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Sample records for afferent nerve endings

  1. Different types of spinal afferent nerve endings in stomach and esophagus identified by anterograde tracing from dorsal root ganglia.

    PubMed

    Spencer, Nick J; Kyloh, Melinda; Beckett, Elizabeth A; Brookes, Simon; Hibberd, Tim

    2016-10-15

    In visceral organs of mammals, most noxious (painful) stimuli as well as innocuous stimuli are detected by spinal afferent neurons, whose cell bodies lie in dorsal root ganglia (DRGs). One of the major unresolved questions is the location, morphology, and neurochemistry of the nerve endings of spinal afferents that actually detect these stimuli in the viscera. In the upper gastrointestinal (GI) tract, there have been many anterograde tracing studies of vagal afferent endings, but none on spinal afferent endings. Recently, we developed a technique that now provides selective labeling of only spinal afferents. We used this approach to identify spinal afferent nerve endings in the upper GI tract of mice. Animals were anesthetized, and injections of dextran-amine were made into thoracic DRGs (T8-T12). Seven days post surgery, mice were euthanized, and the stomach and esophagus were removed, fixed, and stained for calcitonin gene-related peptide (CGRP). Spinal afferent axons were identified that ramified extensively through many rows of myenteric ganglia and formed nerve endings in discrete anatomical layers. Most commonly, intraganglionic varicose endings (IGVEs) were identified in myenteric ganglia of the stomach and varicose simple-type endings in the circular muscle and mucosa. Less commonly, nerve endings were identified in internodal strands, blood vessels, submucosal ganglia, and longitudinal muscle. In the esophagus, only IGVEs were identified in myenteric ganglia. No intraganglionic lamellar endings (IGLEs) were identified in the stomach or esophagus. We present the first identification of spinal afferent endings in the upper GI tract. Eight distinct types of spinal afferent endings were identified in the stomach, and most of them were CGRP immunoreactive. J. Comp. Neurol. 524:3064-3083, 2016. © 2016 Wiley Periodicals, Inc. PMID:27019197

  2. Identification of Different Types of Spinal Afferent Nerve Endings That Encode Noxious and Innocuous Stimuli in the Large Intestine Using a Novel Anterograde Tracing Technique

    PubMed Central

    Spencer, Nick J.; Kyloh, Melinda; Duffield, Michael

    2014-01-01

    In mammals, sensory stimuli in visceral organs, including those that underlie pain perception, are detected by spinal afferent neurons, whose cell bodies lie in dorsal root ganglia (DRG). One of the major challenges in visceral organs has been how to identify the different types of nerve endings of spinal afferents that transduce sensory stimuli into action potentials. The reason why spinal afferent nerve endings have been so challenging to identify is because no techniques have been available, until now, that can selectively label only spinal afferents, in high resolution. We have utilized an anterograde tracing technique, recently developed in our laboratory, which facilitates selective labeling of only spinal afferent axons and their nerve endings in visceral organs. Mice were anesthetized, lumbosacral DRGs surgically exposed, then injected with dextran-amine. Seven days post-surgery, the large intestine was removed. The characteristics of thirteen types of spinal afferent nerve endings were identified in detail. The greatest proportion of nerve endings was in submucosa (32%), circular muscle (25%) and myenteric ganglia (22%). Two morphologically distinct classes innervated myenteric ganglia. These were most commonly a novel class of intraganglionic varicose endings (IGVEs) and occasionally rectal intraganglionic laminar endings (rIGLEs). Three distinct classes of varicose nerve endings were found to innervate the submucosa and circular muscle, while one class innervated internodal strands, blood vessels, crypts of lieberkuhn, the mucosa and the longitudinal muscle. Distinct populations of sensory endings were CGRP-positive. We present the first complete characterization of the different types of spinal afferent nerve endings in a mammalian visceral organ. The findings reveal an unexpectedly complex array of different types of primary afferent endings that innervate specific layers of the large intestine. Some of the novel classes of nerve endings identified

  3. Combined Recording of Mechanically Stimulated Afferent Output and Nerve Terminal Labelling in Mouse Hair Follicle Lanceolate Endings.

    PubMed

    Bewick, Guy S; Cahusac, Peter M B; Banks, Robert W

    2016-01-01

    A novel dissection and recording technique is described for monitoring afferent firing evoked by mechanical displacement of hairs in the mouse pinna. The technique is very cost-effective and easily undertaken with materials commonly found in most electrophysiology laboratories, or easily purchased. The dissection is simple and fast, with the mechanical displacement provided by a generic electroceramic wafer controlled by proprietary software. The same software also records and analyses the electroneurogram output. The recording of the evoked nerve activity is through a commercial differential amplifier connected to fire-polished standard glass microelectrodes. Helpful tips are given for improving the quality of the preparation, the stimulation and the recording conditions to optimize recording quality. The system is suitable for assaying the electrophysiological and optical properties of lanceolate terminals of palisade endings of hair follicles, as well as the outcomes from their pharmacological and/or genetic manipulation. An example of combining electrical recording with mechanical stimulation and labeling with a styryl pyridinium vital dye is given. PMID:27213522

  4. Search for a cardiac nociceptor: stimulation by bradykinin of sympathetic afferent nerve endings in the heart of the cat.

    PubMed Central

    Baker, D G; Coleridge, H M; Coleridge, J C; Nerdrum, T

    1980-01-01

    1. We have examined the effect of bradykinin on impulse traffic in sympathetic afferent fibres from the heart, great vessels and pleura, and have attempted to identify cardiac nociceptors that on the basis of their functional characteristics might have a role in the initiation of cardiac pain. 2. In anaesthetized cats, we recorded afferent impulses from 'single-fibre' slips of the left 2nd--5th thoracic rami communicantes and associated chain, and selected fibres arising from endings in the heart, great vessels, pericardium and pleura. We applied bradykinin solution (0 . 1--1 . 0 microgram/ml.) locally to the site of the ending; we also injected bradykinin (0 . 3--1 . 0 microgram/kg) into the left atrium. 3. Afferent endings excited by bradykinin (159 of 191 tested) were of two types. The larger group (140) were primarily mechanoreceptors with A delta of C fibres (mean conduction velocity, 7 . 5 +/- 0 . 6 m/sec). They were very sensitive to light touch. Those located in the heart, great vessels or overlying pleura had a cardiac rhythm of discharge and were stimulated by an increase in blood pressure or cardiac volume. 4. Bradykinin increased mechanoreceptor firing from 0 . 7 +/- to 5 . 0 +/- 0 . 3 (mean +/- S.E. of mean) impulses/sec. Some endings appeared to be stimulated directly by bradykinin, others sensitized by it so that they responded more vigorously to the pulsatile mechanical stimulation associated with the cardiac cycle. 5. The smaller group of eighteen endings, of which ten were in the left ventricle, were primarily chemosensitive. Most had C fibres, a few had A delta fibres (mean conduction velocity, 2 . 3 +/- 0 . 7 m/sec). They were insensitive to light touch. With one exception they never fired with a cardiac rhythm, and even large increases in aortic or left ventricular pressure had little effect on impulse frequency. 6. Chemosensitive endings were stimulated by bradykinin, impulse activity increasing from 0 . 6 to 15 . 6 +/- 1 . 3 impulses/sec and

  5. In vitro Functional Characterization of Mouse Colorectal Afferent Endings

    PubMed Central

    Feng, Bin; Gebhart, G.F.

    2015-01-01

    This video demonstrates in detail an in vitro single-fiber electrophysiological recording protocol using a mouse colorectum-nerve preparation. The approach allows unbiased identification and functional characterization of individual colorectal afferents. Extracellular recordings of propagated action potentials (APs) that originate from one or a few afferent (i.e., single-fiber) receptive fields (RFs) in the colorectum are made from teased nerve fiber fascicles. The colorectum is removed with either the pelvic (PN) or lumbar splanchnic (LSN) nerve attached and opened longitudinally. The tissue is placed in a recording chamber, pinned flat and perfused with oxygenated Krebs solution. Focal electrical stimulation is used to locate the colorectal afferent endings, which are further tested by three distinct mechanical stimuli (blunt probing, mucosal stroking and circumferential stretch) to functionally categorize the afferents into five mechanosensitive classes. Endings responding to none of these mechanical stimuli are categorized as mechanically-insensitive afferents (MIAs). Both mechanosensitive and MIAs can be assessed for sensitization (i.e., enhanced response, reduced threshold, and/or acquisition of mechanosensitivity) by localized exposure of RFs to chemicals (e.g., inflammatory soup (IS), capsaicin, adenosine triphosphate (ATP)). We describe the equipment and colorectum–nerve recording preparation, harvest of colorectum with attached PN or LSN, identification of RFs in the colorectum, single-fiber recording from nerve fascicles, and localized application of chemicals to the RF. In addition, challenges of the preparation and application of standardized mechanical stimulation are also discussed. PMID:25651300

  6. On the nature of the afferent fibers of oculomotor nerve.

    PubMed

    Manni, E; Draicchio, F; Pettorossi, V E; Carobi, C; Grassi, S; Bortolami, R; Lucchi, M L

    1989-03-01

    The oculogyric nerves contain afferent fibers originating from the ophthalmic territory, the somata of which are located in the ipsilateral semilunar ganglion. These primary sensory neurons project to the Subnucleus Gelatinosus of the Nucleus Caudalis Trigemini, where they make presynaptic contact with the central endings of the primary trigeminal afferents running in the fifth cranial nerve. After complete section of the trigeminal root, the antidromic volleys elicited in the trunk of the third cranial nerve by stimulating SG of NCT consisted of two waves belonging to the A delta and C groups. The area of both components of the antidromic volleys decreased both after bradykinin and hystamine injection into the corresponding cutaneous region and after thermic stimulation of the ipsilateral trigeminal ophthalmic territory. The reduction of such potentials can be explained in terms of collision between the antidromic volleys and those elicited orthodromically by chemical and thermic stimulation. Also, capsaicin applied on the nerve induced an immediate increase, followed by a long lasting decrease, of orthodromic evoked response area. These findings bring further support to the nociceptive nature of the afferent fibers running into the oculomotor nerve. PMID:2719524

  7. Acid-sensing by airway afferent nerves

    PubMed Central

    Lee, Lu-Yuan; Gu, Qihai; Xu, Fadi; Hong, Ju-Lun

    2013-01-01

    Inhalation of acid aerosol or aspiration of acid solution evokes a stimulatory effect on airway C-fiber and Aδ afferents, which in turn causes airway irritation and triggers an array of defense reflex responses (e.g., cough, reflex bronchoconstriction, etc.). Tissue acidosis can also occur locally in the respiratory tract as a result of ischemia or inflammation, such as in the airways of asthmatic patients during exacerbation. The action of proton on the airway sensory neurons is generated by activation of two different current species: a transient (rapidly activating and inactivating) current mediated through the acid-sensing ion channels, and a slowly activating and sustained current mediated through the transient receptor potential vanilloid type 1 (TRPV1) receptor. In view of the recent findings that the expression and/or sensitivity of TRPV1 are up-regulated in the airway sensory nerves during chronic inflammatory reaction, the proton-evoked irritant effects on these nerves may play an important part in the manifestation of various symptoms associated with airway inflammatory diseases. PMID:23524016

  8. Peripheral innervation patterns of vestibular nerve afferents in the bullfrog utriculus

    NASA Technical Reports Server (NTRS)

    Baird, Richard A.; Schuff, N. R.

    1994-01-01

    Vestibular nerve afferents innervating the bullfrog utriculus differ in their response dynamics and sensitivity to natural stimulation. They also supply hair cells that differ markedly in hair bundle morphology. To examine the peripheral innervation patterns of individual utricular afferents more closely, afferent fibers were labeled by the extracellular injection of horseradish peroxidase (HRP) into the vestibular nerve after sectioning the vestibular nerve medial to Scarpa's ganglion to allow the degeneration of sympathetic and efferent fibers. The peripheral arborizations of individual afferents were then correlated with the diameters of their parent axons, the regions of the macula they innervate, and the number and type of hair cells they supply. The utriculus is divided by the striola, a narrow zone of distinctive morphology, into media and lateral parts. Utiricular afferents were classified as striolar or extrastriolar according to the epithelial entrance of their parent axons and the location of their terminal fields. In general, striolar afferents had thicker parent axons, fewer subepithelial bifurcations, larger terminal fields, and more synaptic endings than afferents in extrstriolar regions. Afferents in a juxtastriolar zone, immediately adjacent to the medial striola, had innervation patterns transitional between those in the striola and more peripheral parts of the medial extrastriola. moast afferents innervated only a single macular zone. The terminal fields of striolar afferents, with the notable exception of a few afferents with thin parent axons, were generally confined to one side of the striola. Hair cells in the bullfrog utriculus have perviously been classified into four types based on hair bundle morphology. Afferents in the extrastriolar and juxtastriolar zones largely or exclusively innervated Type B hair cells, the predominant hair cell type in the utricular macula. Striolar afferents supplied a mixture of four hair cell types, but largely

  9. Central changes in primary afferent fibers following peripheral nerve lesions.

    PubMed

    Coggeshall, R E; Lekan, H A; Doubell, T P; Allchorne, A; Woolf, C J

    1997-04-01

    Cutting or crushing rat sciatic nerve does not significantly reduce the number of central myelinated sensory axons in the dorsal roots entering the fourth and fifth lumbar segments even over very extended periods of time. Unmyelinated axons were reduced by approximately 50%, but only long after sciatic nerve lesions (four to eight months), and reinnervation of the peripheral target did not rescue these axons. This indicates that a peripheral nerve lesion sets up a slowly developing but major shift towards large afferent fiber domination of primary afferent input into the spinal cord. In addition, since myelinated axons are never lost, this is good evidence that the cells that give rise to these fibers are also not lost. If this is the case, this would indicate that adult primary sensory neurons with myelinated axons do not depend on peripheral target innervation for survival. PMID:9130791

  10. Afferent neurons of the hypoglossal nerve of the rat as demonstrated by horseradish peroxidase tracing.

    PubMed

    Neuhuber, W; Mysicka, A

    1980-01-01

    Cell bodies of sensory neurons of the rat's hypoglossal nerve were demonstrated by the somatopetal horseradish peroxidase (HRP) transport technique. Labelled perikarya were found within the second and third cervical spinal ganglia and in the vagal sensory ganglia. After application of HRP to the cut peripheral trunk of the hypoglossal nerve about 200 labelled cell bodies were counted in each animal. The vast majority of the axons from cervical spinal ganglion cells reach the hypoglossal nerve via the descending ramus (N. descendens hypoglossi). However, there may exist an additional pathway, probably via the cervical sympathetic trunk. Application of HPR to the medial and lateral end branches led to a labelling of much fewer spinal ganglion cells while the number of labelled vegal sensory neurons remained unchanged. Thus, it is suggested that the majority of the cervical afferents of the hypoglossal nerve originates within the extrinsic tongue musculature and the geniohyoid muscle, whereas the vagal afferents may perhaps derive exclusively from the intrinsic muslces. Histograms of the mean diameters of labelled cell bodies show a predominance of very small perikarya. This contrasts with the diameter distribution of sensory perikarya labelled after HRP application to nerves supplying other skeletal muscles. It is therefore assumed that the afferent component of the hypoglossal nerve is composed mainly of small-calibre axons. PMID:7356184

  11. Mechano- and thermosensitivity of regenerating cutaneous afferent nerve fibers.

    PubMed

    Jänig, Wilfrid; Grossmann, Lydia; Gorodetskaya, Natalia

    2009-06-01

    Crush lesion of a skin nerve is followed by sprouting of myelinated (A) and unmyelinated (C) afferent fibers into the distal nerve stump. Here, we investigate quantitatively both ongoing activity and activity evoked by mechanical or thermal stimulation of the nerve in 43 A- and 135 C-fibers after crush lesion of the sural nerve using neurophysiological recordings in anesthetized rats. The discharge patterns in the injured afferent nerve fibers and in intact (control) afferent nerve fibers were compared. (1) Almost all (98%) A-fibers were mechanosensitive, some of them exhibited additionally weak cold/heat sensitivity; 7% had ongoing activity. (2) Three patterns of physiologically evoked activity were present in the lesioned C-fibers: (a) C-fibers with type 1 cold sensitivity (low cold threshold, inhibition on heating, high level of ongoing and cold-evoked activity; 23%): almost all of them were mechanoinsensitive and 40% of them were additionally heat-sensitive; (b) C-fibers with type 2 cold sensitivity (high cold threshold, low level of ongoing and cold-evoked activity; 23%). All of them were excited by mechanical and/or heat stimuli; (c) cold-insensitive C-fibers (54%), which were heat- and/or mechanosensitive. (3) The proportions of C-fibers exhibiting these three patterns of discharge to physiological stimuli were almost identical in the population of injured C-fibers and in a population of 91 intact cutaneous C-fibers. 4. Ongoing activity was present in 56% of the lesioned C-fibers. Incidence and rate of ongoing activity were the same in the populations of lesioned and intact type 1 cold-sensitive C-fibers. The incidence (but not rate) of ongoing activity was significantly higher in lesioned type 2 cold-sensitive and cold insensitive C-fibers than in the corresponding populations of intact C-fibers (42/93 fibers vs. 11/72 fibers). PMID:19139872

  12. Phrenic nerve afferent activation of neurons in the cat SI cerebral cortex.

    PubMed

    Davenport, Paul W; Reep, Roger L; Thompson, Floyd J

    2010-03-01

    Stimulation of respiratory afferents elicits neural activity in the somatosensory region of the cerebral cortex in humans and animals. Respiratory afferents have been stimulated with mechanical loads applied to breathing and electrical stimulation of respiratory nerves and muscles. It was hypothesized that stimulation of the phrenic nerve myelinated afferents will activate neurons in the 3a and 3b region of the somatosensory cortex. This was investigated in cats with electrical stimulation of the intrathoracic phrenic nerve and C(5) root of the phrenic nerve. The somatosensory cortical response to phrenic afferent stimulation was recorded from the cortical surface, contralateral to the phrenic nerve, ispilateral to the phrenic nerve and with microelectrodes inserted into the cortical site of the surface dipole. Short-latency, primary cortical evoked potentials (1 degrees CEP) were recorded with stimulation of myelinated afferents of the intrathoracic phrenic nerve in the contralateral post-cruciate gyrus of all animals (n = 42). The mean onset and peak latencies were 8.5 +/- 5.7 ms and 21.8 +/- 9.8 ms, respectively. The rostro-caudal surface location of the 1 degrees CEP was found between the rostral edge of the post-cruciate dimple (PCD) and the rostral edge of the ansate sulcus, medio-lateral location was between 2 mm lateral to the sagittal sulcus and the lateral end of the cruciate sulcus. Histological examination revealed that the 1 degrees CEP sites were recorded over areas 3a and 3b of the SI somatosensory cortex. Intracortical activation of 16 neurons with two patterns of neural activity was recorded: (1) short-latency, short-duration activation of neurons and (2) long-latency, long-duration activation of neurons. Short-latency neurons had a mean onset latency of 10.4 +/- 3.1 ms and mean burst duration of 10.1 +/- 3.2 ms. The short-latency units were recorded at an average depth of 1.7 +/- 0.5 mm below the cortical surface. The long-latency neurons had a

  13. A novel method of selective ablation of afferent renal nerves by periaxonal application of capsaicin

    PubMed Central

    Foss, Jason D.; Wainford, Richard D.; Engeland, William C.; Fink, Gregory D.

    2014-01-01

    Renal denervation has been shown to lower arterial pressure in some hypertensive patients, yet it remains unclear whether this is due to ablation of afferent or efferent renal nerves. To investigate the role of afferent renal nerves in arterial pressure regulation, previous studies have used methods that disrupt both renal and nonrenal afferent signaling. The present study was conducted to develop and validate a technique for selective ablation of afferent renal nerves that does not disrupt other afferent pathways. To do this, we adapted a technique for sensory denervation of the adrenal gland by topical application of capsaicin and tested the hypothesis that exposure of the renal nerves to capsaicin (renal-CAP) causes ablation of afferent but not efferent renal nerves. Renal-CAP had no effect on renal content of the efferent nerve markers tyrosine hydroxylase and norepinephrine; however, the afferent nerve marker, calcitonin gene-related peptide was largely depleted from the kidney 10 days after intervention, but returned to roughly half of control levels by 7 wk postintervention. Moreover, renal-CAP abolished the cardiovascular responses to acute pharmacological stimulation of afferent renal nerves. Renal-CAP rats showed normal weight gain, as well as cardiovascular and fluid balance regulation during dietary sodium loading. To some extent, renal-CAP did blunt the bradycardic response and increase the dipsogenic response to increased salt intake. Lastly, renal-CAP significantly attenuated the development of deoxycorticosterone acetate-salt hypertension. These results demonstrate that renal-CAP effectively causes selective ablation of afferent renal nerves in rats. PMID:25411365

  14. The role of the renal afferent and efferent nerve fibers in heart failure

    PubMed Central

    Booth, Lindsea C.; May, Clive N.; Yao, Song T.

    2015-01-01

    Renal nerves contain afferent, sensory and efferent, sympathetic nerve fibers. In heart failure (HF) there is an increase in renal sympathetic nerve activity (RSNA), which can lead to renal vasoconstriction, increased renin release and sodium retention. These changes are thought to contribute to renal dysfunction, which is predictive of poor outcome in patients with HF. In contrast, the role of the renal afferent nerves remains largely unexplored in HF. This is somewhat surprising as there are multiple triggers in HF that have the potential to increase afferent nerve activity, including increased venous pressure and reduced kidney perfusion. Some of the few studies investigating renal afferents in HF have suggested that at least the sympatho-inhibitory reno-renal reflex is blunted. In experimentally induced HF, renal denervation, both surgical and catheter-based, has been associated with some improvements in renal and cardiac function. It remains unknown whether the effects are due to removal of the efferent renal nerve fibers or afferent renal nerve fibers, or a combination of both. Here, we review the effects of HF on renal efferent and afferent nerve function and critically assess the latest evidence supporting renal denervation as a potential treatment in HF. PMID:26483699

  15. Transient contractions of urinary bladder smooth muscle are drivers of afferent nerve activity during filling.

    PubMed

    Heppner, Thomas J; Tykocki, Nathan R; Hill-Eubanks, David; Nelson, Mark T

    2016-04-01

    Activation of afferent nerves during urinary bladder (UB) filling conveys the sensation of UB fullness to the central nervous system (CNS). Although this sensory outflow is presumed to reflect graded increases in pressure associated with filling, UBs also exhibit nonvoiding, transient contractions (TCs) that cause small, rapid increases in intravesical pressure. Here, using an ex vivo mouse bladder preparation, we explored the relative contributions of filling pressure and TC-induced pressure transients to sensory nerve stimulation. Continuous UB filling caused an increase in afferent nerve activity composed of a graded increase in baseline activity and activity associated with increases in intravesical pressure produced by TCs. For each ∼4-mmHg pressure increase, filling pressure increased baseline afferent activity by ∼60 action potentials per second. In contrast, a similar pressure elevation induced by a TC evoked an ∼10-fold greater increase in afferent activity. Filling pressure did not affect TC frequency but did increase the TC rate of rise, reflecting a change in the length-tension relationship of detrusor smooth muscle. The frequency of afferent bursts depended on the TC rate of rise and peaked before maximum pressure. Inhibition of small- and large-conductance Ca(2+)-activated K(+)(SK and BK) channels increased TC amplitude and afferent nerve activity. After inhibiting detrusor muscle contractility, simulating the waveform of a TC by gently compressing the bladder evoked similar increases in afferent activity. Notably, afferent activity elicited by simulated TCs was augmented by SK channel inhibition. Our results show that afferent nerve activity evoked by TCs represents the majority of afferent outflow conveyed to the CNS during UB filling and suggest that the maximum TC rate of rise corresponds to an optimal length-tension relationship for efficient UB contraction. Furthermore, our findings implicate SK channels in controlling the gain of sensory

  16. Effect of copper sulphate on the rate of afferent discharge in the gastric branch of the vagus nerve in the rat

    NASA Technical Reports Server (NTRS)

    Niijima, Akira; Jiang, Zheng-Yao; Daunton, Nancy G.; Fox, Robert A.

    1991-01-01

    The afferent nerve activity was recorded from a nerve filament isolated from the peripheral cut end of the gastric branch of the vagus nerve. The gastric perfusion of 4 ml of two different concentrations (0.04 percent and 0.08 percent) of CuSO4 solution provoked an increase in afferent activity. The stimulating effect of the 0.08 percent solution was stronger than that of the 0.04 percent solution, and lasted for a longer period of time. The observations suggest a possible mechanism by which CuSO4 elicits emesis.

  17. Characterization of Mouse Lumbar Splanchnic and Pelvic Nerve Urinary Bladder Mechanosensory Afferents

    PubMed Central

    Xu, Linjing; Gebhart, G. F.

    2009-01-01

    Sensory information from the urinary bladder is conveyed via lumbar splanchnic (LSN) and sacral pelvic (PN) nerves to the spinal cord. In the present report we compared the mechanosensitive properties of single afferent fibers in these two pathways using an in vitro mouse bladder preparation. Mechanosensitive primary afferents were recorded from the LSN or PN and distinguished based on their response to receptive field stimulation with different mechanical stimuli: probing (160 mg to 2 g), stretch (1–25 g), and stroking of the urothelium (10–1,000 mg). Four different classes of afferent were recorded from the LSN and PN: serosal, muscular, muscular/urothielial, and urothelial. The LSN contained principally serosal and muscular afferents (97% of the total sample), whereas all four afferent classes of afferent were present in the PN (63% of which were muscular afferents). In addition, the respective proportions and receptive field distributions differed between the two pathways. Both low- and high-threshold stretch-sensitive muscular afferents were present in both pathways, and muscular afferents in the PN were shown to sensitize after exposure to an inflammatory soup cocktail. The LSN and PN pathways contain different populations of mechanosensitive afferents capable of detecting a range of mechanical stimuli and individually tuned to detect the type, magnitude, and duration of the stimulus. This knowledge broadens our understanding of the potential roles these two pathways play in conveying mechanical information from the bladder to the spinal cord. PMID:18003875

  18. Interdependency between mechanical parameters and afferent nerve discharge in hypertrophic intestine of rats.

    PubMed

    Yang, Jian; Zhao, Jingbo; Chen, Pengmin; Nakaguchi, Toshiya; Grundy, David; Gregersen, Hans

    2016-03-15

    Partial intestinal obstruction causes smooth muscle hypertrophy, enteric neuronal plasticity, motility disorders, and biomechanical remodeling. In this study we characterized the stimulus-response function of afferent fibers innervating the partially obstructed jejunum. A key question is whether changes in afferent firing arise from remodeled mechanical tissue properties or from adaptive afferent processes. Partial obstruction was created by placing a polyethylene ring for 2 wk in jejunum of seven rats. Sham obstruction was made in six rats and seven rats served as normal controls. Firing from mesenteric afferent nerve bundles was recorded during mechanical ramp, relaxation, and creep tests. Stress-strain, spike rate increase ratio (SRIR), and firing rate in single units were assessed for evaluation of interdependency of the mechanical stimulations, histomorphometry data, and afferent nerve discharge. Partial intestinal obstruction resulted in hypertrophy and jejunal stiffening proximal to the obstruction site. Low SRIR at low strains during fast distension and at high stresses during slow distension was found in the obstructed rats. Single unit analysis showed increased proportion of mechanosensitive units but absent high-threshold (HT) units during slow stimulation, decreased number of HT units during fast stimulation, and shift from HT sensitivity towards low threshold sensitivity in the obstructed jejunum. Biomechanical remodeling and altered afferent response to mechanical stimulations were found in the obstructed jejunum. Afferents from obstructed jejunum preserved their function in encoding ongoing mechanical stimulation but showed changes in their responsiveness. The findings support that mechanical factors rather than adaption are important for afferent remodeling. PMID:26585414

  19. The Feline Dorsal Nerve of the Penis Arises from the Deep Perineal Nerve and Not the Sensory Afferent Branch

    PubMed Central

    Mariano, T. Y.; Boger, A. S.; Gustafson, K. J.

    2012-01-01

    Summary The cat has been used extensively as an animal model for urogenital studies involving the pudendal nerve. However, discrepancies persist in the literature regarding the origin of the dorsal nerve of the penis (DNP). This study used gross dissections and serial histological cross sections to demonstrate that the DNP arises from the deep perineal nerve and not the sensory afferent branch as previously reported. This finding indicates a better than previously appreciated neuroanatomical homology between the cat and human. PMID:18479311

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

    PubMed Central

    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 characteristics of colorectal afferents. The colorectum with PN attached was dissected, opened longitudinally, and pinned flat in a Sylgard-lined chamber. Action potentials of afferent fibers evoked by circumferential stretch (servo-controlled force actuator) were recorded from the PN. Stretch-sensitive fibers were categorized into the following four groups: colonic muscular, colonic muscular/mucosal, rectal muscular, and rectal muscular/mucosal. Seventy-nine stretch-sensitive PN afferents evenly distributed into the above four groups were studied. Rectal muscular afferents had significantly greater stretch-responses than the other three groups. Virtually all rectal afferents (98%) had low thresholds for response and encoded stimulus intensity into the noxious range without obvious saturation. Most colonic afferents (72%) also had low thresholds (<14 mmHg), but a significant proportion (28%) had high thresholds (>18 mmHg) for response. These high-threshold colonic afferents were sensitized to stretch by inflammatory soup; response threshold was significantly reduced (from 23 to 12 mmHg), and response magnitude significantly increased. These results suggest that the encoding of mechanosensory information differs between colonic and rectal stretch-sensitive PN afferents. Rectal afferents have a wide response range to stretch, whereas high-threshold colonic afferents likely contribute to visceral nociception. PMID:20075141

  1. Impaired intestinal afferent nerve satiety signalling and vagal afferent excitability in diet induced obesity in the mouse.

    PubMed

    Daly, Donna M; Park, Sung Jin; Valinsky, William C; Beyak, Michael J

    2011-06-01

    Gastrointestinal vagal afferents transmit satiety signals to the brain via both chemical and mechanical mechanisms. There is indirect evidence that these signals may be attenuated in obesity. We hypothesized that responses to satiety mediators and distension of the gut would be attenuated after induction of diet induced obesity. Obesity was induced by feeding a high fat diet (60% kcal from fat). Low fat fed mice (10% kcal from fat) served as a control. High fat fed mice were obese, with increased visceral fat, but were not hyperglycaemic. Recordings from jejunal afferents demonstrated attenuated responses to the satiety mediators cholecystokinin (CCK, 100 nm) and 5-hydroxytryptamine (5-HT, 10 μm), as was the response to low intensity jejunal distension, while responses to higher distension pressures were preserved. We performed whole cell patch clamp recordings on nodose ganglion neurons, both unlabelled, and those labelled by fast blue injection into the wall of the jejunum. The cell membrane of both labelled and unlabelled nodose ganglion neurons was less excitable in HFF mice, with an elevated rheobase and decreased number of action potentials at twice rheobase. Input resistance of HFF neurons was also significantly decreased. Calcium imaging experiments revealed reduced proportion of nodose ganglion neurons responding to CCK and 5-HT in obese mice. These results demonstrate a marked reduction in afferent sensitivity to satiety related stimuli after a chronic high fat diet. A major mechanism underlying this change is reduced excitability of the neuronal cell membrane. This may explain the development of hyperphagia when a high fat diet is consumed. Improving sensitivity of gastrointestinal afferent nerves may prove useful to limit food intake in obesity. PMID:21486762

  2. Effect of synthetic cationic protein on mechanoexcitability of vagal afferent nerve subtypes in guinea pig esophagus.

    PubMed

    Yu, Shaoyong; Ouyang, Ann

    2011-12-01

    Eosinophilic esophagitis is characterized by increased infiltration and degranulation of eosinophils in the esophagus. Whether eosinophil-derived cationic proteins regulate esophageal sensory nerve function is still unknown. Using synthetic cationic protein to investigate such effect, we performed extracellular recordings from vagal nodose or jugular neurons in ex vivo esophageal-vagal preparations with intact nerve endings in the esophagus. Nerve excitabilities were determined by comparing action potentials evoked by esophageal distensions before and after perfusion of synthetic cationic protein poly-L-lysine (PLL) with or without pretreatment with poly-L-glutamic acid (PLGA), which neutralized cationic charges of PLL. Perfusion with PLL did not evoke action potentials in esophageal nodose C fibers but increased their responses to esophageal distension. This potentiation effect lasted for 30 min after washing out of PLL. Pretreatment with PLGA significantly inhibited PLL-induced mechanohyperexcitability of esophageal nodose C fibers. In esophageal nodose Aδ fibers, perfusion with PLL did not evoke action potentials. In contrast to nodose C fibers, both the spontaneous discharges and the responses to esophageal distension in nodose Aδ fibers were decreased by perfusion with PLL, which can be restored after washing out PLL for 30-60 min. Pretreatment with PLGA attenuated PLL-induced decrease in spontaneous discharge and mechanoexcitability of esophageal nodose Aδ fibers. In esophageal jugular C fibers, PLL neither evoked action potentials nor changed their responses to esophageal distension. Collectively, these data demonstrated that synthetic cationic protein did not evoke action potential discharges of esophageal vagal afferents but had distinctive sensitization effects on their responses to esophageal distension. PMID:21960520

  3. Experimental and computational evidence for an essential role of NaV1.6 in spike initiation at stretch-sensitive colorectal afferent endings

    PubMed Central

    Zhu, Yi; La, Jun-Ho; Wills, Zachary P.; Gebhart, G. F.

    2015-01-01

    Stretch-sensitive afferents comprise ∼33% of the pelvic nerve innervation of mouse colorectum, which are activated by colorectal distension and encode visceral nociception. Stretch-sensitive colorectal afferent endings respond tonically to stepped or ramped colorectal stretch, whereas dissociated colorectal dorsal root ganglion neurons generally fail to spike repetitively upon stepped current stimulation. The present study investigated this difference in the neural encoding characteristics between the soma and afferent ending using pharmacological approaches in an in vitro mouse colon-nerve preparation and complementary computational simulations. Immunohistological staining and Western blots revealed the presence of voltage-gated sodium channel (NaV) 1.6 and NaV1.7 at sensory neuronal endings in mouse colorectal tissue. Responses of stretch-sensitive colorectal afferent endings were significantly reduced by targeting NaV1.6 using selective antagonists (μ-conotoxin GIIIa and μ-conotoxin PIIIa) or tetrodotoxin. In contrast, neither selective NaV1.8 (A803467) nor NaV1.7 (ProTX-II) antagonists attenuated afferent responses to stretch. Computational simulation of a colorectal afferent ending that incorporated independent Markov models for NaV1.6 and NaV1.7, respectively, recapitulated the experimental findings, suggesting a necessary role for NaV1.6 in encoding tonic spiking by stretch-sensitive afferents. In addition, computational simulation of a dorsal root ganglion soma showed that, by adding a NaV1.6 conductance, a single-spiking neuron was converted into a tonic spiking one. These results suggest a mechanism/channel to explain the difference in neural encoding characteristics between afferent somata and sensory endings, likely caused by differential expression of ion channels (e.g., NaV1.6) at different parts of the neuron. PMID:25652923

  4. Afferent vagal nerve stimulation resets baroreflex neural arc and inhibits sympathetic nerve activity

    PubMed Central

    Saku, Keita; Kishi, Takuya; Sakamoto, Kazuo; Hosokawa, Kazuya; Sakamoto, Takafumi; Murayama, Yoshinori; Kakino, Takamori; Ikeda, Masataka; Ide, Tomomi; Sunagawa, Kenji

    2014-01-01

    Abstract It has been established that vagal nerve stimulation (VNS) benefits patients and/or animals with heart failure. However, the impact of VNS on sympathetic nerve activity (SNA) remains unknown. In this study, we investigated how vagal afferent stimulation (AVNS) impacts baroreflex control of SNA. In 12 anesthetized Sprague–Dawley rats, we controlled the pressure in isolated bilateral carotid sinuses (CSP), and measured splanchnic SNA and arterial pressure (AP). Under a constant CSP, increasing the voltage of AVNS dose dependently decreased SNA and AP. The averaged maximal inhibition of SNA was ‐28.0 ± 10.3%. To evaluate the dynamic impacts of AVNS on SNA, we performed random AVNS using binary white noise sequences, and identified the transfer function from AVNS to SNA and that from SNA to AP. We also identified transfer functions of the native baroreflex from CSP to SNA (neural arc) and from SNA to AP (peripheral arc). The transfer function from AVNS to SNA strikingly resembled the baroreflex neural arc and the transfer functions of SNA to AP were indistinguishable whether we perturbed ANVS or CSP, indicating that they likely share common central and peripheral neural mechanisms. To examine the impact of AVNS on baroreflex, we changed CSP stepwise and measured SNA and AP responses with or without AVNS. AVNS resets the sigmoidal neural arc downward, but did not affect the linear peripheral arc. In conclusion, AVNS resets the baroreflex neural arc and induces sympathoinhibition in the same manner as the control of SNA and AP by the native baroreflex. PMID:25194023

  5. TRPM8 function and expression in vagal sensory neurons and afferent nerves innervating guinea pig esophagus.

    PubMed

    Yu, Xiaoyun; Hu, Youtian; Ru, Fei; Kollarik, Marian; Undem, Bradley J; Yu, Shaoyong

    2015-03-15

    Sensory transduction in esophageal afferents requires specific ion channels and receptors. TRPM8 is a new member of the transient receptor potential (TRP) channel family and participates in cold- and menthol-induced sensory transduction, but its role in visceral sensory transduction is still less clear. This study aims to determine TRPM8 function and expression in esophageal vagal afferent subtypes. TRPM8 agonist WS-12-induced responses were first determined in nodose and jugular neurons by calcium imaging and then investigated by whole cell patch-clamp recordings in Dil-labeled esophageal nodose and jugular neurons. Extracellular single-unit recordings were performed in nodose and jugular C fiber neurons using ex vivo esophageal-vagal preparations with intact nerve endings in the esophagus. TRPM8 mRNA expression was determined by single neuron RT-PCR in Dil-labeled esophageal nodose and jugular neurons. The TRPM8 agonist WS-12 elicited calcium influx in a subpopulation of jugular but not nodose neurons. WS-12 activated outwardly rectifying currents in esophageal Dil-labeled jugular but not nodose neurons in a dose-dependent manner, which could be inhibited by the TRPM8 inhibitor AMTB. WS-12 selectively evoked action potential discharges in esophageal jugular but not nodose C fibers. Consistently, TRPM8 transcripts were highly expressed in esophageal Dil-labeled TRPV1-positive jugular neurons. In summary, the present study demonstrated a preferential expression and function of TRPM8 in esophageal vagal jugular but not nodose neurons and C fiber subtypes. This provides a distinctive role of TRPM8 in esophageal sensory transduction and may lead to a better understanding of the mechanisms of esophageal sensation and nociception. PMID:25591866

  6. Afferent fibres from pulmonary arterial baroreceptors in the left cardiac sympathetic nerve of the cat

    PubMed Central

    Nishi, K.; Sakanashi, M.; Takenaka, F.

    1974-01-01

    1. Afferent discharges were recorded from the left cardiac sympathetic nerve or the third sympathetic ramus communicans of anaesthetized cats. Twenty-one single units with baroreceptor activity were obtained. 2. The receptors of each unit were localized to the extrapulmonary part of the pulmonary artery, determined by direct mechanical probing of the wall of the pulmonary artery after death of the animals. Conduction velocity of the fibres ranged from 2·5 to 15·7 m/sec. 3. Afferent discharges occurred irregularly under artificial ventilation. The impulse activity was increased when pulmonary arterial pressure was raised by an intravenous infusion of Locke solution, or by occlusion of lung roots, and decreased by bleeding the animal from the femoral artery. 4. Above a threshold pressure, discharges occurred synchronously with the systolic pressure pulse in the pulmonary artery. A progressive further rise in pressure did not produce an increase in the number of impulses per heart beat. Occlusion of lung roots initially elicited a burst of discharges but the number of impulses for each cardiac cycle gradually decreased. 5. The receptors responded to repetitive mechanical stimuli up to a frequency of 10/sec, but failed to respond to stimuli delivered at 20/sec. 6. The results provide further evidence for the presence of afferent fibres in the cardiac sympathetic nerve. These afferent fibres are likely to provide the spinal cord with specific information only on transient changes in pulmonary arterial pressure. PMID:4850456

  7. Mechanical sensitivity of muscle afferents in a nerve treated with colchicine.

    PubMed

    Proske, U; Luff, A R

    1998-04-01

    The experiments reported here demonstrate that the mechanical sensitivity of peripheral nerve fibres typically seen after injury can be induced without overtly injuring the nerve, but by simply applying colchicine topically to the nerve. In cats anaesthetised with pentobarbitone sodium, the medial gastrocnemius nerve was exposed and 10 mM colchicine applied topically for 15 min. The animals recovered from the operation normally and showed no subsequent motor deficit. Six days later animals were re-anaesthetised, a laminectomy carried out and responses recorded in single afferents at the level of the dorsal root. It was found that many afferents, particularly those with conduction velocities in the group II-III range, had become sensitive to local mechanical stimulation of the nerve in the region treated with colchicine and showed slowly adapting responses to stretch of the nerve. Many of the smaller fibres exhibited spontaneous activity. Mechanically sensitive afferents exhibited impulse conduction blocks at the colchicine-treated site. Some afferents, which appeared to conduct impulses normally through the treated region, were associated with muscle receptors having normal response properties. However, other muscle receptors were clearly abnormal and were insensitive to muscle stretch or contraction or exhibited only phasic responses. When the nerve was cut proximal to the colchicine-treated site, some, but not all, spontaneous activity was abolished. It was subsequently shown using a collision technique that the activity in some axons had its origin in the cell body in the dorsal root ganglion. In one experiment, it was shown that after nerve section proximal to the colchicine-treated region three of five axons switched their activity from a peripheral to a central origin. It is postulated that colchicine disrupts fast axonal transport of mechanically sensitive or voltage-sensitive ion channels, from the cell body to the peripheral terminals of the axons, leading

  8. Somatic modulation of spinal reflex bladder activity mediated by nociceptive bladder afferent nerve fibers in cats.

    PubMed

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

    2014-09-15

    The goal of the present study was to determine if supraspinal pathways are necessary for inhibition of bladder reflex activity induced by activation of somatic afferents in the pudendal or tibial nerve. Cats anesthetized with α-chloralose were studied after acute spinal cord transection at the thoracic T9/T10 level. Dilute (0.25%) acetic acid was used to irritate the bladder, activate nociceptive afferent C-fibers, and trigger spinal reflex bladder contractions (amplitude: 19.3 ± 2.9 cmH2O). Hexamethonium (a ganglionic blocker, intravenously) significantly (P < 0.01) reduced the amplitude of the reflex bladder contractions to 8.5 ± 1.9 cmH2O. Injection of lidocaine (2%, 1-2 ml) into the sacral spinal cord or transection of the sacral spinal roots and spinal cord further reduced the contraction amplitude to 4.2 ± 1.3 cmH2O. Pudendal nerve stimulation (PNS) at frequencies of 0.5-5 Hz and 40 Hz but not at 10-20 Hz inhibited reflex bladder contractions, whereas tibial nerve stimulation (TNS) failed to inhibit bladder contractions at all tested frequencies (0.5-40 Hz). These results indicate that PNS inhibition of nociceptive afferent C-fiber-mediated spinal reflex bladder contractions can occur at the spinal level in the absence of supraspinal pathways, but TNS inhibition requires supraspinal pathways. In addition, this study shows, for the first time, that after acute spinal cord transection reflex bladder contractions can be triggered by activating nociceptive bladder afferent C-fibers using acetic acid irritation. Understanding the sites of action for PNS or TNS inhibition is important for the clinical application of pudendal or tibial neuromodulation to treat bladder dysfunctions. PMID:25056352

  9. Social stress in mice induces urinary bladder overactivity and increases TRPV1 channel-dependent afferent nerve activity.

    PubMed

    Mingin, Gerald C; Heppner, Thomas J; Tykocki, Nathan R; Erickson, Cuixia Shi; Vizzard, Margaret A; Nelson, Mark T

    2015-09-15

    Social stress has been implicated as a cause of urinary bladder hypertrophy and dysfunction in humans. Using a murine model of social stress, we and others have shown that social stress leads to bladder overactivity. Here, we show that social stress leads to bladder overactivity, increased bladder compliance, and increased afferent nerve activity. In the social stress paradigm, 6-wk-old male C57BL/6 mice were exposed for a total of 2 wk, via barrier cage, to a C57BL/6 retired breeder aggressor mouse. We performed conscious cystometry with and without intravesical infusion of the TRPV1 inhibitor capsazepine, and measured pressure-volume relationships and afferent nerve activity during bladder filling using an ex vivo bladder model. Stress leads to a decrease in intermicturition interval and void volume in vivo, which was restored by capsazepine. Ex vivo studies demonstrated that at low pressures, bladder compliance and afferent activity were elevated in stressed bladders compared with unstressed bladders. Capsazepine did not significantly change afferent activity in unstressed mice, but significantly decreased afferent activity at all pressures in stressed bladders. Immunohistochemistry revealed that TRPV1 colocalizes with CGRP to stain nerve fibers in unstressed bladders. Colocalization significantly increased along the same nerve fibers in the stressed bladders. Our results support the concept that social stress induces TRPV1-dependent afferent nerve activity, ultimately leading to the development of overactive bladder symptoms. PMID:26224686

  10. Effects of intravenously administered lidocaine on pulmonary vagal afferents and phrenic nerve activity in cats.

    PubMed

    Aoki, M; Harada, Y; Namiki, A; Ikeda, M; Shimizu, H

    1992-10-01

    The ability of lidocaine to suppress activity of single vagal afferent fiber and that of phrenic nerve was studied in 20 cats anesthetized with pentobarbital. Slowly adapting stretch receptors (SAR, n = 16) and rapidly adapting stretch receptors (RAR, n = 7) were identified by their discharge pattern to pulmonary inflation. Intravenous lidocaine (1 mg.kg(-1) or 2 mg.kg(-1)) produced a suppression of SAR activity but not of RAR activity. Suppression of phrenic nerve activity lasted much longer than that of SAR. These findings indicate that iv lidocaine acts more dominantly on CNS than on peripherals. We conclude that iv lidocaine prevents cough and hemodynamic changes caused by airway manipulation mainly through its action on CNS and not on peripherals (peripheral nerves or their receptor). PMID:15278511

  11. Nerve injury induces a new profile of tactile and mechanical nociceptor input from undamaged peripheral afferents

    PubMed Central

    Gutierrez, Silvia; Aschenbrenner, Carol A.; Houle, Timothy T.; Hayashida, Ken-ichiro; Ririe, Douglas G.; Eisenach, James C.

    2014-01-01

    Chronic pain after nerve injury is often accompanied by hypersensitivity to mechanical stimuli, yet whether this reflects altered input, altered processing, or both remains unclear. Spinal nerve ligation or transection results in hypersensitivity to mechanical stimuli in skin innervated by adjacent dorsal root ganglia, but no previous study has quantified the changes in receptive field properties of these neurons in vivo. To address this, we recorded intracellularly from L4 dorsal root ganglion neurons of anesthetized young adult rats, 1 wk after L5 partial spinal nerve ligation (pSNL) or sham surgery. One week after pSNL, hindpaw mechanical withdrawal threshold in awake, freely behaving animals was decreased in the L4 distribution on the nerve-injured side compared with sham controls. Electrophysiology revealed that high-threshold mechanoreceptive cells of A-fiber conduction velocity in L4 were sensitized, with a seven-fold reduction in mechanical threshold, a seven-fold increase in receptive field area, and doubling of maximum instantaneous frequency in response to peripheral stimuli, accompanied by reductions in after-hyperpolarization amplitude and duration. Only a reduction in mechanical threshold (minimum von Frey hair producing neuronal activity) was observed in C-fiber conduction velocity high-threshold mechanoreceptive cells. In contrast, low-threshold mechanoreceptive cells were desensitized, with a 13-fold increase in mechanical threshold, a 60% reduction in receptive field area, and a 40% reduction in instantaneous frequency to stimulation. No spontaneous activity was observed in L4 ganglia, and the likelihood of recording from neurons without a mechanical receptive field was increased after pSNL. These data suggest massively altered input from undamaged sensory afferents innervating areas of hypersensitivity after nerve injury, with reduced tactile and increased nociceptive afferent response. These findings differ importantly from previous preclinical

  12. NERVE AS MODEL TEMPERATURE END ORGAN

    PubMed Central

    Bernhard, C. G.; Granit, Ragnar

    1946-01-01

    Rapid local cooling of mammalian nerve sets up a discharge which is preceded by a local temperature potential, the cooled region being electronegative relative to a normal portion of the nerve. Heating the nerve locally above its normal temperature similarly makes the heated region electronegative relative to a region at normal temperature, and again a discharge is set up from the heated region. These local temperature potentials, set up by the nerve itself, are held to serve as "generator potentials" and the mechanism found is regarded as the prototype for temperature end organs. PMID:19873460

  13. Concurrent recordings of bladder afferents from multiple nerves using a microfabricated PDMS microchannel electrode array.

    PubMed

    Delivopoulos, Evangelos; Chew, Daniel J; Minev, Ivan R; Fawcett, James W; Lacour, Stéphanie P

    2012-07-21

    In this paper we present a compliant neural interface designed to record bladder afferent activity. We developed the implant's microfabrication process using multiple layers of silicone rubber and thin metal so that a gold microelectrode array is embedded within four parallel polydimethylsiloxane (PDMS) microchannels (5 mm long, 100 μm wide, 100 μm deep). Electrode impedance at 1 kHz was optimized using a reactive ion etching (RIE) step, which increased the porosity of the electrode surface. The electrodes did not deteriorate after a 3 month immersion in phosphate buffered saline (PBS) at 37 °C. Due to the unique microscopic topography of the metal film on PDMS, the electrodes are extremely compliant and can withstand handling during implantation (twisting and bending) without electrical failure. The device was transplanted acutely to anaesthetized rats, and strands of the dorsal branch of roots L6 and S1 were surgically teased and inserted in three microchannels under saline immersion to allow for simultaneous in vivo recordings in an acute setting. We utilized a tripole electrode configuration to maintain background noise low and improve the signal to noise ratio. The device could distinguish two types of afferent nerve activity related to increasing bladder filling and contraction. To our knowledge, this is the first report of multichannel recordings of bladder afferent activity. PMID:22569953

  14. Phenotyping sensory nerve endings in vitro in the mouse

    PubMed Central

    Zimmermann, Katharina; Hein, Alexander; Hager, Ulrich; Kaczmarek, Jan Stefan; Turnquist, Brian P; Clapham, David E; Reeh, Peter W

    2014-01-01

    This protocol details methods to identify and record from cutaneous primary afferent axons in an isolated mammalian skin–saphenous nerve preparation. The method is based on extracellular recordings of propagated action potentials from single-fiber receptive fields. Cutaneous nerve endings show graded sensitivities to various stimulus modalities that are quantified by adequate and controlled stimulation of the superfused skin with heat, cold, touch, constant punctate pressure or chemicals. Responses recorded from single-fibers are comparable with those obtained in previous in vivo experiments on the same species. We describe the components and the setting-up of the basic equipment of a skin–nerve recording station (few days), the preparation of the skin and the adherent saphenous nerve in the mouse (15–45 min) and the isolation and recording of neurons (approximately 1–3 h per recording). In addition, stimulation techniques, protocols to achieve single-fiber recordings, issues of data acquisition and action potential discrimination are discussed in detail. PMID:19180088

  15. Functional classification of afferent phrenic nerve fibres and diaphragmatic receptors in cats.

    PubMed

    Bałkowiec, A; Kukuła, K; Szulczyk, P

    1995-03-15

    1. Single afferent fibres with receptive fields in the diaphragm (272 units) dissected from the right phrenic nerve were classified according to the following properties: reaction to contraction of the diaphragm, resting activity, conduction velocity, location and properties of receptive fields, and reaction to injection of bradykinin and lactic acid into the internal thoracic artery. Nine additional fibres dissected from the phrenic nerve had receptive fields outside the diaphragm. The experiments were performed on chloralose-anaesthetized cats. 2. Ninety-six fibres (36%) had high resting activity when unloaded by contraction of the diaphragm, had low-threshold receptive fields in the muscle and were mostly group II and III fibres. They probably innervated muscle spindles. 3. Eighty-eight fibres (32%) were vigorously activated by contraction of the diaphragm. They had low-threshold receptive fields located in the musculotendinous border and central tendon. Their conduction velocity was in the range for group II and III fibres. We infer that they may innervate tendon organs. 4. Eighty-eight fibres (32%) were slightly affected or not affected by diaphragmatic contraction. They had low- and high-threshold receptive fields located mostly in the muscular part of the diaphragm, and negligible resting activity. Most of them were group III and IV afferent fibres and were activated when bradykinin and lactic acid were applied to their receptive fields. Possibly these low- and high-threshold receptors innervated diaphragmatic ergo- and nociceptors, respectively. 5. Sensory outflow from the diaphragm was found to be somatotopically organized, so that fibres with receptive fields in the sternocostal portion were predominantly located in the upper phrenic nerve root, and those with lumbar receptive fields were in the lower root. 6. It is concluded that the phrenic nerve contains fibres from several distinct classes of sensory receptors: muscle spindles, tendon organs

  16. Functional classification of afferent phrenic nerve fibres and diaphragmatic receptors in cats.

    PubMed Central

    Bałkowiec, A; Kukuła, K; Szulczyk, P

    1995-01-01

    1. Single afferent fibres with receptive fields in the diaphragm (272 units) dissected from the right phrenic nerve were classified according to the following properties: reaction to contraction of the diaphragm, resting activity, conduction velocity, location and properties of receptive fields, and reaction to injection of bradykinin and lactic acid into the internal thoracic artery. Nine additional fibres dissected from the phrenic nerve had receptive fields outside the diaphragm. The experiments were performed on chloralose-anaesthetized cats. 2. Ninety-six fibres (36%) had high resting activity when unloaded by contraction of the diaphragm, had low-threshold receptive fields in the muscle and were mostly group II and III fibres. They probably innervated muscle spindles. 3. Eighty-eight fibres (32%) were vigorously activated by contraction of the diaphragm. They had low-threshold receptive fields located in the musculotendinous border and central tendon. Their conduction velocity was in the range for group II and III fibres. We infer that they may innervate tendon organs. 4. Eighty-eight fibres (32%) were slightly affected or not affected by diaphragmatic contraction. They had low- and high-threshold receptive fields located mostly in the muscular part of the diaphragm, and negligible resting activity. Most of them were group III and IV afferent fibres and were activated when bradykinin and lactic acid were applied to their receptive fields. Possibly these low- and high-threshold receptors innervated diaphragmatic ergo- and nociceptors, respectively. 5. Sensory outflow from the diaphragm was found to be somatotopically organized, so that fibres with receptive fields in the sternocostal portion were predominantly located in the upper phrenic nerve root, and those with lumbar receptive fields were in the lower root. 6. It is concluded that the phrenic nerve contains fibres from several distinct classes of sensory receptors: muscle spindles, tendon organs

  17. Implications for Bidirectional Signaling Between Afferent Nerves and Urothelial Cells—ICI-RS 2014

    PubMed Central

    Kanai, Anthony; Fry, Christopher; Ikeda, Youko; Kullmann, Florenta Aura; Parsons, Brian; Birder, Lori

    2016-01-01

    Aims To present a synopsis of the presentations and discussions from Think Tank I, “Implications for afferent–urothelial bidirectional communication” of the 2014 International Consultation on Incontinence-Research Society (ICI-RS) meeting in Bristol, UK. Methods The participants presented what is new, currently understood or still unknown on afferent–urothelial signaling mechanisms. New avenues of research and experimental methodologies that are or could be employed were presented and discussed. Results It is clear that afferent–urothelial interactions are integral to the regulation of normal bladder function and that its disruption can have detrimental consequences. The urothelium is capable of releasing numerous signaling factors that can affect sensory neurons innervating the suburothelium. However, the understanding of how factors released from urothelial cells and afferent nerve terminals regulate one another is incomplete. Utilization of techniques such as viruses that genetically encode Ca2+ sensors, based on calmodulin and green fluorescent protein, has helped to address the cellular mechanisms involved. Additionally, the epithelial–neuronal interactions in the urethra may also play a significant role in lower urinary tract regulation and merit further investigation. Conclusion The signaling capabilities of the urothelium and afferent nerves are well documented, yet how these signals are integrated to regulate bladder function is unclear. There is unquestionably a need for expanded methodologies to further our understanding of lower urinary tract sensory mechanisms and their contribution to various pathologies. PMID:26872567

  18. Enhanced release of adenosine in rat hind paw following spinal nerve ligation: involvement of capsaicin-sensitive sensory afferents.

    PubMed

    Liu, X J; White, T D; Sawynok, J

    2002-01-01

    Modulation of endogenous adenosine levels by inhibition of adenosine metabolism produces a peripheral antinociceptive effect in a neuropathic pain model. The present study used microdialysis to investigate the neuronal mechanisms modulating extracellular adenosine levels in the rat hind paw following tight ligation of the L5 and L6 spinal nerves. Subcutaneous injection of 50 microl saline into the nerve-injured paw induced a rapid and short-lasting increase in extracellular adenosine levels in the subcutaneous tissues of the rat hind paw ipsilateral to the nerve injury. Saline injection did not increase adenosine levels in sham-operated rats or non-treated rats. The adenosine kinase inhibitor 5'-amino-5'-deoxyadenosine and the adenosine deaminase inhibitor 2'-deoxycoformycin, at doses producing a peripheral antinociceptive effect, did not further enhance subcutaneous adenosine levels in the nerve-injured paw. Systemic pretreatment with capsaicin, a neurotoxin selective for small-diameter sensory afferents, markedly reduced the saline-evoked release of adenosine in rat hind paw following spinal nerve ligation. Systemic pretreatment with 6-hydroxydopamine, a neurotoxin selective for sympathetic afferent nerves, did not affect release. These results suggest that following nerve injury, peripheral capsaicin-sensitive primary sensory afferent nerve terminals are hypersensitive, and are able to release adenosine following a stimulus that does not normally evoke release in sham-operated or intact rats. Sympathetic postganglionic afferents do not appear to be involved in such release. The lack of effect on such release by the inhibitors of adenosine metabolism suggests an altered peripheral adenosine system following spinal nerve ligation. PMID:12204207

  19. An In Vitro Adult Mouse Muscle-nerve Preparation for Studying the Firing Properties of Muscle Afferents

    PubMed Central

    Franco, Joy A.; Kloefkorn, Heidi E.; Hochman, Shawn; Wilkinson, Katherine A.

    2014-01-01

    Muscle sensory neurons innervating muscle spindles and Golgi tendon organs encode length and force changes essential to proprioception. Additional afferent fibers monitor other characteristics of the muscle environment, including metabolite buildup, temperature, and nociceptive stimuli. Overall, abnormal activation of sensory neurons can lead to movement disorders or chronic pain syndromes. We describe the isolation of the extensor digitorum longus (EDL) muscle and nerve for in vitro study of stretch-evoked afferent responses in the adult mouse. Sensory activity is recorded from the nerve with a suction electrode and individual afferents can be analyzed using spike sorting software. In vitro preparations allow for well controlled studies on sensory afferents without the potential confounds of anesthesia or altered muscle perfusion. Here we describe a protocol to identify and test the response of muscle spindle afferents to stretch. Importantly, this preparation also supports the study of other subtypes of muscle afferents, response properties following drug application and the incorporation of powerful genetic approaches and disease models in mice. PMID:25285602

  20. Effect of stimulation of afferent renal nerves on plasma levels of vasopressin

    SciTech Connect

    Caverson, M.M.; Ciriello, J.

    1987-04-01

    Experiments were done in ..cap alpha..-chloralose-anesthetized, paralyzed and artificially ventilated cats with vagus, cervical sympathetic, aortic depressor, and carotid sinus nerves cut bilaterally to investigate the effect of afferent renal nerve (ARN) stimulation on circulating levels of vasopressin (AVP). Electrical stimulation of ARN elicited a pressor response that had two components, a primary (1/sup 0/) component locked in time with the stimulus and a secondary (2/sup 0/) component that had a long onset latency and that outlasted the stimulation period. The 1/sup 0/ and 2/sup 0/ components of the pressor response were largest at stimulation frequencies of 30 and 40 Hz, respectively. Autonomic blockage with hexamethonium bromide and atropine methylbromide abolished the 1/sup 0/ component. Administration of the vasopressin V/sub 1/-vascular receptor antagonist d(CH/sub 2/)/sub 5/ VAVP during autonomic blockade abolished the 2/sup 0/C component. Plasma concentrations of AVP measured by radioimmunoassay increased from control levels of 5.2 +/- 0.9 to 53.6 +/- 18.6 pg/ml during a 5-min period of stimulation of ARN. Plasma AVP levels measured 20-40 min after simulation were not significantly different from control values. These data demonstrate that sensory information originating in the kidney alters the release of vasopressin from the neurohypophysis and suggest that ARN are an important component of the neural circuitry involved in homeostatic mechanisms controlling arterial pressure.

  1. Sympathetic preganglionic efferent and afferent neurons mediated by the greater splanchnic nerve in rabbit

    NASA Technical Reports Server (NTRS)

    Torigoe, Yasuhiro; Cernucan, Roxana D.; Nishimoto, Jo Ann S.; Blanks, Robert H. I.

    1985-01-01

    As a part of the study of the vestibular-autonomic pathways involved in motion sickness, the location and the morphology of preganglionic sympathetic neurons (PSNs) projecting via the greater splanchnic nerve were examined. Retrograde labeling of neurons was obtained by application of horseradish peroxidase to the cut end of the greater splanchnic nerve. Labeled PSNs were found, ipsilaterally, within the T1 to T11 spinal cord segments, with the highest density of neurons in T6. Most PSNs were located within the intermediolateral column, but a significant portion also occurred within the lateral funiculus, the intercalated region, and the central autonomic area; the proportion of labeling between the four regions depended on the spinal cord segment.

  2. Regionally distinct cutaneous afferent populations contribute to reflex modulation evoked by stimulation of the tibial nerve during walking.

    PubMed

    Nakajima, Tsuyoshi; Suzuki, Shinya; Futatsubashi, Genki; Ohtsuska, Hiroyuki; Mezzarane, Rinaldo A; Barss, Trevor S; Klarner, Taryn; Zehr, E Paul; Komiyama, Tomoyoshi

    2016-07-01

    During walking, cutaneous reflexes in ankle flexor muscle [tibialis anterior (TA)] evoked by tibial nerve (TIB) stimulation are predominantly facilitatory at early swing phase but reverse to suppression at late swing phase. Although the TIB innervates a large portion of the skin of the foot sole, the extent to which specific foot-sole regions contribute to the reflex reversals during walking remains unclear. Therefore, we investigated regional cutaneous contributions from discrete portions of the foot sole on reflex reversal in TA following TIB stimulation during walking. Summation effects on reflex amplitudes, when applying combined stimulation from foot-sole regions with TIB, were examined. Middle latency responses (MLRs; 70-120 ms) after TIB stimulation were strongly facilitated during the late stance to mid-swing phases and reversed to suppression just before heel (HL) strike. Both forefoot-medial (f-M) and forefoot-lateral stimulation in the foot sole induced facilitation during stance-to-swing transition phases, but HL stimulation evoked suppression during the late stance to the end of swing phases. At the stance-to-swing transition, a summation of MLR amplitude occurred only for combined f-M&TIB stimulation. However, the same was not true for the combined HL&TIB stimulation. At the swing-to-stance transition, there was a suppressive reflex summation only for HL&TIB stimulation. In contrast, this summation was not observed for the f-M&TIB stimulation. Our results suggest that reflex reversals evoked by TIB stimulation arise from distinct reflex pathways to TA produced by separate afferent populations innervating specific regions of the foot sole. PMID:27075541

  3. Central distribution of the efferent cells and the primary afferent fibers of the trigeminal nerve in Pleurodeles waltlii (Amphibia, Urodela).

    PubMed

    Gonzalez, A; Muñoz, M

    1988-04-22

    As part of a study on the organization of the brainstem in a primitive group of vertebrates, the efferent cells and primary afferent fibers of the urodele amphibian Pleurodeles waltlii were examined by means of retrograde and anterograde axonal transport and anterograde degeneration. The trigeminal motor nucleus is located in the periventricular gray just medial to the sulcus limitans. Its rostral part is a band of pear-shaped cells lying parallel to the wall of the ventricle, whereas its caudal part is a round mass consisting of polygonal cells. In addition, a small group of scattered neurons is situated ventral to the rostral part of the nucleus. The primary afferent fibers enter the brainstem in the dorsal two-thirds of the trigeminal root. They diverge into a short ascending and a long descending tract. The former distributes its axons to the principal sensory trigeminal nucleus, which is an ill-defined cell group located at the ventrolateral edge of the periventricular gray. In the descending tract, the fibers of the ophthalmic nerve are predominantly located ventromedially, and those of the maxillomandibular nerve dorsolaterally. A fascicle of the ophthalmic nerve leaves the descending tract and, apparently, makes contact with the accessory abducens nucleus. The descending tract extends caudally into the three upper cervical segments of the spinal cord. The mesencephalic trigeminal nucleus consists of conspicuous large cells, which are scattered through the tectum of the mesencephalon. The cells with peripheral branches in the ophthalmic nerve are mainly located in the caudal half of the tectum, and those with peripheral branches in the maxillomandibular nerve in the rostral half. Collaterals of the central branches of the mesencephalic trigeminal system were traced to an area of the periventricular gray situated between the motor nucleus and the principal sensory nucleus of the trigeminus. PMID:2836480

  4. Rare human nerve growth factor-β mutation reveals relationship between C-afferent density and acute pain evaluation.

    PubMed

    Perini, Irene; Tavakoli, Mitra; Marshall, Andrew; Minde, Jan; Morrison, India

    2016-08-01

    The rare nerve growth factor-β (NGFB) mutation R221W causes a selective loss of thinly myelinated fibers and especially unmyelinated C-fibers. Carriers of this mutation show altered pain sensation. A subset presents with arthropathic symptoms, with the homozygous most severely affected. The aim of the present study was to investigate the relationship between peripheral afferent loss and pain evaluation by performing a quantification of small-fiber density in the cornea of the carriers, relating density to pain evaluation measures. In vivo corneal confocal microscopy (CCM) was used to quantify C-fiber loss in the cornea of 19 R221W mutation carriers (3 homozygous) and 19 age-matched healthy control subjects. Pain evaluation data via the Situational Pain Questionnaire (SPQ) and the severity of neuropathy based on the Neuropathy Disability Score (NDS) were assessed. Homozygotes, heterozygotes, and control groups differed significantly in corneal C-nerve fiber density, with the homozygotes showing a significant afferent reduction. Importantly, peripheral C-fiber loss correlated negatively with pain evaluation, as revealed by SPQ scores. This study is the first to investigate the contribution of small-fiber density to the perceptual evaluation of pain. It demonstrates that the lower the peripheral small-fiber density, the lower the degree of reported pain intensity, indicating a functional relationship between small-fiber density and higher level pain experience. PMID:27146986

  5. Nitric oxide modulates bladder afferent nerve activity in the in vitro urinary bladder-pelvic nerve preparation from rats with cyclophosphamide induced cystitis.

    PubMed

    Yu, Yongbei; de Groat, William C

    2013-01-15

    Effects of a nitric oxide (NO) donor (SNAP), NO substrate (l-arginine), and NO synthase inhibitor (l-NAME) on bladder afferent nerve (BAN) activity were studied in an in vitro bladder-pelvic nerve preparation from untreated or cyclophosphamide (CYP) treated rats. Distension of the bladder induced phasic bladder contractions (PBC) that were accompanied by multiunit afferent firing. Intravesical administration of SNAP (2mM) which did not change the amplitude of PBC significantly decreased peak afferent firing from 79 ± 15 spikes/s to 44 ± 8 spikes/s in CYP pretreated but not untreated preparations. In CYP treated preparations SNAP also decreased by 33-55% BAN firing induced by isotonic distension of the bladder at 10-40 cmH(2)O pressures. Electrical stimulation on the surface of the bladder elicited action potentials (AP) in BAN. SNAP significantly increased the voltage threshold by 75% (p<0.05) and decreased by 45% (p<0.05) the area of the AP evoked at submaximal stimulus intensity. Bath application of SNAP (2mM) or l-arginine (50mM) elicited similar inhibitory effects on the distension evoked BAN firing. The effects of l-arginine were blocked by bath application of l-NAME (20mM). l-NAME alone did not alter BAN firing. In preparations from normal rats SNAP or l-arginine did not alter BAN activity. These results suggest that exogenous as well as endogenously generated NO depresses the excitability of sensitized but not normal BAN and that NO may have an antinociceptive function and modulate bladder hyperactivity induced by pathological conditions. PMID:23063886

  6. Association between a relative afferent pupillary defect using pupillography and inner retinal atrophy in optic nerve disease

    PubMed Central

    Takizawa, Go; Miki, Atsushi; Maeda, Fumiatsu; Goto, Katsutoshi; Araki, Syunsuke; Ieki, Yoshiaki; Kiryu, Junichi; Yaoeda, Kiyoshi

    2015-01-01

    Purpose The aim of this study was to compare the asymmetrical light reflex of the control subjects and patients with optic nerve disease and to evaluate the relationships among the relative afferent pupillary defect (RAPD), visual acuity (VA), central critical fusion frequency (CFF), ganglion cell complex thickness (GCCT), and circumpapillary retinal nerve fiber layer thickness (cpRNFLT) using spectral-domain optical coherence tomography. Materials and methods Using a pupillography device, the RAPD scores from 15 patients with unilateral optic nerve disease and 35 control subjects were compared. The diagnostic accuracy of the RAPD amplitude and latency scores was compared using the area under the receiver operating characteristic curve. Thereafter, we assessed the relationships among the RAPD scores, VA, central CFF, GCCT, and cpRNFLT. Results The average RAPD amplitude score in patients with optic nerve disease was significantly higher than that of the control subjects (P<0.001). The average RAPD latency score in patients with optic nerve disease was significantly higher than that of the control subjects (P=0.001). The area under the receiver operating characteristic curve for the RAPD amplitude score was significantly higher than that for the latency score (P=0.010). The correlation coefficients for the RAPD amplitude and latency scores were 0.847 (P<0.001) and 0.874 (P<0.001) for VA, −0.868 (P<0.001) and −0.896 (P<0.001) for central CFF, −0.593 (P=0.020) and −0.540 (P=0.038) for GCCT, and −0.267 (P=0.337) and −0.228 (P=0.413) for cpRNFLT, respectively. Conclusion Our results suggest that pupillography is useful for detecting optic nerve disease. PMID:26487800

  7. Response properties of whisker-associated primary afferent neurons following infraorbital nerve transection with microsurgical repair in adult rats.

    PubMed

    Xiao, Bo; Zanoun, Rami R; Carvell, George E; Simons, Daniel J; Washington, Kia M

    2016-03-01

    The rodent whisker/trigeminal system, characterized by high spatial and temporal resolution, provides an experimental model for developing new therapies for improving sensory functions of damaged peripheral nerves. Here, we use controlled whisker stimulation and single-unit recordings of trigeminal ganglion cells to examine in detail the nature and time course of functional recovery of mechanoreceptive afferents following nerve transection with microsurgical repair of the infraorbital nerve (ION) branch of the trigeminal nerve in adult rats. Response measures include rapid vs. slow adaptation, firing rate, interspike intervals, latency, and angular (directional) tuning. Whisker-evoked responses, readily observable by 3 wk post-transection, recover progressively for at least the next 5 wk. All cells in transected animals, as in control cases, responded to deflections of single whiskers only, but topography within the ganglion was clearly disrupted. The time course and extent of recovery of quantitative response measures were receptor dependent. Cells displaying slowly adapting (SA) properties recovered more quickly than rapidly adapting (RA) populations, and for some response measures-notably evoked firing rates-closely approached or attained control levels by 8 wk post-transection. Angular tuning of RA cells was slightly better than control units, whereas SA tuning did not differ from control values. Nerve conduction times and refractory periods, examined separately using electrical stimulation of the ION, were slower than normal in all transected animals and poorly reflected recovery of whisker-evoked response latencies and interspike intervals. Results underscore the need for multiple therapeutic strategies that target different aspects of functional restitution following peripheral nerve injury. PMID:26792886

  8. Evoked Pain Analgesia in Chronic Pelvic Pain Patients using Respiratory-gated Auricular Vagal Afferent Nerve Stimulation

    PubMed Central

    Napadow, Vitaly; Edwards, Robert R; Cahalan, Christine M; Mensing, George; Greenbaum, Seth; Valovska, Assia; Li, Ang; Kim, Jieun; Maeda, Yumi; Park, Kyungmo; Wasan, Ajay D.

    2012-01-01

    Objective Previous Vagus Nerve Stimulation (VNS) studies have demonstrated anti-nociceptive effects, and recent non-invasive approaches; termed transcutaneous-VNS, or t-VNS, have utilized stimulation of the auricular branch of the vagus nerve in the ear. The dorsal medullary vagal system operates in tune with respiration, and we propose that supplying vagal afferent stimulation gated to the exhalation phase of respiration can optimize t-VNS. Design counterbalanced, crossover study. Patients patients with chronic pelvic pain (CPP) due to endometriosis in a specialty pain clinic. Interventions/Outcomes We evaluated evoked pain analgesia for Respiratory-gated Auricular Vagal Afferent Nerve Stimulation (RAVANS) compared with Non-Vagal Auricular Stimulation (NVAS). RAVANS and NVAS were evaluated in separate sessions spaced at least one week apart. Outcome measures included deep tissue pain intensity, temporal summation of pain, and anxiety ratings, which were assessed at baseline, during active stimulation, immediately following stimulation, and 15 minutes after stimulus cessation. Results RAVANS demonstrated a trend for reduced evoked pain intensity and temporal summation of mechanical pain, and significantly reduced anxiety in N=15 CPP patients, compared to NVAS, with moderate to large effect sizes (eta2>0.2). Conclusion Chronic pain disorders such as CPP are in great need of effective, non-pharmacological options for treatment. RAVANS produced promising anti-nociceptive effects for QST outcomes reflective of the noted hyperalgesia and central sensitization in this patient population. Future studies should evaluate longer-term application of RAVANS to examine its effects on both QST outcomes and clinical pain. PMID:22568773

  9. Spike Sorting of Muscle Spindle Afferent Nerve Activity Recorded with Thin-Film Intrafascicular Electrodes

    PubMed Central

    Djilas, Milan; Azevedo-Coste, Christine; Guiraud, David; Yoshida, Ken

    2010-01-01

    Afferent muscle spindle activity in response to passive muscle stretch was recorded in vivo using thin-film longitudinal intrafascicular electrodes. A neural spike detection and classification scheme was developed for the purpose of separating activity of primary and secondary muscle spindle afferents. The algorithm is based on the multiscale continuous wavelet transform using complex wavelets. The detection scheme outperforms the commonly used threshold detection, especially with recordings having low signal-to-noise ratio. Results of classification of units indicate that the developed classifier is able to isolate activity having linear relationship with muscle length, which is a step towards online model-based estimation of muscle length that can be used in a closed-loop functional electrical stimulation system with natural sensory feedback. PMID:20369071

  10. Intact sciatic myelinated primary afferent terminals collaterally sprout in the adult rat dorsal horn following section of a neighbouring peripheral nerve.

    PubMed

    Doubell, T P; Mannion, R J; Woolf, C J

    1997-03-31

    Peripheral nerve section induces sprouting of the central terminals of axotomized myelinated primary afferents outside their normal dorsoventral termination zones in lamina I, III, and IV of the dorsal horn into lamina II, an area that normally only receives unmyelinated C-fiber input. This axotomy-induced regenerative sprouting is confined to the somatotopic boundaries of the injured nerve in the spinal cord. We examined whether intact myelinated sciatic afferents are able to sprout novel terminals into neighbouring areas of the dorsal horn in the adult rat following axotomy of two test nerves, either the posterior cutaneous nerve of the thigh or the saphenous nerve. These peripheral nerves have somatotopically organized terminal areas in the dorsal horn that overlap in some areas and are contiguous in others, with that of the sciatic central terminal field. Two weeks after cutting either the posterior cutaneous or the saphenous nerve, intact sciatic myelinated fibers labelled with the B fragment of cholera toxin conjugated to horseradish peroxidase (B-HRP) sprouted into an area of lamina II normally only innervated by the adjacent injured test nerve. This collateral sprouting was strictly limited, however, to those particular areas of the dorsal horn where the A-fiber terminal field of the control sciatic and the C-fiber terminal field of the injured test nerve overlapped in the dorsoventral plane. No mediolateral sprouting was seen into those areas of neuropil solely innervated by the test nerve. We conclude that intact myelinated primary afferents do have the capacity to collaterally sprout, but that any resultant somatotopic reorganization of central projections is limited to the dorsoventral plane. These changes may contribute to sensory hypersensitivity at the edges of denervated skin. PMID:9073085

  11. Far-Infrared Therapy Promotes Nerve Repair following End-to-End Neurorrhaphy in Rat Models of Sciatic Nerve Injury

    PubMed Central

    Chen, Tai-Yuan; Yang, Yi-Chin; Sha, Ya-Na; Chou, Jiun-Rou

    2015-01-01

    This study employed a rat model of sciatic nerve injury to investigate the effects of postoperative low-power far-infrared (FIR) radiation therapy on nerve repair following end-to-end neurorrhaphy. The rat models were divided into the following 3 groups: (1) nerve injury without FIR biostimulation (NI/sham group); (2) nerve injury with FIR biostimulation (NI/FIR group); and (3) noninjured controls (normal group). Walking-track analysis results showed that the NI/FIR group exhibited significantly higher sciatic functional indices at 8 weeks after surgery (P < 0.05) compared with the NI/sham group. The decreased expression of CD4 and CD8 in the NI/FIR group indicated that FIR irradiation modulated the inflammatory process during recovery. Compared with the NI/sham group, the NI/FIR group exhibited a significant reduction in muscle atrophy (P < 0.05). Furthermore, histomorphometric assessment indicated that the nerves regenerated more rapidly in the NI/FIR group than in the NI/sham group; furthermore, the NI/FIR group regenerated neural tissue over a larger area, as well as nerve fibers of greater diameter and with thicker myelin sheaths. Functional recovery, inflammatory response, muscular reinnervation, and histomorphometric assessment all indicated that FIR radiation therapy can accelerate nerve repair following end-to-end neurorrhaphy of the sciatic nerve. PMID:25722734

  12. [Effect of narcotic analgesics on impulse conduction along the afferent pathways of visceral nerves].

    PubMed

    Churiukanov, V V; Sinitsyn, L N

    1976-06-01

    Experiments were conducted on chloralose-anesthetized cats. The action of morphine and promedol upon the potentials of the cortical and subcortical structures occurring after the visceral nerve stimulation was studied. Morphine proved to depress the potentials evoked by stimulation of the inferior cardiac and vagus nerves, in the specific, associative and nonspecific structures of the brain; promedol produced an analogous effect. Morphine also inhibited the potentials occurring after the stimulation of the splanchnic nerve in the associative and nonspecific structures; depression of the responses in the specific pathways was less pronounced. PMID:953307

  13. Morphology of nerve endings in vocal fold of human newborn.

    PubMed

    Gonçalves da Silva Leite, Janaina; Costa Cavalcante, Maria Luzete; Fechine-Jamacaru, Francisco Vagnaldo; de Lima Pompeu, Margarida Maria; Leite, José Alberto Dias; Nascimento Coelho, Dulce Maria; Rabelo de Freitas, Marcos

    2016-10-01

    Sensory receptors are distributed throughout the oral cavity, pharynx, and larynx. Laryngeal sensitivity is crucial for maintaining safe swallowing, thus avoiding silent aspiration. Morphologic description of different receptor types present in larynx vary because of the study of many different species, from mouse to humans. The most commonly sensory structures described in laryngeal mucosa are free nerve endings, taste buds, muscle spindles, glomerular and corpuscular receptors. This study aimed at describing the morphology and the distribution of nerve endings in premature newborn glottic region. Transversal serial frozen sections of the whole vocal folds of three newborns were analyzed using an immuno-histochemical process with a pan-neuronal marker anti-protein gene product 9.5 (PGP 9.5). Imaging was done using a confocal laser microscope. Nerve fiber density in vocal cord was calculated using panoramic images in software Morphometric Analysis System v1.0. Some sensory structures, i.e. glomerular endings and intraepithelial free nerve endings were found in the vocal cord mucosa. Muscle spindles, complex nerve endings (Meissner-like, spherical, rectangular and growing) spiral-wharves nerve structures were identified in larynx intrinsic muscles. Nervous total mean density in vocal cord was similar in the three newborns, although they had different gestational age. The mean nerve fiber density was higher in the posterior region than anterior region of vocal cord. The present results demonstrate the occurrence of different morphotypes of sensory corpuscles and nerve endings premature newborn glottic region and provide information on their sensory systems. PMID:27619029

  14. High sensitivity recording of afferent nerve activity using ultra-compliant microchannel electrodes: an acute in vivo validation

    NASA Astrophysics Data System (ADS)

    Minev, Ivan R.; Chew, Daniel J.; Delivopoulos, Evangelos; Fawcett, James W.; Lacour, Stéphanie P.

    2012-04-01

    Neuroprostheses interfaced with transected peripheral nerves are technological routes to control robotic limbs as well as convey sensory feedback to patients suffering from traumatic neural injuries or degenerative diseases. To maximize the wealth of data obtained in recordings, interfacing devices are required to have intrafascicular resolution and provide high signal-to-noise ratio (SNR) recordings. In this paper, we focus on a possible building block of a three-dimensional regenerative implant: a polydimethylsiloxane (PDMS) microchannel electrode capable of highly sensitive recordings in vivo. The PDMS 'micro-cuff' consists of a 3.5 mm long (100 µm × 70 µm cross section) microfluidic channel equipped with five evaporated Ti/Au/Ti electrodes of sub-100 nm thickness. Individual electrodes have average impedance of 640 ± 30 kΩ with a phase angle of -58 ± 1 degrees at 1 kHz and survive demanding mechanical handling such as twisting and bending. In proof-of-principle acute implantation experiments in rats, surgically teased afferent nerve strands from the L5 dorsal root were threaded through the microchannel. Tactile stimulation of the skin was reliably monitored with the three inner electrodes in the device, simultaneously recording signal amplitudes of up to 50 µV under saline immersion. The overall SNR was approximately 4. A small but consistent time lag between the signals arriving at the three electrodes was observed and yields a fibre conduction velocity of 30 m s-1. The fidelity of the recordings was verified by placing the same nerve strand in oil and recording activity with hook electrodes. Our results show that PDMS microchannel electrodes open a promising technological path to 3D regenerative interfaces.

  15. High sensitivity recording of afferent nerve activity using ultra-compliant microchannel electrodes: an acute in vivo validation.

    PubMed

    Minev, Ivan R; Chew, Daniel J; Delivopoulos, Evangelos; Fawcett, James W; Lacour, Stéphanie P

    2012-04-01

    Neuroprostheses interfaced with transected peripheral nerves are technological routes to control robotic limbs as well as convey sensory feedback to patients suffering from traumatic neural injuries or degenerative diseases. To maximize the wealth of data obtained in recordings, interfacing devices are required to have intrafascicular resolution and provide high signal-to-noise ratio (SNR) recordings. In this paper, we focus on a possible building block of a three-dimensional regenerative implant: a polydimethylsiloxane (PDMS) microchannel electrode capable of highly sensitive recordings in vivo. The PDMS 'micro-cuff' consists of a 3.5 mm long (100 µm × 70 µm cross section) microfluidic channel equipped with five evaporated Ti/Au/Ti electrodes of sub-100 nm thickness. Individual electrodes have average impedance of 640 ± 30 kΩ with a phase angle of -58 ± 1 degrees at 1 kHz and survive demanding mechanical handling such as twisting and bending. In proof-of-principle acute implantation experiments in rats, surgically teased afferent nerve strands from the L5 dorsal root were threaded through the microchannel. Tactile stimulation of the skin was reliably monitored with the three inner electrodes in the device, simultaneously recording signal amplitudes of up to 50 µV under saline immersion. The overall SNR was approximately 4. A small but consistent time lag between the signals arriving at the three electrodes was observed and yields a fibre conduction velocity of 30 m s(-1). The fidelity of the recordings was verified by placing the same nerve strand in oil and recording activity with hook electrodes. Our results show that PDMS microchannel electrodes open a promising technological path to 3D regenerative interfaces. PMID:22328617

  16. Electrical stimulation of the sural cutaneous afferent nerve controls the amplitude and onset of the swing phase of locomotion in the spinal cat

    PubMed Central

    Ollivier-Lanvin, Karen; Krupka, Alexander J.; AuYong, Nicholas; Miller, Kassi; Prilutsky, Boris I.

    2011-01-01

    Sensory feedback plays a crucial role in the control of locomotion and in the recovery of function after spinal cord injury. Investigations in reduced preparations have shown that the locomotor cycle can be modified through the activation of afferent feedback at various phases of the gait cycle. We investigated the effect of phase-dependent electrical stimulation of a cutaneous afferent nerve on the locomotor pattern of trained spinal cord-injured cats. Animals were first implanted with chronic nerve cuffs on the sural and sciatic nerves and electromyographic electrodes in different hindlimb muscles. Cats were then transected at T12 and trained daily to locomote on a treadmill. We found that electrical stimulation of the sural nerve can enhance the ongoing flexion phase, producing higher (+129%) and longer (+17.4%) swing phases of gait even at very low threshold of stimulation. Sural nerve stimulation can also terminate an ongoing extension and initiate a flexion phase. A higher prevalence of early switching to the flexion phase was observed at higher stimulation levels and if stimulation was applied in the late stance phase. All flexor muscles were activated by the stimulation. These results suggest that electrical stimulation of the sural nerve may be used to increase the magnitude of the swing phase and control the timing of its onset after spinal cord injury and locomotor training. PMID:21389308

  17. Electrical stimulation of the sural cutaneous afferent nerve controls the amplitude and onset of the swing phase of locomotion in the spinal cat.

    PubMed

    Ollivier-Lanvin, Karen; Krupka, Alexander J; AuYong, Nicholas; Miller, Kassi; Prilutsky, Boris I; Lemay, Michel A

    2011-05-01

    Sensory feedback plays a crucial role in the control of locomotion and in the recovery of function after spinal cord injury. Investigations in reduced preparations have shown that the locomotor cycle can be modified through the activation of afferent feedback at various phases of the gait cycle. We investigated the effect of phase-dependent electrical stimulation of a cutaneous afferent nerve on the locomotor pattern of trained spinal cord-injured cats. Animals were first implanted with chronic nerve cuffs on the sural and sciatic nerves and electromyographic electrodes in different hindlimb muscles. Cats were then transected at T12 and trained daily to locomote on a treadmill. We found that electrical stimulation of the sural nerve can enhance the ongoing flexion phase, producing higher (+129%) and longer (+17.4%) swing phases of gait even at very low threshold of stimulation. Sural nerve stimulation can also terminate an ongoing extension and initiate a flexion phase. A higher prevalence of early switching to the flexion phase was observed at higher stimulation levels and if stimulation was applied in the late stance phase. All flexor muscles were activated by the stimulation. These results suggest that electrical stimulation of the sural nerve may be used to increase the magnitude of the swing phase and control the timing of its onset after spinal cord injury and locomotor training. PMID:21389308

  18. Local gene expression in nerve endings.

    PubMed

    Crispino, Marianna; Chun, Jong Tai; Cefaliello, Carolina; Perrone Capano, Carla; Giuditta, Antonio

    2014-03-01

    At the Nobel lecture for physiology in 1906, Ramón y Cajal famously stated that "the nerve elements possess reciprocal relationships in contiguity but not in continuity," summing up the neuron doctrine. Sixty years later, by the time the central dogma of molecular biology formulated the axis of genetic information flow from DNA to mRNA, and then to protein, it became obvious that neurons with extensive ramifications and long axons inevitably incur an innate problem: how can the effect of gene expression be extended from the nucleus to the remote and specific sites of the cell periphery? The most straightforward solution would be to deliver soma-produced proteins to the target sites. The influential discovery of axoplasmic flow has supported this scheme of protein supply. Alternatively, mRNAs can be dispatched instead of protein, and translated locally at the strategic target sites. Over the past decades, such a local system of protein synthesis has been demonstrated in dendrites, axons, and presynaptic terminals. Moreover, the local protein synthesis in neurons might even involve intercellular trafficking of molecules. The innovative concept of glia-neuron unit suggests that the local protein synthesis in the axonal and presynaptic domain of mature neurons is sustained by a local supply of RNAs synthesized in the surrounding glial cells and transferred to these domains. Here, we have reviewed some of the evidence indicating the presence of a local system of protein synthesis in axon terminals, and have examined its regulation in various model systems. PMID:23853157

  19. Involvement of capsaicin-sensitive afferent nerves in the proteinase-activated receptor 2-mediated vasodilatation in the rat dura mater.

    PubMed

    Dux, M; Rosta, J; Sántha, P; Jancsó, G

    2009-07-01

    Neurogenic inflammation of the dura mater encephali has been suggested to contribute to the mechanisms of meningeal nociception and blood flow regulation. Recent findings demonstrated that the rat dura mater is innervated by trigeminal capsaicin-sensitive peptidergic nociceptive afferent nerves which mediate meningeal vascular responses through activation of the transient receptor potential vanilloid type 1 (TRPV1) receptor. The present work explored the functional significance of the capsaicin-sensitive subpopulation of dural afferent nerves via their contribution to the meningeal vascular responses evoked through activation of the proteinase-activated receptor 2 (PAR-2). The vascular responses of the dura mater were studied by laser Doppler flowmetry in a rat open cranial window preparation. Topical applications of trypsin, a PAR-2-activator, or Ser-Leu-Ile-Gly-Arg-Leu-amide (SLIGRL-NH(2)), a selective PAR-2 agonist peptide, resulted in dose-dependent increases in meningeal blood flow. The SLIGRL-NH(2)-induced vasodilatation was significantly reduced following capsaicin-sensitive afferent nerve defunctionalization by prior systemic capsaicin treatment and by pretreatment of the dura mater with the calcitonin gene-related peptide (CGRP) receptor antagonist CGRP(8-37). Nomega-nitro-L-arginine methyl ester hydrochloride (L-NAME) an unspecific inhibitor of nitric oxide (NO) production, but not 1-(2-trifluoromethylphenyl) imidazole (TRIM), a neuronal NO synthase inhibitor, also inhibited the vasodilator response to SLIGRL-NH(2). The vasodilator responses elicited by very low concentrations of capsaicin (10 nM) were significantly enhanced by prior application of SLIGRL-NH(2). The present findings demonstrate that activation of the PAR-2 localized on capsaicin-sensitive trigeminal nociceptive afferent nerves induces vasodilatation in the dural vascular bed by mechanisms involving NO and CGRP release. The results indicate that the PAR-2-mediated activation and

  20. Mimicking the End Organ Architecture of Slowly Adapting Type I Afferents May Increase the Durability of Artificial Touch Sensors

    PubMed Central

    Lesniak, Daine R.; Gerling, Gregory J.

    2015-01-01

    In effort to mimic the sensitivity and efficient information transfer of natural tactile afferents, recent work has combined force transducers and computational models of mechanosensitive afferents. Sensor durability, another feature important to sensor design, might similarly capitalize upon biological rules. In particular, gains in sensor durability might leverage insight from the compound end organ of the slowly adapting type I afferent, especially its multiple sites of spike initiation that reset each other. This work develops models of compound spiking sensors using a computational network of transduction functions and leaky integrate and fire models (together a spike encoder, the software element of a compound spiking sensor), informed by the output of an existing force transducer (hardware sensing elements of a compound spiking sensor). Individual force transducer failures are simulated with and without resetting between spike encoders to test the importance of both resetting and configuration on system durability. The results indicate that the resetting of adjacent spike encoders, upon the firing of a spike by any one, is an essential mechanism to maintain a stable overall response in the midst of transducer failure. Furthermore, results suggest that when resetting is enabled, the durability of a compound sensor is maximized when individual transducers are paired with spike encoders and multiple, paired units are employed. To explore these ideas more fully, use cases examine the design of a compound sensor to either reach a target lifetime with a set probability or determine how often to schedule maintenance to control the probability of failure. PMID:25705703

  1. Effects of peripheral nerve injuries and tissue inflammation on the levels of neuropeptide Y-like immunoreactivity in rat primary afferent neurons.

    PubMed

    Wakisaka, S; Kajander, K C; Bennett, G J

    1992-12-11

    Changes in neuropeptide Y-like immunoreactivity (NPYir) in the rat L4 and L5 spinal cord and dorsal root ganglia (DRG) were examined after different sciatic nerve injuries (transection, loose ligation, and crush) and a localized, painful inflammation of the hind paw. Inflammation had no effect on NPYir. All the nerve injuries produced comparable increases in NPYir in ipsilateral laminae III-V axons and varicosities, and induction of NPYir in many DRG cells. Most NPYir DRG cells were medium to large (mean diameters: 40-45 microns); less than 2% of the cells had diameters of 25 microns or less. We conclude that the nerve injury-evoked increase in NPYir occurs mostly in the somata and intraspinal arbors of low-threshold mechanoreceptors; very few, if any, C-fiber afferents are involved. Nerve injury, rather than a painful condition, appears to be the stimulus for the induction of NPYir synthesis. PMID:1486499

  2. The efficacy of end-to-end and end-to-side nerve repair (neurorrhaphy) in the rat brachial plexus

    PubMed Central

    Liao, Wen-Chieh; Chen, Jeng-Rung; Wang, Yueh-Jan; Tseng, Guo-Fang

    2009-01-01

    Proximal nerve injury often requires nerve transfer to restore function. Here we evaluated the efficacy of end-to-end and end-to-side neurorrhaphy of rat musculocutaneous nerve, the recipient, to ulnar nerve, the donor. The donor was transected for end-to-end, while an epineurial window was exposed for end-to-side neurorrhaphy. Retrograde tracing showed that 70% donor motor and sensory neurons grew into the recipient 3 months following end-to-end neurorrhaphy compared to 40–50% at 6 months following end-to-side neurorrhaphy. In end-to-end neurorrhaphy, regenerating axons appeared as thick fibers which regained diameters comparable to those of controls in 3–4 months. However, end-to-side neurorrhaphy induced slow sprouting fibers of mostly thin collaterals that barely approached control diameters by 6 months. The motor end plates regained their control density at 4 months following end-to-end but remained low 6 months following end-to-side neurorrhaphy. The short-latency compound muscle action potential, typical of that of control, was readily restored following end-to-end neurorrhaphy. End-to-side neurorrhaphy had low amplitude and wide-ranging latency at 4 months and failed to regain control sizes by 6 months. Grooming test recovered successfully at 3 and 6 months following end-to-end and end-to-side neurorrhaphy, respectively, suggesting that powerful muscle was not required. In short, both neurorrhaphies resulted in functional recovery but end-to-end neurorrhaphy was quicker and better, albeit at the expense of donor function. End-to-side neurorrhaphy supplemented with factors to overcome the slow collateral sprouting and weak motor recovery may warrant further exploration. PMID:19682138

  3. Nociceptive responses and spinal plastic changes of afferent C-fibers in three neuropathic pain models induced by sciatic nerve injury in the rat.

    PubMed

    Casals-Díaz, Laura; Vivó, Meritxell; Navarro, Xavier

    2009-05-01

    Peripheral nerve injuries induce plastic changes on primary afferent fibers and on the spinal circuitry, which are related to the emergence of neuropathic pain. In this study we compared three models of sciatic nerve injury in the rat with different degrees of damage and impact on regeneration capability: crush nerve injury, chronic constriction injury (CCI) and spared nerve injury (SNI). All three models were characterized by means of nerve histology, in order to describe the degenerative and regenerative process of injured axons. Nociceptive responses were evaluated by mechanical and thermal algesimetry tests. Crush animals displayed higher withdrawal thresholds on the ipsilateral paw compared to the contralateral during the time of denervation, while CCI and SNI animals showed mechanical and thermal hyperalgesia. Central plasticity was evaluated by immunohistochemical labeling of non-peptidergic (IB4-positive) and peptidergic (substance P-positive) nociceptive C-fibers on L4-L6 spinal cord sections. After crush nerve injury and SNI, we observed progressive and sustained reduction of IB4 and SP immunolabeling at the sciatic projection territory in the superficial laminae of the dorsal horn, which affected only the tibial and peroneal nerves projection areas in the case of SNI. After CCI, changes on SP-immunoreactivity were not observed, and IB4-immunoreactive area decreased initially but recovered to normal levels on the second week post-injury. Thus, nociceptive responses depend on the type of injury, and the immunoreactivity pattern of afferent fibers at the spinal cord display changes less pronounced after partial than complete sciatic nerve injury. Although signs of neuropathic pain appear in all three lesion models, nociceptive responses and central plasticity patterns differ between them. PMID:19416675

  4. ISOLATED NERVE ENDINGS (NEUROSECRETOSOMES) FROM THE POSTERIOR PITUITARY

    PubMed Central

    Bindler, Elliot; Labella, Frank S.; Sanwal, Madhu

    1967-01-01

    Subcellular fractions of the bovine posterior pituitary, including one composed almost exclusively of pinched-off nerve endings (neurosecretosomes), were characterized electron microscopically, hormonally, and enzymically. 15% of the nerve terminals in the gland were isolated as neurosecretosomes, as estimated from determinations of lactic dehydrogenase, a soluble, cytoplasmic enzyme. Neurosecretosomes were subdivided into three fractions by density-gradient centrifugation. The three subfractions, each shown to be nearly homogeneous populations of neurosecretosomes by means of electron microscopic and enzymic criteria, differed from each other in their vasopressin/oxytocin (VP/OT) ratios. The VP/OT ratio increased from the lightest to the densest fraction, indicating that VP is localized to denser and OT to lighter neurosecretosomes; similar results have been obtained previously for subfractions of neurosecretory granules (NSG). No morphological differences were apparent in neurosecretosomes among the three subfractions. Although complete separation of VP and OT was not achieved, the findings suggest that VP and OT are each stored in a different species of nerve ending and support the hypothesis that a given neurosecretory cell synthesizes, stores, and secretes only one of the peptide hormones. Microvesicles, 40–80 mµ diameter and contained in typical neurosecretory cell terminals, are believed to be degradation products of membrane ghosts of depleted NSG; electron micrographs indicative of this transformation are presented. A fraction rich in microvesicles, but containing some NSG membranes, was prepared by density-gradient centrifugation of an osmolysate of neurosecretosomes. Smaller, apparently nonneurosecretory nerve endings, lacking NSG but filled with small vesicles, are occasionally seen in sections from whole gland. The vesicles in these atypical posterior pituitary nerve endings may be true neurohumor-containing, "synaptic" vesicles. PMID:6040535

  5. Excitation of afferent fibres in the cardiac sympathetic nerves induced by coronary occlusion and injection of bradykinin. The influence of acetylsalicylic acid and dipyron.

    PubMed

    Vogt, A; Vetterlein, F; dal Ri, H; Schmidt, G

    1979-05-01

    Afferent impulse activity was recorded in single fibres of the inferior cardiac sympathetic nerve of the cat. When the descending branch of the left coronary artery was ligated for 60 sec an enhancement of afferent impulses was recorded. Elevations in discharge frequency were also induced by injecting bradykinin, epinephrine, and isoprenaline or by general hypoxia due to interruption of the artificial ventilation. When these procedures were after pretreatment with the analgesic agents, acetylsalicylic acid or dipyron a reduction in spike discharge was observed only with bradykinin after application of acetylsalicylic acid. No influence of these pretreatments on the effects of coronary occlusion, general hypoxia and injection of epinephrine and isoprenaline could be observed. These results suggest that bradykinin does not predominate as mediator substance in eliciting ischemic heart pain. PMID:485722

  6. Sensory nerve endings in the rat oro-facial region labeled by the anterograde and transganglionic transport of horseradish peroxidase: a new method for tracing peripheral nerve fibers.

    PubMed

    Marfurt, C F; Turner, D F

    1983-02-14

    The purpose of the present investigation is to introduce the enzyme horseradish peroxidase (HRP) for the study of the morphology and peripheral distribution of sensory nerve endings. HRP was injected into the trigeminal ganglion or trigeminal brainstem nuclear complex (TBNC) in separate adult rats. HRP injected into the trigeminal ganglion was taken up by the neuronal perikarya and transported anterogradely in massive amounts to sensory nerve endings in the cornea, vibrissal hair follicles, tooth pulps, and periodontal ligaments. HRP injected into the TBNC was taken up by trigeminal primary afferent fibers that terminated there and transported transganglionically, i.e., past or through the trigeminal ganglion, to peripheral sensory endings. The results of the present study demonstrate for the first time that: (1) anterograde HRP transport is a highly successful method of labeling with an intracellular marker trigeminal sensory endings in a variety of oro-facial tissues, and (2) trigeminal primary sensory neurons possess intra-axonal transport mechanisms by which HRP, and possibly other substances, taken up in the central nervous system may be transported to the periphery. PMID:6601506

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

    PubMed Central

    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 distal colorectum with the pelvic nerve attached was removed for single-fiber electrophysiological recordings. Colorectal afferent endings were located by electrical stimulation and characterized as mechanosensitive or not by blunt probing, mucosal stroking, and circumferential stretch. Intracolonic zymosan produced persistent colorectal hypersensitivity (>24 days) associated with brief colorectal inflammation. Pelvic nerve muscular-mucosal but not muscular mechanosensitive afferents recorded from mice with colorectal hypersensitivity exhibited persistent sensitization. In addition, the proportion of MIAs (relative to control) was significantly reduced from 27% to 13%, whereas the proportion of serosal afferents was significantly increased from 34% to 53%, suggesting that MIAs acquired mechanosensitivity. PGP9.5 immunostaining revealed no significant loss of colorectal nerve fiber density, suggesting that the reduction in MIAs is not due to peripheral fiber loss after intracolonic zymosan. These results indicate that colorectal MIAs and sensitized muscular-mucosal afferents that respond to stretch contribute significantly to the afferent input that sustains hypersensitivity to CRD, suggesting that targeted management of colorectal afferent input could significantly reduce patients' complaints of pain and hypersensitivity. PMID:22268098

  8. [Changes in the afferent activity of the vagus nerve and the rectal temperature in rats following Escherichia coli endotoxin administration].

    PubMed

    Lapsha, V I; Lukashenko, T M; Utkina, L N; Gurin, V N

    2001-10-01

    In anaesthetised rats, i.p. administration of the Echerichia coli lipopolysaccharide in doses 5 mcg/kg (LPS) increased afferent activity of the cervical vagus, whereas 100 and 1000 mcg/kg doses inhibited the afferent discharges. Pyrogen-free saline (PFS) did not alter the activity. Rectal temperature (RT) was decreased by the PFS and by large doses of the LPS. Sodium salicylate administration prevented the effects. PMID:11767451

  9. Identification and properties of parietal pleural afferents in rabbits

    PubMed Central

    Jammes, Yves; Trousse, Delphine; Delpierre, Stéphane

    2005-01-01

    Although pain and dyspnoea are common symptoms in pleural diseases, there are few studies on the sensory innervation of the pleura. Using rabbits, after removal of all muscles in the intercostal space to be studied, we investigated the afferents of the internal intercostal nerve by applying to the internal thoracic wall pieces of gauze soaked in warmed (37°C), buffered saline (mechanical stimulation) or solutions containing lactic acid, inflammatory mediators or capsaicin (chemical stimulation). The afferent conduction velocity ranged from 0.5 to 14 m s−1. Most units (97%) were activated by mechanical stimulation of the pleura (local positive pressure range = 4.5–8.5 cmH2O) and we found a linear relationship between the discharge rate of afferents and the force applied to the thoracic wall. The majority of mechanosensitive units (70%) also responded to one or several chemical agents. Thus, the afferents were activated by lactic acid (49%) and/or a mixture of inflammatory mediators (50%). Local application of capsaicin elicited an initial increased or decreased background afferent activity in 57% of the afferents, a delayed decrease in firing rate being noted in some units initially activated by capsaicin. Capsaicin blocked the afferent response to a further application of inflammatory mediators but did not affect the mechanosensitive units. Thus, sensory endings connected with thin myelinated and unmyelinated fibres in the internal intercostal nerve detect the mechanical and chemical events of pleural diseases. PMID:15975985

  10. Voluntary activation of spindle endings in human muscles temporarily paralysed by nerve pressure.

    PubMed Central

    Burke, D; Hagbarth, K E; Skuse, N F

    1979-01-01

    1. In normal human subjects, the afferent activity from muscle spindle endings in the pretibial muscles was recorded while a pressure block was applied to the peroneal nerve proximally in the popliteal fossa. 2. In five of ten blocks, spindle activity increased in attempted isometric voluntary contractions when the receptor-bearing muscles were completely paralysed. In the remaining five blocks, voluntary effort still increased spindle activity when maximum voluntary power was reduced by more than 90%, but the ability to activate spindles voluntarily was lost with or slightly before block of the last motor units. When the ability to activate spindle endings in an attempted voluntary contraction was lost sympathetic efferent fibres remained unblocked. 3. It is concluded that the fusimotor effects seen during a voluntary contraction are mediated by myelinated fibres of small calibre which probably innervate intrafusal structures exclusively (gamma fusimotor fibres). There is no necessity to postulate that skeleto-fusimotor (beta) fibres are responsible for the tight 'alpha-gamma co-activation' seen in man during voluntary contractions. PMID:155158

  11. Bipolar spinal cord stimulation attenuates mechanical hypersensitivity at an intensity that activates a small portion of A-fiber afferents in spinal nerve-injured rats.

    PubMed

    Yang, F; Carteret, A F; Wacnik, P W; Chung, C-Y; Xing, L; Dong, X; Meyer, R A; Raja, S N; Guan, Y

    2011-12-29

    Spinal cord stimulation (SCS) is used clinically to treat neuropathic pain states, but the precise mechanism by which it attenuates neuropathic pain remains to be established. The profile of afferent fiber activation during SCS and how it may correlate with the efficacy of SCS-induced analgesia are unclear. After subjecting rats to an L5 spinal nerve ligation (SNL), we implanted a miniature quadripolar electrode similar to that used clinically. Our goal was to determine the population and number of afferent fibers retrogradely activated by SCS in SNL rats by recording the antidromic compound action potential (AP) at the sciatic nerve after examining the ability of bipolar epidural SCS to alleviate mechanical hypersensitivity in this model. Notably, we compared the profiles of afferent fiber activation to SCS between SNL rats that exhibited good SCS-induced analgesia (responders) and those that did not (nonresponders). Additionally, we examined how different contact configurations affect the motor threshold (MoT) and compound AP threshold. Results showed that three consecutive days of SCS treatment (50 Hz, 0.2 ms, 30 min, 80-90% of MoT), but not sham stimulation, gradually alleviated mechanical hypersensitivity in SNL rats. The MoT obtained in the animal behavioral study was significantly less than the Aα/β-threshold of the compound AP determined during electrophysiological recording, suggesting that SCS could attenuate mechanical hypersensitivity with a stimulus intensity that recruits only a small fraction of the A-fiber population in SNL rats. Although both the MoT and compound AP threshold were similar between responders and nonresponders, the size of the compound AP waveform at higher stimulation intensities was larger in the responders, indicating a more efficient activation of the dorsal column structure in responders. PMID:22001681

  12. Re-Innervation of the Bladder through End-to-Side Neurorrhaphy of Autonomic Nerve and Somatic Nerve in Rats

    PubMed Central

    Gao, Wan-sheng; Dong, Chuan-jiang; Li, Shu-qiang; Kunwar, Kiran Jang

    2012-01-01

    Abstract End-to-side neurorrhaphy is widely used in the peripheral nervous system for nerve repair; however, the application of this technique has been limited to somatic nerves. The feasibility of nerve regeneration through end-to-side neurorrhaphy between autonomic and somatic nerves with different characteristics in the peripheral nervous system is still undetermined. In this study, rats were divided into three groups for different treatments (n=10 per group). In the end-to-side neurorrhaphy group, left L6 and S1 were transected in the dura, and the distal stump of L6 ventral root was sutured to the lateral face of L4 ventral root through end-to-side coaptation. In the no repair group, the rats did not undergo neurorrhaphy. In the control group, the left L6 dorsal root and S1 roots were transected, respectively, but the L6 ventral root was kept intact. After 16 weeks, the origin and mechanism of nerve regeneration was evaluated by retrograde double labeling technique as well as histological examination and intravesical pressure measurement. Retrograde double labeling indicated that the reconstructed reflex pathway was successfully established and the primary regeneration mechanism involved axon collateral sprouting. Morphological examination and intravesical pressure measurement indicated prominent nerve regeneration and successful re-innervation of the bladder in the neurorrhaphy group, compared with the “no repair” group (p<0.05). No significant changes were observed in the histology of the donor nerve and the bilateral extensor digitorum longus muscles in the neurorrhaphy group. Nerve regeneration may be achievable for nerve repair through end-to-side neurorrhaphy between autonomic and somatic nerves without apparent impairment of donor somatic nerve. PMID:22332710

  13. Unilateral Multiple Facial Nerve Branch Reconstruction Using “End-to-side Loop Graft” Supercharged by Hypoglossal Nerve

    PubMed Central

    Sasaki, Ryo; Takeuchi, Yuichi; Watanabe, Yorikatsu; Niimi, Yosuke; Sakurai, Hiroyuki; Miyata, Mariko; Yamato, Masayuki

    2014-01-01

    Background: Extensive facial nerve defects between the facial nerve trunk and its branches can be clinically reconstructed by incorporating double innervation into an end-to-side loop graft technique. This study developed a new animal model to evaluate the technique’s ability to promote nerve regeneration. Methods: Rats were divided into the intact, nonsupercharge, and supercharge groups. Artificially created facial nerve defects were reconstructed with a nerve graft, which was end-to-end sutured from proximal facial nerve stump to the mandibular branch (nonsupercharge group), or with the graft of which other end was end-to-side sutured to the hypoglossal nerve (supercharge group). And they were evaluated after 30 weeks. Results: Axonal diameter was significantly larger in the supercharge group than in the nonsupercharge group for the buccal (3.78 ± 1.68 vs 3.16 ± 1.22; P < 0.0001) and marginal mandibular branches (3.97 ± 2.31 vs 3.46 ± 1.57; P < 0.0001), but the diameter was significantly larger in the intact group for all branches except the temporal branch. In the supercharge group, compound muscle action potential amplitude was significantly higher than in the nonsupercharge group (4.18 ± 1.49 mV vs 1.87 ± 0.37 mV; P < 0.0001) and similar to that in the intact group (4.11 ± 0.68 mV). Retrograde labeling showed that the mimetic muscles were double-innervated by facial and hypoglossal nerve nuclei in the supercharge group. Conclusions: Multiple facial nerve branch reconstruction with an end-to-side loop graft was able to achieve axonal distribution. Additionally, axonal supercharge from the hypoglossal nerve significantly improved outcomes. PMID:25426357

  14. A phenotypically restricted set of primary afferent nerve fibers innervate the bone versus skin: therapeutic opportunity for treating skeletal pain

    PubMed Central

    Jimenez-Andrade, Juan Miguel; Mantyh, William G.; Bloom, Aaron P.; Xu, Kevin Haili; Ferng, Alice S.; Dussor, Gregory; Vanderah, Todd W.; Mantyh, Patrick W.

    2009-01-01

    Although musculoskeletal pain is one of the most common causes of chronic pain and physical disability in both developed as well as developing countries, relatively little is known about the nerve fibers and mechanisms that drive skeletal pain. Small diameter sensory nerve fibers, most of which are C-fiber nociceptors, can be separated into two broad populations: the peptide-rich and peptide-poor nerve fibers. Peptide-rich nerve fibers express substance P (SP) and calcitonin gene related peptide (CGRP). In contrast, the peptide-poor nerve fibers bind to isolectin B4 (IB4) and express the purinergic receptor P2X3 and Mas-related G protein-coupled receptor member d (Mrgprd). In the present report, we used mice in which the Mrgprd+ nerve fibers express genetically encoded axonal tracers to determine the peptide-rich and peptide-poor sensory nerve fibers that innervate the glabrous skin of the hindpaw as compared to the bone marrow, mineralized bone and periosteum of the femur. Whereas the skin is richly innervated by CGRP+, SP+, P2X3+ and Mrgprd+ sensory nerve fibers, the bone marrow, mineralized bone and periosteum receive a significant innervation by SP+ and CGRP+, but not Mrgprd+ and P2X3+ nerve fibers. This lack of redundancy in the populations of C-fibers that innervate the bone may present a unique therapeutic opportunity for targeting skeletal pain, as the peptide-rich and peptide-poor sensory nerve fibers generally express a different repertoire of receptors and channels to detect noxious stimuli. Thus, therapies that target the specific types of C-nerve fibers that innervate the bone may be uniquely effective in attenuating skeletal pain as compared to skin pain. PMID:19766746

  15. Mechanical loading of peripheral nerves during remobilisation of the affected member after end-to-end anastomosis.

    PubMed

    Orf, G; Wüst, R

    1979-01-01

    Our study involved simulating end-to-end neurorrhaphy of the sciatic nerve in a number of rabbits and analysing in vivo the mechanical loads acting on the nerve while the affected member was being remobilised. We found both the suture and mobilisation loads to be related to the size of the nerve defect. In each case, traction force, strain, and stress were proportional. The effect which these experimental findings may have on the future use of flexing neighbouring joints as a "manipulative" measure to achieve a tension-free nerve suture will be discussed. PMID:525461

  16. In Vivo Two-Photon Microscopy of Single Nerve Endings in Skin

    PubMed Central

    Yuryev, Mikhail; Molotkov, Dmitry

    2014-01-01

    Nerve endings in skin are involved in physiological processes such as sensing1 as well as in pathological processes such as neuropathic pain2. Their close-to-surface positioning facilitates microscopic imaging of skin nerve endings in living intact animal. Using multiphoton microscopy, it is possible to obtain fine images overcoming the problem of strong light scattering of the skin tissue. Reporter transgenic mice that express EYFP under the control of Thy-1 promoter in neurons (including periphery sensory neurons) are well suited for the longitudinal studies of individual nerve endings over extended periods of time up to several months or even life-long. Furthermore, using the same femtosecond laser as for the imaging, it is possible to produce highly selective lesions of nerve fibers for the studies of the nerve fiber restructuring. Here, we present a simple and reliable protocol for longitudinal multiphoton in vivo imaging and laser-based microsurgery on mouse skin nerve endings. PMID:25178088

  17. Collateral sprouting of uninjured primary afferent A-fibers into the superficial dorsal horn of the adult rat spinal cord after topical capsaicin treatment to the sciatic nerve.

    PubMed

    Mannion, R J; Doubell, T P; Coggeshall, R E; Woolf, C J

    1996-08-15

    That terminals of uninjured primary sensory neurons terminating in the dorsal horn of the spinal cord can collaterally sprout was first suggested by Liu and Chambers (1958), but this has since been disputed. Recently, horseradish peroxidase conjugated to the B subunit of cholera toxin (B-HRP) and intracellular HRP injections have shown that sciatic nerve section or crush produces a long-lasting rearrangement in the organization of primary afferent central terminals, with A-fibers sprouting into lamina II, a region that normally receives only C-fiber input (Woolf et al., 1992). The mechanism of this A-fiber sprouting has been thought to involve injury-induced C-fiber transganglionic degeneration combined with myelinated A-fibers being conditioned into a regenerative growth state. In this study, we ask whether C-fiber degeneration and A-fiber conditioning are both necessary for the sprouting of A-fibers into lamina II. Local application of the C-fiber-specific neurotoxin capsaicin to the sciatic nerve has previously been shown to result in C-fiber damage and degenerative atrophy in lamina II. We have used B-HRP to transganglionically label A-fiber central terminals and have shown that 2 weeks after topical capsaicin treatment to the sciatic nerve, the pattern of B-HRP staining in the dorsal horn is indistinguishable from that seen after axotomy, with lamina II displaying novel staining in the identical region containing capsaicin-treated C-fiber central terminals. These results suggest that after C-fiber injury, uninjured A-fiber central terminals can collaterally sprout into lamina II of the dorsal horn. This phenomenon may help to explain the pain associated with C-fiber neuropathy. PMID:8756447

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

    PubMed

    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 < 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

  19. Inputs from regularly and irregularly discharging vestibular nerve afferents to secondary neurons in squirrel monkey vestibular nuclei. III. Correlation with vestibulospinal and vestibuloocular output pathways

    NASA Technical Reports Server (NTRS)

    Boyle, R.; Goldberg, J. M.; Highstein, S. M.

    1992-01-01

    1. A previous study measured the relative contributions made by regularly and irregularly discharging afferents to the monosynaptic vestibular nerve (Vi) input of individual secondary neurons located in and around the superior vestibular nucleus of barbiturate-anesthetized squirrel monkeys. Here, the analysis is extended to more caudal regions of the vestibular nuclei, which are a major source of both vestibuloocular and vestibulospinal pathways. As in the previous study, antidromic stimulation techniques are used to classify secondary neurons as oculomotor or spinal projecting. In addition, spinal-projecting neurons are distinguished by their descending pathways, their termination levels in the spinal cord, and their collateral projections to the IIIrd nucleus. 2. Monosynaptic excitatory postsynaptic potentials (EPSPs) were recorded intracellularly from secondary neurons as shocks of increasing strength were applied to Vi. Shocks were normalized in terms of the threshold (T) required to evoke field potentials in the vestibular nuclei. As shown previously, the relative contribution of irregular afferents to the total monosynaptic Vi input of each secondary neuron can be expressed as a %I index, the ratio (x100) of the relative sizes of the EPSPs evoked by shocks of 4 x T and 16 x T. 3. Antidromic stimulation was used to type secondary neurons as 1) medial vestibulospinal tract (MVST) cells projecting to spinal segments C1 or C6; 2) lateral vestibulospinal tract (LVST) cells projecting to C1, C6; or L1; 3) vestibulooculo-collic (VOC) cells projecting both to the IIIrd nucleus and by way of the MVST to C1 or C6; and 4) vestibuloocular (VOR) neurons projecting to the IIIrd nucleus but not to the spinal cord. Most of the neurons were located in the lateral vestibular nucleus (LV), including its dorsal (dLV) and ventral (vLV) divisions, and adjacent parts of the medial (MV) and descending nuclei (DV). Cells receiving quite different proportions of their direct inputs

  20. [Effect of narcotic analgesics on the cortical control process of impulse transmission in the afferent pathways of the sciatic nerve].

    PubMed

    Churiukanov, V V; Bilibin, D P

    1976-01-01

    The effect produced by narcotic analgetics with their intravenous administration on the process of cortical control over the transmission of impulses along specific routes of the sciatic nerve was studied. The conditioning stimulation of the cortex was effected by using a monopolar electrode through single electric impulses. The interval between conditioning and test (on sciatic nerve) impulses was of 80-120 ms. Morphine (1-2 mg/kg), promedol (trimeperidin) (1-2 mg/kg) and phentanyl (100 gamma/kg) potentiated the inhibition of evoked potentials in the nucleus gracilis and in VPL, observed upon stimulation of the cortex of optic lobuses. The intensification of inhibitory corticifugal mechanisms occurring under the effect of narcotic analgetics takes place both on the level of the medulla oblongata and of the thalamic one. PMID:6310

  1. [Interaction of abdominal vagus and greater splanchnic nerve activities in the nucleus tractus solitarius of the rabbit].

    PubMed

    Zhang, J; Huang, Z S

    1990-12-01

    Experiments were performed on 67 rabbits. Effects of stimulation of the central ends of abdominal vagus and greater splanchnic nerve on arterial blood pressure before and after destruction of nucleus tractus solitarius (NTS) and the unit discharges in the NTS before destruction were observed. As a result, we suggest that both the afferents coming from the abdominal vagus and greater splanchnic nerve not only converge on NTS neurons but also interact with each other. Subthreshold stimulation elicited from one of the afferent fibers suppresses the arterial blood pressure responses caused by the other afferent. Similarly, background stimulation elicited from one afferent can suppress the NTS unit discharges caused by the other afferent. It is much easier for abdominal vagal afferent to inhibit the NTS unit discharges and the arterial blood pressure changes elicited by stimulation of the splanchnic nerve. A possible mechanism of such relationship was discussed. PMID:2293366

  2. [The Importance of Vagus Nerve Afferent in the Formation of Emotions in Attention-Deficit Hyperactivity Disorder Model Rat].

    PubMed

    Hida, Hideki

    2016-06-01

    It is of interest to know how environmental stimuli contribute to the formation of emotion during development. In a rat model of attention-deficit hyperactivity disorder, monosodium L- glutamate (MSG), a taste substance of umami, was administered for 5 weeks during developmental period, followed by emotional behavior tests such as open-field test and social interaction test in adulthood. Although no significant change was observed in anxiety-like behavior, MSG intake caused a reduction in aggressive behavior. Vagotomy under the level of diaphragm resulted in eliminating the MSG effect on aggression, indicating the importance of neuronal activity of the vagus nerve in this effect. Futher studies will focus on futher questions regarding the gut-brain axis such as the change of microbiota and the mechanism of the axis in the brain. PMID:27279161

  3. Nerve endings in bronchi of the dog that react with antibodies against neurofilament protein.

    PubMed Central

    Yamamoto, Y; Atoji, Y; Suzuki, Y

    1995-01-01

    Tree-like nerve endings in the smooth muscle layer of bronchi of the dog were examined by immunohistochemical staining with antibodies against neurofilament protein (NFP). The endings were revealed as ramified axon terminals, with arborisation at their termini. The endings were 100-300 microns in maximal length and 50-100 microns in minimal length. Most of the endings were arranged parallel to the smooth muscle strands. The endings were densely distributed in the proximal region but their density decreased towards the alveoli. In the histological sections, the endings were seen between smooth muscle cells. Terminal Schwann cells, which reacted with antibodies against glial fibrillary acidic protein and S-100 protein, and putative 'septal cells' with vimentin-like immunoreactivity were distributed near the endings. In addition, the nerve endings with NFP-like immunoreactivity were surrounded dense connective tissue that contained large amounts of fine elastic fibres. These findings indicate the nerve endings with NFP-like immunoreactivity are similar to other slowly adapting receptors (i.e. Golgi tendon organs, Ruffini endings). Some degenerated endings, which found in the unilaterally vagotomised dog, suggest the endings in the bronchi are originated from vagal nerves. Images Fig. 1 Fig. 3 Fig. 4 Fig. 5 PMID:7591986

  4. Degeneration of proprioceptive sensory nerve endings in mice harboring amyotrophic lateral sclerosis-causing mutations.

    PubMed

    Vaughan, Sydney K; Kemp, Zachary; Hatzipetros, Theo; Vieira, Fernando; Valdez, Gregorio

    2015-12-01

    Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that primarily targets the motor system. Although much is known about the effects of ALS on motor neurons and glial cells, little is known about its effect on proprioceptive sensory neurons. This study examines proprioceptive sensory neurons in mice harboring mutations associated with ALS, in SOD1(G93A) and TDP43(A315T) transgenic mice. In both transgenic lines, we found fewer proprioceptive sensory neurons containing fluorescently tagged cholera toxin in their soma five days after injecting this retrograde tracer into the tibialis anterior muscle. We asked whether this is due to neuronal loss or selective degeneration of peripheral nerve endings. We found no difference in the total number and size of proprioceptive sensory neuron soma between symptomatic SOD1(G93A) and control mice. However, analysis of proprioceptive nerve endings in muscles revealed early and significant alterations at Ia/II proprioceptive nerve endings in muscle spindles before the symptomatic phase of the disease. Although these changes occur alongside those at α-motor axons in SOD1(G93A) mice, Ia/II sensory nerve endings degenerate in the absence of obvious alterations in α-motor axons in TDP43(A315T) transgenic mice. We next asked whether proprioceptive nerve endings are similarly affected in the spinal cord and found that nerve endings terminating on α-motor neurons are affected during the symptomatic phase and after peripheral nerve endings begin to degenerate. Overall, we show that Ia/II proprioceptive sensory neurons are affected by ALS-causing mutations, with pathological changes starting at their peripheral nerve endings. PMID:26136049

  5. Effects of Hemodiafiltration and High Flux Hemodialysis on Nerve Excitability in End-Stage Kidney Disease

    PubMed Central

    Arnold, Ria; Pussell, Bruce A.; Pianta, Timothy J.; Grinius, Virginija; Lin, Cindy S-Y.; Kiernan, Matthew C.; Howells, James; Jardine, Meg J.; Krishnan, Arun V.

    2013-01-01

    Objectives Peripheral neuropathy is the most common neurological complication in end-stage kidney disease. While high flux hemodialysis (HFHD) and hemodiafiltration (HDF) have become the preferred options for extracorporeal dialysis therapy, the effects of these treatments on nerve excitability have not yet been examined. Methods An observational proof-of-concept study of nerve excitability and neuropathy was undertaken in an incident dialysis population (n = 17) receiving either HFHD or HDF. Nerve excitability techniques were utilised to assess nerve ion channel function and membrane potential, in conjunction with clinical assessment and standard nerve conduction studies. A mathematical model of axonal excitability was used to investigate the underlying basis of the observed changes. Nerve excitability was recorded from the median nerve, before, during and after a single dialysis session and correlated with corresponding biochemical markers. Differences in nerve excitability were compared to normal controls with longitudinal follow-up over an 18 month period. Results Nerve excitability was performed in patient cohorts treated with either HFHD (n = 9) or online HDF (n = 8), with similar neuropathy status. Nerve excitability measures in HDF-treated patients were significantly closer to normal values compared to HFHD patients obtained over the course of a dialysis session (p<0.05). Longitudinal studies revealed stability of nerve excitability findings, and thus maintenance of improved nerve function in the HDF group. Conclusions This study has provided evidence that nerve excitability in HDF-treated patients is significantly closer to normal values prior to dialysis, across a single dialysis session and at longitudinal follow-up. These findings offer promise for the management of neuropathy in ESKD and should be confirmed in randomised trials. PMID:23536855

  6. Collateral sprouting of sensory axons after end-to-side nerve coaptation--a longitudinal study in the rat.

    PubMed

    Kovacic, Uros; Tomsic, Martin; Sketelj, Janez; Bajrović, Fajko F

    2007-02-01

    The end-to-side nerve coaptation is able to induce collateral sprouting of axons from the donor nerve and to provide functional reinnervation of the target tissue. Sensory axon sprouting and its effects on the donor nerve up to 9 months after the end-to-side nerve coaptation were studied in the rat. Peroneal, tibial and saphenous nerves were transected and ligated, and the distal stump of the transected peroneal nerve was sutured to the side of the uninjured sural nerve. The average skin area of the residual sensitivity to pinch due to the axons sprouting through the recipient peroneal nerve did not change statistically significantly between 4 and 9 months after surgery. Axon counting, measurements of compound action potentials and retrograde neuron labeling indicate that the sprouting of the myelinated sensory axons and unmyelinated axons through the recipient nerve was largely completed by 2 months and 4 months after the end-to-side nerve coaptation, respectively, and remained stable thereafter for at least 9 months. A decrease in the amplitude and area of the CAP of myelinated fibers, observed in the donor nerve up to 4 months after surgery, was probably due to mild degeneration of nerve fibers and a tendency of the diameter of myelinated axons to decline. However, no significant changes in functional, electrophysiological or morphological properties of the donor nerve could be observed at the end of the observational period, indicating that end-to-side nerve coaptation has no detrimental effect on the donor nerve on a long-term scale. PMID:17045263

  7. Second application of low-energy shock waves has a cumulative effect on free nerve endings.

    PubMed

    Takahashi, Norimasa; Ohtori, Seiji; Saisu, Takashi; Moriya, Hideshige; Wada, Yuichi

    2006-02-01

    Some physicians recommend treating tendinopathies with multiple sessions of shock waves. Some evidence, however, suggests shock wave application can induce nerve fiber degeneration. We questioned whether repeated shock wave application provides a cumulative effect on nerve fibers compared with the effect of one application. One thousand shock wave impulses of an energy flux density of 0.08 mJ/mm were applied to the foot pad of 32 rats. After 14 days, 16 rats received a second application. The foot pads were resected on Days 7, 14, 28, and 42. Sections were processed immunohistochemically using antibodies for sensory nerve. We compared the number of epidermal nerve fibers in rats that received one application of shock waves with the fibers in rats that received two applications. During the first 4 weeks, there was nearly complete degeneration of epidermal nerve fibers in both groups. By the end of 6 weeks, reinnervation of the epidermis began in the single-treatment group. Reinnervation occurred slower in the repeated-treatment group. These data show that a second application has a cumulative effect on nerve fibers. Our data suggest multiple applications of low-energy shock waves might a provide longer-lasting antinociceptive effect. PMID:16462457

  8. Nerve ending "signal" proteins GAP-43, MARCKS, and BASP1.

    PubMed

    Mosevitsky, Mark I

    2005-01-01

    Mechanisms of growth cone pathfinding in the course of neuronal net formation as well as mechanisms of learning and memory have been under intense investigation for the past 20 years, but many aspects of these phenomena remain unresolved and even mysterious. "Signal" proteins accumulated mainly in the axon endings (growth cones and the presynaptic area of synapses) participate in the main brain processes. These proteins are similar in several essential structural and functional properties. The most prominent similarities are N-terminal fatty acylation and the presence of an "effector domain" (ED) that dynamically binds to the plasma membrane, to calmodulin, and to actin fibrils. Reversible phosphorylation of ED by protein kinase C modulates these interactions. However, together with similarities, there are significant differences among the proteins, such as different conditions (Ca2+ contents) for calmodulin binding and different modes of interaction with the actin cytoskeleton. In light of these facts, we consider GAP-43, MARCKS, and BASP1 both separately and in conjunction. Special attention is devoted to a discussion of apparent inconsistencies in results and opinions of different authors concerning specific questions about the structure of proteins and their interactions. PMID:16125549

  9. Interleukin-1β sensitizes abdominal visceral afferents of cats to ischaemia and histamine

    PubMed Central

    Fu, Liang-Wu; Longhurst, John C

    1999-01-01

    produced during brief abdominal ischaemia contributes to activation of visceral afferents during ischaemia, at least in part, by sensitizing the afferent nerve endings to ischaemia. Our data also show that exogenous IL-1β sensitizes visceral afferents to histamine. PMID:10562349

  10. TERMINAL ARBORS OF AXONS PROJECTING TO THE SOMATOSENSORY CORTEX OF THE ADULT RAT. 2. THE ALTERED MORPHOLOGY OF THALAMOCORTICAL AFFERENTS FOLLOWING NEONATAL INFRAORBITAL NERVE CUT (JOURNAL VERSION)

    EPA Science Inventory

    The organization of the whisker representation within the neocortex of the rat is dependent on an intact periphery during development. To further investigate how alterations in the cortical map arise the authors examined the organization of thalamocortical afferents to the whiske...

  11. End-to-side nerve suture in traumatic injuries of brachial plexus: review of the literature and personal case series.

    PubMed

    Battiston, B; Artiaco, S; Conforti, L G; Vasario, G; Tos, P

    2009-10-01

    We used end-to-side nerve coaptation combined with standard end-to-end neurotisations to treat 11 patients who presented with complete (six cases) or incomplete (five cases) traumatic brachial plexus injuries. All patients were available for functional evaluation at a minimum of 2 years postoperatively. In three patients with shoulder abduction recovery, electromyographical studies (EMG) showed a contribution from the end-to-side neurotisation. In the remaining cases end-to-side neurotisations were unsuccessful. Our study did not demonstrate a reliable role for end-to-side nerve suture in brachial plexus surgery. We believe that at present end-to-side suture must not be a substitute for standard reconstructive techniques in brachial plexus surgery. Occasionally termino-lateral nerve sutures may represent a support to standard reconstructive procedures especially in case of severe injuries when few undamaged donor nerves are available. PMID:19587073

  12. Characterization of silent afferents in the pelvic and splanchnic innervations of the mouse colorectum

    PubMed Central

    Gebhart, G. F.

    2011-01-01

    Hypersensitivity in inflammatory/irritable bowel syndrome is contributed to in part by changes in the receptive properties of colorectal afferent endings, likely including mechanically insensitive afferents (MIAs; silent afferents) that have the ability to acquire mechanosensitivity. The proportion and attributes of colorectal MIAs, however, have not previously been characterized. The distal ∼3 cm of colorectum with either pelvic (PN) or lumbar splanchnic (LSN) nerve attached was removed, opened longitudinally, pinned flat in a recording chamber, and perfused with oxygenated Krebs solution. Colorectal receptive endings were located by electrical stimulation and characterized as mechanosensitive or not by blunt probing, mucosal stroking, and circumferential stretch. MIA endings were tested for response to and acquisition of mechanosensitivity by localized exposure to an inflammatory soup (IS). Colorectal afferents were also tested with twin-pulse and repetitive electrical stimulation paradigms. PN MIAs represented 23% of 211 afferents studied, 71% (30/42) of which acquired mechanosensitivity after application of IS to their receptive ending. LSN MIAs represented 33% of 156 afferents studied, only 23% (11/48) of which acquired mechanosensitivity after IS exposure. Mechanosensitive PN endings uniformly exhibited significant twin-pulse slowing whereas LSN endings showed no significant twin-pulse difference. PN MIAs displayed significantly greater activity-dependent slowing than LSN MIAs. In conclusion, significant proportions of MIAs are present in the colorectal innervation; significantly more in the PN than LSN acquire mechanosensitivity in an inflammatory environment. This knowledge contributes to our understanding of the possible roles of MIAs in colon-related disorders like inflammatory/irritable bowel syndrome. PMID:21071510

  13. Free calcium concentration in brain nerve endings of spontaneously hypertensive rats

    SciTech Connect

    Orlov, S.N.; Pokudin, N.I.; Kravstov, G.M.; Postnov, Yu.V.; Okun', I.M.; Shukanova, N.A.; Rakovich, A.A.; Aksentsev, S.L.; Konev, S.V.

    1987-10-01

    The frequency of neurotransmitter release from the synaptic vesicles of nerve endings by exocytosis depends primarily on the free calcium concentration in the cytoplasm which is controlled by calcium transporting and calcium binding systems. In this paper, in an attempt to determine the state of these systems in primary hypertension and the effects of neurotransmitter release on the increased resistance in the peripheral circulatory system, the authors study the exchange, uptake, and concentration of calcium 45 cations by synaptosomes.

  14. Activation of guanylate cyclase-C attenuates stretch responses and sensitization of mouse colorectal afferents

    PubMed Central

    Feng, Bin; Kiyatkin, Michael E.; La, Jun-Ho; Ge, Pei; Solinga, Robert; Silos-Santiago, Inmaculada; Gebhart, G.F.

    2013-01-01

    Irritable bowel syndrome (IBS) is characterized by altered bowel habits, persistent pain and discomfort, and typically colorectal hypersensitivity. Linaclotide, a peripherally-restricted 14-amino acid peptide approved for the treatment of IBS with constipation, relieves constipation and reduces IBS-associated pain in these patients presumably by activation of guanylate cyclase-C (GC-C), which stimulates production and release of cyclic guanosine monophosphate (cGMP) from intestinal epithelial cells. We investigated whether activation of GC-C by the endogenous agonist uroguanylin or the primary downstream effector of that activation, cGMP, directly modulates responses and sensitization of mechanosensitive colorectal primary afferents. The distal 2 cm of mouse colorectum with attached pelvic nerve was harvested, pinned flat mucosal side up for in vitro single-fiber recordings and the encoding properties of mechanosensitive afferents (serosal, mucosal, muscular and muscular-mucosal) to probing and circumferential stretch studied. Both cGMP (10–300μM) and uroguanylin (1–1000nM) applied directly to colorectal receptive endings significantly reduced responses of muscular and muscular-mucosal afferents to stretch; serosal and mucosal afferents were not affected. Sensitized responses (i.e., increased responses to stretch) of muscular and muscular-mucosal afferents were reversed by cGMP, returning responses to stretch to control. Blocking the transport of cGMP from colorectal epithelia by probenecid, a mechanism validated by studies in cultured intestinal T84 cells, abolished the inhibitory effect of uroguanylin on muscular-mucosal afferents. These results suggest that GC-C agonists like linaclotide alleviate colorectal pain and hypersensitivity by dampening stretch-sensitive afferent mechanosensitivity and normalizing afferent sensitization. PMID:23739979

  15. Dynamic longitudinal investigation of individual nerve endings in the skin of anesthetized mice using in vivo two-photon microscopy

    NASA Astrophysics Data System (ADS)

    Yuryev, Mikhail; Khiroug, Leonard

    2012-04-01

    Visualization of individual cutaneous nerve endings has previously relied on laborious procedures of tissue excision, fixation, sectioning and staining for light or electron microscopy. We present a method for non-invasive, longitudinal two-photon microscopy of single nerve endings within the skin of anesthetized transgenic mice. Besides excellent signal-to-background ratio and nanometer-scale spatial resolution, this method offers time-lapse ``movies'' of pathophysiological changes in nerve fine structure over minutes, hours, days or weeks. Structure of keratinocytes and dermal matrix is visualized simultaneously with nerve endings, providing clear landmarks for longitudinal analysis. We further demonstrate feasibility of dissecting individual nerve fibers with infra-red laser and monitoring their degradation and regeneration. In summary, our excision-free optical biopsy technique is ideal for longitudinal microscopic analysis of animal skin and skin innervations in vivo and can be applied widely in preclinical models of chronic pain, allergies, skin cancers and a variety of dermatological disorders.

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

    PubMed Central

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

    2014-01-01

    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. PMID:25190475

  17. Skeletal muscle afferent regulation of bioassayable growth hormone in the rat pituitary

    NASA Technical Reports Server (NTRS)

    Gosselink, K. L.; Grindeland, R. E.; Roy, R. R.; Zhong, H.; Bigbee, A. J.; Grossman, E. J.; Edgerton, V. R.

    1998-01-01

    There are forms of growth hormone (GH) in the plasma and pituitary of the rat and in the plasma of humans that are undetected by presently available immunoassays (iGH) but can be measured by bioassay (bGH). Although the regulation of iGH release is well documented, the mechanism(s) of bGH release is unclear. On the basis of changes in bGH and iGH secretion in rats that had been exposed to microgravity conditions, we hypothesized that neural afferents play a role in regulating the release of these hormones. To examine whether bGH secretion can be modulated by afferent input from skeletal muscle, the proximal or distal ends of severed hindlimb fast muscle nerves were stimulated ( approximately 2 times threshold) in anesthetized rats. Plasma bGH increased approximately 250%, and pituitary bGH decreased approximately 60% after proximal nerve trunk stimulation. The bGH response was independent of muscle mass or whether the muscles were flexors or extensors. Distal nerve stimulation had little or no effect on plasma or pituitary bGH. Plasma iGH concentrations were unchanged after proximal nerve stimulation. Although there may be multiple regulatory mechanisms of bGH, the present results demonstrate that the activation of low-threshold afferents from fast skeletal muscles can play a regulatory role in the release of bGH, but not iGH, from the pituitary in anesthetized rats.

  18. Effects of combined treatment with mephedrone and methamphetamine or 3,4-methylenedioxymethamphetamine on serotonin nerve endings of the hippocampus

    PubMed Central

    Angoa-Pérez, Mariana; Kane, Michael J.; Herrera-Mundo, Nieves; Francescutti, Dina M.; Kuhn, Donald M.

    2013-01-01

    Aims Mephedrone is a stimulant drug of abuse with close structural and mechanistic similarities to methamphetamine and 3,4-methylenedioxymethamphetamine (MDMA). Although mephedrone does not damage dopamine nerve endings it increases the neurotoxicity of amphetamine, methamphetamine and MDMA. The effects of mephedrone on serotonin (5HT) nerve endings are not fully understood, with some investigators reporting damage while others conclude it does not. Presently, we investigate if mephedrone given alone or with methamphetamine or MDMA damages 5HT nerve endings of the hippocampus. Main methods The status of 5HT nerve endings in hippocampus of female C57BL mice was assessed through measures of 5HT by HPLC and by immunoblot analysis of serotonin transporter (SERT) and tryptophan hydroxylase 2 (TPH2), selective markers of 5HT nerve endings. Astrocytosis was assessed through measures of glial fibrillary acidic protein (GFAP) (immunoblotting) and microglial activation was determined by histochemical staining with Isolectin B4. Key findings Mephedrone alone did not cause persistent reductions in the levels of 5HT, SERT or TPH2. Methamphetamine and MDMA alone caused mild reductions in 5HT but did not change SERT and TPH2 levels. Combined treatment with mephedrone and methamphetamine or MDMA did not change the status of 5HT nerve endings to an extent that was different from either drug alone. Significance Mephedrone does not cause toxicity to 5HT nerve endings of the hippocampus. When co-administered with methamphetamine or MDMA, drugs that are often co-abused with mephedrone by humans, toxicity is not increased as is the case for dopamine nerve endings when these drugs are taken together. PMID:23892197

  19. Free nerve ending density on skin extracted by circumcision and its relation to premature ejaculation.

    PubMed

    Malkoc, Ercan; Ates, Ferhat; Tekeli, Hakan; Kurt, Bulent; Turker, Turker; Basal, Seref

    2012-01-01

    Many studies have shown that skin tissue extracted by circumcision can cause differences in sexual function, especially at the time of ejaculation. Sensitivity changes in penile skin and sexual satisfaction deriving from circumcision starting from premature ejaculation (PE) are discussed. Furthermore, most of these studies rely on questionnaires. Extracted free nerve endings (FNE) on the foreskin, which can detect temperature, mechanical stimuli (touch, pressure, stretch) or pain (nociception), have not been researched. Our aim is to determine FNEs in foreskin and the affects on sexual function, especially PE. This prospective study was done on adults who voluntarily applied to be circumcised between September 2010 and October 2011. The ejaculation latency times (ELT) before circumcision have been assessed, and a PE diagnostic tool (PEDT) form was filled out by the urologist according to the answers given by the volunteers. The proximal and distal ends of the foreskin were marked before circumcision, and the extracted foreskin was sent to the pathology department to determine FNEs. Twenty volunteers (average age 21.25 ± 0.44 years) were included in the study. The average ELT was 103.55 ± 68.39 seconds, and the average PE score was 4.35 ± 3.13. Proximal, middle, and distal tip nerve densities were compared. Proximal and distal (P = .003) and proximal and middle (P = .011) segments differed from each other, whereas middle and distal were similar (P = .119). There were not any correlations between PEDT scores and total nerve endings number (r = .018, P = .942). Also there were not any correlations between mean ELT and PEDT scores (r = .054, P = .822). The tissue extracted by circumcision has intensive FNEs, yet FNE intensity has no relation to PE. PMID:22604629

  20. Neuroanatomy of extrinsic afferents supplying the gastrointestinal tract.

    PubMed

    Berthoud, H R; Blackshaw, L A; Brookes, S J H; Grundy, D

    2004-04-01

    Here we discuss the neuroanatomy of extrinsic gastrointestinal (GI) afferent neurones, the relationship between structure and function and the role of afferents in disease. Three pathways connect the gut to the central nervous system: vagal afferents signal mainly from upper GI regions, pelvic afferents mainly from the colorectal region and splanchnic afferents from throughout. Vagal afferents mediate reflex regulation of gut function and behaviour, operating mainly at physiological levels. There are two major functional classes - tension receptors, responding to muscular contraction and distension, and mucosal receptors. The function of vagal endings correlates well with their anatomy: tracing studies show intramuscular arrays (IMAs) and intraganglionic laminar endings (IGLEs); IGLEs are now known to respond to tension. Functional mucosal receptors correlate with endings traced to the lamina propria. Pelvic afferents serve similar functions to vagal afferents, and additionally mediate both innocuous and noxious sensations. Splanchnic afferents comprise mucosal and stretch-sensitive afferents with low thresholds in addition to high-threshold serosal/mesenteric afferents suggesting diverse roles. IGLEs, probably of pelvic origin, have been identified recently in the rectum and respond similarly to gastric vagal IGLEs. Gastrointestinal afferents may be sensitized or inhibited by chemical mediators released from several cell types. Whether functional changes have anatomical correlates is not known, but it is likely that they underlie diseases involving visceral hypersensitivity. PMID:15066001

  1. Temperature receptors in cutaneous nerve endings are thermostat molecules that induce thermoregulatory behaviors against thermal load

    PubMed Central

    Kobayashi, Shigeo

    2015-01-01

    When skin temperature falls below a set-point, mammals experience “cold in the skin” and exhibit heat-seeking behaviors for error correction. Physiological thermostats should perform the behavioral thermoregulation, and it is important to identify the thermostats. A classical model of the sensory system states that thermoreceptors (e.g., thermoTRPs) in skin nerve endings are sensors that transform temperature into the firing rate codes that are sent to the brain, where the codes are decoded as “cold” by a labeled line theory. However, the view that the temperature code is transformed into “cold” (not temperature) is conflicting. Another model states that a thermostat exists in the brain based on the view that a skin thermo-receptor is a sensor. However, because animals have no knowledge of the principle of temperature measurement, the brain is unable to measure skin temperature with a thermometer calibrated based on a code table of each sensor in the skin. Thus, these old models cannot identify the thermostats. We have proposed a new model in which temperature receptors in a nerve ending are molecules of the thermostats. When skin temperature falls below a set-point, these molecules as a whole induce impulses as command signals sent to the brain, where these impulses activate their target neurons for “cold” and heat-seeking behaviors for error correction. Our study challenges the famous models that sensory receptor is a sensor and the brain is a code processor. PMID:27227048

  2. Temperature receptors in cutaneous nerve endings are thermostat molecules that induce thermoregulatory behaviors against thermal load.

    PubMed

    Kobayashi, Shigeo

    2015-01-01

    When skin temperature falls below a set-point, mammals experience "cold in the skin" and exhibit heat-seeking behaviors for error correction. Physiological thermostats should perform the behavioral thermoregulation, and it is important to identify the thermostats. A classical model of the sensory system states that thermoreceptors (e.g., thermoTRPs) in skin nerve endings are sensors that transform temperature into the firing rate codes that are sent to the brain, where the codes are decoded as "cold" by a labeled line theory. However, the view that the temperature code is transformed into "cold" (not temperature) is conflicting. Another model states that a thermostat exists in the brain based on the view that a skin thermo-receptor is a sensor. However, because animals have no knowledge of the principle of temperature measurement, the brain is unable to measure skin temperature with a thermometer calibrated based on a code table of each sensor in the skin. Thus, these old models cannot identify the thermostats. We have proposed a new model in which temperature receptors in a nerve ending are molecules of the thermostats. When skin temperature falls below a set-point, these molecules as a whole induce impulses as command signals sent to the brain, where these impulses activate their target neurons for "cold" and heat-seeking behaviors for error correction. Our study challenges the famous models that sensory receptor is a sensor and the brain is a code processor. PMID:27227048

  3. A new technique for the direct demonstration of overlapping cutaneous innervation territories of peptidergic C-fibre afferents of rat hindlimb nerves.

    PubMed

    Dux, M; Jancsó, G

    1994-11-01

    A new technique based on the phenomenon of vascular labelling has been devised for the direct visualisation of overlapping innervation territories of cutaneous nerves. The saphenous, peroneal and sural nerves on one side in anaesthetised rats were exposed, cut centrally and successively stimulated antidromically to induce a neurogenic inflammatory response after an intravenous injection of either a 1% colloidal silver solution or a suspension of 3% Monastral Blue B. Light microscopic examination of transparent preparations of the dorsal hindpaw skin revealed labelled blood vessels of different colours which represented cutaneous territories served by different nerves. Blood vessels labelled with both substances were regarded as areas of overlapping innervation. Such areas were typically localised along the border of adjacent innervation territories. In addition, distinct areas exhibiting double-labelled blood vessels were regularly encountered in regions separate from this border zone. Areas of interest were drawn with the aid of a camera lucida and measured by means of a computerised system. The results indicate a significant, although topographically variable, degree of overlap of these cutaneous innervation areas. This new technique offers a possibility to explore the importance of normally existing overlap in the reinnervation of a denervated skin area by collateral nerve sprouting. PMID:7891461

  4. Optogenetic activation of mechanically insensitive afferents in mouse colorectum reveals chemosensitivity.

    PubMed

    Feng, Bin; Joyce, Sonali C; Gebhart, G F

    2016-05-15

    The sensory innervation of the distal colorectum includes mechanically insensitive afferents (MIAs; ∼25%), which acquire mechanosensitivity in persistent visceral hypersensitivity and thus generate de novo input to the central nervous system. We utilized an optogenetic approach to bypass the process of transduction (generator potential) and focus on transformation (spike initiation) at colorectal MIA sensory terminals, which is otherwise not possible in typical functional studies. From channelrhodopsin2-expressing mice (driven by Advillin-Cre), the distal colorectum with attached pelvic nerve was harvested for ex vivo single-fiber recordings. Afferent receptive fields (RFs) were identified by electrical stimulation and tested for response to mechanical stimuli (probing, stroking, and stretch), and afferents were classified as either MIAs or mechanosensitive afferents (MSAs). All MIA and MSA RFs were subsequently stimulated optically and MIAs were also tested for activation/sensitization with inflammatory soup (IS), acidic hypertonic solution (AHS), and/or bile salts (BS). Responses to pulsed optical stimuli (1-10 Hz) were comparable between MSAs and MIAs whereas 43% of MIAs compared with 86% of MSAs responded tonically to stepped optical stimuli. Tonic-spiking MIAs responded preferentially to AHS (an osmotic stimulus) whereas non-tonic-spiking MIAs responded to IS (an inflammatory stimulus). A significant proportion of MIAs were also sensitized by BS. These results reveal transformation as a critical factor underlying the differences between MIAs (osmosensors vs. inflammatory sensors), revealing a previously unappreciated heterogeneity of MIA endings. The current study draws attention to the sensory encoding of MIA nerve endings that likely contribute to afferent sensitization and thus have important roles in visceral pain. PMID:26950857

  5. Xanthine oxidase, but not neutrophils, contributes to activation of cardiac sympathetic afferents during myocardial ischaemia in cats

    PubMed Central

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

    2002-01-01

    Activation of cardiac sympathetic afferents during myocardial ischaemia causes angina and induces important cardiovascular reflex responses. Reactive oxygen species (ROS) are important chemical stimuli of cardiac afferents during and after ischaemia. Iron-catalysed Fenton chemistry constitutes one mechanism of production of hydroxyl radicals. Another potential source of these species is xanthine oxidase-catalysed oxidation of purines. Polymorphonuclear leukocytes (PMNs) also contribute to the production of ROS in some conditions. The present study tested the hypothesis that both xanthine oxidase-catalysed oxidation of purines and neutrophils provide a source of ROS sufficient to activate cardiac afferents during ischaemia. We recorded single-unit activity of cardiac afferents innervating the ventricles recorded from the left thoracic sympathetic chain (T1-5) of anaesthetized cats to identify the afferents' responses to ischaemia. The role of xanthine oxidase in activation of these afferents was determined by infusion of oxypurinol (10 mg kg−1, i.v.), an inhibitor of xanthine oxidase. The importance of neutrophils as a potential source of ROS in the activation of cardiac afferents during ischaemia was assessed by the infusion of a polyclonal antibody (3 mg ml−1 kg−1, i.v.) raised in rabbits immunized with cat PMNs. This antibody decreased the number of circulating PMNs and, to a smaller extent, platelets. Since previous data suggest that platelets release serotonin (5-HT), which activates cardiac afferents through a serotonin receptor (subtype 3,5-HT3 receptor) mechanism, before treatment with the antibody in another group, we blocked 5-HT3 receptors on sensory nerve endings with tropisetron (300 μg kg−1, i.v.). We observed that oxypurinol significantly decreased the activity of cardiac afferents during myocardial ischaemia from 1.5 ± 0.4 to 0.8 ± 0.4 impulses s−1. Similarly, the polyclonal antibody significantly reduced the discharge frequency of

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

    PubMed Central

    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

  7. Mechanism of nicotine-induced release of noradrenaline from adrenergic nerve endings

    PubMed Central

    Jayasundar, S.; Vohra, M.M.

    1977-01-01

    1 A study of the mechanism of release of [3H]-noradrenaline ([3H]-NA) by nicotine from isolated vas deferens of the rat was made using incubation media of different ionic composition. 2 Nicotine (20 μg/ml)-induced release of [3H]-NA was significantly potentiated in K+-free Krebs solution as compared to that in normal Krebs-Ringer solution. 3 Nicotine-induced release of [3H]-NA was significantly reduced in Na+-deficient Krebs solution (containing only 11 mM Na+) and was abolished in Na+-free Krebs solution. 4 In totally depolarized tissues, nicotine failed to cause an outflow of [3H]-NA but Ca2+ (5 mM) did so. 5 Nicotine required the presence of Ca2+ in the incubation medium to cause release of [3H]-NA from adrenergic nerve terminals, the magnitude of release being dependent upon the concentration of Ca2+. 6 Nicotine-induced release of [3H]-NA was demonstrated in high Ca2+, Na+-free Krebs solution in which all Na+ had been replaced with Ca2+. 7 It is concluded that nicotine increases the membrane permeability to both Na+ and Ca2+. It is also suggested that the increase in permeability to Ca2+ alone is not sufficient but a local depolarizing action of nicotine is necessary to cause release of noradrenaline from adrenergic nerve endings. PMID:922247

  8. Vagal afferent innervation of the rat fundic stomach: morphological characterization of the gastric tension receptor.

    PubMed

    Berthoud, H R; Powley, T L

    1992-05-01

    Although the gastric tension receptor has been characterized behaviorally and electrophysiologically quite well, its location and structure remains elusive. Therefore, the vagal afferents to the rat fundus (forestomach or nonglandular stomach) were anterogradely labeled in vivo with injections of the carbocyanine dye Dil into the nodose ganglia, and the nerves and ganglia of the enteric nervous system were labeled in toto with intraperitoneal Fluorogold injection. Dissected layers and cryostat cross sections of the fundic wall were mounted in glycerin and analyzed by means of conventional and laser scanning confocal microscopy. Particularly in the longitudinal, and to a lesser extent in the circular, smooth muscle layers, Dil-labeled fibers and terminals were abundant. These processes, which originated from fibers coursing through the myenteric ganglia and connectives, entered either muscle coat and then ran parallel to the respective muscle fibers, often for several millimeters. They ran in close association with the Fluorogold-labeled network of interstitial cells of Cajal, upon which they appeared to form multiple spiny appositions or varicosities. In the myenteric plexus, two different types of afferent vagal structures were observed. Up to 300 highly arborizing endings forming dense accumulations of small puncta similar to the esophageal intraganglionic laminar endings (Rodrigo et al., '75 Acta Anat. 92:79-100) were found in the fundic wall ipsilateral to the injected nodose ganglion. They often covered small clusters of myenteric neurons or even single isolated ganglion cells (mean = 5.8 neurons) and tended to extend throughout the neuropil of the ganglia. In a second pattern, fine varicose fibers with less profuse arborizations innervated mainly the central regions of myenteric ganglia. Camera lucida analyses established that single vagal afferent fibers had separate collaterals in both a smooth muscle layer and the myenteric ganglia. Finally, Dil

  9. Regeneration of putative sensory and sympathetic cutaneous nerve endings in the rat foot after sciatic nerve injury.

    PubMed

    Stankovic, N; Johansson, O; Hildebrand, C

    1996-01-01

    The present study examines the occurrence of calcitonin gene-related peptide-, substance P- and tyrosine hydroxylase-like immunoreactive profiles in glabrous and hairy foot skin from normal and nerve-injured rats. After neurotomy/suture, glabrous skin samples contain few calcitonin gene-related peptide-, substance P- and tyrosine hydroxylase-like immunoreactive profies. The number of calcitonin gene-related peptide- and substance P-like immunoreacive profiles in the epidermis is significantly subnormal. Hairy skin from these rats does also contain few calcitonin gene-related peptide-, substance P- and tyrosine hydroxylase-like immunoreactive profiles. In addition, the presence of epidermal calcitonin gene-related peptide-like imunoreactive profiles in glabrous skin is subnormal on the contralateral side. After nerve crush injury, the occurrence of calcitonin gene-related peptide-like, but not substance P-like, immunoreactive profiles in th epidermis of the glabrous skin is significantly subnormal. The occurrence of tyrosine hylase-like immnunoreactive fibres in relation to the digital artery is also subnormal. The occurrence in hairy skin of calcitonin gene-related peptide-like immunoreactive, substance P-like immunoreactive and tyrosine hydroxylase-like immunoreactive profiles is subnormal. In both skin types, the contralateral occurrence of such profiles is subjectively normal. These results show that the occurrence of calcitonin gene-related peptide-, substance P-, and tyrosine hydroxylase-like immunoreactive profiles in glabrous and hairy foot skin is clearly subnormal after neurotomy and suture and less abnormal after nerve crush. After neurotomy and suture the contralateral side is also affected. PMID:10970110

  10. Vagal Afferent Innervation of the Airways in Health and Disease.

    PubMed

    Mazzone, Stuart B; Undem, Bradley J

    2016-07-01

    Vagal sensory neurons constitute the major afferent supply to the airways and lungs. Subsets of afferents are defined by their embryological origin, molecular profile, neurochemistry, functionality, and anatomical organization, and collectively these nerves are essential for the regulation of respiratory physiology and pulmonary defense through local responses and centrally mediated neural pathways. Mechanical and chemical activation of airway afferents depends on a myriad of ionic and receptor-mediated signaling, much of which has yet to be fully explored. Alterations in the sensitivity and neurochemical phenotype of vagal afferent nerves and/or the neural pathways that they innervate occur in a wide variety of pulmonary diseases, and as such, understanding the mechanisms of vagal sensory function and dysfunction may reveal novel therapeutic targets. In this comprehensive review we discuss historical and state-of-the-art concepts in airway sensory neurobiology and explore mechanisms underlying how vagal sensory pathways become dysfunctional in pathological conditions. PMID:27279650

  11. Static γ-motoneurones couple group Ia and II afferents of single muscle spindles in anaesthetised and decerebrate cats

    PubMed Central

    Gladden, M H; Matsuzaki, H

    2002-01-01

    Ideas about the functions of static γ-motoneurones are based on the responses of primary and secondary endings to electrical stimulation of single static γ-axons, usually at high frequencies. We compared these effects with the actions of spontaneously active γ-motoneurones. In anaesthetised cats, afferents and efferents were recorded in intramuscular nerve branches to single muscle spindles. The occurrence of γ-spikes, identified by a spike shape recognition system, was linked to video-taped contractions of type-identified intrafusal fibres in the dissected muscle spindles. When some static γ-motoneurones were active at low frequency (< 15 Hz) they coupled the firing of group Ia and II afferents. Activity of other static γ-motoneurones which tensed the intrafusal fibres appeared to enhance this effect. Under these conditions the secondary ending responded at shorter latency than the primary ending. In another series of experiments on decerebrate cats, responses of primary and secondary endings of single muscle spindles to activation of γ-motoneurones by natural stimuli were compared with their responses to electrical stimulation of single γ-axons supplying the same spindle. Electrical stimulation mimicked the natural actions of γ-motoneurones on either the primary or the secondary ending, but not on both together. However, γ-activity evoked by natural stimuli coupled the firing of afferents with the muscle at constant length, and also when it was stretched. Analysis showed that the timing and tightness of this coupling determined the degree of summation of excitatory postsynaptic potentials (EPSPs) evoked by each afferent in α-motoneurones and interneurones contacted by terminals of both endings, and thus the degree of facilitation of reflex actions of group II afferents. PMID:12181298

  12. Muscarinic cholinergic enhancement of inositide turnover in cerebral nerve endings is not mediated by calcium uptake.

    PubMed

    Van Rooijen, L A; Traber, J

    1986-08-15

    Muscarinic cholinergic stimulation of rat cerebral nerve endings incubated with 32Pi causes an enhancement of the labeling of phosphatidic acid (PA) and phosphatidylinositol (PI). The involvement of Ca2+ in the stimulation of PA and PI labeling by carbamylcholine (CCh) was investigated. Enhancement of Ca2+-influx with veratridine and the Ca2+-ionophore A23187 caused a vast decrease of the labeling of the polyphosphoinositides, which was not accompanied by an enhancement of the labeling of PA and PI. The dihydropyridine Ca2+-agonist BAY K8644 did not affect phospholipid labeling. A23187, veratridine and BAY K 8644 did not enhance stimulation of the labeling of PA and PI by CCh. When Ca2+ was omitted from the incubation, A23187 caused an enhancement of basal and CCh-stimulated labeling of PA and PI, possibly indicating a particular feature of A23187 unrelated to its iontophoretic properties. The Ca2+-channel antagonists nimodipine, verapamil and flunarizine were virtually without effect on basal and CCh-stimulated labeling of PI and PA. These data support the notion that the muscarinic cholinergic inositide response is not mediated or controlled by Ca2+-flux. PMID:2427087

  13. Long-term storage of functional, isolated nerve endings by slow freezing and rapid thawing.

    PubMed

    Drapeau, P

    1988-06-01

    Nerve endings (synaptosomes) were isolated from homogenized rat brain corpora striata following centrifugation on discontinuous sucrose gradients. The synaptosomes (in 0.8 M sucrose) were (i) slowly frozen by placing the tube containing the suspension in a freezer at -10 degrees C for 1 h followed by (ii) swirling in a mixture of acetone and dry ice for 15 min and (iii) were stored in liquid nitrogen for up to 6 weeks. Freshly isolated synaptosomes and synaptosomes from the same preparation that were frozen for 2, 4, or 6 weeks and rapidly thawed in a water bath at 37 degrees C were re-equilibrated with a physiological salt solution and assayed for their ability to accumulate Ca and to release transmitter (dopamine) upon depolarization in high K medium. K-dependent Ca uptake gradually declined to approximately 1/3 the value observed with freshly isolated synaptosomes after 6 weeks of storage. K-stimulated dopamine release (only from intact synaptosomes) was normal over the entire period of storage. It is concluded that synaptosomes retain their physiological properties when stored frozen for a few weeks and that cold storage may be a useful technique for experiments requiring lengthy or repeated assays or accumulation of material. PMID:3405007

  14. Cortical projection of afferent information from tendon organs in the cat.

    PubMed Central

    McIntyre, A K; Proske, U; Rawson, J A

    1984-01-01

    In cats anaesthetized with chloralose, evidence has been sought for the projection of information from tendon organs to the sensory receiving areas of the cerebral cortex. Selective stimulation of afferent fibres from tendon organs has been achieved by raising the threshold to electrical stimulation of the fibres from primary endings of muscle spindles. The method uses longitudinal vibration at 200-250 Hz to elicit, over a period of 20 min, one impulse for each excursion of the vibrator from all of the spindles in the test muscle, soleus or medial gastrocnemius. The accumulated post-spike positivities following passage of the impulses are thought to be responsible for the rise in threshold. Segmental monosynaptic reflex testing after a bout of vibration was used to confirm that the residual Group I volley no longer contained impulses from muscle spindles. The volley in response to stimulating the nerve of the test muscle was timed to facilitate the monosynaptic reflex of a synergist. Before vibration 5- to 10-fold facilitation of reflex amplitude could be produced; however, after vibration, if all the spindle primary endings had been effectively engaged by the stimulus, no detectable facilitation remained. This test was found to be sensitive and reproducible. An afferent volley containing only activity of tendon organ afferents evoked small-amplitude potentials from the post-sigmoid gyrus of the contralateral pericruciate cortex. The field was highly localized and lay caudal to the main receiving area for activity from the sural nerve and from afferents of hip flexor muscles. Recordings with tungsten micro-electrodes revealed that the surface-evoked activity took origin in cellular discharges in the internal pyramidal layer of area 3a. Recent psychophysical experiments have provided evidence for a sense of muscle tension, as distinct from a sense of effort, and the tendon organ has been suggested as the likely receptor of origin. Our electrophysiological

  15. Isolated nerve endings (neurosecretosomes) from the posterior pituitary. Partial separation of vasopressin and oxytocin and the isolation of microvesicles.

    PubMed

    Bindler, E; Labella, F S; Sanwal, M

    1967-07-01

    Subcellular fractions of the bovine posterior pituitary, including one composed almost exclusively of pinched-off nerve endings (neurosecretosomes), were characterized electron microscopically, hormonally, and enzymically. 15% of the nerve terminals in the gland were isolated as neurosecretosomes, as estimated from determinations of lactic dehydrogenase, a soluble, cytoplasmic enzyme. Neurosecretosomes were subdivided into three fractions by density-gradient centrifugation. The three subfractions, each shown to be nearly homogeneous populations of neurosecretosomes by means of electron microscopic and enzymic criteria, differed from each other in their vasopressin/oxytocin (VP/OT) ratios. The VP/OT ratio increased from the lightest to the densest fraction, indicating that VP is localized to denser and OT to lighter neurosecretosomes; similar results have been obtained previously for subfractions of neurosecretory granules (NSG). No morphological differences were apparent in neurosecretosomes among the three subfractions. Although complete separation of VP and OT was not achieved, the findings suggest that VP and OT are each stored in a different species of nerve ending and support the hypothesis that a given neurosecretory cell synthesizes, stores, and secretes only one of the peptide hormones. Microvesicles, 40-80 mmicro diameter and contained in typical neurosecretory cell terminals, are believed to be degradation products of membrane ghosts of depleted NSG; electron micrographs indicative of this transformation are presented. A fraction rich in microvesicles, but containing some NSG membranes, was prepared by density-gradient centrifugation of an osmolysate of neurosecretosomes. Smaller, apparently nonneurosecretory nerve endings, lacking NSG but filled with small vesicles, are occasionally seen in sections from whole gland. The vesicles in these atypical posterior pituitary nerve endings may be true neurohumor-containing, "synaptic" vesicles. PMID:6040535

  16. Blockage of vibrissae afferents: I. Motor effects.

    PubMed

    Prchal, A; Albarracín, A L; Décima, E E

    2004-02-01

    In the past, it has been proposed that the rat vibrissae play an important role in other hand, postural abnormalities, muscle tone decreases and hypomotility after sensory organ destructions were proposed as evidence supporting the "level setting" or "tonic" hypothesis. This hypothesis postulates that afferent activity, besides its well know transductive functions, sets the excitability state of the central nervous system. We thought the vibrissal system to be a good model to dissect these two postulated roles because vibrissae trimming would annul the transductive function without affecting the integrity of nerve activity. Thus we compare the effects of trimming the whiskers with blocking the vibrissal afferent nerves on two types of motor behavior: activity in an open field and walking over a rope connecting two elevated platforms. We found that only vibrissal afferent blockage (both nerve section and local anaesthesia) produced severe failures in the motor performances studied. These effects could not be fully explained by the abolition of the vibrissae as a sensory modality because cutting the whiskers did not significantly affect the motor performance. These data are discussed in reference to a tonic or general excitatory function of sensory inputs upon the central nervous system. PMID:15143620

  17. Spinal inhibition of phrenic motoneurones by stimulation of afferents from leg muscle in the cat: blockade by strychnine.

    PubMed

    Eldridge, F L; Millhorn, D E; Waldrop, T

    1987-08-01

    1. Phrenic nerve responses to stimulation of calf muscle receptors or their afferents were studied in paralysed high (C1) spinal cats whose phrenic nerve activity was evoked by activation of the intercostal-to-phrenic reflex. End-tidal PCO2 was maintained at a constant level by means of a servo-controlled ventilator. 2. Physical stimulation of calf muscles or electrical stimulation of the tibial nerve uniformly caused inhibition of phrenic activity evoked by facilitatory conditioning stimuli. The degree of inhibition gradually decreased as muscle stimulation continued, and there was a post-stimulus augmentation of phrenic activity. 3. Pre-treatment with subconvulsive doses of strychnine, an antagonist of the neurotransmitter glycine, partially or completely blocked the inhibitory effects on phrenic activity of muscle-afferent stimulation. The blockade was reversible with time. 4. Pre-treatment with a subconvulsive dose of bicuculline, an antagonist of the neurotransmitter gamma-aminobutyric acid (GABA), had no effect on the inhibitory mechanism. 5. We conclude that glycine is an important transmitter of the inhibition of phrenic motoneurones induced by muscle-afferent stimulation, but that GABA is not involved in this inhibitory mechanism. PMID:3681723

  18. Mephedrone Does not Damage Dopamine Nerve Endings of the Striatum but Enhances the Neurotoxicity of Methamphetamine, Amphetamine and MDMA

    PubMed Central

    Angoa-Pérez, Mariana; Kane, Michael J.; Briggs, Denise I.; Francescutti, Dina M.; Sykes, Catherine E.; Shah, Mrudang M.; Thomas, David M.; Kuhn, Donald M.

    2012-01-01

    Mephedrone (4-methylmethcathinone) is a β-ketoamphetamine stimulant drug of abuse with close structural and mechanistic similarities to methamphetamine. One of the most powerful actions associated with mephedrone is the ability to stimulate dopamine (DA) release and block its reuptake through its interaction with the dopamine transporter (DAT). Although mephedrone does not cause toxicity to DA nerve endings, its ability to serve as a DAT blocker could provide protection against methamphetamine-induced neurotoxicity like other DAT inhibitors. To test this possibility, mice were treated with mephedrone (10, 20 or 40 mg/kg) prior to each injection of a neurotoxic regimen of methamphetamine (4 injections of 2.5 or 5.0 mg/kg at 2 hr intervals). The integrity of DA nerve endings of the striatum was assessed through measures of DA, DAT and tyrosine hydroxylase levels. The moderate to severe DA toxicity associated with the different doses of methamphetamine was not prevented by any dose of mephedrone but was, in fact, significantly enhanced. The hyperthermia caused by combined treatment with mephedrone and methamphetamine was the same as seen after either drug alone. Mephedrone also enhanced the neurotoxic effects of amphetamine and MDMA on DA nerve endings. In contrast, nomifensine protected against methamphetamine-induced neurotoxicity. Because mephedrone increases methamphetamine neurotoxicity, the present results suggest that it interacts with the DAT in a manner unlike that of other typical DAT inhibitors. The relatively innocuous effects of mephedrone alone on DA nerve endings mask a potentially dangerous interaction with drugs that are often co-abused with it, leading to heightened neurotoxicity. PMID:23205838

  19. The Role of Endogenous Serotonin in Methamphetamine-Induced Neurotoxicity to Dopamine Nerve Endings of the Striatum

    PubMed Central

    Thomas, David M.; Angoa-Pérez, Mariana; Francescutti-Verbeem, Dina M.; Shah, Mrudang M.; Kuhn, Donald M.

    2010-01-01

    Methamphetamine (METH) is a neurotoxic drug of abuse that damages the dopamine (DA) neuronal system in a highly delimited manner. The brain structure most affected by METH is the striatum where long-term DA depletion and microglial activation are maximal. Endogenous DA has been implicated as a critical participant in METH-induced neurotoxicity, most likely as a substrate for non-enzymatic oxidation by METH-generated reactive oxygen species (ROS). The striatum is also extensively innervated by serotonin (5HT) nerve endings and this neurochemical system is modified by METH in much the same manner as seen in DA nerve endings (i.e., increased release of 5HT, loss of function in tryptophan hydroxylase and the serotonin transporter, long-term depletion of 5HT stores). 5HT can also be modified by ROS to form highly reactive species that damage neurons but its role in METH neurotoxicity has not been assessed. Increases in 5HT levels with 5HTP do not change METH-induced neurotoxicity to the DA nerve endings as revealed by reductions in DA, tyrosine hydroxylase and dopamine transporter levels. Partial reductions in 5HT with p-chlorophenylalanine (PCPA) are without effect on METH toxicity, despite the fact that PCPA largely prevents METH-induced hyperthermia. Mice lacking the gene for brain tryptophan hydroxylase 2 are devoid of brain 5HT and respond to METH in the same manner as wild-type controls, despite showing enhanced drug-induced hyperthermia. Taken together, the present results indicate that endogenous 5HT does not appear to play a role in METH-induced damage to DA nerve endings of the striatum. PMID:20722968

  20. The role of endogenous serotonin in methamphetamine-induced neurotoxicity to dopamine nerve endings of the striatum.

    PubMed

    Thomas, David M; Angoa Pérez, Mariana; Francescutti-Verbeem, Dina M; Shah, Mrudang M; Kuhn, Donald M

    2010-11-01

    Methamphetamine (METH) is a neurotoxic drug of abuse that damages the dopamine (DA) neuronal system in a highly delimited manner. The brain structure most affected by METH is the striatum where long-term DA depletion and microglial activation are maximal. Endogenous DA has been implicated as a critical participant in METH-induced neurotoxicity, most likely as a substrate for non-enzymatic oxidation by METH-generated reactive oxygen species. The striatum is also extensively innervated by serotonin (5HT) nerve endings and this neurochemical system is modified by METH in much the same manner as seen in DA nerve endings (i.e., increased release of 5HT, loss of function in tryptophan hydroxylase and the serotonin transporter, long-term depletion of 5HT stores). 5HT can also be modified by reactive oxygen species to form highly reactive species that damage neurons but its role in METH neurotoxicity has not been assessed. Increases in 5HT levels with 5-hydroxytryptophan do not change METH-induced neurotoxicity to the DA nerve endings as revealed by reductions in DA, tyrosine hydroxylase and dopamine transporter levels. Partial reductions in 5HT with p-chlorophenylalanine are without effect on METH toxicity, despite the fact that p-chlorophenylalanine largely prevents METH-induced hyperthermia. Mice lacking the gene for brain tryptophan hydroxylase 2 are devoid of brain 5HT and respond to METH in the same manner as wild-type controls, despite showing enhanced drug-induced hyperthermia. Taken together, the present results indicate that endogenous 5HT does not appear to play a role in METH-induced damage to DA nerve endings of the striatum. PMID:20722968

  1. Mephedrone does not damage dopamine nerve endings of the striatum, but enhances the neurotoxicity of methamphetamine, amphetamine, and MDMA.

    PubMed

    Angoa-Pérez, Mariana; Kane, Michael J; Briggs, Denise I; Francescutti, Dina M; Sykes, Catherine E; Shah, Mrudang M; Thomas, David M; Kuhn, Donald M

    2013-04-01

    Mephedrone (4-methylmethcathinone) is a β-ketoamphetamine stimulant drug of abuse with close structural and mechanistic similarities to methamphetamine. One of the most powerful actions associated with mephedrone is the ability to stimulate dopamine (DA) release and block its re-uptake through its interaction with the dopamine transporter (DAT). Although mephedrone does not cause toxicity to DA nerve endings, its ability to serve as a DAT blocker could provide protection against methamphetamine-induced neurotoxicity like other DAT inhibitors. To test this possibility, mice were treated with mephedrone (10, 20, or 40 mg/kg) prior to each injection of a neurotoxic regimen of methamphetamine (four injections of 2.5 or 5.0 mg/kg at 2 h intervals). The integrity of DA nerve endings of the striatum was assessed through measures of DA, DAT, and tyrosine hydroxylase levels. The moderate to severe DA toxicity associated with the different doses of methamphetamine was not prevented by any dose of mephedrone but was, in fact, significantly enhanced. The hyperthermia caused by combined treatment with mephedrone and methamphetamine was the same as seen after either drug alone. Mephedrone also enhanced the neurotoxic effects of amphetamine and 3,4-methylenedioxymethamphetamine on DA nerve endings. In contrast, nomifensine protected against methamphetamine-induced neurotoxicity. As mephedrone increases methamphetamine neurotoxicity, the present results suggest that it interacts with the DAT in a manner unlike that of other typical DAT inhibitors. The relatively innocuous effects of mephedrone alone on DA nerve endings mask a potentially dangerous interaction with drugs that are often co-abused with it, leading to heightened neurotoxicity. PMID:23205838

  2. Neurochemical characterization of the vestibular nerves in women with vulvar vestibulitis syndrome.

    PubMed

    Bohm-Starke, N; Hilliges, M; Falconer, C; Rylander, E

    1999-01-01

    Women with vulvar vestibulitis syndrome (VVS) have a distinct burning pain provoked by almost any stimuli in the area around the vaginal introitus. In a previous study we observed an increased number of intraepithelial free nerve endings in women with VVS. The aim of the present study was to neurochemically characterize the superficial nerves in the vulvar vestibular mucosa of women with VVS. Immunohistochemical methods were used to detect neuropeptides normally found in various types of nerve fibers. Calcitonin gene-related peptide, which is known to exist in nociceptive afferent nerves, was the only neuropeptide detected in the superficial nerves of the vestibular mucosa. These findings confirm our previous theory that the free nerve endings within the epithelium are nociceptors. PMID:10592432

  3. Neuroanatomical evidence for segregation of nerve fibers conveying light touch and pain sensation in Eimer's organ of the mole.

    PubMed

    Marasco, Paul D; Tsuruda, Pamela R; Bautista, Diana M; Julius, David; Catania, Kenneth C

    2006-06-13

    Talpid moles are small insectivores that live in dark underground tunnels. They depend heavily on touch to navigate and find food. Most species have an array of complex epidermal sensory structures called Eimer's organs that cover the tip of the nose. In this study, the anatomy of Eimer's organ was examined in the coast mole and star-nosed mole by using the fluorescent styryl pyridinium dye AM1-43 and immunocytochemical staining for neurofilament 200 and substance P. In addition, DiI was used to label neural components of Eimer's organ. AM1-43 labeled all of the Eimer's organ receptors after systemic injection, suggesting a role in mechanotransduction. Immunostaining with neurofilament 200 and substance P labeled distinct subtypes of sensory fibers. Substance P labeled a group of free nerve endings along the outer edge of Eimer's organ, indicating a nociceptive role for these fibers. In contrast, neurofilament 200 labeled a more central set of nerve endings, suggesting that these fibers function as low-threshold mechanoreceptors. By labeling subsets of trigeminal afferents distant from the receptor array with DiI, we revealed innervation patterns indicating that one afferent supplies the outer, substance P-positive set of free nerve endings, whereas several afferents differentially innervate the central free nerve endings. Our results suggest that the free nerve endings innervating Eimer's organ are largely mechanosensitive and may play an important role in the rapid sensory discrimination observed in these species. PMID:16751268

  4. Chicken (Gallus domesticus) inner ear afferents

    NASA Technical Reports Server (NTRS)

    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.

  5. ACTIVATION OF TRPA1 ON DURAL AFFERENTS: A POTENTIAL MECHANISM OF HEADACHE PAIN

    PubMed Central

    Edelmayer, Rebecca M.; Le, Larry N.; Yan, Jin; Wei, Xiaomei; Nassini, Romina; Materazzi, Serena; Preti, Delia; Appendino, Giovanni; Geppetti, Pierangelo; Dodick, David W.; Vanderah, Todd W.; Porreca, Frank; Dussor, Gregory

    2012-01-01

    Activation of transient receptor potential ankyrin-1 (TRPA1) on meningeal nerve endings has been suggested to contribute to environmental irritant-induced headache but this channel may also contribute to other forms of headache such as migraine. The preclinical studies described here examined functional expression of TRPA1 on dural afferents and investigated whether activation of TRPA1 contributes to headache-like behaviors. Whole-cell patch-clamp recordings were performed in vitro using two TRPA1 agonists, mustard oil (MO) and the environmental irritant umbellulone (UMB), on dural-projecting trigeminal ganglion neurons. Application of MO and UMB to dural afferents produced TRPA1-like currents in approximately 42% and 38% of cells, respectively. Using an established in vivo behavioral model of migraine-related allodynia, dural application of MO and UMB produced robust time-related tactile facial and hindpaw allodynia that was attenuated by pretreatment with the TRPA1 antagonist HC-030031. Additionally, MO or UMB were applied to the dura and exploratory activity was monitored for 30 minutes using an automated open-field activity chamber. Dural MO and UMB decreased the number of vertical rearing episodes and the time spent rearing in comparison to vehicle treated animals. This change in activity was prevented in rats pretreated with HC-030031 as well as sumatriptan, a clinically effective anti-migraine agent. These data indicate that TRPA1 is expressed on a substantial fraction of dural afferents and activation of meningeal TRPA1 produces behaviors consistent with those seen in patients during migraine attacks. Further, they suggest that activation of meningeal TRPA1 via endogenous or exogenous mechanisms can lead to afferent signaling and headache. PMID:22809691

  6. Differential central projections of vestibular afferents in pigeons

    NASA Technical Reports Server (NTRS)

    Dickman, J. D.; Fang, Q.

    1996-01-01

    The question of whether a differential distribution of vestibular afferent information to central nuclear neurons is present in pigeons was studied using neural tracer compounds. Discrete tracing of afferent fibers innervating the individual semicircular canal and otolith organs was produced by sectioning individual branches of the vestibular nerve that innervate the different receptor organs and applying crystals of horseradish peroxidase, or a horseradish peroxidase/cholera toxin mixture, or a biocytin compound for neuronal uptake and transport. Afferent fibers and their terminal distributions within the brainstem and cerebellum were visualized subsequently. Discrete areas in the pigeon central nervous system that receive primary vestibular input include the superior, dorsal lateral, ventral lateral, medial, descending, and tangential vestibular nuclei; the A and B groups; the intermediate, medial, and lateral cerebellar nuclei; and the nodulus, the uvula, and the paraflocculus. Generally, the vertical canal afferents projected heavily to medial regions in the superior and descending vestibular nuclei as well as the A group. Vertical canal projections to the medial and lateral vestibular nuclei were observed but were less prominent. Horizontal canal projections to the superior and descending vestibular nuclei were much more centrally located than those of the vertical canals. A more substantial projection to the medial and lateral vestibular nuclei was seen with horizontal canal afferents compared to vertical canal fibers. Afferents innervating the utricle and saccule terminated generally in the lateral regions of all vestibular nuclei in areas that were separate from the projections of the semicircular canals. In addition, utricular fibers projected to regions in the vestibular nuclei that overlapped with the horizontal semicircular canal terminal fields, whereas saccular afferents projected to regions that received vertical canal fiber terminations. Lagenar

  7. Effects of acid on vagal nociceptive afferent subtypes in guinea pig esophagus.

    PubMed

    Yu, Xiaoyun; Hu, Youtian; Yu, Shaoyong

    2014-08-15

    Acid reflux-induced heartburn and noncardiac chest pain are processed peripherally by sensory nerve endings in the wall of the esophagus, but the underlying mechanism is still unclear. This study aims to determine the effects of acid on esophageal vagal nociceptive afferent subtypes. Extracellular single-unit recordings were performed in guinea pig vagal nodose or jugular C fiber neurons by using ex vivo esophageal-vagal preparations with intact nerve endings in the esophagus. We recorded action potentials (AP) of esophageal nodose or jugular C fibers evoked by acid perfusion and compared esophageal distension-evoked AP before and after acid perfusion. Acid perfusion for 30 min (pH range 7.4 to 5.8) did not evoke AP in nodose C fibers but significantly decreased their responses to esophageal distension, which could be recovered after washing out acid for 90 min. In jugular C fibers, acid perfusion not only evoked AP but also inhibited their responses to esophageal distension, which were not recovered after washing out acid for 120 min. Lower concentration of capsaicin perfusion mimicked acid-induced effects in nodose and jugular C fibers. Pretreatment with TRPV1 antagonist AMG9810, but not acid-sensing ion channel (ASIC) inhibitor amiloride, significantly inhibited acid-induced effects in nodose and jugular C fiber. These results demonstrate that esophageal vagal nociceptive afferent nerve subtypes display distinctive responses to acid. Acid activates jugular, but not nodose, C fibers and inhibits both of their responses to esophageal distension. These effects are mediated mainly through TRPV1. This inhibitory effect is a novel finding and may contribute to esophageal sensory/motor dysfunction in acid reflux diseases. PMID:24994852

  8. Regeneration of respiratory pathways within spinal peripheral nerve grafts.

    PubMed

    Decherchi, P; Lammari-Barreault, N; Gauthier, P

    1996-01-01

    Central respiratory neurons exhibit normal activity after axonal regeneration within blind-ended peripheral nerve grafts (PNGs) inserted near the corresponding cell bodies in the medullary respiratory centers. Part of these medullary respiratory neurons project toward the spinal cord and contribute to descending respiratory pathways that control respiratory motoneurons. The present work investigates to what extent cervical respiratory pathways could be directed out of the central nervous system within PNGs inserted distant to the medullary respiratory nuclei. In adult rats (n = 13), autologous segments of the peroneal nerve were implanted into the ventrolateral part of the C2 spinal cord at the level of the descending respiratory pathways. Two to four months after grafting, electrophysiological recording of teased graft filaments (n = 562) revealed the presence of regenerated nerve fibers with unitary impulse traffic (n = 164) in all tested PNGs (n = 6). Respiratory discharges (n = 52) corresponded to efferent and afferent activity. Efferent respiratory discharges (n = 32) originated from central respiratory neurons which remained functional and preserved afferent connections. Retrograde horseradish peroxidase labeling applied to the distal cut end of PNGs (n = 7) revealed stained (42/1997) neurons in areas where respiratory cells have been described. Afferent respiratory discharges (n = 20) were synchronized with lung inflation but their origin (stretch pulmonary receptors and/or respiratory muscle receptors) was not determined. On the basis of additional data from light and electron microscopy of PNGs, comparison was made between anatomical, retrograde labeling, and electrophysiological data. The main conclusion is that spinal PNGs appear to be able to promote axonal regeneration of functional respiratory efferent and afferent pathways. PMID:8566201

  9. Human brain somatostatin release from isolated cortical nerve endings and its modulation through GABAB receptors.

    PubMed Central

    Bonanno, G.; Gemignani, A.; Schmid, G.; Severi, P.; Cavazzani, P.; Raiteri, M.

    1996-01-01

    1. The release of somatostatin-like immunoreactivity (SRIF-LI) in the human brain was studied in synaptosomal preparations from fresh neocortical specimens obtained from patients undergoing neurosurgery to remove deeply sited tumours. 2. The basal outflow of SRIF-LI from superfused synaptosomes was increased about 3 fold during exposure to a depolarizing medium containing 15 mM KCl. The K(+)-evoked overflow of SRIF-LI was almost totally dependent on the presence of Ca2+ in the superfusion medium. 3. The GABAB receptor agonist, (-)-baclofen (0.3 - 100 microM), inhibited the overflow of SRIF-LI in a concentration-dependent manner (EC50 = 1.84 +/- 0.20 microM; maximal effect: about 50%). The novel GABAB receptor ligand, 3-aminopropyl(difluoromethyl)phosphinic acid (CGP 47656) mimicked (-)-baclofen in inhibiting the SRIF-LI overflow (EC50 = 3.06 +/- 0.52 microM; maximal effect: about 50%), whereas the GABAA receptor agonist, muscimol, was ineffective up to 100 microM. 4. The inhibition by 10 microM (-)-baclofen of the K(+)-evoked SRIF-LI overflow was concentration-dependently prevented by two selective GABAB receptor antagonists, 3-amino-propyl (diethoxymethyl)-phosphinic acid (CGP 35348) (IC50 = 24.40 +/- 2.52 microM) and [3-[[(3,4-dichlorophenyl) methyl]amino]propyl] (diethoxymethyl) phosphinic acid (CGP 52432) (IC50 = 0.06 +/- 0.005 microM). 5. The inhibition of SRIF-LI overflow caused by 10 microM CGP 47656 was abolished by 1 microM CGP 52432. 6. When human synaptosomes were labelled with [3H]-GABA and depolarized in superfusion with 15 mM KCl, the inhibition by 10 microM (-)-baclofen of the depolarization-evoked [3H]-GABA overflow was largely prevented by 10 microM CGP 47656 which therefore behaved as an autoreceptor antagonist. 7. In conclusion: (a) the characteristics of SRIF-LI release from synaptosomal preparations of human neocortex are compatible with a neuronal origin; (b) the nerve terminals releasing the neuropeptide possess inhibitory receptors of the

  10. The regularity of primary and secondary muscle spindle afferent discharges

    PubMed Central

    Matthews, P. B. C.; Stein, R. B.

    1969-01-01

    1. The patterns of nerve impulses in the afferent fibres from muscle spindles have been studied using the soleus muscle of the decerebrate cat. Impulses from up to five single units were recorded simultaneously on magnetic tape, while the muscle was stretched to a series of different lengths. Various statistics were later determined by computer analysis. 2. After the ventral roots were cut to eliminate any motor outflow to the muscle spindles, both primary and secondary spindle endings discharged very regularly. At frequencies around 30 impulses/sec the coefficient of variation of the interspike interval distributions had a mean value of only 0·02 for the secondary endings and 0·058 for the primary endings. The values obtained for the two kinds of ending did not overlap. 3. When the ventral roots were intact, the `spontaneous' fusimotor activity considerably increased the variability of both kinds of endings. Secondary endings still discharged much more regularly than primary endings, even when the fusimotor activity increased the frequency of firing equally for the two kinds of endings. At frequencies around 30/sec the average coefficient of variation of the interval distributions was then 0·064 for the secondary endings and 0·25 for the primary endings. 4. When the ventral roots were intact there was usually an inverse relation between the values of successive interspike intervals. The first serial correlation coefficient often had values down to - 0·6 for both kinds of ending. Higher order serial correlation coefficients were also computed. 5. Approximate calculations, based on the variability observed when the ventral roots were intact, suggested that when the length of the muscle was constant an observer analysing a 1 sec period of discharge from a single primary ending would only be able to distinguish about six different lengths of the muscle. The corresponding figure for a secondary ending was twenty-five lengths. 6. The increase in variability with

  11. NERVE ENDINGS AND VASCULAR SUPPLY IN SEMITENDINOSUS TENDON OF CEREBRAL PALSY CHILDREN

    PubMed Central

    Grzegorzewski, Andrzej; Synder, Marek; Modrzewski, Tadeusz; Drobniewski, Marek; Polguj, Michał; Sibiński, Marcin

    2015-01-01

    ABSTRACT Objective: To evaluate the distribution of SP (substance P) and S-100 peptide immunoreactivity, as well as the vascular supply of tissues commonly used as grafts for anterior cruciate ligament (ACL) reconstruction. A second aim was to compare the above mentioned distribution in the semitendinosus muscle tendons of cerebral palsy (CP) patients with the semitendinosus muscle tendons and patellar tendons of patients without CP. Methods: The first group consisted of 14 children with cerebral palsy with a mean age of 11.7 years old. At the time of hamstring lengthening operation, a sample of semitendinosus muscle was taken for analysis. The second group comprised 20 patients treated for isolated ACL rupture of the knee (mean age 32 years old). Group three comprised ten patients in the mean age of 14.3 years old treated for recurrent lateral patellar dislocation, and from whom a sample of patellar tendon was obtained. Results: No statistically significant differences were demonstrated with regard to the amount of immunopositive nerve fibers expressing SP or S-100 in all 3 groups of patients. A significant difference was noted in the number of blood vessels between the adult and child semitendinosus muscles, but not between the semitendinosus muscles and patellar tendon of children. Conclusion: The number of nociceptors as well as proprioceptive fibers is similar in patients with CP and patients from a neurologically healthy population. Level of Evidence IV, Cases Series. PMID:26981034

  12. A comparative study of red and blue light-emitting diodes and low-level laser in regeneration of the transected sciatic nerve after an end to end neurorrhaphy in rabbits.

    PubMed

    Takhtfooladi, Mohammad Ashrafzadeh; Sharifi, Davood

    2015-12-01

    This study aimed at evaluating the effects of red and blue light-emitting diodes (LED) and low-level laser (LLL) on the regeneration of the transected sciatic nerve after an end-to-end neurorrhaphy in rabbits. Forty healthy mature male New Zealand rabbits were randomly assigned into four experimental groups: control, LLL (680 nm), red LED (650 nm), and blue LED (450 nm). All animals underwent the right sciatic nerve neurotmesis injury under general anesthesia and end-to-end anastomosis. The phototherapy was initiated on the first postoperative day and lasted for 14 consecutive days at the same time of the day. On the 30th day post-surgery, the animals whose sciatic nerves were harvested for histopathological analysis were euthanized. The nerves were analyzed and quantified the following findings: Schwann cells, large myelinic axons, and neurons. In the LLL group, as compared to other groups, an increase in the number of all analyzed aspects was observed with significance level (P < 0.05). This finding suggests that postoperative LLL irradiation was able to accelerate and potentialize the peripheral nerve regeneration process in rabbits within 14 days of irradiation. PMID:26415928

  13. Directional sound sensitivity in utricular afferents in the toadfish Opsanus tau.

    PubMed

    Maruska, Karen P; Mensinger, Allen F

    2015-06-01

    The inner ear of fishes contains three paired otolithic end organs, the saccule, lagena and utricle, which function as biological accelerometers. The saccule is the largest otolith in most fishes and much of our current understanding on auditory function in this diverse group of vertebrates is derived from anatomical and neurophysiological studies on this end organ. In contrast, less is known about how the utricle contributes to auditory functions. In this study, chronically implanted electrodes were used, along with neural telemetry or tethers to record primary afferent responses from the utricular nerve in free-ranging and naturally behaving oyster toadfish Opsanus tau Linnaeus. The hypothesis was that the utricle plays a role in detecting underwater sounds, including conspecific vocalizations, and exhibits directional sensitivity. Utricular afferents responded best to low frequency (80-200 Hz) pure tones and to playbacks of conspecific boatwhistles and grunts (80-180 Hz fundamental frequency), with the majority of the units (∼75%) displaying a clear, directional response, which may allow the utricle to contribute to sound detection and localization during social interactions. Responses were well within the sound intensity levels of toadfish vocalization (approximately 140 SPL dBrms re. 1 µPa with fibers sensitive to thresholds of approximately 120 SPL dBrms re. 1 µPa). Neurons were also stimulated by self-generated body movements such as opercular movements and swimming. This study is the first to investigate underwater sound-evoked response properties of primary afferents from the utricle of an unrestrained/unanesthetized free-swimming teleost fish. These data provide experimental evidence that the utricle has an auditory function, and can contribute to directional hearing to facilitate sound localization. PMID:25883378

  14. Integrated phrenic responses to carotid afferent stimulation in adult rats following perinatal hyperoxia.

    PubMed Central

    Ling, L; Olson, E B; Vidruk, E H; Mitchell, G S

    1997-01-01

    1. Hypoxic ventilatory responses are greatly attenuated in adult rats exposed to moderate hyperoxia (60% O2) during the first month of life (perinatal treated rats). The present study was designed to test the hypothesis that perinatal hyperoxia impairs central integration of carotid chemoreceptor afferent inputs, thereby diminishing the hypoxic ventilatory response. 2. Time-dependent phrenic nerve responses to electrical stimulation of the carotid sinus nerve (CSN) and steady-state relationships between CSN stimulation frequency and phrenic nerve output were compared in control and perinatal treated rats. The rats were urethane anaesthetized, vagotomized, paralysed and artificially ventilated. End-tidal CO2 was monitored and maintained at isocapnic levels; arterial blood gases were determined. 3. Two stimulation protocols were used: (1) three 2 min episodes of CSN stimulation (20 Hz, 0.2 ms duration, 3 x threshold), separated by 5 min intervals; and (2) nine 45 s episodes of CSN stimulation with stimulus frequencies ranging from 0.5 to 20 Hz (0.2 ms duration, 3 x threshold), separated by 4 min intervals. 4. The mean threshold currents to elicit phrenic responses were similar between groups. Burst frequency (f, burst min-1), peak amplitude of integrated phrenic activity (integral of Phr), and minute phrenic activity (integral of Phr x f) during and after CSN stimulation were not distinguishable between groups in either protocol at any time or at any stimulus intensity (P > 0.05). 5. Perinatal hyperoxia does not alter temporal or steady-state phrenic responses to CSN stimulation, suggesting that the central integration of carotid chemoreceptor afferent inputs is not impaired in perinatal treated rats. It is speculated that carotid chemoreceptors per se are impaired in perinatal treated rats. PMID:9161991

  15. Molecular microdomains in a sensory terminal, the vestibular calyx ending.

    PubMed

    Lysakowski, Anna; Gaboyard-Niay, Sophie; Calin-Jageman, Irina; Chatlani, Shilpa; Price, Steven D; Eatock, Ruth Anne

    2011-07-01

    Many primary vestibular afferents form large cup-shaped postsynaptic terminals (calyces) that envelope the basolateral surfaces of type I hair cells. The calyceal terminals both respond to glutamate released from ribbon synapses in the type I cells and initiate spikes that propagate to the afferent's central terminals in the brainstem. The combination of synaptic and spike initiation functions in these unique sensory endings distinguishes them from the axonal nodes of central neurons and peripheral nerves, such as the sciatic nerve, which have provided most of our information about nodal specializations. We show that rat vestibular calyces express an unusual mix of voltage-gated Na and K channels and scaffolding, cell adhesion, and extracellular matrix proteins, which may hold the ion channels in place. Protein expression patterns form several microdomains within the calyx membrane: a synaptic domain facing the hair cell, the heminode abutting the first myelinated internode, and one or two intermediate domains. Differences in the expression and localization of proteins between afferent types and zones may contribute to known variations in afferent physiology. PMID:21734302

  16. Localization of TRPV1 and P2X3 in unmyelinated and myelinated vagal afferents in the rat.

    PubMed

    Hermes, Sam M; Andresen, Michael C; Aicher, Sue A

    2016-03-01

    The vagus nerve is dominated by afferent fibers that convey sensory information from the viscera to the brain. Most vagal afferents are unmyelinated, slow-conducting C-fibers, while a smaller portion are myelinated, fast-conducting A-fibers. Vagal afferents terminate in the nucleus tractus solitarius (NTS) in the dorsal brainstem and regulate autonomic and respiratory reflexes, as well as ascending pathways throughout the brain. Vagal afferents form glutamatergic excitatory synapses with postsynaptic NTS neurons that are modulated by a variety of channels. The organization of vagal afferents with regard to fiber type and channels is not well understood. In the present study, we used tract tracing methods to identify distinct populations of vagal afferents to determine if key channels are selectively localized to specific groups of afferent fibers. Vagal afferents were labeled with isolectin B4 (IB4) or cholera toxin B (CTb) to detect unmyelinated and myelinated afferents, respectively. We find that TRPV1 channels are preferentially found in unmyelinated vagal afferents identified with IB4, with almost half of all IB4 fibers showing co-localization with TRPV1. These results agree with prior electrophysiological findings. In contrast, we found that the ATP-sensitive channel P2X3 is found in a subset of both myelinated and unmyelinated vagal afferent fibers. Specifically, 18% of IB4 and 23% of CTb afferents contained P2X3. The majority of CTb-ir vagal afferents contained neither channel. Since neither channel was found in all vagal afferents, there are likely further degrees of heterogeneity in the modulation of vagal afferent sensory input to the NTS beyond fiber type. PMID:26706222

  17. Identification of the tracheal and laryngeal afferent neurones mediating cough in anaesthetized guinea-pigs

    PubMed Central

    Canning, Brendan J; Mazzone, Stuart B; Meeker, Sonya N; Mori, Nanako; Reynolds, Sandra M; Undem, Bradley J

    2004-01-01

    We have identified the tracheal and laryngeal afferent nerves regulating cough in anaesthetized guinea-pigs. Cough was evoked by electrical or mechanical stimulation of the tracheal or laryngeal mucosa, or by citric acid applied topically to the trachea or larynx. By contrast, neither capsaicin nor bradykinin challenges to the trachea or larynx evoked cough. Bradykinin and histamine administered intravenously also failed to evoke cough. Electrophysiological studies revealed that the majority of capsaicin-sensitive afferent neurones (both Aδ- and C-fibres) innervating the rostral trachea and larynx have their cell bodies in the jugular ganglia and project to the airways via the superior laryngeal nerves. Capsaicin-insensitive afferent neurones with cell bodies in the nodose ganglia projected to the rostral trachea and larynx via the recurrent laryngeal nerves. Severing the recurrent nerves abolished coughing evoked from the trachea and larynx whereas severing the superior laryngeal nerves was without effect on coughing. The data indicate that the tracheal and laryngeal afferent neurones regulating cough are polymodal Aδ-fibres that arise from the nodose ganglia. These afferent neurones are activated by punctate mechanical stimulation and acid but are unresponsive to capsaicin, bradykinin, smooth muscle contraction, longitudinal or transverse stretching of the airways, or distension. Comparing these physiological properties with those of intrapulmonary mechanoreceptors indicates that the afferent neurones mediating cough are quite distinct from the well-defined rapidly and slowly adapting stretch receptors innervating the airways and lungs. We propose that these airway afferent neurones represent a distinct subtype and that their primary function is regulation of the cough reflex. PMID:15004208

  18. Adjunctive vagus nerve stimulation for treatment-resistant bipolar disorder: managing device failure or the end of battery life.

    PubMed

    Pardo, José V

    2016-01-01

    The vagus nerve stimulation (VNS) device is used not only to treat refractory seizure disorders but also mood disorders; the latter indication received CE Mark approval in 2001 and Food and Drug Administration approval in 2005. Original estimates for the end of battery life (EOBL) were approximately 6-10 years. Many neuropsychiatric patients have or will soon face EOBL. A patient with severe, life-threatening, treatment-resistant bipolar disorder underwent 9 years of stable remission following 20 months of adjunctive VNS. The device ceased operation at EOBL. Because of logistical issues, re-initiation of VNS was delayed over several months. The patient relapsed with depression, mania and mixed states, and regained remission 17 months after device replacement. This case dictates prudence in managing stable patients in remission with VNS. If the device malfunctions, urgent surgical replacement is warranted with subsequent rapid titration to previous parameters as tolerated. Several months' delay may trigger relapse and prove difficult to re-establish remission. PMID:26951440

  19. Effect of Microgravity on Afferent Innervation

    NASA Technical Reports Server (NTRS)

    1998-01-01

    Presentations and publications are: (1) an audiovisual summary web presentation on results from SLM-MIR avian experiments. A color presentation summarizing results from the SLM-MIR and STS-29 avian experiments; (2) color threshold and ratio of S 100B MAP5, NF68/200, GABA and GAD; (3) chicken (Gallus domesticus) inner ear afferents; (4) microgravity in the STS-29 Space Shuttle Discovery affected the vestibular system of chick embryos; (5) expression of S 100B in sensory and secretory cells of the vertebrate inner ear; (6) otoconia biogenesis, phylogeny, composition and functional attributes;(7) the glycan keratin sulfate in inner ear crystals; (8) elliptical-P cells in the avian perilymphatic interface of the tegmentum vasculosum; and (9) LAMP2c and S100B upregulation in brain stem after VIIIth nerve deafferentation.

  20. Neck muscle afferents influence oromotor and cardiorespiratory brainstem neural circuits.

    PubMed

    Edwards, I J; Lall, V K; Paton, J F; Yanagawa, Y; Szabo, G; Deuchars, S A; Deuchars, J

    2015-01-01

    Sensory information arising from the upper neck is important in the reflex control of posture and eye position. It has also been linked to the autonomic control of the cardiovascular and respiratory systems. Whiplash associated disorders (WAD) and cervical dystonia, which involve disturbance to the neck region, can often present with abnormalities to the oromotor, respiratory and cardiovascular systems. We investigated the potential neural pathways underlying such symptoms. Simulating neck afferent activity by electrical stimulation of the second cervical nerve in a working heart brainstem preparation (WHBP) altered the pattern of central respiratory drive and increased perfusion pressure. Tracing central targets of these sensory afferents revealed projections to the intermedius nucleus of the medulla (InM). These anterogradely labelled afferents co-localised with parvalbumin and vesicular glutamate transporter 1 indicating that they are proprioceptive. Anterograde tracing from the InM identified projections to brain regions involved in respiratory, cardiovascular, postural and oro-facial behaviours--the neighbouring hypoglossal nucleus, facial and motor trigeminal nuclei, parabrachial nuclei, rostral and caudal ventrolateral medulla and nucleus ambiguus. In brain slices, electrical stimulation of afferent fibre tracts lateral to the cuneate nucleus monosynaptically excited InM neurones. Direct stimulation of the InM in the WHBP mimicked the response of second cervical nerve stimulation. These results provide evidence of pathways linking upper cervical sensory afferents with CNS areas involved in autonomic and oromotor control, via the InM. Disruption of these neuronal pathways could, therefore, explain the dysphagic and cardiorespiratory abnormalities which may accompany cervical dystonia and WAD. PMID:24595534

  1. Possible role of afferent autonomic signals in abdominal organs in anorexic and cardiovascular responses to nicotine injection in rats.

    PubMed

    Yagi, Shintaro; Tanida, Mamoru; Satomi, Jun

    2015-05-27

    Smoking generally causes an increase in nicotine levels in the blood, affecting the brain components, such as the hypothalamus (feeding-related area) or the brain stem (cardiovascular control area). In terms of nicotine transmission to the brain, a new insight that the afferent vagal nerve in the liver is important for sensing increased nicotine levels in the blood and informing the brain was reported in an experiment with rats. However, it has not been clarified whether the afferent autonomic nerve system is implicated in feeding and cardiovascular responses to nicotine. Here, we examined the possible role of afferent autonomic nerve transmission in rats in regulating feeding behavior and cardiovascular functions by nicotine. An intravenous injection of nicotine dose dependently increased the blood pressure (BP) in urethane-anesthetized rats; high nicotine doses also led to an increase in BP in conscious rats. Further, an intravenous injection of nicotine for 3 days reduced food intake and body weight gain in rats. The weight-reducing action of intravenous nicotine was abolished by blocking the afferent sympathetic signals in the abdominal organs, but not the vagal nerve signals. Moreover, the hypertensive action of nicotine was not abolished either by afferent sympathectomy or by vagotomy. Thus, these data suggest that nicotine injected into the vein acts on the afferent sympathetic nerve in the abdominal organs and transmits signals to the brain for reducing body weight, but not for suppressing appetite or increasing BP. PMID:25875474

  2. Determinants of Spatial and Temporal Coding by Semicircular Canal Afferents

    PubMed Central

    Highstein, Stephen M.; Rabbitt, Richard D.; Holstein, Gay R.; Boyle, Richard D.

    2010-01-01

    The vestibular semicircular canals are internal sensors that signal the magnitude, direction, and temporal properties of angular head motion. Fluid mechanics within the 3-canal labyrinth code the direction of movement and integrate angular acceleration stimuli over time. Directional coding is accomplished by decomposition of complex angular accelerations into 3 biomechanical components—one component exciting each of the 3 ampullary organs and associated afferent nerve bundles separately. For low-frequency angular motion stimuli, fluid displacement within each canal is proportional to angular acceleration. At higher frequencies, above the lower corner frequency, real-time integration is accomplished by viscous forces arising from the movement of fluid within the slender lumen of each canal. This results in angular velocity sensitive fluid displacements. Reflecting this, a subset of afferent fibers indeed report angular acceleration to the brain for low frequencies of head movement and report angular velocity for higher frequencies. However, a substantial number of afferent fibers also report angular acceleration, or a signal between acceleration and velocity, even at frequencies where the endolymph displacement is known to follow angular head velocity. These non-velocity-sensitive afferent signals cannot be attributed to canal biomechanics alone. The responses of non-velocity-sensitive cells include a mathematical differentiation (first-order or fractional) imparted by hair-cell and/or afferent complexes. This mathematical differentiation from velocity to acceleration cannot be attributed to hair cell ionic currents, but occurs as a result of the dynamics of synaptic transmission between hair cells and their primary afferent fibers. The evidence for this conclusion is reviewed below. PMID:15845995

  3. A novel role for TRPM8 in visceral afferent function.

    PubMed

    Harrington, Andrea M; Hughes, Patrick A; Martin, Christopher M; Yang, Jing; Castro, Joel; Isaacs, Nicole J; Blackshaw, L Ashley; Brierley, Stuart M

    2011-07-01

    Transient receptor potential ion channel melastatin subtype 8 (TRPM8) is activated by cold temperatures and cooling agents, such as menthol and icilin. Compounds containing peppermint are reported to reduce symptoms of bowel hypersensitivity; however, the underlying mechanisms of action are unclear. Here we determined the role of TRPM8 in colonic sensory pathways. Laser capture microdissection, quantitative reverse transcription-polymerase chain reaction (RT-PCR), immunofluorescence, and retrograde tracing were used to localise TRPM8 to colonic primary afferent neurons. In vitro extracellular single-fibre afferent recordings were used to determine the effect of TRPM8 channel activation on the chemosensory and mechanosensory function of colonic high-threshold afferent fibres. TRPM8 mRNA was present in colonic DRG neurons, whereas TRPM8 protein was present on nerve fibres throughout the wall of the colon. A subpopulation (24%, n=58) of splanchnic serosal and mesenteric afferents tested responded directly to icilin (5 μmol/L). Subsequently, icilin significantly desensitised afferents to mechanical stimulation (P<.0001; n=37). Of the splanchnic afferents responding to icilin, 21 (33%) also responded directly to the TRPV1 agonist capsaicin (3 μmol/L), and icilin reduced the direct chemosensory response to capsaicin. Icilin also prevented mechanosensory desensitization and sensitization induced by capsaicin and the TRPA1 agonist AITC (40 μmol/L), respectively. TRPM8 is present on a select population of colonic high threshold sensory neurons, which may also co-express TRPV1. TRPM8 couples to TRPV1 and TRPA1 to inhibit their downstream chemosensory and mechanosensory actions. PMID:21489690

  4. Enhanced sympathetic activity and cardiac sympathetic afferent reflex in rats with heart failure induced by adriamycin.

    PubMed

    Zhang, Shujuan; Zhang, Feng; Sun, Haijian; Zhou, Yebo; Han, Ying

    2012-11-01

    Our previous studies have shown that the cardiac sympathetic afferent reflex is enhanced in rats with chronic heart failure (CHF) induced by coronary artery ligation and contributes to the over-excitation of sympathetic activity. We sought to determine whether sympathetic activity and cardiac sympathetic afferent reflex were enhanced in adriamycin-induced CHF and whether angiotensin II (Ang II) in the paraventricular nucleus (PVN) was involved in enhancing sympathetic activity and cardiac sympathetic afferent reflex. Heart failure was induced by intraperitoneal injection of adriamycin for six times during 2 weeks (15 mg/kg). Six weeks after the first injection, the rats underwent anesthesia with urethane and α-chloralose. After vagotomy and baroreceptor denervation, cardiac sympathetic afferent reflex was evaluated by renal sympathetic nerve activity and mean arterial pressure (MAP) response to epicardial application of capsaicin (1.0 nmol). The response of MAP to ganglionic blockade with hexamethonium in conscious rats was performed to evaluate sympathetic activity. The renal sympathetic nerve activity and cardiac sympathetic afferent reflex were enhanced in adriamycin rats and the maximum depressor response of MAP induced by hexamethonium was significantly greater in adriamycin rats than that in control rats. Bilateral PVN microinjection of angiotensin II (Ang II) caused larger responses of the cardiac sympathetic afferent reflex, baseline renal sympathetic nerve activity and MAP in adriamycin rats than control rats. These results indicated that both sympathetic activity and cardiac sympathetic afferent reflex were enhanced and Ang II in the PVN was involved in the enhanced sympathetic activity and cardiac sympathetic afferent reflex in rats with adriamycin-induced heart failure. PMID:23554781

  5. Enhanced sympathetic activity and cardiac sympathetic afferent reflex in rats with heart failure induced by adriamycin

    PubMed Central

    Zhang, Shujuan; Zhang, Feng; Sun, Haijian; Zhou, Yebo; Han, Ying

    2012-01-01

    Our previous studies have shown that the cardiac sympathetic afferent reflex is enhanced in rats with chronic heart failure (CHF) induced by coronary artery ligation and contributes to the over-excitation of sympathetic activity. We sought to determine whether sympathetic activity and cardiac sympathetic afferent reflex were enhanced in adriamycin-induced CHF and whether angiotensin II (Ang II) in the paraventricular nucleus (PVN) was involved in enhancing sympathetic activity and cardiac sympathetic afferent reflex. Heart failure was induced by intraperitoneal injection of adriamycin for six times during 2 weeks (15 mg/kg). Six weeks after the first injection, the rats underwent anesthesia with urethane and α-chloralose. After vagotomy and baroreceptor denervation, cardiac sympathetic afferent reflex was evaluated by renal sympathetic nerve activity and mean arterial pressure (MAP) response to epicardial application of capsaicin (1.0 nmol). The response of MAP to ganglionic blockade with hexamethonium in conscious rats was performed to evaluate sympathetic activity. The renal sympathetic nerve activity and cardiac sympathetic afferent reflex were enhanced in adriamycin rats and the maximum depressor response of MAP induced by hexamethonium was significantly greater in adriamycin rats than that in control rats. Bilateral PVN microinjection of angiotensin II (Ang II) caused larger responses of the cardiac sympathetic afferent reflex, baseline renal sympathetic nerve activity and MAP in adriamycin rats than control rats. These results indicated that both sympathetic activity and cardiac sympathetic afferent reflex were enhanced and Ang II in the PVN was involved in the enhanced sympathetic activity and cardiac sympathetic afferent reflex in rats with adriamycin-induced heart failure. PMID:23554781

  6. Allergen challenge sensitizes TRPA1 in vagal sensory neurons and afferent C-fiber subtypes in guinea pig esophagus.

    PubMed

    Liu, Zhenyu; Hu, Youtian; Yu, Xiaoyun; Xi, Jiefeng; Fan, Xiaoming; Tse, Chung-Ming; Myers, Allen C; Pasricha, Pankaj J; Li, Xingde; Yu, Shaoyong

    2015-03-15

    Transient receptor potential A1 (TRPA1) is a newly defined cationic ion channel, which selectively expresses in primary sensory afferent nerve, and is essential in mediating inflammatory nociception. Our previous study demonstrated that TRPA1 plays an important role in tissue mast cell activation-induced increase in the excitability of esophageal vagal nodose C fibers. The present study aims to determine whether prolonged antigen exposure in vivo sensitizes TRPA1 in a guinea pig model of eosinophilic esophagitis (EoE). Antigen challenge-induced responses in esophageal mucosa were first assessed by histological stains and Ussing chamber studies. TRPA1 function in vagal sensory neurons was then studied by calcium imaging and by whole cell patch-clamp recordings in 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate (DiI)-labeled esophageal vagal nodose and jugular neurons. Extracellular single-unit recordings were performed in vagal nodose and jugular C-fiber neuron subtypes using ex vivo esophageal-vagal preparations with intact nerve endings in the esophagus. Antigen challenge significantly increased infiltrations of eosinophils and mast cells in the esophagus. TRPA1 agonist allyl isothiocyanate (AITC)-induced calcium influx in nodose and jugular neurons was significantly increased, and current densities in esophageal DiI-labeled nodose and jugular neurons were also significantly increased in antigen-challenged animals. Prolonged antigen challenge decreased esophageal epithelial barrier resistance, which allowed intraesophageal-infused AITC-activating nodose and jugular C fibers at their nerve endings. Collectively, these results demonstrated that prolonged antigen challenge sensitized TRPA1 in esophageal sensory neurons and afferent C fibers. This novel finding will help us to better understand the molecular mechanism underlying esophageal sensory and motor dysfunctions in EoE. PMID:25591867

  7. Directional sensitivity of human periodontal mechanoreceptive afferents to forces applied to the teeth.

    PubMed Central

    Trulsson, M; Johansson, R S; Olsson, K A

    1992-01-01

    1. Single-unit impulse activity from thirty-eight mechanoreceptive afferent fibres was recorded in the human inferior alveolar nerve using tungsten microelectrodes. All afferents responded to mechanical stimulation of the teeth and most likely supplied periodontal mechanoreceptors. 2. All afferents showed their highest sensitivity to forces applied to a particular tooth (the lower incisors, the canine or the first premolar). Forces with 'ramp-and-hold' shaped profiles of similar magnitudes were applied to that tooth in the following six directions: lingual, labial, mesial and distal in the horizontal plane, and up and down in the axial direction of the tooth. Both static and dynamic response components were analysed. 3. All afferents were 'slowly adapting' since they discharged continuously in response to static forces in at least one stimulation direction. Twenty-five afferents (66%) were spontaneously active in the sense that they showed an on-going discharge in the absence of external stimulation. 4. Diverse receptive fields were observed. Most afferents (74%) responded to static forces in two or three of the four horizontal directions. Likewise, all units showed excitatory responses to axial loading with a majority (74%) responding in one of the two axial directions and the remainder in both axial directions. Spontaneously active afferents generally decreased their discharge rate when stimulated in directions opposite to the directions exciting the afferent. With regard to population responses, approximately half of the afferents showed excitatory responses to each stimulus direction except for downwards, in which 86% responded. 5. Twenty-three afferents (61%) exhibited the strongest response to forces in one of the horizontal directions. Of those, a majority were most responsive to the lingual direction (52%) and some to the labial direction (30%). Accordingly, the discharge rates during force application averaged over the whole afferent sample were highest in

  8. Can loss of muscle spindle afferents explain the ataxic gait in Riley–Day syndrome?

    PubMed Central

    Norcliffe-Kaufmann, Lucy; Gutiérrez, Joel; Axelrod, Felicia B.; Kaufmann, Horacio

    2011-01-01

    The Riley–Day syndrome is the most common of the hereditary sensory and autonomic neuropathies (Type III). Among the well-recognized clinical features are reduced pain and temperature sensation, absent deep tendon reflexes and a progressively ataxic gait. To explain the latter we tested the hypothesis that muscle spindles, or their afferents, are absent in hereditary sensory and autonomic neuropathy III by attempting to record from muscle spindle afferents from a nerve supplying the leg in 10 patients. For comparison we also recorded muscle spindles from 15 healthy subjects and from two patients with hereditary sensory and autonomic neuropathy IV, who have profound sensory disturbances but no ataxia. Tungsten microelectrodes were inserted percutaneously into fascicles of the common peroneal nerve at the fibular head. Intraneural stimulation within muscle fascicles evoked twitches at normal stimulus currents (10–30 µA), and deep pain (which often referred) at high intensities (1 mA). Microneurographic recordings from muscle fascicles revealed a complete absence of spontaneously active muscle spindles in patients with hereditary sensory and autonomic neuropathy III; moreover, responses to passive muscle stretch could not be observed. Conversely, muscle spindles appeared normal in patients with hereditary sensory and autonomic neuropathy IV, with mean firing rates of spontaneously active endings being similar to those recorded from healthy controls. Intraneural stimulation within cutaneous fascicles evoked paraesthesiae in the fascicular innervation territory at normal stimulus intensities, but cutaneous pain was never reported during high-intensity stimulation in any of the patients. Microneurographic recordings from cutaneous fascicles revealed the presence of normal large-diameter cutaneous mechanoreceptors in hereditary sensory and autonomic neuropathy III. Our results suggest that the complete absence of functional muscle spindles in these patients explains

  9. 3,4-Methylenedioxypyrovalerone prevents while methylone enhances methamphetamine-induced damage to dopamine nerve endings: β-ketoamphetamine modulation of neurotoxicity by the dopamine transporter

    PubMed Central

    Anneken, John H.; Angoa-Pérez, Mariana; Kuhn, Donald M.

    2016-01-01

    Methylone, 3,4-methylenedioxypyrovalerone (MDPV), and mephedrone are psychoactive ingredients of ‘bath salts’ and their abuse represents a growing public health care concern. These drugs are cathinone derivatives and are classified chemically as β-ketoamphetamines. Because of their close structural similarity to the amphetamines, methylone, MDPV, and mephedrone share most of their pharmacological, neurochemical, and behavioral properties. One point of divergence in their actions is the ability to cause damage to the CNS. Unlike methamphetamine, the β-ketoamphetamines do not damage dopamine (DA) nerve endings. However, mephedrone has been shown to significantly accentuate methamphetamine neurotoxicity. Bath salt formulations contain numerous different psychoactive ingredients, and individuals who abuse bath salts also coabuse other illicit drugs. Therefore, we have evaluated the effects of methylone, MDPV, mephedrone, and methamphetamine on DA nerve endings. The β-ketoamphetamines alone or in all possible two-drug combinations do not result in damage to DA nerve endings but do cause hyperthermia. MDPV completely protects against the neurotoxic effects of methamphetamine while methylone accentuates it. Neither MDPV nor methylone attenuates the hyperthermic effects of methamphetamine. The potent neuroprotective effects of MDPV extend to amphetamine-, 3,4-methylenedioxymethamphetamine-, and MPTP-induced neurotoxicity. These results indicate that β-ketoamphetamine drugs that are non-substrate blockers of the DA transporter (i.e., MDPV) protect against methamphetamine neurotoxicity, whereas those that are substrates for uptake by the DA transporter and which cause DA release (i.e., methylone, mephedrone) accentuate neurotoxicity. PMID:25626880

  10. Loss of Aβ-nerve endings associated with the Merkel cell-neurite complex in the lesional oral mucosa epithelium of lichen planus and hyperkeratosis

    PubMed Central

    Carrión, Daniela Calderón; Korkmaz, Yüksel; Cho, Britta; Kopp, Marion; Bloch, Wilhelm; Addicks, Klaus; Niedermeier, Wilhelm

    2016-01-01

    The Merkel cell-neurite complex initiates the perception of touch and mediates Aβ slowly adapting type I responses. Lichen planus is a chronic inflammatory autoimmune disease with T-cell-mediated inflammation, whereas hyperkeratosis is characterized with or without epithelial dysplasia in the oral mucosa. To determine the effects of lichen planus and hyperkeratosis on the Merkel cell-neurite complex, healthy oral mucosal epithelium and lesional oral mucosal epithelium of lichen planus and hyperkeratosis patients were stained by immunohistochemistry (the avidin-biotin-peroxidase complex and double immunofluorescence methods) using pan cytokeratin, cytokeratin 20 (K20, a Merkel cell marker), and neurofilament 200 (NF200, a myelinated Aβ- and Aδ-nerve fibre marker) antibodies. NF200-immunoreactive (ir) nerve fibres in healthy tissues and in the lesional oral mucosa epithelium of lichen planus and hyperkeratosis were counted and statistically analysed. In the healthy oral mucosa, K20-positive Merkel cells with and without close association to the intraepithelial NF200-ir nerve fibres were detected. In the lesional oral mucosa of lichen planus and hyperkeratosis patients, extremely rare NF200-ir nerve fibres were detected only in the lamina propria. Compared with healthy tissues, lichen planus and hyperkeratosis tissues had significantly decreased numbers of NF200-ir nerve fibres in the oral mucosal epithelium. Lichen planus and hyperkeratosis were associated with the absence of Aβ-nerve endings in the oral mucosal epithelium. Thus, we conclude that mechanosensation mediated by the Merkel cell-neurite complex in the oral mucosal epithelium is impaired in lichen planus and hyperkeratosis. PMID:27025263

  11. Transfer characteristics of the hair cell's afferent synapse

    NASA Astrophysics Data System (ADS)

    Keen, Erica C.; Hudspeth, A. J.

    2006-04-01

    The sense of hearing depends on fast, finely graded neurotransmission at the ribbon synapses connecting hair cells to afferent nerve fibers. The processing that occurs at this first chemical synapse in the auditory pathway determines the quality and extent of the information conveyed to the central nervous system. Knowledge of the synapse's input-output function is therefore essential for understanding how auditory stimuli are encoded. To investigate the transfer function at the hair cell's synapse, we developed a preparation of the bullfrog's amphibian papilla. In the portion of this receptor organ representing stimuli of 400-800 Hz, each afferent nerve fiber forms several synaptic terminals onto one to three hair cells. By performing simultaneous voltage-clamp recordings from presynaptic hair cells and postsynaptic afferent fibers, we established that the rate of evoked vesicle release, as determined from the average postsynaptic current, depends linearly on the amplitude of the presynaptic Ca2+ current. This result implies that, for receptor potentials in the physiological range, the hair cell's synapse transmits information with high fidelity. auditory system | exocytosis | glutamate | ribbon synapse | synaptic vesicle

  12. Morphologic Characterization of Nerves in Whole-Mount Airway Biopsies

    PubMed Central

    Canning, Brendan J.; Merlo-Pich, Emilio; Woodcock, Ashley A.; Smith, Jaclyn A.

    2015-01-01

    Rationale: Neuroplasticity of bronchopulmonary afferent neurons that respond to mechanical and chemical stimuli may sensitize the cough reflex. Afferent drive in cough is carried by the vagus nerve, and vagal afferent nerve terminals have been well defined in animals. Yet, both unmyelinated C fibers and particularly the morphologically distinct, myelinated, nodose-derived mechanoreceptors described in animals are poorly characterized in humans. To date there are no distinctive molecular markers or detailed morphologies available for human bronchopulmonary afferent nerves. Objectives: Morphologic and neuromolecular characterization of the afferent nerves that are potentially involved in cough in humans. Methods: A whole-mount immunofluorescence approach, rarely used in human lung tissue, was used with antibodies specific to protein gene product 9.5 (PGP9.5) and, for the first time in human lung tissue, 200-kD neurofilament subunit. Measurements and Main Results: We have developed a robust technique to visualize fibers consistent with autonomic and C fibers and pulmonary neuroendocrine cells. A group of morphologically distinct, 200-kD neurofilament-immunopositive myelinated afferent fibers, a subpopulation of which did not express PGP9.5, was also identified. Conclusions: PGP9.5-immunonegative nerves are strikingly similar to myelinated airway afferents, the cough receptor, and smooth muscle–associated airway receptors described in rodents. These have never been described in humans. Full description of human airway nerves is critical to the translation of animal studies to the clinical setting. PMID:25906337

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

    NASA Technical Reports Server (NTRS)

    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

  14. Characteristic intraepidermal nerve fibre endings of the intervibrissal fur in the mystacial pad of the rat: morphological details revealed by intravital methylene blue staining and the zinc iodide-osmium tetroxide technique

    PubMed Central

    MÜLLER, T.

    1999-01-01

    Light microscopic observations employing intravital methylene blue staining and impregnation by the zinc iodide-osmium tetroxide technique are presented for intraepidermal nerve fibre endings of the intervibrissal fur in the mystacial pad of the rat snout. Both procedures revealed anatomical details of the intraepidermal nerve fibre plexus in epidermal hillocks often located very close to the mouths of hairs. These nerve fibres appeared to resemble those described in previous immunohistochemical studies as cluster or bush endings. The methylene blue preparations demonstrated the existence of an intensely stained enlargement at the site of the branching point of the nerve fibres which seemed to be functionally related to the development of such nerve fibre plexuses. Due to their close association with hairs, these nerve fibre plexuses are most likely to be mechanoreceptive. Additionally, solitary varicose nerve fibres were found loosely distributed within the epidermis. The visualisation of 2 different morphological types of nerve fibre endings extends the validity of the concept of punctate sensibility into the epidermis. Methylene blue staining appeared to be somewhat superior to the zinc iodide-osmium tetroxide technique. Due to their selectivity for intraepidermal nerve fibres, the methods applied here supplement immunohistochemical procedures in a helpful manner. PMID:10473302

  15. Perceptual responses to microstimulation of single afferents innervating joints, muscles and skin of the human hand.

    PubMed Central

    Macefield, G; Gandevia, S C; Burke, D

    1990-01-01

    1. Microneurographic techniques were used to isolate single afferent axons within cutaneous and motor fascicles of the median and ulnar nerves at the wrist in thirteen subjects. Of the sixty-five identified afferents, eleven innervated the interphalangeal and metacarpophalangeal joints, sixteen innervated muscle spindles, three innervated Golgi tendon organs and thirty-five supplied the glabrous skin of the hand. 2. Intrafascicular stimulation through the recording microelectrode, using trains of constant-voltage positive pulses (0.3-0.8 V, 0.1-0.2 ms, 1-100 Hz) or constant-current biphasic pulses (0.4-13.0 microA, 0.2 ms, 1-100 Hz), evoked specific sensations from sites associated with some afferent species but not others. 3. Microstimulation of eight of the eleven joint afferent sites (73%) evoked specific sensations. With four, subjects reported innocuous deep sensations referred to the relevant joint. With the other four, the subjects reported a sensation of joint displacement that partially reflected the responsiveness of the afferents to joint rotation. 4. Microstimulation of fourteen of the sixteen muscle spindle afferent sites (88%) generated no perceptions when the stimuli did not produce overt movement. However, subjects could correctly detect the slight movements generated when the stimuli excited the motor axons to the parent muscle. 5. With seven of the nine rapidly adapting (type RA or FAI) cutaneous afferents (88%) microstimulation evoked sensations of 'flutter-vibration', and with two of eight slowly adapting (type SAI) afferents (25%) it evoked sensations of 'sustained pressure'. Of the eighteen SAII afferents, which were classified as such by their responses to planar skin stretch, the majority (83%) generated no perceptions, confirming previous work, but three evoked sensations of movements or pressure. 6. The present results suggest a relatively secure transmission of joint afferent traffic to perceptual levels, and it is concluded that the

  16. Epineurial Window Is More Efficient in Attracting Axons than Simple Coaptation in a Sutureless (Cyanoacrylate-Bound) Model of End-to-Side Nerve Repair in the Rat Upper Limb: Functional and Morphometric Evidences and Review of the Literature

    PubMed Central

    Papalia, Igor; Magaudda, Ludovico; Righi, Maria; Ronchi, Giulia; Viano, Nicoletta; Geuna, Stefano; Colonna, Michele Rosario

    2016-01-01

    End-to-side nerve coaptation brings regenerating axons from the donor to the recipient nerve. Several techniques have been used to perform coaptation: microsurgical sutures with and without opening a window into the epi(peri)neurial connective tissue; among these, window techniques have been proven more effective in inducing axonal regeneration. The authors developed a sutureless model of end-to-side coaptation in the rat upper limb. In 19 adult Wistar rats, the median and the ulnar nerves of the left arm were approached from the axillary region, the median nerve transected and the proximal stump sutured to the pectoral muscle to prevent regeneration. Animals were then randomly divided in two experimental groups (7 animals each, 5 animals acting as control): Group 1: the distal stump of the transected median nerve was fixed to the ulnar nerve by applying cyanoacrylate solution; Group 2: a small epineurial window was opened into the epineurium of the ulnar nerve, caring to avoid damage to the nerve fibres; the distal stump of the transected median nerve was then fixed to the ulnar nerve by applying cyanoacrylate solution. The grasping test for functional evaluation was repeated every 10–11 weeks starting from week-15, up to the sacrifice (week 36). At week 36, the animals were sacrificed and the regenerated nerves harvested and processed for morphological investigations (high-resolution light microscopy as well as stereological and morphometrical analysis). This study shows that a) cyanoacrylate in end-to-side coaptation produces scarless axon regeneration without toxic effects; b) axonal regeneration and myelination occur even without opening an epineurial window, but c) the window is related to a larger number of regenerating fibres, especially myelinated and mature, and better functional outcomes. PMID:26872263

  17. Epineurial Window Is More Efficient in Attracting Axons than Simple Coaptation in a Sutureless (Cyanoacrylate-Bound) Model of End-to-Side Nerve Repair in the Rat Upper Limb: Functional and Morphometric Evidences and Review of the Literature.

    PubMed

    Papalia, Igor; Magaudda, Ludovico; Righi, Maria; Ronchi, Giulia; Viano, Nicoletta; Geuna, Stefano; Colonna, Michele Rosario

    2016-01-01

    End-to-side nerve coaptation brings regenerating axons from the donor to the recipient nerve. Several techniques have been used to perform coaptation: microsurgical sutures with and without opening a window into the epi(peri)neurial connective tissue; among these, window techniques have been proven more effective in inducing axonal regeneration. The authors developed a sutureless model of end-to-side coaptation in the rat upper limb. In 19 adult Wistar rats, the median and the ulnar nerves of the left arm were approached from the axillary region, the median nerve transected and the proximal stump sutured to the pectoral muscle to prevent regeneration. Animals were then randomly divided in two experimental groups (7 animals each, 5 animals acting as control): Group 1: the distal stump of the transected median nerve was fixed to the ulnar nerve by applying cyanoacrylate solution; Group 2: a small epineurial window was opened into the epineurium of the ulnar nerve, caring to avoid damage to the nerve fibres; the distal stump of the transected median nerve was then fixed to the ulnar nerve by applying cyanoacrylate solution. The grasping test for functional evaluation was repeated every 10-11 weeks starting from week-15, up to the sacrifice (week 36). At week 36, the animals were sacrificed and the regenerated nerves harvested and processed for morphological investigations (high-resolution light microscopy as well as stereological and morphometrical analysis). This study shows that a) cyanoacrylate in end-to-side coaptation produces scarless axon regeneration without toxic effects; b) axonal regeneration and myelination occur even without opening an epineurial window, but c) the window is related to a larger number of regenerating fibres, especially myelinated and mature, and better functional outcomes. PMID:26872263

  18. Changes in monkey horizontal semicircular canal afferent responses after spaceflight

    NASA Technical Reports Server (NTRS)

    Correia, M. J.; Perachio, A. A.; Dickman, J. D.; Kozlovskaia, I. B.; Sirota, M. G.; Iakushin, S. B.; Beloozerova, I. N.

    1992-01-01

    Extracellular responses from single horizontal semicircular canal afferents in two rhesus monkeys were studied after recovery from a 14-day biosatellite (Cosmos 2044) orbital spaceflight. On the 1st postflight day, the mean gain for 9 different horizontal canal afferents, tested using one or several different passive yaw rotation waveforms, was nearly twice that for 20 horizontal canal afferents similarly tested during preflight and postflight control studies. Adaptation of the afferent response to passive yaw rotation on the 1st postflight day was also greater. These results suggest that at least one component of the vestibular end organ (the semicircular canals) is transiently modified after exposure to 14 days of microgravity. It is unclear whether the changes are secondary to other effects of microgravity, such as calcium loss, or an adaptive response. If the response is adaptive, then this report is the first evidence that the response of the vestibular end organ may be modified (presumably by the central nervous system via efferent connections) after prolonged unusual vestibular stimulation. If this is the case, the sites of plasticity of vestibular responses may not be exclusively within central nervous system vestibular structures, as previously believed.

  19. 3,4-Methylenedioxypyrovalerone prevents while methylone enhances methamphetamine-induced damage to dopamine nerve endings: β-ketoamphetamine modulation of neurotoxicity by the dopamine transporter.

    PubMed

    Anneken, John H; Angoa-Pérez, Mariana; Kuhn, Donald M

    2015-04-01

    Methylone, 3,4-methylenedioxypyrovalerone (MDPV), and mephedrone are psychoactive ingredients of 'bath salts' and their abuse represents a growing public health care concern. These drugs are cathinone derivatives and are classified chemically as β-ketoamphetamines. Because of their close structural similarity to the amphetamines, methylone, MDPV, and mephedrone share most of their pharmacological, neurochemical, and behavioral properties. One point of divergence in their actions is the ability to cause damage to the CNS. Unlike methamphetamine, the β-ketoamphetamines do not damage dopamine (DA) nerve endings. However, mephedrone has been shown to significantly accentuate methamphetamine neurotoxicity. Bath salt formulations contain numerous different psychoactive ingredients, and individuals who abuse bath salts also coabuse other illicit drugs. Therefore, we have evaluated the effects of methylone, MDPV, mephedrone, and methamphetamine on DA nerve endings. The β-ketoamphetamines alone or in all possible two-drug combinations do not result in damage to DA nerve endings but do cause hyperthermia. MDPV completely protects against the neurotoxic effects of methamphetamine while methylone accentuates it. Neither MDPV nor methylone attenuates the hyperthermic effects of methamphetamine. The potent neuroprotective effects of MDPV extend to amphetamine-, 3,4-methylenedioxymethamphetamine-, and MPTP-induced neurotoxicity. These results indicate that β-ketoamphetamine drugs that are non-substrate blockers of the DA transporter (i.e., MDPV) protect against methamphetamine neurotoxicity, whereas those that are substrates for uptake by the DA transporter and which cause DA release (i.e., methylone, mephedrone) accentuate neurotoxicity. METH (a) enters DA nerve endings via the DAT, causes leakage of DA into the cytoplasm and then into the synapse via DAT-mediated reverse transport. Methylone (METHY) and mephedrone (MEPH; b), like METH, are substrates for the DAT but release

  20. Vagal afferents, diaphragm fatigue, and inspiratory resistance in anesthetized dogs.

    PubMed

    Adams, J M; Farkas, G A; Rochester, D F

    1988-06-01

    This study tests three hypotheses regarding mechanisms that produce rapid shallow breathing during a severe inspiratory resistive load (IRL): 1) an intact vagal afferent pathway is necessary; 2) diaphragm fatigue contributes to tachypnea; and 3) hypoxia may alter the pattern of respiration. We imposed a severe IRL on pentobarbital sodium-anesthetized dogs, followed by bilateral vagotomy, then by supplemental O2. IRL alone produced rapid shallow breathing associated with hypercapnia and hypoxia. After the vagotomy, the breathing pattern became slow and deep, restoring arterial PCO2 but not arterial PO2 toward the control values. Relief of hypoxia had no effect, and at no time was there any evidence of fatigue of the diaphragm as measured by the response to phrenic nerve stimulation. We conclude that an intact afferent vagal pathway is necessary for the tachypnea resulting from a severe IRL, neither hypoxia nor diaphragm fatigue played a role, and, although we cannot rule out stimulation of vagal afferents, the simplest explanation for the increased frequency in our experiments is increased respiratory drive due to hypercapnia. PMID:3136122

  1. Utricular afferents: morphology of peripheral terminals

    PubMed Central

    Huwe, J. A.; Logan, G. J.; Williams, B.; Rowe, M. H.

    2015-01-01

    The utricle provides critical information about spatiotemporal properties of head movement. It comprises multiple subdivisions whose functional roles are poorly understood. We previously identified four subdivisions in turtle utricle, based on hair bundle structure and mechanics, otoconial membrane structure and hair bundle coupling, and immunoreactivity to calcium-binding proteins. Here we ask whether these macular subdivisions are innervated by distinctive populations of afferents to help us understand the role each subdivision plays in signaling head movements. We quantified the morphology of 173 afferents and identified six afferent classes, which differ in structure and macular locus. Calyceal and dimorphic afferents innervate one striolar band. Bouton afferents innervate a second striolar band; they have elongated terminals and the thickest processes and axons of all bouton units. Bouton afferents in lateral (LES) and medial (MES) extrastriolae have small-diameter axons but differ in collecting area, bouton number, and hair cell contacts (LES >> MES). A fourth, distinctive population of bouton afferents supplies the juxtastriola. These results, combined with our earlier findings on utricular hair cells and the otoconial membrane, suggest the hypotheses that MES and calyceal afferents encode head movement direction with high spatial resolution and that MES afferents are well suited to signal three-dimensional head orientation and striolar afferents to signal head movement onset. PMID:25632074

  2. Withdrawal and Restoration of Central Vagal Afferents Within the Dorsal Vagal Complex Following Subdiaphragmatic Vagotomy

    PubMed Central

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

    2014-01-01

    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. PMID:23749657

  3. Effects of gastric distension and infusion of umami and bitter taste stimuli on vagal afferent activity.

    PubMed

    Horn, Charles C; Murat, Chloé; Rosazza, Matthew; Still, Liz

    2011-10-24

    Until recently, sensory nerve pathways from the stomach to the brain were thought to detect distension and play little role in nutritional signaling. Newer data have challenged this view, including reports on the presence of taste receptors in the gastrointestinal lumen and the stimulation of multi-unit vagal afferent activity by glutamate infusions into the stomach. However, assessing these chemosensory effects is difficult because gastric infusions typically evoke a distension-related vagal afferent response. In the current study, we recorded gastric vagal afferent activity in the rat to investigate the possibility that umami (glutamate, 150 mM) and bitter (denatonium, 10 mM) responses could be dissociated from distension responses by adjusting the infusion rate and opening or closing the drainage port in the stomach. Slow infusions of saline (5 ml over 2 min, open port) produced no significant effects on vagal activity. Using the same infusion rate, glutamate or denatonium solutions produced little or no effects on vagal afferent activity. In an attempt to reproduce a prior report that showed distention and glutamate responses, we produced a distension response by closing the exit port. Under this condition, response to the infusion of glutamate or denatonium was similar to saline. In summary, we found little or no effect of gastric infusion of glutamate or denatonium on gastric vagal afferent activity that could be distinguished from distension responses. The current results suggest that sensitivity to umami or bitter stimuli is not a common property of gastric vagal afferent fibers. PMID:21925651

  4. Activation of κ Opioid Receptors in Cutaneous Nerve Endings by Conorphin-1, a Novel Subtype-Selective Conopeptide, Does Not Mediate Peripheral Analgesia.

    PubMed

    Deuis, Jennifer R; Whately, Ella; Brust, Andreas; Inserra, Marco C; Asvadi, Naghmeh H; Lewis, Richard J; Alewood, Paul F; Cabot, Peter J; Vetter, Irina

    2015-10-21

    Selective activation of peripheral κ opioid receptors (KORs) may overcome the dose-limiting adverse effects of conventional opioid analgesics. We recently developed a vicinal disulfide-stabilized class of peptides with subnanomolar potency at the KOR. The aim of this study was to assess the analgesic effects of one of these peptides, named conorphin-1, in comparison with the prototypical KOR-selective small molecule agonist U-50488, in several rodent pain models. Surprisingly, neither conorphin-1 nor U-50488 were analgesic when delivered peripherally by intraplantar injection at local concentrations expected to fully activate the KOR at cutaneous nerve endings. While U-50488 was analgesic when delivered at high local concentrations, this effect could not be reversed by coadministration with the selective KOR antagonist ML190 or the nonselective opioid antagonist naloxone. Instead, U-50488 likely mediated its peripheral analgesic effect through nonselective inhibition of voltage-gated sodium channels, including peripheral sensory neuron isoforms NaV1.8 and NaV1.7. Our study suggests that targeting the KOR in peripheral sensory nerve endings innervating the skin is not an alternative analgesic approach. PMID:26225903

  5. Mephedrone, an abused psychoactive component of 'bath salts' and methamphetamine congener, does not cause neurotoxicity to dopamine nerve endings of the striatum.

    PubMed

    Angoa-Pérez, Mariana; Kane, Michael J; Francescutti, Dina M; Sykes, Katherine E; Shah, Mrudang M; Mohammed, Abiy M; Thomas, David M; Kuhn, Donald M

    2012-03-01

    Mephedrone (4-methylmethcathinone) is a β-ketoamphetamine with close structural analogy to substituted amphetamines and cathinone derivatives. Abuse of mephedrone has increased dramatically in recent years and has become a significant public health problem in the United States and Europe. Unfortunately, very little information is available on the pharmacological and neurochemical actions of mephedrone. In light of the proven abuse potential of mephedrone and considering its similarity to methamphetamine and methcathinone, it is particularly important to know if mephedrone shares with these agents an ability to cause damage to dopamine nerve endings of the striatum. Accordingly, we treated mice with a binge-like regimen of mephedrone (4 × 20 or 40 mg/kg) and examined the striatum for evidence of neurotoxicity 2 or 7 days after treatment. While mephedrone caused hyperthermia and locomotor stimulation, it did not lower striatal levels of dopamine, tyrosine hydroxylase or the dopamine transporter under any of the treatment conditions used presently. Furthermore, mephedrone did not cause microglial activation in striatum nor did it increase glial fibrillary acidic protein levels. Taken together, these surprising results suggest that mephedrone, despite its numerous mechanistic overlaps with methamphetamine and the cathinone derivatives, does not cause neurotoxicity to dopamine nerve endings of the striatum. PMID:22191803

  6. Augmentation of partially regenerated nerves by end-to-side side-to-side grafting neurotization: experience based on eight late obstetric brachial plexus cases

    PubMed Central

    2006-01-01

    Objective The effect of end-to-side neurotization of partially regenerated recipient nerves on improving motor power in late obstetric brachial plexus lesions, so-called nerve augmentation, was investigated. Methods Eight cases aged 3 – 7 years were operated upon and followed up for 4 years (C5,6 rupture C7,8T1 avulsion: 5; C5,6,7,8 rupture T1 avulsion:1; C5,6,8T1 rupture C7 avulsion:1; C5,6,7 ruptureC8 T1 compression: one 3 year presentation after former neurotization at 3 months). Grade 1–3 muscles were neurotized. Grade0 muscles were neurotized, if the electromyogram showed scattered motor unit action potentials on voluntary contraction without interference pattern. Donor nerves included: the phrenic, accessory, descending and ascending loops of the ansa cervicalis, 3rd and 4th intercostals and contralateral C7. Results Superior proximal to distal regeneration was observed firstly. Differential regeneration of muscles supplied by the same nerve was observed secondly (superior supraspinatus to infraspinatus regeneration). Differential regeneration of antagonistic muscles was observed thirdly (superior biceps to triceps and pronator teres to supinator recovery). Differential regeneration of fibres within the same muscle was observed fourthly (superior anterior and middle to posterior deltoid regeneration). Differential regeneration of muscles having different preoperative motor powers was noted fifthly; improvement to Grade 3 or more occurred more in Grade2 than in Grade0 or Grade1 muscles. Improvements of cocontractions and of shoulder, forearm and wrist deformities were noted sixthly. The shoulder, elbow and hand scores improved in 4 cases. Limitations The sample size is small. Controls are necessary to rule out any natural improvement of the lesion. There is intra- and interobserver variability in testing muscle power and cocontractions. Conclusion Nerve augmentation improves cocontractions and muscle power in the biceps, pectoral muscles, supraspinatus

  7. External QX-314 inhibits evoked cranial primary afferent synaptic transmission independent of TRPV1.

    PubMed

    Hofmann, Mackenzie E; Largent-Milnes, Tally M; Fawley, Jessica A; Andresen, Michael C

    2014-12-01

    The cell-impermeant lidocaine derivative QX-314 blocks sodium channels via intracellular mechanisms. In somatosensory nociceptive neurons, open transient receptor potential vanilloid type 1 (TRPV1) receptors provide a transmembrane passageway for QX-314 to produce long-lasting analgesia. Many cranial primary afferents express TRPV1 at synapses on neurons in the nucleus of the solitary tract and caudal trigeminal nucleus (Vc). Here, we investigated whether QX-314 interrupts neurotransmission from primary afferents in rat brain-stem slices. Shocks to the solitary tract (ST) activated highly synchronous evoked excitatory postsynaptic currents (ST-EPSCs). Application of 300 μM QX-314 increased the ST-EPSC latency from TRPV1+ ST afferents, but, surprisingly, it had similar actions at TRPV1- ST afferents. Continued exposure to QX-314 blocked evoked ST-EPSCs at both afferent types. Neither the time to onset of latency changes nor the time to ST-EPSC failure differed between responses for TRPV1+ and TRPV1- inputs. Likewise, the TRPV1 antagonist capsazepine failed to prevent the actions of QX-314. Whereas QX-314 blocked ST-evoked release, the frequency and amplitude of spontaneous EPSCs remained unaltered. In neurons exposed to QX-314, intracellular current injection evoked action potentials suggesting a presynaptic site of action. QX-314 acted similarly at Vc neurons to increase latency and block EPSCs evoked from trigeminal tract afferents. Our results demonstrate that QX-314 blocked nerve conduction in cranial primary afferents without interrupting the glutamate release mechanism or generation of postsynaptic action potentials. The TRPV1 independence suggests that QX-314 either acted extracellularly or more likely entered these axons through an undetermined pathway common to all cranial primary afferents. PMID:25185814

  8. Altered colorectal afferent function associated with TNBS-induced visceral hypersensitivity in mice

    PubMed Central

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

    2012-01-01

    Inflammation of the distal bowel is often associated with abdominal pain and hypersensitivity, but whether and which colorectal afferents contribute to the hypersensitivity is unknown. Using a mouse model of 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis, we investigated colorectal hypersensitivity following intracolonic TNBS and associated changes in colorectum and afferent functions. C57BL/6 mice were treated intracolonically with TNBS or saline. Visceromotor responses to colorectal distension (15–60 mmHg) were recorded over 8 wk in TNBS- and saline-treated (control) mice. In other mice treated with TNBS or saline, colorectal inflammation was assessed by myeloperoxidase assay and immunohistological staining. In vitro single-fiber recordings were conducted on both TNBS and saline-treated mice to assess colorectal afferent function. Mice exhibited significant colorectal hypersensitivity through day 14 after TNBS treatment that resolved by day 28 with no resensitization through day 56. TNBS induced a neutrophil- and macrophage-based colorectal inflammation as well as loss of nerve fibers, all of which resolved by days 14–28. Single-fiber recordings revealed a net increase in afferent drive from stretch-sensitive colorectal afferents at day 14 post-TNBS and reduced proportions of mechanically insensitive afferents (MIAs) at days 14–28. Intracolonic TNBS-induced colorectal inflammation was associated with the development and recovery of hypersensitivity in mice, which correlated with a transient increase and recovery of sensitization of stretch-sensitive colorectal afferents and MIAs. These results indicate that the development and maintenance of colorectal hypersensitivity following inflammation are mediated by peripheral drive from stretch-sensitive colorectal afferents and a potential contribution from MIAs. PMID:22859364

  9. External QX-314 inhibits evoked cranial primary afferent synaptic transmission independent of TRPV1

    PubMed Central

    Largent-Milnes, Tally M.; Fawley, Jessica A.; Andresen, Michael C.

    2014-01-01

    The cell-impermeant lidocaine derivative QX-314 blocks sodium channels via intracellular mechanisms. In somatosensory nociceptive neurons, open transient receptor potential vanilloid type 1 (TRPV1) receptors provide a transmembrane passageway for QX-314 to produce long-lasting analgesia. Many cranial primary afferents express TRPV1 at synapses on neurons in the nucleus of the solitary tract and caudal trigeminal nucleus (Vc). Here, we investigated whether QX-314 interrupts neurotransmission from primary afferents in rat brain-stem slices. Shocks to the solitary tract (ST) activated highly synchronous evoked excitatory postsynaptic currents (ST-EPSCs). Application of 300 μM QX-314 increased the ST-EPSC latency from TRPV1+ ST afferents, but, surprisingly, it had similar actions at TRPV1− ST afferents. Continued exposure to QX-314 blocked evoked ST-EPSCs at both afferent types. Neither the time to onset of latency changes nor the time to ST-EPSC failure differed between responses for TRPV1+ and TRPV1− inputs. Likewise, the TRPV1 antagonist capsazepine failed to prevent the actions of QX-314. Whereas QX-314 blocked ST-evoked release, the frequency and amplitude of spontaneous EPSCs remained unaltered. In neurons exposed to QX-314, intracellular current injection evoked action potentials suggesting a presynaptic site of action. QX-314 acted similarly at Vc neurons to increase latency and block EPSCs evoked from trigeminal tract afferents. Our results demonstrate that QX-314 blocked nerve conduction in cranial primary afferents without interrupting the glutamate release mechanism or generation of postsynaptic action potentials. The TRPV1 independence suggests that QX-314 either acted extracellularly or more likely entered these axons through an undetermined pathway common to all cranial primary afferents. PMID:25185814

  10. Optical Monitoring of Living Nerve Terminal Labeling in Hair Follicle Lanceolate Endings of the Ex Vivo Mouse Ear Skin.

    PubMed

    Bewick, Guy S; Banks, Robert W

    2016-01-01

    A novel dissection and recording technique is described for optical monitoring staining and de-staining of lanceolate terminals surrounding hair follicles in the skin of the mouse pinna. The preparation is simple and relatively fast, reliably yielding extensive regions of multiple labeled units of living nerve terminals to study uptake and release of styryl pyridinium dyes extensively used in studies of vesicle recycling. Subdividing the preparations before labeling allows test vs. control comparisons in the same ear from a single individual. Helpful tips are given for improving the quality of the preparation, the labeling and the imaging parameters. This new system is suitable for assaying pharmacologically and mechanically-induced uptake and release of these vital dyes in lanceolate terminals in both wild-type and genetically modified animals. Examples of modulatory influences on labeling intensity are given. PMID:27077818

  11. Optical Monitoring of Living Nerve Terminal Labeling in Hair Follicle Lanceolate Endings of the Ex Vivo Mouse Ear Skin

    PubMed Central

    Bewick, Guy S.; Banks, Robert W.

    2016-01-01

    A novel dissection and recording technique is described for optical monitoring staining and de-staining of lanceolate terminals surrounding hair follicles in the skin of the mouse pinna. The preparation is simple and relatively fast, reliably yielding extensive regions of multiple labeled units of living nerve terminals to study uptake and release of styryl pyridinium dyes extensively used in studies of vesicle recycling. Subdividing the preparations before labeling allows test vs. control comparisons in the same ear from a single individual. Helpful tips are given for improving the quality of the preparation, the labeling and the imaging parameters. This new system is suitable for assaying pharmacologically and mechanically-induced uptake and release of these vital dyes in lanceolate terminals in both wild-type and genetically modified animals. Examples of modulatory influences on labeling intensity are given. PMID:27077818

  12. TRPA1 mediates amplified sympathetic responsiveness to activation of metabolically sensitive muscle afferents in rats with femoral artery occlusion

    PubMed Central

    Xing, Jihong; Lu, Jian; Li, Jianhua

    2015-01-01

    Autonomic responses to activation of mechanically and metabolically sensitive muscle afferent nerves during static contraction are augmented in rats with femoral artery occlusion. Moreover, metabolically sensitive transient receptor potential cation channel subfamily A, member 1 (TRPA1) has been reported to contribute to sympathetic nerve activity (SNA) and arterial blood pressure (BP) responses evoked by static muscle contraction. Thus, in the present study, we examined the mechanisms by which afferent nerves' TRPA1 plays a role in regulating amplified sympathetic responsiveness due to a restriction of blood flow directed to the hindlimb muscles. Our data show that 24–72 h of femoral artery occlusion (1) upregulates the protein levels of TRPA1 in dorsal root ganglion (DRG) tissues; (2) selectively increases expression of TRPA1 in DRG neurons supplying metabolically sensitive afferent nerves of C-fiber (group IV); and (3) enhances renal SNA and BP responses to AITC (a TRPA1 agonist) injected into the hindlimb muscles. In addition, our data demonstrate that blocking TRPA1 attenuates SNA and BP responses during muscle contraction to a greater degree in ligated rats than those responses in control rats. In contrast, blocking TRPA1 fails to attenuate SNA and BP responses during passive tendon stretch in both groups. Overall, results of this study indicate that alternations in muscle afferent nerves' TRPA1 likely contribute to enhanced sympathetically mediated autonomic responses via the metabolic component of the muscle reflex under circumstances of chronic muscle ischemia. PMID:26441669

  13. Secreted Herpes Simplex Virus-2 Glycoprotein G Modifies NGF-TrkA Signaling to Attract Free Nerve Endings to the Site of Infection

    PubMed Central

    Cabrera, Jorge Rubén; Viejo-Borbolla, Abel; Martinez-Martín, Nadia; Blanco, Soledad; Wandosell, Francisco; Alcamí, Antonio

    2015-01-01

    Herpes simplex virus type 1 (HSV-1) and HSV-2 are highly prevalent viruses that cause a variety of diseases, from cold sores to encephalitis. Both viruses establish latency in peripheral neurons but the molecular mechanisms facilitating the infection of neurons are not fully understood. Using surface plasmon resonance and crosslinking assays, we show that glycoprotein G (gG) from HSV-2, known to modulate immune mediators (chemokines), also interacts with neurotrophic factors, with high affinity. In our experimental model, HSV-2 secreted gG (SgG2) increases nerve growth factor (NGF)-dependent axonal growth of sympathetic neurons ex vivo, and modifies tropomyosin related kinase (Trk)A-mediated signaling. SgG2 alters TrkA recruitment to lipid rafts and decreases TrkA internalization. We could show, with microfluidic devices, that SgG2 reduced NGF-induced TrkA retrograde transport. In vivo, both HSV-2 infection and SgG2 expression in mouse hindpaw epidermis enhance axonal growth modifying the termination zone of the NGF-dependent peptidergic free nerve endings. This constitutes, to our knowledge, the discovery of the first viral protein that modulates neurotrophins, an activity that may facilitate HSV-2 infection of neurons. This dual function of the chemokine-binding protein SgG2 uncovers a novel strategy developed by HSV-2 to modulate factors from both the immune and nervous systems. PMID:25611061

  14. Characterization and modeling of P-type electrosensory afferent responses to amplitude modulations in a wave-type electric fish.

    PubMed

    Nelson, M E; Xu, Z; Payne, J R

    1997-11-01

    The first stage of information processing in the electrosensory system involves the encoding of local changes in transdermal potential into trains of action potentials in primary electrosensory afferent nerve fibers. To develop a quantitative model of this encoding process for P-type (probability-coding) afferent fibers in the weakly electric fish Apteronotus leptorhynchus, we recorded single unit activity from electrosensory afferent axons in the posterior branch of the anterior lateral line nerve and analyzed responses to electronically generated sinusoidal amplitude modulations of the local transdermal potential. Over a range of AM frequencies from 0.1 to 200 Hz, the modulation transfer function of P-type afferents is high-pass in character, with a gain that increases monotonically up to AM frequencies of 100 Hz where it begins to roll off, and a phase advance with a range of 15-60 degrees. Based on quantitative analysis of the observed gain and phase characteristics, we present a computationally efficient model of P-type afferent response dynamics which accurately characterizes changes in afferent firing rate in response to amplitude modulations of the fish's own electric organ discharge over a wide range of AM frequencies relevant to active electrolocation. PMID:9373958

  15. Naturalistic Stimuli Increase the Rate and Efficiency of Information Transmission by Primary Auditory Afferents

    NASA Astrophysics Data System (ADS)

    Rieke, F.; Bodnar, D. A.; Bialek, W.

    1995-12-01

    Natural sounds, especially communication sounds, have highly structured amplitude and phase spectra. We have quantified how structure in the amplitude spectrum of natural sounds affects coding in primary auditory afferents. Auditory afferents encode stimuli with naturalistic amplitude spectra dramatically better than broad-band stimuli (approximating white noise); the rate at which the spike train carries information about the stimulus is 2-6 times higher for naturalistic sounds. Furthermore, the information rates can reach 90% of the fundamental limit to information transmission set by the statistics of the spike response. These results indicate that the coding strategy of the auditory nerve is matched to the structure of natural sounds; this `tuning' allows afferent spike trains to provide higher processing centres with a more complete description of the sensory world.

  16. Improved gold chloride staining method for anatomical analysis of sensory nerve endings in the shoulder capsule and labrum as examples of loose and dense fibrous tissues

    PubMed Central

    Witherspoon, J W; Smirnova, IV; McIff, TE

    2014-01-01

    Consistency in gold chloride staining is essential for anatomical analysis of sensory nerve endings. The gold chloride stain for this purpose has been modified by many investigators, but often yields inconsistent staining, which makes it difficult to differentiate structures and to determine nerve ending distribution in large tissue samples. We introduce additional steps and major changes to the modified Gairns’ protocol. We controlled the temperature and mixing rate during tissue staining to achieve consistent staining and complete solution penetration. We subjected samples to sucrose dehydration to improve cutting efficiency. We then exposed samples to a solution containing lemon juice, formic acid and paraformaldehyde to produce optimal tissue transparency with minimal tissue deformity. We extended the time for gold chloride impregnation 1.5 fold. Gold chloride was reduced in the labrum using 25% formic acid in water for 18 h and in the capsule using 25% formic acid in citrate phosphate buffer for 2 h. Citrate binds gold nanoparticles, which minimizes aggregation in the tissue. We stored samples in fresh ultrapure water at 4° C to slow reduction and to maintain color contrast in the tissue. Tissue samples were embedded in Tissue Tek and sectioned at 80 and 100 μm instead of using glycerin and teasing the tissue apart as in Gairns’ modified gold chloride method. We attached sections directly to gelatin subbed slides after sectioning with a cryostat. The slides then were processed and coverslipped with Permount. Staining consistency was demonstrated throughout the tissue sections and neural structures were clearly identifiable. PMID:24476562

  17. Reduced C-afferent fibre density affects perceived pleasantness and empathy for touch.

    PubMed

    Morrison, India; Löken, Line S; Minde, Jan; Wessberg, Johan; Perini, Irene; Nennesmo, Inger; Olausson, Håkan

    2011-04-01

    We examined patients with a heritable disorder associated with a mutation affecting the nerve growth factor beta gene. Their condition has been classified as hereditary sensory and autonomic neuropathy type V. Carriers of the mutation show a reduction in density of thin and unmyelinated nerve fibres, including C afferents. A distinct type of unmyelinated, low-threshold mechanoreceptive C fibre, the C-tactile afferent, is present in hairy but not glabrous skin of humans and other mammals. They have been implicated in the coding of pleasant, hedonic touch of the kind that occurs in affiliative social interactions. We addressed the relationship between C fibre function and pleasant touch perception in 10 individuals from a unique population of mutation carriers in Sweden. We also investigated the effect of reduced C-fibre density on patients' evaluation of observed interpersonal touch (empathy). Results showed that patients perceived gentle, slow arm stroking, optimal for eliciting C-tactile afferent responses (1-10  cm/s), as less pleasant than did matched controls and also differed in their rating patterns across stimulation velocities. Further, patients' blood-oxygen-level-dependent responses in posterior insular cortex--a target for C afferents--were not modulated by stimulation optimal for activating C-tactile afferents. Hence, perception of the hedonic aspect of dynamic touch likely depends on C-tactile afferent density. Closely similar patterns between individuals' ratings of felt and seen touch suggest that appraisal of others' touch is anchored in one's own perceptual experience, whether typical or atypical. PMID:21378097

  18. Blockade of B2 receptors attenuates the responses of group III afferents to static contraction.

    PubMed

    Leal, Anna K; Stone, Audrey J; Yamauchi, Katsuya; McCord, Jennifer L; Kaufman, Marc P

    2013-10-25

    Recent evidence has been presented demonstrating that group III mechanoreceptors comprise an important part of the sensory arm of the exercise pressor reflex, which in turn functions to increase arterial blood flow to contracting skeletal muscles. Although group III afferents are stimulated by mechanical distortion of their receptive fields, they are also stimulated by bradykinin, which is produced by skeletal muscle when it contracts. Moreover, blockade of B (bradykinin)2 receptors has been shown to decrease the magnitude of the exercise pressor reflex. Nevertheless, the effect of blockade of B2 receptors on responses of group III afferents to contraction is not known. We therefore determined the effect of B2 receptor blockade with HOE 140 (40μg/kg) on the responses to both static and intermittent contraction of group III afferents with endings in the triceps surae muscle of decerebrated unanesthetized cats. We found that HOE 140 significantly attenuated (P=0.04) the responses of 14 group III afferents to static contraction, but did not significantly attenuate (P=0.16) the responses of 16 group III afferents to intermittent contraction. The attenuation induced by HOE 140 was present throughout the static contraction period, and led us to speculate that blockade of B2 receptors on the endings of group III afferents decreased their sensitivity to mechanical events occurring in the working muscles. PMID:24036460

  19. Primary afferent input critical for maintaining spontaneous pain in peripheral neuropathy.

    PubMed

    Haroutounian, Simon; Nikolajsen, Lone; Bendtsen, Thomas F; Finnerup, Nanna B; Kristensen, Anders D; Hasselstrøm, Jørgen B; Jensen, Troels S

    2014-07-01

    Central sensitization after peripheral nerve injury may result in ectopic neuronal activity in the spinal cord dorsal horn, implying a potential autonomous pain-generating mechanism. This study used peripheral nerve blockade and systemic lidocaine administration, with detailed somatosensory assessment, to determine the contribution of primary afferent input in maintaining peripheral neuropathic pain. Fourteen patients with neuropathic pain (7 with unilateral foot pain due to peripheral nerve injury and 7 with bilateral pain in the feet due to distal polyneuropathy) underwent comprehensive characterization of somatosensory function by quantitative sensory testing. Patients were then administered an ultrasound-guided peripheral nerve block with lidocaine and intravenous lidocaine infusion in randomized order. The effect of these interventions on spontaneous pain intensity and on evoked cold, warm, pinprick, and brush responses was assessed at each session. All patients had sensory disturbances at baseline. The peripheral nerve block resulted in a complete abolition of ipsilateral pain within 10 min (median) in all patients, with lidocaine plasma concentrations being too low to account for a systemic effect of the drug. Intravenous lidocaine infusion reduced the spontaneous pain by 45.5% (±31.7%), and it reduced mechanical and thermal hypersensitivity in most patients who displayed such signs. However, the improvement in evoked hypersensitivity was not related to the effect of the drug on spontaneous pain intensity. This study demonstrated that regardless of the individual somatosensory phenotype and signs of central sensitization, primary afferent input is critical for maintaining neuropathic pain in peripheral nerve injury and distal polyneuropathy. PMID:24704366

  20. Paraventricular nucleus is involved in the central pathway of adipose afferent reflex in rats.

    PubMed

    Shi, Zhen; Wang, Yuan-Fang; Wang, Gui-Hua; Wu, Yu-Long; Ma, Chun-Lei

    2016-05-01

    Increasing evidence indicates a link between sympathetic nervous system activation and obesity, but the underlying mechanisms remain elusive. The adipose afferent reflex (AAR) is a sympathoexcitatory reflex that is activated by afferent neurotransmission from the white adipose tissue (WAT). This study aimed to investigate whether the hypothalamic paraventricular nucleus (PVH) is an important component of the central neurocircuitry of the AAR. In anesthetized rats, the discharge activity of individual PVH neurons was recorded in vivo. Activation of WAT afferents was initiated by capsaicin injection, and the AAR was evaluated by monitoring renal sympathetic nerve activity (RSNA) and mean arterial pressure (MAP) responses. The responses of PVH neurons to activation of WAT afferents were evaluated by c-fos immunoreactivity and the discharge activity of individual PVH neurons, which was recorded using extracellular single-unit recording. After activation of WAT afferents, both individual PVH neuron discharge activity and c-fos immunoreactivity increased. Bilateral selective lesions of the neurons in the PVH with kainic acid abolished the AAR. These results indicate that PVH is an important component of the central neurocircuitry of the AAR. PMID:26963333

  1. Ileal bladder substitute: antireflux nipple or afferent tubular segment?

    PubMed

    Studer, U E; Spiegel, T; Casanova, G A; Springer, J; Gerber, E; Ackermann, D K; Gurtner, F; Zingg, E J

    1991-01-01

    contrast medium back to the reservoir. Our results suggest that the combination of an ileal low-pressure reservoir together with an afferent tubular isoperistaltic limb is at least as good as an antireflux nipple valve. Moreover, the use of the afferent ileal limb makes it possible to resect the distal and often diseased ureters together with the paraureteric lymphatics at a safe distance from the bladder tumor. This avoids also distal ischemic ureteric stenosis and makes possible a simple end-to-side ureterointestinal anastomosis with a small complication rate. PMID:1814749

  2. Imaging of the facial nerve.

    PubMed

    Veillona, F; Ramos-Taboada, L; Abu-Eid, M; Charpiot, A; Riehm, S

    2010-05-01

    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. PMID:20456888

  3. The auriculo-vagal afferent pathway and its role in seizure suppression in rats

    PubMed Central

    2013-01-01

    Background The afferent projections from the auricular branch of the vagus nerve (ABVN) to the nucleus tractus solitaries (NTS) have been proposed as the anatomical basis for the increased parasympathetic tone seen in auriculo-vagal reflexes. As the afferent center of the vagus nerve, the NTS has been considered to play roles in the anticonvulsant effect of cervical vagus nerve stimulation (VNS). Here we proposed an “auriculo-vagal afferent pathway” (AVAP), by which transcutaneous auricular vagus nerve stimulation (ta-VNS) suppresses pentylenetetrazol (PTZ)-induced epileptic seizures by activating the NTS neurons in rats. Results The afferent projections from the ABVN to the NTS were firstly observed in rats. ta-VNS increased the first grand mal latency of the epileptic seizure and decreased the seizure scores in awake rats. Furthermore, when the firing rates of the NTS neurons decreased, epileptiform activity manifested as electroencephalogram (EEG) synchronization increased with 0.37±0.12 s delay in anaesthetized rats. The change of instantaneous frequency, mean frequency of the NTS neurons was negative correlated with the amplitude of the epileptic activity in EEG traces. ta-VNS significantly suppressed epileptiform activity in EEG traces via increasing the firing rates of the neurons of the NTS. In comparison with tan-VNS, the anticonvulsant durations of VNS and ta-VNS were significantly longer (P<0.01). There was no significant difference between the anticonvulsant durations of VNS and ta-VNS (P>0.05). The anticonvulsant effect of ta-VNS was weakened by reversible cold block of the NTS. Conclusions There existed an anatomical relationship between the ABVN and the NTS, which strongly supports the concept that ta-VNS has the potential for suppressing epileptiform activity via the AVAP in rats. ta-VNS will provide alternative treatments for neurological disorders, which can avoid the disadvantage of VNS. PMID:23927528

  4. Electrophysiology of the afferent innervation of the penis of the domestic ram.

    PubMed Central

    Cottrell, D F; Iggo, A; Kitchell, R L

    1978-01-01

    1. The discharge of impulses in afferent fibres dissected from the dorsal nerve of the penis of chloralose-anaesthetized rams was recorded electrophysiologically during controlled natural stimulation of the surgically exposed penis maintained at body temperature and mechanically stabilized in a plaster of Paris mould. 2. Fifty-eight slowly adapting mechanorecptor units were examined and their pressure, velocity and displacement thresholds were determined. Units often responded best to integumental stretch. Few had resting discharges. During a sustained perpendicularly applied displacement most units adapted to silence within 1.5 min. The units were classified into types from an analysis of their adapted impulse trains in response to a sustained mechanical stimulus. 3. Twenty-five mechanoreceptive units had rapidly adapting responses. Most units had typical rapid adapting characteristics and discharged impulses only during the dynamic phase of the application of the displacement. A subgroup had intermediate adapting characteristics, and discharged intermittently during steady displacement of the integument. 4. The mechanical sensitivity of most receptors altered when the temperature of the receptive field was changed with a positive correlation in eleven units, a negative correlation in six. Six slowly adapting units were thermally insensitive. Twelve rapidly adapting units were tested. Six had a positive thermal correlation and four a negative correlation. 5. The conduction velocities of axons of mechanoreceptor units in the dorsal nerve of the penis were in the Aalpha range (12--77 msec-1). 6. Two specific warm and five specific cold units were found. The conduction velocities of the axons supplying warm receptors were 45.4 msec-1 (one unit) and those for cold receptors were 7.5, 7.8, 30, 45.5, 48.7 msec-1. 7. No correlation could be found between the receptor submodality and the profuse receptor end bulb population demonstrated histologically. PMID:722579

  5. Genetic and pharmacological evidence for low-abundance TRPV3 expression in primary vagal afferent neurons.

    PubMed

    Wu, Shaw-Wen; Lindberg, Jonathan E M; Peters, James H

    2016-05-01

    Primary vagal afferent neurons express a multitude of thermosensitive ion channels. Within this family of ion channels, the heat-sensitive capsaicin receptor (TRPV1) greatly influences vagal afferent signaling by determining the threshold for action-potential initiation at the peripheral endings, while controlling temperature-sensitive forms of glutamate release at central vagal terminals. Genetic deletion of TRPV1 does not completely eliminate these temperature-dependent effects, suggesting involvement of additional thermosensitive ion channels. The warm-sensitive, calcium-permeable, ion channel TRPV3 is commonly expressed with TRPV1; however, the extent to which TRPV3 is found in vagal afferent neurons is unknown. Here, we begin to characterize the genetic and functional expression of TRPV3 in vagal afferent neurons using molecular biology (RT-PCR and RT-quantitative PCR) in whole nodose and isolated neurons and fluorescent calcium imaging on primary cultures of nodose ganglia neurons. We confirmed low-level TRPV3 expression in vagal afferent neurons and observed direct activation with putative TRPV3 agonists eugenol, ethyl vanillin (EVA), and farnesyl pyrophosphate (FPP). Agonist activation stimulated neurons also containing TRPV1 and was blocked by ruthenium red. FPP sensitivity overlapped with EVA and eugenol but represented the smallest percentage of vagal afferent neurons, and it was the only agonist that did not stimulate neurons from TRPV3(-/-1) mice, suggesting FPP has the highest selectivity. Further, FPP was predictive of enhanced responses to capsaicin, EVA, and eugenol in rats. From our results, we conclude TRPV3 is expressed in a discrete subpopulation of vagal afferent neurons and may contribute to vagal afferent signaling either directly or in combination with TRPV1. PMID:26843581

  6. Effects of hemodialysis on macular and retinal nerve fiber layer thicknesses in non-diabetic patients with end stage renal failure

    PubMed Central

    Atilgan, Cemile U.; Guven, Dilek; Akarsu, Ozge P.; Sakaci, Tamer; Sendul, Selam Y.; Baydar, Yasemin; Atilgan, Kadir G.; Turker, Ibrahim C.

    2016-01-01

    Objectives: To evaluate the thicknesses of retinal nerve fiber layer (RNFL) and macula by fourier-domain (FD) optical coherence tomography (OCT) in non-diabetic patients with end-stage-renal-failure (ESRF) undergoing hemodialysis (HD). Methods: This is a prospective and observational study. Both eyes of 20 patients receiving HD (group 1) and 34 control patients (group 2) were evaluated by FD-OCT. Macular and RNFL thicknesses were compared between groups and their correlation with age, duration of HD, and gender were examined. In group 1, macular and RNFL thicknesses were evaluated before and shortly after HD in the first day, first and sixth months. Results: In group 1, pre-HD temporal, inferior, average RNFL thicknesses were thinner than group 2. This thinning did not correlate with duration of HD, age and gender. Pre-HD macular thicknesses were thinner than group 2. These thinnings did not correlate with age, but the thinnings at superior, nasal and average thickness correlated negatively with duration of HD. Nasal, temporal, and average macular thicknesses were thinner in female patients. The thickenings of RNFL and macula that were observed in the after HD first day and first month did not showed consistency in the sixth month except superior quadrant RNFL. Conclusion: Macular and RNFL thicknesses of patients receiving HD were less than the normal population. Age has no effect on these thinnings. The duration of HD affects more than gender. Hemodialysis session causes a consistent increase in superior quadrant RNFL. PMID:27279510

  7. Short-latency projections to the cat cerebral cortex from skin and muscle afferents in the contralateral forelimb

    PubMed Central

    Oscarsson, O.; Rosén, I.

    1966-01-01

    1. The potentials evoked in the first sensorimotor area on stimulation of muscle and skin nerves in the contralateral forelimb were recorded in preparations with either the dorsal funiculus (DF) or the spinocervical tract (SCT) interrupted. 2. The short-latency, surface-positive potentials in these preparations are mediated by the remaining path, either the DF or SCT. 3. Cutaneous afferents project through both paths to two discrete areas which correspond to the classical sensory and motor cortices (Fig. 10 A and B). The projection areas are not identical: the DF path seems to activate most effectively the sensory cortex; and the SCT path, most effectively the motor cortex. 4. The potentials evoked from cutaneous nerves have a similar latency in the two areas. On stimulation of the superficial radial nerve the latency was about 4·5 msec in preparations with intact DF, and about 5·3 msec in preparations with intact SCT. 5. High threshold muscle afferents project to the same areas as the cutaneous afferents. 6. Group I muscle afferents project, exclusively through the DF path, to an area distinct from the two cutaneous projection areas (Fig. 10C). It occupies a caudal part of the motor cortex and an intermediate zone between the sensory and motor cortices. 7. The projection areas are compared with the recent cytoarchitectonic map of Hassler & Muhs-Clement (1964) (Fig. 10D). 8. It is suggested that the afferent projections to the motor cortex and the intermediate zone are used in the integration of movements elicited from the cortex. The general similarity in the organization of afferent paths to the motor cortex and the cerebellum is pointed out. PMID:5937410

  8. Role of renal sensory nerves in physiological and pathophysiological conditions

    PubMed Central

    2014-01-01

    Whether activation of afferent renal nerves contributes to the regulation of arterial pressure and sodium balance has been long overlooked. In normotensive rats, activating renal mechanosensory nerves decrease efferent renal sympathetic nerve activity (ERSNA) and increase urinary sodium excretion, an inhibitory renorenal reflex. There is an interaction between efferent and afferent renal nerves, whereby increases in ERSNA increase afferent renal nerve activity (ARNA), leading to decreases in ERSNA by activation of the renorenal reflexes to maintain low ERSNA to minimize sodium retention. High-sodium diet enhances the responsiveness of the renal sensory nerves, while low dietary sodium reduces the responsiveness of the renal sensory nerves, thus producing physiologically appropriate responses to maintain sodium balance. Increased renal ANG II reduces the responsiveness of the renal sensory nerves in physiological and pathophysiological conditions, including hypertension, congestive heart failure, and ischemia-induced acute renal failure. Impairment of inhibitory renorenal reflexes in these pathological states would contribute to the hypertension and sodium retention. When the inhibitory renorenal reflexes are suppressed, excitatory reflexes may prevail. Renal denervation reduces arterial pressure in experimental hypertension and in treatment-resistant hypertensive patients. The fall in arterial pressure is associated with a fall in muscle sympathetic nerve activity, suggesting that increased ARNA contributes to increased arterial pressure in these patients. Although removal of both renal sympathetic and afferent renal sensory nerves most likely contributes to the arterial pressure reduction initially, additional mechanisms may be involved in long-term arterial pressure reduction since sympathetic and sensory nerves reinnervate renal tissue in a similar time-dependent fashion following renal denervation. PMID:25411364

  9. Effects of ankle extensor muscle afferent inputs on hip abductor and adductor activity in the decerebrate walking cat.

    PubMed

    Bolton, D A E; Misiaszek, J E

    2012-12-01

    Electrical stimulation of the lateral gastrocnemius-soleus (LGS) nerve at group I afferent strength leads to adaptations in the amplitude and timing of extensor muscle activity during walking in the decerebrate cat. Such afferent feedback in the stance leg might result from a delay in stance onset of the opposite leg. Concomitant adaptations in hip abductor and adductor activity would then be expected to maintain lateral stability and balance until the opposite leg is able to support the body. As many hip abductors and adductors are also hip extensors, we hypothesized that stimulation of the LGS nerve at group I afferent strength would produce increased activation and prolonged burst duration in hip abductor and adductor muscles in the premammillary decerebrate walking cat. LGS nerve stimulation during the extensor phase of the locomotor cycle consistently increased burst amplitude of the gluteus medius and adductor femoris muscles, but not pectineus or gracilis. In addition, LGS stimulation prolonged the burst duration of both gluteus medius and adductor femoris. Unexpectedly, long-duration LGS stimulus trains resulted in two distinct outcomes on the hip abductor and adductor bursting pattern: 1) a change of burst duration and timing similar to medial gastrocnemius; or 2) to continue rhythmically bursting uninterrupted. These results indicate that activation of muscle afferents from ankle extensors contributes to the regulation of activity of some hip abductor and adductor muscles, but not all. These results have implications for understanding the neural control of stability during locomotion, as well as the organization of spinal locomotor networks. PMID:22972967

  10. [Repair and revision 9. Peripheral trigeminal nerve injury].

    PubMed

    Vriens, J P M; van der Glas, H W; Koole, R

    2002-03-01

    A review is given about long-term incidence of sensory disturbance in the areas of innervation of the n. trigeminus for different types of trauma and/or treatment. Diagnosis, clinical course and possible types of treatment are in addition reviewed. Regarding diagnosis, the outcome of a test on sensory function is not always related to the degree of nerve damage because methods differ in the type of afferent nerve fibers of which function is tested, and some specificity might occur in nerve damage, i.e. either thick or thin afferent fibers might be predominantly affected at a particular time. An initial quick testing of sensory function is recommended. This testing includes examining two sensory modalities, which are related to functioning of thick and thin afferent fibers respectively and which have a dichotomous yes/no outcome on the incidence of a pronounced sensory disturbance. PMID:11933529

  11. Effect of hypergravity on the development of vestibulocerebellar afferent fibers

    NASA Astrophysics Data System (ADS)

    Bruce, L. L.

    Gravity is a critical factor in the normal development of the vestibular system, as prolonged prenatal exposures to either micro- or hypergravity will alter the pattern of projections from specific vestibular organs to specific targets in the vestibular nuclei. This study addresses the effect of gravity on the development of vestibulocerebellar projections. In adult rats the semicircular canal afferents project mainly to the cerebellar nodulus whereas the otolith maculae project mainly to the ventral uvula of the cerebellum. To determine if the distribution pattern of these afferents is altered by exposures to altered gravity, 10 pregnant rats were exposed to hypergravity (1.5g) from embryonic day 12 (before vestibular ganglion neurons contact vestibular nuclei) to embryonic day 21 (near the time when the vestibular system becomes functional). Controls were exposed to Earth's gravity but otherwise received the same treatment. At the end of the exposure the embryos were deeply anesthetized and fixed by transcardiac perfusion with 4% paraformaldehyde in 0.1 M phosphate buffer (pH7.4). Filter strips coated with DiI and PTIR were implanted into the saccule (gravistatic vestibular receptor) or into the posterior vertical canal (angular acceleration receptor), and allowed to diffuse for 2 weeks at 37°C. Then the brains were dissected and sectioned for fluorescent confocal imaging. Examination of the control cerebella revealed that the canal and otolith afferents have reached the nodulus and uvula, and axons extend into the internal granular, Purkinje, and molecular layers. Projections from the saccule and posterior vertical canal were partially segregated into their respective domains, the uvula and nodulus. In contrast, in hypergravity-exposed rat fetuses the saccule and posterior vertical canal projections were poorly segregated, and both organs contributed labeled fibers to all layers of the nodulus and uvula. This contrasts with the increased afferent segregation

  12. Pinched Nerve

    MedlinePlus

    ... Enhancing Diversity Find People About NINDS NINDS Pinched Nerve Information Page Table of Contents (click to jump ... being done? Clinical Trials Organizations What is Pinched Nerve? The term "pinched nerve" is a colloquial term ...

  13. Nerve biopsy

    MedlinePlus

    Nerve biopsy may be done to help diagnose: Axon degeneration (destruction of the axon portion of the nerve cell) Damage to the ... Demyelination Inflammation of the nerve Leprosy Loss of axon tissue Metabolic neuropathies Necrotizing vasculitis Sarcoidosis

  14. Kv1 channels and neural processing in vestibular calyx afferents.

    PubMed

    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. PMID:26082693

  15. Kv1 channels and neural processing in vestibular calyx afferents

    PubMed Central

    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. PMID:26082693

  16. Color threshold and ratio of S100 beta, MAP5, NF68/200, GABA & GAD. I. Distribution in inner ear afferents

    NASA Technical Reports Server (NTRS)

    Fermin, C. D.; Martin, D. S.; Hara, H.

    1997-01-01

    Afferents of chick embryos (Gallus domesticus) VIIIth nerve were examined at E3, E6, E9, E13, El7, and hatching (NH) for anti-S100 beta, anti-MAP5, anti-GABA, anti-GAD and anti-NF68/200 stain. Different ages were processed together to determine if the distribution of these antibodies changed during synaptogenesis and myelination. Color thresholding showed that saturation of pixels changed for S100 beta only 5%, for NF68/200 10%, and for MAP5, 10%, between E9-NH. Color ratio of NF68/200 over MAP5 was 1.00 at E13 and 0.25 at E16 and NH. S100 beta, GABA and GAD were co-expressed on nerve endings at the edge of the maculae and center of the cristae, whereas hair cells in the center of the maculae expressed either S100 beta or GABA, but not both. S100 beta/NF68/200 shared antigenic sites on the chalices, but NF68/200 expression was higher than S100 beta in the chalices at hatching. MAP5 was expressed in more neurons than NF68/200 at E11, whereas NF68/200 was more abundant than MAP5 at hatching. The results suggest that: 1) the immunoexpression of these neuronal proteins is modulated concomitantly with the establishment of afferent synapses and myelination; 2) S100 beta may serve a neurotrophic function in the chalices where it is co-expressed with the neurotransmitter GABA and its synthesizing enzyme GAD.

  17. Identification of bladder and colon afferents in the nodose ganglia of male rats.

    PubMed

    Herrity, April N; Rau, Kristofer K; Petruska, Jeffrey C; Stirling, David P; Hubscher, Charles H

    2014-11-01

    The sensory neurons innervating the urinary bladder and distal colon project to similar regions of the central nervous system and often are affected simultaneously by various diseases and disorders, including spinal cord injury. Anatomical and physiological commonalities between the two organs involve the participation of shared spinally derived pathways, allowing mechanisms of communication between the bladder and colon. Prior electrophysiological data from our laboratory suggest that the bladder also may receive sensory innervation from a nonspinal source through the vagus nerve, which innervates the distal colon as well. The present study therefore aimed to determine whether anatomical evidence exists for vagal innervation of the male rat urinary bladder and to assess whether those vagal afferents also innervate the colon. Additionally, the relative contribution to bladder and colon sensory innervation of spinal and vagal sources was determined. By using lipophilic tracers, neurons that innervated the bladder and colon in both the nodose ganglia (NG) and L6/S1 and L1/L2 dorsal root ganglia (DRG) were quantified. Some single vagal and spinal neurons provided dual innervation to both organs. The proportions of NG afferents labeled from the bladder did not differ from spinal afferents labeled from the bladder when considering the collective population of total neurons from either group. Our results demonstrate evidence for vagal innervation of the bladder and colon and suggest that dichotomizing vagal afferents may provide a neural mechanism for cross-talk between the organs. PMID:24845615

  18. Inhibitory mechanisms following electrical stimulation of tendon and cutaneous afferents in the lower limb.

    PubMed

    Khan, Serajul I; Burne, John A

    2010-01-13

    Electrical stimulation of the Achilles tendon (TES) produced strong reflex depression (duration>250 ms) of a small background contraction in both heads of gastrocnemius (GA) via large diameter electrodes localized to the tendon. The inhibitory responses were produced without electrical (M wave) or mechanical (muscle twitch) signs of direct muscle stimulation. In this study, the contribution of presynaptic and postsynaptic mechanisms to the depression was investigated by studying conditioning effects of tendon afferent stimulation on the mechanical tendon reflex (TR) and magnetic motor evoked potential (MEP). TES completely inhibited the TR over an ISI of 300 ms that commenced before and continued during and after the period of voluntary EMG depression. Tendon afferent conditioning stimuli also partially inhibited the MEP, but over a short time course confined to the period of voluntary EMG depression. The strength and extended time course of tendon afferent conditioning of the TR and its failure to produce a similar depression of the MEP are consistent with a mechanism involving presynaptic inhibition of Ia terminals. Cutaneous (sural nerve) afferent conditioning partially inhibited the TR and MEP over a short time course (ISI <100 ms) resembling the inhibition seen in the voluntary EMG. This was consistent with the postsynaptic origin of cutaneous inhibition of the motoneurons. PMID:19850015

  19. Modeling the spinal pudendo-vesical reflex for bladder control by pudendal afferent stimulation.

    PubMed

    McGee, Meredith J; Grill, Warren M

    2016-06-01

    Electrical stimulation of the pudendal nerve (PN) is a promising approach to restore continence and micturition following bladder dysfunction resulting from neurological disease or injury. Although the pudendo-vesical reflex and its physiological properties are well established, there is limited understanding of the specific neural mechanisms that mediate this reflex. We sought to develop a computational model of the spinal neural network that governs the reflex bladder response to PN stimulation. We implemented and validated a neural network architecture based on previous neuroanatomical and electrophysiological studies. Using synaptically-connected integrate and fire model neurons, we created a network model with realistic spiking behavior. The model produced expected sacral parasympathetic nucleus (SPN) neuron firing rates from prescribed neural inputs and predicted bladder activation and inhibition with different frequencies of pudendal afferent stimulation. In addition, the model matched experimental results from previous studies of temporal patterns of pudendal afferent stimulation and selective pharmacological blockade of inhibitory neurons. The frequency- and pattern-dependent effects of pudendal afferent stimulation were determined by changes in firing rate of spinal interneurons, suggesting that neural network interactions at the lumbosacral level can mediate the bladder response to different frequencies or temporal patterns of pudendal afferent stimulation. Further, the anatomical structure of excitatory and inhibitory interneurons in the network model was necessary and sufficient to reproduce the critical features of the pudendo-vesical reflex, and this model may prove useful to guide development of novel, more effective electrical stimulation techniques for bladder control. PMID:26968615

  20. Afferent Connectivity of the Zebrafish Habenulae

    PubMed Central

    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

  1. Vestibular afferent responses to microrotational stimuli

    NASA Technical Reports Server (NTRS)

    Myers, Steven F.; Lewis, Edwin R.

    1991-01-01

    Intracellular microelectrode recording/labeling techniques were used to investigate vestibular afferent responses in the bullfrog, to very small amplitude (less than 5 deg p-p) sinusoidal rotations in the vertical plane over the frequency range of 0.063-4 Hz. Robust responses to peak accelerations as low as 0.031 deg/sec per sec were obtained from units subsequently traced to either the central portion of the anterior canal crista or the striolar region of the utricle. All of these microrotationally sensitive afferent neurons had irregular resting discharge rates, and the majority had transfer ratios (relative to rotational velocity) of 1-40 spikes/sec per deg/sec. Individual utricular afferent velocity transfer ratios were nearly constant over the frequency range of 0.125-4 Hz. Canal units displayed decreasing response transfer ratios as stimulus frequencies increased. These findings indicate that, although utricular striolar and central crista afferent velocity transfer ratios to microrotations were very similar, utricular striolar afferent neurons were more faithful sensors of very small amplitude rotational velocity in the vertical plane.

  2. Muscle afferent potential (`A-wave') in the surface electromyogram of a phasic stretch reflex in normal humans

    PubMed Central

    Clarke, Alex. M.; Michie, Patricia T.; Glue, Leonard C. T.

    1972-01-01

    The experiments reported in this paper tested the hypothesis that the afferent potential elicited by a tendon tap in an isometrically recorded phasic stretch reflex can be detected in the surface EMG of normal humans when appropriate techniques are used. These techniques involved (1) training the subjects to relax mentally and physically so that the EMG was silent before and immediately after the diphasic MAP which reflects a highly synchronous discharge of afferent impulses from low threshold muscle stretch receptors after a tendon tap, and (2) using a data retrieval computer to summate stimulus-locked potentials in the EMG over a series of 16 samples using taps of uniform peak force and duration on the Achilles tendon to elicit the tendon jerk in the calf muscles. A discrete, diphasic potential (`A-wave') was recorded from EMG electrodes placed on the surface of the skin over the medial gastrocnemius muscle. The `A-wave' afferent potential had the opposite polarity to the corresponding efferent MAP. Under control conditions of relaxation the `A-wave' had a latency after the onset of the tap of 2 msec, the peak to peak amplitude was of the order of 5 μV and the duration was in the range of 6 to 10 msec. Further experiments were conducted to show that the `A-wave' (1) was not an artefact of the instrumentation used, (2) had a threshold at low intensities of stimulation, and (3) could be reliably augmented by using a Jendrassik manoeuvre compared with the potential observed during control (relaxation) conditions. The results support the conclusion that the `A-wave' emanates from the pool of muscle spindles which discharges impulses along group Ia nerve fibres in response to the phasic stretch stimulus because the primary ending of the spindles is known to initiate the stretch reflex and the spindles can be sensitized by fusimotor impulses so that their threshold is lowered as a result of a Jendrassik manoeuvre. The finding has important implications for the

  3. The mechanisms involved in the long-lasting neuroprotective effect of fluoxetine against MDMA (‘ecstasy')-induced degeneration of 5-HT nerve endings in rat brain

    PubMed Central

    Sanchez, V; Camarero, J; Esteban, B; Peter, M J; Green, A R; Colado, M I

    2001-01-01

    It has been reported that co-administration of fluoxetine with 3,4-methylenedioxymethamphetamine (MDMA, ‘ecstasy') prevents MDMA-induced degeneration of 5-HT nerve endings in rat brain. The mechanisms involved have now been investigated. MDMA (15 mg kg−1, i.p.) administration produced a neurotoxic loss of 5-HT and 5-hydroxyindoleacetic acid (5-HIAA) in cortex, hippocampus and striatum and a reduction in cortical [3H]-paroxetine binding 7 days later. Fluoxetine (10 mg kg−1, i.p., ×2, 60 min apart) administered concurrently with MDMA or given 2 and 4 days earlier provided complete protection, and significant protection when given 7 days earlier. Fluvoxamine (15 mg kg−1, i.p., ×2, 60 min apart) only produced neuroprotection when administered concurrently. Fluoxetine (10 mg kg−1, ×2) markedly increased the KD and reduced the Bmax of cortical [3H]-paroxetine binding 2 and 4 days later. The Bmax was still decreased 7 days later, but the KD was unchanged. [3H]-Paroxetine binding characteristics were unchanged 24 h after fluvoxamine (15 mg kg−1, ×2). A significant cerebral concentration of fluoxetine plus norfluoxetine was detected over the 7 days following fluoxetine administration. The fluvoxamine concentration had decreased markedly by 24 h. Pretreatment with fluoxetine (10 mg kg−1, ×2) failed to alter cerebral MDMA accumulation compared to saline pretreated controls. Neither fluoxetine or fluvoxamine altered MDMA-induced acute hyperthermia. These data demonstrate that fluoxetine produces long-lasting protection against MDMA-induced neurodegeneration, an effect apparently related to the presence of the drug and its active metabolite inhibiting the 5-HT transporter. Fluoxetine does not alter the metabolism of MDMA or its rate of cerebral accumulation. PMID:11522596

  4. Transcutaneous vagus nerve stimulation for the treatment of depression: a study protocol for a double blinded randomized clinical trial

    PubMed Central

    2012-01-01

    Background Depressive disorders are the most common form of mental disorders in community and health care settings. Unfortunately, the treatment of Major Depressive Disorder (MDD) is far from satisfactory. Vagus nerve stimulation (VNS) is a relatively new and promising physical treatment for depressive disorders. One particularly appealing element of VNS is the long-term benefit in mood regulation. However, because this intervention involves surgery, perioperative risks, and potentially significant side effects, this treatment has been limited to those patients with treatment-resistant depression who have failed medication trials and exhausted established somatic treatments for major depression, due to intolerance or lack of response. This double-blinded randomized clinical trial aims to overcome these limitations by introducing a novel method of stimulating superficial branches of the vagus nerve on the ear to treat MDD. The rationale is that direct stimulation of the afferent nerve fibers on the ear area with afferent vagus nerve distribution should produce a similar effect as classic VNS in reducing depressive symptoms without the burden of surgical intervention. Design One hundred twenty cases (60 males) of volunteer patients with mild and moderate depression will be randomly divided into transcutaneous vagus nerve stimulation group (tVNS) and sham tVNS group. The treatment period lasts 4 months and all clinical and physiological measurements are acquired at the beginning and the end of the treatment period. Discussion This study has the potential to significantly extend the application of VNS treatment for MDD and other disorders (including epilepsy, bipolar disorder, and morbid obesity), resulting in direct benefit to the patients suffering from these highly prevalent disorders. In addition, the results of this double-blinded clinical trial will shed new light on our understanding of acupuncture point specificity, and development of methodologies in clinical

  5. Peripheral oxytocin activates vagal afferent neurons to suppress feeding in normal and leptin-resistant mice: a route for ameliorating hyperphagia and obesity.

    PubMed

    Iwasaki, Yusaku; Maejima, Yuko; Suyama, Shigetomo; Yoshida, Masashi; Arai, Takeshi; Katsurada, Kenichi; Kumari, Parmila; Nakabayashi, Hajime; Kakei, Masafumi; Yada, Toshihiko

    2015-03-01

    Oxytocin (Oxt), a neuropeptide produced in the hypothalamus, is implicated in regulation of feeding. Recent studies have shown that peripheral administration of Oxt suppresses feeding and, when infused subchronically, ameliorates hyperphagic obesity. However, the route through which peripheral Oxt informs the brain is obscure. This study aimed to explore whether vagal afferents mediate the sensing and anorexigenic effect of peripherally injected Oxt in mice. Intraperitoneal Oxt injection suppressed food intake and increased c-Fos expression in nucleus tractus solitarius to which vagal afferents project. The Oxt-induced feeding suppression and c-Fos expression in nucleus tractus solitarius were blunted in mice whose vagal afferent nerves were blocked by subdiaphragmatic vagotomy or capsaicin treatment. Oxt induced membrane depolarization and increases in cytosolic Ca(2+) concentration ([Ca(2+)]i) in single vagal afferent neurons. The Oxt-induced [Ca(2+)]i increases were markedly suppressed by Oxt receptor antagonist. These Oxt-responsive neurons also responded to cholecystokinin-8 and contained cocaine- and amphetamine-regulated transcript. In obese diabetic db/db mice, leptin failed to increase, but Oxt increased [Ca(2+)]i in vagal afferent neurons, and single or subchronic infusion of Oxt decreased food intake and body weight gain. These results demonstrate that peripheral Oxt injection suppresses food intake by activating vagal afferent neurons and thereby ameliorates obesity in leptin-resistant db/db mice. The peripheral Oxt-regulated vagal afferent neuron provides a novel target for treating hyperphagia and obesity. PMID:25540101

  6. Facilitation of motor evoked potentials by somatosensory afferent stimulation.

    PubMed

    Deletis, V; Schild, J H; Berić, A; Dimitrijević, M R

    1992-10-01

    The effect of an electrically induced peripheral afferent volley upon electrical and magnetic motor evoked potentials (MEPs) from muscles of the upper and lower extremities was studied in 16 healthy volunteers. A standard conditioning-test (C-T) paradigm was employed whereby the test stimulus (transcranial electric or magnetic) was applied at random time intervals, from 10 msec prior to 90 msec after the conditioning stimulus (peripheral nerve stimulus). MEP amplitude facilitation was observed for the majority of the upper extremity muscles tested at two distinct periods, one occurring at short, and the other at long C-T intervals. This bimodal trend of MEP facilitation was found to be equally as prominent in the lower extremity muscles tested. The period of short C-T interval facilitation is consistent with modifications in the spinal excitability of the segmental motoneuron pool. On the other hand, the period of long C-T interval facilitation is suggested to be due to alterations in excitability of the motor cortex as a result of the arrival of the orthodromic sensory volley. Although most pronounced in muscles innervated by the nerve to which the conditioning stimulus was applied, this bimodal facilitatory effect was also observed in adjacent muscles not innervated by the stimulated nerve. Qualitatively, the conditioned MEPs from the upper and lower extremities responded similarly to both electrical and magnetic trans-cranial stimulation. In addition, our study demonstrates that the C-T paradigm has potential for use in the assessment of spinal and cortical sensorimotor integration by providing quantitative information which cannot be obtained through isolated assessment of sensory and/or motor pathways.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1385090

  7. Stimulation of raphe (obscurus) nucleus causes long-term potentiation of phrenic nerve activity in cat.

    PubMed

    Millhorn, D E

    1986-12-01

    1. The respiratory response, measured as integrated phrenic nerve activity, during and for up to an hour following 10 min of continuous electrical stimulation of raphe obscurus was quantitated in anaesthetized, artificially ventilated cats whose carotid sinus nerves and vagus nerves had been cut. End-tidal PCO2 and body temperature were kept constant with servocontrollers. 2. Stimulation of raphe obscurus caused a significant increase in both phrenic tidal activity and respiratory frequency that persisted following cessation of the stimulus. This persistent facilitation is referred to as 'long-term potentiation' of respiration. 3. Control stimulations in the parenchyma of the medulla oblongata failed to stimulate respiration and cause the long-term potentiation. 4. Both the direct facilitatory effects of raphe obscurus stimulation on phrenic nerve activity and the long-term potentiation of respiration following the stimulus were prevented by pre-treating cats with methysergide, a serotonin receptor antagonist. 5. The results are discussed in terms of the raphe obscurus being the potential source of the long-term potentiation of respiration that occurs following stimulation of carotid body afferents (Millhorn, Eldridge & Waldrop, 1980a, b). PMID:3114470

  8. α(5)GABA(A) receptors mediate primary afferent fiber tonic excitability in the turtle spinal cord.

    PubMed

    Loeza-Alcocer, Emanuel; Canto-Bustos, Martha; Aguilar, Justo; González-Ramírez, Ricardo; Felix, Ricardo; Delgado-Lezama, Rodolfo

    2013-11-01

    γ-Amino butyric acid (GABA) plays a key role in the regulation of central nervous system by activating synaptic and extrasynaptic GABAA receptors. It is acknowledged that extrasynaptic GABAA receptors located in the soma, dendrites, and axons may be activated tonically by low extracellular GABA concentrations. The activation of these receptors produces a persistent conductance that can hyperpolarize or depolarize nerve cells depending on the Cl(-) equilibrium potential. In an in vitro preparation of the turtle spinal cord we show that extrasynaptic α5GABAA receptors mediate the tonic state of excitability of primary afferents independently of the phasic primary afferent depolarization mediated by synaptic GABAA receptors. Blockade of α5GABAA receptors with the inverse agonist L-655,708 depressed the dorsal root reflex (DRR) without affecting the phasic increase in excitability of primary afferents. Using RT-PCR and Western blotting, we corroborated the presence of the mRNA and the α5GABAA protein in the dorsal root ganglia of the turtle spinal cord. The receptors were localized in primary afferents in dorsal root, dorsal root ganglia, and peripheral nerve terminals using immunoconfocal microscopy. Considering the implications of the DRR in neurogenic inflammation, α5GABAA receptors may serve as potential pharmacological targets for the treatment of pain. PMID:23966669

  9. Whisker-related afferents in superior colliculus.

    PubMed

    Castro-Alamancos, Manuel A; Favero, Morgana

    2016-05-01

    Rodents use their whiskers to explore the environment, and the superior colliculus is part of the neural circuits that process this sensorimotor information. Cells in the intermediate layers of the superior colliculus integrate trigeminotectal afferents from trigeminal complex and corticotectal afferents from barrel cortex. Using histological methods in mice, we found that trigeminotectal and corticotectal synapses overlap somewhat as they innervate the lower and upper portions of the intermediate granular layer, respectively. Using electrophysiological recordings and optogenetics in anesthetized mice in vivo, we showed that, similar to rats, whisker deflections produce two successive responses that are driven by trigeminotectal and corticotectal afferents. We then employed in vivo and slice experiments to characterize the response properties of these afferents. In vivo, corticotectal responses triggered by electrical stimulation of the barrel cortex evoke activity in the superior colliculus that increases with stimulus intensity and depresses with increasing frequency. In slices from adult mice, optogenetic activation of channelrhodopsin-expressing trigeminotectal and corticotectal fibers revealed that cells in the intermediate layers receive more efficacious trigeminotectal, than corticotectal, synaptic inputs. Moreover, the efficacy of trigeminotectal inputs depresses more strongly with increasing frequency than that of corticotectal inputs. The intermediate layers of superior colliculus appear to be tuned to process strong but infrequent trigeminal inputs and weak but more persistent cortical inputs, which explains features of sensory responsiveness, such as the robust rapid sensory adaptation of whisker responses in the superior colliculus. PMID:26864754

  10. Contractile properties of afferent and efferent arterioles.

    PubMed

    Ito, S; Abe, K

    1997-07-01

    1. The balance of vascular tone of the afferent and efferent arteriole is a crucial determinant of glomerular haemodynamics. Despite their intimate anatomical relationship in the juxtaglomerular apparatus, the mechanisms that regulate afferent and efferent arteriolar tone are different. 2. In the afferent arteriole, two intrinsic mechanisms, the myogenic response and macula densa-mediated tubuloglomerular feedback (TGF) play a dominant role, maintaining the glomerular filtration rate (GFR) at a constant level over a wide range of renal perfusion pressure. Studies have shown that these two mechanisms are modulated by nitric oxide (NO). In addition, an interaction between TGF and angiotensin II (AngII) seems to be essential to maintaining GFR despite large variations in daily intake of salt and water. 3. In the efferent arteriole, neither myogenic response nor TGF seems to be important, while AngII is one major factor involved in the control of vascular resistance. In addition, recent studies have provided evidence that NO and prostaglandins produced by the glomerulus may control resistance of the downstream efferent arteriole. 4. As the early segment of the efferent arteriole resides within the glomerulus, various autacoid hormones produced by the glomerulus may reach and directly act on this segment, thereby controlling the glomerular capillary pressure. Thus, it would be important to understand the differences in the mechanisms operating at the afferent and efferent arteriole, as well as their alterations in various physiological and pathological conditions. PMID:9248673

  11. Peripheral nerve conduits: technology update

    PubMed Central

    Arslantunali, D; Dursun, T; Yucel, D; Hasirci, N; Hasirci, V

    2014-01-01

    Peripheral nerve injury is a worldwide clinical problem which could lead to loss of neuronal communication along sensory and motor nerves between the central nervous system (CNS) and the peripheral organs and impairs the quality of life of a patient. The primary requirement for the treatment of complete lesions is a tension-free, end-to-end repair. When end-to-end repair is not possible, peripheral nerve grafts or nerve conduits are used. The limited availability of autografts, and drawbacks of the allografts and xenografts like immunological reactions, forced the researchers to investigate and develop alternative approaches, mainly nerve conduits. In this review, recent information on the various types of conduit materials (made of biological and synthetic polymers) and designs (tubular, fibrous, and matrix type) are being presented. PMID:25489251

  12. Changes in vagal afferent drive alter tracheobronchial coughing in anesthetized cats.

    PubMed

    Simera, Michal; Poliacek, Ivan; Veternik, Marcel; Babalova, Lucia; Kotmanova, Zuzana; Jakus, Jan

    2016-08-01

    Unilateral cooling of the vagus nerve (<5°C, blocking mainly conductivity of myelinated fibers) and unilateral vagotomy were employed to reduce cough afferent drive in order to evaluate the effects of these interventions on the temporal features of the cough reflex. Twenty pentobarbitone anesthetized, spontaneously breathing cats were used. Cough was induced by mechanical stimulation of the tracheobronchial airways. The number of coughs during vagal cooling was significantly decreased (p<0.001). Inspiratory cough efforts were reduced by approximately 30% (p<0.001) and expiratory motor drive by more than 80% (p<0.001). Temporal analysis showed prolonged inspiratory and expiratory phases, the total cycle duration, its active portion, and the interval between maxima of the diaphragm and the abdominal activity during coughing (p<0.001). There was no significant difference in the average effects on the cough reflex between cooling of the left or the right vagus nerve. Compared to control, vagal cooling produced no significant difference in heart rate and mean arterial blood pressure (p>0.05), however, cold block of vagal conduction reduced respiratory rate (p<0.001). Unilateral vagotomy significantly reduced cough number, cough-related diaphragmatic activity, and relative values of maximum expiratory esophageal pressure (all p<0.05). Our results indicate that reduced cough afferent drive (lower responsiveness) markedly attenuates the motor drive to respiratory pump muscles during coughing and alters cough temporal features. Differences in the effects of unilateral vagal cooling and vagotomy on coughing support an inhibitory role of sensory afferents that are relatively unaffected by cooling of the vagus nerve to 5°C on mechanically induced cough. PMID:27184303

  13. Improved bladder emptying in urinary retention by electrical stimulation of pudendal afferents

    NASA Astrophysics Data System (ADS)

    Peng, Chih-Wei; Chen, Jia-Jin Jason; Cheng, Chen-Li; Grill, Warren M.

    2008-06-01

    Urinary retention is the inability to empty the bladder completely, and may result from bladder hypocontractility, increases in outlet resistance or both. Chronic urinary retention can lead to several urological complications and is often refractory to pharmacologic, behavioral and surgical treatments. We sought to determine whether electrical stimulation of sensory fibers in the pudendal nerve could engage an augmenting reflex and thereby improve bladder emptying in an animal model of urinary retention. We measured the efficiency of bladder emptying with and without concomitant electrical stimulation of pudendal nerve afferents in urethane-anesthetized rats. Voiding efficiency (VE = voided volume/initial volume) was reduced from 72 ± 7% to 29 ± 7% following unilateral transection of the sensory branch of the pudendal nerve (UST) and from 70 ± 5% to 18 ± 4% following bilateral transection (BST). Unilateral electrical stimulation of the proximal transected sensory pudendal nerve during distention-evoked voiding contractions significantly improved VE. Low-intensity stimulation at frequencies of 1-50 Hz increased VE to 40-51% following UST and to 39-49% following BST, while high-intensity stimulation was ineffective at increasing VE. The increase in VE was mediated by increases in the duration of distention-evoked voiding bladder contractions, rather than increases in contraction amplitude. These results are consistent with an essential role for pudendal sensory feedback in efficient bladder emptying, and raise the possibility that electrical activation of pudendal nerve afferents may provide a new approach to restore efficient bladder emptying in persons with urinary retention.

  14. Nerve biopsy

    MedlinePlus

    ... Loss of axon tissue Metabolic neuropathies Necrotizing vasculitis Sarcoidosis Risks Allergic reaction to the local anesthetic Discomfort ... Neurosarcoidosis Peripheral neuropathy Primary amyloidosis Radial nerve dysfunction Sarcoidosis Tibial nerve dysfunction Update Date 6/1/2015 ...

  15. Nerve conduction

    MedlinePlus Videos and Cool Tools

    ... the spinal cord to muscles and sensory receptors. A peripheral nerve is composed of nerve bundles (fascicles) ... two neurons, it must first be converted to a chemical signal, which then crosses a space of ...

  16. Pain processing by spinal microcircuits: afferent combinatorics.

    PubMed

    Prescott, Steven A; Ratté, Stéphanie

    2012-08-01

    Pain, itch, heat, cold, and touch represent different percepts arising from somatosensory input. How stimuli give rise to these percepts has been debated for over a century. Recent work supports the view that primary afferents are highly specialized to transduce and encode specific stimulus modalities. However, cross-modal interactions (e.g. inhibition or exacerbation of pain by touch) support convergence rather than specificity in central circuits. We outline how peripheral specialization together with central convergence could enable spinal microcircuits to combine inputs from distinctly specialized, co-activated afferents and to modulate the output signals thus formed through computations like normalization. These issues will be discussed alongside recent advances in our understanding of microcircuitry in the superficial dorsal horn. PMID:22409855

  17. Three-dimensional Reconstruction of Peripheral Nerve Internal Fascicular Groups

    PubMed Central

    Zhong, Yingchun; Wang, Liping; Dong, Jianghui; Zhang, Yi; Luo, Peng; Qi, Jian; Liu, Xiaolin; Xian, Cory J.

    2015-01-01

    Peripheral nerves are important pathways for receiving afferent sensory impulses and sending out efferent motor instructions, as carried out by sensory nerve fibers and motor nerve fibers. It has remained a great challenge to functionally reconnect nerve internal fiber bundles (or fascicles) in nerve repair. One possible solution may be to establish a 3D nerve fascicle visualization system. This study described the key technology of 3D peripheral nerve fascicle reconstruction. Firstly, fixed nerve segments were embedded with position lines, cryostat-sectioned continuously, stained and imaged histologically. Position line cross-sections were identified using a trained support vector machine method, and the coordinates of their central pixels were obtained. Then, nerve section images were registered using the bilinear method, and edges of fascicles were extracted using an improved gradient vector flow snake method. Subsequently, fascicle types were identified automatically using the multi-directional gradient and second-order gradient method. Finally, a 3D virtual model of internal fascicles was obtained after section images were processed. This technique was successfully applied for 3D reconstruction for the median nerve of the hand-wrist and cubital fossa regions and the gastrocnemius nerve. This nerve internal fascicle 3D reconstruction technology would be helpful for aiding peripheral nerve repair and virtual surgery. PMID:26596642

  18. Intensity and frequency dependence of laryngeal afferent inputs to respiratory hypoglossal motoneurons.

    PubMed

    Mifflin, S W

    1997-12-01

    Inspiratory hypoglossal motoneurons (IHMs) mediate contraction of the genioglossus muscle and contribute to the regulation of upper airway patency. Intracellular recordings were obtained from antidromically identified IHMs in anesthetized, vagotomized cats, and IHM responses to electrical activation of superior laryngeal nerve (SLN) afferent fibers at various frequencies and intensities were examined. SLN stimulus frequencies <2 Hz evoked an excitatory-inhibitory postsynaptic potential (EPSP-IPSP) sequence or only an IPSP in most IHMs that did not change in amplitude as the stimulus was maintained. During sustained stimulus frequencies of 5-10 Hz, there was a reduction in the amplitude of SLN-evoked IPSPs with time with variable changes in the EPSP. At stimulus frequencies >25 Hz, the amplitude of EPSPs and IPSPs was reduced over time. At a given stimulus frequency, increasing stimulus intensity enhanced the decay of the SLN-evoked postsynaptic potentials (PSPs). Frequency-dependent attenuation of SLN inputs to IHMs also occurred in newborn kittens. These results suggest that activation of SLN afferents evokes different PSP responses in IHMs depending on the stimulus frequency. At intermediate frequencies, inhibitory inputs are selectively filtered so that excitatory inputs predominate. At higher frequencies there was no discernible SLN-evoked PSP temporally locked to the SLN stimuli. Alterations in SLN-evoked PSPs could play a role in the coordination of genioglossal contraction during respiration, swallowing, and other complex motor acts where laryngeal afferents are activated. PMID:9390960

  19. Contribution of vagal afferents to respiratory reflexes evoked by acute inhalation of ozone in dogs

    SciTech Connect

    Schelegle, E.S.; Carl, M.L.; Coleridge, H.M.; Coleridge, J.C.; Green, J.F. )

    1993-05-01

    Acute inhalation of ozone induces vagally mediated rapid shallow breathing and bronchoconstriction. In spontaneously breathing anesthetized dogs, we attempted to determine whether afferent vagal C-fibers in the lower airways contributed to these responses. Dogs inhaled 3 ppm ozone for 40-70 min into the lower trachea while cervical vagal temperature was maintained successively at 37, 7, and 0 degrees C. At 37 degrees C, addition of ozone to the inspired air decreased tidal volume and dynamic lung compliance and increased breathing frequency, total lung resistance, and tracheal smooth muscle tension. Ozone still evoked significant effects when conduction in myelinated vagal axons was blocked selectively by cooling the nerves to 7 degrees C. Ozone-induced effects were largely abolished when nonmyelinated vagal axons were blocked by cooling to 0 degree C, breathing during ozone inhalation at 0 degree C being generally similar to that during air breathing at 0 degree C, except that minute volume and inspiratory flow were higher. We conclude that afferent vagal C-fibers in the lower airways make a major contribution to the acute respiratory effects of ozone and that nonvagal afferents contribute to the effects that survive vagal blockade.

  20. Spatial convergence and divergence between cutaneous afferent axons and dorsal horn cells are not constant.

    PubMed

    Brown, P B; Harton, P; Millecchia, R; Lawson, J; Kunjara-Na-Ayudhya, T; Stephens, S; Miller, M A; Hicks, L; Culberson, J

    2000-05-01

    We have proposed a quantitative model of the development of dorsal horn cell receptive fields (RFs) and somatotopic organization (Brown et al. [1997] Somatosens. Motor Res. 14:93-106). One component of that model is a hypothesis that convergence and divergence of connections between low-threshold primary afferent mechanoreceptive axons and dorsal horn cells are invariant over skin location and dorsal horn location. The more limited, and more easily tested, hypothesis that spatial convergence and divergence between cutaneous mechanoreceptors and dorsal horn cell are constant was examined. Spatial divergence is the number of dorsal horn cells whose RFs overlap the RF center of a primary afferent, and spatial convergence is the number of afferent RF centers that lie within the RF of a dorsal horn cell. Innervation density was determined as a function of location on the hindlimb by using peripheral nerve recording and axon counting. A descriptive model of dorsal horn cell receptive fields (Brown et al. [1998] J. Neurophysiol. 31:833-848) was used to simulate RFs of the entire dorsal horn cell population in order to estimate RF area and map scale as a function of location on the hindlimb. Previously reported correlations among innervation density, map scale, and RF size were confirmed. However, these correlations were not linear. The hypothesis that spatial convergence and divergence are constant was rejected. The previously proposed model of development of dorsal horn cell somatotopy and RF geometries must be revised to take variable spatial convergence and divergence into account. PMID:10754502

  1. A quantitative study of cutaneous receptors and afferent fibres in the cat and rabbit

    PubMed Central

    Brown, A. G.; Iggo, A.

    1967-01-01

    1. The discharge in myelinated afferent fibres innervating hairs in anaesthetized cats and rabbits, dissected from the saphenous nerve, was recorded during controlled movements of the hairs. 2. Three types of rapidly adapting afferent unit were found and they innervated three kinds of hair follicle—down hair, guard hair and tylotrich. 3. The down hair units had low thresholds (critical slopes) and some of the guard hairs had the highest thresholds and least sensitivity to displacement. 4. There was a good fit to a power function for the relation between velocity of displacement of a hair and the frequency of discharge in the corresponding afferent fibre. 5. It is concluded that the rapidly adapting hair follicle receptors can function as efficient exact movement detectors. 6. Tylotrich follicles were often associated with touch corpuscles, but there was independent innervation of the rapidly adapting tylotrich follicle receptors and the slowly adapting touch corpuscle receptors. 7. The conduction velocities of large populations of myelinated cutaneous axons innervating cutaneous mechanoreceptors were measured in cats and rabbits. PMID:16992307

  2. In pursuit of P2X3 antagonists: novel therapeutics for chronic pain and afferent sensitization.

    PubMed

    Ford, Anthony P

    2012-02-01

    a realistic chance that this novel mechanism to inhibit afferent nerve sensitization may find its place in the sun and bring some merciful relief to the torment of persistent discomfort and pain. The development philosophy at Afferent is to conduct proof of concept patient studies and best identify target patient groups that may benefit from this new intervention. PMID:22095157

  3. Ginger and Its Pungent Constituents Non-Competitively Inhibit Serotonin Currents on Visceral Afferent Neurons

    PubMed Central

    Jin, Zhenhua; Lee, Goeun; Kim, Sojin; Park, Cheung-Seog; Park, Yong Seek

    2014-01-01

    Nausea and emesis are a major side effect and obstacle for chemotherapy in cancer patients. Employ of antiemetic drugs help to suppress chemotherapy-induced emesis in some patients but not all patients. Ginger, an herbal medicine, has been traditionally used to treat various kinds of diseases including gastrointestinal symptoms. Ginger is effective in alleviating nausea and emesis, particularly, for cytotoxic chemotherapy drug-induced emesis. Ginger-mediated antiemetic effect has been attributed to its pungent constituents-mediated inhibition of serotonin (5-HT) receptor activity but its cellular mechanism of action is still unclear. Emetogenic chemotherapy drugs increase 5-HT concentration and activate visceral vagal afferent nerve activity. Thus, 5-HT mediated vagal afferent activation is essential to provoke emesis during chemotherapy. In this experiment, water extract of ginger and its three major pungent constituent's effect on 5-HT-evoked responses were tested on acutely dispersed visceral afferent neurons with patch-clamp methods. The ginger extract has similar effects to antiemetic drug ondansetron by blocking 5-HT-evoked responses. Pungent constituents of the ginger, [6]-shogaol, [6]-gingerol, and zingerone inhibited 5-HT responses in a dose dependent manner. The order of inhibitory potency for these compounds were [6]-shogaol>[6]-gingerol>zingerone. Unlike well-known competitive 5-HT3 receptor antagonist ondansetron, all tested ginger constituents acted as non-competitive antagonist. Our results imply that ginger and its pungent constituents exert antiemetic effects by blocking 5-HT-induced emetic signal transmission in vagal afferent neurons. PMID:24757377

  4. Ginger and its pungent constituents non-competitively inhibit serotonin currents on visceral afferent neurons.

    PubMed

    Jin, Zhenhua; Lee, Goeun; Kim, Sojin; Park, Cheung-Seog; Park, Yong Seek; Jin, Young-Ho

    2014-04-01

    Nausea and emesis are a major side effect and obstacle for chemotherapy in cancer patients. Employ of antiemetic drugs help to suppress chemotherapy-induced emesis in some patients but not all patients. Ginger, an herbal medicine, has been traditionally used to treat various kinds of diseases including gastrointestinal symptoms. Ginger is effective in alleviating nausea and emesis, particularly, for cytotoxic chemotherapy drug-induced emesis. Ginger-mediated antiemetic effect has been attributed to its pungent constituents-mediated inhibition of serotonin (5-HT) receptor activity but its cellular mechanism of action is still unclear. Emetogenic chemotherapy drugs increase 5-HT concentration and activate visceral vagal afferent nerve activity. Thus, 5-HT mediated vagal afferent activation is essential to provoke emesis during chemotherapy. In this experiment, water extract of ginger and its three major pungent constituent's effect on 5-HT-evoked responses were tested on acutely dispersed visceral afferent neurons with patch-clamp methods. The ginger extract has similar effects to antiemetic drug ondansetron by blocking 5-HT-evoked responses. Pungent constituents of the ginger, [6]-shogaol, [6]-gingerol, and zingerone inhibited 5-HT responses in a dose dependent manner. The order of inhibitory potency for these compounds were [6]-shogaol>[6]-gingerol>zingerone. Unlike well-known competitive 5-HT3 receptor antagonist ondansetron, all tested ginger constituents acted as non-competitive antagonist. Our results imply that ginger and its pungent constituents exert antiemetic effects by blocking 5-HT-induced emetic signal transmission in vagal afferent neurons. PMID:24757377

  5. Bursting stimulation of proximal urethral afferents improves bladder pressures and voiding

    PubMed Central

    Bruns, Tim M; Bhadra, Narendra

    2012-01-01

    Reflex bladder excitation has been evoked via pudendal nerve, pudendal nerve branch and intraurethral stimulation; however, afferent-evoked bladder emptying has been less efficient than direct activation of the bladder via sacral root stimulation. A stimulation method that improves activation of the urethra–bladder excitatory reflex with minimal sphincter recruitment may lead to improved bladder emptying. Fine wire electrodes were placed in the wall of the urethra in five cats. Placement of electrodes near the proximal urethra evoked bladder contractions with minimal sphincter activation. On these electrodes, lower frequency burst-patterned stimuli evoked greater bladder voiding efficiencies (71.2 ± 27.8%) than other stimulus patterns on the same electrodes (50.4 ± 41.5%, p > 0.05) or any stimulus pattern on electrodes that elicited urethral closure (16.5 ± 12.7%, p < 0.05). Fine wire electrodes specifically targeted afferent fibers in the urethra, indicating the feasibility of clinical evaluations using the same method. This work may improve the translation of next generation neuroprostheses for bladder control. PMID:19901447

  6. Factors forming the edge of a receptive field: the presence of relatively ineffective afferent terminals.

    PubMed

    Merrill, E G; Wall, P D

    1972-11-01

    A specialized type of spinal cord cell has its cell body in lamina IV and has a small low threshold cutaneous receptive field which is remarkable for its abrupt edge. No signs could be found of a subliminal fringe to this field since its size remains fixed during wide excursions of the cell's excitability. Reversible blocking of peripheral nerves and dorsal roots showed that the afferents responsible for exciting these cells following natural stimuli, run in a restricted area of peripheral nerve and dorsal root. When the fibres necessary to sustain the natural stimulus receptive field were blocked, it was shown that other large myelinated fibres in neighbouring roots were still capable of firing the cell monosynaptically following electrical stimulation of the root or periphery although no natural stimuli were able to change the cell's excitability. It is necessary to divide the afferent synapses on such cells into a class which is highly effective in firing the cell on natural stimulation and a second class which has no effect yet detected following natural stimuli but which can fire the cell monosynaptically if synchronously activated by electrical stimulation. Suggestions are made for possible presynaptic and post-synaptic mechanisms which might divide the effect of arriving impulses into two such classes. PMID:4637631

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

    PubMed

    Cui, Jian; McQuillan, Patrick M; Blaha, Cheryl; Kunselman, Allen R; Sinoway, Lawrence I

    2012-08-15

    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 < 0.01) and more sustained MSNA and 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

  8. Afferents from Vocal Motor and Respiratory Effectors are Recruited during Vocal Production in Juvenile Songbirds

    PubMed Central

    Bottjer, Sarah W.; To, Michelle

    2012-01-01

    Learned behaviors require coordination of diverse sensory inputs with motivational and motor systems. Although mechanisms underlying vocal learning in songbirds have focused primarily on auditory inputs, it is likely that sensory inputs from vocal effectors also provide essential feedback. We investigated the role of somatosensory and respiratory inputs from vocal effectors of juvenile zebra finches (Taeniopygia guttata) during the stage of sensorimotor integration when they are learning to imitate a previously memorized tutor song. We report that song production induced expression of the immediate early gene product Fos in trigeminal regions that receive hypoglossal afferents from the tongue and syrinx (the main vocal organ). Furthermore, unilateral lesion of hypoglossal afferents greatly diminished singing-induced Fos expression on the side ipsilateral to the lesion, but not on the intact control side. In addition, unilateral lesion of the vagus reduced Fos expression in the ipsilateral nucleus of the solitary tract in singing birds. Lesion of the hypoglossal nerve to the syrinx greatly disrupted vocal behavior, whereas lesion of the hypoglossal nerve to the tongue exerted no obvious disruption and lesions of the vagus caused some alterations to song behavior. These results provide the first functional evidence that somatosensory and respiratory feedback from peripheral effectors is activated during vocal production and conveyed to brainstem regions. Such feedback is likely to play an important role in vocal learning during sensorimotor integration in juvenile birds and in maintaining stereotyped vocal behavior in adults. PMID:22875924

  9. Bursting stimulation of proximal urethral afferents improves bladder pressures and voiding

    NASA Astrophysics Data System (ADS)

    Bruns, Tim M.; Bhadra, Narendra; Gustafson, Kenneth J.

    2009-12-01

    Reflex bladder excitation has been evoked via pudendal nerve, pudendal nerve branch and intraurethral stimulation; however, afferent-evoked bladder emptying has been less efficient than direct activation of the bladder via sacral root stimulation. A stimulation method that improves activation of the urethra-bladder excitatory reflex with minimal sphincter recruitment may lead to improved bladder emptying. Fine wire electrodes were placed in the wall of the urethra in five cats. Placement of electrodes near the proximal urethra evoked bladder contractions with minimal sphincter activation. On these electrodes, lower frequency burst-patterned stimuli evoked greater bladder voiding efficiencies (71.2 ± 27.8%) than other stimulus patterns on the same electrodes (50.4 ± 41.5%, p > 0.05) or any stimulus pattern on electrodes that elicited urethral closure (16.5 ± 12.7%, p < 0.05). Fine wire electrodes specifically targeted afferent fibers in the urethra, indicating the feasibility of clinical evaluations using the same method. This work may improve the translation of next generation neuroprostheses for bladder control.

  10. Time course of post-excitatory effects separates afferent human C fibre classes.

    PubMed

    Weidner, C; Schmidt, R; Schmelz, M; Hilliges, M; Handwerker, H O; Torebjörk, H E

    2000-08-15

    1. To study post-excitatory changes of conduction velocity, action potentials were recorded from 132 unmyelinated nerve fibres (C fibres) in cutaneous fascicles of the peroneal nerve using microneurography in healthy human subjects. The 'marking' technique was used to assess responsiveness to mechanical and heat stimuli or sympathetic reflex provocation. 2. C fibres were classified into three major classes: mechano-responsive afferent (n = 76), mechano-insensitive afferent (n = 48) and sympathetic efferent C fibres (n = 8). 3. During regular stimulation at 0.25 Hz, conditioning pulses were intermittently interposed. Changes of conduction velocity were assessed for different numbers of conditioning impulses and varying interstimulus intervals (ISIs). For all three fibre classes the latency shift following conditioning pulses at an ISI of 1000 ms increased linearly with their number (n = 1, 2 and 4). However, the absolute degree of conduction velocity slowing was much higher in the 32 mechano-insensitive fibres as compared with 56 mechano-responsive or 8 sympathetic fibres. 4. Single additional pulses were interposed at different ISIs from 20 to 2000 ms. For 20 mechano-responsive fibres conduction velocity slowing increased with decreasing ISI (subnormal phase). In contrast, for 16 mechano-insensitive C fibres the conduction velocity slowing decreased with shorter ISIs, and at values lower than 417 +/- 49 ms (mean +/- s.e.m.) the conduction velocity of the conditioned action potential was faster than before (conduction velocity speeding). This supernormal phase had its maximum at 69 +/- 10 ms. 5. In this study we provide, for the first time, direct evidence of relative supernormal conduction in human mechano-insensitive C fibres. The implications for temporal coding in different afferent C fibre classes are discussed. PMID:10944181

  11. Time course of post-excitatory effects separates afferent human C fibre classes

    PubMed Central

    Weidner, C; Schmidt, R; Schmelz, M; Hilliges, M; Handwerker, H O; Torebjörk, H E

    2000-01-01

    To study post-excitatory changes of conduction velocity, action potentials were recorded from 132 unmyelinated nerve fibres (C fibres) in cutaneous fascicles of the peroneal nerve using microneurography in healthy human subjects. The ‘marking’ technique was used to assess responsiveness to mechanical and heat stimuli or sympathetic reflex provocation. C fibres were classified into three major classes: mechano-responsive afferent (n = 76), mechano-insensitive afferent (n = 48) and sympathetic efferent C fibres (n = 8). During regular stimulation at 0.25 Hz, conditioning pulses were intermittently interposed. Changes of conduction velocity were assessed for different numbers of conditioning impulses and varying interstimulus intervals (ISIs). For all three fibre classes the latency shift following conditioning pulses at an ISI of 1000 ms increased linearly with their number (n = 1, 2 and 4). However, the absolute degree of conduction velocity slowing was much higher in the 32 mechano-insensitive fibres as compared with 56 mechano-responsive or 8 sympathetic fibres. Single additional pulses were interposed at different ISIs from 20 to 2000 ms. For 20 mechano-responsive fibres conduction velocity slowing increased with decreasing ISI (subnormal phase). In contrast, for 16 mechano-insensitive C fibres the conduction velocity slowing decreased with shorter ISIs, and at values lower than 417 ± 49 ms (mean ±s.e.m.) the conduction velocity of the conditioned action potential was faster than before (conduction velocity speeding). This supernormal phase had its maximum at 69 ± 10 ms. In this study we provide, for the first time, direct evidence of relative supernormal conduction in human mechano-insensitive C fibres. The implications for temporal coding in different afferent C fibre classes are discussed. PMID:10944181

  12. An afferent explanation for sexual dimorphism in the aortic baroreflex of rat.

    PubMed

    Santa Cruz Chavez, Grace C; Li, Bai-Yan; Glazebrook, Patricia A; Kunze, Diana L; Schild, John H

    2014-09-15

    Sex differences in baroreflex (BRx) function are well documented. Hormones likely contribute to this dimorphism, but many functional aspects remain unresolved. Our lab has been investigating a subset of vagal sensory neurons that constitute nearly 50% of the total population of myelinated aortic baroreceptors (BR) in female rats but less than 2% in male rats. Termed "Ah," this unique phenotype has many of the nonoverlapping electrophysiological properties and chemical sensitivities of both myelinated A-type and unmyelinated C-type BR afferents. In this study, we utilize three distinct experimental protocols to determine if Ah-type barosensory afferents underlie, at least in part, the sex-related differences in BRx function. Electron microscopy of the aortic depressor nerve (ADN) revealed that female rats have less myelin (P < 0.03) and a smaller fiber cross-sectional area (P < 0.05) per BR fiber than male rats. Electrical stimulation of the ADN evoked compound action potentials and nerve conduction profiles that were markedly different (P < 0.01, n = 7 females and n = 9 males). Selective activation of ADN myelinated fibers evoked a BRx-mediated depressor response that was 3-7 times greater in female (n = 16) than in male (n = 17) rats. Interestingly, the most striking hemodynamic difference was functionally dependent upon the rate of myelinated barosensory fiber activation. Only 5-10 Hz of stimulation evoked a rapid, 20- to 30-mmHg reduction in arterial pressure of female rats, whereas rates of 50 Hz or higher were required to elicit a comparable depressor response from male rats. Collectively, our experimental results are suggestive of an alternative myelinated baroreceptor afferent pathway in females that may account for, at least in part, the noted sex-related differences in autonomic control of cardiovascular function. PMID:25038145

  13. Afferent innervation patterns of the saccule in pigeons

    NASA Technical Reports Server (NTRS)

    Zakir, M.; Huss, D.; Dickman, J. D.

    2003-01-01

    The innervation patterns of vestibular saccular afferents were quantitatively investigated in pigeons using biotinylated dextran amine as a neural tracer and three-dimensional computer reconstruction. Type I hair cells were found throughout a large portion of the macula, with the highest density observed in the striola. Type II hair cells were located throughout the macula, with the highest density in the extrastriola. Three classes of afferent innervation patterns were observed, including calyx, dimorph, and bouton units, with 137 afferents being anatomically reconstructed and used for quantitative comparisons. Calyx afferents were located primarily in the striola, innervated a number of type I hair cells, and had small innervation areas. Most calyx afferent terminal fields were oriented parallel to the anterior-posterior axis and the morphological polarization reversal line. Dimorph afferents were located throughout the macula, contained fewer type I hair cells in a calyceal terminal than calyx afferents and had medium sized innervation areas. Bouton afferents were restricted to the extrastriola, with multi-branching fibers and large innervation areas. Most of the dimorph and bouton afferents had innervation fields that were oriented dorso-ventrally but were parallel to the neighboring reversal line. The organizational morphology of the saccule was found to be distinctly different from that of the avian utricle or lagena otolith organs and appears to represent a receptor organ undergoing evolutionary adaptation toward sensing linear motion in terrestrial and aerial species.

  14. Dynamic mechanical allodynia in humans is not mediated by a central presynaptic interaction of A beta-mechanoreceptive and nociceptive C-afferents.

    PubMed

    Wasner, G; Baron, R; Jänig, W

    1999-02-01

    Recently, Cervero and Laird (NeuroReport, 7 (1996) 526-528; Pain, 68 (1996) 13-23) proposed a new pathophysiological mechanism of dynamic mechanical allodynia in skin. Using the capsaicin pain model in humans, they showed that light mechanical stimulation within an area of secondary mechanical allodynia induces vasodilatation measured by laser-Doppler flowmetry. They suggested that the low-threshold A beta-mechanoreceptive fibres depolarize the central terminals of nociceptive primary afferent neurons via interneurons. Consequently, the vasodilatation is produced by impulses conducted antidromically in nociceptive C-axons. The allodynia was proposed to result from depolarization of central terminals of primary afferent neurons with C-fibres with activation of nociceptive dorsal horn neurons. In order to extend these findings, we used the same experimental approach but additionally stimulated the A beta-fibres electrically to evoke secondary allodynia during simultaneous monitoring skin blood flow. Twenty microlitres of a 0.5% capsaicin solution was injected intradermally into the dorsal forearm. Skin sites that demonstrated dynamic mechanical allodynia but were not located within the area of primary hyperalgesia and flare were investigated. Ten mm away from a laser-Doppler probe, dynamic mechanical allodynia was induced for 1 min (1) by moving a cotton swab and (2) by electrically stimulating the afferent nerve endings transdermally. Increasing stimulus intensities were applied (0.3-4 mA, 40 Hz, pulse duration 0.2 ms). After intracutaneous injection of capsaicin, light mechanical stimulation elicited a burning painful sensation (numeric analogue scale (NAS) 1.5-3) and concomitant movement artefacts at the laser signal. Antidromic vasodilatation was never observed. In this area of dynamic allodynia, electrical stimulation at stimulus intensities that were not painful before capsaicin injection (A beta-stimulation) was now able to elicit a burning painful sensation

  15. Amniotic membrane covering for facial nerve repair☆

    PubMed Central

    Karaman, Murat; Tuncel, Arzu; Sheidaei, Shahrouz; Şenol, Mehmet Güney; Karabulut, Murat Hakan; Deveci, Ildem; Karaman, Nihan

    2013-01-01

    Amniotic membranes have been widely used in ophthalmology and skin injury repair because of their anti-inflammatory properties. In this study, we measured therapeutic efficacy and determined if amniotic membranes could be used for facial nerve repair. The facial nerves of eight rats were dissected and end-to-end anastomosis was performed. Amniotic membranes were covered on the anastomosis sites in four rats. Electromyography results showed that, at the end of the 3rd and 8th weeks after amniotic membrane covering, the latency values of the facial nerves covered by amniotic membranes were significantly shortened and the amplitude values were significantly increased. Compared with simple facial nerve anastomosis, after histopathological examination, facial nerve anastomosed with amniotic membrane showed better continuity, milder inflammatory reactions, and more satisfactory nerve conduction. These findings suggest that amniotic membrane covering has great potential in facial nerve repair. PMID:25206390

  16. Perineural capsaicin induces the uptake and transganglionic transport of choleratoxin B subunit by nociceptive C-fiber primary afferent neurons.

    PubMed

    Oszlács, O; Jancsó, G; Kis, G; Dux, M; Sántha, P

    2015-12-17

    The distribution of spinal primary afferent terminals labeled transganglionically with the choleratoxin B subunit (CTB) or its conjugates changes profoundly after perineural treatment with capsaicin. Injection of CTB conjugated with horseradish peroxidase (HRP) into an intact nerve labels somatotopically related areas in the ipsilateral dorsal horn with the exceptions of the marginal zone and the substantia gelatinosa, whereas injection of this tracer into a capsaicin-pretreated nerve also results in massive labeling of these most superficial layers of the dorsal horn. The present study was initiated to clarify the role of C-fiber primary afferent neurons in this phenomenon. In L5 dorsal root ganglia, analysis of the size frequency distribution of neurons labeled after injection of CTB-HRP into the ipsilateral sciatic nerve treated previously with capsaicin or resiniferatoxin revealed a significant increase in the proportion of small neurons. In the spinal dorsal horn, capsaicin or resiniferatoxin pretreatment resulted in intense CTB-HRP labeling of the marginal zone and the substantia gelatinosa. Electron microscopic histochemistry disclosed a dramatic, ∼10-fold increase in the proportion of CTB-HRP-labeled unmyelinated dorsal root axons following perineural capsaicin or resiniferatoxin. The present results indicate that CTB-HRP labeling of C-fiber dorsal root ganglion neurons and their central terminals after perineural treatment with vanilloid compounds may be explained by their phenotypic switch rather than a sprouting response of thick myelinated spinal afferents which, in an intact nerve, can be labeled selectively with CTB-HRP. The findings also suggest a role for GM1 ganglioside in the modulation of nociceptor function and pain. PMID:26520849

  17. Effectively Axonal-supercharged Interpositional Jump-Graft with an Artificial Nerve Conduit for Rat Facial Nerve Paralysis

    PubMed Central

    Niimi, Yosuke; Takeuchi, Yuichi; Sasaki, Ryo; Watanabe, Yorikatsu; Yamato, Masayuki; Miyata, Mariko; Sakurai, Hiroyuki

    2015-01-01

    Background: Interpositional jump graft (IPJG) is a nerve graft axonally supercharged from the hypoglossal nerve. However, for using the technique, an autologous nerve, which should contain the great auricular and sural nerves, must be obtained. Depending on the donor site, unavoidable issues such as nerve disorders and postoperative scarring may appear. To reduce the issues, in this study, the authors developed an end-to-side neurorrhaphy technique with the recipient nerve and an artificial nerve conduit and investigated the efficacy of an IPJG with an artificial nerve conduit in a rat facial nerve paresis model. Methods: A ligature clip was used to crush the facial nerve trunk, thereby creating a partial facial nerve paresis model. An artificial nerve conduit was then prepared with a 10-mm-long silicone tube containing 10 μL type I collagen and used to create an IPJG between the facial nerve trunk and the hypoglossal nerve (the silicone tube group). Thirteen weeks after the surgery, the outcome was histologically and physiologically compared with conventional IPJG with autograft using the great auricular nerve. Results: Retrograde tracer test confirmed a double innervation by the facial and hypoglossal nerve nuclei. In the autograft and silicone tube groups, the regeneration of myelinated axons was observed. Conclusion: In this study, the authors successfully developed an end-to-side neurorrhaphy technique with the recipient nerve and an artificial nerve conduit, and revealed that an IPJG in the conduit was effective in the rat facial nerve paresis model. PMID:26180717

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

    PubMed

    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. PMID:27052583

  19. Angiotensin AT1 receptor-mediated excitation of rat carotid body chemoreceptor afferent activity.

    PubMed

    Allen, A M

    1998-08-01

    1. A high density of angiotensin II receptors was observed in the rat carotid body by in vitro autoradiography employing 125I-[Sar1, Ile8]-angiotensin II as radioligand. Displacement studies demonstrated that the receptors were of the AT1 subtype. 2. The binding pattern indicated that the AT1 receptors occurred over clumps of glomus cells, the principal chemoreceptor cell of the carotid body. Selective lesions of the sympathetic or afferent innervation of the carotid body had little effect on the density of receptor binding, demonstrating that the majority of AT1 receptors were intrinsic to the glomus cells. 3. To determine the direct effect of angiotensin II on chemoreceptor function, without the confounding effects of the vasoconstrictor action of angiotensin II, carotid sinus nerve activity was recorded from the isolated carotid body in vitro. The carotid body was superfused with Tyrode solution saturated with carbogen (95 % O2, 5 % CO2), maintained at 36 C, and multi-unit nerve activity recorded with a suction electrode. 4. Angiotensin II elicited a dose-dependent excitation of carotid sinus nerve activity (maximum increase of 36 +/- 11 % with 10 nM angiotensin II) with a threshold concentration of 1 nM. The response was blocked by the addition of an AT1 receptor antagonist, losartan (1 microM), but not by the addition of an AT2 receptor antagonist, PD123319 (1 microM). 5. In approximately 50 % of experiments the excitation was preceded by an inhibition of activity (maximum decrease of 24 +/- 8 % with 10 nM angiotensin II). This inhibitory response was markedly attenuated by losartan but not affected by PD123319. 6. These observations demonstrate that angiotensin II, acting through AT1 receptors located on glomus cells in the carotid body, can directly alter carotid chemoreceptor afferent activity. This provides a means whereby humoral information about fluid and electrolyte homeostasis might influence control of cardiorespiratory function. PMID:9660892

  20. Angiotensin AT1 receptor-mediated excitation of rat carotid body chemoreceptor afferent activity

    PubMed Central

    Allen, A M

    1998-01-01

    A high density of angiotensin II receptors was observed in the rat carotid body by in vitro autoradiography employing 125I-[Sar1,Ile8]-angiotensin II as radioligand. Displacement studies demonstrated that the receptors were of the AT1 subtype.The binding pattern indicated that the AT1 receptors occurred over clumps of glomus cells, the principal chemoreceptor cell of the carotid body. Selective lesions of the sympathetic or afferent innervation of the carotid body had little effect on the density of receptor binding, demonstrating that the majority of AT1 receptors were intrinsic to the glomus cells.To determine the direct effect of angiotensin II on chemoreceptor function, without the confounding effects of the vasoconstrictor action of angiotensin II, carotid sinus nerve activity was recorded from the isolated carotid body in vitro. The carotid body was superfused with Tyrode solution saturated with carbogen (95% O2, 5% CO2), maintained at 36 °C, and multi-unit nerve activity recorded with a suction electrode.Angiotensin II elicited a dose-dependent excitation of carotid sinus nerve activity (maximum increase of 36 ± 11% with 10 nm angiotensin II) with a threshold concentration of 1 nm. The response was blocked by the addition of an AT1 receptor antagonist, losartan (1 μm), but not by the addition of an AT2 receptor antagonist, PD123319 (1 μm).In approximately 50% of experiments the excitation was preceded by an inhibition of activity (maximum decrease of 24 ± 8% with 10 nm angiotensin II). This inhibitory response was markedly attenuated by losartan but not affected by PD123319.These observations demonstrate that angiotensin II, acting through AT1 receptors located on glomus cells in the carotid body, can directly alter carotid chemoreceptor afferent activity. This provides a means whereby humoral information about fluid and electrolyte homeostasis might influence control of cardiorespiratory function. PMID:9660892

  1. Evidence that antidromically stimulated vagal afferents activate inhibitory neurones innervating guinea-pig trachealis.

    PubMed Central

    Canning, B J; Undem, B J

    1994-01-01

    1. We recently described a capsaicin-sensitive vagal pathway mediating non-adrenergic, non-cholinergic (NANC) relaxations of an isolated, innervated rostral guinea-pig tracheal preparation. These afferent fibres are carried by the superior laryngeal nerves and relaxations elicited by their activation are insensitive to autonomic ganglion blockers such as hexamethonium. In the present study this vagal relaxant pathway was further characterized. 2. Relaxations of the trachealis elicited by electrical stimulation of capsaicin-sensitive vagal afferents were mimicked by bath application of capsaicin. Relaxations elicited by both methods were abolished when the tissue between the trachea and the adjacent oesophagus was disrupted. Indeed, separating the trachea from the oesophagus uncovered a contractile effect of capsaicin administration on the trachealis. 3. Capsaicin-induced, oesophagus-dependent relaxations of the trachealis were blocked by pretreatment with the fast sodium channel blocker tetrodotoxin (TTX). By contrast, capsaicin-induced contractions of the trachealis (obtained in the absence of the oesophagus) were unaffected by tetrodotoxin. 4. Substance P, neurokinin A (NKA) and neurokinin B (NKB) also elicited NANC relaxations of precontracted trachealis that were abolished by separating the trachea from the oesophagus or by TTX pretreatment. Like capsaicin, the tachykinins elicited only contractions of the trachealis following TTX pretreatment or separation of the trachea from the adjacent oesophagus. 5. Relaxations elicited by stimulation of the capsaicin-sensitive nerves were unaffected by a concentration of the tachykinin NK2 receptor-selective antagonist, SR 48968, that is selective for NK2 receptor blockade and were not mimicked by the NK2 receptor-selective agonist [beta-Ala8]-NKA(4-10). This suggests that NK2 receptors are not responsible for these relaxations. By contrast, the NK3 receptor-selective agonist, senktide analogue, and the NK1 receptor

  2. Response properties of pigeon otolith afferents to linear acceleration

    NASA Technical Reports Server (NTRS)

    Si, X.; Angelaki, D. E.; Dickman, J. D.

    1997-01-01

    In the present study, the sensitivity to sinusoidal linear accelerations in the plane of the utricular macula was tested in afferents. The head orientation relative to the translation axis was varied in order to determine the head position that elicited the maximal and minimal responses for each afferent. The response gain and phase values obtained to 0.5-Hz and 2-Hz linear acceleration stimuli were then plotted as a function of head orientation and a modified cosine function was fit to the data. From the best-fit cosine function, the predicted head orientations that would produce the maximal and minimal response gains were estimated. The estimated maximum response gains to linear acceleration in the utricular plane for the afferents varied between 75 and 1420 spikes s-1 g-1. The mean maximal gains for all afferents to 0.5-Hz and 2-Hz sinusoidal linear acceleration stimuli were 282 and 367 spikes s-1 g-1, respectively. The minimal response gains were essentially zero for most units. The response phases always led linear acceleration and remained constant for each afferent, regardless of head orientation. These response characteristics indicate that otolith afferents are cosine tuned and behave as one-dimensional linear accelerometers. The directions of maximal sensitivity to linear acceleration for the afferents varied throughout the plane of the utricle; however, most vectors were directed out of the opposite ear near the interaural axis. The response dynamics of the afferents were tested using stimulus frequencies ranging between 0.25 Hz and 10 Hz (0.1 g peak acceleration). Across stimulus frequencies, most afferents had increasing gains and constant phase values. These dynamic properties for individual afferents were fit with a simple transfer function that included three parameters: a mechanical time constant, a gain constant, and a fractional order distributed adaptation operator.

  3. Effects of changing skin mechanics on the differential sensitivity to surface compliance by tactile afferents in the human finger pad.

    PubMed

    Hudson, Kathryn M; Condon, Melia; Ackerley, Rochelle; McGlone, Francis; Olausson, Håkan; Macefield, Vaughan G; Birznieks, Ingvars

    2015-10-01

    It is not known how changes in skin mechanics affect the responses of cutaneous mechanoreceptors in the finger pads to compression forces. We used venous occlusion to change the stiffness of the fingers and investigated whether this influenced the firing of low-threshold mechanoreceptors to surfaces of differing stiffness. Unitary recordings were made from 10 slowly adapting type I (SAI), 10 fast adapting type I (FAI) and 9 slowly adapting type II (SAII) units via tungsten microelectrodes inserted into the median nerve at the wrist. A servo-controlled stimulator applied ramp-and-hold forces (1, 2, and 4 N) at a constant loading and unloading rate (2 N/s) via a flat 2.5-cm-diameter silicone disk over the center of the finger pad. Nine silicone disks (objects), varying in compliance, were used. Venous occlusion, produced by inflating a sphygmomanometer cuff around the upper arm to 40 ± 5 mmHg, was used to induce swelling of the fingers and increase the compliance of the finger pulp. Venous occlusion had no effect on the firing rates of the SAI afferents, nor on the slopes of the relationship between mean firing rate and object compliance at each amplitude, but did significantly reduce the slopes for the FAI afferents. Although the SAII afferents possess a poor capacity to encode changes in object compliance, mean firing rates were significantly lower during venous occlusion. The finding that venous occlusion had no effect on the firing properties of SAI afferents indicates that these afferents preserve their capacity to encode changes in object compliance, despite changes in skin mechanics. PMID:26269550

  4. Afferent hypersensitivity in a mouse model of post-inflammatory gut dysfunction: role of altered serotonin metabolism

    PubMed Central

    Keating, Christopher; Beyak, Michael; Foley, Stephen; Singh, Gulzar; Marsden, Charles; Spiller, Robin; Grundy, David

    2008-01-01

    Visceral hypersensitivity is an important clinical feature associated with irritable bowel syndrome which in some patients has been linked to prior infection. Here we employ an animal model in which transient infection leads to persistent gut dysfunction to investigate the role of altered 5-HT metabolism upon afferent mechanosensensitivity in the post-infected gut. Jejunal segments isolated from Trichinella spiralis-infected mice were used to assess 5-HT metabolism whilst afferent activity in T. spiralis-infected mice was studied by extracellular recordings from jejunal mesenteric afferent bundles and patch clamp recordings of isolated nodose ganglion neurons (NGNs). During acute infection, intestinal 5-HT content and release increased, 5-HT turnover decreased and afferent discharge in response to mechanical stimulation was attenuated. By day 28 post infection (PI), 5-HT turnover had normalized, but 5-HT content and release were still elevated. This was associated with afferent mechano-hypersensitivity, which persisted for 8 weeks PI and was susceptible to 5-HT3 receptor blockade. NGNs from post-infected animals were more excitable than controls but their current densities in response to 2-methyl-5-HT were lower. T. spiralis infection increased mucosal 5-HT bioavailability and affected the spontaneous activity and mechanosensitivity of gastrointestinal sensory nerves. This involved an initial hyposensitivity occurring during acute infection followed by long-term hypersensitivity in the post-infectious period that was in part mediated by 5-HT acting via 5-HT3 receptors. Functional down-regulation of 5-HT3 receptors also occurs in the post-infected animals, which may represent an adaptive response to increased mucosal 5-HT bioavailability. PMID:18653657

  5. Neuropathic Pain Phenotype Does Not Involve the NLRP3 Inflammasome and Its End Product Interleukin-1β in the Mice Spared Nerve Injury Model

    PubMed Central

    Curto-Reyes, Verdad; Kirschmann, Guylène; Pertin, Marie; Drexler, Stephan K.; Decosterd, Isabelle; Suter, Marc R.

    2015-01-01

    The NACHT, LRR and PYD domains-containing protein 3 (NLRP3) inflammasome is one of the main sources of interleukin-1β (IL-1β) and is involved in several inflammatory-related pathologies. To date, its relationship with pain has not been studied in depth. The aim of our study was to elucidate the role of NLRP3 inflammasome and IL-1β production on neuropathic pain. Results showed that basal pain sensitivity is unaltered in NLRP3-/- mice as well as responses to formalin test. Spared nerve injury (SNI) surgery induced the development of mechanical allodynia and thermal hyperalgesia in a similar way in both genotypes and did not modify mRNA levels of the NLRP3 inflammasome components in the spinal cord. Intrathecal lipopolysaccharide (LPS) injection increases apoptosis-associated speck like protein (ASC), caspase-1 and IL-1β expression in both wildtype and NLRP3-/- mice. Those data suggest that NLRP3 is not involved in neuropathic pain and also that other sources of IL-1β are implicated in neuroinflammatory responses induced by LPS. PMID:26218747

  6. Nerve Demyelination Increases Metabotropic Glutamate Receptor Subtype 5 Expression in Peripheral Painful Mononeuropathy

    PubMed Central

    Ko, Miau-Hwa; Hsieh, Yu-Lin; Hsieh, Sung-Tsang; Tseng, To-Jung

    2015-01-01

    Wallerian degeneration or nerve demyelination, arising from spinal nerve compression, is thought to bring on chronic neuropathic pain. The widely distributed metabotropic glutamate receptor subtype 5 (mGluR5) is involved in modulating nociceptive transmission. The purpose of this study was to investigate the potential effects of mGluR5 on peripheral hypersensitivities after chronic constriction injury (CCI). Sprague-Dawley rats were operated on with four loose ligatures around the sciatic nerve to induce thermal hyperalgesia and mechanical allodynia. Primary afferents in dermis after CCI exhibited progressive decreases, defined as partial cutaneous denervation; importantly, mGluR5 expressions in primary afferents were statistically increased. CCI-induced neuropathic pain behaviors through the intraplantar injections of 2-methyl-6-(phenylethynyl)-pyridine (MPEP), a selective mGluR5 antagonist, were dose-dependently attenuated. Furthermore, the most increased mGluR5 expressions in primary afferents surrounded by reactive Schwann cells were observed at the distal CCI stumps of sciatic nerves. In conclusion, these results suggest that nerve demyelination results in the increases of mGluR5 expression in injured primary afferents after CCI; and further suggest that mGluR5 represents a main therapeutic target in developing pharmacological strategies to prevent peripheral hypersensitivities. PMID:25739080

  7. Electrical potentials from the eye and optic nerve of Strombus: effects of electrical stimulation of the optic nerve.

    PubMed

    Gillary, H L

    1977-02-01

    1. Photic stimulation of the mature eye of Strombus can evoke in the optic nerve 'on' activity in numerous small afferent fibres and repetitive 'off' bursts of afferent impulses in a smaller number of larger fibres. 2. Synchronous invasion of the eye by electrically evoked impulses in small optic nerve fibres (apparently the 'on' afferents, antidromically activated) can evoke a burst of impulses in the larger 'off' fibres which propagate away from the eye. Invasion of the eye via one branch of optic nerve can evoke an answering burst in another branch. 3. Such electrically evoked bursts are similar to light-evoked 'off' bursts with respect to their impulse composition, their ability to be inhibited by illumination of the eye, and their susceptibility to MgCl2 anaesthesia. 4. Invasion of the eye by a train of repetitive electrically evoked impulses in the absence of photic stimulation can give rise to repetitive 'off' bursts as well as concomitant oscillatory potentials in the eye which are similar to those normally evoked by cessation of a photic stimulus. 5. The electrically evoked 'off' bursts appear to be caused by an excitatory rebound following the cessation of inhibitory synaptic input from photoreceptors which can be antidromically activated by electrical stimulation of the optic nerve. 6. The experimental results suggest that the rhythmic discharge of the 'off' fibres evoked by the cessation of a photic stimulus is mediated by the abrupt decrease of inhibitory synaptic input from the receptors. PMID:192827

  8. Early nerve ending rescue from oxidative damage and energy failure by L: -carnitine as post-treatment in two neurotoxic models in rat: recovery of antioxidant and reductive capacities.

    PubMed

    Elinos-Calderón, Diana; Robledo-Arratia, Yolanda; Pérez-De La Cruz, Verónica; Pedraza-Chaverrí, José; Ali, Syed F; Santamaría, Abel

    2009-08-01

    Cell rescue is a primary need during acute and chronic insults to the central nervous system. Functional preservation during the early stages of toxicity in a given degenerative event may represent a significant amelioration of detrimental processes linked to neuronal cell loss. Excitotoxicity and depleted cellular energy are toxic events leading to cell death in several neurodegenerative disorders. In this work, the effects of the well-known antioxidant and energy precursor, L: -carnitine (L: -CAR), were tested as a post-treatment in two neurotoxic models under in vitro and in vivo conditions. The experimental models tested included: (1) a typical excitotoxic and pro-oxidant inducer, quinolinic acid (QUIN); and (2) a mitochondrial energy inhibitor, 3-nitropropionic acid (3-NP). For in vitro studies, increasing concentrations of L: -CAR (10-1,000 microM) were added to the isolated brain synaptosomes at different times (1, 3 and 6 h) after the incubation with toxins (100 microM QUIN and 1 mM 3-NP), and 30 min later, lipid peroxidation (LP) and mitochondrial dysfunction (MD) were evaluated. For in vivo purposes, L: -CAR (100 mg/kg, i.p.) was given to rats either as a single administration 120 min after the intrastriatal infusion of QUIN (240 nmol/microl) or 3-NP (500 nmol/microl), or for 7 consecutive days (starting 120 min post-lesion). LP and MD were evaluated 4 h and 7 days post-lesions in isolated striatal synaptosomes. Our results show that, despite some variations depending on the toxic model tested, the time of exposure, or the biomarker evaluated, nerve ending protection can be mostly achieved by L: -CAR within the first hours after the toxic insults started, suggesting that targeting the ongoing oxidative damage and/or energy depletion during the first stages of neurotoxic events is essential to rescue nerve endings. PMID:19565224

  9. Circadian variation in gastric vagal afferent mechanosensitivity.

    PubMed

    Kentish, Stephen J; Frisby, Claudine L; Kennaway, David J; Wittert, Gary A; Page, Amanda J

    2013-12-01

    Food intake is coordinated to cellular metabolism by clock gene expression with a master clock in the suprachiasmatic nucleus synchronized by light exposure. Gastric vagal afferents play a role in regulating food intake, but it is unknown whether they exhibit circadian variation in their mechanosensitivity. We aimed to determine whether gastric vagal afferents express clock genes and whether their response to mechanical stimuli oscillates throughout the light/dark cycle. Nodose ganglia were collected from 8-week-old female C57BL/6 mice every 3 h starting at lights off (1800 h) to quantify Bmal1, Per1, Per2, and Nr1d1 mRNA by qRT-PCR. Additionally in vitro single-fiber recordings of gastric vagal mechanoreceptors were taken at all time points. Per1, Per2, Bmal1, and Nr1d1 mRNA is expressed in the nodose ganglia and levels oscillated over a 24 h period. In mice fed ad libitum, gastric content was 3 times higher at 0000 h and 0300 h than 1200 h. The response of tension receptors to 3 g stretch was reduced by up to 70% at 2100 h, 0000 h, and 0300 h compared with 1200 h. Gastric mucosal receptor response to stroking with a 50 mg von Frey hair was 3 times greater at 1200 h and 1500 h than the response at 0000 h. Similar findings were obtained in mice fasted for 6 h or maintained in darkness for 3 d before study. Therefore, these changes do not result from food intake or the light/dark cycle. Thus, gastric vagal mechanoreceptors display circadian rhythm, which may act to control food intake differentially at different times of the day. PMID:24305819

  10. Cationic influences upon synaptic transmission at the hair cell-afferent fiber synapse of the frog

    NASA Technical Reports Server (NTRS)

    Cochran, S. L.

    1995-01-01

    The concentrations of inorganic cations (K+, Na+, and Ca2+) bathing the isolated frog labyrinth were varied in order to assess their role in influencing and mediating synaptic transmission at the hair cell-afferent fiber synapse. Experiments employed intracellular recordings of synaptic activity from VIIIth nerve afferents. Recordings were digitized continuously at 50 kHz, and excitatory postsynaptic potentials were detected and parameters quantified by computer algorithms. Particular attention was focused on cationic effects upon excitatory postsynaptic potential frequency of occurrence and excitatory postsynaptic potential amplitude, in order to discriminate between pre- and postsynaptic actions. Because the small size of afferents preclude long term stable recordings, alterations in cationic concentrations were applied transiently and their peak effects on synaptic activity were assessed. Increases in extracellular K+ concentration of a few millimolar produced a large increase in the frequency of occurrence of excitatory postsynaptic potentials with little change in amplitude, indicating that release of transmitter from the hair cell is tightly coupled to its membrane potential. Increasing extracellular Na+ concentration resulted in an increase in excitatory postsynaptic potential amplitude with no significant change in excitatory postsynaptic potential frequency of occurrence, suggesting that the transmitter-gated subsynaptic channel conducts Na+ ions. Decreases in extracellular Ca2+ concentration had little effect upon excitatory postsynaptic potential frequency, but increased excitatory postsynaptic potential frequency and amplitude. These findings suggest that at higher concentrations Ca2+ act presynaptically to prevent transmitter release and postsynaptically to prevent Na+ influx during the generation of the excitatory postsynaptic potential. The influences of these ions on synaptic activity at this synapse are remarkably similar to those reported at the

  11. Unmyelinated type II afferent neurons report cochlear damage

    PubMed Central

    Liu, Chang; Glowatzki, Elisabeth; Fuchs, Paul Albert

    2015-01-01

    In the mammalian cochlea, acoustic information is carried to the brain by the predominant (95%) large-diameter, myelinated type I afferents, each of which is postsynaptic to a single inner hair cell. The remaining thin, unmyelinated type II afferents extend hundreds of microns along the cochlear duct to contact many outer hair cells. Despite this extensive arbor, type II afferents are weakly activated by outer hair cell transmitter release and are insensitive to sound. Intriguingly, type II afferents remain intact in damaged regions of the cochlea. Here, we show that type II afferents are activated when outer hair cells are damaged. This response depends on both ionotropic (P2X) and metabotropic (P2Y) purinergic receptors, binding ATP released from nearby supporting cells in response to hair cell damage. Selective activation of P2Y receptors increased type II afferent excitability by the closure of KCNQ-type potassium channels, a potential mechanism for the painful hypersensitivity (that we term “noxacusis” to distinguish from hyperacusis without pain) that can accompany hearing loss. Exposure to the KCNQ channel activator retigabine suppressed the type II fiber’s response to hair cell damage. Type II afferents may be the cochlea’s nociceptors, prompting avoidance of further damage to the irreparable inner ear. PMID:26553995

  12. Micromotional studies of utricular and canal afferents

    NASA Technical Reports Server (NTRS)

    Lewis, Edwin R.

    1989-01-01

    The long-range goal of this research was to refine our understanding of the sensitivity of the vestibular components of the ear to very-low-amplitude motion, especially, the role of gravity in this sensitivity. We focused on the American bullfrog--a common animal subject for vestibular sensory research. Our principal experimental method was to apply precise, sinusoidal microrotational stimuli to an anesthetized animal subject, to record the resulting responses in an individual vestibular nerve fiber from the intact ear, and to use intracellular dye to trace the fiber and thus identify the vestibular sensor that gave rise to it. In this way, we were able to identify specific micromotional sensitivities and to associate those sensitivities definitely with specific sensors. Furthermore, by recording from nerve fibers after they leave the intact inner-ear cavity, we were able to achieve these identifications without interrupting the delicate micromechanics of the inner ear. We were especially concerned with the relative roles of the utricle and the anterior semicircular canal in the sensing of microrotational motion of the head about horizontal axes, and with the role of gravity in mediating that sensing process in the utricle. The functional characterization of individual nerve fibers was accomplished with a conventional analytical tool, the cycle histogram, in which the nerve impulse rate was plotted against the phase of the sinusoidal stimulus.

  13. Hair-cell counts and afferent innervation patterns in the cristae ampullares of the squirrel monkey with a comparison to the chinchilla

    NASA Technical Reports Server (NTRS)

    Fernandez, C.; Lysakowski, A.; Goldberg, J. M.

    1995-01-01

    1. The numbers of type I and type II hair cells were estimated by dissector techniques applied to semithin, stained sections of the horizontal, superior, and posterior cristae in the squirrel monkey and the chinchilla. 2. The crista in each species was divided into concentrically arranged central, intermediate, and peripheral zones of equal areas. The three zones can be distinguished by the sizes of individual hair cells and calyx endings, by the density of hair cells, and by the relative frequency of calyx endings innervating single or multiple type I hair cells. 3. In the monkey crista, type I hair cells outnumber type II hair cells by a ratio of almost 3:1. The ratio decreases from 4-5:1 in the central and intermediate zones to under 2:1 in the peripheral zone. For the chinchilla, the ratio is near 1:1 for the entire crista and decreases only slightly between the central and peripheral zones. 4. Nerve fibers supplying the cristae in the squirrel monkey were labeled by extracellular injections of horseradish peroxidase (HRP) into the vestibular nerve. Peripheral terminations of individual fibers were reconstructed and related to the zones of the cristae they innervated and to the sizes of their parent axons. Results were similar for the horizontal, superior, and posterior cristae. 5. Axons seldom bifurcate below the neuroepithelium. Most fibers begin branching shortly after crossing the basement membrane. Their terminal arbors are compact, usually extending no more than 50-100 microns from the parent exon. A small number of long intraepithelial fibers enter the intermediate and peripheral zones of the cristae near its base, then run unbranched for long distances through the neuroepithelium to reach the central zone. 6. There are three classes of afferent fibers innervating the monkey crista. Calyx fibers terminate exclusively on type I hair cells, and bouton fibers end only on type II hair cells. Dimorphic fibers provide a mixed innervation, including calyx

  14. The pattern of excitation of human lower limb motoneurones by probable group II muscle afferents.

    PubMed

    Simonetta-Moreau, M; Marque, P; Marchand-Pauvert, V; Pierrot-Deseilligny, E

    1999-05-15

    1. Heteronymous group II effects were investigated in the human lower limb. Changes in firing probability of single motor units in quadriceps (Q), biceps (Bi), semitendinosus (ST), gastrocnemius medialis (GM) and tibialis anterior (TA) were studied after electrical stimuli between 1 and 3 times motor threshold (MT) applied to common peroneal (CP), superficial (SP) and deep (DP) peroneal, Bi and GM nerves in those nerve-muscle combinations without recurrent inhibition. 2. Stimulation of the CP and Bi nerves evoked in almost all of the explored Q motor units a biphasic excitation with a low-threshold early peak, attributable to non-monosynaptic group I excitation, and a higher threshold late peak. When the CP nerve was cooled (or the stimulation applied to a distal branch, DP), the increase in latency was greater for the late than for the early peak, indicating that the late excitation is due to stimulation of afferents with a slower conduction velocity than group I fibres, presumably in the group II range. In ST motor units the group II excitation elicited by stimulation of the GM and SP nerves was particularly large and frequent, and the non-monosynaptic group I excitation was often replaced by an inhibition. 3. A late group II-induced excitation from CP to Q motoneurones and from GM and SP to ST motoneurones was also observed when using the H reflex as a test. 4. The electrical threshold and conduction velocity of the largest diameter fibres evoking the group II excitation were estimated to be 2.1 and 0.65 times those of the fastest Ia afferents, respectively. In the combinations tested in the present investigation the group II input seemed to be primarily of muscle origin. 5. The potent heteronymous group II excitation of motoneurones of both flexors and extensors of the knee contrasted with the absence of a group II effect from DP to GM and from GM to TA. In none of the combinations explored was there any evidence for group II inhibition of motoneurones. The

  15. A synergistic effect of simultaneous TRPA1 and TRPV1 activations on vagal pulmonary C-fiber afferents

    PubMed Central

    Lin, Yu-Jung; Lin, Ruei-Lung; Ruan, Ting; Khosravi, Mehdi

    2014-01-01

    Transient receptor potential ankyrin type 1 (TRPA1) and vanilloid type 1 (TRPV1) receptors are coexpressed in vagal pulmonary C-fiber sensory nerves. Because both these receptors are sensitive to a number of endogenous inflammatory mediators, it is conceivable that they can be activated simultaneously during airway inflammation. This study aimed to determine whether there is an interaction between these two polymodal transducers upon simultaneous activation, and how it modulates the activity of vagal pulmonary C-fiber sensory nerves. In anesthetized, spontaneously breathing rats, the reflex-mediated apneic response to intravenous injection of a combined dose of allyl isothiocyanate (AITC, a TRPA1 activator) and capsaicin (Cap, a TRPV1 activator) was ∼202% greater than the mathematical sum of the responses to AITC and Cap when they were administered individually. Similar results were also observed in anesthetized mice. In addition, the synergistic effect was clearly demonstrated when the afferent activity of single vagal pulmonary C-fiber afferents were recorded in anesthetized, artificially ventilated rats; C-fiber responses to AITC, Cap and AITC + Cap (in combination) were 0.6 ± 0.1, 0.8 ± 0.1, and 4.8 ± 0.6 impulses/s (n = 24), respectively. This synergism was absent when either AITC or Cap was replaced by other chemical activators of pulmonary C-fiber afferents. The pronounced potentiating effect was further demonstrated in isolated vagal pulmonary sensory neurons using the Ca2+ imaging technique. In summary, this study showed a distinct positive interaction between TRPA1 and TRPV1 when they were activated simultaneously in pulmonary C-fiber sensory nerves. PMID:25414245

  16. Morphological studies of the vestibular nerve

    NASA Technical Reports Server (NTRS)

    Bergstroem, B.

    1973-01-01

    The anatomy of the intratemporal part of the vestibular nerve in man, and the possible age related degenerative changes in the nerve were studied. The form and structure of the vestibular ganglion was studied with the light microscope. A numerical analysis of the vestibular nerve, and caliber spectra of the myelinated fibers in the vestibular nerve branches were studied in individuals of varying ages. It was found that the peripheral endings of the vestibular nerve form a complicated pattern inside the vestibular sensory epithelia. A detailed description of the sensory cells and their surface organelles is included.

  17. An autoradiographic study of the afferent innervation of the trachea, syrinx and extrapulmonary primary bronchus of Gallus gallus domesticus.

    PubMed Central

    Bower, A J; Parker, S; Molony, V

    1978-01-01

    A method for injecting a small quantity of tritiated leucine directly into the nodose ganglion of the adult hen is described. The presence of an inner and an outer nerve plexus in the trachea and extrapulmonary primary bronchus is confirmed. Structures in the luminal epithelium of the trachea, syrinx and extrapulmonary primary bronchus having an afferent innervation are described and their possible function is discussed. The question of positive chemography in autoradiographic studies is discussed. Images Fig. 2 Fig. 3 Fig. 4 Fig. 5 Fig. 6 Fig. 7 Fig. 8 PMID:649496

  18. Influences of laryngeal afferent inputs on intralaryngeal muscle activity during vocalization in the cat.

    PubMed

    Shiba, K; Yoshida, K; Nakajima, Y; Konno, A

    1997-01-01

    The present study was undertaken to elucidate the possible role of the laryngeal afferent inputs in the regulation of intralaryngeal muscle activity during vocalization. We studied the influences of airflow and/or pressure applied to the larynx on intralaryngeal muscle activity during vocalization in ketamine-anesthetized cats. Vocalization was induced by airflow applied to the upper airway, which was isolated from the lower airway, during pontine call site stimulation. When the upper airway was open to the atmosphere through the nostrils and mouth, the airflow increased not only the vocal fold adductor and tensor activities but also the duration of these activities. The adductor and tensor activities were increased suddenly at a critical subglottic pressure level equivalent to the subglottic pressure threshold for vocalization. These effects were significantly reduced by sectioning of the internal branch of the superior laryngeal nerve or by lidocaine application to the laryngeal mucosa. Sustained pressure applied to the isolated upper airway, when the mouth and nostrils were occluded, did not affect adductor or tensor activities. These results indicate that the afferent inputs evoked by vocal fold stretching or vibration play an important role in the motor control of intralaryngeal and respiratory muscles during vocalization. PMID:9089702

  19. Cortical Responses to Aδ-Fiber Stimulation: Magnetoencephalographic Recordings in a Subject Lacking Large Myelinated Afferents

    PubMed Central

    Olausson, Håkan; Cole, Jonathan; Jousmäki, Veikko; Hari, Riitta

    2010-01-01

    Controversy persists over the role of the primary somatosensory cortex (SI) in processing small-fiber peripheral afferent input. We therefore examined subject I.W, who, due to sensory neuronopathy syndrome, has no large-fiber afferents below C3 level. Cortical evoked responses were recorded with a whole-scalp neuromagnetometer to high-intensity electrical stimulation of the distal right radial, median, and tibial nerves and skin over the forearm and mechanical stimulation of (neurologically intact) lip. The responses to electrical stimulation in the Aβ-denervated limbs peaked at 110–140 ms in contralateral SI and at 140–220 ms in contralateral secondary somatosensory cortex (SII), consistent with Aδ-mediated input. I.W. was able to localize pin-prick stimuli with 4 cm accuracy. Responses to laser stimuli on the radial dorsum of the hand peaked in contralateral SII cortex at 215 ms, also compatible with Aδ-mediated input. These results support the role of the SI cortex in processing the sensory discriminative aspects of Aδ-mediated input. PMID:19959562

  20. A binocular pupil model for simulation of relative afferent pupil defects and the swinging flashlight test.

    PubMed

    Privitera, Claudio M; Stark, Lawrence W

    2006-03-01

    Many important intracranial neural pathways are involved in the control of the two muscles of the human pupil and the observation and analysis of pupil responses to light or other stimuli is of great interest in many clinical procedures. The binocular pupil model presented in this document has a topology encompassing much of the complexity of the pupil system neurophysiology. The dynamic parameters of the model were matched against pupil experiments under multiple conditions. It is employed here to simulate responses to the swinging flashlight test, a procedure which is routinely practiced in ophthalmology to diagnose different degrees of relative afferent pupil defects often a consequence of severe optic nerve diseases or retinal dysfunctions. Other, not light-dependent, pupil stimuli are briefly discussed. PMID:16404612

  1. From nerve net to nerve ring, nerve cord and brain--evolution of the nervous system.

    PubMed

    Arendt, Detlev; Tosches, Maria Antonietta; Marlow, Heather

    2016-01-01

    The puzzle of how complex nervous systems emerged remains unsolved. Comparative studies of neurodevelopment in cnidarians and bilaterians suggest that this process began with distinct integration centres that evolved on opposite ends of an initial nerve net. The 'apical nervous system' controlled general body physiology, and the 'blastoporal nervous system' coordinated feeding movements and locomotion. We propose that expansion, integration and fusion of these centres gave rise to the bilaterian nerve cord and brain. PMID:26675821

  2. The Potential Role of Catheter-Based Renal Sympathetic Denervation in Chronic and End-Stage Kidney Disease.

    PubMed

    Sata, Yusuke; Schlaich, Markus P

    2016-07-01

    Sympathetic activation is a hallmark of chronic and end-stage renal disease and adversely affects cardiovascular prognosis. Hypertension is present in the vast majority of these patients and plays a key role in the progressive deterioration of renal function and the high rate of cardiovascular events in this patient cohort. Augmentation of renin release, tubular sodium reabsorption, and renal vascular resistance are direct consequences of efferent renal sympathetic nerve stimulation and the major components of neural regulation of renal function. Renal afferent nerve activity directly influences sympathetic outflow to the kidneys and other highly innervated organs involved in blood pressure control via hypothalamic integration. Renal denervation of the kidney has been shown to reduce blood pressure in many experimental models of hypertension. Targeting the renal nerves directly may therefore be specifically useful in patients with chronic and end-stage renal disease. In this review, we will discuss the potential role of catheter-based renal denervation in patients with impaired kidney function and also reflect on the potential impact on other cardiovascular conditions commonly associated with chronic kidney disease such as heart failure and arrhythmias. PMID:26740184

  3. Effect of oblique nerve grafting on peripheral nerve regeneration in rats.

    PubMed

    Kotulska, Katarzyna; Marcol, Wiesław; Larysz-Brysz, Magdalena; Tendera, Zofia; Malinowska-Kołodziej, Izabela; Slusarczyk, Wojciech; Jedrzejowska-Szypułka, Halina; Lewin-Kowalik, Joanna

    2006-01-01

    Current methods of peripheral nerve repair are to rejoin cut nerve stumps directly or to bridge large gaps with autologous nerve grafts. In both cases the surface of nerve stump endings is typically cut perpendicularly to the long axis of the nerve. The outcome of such operations, however, is still not satisfactory. In this study, we examine the effect of oblique nerve cutting and grafting on morphological as well as functional features of regeneration. In adult rats, sciatic nerve was cut and rejoined either directly or using an autologous graft, at 90 degrees or 30 degrees angle. Functional regeneration was assessed by walking track analysis during 12-week follow-up. Afterwards muscle weight was measured and histological studies were performed. The latter included nerve fibers and Schwann cells counting, as well as visualization of scar formation and epineural fibrosis. Nerves cut obliquely and rejoined showed better functional recovery than perpendicularly transected. Similar effect was observed after oblique grafting when compared to perpendicular one. Numbers of nerve fibers growing into the distal stump of the nerve as well as the number of Schwann cells were significantly higher in obliquely than in perpendicularly operated nerves. Moreover, growing axons were arranged more regularly following oblique treatment. These data indicate that joining or grafting the nerve stumps at acute angle is a more profitable method of nerve repair than the standard procedure performed at right angle. PMID:17066410

  4. Reorganization of central terminals of myelinated primary afferents in the rat dorsal horn following peripheral axotomy.

    PubMed

    Woolf, C J; Shortland, P; Reynolds, M; Ridings, J; Doubell, T; Coggeshall, R E

    1995-09-11

    We have investigated the time course and extent to which peripheral nerve lesions cause a morphological reorganization of the central terminals of choleragenoid-horseradish peroxidase (B-HRP)-labelled primary afferent fibers in the mammalian dorsal horn. Choleragenoid-horseradish peroxidase is retrogradely transported by myelinated (A) sensory axons to laminae I, III, IV and V of the normal dorsal horn of the spinal cord, leaving lamina II unlabelled. We previously showed that peripheral axotomy results in the sprouting of numerous B-HRP-labelled large myelinated sensory axons into lamina II. We show here that this spread of B-HRP-labelled axons into lamina II is detectable at 1 week, maximal by 2 weeks and persists for over 6 months postlesion. By 9 months, however, B-HRP fibers no longer appear in lamina II. The sprouting into lamina II occurs whether regeneration is allowed (crush) or prevented (section with ligation), and does not reverse at times when peripheral fibers reinnervate the periphery. We also show that 15 times more synaptic terminals in lamina II are labelled by B-HRP 2 weeks after axotomy than in the normal. We interpret this as indicating that the sprouting fibers are making synaptic contacts with postsynaptic targets. This implies that A-fiber terminal reorganization is a prominent and long-lasting but not permanent feature of peripheral axotomy. We also provide evidence that this sprouting is the consequence of a combination of an atrophic loss of central synaptic terminals and the conditioning of the sensory neurons by peripheral axotomy. The sprouting of large sensory fibers into the spinal territory where postsynaptic targets usually receive only small afferent fiber input may bear on the intractable touch-evoked pain that can follow nerve injury. PMID:7499558

  5. Movement-generated afference paired with transcranial magnetic stimulation: an associative stimulation paradigm

    PubMed Central

    2014-01-01

    Background A peripheral nerve stimulus can enhance or suppress the evoked response to transcranial magnetic stimulation (TMS) depending on the latency of the preceding peripheral nerve stimulation (PNS) pulse. Similarly, somatosensory afference from the passively moving limb can transiently alter corticomotor excitability, in a phase-dependent manner. The repeated association of PNS with TMS is known to modulate corticomotor excitability; however, it is unknown whether repeated passive-movement associative stimulation (MAS) has similar effects. Methods In a proof-of-principle study, using a cross-over design, seven healthy subjects received in separate sessions: (1) TMS (120% of the resting motor threshold-RMT, optimal site for Flexor Carpi Radialis) with muscle at rest; (2) TMS paired with cyclic passive movement during extension cyclic passive movement (400 pairs, 1 Hz), with the intervention order randomly assigned. Normality was tested using the Kolmogorov-Smirnov test, then compared to pre-intervention baseline using repeated measures ANOVA with a Dunnet multiple comparisons test. Results MAS led to a progressive and significant decrease in the motor evoked potential (MEP) amplitude over the intervention (R2 = 0.6665, P < 0.0001), which was not evident with TMS alone (R2 = 0.0068, P = 0.641). Post-intervention excitability reduction, only present with MAS intervention, remained for 20min (0-10min = 68.2 ± 4.9%, P < 0.05; 10-20min = 73.3 ± 9.7%, P < 0.05). Conclusion The association of somatosensory afference from the moving limb with TMS over primary motor cortex in healthy subjects can be used to modulate corticomotor excitability, and may have therapeutic implications. PMID:24597619

  6. Dual Modulation of Nociception and Cardiovascular Reflexes during Peripheral Ischemia through P2Y1 Receptor-Dependent Sensitization of Muscle Afferents

    PubMed Central

    Queme, Luis F.; Ross, Jessica L.; Lu, Peilin; Hudgins, Renita C.

    2016-01-01

    Numerous musculoskeletal pain disorders are based in dysfunction of peripheral perfusion and are often comorbid with altered cardiovascular responses to muscle contraction/exercise. We have recently found in mice that 24 h peripheral ischemia induced by a surgical occlusion of the brachial artery (BAO) induces increased paw-guarding behaviors, mechanical hypersensitivity, and decreased grip strength. These behavioral changes corresponded to increased heat sensitivity as well as an increase in the numbers of chemosensitive group III/IV muscle afferents as assessed by an ex vivo forepaw muscles/median and ulnar nerves/dorsal root ganglion (DRG)/spinal cord (SC) recording preparation. Behaviors also corresponded to specific upregulation of the ADP-responsive P2Y1 receptor in the DRGs. Since group III/IV muscle afferents have separately been associated with regulating muscle nociception and exercise pressor reflexes (EPRs), and P2Y1 has been linked to heat responsiveness and phenotypic switching in cutaneous afferents, we sought to determine whether upregulation of P2Y1 was responsible for the observed alterations in muscle afferent function, leading to modulation of muscle pain-related behaviors and EPRs after BAO. Using an afferent-specific siRNA knockdown strategy, we found that inhibition of P2Y1 during BAO not only prevented the increased mean blood pressure after forced exercise, but also significantly reduced alterations in pain-related behaviors. Selective P2Y1 knockdown also prevented the increased firing to heat stimuli and the BAO-induced phenotypic switch in chemosensitive muscle afferents, potentially through regulating membrane expression of acid sensing ion channel 3. These results suggest that enhanced P2Y1 in muscle afferents during ischemic-like conditions may dually regulate muscle nociception and cardiovascular reflexes. SIGNIFICANCE STATEMENT Our current results suggest that P2Y1 modulates heat responsiveness and chemosensation in muscle afferents

  7. Activation of CB1 inhibits NGF-induced sensitization of TRPV1 in adult mouse afferent neurons

    PubMed Central

    Wang, Zun-Yi; McDowell, Thomas; Wang, Peiqing; Alvarez, Roxanne; Gomez, Timothy; Bjorling, Dale E.

    2015-01-01

    Transient receptor potential vanilloid 1 (TRPV1)-containing afferent neurons convey nociceptive signals and play an essential role in pain sensation. Exposure to nerve growth factor (NGF) rapidly increases TRPV1 activity (sensitization). In the present study, we investigated whether treatment with the selective cannabinoid receptor 1 (CB1) agonist arachidonyl-2'-chloroethylamide (ACEA) affects NGF-induced sensitization of TRPV1 in adult mouse dorsal root ganglion (DRG) afferent neurons. We found that CB1, NGF receptor tyrosine kinase A (trkA), and TRPV1 are present in cultured adult mouse small- to medium-sized afferent neurons and treatment with NGF (100 ng/ml) for 30 minutes significantly increased the number of neurons that responded to capsaicin (as indicated by increased intracellular Ca2+ concentration). Pretreatment with the CB1 agonist ACEA (10 nM) inhibited the NGF-induced response, and this effect of ACEA was reversed by a selective CB1 antagonist. Further, pretreatment with ACEA inhibited NGF-induced phosphorylation of AKT. Blocking PI3 kinase activity also attenuated the NGF-induced increase in the number of neurons that responded to capsaicin. Our results indicate that the analgesic effect of CB1 activation may in part be due to inhibition of NGF-induced sensitization of TRPV1 and also that the effect of CB1 activation is at least partly mediated by attenuation of NGF-induced increased PI3 signaling. PMID:25088915

  8. Contributions of Central Command and Muscle Feedback to Sympathetic Nerve Activity in Contracting Human Skeletal Muscle

    PubMed Central

    Boulton, Daniel; Taylor, Chloe E.; Macefield, Vaughan G.; Green, Simon

    2016-01-01

    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-min isometric dorsiflexion contractions (left leg) separated by 2-min 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-synchronized, negative-going spikes in the neurogram. Compared with pre-contraction values, MSNA increased by 51 ± 34% (P < 0.01) during voluntary contractions but did not change significantly during electrically-evoked contractions (−8 ± 12%, P > 0.05). MSNA analyzed 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. PMID:27242537

  9. Contributions of Central Command and Muscle Feedback to Sympathetic Nerve Activity in Contracting Human Skeletal Muscle.

    PubMed

    Boulton, Daniel; Taylor, Chloe E; Macefield, Vaughan G; Green, Simon

    2016-01-01

    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-min isometric dorsiflexion contractions (left leg) separated by 2-min 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-synchronized, negative-going spikes in the neurogram. Compared with pre-contraction values, MSNA increased by 51 ± 34% (P < 0.01) during voluntary contractions but did not change significantly during electrically-evoked contractions (-8 ± 12%, P > 0.05). MSNA analyzed 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. PMID:27242537

  10. Optic nerve atrophy

    MedlinePlus

    Optic nerve atrophy is damage to the optic nerve. The optic nerve carries images of what the eye sees to ... problem most often affects older adults. The optic nerve can also be damaged by shock, toxins, radiation, ...

  11. Nerve biopsy (image)

    MedlinePlus

    Nerve biopsy is the removal of a small piece of nerve for examination. Through a small incision, a sample ... is removed and examined under a microscope. Nerve biopsy may be performed to identify nerve degeneration, identify ...

  12. Peripheral Nerve Disorders

    MedlinePlus

    ... spinal cord. Like static on a telephone line, peripheral nerve disorders distort or interrupt the messages between the brain ... body. There are more than 100 kinds of peripheral nerve disorders. They can affect one nerve or many nerves. ...

  13. Cobalt iontophoresis of sensory nerves in the rat lung.

    PubMed

    El-Bermani, A W; Chang, T L

    1979-02-01

    By iontophoretically introducing, first, cobalt and, subsequently, sulfide ions into the vagus nerve, it is possible to trace sensory nerves to their endings in the rat lung. Nerve fibers and terminals are found predominantly in the adventitia of the airways and blood vessels. Some nerves are found in the submucosa of the bronchi and bronchioles. Some are found in the cardiac muscle on the periphery of pulmonary veins, and a few nerves are seen to end among smooth muslces of the blood vessels and the airways. At least three types of nerve endings can be identified at the light microscopic level: (1) free nerve endings; (2) brush-like endings; (3) knob-like terminals. PMID:760496

  14. Involvement of sinoaortic afferents in renal sympathoinhibition and vasodilation induced by acute hypernatremia.

    PubMed

    Silva, Elaine F; Sera, Celisa T N; Mourão, Aline A; Lopes, Paulo R; Moreira, Marina C S; Ferreira-Neto, Marcos L; Colombari, Débora A S; Cravo, Sérgio L D; Pedrino, Gustavo R

    2015-11-01

    Despite the abundance of evidence that supports the important role of aortic and carotid afferents to short-term regulation of blood pressure and detection of variation in the arterial PO2 , PCO2 and pH, relatively little is known regarding the role of these afferents during changes in the volume and composition of extracellular compartments. The present study sought to determine the involvement of these afferents in the renal vasodilation and sympathoinhibition induced by hypertonic saline (HS) infusion. Sinoaortic-denervated and sham male Wistar rats were anaesthetised with intravenous (i.v.) urethane (1.2 g/kg body weight (bw)) prior to the measurement of the mean arterial pressure (MAP), renal vascular conductance (RVC) and renal sympathetic nerve activity (RSNA). In the sham group, the HS infusion (3 mol/L NaCl, 1.8 mL/kg bw, i.v.) induced transient hypertension (12 ± 4 mmHg from baseline, peak at 10 min; P < 0.05), an increase in RVC (127 ± 9% and 150 ± 13% from baseline, at 20 and 60 min respectively; P < 0.05) and a decrease in RSNA (-34 ± 10% and -29 ± 5% from baseline, at 10 and 60 min respectively; P < 0.05). In sinoaortic-denervated rats, HS infusion promoted a sustained pressor response (30 ± 5 and 17 ± 6 mmHg of baseline values, at 10 and 30 min respectively; P < 0.05) and abolished the increase in RVC (85 ± 8% from baseline, at 10 min) and decrease in RSNA (-4 ± 3% from baseline, at 10 min). These results suggest that aortic and carotid afferents are involved in cardiovascular and renal sympathoinhibition responses induced by acute hypernatremia. PMID:26440715

  15. Physiological identification of morphologically distinct afferent classes innervating the cristae ampullares of the squirrel monkey

    NASA Technical Reports Server (NTRS)

    Lysakowski, A.; Minor, L. B.; Fernandez, C.; Goldberg, J. M.

    1995-01-01

    1. Semicircular-canal afferents in the squirrel monkey were characterized by their resting discharge, discharge regularity, sensitivity to galvanic currents delivered to the ear (beta *), the gain (g2Hz), and phase lead (phi 2Hz) of their response to 2-Hz sinusoidal head rotations, and their antidromic conduction velocity. Discharge regularity was measured by a normalized coefficient of variation (CV*); the higher the CV*, the more irregular the discharge. g2Hz and phi 2Hz were expressed relative to angular head velocity. 2. These physiological measures were used in an attempt to discern the discharge properties of the three morphological classes of afferents innervating the crista. Presumed bouton (B) fibers were identified as slowly conducting afferents. Presumed calyx (C) fibers were recognized by their irregular discharge and low rotational gains. The remaining fibers were considered to be dimorphic (D) units. Single letters (B, C, and D) are used to emphasize that the classification is based on circumstantial evidence and may be wrong for individual fibers. Of the 125 identified fibers, 13 (10%) were B units, 36 (29%) were C units, and 76 (61%) were D units. 3. B units were regularly discharging D units ranged from regularly to irregularly discharging. C units were the most irregularly discharging afferents encountered. The mean resting discharge for the entire sample was 74 spikes/s. Resting rates were similar for regularly discharging B and D units and higher than those for irregularly discharging C and D units. 4. Except for their lower conduction velocities, the discharge properties of B units are indistinguishable from those of regularly discharging D units. Many of the discharge properties of B and D units vary with discharge regularity. There is a strong, positive relation when beta *, g2Hz, or phi 2Hz is plotted against CV*. For beta * or phi 2Hz, C units conform to the relation for B and D units. In contrast, values of g2Hz for C units are three to

  16. Fiber diameter distributions in the chinchilla's ampullary nerves

    NASA Technical Reports Server (NTRS)

    Hoffman, Larry F.; Honrubia, Vicente

    2002-01-01

    A morphometric study of the chinchilla's ampullary nerves was conducted to produce an unbiased accounting of the diameter distribution of their constituent fibers. Diameter analyses were determined from 1 microm plastic-embedded nerve sections taken at a plane immediately proximal to the sensory epithelium. We found these nerves to be composed of 2094+/-573 fibers, having diameters that ranged from 0.5 to 8 microm. The distributions of diameters were positively skewed, where approximately 75% of the fibers were found to have diameters less than 3.5 microm. An analysis of the spatial distribution of diameters within the nerve section revealed that the lateralmost areas of the nerve contained larger fractions of fibers within the smallest diameter quintiles, and the central area harbored greater proportions of the larger diameter quintiles. However, significant fractions of all quintiles were found in all areas. These data were integrated with available data of Fernandez et al. (1998) to produce diameter estimates of calyx, dimorphic, and bouton morphology subpopulations. In view of a general relationship between diameter, innervation locus, and an afferent's physiologic characteristics, these data provide the basis for developing a perspective for the in situ distribution of afferent response dynamics.

  17. Unilateral optical nerve hypoplasia in a Beagle dog.

    PubMed

    Negishi, H; Hoshiya, T; Tsuda, Y; Doi, K; Kanemaki, N

    2008-07-01

    Unilateral (left eye) optic nerve hypoplasia was detected in a six-month-old male Beagle dog. Vision testing indicated that the left eye had poor vision and testing the pupillary light reflex showed the left eye to have an absence of the afferent pathway of the reflex but it had a normal efferent pathway. Ophthalmoscopy revealed a small-sized optic disc, winding retinal artery and dilated retinal vasculature in the left globe. Electroretinography showed no abnormal findings even in the left globe. Histopathologically, the left optic nerve was markedly hypoplastic and was composed of sparse neural elements and a moderate amount of connective and glial tissues. In the retina of the left globe, the nerve fibre layer and the ganglion cell layer were reduced in thickness, although a small number of ganglion cells were still present. There were no abnormal findings detected in the right globe and the right optic nerve. The brain appeared normal macroscopically. PMID:18625594

  18. Modulation of visceral hypersensitivity by glial cell line-derived neurotrophic factor family receptor α-3 in colorectal afferents

    PubMed Central

    Shinoda, M.; Feng, B.; Albers, K. M.; Gebhart, G. F.

    2011-01-01

    Irritable bowel syndrome is characterized by colorectal hypersensitivity and contributed to by sensitized mechanosensitive primary afferents and recruitment of mechanoinsensitive (silent) afferents. Neurotrophic factors are well known to orchestrate dynamic changes in the properties of sensory neurons. Although pain modulation by proteins in the glial cell line-derived neurotrophic factor (GDNF) family has been documented in various pathophysiological states, their role in colorectal hypersensitivity remains unexplored. Therefore, we investigated the involvement of the GDNF family receptor α-3 (GFRα3) signaling in visceral hypersensitivity by quantifying visceromotor responses (VMR) to colorectal distension before and after intracolonic treatment with 2,4,6-trinitrobenzene sulfonic acid (TNBS). Baseline responses to colorectal distension did not differ between C57BL/6 and GFRα3 knockout (KO) mice. Relative to intracolonic saline treatment, TNBS significantly enhanced the VMR to colorectal distension in C57BL/6 mice 2, 7, 10, and 14 days posttreatment, whereas TNBS-induced visceral hypersensitivity was significantly suppressed in GFRα3 KO mice. The proportion of GFRα3 immunopositive thoracolumbar and lumbosacral colorectal dorsal root ganglion neurons was significantly elevated 2 days after TNBS treatment. In single fiber recordings, responses to circumferential stretch of colorectal afferent endings in C57BL/6 mice were significantly increased (sensitized) after exposure to an inflammatory soup, whereas responses to stretch did not sensitize in GFRα3 KO mice. These findings suggest that enhanced GFRα3 signaling in visceral afferents may contribute to development of colorectal hypersensitivity. PMID:21193524

  19. Chronic recruitment of primary afferent neurons by microstimulation in the feline dorsal root ganglia

    NASA Astrophysics Data System (ADS)

    Fisher, Lee E.; Ayers, Christopher A.; Ciollaro, Mattia; Ventura, Valérie; Weber, Douglas J.; Gaunt, Robert A.

    2014-06-01

    Objective. This study describes results of primary afferent neural microstimulation experiments using microelectrode arrays implanted chronically in the lumbar dorsal root ganglia (DRG) of four cats. The goal was to test the stability and selectivity of these microelectrode arrays as a potential interface for restoration of somatosensory feedback after damage to the nervous system such as amputation. Approach. A five-contact nerve-cuff electrode implanted on the sciatic nerve was used to record the antidromic compound action potential response to DRG microstimulation (2-15 µA biphasic pulses, 200 µs cathodal pulse width), and the threshold for eliciting a response was tracked over time. Recorded responses were segregated based on conduction velocity to determine thresholds for recruiting Group I and Group II/Aβ primary afferent fibers. Main results. Thresholds were initially low (5.1 ± 2.3 µA for Group I and 6.3 ± 2.0 µA for Group II/Aβ) and increased over time. Additionally the number of electrodes with thresholds less than or equal to 15 µA decreased over time. Approximately 12% of tested electrodes continued to elicit responses at 15 µA up to 26 weeks after implantation. Higher stimulation intensities (up to 30 µA) were tested in one cat at 23 weeks post-implantation yielding responses on over 20 additional electrodes. Within the first six weeks after implantation, approximately equal numbers of electrodes elicited only Group I or Group II/Aβ responses at threshold, but the relative proportion of Group II/Aβ responses decreased over time. Significance. These results suggest that it is possible to activate Group I or Group II/Aβ primary afferent fibers in isolation with penetrating microelectrode arrays implanted in the DRG, and that those responses can be elicited up to 26 weeks after implantation, although it may be difficult to achieve a consistent response day-to-day with currently available electrode technology. The DRG are compelling targets

  20. Afferent innervation of the utricular macula in pigeons

    NASA Technical Reports Server (NTRS)

    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

  1. Human brain cortical correlates of short-latency afferent inhibition: a combined EEG-TMS study.

    PubMed

    Ferreri, Florinda; Ponzo, David; Hukkanen, Taina; Mervaala, Esa; Könönen, Mervi; Pasqualetti, Patrizio; Vecchio, Fabrizio; Rossini, Paolo Maria; Määttä, Sara

    2012-07-01

    When linking in time electrical stimulation of the peripheral nerve with transcranial magnetic stimulation (TMS), the excitability of the motor cortex can be modulated to evoke clear inhibition, as reflected by the amplitude decrement in the motor-evoked potentials (MEPs). This specific property, designated short-latency afferent inhibition (SAI), occurs when the nerve-TMS interstimulus interval (ISI) is approximately 25 ms and is considered to be a corticothalamic phenomenon. The aim of the present study was to use the electroencephalographic (EEG) responses to navigated-TMS coregistration to better characterize the neuronal circuits underlying SAI. The present experimental set included magnetic resonance imaging (MRI)-navigated TMS and 60-channel TMS-compatible EEG devices. TMS-evoked EEG responses and MEPs were analyzed in eight healthy volunteers; ISIs between median nerve and cortical stimulation were determined relative to the latency of the individual N20 component of the somatosensory-evoked potential (SEP) obtained after stimulation of the median nerve. ISIs from the latency of the N20 plus 3 ms and N20 plus 10 ms were investigated. In all experimental conditions, TMS-evoked EEG responses were characterized by a sequence of negative deflections peaking at approximately 7, 44, and 100 ms alternating with positive peaks at approximately 30, 60, and 180 ms post-TMS. Moreover, ISI N20+3 ms modulated both EEG-evoked activity and MEPs. In particular, it inhibited MEP amplitudes, attenuated cortical P60 and N100 responses, and induced motor cortex beta rhythm selective decrement of phase locking. The findings of the present experiment suggest the cortical origin of SAI that could result from the cortico-cortical activation of GABAergic-mediated inhibition onto the corticospinal neurons modulated by cholinergic activation able to reducing intralaminar inhibition and promoting intracolumnar inhibition. PMID:22457460

  2. Responses in muscle afferent fibres of slow conduction velocity to contractions and ischaemia in the cat.

    PubMed Central

    Mense, S; Stahnke, M

    1983-01-01

    The aim of the study was to find out to what extent muscle receptors with slowly conducting afferent fibres (group III and IV) are activated by muscular contractions of moderate force, and what kind of muscle afferents could mediate the pain of ischaemic exercise. In chloralose-anaesthetized cats, the impulse activity of single afferent units from the triceps surae muscle was recorded from dorsal root filaments during muscular contractions with intact blood supply and after occlusion of the muscle artery. Two types of responses were observed to contractions without muscular ischaemia. One was characterized by sudden onset and a graded response amplitude to contractions of increasing force. In most cases stretching the muscle was also an effective stimulus. Units showing this response behaviour were labelled c.s.m (contraction-sensitive with mechanical mechanism of activation). The other response type had a more delayed onset and often outlasted the exercise period; because of the unknown mechanism of activation, units of this kind were labelled c.s.x. The proportion of c.s.m receptors was significantly higher amongst group III than amongst group IV units. During ischaemic contractions of comparable force the c.s.m and c.s.x receptors exhibited an unchanged or a decreased response amplitude. Under these conditions another receptor type (N, for nociceptive) was activated which did not respond to contractions with intact blood supply. Vigorous activations during ischaemic work were only observed in group IV receptors. The majority of the 131 group III and IV units tested did not respond to contractions at all. These contraction-insensitive (c.i.) endings probably comprised different receptor populations (nociceptors, thermoreceptors, low-threshold mechanoreceptors). It is concluded that the various central nervous effects of muscular exercise without ischaemia which are known to be due to raised activity in thin muscle afferents (e.g. cardiopulmonary adjustments

  3. [Anatomical variants of the medial calcaneal nerve and the Baxter nerve in the tarsal tunnel].

    PubMed

    Martín-Oliva, X; Elgueta-Grillo, J; Veliz-Ayta, P; Orosco-Villaseñor, S; Elgueta-Grillo, M; Viladot-Perice, R

    2013-01-01

    The tarsal tunnel is composed of the posterior border of the medial malleoulus, the posterior aspect of the talus and the medial aspect of the calcaneus. The medial calcaneal nerve emerges from the posterior aspect of the posterior tibial nerve in 75% of cases and from the lateral plantar nerve in the remaining 25%. Finally, the medial calcaneal nerve ends as a single terminal branch in 79% of cases and in numerous terminal branches in the remaining 21%. To describe the anatomical variants of the posterior tibial nerve and its terminal branches. To describe the steps for tarsal tunnel release. To describe Baxter nerve release. The anatomical variants of the posterior tibial nerve and its terminal branches within the tarsal tunnel were studied. Then the Lam technique was performed; it consists of: 1) opening of the laciniate ligament, 2) opening of the fascia over the abductor hallucis muscle, 3) exoneurolysis of the posterior tibial nerve and its terminal branches, identifying the emergence and pathway of the medial calcaneal branch, the lateral plantar nerve and its Baxter nerve branch and the medial plantar nerve. Baxter nerve was found in 100% of cases. In 100% of cases in our series the nerve going to the abductor digiti minimi muscle of the foot was found; 87.5% of cases had two terminal branches. The dissections proved that a crucial step was the release of the distal tarsal tunnel. PMID:24701749

  4. Transport of cholecystokinin-octapeptide-like immunoreactivity toward the gut in afferent vagal fibres in cat and dog.

    PubMed Central

    Dockray, G J; Gregory, R A; Tracy, H J; Zhu, W Y

    1981-01-01

    1. The distributions of gastrin- and cholecystokinin-like immunoreactivities in the dog and cat vagus nerves have been studied after nerve section and ligation. 2. In dogs, there was an increase in cholecystokinin-octapeptide-like immunoreactive material on the cranial side of ligatures on the thoracic or cervical vagi. When pairs of ligatures were tied on the cervical vagi there was accumulation proximal, and a slight decrease distal to, the upper ligature. There was also a modest increase distal to the lower ligature. 3. In cats, section of the vagus above the nodose ganglion, and hence degeneration of the efferent fibres, did not prevent increases in cholecystokinin-octapeptide-like immunoreactivity on the cranial side of ligatures which were later tied below the ganglion. Removal of the superior cervical ganglion had no effect on the accumulation of immunoreactive material above the ligatures. Section of the vagus below the nodose ganglion, and hence degeneration of both afferent and efferent fibres, abolished the accumulation on the cranial side of ligatures which were later tied below the section. Cholecystokinin-octapeptide-like material is therefore localized to afferent fibres with cell bodies in the nodose ganglion. 4. Immunoreactive forms were characterized by gel filtration and ion exchange chromatography, and the use of region-specific antisera. In all cats, and all but one dog, a molecule with the properties of sulphated cholecystokinin octapeptide was found to predominate. In some cats (30%) and dogs (26%) a molecule with the properties of heptadecapeptide gastrin (G17) was identified; concentrations of G17 were generally low compared with cholecystokinin octapeptide. In three dogs (20%) there was an accumulation of heptadecapeptide gastrin above the ligatures. 5. Axonal transport of cholecystokinin octapeptide in the vagus is consistent with a neuro-regulatory role for this peptide. However, the functional significance of its localization in

  5. The correlated blanching of synaptic bodies and reduction in afferent firing rates caused by transmitter-depleting agents in the frog semicircular canal

    NASA Technical Reports Server (NTRS)

    Guth, P.; Norris, C.; Fermin, C. D.; Pantoja, M.

    1993-01-01

    Synaptic bodies (SBs) associated with rings of synaptic vesicles and well-defined, pre- and post-synaptic membrane structures are indicators of maturity in most hair cell-afferent nerve junctions. The role of the SBs remains elusive despite several experiments showing that they may be involved in storage of neurotransmitter. Our results demonstrate that SBs of the adult posterior semicircular canal (SCC) cristae hair cells become less electron dense following incubation of the SCC with the transmitter-depleting drug tetrabenazine (TBZ). Objective quantification and comparison of the densities of the SBs in untreated and TBZ-treated frog SCC demonstrated that TBZ significantly decreased the electron density of SBs. This reduction in electron density was accompanied by a reduction in firing rates of afferent fibers innervating the posterior SCC. A second transmitter-depleting drug, guanethidine, previously shown to reduce the electron density of hair cell SBs, also reduced the firing rates of afferent fibers innervating the posterior SCC. In contrast, the electron density of dense granules (DG), similar in size and shape to synaptic bodies (SB) in hair cells, did not change after incubation in TBZ, thus indicating that granules and SBs are not similar in regard to their electron density. The role of SBs in synaptic transmission and the transmitter, if any, stored in the SBs remain unknown. Nonetheless, the association of the lessening of electron density with a reduction in afferent firing rate provides impetus for the further investigation of the SB's role in neurotransmission.

  6. Transgenic BDNF induces nerve fiber regrowth into the auditory epithelium in deaf cochleae.

    PubMed

    Shibata, Seiji B; Cortez, Sarah R; Beyer, Lisa A; Wiler, James A; Di Polo, Adriana; Pfingst, Bryan E; Raphael, Yehoash

    2010-06-01

    Sensory organs typically use receptor cells and afferent neurons to transduce environmental signals and transmit them to the CNS. When sensory cells are lost, nerves often regress from the sensory area. Therapeutic and regenerative approaches would benefit from the presence of nerve fibers in the tissue. In the hearing system, retraction of afferent innervation may accompany the degeneration of auditory hair cells that is associated with permanent hearing loss. The only therapy currently available for cases with severe or complete loss of hair cells is the cochlear implant auditory prosthesis. To enhance the therapeutic benefits of a cochlear implant, it is necessary to attract nerve fibers back into the cochlear epithelium. Here we show that forced expression of the neurotrophin gene BDNF in epithelial or mesothelial cells that remain in the deaf ear induces robust regrowth of nerve fibers towards the cells that secrete the neurotrophin, and results in re-innervation of the sensory area. The process of neurotrophin-induced neuronal regeneration is accompanied by significant preservation of the spiral ganglion cells. The ability to regrow nerve fibers into the basilar membrane area and protect the auditory nerve will enhance performance of cochlear implants and augment future cell replacement therapies such as stem cell implantation or induced transdifferentiation. This model also provides a general experimental stage for drawing nerve fibers into a tissue devoid of neurons, and studying the interaction between the nerve fibers and the tissue. PMID:20109446

  7. Transgenic BDNF induces nerve fiber regrowth into the auditory epithelium in deaf cochleae

    PubMed Central

    Shibata, Seiji B.; Cortez, Sarah R.; Beyer, Lisa A.; Wiler, Jim A.; Di Polo, Adriana; Pfingst, Bryan E.; Raphael, Yehoash

    2010-01-01

    Sensory organs typically use receptor cells and afferent neurons to transduce environmental signals and transmit them to the CNS. When sensory cells are lost, nerves often regress from the sensory area. Therapeutic and regenerative approaches would benefit from the presence of nerve fibers in the tissue. In the hearing system, retraction of afferent innervation may accompany the degeneration of auditory hair cells that is associated with permanent hearing loss. The only therapy currently available for cases with severe or complete loss of hair cells is the cochlear implant auditory prosthesis. To enhance the therapeutic benefits of a cochlear implant, it is necessary to attract nerve fibers back into the cochlear epithelium. Here we show that forced expression of the neurotrophin gene BDNF in epithelial or mesothelial cells that remain in the deaf ear, induces robust regrowth of nerve fibers towards the cells that secrete the neurotrophin, and results in re-innervation of the sensory area. The process of neurotrophin-induced neuronal regeneration is accompanied by significant preservation of the spiral ganglion cells. The ability to regrow nerve fibers into the basilar membrane area and protect the auditory nerve will enhance performance of cochlear implants and augment future cell replacement therapies such as stem cell implantation or induced transdifferentiation. This model also provides a general experimental stage for drawing nerve fibers into a tissue devoid of neurons, and studying the interaction between the nerve fibers and the tissue. PMID:20109446

  8. Histaminergic afferent system in the cerebellum: structure and function.

    PubMed

    Li, Bin; Zhu, Jing-Ning; Wang, Jian-Jun

    2014-01-01

    Histaminergic afferent system of the cerebellum, having been considered as an essential component of the direct hypothalamocerebellar circuits, originates from the tuberomammillary nucleus in the hypothalamus. Unlike the mossy fibers and climbing fibers, the histaminergic afferent fibers, a third type of cerebellar afferents, extend fine varicose fibers throughout the cerebellar cortex and nuclei. Histamine receptors, belonging to the family of G protein-coupled receptors, are widely present in the cerebellum. Through these histamine receptors, histamine directly excites Purkinje cells and granule cells in the cerebellar cortex, as well as the cerebellar nuclear neurons. Therefore, the histaminergic afferents parallelly modulate these dominant components in the cerebellar circuitry and consequently influence the final output of the cerebellum. In this way, the histaminergic afferent system actively participates in the cerebellum-mediated motor balance and coordination and nonsomatic functions. Accordingly, histaminergic reagents may become potential drugs for clinical treatment of cerebellar ataxia and other cerebellar disease. On the other hand, considering the hypothalamus is a high regulatory center for autonomic and visceral activities, the hypothalamocerebellar histaminergic fibers/projections, bridging the nonsomatic center to somatic structure, may play a critical role in the somatic-nonsomatic integration. PMID:26331029

  9. Semicircular Canal Geometry, Afferent Sensitivity And Animal Behavior

    PubMed Central

    Hullar, Timothy A.

    2008-01-01

    The geometry of the semicircular canals has been used in evolutionary studies to predict the behaviors of extinct animals. These predictions have relied on an assumption that the responses of the canals can be determined from their dimensions, and that an organism’s behavior can be determined from these responses. However, the relationship between a canal’s sensitivity and its size is not well known. An intraspecies comparison among canal responses in each of three species (cat, squirrel monkey, and pigeon) was undertaken to evaluate various models of canal function and determine how their dimensions may be related to afferent physiology. All models predicted the responses of the cat afferents, but the models performed less well for squirrel monkey and pigeon. Possible causes for this discrepancy include incorrectly assuming that afferent responses accurately represent canal function, or errors in current biophysical models of the canals. These findings leave open the question as to how reliably canal anatomy can be used to estimate afferent responses and how closely afferent responses are related to behavior. Other labyrinthine features—such as orientation of the horizontal canal, which is reliably held near earth-horizontal across many species—may be better to use when extrapolating the posture and related behavior of extinct animals from labyrinthine morphology. PMID:16550591

  10. Compartmental modeling of rat macular primary afferents from three-dimensional reconstructions of transmission electron micrographs of serial sections.

    PubMed

    Chimento, T C; Doshay, D G; Ross, M D

    1994-05-01

    1. We cut serial sections through the medial part of the rat vestibular macula for transmission electron microscopic (TEM) examination, computer-assisted three-dimensional (3-D) reconstruction, and compartmental modeling. The ultrastructural research showed that many primary vestibular neurons have an unmyelinated segment, often branched, that extends between the heminode [putative site of the spike initiation zone (SIZ)] and the expanded terminal(s) (calyx, calyces). These segments, termed the neuron branches, and the calyces frequently have spinelike processes of various dimensions that morphologically are afferent, efferent, or reciprocal to other macular neural elements. The purpose of this research was to determine whether morphometric data obtained ultrastructurally were essential to compartmental models [i.e., they influenced action potential (AP) generation, latency, or amplitude] or whether afferent parts could be collapsed into more simple units without markedly affecting results. We used the compartmental modeling program NEURON for this research. 2. In the first set of simulations we studied the relative importance of small variations in process morphology on distant depolarization. A process was placed midway along an isolated piece of a passive neuron branch. The dimensions of the four processes corresponded to actual processes in the serial sections. A synapse, placed on the head of each process, was activated and depolarization was recorded at the end of the neuron branch. When we used 5 nS synaptic conductance, depolarization varied by 3 mV. In a systematic study over a representative range of stem dimensions, depolarization varied by 15.7 mV. Smaller conductances produced smaller effects. Increasing membrane resistivity from 5,000 to 50,000 omega cm2 had no significant effect. 3. In a second series of simulations, using whole primary afferents, we examined the combined effects of process location and afferent morphology on depolarization magnitude

  11. Differential expression of vesicular glutamate transporters by vagal afferent terminals in rat nucleus of the solitary tract: projections from the heart preferentially express vesicular glutamate transporter 1.

    PubMed

    Corbett, E K A; Sinfield, J K; McWilliam, P N; Deuchars, J; Batten, T F C

    2005-01-01

    The central projections and neurochemistry of vagal afferent neurones supplying the heart in the rat were investigated by injecting cholera toxin B-subunit into the pericardium. Transganglionically transported cholera toxin B-subunit was visualized in the medulla oblongata in axons and varicosities that were predominantly aggregated in the dorsomedial, dorsolateral, ventrolateral and commissural subnuclei of the caudal nucleus of the solitary tract. Unilateral vagal section in control rats prevented cholera toxin B-subunit labeling on the ipsilateral side of the nucleus of the solitary tract. Fluorescent and electron microscopic dual labeling showed colocalization of immunoreactivity for vesicular glutamate transporter 1, but only rarely vesicular glutamate transporters 2 or 3 with cholera toxin B-subunit in terminals in nucleus of the solitary tract, suggesting that cardiac vagal axons release glutamate as a neurotransmitter. In contrast, populations of vagal afferent fibers labeled by injection of cholera toxin B-subunit, tetra-methylrhodamine dextran or biotin dextran amine into the aortic nerve, stomach or nodose ganglion colocalized vesicular glutamate transporter 2 more frequently than vesicular glutamate transporter 1. The presence of other neurochemical markers of primary afferent neurones was examined in nucleus of the solitary tract axons and nodose ganglion cells labeled by pericardial cholera toxin B-subunit injections. Immunoreactivity for a 200-kDa neurofilament protein in many large, cholera toxin B-subunit-labeled nodose ganglion cells indicated that the cardiac afferent fibers labeled are mostly myelinated, whereas binding of Griffonia simplicifolia isolectin B4 to fewer small cholera toxin B-subunit-labeled ganglion cells suggested that tracer was also taken up by some non-myelinated axons. A few labeled nucleus of the solitary tract axons and ganglion cells were positive for substance P and calcitonin gene-related peptide, which are considered as

  12. Neural circuits underlying tongue movements for the prey-catching behavior in frog: distribution of primary afferent terminals on motoneurons supplying the tongue.

    PubMed

    Kecskes, Szilvia; Matesz, Clara; Gaál, Botond; Birinyi, András

    2016-04-01

    The hypoglossal motor nucleus is one of the efferent components of the neural network underlying the tongue prehension behavior of Ranid frogs. Although the appropriate pattern of the motor activity is determined by motor pattern generators, sensory inputs can modify the ongoing motor execution. Combination of fluorescent tracers were applied to investigate whether there are direct contacts between the afferent fibers of the trigeminal, facial, vestibular, glossopharyngeal-vagal, hypoglossal, second cervical spinal nerves and the hypoglossal motoneurons. Using confocal laser scanning microscope, we detected different number of close contacts from various sensory fibers, which were distributed unequally between the motoneurons innervating the protractor, retractor and inner muscles of the tongue. Based on the highest number of contacts and their closest location to the perikaryon, the glossopharyngeal-vagal nerves can exert the strongest effect on hypoglossal motoneurons and in agreement with earlier physiological results, they influence the protraction of the tongue. The second largest number of close appositions was provided by the hypoglossal and second cervical spinal afferents and they were located mostly on the proximal and middle parts of the dendrites of retractor motoneurons. Due to their small number and distal location, the trigeminal and vestibular terminals seem to have minor effects on direct activation of the hypoglossal motoneurons. We concluded that direct contacts between primary afferent terminals and hypoglossal motoneurons provide one of the possible morphological substrates of very quick feedback and feedforward modulation of the motor program during various stages of prey-catching behavior. PMID:25575900

  13. Arnold’s nerve cough reflex: evidence for chronic cough as a sensory vagal neuropathy

    PubMed Central

    Gibson, Peter G.; Birring, Surinder S.

    2014-01-01

    Arnold’s nerve ear-cough reflex is recognised to occur uncommonly in patients with chronic cough. In these patients, mechanical stimulation of the external auditory meatus can activate the auricular branch of the vagus nerve (Arnold’s nerve) and evoke reflex cough. This is an example of hypersensitivity of vagal afferent nerves, and there is now an increasing recognition that many cases of refractory or idiopathic cough may be due to a sensory neuropathy of the vagus nerve. We present two cases where the cause of refractory chronic cough was due to sensory neuropathy associated with ear-cough reflex hypersensitivity. In both cases, the cough as well as the Arnold’s nerve reflex hypersensitivity were successfully treated with gabapentin, a treatment that has previously been shown to be effective in the treatment of cough due to sensory laryngeal neuropathy (SLN). PMID:25383210

  14. Reinnervation of Urethral and Anal Sphincters With Femoral Motor Nerve to Pudendal Nerve Transfer

    PubMed Central

    Ruggieri, Michael R.; Braverman, Alan S.; Bernal, Raymond M.; Lamarre, Neil S.; Brown, Justin M.; Barbe, Mary F.

    2012-01-01

    Aims Lower motor neuron damage to sacral roots or nerves can result in incontinence and a flaccid urinary bladder. We showed bladder reinnervation after transfer of coccygeal to sacral ventral roots, and genitofemoral nerves (L1, 2 origin) to pelvic nerves. This study assesses the feasibility of urethral and anal sphincter reinnervation using transfer of motor branches of the femoral nerve (L2–4 origin) to pudendal nerves (S1, 2 origin) that innervate the urethral and anal sphincters in a canine model. Methods Sacral ventral roots were selected by their ability to stimulate bladder, urethral sphincter, and anal sphincter contraction and transected. Bilaterally, branches of the femoral nerve, specifically, nervus saphenous pars muscularis [Evans HE. Miller’s anatomy of the dog. Philadelphia: W.B. Saunders; 1993], were transferred and end-to-end anastomosed to transected pudendal nerve branches in the perineum, then enclosed in unipolar nerve cuff electrodes with leads to implanted RF micro-stimulators. Results Nerve stimulation induced increased anal and urethral sphincter pressures in five of six transferred nerves. Retrograde neurotracing from the bladder, urethral sphincter, and anal sphincter using fluorogold, fast blue, and fluororuby, demonstrated urethral and anal sphincter labeled neurons in L2–4 cord segments (but not S1–3) in nerve transfer canines, consistent with rein-nervation by the transferred femoral nerve motor branches. Controls had labeled neurons only in S1–3 segments. Postmortem DiI and DiO labeling confirmed axonal regrowth across the nerve repair site. Conclusions These results show spinal cord reinnervation of urethral and anal sphincter targets after sacral ventral root transection and femoral nerve transfer (NT) to the denervated pudendal nerve. These surgical procedures may allow patients to regain continence. PMID:21953679

  15. Evidence for a role of capsaicin-sensitive sensory nerves in the lung oedema induced by Tityus serrulatus venom in rats.

    PubMed

    Andrade, Marcus V M; Souza, Danielle G; de A Castro, Maria Salete; Cunha-Melo, José R; Teixeira, Mauro M

    2002-03-01

    In the most severe cases of human envenoming by Tityus serrulatus, pulmonary oedema is a frequent finding and can be the cause of death. We have previously demonstrated a role for neuropeptides acting on tachykinin NK(1) receptors in the development of lung oedema following i.v. injection of T. serrulatus venom (TsV) in experimental animals. The present work was designed to investigate whether capsaicin-sensitive primary afferent neurons were a potential source of NK(1)-acting neuropeptides. To this end, sensory nerves were depleted of neuropeptides by neonatal treatment of rats with capsaicin. The effectiveness of this strategy at depleting sensory nerves was demonstrated by the inhibition of the neuropeptide-dependent response to intraplantar injection of formalin. Pulmonary oedema, as assessed by the levels of extravasation of Evans blue dye in the bronchoalveolar lavage and in the left lung, was markedly inhibited in capsaicin-treated animals. In contrast, capsaicin treatment failed to alter the increase in arterial blood pressure or the lethality following i.v. injection of TsV. Our results demonstrate an important role for capsaicin-sensitive sensory nerves in the cascade of events leading to lung injury following the i.v. administration of TsV. PMID:11711125

  16. Vagus nerve stimulation in neuropsychiatry: Targeting anatomy-based stimulation sites.

    PubMed

    Trevizol, Alisson; Barros, Mirna Duarte; Liquidato, Bianca; Cordeiro, Quirino; Shiozawa, Pedro

    2015-10-01

    The vagus nerve (VN) is the longest cranial nerve, extending from the brain to the abdominal cavity. The VN consists of both afferent and efferent fibers (respectively 80% and 20%). Vagus nerve stimulation (VNS) is a neuromodulation strategy first developed in the 1980s for epilepsy. More recently, growing efforts in clinical research have been underscoring possible clinical benefits of VNS for different medical conditions such as epilepsy, major depression, anxiety disorders, and Tourette syndrome. Following the rational of VN anatomy and cranial innervation presented above, we hereby hypothesize that transcutaneously placing electrodes over the mastoid process could be a useful study protocol for future tVNS trials. PMID:26262931

  17. Nerve Growth Factor Decreases in Sympathetic and Sensory Nerves of Rats with Chronic Heart Failure

    PubMed Central

    Lu, Jian

    2014-01-01

    Nerve growth factor (NGF) plays a critical role in the maintenance and survival of both sympathetic and sensory nerves. Also, NGF can regulate receptor expression and neuronal activity in the sympathetic and sensory neurons. Abnormalities in NGF regulation are observed in patients and animals with heart failure (HF). Nevertheless, the effects of chronic HF on the levels of NGF within the sympathetic and sensory nerves are not known. Thus, the ELISA method was used to assess the levels of NGF in the stellate ganglion (SG) and dorsal root ganglion (DRG) neurons of control rats and rats with chronic HF induced by myocardial infarction. Our data show for the first time that the levels of NGF were significantly decreased (P < 0.05) in the SG and DRG neurons 6–20 weeks after ligation of the coronary artery. In addition, a close relation was observed between the NGF levels and the left ventricular function. In conclusion, chronic HF impairs the expression of NGF in the sympathetic and sensory nerves. Given that sensory afferent nerves are engaged in the sympathetic nervous responses to somatic stimulation (i.e. muscle activity during exercise) via a reflex mechanism, our data indicate that NGF is likely responsible for the development of muscle reflex-mediated abnormal sympathetic responsiveness observed in chronic HF. PMID:24913185

  18. Involvement of Peripheral Nerves in the Transgenic PLP-α-Syn Model of Multiple System Atrophy: Extending the Phenotype

    PubMed Central

    Kuzdas-Wood, Daniela; Irschick, Regina; Theurl, Markus; Malsch, Philipp; Mair, Norbert; Mantinger, Christine; Wanschitz, Julia; Klimaschewski, Lars; Poewe, Werner; Stefanova, Nadia; Wenning, Gregor K.

    2015-01-01

    Multiple system atrophy (MSA) is a fatal, rapidly progressive neurodegenerative disease with (oligodendro-)glial cytoplasmic α-synuclein (α-syn) inclusions (GCIs). Peripheral neuropathies have been reported in up to 40% of MSA patients, the cause remaining unclear. In a transgenic MSA mouse model featuring GCI-like inclusion pathology based on PLP-promoter driven overexpression of human α-syn in oligodendroglia motor and non-motor deficits are associated with MSA-like neurodegeneration. Since α-syn is also expressed in Schwann cells we aimed to investigate whether peripheral nerves are anatomically and functionally affected in the PLP-α-syn MSA mouse model. Results To this end, heat/cold as well as mechanical sensitivity tests were performed. Furthermore, in vivo and ex vivo nerve conduction and the G-ratios of the sciatic nerve were analyzed, and thermosensitive ion channel mRNA expression in dorsal root ganglia (DRG) was assessed. The presence of human α-syn in Schwann cells was associated with subtle behavioral impairments. The G-ratio of the sciatic nerve, the conduction velocity of myelinated and unmyelinated primary afferents and the expression of thermosensitive ion channels in the sensory neurons, however, were similar to wildtype mice. Conclusion Our results suggest that the PNS appears to be affected by Schwann cell α-syn deposits in the PLP-α-syn MSA mouse model. However, there was no consistent evidence for functional PNS perturbations resulting from such α-syn aggregates suggesting a more central cause of the observed behavioral abnormalities. Nonetheless, our results do not exclude a causal role of α-syn in the pathogenesis of MSA associated peripheral neuropathy. PMID:26496712

  19. The afferent pupillary defect in acute optic neuritis.

    PubMed Central

    Ellis, C J

    1979-01-01

    Twenty-two patients with acute optic neuritis were studied by the techniques of infrared pupillometry and visual evoked responses (VER) to pattern reversal. A relative afferent pupillary defect was found in all cases and the magnitude of this defect was found to be related to the amplitude, but not to the latency, of the VER. During follow-up the afferent defect was found to remain persistently abnormal while other methods of clinical evaluation could not demonstrate abnormality reliably. The amplitude of the VER also remained low. PMID:501365

  20. [Nerve anastomoses. Sutures or fibrinogenic glue? Preliminary results].

    PubMed

    Boedts, D; Bouckaert, J I

    1984-01-01

    A comparative animal experiment was set up between two nerve anastomosis techniques, one by sealing nerve ends with a fibrinogen-thrombine glue and the other by classical perineural suturing. It was concluded that glueing nerve ends, from the surgical-technical point of view is a better method than suturing. It is an easy, time-sparing method which allows excellent coaptation of the severed nerves with minimal iatrogenic trauma. On the long run however some questions remain. There is the problem of induced fibrosis by using high doses of aprotinine and factor XIII at the site of the nerve junctions and on the other hand the influence of fibrinolysis in traumatized tissues, with early decrease of tensile strength at the junctions before nerve healing. So glued nerve ends should be completely free of tension, protected against secondary shearing forces, and also immobilization of the region is required. PMID:6385609

  1. Simulation studies of vestibular macular afferent-discharge patterns using a new, quasi-3-D finite volume method

    NASA Technical Reports Server (NTRS)

    Ross, M. D.; Linton, S. W.; Parnas, B. R.

    2000-01-01

    A quasi-three-dimensional finite-volume numerical simulator was developed to study passive voltage spread in vestibular macular afferents. The method, borrowed from computational fluid dynamics, discretizes events transpiring in small volumes over time. The afferent simulated had three calyces with processes. The number of processes and synapses, and direction and timing of synapse activation, were varied. Simultaneous synapse activation resulted in shortest latency, while directional activation (proximal to distal and distal to proximal) yielded most regular discharges. Color-coded visualizations showed that the simulator discretized events and demonstrated that discharge produced a distal spread of voltage from the spike initiator into the ending. The simulations indicate that directional input, morphology, and timing of synapse activation can affect discharge properties, as must also distal spread of voltage from the spike initiator. The finite volume method has generality and can be applied to more complex neurons to explore discrete synaptic effects in four dimensions.

  2. Cartilage oligomeric matrix protein enhances the vascularization of acellular nerves

    PubMed Central

    Cui, Wei-ling; Qiu, Long-hai; Lian, Jia-yan; Li, Jia-chun; Hu, Jun; Liu, Xiao-lin

    2016-01-01

    Vascularization of acellular nerves has been shown to contribute to nerve bridging. In this study, we used a 10-mm sciatic nerve defect model in rats to determine whether cartilage oligomeric matrix protein enhances the vascularization of injured acellular nerves. The rat nerve defects were treated with acellular nerve grafting (control group) alone or acellular nerve grafting combined with intraperitoneal injection of cartilage oligomeric matrix protein (experimental group). As shown through two-dimensional imaging, the vessels began to invade into the acellular nerve graft from both anastomotic ends at day 7 post-operation, and gradually covered the entire graft at day 21. The vascular density, vascular area, and the velocity of revascularization in the experimental group were all higher than those in the control group. These results indicate that cartilage oligomeric matrix protein enhances the vascularization of acellular nerves. PMID:27127495

  3. Nerve conduction velocity

    MedlinePlus

    Nerve conduction velocity (NCV) is a test to see how fast electrical signals move through a nerve. ... normal body temperature. Being too cold slows nerve conduction. Tell your doctor if you have a cardiac ...

  4. Femoral nerve damage (image)

    MedlinePlus

    The femoral nerve is located in the leg and supplies the muscles that assist help straighten the leg. It supplies sensation ... leg. One risk of damage to the femoral nerve is pelvic fracture. Symptoms of femoral nerve damage ...

  5. Ulnar nerve damage (image)

    MedlinePlus

    The ulnar nerve originates from the brachial plexus and travels down arm. The nerve is commonly injured at the elbow because of elbow fracture or dislocation. The ulnar nerve is near the surface of the body where ...

  6. Diabetes and nerve damage

    MedlinePlus

    ... hot or cold When the nerves that control digestion are affected, you may have trouble digesting food. ... harder to control. Damage to nerves that control digestion almost always occurs in people with severe nerve ...

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

    PubMed

    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. PMID:22323647

  8. Trafficking of Na+/Ca2+ exchanger to the site of persistent inflammation in nociceptive afferents.

    PubMed

    Scheff, Nicole N; Gold, Michael S

    2015-06-01

    Persistent inflammation results in an increase in the amplitude and duration of depolarization-evoked Ca(2+) transients in putative nociceptive afferents. Previous data indicated that these changes were the result of neither increased neuronal excitability nor an increase in the amplitude of depolarization. Subsequent data also ruled out an increase in voltage-gated Ca(2+) currents and recruitment of Ca(2+)-induced Ca(2+) release. Parametric studies indicated that the inflammation-induced increase in the duration of the evoked Ca(2+) transient required a relatively large and long-lasting increase in the concentration of intracellular Ca(2+) implicating the Na(+)/Ca(2+) exchanger (NCX), a major Ca(2+) extrusion mechanism activated with high intracellular Ca(2+) loads. The contribution of NCX to the inflammation-induced increase in the evoked Ca(2+) transient in rat sensory neurons was tested using fura-2 AM imaging and electrophysiological recordings. Changes in NCX expression and protein were assessed with real-time PCR and Western blot analysis, respectively. An inflammation-induced decrease in NCX activity was observed in a subpopulation of putative nociceptive neurons innervating the site of inflammation. The time course of the decrease in NCX activity paralleled that of the inflammation-induced changes in nociceptive behavior. The change in NCX3 in the cell body was associated with a decrease in NCX3 protein in the ganglia, an increase in the peripheral nerve (sciatic) yet no change in the central root. This single response to inflammation is associated with changes in at least three different segments of the primary afferent, all of which are likely to contribute to the dynamic response to persistent inflammation. PMID:26041911

  9. Bradykinin and nerve growth factor release the capsaicin receptor from PtdIns(4,5)P2-mediated inhibition.

    PubMed

    Chuang, H H; Prescott, E D; Kong, H; Shields, S; Jordt, S E; Basbaum, A I; Chao, M V; Julius, D

    2001-06-21

    Tissue injury generates endogenous factors that heighten our sense of pain by increasing the response of sensory nerve endings to noxious stimuli. Bradykinin and nerve growth factor (NGF) are two such pro-algesic agents that activate G-protein-coupled (BK2) and tyrosine kinase (TrkA) receptors, respectively, to stimulate phospholipase C (PLC) signalling pathways in primary afferent neurons. How these actions produce sensitization to physical or chemical stimuli has not been elucidated at the molecular level. Here, we show that bradykinin- or NGF-mediated potentiation of thermal sensitivity in vivo requires expression of VR1, a heat-activated ion channel on sensory neurons. Diminution of plasma membrane phosphatidylinositol-4,5-bisphosphate (PtdIns(4,5)P2) levels through antibody sequestration or PLC-mediated hydrolysis mimics the potentiating effects of bradykinin or NGF at the cellular level. Moreover, recruitment of PLC-gamma to TrkA is essential for NGF-mediated potentiation of channel activity, and biochemical studies suggest that VR1 associates with this complex. These studies delineate a biochemical mechanism through which bradykinin and NGF produce hypersensitivity and might explain how the activation of PLC signalling systems regulates other members of the TRP channel family. PMID:11418861

  10. Presynaptic Inhibition of Diverse Afferents to the Locus Coeruleus by Kappa Opiate Receptors: a Novel Mechanism for Regulating the Central Norepinephrine System

    PubMed Central

    Kreibich, Arati S.; Reyes, Beverly A. S.; Curtis, Andre L.; Ecke, Laurel; Chavkin, Charles; Van Bockstaele, Elisabeth J.; Valentino, Rita J.

    2008-01-01

    The norepinephrine nucleus, locus coeruleus (LC), is activated by diverse stimuli and modulates arousal and behavioral strategies in response to these stimuli through its divergent efferent system. Afferents communicating information to the LC include excitatory amino acids (EAA), corticotropin-releasing factor (CRF) and endogenous opioids acting at μ-opiate receptors. As the LC is also innervated by the endogenous κ-opiate receptor (κ-OR) ligand, dynorphin, and expresses κ-ORs, this study investigated κ-OR regulation of LC neuronal activity in rat. Immunoelectron microscopy revealed a prominent localization of κ-ORs in axon terminals in the LC that also contained either the vesicular glutamate transporter or CRF. Microinfusion of the κ-OR agonist, U50488, into the LC did not alter LC spontaneous discharge but attenuated phasic discharge evoked by stimuli that engage EAA afferents to the LC, including sciatic nerve stimulation and auditory stimuli and the tonic activation associated with opiate withdrawal. Inhibitory effects of the κ-OR agonist were not restricted to EAA afferents, as U50488 also attenuated tonic LC activation by hypotensive stress, an effect mediated by CRF afferents. Together, these results indicate that κ-ORs are poised to presynaptically inhibit diverse afferent signaling to the LC. This is a novel and potentially powerful means of regulating the LC-NE system that can impact on forebrain processing of stimuli and the organization of behavioral strategies in response to environmental stimuli. The results implicate κ-ORs as a novel target for alleviating symptoms of opiate withdrawal, stress-related disorders or disorders characterized by abnormal sensory responses, such as autism. PMID:18562623

  11. Neck afferents and muscle sympathetic activity in humans: implications for the vestibulosympathetic reflex.

    PubMed

    Ray, C A; Hume, K M

    1998-02-01

    We have shown previously that head-down neck flexion (HDNF) in humans elicits increases in muscle sympathetic nerve activity (MSNA). The purpose of this study was to determine the effect of neck muscle afferents on MSNA. We studied this question by measuring MSNA before and after head rotation that would activate neck muscle afferents but not the vestibular system (i.e., no stimulation of the otolith organs or semicircular canals). After a 3-min baseline period with the head in the normal erect position, subjects rotated their head to the side (approximately 90%) and maintained this position for 3 min. Head rotation was performed by the subjects in both the prone (n = 5) and sitting (n = 6) positions. Head rotation did not elicit changes in MSNA. Average MSNA, expressed as burst frequency and total activity, was 13 +/- 1 and 13 +/- 1 bursts/min and 146 +/-34 and 132 +/- 27 units/min during baseline and head rotation, respectively. There were no significant changes in calf blood flow (2.6 +/- 0.3 to 2.5 +/- 0.3 ml.100 ml-1.min-1, n = 8) and calf vascular resistance (39 +/- 4 to 41 +/- 4 units; n = 8). Heart rate (64 +/- 3 to 66 +/- 3 beats/min; P = 0.058) and mean arterial pressure (90 +/- 3 to 93 +/- 3; P < 0.05) increased slightly during head rotation. Additional neck flexion studies were performed with subjects lying on their side (n = 5), MSNA, heart rate, and mean arterial pressure were unchanged during this maneuver, which also does not engage the vestibular system. HDNF was tested in 9 of the 13 subjects. MSNA was significantly increased by 79 +/- 12% (P < 0.001) during HDNF. These findings indicate that neck afferents activated by horizontal neck rotation or flexion in the absence of significant force development do not elicit changes in MSNA. These findings support the concept that HDNF increases MSNA by the activation of the vestibular system. PMID:9475851

  12. Ventral Tegmental Area Afferents and Drug-Dependent Behaviors

    PubMed Central

    Oliva, Idaira; Wanat, Matthew J.

    2016-01-01

    Drug-related behaviors in both humans and rodents are commonly thought to arise from aberrant learning processes. Preclinical studies demonstrate that the acquisition and expression of many drug-dependent behaviors involves the ventral tegmental area (VTA), a midbrain structure comprised of dopamine, GABA, and glutamate neurons. Drug experience alters the excitatory and inhibitory synaptic input onto VTA dopamine neurons, suggesting a critical role for VTA afferents in mediating the effects of drugs. In this review, we present evidence implicating the VTA in drug-related behaviors, highlight the diversity of neuronal populations in the VTA, and discuss the behavioral effects of selectively manipulating VTA afferents. Future experiments are needed to determine which VTA afferents and what neuronal populations in the VTA mediate specific drug-dependent behaviors. Further studies are also necessary for identifying the afferent-specific synaptic alterations onto dopamine and non-dopamine neurons in the VTA following drug administration. The identification of neural circuits and adaptations involved with drug-dependent behaviors can highlight potential neural targets for pharmacological and deep brain stimulation interventions to treat substance abuse disorders. PMID:27014097

  13. Morphologic diversity of cutaneous sensory afferents revealed by genetically directed sparse labeling

    PubMed Central

    Wu, Hao; Williams, John; Nathans, Jeremy

    2012-01-01

    The diversity of cutaneous sensory afferents has been studied by many investigators using behavioral, physiologic, molecular, and genetic approaches. Largely missing, thus far, is an analysis of the complete morphologies of individual afferent arbors. Here we present a survey of cutaneous sensory arbor morphologies in hairy skin of the mouse using genetically-directed sparse labeling with a sensory neuron-specific alkaline phosphatase reporter. Quantitative analyses of 719 arbors, among which 77 were fully reconstructed, reveal 10 morphologically distinct types. Among the two types with the largest arbors, one contacts ∼200 hair follicles with circumferential endings and a second is characterized by a densely ramifying arbor with one to several thousand branches and a total axon length between one-half and one meter. These observations constrain models of receptive field size and structure among cutaneous sensory neurons, and they raise intriguing questions regarding the cellular and developmental mechanisms responsible for this morphological diversity. DOI: http://dx.doi.org/10.7554/eLife.00181.001 PMID:23256042

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

    PubMed

    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. PMID:26279210

  15. Intact subepidermal nerve fibers mediate mechanical hypersensitivity via the activation of protein kinase C gamma in spared nerve injury

    PubMed Central

    Ko, Miau-Hwa; Yang, Ming-Ling; Youn, Su-Chung; Tseng, To-Jung

    2016-01-01

    Background Spared nerve injury is an important neuropathic pain model for investigating the role of intact primary afferents in the skin on pain hypersensitivity. However, potential cellular mechanisms remain poorly understood. In phosphoinositide-3 kinase pathway, pyruvate dehydrogenase kinase 1 (PDK1) participates in the regulation of neuronal plasticity for central sensitization. The downstream cascades of PDK1 include: (1) protein kinase C gamma (PKCγ) controls the trafficking and phosphorylation of ionotropic glutamate receptor; (2) protein kinase B (Akt)/the mammalian target of rapamycin (mTOR) signaling is responsible for local protein synthesis. Under these statements, we therefore hypothesized that an increase of PKCγ activation and mTOR-dependent PKCγ synthesis in intact primary afferents after SNI might contribute to pain hypersensitivity. Results The variants of spared nerve injury were performed in Sprague-Dawley rats by transecting any two of the three branches of the sciatic nerve, leaving only one branch intact. Following SNIt (spared tibial branch), mechanical hyperalgesia and mechanical allodynia, but not thermal hyperalgesia, were significantly induced. In the first footpad, normal epidermal innervations were verified by the protein gene product 9.5 (PGP9.5)- and growth-associated protein 43 (GAP43)-immunoreactive (IR) intraepidermal nerve fibers (IENFs) densities. Furthermore, the rapid increases of phospho-PKCγ- and phospho-mTOR-IR subepidermal nerve fibers (SENFs) areas were distinct gathered from the results of PGP9.5-, GAP43-, and neurofilament 200 (NF200)-IR SENFs areas. The efficacy of PKC inhibitor (GF 109203X) or mTOR complex 1 inhibitor (rapamycin) for attenuating mechanical hyperalgesia and mechanical allodynia by intraplantar injection was dose-dependent. Conclusions From results obtained in this study, we strongly recommend that the intact SENFs persistently increase PKCγ activation and mTOR-dependent PKCγ synthesis participate

  16. A role for nociceptive, myelinated nerve fibers in itch sensation

    PubMed Central

    Ringkamp, M.; Schepers, R. J.; Shimada, S.G.; Johanek, L.M.; Hartke, T.V.; Borzan, J.; Shim, B.; LaMotte, R.H.; Meyer, R.A.

    2011-01-01

    Despite its clinical importance, the underlying neural mechanisms of itch sensation are poorly understood. In many diseases, pruritus is not effectively treated with antihistamines, indicating the involvement of non-histaminergic mechanisms. To investigate the role of small myelinated afferents in non-histaminergic itch, we tested, in psychophysical studies in humans, the effect of a differential nerve block on itch produced by intradermal insertion of spicules from the pods of a cowhage plant (Mucuna pruriens). Electrophysiological experiments in anesthetized monkey were used to investigate the responsiveness of cutaneous, nociceptive, myelinated afferents to different chemical stimuli (cowhage spicules, histamine, capsaicin). Our results provide several lines of evidence for an important role of myelinated fibers in cowhage-induced itch: 1) a selective conduction block in myelinated fibers substantially reduces itch in a sub-group of subjects with A-fiber dominated itch, 2) the time course of itch sensation differs between subjects with A-fiber versus C-fiber dominated itch, 3) cowhage activates a subpopulation of myelinated and unmyelinated afferents in monkey, 4) the time course of the response to cowhage is different in myelinated and unmyelinated fibers, 5) the time of peak itch sensation for subjects with A-fiber dominated itch matches the time for peak response in myelinated fibers, and 6) the time for peak itch sensation for subjects with C-fiber dominated itch matches the time for the peak response in unmyelinated fibers. These findings demonstrate that activity in nociceptive, myelinated afferents contributes to cowhage-induced sensations, and that non-histaminergic itch is mediated through activity in both unmyelinated and myelinated afferents. PMID:22016517

  17. Hypoxia inhibits abdominal expiratory nerve activity.

    PubMed

    Fregosi, R F; Knuth, S L; Ward, D K; Bartlett, D

    1987-07-01

    Our purpose was to examine the influence of steady-state changes in chemical stimuli, as well as discrete peripheral chemoreceptor stimulation, on abdominal expiratory motor activity. In decerebrate, paralyzed, vagotomized, and ventilated cats that had bilateral pneumothoraces, we recorded efferent activity from a phrenic nerve and from an abdominal nerve (cranial iliohypogastric nerve, L1). All cats showed phasic expiratory abdominal nerve discharge at normocapnia [end-tidal PCO2 38 +/- 2 Torr], but small doses (2-6 mg/kg) of pentobarbital sodium markedly depressed this activity. Hyperoxic hypercapnia consistently enhanced abdominal expiratory activity and shortened the burst duration. Isocapnic hypoxia caused inhibition of abdominal nerve discharge in 11 of 13 cats. Carotid sinus nerve denervation (3 cats) exacerbated the hypoxic depression of abdominal nerve activity and depressed phrenic motor output. Stimulation of peripheral chemoreceptors with NaCN increased abdominal nerve discharge in 7 of 10 cats, although 2 cats exhibited marked inhibition. Four cats with intact neuraxis, but anesthetized with ketamine, yielded qualitatively similar results. We conclude that when cats are subjected to steady-state chemical stimuli in isolation (no interference from proprioceptive inputs), hypercapnia potentiates, but hypoxia attenuates, abdominal expiratory nerve activity. Mechanisms to explain the selective inhibition of expiratory motor activity by hypoxia are proposed, and physiological implications are discussed. PMID:3624126

  18. Repair of peripheral nerve with vein wrapping*

    PubMed Central

    LEUZZI, S.; ARMENIO, A.; LEONE, L.; DE SANTIS, V.; DI TURI, A.; ANNOSCIA, P.; BUFANO, L.; PASCONE, M.

    2014-01-01

    Objective The post–traumatic neuro-anastomosis must be protected from the surrounding environment. This barrier must be biologically inert, biodegradable, not compressing but protecting the nerve. Formation of painful neuroma is one of the major issues with neuro-anastomosis; currently there is no consensus on post-repair neuroma prevention. Aim of this study is to evaluate the efficacy of neuroanastomosis performed with venous sheath to reduce painful neuromas formation, improve the electrical conductivity of the repaired nerve, and reduce the discrepancies of the sectioned nerve stumps. Patients and methods From a trauma population of 320 patients treated in a single centre between January 2008 and December 2011, twenty-six patients were identified as having an injury to at least one of the peripheral nerves of the arm and enrolled in the study. Patients were divided into two groups. In the group A (16 patients) the end-to-end nerve suture was wrapped in a vein sheath and compared with the group B (10 patients) in which a simple end-to-end neurorrhaphy was performed. The venous segment used to cover the nerve micro-suture was harvested from the superficial veins of the forearm. The parameters analyzed were: functional recovery of motor nerves, sensitivity and pain. Results Average follow-up was 14 months (range: 12–24 months). The group A showed a more rapid motor and sensory recovery and a reduction of the painful symptoms compared to the control group (B). Conclusions The Authors demonstrated that, in their experience, the venous sheath provides a valid solution to avoid the dispersion of the nerve fibres, to prevent adherent scars and painful neuromas formation. Moreover it can compensate the different size of two nerve stumps, allowing, thereby, a more rapid functional and sensitive recovery without expensive devices. PMID:24841688

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

    PubMed

    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. PMID:23155170

  20. Macrophage-Colony Stimulating Factor Derived from Injured Primary Afferent Induces Proliferation of Spinal Microglia and Neuropathic Pain in Rats.

    PubMed

    Okubo, Masamichi; Yamanaka, Hiroki; Kobayashi, Kimiko; Dai, Yi; Kanda, Hirosato; Yagi, Hideshi; Noguchi, Koichi

    2016-01-01

    Peripheral nerve injury induces proliferation of microglia in the spinal cord, which can contribute to neuropathic pain conditions. However, candidate molecules for proliferation of spinal microglia after injury in rats remain unclear. We focused on the colony-stimulating factors (CSFs) and interleukin-34 (IL-34) that are involved in the proliferation of the mononuclear phagocyte lineage. We examined the expression of mRNAs for macrophage-CSF (M-CSF), granulocyte macrophage-CSF (GM-CSF), granulocyte-CSF (G-CSF) and IL-34 in the dorsal root ganglion (DRG) and spinal cord after spared nerve injury (SNI) in rats. RT-PCR and in situ hybridization revealed that M-CSF and IL-34, but not GM- or G-CSF, mRNAs were constitutively expressed in the DRG, and M-CSF robustly increased in injured-DRG neurons. M-CSF receptor mRNA was expressed in naive rats and increased in spinal microglia following SNI. Intrathecal injection of M-CSF receptor inhibitor partially but significantly reversed the proliferation of spinal microglia and in early phase of neuropathic pain induced by SNI. Furthermore, intrathecal injection of recombinant M-CSF induced microglial proliferation and mechanical allodynia. Here, we demonstrate that M-CSF is a candidate molecule derived from primary afferents that induces proliferation of microglia in the spinal cord and leads to induction of neuropathic pain after peripheral nerve injury in rats. PMID:27071004

  1. Macrophage-Colony Stimulating Factor Derived from Injured Primary Afferent Induces Proliferation of Spinal Microglia and Neuropathic Pain in Rats

    PubMed Central

    Okubo, Masamichi; Yamanaka, Hiroki; Kobayashi, Kimiko; Dai, Yi; Kanda, Hirosato; Yagi, Hideshi; Noguchi, Koichi

    2016-01-01

    Peripheral nerve injury induces proliferation of microglia in the spinal cord, which can contribute to neuropathic pain conditions. However, candidate molecules for proliferation of spinal microglia after injury in rats remain unclear. We focused on the colony-stimulating factors (CSFs) and interleukin-34 (IL-34) that are involved in the proliferation of the mononuclear phagocyte lineage. We examined the expression of mRNAs for macrophage-CSF (M-CSF), granulocyte macrophage-CSF (GM-CSF), granulocyte-CSF (G-CSF) and IL-34 in the dorsal root ganglion (DRG) and spinal cord after spared nerve injury (SNI) in rats. RT-PCR and in situ hybridization revealed that M-CSF and IL-34, but not GM- or G-CSF, mRNAs were constitutively expressed in the DRG, and M-CSF robustly increased in injured-DRG neurons. M-CSF receptor mRNA was expressed in naive rats and increased in spinal microglia following SNI. Intrathecal injection of M-CSF receptor inhibitor partially but significantly reversed the proliferation of spinal microglia and in early phase of neuropathic pain induced by SNI. Furthermore, intrathecal injection of recombinant M-CSF induced microglial proliferation and mechanical allodynia. Here, we demonstrate that M-CSF is a candidate molecule derived from primary afferents that induces proliferation of microglia in the spinal cord and leads to induction of neuropathic pain after peripheral nerve injury in rats. PMID:27071004

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

    PubMed

    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. PMID:7362125

  3. Optical Biopsy of Peripheral Nerve Using Confocal Laser Endomicroscopy: A New Tool for Nerve Surgeons?

    PubMed

    Crowe, Christopher S; Liao, Joseph C; Curtin, Catherine M

    2015-09-01

    Peripheral nerve injuries remain a challenge for reconstructive surgeons with many patients obtaining suboptimal results. Understanding the level of injury is imperative for successful repair. Current methods for distinguishing healthy from damaged nerve are time consuming and possess limited efficacy. Confocal laser endomicroscopy (CLE) is an emerging optical biopsy technology that enables dynamic, high resolution, sub-surface imaging of live tissue. Porcine sciatic nerve was either left undamaged or briefly clamped to simulate injury. Diluted fluorescein was applied topically to the nerve. CLE imaging was performed by direct contact of the probe with nerve tissue. Images representative of both damaged and undamaged nerve fibers were collected and compared to routine H&E histology. Optical biopsy of undamaged nerve revealed bands of longitudinal nerve fibers, distinct from surrounding adipose and connective tissue. When damaged, these bands appear truncated and terminate in blebs of opacity. H&E staining revealed similar features in damaged nerve fibers. These results prompt development of a protocol for imaging peripheral nerves intraoperatively. To this end, improving surgeons' ability to understand the level of injury through real-time imaging will allow for faster and more informed operative decisions than the current standard permits. PMID:26430636

  4. Optical Biopsy of Peripheral Nerve Using Confocal Laser Endomicroscopy: A New Tool for Nerve Surgeons?

    PubMed Central

    Liao, Joseph C; Curtin, Catherine M

    2015-01-01

    Peripheral nerve injuries remain a challenge for reconstructive surgeons with many patients obtaining suboptimal results. Understanding the level of injury is imperative for successful repair. Current methods for distinguishing healthy from damaged nerve are time consuming and possess limited efficacy. Confocal laser endomicroscopy (CLE) is an emerging optical biopsy technology that enables dynamic, high resolution, sub-surface imaging of live tissue. Porcine sciatic nerve was either left undamaged or briefly clamped to simulate injury. Diluted fluorescein was applied topically to the nerve. CLE imaging was performed by direct contact of the probe with nerve tissue. Images representative of both damaged and undamaged nerve fibers were collected and compared to routine H&E histology. Optical biopsy of undamaged nerve revealed bands of longitudinal nerve fibers, distinct from surrounding adipose and connective tissue. When damaged, these bands appear truncated and terminate in blebs of opacity. H&E staining revealed similar features in damaged nerve fibers. These results prompt development of a protocol for imaging peripheral nerves intraoperatively. To this end, improving surgeons' ability to understand the level of injury through real-time imaging will allow for faster and more informed operative decisions than the current standard permits. PMID:26430636

  5. Using Eggshell Membrane as Nerve Guide Channels in Peripheral Nerve Regeneration

    PubMed Central

    Farjah, Gholam Hossein; Heshmatian, Behnam; Karimipour, Mojtaba; Saberi, Ali

    2013-01-01

    Objective(s): The aim of this study was to evaluate the final outcome of nerve regeneration across the eggsell membrane (ESM) tube conduit in comparison with autograft. Materials and Methods: Thirty adult male rats (250-300 g) were randomized into (1) ESM conduit, (2) autograft, and (3) sham surgery groups. The eggs submerged in 5% acetic acid. The decalcifying membranes were cut into four pieces, rotated over the teflon mandrel and dried at 37°C. The left sciatic nerve was surgically cut. A 10-mm nerve segment was cut and removed. In the ESM group, the proximal and distal cut ends of the sciatic nerve were telescoped into the nerve guides. In the autograft group, the 10 mm nerve segment was reversed and used as an autologous nerve graft. All animals were evaluated by sciatic functional index (SFI) and electrophysiology testing. Results: The improvement in SFI from the first to the last evalution in ESM and autograft groups were evaluated. On days 49 and 60 post-operation, the mean SFI of ESM group was significantly greater than the autograft group (P< 0.05). On day 90, the mean nerve conduction velocity (NCV) of ESM group was greater than autograft group, although the difference was not statistically significant (P> 0.05). Conclusion: These findings demonstrate that ESM effectively enhances nerve regeneration and promotes functional recovery in injured sciatic nerve of rat. PMID:24106593

  6. Phase relation changes between the firings of alpha and gamma-motoneurons and muscle spindle afferents in the sacral micturition centre during continence functions in brain-dead human and patients with spinal cord injury.

    PubMed

    Schalow, G

    2010-01-01

    1. Single-nerve fibre action potentials (APs) were recorded with 2 pairs of wire electrodes from lower sacral nerve roots during surgery in patients with spinal cord injury and in a brain-dead human. Conduction velocity distribution histograms were constructed for afferent and efferent fibres, nerve fibre groups were identified and simultaneous impulse patterns of alpha and gamma-motoneurons and secondary muscle spindle afferents (SP2) were constructed. Temporal relations between afferent and efferent APs were analyzed by interspike interval (II) and phase relation changes to explore the coordinated self-organization of somatic and parasympathetic neuronal networks in the sacral micturition centre during continence functions under physiologic (brain-dead) and pathophysiologic conditions (spinal cord injury). 2. In a paraplegic with hyperreflexia of the bladder, urinary bladder stretch (S1) and tension receptor afferents (ST) fired already when the bladder was empty, and showed a several times higher bladder afferent activity increase upon retrograde bladder filling than observed in the brain-dead individual. Two alpha2-motoneurons (FR) innervating the external bladder sphincter were already oscillatory firing to generate high activity levels when the bladder was empty. They showed activity levels with no bladder filling, comparable to those measured at a bladder filling of 600 ml in the brain-dead individual. A bladder storage volume of 600 ml was thus lost in the paraplegic, due to a too high bladder afferent input to the sacral micturition center, secondary to inflammation and hypertrophy of the detrusor. 3. In a brain-dead human, 2 phase relations existed per oscillation period of 160 ms between the APs of a sphincteric oscillatory firing alpha2-motoneuron, a dynamic fusimotor and a secondary muscle spindle afferent fibre. Following stimulation of mainly somatic afferent fibres, the phase relations changed only little. 4. In a paraplegic with dyssynergia of the

  7. Afferent projections to the deep mesencephalic nucleus in the rat

    SciTech Connect

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

    1982-01-10

    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.

  8. Enhanced Muscle Afferent Signals during Motor Learning in Humans.

    PubMed

    Dimitriou, Michael

    2016-04-25

    Much has been revealed concerning human motor learning at the behavioral level [1, 2], but less is known about changes in the involved neural circuits and signals. By examining muscle spindle responses during a classic visuomotor adaptation task [3-6] performed by fully alert humans, I found substantial modulation of sensory afferent signals as a function of adaptation state. Specifically, spindle control was independent of concurrent muscle activity but was specific to movement direction (representing muscle lengthening versus shortening) and to different stages of learning. Increased spindle afferent responses to muscle stretch occurring early during learning reflected individual error size and were negatively related to subsequent antagonist activity (i.e., 60-80 ms thereafter). Relative increases in tonic afferent output early during learning were predictive of the subjects' adaptation rate. I also found that independent spindle control during sensory realignment (the "washout" stage) induced afferent signal "linearization" with respect to muscle length (i.e., signals were more tuned to hand position). The results demonstrate for the first time that motor learning also involves independent and state-related modulation of sensory mechanoreceptor signals. The current findings suggest that adaptive motor performance also relies on the independent control of sensors, not just of muscles. I propose that the "γ" motor system innervating spindles acts to facilitate the acquisition and extraction of task-relevant information at the early stages of sensorimotor adaptation. This designates a more active and targeted role for the human proprioceptive system during motor learning. PMID:27040776

  9. Endothelin-1 induced desensitization in primary afferent neurons

    PubMed Central

    Smith, Terika P.; Smith, Sherika N.; Sweitzer, Sarah M.

    2014-01-01

    Endothelin-1 (ET-1) is a known algogen that causes acute pain and sensitization in humans and spontaneous nociceptive behaviors when injected into the periphery in rats, and is elevated during vaso-occlusive episodes (VOEs) in sickle cell disease (SCD) patients. Previously, our lab has shown that a priming dose of ET-1 produces sensitization to capsaicin-induce secondary hyperalgesia. The goal of this study was to determine if the sensitization induced by ET-1 priming is occurring at the level of the primary afferent neuron. Calcium imaging in cultured dorsal root ganglion (DRG) neurons was utilized to examine the effects of ET-1 on primary afferent neurons. ET-1 induces [Ca2+]i transients in unprimed cells. ET-1 induced [Ca2+]i transients are attenuated by priming with ET-1. This priming effect occurs whether the priming dose is given 0-4 days prior to the challenge dose. Similarly, ET-1 priming decreases capsaicin-induced [Ca2+]i transients. At the level of the primary afferent neuron, ET-1 priming has a desensitizing effect on challenge exposures to ET-1 and capsaicin. PMID:25220703

  10. Subcortical afferent connections of the amygdala in the monkey

    NASA Technical Reports Server (NTRS)

    Mehler, W. R.

    1980-01-01

    The cells of origin of the afferent connections of the amygdala in the rhesus and squirrel monkeys are determined according to the retrograde axonal transport of the enzyme horseradish peroxidase injected into various quadrants of the amygdala. Analysis of the distribution of enzyme-labeled cells reveals afferent amygdalar connections with the ipsilateral halves of the midline nucleus paraventricularis thalami and both the parvo- and magnocellular parts of the nucleus subparafascicularis in the dorsal thalamus, all the subdivisions of the midline nucleus centralis complex, the nucleus reuniens ventralis and the nucleus interventralis. The largest populations of enzyme-labeled cells in the hypothalamus are found to lie in the middle and posterior parts of the ipsilateral, lateral hypothalamus and the ventromedial hypothalamic nucleus, with scattered cells in the supramammillary and dorsomedial nuclei and the posterior hypothalamic area, Tsai's ventral tegmental area, the rostral and caudal subdivisions of the nucleus linearis in the midbrain and the dorsal raphe nucleus. The most conspicuous subdiencephalic source of amygdalar afferent connections is observed to be the pars lateralis of the nucleus parabrachialis in the dorsolateral pontine tegmentum, with a few labeled cells differentiated from pigmented cells in the locus coeruleus.

  11. Neck afferent involvement in cardiovascular control during movement

    NASA Technical Reports Server (NTRS)

    Bolton, P. S.; Ray, C. A.

    2000-01-01

    It is well established that labyrinth and neck afferent information contributes to the regulation of somatomotor function during movement and changes in posture. There is also convincing evidence that the vestibular system participates in the modulation of sympathetic outflow and cardiovascular function during changes in posture, presumably to prevent orthostatic hypotension. However, the labyrinth organs do not provide any signals concerning body movements with respect to the head. In contrast, the neck receptors, particularly muscle spindles, are well located and suited to provide information about changes in body position with respect to the head and vestibular signals. Studies in the cat suggest that neck afferent information may modulate the vestibulosympathetic reflex responses to head-neck movements. There is some evidence in the cat to suggest involvement of low threshold mechanoreceptors. However, human studies do not indicate that low threshold mechanoreceptors in the neck modulate cardiovascular responses. The human studies are consistent with the studies in the cat in that they demonstrate the importance of otolith activation in mediating cardiovascular and sympathetic responses to changes in posture. This paper briefly reviews the current experimental evidence concerning the involvement of neck afferent information in the modulation of cardiovascular control during movement and changes in posture.

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

    PubMed

    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

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

    PubMed Central

    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

  14. Bilirubin induces auditory neuropathy in neonatal guinea pigs via auditory nerve fiber damage.

    PubMed

    Ye, Hai-Bo; Shi, Hai-Bo; Wang, Jian; Ding, Da-Lian; Yu, Dong-Zhen; Chen, Zheng-Nong; Li, Chun-Yan; Zhang, Wei-Tian; Yin, Shan-Kai

    2012-11-01

    Bilirubin can cause temporary or permanent sensorineural deafness in newborn babies with hyperbilirubinemia. However, the underlying targets and physiological effects of bilirubin-induced damage in the peripheral auditory system are unclear. Using cochlear functional assays and electron microscopy imaging of the inner ear in neonatal guinea pigs, we show here that bilirubin exposure resulted in threshold elevation in both compound action potential (CAP) and auditory brainstem response (ABR), which was apparent at 1 hr and peaked 8 hr after drug administration. The threshold elevation was associated with delayed wave latencies and elongated interwave intervals in ABR and CAP. At 72 hr postinjection, these measures returned to control levels, except for the CAP amplitude. Cochlear microphonics remained unchanged during the experiment. Morphological abnormalities were consistent with the electrophysiological dysfunction, revealing fewer auditory nerve fibers (ANFs) in the basal turn, myelin sheath lesions of spiral ganglion neurons (SGNs) and ANFs, and loss of type 1 afferent endings beneath inner hair cells (IHCs) without loss of hair cells at 8 hr posttreatment. Similar to the electrophysiological findings, morphological changes were mostly reversed 10 days after treatment, except for the ANF reduction in the basal turn. These results suggest that hyperbilirubinemia in neonatal guinea pigs impaired auditory peripheral neuromechanisms that targeted mainly the IHC synapses and the myelin sheath of SGNs and their fibers. Our observations indicate a potential connection between hyperbilirubinemia and auditory neuropathy. PMID:22847875

  15. Vestibular afferent responses to linear accelerations in the alert squirrel monkey

    NASA Technical Reports Server (NTRS)

    Somps, Christopher J.; Schor, Robert H.; Tomko, David L.

    1994-01-01

    The spontaneous activity of 40 otolith afferents and 44 canal afferents was recorded in 4 alert, intact squirrel monkeys. Polarization vectors and response properties of otolith afferents were determined during static re-orientations relative to gravity and during Earth-horizontal, sinusoidal, linear oscillations. Canal afferents were tested for sensitivity to linear accelerations. For regular otolith afferents, a significant correlation between upright discharge rate and sensitivity to dynamic acceleration in the horizontal plane was observed. This correlation was not present in irregular units. The sensitivity of otolith afferents to both static tilts and dynamic linear acceleration was much greater in irregularly discharging units than in regularly discharging units. The spontaneous activity and static and dynamic response properties of regularly discharging otolith afferents were similar to those reported in barbiturate-anesthetized squirrel monkeys. Irregular afferents also had similar dynamic response properties when compared to anesthetized monkeys. However, this sample of irregular afferents in alert animals had higher resting discharge rates and greater sensitivity to static tilts. The majority of otolith polarization vectors were oriented near the horizontal in the plane of the utricular maculae; however, directions of maximum sensitivity were different during dynamic and static testing. Canal afferents were not sensitive to static tilts or linear oscillations of the head.

  16. A computational model for estimating recruitment of primary afferent fibers by intraneural stimulation in the dorsal root ganglia

    NASA Astrophysics Data System (ADS)

    Bourbeau, D. J.; Hokanson, J. A.; Rubin, J. E.; Weber, D. J.

    2011-10-01

    Primary afferent microstimulation has been proposed as a method for activating cutaneous and muscle afferent fibers to restore tactile and proprioceptive feedback after limb loss or peripheral neuropathy. Large populations of primary afferent fibers can be accessed directly by implanting microelectrode arrays in the dorsal root ganglia (DRG), which provide a compact and stable target for stimulating a diverse group of sensory fibers. To gain insight into factors affecting the number and types of primary afferents activated, we developed a computational model that simulates the recruitment of fibers in the feline L7 DRG. The model comprises two parts. The first part is a single-fiber model used to describe the current-distance relation and was based on the McIntyre-Richardson-Grill model for excitability. The second part uses the results of the singe-fiber model and published data on fiber size distributions to predict the probability of recruiting a given number of fibers as a function of stimulus intensity. The range of intensities over which exactly one fiber was recruited was approximately 0.5-5 µA (0.1-1 nC per phase); the stimulus intensity at which the probability of recruiting exactly one fiber was maximized was 2.3 µA. However, at 2.3 µA, it was also possible to recruit up to three fibers, albeit with a lower probability. Stimulation amplitudes up to 6 µA were tested with the population model, which showed that as the amplitude increased, the number of fibers recruited increased exponentially. The distribution of threshold amplitudes predicted by the model was similar to that previously reported by in vivo experimentation. Finally, the model suggested that medium diameter fibers (7.3-11.5 µm) may be recruited with much greater probability than large diameter fibers (12.8-16 µm). This model may be used to efficiently test a range of stimulation parameters and nerve morphologies to complement results from electrophysiology experiments and to aid in the

  17. Responsiveness of the somatosensory system after nerve injury and amputation in the human hand.

    PubMed

    Schady, W; Braune, S; Watson, S; Torebjörk, H E; Schmidt, R

    1994-07-01

    We studied the responsiveness of the somatosensory system in humans after prolonged deprivation of peripheral input. Eight patients with traumatic transection of the median or ulnar nerve and 6 patients with amputation of a finger or hand underwent microneurography and intraneural stimulation. Bundles of nerve fibers were electrically stimulated through a microelectrode placed in the affected nerve proximally to the site of damage or in the case of amputees, in a nerve fascicle supplying the stump. During intraneural stimulation the subjects with nerve injuries reported distinct percepts in the hypoesthetic skin. Their projections were usually confined to the territory of a single or two adjacent palmar digital nerves, similar to the fascicular territories of healthy nerves in control subjects, but there was much less microneurographically recordable afferent activity than in normal subjects. In amputees intraneural stimulation evoked sensations in a phantom digit or digits in over three fourths of the fascicles studied. We conclude that (1) the somatosensory system remains able to process information from a nerve fascicle that has lost its cutaneous territory, and (2) somatosensory localization remains accurate despite the presumed central reorganization that takes place after nerve division or amputation. This lack of functional adaptation has important implications with regard to our understanding of human central nervous system plasticity. PMID:8024265

  18. Sciatic nerve repair using adhesive bonding and a modified conduit

    PubMed Central

    Liang, Xiangdang; Cai, Hongfei; Hao, Yongyu; Sun, Geng; Song, Yaoyao; Chen, Wen

    2014-01-01

    When repairing nerves with adhesives, most researchers place glue directly on the nerve stumps, but this method does not fix the nerve ends well and allows glue to easily invade the nerve ends. In this study, we established a rat model of completely transected sciatic nerve injury and repaired it using a modified 1 cm-length conduit with inner diameter of 1.5 mm. Each end of the cylindrical conduit contains a short linear channel, while the enclosed central tube protects the nerve ends well. Nerves were repaired with 2-octyl-cyanoacrylate and suture, which complement the function of the modified conduit. The results demonstrated that for the same conduit, the average operation time using the adhesive method was much shorter than with the suture method. No significant differences were found between the two groups in sciatic function index, motor evoked potential latency, motor evoked potential amplitude, muscular recovery rate, number of medullated nerve fibers, axon diameter, or medullary sheath thickness. Thus, the adhesive method for repairing nerves using a modified conduit is feasible and effective, and reduces the operation time while providing an equivalent repair effect. PMID:25206861

  19. Bilateral sensory deprivation of trigeminal afferent fibres on corticomotor control of human tongue musculature: a preliminary study.

    PubMed

    Kothari, M; Baad-Hansen, L; Svensson, P

    2016-09-01

    Transcranial magnetic stimulation (TMS) has demonstrated changes in motor evoked potentials (MEPs) in human limb muscles following modulation of sensory afferent inputs. The aim of this study was to determine whether bilateral local anaesthesia (LA) of the lingual nerve affects the excitability of the tongue motor cortex (MI) as measured by TMS. The effect on MEPs after bilateral LA of the lingual nerve was studied, while the first dorsal interosseous (FDI) muscle served as a control in ten healthy participants. MEPs were measured on the right side of the tongue dorsum in four different conditions: (i) immediately prior to anaesthesia (baseline), (ii) during bilateral LA block of the lingual nerve, (iii) after anaesthesia had subjectively subsided (recovery) and (iv) 3 h after bilateral lingual block injection. MEPs were assessed using stimulus-response curves in steps of 10% of motor threshold (T). Eight stimuli were given at each stimulus level. The amplitudes of the tongue MEPs were significantly influenced by the stimulus intensity (P < 0·001) but not by condition (P = 0·186). However, post hoc tests showed that MEPS were statistically significantly higher during bilateral LA block condition compared with baseline at T + 40%, T + 50% and T + 60% (P < 0·028) and also compared with recovery at T + 60% (P = 0·010) as well as at 3 h after injection at T + 50% and T + 60% (P < 0·029). Bilateral LA block of the lingual nerve seems to be associated with a facilitation of the corticomotor pathways related to the tongue musculature. PMID:27265155

  20. Deletion of the murine ATP/UTP receptor P2Y2 alters mechanical and thermal response properties in polymodal cutaneous afferents.

    PubMed

    Molliver, Derek C; Rau, Kristofer K; Jankowski, Michael P; Soneji, Deepak J; Baumbauer, Kyle M; Koerber, H Richard

    2016-09-22

    P2Y2 is a member of the P2Y family of G protein-coupled nucleotide receptors that is widely co-expressed with TRPV1 in peripheral sensory neurons of the dorsal root ganglia. To characterize P2Y2 function in cutaneous afferents, intracellular recordings from mouse sensory neurons were made using an ex vivo preparation in which hindlimb skin, saphenous nerve, dorsal root ganglia and spinal cord are dissected intact. The peripheral response properties of individual cutaneous C-fibers were analyzed using digitally controlled mechanical and thermal stimuli in male P2Y2(+/+) and P2Y2(-/-) mice. Selected sensory neurons were labeled with Neurobiotin and further characterized by immunohistochemistry. In wildtype preparations, C-fibers responding to both mechanical and thermal stimuli (CMH or CMHC) preferentially bound the lectin marker IB4 and were always immunonegative for TRPV1. Conversely, cells that fired robustly to noxious heat, but were insensitive to mechanical stimuli, were TRPV1-positive and IB4-negative. P2Y2 gene deletion resulted in reduced firing by TRPV1-negative CMH fibers to a range of heat stimuli. However, we also identified an atypical population of IB4-negative, TRPV1-positive CMH fibers. Compared to wildtype CMH fibers, these TRPV1-positive neurons exhibited lower firing rates in response to mechanical stimulation, but had increased firing to noxious heat (43-51°C). Collectively, these results demonstrate that P2Y2 contributes to response properties of cutaneous afferents, as P2Y2 deletion reduces responsiveness of conventional unmyelinated polymodal afferents to heat and appears to result in the acquisition of mechanical responsiveness in a subset of TRPV1-expressing afferents. PMID:27393251

  1. Role played by NaV 1.7 channels on thin-fiber muscle afferents in transmitting the exercise pressor reflex.

    PubMed

    Stone, Audrey J; Copp, Steven W; Kaufman, Marc P

    2015-11-15

    Voltage-gated sodium channels (NaV) 1.7 are highly expressed on the axons of somatic afferent neurons and are thought to play an important role in the signaling of inflammatory pain. NaV 1.7 channels are classified as tetrodotoxin (TTX)-sensitive, meaning that they are blocked by TTX concentrations of less than 300 nM. These findings prompted us to determine in decerebrated, unanesthetized rats, the role played by NaV 1.7 channels in the transmission of muscle afferent input evoking the exercise pressor reflex. We first showed that the exercise pressor reflex, which was evoked by static contraction of the triceps surae muscles, was reversibly attenuated by application of 50 nM TTX, but not 5 nM TTX, to the L4-L5 dorsal roots (control: 21 ± 1 mmHg, TTX: 8 ± 2 mmHg, recovery: 21 ± 3 mmHg; n = 6; P < 0.01). We next found that the peak pressor responses to contraction were significantly attenuated by dorsal root application of 100 nM Ssm6a, a compound that is a selective NaV 1.7 channel inhibitor. Removal of Ssm6a restored the reflex to its control level (control: 19 ± 3 mmHg, Ssm6a: 10 ± 1 mmHg, recovery: 19 ± 4 mmHg; n = 6; P < 0.05). Compound action potentials recorded from the L4 and L5 dorsal roots and evoked by single-pulse stimulation of the sciatic nerve showed that both TTX and Ssm6a attenuated input from group III, as well as group IV afferents. We conclude that NaV 1.7 channels play a role in the thin-fiber muscle afferent pathway evoking the exercise pressor reflex. PMID:26310938

  2. Ulnar nerve damage (image)

    MedlinePlus

    ... arm. The nerve is commonly injured at the elbow because of elbow fracture or dislocation. The ulnar nerve is near ... surface of the body where it crosses the elbow, so prolonged pressure on the elbow or entrapment ...

  3. Nerve Injuries in Athletes.

    ERIC Educational Resources Information Center

    Collins, Kathryn; And Others

    1988-01-01

    Over a two-year period this study evaluated the condition of 65 athletes with nerve injuries. These injuries represent the spectrum of nerve injuries likely to be encountered in sports medicine clinics. (Author/MT)

  4. Radial nerve dysfunction (image)

    MedlinePlus

    The radial nerve travels down the arm and supplies movement to the triceps muscle at the back of the upper arm. ... the wrist and hand. The usual causes of nerve dysfunction are direct trauma, prolonged pressure on the ...

  5. Tibial nerve dysfunction

    MedlinePlus

    ... a loss of movement or sensation in the foot from damage to the tibial nerve. ... Tibial nerve dysfunction is an unusual form of peripheral ... the calf and foot muscles. A problem in function with a single ...

  6. Nerve conduction velocity

    MedlinePlus

    ... page: //medlineplus.gov/ency/article/003927.htm Nerve conduction velocity To use the sharing features on this page, please enable JavaScript. Nerve conduction velocity (NCV) is a test to see how ...

  7. Assessing nerves in leprosy.

    PubMed

    Garbino, José Antonio; Heise, Carlos Otto; Marques, Wilson

    2016-01-01

    Leprosy neuropathy is dependent on the patient's immune response and expresses itself as a focal or multifocal neuropathy with asymmetric involvement. Leprosy neuropathy evolves chronically but recurrently develops periods of exacerbation during type 1 or type 2 reactions, leading to acute neuropathy. Nerve enlargement leading to entrapment syndromes is also a common manifestation. Pain may be either of inflammatory or neuropathic origin. A thorough and detailed evaluation is mandatory for adequate patient follow-up, including nerve palpation, pain assessment, graded sensory mapping, muscle power testing, and autonomic evaluation. Nerve conduction studies are a sensitive tool for nerve dysfunction, including new lesions during reaction periods or development of entrapment syndromes. Nerve ultrasonography is also a very promising method for nerve evaluation in leprosy. The authors propose a composite nerve clinical score for nerve function assessment that can be useful for longitudinal evaluation. PMID:26773623

  8. Electromechanical Nerve Stimulator

    NASA Technical Reports Server (NTRS)

    Tcheng, Ping; Supplee, Frank H., Jr.; Prass, Richard L.

    1993-01-01

    Nerve stimulator applies and/or measures precisely controlled force and/or displacement to nerve so response of nerve measured. Consists of three major components connected in tandem: miniature probe with spherical tip; transducer; and actuator. Probe applies force to nerve, transducer measures force and sends feedback signal to control circuitry, and actuator positions force transducer and probe. Separate box houses control circuits and panel. Operator uses panel to select operating mode and parameters. Stimulator used in research to characterize behavior of nerve under various conditions of temperature, anesthesia, ventilation, and prior damage to nerve. Also used clinically to assess damage to nerve from disease or accident and to monitor response of nerve during surgery.

  9. Radial nerve dysfunction

    MedlinePlus

    ... nerve leads to problems with movement in the arm and wrist and with sensation in the back of the arm or hand. ... to the radial nerve, which travels down the arm and controls movement of the triceps muscle at ...

  10. Degenerative Nerve Diseases

    MedlinePlus

    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 ...

  11. Patterning of sympathetic nerve activity in response to vestibular stimulation

    NASA Technical Reports Server (NTRS)

    Kerman, I. A.; McAllen, R. M.; Yates, B. J.

    2000-01-01

    Growing evidence suggests a role for the vestibular system in regulation of autonomic outflow during postural adjustments. In the present paper we review evidence for the patterning of sympathetic nerve activity elicited by vestibular stimulation. In response to electrical activation of vestibular afferents, firing of sympathetic nerves located throughout the body is altered. However, activity of the renal nerve is most sensitive to vestibular inputs. In contrast, high-intensity simultaneous activation of cutaneous and muscle inputs elicits equivalent changes in firing of the renal, superior mesenteric and lumbar colonic nerves. Responses of muscle vasoconstrictor (MVC) efferents to vestibular stimulation are either inhibitory (Type I) or are comprised of a combination of excitation and inhibition (Type II). Interestingly, single MVC units located in the hindlimb exhibited predominantly Type I responses while those located in the forelimb and face exhibited Type II responses. Furthermore, brachial and femoral arterial blood flows were dissociated in response to vestibular stimulation, such that brachial vascular resistance increased while femoral resistance decreased. These studies demonstrate that vestibulosympathetic reflexes are patterned according to both the anatomical location and innervation target of a particular sympathetic nerve, and can lead to distinct changes in local blood flow.

  12. Laparoscopic pelvic anatomy of nerve-sparing radical hysterectomy.

    PubMed

    Park, Nae Yoon; Cho, Young Lae; Park, Il Soo; Lee, Yoon Soon

    2010-03-01

    Many reports regarding nerve-sparing radical hysterectomy have been published. However, most reports have been based on systematic descriptions via laparotomy or cadaver dissection. The aim of this work was to describe the pelvic anatomy of nerve-sparing radical hysterectomy via laparoscopy, with specific focus on the inferior hypogastric plexus. This study is based on 125 patients with FIGO stage IB cervical cancer who had undergone laparoscopic nerve-sparing radical hysterectomies since 1999. The inferior hypogastric plexus was demonstrated via laparoscopy and was comprised of afferent fibers from the sacral root (S2, S3, and S4), sacral sympathetic ganglion, and hypogastric nerve, and efferent fibers forming its vesical, uterovaginal, and rectal branches. During the dissection of the posterior leaf of the vesicouterine ligament, various vesical veins were identified. If the cut edge of an inferior vesical vein was pulled medially with upward traction, the vesical branches of the inferior hypogastric plexus were exposed and these were divided into medial and lateral branches. The magnified view of laparoscopy made it possible to dissect nerves and vessels meticulously and to secure a clear resection margin during the dissection of the deep part of the cardinal ligament, uterosacral ligament, and posterior leaf of the vesicouterine ligament. PMID:20108355

  13. Successful Reconstruction of Nerve Defects Using Distraction Neurogenesis with a New Experimental Device

    PubMed Central

    Yousef, Mohamed Abdelhamid Ali; Dionigi, Paolo; Marconi, Stefania; Calligaro, Alberto; Cornaglia, Antonia Icaro; Alfonsi, Enrico; Auricchio, Ferdinando

    2015-01-01

    Introduction: Repair of peripheral nerve injuries is an intensive area of challenge and research in modern reconstructive microsurgery. Intensive research is being carried out to develop effective alternatives to the standard nerve autografting, avoiding its drawbacks. The aim of the study was to evaluate the effectiveness of a newly designed mechanical device for the reconstruction of the sciatic nerve in rats in comparison to nerve autografting and to assess the pain during the period of distraction neurogenesis. Methods: Fourteen Sprague Dawley rats were used and randomly assigned into 2 groups with 7 rats in each group; group A (Nerve Autografting group) in which a 10-mm segment of the sciatic nerve was resected and rotated 180 degrees, then primary end-to-end neurorrhaphy was performed in the reverse direction; group B (Nerve Lengthening group) in which the mechanical device was inserted after surgical resection of 10 mm of the sciatic nerve, then secondary end-to-end neurorrhaphy was performed after completing the nerve lengthening. Thirteen weeks later, assessment of the functional sciatic nerve recovery using static sciatic index (SSI) was performed. Furthermore, fourteen weeks after the nerve resection, assessment of the nerve regeneration with electrophysiological study and histological analysis were performed. Also, gastrocnemius wet weight was measured. For pain assessment in group B, Rat Grimace Scale (RGS) score was used. Results: Significantly better functional recovery rate (using the SSI) was reported in the nerve lengthening group in comparison to autografting group. Also, a statistically significant higher nerve conduction velocity was detected in the nerve lengthening group. On histological analysis of the distal nerve section at 3 mm distal to the nerve repair site, significant myelin sheath thickness was detected in the nerve lengthening group. Discussion: Distraction neurogenesis with the new experimental device is a reliable therapeutic

  14. Differential ATF3 expression in dorsal root ganglion neurons reveals the profile of primary afferents engaged by diverse noxious chemical stimuli

    PubMed Central

    Bráz, João M.; Basbaum, Allan I.

    2010-01-01

    Although transgenic and knockout mice have helped delineate the mechanisms of action of diverse noxious compounds, it is still difficult to determine unequivocally the subpopulations of primary afferent nociceptor that these molecules engage. As most noxious stimuli lead to tissue and/or nerve injury, here we used induction of activating transcription factor 3 (ATF3), a reliable marker of nerve injury, to assess the populations of primary afferent fibers that are activated after peripheral administration of noxious chemical stimuli. In wild-type mice, hindpaw injections of capsaicin, formalin, mustard oil or menthol induce expression of ATF3 in distinct subpopulations of sensory neurons. Interestingly, even though these noxious chemicals are thought to act through subtypes of transient receptor potential (TRP) channels, all compounds also induced ATF3 in neurons that appear not to express the expected TRP channel subtypes. On the other hand, capsaicin failed to induce ATF3 in mice lacking TRPV1, indicating that TRPV1 is required for both the direct and indirect induction of ATF3 in sensory neurons. By contrast, only low doses of formalin or mustard oil failed to induce ATF3 in TRPA1 null mice, indicating that injections of high doses (>0.5%) of formalin or mustard oil recruit both TRPA1 and non-TRPA1 expressing primary afferent fibers. Finally, peripheral injection of menthol, a TRPM8 receptor agonist, induced ATF3 in a wide variety of sensory neurons, but in a TRPM8-independent manner. We conclude that purportedly selective agonists can activate a heterogeneous population of sensory neurons, which ultimately could contribute to the behavioral responses evoked. PMID:20605331

  15. A bioengineered peripheral nerve construct using aligned peptide amphiphile nanofibers

    PubMed Central

    Yalom, Anisa; Berns, Eric J.; Stephanopoulos, Nicholas; McClendon, Mark T.; Segovia, Luis A.; Spigelman, Igor; Stupp, Samuel I.; Jarrahy, Reza

    2014-01-01

    Peripheral nerve injuries can result in lifelong disability. Primary coaptation is the treatment of choice when the gap between transected nerve ends is short. Long nerve gaps seen in more complex injuries often require autologous nerve grafts or nerve conduits implemented into the repair. Nerve grafts, however, cause morbidity and functional loss at donor sites, which are limited in number. Nerve conduits, in turn, lack an internal scaffold to support and guide axonal regeneration, resulting in decreased efficacy over longer nerve gap lengths. By comparison, peptide amphiphiles (PAs) are molecules that can self-assemble into nanofibers, which can be aligned to mimic the native architecture of peripheral nerve. As such, they represent a potential substrate for use in a bioengineered nerve graft substitute. To examine this, we cultured Schwann cells with bioactive PAs (RGDS-PA, IKVAV-PA) to determine their ability to attach to and proliferate within the biomaterial. Next, we devised a PA construct for use in a peripheral nerve critical sized defect model. Rat sciatic nerve defects were created and reconstructed with autologous nerve, PLGA conduits filled with various forms of aligned PAs, or left unrepaired. Motor and sensory recovery were determined and compared among groups. Our results demonstrate that Schwann cells are able to adhere to and proliferate in aligned PA gels, with greater efficacy in bioactive PAs compared to the backbone-PA alone. In vivo testing revealed recovery of motor and sensory function in animals treated with conduit/PA constructs comparable to animals treated with autologous nerve grafts. Functional recovery in conduit/PA and autologous graft groups was significantly faster than in animals treated with empty PLGA conduits. Histological examinations also demonstrated increased axonal and Schwann cell regeneration within the reconstructed nerve gap in animals treated with conduit/PA constructs. These results indicate that PA nanofibers may

  16. Multifunctional Silk Nerve Guides for Axon Outgrowth

    NASA Astrophysics Data System (ADS)

    Tupaj, Marie C.

    Peripheral nerve regeneration is a critical issue as 2.8% of trauma patients present with this type of injury, estimating a total of 200,000 nerve repair procedures yearly in the United States. While the peripheral nervous system exhibits slow regeneration, at a rate of 0.5 mm -- 9 mm/day following trauma, this regenerative ability is only possible under certain conditions. Clinical repairs have changed slightly in the last 30 years and standard methods of treatment include suturing damaged nerve ends, allografting, and autografting, with the autograft the gold standard of these approaches. Unfortunately, the use of autografts requires a second surgery and there is a shortage of nerves available for grafting. Allografts are a second option however allografts have lower success rates and are accompanied by the need of immunosuppressant drugs. Recently there has been a focus on developing nerve guides as an "off the shelf" approach. Although some natural and synthetic guidance channels have been approved by the FDA, these nerve guides are unfunctionalized and repair only short gaps, less than 3 cm in length. The goal of this project was to identify strategies for functionalizing peripheral nerve conduits for the outgrowth of neuron axons in vitro . To accomplish this, two strategies (bioelectrical and biophysical) were indentified for increasing axon outgrowth and promoting axon guidance. Bioelectrical strategies exploited electrical stimulation for increasing neurite outgrowth. Biophysical strategies tested a range of surface topographies for axon guidance. Novel methods were developed for integrating electrical and biophysical strategies into silk films in 2D. Finally, a functionalized nerve conduit system was developed that integrated all strategies for the purpose of attaching, elongating, and guiding nervous tissue in vitro. Future directions of this work include silk conduit translation into a rat sciatic nerve model in vivo for the purpose of repairing long

  17. Laryngeal nerve damage

    MedlinePlus

    Laryngeal nerve damage is injury to one or both of the nerves that are attached to the voice box. ... Injury to the laryngeal nerves is uncommon. When it does occur, it can be from: A complication of neck or chest surgery (especially thyroid, lung, ...

  18. Corneal afferents differentially target thalamic- and parabrachial-projecting neurons in trigeminal subnucleus caudalis

    PubMed Central

    Aicher, Sue A.; Hermes, Sam M.; Hegarty, Deborah M.

    2012-01-01

    Dorsal horn neurons send ascending projections to both thalamic nuclei and parabrachial nuclei; these pathways are thought to be critical pathways for central processing of nociceptive information. Afferents from the corneal surface of the eye mediate nociception from this tissue which is susceptible to clinically important pain syndromes. This study examined corneal afferents to the trigeminal dorsal horn and compared inputs to thalamic- and parabrachial-projecting neurons. We used anterograde tracing with cholera toxin B subunit to identify corneal afferent projections to trigeminal dorsal horn, and the retrograde tracer FluoroGold to identify projection neurons. Studies were conducted in adult male Sprague-Dawley rats. Our analysis was conducted at two distinct levels of the trigeminal subnucleus caudalis (Vc) which receive corneal afferent projections. We found that corneal afferents project more densely to the rostral pole of Vc than the caudal pole. We also quantified the number of thalamic- and parabrachial-projecting neurons in the regions of Vc that receive corneal afferents. Corneal afferent inputs to both groups of projection neurons were also more abundant in the rostral pole of Vc. Finally, by comparing the frequency of corneal afferent appositions to thalamic- versus parabrachial-projecting neurons, we found that corneal afferents preferentially target parabrachial-projecting neurons in trigeminal dorsal horn. These results suggest that nociceptive pain from the cornea may be primarily mediated by a non-thalamic ascending pathway. PMID:23201828

  19. Cerebral blood flow changes during vagus nerve stimulation for depression.

    PubMed

    Conway, Charles R; Sheline, Yvette I; Chibnall, John T; George, Mark S; Fletcher, James W; Mintun, Mark A

    2006-03-31

    Positron emission tomography (PET oxygen-15 labeled water or PET [15O]H2O) was used to identify changes in regional cerebral blood flow (rCBF) in response to acute vagus nerve stimulation (VNS) in four subjects with treatment-resistant major depression (TRMD). Four 90-s PET [15O]H2O scans were performed on each subject in an off-on sequence (2 VNS de-activated; 2 VNS activated). PET images were aligned, normalized for global uptake, and resampled to standard atlas space. Statistical t-images were used to evaluate change. VNS-induced increases in rCBF were found in the bilateral orbitofrontal cortex, bilateral anterior cingulate cortex, and right superior and medial frontal cortex. Decreases were found in the bilateral temporal cortex and right parietal area. Regions of change were consistent with brain structures associated with depression and the afferent pathways of the vagus nerve. PMID:16510266

  20. Modulating mechanosensory afferent excitability by an atypical mGluR.

    PubMed

    Watson, Sonia

    2015-08-01

    Mechanotransduction by proprioceptive sensory organs is poorly understood. Evidence was recently shown that muscle spindle and hair follicle primary afferents (lanceolates) constantly release glutamate from synaptic-like vesicles (SLVs) within the terminals. The secreted glutamate activates a highly unusual metabotropic glutamate receptor (mGluR) to modulate the firing rate (spindles) and SLV recycling (lanceolates). This receptor has yet to be isolated and sequenced. To further investigate this receptor's pharmacology, ligands selective for classical mGluRs have been recently characterised for their ability to alter stretch-evoked spindle firing and SLV endocytosis in these different endings. Here, it is described how the results of these screens facilitated the development of novel compounds to be used in the process of isolating and sequencing of this non-canonical mGluR. This study shows how the compounds were tested for their ability to alter stretch-evoked afferent firing in muscle spindles and SLV endocytosis in the lanceolate endings of hair follicles to ensure they maintained their ability to bind to the receptor. For the development of novel compounds, kainate was chosen as the parent ligand due to its potency and ease of chemical modification. Novel kainate derivatives were then synthesised and tested to find potent analogues suitable for 'click-chemistry', an established technique for relatively quick, cheap, stereospecific and high-yield chemical modifications (Angewandte Chemie (International ed. in English), 40, 2001, pp2004). Of the novel kainate analogues developed, unfortunately ZCZ49 and ZCZ50 lost the ability to produce a significant change in spindle stretch-evoked firing. However, ZCZ90 was as potent as kainate, increasing firing by a similar margin at 1 μm (n = 8; P < 0.001). The addition of either a biotin or a fluorescein side group to ZCZ90, using the click-chemistry technique, did not affect the potency and hence these

  1. Heat pulse excitability of vestibular hair cells and afferent neurons.

    PubMed

    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 <3 ms and decaying with a time constant of ∼24 ms. The inhibitory component dominated whole cell currents in 50% of hair cells at -68 mV and in 67% of hair cells at -60 mV. Responses were quantified and described on the basis of first principles of thermodynamics. Results identify key molecular targets underlying 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

  2. Development and organization of polarity-specific segregation of primary vestibular afferent fibers in mice.

    PubMed

    Maklad, Adel; Kamel, Suzan; Wong, Elaine; Fritzsch, Bernd

    2010-05-01

    A striking feature of vestibular hair cells is the polarized arrangement of their stereocilia as the basis for their directional sensitivity. In mammals, each of the vestibular end organs is characterized by a distinct distribution of these polarized cells. We utilized the technique of post-fixation transganglionic neuronal tracing with fluorescent lipid soluble dyes in embryonic and postnatal mice to investigate whether these polarity characteristics correlate with the pattern of connections between the endorgans and their central targets; the vestibular nuclei and cerebellum. We found that the cerebellar and brainstem projections develop independently from each other and have a non-overlapping distribution of neurons and afferents from E11.5 on. In addition, we show that the vestibular fibers projecting to the cerebellum originate preferentially from the lateral half of the utricular macula and the medial half of the saccular macula. In contrast, the brainstem vestibular afferents originate primarily from the medial half of the utricular macula and the lateral half of the saccular macula. This indicates that the line of hair cell polarity reversal within the striola region segregates almost mutually exclusive central projections. A possible interpretation of this feature is that this macular organization provides an inhibitory side-loop through the cerebellum to produce synergistic tuning effects in the vestibular nuclei. The canal cristae project to the brainstem vestibular nuclei and cerebellum, but the projection to the vestibulocerebellum originates preferentially from the superior half of each of the cristae. The reason for this pattern is not clear, but it may compensate for unequal activation of crista hair cells or may be an evolutionary atavism reflecting a different polarity organization in ancestral vertebrate ears. PMID:20424840

  3. Vascularized Nerve Bypass Graft: A Case Report of an Additional Treatment for Poor Sensory Recovery.

    PubMed

    Usami, Satoshi; Tanaka, Kentaro; Ohkubo, Alisa; Okazaki, Mutsumi

    2016-04-01

    End-to-side neurorrhaphy has proven effective in basic research and in clinical application. One of the methods of end-to-side neurorrhaphy, nerve bypass technique, has been reported and axon regeneration has been proven. In clinical application, the utility of the nerve bypass technique has been revealed in some cases; however, these bypasses were performed using nonvascularized nerves. We initially used the vascularized nerve bypass graft technique with the sural nerve as a secondary clinical procedure after median nerve injury in a 61-year-old patient and achieved motor and sensory nerve regeneration, as supported by a nerve conduction study and clinical sensory test. This technique has the potential to become one of the choices for salvage procedure of severe nerve injury. PMID:27200248

  4. Vascularized Nerve Bypass Graft: A Case Report of an Additional Treatment for Poor Sensory Recovery

    PubMed Central

    Tanaka, Kentaro; Ohkubo, Alisa; Okazaki, Mutsumi

    2016-01-01

    Summary: End-to-side neurorrhaphy has proven effective in basic research and in clinical application. One of the methods of end-to-side neurorrhaphy, nerve bypass technique, has been reported and axon regeneration has been proven. In clinical application, the utility of the nerve bypass technique has been revealed in some cases; however, these bypasses were performed using nonvascularized nerves. We initially used the vascularized nerve bypass graft technique with the sural nerve as a secondary clinical procedure after median nerve injury in a 61-year-old patient and achieved motor and sensory nerve regeneration, as supported by a nerve conduction study and clinical sensory test. This technique has the potential to become one of the choices for salvage procedure of severe nerve injury. PMID:27200248

  5. Bladder afferent hyperexcitability in bladder pain syndrome/interstitial cystitis

    PubMed Central

    Yoshimura, Naoki; Oguchi, Tomohiko; Yokoyama, Hitoshi; Funahashi, Yasuhito; Yoshikawa, Satoru; Sugino, Yoshio; Kawamorita, Naoki; Kashyap, Mahendra P; Chancellor, Michael B; Tyagi, Pradeep; Ogawa, Teruyuki

    2014-01-01

    Bladder pain syndrome/interstitial cystitis is a disease with lower urinary tract symptoms, such as bladder pain and urinary frequency, which results in seriously impaired quality of life of patients. The extreme pain and urinary frequency are often difficult to treat. Although the etiology of bladder pain syndrome/interstitial cystitis is still not known, there is increasing evidence showing that afferent hyperexcitability as a result of neurogenic bladder inflammation and urothelial dysfunction is important to the pathophysiological basis of symptom development. Further investigation of the pathophysiology will lead to the effective treatment of patients with bladder pain syndrome/interstitial cystitis. PMID:24807488

  6. High Median Nerve Injuries.

    PubMed

    Isaacs, Jonathan; Ugwu-Oju, Obinna

    2016-08-01

    The median nerve serves a crucial role in extrinsic and intrinsic motor and sensory function to the radial half of the hand. High median nerve injuries, defined as injuries proximal to the anterior interosseous nerve origin, therefore typically result in significant functional loss prompting aggressive surgical management. Even with appropriate recognition and contemporary nerve reconstruction, however, motor and sensory recovery may be inadequate. With isolated persistent high median nerve palsies, a variety of available tendon transfers can improve key motor functions and salvage acceptable use of the hand. PMID:27387077

  7. Peripheral nerve regeneration with conduits: use of vein tubes

    PubMed Central

    Sabongi, Rodrigo Guerra; Fernandes, Marcela; dos Santos, João Baptista Gomes

    2015-01-01

    Treatment of peripheral nerve injuries remains a challenge to modern medicine due to the complexity of the neurobiological nerve regenerating process. There is a greater challenge when the transected nerve ends are not amenable to primary end-to-end tensionless neurorraphy. When facing a segmental nerve defect, great effort has been made to develop an alternative to the autologous nerve graft in order to circumvent morbidity at donor site, such as neuroma formation, scarring and permanent loss of function. Tubolization techniques have been developed to bridge nerve gaps and have been extensively studied in numerous experimental and clinical trials. The use of a conduit intends to act as a vehicle for moderation and modulation of the cellular and molecular ambience for nerve regeneration. Among several conduits, vein tubes were validated for clinical application with improving outcomes over the years. This article aims to address the investigation and treatment of segmental nerve injury and draw the current panorama on the use of vein tubes as an autogenous nerve conduit. PMID:26170802

  8. [Ganglia of peripheral nerves].

    PubMed

    Tatagiba, M; Penkert, G; Samii, M

    1993-01-01

    The authors present two different types of ganglion affecting the peripheral nerves: extraneural and intraneural ganglion. Compression of peripheral nerves by articular ganglions is well known. The surgical management involves the complete removal of the lesion with preservation of most nerve fascicles. Intraneural ganglion is an uncommon lesion which affects the nerve diffusely. The nerve fascicles are usually intimately involved between the cysts, making complete removal of all cysts impossible. There is no agreement about the best surgical management to be applied in these cases. Two possibilities are available: opening of the epineural sheath lengthwise and pressing out the lesion; or resection of the affected part of the nerve and performing a nerve reconstruction. While in case of extraneural ganglion the postoperative clinical evolution is very favourable, only long follow up studies will reveal in case of intraneural ganglion the best surgical approach. PMID:8128785

  9. Assessment of nerve morphology in nerve activation during electrical stimulation

    NASA Astrophysics Data System (ADS)

    Gomez-Tames, Jose; Yu, Wenwei

    2013-10-01

    The distance between nerve and stimulation electrode is fundamental for nerve activation in Transcutaneous Electrical Stimulation (TES). However, it is not clear the need to have an approximate representation of the morphology of peripheral nerves in simulation models and its influence in the nerve activation. In this work, depth and curvature of a nerve are investigated around the middle thigh. As preliminary result, the curvature of the nerve helps to reduce the simulation amplitude necessary for nerve activation from far field stimulation.

  10. Diving and exercise: the interaction of trigeminal receptors and muscle metaboreceptors on muscle sympathetic nerve activity in humans.

    PubMed

    Fisher, James P; Fernandes, Igor A; Barbosa, Thales C; Prodel, Eliza; Coote, John H; Nóbrega, Antonio Claudio L; Vianna, Lauro C

    2015-03-01

    Swimming involves muscular activity and submersion, creating a conflict of autonomic reflexes elicited by the trigeminal receptors and skeletal muscle afferents. We sought to determine the autonomic cardiovascular responses to separate and concurrent stimulation of the trigeminal cutaneous receptors and metabolically sensitive skeletal muscle afferents (muscle metaboreflex). In eight healthy men (30 ± 2 yr) muscle sympathetic nerve activity (MSNA; microneurography), mean arterial pressure (MAP; Finometer), femoral artery blood flow (duplex Doppler ultrasonography), and femoral vascular conductance (femoral artery blood flow/MAP) were assessed during the following three experimental conditions: 1) facial cooling (trigeminal nerve stimulation), 2) postexercise ischemia (PEI; muscle metaboreflex activation) following isometric handgrip, and 3) trigeminal nerve stimulation with concurrent PEI. Trigeminal nerve stimulation produced significant increases in MSNA total activity (Δ347 ± 167%) and MAP (Δ21 ± 5%) and a reduction in femoral artery vascular conductance (Δ-17 ± 9%). PEI also evoked significant increases in MSNA total activity (Δ234 ± 83%) and MAP (Δ36 ± 4%) and a slight nonsignificant reduction in femoral artery vascular conductance (Δ-9 ± 12%). Trigeminal nerve stimulation with concurrent PEI evoked changes in MSNA total activity (Δ341 ± 96%), MAP (Δ39 ± 4%), and femoral artery vascular conductance (Δ-20 ± 9%) that were similar to those evoked by either separate trigeminal nerve stimulation or separate PEI. Thus, excitatory inputs from the trigeminal nerve and metabolically sensitive skeletal muscle afferents do not summate algebraically in eliciting a MSNA and cardiovascular response but rather exhibit synaptic occlusion, suggesting a high degree of convergent inputs on output neurons. PMID:25527781

  11. Plasmacytoid dendritic cells migrate in afferent skin lymph.

    PubMed

    Pascale, Florentina; Pascale, Florentia; Contreras, Vanessa; Bonneau, Michel; Courbet, Alexandre; Chilmonczyk, Stefan; Bevilacqua, Claudia; Epardaud, Mathieu; Eparaud, Mathieu; Niborski, Violeta; Riffault, Sabine; Balazuc, Anne-Marie; Foulon, Eliane; Guzylack-Piriou, Laurence; Riteau, Beatrice; Hope, Jayne; Bertho, Nicolas; Charley, Bernard; Schwartz-Cornil, Isabelle

    2008-05-01

    Conventional dendritic cells enter lymph nodes by migrating from peripheral tissues via the lymphatic route, whereas plasmacytoid dendritic cells (pDC), also called IFN-producing cells (IPC), are described to gain nodes from blood via the high endothelial venules. We demonstrate here that IPC/pDC migrate in the afferent lymph of two large mammals. In sheep, injection of type A CpG oligodinucleotide (ODN) induced lymph cells to produce type I IFN. Furthermore, low-density lymph cells collected at steady state produced type I IFN after stimulation with type A CpG ODN and enveloped viruses. Sheep lymph IPC were found within a minor B(neg)CD11c(neg) subset expressing CD45RB. They presented a plasmacytoid morphology, expressed high levels of TLR-7, TLR-9, and IFN regulatory factor 7 mRNA, induced IFN-gamma production in allogeneic CD4(pos) T cells, and differentiated into dendritic cell-like cells under viral stimulation, thus fulfilling criteria of bona fide pDC. In mini-pig, a CD4(pos)SIRP(pos) subset in afferent lymph cells, corresponding to pDC homologs, produced type I IFN after type A CpG-ODN triggering. Thus, pDC can link innate and acquired immunity by migrating from tissue to draining node via lymph, similarly to conventional dendritic cells. PMID:18424716

  12. Interactions between visceral afferent signaling and stimulus processing

    PubMed Central

    Critchley, Hugo D.; Garfinkel, Sarah N.

    2015-01-01

    Visceral afferent signals to the brain influence thoughts, feelings and behavior. 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 behaviors, 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. PMID:26379481

  13. Cross-Modal Calibration of Vestibular Afference for Human Balance

    PubMed Central

    Héroux, Martin E; Law, Tammy C. Y.; Fitzpatrick, Richard C.; Blouin, Jean-Sébastien

    2015-01-01

    To determine how the vestibular sense controls balance, we used instantaneous head angular velocity to drive a galvanic vestibular stimulus so that afference would signal that head movement was faster or slower than actual. In effect, this changed vestibular afferent gain. This increased sway 4-fold when subjects (N = 8) stood without vision. However, after a 240 s conditioning period with stable balance achieved through reliable visual or somatosensory cues, sway returned to normal. An equivalent galvanic stimulus unrelated to sway (not driven by head motion) was equally destabilising but in this situation the conditioning period of stable balance did not reduce sway. Reflex muscle responses evoked by an independent, higher bandwidth vestibular stimulus were initially reduced in amplitude by the galvanic stimulus but returned to normal levels after the conditioning period, contrary to predictions that they would decrease after adaptation to increased sensory gain and increase after adaptation to decreased sensory gain. We conclude that an erroneous vestibular signal of head motion during standing has profound effects on balance control. If it is unrelated to current head motion, the CNS has no immediate mechanism of ignoring the vestibular signal to reduce its influence on destabilising balance. This result is inconsistent with sensory reweighting based on disturbances. The increase in sway with increased sensory gain is also inconsistent with a simple feedback model of vestibular reflex action. Thus, we propose that recalibration of a forward sensory model best explains the reinterpretation of an altered reafferent signal of head motion during stable balance. PMID:25894558

  14. Microsecond-Scale Timing Precision in Rodent Trigeminal Primary Afferents

    PubMed Central

    Bale, Michael R.; Campagner, Dario; Erskine, Andrew

    2015-01-01

    Communication in the nervous system occurs by spikes: the timing precision with which spikes are fired is a fundamental limit on neural information processing. In sensory systems, spike-timing precision is constrained by first-order neurons. We found that spike-timing precision of trigeminal primary afferents in rats and mice is limited both by stimulus speed and by electrophysiological sampling rate. High-speed video of behaving mice revealed whisker velocities of at least 17,000°/s, so we delivered an ultrafast “ping” (>50,000°/s) to single whiskers and sampled primary afferent activity at 500 kHz. Median spike jitter was 17.4 μs; 29% of neurons had spike jitter < 10 μs. These results indicate that the input stage of the trigeminal pathway has extraordinary spike-timing precision and very high potential information capacity. This timing precision ranks among the highest in biology. PMID:25878266

  15. Use of Vein Conduit and Isolated Nerve Graft in Peripheral Nerve Repair: A Comparative Study

    PubMed Central

    Ahmad, Imran; Akhtar, Md. Sohaib

    2014-01-01

    Aims and Objectives. The aim of this study was to evaluate the effectiveness of vein conduit in nerve repair compared with isolated nerve graft. Materials and Methods. This retrospective study was conducted at author's centre and included a total of 40 patients. All the patients had nerve defect of more than 3 cm and underwent nerve repair using nerve graft from sural nerve. In 20 cases, vein conduit (study group) was used whereas no conduit was used in other 20 cases. Patients were followed up for 2 years at the intervals of 3 months. Results. Patients had varying degree of recovery. Sensations reached to all the digits at 1 year in study groups compared to 18 months in control group. At the end of second year, 84% patients of the study group achieved 2-point discrimination of <10 mm compared to 60% only in control group. In terms of motor recovery, 82% patients achieved satisfactory hand function in study group compared to 56% in control group (P < .05). Conclusions. It was concluded that the use of vein conduit in peripheral nerve repair is more effective method than isolated nerve graft providing good sensory and motor recovery. PMID:25405029

  16. Possible involvement of convergent nociceptive input to medullary dorsal horn neurons in intraoral hyperalgesia following peripheral nerve injury.

    PubMed

    Terayama, Ryuji; Tsuchiya, Hiroki; Omura, Shinji; Maruhama, Kotaro; Mizutani, Masahide; Iida, Seiji; Sugimoto, Tomosada

    2015-04-01

    Previous studies demonstrated that the number of c-Fos protein-like immunoreactive (c-Fos-IR) neurons in the medullary dorsal horn (MDH) evoked by noxious stimulation was increased after peripheral nerve injury, and such increase has been proposed to reflect the development of neuropathic pain state. The aim of this study was to examine the MDH for convergent collateral primary afferent input to second order neurons deafferented by peripheral nerve injury, and to explore a possibility of its contribution to the c-Fos hyperinducibility. Double immunofluorescence labeling for c-Fos and phosphorylated extracellular signal-regulated kinase (p-ERK) was performed to detect convergent synaptic input. c-Fos expression and the phosphorylation of ERK were induced by the intraoral application of capsaicin and by electrical stimulation of the inferior alveolar nerve (IAN), respectively. The number of c-Fos-IR neurons in the MDH induced by the intraoral application of capsaicin was increased after IAN injury, whereas the number of p-ERK immunoreactive neurons remained unchanged. The number of double-labeled neurons, that presumably received convergent primary afferent input from the lingual nerve and the IAN, was significantly increased after IAN injury. These results indicated that convergent primary nociceptive input through neighboring intact nerves may contribute to the c-Fos hyperinducibility in the MDH and the pathogenesis of neuropathic pain following trigeminal nerve injury. PMID:25407627

  17. Delayed Exercise Is Ineffective at Reversing Aberrant Nociceptive Afferent Plasticity or Neuropathic Pain After Spinal Cord Injury in Rats.

    PubMed

    Detloff, Megan Ryan; Quiros-Molina, Daniel; Javia, Amy S; Daggubati, Lekhaj; Nehlsen, Anthony D; Naqvi, Ali; Ninan, Vinu; Vannix, Kirsten N; McMullen, Mary-Katharine; Amin, Sheena; Ganzer, Patrick D; Houlé, John D

    2016-08-01

    Neuropathic pain is a debilitating consequence of spinal cord injury (SCI) that correlates with sensory fiber sprouting. Recent data indicate that exercise initiated early after SCI prevents the development of allodynia and modulated nociceptive afferent plasticity. This study determined if delaying exercise intervention until pain is detected would similarly ameliorate established SCI-induced pain. Adult, female Sprague-Dawley rats with a C5 unilateral contusion were separated into SCI allodynic and SCI non-allodynic cohorts at 14 or 28 days postinjury when half of each group began exercising on automated running wheels. Allodynia, assessed by von Frey testing, was not ameliorated by exercise. Furthermore, rats that began exercise with no allodynia developed paw hypersensitivity within 2 weeks. At the initiation of exercise, the SCI Allodynia group displayed marked overlap of peptidergic and non-peptidergic nociceptive afferents in the C7 and L5 dorsal horn, while the SCI No Allodynia group had scant overlap. At the end of 5 weeks of exercise both the SCI Allodynia and SCI No Allodynia groups had extensive overlap of the 2 c-fiber types. Our findings show that exercise therapy initiated at early stages of allodynia is ineffective at attenuating neuropathic pain, but rather that it induces allodynia-aberrant afferent plasticity in previously pain-free rats. These data, combined with our previous results, suggest that there is a critical therapeutic window when exercise therapy may be effective at treating SCI-induced allodynia and that there are postinjury periods when exercise can be deleterious. PMID:26671215

  18. Presynaptic inhibition of soleus Ia afferents does not vary with center of pressure displacements during upright standing.

    PubMed

    Johannsson, J; Duchateau, J; Baudry, S

    2015-07-01

    The present work was designed to investigate the presynaptic modulation of soleus Ia afferents with the position and the direction of the displacement of the center of pressure (CoP) during unperturbed upright standing and exaggerated CoP displacements in young adults. Hoffmann (H) reflex was evoked in the soleus by stimulating the tibial nerve at the knee level. Modulation of Ia presynaptic inhibition was assessed by conditioning the H reflex with fibular nerve (D1 inhibition) and femoral nerve (heteronymous facilitation) stimulation. Leg muscle activity was assessed by electromyography (EMG). The results indicate that in unperturbed standing and exaggerated CoP displacements, the H-reflex amplitude was greater during forward than backward CoP direction (p<0.05). However, the amplitude of the conditioned H reflex (expressed relative to unconditioned H reflex) did not vary with CoP displacement, regardless of the experimental condition. The soleus EMG was greater during forward than backward CoP direction and during anterior than posterior position in both experimental conditions (p<0.05). The modulation of the unconditioned H reflex with CoP direction was positively associated with the corresponding changes in soleus EMG (r(2)>0.34). The tibialis anterior EMG did not change during unperturbed standing, but was greater for backward than forward CoP direction during exaggerated CoP displacements. In this experimental condition, soleus EMG was negatively associated with tibialis anterior EMG (r(2)=0.81). These results indicate that Ia presynaptic inhibition is not modulated with CoP direction and position, but rather suggest that CoP displacements induced changes in excitability of the soleus motor neuron pool. PMID:25869621

  19. Microstimulation of primary afferent neurons in the L7 dorsal root ganglia using multielectrode arrays in anesthetized cats: thresholds and recruitment properties

    NASA Astrophysics Data System (ADS)

    Gaunt, R. A.; Hokanson, J. A.; Weber, D. J.

    2009-10-01

    Current research in motor neural prosthetics has focused primarily on issues related to the extraction of motor command signals from the brain (e.g. brain-machine interfaces) to direct the motion of prosthetic limbs. Patients using these types of systems could benefit from a somatosensory neural interface that conveys natural tactile and kinesthetic sensations for the prosthesis. Electrical microstimulation within the dorsal root ganglia (DRG) has been proposed as one method to accomplish this, yet little is known about the recruitment properties of electrical microstimulation in activating nerve fibers in this structure. Current-controlled microstimulation pulses in the range of 1-15 µA (200 µs, leading cathodic pulse) were delivered to the L7 DRG in four anesthetized cats using penetrating microelectrode arrays. Evoked responses and their corresponding conduction velocities (CVs) were measured in the sciatic nerve with a 5-pole nerve cuff electrode arranged as two adjacent tripoles. It was found that in 76% of the 69 electrodes tested, the stimulus threshold was less than or equal to 3 µA, with the lowest recorded threshold being 1.1 µA. The CVs of afferents recruited at threshold had a bimodal distribution with peaks at 70 m s-1 and 85 m s-1. In 53% of cases, the CV of the response at threshold was slower (i.e. smaller diameter fiber) than the CVs of responses observed at increasing stimulation amplitudes. In summary, we found that microstimulation applied through penetrating microelectrodes in the DRG provides selective recruitment of afferent fibers from a range of sensory modalities (as identified by CVs) at very low stimulation intensities. We conclude that the DRG may serve as an attractive location from which to introduce surrogate somatosensory feedback into the nervous system.

  20. Effects of afferent volleys from the limbs on the discharge patterns of interpositus neurones in cats anaesthetized with alpha-chloralose.

    PubMed Central

    Armstrong, D M; Cogdell, B; Harvey, R

    1975-01-01

    1. In cats anaesthetized with alpha-chloralose, micro-electrodes have been used to record the discharge patterns of single neurones in the region of the nucleus interpositus. 2. Almost all cells tested could be antidromically invaded following electrical stimulation of the contralateral red nucleus, showing that they were cerebellar efferent neurones. 3. A little over half of the interpositus neurones were spontaneously active, usually at rates of less than 20 impulses/sec. 4. About 40% of the cells had no spontaneous activity, although they gave brisk responses to electrical stimulation of cutaneous nerves. Such silent units were encountered most frequently in the earlier stages of an experiment, but a number were found more than 15 hr after the beginning of an experiment. 5. Stimulation of cutaneous and mixed nerves of the fore and hind limbs provoked impulse discharges of the cells and also produced phases of deceleration of the resting discharge of spontaneously firing cells. 6. The typical response of an interpositus neurone consisted of a short latency (6-35 msec) discharge, usually separated from a long latency (50-500 msec) discharge by a period of inhibition or return to the resting discharge rate. The two phases of excitation appeared to be independently generated, since in a number of cells one phase appeared without the other. In addition, the later phase of excitation was abolished in all cells tested by a small dose of pentobarbitone which produced very little effect on the earlier phase. The long latency response was quantitatively much greater, sometimes consisting of 50 or more impulses in a response which lasted several hundred msec, but was very variable from one trial to another. 7. The long latency discharge and sometimes the preceding inhibition could readily be mimicked by single shock stimulation of the region of the contralateral inferior olive. Short latency discharges were, however, rarely evoked by olivary stimulation. 8. It is suggested

  1. Estimation of Retinal Ganglion Cell Loss in Glaucomatous Eyes With a Relative Afferent Pupillary Defect

    PubMed Central

    Tatham, Andrew J.; Meira-Freitas, Daniel; Weinreb, Robert N.; Marvasti, Amir H.; Zangwill, Linda M.; Medeiros, Felipe A.

    2014-01-01

    Purpose. To estimate retinal ganglion cell (RGC) losses associated with a relative afferent pupillary defect (RAPD) in glaucoma. Methods. A cross-sectional study was conducted including both eyes of 103 participants from the Diagnostic Innovations in Glaucoma Study. A total of 77 subjects had glaucoma in at least one eye and 26 were healthy. Pupil responses were assessed using an automated pupillometer that records the magnitude of RAPD as an “RAPD score.” Standard automated perimetry (SAP) and optical coherence tomography (OCT) also were performed. Retinal ganglion cell counts were estimated using empirical formulas that combine estimates from SAP and OCT. The estimated percentage RGC loss was calculated using the combined structure function index (CSFI). Results. There was good correlation between RAPD magnitude and intereye differences in estimated RGCs (R2 = 0.492, P < 0.001), mean deviation (R2 = 0.546, P < 0.001), retinal nerve fiber layer thickness (R2 = 0.362, P < 0.001), and CSFI (R2 = 0.484, P < 0.001). Therefore, a high RAPD score is likely to indicate large asymmetric RGC losses. The relationship between intereye difference in RGC counts and RAPD score was described best by the formula; RGC difference = 21,896 + 353,272 * RAPD score. No healthy subjects had an absolute RAPD score > 0.3, which was associated with asymmetry of 105,982 cells (or 12%). Conclusions. Good correlation between the magnitude of RAPD and intereye differences in mean deviation and estimated RGC counts suggests pupillometry may be useful for quantifying asymmetric damage in glaucoma. (ClinicalTrials.gov number, NCT00221897.) PMID:24282221

  2. Effects of levodropropizine on vagal afferent C-fibres in the cat.

    PubMed Central

    Shams, H.; Daffonchio, L.; Scheid, P.

    1996-01-01

    1. Levodropropizine (LVDP) is an effective antitussive drug. Its effects on single-unit discharge of vagal afferent C-fibres were tested in anaesthetized cats to assess whether an inhibition of vagal C-fibres is involved in its antitussive properties. Vagal C-fibres, identified by their response to phenylbiguanide (PBG), were recorded via suction electrodes from the distal part of the cut vagus. Based on their response to lung inflation, C-fibres were classified as pulmonary (19 fibres) or non-pulmonary (6 fibres). 2. PBG increased the discharge rate of both C-fibre types and activated a respiratory reflex causing apnoea. This reflex was abolished when the second vagus nerve was cut as well, while PBG-mediated stimulation of the C-fibres was not affected by vagotomy. 3. LVDP was administered intravenously and the C-fibre response to PBG was compared with that before administration of the drug. LVDP reduced both the duration of apnoea and the response of the C-fibre to PBG. 4. Comparison of the C-fibre responses to PBG and to a mixture of PBG and LVDP revealed that the period of apnoea was shortened and the discharge rate of the C-fibre reduced when LVDP was present. 5. The LVDP-induced inhibition of the C-fibre response to PBG was on average 50% in pulmonary and 25% in non-pulmonary fibres. 6. These results suggest that LVDP significantly reduces the response of vagal C-fibres to chemical stimuli. It is, thus, likely that the antitussive effect of LVDP is mediated through its inhibitory action on C-fibres. PMID:8851501

  3. The effect of deep tissue incision on pH responses of afferent fibers and dorsal root ganglia innervating muscle

    PubMed Central

    Kido, Kanta; Gautam, Mamta; Benson, Christopher J.; Gu, He; Brennan, Timothy J.

    2014-01-01

    Background Understanding the mechanisms underlying deep tissue pain in the postoperative period is critical to improve therapies. Using the in vitro plantar flexor digitorum brevis (FDB) muscle-nerve preparation and patch-clamp recordings from cultured dorsal root ganglia (DRG) neurons innervating incised and unincised muscle, we investigated responses to various pH changes. Methods Incision including the plantar FDB muscle or sham operation was made in the rat hindpaw. On postoperative day one, in vitro single fiber recording was undertaken. Based on previous studies, we recorded from at least 40 fibers per group. Also Di-I labeled DRG innervating muscle from rats undergoing incision and a sham operation were cultured and tested for acid responses using whole cell patch-clamp recordings. Results The prevalence of responsive group IV afferents to lactic acid pH 6.5 in the incision group (15 of 67, 22.3%) was greater than that in the control group (2 of 35, 5.7%, p=0.022). In DRG neurons innervating muscle, incision increased mean current amplitudes of acid-evoked currents; the acid-sensing ion channel blocker, amiloride 300 μM, inhibited more than 75% of the acid-evoked current, whereas the transient receptor vanilloid receptor 1 blocker (AMG9810 1 μM) did not cause significant inhibition. Conclusion Our experiments demonstrated that incision increases the responses of FDB muscle afferent fibers to weak acid solutions, and increased acid-evoked currents in DRG innervating muscle. Our data suggest that upregulation of acid-sensing ion channels might underlie this increased chemosensitivity caused by surgery. PMID:23732174

  4. Electrophysiological Properties of Dural Afferents in the Absence and Presence of Inflammatory Mediators

    PubMed Central

    Harriott, Andrea M.; Gold, Michael S.

    2009-01-01

    Migraine is a debilitating condition characterized by recurrent severe head pain. Although mechanisms underlying a migraine attack remain controversial, one proposal is that inflammatory mediator (IM)–induced activation and sensitization of dural afferents contribute to the initiation of migraine pain. We and others have shown that the electrophysiological properties of afferents, both in the absence and the presence of IM, vary as a function of target of innervation. These differences may account for unique aspects of pain syndromes associated with specific body regions. Therefore the purpose of the present study was to test the hypothesis that the electrophysiological properties of dural afferents differ from those innervating the temporalis muscle (TM), a structure in close proximity to the dura but that is not associated with pain syndromes at all similar to migraine. Acutely dissociated retrograde labeled primary afferents innervating the dura and TM were examined with whole cell current-clamp recordings. Passive and active electrophysiological properties were determined before and after the application of IM: (in μM) prostaglandin E2 (1), bradykinin (10), and histamine (1). In the absence of IM, there were significant differences between the two populations, particularly with respect to the response to suprathreshold stimulation where dural afferents were more excitable than TM afferents. Importantly, although both populations of afferents were sensitized by IM, the pattern of passive and active electrophysiological changes associated with IM-induced sensitization of these two populations of afferents suggested that there were both similarities and marked differences between the two with respect to underlying mechanisms of sensitization. If the differences between dural and TM afferents are due to a differential pattern of ion channel expression rather than differences in the relative density/biophysical properties of the same ion channels, it may be

  5. The Furcal Nerve Revisited

    PubMed Central

    Dabke, Harshad V.

    2014-01-01

    Atypical sciatica and discrepancy between clinical presentation and imaging findings is a dilemma for treating surgeon in management of lumbar disc herniation. It also constitutes ground for failed back surgery and potential litigations thereof. Furcal nerve (Furcal = forked) is an independent nerve with its own ventral and dorsal branches (rootlets) and forms a link nerve that connects lumbar and sacral plexus. Its fibers branch out to be part of femoral and obturator nerves in-addition to the lumbosacral trunk. It is most commonly found at L4 level and is the most common cause of atypical presentation of radiculopathy/sciatica. Very little is published about the furcal nerve and many are unaware of its existence. This article summarizes all the existing evidence about furcal nerve in English literature in an attempt to create awareness and offer insight about this unique entity to fellow colleagues/professionals involved in spine care. PMID:25317309

  6. Sciatic nerve injection injury.

    PubMed

    Jung Kim, Hyun; Hyun Park, Sang

    2014-06-11

    Nerve injury is a common complication following intramuscular injection and the sciatic nerve is the most frequently affected nerve, especially in children, the elderly and underweight patients. The neurological presentation may range from minor transient pain to severe sensory disturbance and motor loss with poor recovery. Management of nerve injection injury includes drug treatment of pain, physiotherapy, use of assistive devices and surgical exploration. Early recognition of nerve injection injury and appropriate management are crucial in order to reduce neurological deficit and to maximize recovery. Sciatic nerve injection injury is a preventable event. Total avoidance of intramuscular injection is recommended if other administration routes can be used. If the injection has to be administered into the gluteal muscle, the ventrogluteal region (gluteal triangle) has a more favourable safety profile than the dorsogluteal region (the upper outer quadrant of the buttock). PMID:24920643

  7. Characteristics of ejaculated rat semen after lesion of scrotal nerves.

    PubMed

    Garcia, Luis I; Soto-Cid, Abraham; Carrillo, Porfirio; Toledo, Rebeca; Hernandez, Maria Elena; Manzo, Jorge

    2007-05-16

    The scrotum, representing the pouch surrounding the testes and their associated structures, plays a significant role in maintaining the gonad at a temperature lower than that of the body. Although thermoregulation of the testes has been ascribed as a main function of the scrotum, here we found that mechanical stimulation of the scrotum is important during mating to facilitate the appropriate expulsion of semen during ejaculation. Previously we showed that the scrotal skin area is innervated by two nerve branches, the proximal (Psb) and distal (Dsb) scrotal branches which supply the proximal or distal half of the scrotum, respectively. The sensory field of each nerve is testosterone-dependent. The decreased androgen levels following castration reduce the sensitive area to mechanical stimuli that can be restored following exogenous administration of the hormone. Here, we tested the effect of scrotal nerve transection on sexual parameters of experienced male rats. Data show that lesion of PSb or DSb alone or combined did not affect the execution of sexual behavior. However, these lesions significantly reduced the proportion of males that expelled semen during ejaculation, with that semen showing a reduced quantity of sperm. Thus, scrotal nerves are important in reproduction not for the appropriate display of sexual behavior, but for the expulsion of a normal quantity of semen and number of sperm during ejaculation. Our suggestion is that scrotal afferents trigger spinal reflexes to activate autonomic efferents supplying the male reproductive tract for the control of seminal emission. PMID:17343882

  8. Fiber components of the recurrent laryngeal nerve in the cat.

    PubMed

    Gacek, R R; Lyon, M J

    1976-01-01

    Experimental neuroanatomical methods were employed in 21 adult cats to determine 1) the number and size of myelinated motor and sensory fibers in the recurrent laryngeal nerve (RLN), and 2) the fiber components originating in the nucleus ambiguus (NA) and retrofacial nucleus (RFN) of the brain stem. Intracranial transection of the X and XI cranial nerves and selective destruction of the NA or RFN were the experimental lesions inflicted in order to obtain the following results. About 55% (312) of the right RLN (565 fibers) is composed of myelinated motor nerve fibers which measure 4 mu - 9 mu in diameter. Nine percent come from the RFN and are smaller (4-6 mu) than the 46% which emanate from the NA and measure 6-9 mu in diameter. The remaining 45% of the RLN is made up of sensory neurons which can be divided into three groups. 1) The largest numerical group (32%) is very small in caliber (1-3 mu) and supplies extralaryngeal regions (trachea, esophagus). 2) The intermediate size fiber group (4-9 mu) comprises 11% of the RLN and probably supplies the subglottic mucosa. 3) The smallest group (2%) of sensory fibers is the largest in diameter (10-15 mu) and may represent either the innervation of muscle spindles or afferents from the superior laryngeal nerve coursing down into the chest. PMID:949153

  9. Reversible differential block of saphenous nerve by cold

    PubMed Central

    Byck, R.; Goldfarb, J.; Schaumburg, H. H.; Sharpless, S. K.

    1972-01-01

    1. This report is concerned with the question of whether the alpha and delta groups of myelinated A fibres show conduction failure at different temperatures. 2. The experiments were done on cat saphenous nerve in vitro. Stimuli were applied to both ends of the nerve and biphasic recordings were taken adjacent to an 11 mm segment of nerve, whose temperature was varied. Before cooling commenced, the stimuli were adjusted so that the action potential which passed through the cold zone and was recorded, collided with the action potential initiated at the opposite end of the nerve. 3. Upon cooling the nerve, it was always observed that the delta peak of the action potential which had been previously occluded by collision reappeared at a temperature at which the alpha peak remained occluded. 4. The reappearance of the delta peak was reversible upon warming the nerve and was not affected by increasing the interstimulus interval. 5. The mean temperature for reappearance of the delta peak was 13·5° C, for reappearance of the alpha peak, 5·3° C. 6. In any given nerve, the blocking temperature was replicable and was dependent on the temperature of the cooled segment rather than the gradient between that segment and the remainder of the nerve. 7. We conclude that in cat saphenous nerve, the delta group of myelinated A fibres shows conduction failure at a higher temperature than does the alpha group. PMID:5037067

  10. Endoscopic Facial Nerve Surgery.

    PubMed

    Marchioni, Daniele; Soloperto, Davide; Rubini, Alessia; Nogueira, João Flávio; Badr-El-Dine, Mohamed; Presutti, Livio

    2016-10-01

    Tympanic facial nerve segment surgery has been traditionally performed using microscopic approaches, but currently, exclusive endoscopic approaches have been performed for traumatic, neoplastic, or inflammatory diseases, specially located at the geniculate ganglion, greater petrosal nerve, and second tract of the facial nerve, until the second genu. The tympanic segment of the facial nerve can be reached and visualized using an exclusive transcanal endoscopic approach, even in poorly accessible regions such as the second genu and geniculate ganglion, avoiding mastoidectomy, bony demolition, and meningeal or cerebral lobe tractions, with low complication rates using a minimally invasive surgical route. PMID:27468633

  11. Effect of nedocromil sodium on airway sensory nerves.

    PubMed

    Barnes, P J

    1993-07-01

    There is increasing evidence that the sensory nerves of the airway play a role in the asthmatic response. Nerve endings are exposed by the epithelial shedding that occurs with asthma. They may become sensitized and activated by inflammatory mediators and may release neuropeptides that then spread and amplify the inflammatory process in the airways. Nedocromil sodium may prevent the sensory nerves from becoming sensitized and inhibit their activation. This possibility is suggested because nedocromil is highly effective against several indirect challenges that involve sensory nerve stimulation. Nedocromil sodium was able to inhibit the bronchoconstriction induced in patients with asthma by exposure to bradykinin, sulfur dioxide, metabisulfite, and ultrasonically nebulized water. Cough, which is a prominent symptom of asthma, is believed to be a result of sensory nerve activation. In several long-term clinical studies, nedocromil sodium reduces the severity of cough among patients with asthma. Studies are needed to define how nedocromil sodium acts on the sensory nerves. PMID:8393025

  12. Treg engage lymphotoxin beta receptor for afferent lymphatic transendothelial migration

    PubMed Central

    Brinkman, C. Colin; Iwami, Daiki; Hritzo, Molly K.; Xiong, Yanbao; Ahmad, Sarwat; Simon, Thomas; Hippen, Keli L.; Blazar, Bruce R.; Bromberg, Jonathan S.

    2016-01-01

    Regulatory T cells (Tregs) are essential to suppress unwanted immunity or inflammation. After islet allo-transplant Tregs must migrate from blood to allograft, then via afferent lymphatics to draining LN to protect allografts. Here we show that Tregs but not non-Treg T cells use lymphotoxin (LT) during migration from allograft to draining LN, and that LT deficiency or blockade prevents normal migration and allograft protection. Treg LTαβ rapidly modulates cytoskeletal and membrane structure of lymphatic endothelial cells; dependent on VCAM-1 and non-canonical NFκB signalling via LTβR. These results demonstrate a form of T-cell migration used only by Treg in tissues that serves an important role in their suppressive function and is a unique therapeutic focus for modulating suppression. PMID:27323847

  13. Functional dopamine D2 receptors on rat vagal afferent neurones.

    PubMed Central

    Lawrence, A J; Krstew, E; Jarrott, B

    1995-01-01

    1. In the present study in vitro electrophysiology and receptor autoradiography were used to determine whether rat vagal afferent neurones possess dopamine D2 receptors. 2. Dopamine (10-300 microM) elicited a temperature- and concentration-dependent depolarization of the rat isolated nodose ganglion preparation. When applied to the tissue 15 min prior to agonist, raclopride (10 microM), clozapine (10 microM) or a mixture of raclopride and clozapine (10 microM each) all produced a threefold parallel shift to the right of the dopamine concentration-response curve. In contrast, SCH 23390 (100 nM), phentolamine and propranolol (1 microM each) failed to antagonize the dopamine-mediated depolarization. 3. [125I]-NCQ 298 (0.5 nM), a D2 selective radioligand, bound topographically to sections of rat brainstem. Densitometric quantification of autoradiograms revealed 93.8 +/- 0.5% specific binding of this salicylamide radioligand, as determined by raclopride (10 microM, n = 10 animals). Binding was highest in the nucleus tractus solitarius (NTS), particularly the medial and gelatinous subnuclei. In addition, specific binding was also observed in the interpolar spinal trigeminal nucleus and the inferior olive. 4. Unilateral nodose ganglionectomy caused a 36.6 +/- 3.0% reduction in specific binding in the denervated NTS compared to the contralateral NTS. Furthermore, the loss of binding was confined to the dorsal aspect of the medial subnucleus of the NTS. Sham surgery had no effect on the binding of [125I]-NCQ 298 in rat brainstem. 5. The present data provide evidence for the presence of functionally relevant dopamine D2 receptors on both the soma and central terminals of rat vagal afferent neurones.(ABSTRACT TRUNCATED AT 250 WORDS) Images Figure 3 PMID:7606337

  14. [Neuropathic pain intensity depends on the degree of peripheral nerve injury in the rat].

    PubMed

    Abuduhadeer, Tayier

    2004-12-01

    Partial peripheral nerve injury produces a persistent neuropathic pain which is difficult to relieve. In order to determine whether different degrees of peripheral nerve injury are related with the severity of neuropathic pain, we examined pain-related behaviors, histological changes and NGF in the skin in rats treated with different types of spinal nerve injury: tight ligation of the left L5 spinal nerve, incomplete ligation of the left L4 and L5 spinal nerves and incomplete crush of the left L4 and L5 spinal nerves. In all model rats, the thresholds of paw withdrawal in response to mechanical and heat stimuli began to decrease on the injured side 1 day after the operation, and the decreases in the thresholds persisted for more than 1 month. Incomplete ligation and incomplete crush of the left L4 and L5 spinal nerves caused more severe allodynia and hyperalgesia than tight ligation of the left L5 spinal nerve on the injured side. In rats treated with incomplete crush, the threshold of withdrawal response to mechanical or heat stimuli was improved on day 32 after the operation as compared with that on day 15. Histological analysis revealed that about 80% of the fibers in the sciatic nerve were injured after incomplete ligation and incomplete crush of the left L4 and L5 spinal nerves on day 15, while about 50% of the fibers were damaged by tight ligation of the left L5 spinal nerve. In accordance with pain-relieving, the sciatic nerve fibers regenerated to about 50% of the number of the intact sciatic nerve fibers on day 32 in the crush model. Nerve growth factor (NGF) in the skin of the hindpaw on the injured side was accumulated after incomplete ligation and incomplete crush of the left L4 and L5 spinal nerves, but not tight ligation of the left L5 spinal nerve, on day 15 after the operation, possibly due to impairment of transport via unmyelinated primary afferents. Regeneration of the sciatic nerve alleviated the accumulation of NGF in the injured side hindpaw

  15. Transposition and Intermingling of Galphai2 and Galphao afferences into single vomeronasal glomeruli in the Madagascan lesser Tenrec Echinops telfairi.

    PubMed

    Suárez, Rodrigo; Villalón, Aldo; Künzle, Heinz; Mpodozis, Jorge

    2009-01-01

    The vomeronasal system (VNS) mediates pheromonal communication in mammals. From the vomeronasal organ, two populations of sensory neurons, expressing either Galphai2 or Galphao proteins, send projections that end in glomeruli distributed either at the rostral or caudal half of the accessory olfactory bulb (AOB), respectively. Neurons at the AOB contact glomeruli of a single subpopulation. The dichotomic segregation of AOB glomeruli has been described in opossums, rodents and rabbits, while Primates and Laurasiatheres present the Galphai2-pathway only, or none at all (such as apes, some bats and aquatic species). We studied the AOB of the Madagascan lesser tenrec Echinops telfairi (Afrotheria: Afrosoricida) and found that Galphai2 and Galphao proteins are expressed in rostral and caudal glomeruli, respectively. However, the segregation of vomeronasal glomeruli at the AOB is not exclusive, as both pathways contained some glomeruli transposed into the adjoining subdomain. Moreover, some glomeruli seem to contain intermingled afferences from both pathways. Both the transposition and heterogeneity of vomeronasal afferences are features, to our knowledge, never reported before. The organization of AOB glomeruli suggests that synaptic integration might occur at the glomerular layer. Whether intrinsic AOB neurons may make synaptic contact with axon terminals of both subpopulations is an interesting possibility that would expand our understanding about the integration of vomeronasal pathways. PMID:19956694

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

    PubMed

    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. PMID:17179381

  17. Distribution of presumptive chemosensory afferents with FMRFamide- or substance P-like immunoreactivity in decapod crustaceans.

    PubMed

    Schmidt, M

    1997-01-23

    In five species of decapod crustaceans--Cherax destructor (crayfish), Carcinus maenas (crab), Homarus americanus (clawed lobster), Eriocheir sinensis (crab), Macrobrachium rosenbergii (shrimp)--immunocytochemical stainings revealed the presence of sensory afferents with FMRFamide-like immunoreactivity in the central nervous system. These afferents were extremely thin, very numerous, and innervated all sensory neuropils except the optic and olfactory lobes. In their target neuropils they gave rise to condensed net- or ball-like terminal structures. Only in Homarus americanus but not in any other studied species immunocytochemistry revealed a separate, non-overlapping class of sensory afferents with substance P-like immunoreactivity. Also the afferents with substance P-like immunoreactivity were very thin and numerous, innervated all sensory neuropils except optic and olfactory lobes, and gave rise to condensed terminal structures. From their morphological characteristics it can be concluded that likely both classes of afferents are chemosensory. The substance P-like immunoreactivity suggests a link with the nociceptor afferents of vertebrates, with which both classes of afferents share several other morphological features. PMID:9037486

  18. Technetium-99m HIDA hepatobiliary scanning in evaluation of afferent loop syndrome

    SciTech Connect

    Sivelli, R.; Farinon, A.M.; Sianesi, M.; Percudani, M.; Ugolotti, G.; Calbiani, B.

    1984-08-01

    A study of 118 patients, operated on with Billroth II gastrectomy for peptic disease and affected by postgastrectomy syndromes, was carried out. Fifty patients were investigated by means of technetium-99m HIDA hepatobiliary scanning. In 18 patients, in whom an afferent loop syndrome was clinically suspected, hepatobiliary scanning demonstrated an altered afferent loop emptying in 8 and atonic distension of the gallbladder without afferent loop motility changes in 10. Among the patients in the first group, four were treated with a biliary diversion surgical procedure and in the second group, two patients underwent cholecystectomy. Our findings indicate that biliary vomiting, right upper abdominal pain pyrosis, and biliary diarrhea in Billroth II gastrectomized patients are not always pathognomonic symptoms of afferent loop syndrome. Technetium-99m HIDA hepatobiliary scanning represents the only diagnostic means of afferent loop syndrome definition. A differential diagnosis of abnormal afferent loop emptying and gallbladder dyskinesia is necessary for the management planning of these patients, and furthermore, when a surgical treatment is required, biliary diversion with Roux-Y anastomosis or Braun's biliary diversion seems the treatment of choice for afferent loop syndrome, whereas cholecystectomy represents the best procedure for atonic distension of the gallbladder.

  19. Frequency response properties of primary afferent neurons in the posterior lateral line system of larval zebrafish.

    PubMed

    Levi, Rafael; Akanyeti, Otar; Ballo, Aleksander; Liao, James C

    2015-01-15

    The ability of fishes to detect water flow with the neuromasts of their lateral line system depends on the physiology of afferent neurons as well as the hydrodynamic environment. Using larval zebrafish (Danio rerio), we measured the basic response properties of primary afferent neurons to mechanical deflections of individual superficial neuromasts. We used two types of stimulation protocols. First, we used sine wave stimulation to characterize the response properties of the afferent neurons. The average frequency-response curve was flat across stimulation frequencies between 0 and 100 Hz, matching the filtering properties of a displacement detector. Spike rate increased asymptotically with frequency, and phase locking was maximal between 10 and 60 Hz. Second, we used pulse train stimulation to analyze the maximum spike rate capabilities. We found that afferent neurons could generate up to 80 spikes/s and could follow a pulse train stimulation rate of up to 40 pulses/s in a reliable and precise manner. Both sine wave and pulse stimulation protocols indicate that an afferent neuron can maintain their evoked activity for longer durations at low stimulation frequencies than at high frequencies. We found one type of afferent neuron based on spontaneous activity patterns and discovered a correlation between the level of spontaneous and evoked activity. Overall, our results establish the baseline response properties of lateral line primary afferent neurons in larval zebrafish, which is a crucial step in understanding how vertebrate mechanoreceptive systems sense and subsequently process information from the environment. PMID:25355959

  20. Hair cell tufts and afferent innervation of the bullfrog crista ampullaris

    NASA Technical Reports Server (NTRS)

    Myers, Steven F.; Lewis, Edwin R.

    1990-01-01

    Within the bullfrog semicircular canal crista, hair cell tuft types were defined and mapped with the aid of scanning electron microscopy. Dye-filled planar afferent axons had mean distal axonal diameters of 1.6-4.9 microns, highly branched arbors, and contacted 11-24 hair cells. Dye-filled isthmus afferent axons had mean distal axonal diameters of 1.8-7.9 microns, with either small or large field arbors contacting 4-9 or 25-31 hair cells. The estimated mean number of contacts per innervated hair cell was 2.2 for planar and 1.3 for isthmus afferent neurons. Data on evoked afferent responses were available only for isthmus units that were observed to respond to our microrotational stimuli. Of 21 such afferent neurons, eight were successfully dye-filled. Within this sample, high-gain units had large field arbors and lower-gain units had small field arbors. The sensitivity of each afferent neuron was analyzed in terms of noise equivalent input (NEI), the stimulus amplitude for which the afferent response amplitude is just equivalent to the rms deviation of the instantaneous spike rate. NEI for isthmus units varied from 0.63 to 8.2 deg/s; the mean was 3.2 deg/s.

  1. Novel Afferent Terminal Structure in the Crista Ampullaris of the Goldfish, Carassius auratus

    NASA Technical Reports Server (NTRS)

    Lanford, Pamela J.; Popper, Arthur N.

    1996-01-01

    Using transmission electron microscopy, we have identified a new type of afferent terminal structure in the crista ampullaris of the goldfish Carassius auratus. In addition to the bouton-type afferent terminals previously described in the ear of this species, the crista also contained enlarged afferent terminals that enveloped a portion of the basolateral hair cell membrane. The hair cell membrane was evaginated and protruded into the afferent terminal in a glove-and-finger configuration. The membranes of the two cells were regularly aligned in the protruded region of the contact and had a distinct symmetrical electron density. The electron-dense profiles of these contacts were easily identified and were present in every crista sampled. In some cases, efferent terminals synapsed onto the afferents at a point where the hair cell protruded into the terminal. The ultrastructural similarities of the goldfish crista afferents to calyx afferents found in amniotes (birds, reptiles, and mammals) are discussed. The results of the study support the hypothesis that structural variation in the vertebrate inner ear may have evolved much earlier in evolution than previously supposed.

  2. Frequency response properties of primary afferent neurons in the posterior lateral line system of larval zebrafish

    PubMed Central

    Levi, Rafael; Akanyeti, Otar; Ballo, Aleksander

    2014-01-01

    The ability of fishes to detect water flow with the neuromasts of their lateral line system depends on the physiology of afferent neurons as well as the hydrodynamic environment. Using larval zebrafish (Danio rerio), we measured the basic response properties of primary afferent neurons to mechanical deflections of individual superficial neuromasts. We used two types of stimulation protocols. First, we used sine wave stimulation to characterize the response properties of the afferent neurons. The average frequency-response curve was flat across stimulation frequencies between 0 and 100 Hz, matching the filtering properties of a displacement detector. Spike rate increased asymptotically with frequency, and phase locking was maximal between 10 and 60 Hz. Second, we used pulse train stimulation to analyze the maximum spike rate capabilities. We found that afferent neurons could generate up to 80 spikes/s and could follow a pulse train stimulation rate of up to 40 pulses/s in a reliable and precise manner. Both sine wave and pulse stimulation protocols indicate that an afferent neuron can maintain their evoked activity for longer durations at low stimulation frequencies than at high frequencies. We found one type of afferent neuron based on spontaneous activity patterns and discovered a correlation between the level of spontaneous and evoked activity. Overall, our results establish the baseline response properties of lateral line primary afferent neurons in larval zebrafish, which is a crucial step in understanding how vertebrate mechanoreceptive systems sense and subsequently process information from the environment. PMID:25355959

  3. Intraepidermal nerves in human skin: PGP 9.5 immunohistochemistry with special reference to the nerve density in skin from different body regions.

    PubMed

    Johansson, O; Wang, L; Hilliges, M; Liang, Y

    1999-01-01

    The intraepidermal nerves of normal adult human skin were demonstrated by employing a powerful marker of neuronal elements, protein gene product (PGP) 9.5. There were two types of epidermal nerves, free nerve endings and nerves in the Merkel cell-neurite complex. The free nerve endings distributed to, and terminated in, all the strata basale, spinosum and granulosum, and they appeared as thin fibers, mostly varicose, branched or single processed, straight or bent. They existed at every site of the human body, including face, trunk and extremities. However, the densities of these nerves varied in different body parts and areas. The number of nerves decreased from the trunk to the distal parts of the limbs, and small denser 'innervation patches' showed up in the epidermis which were identified in confocal microscopy as one morphologic terminal field coming from the same dermal nerve bundle. This study has confirmed the existence of epidermal nerves in normal adult human skin, and presented a more clear picture than earlier. The difference between densities of epidermal nerves at different body areas implies area-specific functions of the intraepidermal nerve terminals. The observed intraepithelial nerve fibers may have a pain-perceiving role, however, also trophic or immunoregulatory roles can not be excluded. PMID:10197064

  4. Intraoperative vagal nerve monitoring.

    PubMed

    Leonetti, J P; Jellish, W S; Warf, P; Hudson, E

    1996-08-01

    A variety of benign and malignant neoplasms occur in the superior cervical neck, parapharyngeal space or the infratemporal fossa. The surgical resection of these lesions may result in postoperative iatrogenic injury to the vagus nerve with associated dysfunctional swallowing and airway protection. Anatomic and functional preservation of this critical cranial nerve will contribute to a favorable surgical outcome. Fourteen patients with tumors of the cervical neck or adjacent skull base underwent intraoperative vagal nerve monitoring in an attempt to preserve neural integrity following tumor removal. Of the 11 patients with anatomically preserved vagal nerves in this group, seven patients had normal vocal cord mobility following surgery and all 11 patients demonstrated normal vocal cord movement by six months. In an earlier series of 23 patients with tumors in the same region who underwent tumor resection without vagal nerve monitoring, 18 patients had anatomically preserved vagal nerves. Within this group, five patients had normal vocal cord movement at one month and 13 patients demonstrated normal vocal cord movement at six months. This paper will outline a technique for intraoperative vagal nerve monitoring utilizing transcricothyroid membrane placement of bipolar hook-wire electrodes in the vocalis muscle. Our results with the surgical treatment of cervical neck and lateral skull base tumors for patients with unmonitored and monitored vagal nerves will be outlined. PMID:8828272

  5. Inferior alveolar nerve repositioning.

    PubMed

    Louis, P J

    2001-09-01

    Nerve repositioning is a viable alternative for patients with an atrophic edentulous posterior mandible. Patients, however, should be informed of the potential risks of neurosensory disturbance. Documentation of the patient's baseline neurosensory function should be performed with a two-point discrimination test or directional brush stroke test preoperatively and postoperatively. Recovery of nerve function should be expected in 3 to 6 months. The potential for mandibular fracture when combining nerve repositioning with implant placement also should be discussed with the patient. This can be avoided by minimizing the amount of buccal cortical plate removal during localization of the nerve and maintaining the integrity of the inferior cortex of the mandible. Additionally, avoid overseating the implant, thus avoiding stress along the inferior border of the mandible. The procedure does allow for the placement of longer implants, which should improve implant longevity. Patients undergoing this procedure have expressed overall satisfaction with the results. Nerve repositioning also can be used to preserve the inferior alveolar nerve during resection of benign tumors or cysts of the mandible. This procedure allows the surgeon to maintain nerve function in situations in which the nerve would otherwise have to be resected. PMID:11665379

  6. Distal median nerve dysfunction

    MedlinePlus

    ... Names Neuropathy - distal median nerve Images Central nervous system and peripheral nervous system References Jarvik JG, Comstock BA, Kliot M, et al. Surgery versus non-surgical therapy for carpal tunnel syndrome: a randomized ... D. Disorders of peripheral nerves. In: Daroff RB, Fenichel GM, Jankovic J, ...

  7. Optic Nerve Decompression

    MedlinePlus

    ... canals). The optic nerve is the “nerve of vision” and extends from the brain, through your skull, and into your eye. A ... limited to, the following: loss of vision, double vision, inadequate ... leakage of brain fluid (CSF), meningitis, nasal bleeding, infection of the ...

  8. The afferent signaling complex: Regulation of type I spiral ganglion neuron responses in the auditory periphery.

    PubMed

    Reijntjes, Daniël O J; Pyott, Sonja J

    2016-06-01

    The spiral ganglion neurons (SGNs) are the first action potential generating neurons in the auditory pathway. The type I SGNs contact the sensory inner hair cells via their peripheral dendrites and relay auditory information to the brainstem via their central axon fibers. Individual afferent fibers show differences in response properties that are essential for normal hearing. The mechanisms that give rise to the heterogeneity of afferent responses are very poorly understood but are likely already in place at the peripheral dendrites where synapses are formed and action potentials are generated. To identify these molecular mechanisms, this review synthesizes a variety of literature and comprehensively outlines the cellular and molecular components positioned to regulate SGN afferent dendrite excitability, especially following glutamate release. These components include 1) proteins of the SGN postsynapses and neighboring supporting cells that together shape glutamatergic signaling, 2) the ion channels and transporters that determine the intrinsic excitability of the SGN afferent dendrites, and 3) the neurotransmitter receptors that extrinsically modify this excitability via synaptic input from the lateral olivocochlear efferents. This cellular and molecular machinery, together with presynaptic specializations of the inner hair cells, can be collectively referred to as the type I afferent signaling complex. As this review underscores, interactions of this signaling complex determine excitability of the SGN afferent dendrites and the afferent fiber responses. Moreover, this complex establishes the environmental milieu critical for the development and maintenance of the SGN afferent dendrites and synapses. Motivated by these important functions, this review also indicates areas of future research to elucidate the contributions of the afferent signaling complex to both normal hearing and also hearing loss. PMID:27018296

  9. Modulation of vagal afferent excitation and reduction of food intake by leptin and cholecystokinin.

    PubMed

    Peters, James H; Simasko, Steven M; Ritter, Robert C

    2006-11-30

    The gut-peptide, cholecystokinin (CCK), reduces food intake by acting at CCK-1 receptors on vagal afferent neurons, whereas the feeding effects of the adipokine hormone, leptin, are associated primarily with its action on receptors (ObRb) in the hypothalamus. Recently, however, ObRb mRNA has been reported in vagal afferent neurons, some of which also express CCK-1 receptor, suggesting that leptin, alone or in cooperation with CCK, might activate vagal afferent neurons, and influence food intake via a vagal route. To evaluate these possibilities we have been examining the cellular and behavioral effects of leptin and CCK on vagal afferent neurons. In cultured vagal afferent neurons leptin and CCK evoked short latency, transient depolarizations, often leading to action potentials, and increases in cytosolic calcium. There was a much higher prevalence of CCK and leptin sensitivity amongst cultured vagal afferent neurons that innervate stomach or duodenum than there was in the overall vagal afferent population. Furthermore, almost all leptin-responsive gastric and duodenal vagal afferents also were sensitive to CCK. Leptin, infused into the upper GI tract arterial supply, reduced meal size, and enhanced satiation evoked by CCK. These results indicate that vagal afferent neurons are activated by leptin, and that this activation is likely to participate in meal termination, perhaps by enhancing vagal sensitivity to CCK. Our findings are consistent with the view that leptin and CCK exert their influence on food intake by accessing multiple neural systems (viscerosensory, motivational, affective and motor) at multiple points along the neuroaxis. PMID:16872644

  10. Enterolith Causing Afferent Loop Obstruction: A Case Report and Literature Review

    SciTech Connect

    Lee, Michael C.; Bui, James T.; Knuttinen, M-Grace; Gaba, Ron C.; Scott Helton, W.; Owens, Charles A.

    2009-09-15

    Enterolith formation is a rare cause of afferent limb obstruction following Billroth II gastrectomy and Roux-en-Y hepaticojejunostomy surgery. A case of ascending cholangitis caused by an enterolith incarcerated in the afferent loop of a 15-year-old Roux-en-Y hepaticojejunostomy was emergently decompressed under direct ultrasound guidance prior to surgery. This is the thirteenth reported case of an enterolith causing afferent loop obstruction. A discussion of our management approach and a review of the relevant literature are presented.

  11. Percutaneous jejunostomy through the liver parenchyma for palliation of afferent loop syndrome.

    PubMed

    Kwon, Jae Hyun; Han, Yoon Hee

    2015-01-01

    In the treatment of afferent loop syndrome, jejunostomy or Roux-en-Y gastrojejunostomy have tended to represent the preferred procedures. In patients who are not good candidates for surgery, palliative treatment-i.e., percutaneous transhepatic biliary drainage or percutaneous direct transperitoneal jejunostomy techniques-have been applied. Transhepatic biliary drainage confers a risk of ascending cholangitis. Direct percutaneous transperitoneal drainage may be impractical when overlying bowel loops prevent access to deeply located afferent loops. In the present case, percutaneous jejunostomy through the liver parenchyma was performed successfully for palliation of afferent loop syndrome. PMID:25433418

  12. Preoperative transcutaneous electrical nerve stimulation for localizing superficial nerve paths.

    PubMed

    Natori, Yuhei; Yoshizawa, Hidekazu; Mizuno, Hiroshi; Hayashi, Ayato

    2015-12-01

    During surgery, peripheral nerves are often seen to follow unpredictable paths because of previous surgeries and/or compression caused by a tumor. Iatrogenic nerve injury is a serious complication that must be avoided, and preoperative evaluation of nerve paths is important for preventing it. In this study, transcutaneous electrical nerve stimulation (TENS) was used for an in-depth analysis of peripheral nerve paths. This study included 27 patients who underwent the TENS procedure to evaluate the peripheral nerve path (17 males and 10 females; mean age: 59.9 years, range: 18-83 years) of each patient preoperatively. An electrode pen coupled to an electrical nerve stimulator was used for superficial nerve mapping. The TENS procedure was performed on patients' major peripheral nerves that passed close to the surgical field of tumor resection or trauma surgery, and intraoperative damage to those nerves was apprehensive. The paths of the target nerve were detected in most patients preoperatively. The nerve paths of 26 patients were precisely under the markings drawn preoperatively. The nerve path of one patient substantially differed from the preoperative markings with numbness at the surgical region. During surgery, the nerve paths could be accurately mapped preoperatively using the TENS procedure as confirmed by direct visualization of the nerve. This stimulation device is easy to use and offers highly accurate mapping of nerves for surgical planning without major complications. The authors conclude that TENS is a useful tool for noninvasive nerve localization and makes tumor resection a safe and smooth procedure. PMID:26420473

  13. Experimental and clinical employment of end-to-side coaptation: our experience.

    PubMed

    Tos, P; Geuna, S; Papalia, I; Conforti, L G; Artiaco, S; Battiston, B

    2011-01-01

    The last 15 years have seen a growing interest regarding a technique for nerve repair named end-to-side coaptation. Since 2000, we have carried out experimental studies on end-to-side nerve repair as well as employed this technique to a series of selected clinical cases. Here we report on the results of this experience.For experimental studies, we have used the model represented by median nerve repair by end-to-side coaptation either on the ulnar (agonistic) or the radial (antagonistic) nerve. For time course assessment of median nerve functional recovery we used the grasping test, a test which permits to assess voluntary control of muscle function. Repaired nerves were processed for resin embedding to allow nerve fibre stereology and electron microscopy. Results showed that, in either experimental group, end-to-side-repaired median nerves were repopulated by axons regenerating from ulnar and radial donor nerves, respectively. Moreover, contrary to previously published data, our results showed that voluntary motor control of the muscles innervated by the median nerve was progressively recovered also when the antagonistic radial nerve was the donor nerve.As regards our clinical experience, results were not so positive. We have treated by end-to-side coaptation patients with both sensory (n = 7, collateral digital nerves) and mixed (n = 8, plexus level) nerve lesions. Results were good, as in other series, in sensory nerves whilst they were very difficult to investigate in mixed nerves at the plexus level.Take together, these results suggest that clinical employment of end-to-side coaptation should still be considered at the moment as the ultima ratio in cases in which no other repair technique can be attempted. Yet, it is clear that more basic research is needed to explain the reasons for the different results between laboratory animal and humans and, especially, to find out how to ameliorate the outcome of end-to-side nerve repair by adequate treatment and

  14. GluA2-Containing AMPA Receptors Distinguish Ribbon-Associated from Ribbonless Afferent Contacts on Rat Cochlear Hair Cells.

    PubMed

    Martinez-Monedero, Rodrigo; Liu, Chang; Weisz, Catherine; Vyas, Pankhuri; Fuchs, Paul Albert; Glowatzki, Elisabeth

    2016-01-01

    Mechanosensory hair cells release glutamate at ribbon synapses to excite postsynaptic afferent neurons, via AMPA-type ionotropic glutamate receptors (AMPARs). However, type II afferent neurons contacting outer hair cells in the mammalian cochlea were thought to differ in this respect, failing to show GluA immunolabeling and with many "ribbonless" afferent contacts. Here it is shown that antibodies to the AMPAR subunit GluA2 labeled afferent contacts below inner and outer hair cells in the rat cochlea, and that synaptic currents in type II afferents had AMPAR-specific pharmacology. Only half the postsynaptic densities of type II afferents that labeled for PSD-95, Shank, or Homer were associated with GluA2 immunopuncta or presynaptic ribbons, the "empty slots" corresponding to ribbonless contacts described previously. These results extend the universality of AMPAergic transmission by hair cells, and support the existence of silent afferent contacts. PMID:27257620

  15. Decreases in endomorphin-2-like immunoreactivity concomitant with chronic pain after nerve injury.

    PubMed

    Smith, R R; Martin-Schild, S; Kastin, A J; Zadina, J E

    2001-01-01

    Nerve injury often leads to chronic, sometimes excruciating, pain. The mechanisms contributing to this syndrome include neurochemical plasticity in neurons involved in the earliest stages of pain transmission. Endomorphin-2 (Tyr-Pro-Phe-Phe-NH(2)) is an endogenous morphine-like substance that binds to the mu-opioid receptor with high affinity and selectivity. Endomorphin-2-like immunoreactivity (LI) is present in the superficial layers of the dorsal horn in the spinal cord and in primary afferents, suggesting a role for this peptide in pain transmission. To determine whether spinal endomorphin-2-LI is altered in an animal model of chronic pain, the left sciatic nerve of Swiss Webster and ICR mice was ligated in a modified Seltzer model of nerve injury. Changes in endomorphin-2-LI were assessed by immunocytochemistry at 2, 4 and 14 days after nerve injury. The side of the spinal cord ipsilateral to the nerve injury exhibited a dramatic decrease in endomorphin-2-LI relative to the contralateral side and to control animals. The change was restricted to the medial dorsal horn in the lumbar segments innervated by the sciatic nerve. Substance P-LI showed a small decrease, while calcitonin gene-related peptide-LI was unchanged. Both thermal hyperalgesia, as evidenced by significantly decreased paw withdrawal latencies, and decreased endomorphin-2-LI were observed within 2 days of injury and were most pronounced at 2 weeks after injury. The decrease in endomorphin-2-LI during the development of chronic pain is consistent with the loss of an inhibitory influence on pain transmission. These results provide the first evidence that reduction of an endogenous opioid in primary afferents is associated with injury-induced chronic pain. PMID:11516840

  16. Intraparotid Neurofibroma of the Facial Nerve: A Case Report

    PubMed Central

    Nofal, Ahmed-Abdel-Fattah; El-Anwar, Mohammad-Waheed

    2016-01-01

    Introduction: Intraparotid neurofibromas of the facial nerve are extremely rare and mostly associated with neurofibromatosis type 1 (NF1). Case Report: This is a case of a healthy 40-year-old man, which underwent surgery for a preoperatively diagnosed benign parotid gland lesion. After identification of the facial nerve main trunk, a single large mass (6 x 3 cm) incorporating the upper nerve division was observed. The nerve portion involved in the mass could not be dissected and was inevitably sacrificed with immediate neuroraphy of the upper division of the facial nerve with 6/0 prolene. The final histopathology revealed the presence of a neurofibroma. Complete left side facial nerve paralysis was observed immediately postoperatively but the function of the lower half was returned within 4 months and the upper half was returned after 1 year. Currently, after 3 years of follow up, there are no signs of recurrence and normal facial nerve function is observed. Conclusion: Neurofibroma should be considered as the diagnosis in a patient demonstrating a parotid mass. In cases where it is diagnosed intraoperatively, excision of part of the nerve with the mass will be inevitable though it can be successfully repaired by end to end anastomosis. PMID:27602341

  17. Chitosan crosslinked flat scaffolds for peripheral nerve regeneration.

    PubMed

    Fregnan, F; Ciglieri, E; Tos, P; Crosio, A; Ciardelli, G; Ruini, F; Tonda-Turo, C; Geuna, S; Raimondo, S

    2016-01-01

    Chitosan (CS) has been widely used in a variety of biomedical applications, including peripheral nerve repair, due to its excellent biocompatibility, biodegradability, readily availability and antibacterial activity. In this study, CS flat membranes, crosslinked with dibasic sodium phosphate (DSP) alone (CS/DSP) or in association with the γ-glycidoxypropyltrimethoxysilane (CS/GPTMS_DSP), were fabricated with a solvent casting technique. The constituent ratio of crosslinking agents and CS were previously selected to obtain a composite material having both adequate mechanical properties and high biocompatibility. In vitro cytotoxicity tests showed that both CS membranes allowed cell survival and proliferation. Moreover, CS/GPTMS_DSP membranes promoted cell adhesion, induced Schwann cell-like morphology and supported neurite outgrowth from dorsal root ganglia explants. Preliminary in vivo tests carried out on both types of nerve scaffolds (CS/DSP and CS/GPTMS_DSP membranes) demonstrated their potential for: (i) protecting, as a membrane, the site of nerve crush or repair by end-to-end surgery and avoiding post-operative nerve adhesion; (ii) bridging, as a conduit, the two nerve stumps after a severe peripheral nerve lesion with substance loss. A 1 cm gap on rat median nerve was repaired using CS/DSP and CS/GPTMS_DSP conduits to further investigate their ability to induce nerve regeneration in vivo. CS/GPTMS_DSP tubes resulted to be more fragile during suturing and, along a 12 week post-operative lapse of time, they detached from the distal nerve stump. On the contrary CS/DSP conduits promoted nerve fiber regeneration and functional recovery, leading to an outcome comparable to median nerve repaired by autograft. PMID:27508969

  18. Response properties of gerbil otolith afferents to small angle pitch and roll tilts

    NASA Technical Reports Server (NTRS)

    Dickman, J. D.; Angelaki, D. E.; Correia, M. J.

    1991-01-01

    The responses from isolated single otolith afferent fibers were obtained to small angle sinusoidal pitch and roll tilts in anesthetized gerbils. The stimulus directions that produced the maximum (response vector) and minimum response sensitivities were determined for each otolith afferent, with response vectors for the units being spread throughout the horizontal plane, similar to those reported for other species. A breadth of tuning measure was derived, with narrowly tuned neurons responding maximally to stimulation in one direction and minimally along an orthogonal ('null') direction. Most (approximately 80%) otolith afferents are narrowly tuned, however, some fibers were broadly tuned responding significantly to stimulations in any direction in the horizontal plane. The number of broadly tuned otolith afferents (approximately 20%) differs significantly from the more substantial number of broadly tuned vestibular nuclei neurons (88%) recently reported in rats.

  19. Functional specializations of primary auditory afferents on the Mauthner cells: interactions between membrane and synaptic properties.

    PubMed

    Curti, Sebastian; Pereda, Alberto E

    2010-01-01

    Primary auditory afferents are usually perceived as passive, timing-preserving, lines of communication. Contrasting this view, a special class of auditory afferents to teleost Mauthner cells, a command neuron that organizes tail-flip escape responses, undergoes potentiation of their mixed (electrical and chemical) synapses in response to high frequency cellular activity. This property is likely to represent a mechanism of input sensitization as these neurons provide the Mauthner cell with essential information for the initiation of an escape response. We review here the anatomical and physiological specializations of these identifiable auditory afferents. In particular, we discuss how their membrane and synaptic properties act in concert to more efficaciously activate the Mauthner cells. The striking functional specializations of these neurons suggest that primary auditory afferents might be capable of more sophisticated contributions to auditory processing than has been generally recognized. PMID:19941953

  20. Radial Nerve Tendon Transfers.

    PubMed

    Cheah, Andre Eu-Jin; Etcheson, Jennifer; Yao, Jeffrey

    2016-08-01

    Radial nerve palsy typically occurs as a result of trauma or iatrogenic injury and leads to the loss of wrist extension, finger extension, thumb extension, and a reduction in grip strength. In the absence of nerve recovery, reconstruction of motor function involves tendon transfer surgery. The most common donor tendons include the pronator teres, wrist flexors, and finger flexors. The type of tendon transfer is classified based on the donor for the extensor digitorum communis. Good outcomes have been reported for most methods of radial nerve tendon transfers as is typical for positional tendon transfers not requiring significant power. PMID:27387076

  1. Influence of map scale on primary afferent terminal field geometry in cat dorsal horn.

    PubMed

    Millecchia, R J; Pubols, L M; Sonty, R V; Culberson, J L; Gladfelter, W E; Brown, P B

    1991-09-01

    1. Thirty-one physiologically identified primary afferent fibers were labeled intracellularly with horseradish peroxidase (HRP). 2. A computer analysis was used to determine whether the distribution of cutaneous mechanoreceptive afferent terminals varies as a function of location within the dorsal horn somatotopic map. 3. An analysis of the geometry of the projections of these afferents has shown that 1) terminal arbors have a greater mediolateral width within the region of the foot representation than lateral to it, 2) terminal arbors have larger length-to-width ratios outside the foot representation than within it, and 3) the orientation of terminal arbors near the boundary of the foot representation reflects the angle of the boundary. Previous attribution of mediolateral width variations to primary afferent type are probably in error, although there appear to be genuine variations of longitudinal extent as a function of primary afferent type. 4. Nonuniform terminal distributions represent the first of a three-component process underlying assembly of the monosynaptic portions of cell receptive fields (RFs) and the somatotopic map. The other two components consist of the elaboration of cell dendritic trees and the establishment of selective connections. 5. The variation of primary afferent terminal distributions with map location is not an absolute requirement for development of the map; for example, the RFs of postsynaptic cells could be assembled with the use of a uniform terminal distribution for all afferents, everywhere in the map, as long as cell dendrites penetrate the appropriate portions of the presynaptic neuropil and receive connections only from afferent axons contributing to their RFs.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1753281

  2. High Ulnar Nerve Injuries: Nerve Transfers to Restore Function.

    PubMed

    Patterson, Jennifer Megan M

    2016-05-01

    Peripheral nerve injuries are challenging problems. Nerve transfers are one of many options available to surgeons caring for these patients, although they do not replace tendon transfers, nerve graft, or primary repair in all patients. Distal nerve transfers for the treatment of high ulnar nerve injuries allow for a shorter reinnervation period and improved ulnar intrinsic recovery, which are critical to function of the hand. PMID:27094893

  3. Identification of Molecular Pathologies Sufficient to Cause Neuropathic Excitability in Primary Somatosensory Afferents Using Dynamical Systems Theory

    PubMed Central

    Rho, Young-Ah; Prescott, Steven A.

    2012-01-01

    Pain caused by nerve injury (i.e. neuropathic pain) is associated with development of neuronal hyperexcitability at several points along the pain pathway. Within primary afferents, numerous injury-induced changes have been identified but it remains unclear which molecular changes are necessary and sufficient to explain cellular hyperexcitability. To investigate this, we built computational models that reproduce the switch from a normal spiking pattern characterized by a single spike at the onset of depolarization to a neuropathic one characterized by repetitive spiking throughout depolarization. Parameter changes that were sufficient to switch the spiking pattern also enabled membrane potential oscillations and bursting, suggesting that all three pathological changes are mechanistically linked. Dynamical analysis confirmed this prediction by showing that excitability changes co-develop when the nonlinear mechanism responsible for spike initiation switches from a quasi-separatrix-crossing to a subcritical Hopf bifurcation. This switch stems from biophysical changes that bias competition between oppositely directed fast- and slow-activating conductances operating at subthreshold potentials. Competition between activation and inactivation of a single conductance can be similarly biased with equivalent consequences for excitability. “Bias” can arise from a multitude of molecular changes occurring alone or in combination; in the latter case, changes can add or offset one another. Thus, our results identify pathological change in the nonlinear interaction between processes affecting spike initiation as the critical determinant of how simple injury-induced changes at the molecular level manifest complex excitability changes at the cellular level. We demonstrate that multiple distinct molecular changes are sufficient to produce neuropathic changes in excitability; however, given that nerve injury elicits numerous molecular changes that may be individually sufficient to

  4. Afference copy as a quantitative neurophysiological model for consciousness.

    PubMed

    Cornelis, Hugo; Coop, Allan D

    2014-06-01

    Consciousness is a topic of considerable human curiosity with a long history of philosophical analysis and debate. We consider there is nothing particularly complicated about consciousness when viewed as a necessary process of the vertebrate nervous system. Here, we propose a physiological "explanatory gap" is created during each present moment by the temporal requirements of neuronal activity. The gap extends from the time exteroceptive and proprioceptive stimuli activate the nervous system until they emerge into consciousness. During this "moment", it is impossible for an organism to have any conscious knowledge of the ongoing evolution of its environment. In our schematic model, a mechanism of "afference copy" is employed to bridge the explanatory gap with consciously experienced percepts. These percepts are fabricated from the conjunction of the cumulative memory of previous relevant experience and the given stimuli. They are structured to provide the best possible prediction of the expected content of subjective conscious experience likely to occur during the period of the gap. The model is based on the proposition that the neural circuitry necessary to support consciousness is a product of sub/preconscious reflexive learning and recall processes. Based on a review of various psychological and neurophysiological findings, we develop a framework which contextualizes the model and briefly discuss further implications. PMID:25012715

  5. State-space decoding of primary afferent neuron firing rates

    NASA Astrophysics Data System (ADS)

    Wagenaar, J. B.; Ventura, V.; Weber, D. J.

    2011-02-01

    Kinematic state feedback is important for neuroprostheses to generate stable and adaptive movements of an extremity. State information, represented in the firing rates of populations of primary afferent (PA) neurons, can be recorded at the level of the dorsal root ganglia (DRG). Previous work in cats showed the feasibility of using DRG recordings to predict the kinematic state of the hind limb using reverse regression. Although accurate decoding results were attained, reverse regression does not make efficient use of the information embedded in the firing rates of the neural population. In this paper, we present decoding results based on state-space modeling, and show that it is a more principled and more efficient method for decoding the firing rates in an ensemble of PA neurons. In particular, we show that we can extract confounded information from neurons that respond to multiple kinematic parameters, and that including velocity components in the firing rate models significantly increases the accuracy of the decoded trajectory. We show that, on average, state-space decoding is twice as efficient as reverse regression for decoding joint and endpoint kinematics.

  6. Control of arousal through neuropeptide afferents of the locus coeruleus.

    PubMed

    Zitnik, Gerard A

    2016-06-15

    The locus coeruleus-norepinephine (LC-NE) system is implicated in mediating several aspects of arousal. Alterations in LC neuronal discharge is associated with distinct changes in behavior, cognition, sensory processing and regulation of the sleep-wake cycle. Changes in LC output and subsequent release of NE in target brain regions help adjust arousal state to respond appropriately to environmental conditions and behavioral circumstances. One way in which LC activity is controlled is through release of endogenous neuropeptides. Based on the sleep-wake cycle and environmental cues specific neuropeptide afferent systems are activated, innervating the LC. These neuropeptides include: corticotropin releasing factor (CRF), orexin (ORX), endogenous opioids, substance P (SP), melanin-concentrating hormone (MCH), neuropeptide Y (NPY) and somatostatin (SS). This review summarizes studies examining the neuroanatomical projections of these neuropeptides, their receptors in the LC, the actions on LC neurons and downstream NE release, as well as the behavioral and cognitive effects associated individual neuropeptide-mediated innervation of the LC. Finally, the relationship between individual neuropeptides, the LC-NE system and various clinical disorders is discussed, providing evidence for possible therapeutic targets for treatment of several arousal- and stress-related disorders. This article is part of a Special Issue entitled SI: Noradrenergic System. PMID:26688115

  7. Inter-hemispheric plasticity in patients with median nerve injury.

    PubMed

    Fornander, Lotta; Nyman, Torbjörn; Hansson, Thomas; Brismar, Tom; Engström, Maria

    2016-08-15

    Peripheral nerve injuries result in reorganization within the contralateral hemisphere. Furthermore, recent animal and human studies have suggested that the plastic changes in response to peripheral nerve injury also include several areas of the ipsilateral hemisphere. The objective of this study was to map the inter-hemispheric plasticity in response to median nerve injury, to investigate normal differences in contra- and ipsilateral activation, and to study the impact of event-related or blocked functional magnetic resonance imaging (fMRI) design on ipsilateral activation. Four patients with median nerve injury at the wrist (injured and epineurally sutured >2 years earlier) and ten healthy volunteers were included. 3T fMRI was used to map the hemodynamic response to brain activity during tactile stimulation of the fingers, and a laterality index (LI) was calculated. Stimulation of Digits II-III of the injured hand resulted in a reduction in contralateral activation in the somatosensory area SI. Patients had a lower LI (0.21±0.15) compared to healthy controls (0.60±0.26) indicating greater ipsilateral activation of the primary somatosensory cortex. The spatial dispersion of the coordinates for areas SI and SII was larger in the ipsilateral than in the contralateral hemisphere in the healthy controls, and was increased in the contralateral hemisphere of the patients compared to the healthy controls. There was no difference in LI between the event-related and blocked paradigms. In conclusion, patients with median nerve injury have increased ipsilateral SI area activation, and spatially more dispersed contralateral SI activation during tactile stimulation of their injured hand. In normal subjects ipsilateral activation has larger spatial distribution than the contralateral. Previous findings in patients performed with the blocked fMRI paradigm were confirmed. The increase in ipsilateral SI activation may be due to an interhemispheric disinhibition associated with

  8. Coarse topographic organization of pheromone-sensitive afferents from different antennal surfaces in the American cockroach.

    PubMed

    Nishino, Hiroshi; Watanabe, Hidehiro; Kamimura, Itsuro; Yokohari, Fumio; Mizunami, Makoto

    2015-05-19

    In contrast to visual, auditory, taste, and mechanosensory neuropils, in which sensory afferents are topographically organized on the basis of their peripheral soma locations, axons of cognate sensory neurons from different locations of the olfactory sense organ converge onto a small spherical neuropil (glomerulus) in the first-order olfactory center. In the cockroach Periplaneta americana, sex pheromone-sensitive afferents with somata in the antero-dorsal and postero-ventral surfaces of a long whip-like antenna are biased toward the anterior and posterior regions of a macroglomerulus, respectively. In each region, afferents with somata in the more proximal antenna project to more proximal region, relative to the axonal entry points. However, precise topography of afferents in the macroglomerulus has remained unknown. Using single and multiple neuronal stainings, we showed that afferents arising from anterior, dorsal, ventral and posterior surfaces of the proximal regions of an antenna were biased progressively from the anterior to posterior region of the macroglomerulus, reflecting chiasmatic axonal re-arrangements that occur immediately before entering the antennal lobe. Morphologies of individual afferents originating from the proximal antenna matched results of mass neuronal stainings, but their three-dimensional origins in the antenna were hardly predictable on the basis of the projection patterns. Such projection biases made by neuronal populations differ from strict somatotopic projections of antennal mechanosensory neurons in the same species, suggesting a unique sensory mechanism to process information about odor location and direction on a single antenna. PMID:25849528

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

    PubMed Central

    Rowe, Michael H.; Neiman, Alexander B.

    2011-01-01

    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; 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. PMID:21890114

  10. Inflammation-induced plasticity of the afferent innervation of the airways.

    PubMed Central

    Carr, M J; Undem, B J

    2001-01-01

    The activation of primary afferent neurons that innervate the airways leads to homeostatic and defensive reflexes. The anatomic and physiologic characteristics of these afferent fibers do not appear to be static properties but rather appear to change rapidly in response to inflammation. The threshold for activation of airway afferent neurons to various stimuli, for example, is not fixed; these fibers can be become sensitized during inflammation. A subset of nociceptive-like (C-fibers) airway afferent neurons not only participates in centrally mediated reflexes but is also thought to release neuropeptides at their peripheral terminals, leading to neurogenic inflammation. An increase in the content of tachykinins is commonly seen in inflamed tissues, and there is accumulating evidence that irritation and inflammation of the airways is associated with the induction of tachykinin synthesis in non-nociceptive airway afferent fibers that under normal conditions do not contain neuropeptides. The release of neurokinins from the peripheral terminals in the airways and their central terminals in the brain stem may contribute to the symptoms of inflammatory airway diseases. Elevated release of neurokinins from peripheral terminals may promote local inflammatory responses, and the release of neurokinins in the brainstem, together with inflammation-induced increases in the excitability of afferent fibers, may culminate in altered visceral autonomic reflex activity, changes in breathing pattern, and cough. PMID:11544165

  11. Vagus nerve stimulation attenuates the systemic inflammatory response to endotoxin

    NASA Astrophysics Data System (ADS)

    Borovikova, Lyudmila V.; Ivanova, Svetlana; Zhang, Minghuang; Yang, Huan; Botchkina, Galina I.; Watkins, Linda R.; Wang, Haichao; Abumrad, Naji; Eaton, John W.; Tracey, Kevin J.

    2000-05-01

    Vertebrates achieve internal homeostasis during infection or injury by balancing the activities of proinflammatory and anti-inflammatory pathways. Endotoxin (lipopolysaccharide), produced by all gram-negative bacteria, activates macrophages to release cytokines that are potentially lethal. The central nervous system regulates systemic inflammatory responses to endotoxin through humoral mechanisms. Activation of afferent vagus nerve fibres by endotoxin or cytokines stimulates hypothalamic-pituitary-adrenal anti-inflammatory responses. However, comparatively little is known about the role of efferent vagus nerve signalling in modulating inflammation. Here, we describe a previously unrecognized, parasympathetic anti-inflammatory pathway by which the brain modulates systemic inflammatory responses to endotoxin. Acetylcholine, the principle vagal neurotransmitter, significantly attenuated the release of cytokines (tumour necrosis factor (TNF), interleukin (IL)-1β, IL-6 and IL-18), but not the anti-inflammatory cytokine IL-10, in lipopolysaccharide-stimulated human macrophage cultures. Direct electrical stimulation of the peripheral vagus nerve in vivo during lethal endotoxaemia in rats inhibited TNF synthesis in liver, attenuated peak serum TNF amounts, and prevented the development of shock.

  12. Ulnar nerve dysfunction

    MedlinePlus

    ... pressure on the elbow An elbow fracture or dislocation Temporary pain and tingling of this nerve can ... Saunders; 2011:chap 428. Read More Broken bone Dislocation Mononeuritis multiplex Mononeuropathy Myelin Peripheral neuropathy Systemic Update ...

  13. Diabetic Nerve Problems

    MedlinePlus

    ... at the wrong times. This damage is called diabetic neuropathy. Over half of people with diabetes get ... you change positions quickly Your doctor will diagnose diabetic neuropathy with a physical exam and nerve tests. ...

  14. Ulnar nerve dysfunction

    MedlinePlus

    ... surface of the body where it crosses the elbow. The damage destroys the nerve covering ( myelin sheath) ... be caused by: Long-term pressure on the elbow An elbow fracture or dislocation Temporary pain and ...

  15. Degenerative Nerve Diseases

    MedlinePlus

    Degenerative nerve diseases affect many of your body's activities, such as balance, movement, talking, breathing, and heart function. Many of these diseases are genetic. Sometimes the cause is a medical ...

  16. Common peroneal nerve dysfunction

    MedlinePlus

    ... people: Who are very thin (for example, from anorexia nervosa ) Who have certain autoimmune conditions, such as ... Elsevier; 2013:chap 22. Read More Alertness - decreased Anorexia Broken bone Diabetes and nerve damage Mononeuritis multiplex ...

  17. Femoral nerve dysfunction

    MedlinePlus

    ... An abnormal knee reflex Smaller than normal quadriceps muscles on the front of the thigh Tests that may be done include: Electromyography ( EMG ) Nerve conduction tests ( NCV ), usually done at ...

  18. Femoral nerve dysfunction

    MedlinePlus

    Neuropathy - femoral nerve; Femoral neuropathy ... Craig EJ, Clinchot DM. Femoral neuropathy. In: Frontera WR, Silver JK, Rizzo TD Jr, eds. Essentials of Physical Medicine and Rehabilitation: Musculoskeletal Disorders, Pain, and Rehabilitation . 3rd ...

  19. Diabetic Nerve Problems

    MedlinePlus

    ... the wrong times. This damage is called diabetic neuropathy. Over half of people with diabetes get it. ... change positions quickly Your doctor will diagnose diabetic neuropathy with a physical exam and nerve tests. Controlling ...

  20. Cortical Brain Mapping of Peripheral Nerves Using Functional Magnetic Resonance Imaging in a Rodent Model

    PubMed Central

    Cho, Younghoon R.; Jones, Seth R.; Pawela, Christopher P.; Li, Rupeng; Kao, Dennis S.; Schulte, Marie L.; Runquist, Matthew L.; Yan, Ji-Geng; Hudetz, Anthony G.; Jaradeh, Safwan S.; Hyde, James S.; Matloub, Hani S.

    2008-01-01

    The regions of the body have cortical and subcortical representation in proportion to their degree of innervation. The rat forepaw has been studied extensively in recent years using functional magnetic resonance imaging (fMRI)—typically by stimulation using electrodes directly inserted into the skin of the forepaw. Here, we stimulate using surgically implanted electrodes. A major distinction is that stimulation of the skin of the forepaw is mostly sensory, whereas direct nerve stimulation reveals not only the sensory system but also deep brain structures associated with motor activity. In this paper, we seek to define both the motor and sensory cortical and subcortical representations associated with the four major nerves of the rodent upper extremity. We electrically stimulated each nerve (median, ulnar, radial, and musculocutaneous) during fMRI acquisition using a 9.4T Bruker scanner. A current level of 0.5-1.0 mA and a frequency of 5 Hz were used while keeping the duration constant. A distinct pattern of cortical activation was found for each nerve that can be correlated with known sensorimotor afferent and efferent pathways to the rat forepaw. This direct nerve stimulation rat model can provide insight into peripheral nerve injury. PMID:18924070

  1. Sensory nerve conduction deficit in experimental monoclonal gammopathy of undetermined significance (MGUS) neuropathy.

    PubMed

    Lawlor, M W; Richards, M P; Fisher, M A; Stubbs, E B

    2001-06-01

    An emerging body of evidence from in vitro studies and in vivo animal models supports a pathogenic role of antibodies in the development of peripheral neuropathy associated with monoclonal gammopathy of undetermined significance (MGUS). Although the assessment of motor and sensory nerve fiber function is of clinical importance, it is seldom applied experimentally. We describe the application of an electrophysiologic method for the evaluation of motor and sensory nerve fiber function using an experimental model of MGUS neuropathy. Supramaximal stimulation of the tibial nerve elicited an early motor response (M-wave, 1.7 +/- 0.1 ms, n = 10) and a late sensory (H-reflex, 7.8 +/- 0.1 ms, n = 10) response that was recorded from the hind foot of anesthetized rats. Intraneural injection of serum antibodies from a MGUS patient with sensorimotor polyneuropathy, but not from an age-matched control subject, produced a marked attenuation of the H-reflex (P < 0.01, n = 10) without affecting the M-wave. Light and electron microscopy of affected nerve showed myelinoaxonal degeneration with sparing of the smaller unmyelinated nerve fibers. The combined electrophysiologic and morphologic findings presented in this study are consistent with a selective sensory conduction deficit in MGUS neuropathy. Selective injury of afferent nerve fibers by this patient's serum antibodies may result from reactivity to neural antigens uniquely expressed by sensory neurons. PMID:11360265

  2. Purinergic 2 receptor blockade prevents the responses of group IV afferents to post-contraction circulatory occlusion

    PubMed Central

    Kindig, Angela E; Hayes, Shawn G; Kaufman, Marc P

    2007-01-01

    ATP, by activating purinergic 2 (P2) receptors on group III and IV afferents, is thought to evoke the metabolic component of the exercise pressor reflex. Previously we have shown that injection of PPADS, a P2 receptor antagonist, into the arterial supply of skeletal muscle of decerebrated cats attenuated the responses of group III and IV afferents to static contraction while the muscles were freely perfused. We have now tested the hypothesis that injection of PPADS (10 mg kg−1) attenuated the responses of group III (n = 13) and group IV afferents (n = 9) to post-contraction circulatory occlusion. In the present study, we found that PPADS attenuated the group III afferent responses to static contraction during circulatory occlusion (P < 0.05). Likewise, PPADS abolished the group IV afferent responses to static contraction during occlusion (P = 0.001). During a 1 minute period of post-contraction circulatory occlusion, four of the 13 group III afferents and eight of the nine group IV afferents maintained their increased discharge. A Fischer's exact probability test revealed that more group IV afferents than group III afferents were stimulated by post-contraction circulatory occlusion (P < 0.02). In addition, the nine group IV afferents increased their mean discharge rate over baseline levels during the post-contraction circulatory occlusion period, whereas the 13 group III afferents did not (P < 0.05). PPADS abolished this post-contraction increase in discharge by the group IV afferents (P < 0.05). Our findings suggest that P2 receptors on group IV afferents play a role in evoking the metabolic component of the exercise pressor reflex. PMID:17038431

  3. Schwannoma of Extraocular Nerves

    PubMed Central

    Niazi, Wasim; Boggan, James E.

    1994-01-01

    An unusual case of schwannoma arising from the third cranial nerve in a thirteen year old male is reported. The patient presented with paresis of the right oculomotor nerve and ipsilateral hemiparesis. The clinical features of this case are discussed and the pertinent medical literature reviewed. ImagesFigure 1p220-bFigure 2Figure 3Figure 4Figure 5Figure 6 PMID:17171175

  4. BDNF contributes to IBS-like colonic hypersensitivity via activating the enteroglia-nerve unit

    PubMed Central

    Wang, Peng; Du, Chao; Chen, Fei-Xue; Li, Chang-Qing; Yu, Yan-Bo; Han, Ting; Akhtar, Suhail; Zuo, Xiu-Li; Tan, Xiao-Di; Li, Yan-Qing

    2016-01-01

    The over-expressed colonic brain-derived neurotrophic factor (BDNF) has been reported to be associated with abdominal pain in patients with irritable bowel syndrome (IBS). However, the neuropathological mechanism is unclear. We here investigated the involvement of enteroglial cells (EGCs) and enteric nerves in IBS-like visceral hypersensitivity. We showed that glial fibrillary acidic protein (GFAP), tyrosine receptor kinase B (TrkB) and substance P (SP) were significantly increased in the colonic mucosa of IBS patients. The upregulation of those proteins was also observed in the colon of mice with visceral hypersensitivity, but not in the colon of BDNF+/− mice. Functionally, TrkB or EGC inhibitors, or BDNF knockdown significantly suppressed visceral hypersensitivity in mice. Using the EGC cell line, we found that recombinant human BDNF (r-HuBDNF) could directly activate EGCs via the TrkB-phospholipase Cγ1 pathway, thereby inducing a significant upregulation of SP. Moreover, supernatants from r-HuBDNF-activated EGC culture medium, rather than r-HuBDNF alone, triggered markedly augmented discharges in isolated intestinal mesenteric afferent nerves. r-HuBDNF alone could cause mesenteric afferent mechanical hypersensitivity independently, and this effect was synergistically enhanced by activated EGCs. We conclude that EGC-enteric nerve unit may be involved in IBS-like visceral hypersensitivity, and this process is likely initiated by BDNF-TrkB pathway activation. PMID:26837784

  5. Sural nerve defects after nerve biopsy or nerve transfer as a sensory regeneration model for peripheral nerve conduit implantation.

    PubMed

    Radtke, C; Kocsis, J D; Reimers, K; Allmeling, C; Vogt, P M

    2013-09-01

    Nerve repair after injury can be effectively accomplished by direct suture approximation of the proximal and distal segments. This is more successful if coadaptation can be achieved without tension. Currently, the gold standard repair of larger deficits is the transplantation of an autologous sensory sural nerve graft. However, a significant disadvantage of this technique is the inevitable donor morbidity (sensory loss, neuroma and scar formation) after harvesting of the sural nerve. Moreover, limitation of autologous donor nerve length and fixed diameter of the available sural nerve are major drawbacks of current autograft treatment. Another approach that was introduced for nerve repair is the implantation of alloplastic nerve tubes made of, for example, poly-L-lactide. In these, nerve stumps of the transected nerves are surgically bridged using the biosynthetic conduit. A number of experimental studies, primarily in rodents, indicate axonal regeneration and remyelination after implantation of various conduits. However, only limited clinical studies with conduit implantation have been performed in acute peripheral nerve injuries particularly on digital nerves. Clinical transfer of animal studies, which can be carefully calibrated for site and extent of injury, to humans is difficult to interpret due to the intrinsic variability in human nerve injuries. This prevents effective quantification of improvement and induces bias in the study. Therefore, standardization of lesion/repair in human studies is warranted. Here we propose to use sural nerve defects, induced due to nerve graft harvesting or from diagnostic nerve biopsies as a model site to enable standardization of nerve conduit implantation. This would help better with the characterization of the implants and its effectiveness in axonal regeneration and remyelination. Nerve regeneration can be assessed, for example, by recovery of sensation, measured non-invasively by threshold to von Frey filaments and cold

  6. S1 nerve is the most efficient nerve rootlet innervating the anal canal and rectum in rats

    PubMed Central

    Fu, Kai; Luo, Pengbo; Zheng, Xianyou; Zhu, Xiaozhong; Wang, Lei; Chai, Yimin

    2015-01-01

    Autonomic and somatic components participate in the defecation process in mammals, combining signals from the brainstem and forebrain. The innervation pattern involved in micturition in rats has been well studied, while defecation has been less studied. The aim of the present study was to identify the most important sensory and motor nerves of the anal canal and rectum involved in defecation. The amplitudes of evoked potential of the anal canal and rectum were higher when L6 and S1 ventral rootlets were stimulated, compared with the other segments (ANOVA and Tukey’s post hoc test, all P < 0.05). The S1 segment was more strongly cholera toxin subunit B conjugated to horseradish peroxidase (CB-HRP) positive compared with the other segments (ANOVA and Tukey’s post hoc test, P < 0.05). Ventral spinal rootlets of L6 and S1 mainly contributed to the pressure change in the anal canal and rectum when the ventral spinal rootlets from L5 to S3 were stimulated electrically. In conclusion, many afferent and efferent nerves innervate the anal canal and rectum and are involved in defecation, but the S1 nerve rootlet could be the most efficient one. These results could provide a basis for defecation reconstruction, especially for patients with spinal cord injuries. PMID:26260583

  7. Facial Nerve Trauma: Evaluation and Considerations in Management

    PubMed Central

    Gordin, Eli; Lee, Thomas S.; Ducic, Yadranko; Arnaoutakis, Demetri

    2014-01-01

    The management of facial paralysis continues to evolve. Understanding the facial nerve anatomy and the different methods of evaluating the degree of facial nerve injury are crucial for successful management. When the facial nerve is transected, direct coaptation leads to the best outcome, followed by interpositional nerve grafting. In cases where motor end plates are still intact but a primary repair or graft is not feasible, a nerve transfer should be employed. When complete muscle atrophy has occurred, regional muscle transfer or free flap reconstruction is an option. When dynamic reanimation cannot be undertaken, static procedures offer some benefit. Adjunctive tools such as botulinum toxin injection and biofeedback can be helpful. Several new treatment modalities lie on the horizon which hold potential to alter the current treatment algorithm. PMID:25709748

  8. Termino-lateral nerve suture in lesions of the digital nerves: clinical experience and literature review.

    PubMed

    Artiaco, S; Tos, P; Conforti, L G; Geuna, S; Battiston, B

    2010-02-01

    Documented experience of treatment of digital nerve lesions with the termino-lateral (end-to-side) nerve suture is limited. Our clinical experience of this technique is detailed here alongside a systematic review of the previous literature. We performed, from 2002 to 2008, seven termino-lateral sutures with epineural window opening for digital nerve lesions. Functional outcome was analysed using the two-point discrimination test and the Semmes-Weinstein monofilament test. The results showed a sensory recovery of S3+ in six cases and S3 in one case. The mean distance found in the two-point discrimination test was 12.7 mm (range 8-18 mm). After a review of the literature, we were able to obtain homogeneous data from 17 additional patients operated by termino-lateral coaptation. The overall number of cases included in our review was 24. A sensory recovery was observed in 23 out of 24 patients. The functional results were S0 in one case, S3 in one case, S3+ in twenty cases and S4 in two cases. Excluding the one unfavourable case, the mean distance in the two-point discrimination test was 9.7 mm (range 3-18 mm). It can thus be concluded that the treatment of digital nerve lesions with termino-lateral suture showed encouraging results. Based on the results obtained in this current study we believe that in case of loss of substance, end-to-side nerve coaptation may be an alternative to biological and synthetic tubulisation when a digital nerve reconstruction by means of nerve autograft is declined by the patient. PMID:19687081

  9. Ultrasound in Dual Nerve Impairment after Proximal Radial Nerve Lesion

    PubMed Central

    Lämmer, Alexandra B; Schwab, Stefan; Schramm, Axel

    2015-01-01

    Introduction Sonography in classical nerve entrapment syndromes is an established and validated method. In contrast, few publications highlight lesions of the radial nerve, particularly of the posterior interosseus nerve (PIN). Method Five patients with a radial nerve lesion were investigated by electromyography, nerve conduction velocity and ultrasound. Further normative values of 26 healthy subjects were evaluated. Results Four patients presented a clinical and electrophysiological proximal axonal radial nerve lesion and one patient showed a typical posterior interosseous nerve syndrome (PINS). The patient with PINS presented an enlargement of the PIN anterior to the supinator muscle. However four patients with proximal lesions showed an unexpected significant enlargement of the PIN within the supinator muscle. Conclusion High-resolution sonography is a feasible method to demonstrate the radial nerve including its distal branches. At least in axonal radial nerve lesions, sonography might reveal abnormalities far distant from a primary proximal lesion site clearly distinct from the appearance in classical PINS. PMID:25992766

  10. Endogenous bradykinin activates ischaemically sensitive cardiac visceral afferents through kinin B2 receptors in cats

    PubMed Central

    Tjen-A-Looi, Stephanie C; Pan, Hui-Lin; Longhurst, John C

    1998-01-01

    Activity of ischaemically sensitive cardiac visceral afferents during myocardial ischaemia induces both angina and cardiovascular reflexes. Increased production of bradykinin (BK) and cyclo-oxygenase products (i.e. prostaglandins (PGs)) occurs during myocardial ischaemia. However, the role of these agents in activation of ischaemically sensitive cardiac afferents has not been established. The present study tested the hypothesis that BK produced during ischaemia activates cardiac afferents through kinin B2 receptors. Single-unit activity of cardiac afferents innervating the left ventricle was recorded from the left thoracic sympathetic chain (T1–T4) of anaesthetized cats. Ischaemically sensitive cardiac afferents were identified according to their response to 5 min of myocardial ischaemia. The mechanism of BK in activation of ischaemically sensitive cardiac afferents was determined by injection of BK (1 μg kg−1 i.a.), des-Arg9-BK (1 μg kg−1 i.a., a specific kinin B1 receptor agonist), kinin B2 receptor antagonists: HOE140 (30 μg kg−1 i.v.) and NPC-17731 (40 μg kg−1 i.v.), cyclo-oxygenase inhibition with indomethacin (5 mg kg−1 i.v.) and NPC-17731 (40 μg kg−1 i.v.) after pretreatment with indomethacin (5 mg kg−1 i.v.). We observed that BK increased the discharge rate of all eleven ischaemically sensitive cardiac afferents from 0.39 ± 0.12 to 1.47 ± 0.37 impulses s−1 (P < 0.05). Conversely, des-Arg9-BK did not significantly increase the activity of eleven ischaemically sensitive fibres (0.58 ± 0.02 vs. 0.50 ± 0.18 impulses s−1). HOE140 significantly attenuated the response of twelve afferents to ischaemia (0.61 ± 0.22 to 1.85 ± 0.5 vs. 0.53 ± 0.16 to 1.09 ± 0.4 impulses s−1). NPC-17731, another kinin B2 receptor antagonist, had similar inhibitory effects on six other ischaemically sensitive cardiac afferents (0.35 ± 0.14 to 1.19 ± 0.29 vs. 0.22 ± 0.08 to 0.23 ± 0.07 impulses s−1). Indomethacin significantly reduced the

  11. Endoscopic management of afferent loop syndrome after a pylorus preserving pancreatoduodenecotomy presenting with obstructive jaundice and ascending cholangitis.

    PubMed

    Kim, Jae Kyung; Park, Chan Hyuk; Huh, Ji Hye; Park, Jeong Youp; Park, Seung Woo; Song, Si Young; Chung, Jaebock; Bang, Seungmin

    2011-09-01

    Afferent loop syndrome is a rare complication of gastrojejunostomy. Patients usually present with abdominal distention and bilious vomiting. Afferent loop syndrome in patients who have undergone a pylorus preserving pancreaticoduodenectomy can present with ascending cholangitis. This condition is related to a large volume of reflux through the biliary-enteric anastomosis and static materials with bacterial overgrowth in the afferent loop. Patients with afferent loop syndrome after pylorus preserving pancreaticoduodenectomy frequently cannot be confirmed as surgical candidates due to poor medical condition. In that situation, a non-surgical palliation should be considered. Herein, we report two patients with afferent loop syndrome presenting with obstructive jaundice and ascending cholangitis. The patients suffered from the recurrence of pancreatic cancer after pylorus preserving pancreaticoduodenectomy. The diagnosis of afferent loop syndrome was confirmed, and the patients were successfully treated by inserting an endoscopic metal stent using a colonoscopic endoscope. PMID:22741115

  12. Basic study on the inf