Text Available Nerve and mast cells are densely distributed around acupoints in connective tissue. To explore the internal relations between them in acupuncture effect, we examined dorsal root potential (DRP response to acupuncture at Zusanli (ST36 under sodium cromoglicate (DSCG, a mast cell stabilizer intervention in anesthetized Sprague-Dawley (SD rats. We used single unit nerve recording techniques to collect nerve signals from DRP afferent nerves for a 45-minute period that includes 4 stages, that is, base, drug absorption, acupuncture, and recovery stages. We analyzed the recorded signals from time-domain and frequency-domain perspectives. The results showed that once acupuncture needle was inserted, twisting needle excited more nerves discharges than those at base discharges in ACU (from 35.1 ± 7.2 to 47 ± 9.2 Hz, P=0.004, and there existed the same trend in Saline + ACU group (from 23.8 ± 2.6 to 29.8 ± 4.2 Hz, P=0.059. There was no change of nerve discharges under twisting needle with injection of DSCG (from 34.8 ± 5.3 to 34.7 ± 4.4 Hz, P=0.480. We conclude that acupuncture manipulation promotes neural signal production and DSCG could partly inhibit nerve discharges.

Activation of GLP-1 receptors on vascular smooth muscle cells reduces the autoregulatory response in afferent arterioles and increases renal blood flow.

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Jensen, Elisa P; Poulsen, Steen S; Kissow, Hannelouise; Holstein-Rathlou, Niels-Henrik; Deacon, Carolyn F; Jensen, Boye L; Holst, Jens J; Sorensen, Charlotte M

2015-04-15

Glucagon-like peptide (GLP)-1 has a range of extrapancreatic effects, including renal effects. The mechanisms are poorly understood, but GLP-1 receptors have been identified in the kidney. However, the exact cellular localization of the renal receptors is poorly described. The aim of the present study was to localize renal GLP-1 receptors and describe GLP-1-mediated effects on the renal vasculature. We hypothesized that renal GLP-1 receptors are located in the renal microcirculation and that activation of these affects renal autoregulation and increases renal blood flow. In vivo autoradiography using (125)I-labeled GLP-1, (125)I-labeled exendin-4 (GLP-1 analog), and (125)I-labeled exendin 9-39 (GLP-1 receptor antagonist) was performed in rodents to localize specific GLP-1 receptor binding. GLP-1-mediated effects on blood pressure, renal blood flow (RBF), heart rate, renin secretion, urinary flow rate, and Na(+) and K(+) excretion were investigated in anesthetized rats. Effects of GLP-1 on afferent arterioles were investigated in isolated mouse kidneys. Specific binding of (125)I-labeled GLP-1, (125)I-labeled exendin-4, and (125)I-labeled exendin 9-39 was observed in the renal vasculature, including afferent arterioles. Infusion of GLP-1 increased blood pressure, RBF, and urinary flow rate significantly in rats. Heart rate and plasma renin concentrations were unchanged. Exendin 9-39 inhibited the increase in RBF. In isolated murine kidneys, GLP-1 and exendin-4 significantly reduced the autoregulatory response of afferent arterioles in response to stepwise increases in pressure. We conclude that GLP-1 receptors are located in the renal vasculature, including afferent arterioles. Activation of these receptors reduces the autoregulatory response of afferent arterioles to acute pressure increases and increases RBF in normotensive rats. Copyright © 2015 the American Physiological Society.

Afferent connectivity of the zebrafish habenulae

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Katherine Jane Turner

2016-04-01

Full Text Available The habenulae are bilateral nuclei located in the dorsal diencephalon that are conserved across vertebrates.Here we describe the main afferents to the habenulae in larval and adult zebrafish.We observe afferents from the subpallium, nucleus rostrolateralis,posterior tuberculum, posterior hypothalamic lobe, median raphe, olfactory bulb to the right habenula and from the parapineal to the lefthabenula.In addition,we find afferents from a ventrolateral telencephalic nucleus that neurochemical and hodological data identify as the ventral entopeduncular nucleus(vENT,confirming and extending observations of Amo et al.(2014.Fate map and marker studies suggest that vENT originates from the diencephalic prethalamic eminence and extends into the lateral telencephalon from 48 to 120 hpf.No afferents to the habenula were observed from the dorsal entopeduncular nucleus(dENT.Consequently,we confirm that the vENT(and not the dENT should be considered as the entopeduncular nucleus proper in zebrafish.Furthermore,comparison with data in other vertebrates suggests that the vENT is a conserved basal ganglia nucleus,being homologous to the entopeduncular nucleus of mammals(internal segment of the globus pallidus of primates by both embryonic origin and projections,as previously suggested by Amo et al.(2014.Key words: habenula,connections,afferents,entopeduncular nucleus,posterior tuberculum,basal ganglia,zebrafish

Afferent Connectivity of the Zebrafish Habenulae

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Turner, Katherine J.; Hawkins, Thomas A.; Yáñez, Julián; Anadón, Ramón; Wilson, Stephen W.; Folgueira, Mónica

2016-01-01

The habenulae are bilateral nuclei located in the dorsal diencephalon that are conserved across vertebrates. Here we describe the main afferents to the habenulae in larval and adult zebrafish. We observe afferents from the subpallium, nucleus rostrolateralis, posterior tuberculum, posterior hypothalamic lobe, median raphe; we also see asymmetric afferents from olfactory bulb to the right habenula, and from the parapineal to the left habenula. In addition, we find afferents from a ventrolateral telencephalic nucleus that neurochemical and hodological data identify as the ventral entopeduncular nucleus (vENT), confirming and extending observations of Amo et al. (2014). Fate map and marker studies suggest that vENT originates from the diencephalic prethalamic eminence and extends into the lateral telencephalon from 48 to 120 hour post-fertilization (hpf). No afferents to the habenula were observed from the dorsal entopeduncular nucleus (dENT). Consequently, we confirm that the vENT (and not the dENT) should be considered as the entopeduncular nucleus “proper” in zebrafish. Furthermore, comparison with data in other vertebrates suggests that the vENT is a conserved basal ganglia nucleus, being homologous to the entopeduncular nucleus of mammals (internal segment of the globus pallidus of primates) by both embryonic origin and projections, as previously suggested by Amo et al. (2014). PMID:27199671

Changes in the frequency of swallowing during electrical stimulation of superior laryngeal nerve in rats.

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Tsuji, Kojun; Tsujimura, Takanori; Magara, Jin; Sakai, Shogo; Nakamura, Yuki; Inoue, Makoto

2015-02-01

The aim of the present study was to investigate the adaptation of the swallowing reflex in terms of reduced swallowing reflex initiation following continuous superior laryngeal nerve stimulation. Forty-four male Sprague Dawley rats were anesthetized with urethane. To identify swallowing, electromyographic activity of the left mylohyoid and thyrohyoid muscles was recorded. To evoke the swallowing response, the superior laryngeal nerve (SLN), recurrent laryngeal nerve, or cortical swallowing area was electrically stimulated. Repetitive swallowing evoked by continuous SLN stimulation was gradually reduced, and this reduction was dependent on the resting time duration between stimulations. Prior SLN stimulation also suppressed subsequent swallowing initiation. The reduction in evoked swallows induced by recurrent laryngeal nerve or cortical swallowing area stimulation was less than that following superior laryngeal nerve stimulation. Decerebration had no effect on the reduction in evoked swallows. Prior subthreshold stimulation reduced subsequent initiation of swallowing, suggesting that there was no relationship between swallowing movement evoked by prior stimulation and the subsequent reduction in swallowing initiation. Overall, these data suggest that reduced sensory afferent nerve firing and/or trans-synaptic responses, as well as part of the brainstem central pattern generator, are involved in adaptation of the swallowing reflex following continuous stimulation of swallow-inducing peripheral nerves and cortical areas. Copyright © 2014 Elsevier Inc. All rights reserved.

Afferent innervation of the utricular macula in pigeons

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Si, Xiaohong; Zakir, Mridha Md; Dickman, J. David

2003-01-01

Biotinylated dextran amine (BDA) was used to retrogradely label afferents innervating the utricular macula in adult pigeons. The pigeon utriclar macula consists of a large rectangular-shaped neuroepithelium with a dorsally curved anterior edge and an extended medioposterior tail. The macula could be demarcated into several regions based on cytoarchitectural differences. The striola occupied 30% of the macula and contained a large density of type I hair cells with fewer type II hair cells. Medial and lateral extrastriola zones were located outside the striola and contained only type II hair cells. A six- to eight-cell-wide band of type II hair cells existed near the center of the striola. The reversal line marked by the morphological polarization of hair cells coursed throughout the epithelium, near the peripheral margin, and through the center of the type II band. Calyx afferents innervated type I hair cells with calyceal terminals that contained between 2 and 15 receptor cells. Calyx afferents were located only in the striola region, exclusive of the type II band, had small total fiber innervation areas and low innervation densities. Dimorph afferents innervated both type I and type II hair cells with calyceal and bouton terminals and were primarily located in the striola region. Dimorph afferents had smaller calyceal terminals with few type I hair cells, extended fiber branches with bouton terminals and larger innervation areas. Bouton afferents innervated only type II hair cells in the extrastriola and type II band regions. Bouton afferents innervating the type II band had smaller terminal fields with fewer bouton terminals and smaller innervation areas than fibers located in the extrastriolar zones. Bouton afferents had the most bouton terminals on the longest fibers, the largest innervation areas with the highest innervation densities of all afferents. Among all afferents, smaller terminal innervation fields were observed in the striola and large fields were

[Acute pancreatitis and afferent loop syndrome. Case report].

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Barajas-Fregoso, Elpidio Manuel; Romero-Hernández, Teodoro; Macías-Amezcua, Michel Dassaejv

2013-01-01

The afferent syndrome loop is a mechanic obstruction of the afferent limb before a Billroth II or Roux-Y reconstruction, secondary in most of case to distal or subtotal gastrectomy. Clinical case: Male 76 years old, with antecedent of cholecystectomy, gastric adenocarcinoma six years ago, with subtotal gastrectomy and Roux-Y reconstruction. Beginning a several abdominal pain, nausea and vomiting, abdominal distension, without peritoneal irritation sings. Amylase 1246 U/L, lipase 3381 U/L. Computed Tomography with thickness wall and dilatation of afferent loop, pancreas with diffuse enlargement diagnostic of acute pancreatitis secondary an afferent loop syndrome. The afferent loop syndrome is presented in 0.3%-1% in all cases with Billroth II reconstruction, with a mortality of up to 57%, the obstruction lead accumulation of bile, pancreatic and intestinal secretions, increasing the pressure and resulting in afferent limb, bile conduct and Wirsung conduct dilatation, triggering an inflammatory response that culminates in pancreatic inflammation. The severity of the presentation is related to the degree and duration of the blockage.

Electrophysiologic studies of cutaneous nerves of the thoracic limb of the dog.

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Kitchell, R L; Whalen, L R; Bailey, C S; Lohse, C L

1980-01-01

The cutaneous innervation of the thoracic limb was investigated in 36 barbiturate-anesthetized dogs, using electrophysiologic techniques. The cutaneous area (CA) innervated by each cutaneous nerve was delineated in at least five dogs by stroking the hair in the area with a small watercolor brush while recording from the nerve. Mapping of adjacent CA revealed areas of considerable overlapping. The part of the CA of a given nerve supplied by only that nerve is referred to as its autonomous zone. Of all nerves arising from the brachial plexus, only the suprascapular, subscapular, lateral thoracic, thoracodorsal, and cranial and caudal pectoral nerves lacked cutaneous afferents. The dorsal cutaneous branch of C6 had a CA, but no grossly demonstrable dorsal cutaneous branches for C7 C8, or T1 were found. The cervical nerves had ventral cutaneous branches, but no lateral cutaneous branches. Thoracic nerves T2-T4 had dorsal, ventral, and lateral cutaneous branches. The cutaneous branches of the brachiocephalic, axillary, musculocutaneous, radial, median, and ulnar nerves all had CA which were overlapped by adjacent CA, thus their autonomous zones were much smaller than the cutaneous areas usually depicted for these nerves in anatomy and neurology textbooks.

Urethral sensation following reconstructive pelvic surgery.

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Abernethy, M G; Davis, C; Lowenstein, L; Mueller, E R; Brubaker, L; Kenton, K

2014-11-01

Most urethral neuromuscular function data focus on efferent rather than afferent innervation. We aimed to determine if changes exist in urethral afferent nerve function before and after reconstructive pelvic surgery (RPS). Secondarily, we compared afferent urethral innervation in women with and without stress urinary incontinence undergoing RPS. Participants underwent current perception threshold (CPT) and urethral anal reflex (UAR) testing prior to surgery and again post-operatively. Wilcoxon signed ranked test and Spearman's correlations were used and all tests were two-sided. p = 0.05 was considered to indicate statistical significance. Urethral CPT thresholds increased significantly after RPS, consistent with decreased urethral afferent function. Pre-operative urethral CPT thresholds at 5 and 250 Hz were lower in SUI women (10 [IQR 5-29], 40 [32-750]) compared with continent women (63 [14-99], 73 [51-109]; p = 0.45, p = 0.020), signifying increased urethral sensation or easier activation of urethral afferents in SUI women. Reconstructive pelvic surgery is associated with a short-term deleterious impact on urethral afferent function, as demonstrated by the higher levels of stimuli required to activate urethral afferent nerves (decreased urethral sensation) immediately after RPS. Women with SUI required lower levels of stimuli to activate urethral afferent nerves prior to RPS, although UAR latencies were similar regardless of concomitant SUI.

Cellular mechanisms for presynaptic inhibition of sensory afferents

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Perrier, Jean-Francois Marie; delgado-lezama, rodolfo; Christensen, Rasmus Kordt

It is well established that presynaptic inhibition of primary afferents involves the activation of GABAA receptors located on presynaptic terminals. However, the source of GABA remains unknown. In an integrated preparation of the spinal cord of the adult turtle, we evoked dorsal root potentials...

Trigemino-gustatory interactions: a randomized controlled clinical trial assessing the effects of selective anesthesia of dental afferents on taste thresholds.

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Lecor, Papa Abdou; Touré, Babacar; Boucher, Yves

2018-03-01

This study aimed at analyzing the effect of the temporary removal of trigeminal dental afferents on electrogustometric thresholds (EGMt). EGMt were measured in 300 healthy subjects randomized in three groups, in nine loci on the right and left side (RS, LS) of the tongue surface before and after anesthesia. Group IAN (n = 56 RS, n = 44 LS) received intraosseous local anesthesia of the inferior alveolar nerve (IAN). Group MdN received mandibular nerve (MdN) block targeting IAN before its entrance into the mandibular foramen (n = 60, RS, and n = 40, LS); group MxN receiving maxillary nerve (MxN) anesthesia (n = 56 RS and n = 44 LS) was the control group. Differences between mean EGMt were analyzed with the Wilcoxon test; correlation between type of anesthesia and EGMt was performed with Spearman's rho, all with a level of significance set at p ≤ 0.05. Significant EGMt (μA) differences before and after anesthesia were found in all loci with MdN and IAN on the ipsilateral side (p Anesthesia of the MdN was positively correlated with the increase in EGMt (p anesthesia of IAN was positively correlated only with the increase in EGMt measured at posterior and dorsal loci of the tongue surface (p anesthesia suggests a participation of dental afferents in taste perception. Extraction of teeth may impair food intake not only due to impaired masticatory ability but also to alteration of neurological trigemino-gustatory interactions. PACTR201602001452260.

Giant renin secretory granules in beige mouse renal afferent arterioles

DEFF Research Database (Denmark)

Jensen, B L; Rasch, Ruth; Nyengaard, Jens Randel

1997-01-01

The mutant beige mouse (C57BL/6 bg) has a disease characterised by abnormally enlarged cytoplasmic granules in a variety of cells. With the purpose of establishing a suitable cellular model for studying renin secretion, the present study was undertaken to compare renin granule morphology in beige...... (average granular volume 0.681 microm3), whereas 1-2 large granules were present per cell in beige mice. The volume of afferent arteriole that contained secretory granules was lower in the beige mice. We conclude that the beige mouse synthesizes, stores and releases active renin. Renin secretory granules...... in beige mice are grossly enlarged with 1-2 granules per juxtaglomerular cell. Compared with control mice, a similar amount of total renin granule volume per afferent arteriole is contained in a smaller part of beige mouse afferent arteriole. Granular cells from beige mice could therefore be a valuable...

TRPV1 marks synaptic segregation of multiple convergent afferents at the rat medial solitary tract nucleus.

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James H Peters

Full Text Available TRPV1 receptors are expressed on most but not all central terminals of cranial visceral afferents in the caudal solitary tract nucleus (NTS. TRPV1 is associated with unmyelinated C-fiber afferents. Both TRPV1+ and TRPV1- afferents enter NTS but their precise organization remains poorly understood. In horizontal brainstem slices, we activated solitary tract (ST afferents and recorded ST-evoked glutamatergic excitatory synaptic currents (ST-EPSCs under whole cell voltage clamp conditions from neurons of the medial subnucleus. Electrical shocks to the ST produced fixed latency EPSCs (jitter<200 µs that identified direct ST afferent innervation. Graded increases in shock intensity often recruited more than one ST afferent and ST-EPSCs had consistent threshold intensity, latency to onset, and unique EPSC waveforms that characterized each unitary ST afferent contact. The TRPV1 agonist capsaicin (100 nM blocked the evoked TRPV1+ ST-EPSCs and defined them as either TRPV1+ or TRPV1- inputs. No partial responses to capsaicin were observed so that in NTS neurons that received one or multiple (2-5 direct ST afferent inputs--all were either blocked by capsaicin or were unaltered. Since TRPV1 mediates asynchronous release following TRPV1+ ST-evoked EPSCs, we likewise found that recruiting more than one ST afferent further augmented the asynchronous response and was eliminated by capsaicin. Thus, TRPV1+ and TRPV1- afferents are completely segregated to separate NTS neurons. As a result, the TRPV1 receptor augments glutamate release only within unmyelinated afferent pathways in caudal medial NTS and our work indicates a complete separation of C-type from A-type afferent information at these first central neurons.

The Role of 5-HT3 Receptors in Signaling from Taste Buds to Nerves.

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Larson, Eric D; Vandenbeuch, Aurelie; Voigt, Anja; Meyerhof, Wolfgang; Kinnamon, Sue C; Finger, Thomas E

2015-12-02

Activation of taste buds triggers the release of several neurotransmitters, including ATP and serotonin (5-hydroxytryptamine; 5-HT). Type III taste cells release 5-HT directly in response to acidic (sour) stimuli and indirectly in response to bitter and sweet tasting stimuli. Although ATP is necessary for activation of nerve fibers for all taste stimuli, the role of 5-HT is unclear. We investigated whether gustatory afferents express functional 5-HT3 receptors and, if so, whether these receptors play a role in transmission of taste information from taste buds to nerves. In mice expressing GFP under the control of the 5-HT(3A) promoter, a subset of cells in the geniculate ganglion and nerve fibers in taste buds are GFP-positive. RT-PCR and in situ hybridization confirmed the presence of 5-HT(3A) mRNA in the geniculate ganglion. Functional studies show that only those geniculate ganglion cells expressing 5-HT3A-driven GFP respond to 10 μM 5-HT and this response is blocked by 1 μM ondansetron, a 5-HT3 antagonist, and mimicked by application of 10 μM m-chlorophenylbiguanide, a 5-HT3 agonist. Pharmacological blockade of 5-HT3 receptors in vivo or genetic deletion of the 5-HT3 receptors reduces taste nerve responses to acids and other taste stimuli compared with controls, but only when urethane was used as the anesthetic. We find that anesthetic levels of pentobarbital reduce taste nerve responses apparently by blocking the 5-HT3 receptors. Our results suggest that 5-HT released from type III cells activates gustatory nerve fibers via 5-HT3 receptors, accounting for a significant proportion of the neural taste response. Copyright © 2015 the authors 0270-6474/15/3515984-12$15.00/0.

Effect of neonatal capsaicin treatment on neural activity in the medullary dorsal horn of neonatal rats evoked by electrical stimulation to the trigeminal afferents: an optical, electrophysiological, and quantitative study.

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Takuma, S

2001-07-06

To elucidate which glutamate receptors, NMDA or non-NMDA, have the main role in synaptic transmission via unmyelinated afferents in the trigeminal subnucleus caudalis (the medullary dorsal horn), and to examine the early functional effects of neonatal capsaicin treatment to the subnucleus caudalis, optical recording, field potential recording, and quantitative study using electron micrographs were employed. A medulla oblongata isolated from a rat 5--7 days old was sectioned horizontally 400-microm thick or parasagittally and stained with a voltage-sensitive dye, RH482 or RH795. Single-pulse stimulation with high intensity to the trigeminal afferents evoked optical responses mainly in the subnucleus caudalis. The optical signals were composed of two phases, a fast component followed by a long-lasting component. The spatiotemporal properties of the optical signals were well correlated to those of the field potentials recorded simultaneously. The fast component was eliminated by 6-cyano-7-nitro-quinoxaline-2,3-dione (CNQX; 10 microM), while the long-lasting component was not. The latter increased in amplitude under a condition of low Mg(2+) but was significantly reduced by DL-2-amino-5-phosphonovaleric acid (AP5; 30 microM). Neonatal capsaicin treatment also reduced the long-lasting component markedly. In addition, the decreases in the ratio of unmyelinated axons to myelinated axons and in the ratio of unmyelinated axons to Schwann cell subunits of trigeminal nerve roots both showed significant differences (P<0.05, Student's t-test) between the control group and the neonatal capsaicin treatment group. This line of evidence indirectly suggests that synaptic transmission via unmyelinated afferents in the subnucleus caudalis is mediated substantially by NMDA glutamate receptors and documented that neonatal capsaicin treatment induced a functional alteration of the neural transmission in the subnucleus caudalis as well as a morphological alteration of primary afferents

Postsynaptic P2X3-containing receptors in gustatory nerve fibres mediate responses to all taste qualities in mice.

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Vandenbeuch, Aurelie; Larson, Eric D; Anderson, Catherine B; Smith, Steven A; Ford, Anthony P; Finger, Thomas E; Kinnamon, Sue C

2015-03-01

Taste buds release ATP to activate ionotropic purinoceptors composed of P2X2 and P2X3 subunits, present on the taste nerves. Mice with genetic deletion of P2X2 and P2X3 receptors (double knockout mice) lack responses to all taste stimuli presumably due to the absence of ATP-gated receptors on the afferent nerves. Recent experiments on the double knockout mice showed, however, that their taste buds fail to release ATP, suggesting the possibility of pleiotropic deficits in these global knockouts. To test further the role of postsynaptic P2X receptors in afferent signalling, we used AF-353, a selective antagonist of P2X3-containing receptors to inhibit the receptors acutely during taste nerve recording and behaviour. The specificity of AF-353 for P2X3-containing receptors was tested by recording Ca(2+) transients to exogenously applied ATP in fura-2 loaded isolated geniculate ganglion neurons from wild-type and P2X3 knockout mice. ATP responses were completely inhibited by 10 μm or 100 μm AF-353, but neither concentration blocked responses in P2X3 single knockout mice wherein the ganglion cells express only P2X2-containing receptors. Furthermore, AF-353 had no effect on taste-evoked ATP release from taste buds. In wild-type mice, i.p. injection of AF-353 or simple application of the drug directly to the tongue, inhibited taste nerve responses to all taste qualities in a dose-dependent fashion. A brief access behavioural assay confirmed the electrophysiological results and showed that preference for a synthetic sweetener, SC-45647, was abolished following i.p. injection of AF-353. These data indicate that activation of P2X3-containing receptors is required for transmission of all taste qualities. © 2015 The Authors. The Journal of Physiology © 2015 The Physiological Society.

Microstimulation of the lumbar DRG recruits primary afferent neurons in localized regions of lower limb.

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Ayers, Christopher A; Fisher, Lee E; Gaunt, Robert A; Weber, Douglas J

2016-07-01

Patterned microstimulation of the dorsal root ganglion (DRG) has been proposed as a method for delivering tactile and proprioceptive feedback to amputees. Previous studies demonstrated that large- and medium-diameter afferent neurons could be recruited separately, even several months after implantation. However, those studies did not examine the anatomical localization of sensory fibers recruited by microstimulation in the DRG. Achieving precise recruitment with respect to both modality and receptive field locations will likely be crucial to create a viable sensory neuroprosthesis. In this study, penetrating microelectrode arrays were implanted in the L5, L6, and L7 DRG of four isoflurane-anesthetized cats instrumented with nerve cuff electrodes around the proximal and distal branches of the sciatic and femoral nerves. A binary search was used to find the recruitment threshold for evoking a response in each nerve cuff. The selectivity of DRG stimulation was characterized by the ability to recruit individual distal branches to the exclusion of all others at threshold; 84.7% (n = 201) of the stimulation electrodes recruited a single nerve branch, with 9 of the 15 instrumented nerves recruited selectively. The median stimulation threshold was 0.68 nC/phase, and the median dynamic range (increase in charge while stimulation remained selective) was 0.36 nC/phase. These results demonstrate the ability of DRG microstimulation to achieve selective recruitment of the major nerve branches of the hindlimb, suggesting that this approach could be used to drive sensory input from localized regions of the limb. This sensory input might be useful for restoring tactile and proprioceptive feedback to a lower-limb amputee. Copyright © 2016 the American Physiological Society.

M. leprae components induce nerve damage by complement activation: identification of lipoarabinomannan as the dominant complement activator.

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Bahia El Idrissi, Nawal; Das, Pranab K; Fluiter, Kees; Rosa, Patricia S; Vreijling, Jeroen; Troost, Dirk; Morgan, B Paul; Baas, Frank; Ramaglia, Valeria

2015-05-01

Peripheral nerve damage is the hallmark of leprosy pathology but its etiology is unclear. We previously identified the membrane attack complex (MAC) of the complement system as a key determinant of post-traumatic nerve damage and demonstrated that its inhibition is neuroprotective. Here, we determined the contribution of the MAC to nerve damage caused by Mycobacterium leprae and its components in mouse. Furthermore, we studied the association between MAC and the key M. leprae component lipoarabinomannan (LAM) in nerve biopsies of leprosy patients. Intraneural injections of M. leprae sonicate induced MAC deposition and pathological changes in the mouse nerve, whereas MAC inhibition preserved myelin and axons. Complement activation occurred mainly via the lectin pathway and the principal activator was LAM. In leprosy nerves, the extent of LAM and MAC immunoreactivity was robust and significantly higher in multibacillary compared to paucibacillary donors (p = 0.01 and p = 0.001, respectively), with a highly significant association between LAM and MAC in the diseased samples (r = 0.9601, p = 0.0001). Further, MAC co-localized with LAM on axons, pointing to a role for this M. leprae antigen in complement activation and nerve damage in leprosy. Our findings demonstrate that MAC contributes to nerve damage in a model of M. leprae-induced nerve injury and its inhibition is neuroprotective. In addition, our data identified LAM as the key pathogen associated molecule that activates complement and causes nerve damage. Taken together our data imply an important role of complement in nerve damage in leprosy and may inform the development of novel therapeutics for patients.

Activation of GLP-1 receptors on vascular smooth muscle cells reduces the autoregulatory response in afferent arterioles and increases renal blood flow

DEFF Research Database (Denmark)

Jensen, Elisa Pouline; Poulsen, Steen Seier; Kissow, Hannelouise

2015-01-01

was to localize renal GLP-1 receptors and describe GLP-1 mediated effects on the renal vasculature. We hypothesized that renal GLP-1 receptors are located in the renal microcirculation and activation of these affects renal autoregulation and increases renal blood flow. In vivo autoradiography using 125I-GLP-1......, 125I-exendin-4 (GLP-1 analog) and 125I-exendin 9-39 (GLP-1 receptor antagonist) was performed in rodents to localize specific GLP-1 receptor binding. GLP-1 mediated effects on blood pressure (BP), renal blood flow (RBF), heart rate (HR), renin secretion, urinary flow rate and Na+ and K+ excretion were...... conclude that GLP-1 receptors are located in the renal vasculature including afferent arterioles. Activation of these receptors reduces the autoregulatory response of afferent arterioles to acute pressure increases and increases renal blood flow in normotensive rats....

Evolutionary origins of taste buds: phylogenetic analysis of purinergic neurotransmission in epithelial chemosensors

OpenAIRE

Kirino, Masato; Parnes, Jason; Hansen, Anne; Kiyohara, Sadao; Finger, Thomas E.

2013-01-01

Taste buds are gustatory endorgans which use an uncommon purinergic signalling system to transmit information to afferent gustatory nerve fibres. In mammals, ATP is a crucial neurotransmitter released by the taste cells to activate the afferent nerve fibres. Taste buds in mammals display a characteristic, highly specific ecto-ATPase (NTPDase2) activity, suggesting a role in inactivation of the neurotransmitter. The purpose of this study was to test whether the presence of markers of purinergi...

Afferent loop syndrome: Role of sonography and CT

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Lee, Dong Ho; Lim, Jae Hoon; Ko, Young Tae [Kyung Hee University Hospital, Seoul (Korea, Republic of)

1992-03-15

Afferent loop syndrome(ALS) is caused by obstruction of the afferent loop after subtotal gastrectomy with Billroth II gastrojejunostomy. Prompt diagnosis of ALS is important as perforation of the loop occurs. The aim of study is to ascertain the sonography and CT to diagnose ALS. We describe the radiologic findings in ten patients with ALS. The cause of ALS, established at surgery, included cancer recurrence (n=4), internal hernia (n=4), marginal ulcer (n=1), and development of cancer at the anastomosis site (n=1). Abdominal X-ray and sonography were performed in all cases, upper GI series in five cases and computed tomography in two cases. The dilated afferent loop was detected in only two cases out often patients in retrospective review of abdominal X-ray. ALS with recurrence of cancer was diagnosed in three cases by upper GI series. Of the cases that had sonography, the afferent loop was seen in the upper abdomen crossing transversely over the midline in all ten patients. The cause of ALS were predicated on the basis of the sonograms in three of the five patients. In two cases of computed tomography, the dilated afferent loop and recurrent cancer at the remnant stomach were seen.Our experience suggests that the diagnosis of afferent syndrome can be made on the basis of the typical anatomic location and shape of the dilated bowel loop in both sonography and computed tomography.

Profiling of G protein-coupled receptors in vagal afferents reveals novel gut-to-brain sensing mechanisms.

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Egerod, Kristoffer L; Petersen, Natalia; Timshel, Pascal N; Rekling, Jens C; Wang, Yibing; Liu, Qinghua; Schwartz, Thue W; Gautron, Laurent

2018-06-01

G protein-coupled receptors (GPCRs) act as transmembrane molecular sensors of neurotransmitters, hormones, nutrients, and metabolites. Because unmyelinated vagal afferents richly innervate the gastrointestinal mucosa, gut-derived molecules may directly modulate the activity of vagal afferents through GPCRs. However, the types of GPCRs expressed in vagal afferents are largely unknown. Here, we determined the expression profile of all GPCRs expressed in vagal afferents of the mouse, with a special emphasis on those innervating the gastrointestinal tract. Using a combination of high-throughput quantitative PCR, RNA sequencing, and in situ hybridization, we systematically quantified GPCRs expressed in vagal unmyelinated Na v 1.8-expressing afferents. GPCRs for gut hormones that were the most enriched in Na v 1.8-expressing vagal unmyelinated afferents included NTSR1, NPY2R, CCK1R, and to a lesser extent, GLP1R, but not GHSR and GIPR. Interestingly, both GLP1R and NPY2R were coexpressed with CCK1R. In contrast, NTSR1 was coexpressed with GPR65, a marker preferentially enriched in intestinal mucosal afferents. Only few microbiome-derived metabolite sensors such as GPR35 and, to a lesser extent, GPR119 and CaSR were identified in the Na v 1.8-expressing vagal afferents. GPCRs involved in lipid sensing and inflammation (e.g. CB1R, CYSLTR2, PTGER4), and neurotransmitters signaling (CHRM4, DRD2, CRHR2) were also highly enriched in Na v 1.8-expressing neurons. Finally, we identified 21 orphan GPCRs with unknown functions in vagal afferents. Overall, this study provides a comprehensive description of GPCR-dependent sensing mechanisms in vagal afferents, including novel coexpression patterns, and conceivably coaction of key receptors for gut-derived molecules involved in gut-brain communication. Copyright © 2018 The Authors. Published by Elsevier GmbH.. All rights reserved.

Reinnervation following catheter-based radio-frequency renal denervation.

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Booth, Lindsea C; Nishi, Erika E; Yao, Song T; Ramchandra, Rohit; Lambert, Gavin W; Schlaich, Markus P; May, Clive N

2015-04-20

What is the topic of this review? Does catheter-based renal denervation effectively denervate the afferent and efferent renal nerves and does reinnervation occur? What advances does it highlight? Following catheter-based renal denervation, the afferent and efferent responses to electrical stimulation were abolished, renal sympathetic nerve activity was absent, and levels of renal noradrenaline and immunohistochemistry for tyrosine hydroxylase and calcitonin gene-related peptide were significantly reduced. By 11 months after renal denervation, both the functional responses and anatomical markers of afferent and efferent renal nerves had returned to normal, indicating reinnervation. Renal denervation reduces blood pressure in animals with experimental hypertension and, recently, catheter-based renal denervation was shown to cause a prolonged decrease in blood pressure in patients with resistant hypertension. The randomized, sham-controlled Symplicity HTN-3 trial failed to meet its primary efficacy end-point, but there is evidence that renal denervation was incomplete in many patients. Currently, there is little information regarding the effectiveness of catheter-based renal denervation and the extent of reinnervation. We assessed the effectiveness of renal nerve denervation with the Symplicity Flex catheter and the functional and anatomical reinnervation at 5.5 and 11 months postdenervation. In anaesthetized, non-denervated sheep, there was a high level of renal sympathetic nerve activity, and electrical stimulation of the renal nerve increased blood pressure and reduced heart rate (afferent response) and caused renal vasoconstriction and reduced renal blood flow (efferent response). Immediately after renal denervation, renal sympathetic nerve activity and the responses to electrical stimulation were absent, indicating effective denervation. By 11 months after denervation, renal sympathetic nerve activity was present and the responses to electrical stimulation

Reflex vocal fold adduction in the porcine model: the effects of stimuli delivered to various sensory nerves.

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Woo, Jeong-Soo; Hundal, Jagdeep S; Sasaki, Clarence T; Abdelmessih, Mikhail W; Kelleher, Stephen P

2008-10-01

The aim of this study was to identify a panel of sensory nerves capable of eliciting an evoked glottic closure reflex (GCR) and to quantify the glottic closing force (GCF) of these responses in a porcine model. In 5 pigs, the internal branch of the superior laryngeal nerve (iSLN) and the trigeminal, pharyngeal plexus, glossopharyngeal, radial, and intercostal nerves were surgically isolated and electrically stimulated. During stimulation of each nerve, the GCR was detected by laryngeal electromyography and the GCF was measured with a pressure transducer. The only nerve that elicited the GCR in the 5 pigs was the iSLN. The average GCF was 288.9 mm Hg. This study demonstrates that the only afferent nerve that elicits the GCR in pigs is the iSLN, and that it should remain the focus of research for the rehabilitation of patients with absent or defective reflex vocal fold adduction.

Decoding tactile afferent activity to obtain an estimate of instantaneous force and torque applied to the fingerpad

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Birznieks, Ingvars; Redmond, Stephen J.

2015-01-01

Dexterous manipulation is not possible without sensory information about object properties and manipulative forces. Fundamental neuroscience has been unable to demonstrate how information about multiple stimulus parameters may be continuously extracted, concurrently, from a population of tactile afferents. This is the first study to demonstrate this, using spike trains recorded from tactile afferents innervating the monkey fingerpad. A multiple-regression model, requiring no a priori knowledge of stimulus-onset times or stimulus combination, was developed to obtain continuous estimates of instantaneous force and torque. The stimuli consisted of a normal-force ramp (to a plateau of 1.8, 2.2, or 2.5 N), on top of which −3.5, −2.0, 0, +2.0, or +3.5 mNm torque was applied about the normal to the skin surface. The model inputs were sliding windows of binned spike counts recorded from each afferent. Models were trained and tested by 15-fold cross-validation to estimate instantaneous normal force and torque over the entire stimulation period. With the use of the spike trains from 58 slow-adapting type I and 25 fast-adapting type I afferents, the instantaneous normal force and torque could be estimated with small error. This study demonstrated that instantaneous force and torque parameters could be reliably extracted from a small number of tactile afferent responses in a real-time fashion with stimulus combinations that the model had not been exposed to during training. Analysis of the model weights may reveal how interactions between stimulus parameters could be disentangled for complex population responses and could be used to test neurophysiologically relevant hypotheses about encoding mechanisms. PMID:25948866

The mast cell degranulator compound 48/80 directly activates neurons.

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Michael Schemann

Full Text Available BACKGROUND: Compound 48/80 is widely used in animal and tissue models as a "selective" mast cell activator. With this study we demonstrate that compound 48/80 also directly activates enteric neurons and visceral afferents. METHODOLOGY/PRINCIPAL FINDINGS: We used in vivo recordings from extrinsic intestinal afferents together with Ca(++ imaging from primary cultures of DRG and nodose neurons. Enteric neuronal activation was examined by Ca(++ and voltage sensitive dye imaging in isolated gut preparations and primary cultures of enteric neurons. Intraluminal application of compound 48/80 evoked marked afferent firing which desensitized on subsequent administration. In egg albumen-sensitized animals, intraluminal antigen evoked a similar pattern of afferent activation which also desensitized on subsequent exposure to antigen. In cross-desensitization experiments prior administration of compound 48/80 failed to influence the mast cell mediated response. Application of 1 and 10 µg/ml compound 48/80 evoked spike discharge and Ca(++ transients in enteric neurons. The same nerve activating effect was observed in primary cultures of DRG and nodose ganglion cells. Enteric neuron cultures were devoid of mast cells confirmed by negative staining for c-kit or toluidine blue. In addition, in cultured enteric neurons the excitatory action of compound 48/80 was preserved in the presence of histamine H(1 and H(2 antagonists. The mast cell stabilizer cromolyn attenuated compound 48/80 and nicotine evoked Ca(++ transients in mast cell-free enteric neuron cultures. CONCLUSIONS/SIGNIFICANCE: The results showed direct excitatory action of compound 48/80 on enteric neurons and visceral afferents. Therefore, functional changes measured in tissue or animal models may involve a mast cell independent effect of compound 48/80 and cromolyn.

Isolation of TRPV1 independent mechanisms of spontaneous and asynchronous glutamate release at primary afferent to NTS synapses.

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Axel J. Fenwick

2014-01-01

Full Text Available Cranial visceral afferents contained within the solitary tract (ST contact second-order neurons in the nucleus of the solitary tract (NTS and release the excitatory amino acid glutamate via three distinct exocytosis pathways; synchronous, asynchronous, and spontaneous release. The presence of TRPV1 in the central terminals of a majority of ST afferents conveys activity-dependent asynchronous glutamate release and provides a temperature sensitive calcium conductance which largely determines the rate of spontaneous vesicle fusion. TRPV1 is present in unmyelinated C-fiber afferents and these facilitated forms of glutamate release may underlie the relative strength of C-fibers in activating autonomic reflex pathways. However, pharmacological blockade of TRPV1 signaling eliminates only ~50% of the asynchronous profile and attenuates the temperature sensitivity of spontaneous release indicating additional thermosensitive calcium influx pathways may exist which mediate these forms of vesicle release. In the present study we isolate the contribution of TRPV1 independent forms of glutamate release at ST-NTS synapses. We found ST afferent innervation at NTS neurons and synchronous vesicle release from TRPV1 KO mice was not different to control animals; however, only half of TRPV1 KO ST afferents completely lacked asynchronous glutamate release. Further, temperature driven spontaneous rates of vesicle release were not different from 33˚ - 37˚C between control and TRPV1 KO afferents. These findings suggest additional temperature dependent mechanisms controlling asynchronous and thermosensitive spontaneous release at physiological temperatures, possibly mediated by additional thermosensitive TRP channels in primary afferent terminals.

Decreased contribution from afferent feedback to the soleus muscle during walking in patients with spastic stroke

DEFF Research Database (Denmark)

Mazzaro, Nazarena; Nielsen, Jørgen Feldbæk; Grey, Michael James

2007-01-01

We investigated the contribution of afferent feedback to the soleus (SOL) muscle activity during the stance phase of walking in patients with spastic stroke. A total of 24 patients with hemiparetic spastic stroke and age-matched healthy volunteers participated in the study. A robotic actuator...... by the Ashworth score. These results indicate that although the stretch reflex response is facilitated during spastic gait, the contribution of afferent feedback to the ongoing locomotor SOL activity is depressed in patients with spastic stroke....

Expression of the transient receptor potential channels TRPV1, TRPA1 and TRPM8 in mouse trigeminal primary afferent neurons innervating the dura

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2012-01-01

Background Migraine and other headache disorders affect a large percentage of the population and cause debilitating pain. Activation and sensitization of the trigeminal primary afferent neurons innervating the dura and cerebral vessels is a crucial step in the “headache circuit”. Many dural afferent neurons respond to algesic and inflammatory agents. Given the clear role of the transient receptor potential (TRP) family of channels in both sensing chemical stimulants and mediating inflammatory pain, we investigated the expression of TRP channels in dural afferent neurons. Methods We used two fluorescent tracers to retrogradely label dural afferent neurons in adult mice and quantified the abundance of peptidergic and non-peptidergic neuron populations using calcitonin gene-related peptide immunoreactivity (CGRP-ir) and isolectin B4 (IB4) binding as markers, respectively. Using immunohistochemistry, we compared the expression of TRPV1 and TRPA1 channels in dural afferent neurons with the expression in total trigeminal ganglion (TG) neurons. To examine the distribution of TRPM8 channels, we labeled dural afferent neurons in mice expressing farnesylated enhanced green fluorescent protein (EGFPf) from a TRPM8 locus. We used nearest-neighbor measurement to predict the spatial association between dural afferent neurons and neurons expressing TRPA1 or TRPM8 channels in the TG. Results and conclusions We report that the size of dural afferent neurons is significantly larger than that of total TG neurons and facial skin afferents. Approximately 40% of dural afferent neurons exhibit IB4 binding. Surprisingly, the percentage of dural afferent neurons containing CGRP-ir is significantly lower than those of total TG neurons and facial skin afferents. Both TRPV1 and TRPA1 channels are expressed in dural afferent neurons. Furthermore, nearest-neighbor measurement indicates that TRPA1-expressing neurons are clustered around a subset of dural afferent neurons. Interestingly, TRPM

RESISTIN, AN ADIPOKINE WITH NON-GENERALISED ACTIONS ON SYMPATHETIC NERVE ACTIVITY

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Emilio eBadoer

2015-11-01

Full Text Available The World Health Organisation has called obesity a global epidemic. There is a strong association between body weight gain and blood pressure. A major determinant of blood pressure is the level of activity in sympathetic nerves innervating cardiovascular organs. A characteristic of obesity, in both humans and in animal models, is an increase in sympathetic nerve activity to the skeletal muscle vasculature and to the kidneys. Obesity is now recognised as a chronic, low level inflammatory condition and pro-inflammatory cytokines are elevated including those produced by adipose tissue. The most well known adipokine released from fat tissue is leptin. The adipokine, resistin,, is also released from adipose tissue. Resistin can act in the central nervous system to influence the sympathetic nerve activity. Here, we review the effects of resistin on sympathetic nerve activity and compare them with leptin. We build an argument that resistin and leptin may have complex interactions. Firstly, they may augment each other as both are excitatory on sympathetic nerves innervating cardiovascular organs; In contrast, they could antagonize each other’s actions on brown adipose tissue, a key metabolic organ. These interactions may be important in conditions in which leptin and resistin are elevated, such as in obesity.

Resveratrol Promotes Nerve Regeneration via Activation of p300 Acetyltransferase-Mediated VEGF Signaling in a Rat Model of Sciatic Nerve Crush Injury.

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Ding, Zhuofeng; Cao, Jiawei; Shen, Yu; Zou, Yu; Yang, Xin; Zhou, Wen; Guo, Qulian; Huang, Changsheng

2018-01-01

Peripheral nerve injuries are generally associated with incomplete restoration of motor function. The slow rate of nerve regeneration after injury may account for this. Although many benefits of resveratrol have been shown in the nervous system, it is not clear whether resveratrol could promote fast nerve regeneration and motor repair after peripheral nerve injury. This study showed that the motor deficits caused by sciatic nerve crush injury were alleviated by daily systematic resveratrol treatment within 10 days. Resveratrol increased the number of axons in the distal part of the injured nerve, indicating enhanced nerve regeneration. In the affected ventral spinal cord, resveratrol enhanced the expression of several vascular endothelial growth factor family proteins (VEGFs) and increased the phosphorylation of p300 through Akt signaling, indicating activation of p300 acetyltransferase. Inactivation of p300 acetyltransferase reversed the resveratrol-induced expression of VEGFs and motor repair in rats that had undergone sciatic nerve crush injury. The above results indicated that daily systematic resveratrol treatment promoted nerve regeneration and led to rapid motor repair. Resveratrol activated p300 acetyltransferase-mediated VEGF signaling in the affected ventral spinal cord, which may have thus contributed to the acceleration of nerve regeneration and motor repair.

Flexible adaptation to an artificial recurrent connection from muscle to peripheral nerve in man.

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Kato, Kenji; Sasada, Syusaku; Nishimura, Yukio

2016-02-01

Controlling a neuroprosthesis requires learning a novel input-output transformation; however, how subjects incorporate this into limb control remains obscure. To elucidate the underling mechanisms, we investigated the motor adaptation process to a novel artificial recurrent connection (ARC) from a muscle to a peripheral nerve in healthy humans. In this paradigm, the ulnar nerve was electrically stimulated in proportion to the activation of the flexor carpi ulnaris (FCU), which is ulnar-innervated and monosynaptically innervated from Ia afferents of the FCU, defined as the "homonymous muscle," or the palmaris longus (PL), which is not innervated by the ulnar nerve and produces similar movement to the FCU, defined as the "synergist muscle." The ARC boosted the activity of the homonymous muscle and wrist joint movement during a visually guided reaching task. Participants could control muscle activity to utilize the ARC for the volitional control of wrist joint movement and then readapt to the absence of the ARC to either input muscle. Participants reduced homonymous muscle recruitment with practice, regardless of the input muscle. However, the adaptation process in the synergist muscle was dependent on the input muscle. The activity of the synergist muscle decreased when the input was the homonymous muscle, whereas it increased when it was the synergist muscle. This reorganization of the neuromotor map, which was maintained as an aftereffect of the ARC, was observed only when the input was the synergist muscle. These findings demonstrate that the ARC induced reorganization of neuromotor map in a targeted and sustainable manner. Copyright © 2016 the American Physiological Society.

Peripheral nerve injury induces glial activation in primary motor cortex

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Julieta Troncoso

2015-02-01

Full Text Available Preliminary evidence suggests that peripheral facial nerve injuries are associated with sensorimotor cortex reorganization. We have characterized facial nerve lesion-induced structural changes in primary motor cortex layer 5 pyramidal neurons and their relationship with glial cell density using a rodent facial paralysis model. First, we used adult transgenic mice expressing green fluorescent protein in microglia and yellow fluorescent protein in pyramidal neurons which were subjected to either unilateral lesion of the facial nerve or sham surgery. Two-photon excitation microscopy was then used for evaluating both layer 5 pyramidal neurons and microglia in vibrissal primary motor cortex (vM1. It was found that facial nerve lesion induced long-lasting changes in dendritic morphology of vM1 layer 5 pyramidal neurons and in their surrounding microglia. Pyramidal cells’ dendritic arborization underwent overall shrinkage and transient spine pruning. Moreover, microglial cell density surrounding vM1 layer 5 pyramidal neurons was significantly increased with morphological bias towards the activated phenotype. Additionally, we induced facial nerve lesion in Wistar rats to evaluate the degree and extension of facial nerve lesion-induced reorganization processes in central nervous system using neuronal and glial markers. Immunoreactivity to NeuN (neuronal nuclei antigen, GAP-43 (growth-associated protein 43, GFAP (glial fibrillary acidic protein, and Iba 1 (Ionized calcium binding adaptor molecule 1 were evaluated 1, 3, 7, 14, 28 and 35 days after either unilateral facial nerve lesion or sham surgery. Patches of decreased NeuN immunoreactivity were found bilaterally in vM1 as well as in primary somatosensory cortex (CxS1. Significantly increased GAP-43 immunoreactivity was found bilaterally after the lesion in hippocampus, striatum, and sensorimotor cortex. One day after lesion GFAP immunoreactivity increased bilaterally in hippocampus, subcortical white

Optic Nerve Injury in a Patient with Chronic Allergic Conjunctivitis

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Ribhi Hazin

2014-01-01

Full Text Available Manipulation of the optic nerve can lead to irreversible vision changes. We present a patient with a past medical history of skin allergy and allergic conjunctivitis (AC who presented with insidious unexplained unilateral vision loss. Physical exam revealed significant blepharospasm, mild lid edema, bulbar conjunctival hyperemia, afferent pupillary defect, and slight papillary hypertrophy. Slit lamp examination demonstrated superior and inferior conjunctival scarring as well as superior corneal scarring but no signs of external trauma or neurological damage were noted. Conjunctival cultures and cytologic evaluation demonstrated significant eosinophilic infiltration. Subsequent ophthalmoscopic examination revealed optic nerve atrophy. Upon further questioning, the patient admitted to vigorous itching of the affected eye for many months. Given the presenting symptoms, history, and negative ophthalmological workup, it was determined that the optic nerve atrophy was likely secondary to digital pressure from vigorous itching. Although AC can be a significant source of decreased vision via corneal ulceration, no reported cases have ever described AC-induced vision loss of this degree from vigorous itching and chronic pressure leading to optic nerve damage. Despite being self-limiting in nature, allergic conjunctivitis should be properly managed as extreme cases can result in mechanical compression of the optic nerve and compromise vision.

Somatosympathetic vasoconstrictor reflexes in human spinal cord injury: responses to innocuous and noxious sensory stimulation below lesion

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Vaughan G Macefield

2012-06-01

Full Text Available It is known that the sudden increases in blood pressure associated with autonomic dysreflexia in people with spinal cord injury (SCI is due to a spinally-mediated reflex activation of sympathetic vasoconstrictor neurones supplying skeletal muscle and the gut. Apart from visceral inputs, such as those originating from a distended bladder, there is a prevailing opinion that autonomic dysreflexia can be triggered by noxious stimulation below the lesion. However, do noxious inputs really cause an increase in blood pressure in SCI? Using microelectrodes inserted into a peripheral nerve to record sympathetic nerve activity we had previously shown that selective stimulation of small-diameter afferents in muscle or skin, induced by bolus injection of hypertonic saline into the tibialis anterior muscle or the overlying skin, evokes a sustained increase in muscle sympathetic nerve activity and blood pressure and a transient increase in skin sympathetic nerve activity and decrease in skin blood flow. We postulated that these sympathetic responses would be exaggerated in SCI, with a purely noxious stimulus causing long-lasting increases in blood pressure and long-lasting decreases in skin blood flow. Surprisingly, though, we found that intramuscular or subcutaneous injection of hypertonic saline into the leg caused negligible changes in these parameters. Conversely, weak electrical stimulation over the abdominal wall, which in able-bodied subjects is not painful and activates large-diameter cutaneous afferents, caused a marked increase in blood pressure in SCI but not in able-bodied subjects. This suggests that it is activation of large-diameter somatic afferents, not small-diameter afferents, that triggers increases in sympathetic outflow in SCI. Whether the responses to activation of large-diameter afferents reflect plastic changes in the spinal cord in SCI is unknown.

Central-peripheral neural network interactions evoked by vagus nerve stimulation: functional consequences on control of cardiac function.

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Ardell, Jeffrey L; Rajendran, Pradeep S; Nier, Heath A; KenKnight, Bruce H; Armour, J Andrew

2015-11-15

Using vagus nerve stimulation (VNS), we sought to determine the contribution of vagal afferents to efferent control of cardiac function. In anesthetized dogs, the right and left cervical vagosympathetic trunks were stimulated in the intact state, following ipsilateral or contralateral vagus nerve transection (VNTx), and then following bilateral VNTx. Stimulations were performed at currents from 0.25 to 4.0 mA, frequencies from 2 to 30 Hz, and a 500-μs pulse width. Right or left VNS evoked significantly greater current- and frequency-dependent suppression of chronotropic, inotropic, and lusitropic function subsequent to sequential VNTx. Bradycardia threshold was defined as the current first required for a 5% decrease in heart rate. The threshold for the right vs. left vagus-induced bradycardia in the intact state (2.91 ± 0.18 and 3.47 ± 0.20 mA, respectively) decreased significantly with right VNTx (1.69 ± 0.17 mA for right and 3.04 ± 0.27 mA for left) and decreased further following bilateral VNTx (1.29 ± 0.16 mA for right and 1.74 ± 0.19 mA for left). Similar effects were observed following left VNTx. The thresholds for afferent-mediated effects on cardiac parameters were 0.62 ± 0.04 and 0.65 ± 0.06 mA with right and left VNS, respectively, and were reflected primarily as augmentation. Afferent-mediated tachycardias were maintained following β-blockade but were eliminated by VNTx. The increased effectiveness and decrease in bradycardia threshold with sequential VNTx suggest that 1) vagal afferents inhibit centrally mediated parasympathetic efferent outflow and 2) the ipsilateral and contralateral vagi exert a substantial buffering capacity. The intact threshold reflects the interaction between multiple levels of the cardiac neural hierarchy. Copyright © 2015 the American Physiological Society.

Laser-activated solid protein bands for peripheral nerve repair: an vivo study.

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Lauto, A; Trickett, R; Malik, R; Dawes, J M; Owen, E R

1997-01-01

Severed tibial nerves in rats were repaired using a novel technique, utilizing a semiconductor diode-laser-activated protein solder applied longitudinally across the join. Welding was produced by selective laser denaturation of solid solder bands containing the dye indocyanine green. An in vivo study, using 48 adult male Wistar rats, compared conventional microsuture-repaired tibial nerves with laser solder-repaired nerves. Nerve repairs were characterised immediately after surgery and after 3 months. Successful regeneration with average compound muscle action potentials of 2.5 +/- 0.5 mV and 2.7 +/- 0.3 mV (mean and standard deviation) was demonstrated for the laser-soldered nerves and the sutured nerves, respectively. Histopathology confirmed comparable regeneration of axons in laser- and suture-operated nerves. The laser-based nerve repair technique was easier and faster than microsuture repair, minimising manipulation damage to the nerve.

Bone conducted vibration selectively activates irregular primary otolithic vestibular neurons in the guinea pig.

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Curthoys, Ian S; Kim, Juno; McPhedran, Samara K; Camp, Aaron J

2006-11-01

The main objective of this study was to determine whether bone-conducted vibration (BCV) is equally effective in activating both semicircular canal and otolith afferents in the guinea pig or whether there is preferential activation of one of these classes of vestibular afferents. To answer this question a large number (346) of single primary vestibular neurons were recorded extracellularly in anesthetized guinea pigs and were identified by their location in the vestibular nerve and classed as regular or irregular on the basis of the variability of their spontaneous discharge. If a neuron responded to angular acceleration it was classed as a semicircular canal neuron, if it responded to maintained roll or pitch tilts it was classified as an otolith neuron. Each neuron was then tested by BCV stimuli-either clicks, continuous pure tones (200-1,500 Hz) or short tone bursts (500 Hz lasting 7 ms)-delivered by a B-71 clinical bone-conduction oscillator cemented to the guinea pig's skull. All stimulus intensities were referred to that animal's own auditory brainstem response (ABR) threshold to BCV clicks, and the maximum intensity used was within the animal's physiological range and was usually around 70 dB above BCV threshold. In addition two sensitive single axis linear accelerometers cemented to the skull gave absolute values of the stimulus acceleration in the rostro-caudal direction. The criterion for a neuron being classed as activated was an audible, stimulus-locked increase in firing rate (a 10% change was easily detectable) in response to the BCV stimulus. At the stimulus levels used in this study, semicircular canal neurons, both regular and irregular, were insensitive to BCV stimuli and very few responded: only nine of 189 semicircular canal neurons tested (4.7%) showed a detectable increase in firing in response to BCV stimuli up to the maximum 2 V peak-to-peak level we delivered to the B-71 oscillator (which produced a peak-to-peak skull acceleration of around

TRPV1 Channels and Gastric Vagal Afferent Signalling in Lean and High Fat Diet Induced Obese Mice.

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Stephen J Kentish

Full Text Available Within the gastrointestinal tract vagal afferents play a role in control of food intake and satiety signalling. Activation of mechanosensitive gastric vagal afferents induces satiety. However, gastric vagal afferent responses to mechanical stretch are reduced in high fat diet mice. Transient receptor potential vanilloid 1 channels (TRPV1 are expressed in vagal afferents and knockout of TRPV1 reduces gastro-oesophageal vagal afferent responses to stretch. We aimed to determine the role of TRPV1 on gastric vagal afferent mechanosensitivity and food intake in lean and HFD-induced obese mice.TRPV1+/+ and -/- mice were fed either a standard laboratory diet or high fat diet for 20wks. Gastric emptying of a solid meal and gastric vagal afferent mechanosensitivity was determined.Gastric emptying was delayed in high fat diet mice but there was no difference between TRPV1+/+ and -/- mice on either diet. TRPV1 mRNA expression in whole nodose ganglia of TRPV1+/+ mice was similar in both dietary groups. The TRPV1 agonist N-oleoyldopamine potentiated the response of tension receptors in standard laboratory diet but not high fat diet mice. Food intake was greater in the standard laboratory diet TRPV1-/- compared to TRPV1+/+ mice. This was associated with reduced response of tension receptors to stretch in standard laboratory diet TRPV1-/- mice. Tension receptor responses to stretch were decreased in high fat diet compared to standard laboratory diet TRPV1+/+ mice; an effect not observed in TRPV1-/- mice. Disruption of TRPV1 had no effect on the response of mucosal receptors to mucosal stroking in mice on either diet.TRPV1 channels selectively modulate gastric vagal afferent tension receptor mechanosensitivity and may mediate the reduction in gastric vagal afferent mechanosensitivity in high fat diet-induced obesity.

Coordinated Respiratory Motor Activity in Nerves Innervating the Upper Airway Muscles in Rats.

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Satoshi Tachikawa

Full Text Available Maintaining the patency of the upper airway during breathing is of vital importance. The activity of various muscles is related to the patency of the upper airway. In the present study, we examined the respiratory motor activity in the efferent nerves innervating the upper airway muscles to determine the movements of the upper airway during respiration under normocapnic conditions (pH = 7.4 and in hypercapnic acidosis (pH = 7.2. Experiments were performed on arterially perfused decerebrate rats aged between postnatal days 21-35. We recorded the efferent nerve activity in a branch of the cervical spinal nerve innervating the infrahyoid muscles (CN, the hypoglossal nerve (HGN, the external branch of the superior laryngeal nerve (SLN, and the recurrent laryngeal nerve (RLN with the phrenic nerve (PN. Inspiratory nerve discharges were observed in all these nerves under normocapnic conditions. The onset of inspiratory discharges in the CN and HGN was slightly prior to those in the SLN and RLN. When the CO2 concentration in the perfusate was increased from 5% to 8% to prepare for hypercapnic acidosis, the peak amplitudes of the inspiratory discharges in all the recorded nerves were increased. Moreover, hypercapnic acidosis induced pre-inspiratory discharges in the CN, HGN, SLN, and RLN. The onset of pre-inspiratory discharges in the CN, HGN, and SLN was prior to that of discharges in the RLN. These results suggest that the securing of the airway that occurs a certain time before dilation of the glottis may facilitate ventilation and improve hypercapnic acidosis.

Asymmetric Macular Structural Damage Is Associated With Relative Afferent Pupillary Defects in Patients With Glaucoma

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Gracitelli, Carolina P. B.; Tatham, Andrew J.; Zangwill, Linda M.; Weinreb, Robert N.; Abe, Ricardo Y.; Diniz-Filho, Alberto; Paranhos, Augusto; Baig, Saif; Medeiros, Felipe A.

2016-01-01

Purpose We examined the relationship between relative afferent pupillary defects (RAPDs) and macular structural damage measured by macular thickness and macular ganglion cell-inner plexiform layer (mGCIPL) thickness in patients with glaucoma. Methods A cross-sectional study was done of 106 glaucoma patients and 85 healthy individuals from the Diagnostic Innovations in Glaucoma Study. All subjects underwent standard automated perimetry (SAP) and optic nerve and macular imaging using Cirrus Spectral Domain Optical Coherence Tomography (SDOCT). Glaucoma was defined as repeatable abnormal SAP or progressive glaucomatous changes on stereo photographs. Pupil responses were assessed using an automated pupillometer, which records the magnitude of RAPD (RAPD score), with additional RAPD scores recorded for each of a series of colored stimuli (blue, red, green, and yellow). The relationship between RAPD score and intereye differences (right minus left eye) in circumpapillary retinal nerve fiber layer (cpRNFL) thickness, mGCIPL, macular thickness, and SAP mean deviation (MD), was examined using linear regression. Results There was fair correlation between RAPD score and asymmetric macular structural damage measured by intereye difference in mGCIPL thickness (R2 = 0.285, P glaucoma. PMID:27064394

Defining the neural fulcrum for chronic vagus nerve stimulation: implications for integrated cardiac control.

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Ardell, Jeffrey L; Nier, Heath; Hammer, Matthew; Southerland, E Marie; Ardell, Christopher L; Beaumont, Eric; KenKnight, Bruce H; Armour, J Andrew

2017-11-15

The evoked cardiac response to bipolar cervical vagus nerve stimulation (VNS) reflects a dynamic interaction between afferent mediated decreases in central parasympathetic drive and suppressive effects evoked by direct stimulation of parasympathetic efferent axons to the heart. The neural fulcrum is defined as the operating point, based on frequency-amplitude-pulse width, where a null heart rate response is reproducibly evoked during the on-phase of VNS. Cardiac control, based on the principal of the neural fulcrum, can be elicited from either vagus. Beta-receptor blockade does not alter the tachycardia phase to low intensity VNS, but can increase the bradycardia to higher intensity VNS. While muscarinic cholinergic blockade prevented the VNS-induced bradycardia, clinically relevant doses of ACE inhibitors, beta-blockade and the funny channel blocker ivabradine did not alter the VNS chronotropic response. While there are qualitative differences in VNS heart control between awake and anaesthetized states, the physiological expression of the neural fulcrum is maintained. Vagus nerve stimulation (VNS) is an emerging therapy for treatment of chronic heart failure and remains a standard of therapy in patients with treatment-resistant epilepsy. The objective of this work was to characterize heart rate (HR) responses (HRRs) during the active phase of chronic VNS over a wide range of stimulation parameters in order to define optimal protocols for bidirectional bioelectronic control of the heart. In normal canines, bipolar electrodes were chronically implanted on the cervical vagosympathetic trunk bilaterally with anode cephalad to cathode (n = 8, 'cardiac' configuration) or with electrode positions reversed (n = 8, 'epilepsy' configuration). In awake state, HRRs were determined for each combination of pulse frequency (2-20 Hz), intensity (0-3.5 mA) and pulse widths (130-750 μs) over 14 months. At low intensities and higher frequency VNS, HR increased during the

Nerve transection repair using laser-activated chitosan in a rat model.

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Bhatt, Neel K; Khan, Taleef R; Mejias, Christopher; Paniello, Randal C

2017-08-01

Cranial nerve transection during head and neck surgery is conventionally repaired with microsuture. Previous studies have demonstrated recovery with laser nerve welding (LNW), a novel alternative to microsuture. LNW has been reported to have poorer tensile strength, however. Laser-activated chitosan, an adhesive biopolymer, may promote nerve recovery while enhancing the tensile strength of the repair. Using a rat posterior tibial nerve injury model, we compared four different methods of nerve repair in this pilot study. Animal study. Animals underwent unilateral posterior tibial nerve transection. The injury was repaired by potassium titanyl phosphate (KTP) laser alone (n = 20), KTP + chitosan (n = 12), microsuture + chitosan (n = 12), and chitosan alone (n = 14). Weekly walking tracks were conducted to measure functional recovery (FR). Tensile strength (TS) was measured at 6 weeks. At 6 weeks, KTP laser alone had the best recovery (FR = 93.4% ± 8.3%). Microsuture + chitosan, KTP + chitosan, and chitosan alone all showed good FR (87.4% ± 13.5%, 84.6% ± 13.0%, and 84.1% ± 10.0%, respectively). One-way analysis of variance was performed (F(3,56) = 2.6, P = .061). A TS threshold of 3.8 N was selected as a control mean recovery. Three groups-KTP alone, KTP + chitosan, and microsuture + chitosan-were found to meet threshold 60% (95% confidence interval [CI]: 23.1%-88.3%), 75% (95% CI: 46.8%-91.1%), and 100% (95% CI: 75.8%-100.0%), respectively. In the posterior tibial nerve model, all repair methods promoted nerve recovery. Laser-activated chitosan as a biopolymer anchor provided good TS and appears to be a novel alternative to microsuture. This repair method may have surgical utility following cranial nerve injury during head and neck surgery. NA Laryngoscope, 127:E253-E257, 2017. © 2017 The American Laryngological, Rhinological and Otological Society, Inc.

Differential roles of galanin on mechanical and cooling responses at the primary afferent nociceptor

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Hulse Richard P

2012-06-01

Full Text Available Abstract Background Galanin is expressed in a small percentage of intact small diameter sensory neurons of the dorsal root ganglia and in the afferent terminals of the superficial lamina of the dorsal horn of the spinal cord. The neuropeptide modulates nociception demonstrating dose-dependent pro- and anti-nociceptive actions in the naïve animal. Galanin also plays an important role in chronic pain, with the anti-nociceptive actions enhanced in rodent neuropathic pain models. In this study we compared the role played by galanin and its receptors in mechanical and cold allodynia by identifying individual rat C-fibre nociceptors and characterising their responses to mechanical or acetone stimulation. Results Mechanically evoked responses in C-fibre nociceptors from naive rats were sensitised after close intra-arterial infusion of galanin or Gal2-11 (a galanin receptor-2/3 agonist confirming previous data that galanin modulates nociception via activation of GalR2. In contrast, the same dose and route of administration of galanin, but not Gal2-11, inhibited acetone and menthol cooling evoked responses, demonstrating that this inhibitory mechanism is not mediated by activation of GalR2. We then used the partial saphenous nerve ligation injury model of neuropathic pain (PSNI and the complete Freund’s adjuvant model of inflammation in the rat and demonstrated that close intra-arterial infusion of galanin, but not Gal2-11, reduced cooling evoked nociceptor activity and cooling allodynia in both paradigms, whilst galanin and Gal2-11 both decreased mechanical activation thresholds. A previously described transgenic mouse line which inducibly over-expresses galanin (Gal-OE after nerve injury was then used to investigate whether manipulating the levels of endogenous galanin also modulates cooling evoked nociceptive behaviours after PSNI. Acetone withdrawal behaviours in naive mice showed no differences between Gal-OE and wildtype (WT mice. 7-days after

Activity-dependent intracellular Ca2+ transients in unmyelinated nerve fibres of the isolated adult rat vagus nerve.

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Wächtler, J; Mayer, C; Grafe, P

1998-04-01

Confocal laser scanning microscopy was used to follow changes in the free intracellular calcium concentration ([Ca2+]i) in nerve fibres and adjacent Schwann cells in isolated rat vagus nerves. [Ca2+]i was monitored by the Ca2+-sensitive fluorescent dyes Calcium Green-1 and Fura Red. Intracellular Ca2+ transients were observed during repetitive (1-50 Hz) supramaximal electrical stimulation or by bath application of ATP. Trains of action potentials were more effective at elongated, fibre-like structures of the vagus nerves, whereas ATP-induced Ca2+ transients were found predominantly in regions of Schwann cell bodies. Activity-induced Ca2+ signals were unaffected by pharmacological manipulation of intracellular Ca2+ stores, during long-lasting application of purinergic receptor agonists, or by substitution of extracellular Na+ with Li+. However, they were abolished in the presence of Ca2+-free bathing solution or after the blocking of Ca2+ channels with Cd2+. Ca2+ transients were also observed during Ca2+ action potentials. Such "Ca2+ spikes" were elicited by electrical stimulation in the presence of a combination of tetrodotoxin and K+ channel blockers. These data suggest that voltage-dependent Ca2+ channels, activated during short trains of Na+ action potentials, produce an increase in intra-axonal [Ca2+] of rat vagus nerves. We did not find evidence for activity-dependent Ca2+ transients in the Schwann cells surrounding the unmyelinated axons.

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

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McVey Neufeld, K A; Perez-Burgos, A; Mao, Y K; Bienenstock, J; Kunze, W A

2015-05-01

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. © 2015 John Wiley & Sons Ltd.

Interplay between mast cells, enterochromaffin cells, and sensory signaling in the aging human bowel.

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Yu, Y; Daly, D M; Adam, I J; Kitsanta, P; Hill, C J; Wild, J; Shorthouse, A; Grundy, D; Jiang, W

2016-10-01

Advanced age is associated with a reduction in clinical visceral pain perception. However, the underlying mechanisms remain largely unknown. Previous studies have suggested that an abnormal interplay between mast cells, enterochromaffin (EC) cells, and afferent nerves contribute to nociception in gastrointestinal disorders. The aim of this study was to investigate how aging affects afferent sensitivity and neuro-immune association in the human bowel. Mechanical and chemical sensitivity of human bowel afferents were examined by ex vivo afferent nerve recordings. Age-related changes in the density of mast cells, EC cells, sensory nerve terminals, and mast cell-nerve micro-anatomical association were investigated by histological and immune staining. Human afferents could be broadly classified into subpopulations displaying mechanical and chemical sensitivity, adaptation, chemo-sensitization, and recruitment. Interestingly human bowel afferent nerve sensitivity was attenuated with age. The density of substance P-immunoreactive (SP-IR) nerve varicosities was also reduced with age. In contrast, the density of ileal and colonic mucosal mast cells was increased with age, as was ileal EC cell number. An increased proportion of mast cells was found in close apposition to SP-IR nerves. Afferent sensitivity in human bowel was reduced with advancing age. Augmentation of mast cells and EC cell numbers and the mast cell-nerve association suggest a compensatory mechanism for sensory neurodegeneration. © 2016 The Authors. Neurogastroenterology & Motility Published by John Wiley & Sons Ltd.

Sensorimotor peripheral nerve function and physical activity in older men

DEFF Research Database (Denmark)

Lange-Maia, B. S.; Cauley, J A; Newman, Anne B

2016-01-01

We determined whether sensorimotor peripheral nerve (PN) function was associated with physical activity (PA) in older men. The Osteoporotic Fractures in Men Study Pittsburgh, PA, site (n = 328, age 78.8 ± 4.7 years) conducted PN testing, including: peroneal motor and sural sensory nerve conduction...... (latencies, amplitudes: CMAP and SNAP for motor and sensory amplitude, respectively), 1.4g/10g monoflament (dorsum of the great toe), and neuropathy symptoms. ANOVA and multivariate linear regression modeled PN associations with PA (Physical Activity Scale for the Elderly [PASE] and SenseWear Armband). After...

The oculomotor system of decapod cephalopods: eye muscles, eye muscle nerves, and the oculomotor neurons in the central nervous system.

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Budelmann, B U; Young, J Z

1993-04-29

Fourteen extraocular eye muscles are described in the decapods Loligo and Sepioteuthis, and thirteen in Sepia; they are supplied by four eye muscle nerves. The main action of most of the muscles is a linear movement of the eyeball, only three muscles produce strong rotations. The arrangement, innervation and action of the decapod eye muscles are compared with those of the seven eye muscles and seven eye muscle nerves in Octopus. The extra muscles in decapods are attached to the anterior and superior faces of the eyes. At least, the anterior muscles, and presumably also the superior muscles, are concerned with convergent eye movements for binocular vision during fixation and capture of prey by the tentacles. The remaining muscles are rather similar in the two cephalopod groups. In decapods, the anterior muscles include conjunctive muscles; these cross the midline and each presumably moves both eyes at the same time during fixation. In the squids Loligo and Sepioteuthis there is an additional superior conjunctive muscle of perhaps similar function. Some of the anterior muscles are associated with a narrow moveable plate, the trochlear cartilage; it is attached to the eyeball by trochlear membranes. Centripetal cobalt fillings showed that all four eye muscle nerves have fibres that originate from somata in the ipsilateral anterior lateral pedal lobe, which is the oculomotor centre. The somata of the individual nerves show different but overlapping distributions. Bundles of small presumably afferent fibres were seen in two of the four nerves. They do not enter the anterior lateral pedal lobe but run to the ventral magnocellular lobe; some afferent fibres enter the brachio-palliovisceral connective and run perhaps as far as the palliovisceral lobe.

DC-Evoked Modulation of Excitability of Myelinated Nerve Fibers and Their Terminal Branches; Differences in Sustained Effects of DC.

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Kaczmarek, Dominik; Jankowska, Elzbieta

2018-03-15

Direct current (DC) evokes long-lasting changes in neuronal networks both presynaptically and postsynaptically and different mechanisms were proposed to be involved in them. Different mechanisms were also suggested to account for the different dynamics of presynaptic DC actions on myelinated nerve fibers stimulated before they entered the spinal gray matter and on their terminal branches. The aim of the present study was to examine whether these different dynamics might be related to differences in the involvement of K + channels. To this end, we compared effects of the K + channel blocker 4-amino-pyridine (4-AP) on DC-evoked changes in the excitability of afferent fibers stimulated within the dorsal columns (epidurally) and within their projection areas in the dorsal horn and motor nuclei (intraspinally). 4-AP was applied systemically in deeply anesthetized rats. DC-evoked increases in the excitability of epidurally stimulated afferent nerve fibers, and increases in field potentials evoked by these fibers, were not affected by 4-AP. In contrast, sustained decreases rather than increases in the excitability of intraspinally stimulated terminal nerve branches were evoked by local application of DC in conjunction with 4-AP. The study leads to the conclusion that 4-AP-sensitive K + channels contribute to the sustained DC-evoked post-polarization increases in the excitability at the level of terminal branches of nerve fibers but not of the nodes of Ranvier nor within the juxta-paranodal regions where other mechanisms would be involved in inducing the sustained DC-evoked changes. Copyright © 2018 IBRO. Published by Elsevier Ltd. All rights reserved.

Nerve growth factor promotes human hemopoietic colony growth and differentiation

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Matsuda, H.; Coughlin, M.D.; Bienenstock, J.; Denburg, J.A.

1988-01-01

Nerve growth factor (NGF) is a neurotropic polypeptide necessary for the survival and growth of some central neurons, as well as sensory afferent and sympathetic neurons. Much is now known of the structural and functional characteristics of NGF, whose gene has recently been clones. Since it is synthesized in largest amounts by the male mouse submandibular gland, its role exclusively in nerve growth is questionable. These experiments indicate that NGF causes a significant stimulation of granulocyte colonies grown from human peripheral blood in standard hemopoietic methylcellulose assays. Further, NGF appears to act in a relatively selective fashion to induce the differentiation of eosinophils and basophils/mast cells. Depletion experiments show that the NGF effect may be T-cell dependent and that NGF augments the colony-stimulating effect of supernatants from the leukemic T-cell (Mo) line. The hemopoietic activity of NGF is blocked by 125 I-polyclonal and monoclonal antibodies to NGF. The authors conclude that NGF may indirectly act as a local growth factor in tissues other than those of the nervous system by causing T cells to synthesize or secrete molecules with colony-stimulating activity. In view of the synthesis of NGF in tissue injury, the involvement of basophils/mast cells and eosinophils in allergic and other inflammatory processes, and the association of mast cells with fibrosis and tissue repair, they postulate that NGF plays an important biological role in a variety of repair processes

Interactions between visceral afferent signaling and stimulus processing

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Hugo D Critchley

2015-08-01

Full Text Available Visceral afferent signals to the brain influence thoughts, feelings and behaviour. Here we highlight the findings of a set of empirical investigations in humans concerning body-mind interaction that focus on how feedback from states of autonomic arousal shapes cognition and emotion. There is a longstanding debate regarding the contribution of the body, to mental processes. Recent theoretical models broadly acknowledge the role of (autonomically-mediated physiological arousal to emotional, social and motivational behaviours, yet the underlying mechanisms are only partially characterized. Neuroimaging is overcoming this shortfall; first, by demonstrating correlations between autonomic change and discrete patterns of evoked, and task-independent, neural activity; second, by mapping the central consequences of clinical perturbations in autonomic response and; third, by probing how dynamic fluctuations in peripheral autonomic state are integrated with perceptual, cognitive and emotional processes. Building on the notion that an important source of the brain’s representation of physiological arousal is derived from afferent information from arterial baroreceptors, we have exploited the phasic nature of these signals to show their differential contribution to the processing of emotionally-salient stimuli. This recent work highlights the facilitation at neural and behavioral levels of fear and threat processing that contrasts with the more established observations of the inhibition of central pain processing during baroreceptors activation. The implications of this body-brain-mind axis are discussed.

Development of Kinematic Graphs of Median Nerve during Active Finger Motion: Implications of Smartphone Use.

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Hoi-Chi Woo

Full Text Available Certain hand activities cause deformation and displacement of the median nerve at the carpal tunnel due to the gliding motion of tendons surrounding it. As smartphone usage escalates, this raises the public's concern whether hand activities while using smartphones can lead to median nerve problems.The aims of this study were to 1 develop kinematic graphs and 2 investigate the associated deformation and rotational information of median nerve in the carpal tunnel during hand activities.Dominant wrists of 30 young adults were examined with ultrasonography by placing a transducer transversely on their wrist crease. Ultrasound video clips were recorded when the subject performing 1 thumb opposition with the wrist in neutral position, 2 thumb opposition with the wrist in ulnar deviation and 3 pinch grip with the wrist in neutral position. Six still images that were separated by 0.2-second intervals were then captured from the ultrasound video for the determination of 1 cross-sectional area (CSA, 2 flattening ratio (FR, 3 rotational displacement (RD and 4 translational displacement (TD of median nerve in the carpal tunnel, and these collected information of deformation, rotational and displacement of median nerve were compared between 1 two successive time points during a single hand activity and 2 different hand motions at the same time point. Finally, kinematic graphs were constructed to demonstrate the mobility of median nerve during different hand activities.Performing different hand activities during this study led to a gradual reduction in CSA of the median nerve, with thumb opposition together with the wrist in ulnar deviation causing the greatest extent of deformation of the median nerve. Thumb opposition with the wrist in ulnar deviation also led to the largest extent of TD when compared to the other two hand activities of this study. Kinematic graphs showed that the motion pathways of median nerve during different hand activities were complex

Corticospinal and Spinal Excitabilities Are Modulated during Motor Imagery Associated with Somatosensory Electrical Nerve Stimulation

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E. Traverse

2018-01-01

Full Text Available Motor imagery (MI, the mental simulation of an action, influences the cortical, corticospinal, and spinal levels, despite the lack of somatosensory afferent feedbacks. The aim of this study was to analyze the effect of MI associated with somatosensory stimulation (SS on the corticospinal and spinal excitabilities. We used transcranial magnetic stimulation and peripheral nerve stimulation to induce motor-evoked potentials (MEP and H-reflexes, respectively, in soleus and medialis gastrocnemius (MG muscles of the right leg. Twelve participants performed three tasks: (1 MI of submaximal plantar flexion, (2 SS at 65 Hz on the posterior tibial nerve with an intensity below the motor threshold, and (3 MI + SS. MEP and H-reflex amplitudes were recorded before, during, and after the tasks. Our results confirmed that MI increased corticospinal excitability in a time-specific manner. We found that MI+SS tended to potentiate MEP amplitude of the MG muscle compared to MI alone. We confirmed that SS decreased spinal excitability, and this decrease was partially compensated when combined with MI, especially for the MG muscle. The increase of CSE could be explained by a modulation of the spinal inhibitions induced by SS, depending on the amount of afferent feedbacks.

Evaluation of high-density, multi-contact nerve cuffs for activation of grasp muscles in monkeys

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Brill, N. A.; Naufel, S. N.; Polasek, K.; Ethier, C.; Cheesborough, J.; Agnew, S.; Miller, L. E.; Tyler, D. J.

2018-06-01

Objective. The objective of this work was to evaluate whether nerve cuffs can selectively activate hand muscles for functional electrical stimulation (FES). FES typically involves identifying and implanting electrodes in many individual muscles, but nerve cuffs only require implantation at a single site around the nerve. This method is surgically more attractive. Nerve cuffs may also more effectively stimulate intrinsic hand muscles, which are difficult to implant and stimulate without spillover to adjacent muscles. Approach. To evaluate its ability to selectively activate muscles, we implanted and tested the flat interface nerve electrode (FINE), which is designed to selectively stimulate peripheral nerves that innervate multiple muscles (Tyler and Durand 2002 IEEE Trans. Neural Syst. Rehabil. Eng. 10 294-303). We implanted FINEs on the nerves and bipolar intramuscular wires for recording compound muscle action potentials (CMAPs) from up to 20 muscles in each arm of six monkeys. We then collected recruitment curves while the animals were anesthetized. Main result. A single FINE implanted on an upper extremity nerve in the monkey can selectively activate muscles or small groups of muscles to produce multiple, independent hand functions. Significance. FINE cuffs can serve as a viable supplement to intramuscular electrodes in FES systems, where they can better activate intrinsic and extrinsic muscles with lower currents and less extensive surgery.

Central projections of antennular chemosensory and mechanosensory afferents in the brain of the terrestrial hermit crab (Coenobita clypeatus; Coenobitidae, Anomura)

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Tuchina, Oksana; Koczan, Stefan; Harzsch, Steffen; Rybak, Jürgen; Wolff, Gabriella; Strausfeld, Nicholas J.; Hansson, Bill S.

2015-01-01

The Coenobitidae (Decapoda, Anomura, Paguroidea) is a taxon of hermit crabs that includes two genera with a fully terrestrial life style as adults. Previous studies have shown that Coenobitidae have evolved a sense of spatial odor localization that is behaviorally highly relevant. Here, we examined the central olfactory pathway of these animals by analyzing central projections of the antennular nerve of Coenobita clypeatus, combining backfilling of the nerve with dextran-coupled dye, Golgi impregnations and three-dimensional reconstruction of the primary olfactory center, the antennular lobe. The principal pattern of putative olfactory sensory afferents in C. clypeatus is in many aspects similar to what have been established for aquatic decapod crustaceans, such as the spiny lobster Panulirus argus. However, there are also obvious differences that may, or may not represent adaptations related to a terrestrial lifestyle. In C. clypeatus, the antennular lobe dominates the deutocerebrum, having more than one thousand allantoid-shaped subunits. We observed two distinct patterns of sensory neuron innervation: putative olfactory afferents from the aesthetascs either supply the cap/subcap region of the subunits or they extend through its full depth. Our data also demonstrate that any one sensory axon can supply input to several subunits. Putative chemosensory (non-aesthetasc) and mechanosensory axons represent a different pathway and innervate the lateral and median antennular neuropils. Hence, we suggest that the chemosensory input in C. clypeatus might be represented via a dual pathway: aesthetascs target the antennular lobe, and bimodal sensilla target the lateral antennular neuropil and median antennular neuropil. The present data is compared to related findings in other decapod crustaceans. PMID:26236202

Does Sacral Nerve Stimulation Improve Continence Through Enhanced Sensitivity of the Anal Canal?

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Haas, S; Brock, C; Krogh, K

2016-01-01

. DESIGN: This is an explorative study. PATIENTS: Fifteen women with idiopathic fecal incontinence (mean age, 58 ± 12.2 years) were selected. INTERVENTIONS: Cortical evoked potentials were recorded during repeated rapid balloon distension of the rectum and the anal canal both before and during temporary...... the threshold for urge to defecate elicited from the anal canal, whereas supraspinal responses remained unaltered. This may suggest that sacral nerve stimulation, at least in part, acts via somatic afferent fibers enhancing anal sensation....

Severe hypoxia affects exercise performance independently of afferent feedback and peripheral fatigue.

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Millet, Guillaume Y; Muthalib, Makii; Jubeau, Marc; Laursen, Paul B; Nosaka, Kazunori

2012-04-01

To test the hypothesis that hypoxia centrally affects performance independently of afferent feedback and peripheral fatigue, we conducted two experiments under complete vascular occlusion of the exercising muscle under different systemic O(2) environmental conditions. In experiment 1, 12 subjects performed repeated submaximal isometric contractions of the elbow flexor to exhaustion (RCTE) with inspired O(2) fraction fixed at 9% (severe hypoxia, SevHyp), 14% (moderate hypoxia, ModHyp), 21% (normoxia, Norm), or 30% (hyperoxia, Hyper). The number of contractions (performance), muscle (biceps brachii), and prefrontal near-infrared spectroscopy (NIRS) parameters and high-frequency paired-pulse (PS100) evoked responses to electrical muscle stimulation were monitored. In experiment 2, 10 subjects performed another RCTE in SevHyp and Norm conditions in which the number of contractions, biceps brachii electromyography responses to electrical nerve stimulation (M wave), and transcranial magnetic stimulation responses (motor-evoked potentials, MEP, and cortical silent period, CSP) were recorded. Performance during RCTE was significantly reduced by 10-15% in SevHyp (arterial O(2) saturation, SpO(2) = ∼75%) compared with ModHyp (SpO(2) = ∼90%) or Norm/Hyper (SpO(2) > 97%). Performance reduction in SevHyp occurred despite similar 1) metabolic (muscle NIRS parameters) and functional (changes in PS100 and M wave) muscle states and 2) MEP and CSP responses, suggesting comparable corticospinal excitability and spinal and cortical inhibition between SevHyp and Norm. It is concluded that, in SevHyp, performance and central drive can be altered independently of afferent feedback and peripheral fatigue. It is concluded that submaximal performance in SevHyp is partly reduced by a mechanism related directly to brain oxygenation.

Role of TRPV1 in acupuncture modulation of reflex excitatory cardiovascular responses.

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Guo, Zhi-Ling; Fu, Liang-Wu; Su, Hou-Fen; Tjen-A-Looi, Stephanie C; Longhurst, John C

2018-05-01

We have shown that acupuncture, including manual and electroacupuncture (MA and EA), at the P5-6 acupoints stimulates afferent fibers in the median nerve (MN) to modulate sympathoexcitatory cardiovascular reflexes through central regulation of autonomic function. However, the mechanisms underlying acupuncture activation of these sensory afferent nerves and their cell bodies in the dorsal root ganglia (DRG) are unclear. Transient receptor potential vanilloid type 1 (TRPV1) is present in sensory nerve fibers distributed in the general region of acupoints like ST36 and BL 40 located in the hindlimb. However, the contribution of TRPV1 to activation of sensory nerves by acupuncture, leading to modulation of pressor responses, has not been studied. We hypothesized that TRPV1 participates in acupuncture's activation of sensory afferents and their associated cell bodies in the DRG to modulate pressor reflexes. Local injection of iodoresiniferatoxin (Iodo-RTX; a selective TRPV1 antagonist), but not 5% DMSO (vehicle), into the P6 acupoint on the forelimb reversed the MA's inhibition of pressor reflexes induced by gastric distension (GD). Conversely, inhibition of GD-induced sympathoexcitatory responses by EA at P5-6 was unchanged after administration of Iodo-RTX into P5-6. Single-unit activity of Group III or IV bimodal afferents sensitive to both mechanical and capsaicin stimuli responded to MA stimulation at P6. MA-evoked activity was attenuated significantly ( P < 0.05) by local administration of Iodo-RTX ( n = 12) but not by 5% DMSO ( n = 12) into the region of the P6 acupoint in rats. Administration of Iodo-RTX into P5-6 did not reduce bimodal afferent activity evoked by EA stimulation ( n = 8). Finally, MA at P6 and EA at P5-6 induced phosphorylation of extracellular signal-regulated kinases (ERK; an intracellular signaling messenger involved in cellular excitation) in DRG neurons located at C 7-8 spinal levels receiving MN inputs. After TRPV1 was knocked down in the

Non-invasive stimulation of the vibrissal pad improves recovery of whisking function after simultaneous lesion of the facial and infraorbital nerves in rats.

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Bendella, H; Pavlov, S P; Grosheva, M; Irintchev, A; Angelova, S K; Merkel, D; Sinis, N; Kaidoglou, K; Skouras, E; Dunlop, S A; Angelov, Doychin N

2011-07-01

We have recently shown that manual stimulation of target muscles promotes functional recovery after transection and surgical repair to pure motor nerves (facial: whisking and blink reflex; hypoglossal: tongue position). However, following facial nerve repair, manual stimulation is detrimental if sensory afferent input is eliminated by, e.g., infraorbital nerve extirpation. To further understand the interplay between sensory input and motor recovery, we performed simultaneous cut-and-suture lesions on both the facial and the infraorbital nerves and examined whether stimulation of the sensory afferents from the vibrissae by a forced use would improve motor recovery. The efficacy of 3 treatment paradigms was assessed: removal of the contralateral vibrissae to ensure a maximal use of the ipsilateral ones (vibrissal stimulation; Group 2), manual stimulation of the ipsilateral vibrissal muscles (Group 3), and vibrissal stimulation followed by manual stimulation (Group 4). Data were compared to controls which underwent surgery but did not receive any treatment (Group 1). Four months after surgery, all three treatments significantly improved the amplitude of vibrissal whisking to 30° versus 11° in the controls of Group 1. The three treatments also reduced the degree of polyneuronal innervation of target muscle fibers to 37% versus 58% in Group 1. These findings indicate that forced vibrissal use and manual stimulation, either alone or sequentially, reduce target muscle polyinnervation and improve recovery of whisking function when both the sensory and the motor components of the trigemino-facial system regenerate.

The role in masseter muscle activities of functionally elicited periodontal afferents from abutment teeth under overdentures.

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Mushimoto, E

1981-09-01

Five overdenture wearers with a small number of remaining natural teeth were selected to evaluate the effect of the afferent input from periodontal mechanoreceptors on masseter activity in man. As a control, a full denture wearer was included. The subjects were instructed to chew a piece of gum, and/or tap their teeth. Surface EmG from the bilateral masseter muscles were recorded and analysed. When functional pressure was applied, during chewing, to the abutment teeth as well as to mucosa through the denture base, masseter activities were encouraged. Following application of anaesthesia to the periodontal membrane of the abutments, masseter activities were reduced. The duration of the silent period (SP) appearing in the EMG burst following tooth tapping was significantly increased with root support compared to mucosal support only. With topical anaesthesia of the periodontal tissues, SP duration decreased significantly. In conclusion, it has become apparent that the pressure sensibility of abutment teeth bearing functional pressure under an overdenture base is capable of facilitating masseter activity, as one of the sources of oral sensory input during mastication.

Chloride is essential for contraction of afferent arterioles after agonists and potassium

DEFF Research Database (Denmark)

Jensen, B L; Ellekvist, Peter; Skøtt, O

1997-01-01

to norepinephrine, angiotensin II (ANG II), and potassium were measured after chloride depletion and compared with controls. Chloride depletion did not change arteriolar diameters, but the response to norepinephrine was markedly reduced when chloride was substituted with gluconate (n = 6) or isethionate (n = 6......). Reintroduction of chloride fully restored the sensitivity to norepinephrine. Contractions after ANG II and potassium were totally abolished in the absence of chloride (n = 6). In additional experiments (n = 7), the arteriolar contraction to 100 mM potassium was abolished only 1 min after removal of extracellular......A depolarizing chloride efflux has been suggested to activate voltage-dependent calcium channels in renal afferent arteriolar smooth muscle cells in response to vasoconstrictors. To test this proposal, rabbit afferent arterioles were microperfused, and the contractile dose responses...

A comparative analysis of the encapsulated end-organs of mammalian skeletal muscles and of their sensory nerve endings.

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Banks, R W; Hulliger, M; Saed, H H; Stacey, M J

2009-06-01

The encapsulated sensory endings of mammalian skeletal muscles are all mechanoreceptors. At the most basic functional level they serve as length sensors (muscle spindle primary and secondary endings), tension sensors (tendon organs), and pressure or vibration sensors (lamellated corpuscles). At a higher functional level, the differing roles of individual muscles in, for example, postural adjustment and locomotion might be expected to be reflected in characteristic complements of the various end-organs, their sensory endings and afferent nerve fibres. This has previously been demonstrated with regard to the number of muscle-spindle capsules; however, information on the other types of end-organ, as well as the complements of primary and secondary endings of the spindles themselves, is sporadic and inconclusive regarding their comparative provision in different muscles. Our general conclusion that muscle-specific variability in the provision of encapsulated sensory endings does exist demonstrates the necessity for the acquisition of more data of this type if we are to understand the underlying adaptive relationships between motor control and the structure and function of skeletal muscle. The present quantitative and comparative analysis of encapsulated muscle afferents is based on teased, silver-impregnated preparations. We begin with a statistical analysis of the number and distribution of muscle-spindle afferents in hind-limb muscles of the cat, particularly tenuissimus. We show that: (i) taking account of the necessity for at least one primary ending to be present, muscles differ significantly in the mean number of additional afferents per spindle capsule; (ii) the frequency of occurrence of spindles with different sensory complements is consistent with a stochastic, rather than deterministic, developmental process; and (iii) notwithstanding the previous finding, there is a differential distribution of spindles intramuscularly such that the more complex ones tend

Serotonin, dopamine and noradrenaline adjust actions of myelinated afferents via modulation of presynaptic inhibition in the mouse spinal cord.

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David L García-Ramírez

Full Text Available Gain control of primary afferent neurotransmission at their intraspinal terminals occurs by several mechanisms including primary afferent depolarization (PAD. PAD produces presynaptic inhibition via a reduction in transmitter release. While it is known that descending monoaminergic pathways complexly regulate sensory processing, the extent these actions include modulation of afferent-evoked PAD remains uncertain. We investigated the effects of serotonin (5HT, dopamine (DA and noradrenaline (NA on afferent transmission and PAD. Responses were evoked by stimulation of myelinated hindlimb cutaneous and muscle afferents in the isolated neonatal mouse spinal cord. Monosynaptic responses were examined in the deep dorsal horn either as population excitatory synaptic responses (recorded as extracellular field potentials; EFPs or intracellular excitatory postsynaptic currents (EPSCs. The magnitude of PAD generated intraspinally was estimated from electrotonically back-propagating dorsal root potentials (DRPs recorded on lumbar dorsal roots. 5HT depressed the DRP by 76%. Monosynaptic actions were similarly depressed by 5HT (EFPs 54%; EPSCs 75% but with a slower time course. This suggests that depression of monosynaptic EFPs and DRPs occurs by independent mechanisms. DA and NA had similar depressant actions on DRPs but weaker effects on EFPs. IC50 values for DRP depression were 0.6, 0.8 and 1.0 µM for 5HT, DA and NA, respectively. Depression of DRPs by monoamines was nearly-identical in both muscle and cutaneous afferent-evoked responses, supporting a global modulation of the multimodal afferents stimulated. 5HT, DA and NA produced no change in the compound antidromic potentials evoked by intraspinal microstimulation indicating that depression of the DRP is unrelated to direct changes in the excitability of intraspinal afferent fibers, but due to metabotropic receptor activation. In summary, both myelinated afferent-evoked DRPs and monosynaptic

MR features of a case of afferent loop syndrome presenting as obstructive jaundice

International Nuclear Information System (INIS)

Chevallier, P.; Souci, J.; Oddo, F.; Diaine, B.; Padovani, B.; Gueyffier, C.

2001-01-01

The afferent loop syndrome corresponds to an acute or chronic obstruction of the afferent loop following a partial gastrectomy with Billroth II gastro-jejunal anastomosis. We describe the case of a 77-year-old man with history of partial gastrectomy for peptic ulcer disease performed 31 years ago and currently admitted for jaundice and poor general status. MR imaging showed dilatation of biliary and pancreatic ducts and showed a soft tissue mass between the afferent loop and the residual stomach. Endoscopy showed complete obstruction of the afferent loop by a biopsy-proven adenocarcinoma. The patient died of sepsis shortly after endoscopy of septicemia. (authors)

Physiological properties of afferents to the rat cerebellum during normal development and after postnatal x irradiation

International Nuclear Information System (INIS)

Puro, D.G.

1975-01-01

The consequences of an altered cerebellar cortical development on afferent transmission and terminal organization were analyzed in adult rats which had received x irradiation to the cerebellum postnatally. Rats, anesthetized with 0.5 percent halothane, were studied in various ages from day 3 to adult. The ascending mossy and climbing fiber systems were activated by electrical stimulation of the limbs with needle electrodes. Stimulation of the motor cortex activated the descending climbing fiber pathways. Extracellular responses from cerebellar Purkinje cells were observed on an oscilloscope as poststimulus time histograms were constructed ''on-line''. Conclusions and assertions include: (1) Synaptogenesis between incoming afferent fibers and target neurons takes place early in cerebellar cortical development. (2) Mossy fiber transmission is mature before the bulk of cerebellar synaptogenesis occurs. (3) The ascending and descending components of the climbing fiber system mature, with respect to latency, in synchrony. (4) The terminal synaptic organization has little effect on the development of transmission characteristics in these afferent systems. (5) One possible mechanism by which an adult neural structure can have an abnormal synaptic organization is to maintain immature synaptic relationships due to the neonatal loss of interneurons

Dural afferents express acid-sensing ion channels: a role for decreased meningeal pH in migraine headache.

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Yan, Jin; Edelmayer, Rebecca M; Wei, Xiaomei; De Felice, Milena; Porreca, Frank; Dussor, Gregory

2011-01-01

Migraine headache is one of the most common neurological disorders. The pathological conditions that directly initiate afferent pain signaling are poorly understood. In trigeminal neurons retrogradely labeled from the cranial meninges, we have recorded pH-evoked currents using whole-cell patch-clamp electrophysiology. Approximately 80% of dural-afferent neurons responded to a pH 6.0 application with a rapidly activating and rapidly desensitizing ASIC-like current that often exceeded 20nA in amplitude. Inward currents were observed in response to a wide range of pH values and 30% of the neurons exhibited inward currents at pH 7.1. These currents led to action potentials in 53%, 30% and 7% of the dural afferents at pH 6.8, 6.9 and 7.0, respectively. Small decreases in extracellular pH were also able to generate sustained window currents and sustained membrane depolarizations. Amiloride, a non-specific blocker of ASIC channels, inhibited the peak currents evoked upon application of decreased pH while no inhibition was observed upon application of TRPV1 antagonists. The desensitization time constant of pH 6.0-evoked currents in the majority of dural afferents was less than 500ms which is consistent with that reported for ASIC3 homomeric or heteromeric channels. Finally, application of pH 5.0 synthetic-interstitial fluid to the dura produced significant decreases in facial and hind-paw withdrawal threshold, an effect blocked by amiloride but not TRPV1 antagonists, suggesting that ASIC activation produces migraine-related behavior in vivo. These data provide a cellular mechanism by which decreased pH in the meninges following ischemic or inflammatory events directly excites afferent pain-sensing neurons potentially contributing to migraine headache. Copyright © 2010 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

Transmission between type II hair cells and bouton afferents in the turtle posterior crista.

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Holt, Joseph C; Xue, Jin-Tang; Brichta, Alan M; Goldberg, Jay M

2006-01-01

Synaptic activity was recorded with sharp microelectrodes during rest and during 0.3-Hz sinusoidal stimulation from bouton afferents identified by their efferent-mediated inhibitory responses. A glutamate antagonist, 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) decreased quantal size (qsize) while lowering external Ca(2+) decreased quantal rate (qrate). Miniature excitatory postsynaptic potentials (mEPSPs) had effective durations (qdur) of 3.5-5 ms. Their timing was consistent with Poisson statistics. Mean qsizes ranged in different units from 0.25 to 0.73 mV and mean qrates from 200 to 1,500/s; there was an inverse relation across the afferent population between qrate and qsize. qsize distributions were consistent with the independent release of variable-sized quanta. Channel noise, measured during AMPA-induced depolarizations, was small compared with quantal noise. Excitatory responses were larger than inhibitory responses. Peak qrates, which could approach 3,000/s, led peak excitatory mechanical stimulation by 40 degrees . Quantal parameters varied with stimulation phase with qdur and qsize being maximal during inhibitory stimulation. Voltage modulation (vmod) was in phase with qrate and had a peak depolarization of 1.5-3 mV. On average, 80% of vmod was accounted for by quantal activity; the remaining 20% was a nonquantal component that persisted in the absence of quantal activity. The extracellular accumulation of glutamate and K(+) are potential sources of nonquantal transmission and may provide a basis for the inverse relation between qrate and qsize. Comparison of the phases of synaptic and spike activity suggests that both presynaptic and postsynaptic mechanisms contribute to variations across afferents in the timing of spikes during sinusoidal stimulation.

Gut vagal afferents differentially modulate innate anxiety and learned fear.

Science.gov (United States)

Klarer, Melanie; Arnold, Myrtha; Günther, Lydia; Winter, Christine; Langhans, Wolfgang; Meyer, Urs

2014-05-21

Vagal afferents are an important neuronal component of the gut-brain axis allowing bottom-up information flow from the viscera to the CNS. In addition to its role in ingestive behavior, vagal afferent signaling has been implicated modulating mood and affect, including distinct forms of anxiety and fear. Here, we used a rat model of subdiaphragmatic vagal deafferentation (SDA), the most complete and selective vagal deafferentation method existing to date, to study the consequences of complete disconnection of abdominal vagal afferents on innate anxiety, conditioned fear, and neurochemical parameters in the limbic system. We found that compared with Sham controls, SDA rats consistently displayed reduced innate anxiety-like behavior in three procedures commonly used in preclinical rodent models of anxiety, namely the elevated plus maze test, open field test, and food neophobia test. On the other hand, SDA rats exhibited increased expression of auditory-cued fear conditioning, which specifically emerged as attenuated extinction of conditioned fear during the tone re-exposure test. The behavioral manifestations in SDA rats were associated with region-dependent changes in noradrenaline and GABA levels in key areas of the limbic system, but not with functional alterations in the hypothalamus-pituitary-adrenal grand stress. Our study demonstrates that innate anxiety and learned fear are both subjected to visceral modulation through abdominal vagal afferents, possibly via changing limbic neurotransmitter systems. These data add further weight to theories emphasizing an important role of afferent visceral signals in the regulation of emotional behavior. Copyright © 2014 the authors 0270-6474/14/347067-10$15.00/0.

Vagus nerve stimulation for epilepsy activates the vocal folds maximally at therapeutic levels.

NARCIS (Netherlands)

Ardesch, J.J.; Sikken, J.R.; Veltink, Petrus H.; van der Aa, H.E.; Hageman, G.; Buschman, H.P.J.

Purpose Vagus nerve stimulation (VNS) for medically refractory epilepsy can give hoarseness due to stimulation of the recurrent laryngeal nerve. For a group of VNS-therapy users this side-effect interferes severely with their daily activities. Our goal was to investigate the severity of

Chewing-induced hypertension in afferent baroreflex failure: a sympathetic response?

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Fuente Mora, Cristina; Norcliffe-Kaufmann, Lucy; Palma, Jose-Alberto; Kaufmann, Horacio

2015-11-01

What is the central question of this study? Our goal was to understand the autonomic responses to eating in patients with congenital afferent baroreflex failure, by documenting changes in blood pressure and heart rate with chewing, swallowing and stomach distension. What is the main finding and its importance? Patients born with lesions in the afferent baroreceptor pathways have an exaggerated pressor response to food intake. This appears to be a sympathetically mediated response, triggered by chewing, that occurs independently of swallowing or distension of the stomach. The chewing-induced pressor response may be useful as a counter-manoeuvre to prevent orthostatic hypotension in these patients. Familial dysautonomia (FD) is a rare genetic disease with extremely labile blood pressure resulting from baroreflex deafferentation. Patients have marked surges in sympathetic activity, frequently surrounding meals. We conducted an observational study to document the autonomic responses to eating in patients with FD and to determine whether sympathetic activation was caused by chewing, swallowing or stomach distension. Blood pressure and R-R intervals were measured continuously while chewing gum (n = 15), eating (n = 20) and distending the stomach by percutaneous endoscopic gastrostomy tube feeding (n = 9). Responses were compared with those of normal control subjects (n = 10) and of patients with efferent autonomic failure (n = 10) who have chronically impaired sympathetic outflow. In patients with FD, eating was associated with a marked but transient pressor response (P Chewing gum evoked a similar increase in blood pressure that was higher in patients with FD than in control subjects (P = 0.0001), but was absent in patients with autonomic failure. In patients with FD, distending the stomach by percutaneous endoscopic gastrostomy tube feeding failed to elicit a pressor response. The results provide indirect evidence that chewing triggers sympathetic

Thermal detection thresholds of Aδ- and C-fibre afferents activated by brief CO2 laser pulses applied onto the human hairy skin.

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Maxim Churyukanov

Full Text Available Brief high-power laser pulses applied onto the hairy skin of the distal end of a limb generate a double sensation related to the activation of Aδ- and C-fibres, referred to as first and second pain. However, neurophysiological and behavioural responses related to the activation of C-fibres can be studied reliably only if the concomitant activation of Aδ-fibres is avoided. Here, using a novel CO(2 laser stimulator able to deliver constant-temperature heat pulses through a feedback regulation of laser power by an online measurement of skin temperature at target site, combined with an adaptive staircase algorithm using reaction-time to distinguish between responses triggered by Aδ- and C-fibre input, we show that it is possible to estimate robustly and independently the thermal detection thresholds of Aδ-fibres (46.9±1.7°C and C-fibres (39.8±1.7°C. Furthermore, we show that both thresholds are dependent on the skin temperature preceding and/or surrounding the test stimulus, indicating that the Aδ- and C-fibre afferents triggering the behavioural responses to brief laser pulses behave, at least partially, as detectors of a change in skin temperature rather than as pure level detectors. Most importantly, our results show that the difference in threshold between Aδ- and C-fibre afferents activated by brief laser pulses can be exploited to activate C-fibres selectively and reliably, provided that the rise in skin temperature generated by the laser stimulator is well-controlled. Our approach could constitute a tool to explore, in humans, the physiological and pathophysiological mechanisms involved in processing C- and Aδ-fibre input, respectively.

Age-related changes of neurochemically different subpopulations of cardiac spinal afferent neurons in rats.

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Guić, Maja Marinović; Runtić, Branka; Košta, Vana; Aljinović, Jure; Grković, Ivica

2013-08-01

This study investigated the effect of aging on cardiac spinal afferent neurons in the rat. A patch loaded with retrograde tracer Fast Blue (FB) was applied to all chambers of the rat heart. Morphological and neurochemical characteristics of labeled cardiac spinal afferent neurons were assessed in young (2 months) and old (2 years) rats using markers for likely unmyelinated (isolectin B4; IB4) and myelinated (neurofilament 200; N52) neurons. The number of cardiac spinal afferent neurons decreased in senescence to 15% of that found in young rats (1604 vs. 248). The size of neuronal soma as well as proportion of IB4+ neurons increased significantly, whereas the proportion of N52+ neurons decreased significantly in senescence. Unlike somatic spinal afferents, neurochemically different populations of cardiac spinal afferent neurons experience morphological and neurochemical changes related to aging. A major decrease in total number of cardiac spinal afferent neurons occurs in senescence. The proportion of N52+ neurons decreased in senescence, but it seems that nociceptive innervation is preserved due to increased proportion and size of IB4+ unmyelinated neurons. Copyright © 2013 Elsevier Inc. All rights reserved.

Information analysis of posterior canal afferents in the turtle, Trachemys scripta elegans.

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Rowe, Michael H; Neiman, Alexander B

2012-01-24

We have used sinusoidal and band-limited Gaussian noise stimuli along with information measures to characterize the linear and non-linear responses of morpho-physiologically identified posterior canal (PC) afferents and to examine the relationship between mutual information rate and other physiological parameters. Our major findings are: 1) spike generation in most PC afferents is effectively a stochastic renewal process, and spontaneous discharges are fully characterized by their first order statistics; 2) a regular discharge, as measured by normalized coefficient of variation (cv*), reduces intrinsic noise in afferent discharges at frequencies below the mean firing rate; 3) coherence and mutual information rates, calculated from responses to band-limited Gaussian noise, are jointly determined by gain and intrinsic noise (discharge regularity), the two major determinants of signal to noise ratio in the afferent response; 4) measures of optimal non-linear encoding were only moderately greater than optimal linear encoding, indicating that linear stimulus encoding is limited primarily by internal noise rather than by non-linearities; and 5) a leaky integrate and fire model reproduces these results and supports the suggestion that the combination of high discharge regularity and high discharge rates serves to extend the linear encoding range of afferents to higher frequencies. These results provide a framework for future assessments of afferent encoding of signals generated during natural head movements and for comparison with coding strategies used by other sensory systems. This article is part of a Special Issue entitled: Neural Coding. Copyright © 2011 Elsevier B.V. All rights reserved.

Effect of nerve activity on transport of nerve growth factor and dopamine β-hydroxylase antibodies in sympathetic neurones

International Nuclear Information System (INIS)

Lees, G.; Chubb, I.; Freeman, C.; Geffen, L.; Rush, R.

1981-01-01

The effect of nerve activity on the uptake and retrograde transport of nerve growth factor (NGF) and dopamine β-hydroxylase (DBH) antibodies was studied by injecting 125 I-labelled NGF and anti-DBH into the anterior eye chamber of guinea-pigs. Decentralization of the ipsilateral superior cervical ganglion (SCG) had no significant effect on the retrograde transport of either NGF or anti-DBH. Phenoxybenzamine produced a 50% increase in anti-DBH but not NGF accumulation and this effect was prevented by prior decentralization. This demonstrates that NGF is taken up independently of the retrieval of synaptic vesicle components. (Auth.)

Cardiac effects of electrically induced intrathoracic autonomic reflexes.

Science.gov (United States)

Armour, J A

1988-06-01

Electrical stimulation of the afferent components in one cardiopulmonary nerve (the left vagosympathetic complex at a level immediately caudal to the origin of the left recurrent laryngeal nerve) in acutely decentralized thoracic autonomic ganglionic preparations altered cardiac chronotropism and inotropism in 17 of 44 dogs. Since these neural preparations were acutely decentralized, the effects were mediated presumably via intrathoracic autonomic reflexes. The lack of consistency of these reflexly generated cardiac responses presumably were due in part to anatomical variation of afferent axons in the afferent nerve stimulated. As stimulation of the afferent components in the same neural structure caudal to the heart (where cardiopulmonary afferent axons are not present) failed to elicit cardiac responses in any dog, it is presumed that when cardiac responses were elicited by the more cranially located stimulations, these were due to activation of afferent axons arising from the heart and (or) lungs. When cardiac responses were elicited, intramyocardial pressures in the right ventricular conus as well as the ventral and lateral walls of the left ventricle were augmented. Either bradycardia or tachycardia was elicited. Following hexamethonium administration no responses were produced, demonstrating that nicotonic cholinergic synaptic mechanisms were involved in these intrathoracic cardiopulmonary-cardiac reflexes. In six of the animals, when atropine was administered before hexamethonium, reflexly generated responses were attenuated. The same thing occurred when morphine was administered in four animals. In contrast, in four animals following administration of phentolamine, the reflexly generated changes were enhanced.(ABSTRACT TRUNCATED AT 250 WORDS)

Long-term sensitization of mechanosensitive and -insensitive afferents in mice with persistent colorectal hypersensitivity

OpenAIRE

Feng, Bin; La, Jun-ho; Schwartz, Erica S.; Tanaka, Takahiro; McMurray, Timothy P.; Gebhart, G. F.

2012-01-01

Afferent input contributes significantly to the pain and colorectal hypersensitivity that characterize irritable bowel syndrome. In the present study, we investigated the contributions of mechanically sensitive and mechanically insensitive afferents (MIAs; or silent afferents) to colorectal hypersensitivity. The visceromotor response to colorectal distension (CRD; 15–60 mmHg) was recorded in mice before and for weeks after intracolonic treatment with zymosan or saline. After CRD tests, the di...

Laser-activated protein solder for peripheral nerve repair

Science.gov (United States)

Trickett, Rodney I.; Lauto, Antonio; Dawes, Judith M.; Owen, Earl R.

1995-05-01

A 100 micrometers core optical fiber-coupled 75 mW diode laser operating at a wavelength of 800 nm has been used in conjunction with a protein solder to stripe weld severed rat tibial nerves, reducing the long operating time required for microsurgical nerve repair. Welding is produced by selective laser denaturation of the albumin based solder which contains the dye indocyanine green. Operating time for laser soldering was 10 +/- 5 min. (n equals 20) compared to 23 +/- 9 min. (n equals 10) for microsuturing. The laser solder technique resulted in patent welds with a tensile strength of 15 +/- 5 g, while microsutured nerves had a tensile strength of 40 +/- 10 g. Histopathology of the laser soldered nerves, conducted immediately after surgery, displayed solder adhesion to the outer membrane with minimal damage to the inner axons of the nerves. An in vivo study is under way comparing laser solder repaired tibial nerves to conventional microsuture repair. At the time of submission 15 laser soldered nerves and 7 sutured nerves were characterized at 3 months and showed successful regeneration with compound muscle action potentials of 27 +/- 8 mV and 29 +/- 8 mW respectively. A faster, less damaging and long lasting laser based anastomotic technique is presented.

Cranial nerve clock. Part II: functional MR imaging of brain activation during a declarative memory task.

Science.gov (United States)

Weiss, K L; Welsh, R C; Eldevik, P; Bieliauskas, L A; Steinberg, B A

2001-12-01

The authors performed this study to assess brain activation during encoding and successful recall with a declarative memory paradigm that has previously been demonstrated to be effective for teaching students about the cranial nerves. Twenty-four students underwent functional magnetic resonance (MR) imaging during encoding and recall of the name, number, and function of the 12 cranial nerves. The students viewed mnemonic graphic and text slides related to individual nerves, as well as their respective control slides. For the recall paradigm, students were prompted with the numbers 1-12 (test condition) intermixed with the number 14 (control condition). Subjects were tested about their knowledge of cranial nerves outside the MR unit before and after functional MR imaging. Students learned about the cranial nerves while undergoing functional MR imaging (mean post- vs preparadigm score, 8.1 +/- 3.4 [of a possible 12] vs 0.75 +/- 0.94, bilateral prefrontal cortex, left greater than right; P brain activation. Encoding revealed statistically significant activation in the bilateral prefrontal cortex, left greater than right [corrected]; bilateral occipital and parietal associative cortices, parahippocampus region, fusiform gyri, and cerebellum. Successful recall activated the left much more than the right prefrontal, parietal associative, and anterior cingulate cortices; bilateral precuneus and cerebellum; and right more than the left posterior cingulate. A predictable pattern of brain activation at functional MR imaging accompanies the encoding and successful recall of the cranial nerves with this declarative memory paradigm.

Pulp nerve fibers distribution of human carious teeth: An immunohistochemical study

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Tetiana Haniastuti

2010-12-01

Full Text Available Background: Human dental pulp is richly innervated by trigeminal afferent axons that subserve nociceptive function. Accordingly, they respond to stimuli that induce injury to the pulp tissue. An injury to the nerve terminals and other tissue components in the pulp stimulate metabolic activation of the neurons in the trigeminal ganglion which result in morphological changes in the peripheral nerve terminals. Purpose: The aim of the study was to observe caries-related changes in the distribution of human pulpal nerve. Methods: Under informed consents, 15 third molars with caries at various stages of decay and 5 intact third molars were extracted because of orthodontic or therapeutic reasons. All samples were observed by micro-computed tomography to confirm the lesion condition 3-dimensionally, before decalcifying with 10% EDTA solution (pH 7.4. The specimens were then processed for immunohistochemistry using anti-protein gene products (PGP 9.5, a specific marker for the nerve fiber. Results: In normal intact teeth, PGP 9.5 immunoreactive nerve fibers were seen concentrated beneath the odontoblast cell layer. Nerve fibers exhibited an increased density along the pulp-dentin border corresponding to the carious lesions. Conclusion: Neural density increases throughout the pulp chamber with the progression of caries. The activity and pathogenicity of the lesion as well as caries depth, might influence the degree of neural sprouting.Latar belakang: Pulpa gigi manusia diinervasi oleh serabut saraf trigeminal yang berespon terhadap stimuli penyebab perlukaan dengan menimbulkan rasa sakit. Perlukaan pada akhiran saraf dan komponen lain dari pulpa akan menstimulasi aktivasi metabolik dari neuron pada ganglion trigeminal sehingga mengakibatkan perubahan morfologi pada akhiran saraf perifer. Tujuan: Penelitian ini bertujuan untuk mengamati perubahan distribusi saraf pada pulpa gigi manusia yang disebabkan oleh proses karies. Metode: Penelitian ini menggunakan

Laser-activated protein bands for peripheral nerve repair

Science.gov (United States)

Lauto, Antonio; Trickett, Rodney I.; Malik, Richard; Dawes, Judith M.; Owen, Earl R.

1996-01-01

A 100 micrometer core optical fiber-coupled 75 mW diode laser operating at a wavelength of 800 nm has been used in conjunction with a protein solder to stripe weld severed rat tibial nerves, reducing the long operating time required for microsurgical nerve repair. Welding is produced by selective laser denaturation of the protein based solder which contains the dye indocyanine green. Operating time for laser soldering was 10 plus or minus 5 min. (n equals 24) compared to 23 plus or minus 9 min (n equals 13) for microsuturing. The laser solder technique resulted in patent welds with a tensile strength of 15 plus or minus 5 g, while microsutured nerves had a tensile strength of 40 plus or minus 10 g. Histopathology of the laser soldered nerves, conducted immediately after surgery, displayed solder adhesion to the outer membrane with minimal damage to the inner axons of the nerves. An in vivo study, with a total of fifty-seven adult male wistar rats, compared laser solder repaired tibial nerves to conventional microsuture repair. Twenty-four laser soldered nerves and thirteen sutured nerves were characterized at three months and showed successful regeneration with average compound muscle action potentials (CMAP) of 2.4 plus or minus 0.7 mV and 2.7 plus or minus 0.8 mV respectively. Histopathology of the in vivo study, confirmed the comparable regeneration of axons in laser and suture operated nerves. A faster, less damaging and long lasting laser based anastomotic technique is presented.

Peripheral injury of pelvic visceral sensory nerves alters GFRa (GDNF family receptor alpha localization in sensory and autonomic pathways of the sacral spinal cord

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Shelley Lynne Forrest

2015-04-01

Full Text Available GDNF (glial cell line-derived neurotrophic factor, neurturin and artemin use their co-receptors (GFRα1, GFRα2 and GFRα3, respectively and the tyrosine kinase Ret for downstream signalling. In rodent dorsal root ganglia (DRG most of the unmyelinated and some myelinated sensory afferents express at least one GFRα. The adult function of these receptors is not completely elucidated but their activity after peripheral nerve injury can facilitate peripheral and central axonal regeneration, recovery of sensation, and sensory hypersensitivity that contributes to pain. Our previous immunohistochemical studies of spinal cord and sciatic nerve injuries in adult rodents have identified characteristic changes in GFRα1, GFRα2 or GFRα3 in central spinal cord axons of sensory neurons located in dorsal root ganglia. Here we extend and contrast this analysis by studying injuries of the pelvic and hypogastric nerves that contain the majority of sensory axons projecting to the pelvic viscera (e.g., bladder and lower bowel. At 7 d, we detected some effects of pelvic but not hypogastric nerve transection on the ipsilateral spinal cord. In sacral (L6-S1 cord ipsilateral to nerve injury, GFRα1-immunoreactivity (IR was increased in medial dorsal horn and CGRP-IR was decreased in lateral dorsal horn. Pelvic nerve injury also upregulated GFRα1- and GFRα3-IR terminals and GFRα1-IR neuronal cell bodies in the sacral parasympathetic nucleus that provides the spinal parasympathetic preganglionic output to the pelvic nerve. This evidence suggests peripheral axotomy has different effects on somatic and visceral sensory input to the spinal cord, and identifies sensory-autonomic interactions as a possible site of post-injury regulation.

Hemifacial Pain and Hemisensory Disturbance Referred from Occipital Neuralgia Caused by Pathological Vascular Contact of the Greater Occipital Nerve.

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Son, Byung-Chul; Choi, Jin-Gyu

2017-01-01

Here we report a unique case of chronic occipital neuralgia caused by pathological vascular contact of the left greater occipital nerve. After 12 months of left-sided, unremitting occipital neuralgia, a hypesthesia and facial pain developed in the left hemiface. The decompression of the left greater occipital nerve from pathological contacts with the occipital artery resulted in immediate relief for hemifacial sensory change and facial pain, as well as chronic occipital neuralgia. Although referral of pain from the stimulation of occipital and cervical structures innervated by upper cervical nerves to the frontal head of V1 trigeminal distribution has been reported, the development of hemifacial sensory change associated with referred trigeminal pain from chronic occipital neuralgia is extremely rare. Chronic continuous and strong afferent input of occipital neuralgia caused by pathological vascular contact with the greater occipital nerve seemed to be associated with sensitization and hypersensitivity of the second-order neurons in the trigeminocervical complex, a population of neurons in the C2 dorsal horn characterized by receiving convergent input from dural and cervical structures.

Afferent loop syndrome - a case report

International Nuclear Information System (INIS)

Borges, Ana Karina Nascimento; Pinheiro, Marco Antonio Lopes; Galvao, Cristine Norwig

2000-01-01

The afferent loop syndrome occurs in patients with previous gastric surgery for tumor, when there is anastomotic edema, use of inappropriate reconstruction technique for gastro jejunostomy or recurrent gastric cancer. Complaints such jaundice, intermittent abdominal distension associated with pain, and vomiting should be investigated in order to rule out this syndrome. (author)

Acute cholangitis due to afferent loop syndrome after a Whipple procedure: a case report.

Science.gov (United States)

Spiliotis, John; Karnabatidis, Demetrios; Vaxevanidou, Archodoula; Datsis, Anastasios C; Rogdakis, Athanasios; Zacharis, Georgios; Siamblis, Demetrios

2009-08-25

Patients with resection of stomach and especially with Billroth II reconstruction (gastro jejunal anastomosis), are more likely to develop afferent loop syndrome which is a rare complication. When the afferent part is obstructed, biliary and pancreatic secretions accumulate and cause the distention of this part. In the case of a complete obstruction (rare), there is a high risk developing necrosis and perforation. This complication has been reported once in the literature. A 54-year-old Greek male had undergone a pancreato-duodenectomy (Whipple procedure) one year earlier due to a pancreatic adenocarcinoma. Approximately 10 months after the initial operation, the patient started having episodes of cholangitis (fever, jaundice) and abdominal pain. This condition progressively worsened and the suspicion of local recurrence or stenosis of the biliary-jejunal anastomosis was discussed. A few days before his admission the patient developed signs of septic cholangitis. Our case demonstrates a rare complication with serious clinical manifestation of the afferent loop syndrome. This advanced form of afferent loop syndrome led to the development of huge enterobiliary reflux, which had a serious clinical manifestation as cholangitis and systemic sepsis, due to bacterial overgrowth, which usually present in the afferent loop. The diagnosis is difficult and the interventional radiology gives all the details to support the therapeutic decision making. A variety of factors can contribute to its development including adhesions, kinking and angulation of the loop, stenosis of gastro-jejunal anastomosis and internal herniation. In order to decompress the afferent loop dilatation due to adhesions, a lateral-lateral jejunal anastomosis was performed between the afferent loop and a small bowel loop.

Facial nerve activity disrupts psychomotor rhythms in the forehead microvasculature.

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Drummond, Peter D; O'Brien, Geraldine

2011-10-28

Forehead blood flow was monitored in seven participants with a unilateral facial nerve lesion during relaxation, respiratory biofeedback and a sad documentary. Vascular waves at 0.1Hz strengthened during respiratory biofeedback, in tune with breathing cycles that also averaged 0.1Hz. In addition, a psychomotor rhythm at 0.15Hz was more prominent in vascular waveforms on the denervated than intact side of the forehead, both before and during relaxation and the sad documentary. These findings suggest that parasympathetic activity in the facial nerve interferes with the psychomotor rhythm in the forehead microvasculature. Copyright © 2011 Elsevier B.V. All rights reserved.

Development of regenerative peripheral nerve interfaces for motor control of neuroprosthetic devices

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Kemp, Stephen W. P.; Urbanchek, Melanie G.; Irwin, Zachary T.; Chestek, Cynthia A.; Cederna, Paul S.

2017-05-01

Traumatic peripheral nerve injuries suffered during amputation commonly results in debilitating neuropathic pain in the affected limb. Modern prosthetic technologies allow for intuitive, simultaneous control of multiple degrees of freedom. However, these state-of-the-art devices require separate, independent control signals for each degree of freedom, which is currently not possible. As a result, amputees reject up to 75% of myoelectric devices preferring instead to use body-powered artificial limbs which offer subtle sensory feedback. Without meaningful and intuitive sensory feedback, even the most advanced myoelectric prostheses remain insensate, burdensome, and are associated with enormous cognitive demand and mental fatigue. The ideal prosthetic device is one which is capable of providing intuitive somatosensory feedback essential for interaction with the environment. Critical to the design of such a bioprosthetic device is the development of a reliable biologic interface between human and machine. This ideal patient-prosthetic interface allows for transmission of both afferent somatosensory information and efferent motor signals for a closed-loop feedback system of neural control. Our lab has developed the Regenerative Peripheral Nerve Interface (RPNI) as a biologic nerve interface designed for stable integration of a prosthetic device with transected peripheral nerves in a residual limb. The RPNI is constructed by surgically implanting the distal end of a transected peripheral nerve into an autogenous muscle graft. Animal experiments in our lab have shown recording of motor signals from RPNI's implanted into both rodents and monkeys. Here, we achieve high amplitude EMG signals with a high signal to noise (SNR) ratio.

Selective activation of primary afferent fibers evaluated by sine-wave electrical stimulation

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Katafuchi Toshihiko

2005-03-01

Full Text Available Abstract Transcutaneous sine-wave stimuli at frequencies of 2000, 250 and 5 Hz (Neurometer are thought to selectively activate Aβ, Aδ and C afferent fibers, respectively. However, there are few reports to test the selectivity of these stimuli at the cellular level. In the present study, we analyzed action potentials (APs generated by sine-wave stimuli applied to the dorsal root in acutely isolated rat dorsal root ganglion (DRG preparations using intracellular recordings. We also measured excitatory synaptic responses evoked by transcutaneous stimuli in substantia gelatinosa (SG neurons of the spinal dorsal horn, which receive inputs predominantly from C and Aδ fibers, using in vivo patch-clamp recordings. In behavioral studies, escape or vocalization behavior of rats was observed with both 250 and 5 Hz stimuli at intensity of ~0.8 mA (T5/ T250, whereas with 2000 Hz stimulation, much higher intensity (2.14 mA, T2000 was required. In DRG neurons, APs were generated at T5/T250 by 2000 Hz stimulation in Aβ, by 250 Hz stimulation both in Aβ and Aδ, and by 5 Hz stimulation in all three classes of DRG neurons. However, the AP frequencies elicited in Aβ and Aδ by 5 Hz stimulation were much less than those reported previously in physiological condition. With in vivo experiments large amplitude of EPSCs in SG neurons were elicited by 250 and 5 Hz stimuli at T5/ T250. These results suggest that 2000 Hz stimulation excites selectively Aβ fibers and 5 Hz stimulation activates noxious transmission mediated mainly through C fibers. Although 250 Hz stimulation activates both Aδ and Aβ fibers, tactile sensation would not be perceived when painful sensation is produced at the same time. Therefore, 250 Hz was effective stimulus frequency for activation of Aδ fibers initiating noxious sensation. Thus, the transcutaneous sine-wave stimulation can be applied to evaluate functional changes of sensory transmission by comparing thresholds with the three

Myocardial adrenergic nerve activity in valvular diseases assessed by iodine-123-metaiodobenzylguanidine myocardial scintigraphy

International Nuclear Information System (INIS)

Imamura, Yoshihiro; Fukuyama, Takaya

1997-01-01

Iodine-123-metaiodobenzylguanidine (MIBG) imaging was used to assess myocardial adrenergic nerve activity in patients with heart failure. MIBG planar images were obtained in 94 patients. The uptake of MIBG, calculated as the heart-to-mediastinum activity ratio in the immediate image (15 min), showed a significant decrease only in patients with severe heart failure due to cardiomyopathy, but was not changed in those with valvular diseases. Storage and release of MIBG, calculated as the percentage myocardial MIBG washout from 15 min to 4 hours after isotope injection, was substantially accelerated in both patients with cardiomyopathy and valvular diseases in proportion to the severity of heart failure. These data suggest that, in severe heart failure associated with cardiomyopathy, norepinephrine uptake is reduced. Also, myocardial adrenergic nerve activity is accelerated in proportion to the severity of heart failure independent of the underlying cause. MIBG images were analyzed in 20 patients with mitral stenosis with the same methods to clarify whether myocardial adrenergic nerve activity is different in patients with heart failure without left ventricular volume or pressure overload. Myocardial uptake of MIBG did not show any significant difference. The percentage myocardial MIBG washout was increased in patients with severe heart failure. The closest correlation was between myocardial washout and cardiac output. In heart failure due to mitral stenosis, myocardial adrenergic nerve activity is intensified. Decrease in cardiac output associated with mitral stenosis acts as a potent stimulus for this intensification. (author)

Inhibitory effects of silodosin on the bladder mechanosensitive afferent activities and their relation with bladder myogenic contractions in male rats with bladder outlet obstruction.

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Aizawa, Naoki; Watanabe, Daiji; Fukuhara, Hiroshi; Fujimura, Tetsuya; Kume, Haruki; Homma, Yukio; Igawa, Yasuhiko

2018-03-06

We investigated the effects of silodosin, an α1A-adrenoceptor (AR) antagonist, on bladder function, especially on non-voiding contractions (NVCs), in a male rat model of bladder outlet obstruction (BOO) by evaluating cystometry (CMG) findings and bladder mechanosensitive single-unit afferent activities (SAAs), related with microcontractions, which may be similar with NVCs and to be of myogenic origin, in the rat model. BOO was created by partial ligation of the posterior urethra. At 4 days after surgery for BOO, an osmotic pump filled with silodosin (0.12 mg/kg/day) or its vehicle was subcutaneously implanted. At 10 days after surgery, CMG and SAAs measurements were taken under conscious and urethane-anesthetized conditions, respectively. The SAAs of Aδ- and C-fibers, which were identified by electrical stimulation of the pelvic nerve and by bladder distention, and intravesical pressure were recorded during constant bladder-filling with saline. Microcontractions were divided into three phases: "ascending," "descending," and "stationary." The silodosin-treated group showed a smaller number of NVCs in CMG measurements and lower SAAs of both Aδ- and C-fibers than the vehicle-treated group during bladder-filling. Moreover, in the vehicle-treated groups, the SAAs of both fibers for the ascending phase of microcontractions were significantly higher than those for the other two phases. On the contrary, no significant change was found between any of these three phases in the silodosin-treated group. The present results suggest that silodosin inhibits the SAAs of mechanosensitive Aδ- and C-fibers at least partly due to suppressing myogenic bladder contractions in male BOO rats. © 2018 Wiley Periodicals, Inc.

Traditional Chinese herbal formula relieves snoring by modulating activities of upper airway related nerves in aged rats

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Chung KT

2018-05-01

Full Text Available Kou-Toung Chung,* Chih-Hsiang Hsu,* Ching-Lung Lin, Sheue-Er Wang, Chung-Hsin WuDepartment of Life Science, National Taiwan Normal University, Taipei, Taiwan*These authors contributed equally to this workAim: The present study investigated whether intraperitoneal treatment with the herbal formula B210 ([B210]; a herbal composition of Gastrodia elata and Cinnamomum cassia can reduce snoring in aged rats. Also, we studied possible neural mechanisms involved in B210 treatment and subsequent reduced snoring in rats.Methods and result: We compared pressure and frequency of snoring, activities of phrenic nerve (PNA, activities of recurrent laryngeal nerve (RLNA and activities of hypoglossal nerve (HNA, inspiratory time (TI and expiratory time (TE of PNA, and pre-inspiratory time (Pre-TI of HNA in aged rats between sham and B210 treatment groups (30 mg/mL dissolved in DMSO. We found that aged rats that received B210 treatment had significantly reduced pressure and frequency of snoring than rats who received sham treatment. Also, we observed that aged rats that received B210 treatment had significantly increased PNA, RLNA, and HNA, extended TI and TE of PNA, and prolonged Pre-TI of HNA compared to rats that received sham treatment. In other words, B210 treatment may relieve snoring through modulating activities and breathing time of upper airway related nerves in aged rats.Conclusion: We suggested that the B210 might be a potential herbal formula for snoring remission.Keywords: Chinese herbal medicine, snoring remission, upper airway, phrenic nerve, recurrent laryngeal nerve, hypoglossal nerve

Nanomolar oxytocin synergizes with weak electrical afferent stimulation to activate the locomotor CpG of the rat spinal cord in vitro.

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Francesco Dose

Full Text Available Synergizing the effect of afferent fibre stimulation with pharmacological interventions is a desirable goal to trigger spinal locomotor activity, especially after injury. Thus, to better understand the mechanisms to optimize this process, we studied the role of the neuropeptide oxytocin (previously shown to stimulate locomotor networks on network and motoneuron properties using the isolated neonatal rat spinal cord. On motoneurons oxytocin (1 nM-1 μM generated sporadic bursts with superimposed firing and dose-dependent depolarization. No desensitization was observed despite repeated applications. Tetrodotoxin completely blocked the effects of oxytocin, demonstrating the network origin of the responses. Recording motoneuron pool activity from lumbar ventral roots showed oxytocin mediated depolarization with synchronous bursts, and depression of reflex responses in a stimulus and peptide-concentration dependent fashion. Disinhibited bursting caused by strychnine and bicuculline was accelerated by oxytocin whose action was blocked by the oxytocin antagonist atosiban. Fictive locomotion appeared when subthreshold concentrations of NMDA plus 5HT were coapplied with oxytocin, an effect prevented after 24 h incubation with the inhibitor of 5HT synthesis, PCPA. When fictive locomotion was fully manifested, oxytocin did not change periodicity, although cycle amplitude became smaller. A novel protocol of electrical stimulation based on noisy waveforms and applied to one dorsal root evoked stereotypic fictive locomotion. Whenever the stimulus intensity was subthreshold, low doses of oxytocin triggered fictive locomotion although oxytocin per se did not affect primary afferent depolarization evoked by dorsal root pulses. Among the several functional targets for the action of oxytocin at lumbar spinal cord level, the present results highlight how small concentrations of this peptide could bring spinal networks to threshold for fictive locomotion in

Renal hemodynamic effects of activation of specific renal sympathetic nerve fiber groups.

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DiBona, G F; Sawin, L L

1999-02-01

To examine the effect of activation of a unique population of renal sympathetic nerve fibers on renal blood flow (RBF) dynamics, anesthetized rats were instrumented with a renal sympathetic nerve activity (RSNA) recording electrode and an electromagnetic flow probe on the ipsilateral renal artery. Peripheral thermal receptor stimulation (external heat) was used to activate a unique population of renal sympathetic nerve fibers and to increase total RSNA. Total RSNA was reflexly increased to the same degree with somatic receptor stimulation (tail compression). Arterial pressure and heart rate were increased by both stimuli. Total RSNA was increased to the same degree by both stimuli but external heat produced a greater renal vasoconstrictor response than tail compression. Whereas both stimuli increased spectral density power of RSNA at both cardiac and respiratory frequencies, modulation of RBF variability by fluctuations of RSNA was small at these frequencies, with values for the normalized transfer gain being approximately 0.1 at >0.5 Hz. During tail compression coherent oscillations of RSNA and RBF were found at 0.3-0.4 Hz with normalized transfer gain of 0.33 +/- 0.02. During external heat coherent oscillations of RSNA and RBF were found at both 0.2 and 0.3-0.4 Hz with normalized transfer gains of 0. 63 +/- 0.05 at 0.2 Hz and 0.53 +/- 0.04 to 0.36 +/- 0.02 at 0.3-0.4 Hz. Renal denervation eliminated the oscillations in RBF at both 0.2 and 0.3-0.4 Hz. These findings indicate that despite similar increases in total RSNA, external heat results in a greater renal vasoconstrictor response than tail compression due to the activation of a unique population of renal sympathetic nerve fibers with different frequency-response characteristics of the renal vasculature.

Glucose-dependent trafficking of 5-HT3 receptors in rat gastrointestinal vagal afferent neurons

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Babic, Tanja; Troy, Amanda E; Fortna, Samuel R; Browning, Kirsteen N

2012-01-01

Background Intestinal glucose induces gastric relaxation via vagally mediated sensory-motor reflexes. Glucose can alter the activity of gastrointestinal (GI) vagal afferent (sensory) neurons directly, via closure of ATP-sensitive potassium channels, as well as indirectly, via the release of 5-hydroxytryptamine (5-HT) from mucosal enteroendocrine cells. We hypothesized that glucose may also be able to modulate the ability of GI vagal afferent neurons to respond to the released 5-HT, via regulation of neuronal 5-HT3 receptors. Methods Whole cell patch clamp recordings were made from acutely dissociated GI-projecting vagal afferent neurons exposed to equiosmolar Krebs’ solution containing different concentrations of D-glucose (1.25–20mM) and the response to picospritz application of 5-HT assessed. The distribution of 5-HT3 receptors in neurons exposed to different glucose concentrations was also assessed immunohistochemically. Key Results Increasing or decreasing extracellular D-glucose concentration increased or decreased, respectively, the 5-HT-induced inward current as well as the proportion of 5-HT3 receptors associated with the neuronal membrane. These responses were blocked by the Golgi-disrupting agent Brefeldin-A (5µM) suggesting involvement of a protein trafficking pathway. Furthermore, L-glucose did not mimic the response of D-glucose implying that metabolic events downstream of neuronal glucose uptake are required in order to observe the modulation of 5-HT3 receptor mediated responses. Conclusions & Inferences These results suggest that, in addition to inducing the release of 5-HT from enterochromaffin cells, glucose may also increase the ability of GI vagal sensory neurons to respond to the released 5-HT, providing a means by which the vagal afferent signal can be amplified or prolonged. PMID:22845622

Degenerative Nerve Diseases

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Degenerative nerve diseases affect many of your body's activities, such as balance, movement, talking, breathing, and heart function. Many ... viruses. Sometimes the cause is not known. Degenerative nerve diseases include Alzheimer's disease Amyotrophic lateral sclerosis Friedreich's ...

Adenosine induces vasoconstriction through Gi-dependent activation of phospholipase C in isolated perfused afferent arterioles of mice

DEFF Research Database (Denmark)

Hansen, Pernille B; Castrop, Hayo; Briggs, Josie

2003-01-01

-induced vasoconstriction was stable for up to 30 min and was most pronounced in the most distal part of the afferent arterioles. Adenosine did not cause vasoconstriction in arterioles from A1AR-/- mice. Pretreatment with pertussis toxin (PTX) (400 ng/ml) for 2 h blocked the vasoconstricting action of adenosine or N(6...

Group Ia afferents likely contribute to short-latency interlimb reflexes in the human biceps femoris muscle

DEFF Research Database (Denmark)

Stevenson, Andrew James Thomas; Kamavuako, Ernest Nlandu; Geertsen, Svend Sparre

2017-01-01

amplitudes (4 vs. 8°) at the same 150°/s velocity (p’s > 0.08). Conclusion: Because fast conducting group Ia muscle spindle afferents are sensitive to changes in muscle stretch velocity, while group II spindle afferents are sensitive to changes in amplitude (Grey et al., JPhysiol., 2001; Matthews, Trends...... Neurosci., 1991), group Ia velocity sensitive muscle spindle afferents likely contribute to the short-latency crossed spinal reflexes in the cBF muscle following iKnee joint rotations. This supports the findings for the short-latency crossed responses in the human soleus muscle (Stubbs & Mrachacz...... neurons in humans, with primary contributions from group Ia muscle spindle afferents....

Neuroprotective effect of lurasidone via antagonist activities on histamine in a rat model of cranial nerve involvement.

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He, Baoming; Yu, Liang; Li, Suping; Xu, Fei; Yang, Lili; Ma, Shuai; Guo, Yi

2018-04-01

Cranial nerve involvement frequently involves neuron damage and often leads to psychiatric disorder caused by multiple inducements. Lurasidone is a novel antipsychotic agent approved for the treatment of cranial nerve involvement and a number of mental health conditions in several countries. In the present study, the neuroprotective effect of lurasidone by antagonist activities on histamine was investigated in a rat model of cranial nerve involvement. The antagonist activities of lurasidone on serotonin 5‑HT7, serotonin 5‑HT2A, serotonin 5‑HT1A and serotonin 5‑HT6 were analyzed, and the preclinical therapeutic effects of lurasidone were examined in a rat model of cranial nerve involvement. The safety, maximum tolerated dose (MTD) and preliminary antitumor activity of lurasidone were also assessed in the cranial nerve involvement model. The therapeutic dose of lurasidone was 0.32 mg once daily, administered continuously in 14‑day cycles. The results of the present study found that the preclinical prescriptions induced positive behavioral responses following treatment with lurasidone. The MTD was identified as a once daily administration of 0.32 mg lurasidone. Long‑term treatment with lurasidone for cranial nerve involvement was shown to improve the therapeutic effects and reduce anxiety in the experimental rats. In addition, treatment with lurasidone did not affect body weight. The expression of the language competence protein, Forkhead‑BOX P2, was increased, and the levels of neuroprotective SxIP motif and microtubule end‑binding protein were increased in the hippocampal cells of rats with cranial nerve involvement treated with lurasidone. Lurasidone therapy reinforced memory capability and decreased anxiety. Taken together, lurasidone treatment appeared to protect against language disturbances associated with negative and cognitive impairment in the rat model of cranial nerve involvement, providing a basis for its use in the clinical treatment of

Renal artery nerve distribution and density in the porcine model: biologic implications for the development of radiofrequency ablation therapies.

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Tellez, Armando; Rousselle, Serge; Palmieri, Taylor; Rate, William R; Wicks, Joan; Degrange, Ashley; Hyon, Chelsea M; Gongora, Carlos A; Hart, Randy; Grundy, Will; Kaluza, Greg L; Granada, Juan F

2013-12-01

Catheter-based renal artery denervation has demonstrated to be effective in decreasing blood pressure among patients with refractory hypertension. The anatomic distribution of renal artery nerves may influence the safety and efficacy profile of this procedure. We aimed to describe the anatomic distribution and density of periarterial renal nerves in the porcine model. Thirty arterial renal sections were included in the analysis by harvesting a tissue block containing the renal arteries and perirenal tissue from each animal. Each artery was divided into 3 segments (proximal, mid, and distal) and assessed for total number, size, and depth of the nerves according to the location. Nerve counts were greatest proximally (45.62% of the total nerves) and decreased gradually distally (mid, 24.58%; distal, 29.79%). The distribution in nerve size was similar across all 3 sections (∼40% of the nerves, 50-100 μm; ∼30%, 0-50 μm; ∼20%, 100-200 μm; and ∼10%, 200-500 μm). In the arterial segments ∼45% of the nerves were located within 2 mm from the arterial wall whereas ∼52% of all nerves were located within 2.5 mm from the arterial wall. Sympathetic efferent fibers outnumbered sensory afferent fibers overwhelmingly, intermixed within the nerve bundle. In the porcine model, renal artery nerves are seen more frequently in the proximal segment of the artery. Nerve size distribution appears to be homogeneous throughout the artery length. Nerve bundles progress closer to the arterial wall in the distal segments of the artery. This anatomic distribution may have implications for the future development of renal denervation therapies. Crown Copyright © 2013. Published by Mosby, Inc. All rights reserved.

Role of neuronal activity in regulating the structure and function of auditory neurons

International Nuclear Information System (INIS)

Born, D.E.

1986-01-01

The role of afferent activity in maintaining neuronal structure and function was investigated in second order auditory neurons in nucleus magnocellularis (NM) of the chicken. The cochlea provides the major excitatory input to NM neurons via the eighth nerve. Removal of the cochlea causes dramatic changes in NM neurons. To determine if the elimination of neuronal activity is responsible for the changes in NM seen after cochlea removal, tetrodotoxin was used block action potentials in the cochlear ganglion cells. Tetrodotoxin injections into the perilymph reliably blocked neuronal activity in the cochlear nerve and NM. Far field recordings of sound-evoked potentials revealed that responses returned within 6 hours. Changes in amino acid incorporation in NM neurons were measured by giving intracardiac injections of 3 H-leucine and preparing tissue for autoradiographic demonstration of incorporated amino acid. Grain counts over individual neurons revealed that a single injection of tetrodotoxin produced a 40% decrease in grain density in ipsilateral NM neurons. It is concluded that neuronal activity plays an important contribution to the maintenance of the normal properties of NM neurons

Monosynaptic connections between primary afferents and giant neurons in the turtle spinal dorsal horn

DEFF Research Database (Denmark)

Fernández, A; Radmilovich, M; Russo, R E

1996-01-01

This paper reports the occurrence of monosynaptic connections between dorsal root afferents and a distinct cell type-the giant neuron-deep in the dorsal horn of the turtle spinal cord. Light microscope studies combining Nissl stain and transganglionic HRP-labeling of the primary afferents have...

Which nerve conduction parameters can predict spontaneous electromyographic activity in carpal tunnel syndrome?

Science.gov (United States)

Chang, Chia-Wei; Lee, Wei-Ju; Liao, Yi-Chu; Chang, Ming-Hong

2013-11-01

We investigate electrodiagnostic markers to determine which parameters are the best predictors of spontaneous electromyographic (EMG) activity in carpal tunnel syndrome (CTS). We enrolled 229 patients with clinically proven and nerve conduction study (NCS)-proven CTS, as well as 100 normal control subjects. All subjects were evaluated using electrodiagnostic techniques, including median distal sensory latencies (DSLs), sensory nerve action potentials (SNAPs), distal motor latencies (DMLs), compound muscle action potentials (CMAPs), forearm median nerve conduction velocities (FMCVs) and wrist-palm motor conduction velocities (W-P MCVs). All CTS patients underwent EMG examination of the abductor pollicis brevis (APB) muscle, and the presence or absence of spontaneous EMG activities was recorded. Normal limits were determined by calculating the means ± 2 standard deviations from the control data. Associations between parameters from the NCS and EMG findings were investigated. In patients with clinically diagnosed CTS, abnormal median CMAP amplitudes were the best predictors of spontaneous activity during EMG examination (p95% (positive predictive rate >95%). If the median CMAP amplitude was higher than the normal limit (>4.9 mV), the rate of no spontaneous EMG activity was >94% (negative predictive rate >94%). An abnormal SNAP amplitude was the second best predictor of spontaneous EMG activity (p<0.001; OR 4.13; 95% CI 2.16-7.90), and an abnormal FMCV was the third best predictor (p=0.01; OR 2.10; 95% CI 1.20-3.67). No other nerve conduction parameters had significant power to predict spontaneous activity upon EMG examination. The CMAP amplitudes of the APB are the most powerful predictors of the occurrence of spontaneous EMG activity. Low CMAP amplitudes are strongly associated with spontaneous activity, whereas high CMAP amplitude are less associated with spontaneous activity, implying that needle EMG examination should be recommended for the detection of

In vitro activation of murine DRG neurons by CGRP-mediated mucosal mast cell degranulation

NARCIS (Netherlands)

De Jonge, F; De Laet, A; Van Nassauw, L; Miller, HRP; van Bogaert, PP; Timmermans, JP; Kroese, ABA

Upregulation of CGRP-immunoreactive (IR) primary afferent nerve fibers accompanied by mastocytosis is characteristic for the Schistosoma mansoni-infected murine ileum. These mucosal mast cells (MMC) and CGRP-IR fibers, which originate from dorsal root (DRG) and nodose ganglia, are found in close

Vagus nerve stimulation modulates visceral pain-related affective memory.

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Zhang, Xu; Cao, Bing; Yan, Ni; Liu, Jin; Wang, Jun; Tung, Vivian Oi Vian; Li, Ying

2013-01-01

Within a biopsychosocial model of pain, pain is seen as a conscious experience modulated by mental, emotional and sensory mechanisms. Recently, using a rodent visceral pain assay that combines the colorectal distension (CRD) model with the conditioned place avoidance (CPA) paradigms, we measured a learned behavior that directly reflects the affective component of visceral pain, and showed that perigenual anterior cingulate cortex (pACC) activation is critical for memory processing involved in long-term visceral affective state and prediction of aversive stimuli by contextual cue. Electrical vagus nerve stimulation (VNS) has become an established therapy for treatment-resistant epilepsy. VNS has also been shown to enhance memory performance in rats and humans. High-intensity VNS (400 μA) immediately following conditional training significantly increases the CRD-induced CPA scores, and enhanced the pain affective memory retention. In contrast, VNS (400 μA) had no effect on CPA induced by non-nociceptive aversive stimulus (U69,593). Low-intensity VNS (40 μA) had no effect on CRD-induced CPA. Electrophysiological recording showed that VNS (400 μA) had no effect on basal and CRD-induced ACC neuronal firing. Further, VNS did not alter CRD-induced visceral pain responses suggesting high intensity VNS facilitates visceral pain aversive memory independent of sensory discriminative aspects of visceral pain processing. The findings that vagus nerve stimulation facilities visceral pain-related affective memory underscore the importance of memory in visceral pain perception, and support the theory that postprandial factors may act on vagal afferents to modulate ongoing nature of visceral pain-induced affective disorder observed in the clinic, such as irritable bowel syndrome. Copyright © 2012 Elsevier B.V. All rights reserved.

CNS sites activated by renal pelvic epithelial sodium channels (ENaCs) in response to hypertonic saline in awake rats.

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Goodwill, Vanessa S; Terrill, Christopher; Hopewood, Ian; Loewy, Arthur D; Knuepfer, Mark M

2017-05-01

In some patients, renal nerve denervation has been reported to be an effective treatment for essential hypertension. Considerable evidence suggests that afferent renal nerves (ARN) and sodium balance play important roles in the development and maintenance of high blood pressure. ARN are sensitive to sodium concentrations in the renal pelvis. To better understand the role of ARN, we infused isotonic or hypertonic NaCl (308 or 500mOsm) into the left renal pelvis of conscious rats for two 2hours while recording arterial pressure and heart rate. Subsequently, brain tissue was analyzed for immunohistochemical detection of the protein Fos, a marker for neuronal activation. Fos-immunoreactive neurons were identified in numerous sites in the forebrain and brainstem. These areas included the nucleus tractus solitarius (NTS), the lateral parabrachial nucleus, the paraventricular nucleus of the hypothalamus (PVH) and the supraoptic nucleus (SON). The most effective stimulus was 500mOsm NaCl. Activation of these sites was attenuated or prevented by administration of benzamil (1μM) or amiloride (10μM) into the renal pelvis concomitantly with hypertonic saline. In anesthetized rats, infusion of hypertonic saline but not isotonic saline into the renal pelvis elevated ARN activity and this increase was attenuated by simultaneous infusion of benzamil or amiloride. We propose that renal pelvic epithelial sodium channels (ENaCs) play a role in activation of ARN and, via central visceral afferent circuits, this system modulates fluid volume and peripheral blood pressure. These pathways may contribute to the development of hypertension. Copyright © 2016 Elsevier B.V. All rights reserved.

Glucagon-like peptide-1 reduces pancreatic β-cell mass through hypothalamic neural pathways in high-fat diet-induced obese rats.

Science.gov (United States)

Ando, Hisae; Gotoh, Koro; Fujiwara, Kansuke; Anai, Manabu; Chiba, Seiichi; Masaki, Takayuki; Kakuma, Tetsuya; Shibata, Hirotaka

2017-07-17

We examined whether glucagon-like peptide-1 (GLP-1) affects β-cell mass and proliferation through neural pathways, from hepatic afferent nerves to pancreatic efferent nerves via the central nervous system, in high-fat diet (HFD)-induced obese rats. The effects of chronic administration of GLP-1 (7-36) and liraglutide, a GLP-1 receptor agonist, on pancreatic morphological alterations, c-fos expression and brain-derived neurotrophic factor (BDNF) content in the hypothalamus, and glucose metabolism were investigated in HFD-induced obese rats that underwent hepatic afferent vagotomy (VgX) and/or pancreatic efferent sympathectomy (SpX). Chronic GLP-1 (7-36) administration to HFD-induced obese rats elevated c-fos expression and BDNF content in the hypothalamus, followed by a reduction in pancreatic β-cell hyperplasia and insulin content, thus resulting in improved glucose tolerance. These responses were abolished by VgX and SpX. Moreover, administration of liraglutide similarly activated the hypothalamic neural pathways, thus resulting in a more profound amelioration of glucose tolerance than native GLP-1 (7-36). These data suggest that GLP-1 normalizes the obesity-induced compensatory increase in β-cell mass and glucose intolerance through a neuronal relay system consisting of hepatic afferent nerves, the hypothalamus, and pancreatic efferent nerves.

Heat pulse excitability of vestibular hair cells and afferent neurons.

Science.gov (United States)

Rabbitt, Richard D; Brichta, Alan M; Tabatabaee, Hessam; Boutros, Peter J; Ahn, JoongHo; Della Santina, Charles C; Poppi, Lauren A; Lim, Rebecca

2016-08-01

In the present study we combined electrophysiology with optical heat pulse stimuli to examine thermodynamics of membrane electrical excitability in mammalian vestibular hair cells and afferent neurons. We recorded whole cell currents in mammalian type II vestibular hair cells using an excised preparation (mouse) and action potentials (APs) in afferent neurons in vivo (chinchilla) in response to optical heat pulses applied to the crista (ΔT ≈ 0.25°C per pulse). Afferent spike trains evoked by heat pulse stimuli were diverse and included asynchronous inhibition, asynchronous excitation, and/or phase-locked APs synchronized to each infrared heat pulse. Thermal responses of membrane currents responsible for APs in ganglion neurons were strictly excitatory, with Q10 ≈ 2. In contrast, hair cells responded with a mix of excitatory and inhibitory currents. Excitatory hair cell membrane currents included a thermoelectric capacitive current proportional to the rate of temperature rise (dT/dt) and an inward conduction current driven by ΔT An iberiotoxin-sensitive inhibitory conduction current was also evoked by ΔT, rising in protein biophysics and manipulate cellular excitability. Copyright © 2016 the American Physiological Society.

De Novo Intraneural Arachnoid Cyst Presenting with Complete Third Nerve Palsy: Case Report and Literature Review.

Science.gov (United States)

Brewington, Danielle; Petrov, Dmitriy; Whitmore, Robert; Liu, Grant; Wolf, Ronald; Zager, Eric L

2017-02-01

Intraneural arachnoid cyst is an extremely rare etiology of isolated cranial nerve palsy. Although seldom encountered in clinical practice, this pathology is amenable to surgical intervention. Correct identification and treatment of the cyst are required to prevent permanent nerve damage and potentially reverse the deficits. We describe a rare case of isolated third nerve palsy caused by an intraneural arachnoid cyst. A 49-year-old woman with a recent history of headaches experienced acute onset of painless left-sided third nerve palsy. According to hospital records ptosis, mydriasis, absence of adduction, elevation, and intorsion were noted in the left eye. Computed tomography and magnetic resonance imaging studies showed an extra-axial, 1-cm lesion along the left paraclinoid region, causing mild indentation on the uncus. There was dense fluid layering dependently concerning for hemorrhage, but no evidence of aneurysms. A pterional craniotomy was performed, revealing a completely intraneural arachnoid cyst in the third nerve. The cyst was successfully fenestrated. At 7-month follow-up, the left eye had recovered intact intorsion and some adduction, but the left pupil remained dilated and nonreactive. There was still no elevation and no afferent pupillary defect. Double vision persisted with partial improvement in the ptosis, opening up to more than 75% early in the day. To our knowledge, this is the first report of an intraneural arachnoid cyst causing isolated third nerve palsy. This rare pathology proves to be both a diagnostic and therapeutic challenge. Copyright © 2016 Elsevier Inc. All rights reserved.

Persistent alterations in active and passive electrical membrane properties of regenerated nerve fibers of man and mice

DEFF Research Database (Denmark)

Moldovan, Mihai; Alvarez Herrero, Susana; Rosberg, Mette R.

2016-01-01

Excitability of regenerated fibers remains impaired due to changes in both passive cable properties and alterations in the voltage-dependent membrane function. These abnormalities were studied by mathematical modeling in human regenerated nerves and experimental studies in mice. In three adult male...... activity protocol triggered partial Wallerian degeneration in regenerated nerves but not in control nerves from age-matched mice. The current data suggest that the nodal voltage-gated ion channel machinery is restored in regenerated axons, although the electrical separation from the internodal compartment...... remains compromised. Due to the persistent increase in number of nodes, the increased activity-dependent Na+ influx could lead to hyperactivity of the Na+/K+ pump resulting in membrane hyperpolarization and neurotoxic energy insufficiency during strenuous activity....

Peptide and lipid modulation of glutamatergic afferent synaptic transmission in the solitary tract nucleus

Directory of Open Access Journals (Sweden)

Michael C. Andresen

2013-01-01

Full Text Available The brainstem nucleus of the solitary tract (NTS holds the first central neurons in major homeostatic reflex pathways. These homeostatic reflexes regulate and coordinate multiple organ systems from gastrointestinal to cardiopulmonary functions. The core of many of these pathways arise from cranial visceral afferent neurons that enter the brain as the solitary tract (ST with more than two-thirds arising from the gastrointestinal system. About one quarter of ST afferents have myelinated axons but the majority are classed as unmyelinated C-fibers. All ST afferents release the fast neurotransmitter glutamate with remarkably similar, high-probability release characteristics. Second order NTS neurons receive surprisingly limited primary afferent information with one or two individual inputs converging on single second order NTS neurons. A- and C-fiber afferents never mix at NTS second order neurons. Many transmitters modify the basic glutamatergic excitatory postsynaptic current (EPSC often by reducing glutamate release or interrupting terminal depolarization. Thus, a distinguishing feature of ST transmission is presynaptic expression of G-protein coupled receptors for peptides common to peripheral or forebrain (e.g. hypothalamus neuron sources. Presynaptic receptors for angiotensin (AT1, vasopressin (V1a, oxytocin (OT, opioid (MOR, ghrelin (GHSR1 and cholecystokinin (CCK differentially control glutamate release on particular subsets of neurons with most other ST afferents unaffected. Lastly, lipid-like signals are transduced by two key ST presynaptic receptors, the transient receptor potential vanilloid type 1 (TRPV1 and the cannabinoid receptor (CB1 that oppositely control glutamate release. Increasing evidence suggests that peripheral nervous signaling mechanisms are repurposed at central terminals to control excitation and are major sites of signal integration of peripheral and central inputs particularly from the hypothalamus.

Efficacy of kilohertz-frequency and conventional spinal cord stimulation in rat models of different pain conditions.

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Song, Zhiyang; Viisanen, Hanna; Meyerson, Björn A; Pertovaara, Antti; Linderoth, Bengt

2014-04-01

The aim was to compare the effects of high-frequency spinal cord stimulation (HF-SCS) at subparesthetic intensity with conventional SCS in rat models of different types of pain. In addition, microrecordings of afferent activity in the dorsal columns during both types of SCS were performed to elucidate their mode of action. Miniature SCS electrodes were implanted in all rats. One group was submitted to the spared nerve injury procedure (SNI) and another to inflammatory pain after carrageenan injection into a hind paw. All animals were tested for hypersensitivity to normally innocuous tactile and thermal stimuli. One group of normal healthy rats was submitted to acute nociceptive (pinch, heat) pain. Microrecording of afferent activity in the gracile nucleus (GN) was performed in a group of nerve-lesioned rats responding to conventional SCS. HF-SCS at 500, 1,000, or 10,000 Hz at subparesthetic amplitudes produced similar reductions in hypersensitivity due to nerve lesion as did conventional SCS at 50 Hz. HF-SCS showed no effect on thermal pain. A trial to rescue non-responders to conventional SCS using HF-SCS was not successful. There were no effects either of conventional or of HF-SCS on acute or inflammatory pain. Conventional SCS produced massive activation in the GN but no activation during HF-SCS, though normal peripherally evoked afferent activity remained. Conventional SCS proved equally effective to HF-SCS in various pain models. As no activity is conveyed rostrally in subparesthetic HF-SCS, we hypothesize that its mechanisms of action are primarily segmental. © 2014 International Neuromodulation Society.

Attenuation of early phase inflammation by cannabidiol prevents pain and nerve damage in rat osteoarthritis.

Science.gov (United States)

Philpott, Holly T; OʼBrien, Melissa; McDougall, Jason J

2017-12-01

Osteoarthritis (OA) is a multifactorial joint disease, which includes joint degeneration, intermittent inflammation, and peripheral neuropathy. Cannabidiol (CBD) is a noneuphoria producing constituent of cannabis that has the potential to relieve pain. The aim of this study was to determine whether CBD is anti-nociceptive in OA, and whether inhibition of inflammation by CBD could prevent the development of OA pain and joint neuropathy. Osteoarthritis was induced in male Wistar rats (150-175 g) by intra-articular injection of sodium monoiodoacetate (MIA; 3 mg). On day 14 (end-stage OA), joint afferent mechanosensitivity was assessed using in vivo electrophysiology, whereas pain behaviour was measured by von Frey hair algesiometry and dynamic incapacitance. To investigate acute joint inflammation, blood flow and leukocyte trafficking were measured on day 1 after MIA. Joint nerve myelination was calculated by G-ratio analysis. The therapeutic and prophylactic effects of peripheral CBD (100-300 μg) were assessed. In end-stage OA, CBD dose-dependently decreased joint afferent firing rate, and increased withdrawal threshold and weight bearing (P < 0.0001; n = 8). Acute, transient joint inflammation was reduced by local CBD treatment (P < 0.0001; n = 6). Prophylactic administration of CBD prevented the development of MIA-induced joint pain at later time points (P < 0.0001; n = 8), and was also found to be neuroprotective (P < 0.05; n = 6-8). The data presented here indicate that local administration of CBD blocked OA pain. Prophylactic CBD treatment prevented the later development of pain and nerve damage in these OA joints. These findings suggest that CBD may be a safe, useful therapeutic for treating OA joint neuropathic pain.

Afferent projections to the deep mesencephalic nucleus in the rat

International Nuclear Information System (INIS)

Veazey, R.B.; Severin, C.M.

1982-01-01

Afferent projections to the deep mesencephalic nucleus (DMN) of the rat were demonstrated with axonal transport techniques. Potential sources for projections to the DMN were first identified by injecting the nucleus with HRP and examining the cervical spinal cord, brain stem, and cortex for retrogradely labeled neurons. Areas consistently labeled were then injected with a tritiated radioisotope, the tissue processed for autoradiography, and the DMN examined for anterograde labeling. Afferent projections to the medial and/or lateral parts of the DMN were found to originate from a number of spinal, bulbar, and cortical centers. Rostral brain centers projecting to both medial and lateral parts of the DMN include the ipsilateral motor and somatosensory cortex, the entopeduncular nucleus, and zona incerta. at the level of the midbrain, the ipsilateral substantia nigra and contralateral DMN likewise project to the DMN. Furthermore, the ipsilateral superior colliculus projects to the DMN, involving mainly the lateral part of the nucleus. Afferents from caudal centers include bilateral projections from the sensory nucleus of the trigeminal complex and the nucleus medulla oblongata centralis, as well as from the contralateral dentate nucleus. The projections from the trigeminal complex and nucleus medullae oblongatae centralis terminate in the intermediate and medial parts of the DMN, whereas projections from the contralateral dentate nucleus terminate mainly in its lateral part. In general, the afferent connections of the DMN arise from diverse areas of the brain. Although most of these projections distribute throughout the entire extent of the DMN, some of them project mainly to either medial or lateral parts of the nucleus, thus suggesting that the organization of the DMN is comparable, at least in part, to that of the reticular formation of the pons and medulla, a region in which hodological differences between medial and lateral subdivisions are known to exist

Active patient decision making regarding nerve sparing during radical prostatectomy: a novel approach.

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Lavery, Hugh J; Prall, David N; Abaza, Ronney

2011-08-01

The motivation to preserve sexual function can vary widely among patients before prostatectomy. Increasing patient involvement may allow a more personalized experience and may improve satisfaction. We assessed a strategy of surgeon deference to patient choice in regard to nerve sparing to determine to what degree patients are rational actors and capable of active decision making. A total of 150 patients treated with prostatectomy participated in a standardized preoperative discussion regarding the concept of nerve sparing, extracapsular extension and the potential need for adjuvant radiation in the event of local recurrence. Each patient was given his nomogram predicted risk of extracapsular extension and then elected nerve sparing or nonnerve sparing. The corresponding procedure was performed unless grossly invasive disease was encountered. Of the 150 patients 109 chose nerve sparing (73%) and 41 chose nonnerve sparing (27%). In patients with a nomogram predicted risk of extracapsular extension less than 20%, 20% to 50% and greater than 50%, nerve sparing was elected by 88%, 41% and 25%, respectively. Patients with lower risks of extracapsular extension electing nonnerve sparing were older and had higher rates of erectile dysfunction. Empowering patients to decide on their nerve sparing status is a reasonable strategy that did not lead to a high rate of patients with a high risk of extracapsular extension electing nerve sparing. With proper counseling informed patients made reasonable decisions, and appeared to be conservative, prioritizing cancer control in the majority of instances where extracapsular extension risk was high. In addition, they may have been overly conservative in electing nonnerve sparing when the risk was low. Copyright © 2011 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Population coding of forelimb joint kinematics by peripheral afferents in monkeys.

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Tatsuya Umeda

Full Text Available Various peripheral receptors provide information concerning position and movement to the central nervous system to achieve complex and dexterous movements of forelimbs in primates. The response properties of single afferent receptors to movements at a single joint have been examined in detail, but the population coding of peripheral afferents remains poorly defined. In this study, we obtained multichannel recordings from dorsal root ganglion (DRG neurons in cervical segments of monkeys. We applied the sparse linear regression (SLiR algorithm to the recordings, which selects useful input signals to reconstruct movement kinematics. Multichannel recordings of peripheral afferents were performed by inserting multi-electrode arrays into the DRGs of lower cervical segments in two anesthetized monkeys. A total of 112 and 92 units were responsive to the passive joint movements or the skin stimulation with a painting brush in Monkey 1 and Monkey 2, respectively. Using the SLiR algorithm, we reconstructed the temporal changes of joint angle, angular velocity, and acceleration at the elbow, wrist, and finger joints from temporal firing patterns of the DRG neurons. By automatically selecting a subset of recorded units, the SLiR achieved superior generalization performance compared with a regularized linear regression algorithm. The SLiR selected not only putative muscle units that were responsive to only the passive movements, but also a number of putative cutaneous units responsive to the skin stimulation. These results suggested that an ensemble of peripheral primary afferents that contains both putative muscle and cutaneous units encode forelimb joint kinematics of non-human primates.

Phrenic and hypoglossal nerve activity during respiratory response to hypoxia in 6-OHDA unilateral model of Parkinson's disease.

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Andrzejewski, Kryspin; Budzińska, Krystyna; Kaczyńska, Katarzyna

2017-07-01

Parkinson's disease (PD) patients apart from motor dysfunctions exhibit respiratory disturbances. Their mechanism is still unknown and requires investigation. Our research was designed to examine the activity of phrenic (PHR) and hypoglossal (HG) nerves activity during a hypoxic respiratory response in the 6-hydroxydopamine (6-OHDA) model of PD. Male adult Wistar rats were injected unilaterally with 6-OHDA (20μg) or the vehicle into the right medial forebrain bundle (MFB). Two weeks after the surgery the activity of the phrenic and hypoglossal nerve was registered in anesthetized, vagotomized, paralyzed, and mechanically ventilated rats under normoxic and hypoxic conditions. Lesion effectiveness was confirmed by the cylinder test, performed before the MFB injection and 14days after, before the respiratory experiment. 6-OHDA lesioned animals showed a significant increase in normoxic inspiratory time. Expiratory time and total time of the respiratory cycle were prolonged in PD rats after hypoxia. The amplitude of the PHR activity and its minute activity were increased in comparison to the sham group at recovery time and during 30s of hypoxia. The amplitude of the HG activity was increased in response to hypoxia in 6-OHDA lesioned animals. The degeneration of dopaminergic neurons decreased the pre-inspiratory/inspiratory ratio of the hypoglossal burst amplitude during and after hypoxia. Unilateral MFB lesion changed the activity of the phrenic and hypoglossal nerves. The altered pre-inspiratory hypoglossal nerve activity indicates modifications to the central mechanisms controlling the activity of the HG nerve and may explain respiratory disorders seen in PD, i.e. apnea. Copyright © 2017 Elsevier Inc. All rights reserved.

MR imaging and T2 measurements in peripheral nerve repair with activation of Toll-like receptor 4 of neurotmesis

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Zhang, Xiang; Zhang, Fang; Lu, Liejing; Li, Haojiang; Wen, Xuehua; Shen, Jun [Sun Yat-Sen University, Department of Radiology, Sun Yat-Sen Memorial Hospital, Guangzhou, Guangdong (China)

2014-05-15

To investigate the role of MR imaging in neurotmesis combined with surgical repair and Toll-like receptor 4 (TLR4) activation. Forty-eight rats received subepineurial microinjection of the TLR4 agonist lipopolysaccharide (LPS, n = 24) or phosphate buffered saline (PBS, n = 24) immediately after surgical repair of the transected sciatic nerve. Sequential fat-suppressed T2-weighted imaging and quantitative T2 measurements were obtained at 3, 7, 14 and 21 days after surgery, with histologic assessments performed at regular intervals. T2 relaxation times and histological quantification of the distal stumps were measured and compared. The distal stumps of transected nerves treated with LPS or PBS both showed persistent enlargement and hyperintense signal. T2 values of the distal stumps showed a rapid rise to peak level followed by a rapid decline pattern in nerves treated with LPS, while exhibiting a slow rise to peak value followed by a slow decline in nerves treated with PBS. Nerves treated with LPS exhibited more prominent macrophage recruitment, faster myelin debris clearance and more pronounced nerve regeneration. Nerves treated with TLR4 activation had a characteristic pattern of T2 value change over time. Longitudinal T2 measurements can be used to detect the enhanced repair effect associated with TLR4 activation in the surgical repair of neurotmesis. (orig.)

Denervation (ablation) of nerve terminalis in renal arteries: early results of interventional treatment of arterial hypertension in Poland.

Science.gov (United States)

Bartuś, Krzysztof; Sadowski, Jerzy; Kapelak, Bogusław; Zajdel, Wojciech; Godlewski, Jacek; Bartuś, Stanisław; Bochenek, Maciej; Bartuś, Magdalena; Żmudka, Krzysztof; Sobotka, Paul A

2013-01-01

Arterial hypertension is one of the main causes of cardiovascular disease morbidity and overall mortality. To report the single centre experiences with changes in arterial blood pressure (BP) in patients after intra-arterial application of radiofrequency (RF) energy to cause renal sympathetic efferent and somatic afferent nerve and report vascular and kidney safety in a six month follow up. Twenty-eight patients, with hypertension despite medical therapy (median age 52.02 years, range 42-72 years) consented to therapeutic renal nerve ablation. SIMPLICITY RF catheters and generator provided by Ardian (currently Medtronic Inc., USA) were used to perform renal artery angiography and ablation. The mean BP at baseline, and after one month, three months and six months were measured [mm Hg]: systolic 176.6; 162.3 (p = 0.004); 150.6 (p arterial renal nerve denervation was not associated with either vascular or renal complications out to six months. Nerve ablation of renal arteries led to significant reduction of mean values of arterial systolic, diastolic BP and significant reduction of pulse pressure. The Polish experience is not significantly different compared to that reported in the Symplicity I and Symplicity II international cohorts. The long term durability of this therapy and its application to earlier stages of hypertension or other disease states will require further investigation.

Heat pulse excitability of vestibular hair cells and afferent neurons

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Brichta, Alan M.; Tabatabaee, Hessam; Boutros, Peter J.; Ahn, JoongHo; Della Santina, Charles C.; Poppi, Lauren A.; Lim, Rebecca

2016-01-01

In the present study we combined electrophysiology with optical heat pulse stimuli to examine thermodynamics of membrane electrical excitability in mammalian vestibular hair cells and afferent neurons. We recorded whole cell currents in mammalian type II vestibular hair cells using an excised preparation (mouse) and action potentials (APs) in afferent neurons in vivo (chinchilla) in response to optical heat pulses applied to the crista (ΔT ≈ 0.25°C per pulse). Afferent spike trains evoked by heat pulse stimuli were diverse and included asynchronous inhibition, asynchronous excitation, and/or phase-locked APs synchronized to each infrared heat pulse. Thermal responses of membrane currents responsible for APs in ganglion neurons were strictly excitatory, with Q10 ≈ 2. In contrast, hair cells responded with a mix of excitatory and inhibitory currents. Excitatory hair cell membrane currents included a thermoelectric capacitive current proportional to the rate of temperature rise (dT/dt) and an inward conduction current driven by ΔT. An iberiotoxin-sensitive inhibitory conduction current was also evoked by ΔT, rising in heat pulse excitability in vestibular sensory organs and provide quantitative methods for rational application of optical heat pulses to examine protein biophysics and manipulate cellular excitability. PMID:27226448

Development of fusimotor innervation correlates with group Ia afferents but is independent of neurotrophin-3

NARCIS (Netherlands)

Ringstedt, T; Copray, S; Walro, J; Kucera, J

1998-01-01

Fusimotor neurons, group Ia afferents and muscle spindles are absent in mutant mice lacking the gene for neurotrophin-3 (NT3). To partition the effect of Ia afferent or spindle absence from that of NT3 deprivation on fusimotor neuron development, we examined the fusimotor system in a mutant mouse

Chloride regulates afferent arteriolar contraction in response to depolarization

DEFF Research Database (Denmark)

Hansen, P B; Jensen, B L; Skott, O

1998-01-01

-Renal vascular reactivity is influenced by the level of dietary salt intake. Recent in vitro data suggest that afferent arteriolar contractility is modulated by extracellular chloride. In the present study, we assessed the influence of chloride on K+-induced contraction in isolated perfused rabbit...... afferent arterioles. In 70% of vessels examined, K+-induced contraction was abolished by acute substitution of bath chloride. Consecutive addition of Cl- (30, 60, 80, 100, 110, and 117 mmol/L) restored the sensitivity to K+, and half-maximal response was observed at 82 mmol/L chloride. The calcium channel...... antagonist diltiazem (10(-6) mol/L) abolished K+-induced contractions. Bicarbonate did not modify the sensitivity to chloride. Norepinephrine (10(-6) mol/L) induced full contraction in depolarized vessels even in the absence of chloride. Iodide and nitrate were substituted for chloride with no inhibitory...

Role of the Sympathetic Nervous System and Its Modulation in Renal Hypertension.

Science.gov (United States)

Sata, Yusuke; Head, Geoffrey A; Denton, Kate; May, Clive N; Schlaich, Markus P

2018-01-01

The kidneys are densely innervated with renal efferent and afferent nerves to communicate with the central nervous system. Innervation of major structural components of the kidneys, such as blood vessels, tubules, the pelvis, and glomeruli, forms a bidirectional neural network to relay sensory and sympathetic signals to and from the brain. Renal efferent nerves regulate renal blood flow, glomerular filtration rate, tubular reabsorption of sodium and water, as well as release of renin and prostaglandins, all of which contribute to cardiovascular and renal regulation. Renal afferent nerves complete the feedback loop via central autonomic nuclei where the signals are integrated and modulate central sympathetic outflow; thus both types of nerves form integral parts of the self-regulated renorenal reflex loop. Renal sympathetic nerve activity (RSNA) is commonly increased in pathophysiological conditions such as hypertension and chronic- and end-stage renal disease. Increased RSNA raises blood pressure and can contribute to the deterioration of renal function. Attempts have been made to eliminate or interfere with this important link between the brain and the kidneys as a neuromodulatory treatment for these conditions. Catheter-based renal sympathetic denervation has been successfully applied in patients with resistant hypertension and was associated with significant falls in blood pressure and renal protection in most studies performed. The focus of this review is the neural contribution to the control of renal and cardiovascular hemodynamics and renal function in the setting of hypertension and chronic kidney disease, as well as the specific roles of renal efferent and afferent nerves in this scenario and their utility as a therapeutic target.

Receptor units responding to movement in the octopus mantle.

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Boyle, P R

1976-08-01

1. A preparation of the mantle of Octopus which is inverted over a solid support and which exposes the stellate ganglion and associated nerves is described. 2. Afferent activity can be recorded from stellar nerves following electrical stimulation of the pallial nerve. The latency and frequency of the phasic sensory response is correlated with the contraction of the mantle musculature. 3. It is proposed that receptors cells located in the muscle, and their activity following mantle contraction, form part of a sensory feedback system in the mantle. Large, multipolar nerve cells that were found between the two main layers of circular muscle in the mantle could be such receptors.

Facial reanimation by muscle-nerve neurotization after facial nerve sacrifice. Case report.

Science.gov (United States)

Taupin, A; Labbé, D; Babin, E; Fromager, G

2016-12-01

Recovering a certain degree of mimicry after sacrifice of the facial nerve is a clinically recognized finding. The authors report a case of hemifacial reanimation suggesting a phenomenon of neurotization from muscle-to-nerve. A woman benefited from a parotidectomy with sacrifice of the left facial nerve indicated for recurrent tumor in the gland. The distal branches of the facial nerve, isolated at the time of resection, were buried in the masseter muscle underneath. The patient recovered a voluntary hémifacial motricity. The electromyographic analysis of the motor activity of the zygomaticus major before and after block of the masseter nerve showed a dependence between mimic muscles and the masseter muscle. Several hypotheses have been advanced to explain the spontaneous reanimation of facial paralysis. The clinical case makes it possible to argue in favor of muscle-to-nerve neurotization from masseter muscle to distal branches of the facial nerve. It illustrates the quality of motricity that can be obtained thanks to this procedure. The authors describe a simple implantation technique of distal branches of the facial nerve in the masseter muscle during a radical parotidectomy with facial nerve sacrifice and recovery of resting tone but also a quality voluntary mimicry. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

A comparison between complete immobilisation and protected active mobilisation in sensory nerve recovery following isolated digital nerve injury.

LENUS (Irish Health Repository)

Henry, F P

2012-06-01

Post-operative immobilisation following isolated digital nerve repair remains a controversial issue amongst the microsurgical community. Protocols differ from unit to unit and even, as evidenced in our unit, may differ from consultant to consultant. We undertook a retrospective review of 46 patients who underwent isolated digital nerve repair over a 6-month period. Follow-up ranged from 6 to 18 months. Twenty-four were managed with protected active mobilisation over a 4-week period while 22 were immobilised over the same period. Outcomes such as return to work, cold intolerance, two-point discrimination and temperature differentiation were used as indicators of clinical recovery. Our results showed that there was no significant difference noted in either clinical assessment of recovery or return to work following either post-operative protocol, suggesting that either regime may be adopted, tailored to the patient\\'s needs and resources of the unit.

Physiological basis of tingling paresthesia evoked by hydroxy-α-sanshool

Science.gov (United States)

Lennertz, Richard C; Tsunozaki, Makoto; Bautista, Diana M; Stucky, Cheryl L

2010-01-01

Hydroxy-α-sanshool, the active ingredient in plants of the prickly ash plant family, induces robust tingling paresthesia by activating a subset of somatosensory neurons. However, the subtypes and physiological function of sanshool-sensitive neurons remain unknown. Here we use the ex vivo skin-nerve preparation to examine the pattern and intensity with which the sensory terminals of cutaneous neurons respond to hydroxy-α-sanshool. We found that sanshool excites virtually all D-hair afferents, a distinct subset of ultra-sensitive light touch receptors in the skin, and targets novel populations of Aβ and C-fiber nerve afferents. Thus, sanshool provides a novel pharmacological tool for discriminating functional subtypes of cutaneous mechanoreceptors. The identification of sanshool-sensitive fibers represents an essential first step in identifying the cellular and molecular mechanisms underlying tingling paresthesia that accompanies peripheral neuropathy and injury. PMID:20335471

Physiological basis of tingling paresthesia evoked by hydroxy-alpha-sanshool.

Science.gov (United States)

Lennertz, Richard C; Tsunozaki, Makoto; Bautista, Diana M; Stucky, Cheryl L

2010-03-24

Hydroxy-alpha-sanshool, the active ingredient in plants of the prickly ash plant family, induces robust tingling paresthesia by activating a subset of somatosensory neurons. However, the subtypes and physiological function of sanshool-sensitive neurons remain unknown. Here we use the ex vivo skin-nerve preparation to examine the pattern and intensity with which the sensory terminals of cutaneous neurons respond to hydroxy-alpha-sanshool. We found that sanshool excites virtually all D-hair afferents, a distinct subset of ultrasensitive light-touch receptors in the skin and targets novel populations of Abeta and C fiber nerve afferents. Thus, sanshool provides a novel pharmacological tool for discriminating functional subtypes of cutaneous mechanoreceptors. The identification of sanshool-sensitive fibers represents an essential first step in identifying the cellular and molecular mechanisms underlying tingling paresthesia that accompanies peripheral neuropathy and injury.

Reciprocal synapses between outer hair cells and their afferent terminals: evidence for a local neural network in the mammalian cochlea.

Science.gov (United States)

Thiers, Fabio A; Nadol, Joseph B; Liberman, M Charles

2008-12-01

Cochlear outer hair cells (OHCs) serve both as sensory receptors and biological motors. Their sensory function is poorly understood because their afferent innervation, the type-II spiral ganglion cell, has small unmyelinated axons and constitutes only 5% of the cochlear nerve. Reciprocal synapses between OHCs and their type-II terminals, consisting of paired afferent and efferent specialization, have been described in the primate cochlea. Here, we use serial and semi-serial-section transmission electron microscopy to quantify the nature and number of synaptic interactions in the OHC area of adult cats. Reciprocal synapses were found in all OHC rows and all cochlear frequency regions. They were more common among third-row OHCs and in the apical half of the cochlea, where 86% of synapses were reciprocal. The relative frequency of reciprocal synapses was unchanged following surgical transection of the olivocochlear bundle in one cat, confirming that reciprocal synapses were not formed by efferent fibers. In the normal ear, axo-dendritic synapses between olivocochlear terminals and type-II terminals and/or dendrites were as common as synapses between olivocochlear terminals and OHCs, especially in the first row, where, on average, almost 30 such synapses were seen in the region under a single OHC. The results suggest that a complex local neuronal circuitry in the OHC area, formed by the dendrites of type-II neurons and modulated by the olivocochlear system, may be a fundamental property of the mammalian cochlea, rather than a curiosity of the primate ear. This network may mediate local feedback control of, and bidirectional communication among, OHCs throughout the cochlear spiral.

Hyperosmolar Tears Induce Functional and Structural Alterations of Corneal Nerves: Electrophysiological and Anatomical Evidence Toward Neurotoxicity.

Science.gov (United States)

Hirata, Harumitsu; Mizerska, Kamila; Marfurt, Carl F; Rosenblatt, Mark I

2015-12-01

In an effort to elucidate possible neural mechanisms underlying diminished tearing in dry eye disease, this study sought to determine if hyperosmolar tears, a ubiquitous sign of dry eye disease, produce functional changes in corneal nerve responses to drying of the cornea and if these changes correlate with alterations in corneal nerve morphology. In vivo extracellular electrophysiological recordings were performed in rat trigeminal ganglion neurons that innervated the cornea before, and up to 3 hours after, the ocular application of continuous hyperosmolar tears or artificial tears. In corollary experiments, immunohistochemical staining was performed to compare corneal nerve morphology in control and in eyes treated with hyperosmolar solutions. Our previous studies identified a population of corneal afferents, dry-sensitive neurons that are strongly excited by corneal dessication ("dry response"), a response thought to trigger the lacrimation reflex. In the present study, we found that the dry responses of corneal dry-sensitive neurons were depressed or even completely abolished by hyperosmolar tears in a time- (30 minutes to 3 hours) and dose (450- to 1000-mOsm solutions)-dependent manner. Furthermore, eyes treated with hyperosmolar tears for 3 hours contained large numbers of morphologically abnormal (granular, fragmented, or prominently beaded) subbasal nerves that appeared to be undergoing degeneration. These results demonstrate that tear hyperosmolarity, considered to be a "core" mechanism of dry eye disease, significantly decreases physiological sensitivity and morphologic integrity of the corneal nerves important in tear production. These alterations might contribute to the diminished tearing seen clinically in dry eye patients.

Identification of the main generator source of longitudinal muscle contraction in the earthworm ventral nerve cord

Directory of Open Access Journals (Sweden)

Chang Y.C.

1998-01-01

Full Text Available The main generator source of a longitudinal muscle contraction was identified as an M (mechanical-stimulus-sensitive circuit composed of a presynaptic M-1 neuron and a postsynaptic M-2 neuron in the ventral nerve cord of the earthworm, Amynthas hawayanus, by simultaneous intracellular response recording and Lucifer Yellow-CH injection with two microelectrodes. Five-peaked responses were evoked in both neurons by a mechanical, but not by an electrical, stimulus to the mechanoreceptor in the shaft of a seta at the opposite side of an epidermis-muscle-nerve-cord preparation. This response was correlated to 84% of the amplitude, 73% of the rising rate and 81% of the duration of a longitudinal muscle contraction recorded by a mechano-electrical transducer after eliminating the other possible generator sources by partitioning the epidermis-muscle piece of this preparation. The pre- and postsynaptic relationship between these two neurons was determined by alternately stimulating and recording with two microelectrodes. Images of the Lucifer Yellow-CH-filled M-1 and M-2 neurons showed that both of them are composed of bundles of longitudinal processes situated on the side of the nerve cord opposite to stimulation. The M-1 neuron has an afferent process (A1 in the first nerve at the stimulated side of this preparation and the M-2 neuron has two efferent processes (E1 and E3 in the first and third nerves at the recording side where their effector muscle cell was identified by a third microelectrode.

Structure of the afferent terminals in terminal ganglion of a cricket and persistent homology.

Directory of Open Access Journals (Sweden)

Jacob Brown

Full Text Available We use topological data analysis to investigate the three dimensional spatial structure of the locus of afferent neuron terminals in crickets Acheta domesticus. Each afferent neuron innervates a filiform hair positioned on a cercus: a protruding appendage at the rear of the animal. The hairs transduce air motion to the neuron signal that is used by a cricket to respond to the environment. We stratify the hairs (and the corresponding afferent terminals into classes depending on hair length, along with position. Our analysis uncovers significant structure in the relative position of these terminal classes and suggests the functional relevance of this structure. Our method is very robust to the presence of significant experimental and developmental noise. It can be used to analyze a wide range of other point cloud data sets.

Accumulation of Kv7.2 channels in putative ectopic transduction zones of mice nerve-end neuromas

Directory of Open Access Journals (Sweden)

Lopez-García Jose A

2011-08-01

Full Text Available Abstract Background Modulation of M-type currents has been proposed as a new strategy for the treatment of neuropathic pain due to their role in regulating neuronal excitability. Using electrophysiological techniques we showed previously that the opening of Kv7 channels with retigabine, blocked ectopic discharges from axotomized fibers but did not alter transduction at intact skin afferents. We hypothesized that after nerve damage, accumulation of Kv7 channels in afferent fibers may increase M-type currents which then acquired a more important role at regulating fiber excitability. Findings In this study, we used an immunohistochemical approach to examine patterns of expression of Kv7.2 channels in afferent fibers after axotomy and compared them to patterns of expression of voltage gated Na+ channels (Nav which are key electrogenic elements in peripheral axons known to accumulate in experimental and human neuromas. Axotomy induced an enlargement and narrowing of the nodes of Ranvier at the proximal end of the neuroma together with a dramatic demyelination and loss of structure at its distal end in which naked accumulations of Nav were present. In addition, axotomy also induced accumulations of Kv7.2 that co-localized with those of Nav channels. Conclusions Whilst Nav channels are mandatory for initiation of action potentials, (i.e. responsible for the generation/propagation of ectopic discharges an increased accumulation of Kv7.2 channels after axotomy may represent a homeostatic compensation to over excitability in axotomized fibers, opening a window for a peripheral action of M-current modulators under conditions of neuropathy.

Terminal nerve: cranial nerve zero

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Jorge Eduardo Duque Parra

2006-12-01

Full Text Available It has been stated, in different types of texts, that there are only twelve pairs of cranial nerves. Such texts exclude the existence of another cranial pair, the terminal nerve or even cranial zero. This paper considers the mentioned nerve like a cranial pair, specifying both its connections and its functional role in the migration of liberating neurons of the gonadotropic hormone (Gn RH. In this paper is also stated the hypothesis of the phylogenetic existence of a cerebral sector and a common nerve that integrates the terminal nerve with the olfactory nerves and the vomeronasals nerves which seem to carry out the odors detection function as well as in the food search, pheromone detection and nasal vascular regulation.

Treatment of peroneal nerve injuries with simultaneous tendon transfer and nerve exploration.

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Ho, Bryant; Khan, Zubair; Switaj, Paul J; Ochenjele, George; Fuchs, Daniel; Dahl, William; Cederna, Paul; Kung, Theodore A; Kadakia, Anish R

2014-08-06

Common peroneal nerve palsy leading to foot drop is difficult to manage and has historically been treated with extended bracing with expectant waiting for return of nerve function. Peroneal nerve exploration has traditionally been avoided except in cases of known traumatic or iatrogenic injury, with tendon transfers being performed in a delayed fashion after exhausting conservative treatment. We present a new strategy for management of foot drop with nerve exploration and concomitant tendon transfer. We retrospectively reviewed a series of 12 patients with peroneal nerve palsies that were treated with tendon transfer from 2005 to 2011. Of these patients, seven were treated with simultaneous peroneal nerve exploration and repair at the time of tendon transfer. Patients with both nerve repair and tendon transfer had superior functional results with active dorsiflexion in all patients, compared to dorsiflexion in 40% of patients treated with tendon transfers alone. Additionally, 57% of patients treated with nerve repair and tendon transfer were able to achieve enough function to return to running, compared to 20% in patients with tendon transfer alone. No patient had full return of native motor function resulting in excessive dorsiflexion strength. The results of our limited case series for this rare condition indicate that simultaneous nerve repair and tendon transfer showed no detrimental results and may provide improved function over tendon transfer alone.

Bradykinin receptor blockade restores the baroreflex control of renal sympathetic nerve activity in cisplatin-induced renal failure rats.

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Abdulla, M H; Duff, M; Swanton, H; Johns, E J

2016-11-01

This study investigated the effect of renal bradykinin B1 and B2 receptor blockade on the high- and low-pressure baroreceptor reflex regulation of renal sympathetic nerve activity (RSNA) in rats with cisplatin-induced renal failure. Cisplatin (5 mg/kg) or saline was given intraperitoneally 4 days prior to study. Following chloralose/urethane anaesthesia, rats were prepared for measurement of mean arterial pressure (MAP), heart rate and RSNA and received intrarenal infusions of either Lys-[des-Arg 9 , Leu 8 ]-bradykinin (LBK), a bradykinin B1 receptor blocker, or bradyzide (BZ), a bradykinin B2 receptor blocker. RSNA baroreflex gain curves and renal sympatho-inhibitory responses to volume expansion (VE) were obtained. In the control and renal failure groups, basal MAP (89 ± 3 vs. 80 ± 8 mmHg) and RSNA (2.0 ± 0.3 vs. 1.7 ± 0.6 μV.s) were similar but HR was lower in the latter group (331 ± 8 vs. 396 ± 9 beats/min). The baroreflex gain for RSNA in the renal failure rats was 39% (P renal failure rats. Intrarenal LBK infusion in the renal failure rats normalized the VE induced renal sympatho-inhibition whereas BZ only partially restored the response. These findings suggest that pro-inflammatory bradykinin acting at different receptors within the kidney generates afferent neural signals which impact differentially within the central nervous system on high- and low-pressure regulation of RSNA. © 2016 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd.

Gastric electrical stimulation decreases gastric distension-induced central nociception response through direct action on primary afferents.

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Wassila Ouelaa

Full Text Available BACKGROUND & AIMS: Gastric electrical stimulation (GES is an effective therapy to treat patients with chronic dyspepsia refractory to medical management. However, its mechanisms of action remain poorly understood. METHODS: Gastric pain was induced by performing gastric distension (GD in anesthetized rats. Pain response was monitored by measuring the pseudo-affective reflex (e.g., blood pressure variation, while neuronal activation was determined using c-fos immunochemistry in the central nervous system. Involvement of primary afferents was assessed by measuring phosphorylation of ERK1/2 in dorsal root ganglia. RESULTS: GES decreased blood pressure variation induced by GD, and prevented GD-induced neuronal activation in the dorsal horn of the spinal cord (T9-T10, the nucleus of the solitary tract and in CRF neurons of the hypothalamic paraventricular nucleus. This effect remained unaltered within the spinal cord when sectioning the medulla at the T5 level. Furthermore, GES prevented GD-induced phosphorylation of ERK1/2 in dorsal root ganglia. CONCLUSIONS: GES decreases GD-induced pain and/or discomfort likely through a direct modulation of gastric spinal afferents reducing central processing of visceral nociception.

Modulation of experimental arthritis by vagal sensory and central brain stimulation.

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Bassi, Gabriel Shimizu; Dias, Daniel Penteado Martins; Franchin, Marcelo; Talbot, Jhimmy; Reis, Daniel Gustavo; Menezes, Gustavo Batista; Castania, Jaci Airton; Garcia-Cairasco, Norberto; Resstel, Leonardo Barbosa Moraes; Salgado, Helio Cesar; Cunha, Fernando Queiróz; Cunha, Thiago Mattar; Ulloa, Luis; Kanashiro, Alexandre

2017-08-01

Articular inflammation is a major clinical burden in multiple inflammatory diseases, especially in rheumatoid arthritis. Biological anti-rheumatic drug therapies are expensive and increase the risk of systemic immunosuppression, infections, and malignancies. Here, we report that vagus nerve stimulation controls arthritic joint inflammation by inducing local regulation of innate immune response. Most of the previous studies of neuromodulation focused on vagal regulation of inflammation via the efferent peripheral pathway toward the viscera. Here, we report that vagal stimulation modulates arthritic joint inflammation through a novel "afferent" pathway mediated by the locus coeruleus (LC) of the central nervous system. Afferent vagal stimulation activates two sympatho-excitatory brain areas: the paraventricular hypothalamic nucleus (PVN) and the LC. The integrity of the LC, but not that of the PVN, is critical for vagal control of arthritic joint inflammation. Afferent vagal stimulation suppresses articular inflammation in the ipsilateral, but not in the contralateral knee to the hemispheric LC lesion. Central stimulation is followed by subsequent activation of joint sympathetic nerve terminals inducing articular norepinephrine release. Selective adrenergic beta-blockers prevent the effects of articular norepinephrine and thereby abrogate vagal control of arthritic joint inflammation. These results reveals a novel neuro-immune brain map with afferent vagal signals controlling side-specific articular inflammation through specific inflammatory-processing brain centers and joint sympathetic innervations. Copyright © 2017 Elsevier Inc. All rights reserved.

Influence of local noxious heat stimulation on sensory nerve activity in the feline dental pulp.

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Ahlberg, K F

1978-05-01

The present investigation was undertaken to develop an experimental model in which noxious heat stimulation was used to produce increased intradental sensory nerve activity in canine teeth of anesthetized cats. Two techniques were evaluated in which both the method of recording and the nature of the stimulus varied. Slow heating (approx 1 degree C/s) to 47 degree C of the tooth surface (combined with recording from electrodes in open dentinal cavities) did not produce any persistent nerve activity. Repeated periods of brief intense heating (approx 60 degrees C/s) (combined with recording from amalgam electrodes placed on cavity floors) resulted in an immediate response and an afterdischarge (phase 3) generally persisting for 20--60 min. Maximum phase 3 activity was characteristic for the individual cat and ranged from 0.2 to 50.2 imp/s. mean value 10.6 imp/s (S.D. +/- 9.2). A systematically higher phase 3 activity was recorded in lower compared to upper canine teeth (p less than 0.05). The maximum phase 3 response generally occurred after 3-8 stimulations; the median number of required stimuli was 3. Repeated brief heat stimulations combined with the closed cavity recording technique may be used as an experimental model by which the mechanisms behind increases in intradental sensory nerve activity associated with tissue damage can be studied.

Spinal afferent neurons projecting to the rat lung and pleura express acid sensitive channels

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Kummer Wolfgang

2006-07-01

Full Text Available Abstract Background The acid sensitive ion channels TRPV1 (transient receptor potential vanilloid receptor-1 and ASIC3 (acid sensing ion channel-3 respond to tissue acidification in the range that occurs during painful conditions such as inflammation and ischemia. Here, we investigated to which extent they are expressed by rat dorsal root ganglion neurons projecting to lung and pleura, respectively. Methods The tracer DiI was either injected into the left lung or applied to the costal pleura. Retrogradely labelled dorsal root ganglion neurons were subjected to triple-labelling immunohistochemistry using antisera against TRPV1, ASIC3 and neurofilament 68 (marker for myelinated neurons, and their soma diameter was measured. Results Whereas 22% of pulmonary spinal afferents contained neither channel-immunoreactivity, at least one is expressed by 97% of pleural afferents. TRPV1+/ASIC3- neurons with probably slow conduction velocity (small soma, neurofilament 68-negative were significantly more frequent among pleural (35% than pulmonary afferents (20%. TRPV1+/ASIC3+ neurons amounted to 14 and 10% respectively. TRPV1-/ASIC3+ neurons made up between 44% (lung and 48% (pleura of neurons, and half of them presumably conducted in the A-fibre range (larger soma, neurofilament 68-positive. Conclusion Rat pleural and pulmonary spinal afferents express at least two different acid-sensitive channels that make them suitable to monitor tissue acidification. Patterns of co-expression and structural markers define neuronal subgroups that can be inferred to subserve different functions and may initiate specific reflex responses. The higher prevalence of TRPV1+/ASIC3- neurons among pleural afferents probably reflects the high sensitivity of the parietal pleura to painful stimuli.

Altered brain morphometry in carpal tunnel syndrome is associated with median nerve pathology☆☆☆

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Maeda, Yumi; Kettner, Norman; Sheehan, James; Kim, Jieun; Cina, Stephen; Malatesta, Cristina; Gerber, Jessica; McManus, Claire; Mezzacappa, Pia; Morse, Leslie R.; Audette, Joseph; Napadow, Vitaly

2013-01-01

Objective Carpal tunnel syndrome (CTS) is a common median nerve entrapment neuropathy characterized by pain, paresthesias, diminished peripheral nerve conduction velocity (NCV) and maladaptive functional brain neuroplasticity. We evaluated structural reorganization in brain gray matter (GM) and white matter (WM) and whether such plasticity is linked to altered median nerve function in CTS. Methods We performed NCV testing, T1-weighted structural MRI, and diffusion tensor imaging (DTI) in 28 CTS and 28 age-matched healthy controls (HC). Voxel-based morphometry (VBM) contrasted regional GM volume for CTS versus HC. Significant clusters were correlated with clinical metrics and served as seeds to define associated WM tracts using DTI data and probabilistic tractography. Within these WM tracts, fractional anisotropy (FA), axial (AD) and radial (RD) diffusivity were evaluated for group differences and correlations with clinical metrics. Results For CTS subjects, GM volume was significantly reduced in contralesional S1 (hand-area), pulvinar and frontal pole. GM volume in contralesional S1 correlated with median NCV. NCV was also correlated with RD and was negatively correlated with FA within U-fiber cortico-cortical association tracts identified from the contralesional S1 VBM seed. Conclusions Our study identified clear morphometric changes in the CTS brain. This central morphometric change is likely secondary to peripheral nerve pathology and altered somatosensory afference. Enhanced axonal coherence and myelination within cortico-cortical tracts connecting primary somatosensory and motor areas may accompany peripheral nerve deafferentation. As structural plasticity was correlated with NCV and not symptomatology, the former may be a better determinant of appropriate clinical intervention for CTS, including surgery. PMID:23799199

Unmyelinated tactile cutaneous nerves signal erotic sensations.

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Jönsson, Emma H; Backlund Wasling, Helena; Wagnbeck, Vicktoria; Dimitriadis, Menelaos; Georgiadis, Janniko R; Olausson, Håkan; Croy, Ilona

2015-06-01

Intrapersonal touch is a powerful tool for communicating emotions and can among many things evoke feelings of eroticism and sexual arousal. The peripheral neural mechanisms of erotic touch signaling have been less studied. C tactile afferents (unmyelinated low-threshold mechanoreceptors), known to underpin pleasant aspects of touch processing, have been posited to play an important role. In two studies, we investigated the relationship between C tactile activation and the perception of erotic and pleasant touch, using tactile brushing stimulation. In total, 66 healthy subjects (37 women, age range 19-51 years) were examined. In study 1 (n = 20), five different stroking velocities were applied to the forearm and the inner thigh. The participants answered questions about partnership, mood, and touch. In study 2 (n = 46), the same five stroking velocities were applied to the forearm. The participants answered questions about partnership, touch, and sexuality. Both touch eroticism and pleasantness were rated significantly higher for C tactile optimal velocities compared with suboptimal velocities. No difference was found between the ratings of the thigh and the forearm. The velocity-dependent rating curves of pleasantness, intensity, and eroticism differed from each other. Pleasantness was best explained by a quadratic fit, intensity by a linear fit, and eroticism by both. A linear transformation of pleasantness and intensity predicted the observed eroticism ratings reliably. Eroticism ratings were negatively correlated with length of relationship. Touch was rated most erotic when perceived as pleasant and weak. In human hairy skin, perception of pleasantness is correlated with the firing rate of C tactile afferents, and perception of intensity is correlated with the firing rate of Aβ afferents. Accordingly, eroticism may be perceived most readily for touch stimuli that induce high activity in C tactile fibers and low activity in Aβ fibers. © 2015 International

Fine structure of primary afferent axon terminals projecting from rapidly adapting mechanoreceptors of the toe and foot pads of the cat.

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Maxwell, D J; Bannatyne, B A; Fyffe, R E; Brown, A G

1984-04-01

Two Pacinian corpuscle afferents and two rapidly adapting afferents from Krause corpuscles were intra-axonally labelled with horseradish peroxidase in the lumbosacral enlargement of the cat's spinal cord. Tissue was prepared for combined light and electron microscopical analysis. Boutons from both classes of afferent had similar ultrastructural appearances. They both formed from one to three synaptic junctions with dendritic shafts and spines and received axo-axonic synapses. In addition, both categories of bouton were seen to be presynaptic to structures interpreted as vesicle-containing dendrites. It is concluded that both types of afferent fibre are subject to presynaptic control and that they synapse with dorsal horn neurones which are possibly interneurones involved in primary afferent depolarization and post-synaptic dorsal column neurones.

Selective detrusor activation by electrical sacral nerve root stimulation in spinal cord injury

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Rijkhoff, N. J.; Wijkstra, H.; van Kerrebroeck, P. E.; Debruyne, F. M.

1997-01-01

Electrical sacral nerve root stimulation can be used in spinal cord injury patients to induce urinary bladder contraction. However, existing stimulation methods activate simultaneously both the detrusor muscle and the urethral sphincter. Urine evacuation is therefore only possible using poststimulus

Vagus nerve stimulation inhibits activation of coagulation and fibrinolysis during endotoxemia in rats

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van Westerloo, D. J.; Giebelen, I. A. J.; Meijers, J. C. M.; Daalhuisen, J.; de Vos, A. F.; Levi, M. [=Marcel M.; van der Poll, T.

2006-01-01

BACKGROUND: Sepsis and endotoxemia are associated with concurrent activation of inflammation and the hemostatic mechanism, which both contribute to organ dysfunction and death. Electrical vagus nerve stimulation (VNS) has been found to inhibit tumor necrosis factor (TNF)-alpha release during

Combined KHFAC + DC nerve block without onset or reduced nerve conductivity after block

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Franke, Manfred; Vrabec, Tina; Wainright, Jesse; Bhadra, Niloy; Bhadra, Narendra; Kilgore, Kevin

2014-10-01

Objective. Kilohertz frequency alternating current (KHFAC) waveforms have been shown to provide peripheral nerve conductivity block in many acute and chronic animal models. KHFAC nerve block could be used to address multiple disorders caused by neural over-activity, including blocking pain and spasticity. However, one drawback of KHFAC block is a transient activation of nerve fibers during the initiation of the nerve block, called the onset response. The objective of this study is to evaluate the feasibility of using charge balanced direct current (CBDC) waveforms to temporarily block motor nerve conductivity distally to the KHFAC electrodes to mitigate the block onset-response. Approach. A total of eight animals were used in this study. A set of four animals were used to assess feasibility and reproducibility of a combined KHFAC + CBDC block. A following randomized study, conducted on a second set of four animals, compared the onset response resulting from KHFAC alone and combined KHFAC + CBDC waveforms. To quantify the onset, peak forces and the force-time integral were measured during KHFAC block initiation. Nerve conductivity was monitored throughout the study by comparing muscle twitch forces evoked by supra-maximal stimulation proximal and distal to the block electrodes. Each animal of the randomized study received at least 300 s (range: 318-1563 s) of cumulative dc to investigate the impact of combined KHFAC + CBDC on nerve viability. Main results. The peak onset force was reduced significantly from 20.73 N (range: 18.6-26.5 N) with KHFAC alone to 0.45 N (range: 0.2-0.7 N) with the combined CBDC and KHFAC block waveform (p conductivity was observed after application of the combined KHFAC + CBDC block relative to KHFAC waveforms. Significance. The distal application of CBDC can significantly reduce or even completely prevent the KHFAC onset response without a change in nerve conductivity.

G-CSF prevents caspase 3 activation in Schwann cells after sciatic nerve transection, but does not improve nerve regeneration.

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Frost, Hanna K; Kodama, Akira; Ekström, Per; Dahlin, Lars B

2016-10-15

Exogenous granulocyte-colony stimulating factor (G-CSF) has emerged as a drug candidate for improving the outcome after peripheral nerve injuries. We raised the question if exogenous G-CSF can improve nerve regeneration following a clinically relevant model - nerve transection and repair - in healthy and diabetic rats. In short-term experiments, distance of axonal regeneration and extent of injury-induced Schwann cell death was quantified by staining for neurofilaments and cleaved caspase 3, respectively, seven days after repair. There was no difference in axonal outgrowth between G-CSF-treated and non-treated rats, regardless if healthy Wistar or diabetic Goto-Kakizaki (GK) rats were examined. However, G-CSF treatment caused a significant 13% decrease of cleaved caspase 3-positive Schwann cells at the lesion site in healthy rats, but only a trend in diabetic rats. In the distal nerve segments of healthy rats a similar trend was observed. In long-term experiments of healthy rats, regeneration outcome was evaluated at 90days after repair by presence of neurofilaments, wet weight of gastrocnemius muscle, and perception of touch (von Frey monofilament testing weekly). The presence of neurofilaments distal to the suture line was similar in G-CSF-treated and non-treated rats. The weight ratio of ipsi-over contralateral gastrocnemius muscles, and perception of touch at any time point, were likewise not affected by G-CSF treatment. In addition, the inflammatory response in short- and long-term experiments was studied by analyzing ED1 stainable macrophages in healthy rats, but in neither case was any attenuation seen at the injury site or distal to it. G-CSF can prevent caspase 3 activation in Schwann cells in the short-term, but does not detectably affect the inflammatory response, nor improve early or late axonal outgrowth or functional recovery. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

End-to-side neurorrhaphy repairs peripheral nerve injury: sensory nerve induces motor nerve regeneration.

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Yu, Qing; Zhang, She-Hong; Wang, Tao; Peng, Feng; Han, Dong; Gu, Yu-Dong

2017-10-01

End-to-side neurorrhaphy is an option in the treatment of the long segment defects of a nerve. It involves suturing the distal stump of the disconnected nerve (recipient nerve) to the side of the intimate adjacent nerve (donor nerve). However, the motor-sensory specificity after end-to-side neurorrhaphy remains unclear. This study sought to evaluate whether cutaneous sensory nerve regeneration induces motor nerves after end-to-side neurorrhaphy. Thirty rats were randomized into three groups: (1) end-to-side neurorrhaphy using the ulnar nerve (mixed sensory and motor) as the donor nerve and the cutaneous antebrachii medialis nerve as the recipient nerve; (2) the sham group: ulnar nerve and cutaneous antebrachii medialis nerve were just exposed; and (3) the transected nerve group: cutaneous antebrachii medialis nerve was transected and the stumps were turned over and tied. At 5 months, acetylcholinesterase staining results showed that 34% ± 16% of the myelinated axons were stained in the end-to-side group, and none of the myelinated axons were stained in either the sham or transected nerve groups. Retrograde fluorescent tracing of spinal motor neurons and dorsal root ganglion showed the proportion of motor neurons from the cutaneous antebrachii medialis nerve of the end-to-side group was 21% ± 5%. In contrast, no motor neurons from the cutaneous antebrachii medialis nerve of the sham group and transected nerve group were found in the spinal cord segment. These results confirmed that motor neuron regeneration occurred after cutaneous nerve end-to-side neurorrhaphy.

Role of the Sympathetic Nervous System and Its Modulation in Renal Hypertension

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Yusuke Sata

2018-03-01

Full Text Available The kidneys are densely innervated with renal efferent and afferent nerves to communicate with the central nervous system. Innervation of major structural components of the kidneys, such as blood vessels, tubules, the pelvis, and glomeruli, forms a bidirectional neural network to relay sensory and sympathetic signals to and from the brain. Renal efferent nerves regulate renal blood flow, glomerular filtration rate, tubular reabsorption of sodium and water, as well as release of renin and prostaglandins, all of which contribute to cardiovascular and renal regulation. Renal afferent nerves complete the feedback loop via central autonomic nuclei where the signals are integrated and modulate central sympathetic outflow; thus both types of nerves form integral parts of the self-regulated renorenal reflex loop. Renal sympathetic nerve activity (RSNA is commonly increased in pathophysiological conditions such as hypertension and chronic- and end-stage renal disease. Increased RSNA raises blood pressure and can contribute to the deterioration of renal function. Attempts have been made to eliminate or interfere with this important link between the brain and the kidneys as a neuromodulatory treatment for these conditions. Catheter-based renal sympathetic denervation has been successfully applied in patients with resistant hypertension and was associated with significant falls in blood pressure and renal protection in most studies performed. The focus of this review is the neural contribution to the control of renal and cardiovascular hemodynamics and renal function in the setting of hypertension and chronic kidney disease, as well as the specific roles of renal efferent and afferent nerves in this scenario and their utility as a therapeutic target.

Afferent Loop Syndrome after Roux-en-Y Total Gastrectomy Caused by Volvulus of the Roux-Limb

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Hideki Katagiri

2016-01-01

Full Text Available Afferent loop syndrome is a rare complication of gastric surgery. An obstruction of the afferent limb can present in various ways. A 73-year-old man presented with one day of persistent abdominal pain, gradually radiating to the back. He had a history of total gastrectomy with a Roux-en-Y reconstruction. Abdominal computed tomography scan revealed dilation of the duodenum and small intestine in the left upper quadrant. Exploratory laparotomy showed volvulus of the biliopancreatic limb that caused afferent loop syndrome. In this patient, the 50 cm long limb was the cause of volvulus. It is important to fashion a Roux-limb of appropriate length to prevent this complication.

Right-sided vagus nerve stimulation inhibits induced spinal cord seizures.

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Tubbs, R Shane; Salter, E George; Killingsworth, Cheryl; Rollins, Dennis L; Smith, William M; Ideker, Raymond E; Wellons, John C; Blount, Jeffrey P; Oakes, W Jerry

2007-01-01

We have previously shown that left-sided vagus nerve stimulation results in cessation of induced spinal cord seizures. To test our hypothesis that right-sided vagus nerve stimulation will also abort seizure activity, we have initiated seizures in the spinal cord and then performed right-sided vagus nerve stimulation in an animal model. Four pigs were anesthetized and placed in the lateral position and a small laminectomy performed in the lumbar region. Topical penicillin, a known epileptogenic drug to the cerebral cortex and spinal cord, was next applied to the dorsal surface of the exposed cord. With the exception of the control animal, once seizure activity was discernible via motor convulsion or increased electrical activity, the right vagus nerve previously isolated in the neck was stimulated. Following multiple stimulations of the vagus nerve and with seizure activity confirmed, the cord was transected in the midthoracic region and vagus nerve stimulation performed. Right-sided vagus nerve stimulation resulted in cessation of spinal cord seizure activity in all animals. Transection of the spinal cord superior to the site of seizure induction resulted in the ineffectiveness of vagus nerve stimulation in causing cessation of seizure activity in all study animals. As with left-sided vagus nerve stimulation, right-sided vagus nerve stimulation results in cessation of induced spinal cord seizures. Additionally, the effects of right-sided vagus nerve stimulation on induced spinal cord seizures involve descending spinal pathways. These data may aid in the development of alternative mechanisms for electrical stimulation for patients with medically intractable seizures and add to our knowledge regarding the mechanism for seizure cessation following peripheral nerve stimulation.

Effect of Atorvastatin vs. Rosuvastatin on cardiac sympathetic nerve activity in non-diabetic patients with dilated cardiomyopathy

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Tsutamoto, Takayoshi; Ibe, Kunihiro [Toyosato Hospital, Toyosato, Shiga (Japan); Sakai, Hiroshi; Yamaji, Masayuki; Kawahara, Chiho; Nakae, Ichiro; Fujii, Masanori; Yamamoto, Takashi; Horie, Minoru [Shiga Univ. of Medical Science, Faculty of Medicine, Otsu, Shiga (Japan)

2011-08-15

Effects of statin therapy on cardiac sympathetic nerve activity in patients with chronic heart failure (CHF) have not previously been evaluated. To compare the effects of lipophilic atorvastatin and hydrophilic rosuvastatin on cardiac sympathetic nerve activity in CHF patients with dilated cardiomyopathy (DCM), 63 stable outpatients with DCM, who were already receiving standard therapy for CHF, were randomized to atorvastatin (n=32) or rosuvastatin (n=31). We evaluated cardiac sympathetic nerve activity by cardiac {sup 123}I-metaiodobenzylguanidine (MIBG) scintigraphy, hemodynamic parameters and neurohumoral factors before and after 6 months of treatment. There were no differences in the baseline characteristics of the 2 groups. In the rosuvastatin group, there were no changes in MIBG parameters, left ventricular ejection fraction or plasma levels of N-terminal pro-B-type natriuretic peptide (NT-proBNP) after 6 months of treatment. In contrast, the atorvastatin group showed a significant increase in the delayed heart/mediastinum count ratio (2.18{+-}0.4 vs. 2.36{+-}0.4, P<0.0001), and the washout rate was significantly decreased (34.8{+-}5.7 vs. 32.6{+-}6.3%, P=0.0001) after 6 months of treatment compared with the baseline values. The plasma NT-proBNP level was also significantly decreased (729{+-}858 vs. 558{+-}747 pg/ml, P=0.0139). Lipophilic atorvastatin but not hydrophilic rosuvastatin improves cardiac sympathetic nerve activity in CHF patients with DCM. (author)

Protease signaling through protease activated receptor 1 mediate nerve activation by mucosal supernatants from irritable bowel syndrome but not from ulcerative colitis patients.

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Buhner, Sabine; Hahne, Hannes; Hartwig, Kerstin; Li, Qin; Vignali, Sheila; Ostertag, Daniela; Meng, Chen; Hörmannsperger, Gabriele; Braak, Breg; Pehl, Christian; Frieling, Thomas; Barbara, Giovanni; De Giorgio, Roberto; Demir, Ihsan Ekin; Ceyhan, Güralp Onur; Zeller, Florian; Boeckxstaens, Guy; Haller, Dirk; Kuster, Bernhard; Schemann, Michael

2018-01-01

The causes of gastrointestinal complaints in irritable bowel syndrome (IBS) remain poorly understood. Altered nerve function has emerged as an important pathogenic factor as IBS mucosal biopsy supernatants consistently activate enteric and sensory neurons. We investigated the neurally active molecular components of such supernatants from patients with IBS and quiescent ulcerative colitis (UC). Effects of supernatants from 7 healthy controls (HC), 20 IBS and 12 UC patients on human and guinea pig submucous neurons were studied with neuroimaging techniques. We identify differentially expressed proteins with proteome analysis. Nerve activation by IBS supernatants was prevented by the protease activated receptor 1 (PAR1) antagonist SCHE79797. UC supernatants also activated enteric neurons through protease dependent mechanisms but without PAR1 involvement. Proteome analysis of the supernatants identified 204 proteins, among them 17 proteases as differentially expressed between IBS, UC and HC. Of those the four proteases elastase 3a, chymotrypsin C, proteasome subunit type beta-2 and an unspecified isoform of complement C3 were significantly more abundant in IBS compared to HC and UC supernatants. Of eight proteases, which were upregulated in IBS, the combination of elastase 3a, cathepsin L and proteasome alpha subunit-4 showed the highest prediction accuracy of 98% to discriminate between IBS and HC groups. Elastase synergistically potentiated the effects of histamine and serotonin-the two other main neuroactive substances in the IBS supernatants. A serine protease inhibitor isolated from the probiotic Bifidobacterium longum NCC2705 (SERPINBL), known to inhibit elastase-like proteases, prevented nerve activation by IBS supernatants. Proteases in IBS and UC supernatants were responsible for nerve activation. Our data demonstrate that proteases, particularly those signalling through neuronal PAR1, are biomarker candidates for IBS, and protease profiling may be used to

Renal sympathetic nerve ablation for treatment-resistant hypertension

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Krum, Henry; Schlaich, Markus; Sobotka, Paul

2013-01-01

Hypertension is a major risk factor for increased cardiovascular events with accelerated sympathetic nerve activity implicated in the pathogenesis and progression of disease. Blood pressure is not adequately controlled in many patients, despite the availability of effective pharmacotherapy. Novel procedure- as well as device-based strategies, such as percutaneous renal sympathetic nerve denervation, have been developed to improve blood pressure in these refractory patients. Renal sympathetic denervation not only reduces blood pressure but also renal as well as systemic sympathetic nerve activity in such patients. The reduction in blood pressure appears to be sustained over 3 years after the procedure, which suggests absence of re-innervation of renal sympathetic nerves. Safety appears to be adequate. This approach may also have potential in other disorders associated with enhanced sympathetic nerve activity such as congestive heart failure, chronic kidney disease and metabolic syndrome. This review will focus on the current status of percutaneous renal sympathetic nerve denervation, clinical efficacy and safety outcomes and prospects beyond refractory hypertension. PMID:23819768

Negative temperature coefficient of the action of DDT in a sense organ

NARCIS (Netherlands)

Bercken, J. van den; Akkermans, L.M.A.

1972-01-01

DDT induced repetitive spontaneuos activity inthe afferent nerve fibers of the lateral-line organ of the clawed toad, Xenopus laevis. The action of DDT increased markedly with lowered temperature. This temperature-effect was easily reversible. The results demonstrate that DDT has a definite negative

Slow and deep respiration suppresses steady-state sympathetic nerve activity in patients with chronic heart failure: from modeling to clinical application.

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Harada, Daisuke; Asanoi, Hidetsugu; Takagawa, Junya; Ishise, Hisanari; Ueno, Hiroshi; Oda, Yoshitaka; Goso, Yukiko; Joho, Shuji; Inoue, Hiroshi

2014-10-15

Influences of slow and deep respiration on steady-state sympathetic nerve activity remain controversial in humans and could vary depending on disease conditions and basal sympathetic nerve activity. To elucidate the respiratory modulation of steady-state sympathetic nerve activity, we modeled the dynamic nature of the relationship between lung inflation and muscle sympathetic nerve activity (MSNA) in 11 heart failure patients with exaggerated sympathetic outflow at rest. An autoregressive exogenous input model was utilized to simulate entire responses of MSNA to variable respiratory patterns. In another 18 patients, we determined the influence of increasing tidal volume and slowing respiratory frequency on MSNA; 10 patients underwent a 15-min device-guided slow respiration and the remaining 8 had no respiratory modification. The model predicted that a 1-liter, step increase of lung volume decreased MSNA dynamically; its nadir (-33 ± 22%) occurred at 2.4 s; and steady-state decrease (-15 ± 5%), at 6 s. Actually, in patients with the device-guided slow and deep respiration, respiratory frequency effectively fell from 16.4 ± 3.9 to 6.7 ± 2.8/min (P state MSNA was decreased by 31% (P state MSNA. Thus slow and deep respiration suppresses steady-state sympathetic nerve activity in patients with high levels of resting sympathetic tone as in heart failure. Copyright © 2014 the American Physiological Society.

Measurement of the relative afferent pupillary defect in retinal detachment.

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Bovino, J A; Burton, T C

1980-07-01

A swinging flashlight test and calibrated neutral density filters were used to quantitate the depth of relative afferent pupillary defects in ten patients with retinal detachment. Postoperatively, the pupillary responses returned to normal in seven of nine patients with anatomically successful surgery.

Deficient functional recovery after facial nerve crush in rats is associated with restricted rearrangements of synaptic terminals in the facial nucleus.

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Hundeshagen, G; Szameit, K; Thieme, H; Finkensieper, M; Angelov, D N; Guntinas-Lichius, O; Irintchev, A

2013-09-17

Crush injuries of peripheral nerves typically lead to axonotmesis, axonal damage without disruption of connective tissue sheaths. Generally, human patients and experimental animals recover well after axonotmesis and the favorable outcome has been attributed to precise axonal reinnervation of the original peripheral targets. Here we assessed functionally and morphologically the long-term consequences of facial nerve axonotmesis in rats. Expectedly, we found that 5 months after crush or cryogenic nerve lesion, the numbers of motoneurons with regenerated axons and their projection pattern into the main branches of the facial nerve were similar to those in control animals suggesting precise target reinnervation. Unexpectedly, however, we found that functional recovery, estimated by vibrissal motion analysis, was incomplete at 2 months after injury and did not improve thereafter. The maximum amplitude of whisking remained substantially, by more than 30% lower than control values even 5 months after axonotmesis. Morphological analyses showed that the facial motoneurons ipsilateral to injury were innervated by lower numbers of glutamatergic terminals (-15%) and cholinergic perisomatic boutons (-26%) compared with the contralateral non-injured motoneurons. The structural deficits were correlated with functional performance of individual animals and associated with microgliosis in the facial nucleus but not with polyinnervation of muscle fibers. These results support the idea that restricted CNS plasticity and insufficient afferent inputs to motoneurons may substantially contribute to functional deficits after facial nerve injuries, possibly including pathologic conditions in humans like axonotmesis in idiopathic facial nerve (Bell's) palsy. Copyright © 2013 IBRO. Published by Elsevier Ltd. All rights reserved.

Superoxide Anions and NO in the Paraventricular Nucleus Modulate the Cardiac Sympathetic Afferent Reflex in Obese Rats

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Qing-Bo Lu

2017-12-01

Full Text Available This study was conducted to explore the hypothesis that the endogenous superoxide anions (O2− and nitric oxide (NO system of the paraventricular nucleus (PVN regulates the cardiac sympathetic afferent reflex (CSAR contributing to sympathoexcitation in obese rats induced by a high-fat diet (42% kcal as fat for 12 weeks. CSAR was evaluated by monitoring the changes of renal sympathetic nerve activity (RSNA and the mean arterial pressure (MAP responses to the epicardial application of capsaicin (CAP in anaesthetized rats. In obese rats with hypertension (OH group or without hypertension (OB group, the levels of PVN O2−, angiotensinII (Ang II, Ang II type 1 receptor (AT1R, and nicotinamide adenine dinucleotide phosphate (NADPH oxidase were elevated, whereas neural NO synthase (nNOS and NO were significantly reduced. Moreover, CSAR was markedly enhanced, which promoted the elevation of plasma norepinephrine levels. The enhanced CSAR was attenuated by PVN application of the superoxide scavenger polyethylene glycol-superoxide dismutase (PEG-SOD and the NO donor sodium nitroprusside (SNP, and was strengthened by the superoxide dismutase inhibitor diethyldithiocarbamic acid (DETC and the nNOS inhibitor N(ω-propyl-l-arginine hydrochloride (PLA; conversely, there was a smaller CSAR response to PLA or SNP in rats that received a low-fat (12% kcal diet. Furthermore, PVN pretreatment with the AT1R antagonist losartan or with PEG-SOD, but not SNP, abolished Ang II-induced CSAR enhancement. These findings suggest that obesity alters the PVN O2− and NO system that modulates CSAR and promotes sympathoexcitation.

Afferent and Efferent Connections of the Cortex-Amygdala Transition Zone in Mice.

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Cádiz-Moretti, Bernardita; Abellán-Álvaro, María; Pardo-Bellver, Cecília; Martínez-García, Fernando; Lanuza, Enrique

2016-01-01

The transitional zone between the ventral part of the piriform cortex and the anterior cortical nucleus of the amygdala, named the cortex-amygdala transition zone (CxA), shows two differential features that allow its identification as a particular structure. First, it receives dense cholinergic and dopaminergic innervations as compared to the adjacent piriform cortex and amygdala, and second, it receives projections from the main and accessory olfactory bulbs. In this work we have studied the pattern of afferent and efferent projections of the CxA, which are mainly unknown, by using the retrograde tracer Fluorogold and the anterograde tracer biotinylated dextranamine. The results show that the CxA receives a relatively restricted set of intratelencephalic connections, originated mainly by the olfactory system and basal forebrain, with minor afferents from the amygdala. The only relevant extratelencephalic afference originates in the ventral tegmental area (VTA). The efferent projections of the CxA reciprocate the inputs from the piriform cortex and olfactory amygdala. In addition, the CxA projects densely to the basolateral amygdaloid nucleus and the olfactory tubercle. The extratelencephalic projections of the CxA are very scarce, and target mainly hypothalamic structures. The pattern of connections of the CxA suggests that it is indeed a transitional area between the piriform cortex and the cortical amygdala. Double labeling with choline acetyltransferase indicates that the afferent projection from the basal forebrain is the origin of its distinctive cholinergic innervation, and double labeling with dopamine transporter shows that the projection from the VTA is the source of dopaminergic innervation. These connectivity and neurochemical features, together with the fact that it receives vomeronasal in addition to olfactory information, suggest that the CxA may be involved in processing olfactory information endowed with relevant biological meaning, such as odors

More sensitive correlation of afferent pupillary defect with ganglion cell complex

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Eulogio Besada

2018-04-01

Full Text Available Purpose: This study investigated the correlation between the relative afferent pupillary defect (RAPD and retinal nerve fiber layer thickness (RNFLT in optic neuropathy. Methods: RAPD assessment was performed using a log unit neutral density filter bar. Spectral domain optical coherence tomography RTVue-100 (Optovue was used to examine the subjects. The optic nerve head pattern (ONH was subdivided and identified for the purpose of the study into circumpapillary RNFLT (cpRNFLT and peripheral circumpapillary RNFLT (pcpRNFLT. The cpRNFLT, pcpRNFLT and ganglion cell complex (GCC parameters were analyzed. Results: Eighteen females and twenty three males with asymmetric optic neuropathy and a RAPD participated. Thirty-three subjects had glaucoma and eight had optic neuropathy other than glaucoma. Significant correlations (p < 0.02 were obtained for the RAPD and the percentage difference loss of the GCC and RNFLT parameters. The grouped mean percentage difference loss for RNFLT was significantly different from that of the GCC (p < 0.001. At a 0.6 log unit RAPD, the average mean percentage difference loss was 23% for the CRNFLT, 15% for the GCC, 12% for the global loss volume percentage and 6% for the focal loss volume percentage (FLV%. Conclusions: Significant correlations between RNFLT loss for cpRNFLT, pcpRNFLT and GCC parameters with RAPD were observed. Approximately a 35% higher sensitivity was obtained using GCC compared to CRNFL parameters. The expected change in GCC average for every 0.3 log unit increment was approximately 8.49 μm. The FLV% corresponded more sensitively to a RAPD but appeared to be influenced by disease severity. Resumen: Objetivo: Este estudio investigó la correlación entre el defecto pupilar aferente relativo (DPAR y el grosor de la capa de fibras nerviosas de la retina (RNFLT en la neuropatía óptica. Métodos: La valoración del DPAR se realizó utilizando una barra de filtro de densidad neutra de unidades logar

Influence of limb temperature on cutaneous silent periods.

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Kofler, Markus; Valls-Solé, Josep; Vasko, Peter; Boček, Václav; Štetkárová, Ivana

2014-09-01

The cutaneous silent period (CSP) is a spinal inhibitory reflex mediated by small-diameter afferents (A-delta fibers) and large-diameter efferents (alpha motoneurons). The effect of limb temperature on CSPs has so far not been assessed. In 27 healthy volunteers (11 males; age 22-58 years) we recorded median nerve motor and sensory action potentials, median nerve F-wave and CSPs induced by noxious digit II stimulation in thenar muscles in a baseline condition at room temperature, and after randomly submersing the forearm in 42 °C warm or 15 °C cold water for 20 min each. In cold limbs, distal and proximal motor and sensory latencies as well as F-wave latencies were prolonged. Motor and sensory nerve conduction velocities were reduced. Compound motor and sensory nerve action potential amplitudes did not differ significantly from baseline. CSP onset and end latencies were more delayed than distal and proximal median nerve motor and sensory latencies, whereas CSP duration was not affected. In warm limbs, opposite but smaller changes were seen in nerve conduction studies and CSPs. The observed CSP shift "en bloc" towards longer latencies without affecting CSP duration during limb cooling concurs with slower conduction velocity in both afferent and efferent fibers. Disparate conduction slowing in afferents and efferents, however, suggests that nociceptive EMG suppression is mediated by fibers of different size in the afferent than in the efferent arm, indirectly supporting the contribution of A-delta fibers as the main afferent input. Limb temperature should be taken into account when testing CSPs in the clinical setting, as different limb temperatures affect CSP latencies more than large-diameter fiber conduction function. Copyright © 2014 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

Absence of synergy for monosynaptic Group I inputs between abdominal and internal intercostal motoneurons

DEFF Research Database (Denmark)

Ford, T W; Meehan, Claire Francesca; Kirkwood, P A

2014-01-01

Internal intercostal and abdominal motoneurons are strongly coactivated during expiration. We investigated whether that synergy was paralleled by synergistic Group I reflex excitation. Intracellular recordings were made from motoneurons of the internal intercostal nerve of T8 in anesthetized cats...... that are synergistically activated in expiration leads us to conclude that such connections from muscle spindle afferents of the thoracic nerves have little role in controlling expiratory movements but, where present, support other motor acts....

Phrenicotomy alters phrenic long-term facilitation following intermittent hypoxia in anesthetized rats

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Sandhu, M. S.; Lee, K. Z.; Fregosi, R. F.; Fuller, D. D.

2010-01-01

Intermittent hypoxia (IH) can induce a persistent increase in neural drive to the respiratory muscles known as long-term facilitation (LTF). LTF of phrenic inspiratory activity is often studied in anesthetized animals after phrenicotomy (PhrX), with subsequent recordings being made from the proximal stump of the phrenic nerve. However, severing afferent and efferent axons in the phrenic nerve has the potential to alter the excitability of phrenic motoneurons, which has been hypothesized to be...

Kv1 channels and neural processing in vestibular calyx afferents

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Frances L Meredith

2015-06-01

Full Text Available Potassium-selective ion channels are important for accurate transmission of signals from auditory and vestibular sensory end organs to their targets in the central nervous system. During different gravity conditions, astronauts experience altered input signals from the peripheral vestibular system resulting in sensorimotor dysfunction. Adaptation to altered sensory input occurs, but it is not explicitly known whether this involves synaptic modifications within the vestibular epithelia. Future investigations of such potential plasticity require a better understanding of the electrophysiological mechanisms underlying the known heterogeneity of afferent discharge under normal conditions. This study advances this understanding by examining the role of the Kv1 potassium channel family in mediating action potentials in specialized vestibular afferent calyx endings in the gerbil crista and utricle. Pharmacological agents selective for different sub-types of Kv1 channels were tested on membrane responses in whole cell recordings in the crista. Kv1 channels sensitive to α-dendrotoxin and dendrotoxin-K were found to prevail in the central regions, whereas K+ channels sensitive to margatoxin, which blocks Kv1.3 and 1.6 channels, were more prominent in peripheral regions. Margatoxin-sensitive currents showed voltage-dependent inactivation. Dendrotoxin-sensitive currents showed no inactivation and dampened excitability in calyces in central neuroepithelial regions. The differential distribution of Kv1 potassium channels in vestibular afferents supports their importance in accurately relaying gravitational and head movement signals through specialized lines to the central nervous system. Pharmacological modulation of specific groups of K+ channels could help alleviate vestibular dysfunction on earth and in space.

Kv1 channels and neural processing in vestibular calyx afferents.

Science.gov (United States)

Meredith, Frances L; Kirk, Matthew E; Rennie, Katherine J

2015-01-01

Potassium-selective ion channels are important for accurate transmission of signals from auditory and vestibular sensory end organs to their targets in the central nervous system. During different gravity conditions, astronauts experience altered input signals from the peripheral vestibular system resulting in sensorimotor dysfunction. Adaptation to altered sensory input occurs, but it is not explicitly known whether this involves synaptic modifications within the vestibular epithelia. Future investigations of such potential plasticity require a better understanding of the electrophysiological mechanisms underlying the known heterogeneity of afferent discharge under normal conditions. This study advances this understanding by examining the role of the Kv1 potassium channel family in mediating action potentials in specialized vestibular afferent calyx endings in the gerbil crista and utricle. Pharmacological agents selective for different sub-types of Kv1 channels were tested on membrane responses in whole cell recordings in the crista. Kv1 channels sensitive to α-dendrotoxin and dendrotoxin-K were found to prevail in the central regions, whereas K(+) channels sensitive to margatoxin, which blocks Kv1.3 and 1.6 channels, were more prominent in peripheral regions. Margatoxin-sensitive currents showed voltage-dependent inactivation. Dendrotoxin-sensitive currents showed no inactivation and dampened excitability in calyces in central neuroepithelial regions. The differential distribution of Kv1 potassium channels in vestibular afferents supports their importance in accurately relaying gravitational and head movement signals through specialized lines to the central nervous system. Pharmacological modulation of specific groups of K(+) channels could help alleviate vestibular dysfunction on earth and in space.

Should we routinely expose recurrent laryngeal nerve(s) during thyroid surgery

International Nuclear Information System (INIS)

Ahmed, M.; Aurangzeb, A.; Rashid, A.Z.; Qureshi, M.A.; Iqbal, N.; Boota, M.; Ashfaq, M.

2013-01-01

Objective: To compare the frequency of recurrent laryngeal nerve(s) (RLNs) palsy after various thyroid procedures with and without identification of recurrent laryngeal nerve during the operation. Study Design: Randomized controlled trial. Place and Duration of Study: Department of Surgery, Military Hospital, Rawalpindi, from August 2008 to April 2010. Methodology: Patients undergoing indirect laryngoscopy with normal vocal cords and those with carcinoma and re-do surgery having normal vocal cord were included in the study. Patients with hoarseness of voice, abnormal vocal cord movements and with solitary nodule in the isthmus were excluded. These patients were randomly divided into 2 groups of 50 each using random number tables. RLN was identified by exposing the inferior thyroid artery and traced along its entire course in group-A. Whereas, in group-B, nerves were not identified during the operations. Immediate postoperative direct laryngoscopy was performed by a surgeon with the help of an anaesthesiologist for the assessment of vocal cords. Patients with persistent hoarseness of voice were followed-up with indirect laryngoscopy at 3 and 6 months. Results: Temporary unilateral recurrent laryngeal nerve palsies occurred in 2 (4%) patients in group-A where the voice and cord movements returned to normal in 6 months. In group-B, it occurred in 8 (16%) patients, 2 bilateral (4%) injuries requiring tracheostomy and 6 unilateral injuries (12%). Among the 2 bilateral recurrent laryngeal nerve injuries, the tracheostomy was removed in one case after 6 months with persistent hoarseness of voice but no respiratory difficulty during routine activities. Tracheostomy was permanent in the other case. Among the 6 cases of unilateral nerve injuries, the voice improved considerably in 4 cases within 6 months but in 2 cases hoarseness persisted even after 6 months. Frequency of recurrent laryngeal nerve palsies was significantly lower in group-A as compared to group-B (p = 0

Afferent projections to the pontine micturition center in the cat

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Kuipers, R; Mouton, LJ; Holstege, G; Kuiper, Rutger

2006-01-01

The pontine micturition center (PMC) or Barrington's nucleus controls micturition by way of its descending projections to the sacral spinal cord. However, little is known about the afferents to the PMC that control its function and may be responsible for dysfunction in patients with

Reconstruction of facial nerve injuries in children.

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Fattah, Adel; Borschel, Gregory H; Zuker, Ron M

2011-05-01

Facial nerve trauma is uncommon in children, and many spontaneously recover some function; nonetheless, loss of facial nerve activity leads to functional impairment of ocular and oral sphincters and nasal orifice. In many cases, the impediment posed by facial asymmetry and reduced mimetic function more significantly affects the child's psychosocial interactions. As such, reconstruction of the facial nerve affords great benefits in quality of life. The therapeutic strategy is dependent on numerous factors, including the cause of facial nerve injury, the deficit, the prognosis for recovery, and the time elapsed since the injury. The options for treatment include a diverse range of surgical techniques including static lifts and slings, nerve repairs, nerve grafts and nerve transfers, regional, and microvascular free muscle transfer. We review our strategies for addressing facial nerve injuries in children.

Catheter based radiofrequency ablation of renal nerves for the treatment of resistant hypertension

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Markus P. Schlaich

2013-03-01

Full Text Available Introduction Resistant hypertension is a common and growing clinical problem characterized by the failure to attain target blood pressure levels despite adequate use of at least three antihypertensive agents. Objectives The aim of this article is to emphasize the role of novel approaches to treat resistant hypertension. Materials and methods After an excursus on the physiological role of renal nerves on kidney function, volume homeostasis and blood pressure control, this article describes the radiofrequency ablation technology to obtain kidneys denervation. Results Activation of the sympathetic nervous system plays a prominent role as a major regulator of circulatory and metabolic control. The kidneys have a particularly dense afferent sensory and efferent sympathetic innervation and are thereby strategically positioned to be origin as well as target of sympathetic activation. In this context, recent evidence suggests that a novel catheter-based approach to functionally denervate the human kidneys using radiofrequency ablation technology may provide a safe and effective treatment alternative for resistant hypertension and its adverse consequences. Conclusions Despite the availability of numerous safe and effective pharmacological therapies to treat elevated blood pressure, novel therapeutic approaches are warranted to improve the management and prognosis of patients with refractory hypertension. Several clinical trials are currently conducted and planned to further substantiate the blood pressure lowering efficacy of this novel renal denervation procedure.

Anodal Direct Current Stimulation of the Cerebellum Reduces Cerebellar Brain Inhibition but Does Not Influence Afferent Input from the Hand or Face in Healthy Adults.

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Doeltgen, Sebastian H; Young, Jessica; Bradnam, Lynley V

2016-08-01

The cerebellum controls descending motor commands by outputs to primary motor cortex (M1) and the brainstem in response to sensory feedback. The cerebellum may also modulate afferent input en route to M1 and the brainstem. The objective of this study is to determine if anodal transcranial direct current stimulation (tDCS) to the cerebellum influences cerebellar brain inhibition (CBI), short afferent inhibition (SAI) and trigeminal reflexes (TRs) in healthy adults. Data from two studies evaluating effects of cerebellar anodal and sham tDCS are presented. The first study used a twin coil transcranial magnetic stimulation (TMS) protocol to investigate CBI and combined TMS and cutaneous stimulation of the digit to assess SAI. The second study evaluated effects on trigemino-cervical and trigemino-masseter reflexes using peripheral nerve stimulation of the face. Fourteen right-handed healthy adults participated in experiment 1. CBI was observed at baseline and was reduced by anodal cerebellar DCS only (P < 0.01). There was SAI at interstimulus intervals of 25 and 30 ms at baseline (both P < 0.0001), but cerebellar tDCS had no effect. Thirteen right-handed healthy adults participated in experiment 2. Inhibitory reflexes were evoked in the ipsilateral masseter and sternocleidomastoid muscles. There was no effect of cerebellar DCS on either reflex. Anodal DCS reduced CBI but did not change SAI or TRs in healthy adults. These results require confirmation in individuals with neurological impairment.

The urodelean Mauthner cell. Morphology of the afferent synapses to the M-cell of larval Salamandra salamandra

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Cioni, C.; De Palma, F.; De Vito, L.; Stefanelli, A. [Rome, Univ. (Italy). Dipt. di Biologia Animale e dell`Uomo

1997-12-31

In the present work the fine morphology and the distribution of the afferent synapses to the Mauthner cell of larval Salamandra salamandra are described. The aim of the study is to characterize the synaptic bed in the larvae of this terrestrial salamander in order to compare it with that of larval axolotl and larval anurans. Four main types of afferent endings have been identified: myelinated club endings, round-vesicle end bulbs, flattened-vesicle end bulbs and spiral fibers endings. The M-cell afferent synaptology of larval stages of terrestrial amphibians is quite similar to that previously observed in larval stages of aquatic species. This fact can be related to the fundamental similarities between the larval lifestyles.

The urodelean Mauthner cell. Morphology of the afferent synapses to the M-cell of larval Salamandra salamandra

Energy Technology Data Exchange (ETDEWEB)

Cioni, C; De Palma, F; De Vito, L; Stefanelli, A [Rome, Univ. (Italy). Dipt. di Biologia Animale e dell` Uomo

1998-12-31

In the present work the fine morphology and the distribution of the afferent synapses to the Mauthner cell of larval Salamandra salamandra are described. The aim of the study is to characterize the synaptic bed in the larvae of this terrestrial salamander in order to compare it with that of larval axolotl and larval anurans. Four main types of afferent endings have been identified: myelinated club endings, round-vesicle end bulbs, flattened-vesicle end bulbs and spiral fibers endings. The M-cell afferent synaptology of larval stages of terrestrial amphibians is quite similar to that previously observed in larval stages of aquatic species. This fact can be related to the fundamental similarities between the larval lifestyles.

Sodium Channel Nav1.8 Underlies TTX-Resistant Axonal Action Potential Conduction in Somatosensory C-Fibers of Distal Cutaneous Nerves.

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Klein, Amanda H; Vyshnevska, Alina; Hartke, Timothy V; De Col, Roberto; Mankowski, Joseph L; Turnquist, Brian; Bosmans, Frank; Reeh, Peter W; Schmelz, Martin; Carr, Richard W; Ringkamp, Matthias

2017-05-17

Voltage-gated sodium (Na V ) channels are responsible for the initiation and conduction of action potentials within primary afferents. The nine Na V channel isoforms recognized in mammals are often functionally divided into tetrodotoxin (TTX)-sensitive (TTX-s) channels (Na V 1.1-Na V 1.4, Na V 1.6-Na V 1.7) that are blocked by nanomolar concentrations and TTX-resistant (TTX-r) channels (Na V 1.8 and Na V 1.9) inhibited by millimolar concentrations, with Na V 1.5 having an intermediate toxin sensitivity. For small-diameter primary afferent neurons, it is unclear to what extent different Na V channel isoforms are distributed along the peripheral and central branches of their bifurcated axons. To determine the relative contribution of TTX-s and TTX-r channels to action potential conduction in different axonal compartments, we investigated the effects of TTX on C-fiber-mediated compound action potentials (C-CAPs) of proximal and distal peripheral nerve segments and dorsal roots from mice and pigtail monkeys ( Macaca nemestrina ). In the dorsal roots and proximal peripheral nerves of mice and nonhuman primates, TTX reduced the C-CAP amplitude to 16% of the baseline. In contrast, >30% of the C-CAP was resistant to TTX in distal peripheral branches of monkeys and WT and Na V 1.9 -/- mice. In nerves from Na V 1.8 -/- mice, TTX-r C-CAPs could not be detected. These data indicate that Na V 1.8 is the primary isoform underlying TTX-r conduction in distal axons of somatosensory C-fibers. Furthermore, there is a differential spatial distribution of Na V 1.8 within C-fiber axons, being functionally more prominent in the most distal axons and terminal regions. The enrichment of Na V 1.8 in distal axons may provide a useful target in the treatment of pain of peripheral origin. SIGNIFICANCE STATEMENT It is unclear whether individual sodium channel isoforms exert differential roles in action potential conduction along the axonal membrane of nociceptive, unmyelinated peripheral nerve

Different Mode of Afferents Determines the Frequency Range of High Frequency Activities in the Human Brain: Direct Electrocorticographic Comparison between Peripheral Nerve and Direct Cortical Stimulation.

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Katsuya Kobayashi

Full Text Available Physiological high frequency activities (HFA are related to various brain functions. Factors, however, regulating its frequency have not been well elucidated in humans. To validate the hypothesis that different propagation modes (thalamo-cortical vs. cortico-coritcal projections, or different terminal layers (layer IV vs. layer II/III affect its frequency, we, in the primary somatosensory cortex (SI, compared HFAs induced by median nerve stimulation with those induced by electrical stimulation of the cortex connecting to SI. We employed 6 patients who underwent chronic subdural electrode implantation for presurgical evaluation. We evaluated the HFA power values in reference to the baseline overriding N20 (earliest cortical response and N80 (late response of somatosensory evoked potentials (HFA(SEP(N20 and HFA(SEP(N80 and compared those overriding N1 and N2 (first and second responses of cortico-cortical evoked potentials (HFA(CCEP(N1 and HFA(CCEP(N2. HFA(SEP(N20 showed the power peak in the frequency above 200 Hz, while HFA(CCEP(N1 had its power peak in the frequency below 200 Hz. Different propagation modes and/or different terminal layers seemed to determine HFA frequency. Since HFA(CCEP(N1 and HFA induced during various brain functions share a similar broadband profile of the power spectrum, cortico-coritcal horizontal propagation seems to represent common mode of neural transmission for processing these functions.

β-adrenoceptor agonist effects in experimental models of bladder dysfunction

NARCIS (Netherlands)

Michel, Martin C.; Ochodnicky, Peter; Homma, Yukio; Igawa, Yasuhiko

2011-01-01

β-adrenoceptor stimulation can enhance the storage function of the urinary bladder by acting on detrusor smooth muscle tone, mediator release from the urothelium and/or afferent nerve activity. In humans this may occur predominantly if not exclusively via the β₃-subtype. The effects of

Ultrasound-Guided Phrenic Nerve Block for Intractable Hiccups following Placement of Esophageal Stent for Esophageal Squamous Cell Carcinoma.

Science.gov (United States)

Arsanious, David; Khoury, Spiro; Martinez, Edgar; Nawras, Ali; Filatoff, Gregory; Ajabnoor, Hossam; Darr, Umar; Atallah, Joseph

2016-05-01

Hiccups are actions consisting of sudden contractions of the diaphragm and intercostals followed by a sudden inspiration and transient closure of the vocal cords. They are generally short lived and benign; however, in extreme and rare cases, such as esophageal carcinoma, they can become persistent or intractable, up to and involving significant pain, dramatically impacting the patient's quality of life. This case involves a 60-year-old man with a known history of squamous cell carcinoma of the esophagus. He was considered to have high surgical risk, and therefore he received palliative care through the use of fully covered metallic esophageal self-expandable stents due to a spontaneous perforated esophagus, after which he developed intractable hiccups and associated mediastinal pain. Conservative treatment, including baclofen, chlorpromazine, metoclopramide, and omeprazole, provided no relief for his symptoms. The patient was referred to pain management from gastroenterology for consultation on pain control. He ultimately received an ultrasound-guided left phrenic nerve block with bupivacaine and depomedrol, and 3 days later underwent the identical procedure on the right phrenic nerve. This led to complete resolution of his hiccups and associated mediastinal pain. At follow-up, 2 and 4 weeks after the left phrenic nerve block, the patient was found to maintain complete alleviation of the hiccups. Esophageal dilatation and/or phrenic or vagal afferent fiber irritation can be suspected in cases of intractable hiccups secondary to esophageal stenting. Regional anesthesia of the phrenic nerve through ultrasound guidance offers a long-term therapeutic option for intractable hiccups and associated mediastinal pain in selected patients with esophageal carcinoma after stent placement. Esophageal stent, esophageal stenting, intractable hiccups, intractable singultus, phrenic nerve block, phrenic nerve, ultrasound, palliative care, esophageal carcinoma.

Implantable electrode for recording nerve signals in awake animals

Science.gov (United States)

Ninomiya, I.; Yonezawa, Y.; Wilson, M. F.

1976-01-01

An implantable electrode assembly consisting of collagen and metallic electrodes was constructed to measure simultaneously neural signals from the intact nerve and bioelectrical noises in awake animals. Mechanical artifacts, due to bodily movement, were negligibly small. The impedance of the collagen electrodes, measured in awake cats 6-7 days after implantation surgery, ranged from 39.8-11.5 k ohms at a frequency range of 20-5 kHz. Aortic nerve activity and renal nerve activity, measured in awake conditions using the collagen electrode, showed grouped activity synchronous with the cardiac cycle. Results indicate that most of the renal nerve activity was from postganglionic sympathetic fibers and was inhibited by the baroceptor reflex in the same cardiac cycle.

Cerebellar ataxia, neuropathy, vestibular areflexia syndrome (CANVAS) with chronic cough and preserved muscle stretch reflexes: evidence for selective sparing of afferent Ia fibres.

Science.gov (United States)

Infante, Jon; García, Antonio; Serrano-Cárdenas, Karla M; González-Aguado, Rocío; Gazulla, José; de Lucas, Enrique M; Berciano, José

2018-04-25

The aim of this study was to describe five patients with cerebellar ataxia, neuropathy and vestibular areflexia syndrome (CANVAS) with chronic cough and preserved limb muscle stretch reflexes. All five patients were in the seventh decade of age, their gait imbalance having been initiated in the fifth decade. In four patients cough antedated gait imbalance between 15 and 29 years; cough was spasmodic and triggered by variable factors. Established clinical picture included severe hypopallesthesia predominating in the lower limbs with postural imbalance, and variable degree of cerebellar axial and appendicular ataxia, dysarthria and horizontal gaze-evoked nystagmus. Upper- and lower-limb tendon jerks were preserved, whereas jaw jerk was absent. Vestibular function testing showed bilateral impairment of the vestibulo-ocular reflex. Nerve conduction studies demonstrated normal motor conduction parameters and absence or severe attenuation of sensory nerve action potentials. Somatosensory evoked potentials were absent or severely attenuated. Biceps and femoral T-reflex recordings were normal, while masseter reflex was absent or attenuated. Sympathetic skin responses were normal. Cranial MRI showed vermian and hemispheric cerebellar atrophy predominating in lobules VI, VII and VIIa. We conclude that spasmodic cough may be an integral part of the clinical picture in CANVAS, antedating the appearance of imbalance in several decades and that sparing of muscle spindle afferents (Ia fibres) is probably the pathophysiological basis of normoreflexia.

Muscle weakness, afferent sensory dysfunction and exercise in knee osteoarthritis

DEFF Research Database (Denmark)

Roos, Ewa M.; Herzog, Walter; Block, Joel A

2011-01-01

Lower-extremity muscle strength and afferent sensory dysfunction, such as reduced proprioceptive acuity, are potentially modifiable putative risk factors for knee osteoarthritis (OA). Findings from current studies suggest that muscle weakness is a predictor of knee OA onset, while there is confli...... with previous knee injuries) are easily identified, and may benefit from exercise interventions to prevent or delay OA onset....... there is conflicting evidence regarding the role of muscle weakness in OA progression. In contrast, the literature suggests a role for afferent sensory dysfunction in OA progression but not necessarily in OA onset. The few pilot exercise studies performed in patients who are at risk of incident OA indicate...... a possibility for achieving preventive structure or load modifications. In contrast, large randomized controlled trials of patients with established OA have failed to demonstrate beneficial effects of strengthening exercises. Subgroups of individuals who are at increased risk of knee OA (such as those...

Thyroid hormone is required for pruning, functioning and long-term maintenance of afferent inner hair cell synapses.

Science.gov (United States)

Sundaresan, Srividya; Kong, Jee-Hyun; Fang, Qing; Salles, Felipe T; Wangsawihardja, Felix; Ricci, Anthony J; Mustapha, Mirna

2016-01-01

Functional maturation of afferent synaptic connections to inner hair cells (IHCs) involves pruning of excess synapses formed during development, as well as the strengthening and survival of the retained synapses. These events take place during the thyroid hormone (TH)-critical period of cochlear development, which is in the perinatal period for mice and in the third trimester for humans. Here, we used the hypothyroid Snell dwarf mouse (Pit1(dw)) as a model to study the role of TH in afferent type I synaptic refinement and functional maturation. We observed defects in afferent synaptic pruning and delays in calcium channel clustering in the IHCs of Pit1(dw) mice. Nevertheless, calcium currents and capacitance reached near normal levels in Pit1(dw) IHCs by the age of onset of hearing, despite the excess number of retained synapses. We restored normal synaptic pruning in Pit1(dw) IHCs by supplementing with TH from postnatal day (P)3 to P8, establishing this window as being critical for TH action on this process. Afferent terminals of older Pit1(dw) IHCs showed evidence of excitotoxic damage accompanied by a concomitant reduction in the levels of the glial glutamate transporter, GLAST. Our results indicate that a lack of TH during a critical period of inner ear development causes defects in pruning and long-term homeostatic maintenance of afferent synapses. © 2015 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

Effect of low frequency transcutaneous magnetic stimulation on sensory and motor transmission.

Science.gov (United States)

Leung, Albert; Shukla, Shivshil; Lee, Jacquelyn; Metzger-Smith, Valerie; He, Yifan; Chen, Jeffrey; Golshan, Shahrokh

2015-09-01

Peripheral nerve injury diminishes fast conducting large myelinated afferent fibers transmission but enhances smaller pain transmitting fibers firing. This aberrant afferent neuronal behavior contributes to development of chronic post-traumatic peripheral neuropathic pain (PTP-NP). Non-invasive dynamic magnetic flux stimulation has been implicated in treating PTP-NP, a condition currently not adequately addressed by other therapies including transcutaneous electrical nerve stimulation (TENS). The current study assessed the effect of low frequency transcutaneous magnetic stimulation (LFTMS) on peripheral sensory thresholds, nerve conduction properties, and TENS induced fast afferent slowing effect as measured by motor and sensory conduction studies in the ulnar nerve. Results indicated sham LFTMS with TENS (Sham + TENS) significantly (P = 0.02 and 0.007, respectively) reduces sensory conduction velocity (CV) and increases sensory onset latency (OL), and motor peak latency (PL) whereas, real LFTMS with TENS (Real + TENS) reverses effects of TENS on sensory CV and OL, and significantly (P = 0.036) increases the sensory PL. LFTMS alone significantly (P sensory PL and onset-to-peak latency. LFTMS appears to reverse TENS slowing effect on fast conducting fibers and casts a selective peripheral modulatory effect on slow conducting pain afferent fibers. © 2015 Wiley Periodicals, Inc.

Transcutaneous electrical nerve stimulation (TENS) improves the rest-activity rhythm in midstage Alzheimer's disease

NARCIS (Netherlands)

Scherder, E. J.; van Someren, E. J.; Swaab, D. F.

1999-01-01

Nightly restlessness in patients with Alzheimer's disease (AD) is probably due to a disorder of circadian rhythms. Transcutaneous electrical nerve stimulation (TENS) was previously reported to increase the strength of coupling of the circadian rest activity rhythm to Zeitgebers in early stage

Continuous detection of weak sensory signals in afferent spike trains: the role of anti-correlated interspike intervals in detection performance.

Science.gov (United States)

Goense, J B M; Ratnam, R

2003-10-01

An important problem in sensory processing is deciding whether fluctuating neural activity encodes a stimulus or is due to variability in baseline activity. Neurons that subserve detection must examine incoming spike trains continuously, and quickly and reliably differentiate signals from baseline activity. Here we demonstrate that a neural integrator can perform continuous signal detection, with performance exceeding that of trial-based procedures, where spike counts in signal- and baseline windows are compared. The procedure was applied to data from electrosensory afferents of weakly electric fish (Apteronotus leptorhynchus), where weak perturbations generated by small prey add approximately 1 spike to a baseline of approximately 300 spikes s(-1). The hypothetical postsynaptic neuron, modeling an electrosensory lateral line lobe cell, could detect an added spike within 10-15 ms, achieving near ideal detection performance (80-95%) at false alarm rates of 1-2 Hz, while trial-based testing resulted in only 30-35% correct detections at that false alarm rate. The performance improvement was due to anti-correlations in the afferent spike train, which reduced both the amplitude and duration of fluctuations in postsynaptic membrane activity, and so decreased the number of false alarms. Anti-correlations can be exploited to improve detection performance only if there is memory of prior decisions.

Origin and pharmacological response of atrial tachyarrhythmias induced by activation of mediastinal nerves in canines.

Science.gov (United States)

Armour, J Andrew; Richer, Louis-Philippe; Pagé, Pierre; Vinet, Alain; Kus, Teresa; Vermeulen, Michel; Nadeau, Réginald; Cardinal, René

2005-03-31

We sought to determine the sites of origin of atrial tachyarrhythmias induced by activating mediastinal nerves, as well as the response of such arrhythmias to autonomic modulation. Under general anaesthesia, atrioventricular block was induced after thoracotomy in 19 canines. Brief trains of 5 electrical stimuli were delivered to right-sided mediastinal nerves during the atrial refractory period. Unipolar electrograms were recorded from 191 right and left atrial epicardial sites under several conditions, i.e. (i) with intact nervous systems and following (ii) acute decentralization of the intrathoracic nervous system or administration of (iii) atropine, (iv) timolol, (v) hexamethonium. Concomitant right atrial endocardial mapping was performed in 7 of these dogs. Mediastinal nerve stimulation consistently initiated bradycardia followed by atrial tachyarrhythmias. In the initial tachyarrhythmia beats, early epicardial breakthroughs were identified in the right atrial free wall (28/50 episodes) or Bachmann bundle region (22/50), which corresponded to endocardial sites of origin associated with the right atrial subsidiary pacemaker complex, i.e. the crista terminalis and dorsal locations including the right atrial aspect of the interatrial septum. Neuronally induced responses were eliminated by atropine, modified by timolol and unaffected by acute neuronal decentralization. After hexamethonium, responses to extra-pericardial but not intra-pericardial nerve stimulation were eliminated. It is concluded that concomitant activation of cholinergic and adrenergic efferent intrinsic cardiac neurons induced by right-sided efferent neuronal stimulation initiates atrial tachyarrhythmias that originate from foci anatomically related to the right atrial pacemaker complex and tissues underlying major atrial ganglionated plexuses.

Nerve Blocks

Science.gov (United States)

... News Physician Resources Professions Site Index A-Z Nerve Blocks A nerve block is an injection to ... the limitations of Nerve Block? What is a Nerve Block? A nerve block is an anesthetic and/ ...

US and MR imaging of peripheral nerves in leprosy

International Nuclear Information System (INIS)

Martinoli, C.; Derchi, L.E.; Gandolfo, N.; Bertolotto, M.; Bianchi, S.; Fiallo, P.; Nunzi, E.

2000-01-01

Objective. To analyze peripheral nerves with ultrasonography (US) and magnetic resonance imaging (MR) in leprosy and assess the role of imaging in leprosy patients. Results. Leprosy nerves were classified into three groups based on imaging appearance: group I consisted of 17 normal-appearing nerves; group II, of 30 enlarged nerves with fascicular abnormalities; group III, of 11 nerves with absent fascicular structure. Group II nerves were from patients subjected to reversal reactions; 75% of patients with group III nerves had a history of erythema nodosum leprosum. Nerve compression in osteofibrous tunnels was identified in 33% of group II and 18% of group III nerves. Doppler US and MR imaging were 74% and 92% sensitive in identifying active reactions, based on detection of endoneural color flow signals, long T2 and Gd enhancement. In 64% of cases, follow-up studies showed decreased color flow and Gd uptake after steroids and decompressive surgery.Conclusions. US and MR imaging are able to detect nerves abnormalities in leprosy. Active reversal reactions are indicated by endoneural color flow signals as well as by an increased T2 signal and Gd enhancement. These signs would suggest rapid progression of nerve damage and a poor prognosis unless antireactional treatment is started. (orig.)

US and MR imaging of peripheral nerves in leprosy

Energy Technology Data Exchange (ETDEWEB)

Martinoli, C. [Department of Radiology ' ' R' ' , DICMI, University of Genoa, Genoa (Italy); Cattedra di Radiologia ' ' R' ' , Universita di Genova, Largo Rosanna Benzi, 8, I-16132 Genoa (Italy); Derchi, L.E.; Gandolfo, N. [Department of Radiology ' ' R' ' , DICMI, University of Genoa, Genoa (Italy); Bertolotto, M. [Department of Radiology, University of Trieste, Strada di Fiume, I-34149 Trieste (Italy); Bianchi, S. [Division de Radiodiagnostic. Hopital Cantonal Huniversitaire, Rue Micheli du Crest, Geneva (Switzerland); Fiallo, P.; Nunzi, E. [Department of Tropical Medicine, University of Genoa, Largo Rosanna Benzi 8, I-16132 Genoa (Italy)

2000-03-30

Objective. To analyze peripheral nerves with ultrasonography (US) and magnetic resonance imaging (MR) in leprosy and assess the role of imaging in leprosy patients. Results. Leprosy nerves were classified into three groups based on imaging appearance: group I consisted of 17 normal-appearing nerves; group II, of 30 enlarged nerves with fascicular abnormalities; group III, of 11 nerves with absent fascicular structure. Group II nerves were from patients subjected to reversal reactions; 75% of patients with group III nerves had a history of erythema nodosum leprosum. Nerve compression in osteofibrous tunnels was identified in 33% of group II and 18% of group III nerves. Doppler US and MR imaging were 74% and 92% sensitive in identifying active reactions, based on detection of endoneural color flow signals, long T2 and Gd enhancement. In 64% of cases, follow-up studies showed decreased color flow and Gd uptake after steroids and decompressive surgery.Conclusions. US and MR imaging are able to detect nerves abnormalities in leprosy. Active reversal reactions are indicated by endoneural color flow signals as well as by an increased T2 signal and Gd enhancement. These signs would suggest rapid progression of nerve damage and a poor prognosis unless antireactional treatment is started. (orig.)

Nerve cell-mimicking liposomes as biosensor for botulinum neurotoxin complete physiological activity

Energy Technology Data Exchange (ETDEWEB)

Weingart, Oliver G., E-mail: Oliver.Weingart@hest.ethz.ch; Loessner, Martin J.

2016-12-15

Botulinum neurotoxins (BoNT) are the most toxic substances known, and their neurotoxic properties and paralysing effects are exploited for medical treatment of a wide spectrum of disorders. To accurately quantify the potency of a pharmaceutical BoNT preparation, its physiological key activities (binding to membrane receptor, translocation, and proteolytic degradation of SNARE proteins) need to be determined. To date, this was only possible using animal models, or, to a limited extent, cell-based assays. We here report a novel in vitro system for BoNT/B analysis, based on nerve-cell mimicking liposomes presenting motoneuronal membrane receptors required for BoNT binding. Following triggered membrane translocation of the toxin's Light Chain, the endopeptidase activity can be quantitatively monitored employing a FRET-based reporter assay within the functionalized liposomes. We were able to detect BoNT/B physiological activity at picomolar concentrations in short time, opening the possibility for future replacement of animal experimentation in pharmaceutical BoNT testing. - Highlights: • A cell-free in vitro system was used to measure BoNT/B physiological function. • The system relies on nerve-cell mimicking liposomes as a novel detection system. • A FRET-based reporter assay is used as final readout of the test system. • BoNT/B physiological activity was detected at picogram quantities in short time. • The method opens the possibility to replace animal experimentation in BoNT testing.

Nerve cell-mimicking liposomes as biosensor for botulinum neurotoxin complete physiological activity

International Nuclear Information System (INIS)

Weingart, Oliver G.; Loessner, Martin J.

2016-01-01

Botulinum neurotoxins (BoNT) are the most toxic substances known, and their neurotoxic properties and paralysing effects are exploited for medical treatment of a wide spectrum of disorders. To accurately quantify the potency of a pharmaceutical BoNT preparation, its physiological key activities (binding to membrane receptor, translocation, and proteolytic degradation of SNARE proteins) need to be determined. To date, this was only possible using animal models, or, to a limited extent, cell-based assays. We here report a novel in vitro system for BoNT/B analysis, based on nerve-cell mimicking liposomes presenting motoneuronal membrane receptors required for BoNT binding. Following triggered membrane translocation of the toxin's Light Chain, the endopeptidase activity can be quantitatively monitored employing a FRET-based reporter assay within the functionalized liposomes. We were able to detect BoNT/B physiological activity at picomolar concentrations in short time, opening the possibility for future replacement of animal experimentation in pharmaceutical BoNT testing. - Highlights: • A cell-free in vitro system was used to measure BoNT/B physiological function. • The system relies on nerve-cell mimicking liposomes as a novel detection system. • A FRET-based reporter assay is used as final readout of the test system. • BoNT/B physiological activity was detected at picogram quantities in short time. • The method opens the possibility to replace animal experimentation in BoNT testing.

Anoxia increases potassium conductance in hippocampal nerve cells.

Science.gov (United States)

Hansen, A J; Hounsgaard, J; Jahnsen, H

1982-07-01

The effect of anoxia on nerve cell function was studied by intra- and extracellular microelectrode recordings from the CA1 and CA3 region in guinea pig hippocampal slices. Hyperpolarization and concomitant reduction of the nerve cell input resistance was observed early during anoxia. During this period the spontaneous activity first disappeared, then the evoked activity gradually disappeared. The hyperpolarization was followed by depolarization and an absence of a measurable input resistance. All the induced changes were reversed when the slice was reoxygenated. Reversal of the electro-chemical gradient for Cl- across the nerve cell membrane did not affect the course of events during anoxia. Aminopyridines blocked the anoxic hyperpolarization and attenuated the decrease of membrane resistance, but had no effect on the later depolarization. Blockers of synaptic transmission. Mn++, Mg++ and of Na+-channels (TTX) were without effect on the nerve cell changes during anoxia. It is suggested that the reduction of nerve cell excitability in anoxia is primarily due to increased K+-conductance. Thus, the nerve cells are hyperpolarized and the input resistance reduced, causing higher threshold and reduction of synaptic potentials. The mechanism of the K+-conductance activation is unknown at present.

Differential vulnerability of 3 rapidly conducting somatosensory pathways in the dog with vitamin B6 neuropathy.

Science.gov (United States)

Schaeppi, U; Krinke, G

1985-09-01

In anesthetized dogs with chronically implanted cortical electrodes somatic sensory-evoked potentials (SEPs) were produced by electrical stimulation at neural, muscular or cutaneous sites of the contralateral hind leg. Stimulation of the tibial nerve at the calcaneus or of the short flexor muscles of the hind paw caused SEPs having characteristics following activation of rapidly conducting afferents from muscle spindles. Stimulation of the glabrous skin of the central pad resulted in SEPs arriving after a more protracted latency evidently related to activation of afferents from Merkel cells, Krause and Pacinian corpuscles known to be located at these sites. Stimulation of the hairy skin from the dorsal surface of the hindpaw produced a further type of SEP presumably resulting from activation of afferents from receptors of tylotrich hair follicles. Vitamin B6-induced neuropathy involves the selective degeneration of the largest neurons in the spinal ganglia and of associated long peripheral and central neurites performing rapid impulse transmission. In the course of vitamin B6 neuropathy the relatively slow impulse transmission following stimulation of the central pad was more severely impaired than the faster one after activation of afferents from muscle spindles or receptors from hair follicles. This allows us to conclude that in the dog afferents from the glabrous skin of the central pad conduct centrally via the dorsal columns, susceptible to vitamin B6 intoxication, while muscle and hair receptor afferents ascend in the dorsal spinocerebellar and spinocervical tract, respectively, which are vitamin B6 resistant.

Vagus nerve stimulation mediates protection from kidney ischemia-reperfusion injury through α7nAChR+ splenocytes.

Science.gov (United States)

Inoue, Tsuyoshi; Abe, Chikara; Sung, Sun-Sang J; Moscalu, Stefan; Jankowski, Jakub; Huang, Liping; Ye, Hong; Rosin, Diane L; Guyenet, Patrice G; Okusa, Mark D

2016-05-02

The nervous and immune systems interact in complex ways to maintain homeostasis and respond to stress or injury, and rapid nerve conduction can provide instantaneous input for modulating inflammation. The inflammatory reflex referred to as the cholinergic antiinflammatory pathway regulates innate and adaptive immunity, and modulation of this reflex by vagus nerve stimulation (VNS) is effective in various inflammatory disease models, such as rheumatoid arthritis and inflammatory bowel disease. Effectiveness of VNS in these models necessitates the integration of neural signals and α7 nicotinic acetylcholine receptors (α7nAChRs) on splenic macrophages. Here, we sought to determine whether electrical stimulation of the vagus nerve attenuates kidney ischemia-reperfusion injury (IRI), which promotes the release of proinflammatory molecules. Stimulation of vagal afferents or efferents in mice 24 hours before IRI markedly attenuated acute kidney injury (AKI) and decreased plasma TNF. Furthermore, this protection was abolished in animals in which splenectomy was performed 7 days before VNS and IRI. In mice lacking α7nAChR, prior VNS did not prevent IRI. Conversely, adoptive transfer of VNS-conditioned α7nAChR splenocytes conferred protection to recipient mice subjected to IRI. Together, these results demonstrate that VNS-mediated attenuation of AKI and systemic inflammation depends on α7nAChR-positive splenocytes.

Functional restoration of the paralyzed diaphragm in high cervical quadriplegia via phrenic nerve neurotization utilizing the functional spinal accessory nerve.

Science.gov (United States)

Yang, Ming-liang; Li, Jian-jun; Zhang, Shao-cheng; Du, Liang-jie; Gao, Feng; Li, Jun; Wang, Yu-ming; Gong, Hui-ming; Cheng, Liang

2011-08-01

The authors report a case of functional improvement of the paralyzed diaphragm in high cervical quadriplegia via phrenic nerve neurotization using a functional spinal accessory nerve. Complete spinal cord injury at the C-2 level was diagnosed in a 44-year-old man. Left diaphragm activity was decreased, and the right diaphragm was completely paralyzed. When the level of metabolism or activity (for example, fever, sitting, or speech) slightly increased, dyspnea occurred. The patient underwent neurotization of the right phrenic nerve with the trapezius branch of the right spinal accessory nerve at 11 months postinjury. Four weeks after surgery, training of the synchronous activities of the trapezius muscle and inspiration was conducted. Six months after surgery, motion was observed in the previously paralyzed right diaphragm. The lung function evaluation indicated improvements in vital capacity and tidal volume. This patient was able to sit in a wheelchair and conduct outdoor activities without assisted ventilation 12 months after surgery.

Use of Processed Nerve Allografts to Repair Nerve Injuries Greater Than 25 mm in the Hand.

Science.gov (United States)

Rinker, Brian; Zoldos, Jozef; Weber, Renata V; Ko, Jason; Thayer, Wesley; Greenberg, Jeffrey; Leversedge, Fraser J; Safa, Bauback; Buncke, Gregory

2017-06-01

Processed nerve allografts (PNAs) have been demonstrated to have improved clinical results compared with hollow conduits for reconstruction of digital nerve gaps less than 25 mm; however, the use of PNAs for longer gaps warrants further clinical investigation. Long nerve gaps have been traditionally hard to study because of low incidence. The advent of the RANGER registry, a large, institutional review board-approved, active database for PNA (Avance Nerve Graft; AxoGen, Inc, Alachua, FL) has allowed evaluation of lower incidence subsets. The RANGER database was queried for digital nerve repairs of 25 mm or greater. Demographics, injury, treatment, and functional outcomes were recorded on standardized forms. Patients younger than 18 and those lacking quantitative follow-up data were excluded. Recovery was graded according to the Medical Research Council Classification for sensory function, with meaningful recovery defined as S3 or greater level. Fifty digital nerve injuries in 28 subjects were included. There were 22 male and 6 female subjects, and the mean age was 45. Three patients gave a previous history of diabetes, and there were 6 active smokers. The most commonly reported mechanisms of injury were saw injuries (n = 13), crushing injuries (n = 9), resection of neuroma (n = 9), amputation/avulsions (n = 8), sharp lacerations (n = 7), and blast/gunshots (n = 4). The average gap length was 35 ± 8 mm (range, 25-50 mm). Recovery to the S3 or greater level was reported in 86% of repairs. Static 2-point discrimination (s2PD) and Semmes-Weinstein monofilament (SWF) were the most common completed assessments. Mean s2PD in 24 repairs reporting 2PD data was 9 ± 4 mm. For the 38 repairs with SWF data, protective sensation was reported in 33 repairs, deep pressure in 2, and no recovery in 3. These data compared favorably with historical data for nerve autograft repairs, with reported levels of meaningful recovery of 60% to 88%. There were no reported adverse effects

Percutaneous Transhepatic Duodenal Drainage as an Alternative Approach in Afferent Loop Obstruction with Secondary Obstructive Jaundice in Recurrent Gastric Cancer

International Nuclear Information System (INIS)

Yao, N.-S.; Wu, C.-W.; Tiu, Chui-Mei; Liu, Jacqueline M.; Whang-Peng, Jacqueline; Chen, L.-T.

1998-01-01

Two cases are reported of chronic, partial afferent loop obstruction with resultant obstructive jaundice in recurrent gastric cancer. The diagnosis was made by characteristic clinical presentations, abdominal computed tomography, and cholescintigraphy. Percutaneous transhepatic duodenal drainage (PTDD) provided effective palliation for both afferent loop obstruction and biliary stasis. We conclude that cholescintigraphy is of value in making the diagnosis of partial afferent loop obstruction and in differentiating the cause of obstructive jaundice in such patients, and PTDD provides palliation for those patients in whom surgical intervention is not feasible

Afferent Endocrine Control of Eating

DEFF Research Database (Denmark)

Langhans, Wolfgang; Holst, Jens Juul

2016-01-01

The afferent endocrine factors that control eating can be separated into different categories. One obvious categorization is by the time course of their effects, with long-term factors that signal adiposity and short-term factors that operate within the time frame of single meals. The second...... obvious categorization is by the origin of the endocrine signalling molecules. The level of knowledge concerning the physiological mechanisms and relevance of the hormones that are implicated in the control of eating is clearly different. With the accumulating knowledge about the hormones' actions......, various criteria have been developed for when the effect of a hormone can be considered 'physiologic'. This chapter treats the hormones separately and categorizes them by origin. It discusses ALL hormones that are implicated in eating control such as Gastrointestinal (GI) hormone and glucagon-like peptide...

Role of spinal metabotropic glutamate receptor 5 in pudendal inhibition of the nociceptive bladder reflex in cats.

Science.gov (United States)

Reese, Jeremy N; Rogers, Marc J; Xiao, Zhiying; Shen, Bing; Wang, Jicheng; Schwen, Zeyad; Roppolo, James R; de Groat, William C; Tai, Changfeng

2015-04-15

This study examined the role of spinal metabotropic glutamate receptor 5 (mGluR5) in the nociceptive C-fiber afferent-mediated spinal bladder reflex and in the inhibtion of this reflex by pudendal nerve stimulation (PNS). In α-chloralose-anesthetized cats after spinal cord transection at the T9/T10 level, intravesical infusion of 0.25% acetic acid irritated the bladder, activated nociceptive C-fiber afferents, and induced spinal reflex bladder contractions of low amplitude (reflexes were responsible for a major component of the contractions. This study shows that spinal mGluR5 plays an important role in the nociceptive C-fiber afferent-mediated spinal bladder reflex and in pudendal inhibition of this spinal reflex. Copyright © 2015 the American Physiological Society.

Large A-fiber activity is required for microglial proliferation and p38 MAPK activation in the spinal cord: different effects of resiniferatoxin and bupivacaine on spinal microglial changes after spared nerve injury

Directory of Open Access Journals (Sweden)

Decosterd Isabelle

2009-09-01

Full Text Available Abstract Background After peripheral nerve injury, spontaneous ectopic activity arising from the peripheral axons plays an important role in inducing central sensitization and neuropathic pain. Recent evidence indicates that activation of spinal cord microglia also contributes to the development of neuropathic pain. In particular, activation of p38 mitogen-activated protein kinase (MAPK in spinal microglia is required for the development of mechanical allodynia. However, activity-dependent activation of microglia after nerve injury has not been fully addressed. To determine whether spontaneous activity from C- or A-fibers is required for microglial activation, we used resiniferatoxin (RTX to block the conduction of transient receptor potential vanilloid subtype 1 (TRPV1 positive fibers (mostly C- and Aδ-fibers and bupivacaine microspheres to block all fibers of the sciatic nerve in rats before spared nerve injury (SNI, and observed spinal microglial changes 2 days later. Results SNI induced robust mechanical allodynia and p38 activation in spinal microglia. SNI also induced marked cell proliferation in the spinal cord, and all the proliferating cells (BrdU+ were microglia (Iba1+. Bupivacaine induced a complete sensory and motor blockade and also significantly inhibited p38 activation and microglial proliferation in the spinal cord. In contrast, and although it produced an efficient nociceptive block, RTX failed to inhibit p38 activation and microglial proliferation in the spinal cord. Conclusion (1 Blocking peripheral input in TRPV1-positive fibers (presumably C-fibers is not enough to prevent nerve injury-induced spinal microglial activation. (2 Peripheral input from large myelinated fibers is important for microglial activation. (3 Microglial activation is associated with mechanical allodynia.

Light and electron microscopy of contacts between primary afferent fibres and neurones with axons ascending the dorsal columns of the feline spinal cord.

Science.gov (United States)

Maxwell, D J; Koerber, H R; Bannatyne, B A

1985-10-01

In addition to primary afferent fibres, the dorsal columns of the cat spinal cord contain ascending second-order axons which project to the dorsal column nuclei. The aim of the present study was to obtain morphological evidence that certain primary afferent axons form monosynaptic contacts with cells of origin of this postsynaptic dorsal column pathway. In ten adult cats, neurones with axons ascending the dorsal columns were retrogradely labelled with horseradish peroxidase using a pellet implantation method in the thoracic dorsal columns. In the lumbosacral regions of the same animals, primary afferent fibres were labelled intra-axonally with ionophoretic application of horseradish peroxidase. Tissue containing labelled axons was prepared for light and combined light and electron microscopy. Ultrastructural examination demonstrated that slowly adapting (Type I), hair follicle, Pacinian corpuscle and group Ia muscle spindle afferents formed monosynaptic contacts with labelled cells and light microscopical analysis suggested that they also received monosynaptic input from rapidly adapting (Krause) afferents. This evidence suggests that sensory information from large-diameter cutaneous and muscle spindle afferent fibres is conveyed disynaptically via the postsynaptic dorsal column pathway to the dorsal column nuclei. Some of the input to this pathway is probably modified in the spinal cord as the majority of primary afferent boutons forming monosynaptic contacts were postsynaptic to other axon terminals. The postsynaptic dorsal column system appears to constitute a major somatosensory pathway in the cat.

Raman spectroscopic detection of peripheral nerves towards nerve-sparing surgery

Science.gov (United States)

Minamikawa, Takeo; Harada, Yoshinori; Takamatsu, Tetsuro

2017-02-01

The peripheral nervous system plays an important role in motility, sensory, and autonomic functions of the human body. Preservation of peripheral nerves in surgery, namely nerve-sparing surgery, is now promising technique to avoid functional deficits of the limbs and organs following surgery as an aspect of the improvement of quality of life of patients. Detection of peripheral nerves including myelinated and unmyelinated nerves is required for the nerve-sparing surgery; however, conventional nerve identification scheme is sometimes difficult to identify peripheral nerves due to similarity of shape and color to non-nerve tissues or its limited application to only motor peripheral nerves. To overcome these issues, we proposed a label-free detection technique of peripheral nerves by means of Raman spectroscopy. We found several fingerprints of peripheral myelinated and unmyelinated nerves by employing a modified principal component analysis of typical spectra including myelinated nerve, unmyelinated nerve, and adjacent tissues. We finally realized the sensitivity of 94.2% and the selectivity of 92.0% for peripheral nerves including myelinated and unmyelinated nerves against adjacent tissues. Although further development of an intraoperative Raman spectroscopy system is required for clinical use, our proposed approach will serve as a unique and powerful tool for peripheral nerve detection for nerve-sparing surgery in the future.

Beneficial effects of gamma linolenic acid supplementation on nerve conduction velocity, Na+, K+ ATPase activity, and membrane fatty acid composition in sciatic nerve of diabetic rats.

Science.gov (United States)

Coste, T; Pierlovisi, M; Leonardi, J; Dufayet, D; Gerbi, A; Lafont, H; Vague, P; Raccah, D

1999-07-01

Metabolic and vascular abnormalities are implicated in the pathogenesis of diabetic neuropathy. Two principal metabolic defects are altered lipid metabolism resulting from the impairment of delta-6-desaturase, which converts linoleic acid (LA) into gamma linolenic acid (GLA), and reduced nerve Na+, K+ ATPase activity. This reduction may be caused by a lack of incorporation of (n-6) fatty acids in membrane phospholipids. Because this ubiquitous enzyme maintains the membrane electrical potential and allows repolarization, disturbances in its activity can alter the process of nerve conduction velocity (NCV). We studied the effects of supplementation with GLA (260 mg per day) on NCV, fatty acid phospholipid composition, and Na+, K+ ATPase activity in streptozotocin-diabetic rats. Six groups of 10 rats were studied. Two groups served as controls supplemented with GLA or sunflower oil (GLA free). Two groups with different durations of diabetes were studied: 6 weeks with no supplementation and 12 weeks supplemented with sunflower oil. To test the ability of GLA to prevent or reverse the effects of diabetes, two groups of diabetic rats were supplemented with GLA, one group for 12 weeks and one group for 6 weeks, starting 6 weeks after diabetes induction. Diabetes resulted in a 25% decrease in NCV (P < 0.0001), a 45% decrease in Na+, K+ ATPase activity (P < 0.0001), and an abnormal phospholipid fatty acid composition. GLA restored NCV both in the prevention and reversal studies and partially restored Na+, K+ ATPase activity in the preventive treatment group (P < 0.0001). These effects were accompanied by a modification of phospholipid fatty acid composition in nerve membranes. Overall, the results suggest that membrane fatty acid composition plays a direct role in NCV and confirm the beneficial effect of GLA supplementation in diabetic neuropathy.

Comparing the Efficacy of Triple Nerve Transfers with Nerve Graft Reconstruction in Upper Trunk Obstetric Brachial Plexus Injury.

Science.gov (United States)

O'Grady, Kathleen M; Power, Hollie A; Olson, Jaret L; Morhart, Michael J; Harrop, A Robertson; Watt, M Joe; Chan, K Ming

2017-10-01

Upper trunk obstetric brachial plexus injury can cause profound shoulder and elbow dysfunction. Although neuroma excision with interpositional sural nerve grafting is the current gold standard, distal nerve transfers have a number of potential advantages. The goal of this study was to compare the clinical outcomes and health care costs between nerve grafting and distal nerve transfers in children with upper trunk obstetric brachial plexus injury. In this prospective cohort study, children who underwent triple nerve transfers were followed with the Active Movement Scale for 2 years. Their outcomes were compared to those of children who underwent nerve graft reconstruction. To assess health care use, a cost analysis was also performed. Twelve patients who underwent nerve grafting were compared to 14 patients who underwent triple nerve transfers. Both groups had similar baseline characteristics and showed improved shoulder and elbow function following surgery. However, the nerve transfer group displayed significantly greater improvement in shoulder external rotation and forearm supination 2 years after surgery (p The operative time and length of hospital stay were significantly lower (p the overall cost was approximately 50 percent less in the nerve transfer group. Triple nerve transfer for upper trunk obstetric brachial plexus injury is a feasible option, with better functional shoulder external rotation and forearm supination, faster recovery, and lower cost compared with traditional nerve graft reconstruction. Therapeutic, II.

Cell proliferation and apoptosis in optic nerve and brain integration centers of adult trout Oncorhynchus mykiss after optic nerve injury

Science.gov (United States)

Pushchina, Evgeniya V.; Shukla, Sachin; Varaksin, Anatoly A.; Obukhov, Dmitry K.

2016-01-01

Fishes have remarkable ability to effectively rebuild the structure of nerve cells and nerve fibers after central nervous system injury. However, the underlying mechanism is poorly understood. In order to address this issue, we investigated the proliferation and apoptosis of cells in contralateral and ipsilateral optic nerves, after stab wound injury to the eye of an adult trout Oncorhynchus mykiss. Heterogenous population of proliferating cells was investigated at 1 week after injury. TUNEL labeling gave a qualitative and quantitative assessment of apoptosis in the cells of optic nerve of trout 2 days after injury. After optic nerve injury, apoptotic response was investigated, and mass patterns of cell migration were found. The maximal concentration of apoptotic bodies was detected in the areas of mass clumps of cells. It is probably indicative of massive cell death in the area of high phagocytic activity of macrophages/microglia. At 1 week after optic nerve injury, we observed nerve cell proliferation in the trout brain integration centers: the cerebellum and the optic tectum. In the optic tectum, proliferating cell nuclear antigen (PCNA)-immunopositive radial glia-like cells were identified. Proliferative activity of nerve cells was detected in the dorsal proliferative (matrix) area of the cerebellum and in parenchymal cells of the molecular and granular layers whereas local clusters of undifferentiated cells which formed neurogenic niches were observed in both the optic tectum and cerebellum after optic nerve injury. In vitro analysis of brain cells of trout showed that suspension cells compared with monolayer cells retain higher proliferative activity, as evidenced by PCNA immunolabeling. Phase contrast observation showed mitosis in individual cells and the formation of neurospheres which gradually increased during 1–4 days of culture. The present findings suggest that trout can be used as a novel model for studying neuronal regeneration. PMID:27212918

Characteristics of the mechanosensitive bladder afferent activities in relation with microcontractions in male rats with bladder outlet obstruction.

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Aizawa, Naoki; Ichihara, Koji; Fukuhara, Hiroshi; Fujimura, Tetsuya; Andersson, Karl-Erik; Homma, Yukio; Igawa, Yasuhiko

2017-08-09

We investigated the characteristics of bladder mechanosensitive single-unit afferent activities (SAAs) in rats with a bladder outlet obstruction (BOO) and their relationship with bladder microcontractions. Male Wistar rats were divided into Sham and BOO groups. Four or 10 days after the surgery, rats were anesthetized with urethane. The SAAs of Aδ- or C-fibers from the L6 dorsal roots were recorded during bladder filling. The BOO group showed a higher number of microcontractions and lower SAAs of Aδ-fibers compared with those of the Sham group. These findings were significant at day 10 post-operatively. In contrast, SAAs of C-fibers were not significantly different between the groups at either day 4 or 10. In the BOO group at day 10, the SAAs of both Aδ- and C-fibers at the "ascending" phase of microcontractions were significantly higher than those at the other phases (descending or stationary), and a similar tendency was also observed at day 4. Taken together, during bladder filling, the bladder mechanosensitive SAAs of Aδ-fibers were attenuated, but SAAs of both Aδ- and C-fibers were intermittently enhanced by propagation of microcontractions.

Acellular Nerve Allografts in Peripheral Nerve Regeneration: A Comparative Study

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Moore, Amy M.; MacEwan, Matthew; Santosa, Katherine B.; Chenard, Kristofer E.; Ray, Wilson Z.; Hunter, Daniel A.; Mackinnon, Susan E.; Johnson, Philip J.

2011-01-01

Background Processed nerve allografts offer a promising alternative to nerve autografts in the surgical management of peripheral nerve injuries where short deficits exist. Methods Three established models of acellular nerve allograft (cold-preserved, detergent-processed, and AxoGen® -processed nerve allografts) were compared to nerve isografts and silicone nerve guidance conduits in a 14 mm rat sciatic nerve defect. Results All acellular nerve grafts were superior to silicone nerve conduits in support of nerve regeneration. Detergent-processed allografts were similar to isografts at 6 weeks post-operatively, while AxoGen®-processed and cold-preserved allografts supported significantly fewer regenerating nerve fibers. Measurement of muscle force confirmed that detergent-processed allografts promoted isograft-equivalent levels of motor recovery 16 weeks post-operatively. All acellular allografts promoted greater amounts of motor recovery compared to silicone conduits. Conclusions These findings provide evidence that differential processing for removal of cellular constituents in preparing acellular nerve allografts affects recovery in vivo. PMID:21660979

Vascularized nerve grafts for lower extremity nerve reconstruction.

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Terzis, Julia K; Kostopoulos, Vasileios K

2010-02-01

Vascularized nerve grafts (VNG) were introduced in 1976 but since then, there have been no reports of their usage in lower extremity reconstruction systematically. The factors influencing outcomes as well as a comparison with conventional nerve grafts will be presented.Since 1981, 14 lower extremity nerve injuries in 12 patients have been reconstructed with VNG. Common peroneal nerve was injured in 12 and posterior tibial nerve in 5 patients. The level of the injury was at the knee or thigh. Twelve sural nerves were used as VNG with or without concomitant vascularized posterior calf fascia.All patients regained improved sensibility and adequate posterior tibial nerve function. For common peroneal nerve reconstructions, all patients with denervation time less than 6 months regained muscle strength of grade at least 4, even when long grafts were used for defects of 20 cm or more. Late cases, yielded inadequate muscle function even with the use of VNG.Denervation time of 6 months or less was critical for reconstruction with vascularized nerve graft. Not only the results were statistically significant compared with late cases, but also all early operated patients achieved excellent results. VNG are strongly recommended in traction avulsion injuries of the lower extremity with lengthy nerve damage.

Matrix metalloproteinase-2 is downregulated in sciatic nerve by streptozotocin induced diabetes and/or treatment with minocycline: Implications for nerve regeneration

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Ali, Sumia; Driscoll, Heather E.; Newton, Victoria L.; Gardiner, Natalie J.

2014-01-01

Minocycline is an inhibitor of matrix metalloproteinases (MMPs) and has been shown to have analgesic effects. Whilst increased expression of MMPs is associated with neuropathic pain, MMPs also play crucial roles in Wallerian degeneration and nerve regeneration. In this study we examined the expression of MMP-2, MMP-9 and tissue inhibitor of metalloproteinase (TIMP)-1/-2 in the sciatic nerve of control and streptozotocin-induced diabetic rats treated with either vehicle or minocycline by quantitative PCR and gelatin zymography. We assessed the effects of minocycline on nerve conduction velocity and intraepidermal nerve fibre (IENF) deficits in diabetic neuropathy and investigated the effects of minocycline or MMP-2 on neurite outgrowth from primary cultures of dissociated adult rat sensory neurons. We show that MMP-2 is expressed constitutively in the sciatic nerve in vivo and treatment with minocycline or diabetes leads to downregulation of MMP-2 expression and activity. The functional consequence of this is IENF deficits in minocycline-treated nondiabetic rats and an unsupportive microenvironment for regeneration in diabetes. Minocycline reduces levels of MMP-2 mRNA and nerve growth factor-induced neurite outgrowth. Furthermore, in vivo minocycline treatment reduces preconditioning-induced in vitro neurite outgrowth following a sciatic nerve crush. In contrast, the addition of active MMP-2 facilitates neurite outgrowth in the absence of neurotrophic support and pre-treatment of diabetic sciatic nerve substrata with active MMP-2 promotes a permissive environment for neurite outgrowth. In conclusion we suggest that MMP-2 downregulation may contribute to the regenerative deficits in diabetes. Minocycline treatment also downregulates MMP-2 activity and is associated with inhibitory effects on sensory neurons. Thus, caution should be exhibited with its use as the balance between beneficial and detrimental outcomes may be critical in assessing the benefits of using

[Nerve growth factor and the physiology of pain: the relationships among interoception, sympathetic neurons and the emotional response indicated by the molecular pathophysiology of congenital insensitivity to pain with anhidrosis].

Science.gov (United States)

Indo, Yasuhiro

2015-05-01

Nerve growth factor (NGF) is a neurotrophic factor essential for the survival and maintenance of neurons. Congenital insensitivity to pain with anhidrosis (CIPA) is caused by loss-of-function mutations in NTRK1, which encodes a receptor tyrosine kinase, TrkA, for NGF. Mutations in NTRK1 cause the selective loss of NGF-dependent neurons, including both NGF-dependent primary afferents and sympathetic postganglionic neurons, in otherwise intact systems. The NGF-dependent primary afferents are thinly myelinated AΔ or unmyelinated C-fibers that are dependent on the NGF-TrkA system during development. NGF-dependent primary afferents are not only nociceptive neurons that transmit pain and temperature sensation, but also are polymodal receptors that play essential roles for interoception by monitoring various changes in the physiological status of all tissues in the body. In addition, they contribute to various inflammatory processes in acute, chronic and allergic inflammation. Together with sympathetic postganglionic neurons, they maintain the homeostasis of the body and emotional responses via interactions with the brain, immune and endocrine systems. Pain is closely related to emotions that accompany physical responses induced by systemic activation of the sympathetic nervous system. In contrast to a negative image of emotions in daily life, Antonio Damasio proposed the 'Somatic Marker Hypothesis', wherein emotions play critical roles in the decision-making and reasoning processes. According to this hypothesis, reciprocal communication between the brain and the body-proper are essential for emotional responses. Using the pathophysiology of CIPA as a foundation, this article suggests that NGF-dependent neurons constitute a part of the neuronal network required for homeostasis and emotional responses, and indicates that this network plays important roles in mediating the reciprocal communication between the brain and the body-proper.

Asynchronous recruitment of low-threshold motor units during repetitive, low-current stimulation of the human tibial nerve.

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Dean, Jesse C; Clair-Auger, Joanna M; Lagerquist, Olle; Collins, David F

2014-01-01

Motoneurons receive a barrage of inputs from descending and reflex pathways. Much of our understanding about how these inputs are transformed into motor output in humans has come from recordings of single motor units during voluntary contractions. This approach, however, is limited because the input is ill-defined. Herein, we quantify the discharge of soleus motor units in response to well-defined trains of afferent input delivered at physiologically-relevant frequencies. Constant frequency stimulation of the tibial nerve (10-100 Hz for 30 s), below threshold for eliciting M-waves or H-reflexes with a single pulse, recruited motor units in 7/9 subjects. All 25 motor units recruited during stimulation were also recruited during weak (recruited more units (n = 3/25 at 10 Hz; n = 25/25 at 100 Hz) at shorter latencies (19.4 ± 9.4 s at 10 Hz; 4.1 ± 4.0 s at 100 Hz) than lower frequencies. When a second unit was recruited, the discharge of the already active unit did not change, suggesting that recruitment was not due to increased synaptic drive. After recruitment, mean discharge rate during stimulation at 20 Hz (7.8 Hz) was lower than during 30 Hz (8.6 Hz) and 40 Hz (8.4 Hz) stimulation. Discharge was largely asynchronous from the stimulus pulses with "time-locked" discharge occurring at an H-reflex latency with only a 24% probability. Motor units continued to discharge after cessation of the stimulation in 89% of trials, although at a lower rate (5.8 Hz) than during the stimulation (7.9 Hz). This work supports the idea that the afferent volley evoked by repetitive stimulation recruits motor units through the integration of synaptic drive and intrinsic properties of motoneurons, resulting in "physiological" recruitment which adheres to Henneman's size principle and results in relatively low discharge rates and asynchronous firing.

Primary afferent terminal sprouting after a cervical dorsal rootlet section in the macaque monkey.

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Darian-Smith, Corinna

2004-03-01

We examined the role of primary afferent neurons in the somatosensory cortical "reactivation" that occurs after a localized cervical dorsal root lesion (Darian-Smith and Brown [2000] Nat. Neurosci. 3:476-481). After section of the dorsal rootlets that enervate the macaque's thumb and index finger (segments C6-C8), the cortical representation of these digits was initially silenced but then re-emerged for these same digits over 2-4 postlesion months. Cortical reactivation was accompanied by the emergence of physiologically detectable input from these same digits within dorsal rootlets bordering the lesion site. We investigated whether central axonal sprouting of primary afferents spared by the rhizotomy could mediate this cortical reactivation. The cortical representation of the hand was mapped electrophysiologically 15-25 weeks after the dorsal rootlet section to define this reactivation. Cholera toxin subunit B conjugated to horseradish peroxidase was then injected into the thumb and index finger pads bilaterally to label the central terminals of any neurons that innervated these digits. Primary afferent terminal proliferation was assessed in the spinal dorsal horn and cuneate nucleus at 7 days and 15-25 postlesion weeks. Labeled terminal bouton distributions were reconstructed and the "lesion" and control sides compared within each monkey. Distributions were significantly larger on the side of the lesion in the dorsal horn and cuneate nucleus at 15-25 weeks after the dorsal rootlet section, than those mapped only 7 days postlesion. Our results provide direct evidence for localized sprouting of spared (uninjured) primary afferent terminals in the dorsal horn and cuneate nucleus after a restricted dorsal root injury. Copyright 2004 Wiley-Liss, Inc.

Localization of substance P, calcitonin gene related peptide and galanin in the nerve fibers of porcine cystic ovaries

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Mariusz Majewski

2012-01-01

Full Text Available In a previous study, we showed that both the noradrenergic and cholinergic component of ovarian innervation is markedly changed in porcine cystic ovaries. The present study is aimed at elucidating the distribution pattern of substance P- (SP, calcitonin gene related peptide CGRP- and/or galanin (GAL-containing nerve fibers within porcine cystic ovaries. The status polycysticus was induced by dexamethasone phosphate disodium salt i.m. injections performed from the 7^th until the 21^st day of the first studied estrous cycle. During the same period of time, gilts of the control group received saline. All animals were slaughtered on the expected 11^th day of the second studied estrous cycle, and their ovaries were collected. When compared to control gonad, a distinct difference in the distribution pattern and the density of SP-, CGRP- and/or GAL-immunoreactive (GAL-IR nerve fibers was observed. Thus, unlike in the control gonad, SP- and/or CGRP-IR perivascular nerve fibers were found to supply medullar blood vessels of polycystic ovary. Furthermore, the number of GAL-IR nerve fibers contributing to the ground plexus in polycystic ovaries was higher than that observed in the control gonads. Thus, as may be judged from the profound changes in the distribution pattern of differently chemically coded afferent terminals within polycystic gonads, it appears possible that neuropeptides released from these terminals may take part in the etiopathogenesis of this disorder. (Folia Histochemica et Cytobiologica 2011; Vol. 49, No. 4, pp. 622–630

Extracellular adenosine 5'-triphosphate concentrations changes in rat spinal cord associated with the activation of urinary bladder afferents. A microdialysis study.

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Rocha, Jeová Nina

2016-01-01

To determine adenosine 5'-triphosphate levels in the interstice of spinal cord L6-S1 segment, under basal conditions or during mechanical and chemical activation of urinary bladder afferents. A microdialysis probe was transversally implanted in the dorsal half of spinal cord L6-S1 segment in female rats. Microdialysate was collected at 15 minutes intervals during 135 minutes, in anesthetized animals. Adenosine 5'-triphosphate concentrations were determined with a bioluminescent assay. In one group of animals (n=7) microdialysate samples were obtained with an empty bladder during a 10-minutes bladder distension to 20 or 40cmH2O with either saline, saline with acetic acid or saline with capsaicin. In another group of animals (n=6) bladder distention was performed and the microdialysis solution contained the ectonucleotidase inhibitor ARL 67156. Basal extracellular adenosine triphosphate levels were 110.9±35.34fmol/15 minutes, (mean±SEM, n=13), and bladder distention was associated with a significant increase in adenosine 5'-triphosphate levels which was not observed after bladder distention with saline solution containing capsaicin (10µM). Microdialysis with solution containing ARL 67156 (1mM) was associated with significantly higher extracellular adenosine 5'-triphosphate levels and no further increase in adenosine 5'-triphosphate was observed during bladder distension. Adenosine 5'-triphosphate was present in the interstice of L6-S1 spinal cord segments, was degraded by ectonucleotidase, and its concentration increased following the activation of bladder mechanosensitive but not of the chemosensitive afferents fibers. Adenosine 5'-triphosphate may originate either from the central endings of bladder mechanosensitive primary afferent neurons, or most likely from intrinsic spinal neurons, or glial cells and its release appears to be modulated by capsaicin activated bladder primary afferent or by adenosine 5'-triphosphate itself. Determinar as concentra

Nerve Cross-Bridging to Enhance Nerve Regeneration in a Rat Model of Delayed Nerve Repair

Science.gov (United States)

2015-01-01

There are currently no available options to promote nerve regeneration through chronically denervated distal nerve stumps. Here we used a rat model of delayed nerve repair asking of prior insertion of side-to-side cross-bridges between a donor tibial (TIB) nerve and a recipient denervated common peroneal (CP) nerve stump ameliorates poor nerve regeneration. First, numbers of retrogradely-labelled TIB neurons that grew axons into the nerve stump within three months, increased with the size of the perineurial windows opened in the TIB and CP nerves. Equal numbers of donor TIB axons regenerated into CP stumps either side of the cross-bridges, not being affected by target neurotrophic effects, or by removing the perineurium to insert 5-9 cross-bridges. Second, CP nerve stumps were coapted three months after inserting 0-9 cross-bridges and the number of 1) CP neurons that regenerated their axons within three months or 2) CP motor nerves that reinnervated the extensor digitorum longus (EDL) muscle within five months was determined by counting and motor unit number estimation (MUNE), respectively. We found that three but not more cross-bridges promoted the regeneration of axons and reinnervation of EDL muscle by all the CP motoneurons as compared to only 33% regenerating their axons when no cross-bridges were inserted. The same 3-fold increase in sensory nerve regeneration was found. In conclusion, side-to-side cross-bridges ameliorate poor regeneration after delayed nerve repair possibly by sustaining the growth-permissive state of denervated nerve stumps. Such autografts may be used in human repair surgery to improve outcomes after unavoidable delays. PMID:26016986

Regeneration of baroafferents after implantation into different vessels

NARCIS (Netherlands)

Stevens, Markus F.; Hermanns, Henning; Freynhagen, Rainer; Novotny, Gerd E. K.; Lipfert, Peter

2007-01-01

Regeneration of peripheral nerves involves an essential contribution by surrounding tissues. This study focuses on the role of the target tissue on the regeneration of afferent peripheral nerves. We hypothesized that nerves implanted into the appropriate target tissue regain their function, whereas

Nerve conduction and excitability studies in peripheral nerve disorders

DEFF Research Database (Denmark)

Krarup, Christian; Moldovan, Mihai

2009-01-01

counterparts in the peripheral nervous system, in some instances without peripheral nervous system symptoms. Both hereditary and acquired demyelinating neuropathies have been studied and the effects on nerve pathophysiology have been compared with degeneration and regeneration of axons. SUMMARY: Excitability......PURPOSE OF REVIEW: The review is aimed at providing information about the role of nerve excitability studies in peripheral nerve disorders. It has been known for many years that the insight into peripheral nerve pathophysiology provided by conventional nerve conduction studies is limited. Nerve...... excitability studies are relatively novel but are acquiring an increasingly important role in the study of peripheral nerves. RECENT FINDINGS: By measuring responses in nerve that are related to nodal function (strength-duration time constant, rheobase and recovery cycle) and internodal function (threshold...

Effect of endoscopic brow lift on contractures and synkinesis of the facial muscles in patients with a regenerated postparalytic facial nerve syndrome.

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Bran, Gregor M; Börjesson, Pontus K E; Boahene, Kofi D; Gosepath, Jan; Lohuis, Peter J F M

2014-01-01

Delayed recovery after facial palsy results in aberrant nerve regeneration with symptomatic movement disorders, summarized as the postparalytic facial nerve syndrome. The authors present an alternative surgical approach for improvement of periocular movement disorders in patients with postparalytic facial nerve syndrome. The authors proposed that endoscopic brow lift leads to an improvement of periocular movement disorders by reducing pathologically raised levels of afferent input. Eleven patients (seven women and four men) with a mean age of 54 years (range, 33 to 85 years) and with postparalytic facial nerve syndrome underwent endoscopic brow lift under general anesthesia. Patients' preoperative condition was compared with their postoperative condition using a retrospective questionnaire. Subjects were also asked to compare the therapeutic effectiveness of endoscopic brow lift and botulinum toxin type A. Mean follow-up was 52 months (range, 22 to 83 months). No intraoperative or postoperative complications occurred. During follow-up, patients and physicians observed an improvement of periorbital contractures and oculofacial synkinesis. Scores on quality of life improved significantly after endoscopic brow lift. Best results were obtained when botulinum toxin type A was adjoined after the endoscopic brow lift. Patients described a cumulative therapeutic effect. These findings suggest endoscopic brow lift as a promising additional treatment modality for the treatment of periocular postparalytic facial nerve syndrome-related symptoms, leading to an improved quality of life. Even though further prospective investigation is needed, a combination of endoscopic brow lift and postsurgical botulinum toxin type A administration could become a new therapeutic standard.

Selective activation of microglia in spinal cord but not higher cortical regions following nerve injury in adult mouse

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Shang Yuze

2008-04-01

Full Text Available Abstract Neuronal plasticity along the pathway for sensory transmission including the spinal cord and cortex plays an important role in chronic pain, including inflammatory and neuropathic pain. While recent studies indicate that microglia in the spinal cord are involved in neuropathic pain, a systematic study has not been performed in other regions of the central nervous system (CNS. In the present study, we used heterozygous Cx3cr1GFP/+mice to characterize the morphological phenotypes of microglia following common peroneal nerve (CPN ligation. We found that microglia showed a uniform distribution throughout the CNS, and peripheral nerve injury selectively activated microglia in the spinal cord dorsal horn and related ventral horn. In contrast, microglia was not activated in supraspinal regions of the CNS, including the anterior cingulate cortex (ACC, prefrontal cortex (PFC, primary and secondary somatosensory cortex (S1 and S2, insular cortex (IC, amygdala, hippocampus, periaqueductal gray (PAG and rostral ventromedial medulla (RVM. Our results provide strong evidence that nerve injury primarily activates microglia in the spinal cord of adult mice, and pain-related cortical plasticity is likely mediated by neurons.

Retrograde and transganglionic transport of horseradish peroxidase-conjugated cholera toxin B subunit, wheatgerm agglutinin and isolectin B4 from Griffonia simplicifolia I in primary afferent neurons innervating the rat urinary bladder.

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Wang, H F; Shortland, P; Park, M J; Grant, G

1998-11-01

myelinated fibres). Double labelling with other neuronal markers showed that 71%, 43% and 36% of the cholera toxin B subunit-immunoreactive cells were calcitonin gene-related peptide-, isolectin B4-binding- and substance P-positive, respectively. A few cholera toxin B subunit cells showed galanin-immunoreactivity, but none were somatostatin-, vasoactive intestinal polypeptide-, or neuropeptide Y-immunoreactive or contained fluoride-resistant acid phosphatase. The results show that cholera toxin B subunit-horseradish peroxidase is a more effective retrograde and transganglionic tracer for pelvic primary afferents from the urinary bladder than wheat germ agglutinin-horseradish peroxidase and isolectin B4-horseradish peroxidase, but in contrast to somatic nerves, it is transported mainly by unmyelinated fibres in the visceral afferents.

External laryngeal nerve in thyroid surgery: is the nerve stimulator necessary?

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Aina, E N; Hisham, A N

2001-09-01

To find out the incidence and type of external laryngeal nerves during operations on the thyroid, and to assess the role of a nerve stimulator in detecting them. Prospective, non-randomised study. Teaching hospital, Malaysia. 317 patients who had 447 dissections between early January 1998 and late November 1999. Number and type of nerves crossing the cricothyroid space, and the usefulness of the nerve stimulator in finding them. The nerve stimulator was used in 206/447 dissections (46%). 392 external laryngeal nerves were seen (88%), of which 196/206 (95%) were detected with the stimulator. However, without the stimulator 196 nerves were detected out of 241 dissections (81%). The stimulator detected 47 (23%) Type I nerves (nerve > 1 cm from the upper edge of superior pole); 86 (42%) Type IIa nerves (nerve edge of superior pole); and 63 (31%) Type IIb nerves (nerve below upper edge of superior pole). 10 nerves were not detected. When the stimulator was not used the corresponding figures were 32 (13%), 113 (47%), and 51 (21%), and 45 nerves were not seen. If the nerve cannot be found we recommend dissection of capsule close to the medial border of the upper pole of the thyroid to avoid injury to the nerve. Although the use of the nerve stimulator seems desirable, it confers no added advantage in finding the nerve. In the event of uncertainty about whether a structure is the nerve, the stimulator may help to confirm it. However, exposure of the cricothyroid space is most important for good exposure in searching for the external laryngeal nerve.

A Proposed Neurologic Pathway for Scalp Acupuncture: Trigeminal Nerve-Meninges-Cerebrospinal Fluid-Contacting Neurons-Brain.

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Wang, Shuya; Liu, Kun; Wang, Yuan; Wang, Shuyou; He, Xun; Cui, Xiang; Gao, Xinyan; Zhu, Bing

2017-10-01

Objective: Scalp acupuncture is a somatic stimulation therapy that produces prominent clinical effects when used to treat cerebral diseases. However, this acupuncture's therapeutic mechanisms have not yet been well-addressed. Scalp acupoints are innervated by the trigeminal nerve, which is coincident with the intracranial sensory afferents as well as with the meningeal vessels. In recent years, cerebrospinal fluid-contacting neurons have been found and proved to transmit allergic substances between brain the parenchyma and meninges, representing a possible network between scalp acupuncture and the brain. The aim of the current study was to observe the connections between scalp acupoints and the meninges and to establish a possible mechanism for scalp acupuncture. Materials and Methods: Twenty-five adult Sprague-Dawley rats were used for the present study. Evans Blue dye (Sigma Chemical Co, St. Louis, MO) was injected though each rat's caudal vein after trigeminal stimulation for plasma extravasation observation. Cerebral blood flow (CBF) values of the rat's brain surface were measured at different timepoints before and after electroacupuncture (EA) on GB 15 ( Toulinqi ) or ST 36 ( Zusanli ). Results: These preliminary studies indicated that neurogenic plasma extravasation on a rat's skin and dura mater after mechanical or electrical stimulation of the trigeminal nerves is a reliable way to show the pathologic connection between scalp acupoints and the meninges. Moreover, CBF of the rat's brain surface is increased significantly after EA stimulation at GB 15 ( Toulinqi ), which is located in the receptive field of the supraorbital nerve. Conclusions: These findings suggest that the mechanism of scalp acupuncture might lie in the specific neurologic pathway that could be termed as trigeminal nerve-meninges-cerebrospinal fluid-contacting neurons-brain , which is a possible shortcut to brain functional regulation and cerebral disease treatment.

Chitin biological absorbable catheters bridging sural nerve grafts transplanted into sciatic nerve defects promote nerve regeneration.

Science.gov (United States)

Wang, Zhi-Yong; Wang, Jian-Wei; Qin, Li-Hua; Zhang, Wei-Guang; Zhang, Pei-Xun; Jiang, Bao-Guo

2018-06-01

To investigate the efficacy of chitin biological absorbable catheters in a rat model of autologous nerve transplantation. A segment of sciatic nerve was removed to produce a sciatic nerve defect, and the sural nerve was cut from the ipsilateral leg and used as a graft to bridge the defect, with or without use of a chitin biological absorbable catheter surrounding the graft. The number and morphology of regenerating myelinated fibers, nerve conduction velocity, nerve function index, triceps surae muscle morphology, and sensory function were evaluated at 9 and 12 months after surgery. All of the above parameters were improved in rats in which the nerve graft was bridged with chitin biological absorbable catheters compared with rats without catheters. The results of this study indicate that use of chitin biological absorbable catheters to surround sural nerve grafts bridging sciatic nerve defects promotes recovery of structural, motor, and sensory function and improves muscle fiber morphology. © 2018 John Wiley & Sons Ltd.

A novel method of lengthening the accessory nerve for direct coaptation during nerve repair and nerve transfer procedures.

Science.gov (United States)

Tubbs, R Shane; Maldonado, Andrés A; Stoves, Yolanda; Fries, Fabian N; Li, Rong; Loukas, Marios; Oskouian, Rod J; Spinner, Robert J

2018-01-01

OBJECTIVE The accessory nerve is frequently repaired or used for nerve transfer. The length of accessory nerve available is often insufficient or marginal (under tension) for allowing direct coaptation during nerve repair or nerve transfer (neurotization), necessitating an interpositional graft. An attractive maneuver would facilitate lengthening of the accessory nerve for direct coaptation. The aim of the present study was to identify an anatomical method for such lengthening. METHODS In 20 adult cadavers, the C-2 or C-3 connections to the accessory nerve were identified medial to the sternocleidomastoid (SCM) muscle and the anatomy of the accessory nerve/cervical nerve fibers within the SCM was documented. The cervical nerve connections were cut. Lengths of the accessory nerve were measured. Samples of the cut C-2 and C-3 nerves were examined using immunohistochemistry. RESULTS The anatomy and adjacent neural connections within the SCM are complicated. However, after the accessory nerve was "detethered" from within the SCM and following transection, the additional length of the accessory nerve increased from a mean of 6 cm to a mean of 10.5 cm (increase of 4.5 cm) after cutting the C-2 connections, and from a mean of 6 cm to a mean length of 9 cm (increase of 3.5 cm) after cutting the C-3 connections. The additional length of accessory nerve even allowed direct repair of an infraclavicular target (i.e., the proximal musculocutaneous nerve). The cervical nerve connections were shown not to contain motor fibers. CONCLUSIONS An additional length of the accessory nerve made available in the posterior cervical triangle can facilitate direct repair or neurotization procedures, thus eliminating the need for an interpositional nerve graft, decreasing the time/distance for regeneration and potentially improving clinical outcomes.

Dynamic modulation of corticospinal excitability and short-latency afferent inhibition during onset and maintenance phase of selective finger movement.

Science.gov (United States)

Cho, Hyun Joo; Panyakaew, Pattamon; Thirugnanasambandam, Nivethida; Wu, Tianxia; Hallett, Mark

2016-06-01

During highly selective finger movement, corticospinal excitability is reduced in surrounding muscles at the onset of movement but this phenomenon has not been demonstrated during maintenance of movement. Sensorimotor integration may play an important role in selective movement. We sought to investigate how corticospinal excitability and short-latency afferent inhibition changes in active and surrounding muscles during onset and maintenance of selective finger movement. Using transcranial magnetic stimulation (TMS) and paired peripheral stimulation, input-output recruitment curve and short-latency afferent inhibition (SAI) were measured in the first dorsal interosseus and abductor digiti minimi muscles during selective index finger flexion. Motor surround inhibition was present only at the onset phase, but not at the maintenance phase of movement. SAI was reduced at onset but not at the maintenance phase of movement in both active and surrounding muscles. Our study showed dynamic changes in corticospinal excitability and sensorimotor modulation for active and surrounding muscles in different movement states. SAI does not appear to contribute to motor surround inhibition at the movement onset phase. Also, there seems to be different inhibitory circuit(s) other than SAI for the movement maintenance phase in order to delineate the motor output selectively when corticospinal excitability is increased in both active and surrounding muscles. This study enhances our knowledge of dynamic changes in corticospinal excitability and sensorimotor interaction in different movement states to understand normal and disordered movements. Published by Elsevier Ireland Ltd.

Afferent Neural Feedback Overrides the Modulating Effects of Arousal, Hypercapnia and Hypoxemia on Neonatal Cardio-respiratory Control.

Science.gov (United States)

Lumb, Kathleen J; Schneider, Jennifer M; Ibrahim, Thowfique; Rigaux, Anita; Hasan, Shabih U

2018-04-20

Evidence at whole animal, organ-system, and cellular and molecular levels suggests that afferent volume feedback is critical for establishment of adequate ventilation at birth. Due to the irreversible nature of vagal ablation studies to date, it was difficult to quantify the roles of afferent volume input, arousal and changes in blood gas tensions on neonatal respiratory control. During reversible perineural vagal block, profound apneas, and hypoxemia and hypercarbia were observed necessitating termination of perineural blockade. Respiratory depression and apneas were independent of the sleep states. We demonstrate that profound apneas and life-threatening respiratory failure in vagally denervated animals do not result from lack of arousal or hypoxemia. Change in sleep state and concomitant respiratory depression result from lack of afferent volume feedback, which appears to be critical for the maintenance of normal breathing patterns and adequate gas exchange during the early postnatal period. Afferent volume feedback plays a vital role in neonatal respiratory control. Mechanisms for the profound respiratory depression and life-threatening apneas observed in vagally denervated neonatal animals remain unclear. We investigated the roles of sleep states, hypoxic-hypercapnia and afferent volume feedback on respiratory depression using reversible perineural vagal block during early postnatal period. Seven lambs were instrumented during the first 48h of life to record/analyze sleep states, diaphragmatic electromyograph, arterial blood gas tensions, systemic arterial blood pressure and rectal temperature. Perineural cuffs were placed around the vagi to attain reversible blockade. Post-operatively, during the awake state, both vagi were blocked using 2% xylocaine for up to 30 minutes. Compared with baseline values, pHa, PaO 2 and SaO 2 decreased and PaCO 2 increased during perineural blockade (P Respiratory depression and apneas were independent of sleep states. This

Effects of drugs of abuse on putative rostromedial tegmental neurons, inhibitory afferents to midbrain dopamine cells.

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Lecca, Salvatore; Melis, Miriam; Luchicchi, Antonio; Ennas, Maria Grazia; Castelli, Maria Paola; Muntoni, Anna Lisa; Pistis, Marco

2011-02-01

Recent findings have underlined the rostromedial tegmental nucleus (RMTg), a structure located caudally to the ventral tegmental area, as an important site involved in the mechanisms of aversion. RMTg contains γ-aminobutyric acid neurons responding to noxious stimuli, densely innervated by the lateral habenula and providing a major inhibitory projection to reward-encoding midbrain dopamine (DA) neurons. One of the key features of drug addiction is the perseverance of drug seeking in spite of negative and unpleasant consequences, likely mediated by response suppression within neural pathways mediating aversion. To investigate whether the RMTg has a function in the mechanisms of addicting drugs, we studied acute effects of morphine, cocaine, the cannabinoid agonist WIN55212-2 (WIN), and nicotine on putative RMTg neurons. We utilized single unit extracellular recordings in anesthetized rats and whole-cell patch-clamp recordings in brain slices to identify and characterize putative RMTg neurons and their responses to drugs of abuse. Morphine and WIN inhibited both firing rate in vivo and excitatory postsynaptic currents (EPSCs) evoked by stimulation of rostral afferents in vitro, whereas cocaine inhibited discharge activity without affecting EPSC amplitude. Conversely, nicotine robustly excited putative RMTg neurons and enhanced EPSCs, an effect mediated by α7-containing nicotinic acetylcholine receptors. Our results suggest that activity of RMTg neurons is profoundly influenced by drugs of abuse and, as important inhibitory afferents to midbrain DA neurons, they might take place in the complex interplay between the neural circuits mediating aversion and reward.

Long-Term Effects of Botulinum Toxin Complex Type A Injection on Mechano- and Metabo-Sensitive Afferent Fibers Originating from Gastrocnemius Muscle.

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Guillaume Caron

Full Text Available The aim of the present study was to investigate long term effects of motor denervation by botulinum toxin complex type A (BoNT/A from Clostridium Botulinum, on the afferent fibers originating from the gastrocnemius muscle of rats. Animals were divided in 2 experimental groups: 1 untreated animals acting as control and 2 treated animals in which the toxin was injected in the left muscle, the latter being itself divided into 3 subgroups according to their locomotor recovery with the help of a test based on footprint measurements of walking rats: i no recovery (B0, ii 50% recovery (B50 and iii full recovery (B100. Then, muscle properties, metabosensitive afferent fiber responses to potassium chloride (KCl and lactic acid injections and Electrically-Induced Fatigue (EIF, and mechanosensitive responses to tendon vibrations were measured. At the end of the experiment, rats were killed and the toxin injected muscles were weighted. After toxin injection, we observed a complete paralysis associated to a loss of force to muscle stimulation and a significant muscle atrophy, and a return to baseline when the animals recover. The response to fatigue was only decreased in the B0 group. The responses to KCl injections were only altered in the B100 groups while responses to lactic acid were altered in the 3 injected groups. Finally, our results indicated that neurotoxin altered the biphasic pattern of response of the mechanosensitive fiber to tendon vibrations in the B0 and B50 groups. These results indicated that neurotoxin injection induces muscle afferent activity alterations that persist and even worsen when the muscle has recovered his motor activity.

Long-Term Effects of Botulinum Toxin Complex Type A Injection on Mechano- and Metabo-Sensitive Afferent Fibers Originating from Gastrocnemius Muscle.

Science.gov (United States)

Caron, Guillaume; Marqueste, Tanguy; Decherchi, Patrick

2015-01-01

The aim of the present study was to investigate long term effects of motor denervation by botulinum toxin complex type A (BoNT/A) from Clostridium Botulinum, on the afferent fibers originating from the gastrocnemius muscle of rats. Animals were divided in 2 experimental groups: 1) untreated animals acting as control and 2) treated animals in which the toxin was injected in the left muscle, the latter being itself divided into 3 subgroups according to their locomotor recovery with the help of a test based on footprint measurements of walking rats: i) no recovery (B0), ii) 50% recovery (B50) and iii) full recovery (B100). Then, muscle properties, metabosensitive afferent fiber responses to potassium chloride (KCl) and lactic acid injections and Electrically-Induced Fatigue (EIF), and mechanosensitive responses to tendon vibrations were measured. At the end of the experiment, rats were killed and the toxin injected muscles were weighted. After toxin injection, we observed a complete paralysis associated to a loss of force to muscle stimulation and a significant muscle atrophy, and a return to baseline when the animals recover. The response to fatigue was only decreased in the B0 group. The responses to KCl injections were only altered in the B100 groups while responses to lactic acid were altered in the 3 injected groups. Finally, our results indicated that neurotoxin altered the biphasic pattern of response of the mechanosensitive fiber to tendon vibrations in the B0 and B50 groups. These results indicated that neurotoxin injection induces muscle afferent activity alterations that persist and even worsen when the muscle has recovered his motor activity.

Increase of transcription factor EB (TFEB) and lysosomes in rat DRG neurons and their transportation to the central nerve terminal in dorsal horn after nerve injury.

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Jung, J; Uesugi, N; Jeong, N Y; Park, B S; Konishi, H; Kiyama, H

2016-01-28

In the spinal dorsal horn (DH), nerve injury activates microglia and induces neuropathic pain. Several studies clarified an involvement of adenosine triphosphate (ATP) in the microglial activation. However, the origin of ATP together with the release mechanism is unclear. Recent in vitro study revealed that an ATP marker, quinacrine, in lysosomes was released from neurite terminal of dorsal root ganglion (DRG) neurons to extracellular space via lysosomal exocytosis. Here, we demonstrate a possibility that the lysosomal ingredient including ATP released from DRG neurons by lysosomal-exocytosis is an additional source of the glial activation in DH after nerve injury. After rat L5 spinal nerve ligation (SNL), mRNA for transcription factor EB (TFEB), a transcription factor controlling lysosomal activation and exocytosis, was induced in the DRG. Simultaneously both lysosomal protein, LAMP1- and vesicular nuclear transporter (VNUT)-positive vesicles were increased in L5 DRG neurons and ipsilateral DH. The quinacrine staining in DH was increased and co-localized with LAMP1 immunoreactivity after nerve injury. In DH, LAMP1-positive vesicles were also co-localized with a peripheral nerve marker, Isolectin B4 (IB4) lectin. Injection of the adenovirus encoding mCherry-LAMP1 into DRG showed that mCherry-positive lysosomes are transported to the central nerve terminal in DH. These findings suggest that activation of lysosome synthesis including ATP packaging in DRG, the central transportation of the lysosome, and subsequent its exocytosis from the central nerve terminal of DRG neurons in response to nerve injury could be a partial mechanism for activation of microglia in DH. This lysosome-mediated microglia activation mechanism may provide another clue to control nociception and pain. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

Macrophage presence is essential for the regeneration of ascending afferent fibres following a conditioning sciatic nerve lesion in adult rats

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Smith Malcolm

2011-01-01

Full Text Available Abstract Background Injury to the peripheral branch of dorsal root ganglia (DRG neurons prior to injury to the central nervous system (CNS DRG branch results in the regeneration of the central branch. The exact mechanism mediating this regenerative trigger is not fully understood. It has been proposed that following peripheral injury, the intraganglionic inflammatory response by macrophage cells plays an important role in the pre-conditioning of injured CNS neurons to regenerate. In this study, we investigated whether the presence of macrophage cells is crucial for this type of regeneration to occur. We used a clodronate liposome technique to selectively and temporarily deplete these cells during the conditioning phase of DRG neurons. Results Retrograde and anterograde tracing results indicated that in macrophage-depleted animals, the regenerative trigger characteristic of pre-conditioned DRG neurons was abolished as compared to injury matched-control animals. In addition, depletion of macrophage cells led to: (i a reduction in macrophage infiltration into the CNS compartment even after cellular repopulation, (ii astrocyte up-regulation at rostral regions and down-regulation in brain derived neurotrophic factor (BDNF concentration in the serum. Conclusion Activation of macrophage cells in response to the peripheral nerve injury is essential for the enhanced regeneration of ascending sensory neurons.

Temporal code in the vibrissal system-Part II: Roughness surface discrimination

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Farfan, F D [Departamento de BioingenierIa, FACET, Universidad Nacional de Tucuman, INSIBIO - CONICET, CC 327, Postal Code CP 4000 (Argentina); AlbarracIn, A L [Catedra de Neurociencias, Facultad de Medicina, Universidad Nacional de Tucuman (Argentina); Felice, C J [Departamento de BioingenierIa, FACET, Universidad Nacional de Tucuman, INSIBIO - CONICET, CC 327, Postal Code CP 4000 (Argentina)

2007-11-15

Previous works have purposed hypotheses about the neural code of the tactile system in the rat. One of them is based on the physical characteristics of vibrissae, such as frequency of resonance; another is based on discharge patterns on the trigeminal ganglion. In this work, the purpose is to find a temporal code analyzing the afferent signals of two vibrissal nerves while vibrissae sweep surfaces of different roughness. Two levels of pressure were used between the vibrissa and the contact surface. We analyzed the afferent discharge of DELTA and GAMMA vibrissal nerves. The vibrissae movements were produced using electrical stimulation of the facial nerve. The afferent signals were analyzed using an event detection algorithm based on Continuous Wavelet Transform (CWT). The algorithm was able to detect events of different duration. The inter-event times detected were calculated for each situation and represented in box plot. This work allowed establishing the existence of a temporal code at peripheral level.

Temporal code in the vibrissal system-Part II: Roughness surface discrimination

International Nuclear Information System (INIS)

Farfan, F D; AlbarracIn, A L; Felice, C J

2007-01-01

Previous works have purposed hypotheses about the neural code of the tactile system in the rat. One of them is based on the physical characteristics of vibrissae, such as frequency of resonance; another is based on discharge patterns on the trigeminal ganglion. In this work, the purpose is to find a temporal code analyzing the afferent signals of two vibrissal nerves while vibrissae sweep surfaces of different roughness. Two levels of pressure were used between the vibrissa and the contact surface. We analyzed the afferent discharge of DELTA and GAMMA vibrissal nerves. The vibrissae movements were produced using electrical stimulation of the facial nerve. The afferent signals were analyzed using an event detection algorithm based on Continuous Wavelet Transform (CWT). The algorithm was able to detect events of different duration. The inter-event times detected were calculated for each situation and represented in box plot. This work allowed establishing the existence of a temporal code at peripheral level

Nanofiber Nerve Guide for Peripheral Nerve Repair and Regeneration

Science.gov (United States)

2016-04-01

1 Award Number: W81XWH-11-2-0047 TITLE: Nanofiber Nerve Guide for Peripheral Nerve Repair and Regeneration PRINCIPAL INVESTIGATOR: Ahmet Höke...TITLE AND SUBTITLE 5a. CONTRACT NUMBER W81XWH-11-2-0047 Nanofiber nerve guide for peripheral nerve repair and regeneration 5b. GRANT NUMBER...goal of this collaborative research project was to develop next generation engineered nerve guide conduits (NGCs) with aligned nanofibers and

Peripheral nerve injury induces glial activation in primary motor cortex

OpenAIRE

Julieta Troncoso; Julieta Troncoso; Efraín Buriticá; Efraín Buriticá

2015-01-01

Preliminary evidence suggests that peripheral facial nerve injuries are associated with sensorimotor cortex reorganization. We have characterized facial nerve lesion-induced structural changes in primary motor cortex layer 5 pyramidal neurons and their relationship with glial cell density using a rodent facial paralysis model. First, we used adult transgenic mice expressing green fluorescent protein in microglia and yellow fluorescent protein in pyramidal neurons which were subjected to eithe...

A fine structural localization of the non-specific cholinesterase activity in glomerular nerve formations (endings).

Science.gov (United States)

Dubový, P

1990-01-01

Snout glabrous skin (rhinarium) of the cat is innervated not only by typical simple lamellar corpuscles but also glomerular formations. In contrast to simple lamellar corpuscles, glomerular nerve formations are located away the dermal papillae. In cross sections, glomerular nerve formation consists of several axonal profiles enveloped by 1-2 cytoplasmic lamellae of Schwann cells. The space among them is filled by collagenous microfibrils and the basal lamina-like material. Capsule was composed from fibroblast-like cells without definite basal lamina. An electron-dense reaction product due to non-specific cholinesterase activity was associated with Schwann cells and their processes surrounding unmyelinated terminal portion of the sensory axons. Abundant reaction product was bound to the collagenous microfibrils and was deposited in extracellular matrix between Schwann cell processes. These results are further evidence for the presence of the non-specific cholinesterase molecules as integral component of the extracellular matrix in sensory corpuscles. On the basis of histochemical study two possible explanation are considered for functional involving of this enzyme in sensory nerve formations.

Radial nerve dysfunction

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Neuropathy - radial nerve; Radial nerve palsy; Mononeuropathy ... Damage to one nerve group, such as the radial nerve, is called mononeuropathy . Mononeuropathy means there is damage to a single nerve. Both ...

Malignant peripheral nerve sheath tumor of the oculomotor nerve

DEFF Research Database (Denmark)

Kozic, D; Nagulic, M; Ostojic, J

2006-01-01

We present the short-term follow-up magnetic resonance (MR) studies and 1H-MR spectroscopy in a child with malignant peripheral nerve sheath tumor of the oculomotor nerve associated with other less aggressive cranial nerve schwannomas. The tumor revealed perineural extension and diffuse nerve...

An implantable nerve cooler for the exercising dog.

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Borgdorff, P; Versteeg, P G

1984-01-01

An implantable nerve cooler has been constructed to block cervical vago-sympathetic activity in the exercising dog reversibly. An insulated gilt brass container implanted around the nerve is perfused with cooled alcohol via silicone tubes. The flow of alcohol is controlled by an electromagnetic valve to keep nerve temperature at the required value. Nerve temperature is measured by a thermistor attached to the housing and in contact with the nerve. It is shown that, during cooling, temperature at this location differs less than 2 degrees C from nerve core temperature. Measurement of changes in heart rate revealed that complete vagal block in the conscious animal is obtained at a nerve temperature of 2 degrees C and can be achieved within 50 s. During steady-state cooling in the exercising animal nerve temperature varied less than 0.5 degree C. When the coolers after 2 weeks of implantation were removed they showed no oxydation and could be used again.

Scaffoldless tissue-engineered nerve conduit promotes peripheral nerve regeneration and functional recovery after tibial nerve injury in rats

Institute of Scientific and Technical Information of China (English)

Aaron M. Adams; Keith W. VanDusen; Tatiana Y. Kostrominova; Jacob P. Mertens; Lisa M. Larkin

2017-01-01

Damage to peripheral nerve tissue may cause loss of function in both the nerve and the targeted muscles it innervates. This study compared the repair capability of engineered nerve conduit (ENC), engineered fibroblast conduit (EFC), and autograft in a 10-mm tibial nerve gap. ENCs were fabricated utilizing primary fibroblasts and the nerve cells of rats on embryonic day 15 (E15). EFCs were fabricated utilizing primary fi-broblasts only. Following a 12-week recovery, nerve repair was assessed by measuring contractile properties in the medial gastrocnemius muscle, distal motor nerve conduction velocity in the lateral gastrocnemius, and histology of muscle and nerve. The autografts, ENCs and EFCs reestablished 96%, 87% and 84% of native distal motor nerve conduction velocity in the lateral gastrocnemius, 100%, 44% and 44% of native specific force of medical gastrocnemius, and 63%, 61% and 67% of native medial gastrocnemius mass, re-spectively. Histology of the repaired nerve revealed large axons in the autograft, larger but fewer axons in the ENC repair, and many smaller axons in the EFC repair. Muscle histology revealed similar muscle fiber cross-sectional areas among autograft, ENC and EFC repairs. In conclusion, both ENCs and EFCs promot-ed nerve regeneration in a 10-mm tibial nerve gap repair, suggesting that the E15 rat nerve cells may not be necessary for nerve regeneration, and EFC alone can suffice for peripheral nerve injury repair.

Communication between radial nerve and medial cutaneous nerve of forearm

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R R Marathe

2010-01-01

Full Text Available Radial nerve is usually a branch of the posterior cord of the brachial plexus. It innervates triceps, anconeous, brachialis, brachioradialis, extensor carpi radialis longus muscles and gives the posterior cutaneous nerve of the arm, lower lateral cutaneous nerve of arm, posterior cutaneous nerve of forearm; without exhibiting any communication with the medial cutaneous nerve of forearm or any other nerve. We report communication between the radial nerve and medial cutaneous nerve of forearm on the left side in a 58-year-old male cadaver. The right sided structures were found to be normal. Neurosurgeons should keep such variations in mind while performing the surgeries of axilla and upper arm.

Ultrasound and nerve stimulator guided continuous femoral nerve block analgesia after total knee arthroplasty: a multicenter randomized controlled study

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Fen Wang

2015-02-01

Full Text Available BACKGROUND AND OBJECTIVES: Postoperative analgesia is crucial for early functional excise after total knee arthroplasty. To investigate the clinical efficacy of ultrasound and nerve stimulator guided continuous femoral nerve block analgesia after total knee arthroplasty. METHODS: 46 patients with ASA grade I-III who underwent total knee arthroplasty received postoperative analgesia from October 2012 to January 2013. In 22 patients, ultrasound and nerve stimulator guided continuous femoral nerve block were performed for analgesia (CFNB group; in 24 patients, epidural analgesia was done (PCEA group. The analgesic effects, side effects, articular recovery and complications were compared between two groups. RESULTS: At 6 h and 12 h after surgery, the knee pain score (VAS score during functional tests after active exercise and after passive excise in CFNB were significantly reduced when compared with PCEA group. The amount of parecoxib used in CFNB patients was significantly reduced when compared with PCEA group. At 48 h after surgery, the muscle strength grade in CFNB group was significantly higher, and the time to ambulatory activity was shorter than those in PCEA group. The incidence of nausea and vomiting in CFNB patients was significantly reduced when compared with PCEA group. CONCLUSION: Ultrasound and nerve stimulator guided continuous femoral nerve block provide better analgesia at 6 h and 12 h, demonstrated by RVAS and PVAS. The amount of parecoxib also reduces, the incidence of nausea and vomiting decreased, the influence on muscle strength is compromised and patients can perform ambulatory activity under this condition.

Ulnar nerve dysfunction

Science.gov (United States)

Neuropathy - ulnar nerve; Ulnar nerve palsy; Mononeuropathy; Cubital tunnel syndrome ... Damage to one nerve group, such as the ulnar nerve, is called mononeuropathy . Mononeuropathy means there is damage to a single nerve. Both ...

Effects of combined treatment of tadalafil and tamsulosin on bladder dysfunction via the inhibition of afferent nerve activities in a rat model of bladder outlet obstruction.

Science.gov (United States)

Furuta, Akira; Suzuki, Yasuyuki; Igarashi, Taro; Koike, Yusuke; Egawa, Shin; Yoshimura, Naoki

2018-03-08

To investigate the effects of combined treatment of tadalafil (a phosphodiesterase-5 inhibitor) and tamsulosin (an α 1 -adrenoceptor antagonist) on bladder dysfunction in a rat model of bladder outlet obstruction (BOO). Cystometry was performed in conscious female BOO rats 6 weeks after partially ligation of the urethra. Either tadalafil (0.03, 0.1 and 0.3 mg/kg) or tamsulosin (0.001, 0.003 and 0.01 mg/kg) was cumulatively applied intravenously at 30-min intervals to examine changes in cystometric parameters and blood pressures. Changes in cystometric parameters and blood pressures were also checked when tadalafil (0.3 mg/kg), tamsulosin (0.003 mg/kg) or both were intravenously applied. In BOO rats, application of either tadalafil (0.3 mg/kg) or tamsulosin (0.003, 0.01 mg/kg) alone significantly increased threshold pressures and intercontraction intervals whereas there were no significant changes in other cystometric parameters. In addition, because a significant reduction in blood pressures was detected after the administration of tamsulosin (0.01 mg/kg), tamsulosin at a lower dose (0.003 mg/kg) was used for the combined treatment. The combination therapy of tadalafil and tamsulosin induced a significantly larger rate of increase in intercontraction intervals (1.7 times) compared with monotherapy of either drug (1.3 times each) although the combined therapy did not affect blood pressures. These results suggest that the combination therapy of tadalafil and tamsulosin can induce the additive inhibitory effects on urinary frequency compared with monotherapy, more likely via inhibition of the afferent limb of micturition reflex rather than the efferent function as evidenced by the increases in threshold pressures and intercontraction intervals without affecting bladder contractile function.

A Physiologic Role for Serotonergic Transmission in Adult Rat Taste Buds

Science.gov (United States)

Jaber, Luc; Zhao, Fang-li; Kolli, Tamara; Herness, Scott

2014-01-01

Of the multiple neurotransmitters and neuropeptides expressed in the mammalian taste bud, serotonin remains both the most studied and least understood. Serotonin is expressed in a subset of taste receptor cells that form synapses with afferent nerve fibers (type III cells) and was once thought to be essential to neurotransmission (now understood as purinergic). However, the discovery of the 5-HT1A serotonin receptor in a subset of taste receptor cells paracrine to type III cell suggested a role in cell-to-cell communication during the processing of taste information. Functional data describing this role are lacking. Using anatomical and neurophysiological techniques, this study proposes a modulatory role for serotonin during the processing of taste information. Double labeling immunocytochemical and single cell RT-PCR technique experiments documented that 5-HT1A-expressing cells co-expressed markers for type II cells, cells which express T1R or T2R receptors and release ATP. These cells did not co-express type III cells markers. Neurophysiological recordings from the chorda tympani nerve, which innervates anterior taste buds, were performed prior to and during intravenous injection of a 5-HT1A receptor antagonist. These experiments revealed that serotonin facilitates processing of taste information for tastants representing sweet, sour, salty, and bitter taste qualities. On the other hand, injection of ondansetron, a 5-HT3 receptor antagonist, was without effect. Collectively, these data support the hypothesis that serotonin is a crucial element in a finely-tuned feedback loop involving the 5-HT1A receptor, ATP, and purinoceptors. It is hypothesized that serotonin facilitates gustatory signals by regulating the release of ATP through ATP-release channels possibly through phosphatidylinositol 4,5-bisphosphate resynthesis. By doing so, 5-HT1A activation prevents desensitization of post-synaptic purinergic receptors expressed on afferent nerve fibers and enhances the

A physiologic role for serotonergic transmission in adult rat taste buds.

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Luc Jaber

Full Text Available Of the multiple neurotransmitters and neuropeptides expressed in the mammalian taste bud, serotonin remains both the most studied and least understood. Serotonin is expressed in a subset of taste receptor cells that form synapses with afferent nerve fibers (type III cells and was once thought to be essential to neurotransmission (now understood as purinergic. However, the discovery of the 5-HT1A serotonin receptor in a subset of taste receptor cells paracrine to type III cell suggested a role in cell-to-cell communication during the processing of taste information. Functional data describing this role are lacking. Using anatomical and neurophysiological techniques, this study proposes a modulatory role for serotonin during the processing of taste information. Double labeling immunocytochemical and single cell RT-PCR technique experiments documented that 5-HT1A-expressing cells co-expressed markers for type II cells, cells which express T1R or T2R receptors and release ATP. These cells did not co-express type III cells markers. Neurophysiological recordings from the chorda tympani nerve, which innervates anterior taste buds, were performed prior to and during intravenous injection of a 5-HT1A receptor antagonist. These experiments revealed that serotonin facilitates processing of taste information for tastants representing sweet, sour, salty, and bitter taste qualities. On the other hand, injection of ondansetron, a 5-HT3 receptor antagonist, was without effect. Collectively, these data support the hypothesis that serotonin is a crucial element in a finely-tuned feedback loop involving the 5-HT1A receptor, ATP, and purinoceptors. It is hypothesized that serotonin facilitates gustatory signals by regulating the release of ATP through ATP-release channels possibly through phosphatidylinositol 4,5-bisphosphate resynthesis. By doing so, 5-HT1A activation prevents desensitization of post-synaptic purinergic receptors expressed on afferent nerve fibers

A physiologic role for serotonergic transmission in adult rat taste buds.

Science.gov (United States)

Jaber, Luc; Zhao, Fang-li; Kolli, Tamara; Herness, Scott

2014-01-01

Of the multiple neurotransmitters and neuropeptides expressed in the mammalian taste bud, serotonin remains both the most studied and least understood. Serotonin is expressed in a subset of taste receptor cells that form synapses with afferent nerve fibers (type III cells) and was once thought to be essential to neurotransmission (now understood as purinergic). However, the discovery of the 5-HT1A serotonin receptor in a subset of taste receptor cells paracrine to type III cell suggested a role in cell-to-cell communication during the processing of taste information. Functional data describing this role are lacking. Using anatomical and neurophysiological techniques, this study proposes a modulatory role for serotonin during the processing of taste information. Double labeling immunocytochemical and single cell RT-PCR technique experiments documented that 5-HT1A-expressing cells co-expressed markers for type II cells, cells which express T1R or T2R receptors and release ATP. These cells did not co-express type III cells markers. Neurophysiological recordings from the chorda tympani nerve, which innervates anterior taste buds, were performed prior to and during intravenous injection of a 5-HT1A receptor antagonist. These experiments revealed that serotonin facilitates processing of taste information for tastants representing sweet, sour, salty, and bitter taste qualities. On the other hand, injection of ondansetron, a 5-HT3 receptor antagonist, was without effect. Collectively, these data support the hypothesis that serotonin is a crucial element in a finely-tuned feedback loop involving the 5-HT1A receptor, ATP, and purinoceptors. It is hypothesized that serotonin facilitates gustatory signals by regulating the release of ATP through ATP-release channels possibly through phosphatidylinositol 4,5-bisphosphate resynthesis. By doing so, 5-HT1A activation prevents desensitization of post-synaptic purinergic receptors expressed on afferent nerve fibers and enhances the

Afferent projections to the different medial amygdala subdivisions: a retrograde tracing study in the mouse.

Science.gov (United States)

Cádiz-Moretti, Bernardita; Otero-García, Marcos; Martínez-García, Fernando; Lanuza, Enrique

2016-03-01

The medial amygdaloid nucleus (Me) is a key node in the socio-sexual brain, composed of anterior (MeA), posteroventral (MePV) and posterodorsal (MePD) subdivisions. These subdivisions have been suggested to play a different role in reproductive and defensive behaviours. In the present work we analyse the afferents of the three Me subdivisions using restricted injections of fluorogold in female outbred CD1 mice. The results reveal that the MeA, MePV and MePD share a common pattern of afferents, with some differences in the density of retrograde labelling in several nuclei. Common afferents to Me subdivisions include: the accessory olfactory bulbs, piriform cortex and endopiriform nucleus, chemosensory amygdala (receiving direct inputs from the olfactory bulbs), posterior part of the medial bed nucleus of the stria terminalis (BSTM), CA1 in the ventral hippocampus and posterior intralaminar thalamus. Minor projections originate from the basolateral amygdala and amygdalo-hippocampal area, septum, ventral striatum, several allocortical and periallocortical areas, claustrum, several hypothalamic structures, raphe and parabrachial complex. MeA and MePV share minor inputs from the frontal cortex (medial orbital, prelimbic, infralimbic and dorsal peduncular cortices), but differ in the lack of main olfactory projections to the MePV. By contrast, the MePD receives preferential projections from the rostral accessory olfactory bulb, the posteromedial BSTM and the ventral premammillary nucleus. In summary, the common pattern of afferents to the Me subdivisions and their interconnections suggest that they play cooperative instead of differential roles in the various behaviours (e.g., sociosexual, defensive) in which the Me has been shown to be involved.

Thyroid hormone is required for the pruning of afferent type II spiral ganglion neurons in the mouse cochlea

Science.gov (United States)

Sundaresan, Srividya; Balasubbu, Suganthalakshmi; Mustapha, Mirna

2015-01-01

Afferent connections to the sensory inner and outer hair cells in the cochlea refine and functionally mature during the thyroid hormone (TH)- critical period of inner ear development that occurs perinatally in rodents. In this study, we investigated the effects of hypothyroidism on afferent type II innervation to outer hair cells (OHCs) using the Snell dwarf mouse (Pit1dw). Using a transgenic approach to specifically label type II spiral ganglion neurons, we found that a lack of TH causes persistence of excess type II SGN connections to the OHCs, as well as continued expression of the hair cell functional marker, otoferlin, in the OHCs beyond the maturation period. We also observed a concurrent delay in efferent attachment to the OHCs. Supplementing with TH during the early postnatal period from postnatal day (P) 3 to P4 reversed the defect in type II SGN pruning but did not alter otoferlin expression. Our results show that hypothyroidism causes a defect in the large-scale pruning of afferent type II spiral ganglion neurons in the cochlea, and a delay in efferent attachment and the maturation of otoferlin expression. Our data suggest that the state of maturation of hair cells, as determined by otoferlin expression, may not regulate the pruning of their afferent innervation. PMID:26592716

Optogenetic probing of nerve and muscle function after facial nerve lesion in the mouse whisker system

Science.gov (United States)

Bandi, Akhil; Vajtay, Thomas J.; Upadhyay, Aman; Yiantsos, S. Olga; Lee, Christian R.; Margolis, David J.

2018-02-01

Optogenetic modulation of neural circuits has opened new avenues into neuroscience research, allowing the control of cellular activity of genetically specified cell types. Optogenetics is still underdeveloped in the peripheral nervous system, yet there are many applications related to sensorimotor function, pain and nerve injury that would be of great benefit. We recently established a method for non-invasive, transdermal optogenetic stimulation of the facial muscles that control whisker movements in mice (Park et al., 2016, eLife, e14140)1. Here we present results comparing the effects of optogenetic stimulation of whisker movements in mice that express channelrhodopsin-2 (ChR2) selectively in either the facial motor nerve (ChAT-ChR2 mice) or muscle (Emx1-ChR2 or ACTA1-ChR2 mice). We tracked changes in nerve and muscle function before and up to 14 days after nerve transection. Optogenetic 460 nm transdermal stimulation of the distal cut nerve showed that nerve degeneration progresses rapidly over 24 hours. In contrast, the whisker movements evoked by optogenetic muscle stimulation were up-regulated after denervation, including increased maximum protraction amplitude, increased sensitivity to low-intensity stimuli, and more sustained muscle contractions (reduced adaptation). Our results indicate that peripheral optogenetic stimulation is a promising technique for probing the timecourse of functional changes of both nerve and muscle, and holds potential for restoring movement after paralysis induced by nerve damage or motoneuron degeneration.

Meal parameters and vagal gastrointestinal afferents in mice that experienced early postnatal overnutrition.

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Biddinger, Jessica E; Fox, Edward A

2010-08-04

Early postnatal overnutrition results in a predisposition to develop obesity due in part to hypothalamic and sympathetic dysfunction. Potential involvement of another major regulatory system component--the vagus nerve--has not been examined. Moreover, feeding disturbances have rarely been investigated prior to development of obesity when confounds due to obesity are minimized. To examine these issues, litters were culled on the day of birth to create small litters (SL; overnutrition), or normal size litters (NL; normal nutrition). Body weight, fat pad weight, meal patterns, and vagal sensory duodenal innervation were compared between SL and NL adult mice prior to development of obesity. Meal patterns were studied 18 h/day for 3 weeks using a balanced diet. Then vagal mechanoreceptors were labeled using anterograde transport of wheatgerm agglutinin-horseradish peroxidase injected into the nodose ganglion and their density and morphology were examined. Between postnatal day 1 and weaning, body weight of SL mice was greater than for NL mice. By young adulthood it was similar in both groups, whereas SL fat pad weight was greater in males, suggesting postnatal overnutrition produced a predisposition to obesity. SL mice exhibited increased food intake, decreased satiety ratio, and increased first meal rate (following mild food deprivation) compared to NL mice, suggesting postnatal overnutrition disrupted satiety. The density and structure of intestinal IGLEs appeared similar in SL and NL mice. Thus, although a vagal role cannot be excluded, our meal parameter and anatomical findings provided no evidence for significant postnatal overnutrition effects on vagal gastrointestinal afferents. Copyright 2010 Elsevier Inc. All rights reserved.

Na+-independent, nifedipine-resistant rat afferent arteriolar Ca2+ responses to noradrenaline

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Salomonsson, Max; Braunstein, Thomas Hartig; von Holstein-Rathlou, Niels-Henrik

2010-01-01

Abstract Aim: In rat afferent arterioles we investigated the role of Na(+) entry in noradrenaline (NA)-induced depolarization and voltage-dependent Ca(2+) entry together with the importance of the transient receptor potential channel (TRPC) subfamily for non-voltage-dependent Ca(2+) entry. Methods...

The First Experience of Triple Nerve Transfer in Proximal Radial Nerve Palsy.

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Emamhadi, Mohammadreza; Andalib, Sasan

2018-01-01

Injury to distal portion of posterior cord of brachial plexus leads to palsy of radial and axillary nerves. Symptoms are usually motor deficits of the deltoid muscle; triceps brachii muscle; and extensor muscles of the wrist, thumb, and fingers. Tendon transfers, nerve grafts, and nerve transfers are options for surgical treatment of proximal radial nerve palsy to restore some motor functions. Tendon transfer is painful, requires a long immobilization, and decreases donor muscle strength; nevertheless, nerve transfer produces promising outcomes. We present a patient with proximal radial nerve palsy following a blunt injury undergoing triple nerve transfer. The patient was involved in a motorcycle accident with complete palsy of the radial and axillary nerves. After 6 months, on admission, he showed spontaneous recovery of axillary nerve palsy, but radial nerve palsy remained. We performed triple nerve transfer, fascicle of ulnar nerve to long head of the triceps branch of radial nerve, flexor digitorum superficialis branch of median nerve to extensor carpi radialis brevis branch of radial nerve, and flexor carpi radialis branch of median nerve to posterior interosseous nerve, for restoration of elbow, wrist, and finger extensions, respectively. Our experience confirmed functional elbow, wrist, and finger extensions in the patient. Triple nerve transfer restores functions of the upper limb in patients with debilitating radial nerve palsy after blunt injuries. Copyright © 2017 Elsevier Inc. All rights reserved.

Acid-sensing ion channels (ASICs) in mouse skeletal muscle afferents are heteromers composed of ASIC1a, ASIC2, and ASIC3 subunits

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Gautam, Mamta; Benson, Christopher J.

2013-01-01

Acid-sensing ion channels (ASICs) are expressed in skeletal muscle afferents, in which they sense extracellular acidosis and other metabolites released during ischemia and exercise. ASICs are formed as homotrimers or heterotrimers of several isoforms (ASIC1a, ASIC1b, ASIC2a, ASIC2b, and ASIC3), with each channel displaying distinct properties. To dissect the ASIC composition in muscle afferents, we used whole-cell patch-clamp recordings to study the properties of acid-evoked currents (amplitude, pH sensitivity, the kinetics of desensitization and recovery from desensitization, and pharmacological modulation) in isolated, labeled mouse muscle afferents from wild-type (C57BL/6J) and specific ASIC−/− mice. We found that ASIC-like currents in wild-type muscle afferents displayed fast desensitization, indicating that they are carried by heteromeric channels. Currents from ASIC1a−/− muscle afferents were less pH-sensitive and displayed faster recovery, currents from ASIC2−/− mice showed diminished potentiation by zinc, and currents from ASIC3−/− mice displayed slower desensitization than those from wild-type mice. Finally, ASIC-like currents were absent from triple-null mice lacking ASIC1a, ASIC2a, and ASIC3. We conclude that ASIC1a, ASIC2a, and ASIC3 heteromers are the principle channels in skeletal muscle afferents. These results will help us understand the role of ASICs in exercise physiology and provide a molecular target for potential drug therapies to treat muscle pain.—Gautam, M., Benson, C. J. Acid-sensing ion channels (ASICs) in mouse skeletal muscle afferents are heteromers composed of ASIC1a, ASIC2, and ASIC3 subunits. PMID:23109675

Axonal and glial currents activated during the post-tetanic hyperpolarization in non-myelinated nerve.

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Robert, A; Jirounek, P

1998-07-01

Changes in membrane potential and potassium concentration in the extracellular space ([K+]e) of rabbit vagus nerve were measured simultaneously during electrical activity and during the period of recovery using a modified sucrose-gap method and potassium-sensitive microelectrodes. After stimulation for 15 s at 15 Hz the main activity-induced increase in [K+]e reached 16.9 mM. This increase in [K+]e was paralleled by a depolarization of the preparation. The period of activity was followed by a post-tetanic hyperpolarization (PTH) lasting tens of seconds, generated by the axonal electrogenic Na+-K+ pump and to a lesser extent by the pump of the surrounding Schwann cells. The amplitude of the PTH dramatically increased in experiments in which inward currents were blocked by removal of Cl– or after application of Cs+ or Ba2+, indicating that under normal conditions the current generated by the Na+-K+ pump is strongly short-circuited. A pharmacological and kinetic study showed that these currents are: (1) the hyperpolarization-activated current I h, and (2) the inwardly rectifying I KIR current. The results show that the latter originates from Schwann cells. Our data indicate that in non-myelinated nerves there is a subtle association of inward ionic channels which (1) helps the cell to maintain an optimal membrane potential after a period of activity, and (2) contributes to the removal of excess K+ from the extracellular space.

Perceptual embodiment of prosthetic limbs by transcutaneous electrical nerve stimulation.

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Mulvey, Matthew R; Fawkner, Helen J; Radford, Helen E; Johnson, Mark I

2012-01-01

  In able-bodied participants, it is possible to induce a sense of perceptual embodiment in an artificial hand using a visual-tactile illusion. In amputee patients, electrical stimulation of sensory afferents using transcutaneous electrical nerve stimulation (TENS) has been shown to generate somatic sensations in an amputee's phantom limb(s). However, the effects of TENS on the perceptual embodiment of an artificial limb are not known. Our objective was to investigate the effects of TENS on the perceptual embodiment of an artificial limb in fully intact able-bodied participants.   We used a modified version of the rubber hand illusion presented to 30 able-bodied participants (16 women, 14 men) to convey TENS paresthesia to an artificial hand. TENS electrodes were located over superficial radial nerve on the lateral aspect of the right forearm (1 cm proximal to the wrist), which was hidden from view. TENS intensity was increased to a strong non-painful TENS sensation (electrical paresthesia) was felt beneath the electrodes and projecting into the fingers of the hand. The electrical characteristics of TENS were asymmetric biphasic electrical pulsed waves, continuous pulse pattern, 120 Hz pulse frequency (rate), and 80 µs pulse duration (width).   Participants reported significantly higher intensities of the rubber hand illusion during the two TENS conditions (mean = 5.8, standard deviation = 1.9) compared with the two non-TENS conditions (mean = 4.9, standard deviation = 1.7), p embodiment of an artificial hand. Further exploratory studies involving an amputee population are warranted. © 2011 International Neuromodulation Society.

One-stage human acellular nerve allograft reconstruction for digital nerve defects

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Xue-yuan Li

2015-01-01

Full Text Available Human acellular nerve allografts have a wide range of donor origin and can effectively avoid nerve injury in the donor area. Very little is known about one-stage reconstruction of digital nerve defects. The present study observed the feasibility and effectiveness of human acellular nerve allograft in the reconstruction of < 5-cm digital nerve defects within 6 hours after injury. A total of 15 cases of nerve injury, combined with nerve defects in 18 digits from the Department of Emergency were enrolled in this study. After debridement, digital nerves were reconstructed using human acellular nerve allografts. The patients were followed up for 6-24 months after reconstruction. Mackinnon-Dellon static two-point discrimination results showed excellent and good rates of 89%. Semmes-Weinstein monofilament test demonstrated that light touch was normal, with an obvious improvement rate of 78%. These findings confirmed that human acellular nerve allograft for one-stage reconstruction of digital nerve defect after hand injury is feasible, which provides a novel trend for peripheral nerve reconstruction.

Nerves and nerve endings in the skin of tropical cattle.

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Amakiri, S F; Ozoya, S E; Ogunnaike, P O

1978-01-01

The nerves and nerve endings in the skin of tropical cattle were studied using histological and histochemical techniques. Many nerve trunks and fibres were present in the reticular and papillary dermis in both hairy and non-hairy skin sites. In non-hairy skin locations such as the muzzle and lower lip, encapsulated endings akin to Krause and Ruffini end bulbs, which arise from myelinated nerve trunks situated lower down the dermis were observed at the upper papillary layer level. Some fibre trunks seen at this level extended upwards to terminate within dermal papillae as bulb-shaped longitudinally lamellated Pacinian-type endings, while other onion-shaped lamellated nerve structures were located either within dermal papillae or near the dermo-epidermal area. Intraepidermal free-ending nerve fibres, appearing non-myelinated were observed in areas with thick epidermis. Intraepidermal free-ending nerve fibres, appearing non-myelinated were observed in areas with thick epidermis. On hairy skin sites, however, organized nerve endings or intraepidermal nerve endings were not readily identifiable.

The pedunculopontine tegmentum controls renal sympathetic nerve activity and cardiorespiratory activities in nembutal-anesthetized rats.

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Anne M Fink

Full Text Available Elevated renal sympathetic nerve activity (RSNA accompanies a variety of complex disorders, including obstructive sleep apnea, heart failure, and chronic kidney disease. Understanding pathophysiologic renal mechanisms is important for determining why hypertension is both a common sequelae and a predisposing factor of these disorders. The role of the brainstem in regulating RSNA remains incompletely understood. The pedunculopontine tegmentum (PPT is known for regulating behaviors including alertness, locomotion, and rapid eye movement sleep. Activation of PPT neurons in anesthetized rats was previously found to increase splanchnic sympathetic nerve activity and blood pressure, in addition to altering breathing. The present study is the first investigation of the PPT and its potential role in regulating RSNA. Microinjections of DL-homocysteic acid (DLH were used to probe the PPT in 100-μm increments in Nembutal-anesthetized rats to identify effective sites, defined as locations where changes in RSNA could be evoked. A total of 239 DLH microinjections were made in 18 rats, which identified 20 effective sites (each confirmed by the ability to evoke a repeatable sympathoexcitatory response. Peak increases in RSNA occurred within 10-20 seconds of PPT activation, with RSNA increasing by 104.5 ± 68.4% (mean ± standard deviation from baseline. Mean arterial pressure remained significantly elevated for 30 seconds, increasing from 101.6 ± 18.6 mmHg to 135.9 ± 36.4 mmHg. DLH microinjections also increased respiratory rate and minute ventilation. The effective sites were found throughout the rostal-caudal extent of the PPT with most located in the dorsal regions of the nucleus. The majority of PPT locations tested with DLH microinjections did not alter RSNA (179 sites, suggesting that the neurons that confer renal sympathoexcitatory functions comprise a small component of the PPT. The study also underscores the importance of further investigation to

Diagnostic nerve ultrasonography

International Nuclear Information System (INIS)

Baeumer, T.; Grimm, A.; Schelle, T.

2017-01-01

For the diagnostics of nerve lesions an imaging method is necessary to visualize peripheral nerves and their surrounding structures for an etiological classification. Clinical neurological and electrophysiological investigations provide functional information about nerve lesions. The information provided by a standard magnetic resonance imaging (MRI) examination is inadequate for peripheral nerve diagnostics; however, MRI neurography is suitable but on the other hand a resource and time-consuming method. Using ultrasonography for peripheral nerve diagnostics. With ultrasonography reliable diagnostics of entrapment neuropathies and traumatic nerve lesions are possible. The use of ultrasonography for neuropathies shows that a differentiation between different forms is possible. Nerve ultrasonography is an established diagnostic tool. In addition to the clinical examination and clinical electrophysiology, structural information can be obtained, which results in a clear improvement in the diagnostics. Ultrasonography has become an integral part of the diagnostic work-up of peripheral nerve lesions in neurophysiological departments. Nerve ultrasonography is recommended for the diagnostic work-up of peripheral nerve lesions in addition to clinical and electrophysiological investigations. It should be used in the clinical work-up of entrapment neuropathies, traumatic nerve lesions and spacy-occupying lesions of nerves. (orig.) [de

Nerve ultrasound shows subclinical peripheral nerve involvement in neurofibromatosis type 2.

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Telleman, Johan A; Stellingwerff, Menno D; Brekelmans, Geert J; Visser, Leo H

2018-02-01

Neurofibromatosis type 2 (NF2) is mainly associated with central nervous system (CNS) tumors. Peripheral nerve involvement is described in symptomatic patients, but evidence of subclinical peripheral nerve involvement is scarce. We conducted a cross-sectional pilot study in 2 asymptomatic and 3 minimally symptomatic patients with NF2 to detect subclinical peripheral nerve involvement. Patients underwent clinical examination, nerve conduction studies (NCS), and high-resolution ultrasonography (HRUS). A total of 30 schwannomas were found, divided over 20 nerve segments (33.9% of all investigated nerve segments). All patients had at least 1 schwannoma. Schwannomas were identified with HRUS in 37% of clinically unaffected nerve segments and 50% of nerve segments with normal NCS findings. HRUS shows frequent subclinical peripheral nerve involvement in NF2. Clinicians should consider peripheral nerve involvement as a cause of weakness and sensory loss in the extremities in patients with this disease. Muscle Nerve 57: 312-316, 2018. © 2017 Wiley Periodicals, Inc.

Whole-Brain Monosynaptic Afferent Inputs to Basal Forebrain Cholinergic System

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Rongfeng Hu

2016-10-01

Full Text Available The basal forebrain cholinergic system (BFCS robustly modulates many important behaviors, such as arousal, attention, learning and memory, through heavy projections to cortex and hippocampus. However, the presynaptic partners governing BFCS activity still remain poorly understood. Here, we utilized a recently developed rabies virus-based cell-type-specific retrograde tracing system to map the whole-brain afferent inputs of the BFCS. We found that the BFCS receives inputs from multiple cortical areas, such as orbital frontal cortex, motor cortex, and insular cortex, and that the BFCS also receives dense inputs from several subcortical nuclei related to motivation and stress, including lateral septum (LS, central amygdala (CeA, paraventricular nucleus of hypothalamus (PVH, dorsal raphe (DRN and parabrachial nucleus (PBN. Interestingly, we found that the BFCS receives inputs from the olfactory areas and the entorhinal-hippocampal system. These results greatly expand our knowledge about the connectivity of the mouse BFCS and provided important preliminary indications for future exploration of circuit function.

Force sensor in simulated skin and neural model mimic tactile SAI afferent spiking response to ramp and hold stimuli.

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Kim, Elmer K; Wellnitz, Scott A; Bourdon, Sarah M; Lumpkin, Ellen A; Gerling, Gregory J

2012-07-23

The next generation of prosthetic limbs will restore sensory feedback to the nervous system by mimicking how skin mechanoreceptors, innervated by afferents, produce trains of action potentials in response to compressive stimuli. Prior work has addressed building sensors within skin substitutes for robotics, modeling skin mechanics and neural dynamics of mechanotransduction, and predicting response timing of action potentials for vibration. The effort here is unique because it accounts for skin elasticity by measuring force within simulated skin, utilizes few free model parameters for parsimony, and separates parameter fitting and model validation. Additionally, the ramp-and-hold, sustained stimuli used in this work capture the essential features of the everyday task of contacting and holding an object. This systems integration effort computationally replicates the neural firing behavior for a slowly adapting type I (SAI) afferent in its temporally varying response to both intensity and rate of indentation force by combining a physical force sensor, housed in a skin-like substrate, with a mathematical model of neuronal spiking, the leaky integrate-and-fire. Comparison experiments were then conducted using ramp-and-hold stimuli on both the spiking-sensor model and mouse SAI afferents. The model parameters were iteratively fit against recorded SAI interspike intervals (ISI) before validating the model to assess its performance. Model-predicted spike firing compares favorably with that observed for single SAI afferents. As indentation magnitude increases (1.2, 1.3, to 1.4 mm), mean ISI decreases from 98.81 ± 24.73, 54.52 ± 6.94, to 41.11 ± 6.11 ms. Moreover, as rate of ramp-up increases, ISI during ramp-up decreases from 21.85 ± 5.33, 19.98 ± 3.10, to 15.42 ± 2.41 ms. Considering first spikes, the predicted latencies exhibited a decreasing trend as stimulus rate increased, as is observed in afferent recordings. Finally, the SAI afferent's characteristic response

Characterization of spinal afferent neurons projecting to different chambers of the rat heart.

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Guić, Maja Marinović; Kosta, Vana; Aljinović, Jure; Sapunar, Damir; Grković, Ivica

2010-01-29

The pattern of distribution of spinal afferent neurons (among dorsal root ganglia-DRGs) that project to anatomically and functionally different chambers of the rat heart, as well as their morphological and neurochemical characteristics were investigated. Retrograde tracing using a patch loaded with Fast blue (FB) was applied to all four chambers of the rat heart and labeled cardiac spinal afferents were characterized by using three neurochemical markers. The majority of cardiac projecting neurons were found from T1 to T4 DRGs, whereas the peak was at T2 DRG. There was no difference in the total number of FB-labeled neurons located in ipsilateral and contralateral DRGs regardless of the chambers marked with the patch. However, significantly more FB-labeled neurons projected to the ventricles compared to the atria (859 vs. 715). The proportion of isolectin B(4) binding in FB-labeled neurons was equal among all neurons projecting to different heart chambers (2.4%). Neurofilament 200 positivity was found in greater proportions in DRG neurons projecting to the left side of the heart, whereas calretinin-immunoreactivity was mostly represented in neurons projecting to the left atrium. Spinal afferent neurons projecting to different chambers of the rat heart exhibit a variety of neurochemical phenotypes depending on binding capacity for isolectin B(4) and immunoreactivity for neurofilament 200 and calretinin, and thus represent important baseline data for future studies. (c) 2009 Elsevier Ireland Ltd. All rights reserved.

Afferent and efferent projections of the anterior cortical amygdaloid nucleus in the mouse.

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Cádiz-Moretti, Bernardita; Abellán-Álvaro, María; Pardo-Bellver, Cecília; Martínez-García, Fernando; Lanuza, Enrique

2017-09-01

The anterior cortical amygdaloid nucleus (ACo) is a chemosensory area of the cortical amygdala that receives afferent projections from both the main and accessory olfactory bulbs. The role of this structure is unknown, partially due to a lack of knowledge of its connectivity. In this work, we describe the pattern of afferent and efferent projections of the ACo by using fluorogold and biotinylated dextranamines as retrograde and anterograde tracers, respectively. The results show that the ACo is reciprocally connected with the olfactory system and basal forebrain, as well as with the chemosensory and basomedial amygdala. In addition, it receives dense projections from the midline and posterior intralaminar thalamus, and moderate projections from the posterior bed nucleus of the stria terminalis, mesocortical structures and the hippocampal formation. Remarkably, the ACo projects moderately to the central nuclei of the amygdala and anterior bed nucleus of the stria terminalis, and densely to the lateral hypothalamus. Finally, minor connections are present with some midbrain and brainstem structures. The afferent projections of the ACo indicate that this nucleus might play a role in emotional learning involving chemosensory stimuli, such as olfactory fear conditioning. The efferent projections confirm this view and, given its direct output to the medial part of the central amygdala and the hypothalamic 'aggression area', suggest that the ACo can initiate defensive and aggressive responses elicited by olfactory or, to a lesser extent, vomeronasal stimuli. © 2017 Wiley Periodicals, Inc.

Polymeric Nerve Conduits with Contact Guidance Cues Used in Nerve Repair

Institute of Scientific and Technical Information of China (English)

G DAI; X NIU; J YIN

2016-01-01

In the modern life, the nerve injury frequently happens due to mechanical, chemical or thermal accidents. In the trivial injuries, the peripheral nerves can regenerate on their own; however, in most of the cases the clinical treatments are required, where relatively large nerve injury gaps are formed. Currently, the nerve repair can be accomplished by direct suture when the injury gap is not too large;while the autologous nerve graft working as the gold standard of peripheral nerve injury treatment for nerve injuries with larger gaps. However, the direct suture is limited by heavy tension at the suture sites, and the autologous nerve graft also has the drawbacks of donor site morbidity and insufifcient donor tissue. Recently, artiifcial nerve conduits have been developed as an alternative for clinical nerve repair to overcome the limitations associated with the above treatments. In order to further improve the efifciency of nerve conduits, various guidance cues are incorporated, including physical cues, biochemical signals, as well as support cells. First, this paper reviewed the contact guidance cues applied in nerve conduits, such as lumen ifllers, multi-channels and micro-patterns on the inner surface. Then, the paper focused on the polymeric nerve conduits with micro inner grooves. The polymeric nerve conduits were fabricated using the phase inversion-based ifber spinning techniques. The smart spinneret with grooved die was designed in the spinning platform, while different spinning conditions, including flow rates, air-gap distances, and polymer concentrations, were adjusted to investigate the inlfuence of fabrication conditions on the geometry of nerve conduits. The inner groove size in the nerve conduits can be precisely controlled in our hollow ifber spinning process, which can work as the efifcient contact guidance cue for nerve regeneration.

Tissue-engineered spiral nerve guidance conduit for peripheral nerve regeneration.

Science.gov (United States)

Chang, Wei; Shah, Munish B; Lee, Paul; Yu, Xiaojun

2018-06-01

Recently in peripheral nerve regeneration, preclinical studies have shown that the use of nerve guidance conduits (NGCs) with multiple longitudinally channels and intra-luminal topography enhance the functional outcomes when bridging a nerve gap caused by traumatic injury. These features not only provide guidance cues for regenerating nerve, but also become the essential approaches for developing a novel NGC. In this study, a novel spiral NGC with aligned nanofibers and wrapped with an outer nanofibrous tube was first developed and investigated. Using the common rat sciatic 10-mm nerve defect model, the in vivo study showed that a novel spiral NGC (with and without inner nanofibers) increased the successful rate of nerve regeneration after 6 weeks recovery. Substantial improvements in nerve regeneration were achieved by combining the spiral NGC with inner nanofibers and outer nanofibrous tube, based on the results of walking track analysis, electrophysiology, nerve histological assessment, and gastrocnemius muscle measurement. This demonstrated that the novel spiral NGC with inner aligned nanofibers and wrapped with an outer nanofibrous tube provided a better environment for peripheral nerve regeneration than standard tubular NGCs. Results from this study will benefit for future NGC design to optimize tissue-engineering strategies for peripheral nerve regeneration. We developed a novel spiral nerve guidance conduit (NGC) with coated aligned nanofibers. The spiral structure increases surface area by 4.5 fold relative to a tubular NGC. Furthermore, the aligned nanofibers was coated on the spiral walls, providing cues for guiding neurite extension. Finally, the outside of spiral NGC was wrapped with randomly nanofibers to enhance mechanical strength that can stabilize the spiral NGC. Our nerve histological data have shown that the spiral NGC had 50% more myelinated axons than a tubular structure for nerve regeneration across a 10 mm gap in a rat sciatic nerve

CRF1 receptor activation increases the response of neurons in the basolateral nucleus of the amygdala to afferent stimulation

Directory of Open Access Journals (Sweden)

2008-07-01

Full Text Available The basolateral nucleus (BLA of the amygdala contributes to the consolidation of memories for emotional or stressful events. The nucleus contains a high density of CRF1 receptors that are activated by corticotropin-releasing factor (CRF. Modulation of the excitability of neurons in the BLA by CRF may regulate the immediate response to stressful events and the formation of associated memories. In the present study, CRF was found to increase the amplitude of field potentials recorded in the BLA following excitatory afferent stimulation, in vitro. The increase was mediated by CRF1 receptors, since it could be blocked by the selective, non-peptide antagonists, NBI30775 and NBI35583, but not by the CRF2-selective antagonist, astressin 2B. Furthermore, the CRF2-selective agonist, urocortin II had no effect on field potential amplitude. The increase induced by CRF was long-lasting, could not be reversed by subsequent administration of NBI35583, and required the activation of protein kinase C. This effect of CRF in the BLA may be important for increasing the salience of aversive stimuli under stressful conditions, and for enhancing the consolidation of associated memories. The results provide further justification for studying the efficacy of selective antagonists of the CRF1 receptor to reduce memory formation linked to emotional or traumatic events, and suggest that these compounds might be useful as prophylactic treatment for stress-related illness such as post-traumatic stress disorder.

Sensation, mechanoreceptor, and nerve fiber function after nerve regeneration

DEFF Research Database (Denmark)

Krarup, Christian; Rosén, Birgitta; Boeckstyns, Michel

2017-01-01

Objective: Sensation is essential for recovery after peripheral nerve injury. However, the relationship between sensory modalities and function of regenerated fibers is uncertain. We have investigated the relationships between touch threshold, tactile gnosis, and mechanoreceptor and sensory fiber...... function after nerve regeneration. Methods: Twenty-one median or ulnar nerve lesions were repaired by a collagen nerve conduit or direct suture. Quantitative sensory hand function and sensory conduction studies by near-nerve technique, including tactile stimulation of mechanoreceptors, were followed for 2...... years, and results were compared to noninjured hands. Results: At both repair methods, touch thresholds at the finger tips recovered to 81 ± 3% and tactile gnosis only to 20 ± 4% (p nerve action potentials (SNAPs) remained dispersed and areas recovered to 23 ± 2...