The purpose of this study was to examine the potential functional significance of the sensory nerve inhibitory system in modulating contraction. Tension development in response to electrical field stimulation (EFS) and exogenous acetylcholine was monitored in segments of intrapulmonary bronchi isolated from male Sprague-Dawley rats. Contractile responses to EFS were enhanced by desensitization of sensory nerves with capsaicin, by antagonizing neurokinin NK1 receptors with RP-67580, and by inhibition of cyclooxygenase with meclofenamate. Except for RP-67580, which had a slight inhibitory effect on acetylcholine-induced contractions, these interventions were without effect on contraction to acetylcholine. Incubation of capsaicin-desensitized airway segments with substance P attenuated contractions evoked by a half-maximal frequency of EFS by approximately 92%, whereas contractions elicited by a half-maximal concentration of acetylcholine were not affected. Contractile responses elicited by a lower concentration of acetylcholine were inhibited by approximately 50% by substance P. The inhibitory effect of substance P was blocked by RP-67580, meclofenamate, and epithelial denudation. We conclude that the sensory nerve inhibitory system modulates cholinergic contractions and thus plays a role in the regulation of airway smooth muscle tone. PMID:8828673
Szarek, J L; Spurlock, B
Before a tussive stimulus in the airways can evoke a cough reflex it must first cause action potential discharge in cough-associated vagal sensory nerves. This is initiated by the stimulus first interacting with the receptors and ion channels in the terminal membrane of the sensory fiber in a manner that leads to membrane depolarization. If the stimulus-induced membrane depolarization, referred
Marian Kollarik; Bradley J. Undem
Sensory nerves innervating the lung and airways play an important role in regulating various cardiopulmonary functions and maintaining homeostasis under both healthy and disease conditions. Their activities conducted by both vagal and sympathetic afferents are also responsible for eliciting important defense reflexes that protect the lung and body from potential health-hazardous effects of airborne particulates and chemical irritants. This article reviews the morphology, transduction properties, reflex functions, and respiratory sensations of these receptors, focusing primarily on recent findings derived from using new technologies such as neural immunochemistry, isolated airway-nerve preparation, cultured airway neurons, patch-clamp electrophysiology, transgenic mice, and other cellular and molecular approaches. Studies of the signal transduction of mechanosensitive afferents have revealed a new concept of sensory unit and cellular mechanism of activation, and identified additional types of sensory receptors in the lung. Chemosensitive properties of these lung afferents are further characterized by the expression of specific ligand-gated ion channels on nerve terminals, ganglion origin, and responses to the action of various inflammatory cells, mediators, and cytokines during acute and chronic airway inflammation and injuries. Increasing interest and extensive investigations have been focused on uncovering the mechanisms underlying hypersensitivity of these airway afferents, and their role in the manifestation of various symptoms under pathophysiological conditions. Several important and challenging questions regarding these sensory nerves are discussed. Searching for these answers will be a critical step in developing the translational research and effective treatments of airway diseases. PMID:24692141
Lee, Lu-Yuan; Yu, Jerry
diagnostic tool in idiopathic small-fiber sensory neuropathy3,4 and diabetic neuropathy,5 but has not yetReduced intraepidermal nerve fiber density in HIV-associated sensory neuropathy M. Polydefkis, MD nerve fiber (IENF) density in HIV-associated sensory neuropathy (HIV-SN) to measurements of neuropathy
Steinbach, Joe Henry
Menthol and cinnamaldehyde (CA) are plant-derived spices commonly used in oral hygiene products, chewing gum, and many other applications. However, little is known regarding their sensory interactions in the oral cavity. We used a human psychophysics approach to investigate the temporal dynamics of oral irritation elicited by sequential application of menthol and/or CA, and ratiometric calcium imaging methods to investigate activation of rat trigeminal ganglion (TG) cells by these agents. Irritancy decreased significantly with sequential oral application of menthol and CA (self-desensitization). Menthol cross-desensitized irritation elicited by CA, and vice versa, over a time course of at least 60 min. Seventeen and 19% of TG cells were activated by menthol and CA, respectively, with ?50% responding to both. TG cells exhibited significant self-desensitization to menthol applied at a 5, but not 10, min interval. They also exhibited significant self-desensitization to CA at 400 but not 200 ?M. Menthol cross-desensitized TG cell responses to CA. CA at a concentration of 400 but not 200 ?M also cross-desensitized menthol-evoked responses. The results support the argument that the perceived reductions in oral irritancy and cross-interactions between menthol and CA and menthol observed (at least at short interstimulus intervals) can be largely accounted for by the properties of trigeminal sensory neurons innervating the tongue. PMID:21059698
Klein, Amanda H; Carstens, Mirela Iodi; Zanotto, Karen L; Sawyer, Carolyn M; Ivanov, Margaret; Cheung, Susan; Carstens, E
Vagal and spinal afferent innervation of the portal hepatic area has not been studied as thoroughly as the innervation of other important organs. It is generally agreed that unlike noradrenergic sympathetic efferent nerve fibers, sensory nerve fibers of either vagal or dorsal root/spinal origin do not directly innervate hepatocytes, but are restricted to the stroma surrounding triades of hepatic vasculature and bile ducts, and to extrahepatic portions of the portal vein and bile ducts. For vagal afferent innervation, retrograde and anterograde tracing studies in the rat have clearly shown that only a minor portion of the common hepatic branch innervates the liver area, while the major portion descends in the gastroduodenal branch toward duodenum, pancreas, and pylorus. Hepatic paraganglia, bile ducts, and portal vein receive the densest vagal afferent innervation. Calretinin may be a relatively specific marker for vagal afferent innervation of the portal-hepatic space. Calcitonin gene-related peptide (CGRP) is a specific marker for dorsal root afferents, and CGRP-immunoreactive fibers are mainly present near the intrahepatic vascular bundles and bile ducts, and in the same extrahepatic compartments that contain vagal afferents. Because of the specific anatomical organization of hepatic nerves, selective hepatic denervation, whether selective for the vagal or sympathetic division, or for efferents and afferents, is nearly impossible. Great caution is therefore necessary when interpreting functional outcomes of so-called specific hepatic denervation studies. PMID:15382018
Background and Purpose Palmitoylethanolamide (PEA) is an endogenous fatty acid amide displaying anti-inflammatory and analgesic actions. To investigate the molecular mechanism responsible for these effects, the ability of PEA and of pain-inducing stimuli such as capsaicin (CAP) or bradykinin (BK) to influence intracellular calcium concentrations ([Ca2+]i) in peripheral sensory neurons, has been assessed in the present study. The potential involvement of the transcription factor PPAR? and of TRPV1 channels in PEA-induced effects was also studied. Experimental Approach [Ca2+]i was evaluated by single-cell microfluorimetry in differentiated F11 cells. Activation of TRPV1 channels was assessed by imaging and patch-clamp techniques in CHO cells transiently-transfected with rat TRPV1 cDNA. Key Results In F11 cells, PEA (1–30 ?M) dose-dependently increased [Ca2+]i. The TRPV1 antagonists capsazepine (1 ?M) and SB-366791 (1 ?M), as well as the PPAR? antagonist GW-6471 (10 ?M), inhibited PEA-induced [Ca2+]i increase; blockers of cannabinoid receptors were ineffective. PEA activated TRPV1 channels heterologously expressed in CHO cells; this effect appeared to be mediated at least in part by PPAR?. When compared with CAP, PEA showed similar potency and lower efficacy, and caused stronger TRPV1 currents desensitization. Sub-effective PEA concentrations, closer to those found in vivo, counteracted CAP- and BK-induced [Ca2+]i transients, as well as CAP-induced TRPV1 activation. Conclusions and Implications Activation of PPAR? and TRPV1 channels, rather than of cannabinoid receptors, largely mediate PEA-induced [Ca2+]i transients in sensory neurons. Differential TRPV1 activation and desensitization by CAP and PEA might contribute to their distinct pharmacological profile, possibly translating into potentially relevant clinical differences. PMID:23083124
Ambrosino, Paolo; Soldovieri, Maria Virginia; Russo, Claudio; Taglialatela, Maurizio
Mitochondrial dysfunction and subsequent oxidative stress has been reported for a variety of cell types in inflammatory diseases. Given the abundance of mitochondria at the peripheral terminals of sensory nerves and the sensitivity of transient receptor potential (TRP) ankyrin 1 (A1) and TRP vanilloid 1 (V1) to reactive oxygen species (ROS) and their downstream products of lipid peroxidation, we investigated the effect of nerve terminal mitochondrial dysfunction on airway sensory nerve excitability. Here we show that mitochondrial dysfunction evoked by acute treatment with antimycin A (mitochondrial complex III Qi site inhibitor) preferentially activated TRPA1-expressing “nociceptor-like” mouse bronchopulmonary C-fibers. Action potential discharge was reduced by the TRPA1 antagonist HC-030031. Inhibition of TRPV1 further reduced C-fiber activation. In mouse dissociated vagal neurons, antimycin A induced Ca2+ influx that was significantly reduced by pharmacological inhibition or genetic knockout of either TRPA1 or TRPV1. Inhibition of both TRPA1 and TRPV1 was required to abolish antimycin A-induced Ca2+ influx in vagal neurons. Using an HEK293 cell expression system, antimycin A induced concentration-dependent activation of both hTRPA1 and hTRPV1 but failed to activate nontransfected cells. Myxothiazol (complex III Qo site inhibitor) inhibited antimycin A-induced TRPA1 activation, as did the reducing agent dithiothreitol. Scavenging of both superoxide and hydrogen peroxide inhibited TRPA1 activation following mitochondrial modulation. In conclusion, we present evidence that acute mitochondrial dysfunction activates airway sensory nerves preferentially via TRPA1 through the actions of mitochondrially-derived ROS. This represents a novel mechanism by which inflammation may be transduced into nociceptive electrical signaling. PMID:23444014
Nesuashvili, Lika; Hadley, Stephen H.; Bahia, Parmvir K.
The effects of extreme cold on sensory nerves are discussed and a clinical application of these effects is proposed. The structural changes observed following the freezing of sensory nerves in the rat are described and correlated with the clinical results in patients with chronic facial pain treated by cryogenic peripheral nerve blockade. It is suggested that this technique offers features which are not shown by any other method for interrupting peripheral pain pathways and provides a useful alternative to existing methods of treatment for chronic pain. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 Fig. 5 Fig. 6 Fig. 7 PMID:7396346
The goal of this study was to determine the contribution of the distal nerve sheath to sensory protection. Following tibial nerve transection, rats were assigned to one of the following groups: (1) saphenous-to-tibial nerve neurorrhaphy; (2) saphenous-to-gastrocnemius neurotization; (3) unprotected controls (tibial nerve transection); or (4) immediate common peroneal-to-tibial nerve neurorrhaphy. After a 6-month denervation period and motor reinnervation, ultrastructural, histologic, and morphometric analyses were performed on the distal tibial nerve and gastrocnemius muscle cross-sections. Sensory axons neurotized to muscle maintain existing muscle integrity, as demonstrated by less fibrosis, collagenization, and fat deposition, more than unprotected muscle, and preserve the distribution pattern of fast twitch fibers. However, neurorrhaphy of the sensory nerve to the distal tibial nerve (involving the distal nerve sheath) improves existing endoneurial sheath structure, demonstrated by reduced collagen, and enhances regeneration, shown by improved axon-to-Schwann cell coupling and increased axon area. The authors conclude that sensory protection of muscle does not require the distal nerve sheath, but that preservation of the distal sheath may contribute to enhanced nerve regeneration. PMID:15672322
Veltri, Karen; Kwiecien, Jacek M; Minet, Wyatt; Fahnestock, Margaret; Bain, James R
This study reported preliminary clinical experience of using decelluarised nerve allograft material for repair of digital nerve defect in five hand injury patients. From October 2009 to July 2010, five patients with traumatic nerve defect were treated with nerve repair using AxoGen® nerve allograft (AxoGen Inc, Alachua, FL) in California Hospital Medical Center. All patients were followed at least for 12 months, and sensory recovery and signs of infection or rejection were documented by a hand therapist. Average two-point discrimination was 6 mm, and average Semmes-Weinstein Monofilaments test was 4.31. No wound infections or signs of rejections were observed at wound site. All patients reported sensory improvement during the follow-up period after operation. It is believed that decellularised nerve allografts may provide a readily available option for repair of segmental nerve defect. PMID:23848418
Guo, Yang; Chen, Gary; Tian, Guanglei; Tapia, Carla
AIM: Cardiovascular autonomic and peripheral sensory neuropathy is a known complication of chronic alcoholic and non-alcoholic liver diseases. We aimed to assess the prevalence and risk factors for peripheral sensory nerve and autonomic dysfunction using sensitive methods in patients with primary biliary cirrhosis (PBC). METHODS: Twenty-four AMA M2 positive female patients with clinical, biochemical and histological evidence of PBC and
Katalin Keresztes; Ildikó Istenes; Aniko Folhoffer; Peter L Lakatos; Andrea Horvath; Timea Csak; Peter Varga; Peter Kempler; Ferenc Szalay; Lakatos PL
Leptin, the primary white adipose tissue (WAT) adipokine, is thought to convey lipid reserve information to the brain via the circulation. Because WAT responds to environmental/internal signals in a fat pad-specific (FPS) manner, systemic signals such as leptin would fail to communicate such distinctive information. Saturation of brain leptin transport systems also would fail to convey increased lipid levels beyond that point. WAT possesses sensory innervation exemplified by proven sensory-associated peptides in nerves within the tissue and by viral sensory nerve-specific transneuronal tract tracer, H129 strain of herpes simplex virus 1 labeling of dorsal root ganglia (DRG) pseudounipolar neurons, spinal cord and central sensory circuits. Leptin as a paracrine factor activating WAT sensory innervation could supply the brain with FPS information. Therefore, we tested for and found the presence of the long form of the leptin receptor (Ob-Rb) on DRG pseudounipolar neurons immunohistochemically labeled after injections of Fluorogold, a retrograde tract tracer, into inguinal WAT (IWAT). Intra-IWAT leptin injections (300 ng) significantly elevated IWAT nerve spike rate within 5 min and persisted for at least 30 min. Intra-IWAT leptin injections also induced significant c-Fos immunoreactivity (ir), indicating neural activation across DRG pseudounipolar sensory neurons labeled with Fluorogold IWAT injections. Intraperitoneal leptin injection did not increase c-Fos-ir in DRG or the arcuate nucleus, nor did it increase arcuate signal transducer and activator of transcription 3 phosphorylation-ir. Collectively, these results strongly suggest that endogenous leptin secreted from white adipocytes functions as a paracrine factor to activate spinal sensory nerves innervating the tissue. PMID:23612999
Murphy, Keegan T.; Schwartz, Gary J.; Nguyen, Ngoc Ly T.; Mendez, Jennifer M.; Ryu, Vitaly
An examination of the pattern of outflow of radioactivity in sciatic nerves was made at times from 1 to 82 days in the rat and up to 132 days in the cat after injecting the L5 and L7 dorsal root ganglia, respectively, with 3H-leucine. Slow waves moving at a rate of 1-2 mm\\/day were looked for on the basis of
D. P. Stromska; S. Ochs
Guillain-Barré syndrome is divided into acute inflammatory demyelinating polyneuropathy (AIDP) and acute motor axonal neuropathy (AMAN) based on motor nerve conduction studies. We investigated whether sensory nerve conduction studies contribute to the electrodiagnosis of AIDP and AMAN. In consecutive 59 patients with AIDP (n = 26) or AMAN (n = 33), results of sensory nerve conduction studies in the median,
Satoshi Kuwabara; Kazue Ogawara; Sonoko Misawa; Keiko Mizobuchi; Jia-Ying Sung; Yukiko Kitano; Masahiro Mori; Takamichi Hattori
Skeletal muscle atrophy occurs after denervation. The present study dissected the rat left ventral root and dorsal root at L4-6 or the sciatic nerve to establish a model of simple motor nerve injury, sensory nerve injury or mixed nerve injury. Results showed that with prolonged denervation time, rats with simple motor nerve injury, sensory nerve injury or mixed nerve injury exhibited abnormal behavior, reduced wet weight of the left gastrocnemius muscle, decreased diameter and cross-sectional area and altered ultrastructure of muscle cells, as well as decreased cross-sectional area and increased gray scale of the gastrocnemius muscle motor end plate. Moreover, at the same time point, the pathological changes were most severe in mixed nerve injury, followed by simple motor nerve injury, and the changes in simple sensory nerve injury were the mildest. These findings indicate that normal skeletal muscle morphology is maintained by intact innervation. Motor nerve injury resulted in larger damage to skeletal muscle and more severe atrophy than sensory nerve injury. Thus, reconstruction of motor nerves should be considered first in the clinical treatment of skeletal muscle atrophy caused by denervation. PMID:25337102
Zhao, Lei; Lv, Guangming; Jiang, Shengyang; Yan, Zhiqiang; Sun, Junming; Wang, Ling; Jiang, Donglin
While it is well established that nerve growth factor is growth promoting for sensory neurons in culture, it is unclear whether it serves such a function in vivo. In fact, our previous studies led to the hypothesis that nerve growth factor could actually impair axonal regeneration by reducing the neuronal cell body response to injury. In the present study, the consequence of continuous intrathecal infusion of nerve growth factor on regeneration of sensory neurons was examined in rats given a bilateral sciatic nerve crush. Rats received nerve growth factor (125 ng/h) as a continuous infusion into the subarachnoid space of the lumbar spinal cord via an osmotic minipump (Alzet); controls received cytochrome C. At seven or 10 days, the pump was removed and L4 or L5 dorsal root ganglion exposed and injected with 50 microCi of (3H)leucine. Animals were killed 24 h later, the sciatic nerves removed, cut into 3 mm segments and the radioactivity in each segment determined by liquid scintillation spectrophotometry. Maximal regeneration distances (determined from the front of the resultant transport curves) were similarly reduced (by approximately 6 mm) in nerve growth factor-infused compared to cytochrome C-infused rats. Thus, regeneration rates (determined between eight and 11 days) were unaltered by nerve growth factor infusion; regeneration rates from cytochrome C-infused and nerve growth factor-infused animals were 2.8 mm/day and 3.1 mm/day, respectively. However, nerve growth factor significantly (P < 0.005) increased the delay to onset for regeneration by two days. Taken together, the present study demonstrates that nerve growth factor delays the onset of regeneration without affecting the rate of regeneration. The results implicate the involvement of at least two signals in the regulation of axonal regeneration in dorsal root ganglion neurons. It is suggested that the loss of nerve growth factor serves as an early, induction signal regulating the onset of regeneration and that a second, unidentified signal independently serves to maintain regeneration. PMID:9027875
Gold, B G
Skin biopsy is a valuable diagnostic tool for small-fiber-predominant neuropathy by the quantification of intra-epidermal nerve fiber density (IENFD). It has the unique advantage of being a minimally invasive procedure with the potential for longitudinal evaluation of both sensory and autonomic fibers. Unmyelinated small fibers are not otherwise quantified objectively with such a level of sensitivity as has been reported with IENFD. Recent advances include an expansion of the skin punch biopsy technique to evaluate larger myelinated fibers and mechanoreceptors, and recent work has also focused on additional methods of quantifying dermal fibers and densely innervated autonomic structures. This review discusses current work using skin biopsy for the pathologic analysis of peripheral nerve fibers in neuropathy of various causes as well as its use in clinical trials. PMID:23250768
Myers, M. Iliza; Peltier, Amanda C.
Functional recovery is usually poor following peripheral nerve injury when reinnervation is delayed. Early innervation by sensory nerve has been indicated to prevent atrophy of the denervated muscle. It is hypothesized that early protection with sensory axons is adequate to improve functional recovery of skeletal muscle following prolonged denervation of mixed nerve injury. In this study, four groups of rats received surgical denervation of the tibial nerve. The proximal and distal stumps of the tibial nerve were ligated in all animals except for those in the immediate repair group. The experimental groups underwent denervation with nerve protection of peroneal nerve (mixed protection) or sural nerve (sensory protection). The experimental and unprotected groups had a stage II surgery in which the trimmed proximal and distal tibial nerve stumps were sutured together. After 3 months of recovery, electrophysiological, histological and morphometric parameters were assessed. It was detected that the significant muscle atrophy and a good preserved structure of the muscle were observed in the unprotected and protective experimental groups, respectively. Significantly fewer numbers of regenerated myelinated axons were observed in the sensory-protected group. Enhanced recovery in the mixed protection group was indicated by the results of the muscle contraction force tests, regenerated myelinated fiber, and the results of the histological analysis. Our results suggest that early axons protection by mixed nerve may complement sensory axons which are required for promoting functional recovery of the denervated muscle natively innervated by mixed nerve. PMID:24244555
Li, Qing Tian; Zhang, Pei Xun; Yin, Xiao Feng; Han, Na; Kou, Yu Hui; Deng, Jiu Xu; Jiang, Bao Guo
F-spondin, an extracellular matrix protein, is present in periph- eral nerve during embryonic development, but its amount di- minishes by birth. Axotomy of adult rat sciatic nerve, however, causes a massive upregulation of both F-spondin mRNA and protein distal to the lesion. F-spondin in the distal stump of axotomized nerve promotes neurite outgrowth of sensory neu-
Tal Burstyn-Cohen; Ayala Frumkin; Yi-Tian Xu; Steven S. Scherer; Avihu Klar
We studied the effect of infrared (IR) stimulation on rat sensory neurons. Primary sensory neurons were prepared by enzymatic dissociation of the inferior (or "nodose") ganglia from the vagus nerves of rats. The 1.85-?m output of a diode laser, delivered through a 200-?m silica fiber, was used for photostimulation. Nodose neurons express the vanilloid receptor, TRPV1, which is a non-selective cation channel that opens in response to significant temperature jumps above 37 C. Opening TRPV1 channels allows entry of cations, including calcium (Ca 2+), into the cell to cause membrane depolarization. Therefore, to monitor TRPV1 activation consequent to photostimulation, we used fura-2, a fluorescent Ca 2+ indicator, to monitor the rise in intracellular Ca 2+ concentration ([Ca 2+]i). Brief trains of 2-msec IR pulses activated TRPV1 rapidly and reversibly, as evidenced by transient rises in [Ca 2+]i (referred to as Ca 2+ transients). Consistent with the Ca 2+ transients arising from influx of Ca 2+, identical photostimulation failed to evoke Ca 2+ responses in the absence of extracellular Ca 2+. Furthermore, the photo-induced Ca 2+ signals were abolished by capsazepine, a specific blocker of TRPV1, indicating that the responses were indeed mediated by TRPV1. We discuss the feasibility of using focal IR stimulation to probe neuronal circuit properties in intact neural tissue, and compare IR stimulation with another photostimulation technique-focal photolytic release of "caged" molecules.
Rhee, Albert Y.; Li, Gong; Wells, Jonathon; Kao, Joseph P. Y.
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
Gibson, Peter G.; Birring, Surinder S.
The aim of this study was to evaluate the degeneration and regeneration of a sensory nerve and a motor nerve at the histological level after a crush injury. Twenty-five female Wistar rats had their mental nerve and the buccal branch of their facial nerve compressed unilaterally against a glass rod for 30s. Specimens of the compressed nerves and the corresponding control nerves were dissected at 3, 7, and 19 days after surgery. Nerve cross-sections were stained with osmium tetroxide and toluidine blue and analysed using two-dimensional stereology. We found differences between the two nerves both in the normal anatomy and in the regenerative pattern. The mental nerve had a larger cross-sectional area including all tissue components. The mental nerve had a larger volume fraction of myelinated axons and a correspondingly smaller volume fraction of endoneurium. No differences were observed in the degenerative pattern; however, at day 19 the buccal branch had regenerated to the normal number of axons, whereas the mental nerve had only regained 50% of the normal number of axons. We conclude that the regenerative process is faster and/or more complete in the facial nerve (motor function) than it is in the mental nerve (somatosensory function). PMID:23731889
Barghash, Z; Larsen, J O; Al-Bishri, A; Kahnberg, K-E
Peripheral neural mechanisms underlying the sensations of irritation, discomfort, and itch accompanying the eye allergic response have not been hitherto analyzed. We explored this question recording the changes in the electrical activity of corneoconjunctival sensory nerve fibers of the guinea pig after an ocular allergic challenge. Sensitization was produced by i.p. ovalbumin followed by repeated application in the eye of 10% ovalbumin on days 14 to 18. Blinking and tearing rate were measured. Spontaneous and stimulus-evoked (mechanical, thermal, chemical) impulse activity was recorded from mechanonociceptor, polymodal nociceptor and cold corneoscleral sensory afferent fibers. After a single (day 14) or repeated daily exposures to the allergen during the following 3 to 4days, tearing and blinking rate increased significantly. Also, sensitization was observed in mechanonociceptors (transient reduction of mechanical threshold only on day 14) and in polymodal nociceptors (sustained enhancement of the impulse response to acidic stimulation). In contrast, cold thermoreceptors showed a significant decrease in basal ongoing activity and in the response to cooling. Treatment with the TRPV1 and TRPA1 blockers capsazepine and HC-030031 reversed the augmented blinking. Only capsazepine attenuated tearing rate increase and sensitization of the polymodal nociceptors response to CO2. Capsazepine also prevented the decrease in cold thermoreceptor activity caused by the allergic challenge. We conclude that changes in nerve impulse activity accompanying the ocular allergic response, primarily mediated by activation of nociceptor's TRPV1 and to a lesser degree by activation of TRPA1 channels, explain the eye discomfort sensations accompanying allergic episodes. PMID:23867735
Acosta, M Carmen; Luna, Carolina; Quirce, Susana; Belmonte, Carlos; Gallar, Juana
Prolonged muscle denervation results in poor functional recovery after nerve repair. The possible protective effect of temporary sensory innervation of denervated muscle, prior to motor nerve repair, has been examined in the rat. Soleus and gastrocnemius muscles were denervated by cutting the tibial nerve, and the peroneal nerve was then sutured to the transected distal tibial nerve stump either immediately or after two, four or six months. In half of the animals with delayed repair, the saphenous (sensory) nerve was temporarily attached to the distal nerve stump. Muscles were evaluated three months after the peroneal-to-tibial union, and were compared with each other, with unoperated control muscles and with untreated denervated muscles. After four to six months of sensory "protection", gastrocnemius muscles weighed significantly more than unprotected muscles, and both gastrocnemius and soleus muscles exhibited better preservation of their structure, with less fiber atrophy and connective tissue hyperplasia. The maximum compound action potentials were significantly larger in gastrocnemius and soleus muscles following sensory protection, irrespective of the delay in motor nerve union. Isometric force, although less than in control animals and in those with immediate nerve repair, remained reasonably constant after sensory protection, while in unprotected muscles there was a progressive and significant decline as the period of denervation lengthened. We interpret these results as showing that, although incapable of forming excitable neuromuscular junctions, sensory nerves can nevertheless exert powerful trophic effects on denervated muscle fibers. We propose that these findings indicate a useful strategy for improving the outcome of peripheral nerve surgery. PMID:11246164
Bain, J R; Veltri, K L; Chamberlain, D; Fahnestock, M
Nerve conduction studies and analysis of the sensory action potential (110 nerves investigated) demons treated abnormalities in 15 to 20 patients with rheumatoid arthritis. It is concluded that moderate, often subclinical peripheral neuropathy is a common complication in rheumatoid arthritis. PMID:184511
Frenay, J; Goor, C; Kievitis, J H; Endtz, J
Background Skeletal muscle structure and function are dependent on intact Richard Butler, Ph.D. innervation. Prolonged muscle denervation results in irreversible muscle fiber James R. Bain, M.D. atrophy, connective tissue hyperplasia, and deterioration of muscle spindles, Margaret Fahnestock, Ph.D. specialized sensory receptors necessary for proper skeletal muscle function. The protective effect of temporary sensory innervation on denervated muscle, before motor nerve repair, has been shown in the rat. Sensory-protected muscles exhibit less fiber atrophy and connective tissue hyperplasia and maintain greater functional capacity than denervated muscles. The purpose of this study was to determine whether temporary sensory innervation also protects muscle spindles from degeneration. Methods Rat tibial nerve was transected and repaired with either the saphenous or the original transected nerve. Negative controls remained denervated. After 3 to 6 months, the electrophysiologic response of the nerve to stretch in the rat gastrocnemius muscle was measured (n = 3 per group). After the animals were euthanized, the gastrocnemius muscle was removed, sectioned, stained, and examined for spindle number (n = 3 per group) and morphology (one rat per group). Immunohistochemical assessment of muscle spindle innervation was examined in four additional animals. Results Significant deterioration of muscle spindles was seen in denervated muscle, whereas in muscle reinnervated with the tibial or the saphenous nerve, spindle number and morphology were improved. Histologic and functional evidence of spindle reinnervation by the sensory nerve was obtained. Conclusion These findings add to the known means by which motor or sensory nerves exert protective effects on denervated muscle, and further promote the use of sensory protection for improving the outcome after peripheral nerve injury. PMID:19952642
Elsohemy, Amal; Butler, Richard; Bain, James R.; Fahnestock, Margaret
Histochemical staining for carbonic anhydrase and cholinesterase (CE) activities was used to analyze sensory and motor axon regeneration, respectively, during neuroma formation in transected and tube-encapsulated peripheral nerves. Median-ulnar and sciatic nerves in the rodent model permitted testing whether a 4 cm greater distance of the motor neuron soma from axotomy site or intrinsic differences between motor and sensory neurons influenced regeneration and neuroma formation 10, 30, and 90 days later. Ventral root radiculotomy confirmed that CE-stained axons were 97% alpha motor axons. Distance significantly delayed axon regeneration. When distance was negligible, sensory axons grew out sooner than motor axons, but motor axons regenerated to a greater quantity. These results indicate regeneration differences between axon subtypes and suggest more extensive branching of motor axons within the neuroma. Thus, both distance from injury site to soma and inherent motor and sensory differences should be considered in peripheral nerve repair strategies.
Macias, M. Y.; Lehman, C. T.; Sanger, J. R.; Riley, D. A.
A prior peripheral nerve injury in vivo, promotes a rapid elongated mode of sensory neurons neurite regrowth in vitro. This in vitro model of conditioned axotomy allows analysis of the cellular and molecular mechanisms leading to an improved neurite re-growth. Our differential interference contrast microscopy and immunocytochemistry results show that conditioned axotomy, induced by sciatic nerve injury, did not increase somatic size of adult lumbar sensory neurons from mice dorsal root ganglia sensory neurons but promoted the appearance of larger neurites and growth cones. Using atomic force microscopy on live neurons, we investigated whether membrane mechanical properties of growth cones of axotomized neurons were modified following sciatic nerve injury. Our data revealed that neurons having a regenerative growth were characterized by softer growth cones, compared to control neurons. The increase of the growth cone membrane elasticity suggests a modification in the ratio and the inner framework of the main structural proteins. PMID:23418549
Szabo, Vivien; Vegh, Attila-Gergely; Lucas, Olivier; Cloitre, Thierry; Scamps, Frederique; Gergely, Csilla
Thousands of odors are sensed and discriminated by G protein-coupled odorant receptors (ORs) expressed in olfactory sensory neurons (OSNs). G protein-coupled receptor kinases (GRKs) may have a role in desensitization of ORs. However, whether ORs are susceptible to agonist-dependent desensitization and whether GRKs affect odorant responsiveness of OSNs are currently unknown. Here we show that GRK3 attenuated the agonist responsiveness of a specific mouse odorant receptor for eugenol (mOR-EG) upon agonist pretreatment in HEK293 cells, but GRK3 did not affect the response amplitude or the recovery kinetics upon repeated agonist stimulation. We performed electrophysiological recordings of single OSNs which expressed mOR-EG and green fluorescent protein (GFP) in the presence or absence of GRK3. The kinetics and amplitude of agonist responsiveness of individual GFP-labeled mOR-EG neurons were not significantly affected by the absence of GRK3. These results indicate that the role of GRK3 in attenuating ORs responsiveness in OSNs may have been overestimated. PMID:25313015
Kato, Aya; Reisert, Johannes; Ihara, Sayoko; Yoshikawa, Keiichi; Touhara, Kazushige
Over the past ten years there has been an increasing interest in the use of lasers for neurosurgical and neurological procedures. Novel recent applications range from neurosurgical procedures such as dorsal root entry zone lesions made with argon and carbon dioxide microsurgical lasers to pain relief by low power laser irradiation of the appropriate painful nerve or affected region1 '2 However, despite the widespread clinical applications of laser light, very little is known about the photobiological interactions between laser light and nervous tissue. The present studies were designed to evaluate the effects of pulsed Nd:YAG laser light on neural impulse conduction and axoplasmic transport in sensory nerves in rats and cats. Our data indicate that Q-switched Nd:YAG laser irradiation can induce a preferential impairment of (1) the synaptic effects of small afferent fibers on dorsal horn cells in the spinal cord and of (2) small slow conducting sensory nerve fibers in dorsal roots and peripheral nerves. These results imply that laser light might have selective effects on impulse conduction in slow conducting sensory nerve fibers. In agreement with our elecirophysiological observations recent histological data from our laboratory show, that axonal transport of the enzyme horseradish peroxidase is selectively impaired in small sensory nerve fibers. In summary these data indicate, that Q-switched Nd:YAG laser irradiation can selectively impair neural conduction and axoplasmic transport in small sensory nerve fibers as compared to fast conducting fibers. A selective influence of laser irradiation on slow conducting fibers could have important clinical applications, especially for the treatment of chronic pain.
Wesselmann, Ursula; Rymer, William Z.; Lin, Shien-Fong
High-count microelectrode arrays implanted in peripheral nerves could restore motor function after spinal cord injury or sensory function after limb loss. In this study, we implanted Utah Slanted Electrode Arrays (USEAs) intrafascicularly at the elbow or shoulder in arm nerves of rhesus monkeys (n = 4) under isoflurane anesthesia. Input-output curves indicated that pulse-width-modulated single-electrode stimulation in each arm nerve could recruit single muscles with little or no recruitment of other muscles. Stimulus trains evoked specific, natural, hand movements, which could be combined via multielectrode stimulation to elicit coordinated power or pinch grasp. Stimulation also elicited short-latency evoked potentials (EPs) in primary somatosensory cortex, which might be used to provide sensory feedback from a prosthetic limb. These results demonstrate a high-resolution, high-channel-count interface to the peripheral nervous system for restoring hand function after neural injury or disruption or for examining nerve structure. PMID:23076108
Ledbetter, Noah M; Ethier, Christian; Oby, Emily R; Hiatt, Scott D; Wilder, Andrew M; Ko, Jason H; Agnew, Sonya P; Miller, Lee E; Clark, Gregory A
The purpose of this randomized, double-blind study was to determine the effect of a helium-neon (He-Ne) laser on latency of peripheral sensory nerve. Forty healthy subjects with no history of right upper extremity pathological conditions were assigned to either a Laser or a Placebo Group. Six 1-cm2 blocks along a 12-cm segment of the subjects' right superficial radial nerve received 20-second applications of either the He-Ne laser or a placebo. We assessed differences between pretest and posttest latencies with t tests for correlated and independent samples. The Laser Group showed a statistically significant increase in latency that corresponded to a decrease in sensory nerve conduction velocity. Short-duration He-Ne laser application significantly increased the distal latency of the superficial radial nerve. This finding provides information about the mechanism of the reported pain-relieving effect of the He-Ne laser.
Snyder-Mackler, L.; Bork, C.E.
The neurotransmitters\\/modulators involved in the interaction between pulmonary neuroepithelial bodies (NEBs) and the va- gal sensory component of their innervation have not yet been elucidated. Because P2X 3 purinoreceptors are known to be strongly expressed in peripheral sensory neurons, the aim of the present study was to examine the localization of nerve endings expressing P2X 3 purinoreceptors in the rat
Inge Brouns; Dirk Adriaensen; Geoff Burnstock; Jean-Pierre Timmermans
Several factors have been proposed to account for poor motor recovery after prolonged denervation, including motor neuron cell death and incomplete or poor regeneration of motor fibers into the muscle. Both may result from failure of the muscle and the distal motor nerve stump to continue expression of neurotrophic factors following delayed muscle reinnervation. This study investigated whether regenerating motor or sensory axons modulate distal nerve neurotrophic factor expression. We found that transected distal tibial nerve up-regulated brain-derived neurotrophic factor (BDNF) and glial cell line-derived neurotrophic factor (GDNF) mRNA, down-regulated neuro-trophin-3 and ciliary neurotrophic factor mRNA, and that although these levels returned to normal with regeneration, the chronically denervated distal nerve stump continued to express these neurotrophic factors for at least 6 months following injury. A sensory nerve (the cutaneous saphenous nerve) sutured to distal tibial nerve lowered injury-induced BDNF and GDNF mRNA levels in distal stump, but repair with a mixed nerve (peroneal, containing muscle and cutaneous axons) was more effective. Repair with sensory or mixed nerves did not affect nerve growth factor or neurotrophin-3 expression. Thus, distal nerve contributed to a neurotrophic environment for nerve regeneration for at least 6 months, and sensory nerve repair helped normalize distal nerve neurotrophic factor mRNA expression following denervation. Furthermore, as BDNF and GDNF levels in distal stump increased following denervation and returned to control levels following reinnervation, their levels serve as markers for the status of regeneration by either motor or sensory nerve. PMID:18194437
Michalski, B.; Bain, J. R.; Fahnestock, M.
Several factors have been proposed to account for poor motor recovery after prolonged denervation, including motor neuron cell death and incomplete or poor regeneration of motor fibers into the muscle. Both may result from failure of the muscle and the distal motor nerve stump to continue expression of neurotrophic factors following delayed muscle reinnervation. This study investigated whether regenerating motor or sensory axons modulate distal nerve neurotrophic factor expression. We found that transected distal tibial nerve up-regulated brain-derived neurotrophic factor (BDNF) and glial cell line-derived neurotrophic factor (GDNF) mRNA, down-regulated neurotrophin-3 and ciliary neurotrophic factor mRNA, and that although these levels returned to normal with regeneration, the chronically denervated distal nerve stump continued to express these neurotrophic factors for at least 6 months following injury. A sensory nerve (the cutaneous saphenous nerve) sutured to distal tibial nerve lowered injury-induced BDNF and GDNF mRNA levels in distal stump, but repair with a mixed nerve (peroneal, containing muscle and cutaneous axons) was more effective. Repair with sensory or mixed nerves did not affect nerve growth factor or neurotrophin-3 expression. Thus, distal nerve contributed to a neurotrophic environment for nerve regeneration for at least 6 months, and sensory nerve repair helped normalize distal nerve neurotrophic factor mRNA expression following denervation. Furthermore, as BDNF and GDNF levels in distal stump increased following denervation and returned to control levels following reinnervation, their levels serve as markers for the status of regeneration by either motor or sensory nerve. PMID:18194437
Michalski, B; Bain, J R; Fahnestock, M
Important physiological functions of neurotrophins (NTs) in airways and lungs are the early development, differentiation and maintenance of peripheral sensory neurons. The main pulmonary sensory innervation is of vagal origin, with several nerve fibre populations that selectively contact complex morphologically well-characterized receptor end-organs, called neuroepithelial bodies (NEBs). NEBs in mouse lungs are innervated by at least two separate myelinated vagal sensory nerve fibre populations, of which the neurochemical coding is suggestive of a mechanosensory function. Since neurotrophin-4 (NT-4) has been especially described to be important for the maintenance of mechanosensory nerve terminals, the present study aimed at investigating the NT-4 dependency of the two myelinated vagal sensory nerve fibre populations innervating mouse pulmonary NEBs. Multiple immunostaining in 21-day-old and adult mouse lungs revealed the expression of the NT-4 receptor TrkB on the two different myelinated vagal sensory nerve fibre populations, i.e., the vesicular glutamate transporter/calbindin-positive and the P2X2/3-positive fibres, which selectively contact pulmonary NEBs. Examination of the effect of the lack of NT-4 on these NEB-related nerve fibre populations, by comparing adult NT-4-/- and wild-type mice, revealed that in NT-4-/- mice the percentage of NEBs contacted by P2X2/3+ is reduced by 75%, while the VGLUT+/CB+ population seemed to be unaffected. This study demonstrated that although mouse pulmonary NEBs are contacted by two distinct TrkB expressing populations of vagal myelinated afferents, only one is distinctly reduced in NT-4 deficient mice, suggesting the involvement of NTs. In view of the growing evidence for the involvement of NTs in neuronal plasticity associated with airway diseases, pulmonary NEBs innervated by NT-sensitive vagal afferents may play a significant role. PMID:20552548
Oztay, Fusun; Brouns, Inge; Pintelon, Isabel; Raab, Marion; Neuhuber, Winfried; Timmermans, Jean-Pierre; Adriaensen, Dirk
We developed a new histochemical method based on endogenous oxidase activity for the detection of cutaneous nerves in guinea-pig lips. After the application of a reaction mixture containing 0.14 mM 3,3'-diaminobenzidine(DAB) and 15 mM nickel ammonium sulfate in Tris-HCl buffer (pH 7.6), many blue-black sensory fibers were observed, i.e., dermal nerve fiber bundles, perifollicular plexuses, Merkel-cell endings, and Meissner-like nerve
A. Kaji; H. Imai; T. Maeda; S. Watanabe
Blood pressure regulation by 5-HT has proven to be a complex story to unravel. The work by Cuesta et al., in this issue of Vascular Pharmacology adds another layer of complexity by providing sound in vivo data that 5-HT, through the 5-HT7 receptor, can inhibit the vasodepressor actions of the sensory nervous system and thereby promote blood pressure maintenance. This interaction of 5-HT with the sensory nervous system is inhibitory, whereas 5-HT is understood to be stimulatory in other systems. Moreover, activation of the 5-HT7 receptor has been linked to both reduction and elevation of blood pressure. These interactions are discussed in this mini-review, as are potential steps forward in understanding the interplay of 5-HT, the sensory nervous system and blood pressure. PMID:25181552
Watts, Stephanie W
Mirror neurons allow us to covertly simulate the sensation and movement of others. If mirror neurons are sensory and motor neurons, why do we not actually feel this simulation- like "mirror-touch synesthetes"? Might afferent sensation normally inhibit mirror representations from reaching consciousness? We and others have reported heightened sensory referral to phantom limbs and temporarily anesthetized arms. These patients, however, had experienced illness or injury of the deafferented limb. In the current study we observe heightened sensory and motor referral to the face after unilateral nerve block for routine dental procedures. We also obtain double-blind, quantitative evidence of heightened sensory referral in healthy participants completing a mirror-touch confusion task after topical anesthetic cream is applied. We suggest that sensory and motor feedback exist in dynamic equilibrium with mirror representations; as feedback is reduced, the brain draws more upon visual information to determine- perhaps in a Bayesian manner- what to feel. PMID:23791606
Case, Laura K; Gosavi, Radhika; Ramachandran, Vilayanur S
The authors have determined that epineurial arterioles of the sciatic nerve are innervated by nonadrenergic, noncholinergic nerves that contribute to the regulation of vasodilation. Using immunohistochemistry, the authors determined that nerves innervating epineurial arterioles contain the neuropeptide calcitonin gene–related peptide (CGRP). Using streptozotocin-induced diabetic rats, the authors demonstrated that CGRP content in sensory nerves innervating epineurial arterioles and vasodilation in response to exogenous CGRP was decreased. In summary, epineurial arterioles of the sciatic nerve are innervated by sensory nerves containing the neuropeptide CGRP. The diabetes-like condition induced by streptozotocin reduces the content of CGRP in these nerves and exogenous CGRPmediated vasodilation. CGRP is likely an important regulator of vascular tone and compromising its function could contribute to nerve ischemia and diabetic neuropathy. PMID:15512786
Coppey, L. J.; Gellett, J. S.; Davidson, E. P.
The authors have determined that epineurial arterioles of the sciatic nerve are innervated by nonadrenergic, noncholinergic nerves that contribute to the regulation of vasodilation. Using immunohistochemistry, the authors determined that nerves innervating epineurial arterioles contain the neuropeptide calcitonin gene-related peptide (CGRP). Using streptozotocin-induced diabetic rats, the authors demonstrated that CGRP content in sensory nerves innervating epineurial arterioles and vasodilation in response to exogenous CGRP was decreased. In summary, epineurial arterioles of the sciatic nerve are innervated by sensory nerves containing the neuropeptide CGRP. The diabetes-like condition induced by streptozotocin reduces the content of CGRP in these nerves and exogenous CGRP-mediated vasodilation. CGRP is likely an important regulator of vascular tone and compromising its function could contribute to nerve ischemia and diabetic neuropathy. PMID:15512786
Yorek, M A; Coppey, L J; Gellett, J S; Davidson, E P
Sensory and social deprivation from the mother and littermates during early life disturbs the development of the central nervous system, but little is known about its effect on the development of the peripheral nervous system. To assess peripheral effects of early isolation, male rat pups were reared artificially in complete social isolation (AR); reared artificially with two same-age conspecifics (AR-Social); or reared by their mothers and with littermates (MR). As adults, the electrophysiological properties of the sensory sural (SU) nerve were recorded. We found that the amplitude and normalized area (with respect to body weight) of the compound action potential (CAP) response provoked by single electrical pulses of graded intensity in the SU nerves of AR animals were shorter than the CAP recorded in SU nerves from MR and AR-Social animals. The slope of the stimulus-response curve of AR SU nerves was smaller than that of the other nerves. The histological characterization of axons in the SU nerves was made and showed that the myelin thickness of axons in AR SU nerves was significant lower (2-7µm) than that of the axons in the other nerves. Furthermore, the area and axon diameter of SU nerves of both AR and AR-Social animals were significant lower than in MR animals. This is the first report to show that maternal and littermate deprivation by AR disturbs the development of the myelination and electrophysiological properties of axons in the SU nerve; the replacement of social cues prevents most of the effects. © 2014 Wiley Periodicals, Inc. Develop Neurobiol 74: 1184-1193, 2014. PMID:24897933
Segura, Bertha; Melo, Angel I; Fleming, Alison S; Mendoza-Garrido, Maria Eugenia; González Del Pliego, Margarita; Aguirre-Benitez, Elsa L; Hernández-Falcón, Jesús; Jiménez-Estrada, Ismael
Summary Ca2+/calmodulin-mediated negative feedback is a prototypical regulatory mechanism for Ca2+ permeable ion channels. In olfactory sensory neurons (OSNs) such regulation on the cyclic nucleotide-gated (CNG) channel is considered a major mechanism of OSN adaptation. To determine the role of Ca2+/calmodulin desensitization of the olfactory CNG channel, we introduced a mutation in the channel subunit CNGB1b in mice that rendered the channel resistant to fast desensitization by Ca2+/calmodulin. Contrary to expectations, mutant OSNs showed normal receptor current adaptation to repeated stimulation. Rather, they displayed slower response termination and consequently, a reduced ability to transmit olfactory information to the olfactory bulb. They also displayed reduced response decline during sustained odorant exposure. These results suggest that Ca2+/calmodulin-mediated CNG channel fast desensitization is less important in regulating the sensitivity to recurring stimulation than previously thought and instead functions primarily to terminate OSN responses. PMID:18466748
Song, Yijun; Cygnar, Katherine D.; Sagdullaev, Botir; Valley, Matthew; Hirsh, Sarah; Stephan, Aaron; Reisert, Johannes; Zhao, Haiqing
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
Zimmermann, Katharina; Hein, Alexander; Hager, Ulrich; Kaczmarek, Jan Stefan; Turnquist, Brian P; Clapham, David E; Reeh, Peter W
Peripheral nerve injury in vivo promotes a regenerative growth in vitro characterized by an improved neurite regrowth. Knowledge of the conditioning injury effects on both morphology and mechanical properties of live sensory neurons could be instrumental to understand the cellular and molecular mechanisms leading to this regenerative growth. In the present study, we use differential interference contrast microscopy, fluorescence microscopy and atomic force microscopy (AFM) to show that conditioned axotomy, induced by sciatic nerve injury, does not increase somatic size of sensory neurons from adult mice lumbar dorsal root ganglia but promotes the appearance of longer and larger neurites and growth cones. AFM on live neurons is also employed to investigate changes in morphology and membrane mechanical properties of somas of conditioned neurons following sciatic nerve injury. Mechanical analysis of the soma allows distinguishing neurons having a regenerative growth from control ones, although they show similar shapes and sizes.
Benzina, Ouafa; Szabo, Vivien; Lucas, Olivier; Saab, Marie-belle; Cloitre, Thierry; Scamps, Frédérique; Gergely, Csilla; Martin, Marta
The neuralb pathways that relay information from cutaneous receptors to the cortex provide the somatic sensory information needed for cortical function. The last sensory relay neurons in this pathway have cell bodies in the thalamus and axons that synapse on neurons in the somatosensory cortex. After cortical lesions that damage mature thalamocortical fibers in the somatosensory cortex, we have attempted to reestablish somatosensory cortical function by grafting embryonic neocortical cells into the lesioned area. Such grafts survive in adult host animals but are not innervated by thalamic neurons, and consequently the grafted neurons show little if any spontaneous activity and no responses to cutaneous stimuli. We have reported that transection of peripheral sensory nerves prior to grafting ``conditions'' or ``primes'' the thalamic neurons in the ventrobasal complex so that they extend axons into grafts subsequently placed in the cortical domain of the cut nerve. In this report we present evidence that the ingrowth of ventrobasal fibers leads to graft neurons that become functionally integrated into the sensory circuitry of the host brain. Specifically, the conditioning lesions made prior to grafting produce graft neurons that are spontaneously active and can be driven by natural activation of cutaneous receptors or electrical stimulation of the transected nerve after it regenerates. Furthermore, oxidative metabolism in these grafts reaches levels that are comparable to normal cortex, whereas without prior nerve cut, oxidative metabolism is abnormally low in neocortical grafts. We conclude that damage to the sensory periphery transsynaptically stimulates reorganization of sensory pathways through mechanisms that include axonal elongation and functional synaptogenesis.
Ebner, Ford F.; Erzurumlu, Reha S.; Lee, Stefan M.
Two dermatologic patients displaying peripheral and central nerve damage, respectively, are described. Cutaneous nerve fibers in both patients were studied in skin biopsy specimens taken from neuropathic areas and from the contralateral side, immunocytochemistry being applied to a pan-neuronal marker, a protein gene-product (PGP 9.5). One of the patients, suffering from compression of the ulnar nerve, had dyshidrotic eczema of
Joanna Wallengren; Eva Tegner; Frank Sundler
We have recently shown in rat that daily manual stimulation (MS) of vibrissal muscles promotes recovery of whisking and reduces polyinnervation of muscle fibers following repair of the facial nerve (facial-facial anastomosis, FFA). Here, we examined whether these positive effects were: (1) correlated with alterations of the afferent connections of regenerated facial motoneurons, and (2) whether they were achieved by enhanced sensory input through the intact trigeminal nerve. First, we quantified the extent of total synaptic input to motoneurons in the facial nucleus using synaptophysin immunocytochemistry following FFA with and without subsequent MS. We found that, without MS, this input was reduced compared to intact animals. The number of synaptophysin-positive terminals returned to normal values following MS. Thus, MS appears to counteract the deafferentation of regenerated facial motoneurons. Second, we performed FFA and, in addition, eliminated the trigeminal sensory input to facial motoneurons by extirpation of the ipsilateral infraorbital nerve (IONex). In this paradigm, without MS, vibrissal motor performance and pattern of end-plate reinnervation were as aberrant as after FFA without MS. MS did not influence the reinnervation pattern after IONex and functional recovery was even worse than after IONex without MS. Thus, when the sensory system is intact, MS restores normal vibrissal function and reduces the degree of polyinnervation. When afferent inputs are abolished, these effects are eliminated or even reversed. We conclude that rehabilitation strategies must be carefully designed to take into account the extent of motor and/or sensory damage. PMID:18381213
Pavlov, Stoyan P; Grosheva, Maria; Streppel, Michael; Guntinas-Lichius, Orlando; Irintchev, Andrey; Skouras, Emmanouil; Angelova, Srebrina K; Kuerten, Stefanie; Sinis, Nektarios; Dunlop, Sarah A; Angelov, Doychin N
Neuroimmune interactions play a critical role in the pathogenesis of asthma. Symptoms like wheezing and cough have been attributed to neural dysregulation, whereas sensitization and the induction of allergic inflammation have been linked with the activity of dendritic cells. Neuropeptides were previously shown to control dendritic cell function in vitro, suggesting interactions between dendritic cells and sensory nerves. Here we characterized the anatomical basis of the interactions between dendritic cells and nerves in the airways of mice and monitored the changes during allergic inflammation. Airway microdissection, whole-mount immunohistology, and confocal microscopy were used for the three-dimensional quantitative mapping of airway nerves and dendritic cells along the main axial pathway of nonsensitized versus ovalbumin-sensitized and -challenged CD11c-enhanced yellow fluorescent protein (CD11c-EYFP) transgenic mice. CD11c-EYFP-positive airway mucosal dendritic cells were contacted by calcitonin gene-related peptide-immunoreactive sensory fibers and their co-localization increased in allergic inflammation. Moreover, protein gene product 9.5-positive neuroepithelial bodies and airway ganglia were associated with dendritic cells. In human airways, human leukocyte antigen DR-positive mucosal dendritic cells were found in the close proximity of sensory nerves and neuroepithelial cells. These results provide morphologic evidence of the interactions between dendritic cells and the neural network of the airways at multiple anatomical sites. PMID:17600312
Veres, Tibor Z; Rochlitzer, Sabine; Shevchenko, Marina; Fuchs, Barbara; Prenzler, Frauke; Nassenstein, Christina; Fischer, Axel; Welker, Lutz; Holz, Olaf; Müller, Meike; Krug, Norbert; Braun, Armin
The peroneal nerve anatomy of the rabbit distal hindlimb is similar to humans, but reports of distal peroneal nerve conduction studies were not identified with a literature search. Distal sensorimotor recordings may be useful for studying rabbit models of length-dependent peripheral neuropathy. Surface electrodes were adhered to the dorsal rabbit foot overlying the extensor digitorum brevis muscle and the superficial peroneal nerve. The deep and superficial peroneal nerves were stimulated above the ankle and the common peroneal nerve was stimulated at the knee. The nerve conduction studies were repeated twice with a one-week intertest interval to determine measurement variability. Intravenous vincristine was used to produce a peripheral neuropathy. Repeat recordings measured the response to vincristine. A compound muscle action potential and a sensory nerve action potential were evoked in all rabbits. The compound muscle action potential mean amplitude was 0.29 mV (SD ± 0.12) and the fibula head to ankle mean motor conduction velocity was 46.5 m/s (SD ± 2.9). The sensory nerve action potential mean amplitude was 22.8 ?V (SD ± 2.8) and the distal sensory conduction velocity was 38.8 m/s (SD ± 2.2). Sensorimotor latencies and velocities were least variable between two test sessions (coefficient of variation ?=? 2.6–5.9%), sensory potential amplitudes were intermediate (coefficient of variation ?=? 11.1%) and compound potential amplitudes were the most variable (coefficient of variation ?=?19.3%). Vincristine abolished compound muscle action potentials and reduced sensory nerve action potential amplitudes by 42–57% while having little effect on velocity. Rabbit distal hindlimb nerve conduction studies are feasible with surface recordings and stimulation. The evoked distal sensory potentials have amplitudes, configurations and recording techniques that are similar to humans and may be valuable for measuring large sensory fiber function in chronic models of peripheral neuropathies. PMID:24658286
Hotson, John R.
Surprisingly little is known about the impact of entrapment neuropathy on target innervation and the relationship of nerve fibre pathology to sensory symptoms and signs. Carpal tunnel syndrome is the most common entrapment neuropathy; the aim of this study was to investigate its effect on the morphology of small unmyelinated as well as myelinated sensory axons and relate such changes to somatosensory function and clinical symptoms. Thirty patients with a clinical and electrophysiological diagnosis of carpal tunnel syndrome [17 females, mean age (standard deviation) 56.4 (15.3)] and 26 age and gender matched healthy volunteers [18 females, mean age (standard deviation) 51.0 (17.3)] participated in the study. Small and large fibre function was examined with quantitative sensory testing in the median nerve territory of the hand. Vibration and mechanical detection thresholds were significantly elevated in patients with carpal tunnel syndrome (P < 0.007) confirming large fibre dysfunction and patients also presented with increased thermal detection thresholds (P < 0.0001) indicative of C and A?-fibre dysfunction. Mechanical and thermal pain thresholds were comparable between groups (P > 0.13). A skin biopsy was taken from a median nerve innervated area of the proximal phalanx of the index finger. Immunohistochemical staining for protein gene product 9.5 and myelin basic protein was used to evaluate morphological features of unmyelinated and myelinated axons. Evaluation of intraepidermal nerve fibre density showed a striking loss in patients (P < 0.0001) confirming a significant compromise of small fibres. The extent of Meissner corpuscles and dermal nerve bundles were comparable between groups (P > 0.07). However, patients displayed a significant increase in the percentage of elongated nodes (P < 0.0001), with altered architecture of voltage-gated sodium channel distribution. Whereas neither neurophysiology nor quantitative sensory testing correlated with patients' symptoms or function deficits, the presence of elongated nodes was inversely correlated with a number of functional and symptom related scores (P < 0.023). Our findings suggest that carpal tunnel syndrome does not exclusively affect large fibres but is associated with loss of function in modalities mediated by both unmyelinated and myelinated sensory axons. We also document for the first time that entrapment neuropathies lead to a clear reduction in intraepidermal nerve fibre density, which was independent of electrodiagnostic test severity. The presence of elongated nodes in the target tissue further suggests that entrapment neuropathies affect nodal structure/myelin well beyond the focal compression site. Interestingly, nodal lengthening may be an adaptive phenomenon as it inversely correlates with symptom severity. PMID:25348629
Schmid, Annina B; Bland, Jeremy D P; Bhat, Manzoor A; Bennett, David L H
Surprisingly little is known about the impact of entrapment neuropathy on target innervation and the relationship of nerve fibre pathology to sensory symptoms and signs. Carpal tunnel syndrome is the most common entrapment neuropathy; the aim of this study was to investigate its effect on the morphology of small unmyelinated as well as myelinated sensory axons and relate such changes to somatosensory function and clinical symptoms. Thirty patients with a clinical and electrophysiological diagnosis of carpal tunnel syndrome [17 females, mean age (standard deviation) 56.4 (15.3)] and 26 age and gender matched healthy volunteers [18 females, mean age (standard deviation) 51.0 (17.3)] participated in the study. Small and large fibre function was examined with quantitative sensory testing in the median nerve territory of the hand. Vibration and mechanical detection thresholds were significantly elevated in patients with carpal tunnel syndrome (P < 0.007) confirming large fibre dysfunction and patients also presented with increased thermal detection thresholds (P < 0.0001) indicative of C and A?-fibre dysfunction. Mechanical and thermal pain thresholds were comparable between groups (P > 0.13). A skin biopsy was taken from a median nerve innervated area of the proximal phalanx of the index finger. Immunohistochemical staining for protein gene product 9.5 and myelin basic protein was used to evaluate morphological features of unmyelinated and myelinated axons. Evaluation of intraepidermal nerve fibre density showed a striking loss in patients (P < 0.0001) confirming a significant compromise of small fibres. The extent of Meissner corpuscles and dermal nerve bundles were comparable between groups (P > 0.07). However, patients displayed a significant increase in the percentage of elongated nodes (P < 0.0001), with altered architecture of voltage-gated sodium channel distribution. Whereas neither neurophysiology nor quantitative sensory testing correlated with patients’ symptoms or function deficits, the presence of elongated nodes was inversely correlated with a number of functional and symptom related scores (P < 0.023). Our findings suggest that carpal tunnel syndrome does not exclusively affect large fibres but is associated with loss of function in modalities mediated by both unmyelinated and myelinated sensory axons. We also document for the first time that entrapment neuropathies lead to a clear reduction in intraepidermal nerve fibre density, which was independent of electrodiagnostic test severity. The presence of elongated nodes in the target tissue further suggests that entrapment neuropathies affect nodal structure/myelin well beyond the focal compression site. Interestingly, nodal lengthening may be an adaptive phenomenon as it inversely correlates with symptom severity. PMID:25348629
Schmid, Annina B.; Bland, Jeremy D. P.; Bhat, Manzoor A.
Cough is a persistent symptom of many inflammatory airways' diseases. Cough is mediated by receptors sited on sensory nerves\\u000a and then through vagal afferent pathways, which terminate in the brainstem respiratory centre. Cough is often described as\\u000a an unmet clinical need. Opioids are the only prescription-based anti-tussives currently available in the UK. They possess\\u000a limited efficacy and exhibit serious unwanted
M. G. Belvisi; D. J. Hele
Background Several groups have shown that the performance of motor neuroprostheses can be significantly improved by detecting specific sensory events related to the ongoing motor task (e.g., the slippage of an object during grasping). Algorithms have been developed to achieve this goal by processing electroneurographic (ENG) afferent signals recorded by using single-channel cuff electrodes. However, no efforts have been made so far to understand the number and type of detectable sensory events that can be differentiated from whole nerve recordings using this approach. Methods To this aim, ENG afferent signals, evoked by different sensory stimuli were recorded using single-channel cuff electrodes placed around the sciatic nerve of anesthetized rats. The ENG signals were digitally processed and several features were extracted and used as inputs for the classification. The work was performed on integral datasets, without eliminating any noisy parts, in order to be as close as possible to real application. Results The results obtained showed that single-channel cuff electrodes are able to provide information on two to three different afferent (proprioceptive, mechanical and nociceptive) stimuli, with reasonably good discrimination ability. The classification performances are affected by the SNR of the signal, which in turn is related to the diameter of the fibers encoding a particular type of neurophysiological stimulus. Conclusions Our findings indicate that signals of acceptable SNR and corresponding to different physiological modalities (e.g. mediated by different types of nerve fibers) may be distinguished. PMID:20423488
The sarco-endoplasmic reticulum Ca(2+)-ATPase (SERCA) is a critical pathway by which sensory neurons sequester cytosolic Ca(2+) and thereby maintain intracellular Ca(2+) homeostasis. We have previously demonstrated decreased intraluminal endoplasmic reticulum Ca(2+) concentration in traumatized sensory neurons. Here we examine SERCA function in dissociated sensory neurons using Fura-2 fluorometry. Blocking SERCA with thapsigargin (1 ?M) increased resting [Ca(2+)](c) and prolonged recovery (?) from transients induced by neuronal activation (elevated bath K(+)), demonstrating SERCA contributes to control of resting [Ca(2+)](c) and recovery from transient [Ca(2+)](c) elevation. To evaluate SERCA in isolation, plasma membrane Ca(2+) ATPase was blocked with pH 8.8 bath solution and mitochondrial buffering was avoided by keeping transients small (? 400 nM). Neurons axotomized by spinal nerve ligation (SNL) showed a slowed rate of transient recovery compared to control neurons, representing diminished SERCA function, whereas neighboring non-axotomized neurons from SNL animals were unaffected. Injury did not affect SERCA function in large neurons. Repeated depolarization prolonged transient recovery, showing that neuronal activation inhibits SERCA function. These findings suggest that injury-induced loss of SERCA function in small sensory neurons may contribute to the generation of pain following peripheral nerve injury. PMID:23219911
Duncan, C; Mueller, S; Simon, E; Renger, J J; Uebele, V N; Hogan, Q H; Wu, H-E
Sciatic nerve crushing, transection, and ligation models were used in rats to study the reactions of and changes in the numbers of satellite cells (SC) in spinal dorsal root ganglia in the lumbar segment. Nerve transection was followed by the appearance of neurons surrounded by two layers of SC. The thickness of SC processes and the areas of contacts with neurons increased as a result of invaginations into neuron perikarya. After nerve ligation, SC and their processes were located around parts of large and intermediate neurons in several tightly appressed layers; the area of contact between SC and neuron perikarya showed increased development of invaginations such that lamellar structures appeared in the SC cytoplasm, along with contacts with SC processes surrounding neighboring neurons. The greatest increases in SC numbers were seen after ligation of the nerve. Transection was followed by increases in the numbers of small and intermediate neurons surrounded by vimentin-positive SC. The number of large neurons surrounded by these cells decreased. At all time points following ligation of the nerve, all neurons in the study ganglia were surrounded by vimentin-positive SC. Post-traumatic changes in structure and numbers differed in SC associated with sensory neurons of individual size populations and depended on the type of trauma applied to efferent conductors. PMID:20532986
Arkhipova, S S; Raginov, I S; Mukhitov, A R; Chelyshev, Y A
Biopsies of the superficial sensory branch of the radial nerve are contested. Some authors mention it to be simple and without harm, but others are formally against this procedure. At ILAD, 274 biopsies were made between 1986 to 1992. We present a review of 112 leprosy patients for whom biopsy was done. On 112 reexamined patients, we observed 2 benign neuroma, hence 2%. The comparison of nerve function before biopsy and after, of 63 of the 112 patients, reexamination shows no significant modification of the functional score. Given even the occurrence of benign neuroma in only 2% of the cases, the authors do not recommend the biopsy of the superficial sensory branch of the radial nerve. For research purposes on neuritis in leprosy, as well as to assure diagnosis in primary neuritic leprosy, we propose the biopsy of the sensory branch of the musculo cutaneous nerve at elbow level. PMID:9131938
Grauwin, M Y; Dieye, M; Mane, I; Cartel, J L
Growth hormone (GH) secretion is stimulated by aerobic and resistive exercise and inhibited by exposure to actual or simulated (bedrest, hindlimb suspension) microgravity. Moreover, hypothalamic growth hormone-releasing factor (GRF) and preproGRF mRNA are markedly decreased in spaceflight rats. These observations suggest that reduced sensory input from inactive muscles may contribute to the reduced secretion of GH seen in "0 G". Thus, the aim of this study was to determine the effect of muscle sensory nerve stimulation on secretion of GH. Fed male Wistar rats (304 +/- 23 g) were anesthetized (pentobarbital) and the right peroneal (Pe), tibial (T), and sural (S) nerves were cut. Electrical stimulation of the distal (D) or proximal (P) ends of the nerves was implemented for 15 min. to mimic the EMG activity patterns of ankle extensor muscles of a rat walking 1.5 mph. The rats were bled by cardiac puncture and their anterior pituitaries collected. Pituitary and plasma bioactive (BGH) and immunoactive (IGH) GH were measured by bioassay and RIA.
Grindeland, Richard E.; Roy, R. R.; Edgerton, V. R.; Gosselink, K. L.; Grossman, E. J.; Sawchenko, P. E.; Wade, Charles E. (Technical Monitor)
The normal intervertebral disc (IVD) is a poorly innervated organ supplied only by sensory (mainly nociceptive) and postganglionic sympathetic (vasomotor efferents) nerve fibers. Interestingly, upon degeneration, the IVD becomes densely innervated even in regions that in normal conditions lack innervation. This increased innervation has been associated with pain of IVD origin. The mechanisms responsible for nerve growth and hyperinnervation of pathological IVDs have not been fully elucidated. Among the molecules that are presumably involved in this process are some members of the family of neurotrophins (NTs), which are known to have both neurotrophic and neurotropic properties and regulate the density and distribution of nerve fibers in peripheral tissues. NTs and their receptors are expressed in healthy IVDs but much higher levels have been observed in pathological IVDs, thus suggesting a correlation between levels of expression of NTs and density of innervation in IVDs. In addition, NTs also play a role in inflammatory responses and pain transmission by increasing the expression of pain-related peptides and modulating synapses of nociceptive neurons at the spinal cord. This article reviews current knowledge about the innervation of IVDs, NTs and NT receptors, expression of NTs and their receptors in IVDs as well as in the sensory neurons innervating the IVDs, the proinflammatory role of NTs, NTs as nociception regulators, and the potential network of discogenic pain involving NTs. PMID:20456524
García-Cosamalón, José; del Valle, Miguel E; Calavia, Marta G; García-Suárez, Olivia; López-Muñiz, Alfonso; Otero, Jesús; Vega, José A
The innervation of bony arteries was studied in 19 fishes (6 perches, 11 breams and 2 pikes) by the silver impregnation method after Kajal--Faworski and Bielschowski--Gross. In the first branchial arc as well as in others the receptors of two kinds were revealed: those having the main type of branching and diffuse arborescent vessels. In rare cases granular terminations were revealed. The number of terminations found in the first branchial arc was twice as great as that in each of the rest arcs. A characteristic feature of the sensory nerve terminations of the branchial apparatus in fishes is their arborescent structure, a diffuse disposition of terminal branches and absence of special cells from the receptor. The structure of the receptory terminations in the first branchial arc of fishes is morphologically similar to the de Castro Ist type sensory terminations which he has found in the carotid sinus wall of mammals. PMID:999536
Morozov, E K
The current use of hearing aids and artificial cochleas for deaf-mute individuals depends on their auditory nerve. Skin-hearing technology, a patented system developed by our group, uses a cutaneous sensory nerve to substitute for the auditory nerve to help deaf-mutes to hear sound. This paper introduces a new solution, multi-channel-array skin-hearing technology, to solve the problem of speech discrimination. Based on the filtering principle of hair cells, external voice signals at different frequencies are converted to current signals at corresponding frequencies using electronic multi-channel bandpass filtering technology. Different positions on the skin can be stimulated by the electrode array, allowing the perception and discrimination of external speech signals to be determined by the skin response to the current signals. Through voice frequency analysis, the frequency range of the band-pass filter can also be determined. These findings demonstrate that the sensory nerves in the skin can help to transfer the voice signal and to distinguish the speech signal, suggesting that the skin sensory nerves are good candidates for the replacement of the auditory nerve in addressing deaf-mutes' hearing problems. Scientific hearing experiments can be more safely performed on the skin. Compared with the artificial cochlea, multi-channel-array skin-hearing aids have lower operation risk in use, are cheaper and are more easily popularized. PMID:25317171
Li, Jianwen; Li, Yan; Zhang, Ming; Ma, Weifang; Ma, Xuezong
The current use of hearing aids and artificial cochleas for deaf-mute individuals depends on their auditory nerve. Skin-hearing technology, a patented system developed by our group, uses a cutaneous sensory nerve to substitute for the auditory nerve to help deaf-mutes to hear sound. This paper introduces a new solution, multi-channel-array skin-hearing technology, to solve the problem of speech discrimination. Based on the filtering principle of hair cells, external voice signals at different frequencies are converted to current signals at corresponding frequencies using electronic multi-channel bandpass filtering technology. Different positions on the skin can be stimulated by the electrode array, allowing the perception and discrimination of external speech signals to be determined by the skin response to the current signals. Through voice frequency analysis, the frequency range of the band-pass filter can also be determined. These findings demonstrate that the sensory nerves in the skin can help to transfer the voice signal and to distinguish the speech signal, suggesting that the skin sensory nerves are good candidates for the replacement of the auditory nerve in addressing deaf-mutes’ hearing problems. Scientific hearing experiments can be more safely performed on the skin. Compared with the artificial cochlea, multi-channel-array skin-hearing aids have lower operation risk in use, are cheaper and are more easily popularized. PMID:25317171
Li, Jianwen; Li, Yan; Zhang, Ming; Ma, Weifang; Ma, Xuezong
Nonspecific manifestations (sickness symptoms) of inflammation and infection occur as two sequential syndromes, the early and late. This review deals with the early sickness syndrome, which occurs at the onset of the inflammatory process and manifests itself with a high deep body temperature, hyperalgesia/allodynia, arousal, motor agitation, and arterial hypertension. Two rat models of intravenous lipopolysaccharide (LPS)-induced fever are used to study the early syndrome: 1) a monophasic response to low, just suprathreshold doses of LPS and 2) the first rise in body temperature (Phase I) of the polyphasic response to higher doses. Experiments in the first model reveal a blockade of monophasic fever by total subdiaphragmatic or selective hepatic vagotomy, thus suggesting mediation of this response by the hepatic vagal fibers, presumably afferent. Experiments in the second model show that Phase I of polyphasic fever is insensitive to surgical vagotomy but does not occur in animals desensitized with low intraperitoneal doses of capsaicin (an agonist of the vanilloid receptor VR1). These findings suggest that Phase I is mediated by intra-abdominal, VR1-receptor-bearing afferents, either splanchnic or possibly splanchnic and vagal. The involvement of the splanchnic nerve and VR1 receptor in Phase I of LPS fever is currently under investigation in our laboratory. Based on studies completed so far, neural signaling mechanisms are involved in both monophasic fever and Phase I of polyphasic fever. We speculate that these mechanisms are triggered by peripherally originated, blood-borne prostaglandin E2. PMID:14766385
Romanovsky, Andrej A
The aim of this study was to examine the changes of sensory nerve conduction velocity (SNCV) and F-wave for colistin-induced peripheral neurotoxicity using a mouse model. Mice were administered with colistin 5, 7.5 and 15 mg/kg/day via a 3-min. intravenous infusion. The sensory nerve conduction velocity (SNCV) and F-wave were measured using the bipolar recording electrodes. The SNCV and F-wave latency changed in a dose- and time-dependent manner. The significant increase of F-wave latency and significant decrease of SNCV appeared on day 3 (p < 0.05 and 0.01, respectively) in the 15 mg/kg/day group, and they were markedly changed on day 7 in the 7.5 mg/kg/day (p < 0.01 and 0.05, respectively) and 15 mg/kg/day groups (both p < 0.01). In addition, F-wave latency also significantly increased on day 7 in the 5 mg/kg/day group (p < 0.05) without any clinical signs. These results indicate that SNCV and F-wave latency were more sensitive in colistin-induced neurotoxicity in mice, which highlights the early monitoring tool of polymyxins neurotoxicity in the clinic. PMID:24861773
Dai, Chongshan; Tang, Shusheng; Li, Jichang; Wang, Jiping; Xiao, Xilong
The effect of 1 mW helium neon continuous-wave (0.633 microns) laser irradiation on superficial radical sensory and median sensory nerve function was examined in a double-blind, controlled study involving 40 volunteers. No differences in action potential amplitudes, distal latencies, or forearm skin temperatures were found between the treated and control groups either at the time of irradiation or at subsequent evaluations 15 and 30 minutes later. As a result, we are unable to confirm reports that low-energy lasers of this power and wavelength alter nerve function.
Basford, J.R.; Daube, J.R.; Hallman, H.O.; Millard, T.L.; Moyer, S.K. (Mayo Clinic and Foundation, Rochester, MN (USA))
Hereditary sensory and autonomic neuropathy type V (HSAN V) is an autosomal recessive disorder characterized by the loss of deep pain perception. The anomalous pain and temperature sensations are due to the absence of nociceptive sensory innervation. The neurotrophin nerve growth factor (NGF), by binding to tropomyosin receptor A (TrkA) and p75NTR receptors, is essential for the development and survival of sensory neurons, and for pain perception during adulthood. Recently a homozygous missense mutation (R100W) in the NGF gene has been identified in HSAN V patients. Interestingly, alterations in NGF signalling, due to mutations in the NGF TRKA gene, have also been involved in another congenital insensitivity to pain, HSAN IV, characterized not only by absence of reaction to painful stimuli, but also anhidrosis and mental retardation. These symptoms are absent in HSAN V patients. Unravelling the mechanisms that underlie the differences between HSAN IV and V could assist in better understanding NGF biology. This review highlights the recent key findings in the understanding of HSAN V, including insights into the molecular mechanisms of the disease, derived from genetic studies of patients with this disorder. PMID:24494679
Increasing afferent renal nerve activity decreases efferent renal nerve activity and increases urinary sodium excretion. Activation of renal pelvic mechanosensory nerves is impaired in streptozotocin (STZ)-treated rats (model of type 1 diabetes). Decreased activation of renal sensory nerves would lead to increased efferent renal nerve activity, sodium retention, and hypertension. We examined whether the reduced activation of renal sensory nerves in STZ rats was due to increased renal angiotensin activity and whether activation of the renal sensory nerves was impaired in obese Zucker diabetic fatty (ZDF) rats (model of type 2 diabetes). In an isolated renal pelvic wall preparation from rats treated with STZ for 2 wk, PGE2 failed to increase the release of substance P, from 5 +/- 1 to 6 +/- 1 pg/min. In pelvises from sham STZ rats, PGE2 increased substance P release from 6 +/- 1 to 13 +/- 2 pg/min. Adding losartan to the incubation bath increased PGE2-mediated release of substance P in STZ rats, from 5 +/- 1 to 10 +/- 2 pg/min, but had no effect in sham STZ rats. In pelvises from obese ZDF rats (22-46 wk old), PGE2 increased substance P release from 12.0 +/- 1.2 to 18.3 +/- 1.2 pg/min, which was less than that from lean ZDF rats (10.3 +/- 1.6 to 22.5 +/- 2.4 pg/min). Losartan had no effect on the PGE2-mediated substance P release in obese or lean ZDF rats. We conclude that the mechanisms involved in the decreased responsiveness of the renal sensory nerves in STZ rats involve activation of the renin angiotensin system in STZ but not in obese ZDF rats. PMID:18199587
Kopp, Ulla C; Cicha, Michael Z; Yorek, Mark A
The eyes and skin are highly innervated by sensory nerves; stimulation of these nerves by irritants may give rise to neurogenic inflammation, leading to sensory irritation and pain. Few in vitro models of neurogenic inflammation have been described in conjunction with alternative skin and eye irritation methods, despite the fact that the sensory innervation of these organs is well-documented. To date, alternative approaches to the Draize skin and eye irritation tests have proved largely successful at classifying severe irritants, but are generally poor at discriminating between agents with mild to moderate irritant potential. We propose that the development of in vitro models for the prediction of sensory stimulation will assist in the re-classification of the irritant potential of agents that are under-predicted by current in vitro strategies. This review describes the range of xenobiotics known to cause inflammation and pain through the stimulation of sensory nerves, as well as the endogenous mediators and receptor types that are involved. In particular, it focuses on the vanilloid receptor, its activators and its regulation, as these receptors function as integrators of responses to numerous noxious stimuli. Cell culture models and ex vivo preparations that have the potential to serve as predictors of sensory irritation are also described. In addition, as readily available sensory neuron cell line models are few in number, stem cell lines (with the capacity to differentiate into sensory neurons) are explored. Finally, a preliminary strategy to enable assessment of whether incorporation of a sensory component will enhance the predictive power of current in vitro eye and skin testing strategies is proposed. PMID:15612874
Garle, Michael J; Fry, Jeffrey R
Nitro-oleic acid (OA-NO2), an electrophilic fatty acid nitroalkene byproduct of redox reactions, activates transient receptor potential ion channels (TRPA1 and TRPV1) in primary sensory neurons. To test the possibility that signaling actions of OA-NO2 might modulate TRP channels, we examined: (1) interactions between OA-NO2 and other agonists for TRPA1 (allyl-isothiocyanate, AITC) and TRPV1 (capsaicin) in rat dissociated dorsal root ganglion cells using Ca(2+) imaging and patch clamp techniques and (2) interactions between these agents on sensory nerves in the rat hindpaw. Ca(2+) imaging revealed that brief application (15-30 s) of each of the three agonists induced homologous desensitization. Heterologous desensitization also occurred when one agonist was applied prior to another agonist. OA-NO2 was more effective in desensitizing the response to AITC than the response to capsaicin. Prolonged exposure to OA-NO2 (20 min) had a similar desensitizing effect on AITC or capsaicin. Homologous and heterologous desensitizations were also demonstrated with patch clamp recording. Deltamethrin, a phosphatase inhibitor, reduced the capsaicin or AITC induced desensitization of OA-NO2 but did not suppress the OA-NO2 induced desensitization of AITC or capsaicin, indicating that heterologous desensitization induced by either capsaicin or AITC occurs by a different mechanism than the desensitization produced by OA-NO2. Subcutaneous injection of OA-NO2 (2.5mM, 35 ?l) into a rat hindpaw induced delayed and prolonged nociceptive behavior. Homologous desensitization occurred with AITC and capsaicin when applied at 15 minute intervals, but did not occur with OA-NO2 when applied at a 30 min interval. Pretreatment with OA-NO2 reduced AITC-evoked nociceptive behaviors but did not alter capsaicin responses. These results raise the possibility that OA-NO2 might be useful clinically to reduce neurogenic inflammation and certain types of painful sensations by desensitizing TRPA1 expressing nociceptive afferents. PMID:24212047
Zhang, Xiulin; Koronowski, Kevin B; Li, Lu; Freeman, Bruce A; Woodcock, Stephen; de Groat, William C
As humans age there is a decline in most sensory systems including vision, hearing, taste, smell, and tactile acuity. In contrast, the frequency and severity of musculoskeletal pain generally increases with age. To determine whether the density of sensory nerve fibers that transduce skeletal pain changes with age, calcitonin gene related peptide (CGRP) and neurofilament 200 kDa (NF200) sensory nerve fibers that innervate the femur were examined in the femurs of young (4 month old), middle-aged (13 month) and old (36 month) male F344/BNF1 rats. Whereas the bone quality showed a significant age-related decline, the density of CGRP+ and NF200+ nerve fibers that innervate the bone remained remarkably unchanged as well as the severity of acute skeletal fracture pain. Thus, while bone mass, quality and strength undergo a significant decline with age, the density of sensory nerve fibers that transduce noxious stimuli remain largely intact. These data may in part explain why musculoskeletal pain increases with age. PMID:20947214
Jimenez-Andrade, Juan M.; Mantyh, William G.; Bloom, Aaron P.; Freeman, Katie T.; Ghilardi, Joseph R.; Kuskowski, Michael A.; Mantyh, Patrick W.
The purpose of this study was to evaluate the value of utilizing longitudinal intrafascicular electrodes (LIFEs) in collecting and analyzing sensory signals from the peripheral nerve. The longitudinal intrafascicular electrodes were made of 25-microm Teflon-insulated Pt/Ir wire and implanted into the fascicle of the superficial peroneal nerves in a feline model. The sensory signals at rest status and induced with various stimulations were recorded. The action potential area, frequency, coefficient of variation (CV) of the peak, and functional spectrum were then analyzed by the MF Lab version 3.01 software package. The results showed that the sensory nerve action potentials (SNAPs) were 0-2 spikes per second at rest state; the count was increased when stimulation was administered. SNAPs were 16-24 spikes per second when scraping stimulation was applied. The pulse intervals and the waveform remained consistent. SNAPs burst and were clustered when stress stimulation was given. The comparison of area, frequency, and CV of the peak showed statistically significant differences between these parameters receiving different stimulations. The functional spectrum analysis showed that the frequency of action potential increased when the stress stimulation was applied. In conclusion, LIFEs can sensitively collect sensory signals and provide a good interface to analyze sensory information from peripheral fasciculi. These data provide useful information for further study of control of electronic prostheses. PMID:16145684
Li, Li-Jun; Zhang, Jian; Zhang, Feng; Lineaweaver, William C; Chen, Tong-Yi; Chen, Zhong-Wei
The pharmacological ablation of capsaicin-sensitive afferents by means of capsaicin desensitization is usually utilized as a first functional criterion to identify substances whose biological effects might involve activation of this type of nerves. We have studied, in guinea pig epithelium-denuded bronchial rings (in the presence of the neutral endopeptidase inhibitor thiorphan), the effect of in vitro capsaicin desensitization (10 microM for 15 min) on bronchomotor responses elicited by leukotriene D4 (10-100 nM), 15-HETE (3-6 microM) and lipoxin A4 (3-6 microM). While all these three lipid mediators contract bronchial preparations, only lipoxin A4 effects were markedly depressed by previous capsaicin challenge. As expected, capsaicin desensitization abolished subsequent motor responses to capsaicin itself or stimulation of non-adrenergic non-cholinergic nerves, while it left unaffected cholinergic responses. It is proposed that endogenously-generated lipoxin A4 acts, at least partially, through the activation of capsaicin-sensitive sensory nerve fibers. PMID:1773033
Manzini, S; Meini, S
Chronic pain is a major clinical problem and opiates are often the only treatment, but they cause significant problems ranging from sedation to deadly respiratory depression. Resiniferatoxin (RTX), a potent agonist of Transient Receptor Potential Vanilloid 1 (TRPV1), causes a slow, sustained and irreversible activation of TRPV1 and increases the frequency of spontaneous excitatory postsynaptic currents, but causes significant depression of evoked EPSCs due to nerve terminal depolarization block. Intrathecal administration of RTX to rats in the short-term inhibits nociceptive synaptic transmission, and in the long-term causes a localized, selective ablation of TRPV1-expressing central sensory nerve terminals leading to long lasting analgesia in behavioral models. Since RTX actions are selective for central sensory nerve terminals, other efferent functions of dorsal root ganglion neurons can be preserved. Preventing nociceptive transmission at the level of the spinal cord can be a useful strategy to treat chronic, debilitating and intractable pain. PMID:19753113
Sikand, Parul; Parihar, Arti; Evans, M. Steven; Premkumar, Louis S.
Purpose: Radiation-induced heart disease (RIHD) is a chronic severe side effect of radiation therapy of intrathoracic and chest wall tumors. The heart contains a dense network of sensory neurons that not only are involved in monitoring of cardiac events such as ischemia and reperfusion but also play a role in cardiac tissue homeostasis, preconditioning, and repair. The purpose of this study was to examine the role of sensory nerves in RIHD. Methods and Materials: Male Sprague-Dawley rats were administered capsaicin to permanently ablate sensory nerves, 2 weeks before local image-guided heart x-ray irradiation with a single dose of 21 Gy. During the 6 months of follow-up, heart function was assessed with high-resolution echocardiography. At 6 months after irradiation, cardiac structural and molecular changes were examined with histology, immunohistochemistry, and Western blot analysis. Results: Capsaicin pretreatment blunted the effects of radiation on myocardial fibrosis and mast cell infiltration and activity. By contrast, capsaicin pretreatment caused a small but significant reduction in cardiac output 6 months after irradiation. Capsaicin did not alter the effects of radiation on cardiac macrophage number or indicators of autophagy and apoptosis. Conclusions: These results suggest that sensory nerves, although they play a predominantly protective role in radiation-induced cardiac function changes, may eventually enhance radiation-induced myocardial fibrosis and mast cell activity.
Sridharan, Vijayalakshmi; Tripathi, Preeti [Department of Pharmaceutical Sciences, Division of Radiation Health, University of Arkansas for Medical Sciences, Little Rock, Arkansas (United States); Sharma, Sunil [Department of Radiation Oncology, Division of Radiation Health, University of Arkansas for Medical Sciences, Little Rock, Arkansas (United States); Moros, Eduardo G. [Department of Radiation Oncology, Moffitt Cancer Center and Research Institute, Tampa, Florida (United States); Zheng, Junying [Department of Pharmaceutical Sciences, Division of Radiation Health, University of Arkansas for Medical Sciences, Little Rock, Arkansas (United States); Hauer-Jensen, Martin [Department of Pharmaceutical Sciences, Division of Radiation Health, University of Arkansas for Medical Sciences, Little Rock, Arkansas (United States); Surgical Service, Central Arkansas Veterans Healthcare System, Little Rock, Arkansas (United States); Boerma, Marjan, E-mail: email@example.com [Department of Pharmaceutical Sciences, Division of Radiation Health, University of Arkansas for Medical Sciences, Little Rock, Arkansas (United States)
The immediate responses of the upper respiratory tract (URT) to the irritants acrolein and acetic acid were examined in healthy and allergic airway-diseased C57Bl/6J mice. Acrolein (1.1 ppm) and acetic acid (330 ppm) vapors induced an immediate increase in flow resistance, as measured in the surgically isolated URT of urethane-anesthetized healthy animals. Acrolein, but not acetic acid, induced a small URT vasodilatory response. In awake spontaneously breathing mice, both vapors induced a prolonged pause at the start of expiration (a response mediated via stimulation of nasal trigeminal nerves) and an increase in total respiratory specific airway flow resistance, the magnitude of which was similar to that observed in the isolated URT. Both responses were significantly reduced in animals pretreated with large doses of capsaicin to defunctionalize sensory nerves, strongly suggesting a role for sensory nerves in development of these responses. The breathing pattern and/or obstructive responses were enhanced in mice with ovalbumin-induced allergic airway disease. These results suggest that the primary responses to acrolein and acetic acid vapors are altered breathing patterns and airway obstruction, that sensory nerves play an important role in these responses, and that these responses are enhanced in animals with allergic airway disease. PMID:12626476
Morris, John B; Symanowicz, Peter T; Olsen, Joshua E; Thrall, Roger S; Cloutier, Michelle M; Hubbard, Andrea K
Diabetic polyneuropathy (DPN), characterized by early hyperalgesia and increased nerve growth factor (NGF), evolves in late irreversible neuropathic symptoms with reduced NGF support to sensory neurons. Electroacupuncture (EA) modulates NGF in the peripheral nervous system, being effective for the treatment of DPN symptoms. We hypothesize that NGF plays an important pathogenic role in DPN development, while EA could be useful in the therapy of DPN by modulating NGF expression/activity. Diabetes was induced in rats by streptozotocin (STZ) injection. One week after STZ, EA was started and continued for three weeks. NGF system and hyperalgesia-related mediators were analyzed in the dorsal root ganglia (DRG) and in their spinal cord and skin innervation territories. Our results show that four weeks long diabetes increased NGF and NGF receptors and deregulated intracellular signaling mediators of DRG neurons hypersensitization; EA in diabetic rats decreased NGF and NGF receptors, normalized c-Jun N-terminal and p38 kinases activation, decreased transient receptor potential vanilloid-1 ion channel, and possibly activated the nuclear factor kappa-light-chain-enhancer of activated B cells (Nf-?B). In conclusion, NGF signaling deregulation might play an important role in the development of DPN. EA represents a supportive tool to control DPN development by modulating NGF signaling in diabetes-targeted neurons. PMID:23710226
Nori, Stefania Lucia; Rocco, Maria Luisa; Florenzano, Fulvio; Ciotti, Maria Teresa; Aloe, Luigi
In vitro anterograde tracing of axons in mesenteric nerve trunks using biotinamide in combination with immunohistochemical labelling was used to characterize the extrinsic nerve projections in the myenteric plexus of the mouse jejunum. Anterogradely-labelled spinal sensory fibres innervating the enteric nervous system were identified by their immunoreactivity for calcitonin gene-related peptide (CGRP), while sympathetic noradrenergic fibres were detected with tyrosine
L. L. Tan; J. C. Bornstein; C. R. Anderson
Post-operative immobilisation following isolated digital nerve repair remains a controversial issue amongst the microsurgical community. Protocols differ from unit to unit and even, as evidenced in our unit, may differ from consultant to consultant. We undertook a retrospective review of 46 patients who underwent isolated digital nerve repair over a 6-month period. Follow-up ranged from 6 to 18 months. Twenty-four
F. P. Henry; R. I. Farkhad; F. S. Butt; M. O’Shaughnessy; S. T. O’Sullivan
In previous studies it has been shown that nerve growth factor (NGF) is taken up with a high selectivity by adrenergic nerve terminals and is transported retrogradely to the perikaryon11,22. It was the aim of the present experiments to investigate whether the sensory neurons exhibit the same high degree of selectivity for retrograde transport throughout the whole life cycle, although it is known that their dramatic response to NGF is confined to a short period of ontogenetic development. Unilateral injection of [125I]NGF into the forepaw of adult rats was followed by a preferential accumulation of radioactivity in the sensory ganglia (C6-C7) of the injected side. However, this preferential accumulation was not detectable earlier than 6 h after injection and reached a maximum (ratio between injected and non-injected side, 5:1) after 11-16 h. Transection of the plexus brachialis abolished and local administration of colchicine prior to that of [125I]NGF greatly reduced the preferential accumulation of radioactivity in the ganglia of the injected side. The rate of retrograde transport of NGF in sensory neurons was calculated to be 13 mm/h which is about 5 times faster than that in adrenergic neurons. The selectivity of this retrograde transport was demonstrated by the fact that injection of 125I-labeled bovine serum albumin and cytochrome c did not result in a preferential accumulation of radioactivity in the sensory ganglia of the injected side. Light microscopic autoradiography revealed heavily labeled cells in the sensory ganglia (C6-C7) of the injected side after administration of [125I]NGF into the forepaw. Only cells belonging to the large cell type were labeled. Prolonged (7 mug/g/day over 5 days) injection of NGF into the forepaw of 10-day-old rats did not result in a hypertropic response of the sensory neurons as far as can be judged from morphometric studies at the light microscopic level. PMID:50114
Stoeckel, K; Schwab, M; Thoenen, H
After nerve transection, cutaneous type I mechanoreceptors (Haarscheiben or tactile domes) preferentially reappear at old loci, although some do appear at new locations. The mechanism by which this topological specificity is maintained was studied by transecting the femoral cutaneous nerve in cats in which about half of the Haarscheiben were removed by cauterization. Thirteen months after nerve transection, domes were found on uncauterized sites at a rate significantly greater than that expected by chance alone, but on cauterized old dome sites at a rate expected by chance alone. It is concluded the reappearance of type I receptors at old receptor sites following nerve transection is primarily due to intrinsic properties of the receptor sites, rather than to guidance of regenerating axonal sprouts to these sites by the endoneurial matrix of the distal stump of the lesioned nerve. PMID:7177492
In 1979 in Taiwan, more than 2000 people were poisoned with rice cooking oil contaminated with polychlorinated biphenyls (PCB). One hundred ten patients were studied within one year of the exposure. The blood PCB levels were 39.3 +/- 16.6 ppb. The blood levels of the PCB derivatives, polychlorinated quaterphenyls (PCQ) and polychlorinated dibenzofurans (PCDF), were 8.6 +/- 4.8 and 0.076 +/- 0.038 ppb, respectively. Both the sensory and motor nerve conduction velocities (NCV) of the patients were significantly lower than the control. Abnormal slowing of sensory NCV was found in 43.6% and abnormal slowing of motor NCV was seen in 21.8%. Patients who had higher PCQ blood levels had significantly slower median nerve sensory NCV than those with lower PCQ levels. Patients with higher PCB blood levels had significantly slower peroneal nerve motor NCV than those with lower PCB levels. PMID:3926478
Chen, R C; Tang, S Y; Miyata, H; Kashimoto, T; Chang, Y C; Chang, K J; Tung, T C
Activation of efferent renal sympathetic nerve activity (ERSNA) increases afferent renal nerve activity (ARNA), which then reflexively decreases ERSNA via activation of the renorenal reflexes to maintain low ERSNA. The ERSNA-ARNA interaction is mediated by norepinephrine (NE) that increases and decreases ARNA by activation of renal ?1-and ?2-adrenoceptors (AR), respectively. The ERSNA-induced increases in ARNA are suppressed during a low-sodium (2,470 ± 770% s) and enhanced during a high-sodium diet (5,670 ± 1,260% s). We examined the role of ?2-AR in modulating the responsiveness of renal sensory nerves during low- and high-sodium diets. Immunohistochemical analysis suggested the presence of ?2A-AR and ?2C-AR subtypes on renal sensory nerves. During the low-sodium diet, renal pelvic administration of the ?2-AR antagonist rauwolscine or the AT1 receptor antagonist losartan alone failed to alter the ARNA responses to reflex increases in ERSNA. Likewise, renal pelvic release of substance P produced by 250 pM NE (from 8.0 ± 1.3 to 8.5 ± 1.6 pg/min) was not affected by rauwolscine or losartan alone. However, rauwolscine+losartan enhanced the ARNA responses to reflex increases in ERSNA (4,680 ± 1,240%·s), and renal pelvic release of substance P by 250 pM NE, from 8.3 ± 0.6 to 14.2 ± 0.8 pg/min. During a high-sodium diet, rauwolscine had no effect on the ARNA response to reflex increases in ERSNA or renal pelvic release of substance P produced by NE. Losartan was not examined because of low endogenous ANG II levels in renal pelvic tissue during a high-sodium diet. Increased activation of ?2-AR contributes to the reduced interaction between ERSNA and ARNA during low-sodium intake, whereas no/minimal activation of ?2-AR contributes to the enhanced ERSNA-ARNA interaction under conditions of high sodium intake. PMID:21106912
Cicha, Michael Z.; Smith, Lori A.; Ruohonen, Saku; Scheinin, Mika; Fritz, Nicolas; Hokfelt, Tomas
Background Bilateral sagittal split ramus osteotomy (BSSRO) is a common orthognatic surgical procedure. Sensory disturbances in the inferior alveolar nerve, including hypoesthesia and dysesthesia, are frequently observed after BSSRO, even without distinct nerve injury. The mechanisms that underlie individual differences in the vulnerability to sensory disturbances have not yet been elucidated. Methods The present study investigated the relationships between genetic polymorphisms and the vulnerability to sensory disturbances after BSSRO in a genome-wide association study (GWAS). A total of 304 and 303 patients who underwent BSSRO were included in the analyses of hypoesthesia and dysesthesia, respectively. Hypoesthesia was evaluated using the tactile test 1 week after surgery. Dysesthesia was evaluated by interview 4 weeks after surgery. Whole-genome genotyping was conducted using Illumina BeadChips including approximately 300,000 polymorphism markers. Results Hypoesthesia and dysesthesia occurred in 51 (16.8%) and 149 (49.2%) subjects, respectively. Significant associations were not observed between the clinical data (i.e., age, sex, body weight, body height, loss of blood volume, migration length of bone fragments, nerve exposure, duration of anesthesia, and duration of surgery) and the frequencies of hypoesthesia and dysesthesia. Significant associations were found between hypoesthesia and the rs502281 polymorphism (recessive model: combined ?2 = 24.72, nominal P = 6.633 × 10-7), between hypoesthesia and the rs2063640 polymorphism (recessive model: combined ?2 = 23.07, nominal P = 1.563 × 10-6), and between dysesthesia and the nonsynonymous rs2677879 polymorphism (trend model: combined ?2 = 16.56, nominal P = 4.722 × 10-5; dominant model: combined ?2 = 16.31, nominal P = 5.369 × 10-5). The rs502281 and rs2063640 polymorphisms were located in the flanking region of the ARID1B and ZPLD1 genes on chromosomes 6 and 3, whose official names are “AT rich interactive domain 1B (SWI1-like)” and “zona pellucida-like domain containing 1”, respectively. The rs2677879 polymorphism is located in the METTL4 gene on chromosome 18, whose official name is “methyltransferase like 4”. Conclusions The GWAS of sensory disturbances after BSSRO revealed associations between genetic polymorphisms located in the flanking region of the ARID1B and ZPLD1 genes and hypoesthesia and between a nonsynonymous genetic polymorphism in the METTL4 gene and dysesthesia. PMID:23834954
Nerve conduction velocity and the amplitude of nerve and muscle action potentials have been measured in the median and anterior tibial nerves of normal adult and infant baboons. The effect of altered temperature on velocity has also been investigated. Seven adult baboons were intoxicated with acrylamide. In animals given 10-15 mg/kg/day, the gradual development of a peripheral neuropathy was accompanied by a decline in the amplitude of both muscle and nerve action potentials. There was also a gradual fall in conduction velocity. In some cases maximal motor velocity in the median nerve fell by as much as 34%, and in the anterior tibial nerve by as much as 49%, the largest falls being seen in animals showing the greatest reductions in response amplitude. Histological studies, reported elsewhere, have shown that the main pathological change in our animals was a degeneration of the peripheral nerves, with little demyelination. Fibre diameter histograms indicated that large fibres were particularly severely affected, and it seems likely that the reduced maximal conduction velocities were due to this selective loss of large-diameter fibres. PMID:4328885
Hopkins, A. P.; Gilliatt, R. W.
OBJECTIVE The goal of this study was to characterize glycation adducts formed in both in vivo extracellular matrix (ECM) proteins of endoneurium from streptozotocin (STZ)-induced diabetic rats and in vitro by glycation of laminin and fibronectin with methylglyoxal and glucose. We also investigated the impact of advanced glycation end product (AGE) residue content of ECM on neurite outgrowth from sensory neurons. RESEARCH DESIGN AND METHODS Glycation, oxidation, and nitration adducts of ECM proteins extracted from the endoneurium of control and STZ-induced diabetic rat sciatic nerve (3–24 weeks post-STZ) and of laminin and fibronectin that had been glycated using glucose or methylglyoxal were examined by liquid chromatography with tandem mass spectrometry. Methylglyoxal-glycated or unmodified ECM proteins were used as substrata for dissociated rat sensory neurons as in vitro models of regeneration. RESULTS STZ-induced diabetes produced a significant increase in early glycation N?-fructosyl-lysine and AGE residue contents of endoneurial ECM. Glycation of laminin and fibronectin by methylglyoxal and glucose increased glycation adduct residue contents with methylglyoxal-derived hydroimidazolone and N?-fructosyl-lysine, respectively, of greatest quantitative importance. Glycation of laminin caused a significant decrease in both neurotrophin-stimulated and preconditioned sensory neurite outgrowth. This decrease was prevented by aminoguanidine. Glycation of fibronectin also decreased preconditioned neurite outgrowth, which was prevented by aminoguanidine and nerve growth factor. CONCLUSIONS Early glycation and AGE residue content of endoneurial ECM proteins increase markedly in STZ-induced diabetes. Glycation of laminin and fibronectin causes a reduction in neurotrophin-stimulated neurite outgrowth and preconditioned neurite outgrowth. This may provide a mechanism for the failure of collateral sprouting and axonal regeneration in diabetic neuropathy. PMID:19720799
Duran-Jimenez, Beatriz; Dobler, Darin; Moffatt, Sarah; Rabbani, Naila; Streuli, Charles H.; Thornalley, Paul J.; Tomlinson, David R.; Gardiner, Natalie J.
Several hundred thousand peripheral nerve injuries occur each year in Europe alone. Largely due to the death of around 40%\\u000a of primary sensory neurons, sensory outcome remains disappointingly poor despite considerable advances in surgical technique;\\u000a yet no clinical therapies currently exist to prevent this neuronal death. Acetyl-l-carnitine (ALCAR) is a physiological peptide with roles in mitochondrial bioenergetic function, which may
Andrew McKay Hart; Mikael Wiberg; Mike Youle; Giorgio Terenghi
Abstract The influence of breaching the connective sheaths of the donor sural nerve on axonal sprouting into the end-to-side coapted peroneal nerve was examined in the rat. In parallel, the effect of these procedures on the donor nerve was assessed. The sheaths of the donor nerve at the coaptation site were either left completely intact (group A) or they were breached by epineurial sutures (group B), an epineurial window (group C), or a perineurial window (group D). In group A, the compound action potential (CAP) of sensory axons was detected in ?10% and 40% of the recipient nerves at 4 and 8 weeks, respectively, which was significantly less frequently than in group D at both recovery periods. In addition, the number of myelinated axons in the recipient nerve was significantly larger in group D than in other groups at 4 weeks. At 8 weeks, the number of axons in group A was only ?15% of the axon numbers in other groups (p<0.05). Focal subepineurial degenerative changes in the donor nerves were only seen after 4 weeks, but not later. The average CAP area and the total number of myelinated axons in the donor nerves were not different among the experimental groups. In conclusion, myelinated sensory axons are able to penetrate the epiperineurium of donor nerves after end-to-side nerve coaption; however, their ingrowth into recipient nerves is significantly enhanced by breaching the epiperineurial sheets at the coaptation site. Breaching does not cause permanent injury to the donor nerve. PMID:22873667
Zele, Tilen; Tomsic, Martin; Sketelj, Janez; Bajrovic, Fajko F.
The transient receptor potential vanilloid type 1 (TRPV1) channel is a ligand-gated cation channel expressed by sensory nerves. P2Y receptors are G protein-coupled receptors that are also expressed by TRPV1-positive sensory neurons. Therefore, we studied interactions between P2Y receptors and TRPV1 function on kidney projecting sensory neurons. Application of Fast Blue (FB) to nerves surrounding the renal artery retrogradely labeled neurons in dorsal root ganglia of rats. Whole cell recording was performed on FB-labeled neurons maintained in primary culture. Capsaicin was used to activate TRPV1. Four types of kidney projecting neurons were identified based on capsaicin responses: 1) desensitizing (35%), 2) nondesensitizing (29%), 3) silent (3%), and 4) insensitive (30%). Silent neurons responded to capsaicin only after ATP (100 microM) pretreatment. ATP reversed desensitization in desensitizing neurons. Insensitive neurons never responded to capsaicin. UTP, a P2Y purinoceptor 2 (P2Y(2))/P2Y(4) receptor agonist, reversed capsaicin-induced TRPV1 desensitization. 2-methyl-thio-ATP (2-Me-S-ATP), a P2Y(1) receptor agonist, did not change desensitization. MRS 2179 and pyridoxal-phosphate-6-azophenyl-2',4'-disulfonic acid (PPADS), drugs that block P2Y(1) receptors, did not block ATP-induced resensitization of TRPV1. Suramin, a P2Y(2) receptor antagonist, blocked resensitization caused by UTP. Immunocytochemical studies showed that FB-labeled neurons coexpressed P2Y(2) receptors and TRPV1. We conclude that P2Y(2) receptor activation can maintain TRPV1 function perhaps during sustained episodes of activity of kidney projecting sensory neurons. PMID:20335377
Wang, Hui; Wang, Donna H; Galligan, James J
This study arose from the impression that there is a wide variation in the amplitude of the compound sensory nerve action potential (SNAP) when recorded using surface electrodes. Both the physiological factors influencing the SNAP and the method of measurement itself can be viewed as inputs to a system that produces the recorded value as its output. Taking a systems
Matthew C. Pitt
Summary The sensory ending of the frog muscle spindle consists of bulbous swellings interconnected by thin, tube-like axonal branches. This study was made to determine if the bulb or thin tube regions are deformed to the same degree during dynamic stretch, by comparing spindles prepared in the relaxed and stretched states. Isolated muscle spindles were rapidly frozen, either in a
Nobuhiro Kim; Noriaki Fujitsuka; Fumio Ito
Transient Receptor Potential A1 (TRPA1) is a nonselective cation channel, preferentially expressed on a subset of nociceptive sensory neurons, that is activated by a variety of reactive irritants via the covalent modification of cysteine residues. Excessive nitric oxide during inflammation (nitrative stress), leads to the nitration of phospholipids, resulting in the formation of highly reactive cysteine modifying agents, such as nitrooleic acid (9-OA-NO2). Using calcium imaging and electrophysiology, we have shown that 9-OA-NO2 activates human TRPA1 channels (EC50, 1 ?M), whereas oleic acid had no effect on TRPA1. 9-OA-NO2 failed to activate TRPA1 in which the cysteines at positions 619, 639, and 663 and the lysine at 708 had been mutated. TRPA1 activation by 9-OA-NO2 was not inhibited by the NO scavenger carboxy-PTIO. 9-OA-NO2 had no effect on another nociceptive-specific ion channel, TRPV1. 9-OA-NO2 activated a subset of mouse vagal and trigeminal sensory neurons, which also responded to the TRPA1 agonist allyl isothiocyanate and the TRPV1 agonist capsaicin. 9-OA-NO2 failed to activate neurons derived from TRPA1(-/-) mice. The action of 9-OA-NO2 at nociceptive nerve terminals was investigated using an ex vivo extracellular recording preparation of individual bronchopulmonary C fibers in the mouse. 9-OA-NO2 evoked robust action potential discharge from capsaicin-sensitive fibers with slow conduction velocities (0.4-0.7 m/s), which was inhibited by the TRPA1 antagonist AP-18. These data demonstrate that nitrooleic acid, a product of nitrative stress, can induce substantial nociceptive nerve activation through the selective and direct activation of TRPA1 channels. PMID:19171673
Taylor-Clark, Thomas E.; Ghatta, Srinivas; Bettner, Weston; Undem, Bradley J.
olfactory bulb glomeruli. To better understand the process by which information contained in the odorant-evoked firing of ORNs is transmitted to the brain, we examined the properties of glutamate release from olfactory nerve (ON) terminals in slices of the rat olfactory bulb. We show that marked paired pulse depression is the same in simultaneously recorded periglomerular and tufted neurons, and
Gabe J. Murphy; Lindsey L. Glickfeld; Zev Balsen; Jeffry S. Isaacson
This report describes the waveform and properties of somatosensory evoked potentials recorded from various levels of the human spinal cord, with electrodes inserted into the epidural space and the stimulus delivered to the posterior tibial nerve at the knee. The object was to provide a means of monitoring spinal cord function during surgery for the correction of spinal deformities. The
S J Jones; M A Edgar; A O Ransford
The electrodiagnostic yield of the medial plantar nerve action potential (NAP) amplitude versus the sural/radial amplitude ratio (SRAR) was determined in 110 consecutive patients with clinically diagnosed distal sensory polyneuropathy (SN) and normal sural responses. Forty-five consecutive patients with clinically diagnosed lumbosacral radiculopathy served as disease controls. Of the 110 SN patients, 32 were classified clinically as SN with large-fiber involvement (SN-LFI), whereas 78 had clinically pure small-fiber SN. Plantar NAP amplitudes were abnormal in 18 of 32 patients (56%) with SN-LFI, and 15 of 78 (19%) with small-fiber SN. A SRAR <0.21 (fifth percentile of normal) was found in 7 of 32 patients (22%) with SN-LFI and 8 of 78 (10%) with small-fiber SN. In the control group, the medial plantar NAP was normal in all 45 subjects (100%), whereas the SRAR was >0.21 in 43 subjects (96%). Thus, for a 50% pretest probability of SN-LFI, the positive predictive value of an abnormal medial plantar was 100% versus 85% for a SRAR <0.21. The medial plantar NAP amplitude is a more useful measure of SN, than is the SRAR, in patients under age 70, with suspected SN-LFI. The yield of the SRAR and plantar NAP amplitude is poor when clinical signs of large-fiber sensory dysfunction are lacking. PMID:18340276
Sullivan, John P; Logigian, Eric L; Kocharian, Naira; Herrmann, David N
Abstract The purposes of this study were to determine if induced radiating paresthesia interferes with (a) acquisition and/or (b) utilization of complex tactile information, and (c) identify whether interference reflects tactile masking or response competition. Radiating ulnar (experiment 1) and median (experiment 2) nerve paresthesia was quantified on ulnar innervated vibrotactile Morse code letter acquisition and recollection tasks. Induced paresthesia differentially impacted letter acquisition and recollection, but only when presented to the same anatomical spatial location. PMID:24844345
Passmore, Steven R; Bosse, Jessica; Murphy, Bernadette; Lee, Timothy D
After nerve injury, adult sensory neurons can regenerate peripheral axons and reconnect with their target tissue. Initiation of outgrowth, as well as elongation of neurites over long distances, depends on the signaling of receptors for neurotrophic growth factors. Here, we investigated the importance of gp130, the signaling subunit of neuropoietic cytokine receptors in peripheral nerve regeneration. After sciatic nerve crush, functional recovery in vivo was retarded in SNS-gp130(-/-) mice, which specifically lack gp130 in sensory neurons. Correspondingly, a significantly reduced number of free nerve endings was detected in glabrous skin from SNS-gp130(-/-) compared with control mice after nerve crush. Neurite outgrowth and STAT3 activation in vitro were severely reduced in cultures in gp130-deficient cultured neurons. Surprisingly, in neurons obtained from SNS-gp130(-/-) mice the increase in neurite length was reduced not only in response to neuropoietic cytokine ligands of gp130 but also to nerve growth factor (NGF), which does not bind to gp130-containing receptors. Neurite outgrowth in the absence of neurotrophic factors was partially rescued in gp130-deficient neurons by leptin, which activates STAT3 downstream of leptic receptor and independent of gp130. The neurite outgrowth response of gp130-deficient neurons to NGF was fully restored in the presence of leptin. Based on these findings, gp130 signaling via STAT3 activation is suggested not only to be an important regulator of peripheral nerve regeneration in vitro and in vivo, but as determining factor for the growth promoting action of NGF in adult sensory neurons. PMID:25253866
Quarta, Serena; Baeumer, Bastian E; Scherbakov, Nadja; Andratsch, Manfred; Rose-John, Stefan; Dechant, Georg; Bandtlow, Christine E; Kress, Michaela
After nerve injury, adult sensory neurons can regenerate peripheral axons and reconnect with their target tissue. Initiation of outgrowth, as well as elongation of neurites over long distances, depends on the signaling of receptors for neurotrophic growth factors. Here, we investigated the importance of gp130, the signaling subunit of neuropoietic cytokine receptors in peripheral nerve regeneration. After sciatic nerve crush, functional recovery in vivo was retarded in SNS-gp130?/? mice, which specifically lack gp130 in sensory neurons. Correspondingly, a significantly reduced number of free nerve endings was detected in glabrous skin from SNS-gp130?/? compared with control mice after nerve crush. Neurite outgrowth and STAT3 activation in vitro were severely reduced in cultures in gp130-deficient cultured neurons. Surprisingly, in neurons obtained from SNS-gp130?/? mice the increase in neurite length was reduced not only in response to neuropoietic cytokine ligands of gp130 but also to nerve growth factor (NGF), which does not bind to gp130-containing receptors. Neurite outgrowth in the absence of neurotrophic factors was partially rescued in gp130-deficient neurons by leptin, which activates STAT3 downstream of leptic receptor and independent of gp130. The neurite outgrowth response of gp130-deficient neurons to NGF was fully restored in the presence of leptin. Based on these findings, gp130 signaling via STAT3 activation is suggested not only to be an important regulator of peripheral nerve regeneration in vitro and in vivo, but as determining factor for the growth promoting action of NGF in adult sensory neurons. PMID:25253866
Quarta, Serena; Baeumer, Bastian E.; Scherbakov, Nadja; Andratsch, Manfred; Rose-John, Stefan; Dechant, Georg; Bandtlow, Christine E.
Substitution of natural sensory input by artificial neurostimulation of an amputated trigeminal nerve does not prevent the degeneration of basal forebrain cholinergic circuits projecting to the somatosensory cortex
Peripheral deafferentation downregulates acetylcholine (ACh) synthesis in sensory cortices. However, the responsible neural circuits and processes are not known. We irreversibly transected the rat infraorbital nerve and implanted neuroprosthetic microdevices for proximal stump stimulation, and assessed cytochrome-oxidase and choline- acetyl-transferase (ChAT) in somatosensory, auditory and visual cortices; estimated the number and density of ACh-neurons in the magnocellular basal nucleus (MBN); and localized down-regulated ACh-neurons in basal forebrain using retrograde labeling from deafferented cortices. Here we show that nerve transection, causes down regulation of MBN cholinergic neurons. Stimulation of the cut nerve reverses the metabolic decline but does not affect the decrease in cholinergic fibers in cortex or cholinergic neurons in basal forebrain. Artifical stimulation of the nerve also has no affect of ACh-innervation of other cortices. Cortical ChAT depletion is due to loss of corticopetal MBN ChAT-expressing neurons. MBN ChAT downregulation is not due to a decrease of afferent activity or to a failure of trophic support. Basalocortical ACh circuits are sensory specific, ACh is provided to each sensory cortex “on demand” by dedicated circuits. Our data support the existence of a modality-specific cortex-MBN-cortex circuit for cognitive information processing.
Herrera-Rincon, Celia; Panetsos, Fivos
Topical application of lidocaine is an effective approach for treatment of post-herpetic neuralgia and other painful neuropathies. Lidocaine inhibits voltage-gated Na(+) channels and it most likely reduces excitability of cutaneous sensory neurons which can be hyperexcitable or spontaneously active in states of neuropathic pain. However, lidocaine and other local anesthetics also exert a pronounced neurotoxicity and they activate the irritant receptors TRPV1 and TRPA1. In this randomized and double-blinded study, we explored the ability of lidocaine patches (5%) to alter sensory function and epidermal nerve fiber density in skin of healthy volunteers. As assessed by quantitative sensory testing, significantly elevated thresholds for touch, pin prick pain and mechanically induced wind-up were observed in skin treated with lidocaine patches. These effects reversed to baseline values within 2days after termination of the treatment. Pressure pain and thresholds for heat and cold-induced pain were not affected by the lidocaine patch. A moderate but significant decrease in epidermal nerve fiber density was observed in skin blister roofs obtained after 42days of treatment with lidocaine patches. The placebo patch did not induce any changes in sensory thresholds or nerve fiber density. In conclusion, lidocaine patches seem to have differential effects on sensory modalities in healthy skin. A degeneration of epidermal nerve fibers has previously been demonstrated for patches containing the TRPV1-agonist capsaicin and our findings suggest that this effect might also be relevant for lidocaine patches. These data warrant further studies on molecular mechanisms mediating a relief of neuropathic pain by topical lidocaine. PMID:21530339
Wehrfritz, Andreas; Namer, Barbara; Ihmsen, Harald; Mueller, Christiane; Filitz, Jörg; Koppert, Wolfgang; Leffler, Andreas
Although autogenous nerve grafting remains the gold standard for repair of peripheral nerve defects, the use of various conduits can be a substitute provided these conduits meet the above-mentioned prerequisites. For the moment, autogenous vein grafts or denatured muscle grafts can be used to bridge short defects, especially in distal sensory nerves. Incorporation of muscle into a vein graft expands
Huan Wang; William C. Lineaweaver
Administration of human recombinant nerve growth factor (rhNGF) into one hindpaw of capsaicin-treated rats can locally facilitate the regeneration of calcitonin gene-related peptide (CGRP)-containing primary sensory neurons (Schicho, R., Skofitsch, G., Donnerer, J., 1999. Brain Res. 815, 60–69). In this study we used in situ hybridization histochemistry (ISH) to determine synthesis of CGRP mRNA in lumbar L4 dorsal root ganglion
Rudolf Schicho; Josef Donnerer
Elevating levels of nerve growth factor (NGF) can have pronounced effects on the survival and maintenance of distinct populations of neurons. We have generated a line of transgenic mice in which NGF is expressed under the control of the smooth muscle ?-actin promoter. These transgenic mice have augmented levels of NGF protein in the descending colon and urinary bladder, so these tissues display increased densities of NGF-sensitive sympathetic efferents and sensory afferents. Here we provide a thorough examination of sympathetic and sensory axonal densities in the descending colon and urinary bladder of NGF transgenic mice with and without the expression of the p75 neurotrophin receptor (p75NTR). In response to elevated NGF levels, sympathetic axons (immunostained for tyrosine hydroxylase) undergo robust collateral sprouting in the descending colon and urinary bladder of adult transgenic mice (i.e., those tissues having smooth muscle cells); this sprouting is not augmented in the absence of p75NTR expression. As for sensory axons (immunostained for calcitonin gene-related peptide) in the urinary bladders of transgenic mice, fibers undergo sprouting that is further increased in the absence of p75NTR expression. Sympathetic axons are also seen invading the sensory ganglia of transgenic mice; these fibers form perineuronal plexi around a subpopulation of sensory somata. Our results reveal that elevated levels of NGF in target tissues stimulate sympathetic and sensory axonal sprouting and that an absence of p75NTR by sensory afferents (but not by sympathetic efferents) leads to a further increase of terminal arborization in certain NGF-rich peripheral tissues. PMID:23322532
Petrie, Casey N; Smithson, Laura J; Crotty, Anne-Marie; Michalski, Bernadeta; Fahnestock, Margaret; Kawaja, Michael D
1.Intravesical instillation of xylene (10–100%, dissolved in silicone oil) through a catheter implanted into the bladder of conscious, freely-moving rats produced behavioural effects (licking of lower abdomen or perineal region) suggestive of intense visceral pain, not mimicked by topical application of the irritant on the urethral outlet.2.The xylene-induced visceral pain was prevented, to the same extent, by systemic desensitization to
Luigi Abelli; Bruno Conte; Vincenzo Somma; Carlo Alberto Maggi; Sandro Giuliani; Pierangelo Geppetti; Massimo Alessandri; Elvar Theodorsson; Alberto Meli
Damage-induced neuronal endopeptidase (DINE) is a novel metallopeptidase and is expressed in response to various neu- ronal injuries. The expression regulation of DINE mRNA in the dorsal root ganglia (DRGs) after sciatic nerve injury is examined. A substantial increase of DINE mRNA expression was observed in relatively small-sized DRG neurons after nerve injury. The expression was observed in isolectin B4-negative
Ryuichi Kato; Sumiko Kiryu-Seo; Hiroshi Kiyama
To clarify the generator mechanism of sensory and motor facial responses ipsilateral to electrical stimulation of the inferior fronto-temporal cortex in epilepsy patients. Out of 30 patients who have been evaluated with chronically implanted subdural electrodes for medically intractable partial seizure or brain tumor involving the basal frontal or temporal cortex, 4 patients (age ranging 24–57 years) showed sensory and
Tahamina Begum; Akio Ikeda; Masao Matsuhashi; Nobuhiro Mikuni; Susumu Miyamoto; Nobuo Hashimoto; Takashi Nagamine; Hidenao Fukuyama; Hiroshi Shibasaki
Background: Patients with aspirin-sensitive rhinosi- nusitis, which is frequently associated with intrinsic bron- chial asthma, can be desensitized by long-term treat- ment with oral aspirin. The exact mechanisms of this desensitization remain obscure, but modulations of the eicosanoid pathway occur and can be monitored with the help of a practicable in vitro assay on mixed leukocyte cultures. some improvement, and
Jan Gosepath; Dirk Schaefer; Ronald G. Amedee; Wolf J. Mann
BACKGROUND: The lateral sciatic mid-femoral block (LSMF), proved to be reliable, safe, and effective on both branches of the sciatic nerve with a single injection. However, we do not know which component of the sciatic nerve (the tibial (T) or the common peroneal (CP)) produces a better success rate when performing a LSMF with a single injection technique. In this
Antoine Pianezza; Marie-Luce Gilbert; Vincent Minville; Daren Filsinger; Quentin Gobert; Olivier Fourcade
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 ?l saline into the nerve-injured paw induced
X. J Liu; T. D White; J Sawynok
We examined whether nerve growth factor (NGF), an inflammatory mediator that contributes to chronic hypersensitivity, alters the intracellular signaling that mediates the sensitizing actions of PGE2 from activation of protein kinase A (PKA) to exchange proteins directly activated by cAMP (Epacs). When isolated sensory neurons are grown in the absence of added NGF, but not in cultures grown with 30 ng/ml NGF, inhibiting protein kinase A (PKA) activity blocks the ability of PGE2 to augment capsaicin-evoked release of the neuropeptide CGRP and to increase the number of action potentials (APs) evoked by a ramp of current. Growing sensory neurons in culture in the presence of increasing concentrations of NGF increases the expression of Epac2, but not Epac1. An intradermal injection of complete Freund's adjuvant into the rat hindpaw also increases the expression of Epac2, but not Epac1 in the dorsal root ganglia and spinal cord: an effect blocked by intraplantar administration of NGF antibodies. Treating cultures grown in the presence of 30 ng/ml NGF with Epac1siRNA significantly reduced the expression of Epac1, but not Epac2, and did not block the ability of PGE2 to augment capsaicin-evoked release of CGRP from sensory neurons. Exposing neuronal cultures grown in NGF to Epac2siRNAreduced the expression of Epac2, but not Epac1 and prevented the PGE2-induced augmentation of capsaicin and potassium-evoked CGRP release in sensory neurons and the PGE2-induced increase in the number of APs generated by a ramp of current. In neurons grown with no added NGF, Epac siRNAs did not attenuate PGE2-induced sensitization. These results demonstrate that NGF, through increasing Epac2 expression, alters the signaling cascade that mediates PGE2-induced sensitization of sensory neurons, thus providing a novel mechanism for maintaining PGE2-induced hypersensitivity during inflammation. PMID:25126967
Vasko, Michael R.; Habashy Malty, Ramy; Guo, Chunlu; Duarte, Djane B.; Zhang, Yihong; Nicol, Grant D.
The crayfish stretch receptor consisting of the single mechanoreceptor neurons enveloped by satellite glial cells is the simplest functioning neuroglial preparation. However, during isolation, its axons are usually transected that eliminates afferent regulation and induces complex axotomy-related signaling responses in neurons and satellite glia. We developed new microsurgical method of crayfish stretch receptor isolation, which preserves connections of sensory neurons to the ventral nerve cord ganglion. The stretch receptor may either remain on the abdominal carapace, or be completely isolated. In both cases, it may be either intact, or axotomized. The integrity of axons was confirmed by firing recording from proximal and distal axon points. Normal, necrotic and apoptotic cells were visualized using double fluorochroming with Hoechst 33342 and propidium iodide. The isolated mechanoreceptor neurons maintain regular firing during 8-10 or more hours. Glial cells surrounding non-axotomized neurons demonstrate lower necrosis and apoptosis levels than the axotomized ones. Unlike the existing method, in which the sensory neurons were axotomized, the present method preserves links between the sensory neurons and the ganglion and makes possible to avoid consequences of axotomy in neurons and satellite glia. The present neuroglial preparation may be used as a simple but informative model object in studies of axotomy-induced degeneration and survival of peripheral neurons, the role of glia in neuron injury, the signaling mechanisms of neuroglial interactions, and the effects of diverse physical and chemical factors on neuronal and glial cells. PMID:25374161
Khaitin, Andrej M; Rudkovskii, Mikhail V; Uzdensky, Anatoly B
Background Paclitaxel, a widely-used antineoplastic drug, produces a painful peripheral neuropathy that in rodents is associated with peripheral-nerve mitochondrial alterations. The sigma-1 receptor (?1R) is a ligand-regulated molecular chaperone involved in mitochondrial calcium homeostasis and pain hypersensitivity. This receptor plays a key role in paclitaxel-induced neuropathic pain, but it is not known whether it also modulates mitochondrial abnormalities. In this study, we used a mouse model of paclitaxel-induced neuropathic pain to test the involvement of the ?1R in the mitochondrial abnormalities associated with paclitaxel, by using genetic (?1R knockout mice) and pharmacological (?1R antagonist) approaches. Results Paclitaxel administration to wild-type (WT) mice produced cold- and mechanical-allodynia, and an increase in the frequency of swollen and vacuolated mitochondria in myelinated A-fibers, but not in C-fibers, of the saphenous nerve. Behavioral and mitochondrial alterations were marked at 10 days after paclitaxel-administration and had resolved at day 28. In contrast, paclitaxel treatment did not induce allodynia or mitochondrial abnormalities in ?1R knockout mice. Moreover, the prophylactic treatment of WT mice with BD-1063 also prevented the neuropathic pain and mitochondrial abnormalities induced by paclitaxel. Conclusions These results suggest that activation of the ?1R is necessary for development of the sensory nerve mitochondrial damage and neuropathic pain produced by paclitaxel. Therefore, ?1R antagonists might have therapeutic value for the prevention of paclitaxel-induced neuropathy. PMID:24517272
The Center for Disease Control guidelines recommend desensitization to metronidazole in patients with trichomoniasis and hypersensitivity to metronidazole. There is only one published oral metronidazole desensitization protocol. The purpose of this study was to design a new, more gradual oral desensitization protocol to decrease systemic reactions that may occur when using the previously published protocol. We present two patients with presumed IgE-mediated allergy to metronidazole who underwent oral desensitization using our modified protocol. Case 1 was a 65-year-old woman with trichomoniasis who presented for metronidazole desensitization with a history of intraoperative anaphylaxis and positive skin tests to metronidazole. The patient tolerated six doses of the modified desensitization but developed systemic symptoms of nasal congestion and diffuse pruritus after the 25- and 100-mg doses. Both reactions were treated with intravenous (i.v.) antihistamines. Because of gastrointestinal irritation, the desensitization was completed at a dose of 250 mg orally every 6 hours. Case 2 was a 42-year-old woman with trichomoniasis and a history of hives immediately after administration of i.v. metronidazole who presented for desensitization. The patient had negative skin-prick and intradermal testing to metronidazole. She developed lip tingling and pruritus on her arms 15 minutes after the 10-mg dose. Fexofenadine at 180 mg was given orally and symptoms resolved. She tolerated the rest of the protocol without reaction and received a total dose of 2 g of metronidazole. Our oral metronidazole desensitization for presumed IgE-mediated reactions offers a second option for physicians wishing to use a more gradual escalation in dose. PMID:24612959
Pien, Lily C.; Gutta, Ravi C.; Abouhassan, Susan R.
Background and Purpose Hydrogen sulphide (H2S) is a gas that has recently been shown to have biological activity. In the majority of blood vessels studied so far, H2S has been shown to cause vasorelaxation, although contractile responses have been reported. In the present study, we have made a pharmacological assessment of the effects of H2S in mesenteric small arteries isolated from rats. Experimental Approach Rat mesenteric small arteries were studied using pressure myography. In pressurised arteries, responses were obtained to the H2S donor, sodium hydrogen sulphide (NaHS), in the absence and presence of the NOS inhibitor L-NAME, raised extracellular potassium, the KATP channel inhibitor glibenclamide, the Cl– channel blockers DIDS, NPPB and A9C, the TRPV1 receptor desensitizing agent, capsaicin, the CGRP antagonist, olcegepant, the TRPV1 channel blocker capsazepine and the TRPA1 channel blocker HC-030031. Key Results NaHS produced a vasodilator response in rat mesenteric small arteries held at 90 mmHg. Responses to NaHS were not reproducible. Neither, glibenclamide nor, L-NAME inhibited responses to NaHS. DIDS abolished vasodilator responses to NaHS, but these were unaffected by the chloride channel blockers, NPPB and A9C. Responses to NaHS were attenuated after capsaicin pre-treatment, by a CGRP receptor antagonist and an inhibitor of TRPA1 channels. Conclusions and Implications In small arteries isolated from the rat mesentery, NaHS caused a vasodilatation. This response was not reproducible in vitro, since it was mediated by the release of sensory neurotransmitters in a capsaicin-like action. This release was mediated by a H2S-induced activation of TRPA1 channels. PMID:22928888
White, Benjamin J O; Smith, Paul A; Dunn, William R
ATP-gated P2X3 receptors are mostly expressed by nociceptive sensory neurons and participate in transduction of pain signals. P2X3 receptors show a combination of fast desensitization onset and slow recovery. Moreover, even low nanomolar agonist concentrations unable to evoke a response, can induce desensitization via a phenomenon called “high affinity desensitization.” We have also observed that recovery from desensitization is agonist-specific and can range from seconds to minutes. The recovery process displays unusually high temperature dependence. Likewise, recycling of P2X3 receptors in peri-membrane regions shows unexpectedly large temperature sensitivity. By applying kinetic modeling, we have previously shown that desensitization characteristics of P2X3 receptor are best explained with a cyclic model of receptor operation involving three agonist molecules binding a single receptor and that desensitization is primarily developing from the open receptor state. Mutagenesis experiments suggested that desensitization depends on a certain conformation of the ATP binding pocket and on the structure of the transmembrane domains forming the ion pore. Further molecular determinants of desensitization have been identified by mutating the intracellular N- and C-termini of P2X3 receptor. Unlike other P2X receptors, the P2X3 subtype is facilitated by extracellular calcium that acts via specific sites in the ectodomain neighboring the ATP binding pocket. Thus, substitution of serine275 in this region (called “left flipper”) converts the natural facilitation induced by extracellular calcium to receptor inhibition. Given their strategic location in nociceptive neurons and unique desensitization properties, P2X3 receptors represent an attractive target for development of new analgesic drugs via promotion of desensitization aimed at suppressing chronic pain. PMID:24367291
Giniatullin, Rashid; Nistri, Andrea
Capsaicin (Cap) is a pungent extract of the Capsicum pepper family, which activates nociceptive primary sensory neurons. Inward current and membrane potential responses of cultured neonatal rat dorsal root ganglion neurons to capsaicin were examined using whole-cell and perforated patch recording methods. The responses exhibited strong desensitization operationally classified as acute (diminished response during constant Cap exposure) and tachyphylaxis (diminished response to successive applications of Cap). Both acute desensitization and tachyphylaxis were greatly diminished by reductions in external Ca2+ concentration. Furthermore, chelation of intracellular Ca2+ by addition of either EGTA or bis(2-aminophenoxy)ethane-N,N,N',N'-tetra-acetic acid to the patch pipette attenuated both forms of desensitization even in normal Ca2+. Release of intracellular Ca2+ by caffeine triggered acute desensitization in the absence of extracellular Ca2+, and barium was found to effectively substitute for calcium in supporting desensitization. Cap activated inward current at an ED50 of 728 nM, exhibiting cooperativity (Hill coefficient, 2.2); however, both forms of desensitization were only weakly dependent on [Cap], suggesting a dissociation between activation of Cap-sensitive channels and desensitization. Removal of ATP and GTP from the intracellular solutions resulted in nearly complete tachyphylaxis even with intracellular Ca2+ buffered to low levels, whereas changes in nucleotide levels did not significantly alter the acute form of desensitization. These data suggest a key role for intracellular Ca2+ in desensitization of Cap responses, perhaps through Ca2+-dependent dephosphorylation at a locus that normally sustains Cap responsiveness via ATP-dependent phosphorylation. It also seems that the signaling mechanisms underlying the two forms of desensitization are not identical in detail. PMID:9133377
Koplas, P A; Rosenberg, R L; Oxford, G S
Melanocortin receptor ligands accelerate functional recovery after peripheral nerve crush. It is not known which mechanism is involved or via which melanocortin receptor this effect occurs, albeit indirect evidence favours the melanocortin MC4 receptor. To test whether the melanocortin MC4 receptor is involved in the effects of melanocortins on functional recovery, we used melanocortin compounds that distinguish the melanocortin MC4
Wouter A. J. Nijenhuis; Nienke Wanders; John A. W. Kruijtzer; Rob M. Liskamp; Willem Hendrik Gispen; Roger A. H. Adana
We examined the contribution of potassium channels to the inhibitory effect of morphine on the increase in substance P release and cutaneous blood flow evoked by antidromic stimulation of the sectioned sciatic nerve. Cutaneous blood flow in the instep of the rat hind paw was measured by the non-invasive technique of laser Doppler flowmetry. Antidromic stimulation of the sectioned sciatic
Norifumi Yonehara; Sou Takiuchi
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 ?m 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
Witherspoon, J W; Smirnova, I V; McIff, T E
The ?2?-1 protein is an auxiliary subunit of voltage-gated calcium channels, critical for neurotransmitter release. It is upregulated in dorsal root ganglion (DRG) neurons following sensory nerve injury, and is also the therapeutic target of the gabapentinoid drugs, which are efficacious in both experimental and human neuropathic pain conditions. ?2?-1 has 3 spliced regions: A, B, and C. A and C are cassette exons, whereas B is introduced via an alternative 3? splice acceptor site. Here we have examined the presence of ?2?-1 splice variants in DRG neurons, and have found that although the main ?2?-1 splice variant in DRG is the same as that in brain (?2?-1 ?A+B+C), there is also another ?2?-1 splice variant (?A+B?C), which is expressed in DRG neurons and is differentially upregulated compared to the main DRG splice variant ?2?-1 ?A+B+C following spinal nerve ligation. Furthermore, this differential upregulation occurs preferentially in a small nonmyelinated DRG neuron fraction, obtained by density gradient separation. The ?2?-1 ?A+B?C splice variant supports CaV2 calcium currents with unaltered properties compared to ?2?-1 ?A+B+C, but shows a significantly reduced affinity for gabapentin. This variant could therefore play a role in determining the efficacy of gabapentin in neuropathic pain. PMID:24315988
Lana, Beatrice; Schlick, Bettina; Martin, Stuart; Pratt, Wendy S.; Page, Karen M.; Goncalves, Leonor; Rahman, Wahida; Dickenson, Anthony H.; Bauer, Claudia S.; Dolphin, Annette C.
fibers and the subepidermal neural plexus in capsaicin-treated skin, as indicated by the loss of immunoreactivity for PGP 9.5 and CGRP. The effect of capsaicin on dermal nerve fibers immunoreactive for SP was less obvious. Capsaicin decreased sensitivity to pain produced by sharp mechanical stimuli and nearly eliminated heat-evoked pain within the injected area. Limited reinnervation of the epidermis and
Donald A. Simone; Maria Nolano; Timothy Johnson; Gwen Wendelschafer-Crabb; William R. Kennedy
Information about the activity of airway sensory afferent nerves in vivo can be obtained electrophysiologically by extracellular recording of action potentials. Apart from data capture, the basic techniques used for recording sensory nerve activity have not advanced greatly in 50 years. However, clearly they continue to contribute vastly to our understanding of the role of these nerves in the control
John J Adcock
This article reviews self-control desensitization research with test anxious college students. The first section presents a discussion of the development of self-control desensitization (SCD) as a modification of systematic desensitization (SD), and procedures which differentiate SCD from SD including treatment rationale, the nature of anxiety…
Capsaicin activates a non-specific cation conductance in mammalian sensory neurones. If capsaicin is applied continuously\\u000a or repeatedly then there is a progressive decline in responsiveness. We have studied the mechanism of this desensitization\\u000a using electro-physiological methods in cultured dorsal root ganglion neurones from adult rats. The rate of desensitization\\u000a of capsaicin-induced responses is partly dependent on the extracellular calcium concentration
R. J. Docherty; J. C. Yeats; S. Bevan; H. W. G. M. Boddeke
The direct effect of guidance cues on developing and regenerating axons in vivo is not fully understood, as the process involves a multiplicity of attractive and repulsive signals, presented both as soluble and membrane-bound ligands. A better understanding of axon guidance is critical to functional recovery following injury to the nervous system through improved outgrowth and mapping of damaged nerves. Due to their implications as inhibitors to central nervous system regeneration, we investigated the repulsive properties of semaphorin 6A and ephrin-B3 on E15 rat dorsal root ganglion explants, as well as possible interactions with soluble gradients of chemoattractive nerve growth factor (NGF). We employed a 3D biomimetic in vitro choice point model, which enabled the simple and rapid preparation of patterned gel growth matrices with quantifiable presentation of guidance cues in a specifiable manner that resembles the in vivo presentation of soluble and/or immobilized ligands. Neurites demonstrated an inhibitory response to immobilized Sema6A by lumbosacral dorsal root ganglion explants, while no such repulsion was observed for immobilized ephrin-B3 by explants at any spinal level. Interestingly, Sema6A inhibition could be partially attenuated in a concentration-dependent manner through the simultaneous presentation of soluble NGF gradients. The in vitro model described herein represents a versatile and valuable investigative tool in the quest for understanding developmental processes and improving regeneration following nervous system injury. PMID:25189126
Curley, J Lowry; Catig, Gary C; Horn-Ranney, Elaine L; Moore, Michael J
The T-junction of sensory neurons in the dorsal root ganglion (DRG) is a potential impediment to action potential (AP) propagation towards the CNS. Using intracellular recordings from rat DRG neuronal somata during stimulation of the dorsal root, we determined that the maximal rate at which all of 20 APs in a train could successfully transit the T-junction (following frequency) was lowest in C-type units, followed by A-type units with inflected descending limbs of the AP, and highest in A-type units without inflections. In C-type units, following frequency was slower than the rate at which AP trains could be produced in either dorsal root axonal segments or in the soma alone, indicating that the T-junction is a site that acts as a low-pass filter for AP propagation. Following frequency was slower for a train of 20 APs than for two, indicating that a cumulative process leads to propagation failure. Propagation failure was accompanied by diminished somatic membrane input resistance, and was enhanced when Ca2+-sensitive K+ currents were augmented or when Ca2+-sensitive Cl? currents were blocked. After peripheral nerve injury, following frequencies were increased in axotomized C-type neurons and decreased in axotomized non-inflected A-type neurons. These findings reveal that the T-junction in sensory neurons is a regulator of afferent impulse traffic. Diminished filtering of AP trains at the T-junction of C-type neurons with axotomized peripheral processes could enhance the transmission of activity that is ectopically triggered in a neuroma or the neuronal soma, possibly contributing to pain generation. PMID:23148321
Gemes, Geza; Koopmeiners, Andrew; Rigaud, Marcel; Lirk, Philipp; Sapunar, Damir; Bangaru, Madhavi Latha; Vilceanu, Daniel; Garrison, Sheldon R; Ljubkovic, Marko; Mueller, Samantha J; Stucky, Cheryl L; Hogan, Quinn H
Nesfatin-1 belongs to a family of anorexigenic peptides, which are responsible for satiety and are identified in the neurons and endocrine cells within the gut. These peptides have been implicated in the control of food intake; however, very little is known concerning its contribution to gastric secretion and gastric mucosal integrity. In this study the effects of nesfatin-1 on gastric secretion and gastric lesions induced in rats by 3.5h of water immersion and restraint stress (WRS) were determined. Exogenous nesfatin-1 (5-40?g/kg i.p.) significantly decreased gastric acid secretion and attenuated gastric lesions induced by WRS, and this was accompanied by a significant rise in plasma NUCB2/nefatin-1 levels, the gastric mucosal blood flow (GBF), luminal NO concentration, generation of PGE2 in the gastric mucosa, an overexpression of mRNA for NUBC2 and cNOS, as well as a suppression of iNOS and proinflammatory cytokine IL-1? and TNF-? mRNAs. Nesfatin-1-induced protection was attenuated by suppression of COX-1 and COX-2 activity, the inhibition of NOS with L-NNA, the deactivation of afferent nerves with neurotoxic doses of capsaicin, and the pretreatment with capsazepine to inhibit vanilloid VR1 receptors. This study shows for the first time that nesfatin-1 exerts a potent protective action in the stomach of rats exposed to WRS and these effects depend upon decrease in gastric secretion, hyperemia mediated by COX-PG and NOS-NO systems, the activation of vagal and sensory nerves and vanilloid receptors. PMID:23978788
Szlachcic, Alexandra; Sliwowski, Zbigniew; Krzysiek-Maczka, Gracjana; Majka, Jolanta; Surmiak, Marcin; Pajdo, Robert; Drozdowicz, Danuta; Konturek, Stanislaw J; Brzozowski, Tomasz
Indirect chronic electrical stimulation of skeletal muscle activates not only efferent but also afferent nerve fibres. To investigate effects specific to this on capillary growth, one of the earliest changes, cell proliferation and capillary ultrastructure were studied in ankle flexors of rats with and without deafferentation of the stimulated side. Two weeks after preganglionic section of dorsal roots L4-L6, the peroneal nerve was stimulated (10 Hz, 8 h day?1) for 2 or 7 days. Proliferating nuclei labelled by bromodeoxyuridine or proliferating cell nuclear antigen staining were colocalized to alkaline phosphatase-stained capillaries (Lc) or other interstitial nuclei (Li) in frozen sections of extensor digitorum longus. Capillary fine structure was examined in extensor hallucis proprius by transmission electron microscopy. The stimulation-induced increase in capillary and interstitial proliferation (Lc 9.9 ± 1.9 %, Li 8.8 ± 2.1 % vs. Lc 2.6 ± 0.4 %, Li 1.9 ± 0.3 % in controls, P < 0.05) was depressed at 2 days by dorsal root section (Lc 4.8 ± 0.7 %, Li 3.2 ± 0.9 %, P < 0.05), an effect likely to be mainly on fibroblasts; no depression was seen at 7 days. Dorsal root section reduced stimulation-induced capillary endothelial swelling at both time points. In contralateral muscles of intact rats, stimulation increased interstitial cell proliferation and capillary swelling, both effects being eliminated by dorsal root section. Capillary growth induced by stimulation (24 % increase in capillary:fibre ratio at 7 days) was unaffected by deafferentation. The reduction in capillary ultrastructural changes and interstitial proliferation in both stimulated and contralateral muscles implies that stimulation of afferent fibres leads directly to release of humoral factors and/or activation via dorsal roots of fibres that release humoral substances. Contralateral muscles are an inadequate control for the effects of chronic stimulation in the intact animal. PMID:12563006
Hudlicka, Olga; Graciotti, Laura; Fulgenzi, Gianluca; Brown, Margaret D; Egginton, S; Milkiewicz, Malgorzata; Granata, Anna-Luisa
A method to substantially desensitize a metastable intermolecular composite material to electrostatic discharge and friction comprising mixing the composite material with an organic diluent and removing enough organic diluent from the mixture to form a mixture with a substantially putty-like consistency, as well as a concomitant method of recovering the metastable intermolecular composite material.
Busse, James R. (South Fork, CO); Dye, Robert C. (Los Alamos, NM); Foley, Timothy J. (Los Alamos, NM); Higa, Kelvin T. (Ridgecrest, CA); Jorgensen, Betty S. (Jemez Springs, NM); Sanders, Victor E. (White Rock, NM); Son, Steven F. (Los Alamos, NM)
The stretch receptor organs of Alexandrowicz in lobster and crayfish possess sensory neurons which have their cell bodies in the periphery. The cell bodies send dendrites into a fine nearby muscle strand and at the opposite pole they give rise to an axon running to the central nervous system. Mechanisms of excitation between dendrites, cell soma, and axon have been studied in completely isolated receptor structures with the cell components under visual observation. Two sensory neuron types were investigated, those which adapt rapidly to stretch, the fast cells, and those which adapt slowly, the slow cells. 1. Potentials recorded from the cell body of the neurons with intracellular leads gave resting potentials of 70 to 80 mv. and action potentials which in fresh preparations exceeded the resting potentials by about 10 to 20 mv. In some experiments chymotrypsin or trypsin was used to make cell impalement easier. They did not appreciably alter resting or action potentials. 2. It has been shown that normally excitation starts in the distal portion of dendrites which are depolarized by stretch deformation. The changed potential within the dendritic terminals can persist for the duration of stretch and is called the generator potential. Secondarily, by electrotonic spread, the generator potential reduces the resting potential of the nearby cell soma. This excitation spread between dendrites and soma is seen best during subthreshold excitation by relatively small stretches of normal cells. It is also seen during the whole range of receptor stretch in neurons in which nerve conduction has been blocked by an anesthetic. The electrotonic changes in the cells are graded, reflecting the magnitude and rate of rise of stretch, and presumably the changing levels of the generator potential. Thus in the present neurons the resting potential and the excitability level of the cell soma can be set and controlled over a wide range by local events within the dendrites. 3. Whenever stretch reduces the resting membrane potential, measured in the relaxed state in the cell body, by 8 to 12 mv. in slow cells and by 17 to 22 mv. in fast cells, conducted impulses are initiated. It is thought that in slow cells conducted impulses are initiated in the dendrites while in fast cells they arise in the cell body or near to it. In fresh preparations the speed of stretch does not appreciably influence the membrane threshold for discharges, while during developing fatigue the firing level is higher when extension is gradual. 4. Some of the specific neuron characteristics are: Fast receptor cells have a relatively high threshold to stretch. During prolonged stretch the depolarization of the cell soma is not well maintained, presumably due to a decline in the generator potential, resulting in cessation of discharges in less than a minute. This appears to be the basis of the relatively rapid adaptation. A residual subthreshold depolarization can persist for many minutes of stretch. Slow cells which resemble the sensory fibers of vertebrate spindles are excited by weak stretch. Their discharge rate remains remarkably constant for long periods. It is concluded that, once threshold excitation is reached, the generator potential within slow cell dendrites is well maintained for the duration of stretch. Possible reasons for differences in discharge properties between fast and slow cells are discussed. 5. If stretch of receptor cells is gradually continued above threshold, the discharge frequency first increases over a considerable range without an appreciable change in the firing level for discharges. Beyond that range the membrane threshold for conducted responses of the cell soma rises, the impulses become smaller, and partial conduction in the soma-axon boundary region occurs. At a critical depolarization level which may be maintained for many minutes, all conduction ceases. These overstretch phenomena are reversible and resemble cathodal block. 6. The following general scheme of excitation is proposed: stretch deformation of dendritic terminals ? generat
Eyzaguirre, Carlos; Kuffler, Stephen W.
The capsaicin receptor, VR1 (also known as TRPV1), is a ligand-gated ion channel expressed on nociceptive sensory neurons that responds to noxious thermal and chemical stimuli. Capsaicin responses in sensory neurons exhibit robust potentiation by cAMP-dependent protein kinase (PKA). In this study, we demonstrate that PKA reduces VR1 desensitization and directly phosphorylates VR1. In vitro phosphorylation, phosphopeptide mapping, and protein
Gautam Bhave; Weiguo Zhu; Haibin Wang; D. J Brasier; Gerry S Oxford; Robert W Gereau IV
To find if children do become desensitized to violence, a test for a measurable physiological difference in emotional response to filmed violence was administered to children who are high exposure and low exposure television viewers. (Author/KM)
Cline, Victor B.; And Others
The effect of proximal and distal peripheral nerve injuries on the histochemistry of carbonic anhydrase (CA) in rat dorsal root ganglion (DRG) neurons, and myelinated (MyF) dorsal and ventral root fibers was studied. Sciatic neurectomy induced no change. Contrariwise, 7 days after lumbar spinal nerve section the numbers of CA-stained ventral root MyF and DRG cells at the L4 and
J. M. Peyronnard; L. F. Charron; J. P. Messier; J. Lavoie
Peripheral nerve injury impairs motor, sensory, and autonomic function, incurring substantial financial costs and diminished quality of life. For large nerve gaps, proximal lesions, or chronic nerve injury, the prognosis for recovery is particularly poor, even with autografts, the current gold standard for treating small to moderate nerve gaps. In vivo elongation of intact proximal stumps towards the injured distal stumps of severed peripheral nerves may offer a promising new strategy to treat nerve injury. This review describes several nerve lengthening strategies, including a novel internal fixator device that enables rapid and distal reconnection of proximal and distal nerve stumps.
Vaz, Kenneth M.; Brown, Justin M.; Shah, Sameer B.
Peripheral nerve surgery represents a broad field of pathologic conditions, medical specialties, and anatomic regions of the body. Anatomic understanding of hierarchical nerve structure and the peripheral nervous system aids diagnosis and management of nerve lesions. Many peripheral nerves coalesce into organized arrays, including the cervical, brachial, and lumbosacral plexuses, controlling motor and sensory functions of the trunk and extremities. Individual or groups of nerves may be affected by various pathologic conditions, including trauma, entrapment, tumor, or iatrogenic damage. Current research efforts focus on enhancing the peripheral nerve regenerative process by targeting Schwann cells, nerve growth factors, and nerve allografts. PMID:24210320
Pindrik, Jonathan; Belzberg, Allan J
Summary A previously unrecognized neuropathy was identified in Bulgarian gypsies, and was designated hereditary motor and sensory neuropathy-Lom (HMSNL) after the town where the initial cases were found. It was subsequently identified in other gypsy communities. The disorder, which is of autosomal recessive inheritance, was mapped to chromosome 8q24. It begins consistently in the first decade of life with gait
Luba Kalaydjieva; Amelia Nikolova; Ivo Turnev; Julia Petrova; Anna Hristova; Boryana Ishpekova; Iva Petkova; Alexander Shmarov; Stella Stancheva; L. Middleton; Luciano Merlini; A. Trogu; J. R. Muddle; R. H. M. King; P. K. Thomas
We studied whether tissue levels of nitric oxide (NO) and cGMP are regulated by sensory nerves in normoxic and ischemic hearts. Wistar rats were treated with capsaicin to deplete neurotransmitters from capsaicin-sensitive sensory nerves. In separate experiments, capsaicin was applied perineurally to both vagus nerves for selective chemodenervation of vagal cardiac afferent nerves. Systemic capsaicin administration significantly decreased basal myocardial
Tamás Csont; Csaba Csonka; Péter Kovács; Gábor Jancsó; Péter Ferdinandy
BACKGROUND: The role of the neurotrophin regulated polypeptide, VGF, has been investigated in a rat spared injury model of neuropathic pain. This peptide has been shown to be associated with synaptic strengthening and learning in the hippocampus and while it is known that VGFmRNA is upregulated in dorsal root ganglia following peripheral nerve injury, the role of this VGF peptide
Andrew Moss; Rachel Ingram; Stephanie Koch; Andria Theodorou; Lucie Low; Mark Baccei; Gareth J Hathway; Michael Costigan; Stephen R Salton; Maria Fitzgerald
Following proximal peripheral nerve injury, motor recovery is often poor due to prolonged muscle denervation and loss of regenerative potential. The transfer of a sensory nerve to denervated muscle results in improved functional recovery in experimental models. The authors here report the first clinical case of sensory protection. Following a total hip arthroplasty, this patient experienced a complete sciatic nerve palsy with no recovery at 3 months postsurgery and profound denervation confirmed electrodiagnostically. He underwent simultaneous neurolysis of the sciatic nerve and saphenous nerve transfers to the tibialis anterior branch of the peroneal nerve and gastrocnemius branch from the tibial nerve. He noted an early proprioceptive response. Electromyography demonstrated initially selective amelioration of denervation potentials followed by improved motor recovery in sensory protected muscles only. The patient reported clinically significant functional improvements in activities of daily living. The authors hypothesize that the presence of a sensory nerve during muscle denervation can improve functional motor recovery. PMID:18976091
Bain, James R; Hason, Yaniv; Veltri, Karen; Fahnestock, Margaret; Quartly, Caroline
Genetics of congenital insensitivity to pain with anhidrosis (CIPA) or hereditary sensory and autonomic neuropathy type IV. Clinical, biological and molecular aspects of mutations in TRKA(NTRK1) gene encoding the receptor tyrosine kinase for nerve growth factor.
Congenital insensitivity to pain with anhidrosis (CIPA) or hereditary sensory and autonomic neuropathy type IV (HSAN-IV) is an autosomal recessive disorder characterized by recurrent episodic fevers, anhidrosis (inability to sweat), absence of reaction to noxious (or painful) stimuli, self-mutilating behavior and mental retardation. The anomalous pain and temperature sensation and anhidrosis in CIPA are due to the absence of afferent neurons activated by tissue-damaging stimuli and a loss of innervation of eccrine sweat glands, respectively. Nerve growth factor (NGF) supports the survival of nociceptive sensory and autonomic sympathetic neurons as well as cholinergic neurons of the basal forebrain. The human TRKA (NTRKI) gene located on chromosome 1 (1q21-q22) encodes a receptor tyrosine kinase (RTK) which is autophosphorylated in response to NGF, thus, activating various pathways of intracellular signal transduction. We earlier identified the genetic basis of CIPA by detecting mutations in TRKA gene of patients. Defects in NGF signal transduction at its receptor lead to failure to survive as various NGF dependent neurons are not maintained, most probably due to apoptosis during development. TRKA mutations are distributed in an extracellular domain involved in NGF binding, as well as in the intracellular signal-transduction domain. Missense mutations with loss of function provide considerable insight into the structure-function relationship in the RTK family. In view of the fact that defects in TRKA cause CIPA, the molecular pathology of CIPA provides unique opportunities to explore critical roles of the NGF-TRKA receptor system. Thus, CIPA can serve as a useful model to determine mechanisms of development and maintenance of NGF-dependent neurons in autonomic, sensory and central nervous systems, as well as the physiology of these neurons in humans. PMID:12102460
CC-63 TIP DESENSITIZATION OF AN AXIAL TURBINE ROTOR USING PARTIAL SQUEALER RIMS Debashis Dey1 to a significant degree. INTRODUCTION The gap required between the tips of rotating blades and the stationary casing of an axial flow turbine is a significant source of inefficiency. The leakage flow mainly induced
A method to substantially desensitize a metastable intermolecular composite material to electrostatic discharge and friction comprising mixing the composite material with an organic diluent and removing enough organic diluent from the mixture to form a mixture with a substantially putty-like consistency, as well as a concomitant method of recovering the metastable intermolecular composite material.
Busse, James R. (South Fork, CO); Dye, Robert C. (Los Alamos, NM); Foley, Timothy J. (Los Alamos, NM); Higa, Kelvin T. (Ridgecrest, CA); Jorgensen, Betty S. (Jemez Springs, NM); Sanders, Victor E. (White Rock, NM); Son, Steven F. (Los Alamos, NM)
to achieve long-term survival of human neural grafts in the adult mammalian brain, based on desensitizing in Table 1. All experimental and surgical procedures were conducted under the UK Animals (Scientific Procedures) Act 1986, and subject to local ethical review and the relevant personal, project and institution
A six-to nine-month interview follow-up showed that five of the seven traceable Ss given the interpersonal aversion-systematic desensitization treatment had been abstinent, compared with only one of seven treated by the interpersonal aversion-control procedure. (Author)
Primo, Richard V.; And Others
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.
Background Whether the method of local anesthetic administration for continuous femoral nerve blocks —basal infusion versus repeated hourly bolus doses —influences block effects remains unknown. Methods Bilateral femoral perineural catheters were inserted in volunteers (n = 11). Ropivacaine 0.1% was administered through both catheters concurrently: a 6-h continuous 5 ml/h basal infusion on one side and 6 hourly bolus doses on the contralateral side. The primary endpoint was the maximum voluntary isometric contraction (MVIC) of the quadriceps femoris muscle at Hour 6. Secondary end points included quadriceps MVIC at other time points, hip adductor MVIC, and cutaneous sensation 2 cm medial to the distal quadriceps tendon in the 22 h following local anesthetic administration initiation. Results Quadriceps MVIC for limbs receiving 0.1% ropivacaine as a basal infusion declined by a mean (SD) of 84% (19) compared with 83% (24) for limbs receiving 0.1% ropivacaine as repeated bolus doses between baseline and Hour 6 (paired t test P = 0.91). Intrasubject comparisons (left vs. right) reflected a lack of difference as well: the mean basal-bolus difference in quadriceps MVIC at Hour 6 was ?1.1% (95% CI ?22.0 to 19.8%). The similarity did not reach our a priori threshold for concluding equivalence, which was the 95% CI falling within ± 20%. There were similar minimal differences in the secondary endpoints during local anesthetic administration. Conclusions This study did not find evidence to support the hypothesis that varying the method of local anesthetic administration —basal infusion versus repeated bolus doses —influences continuous femoral nerve block effects to a clinically significant degree. PMID:21394001
Charous, Matthew T.; Madison, Sarah J.; Suresh, J.; Sandhu, NavParkash S.; Loland, Vanessa J.; Mariano, Edward R.; Donohue, Michael C.; Dutton, Pascual H.; Ferguson, Eliza J.; Ilfeld, Brian M.
The characteristics of the different populations of sensory nerve The correlation between the physiologically and mor- terminals that selectively contact pulmonary neuroepithelial phologically defined lung receptors, however, is far from bodies (NEBs) in rat lungs were investigated after chemical satisfactory. Although the number of studies dealing with denervation with capsaicin and compared with control lungs. the morphology of the sensory
Inge Brouns; Jeroen Van Genechten; Hiroyuki Hayashi; Mariusz Gajda; Toshiaki Gomi; Geoff Burnstock; Jean-Pierre Timmermans; Dirk Adriaensen
Since the last update on nerve conduits and allograft in 2000, investigations have established the efficacy of these alternatives to autograft in the repair of small sensory neural gaps. However, limited insights into the biology of the regenerating nerve continue to preclude intelligent conduit design. Ongoing discoveries in neuroscience and biomaterial engineering hold promise for the eventual development of allograft and conduits with potential of surpassing nerve autografts in clinical efficacy. In this review, we summarize the history, recent advances, and emerging developments in nerve conduits and allograft. PMID:23895714
Lin, Michael Y; Manzano, Givenchy; Gupta, Ranjan
Cranial nociceptive perception shows a distinct topographic distribution, with the trigeminal nerve receiving sensory information\\u000a from the anterior portions of the head, the greater occipital nerve, and branches of the upper cervical roots in the posterior\\u000a regions. However, this distribution is not respected during headache attacks, even if the etiology of the headache is specific\\u000a for only one nerve. Nociceptive
Elcio J. Piovesan; Pedro A. Kowacs; Michael L. Oshinsky
Identification of the molecule(s) that globally induce a robust regenerative state in sensory neurons following peripheral nerve injury remains elusive. A potential candidate is brain-derived neurotrophic factor (BDNF), the sole neurotrophin upregulated in sensory neurons after peripheral nerve injury. Here we tested the hypothesis that BDNF plays a critical role in the regenerative response of mature rat sensory neurons following
Nicole M. Geremia; Lina M. E. Pettersson; J. C. Hasmatali; Todd Hryciw; Nils Danielsen; David J. Schreyer; Valerie M. K. Verge
Aspirin sensitivity is relatively frequent and can be a major problem in patients who need percutaneous coronary intervention and stenting with subsequent dual antiplatelet therapy. Desensitization is often the therapy in these patients, but this can prolong the time to revascularization significantly. Rapid oral aspirin desensitization protocols have been described since 2000. However, data are lacking on the optimal strategy for aspirin desensitization and determining which patients are mostly benefited from this desensitization. The authors describe the use of a Wong-modified protocol in 3 patients who had known aspirin sensitivity and who had unstable angina and an indication for percutaneous coronary intervention. PMID:20739873
Ortega-Loayza, Alex G; Raza, Syed; Minisi, Anthony J; Topaz, On; Heller, Andrew; Jovin, Ion S
Recent studies have demonstrated that in vivo administration of 1-deamino-8-D-arginine-vasopressin, an analog of arginine-8-vasopressin, induces homologous desensitization to vasopressin in the thick ascending limb of the loop of Henle. Desensitization has been documented by a decreased physiological response to vasopressin in vivo and by a reduced cAMP accumulation in the cortical thick ascending limb (CTAL). By measuring cAMP content in single isolated medullary thick ascending limbs (MTALs), we now report that desensitization can occur all along the thick ascending limb and, more importantly, that it can also be induced in vitro. In a first series of experiments, we observed that 1 hr after in vivo injection of 1-deamino-8-D-arginine-vasopressin, MTALs were desensitized by 80% to vasopressin, whereas the effects of the other hormones acting on the same cyclase pool (glucagon, calcitonin) were fully maintained. In a second set of experiments, desensitization was induced in vitro by vasopressin, the natural hormone. A 60-min preincubation of MTALs with vasopressin caused a marked (up to 86%) and highly reproducible desensitization. The process was dose and time dependent. The apparent Ka for desensitization was 0.2 nM, and the half-maximal effect was obtained within 20 min. The desensitization induced in vitro by vasopressin was again essentially homologous in nature, with 80% of the maximal stimulation of cAMP accumulation being obtained in the presence of glucagon. Desensitization to vasopressin was observed in the presence and absence of indomethacin, indicating that it is independent of prostaglandin synthesis. It is concluded that (i) vasopressin and its analog 1-deamino-8-D-arginine-vasopressin cause marked desensitization in the CTAL and MTAL and (ii) the low vasopressin concentrations required to induce desensitization and the rapid onset of the process suggest that it has a physiological significance. PMID:1699229
Dublineau, I; Pradelles, P; de Rouffignac, C; Elalouf, J M
Leprosy neuropathy is characterized by initial involvement of the small nerve fibers, later followed by involvement of the large fibers, when routine nerve conduction studies become abnormal. To increase the diagnostic yield and precocity of these studies, we applied the near nerve technique to the sural nerve of 8 leprosy patients. Contrary to our expectations, the main component of the sural nerve sensory action potential was abnormal in all patients, but the minimum conduction velocity originating from small 3-6 mm fibers was normal or only mildly involved in three patients. Also, although Schwann cells are the first to be involved in leprosy, the results are suggestive of axonal degeneration instead of demyelination. To better understand the neurophysiology and physiology of leprosy and to increase the accuracy and precocity of the diagnosis, it will be necessary to investigate patients in the very early stages of the disease and to correlate these findings with the corresponding nerve pathology. PMID:15334210
Arruda, Ana Paula M; Marques, Wilson; Foss, Norma T; Garbino, José A; Virmond, Marcos; Barreira, Amilton A
Until now, more than 800 distinct G protein-coupled receptors (GPCRs) have been identified in the human genome. The four subtypes of the adenosine receptor (A1, A2A, A2B and A3 receptor) belong to this large family of GPCRs that represent the most widely targeted pharmacological protein class. Since adenosine receptors are widespread throughout the body and involved in a variety of physiological processes and diseases, there is great interest in understanding how the different subtypes are regulated, as a basis for designing therapeutic drugs that either avoid or make use of this regulation. The major GPCR regulatory pathway involves phosphorylation of activated receptors by G protein-coupled receptor kinases (GRKs), a process that is followed by binding of arrestin proteins. This prevents receptors from activating downstream heterotrimeric G protein pathways, but at the same time allows activation of arrestin-dependent signalling pathways. Upon agonist treatment, adenosine receptor subtypes are differently regulated. For instance, the A1Rs are not (readily) phosphorylated and internalize slowly, showing a typical half-life of several hours, whereas the A2AR and A2BR undergo much faster downregulation, usually shorter than 1 h. The A3R is subject to even faster downregulation, often a matter of minutes. The fast desensitization of the A3R after agonist exposure may be therapeutically equivalent to antagonist occupancy of the receptor. This review describes the process of desensitization and internalization of the different adenosine subtypes in cell systems, tissues and in vivo studies. In addition, molecular mechanisms involved in adenosine receptor desensitization are discussed. PMID:18368531
Klaasse, Elisabeth C.; de Grip, Willem J.; Beukers, Margot W.
Biofeedback training to reduce test anxiety among university students was investigated. Biofeedback training with systematic desensitization was compared to an automated systematic desensitization program not using EMG feedback. Biofeedback training is a useful technique for reducing test anxiety, but not necessarily more effective than systematic…
Romano, John L.; Cabianca, William A.
Somatosensory deficit syndromes represent a common impairment following stroke and have a prevalence rate of around 80% in stroke survivors. These deficits restrict the ability of survivors to explore and manipulate their environment and are generally associated with a negative impact on quality of life and personal safety. Sensory impairments affect different sensory modalities in diverse locations at varying degrees, ranging from complete hemianesthesia of multiple modalities to dissociated impairment of somatosensory submodalities within a particular region of the body. Sensory impairments induce typical syndromal patterns which can be differentiated by means of a careful neurological examination, allowing the investigator to deduce location and size of the underlying stroke. In particular, a stroke located in the brainstem, thalamus, and the corticoparietal cortex result in well-differentiable sensory syndromes. Sensory function following stroke can be regained during rehabilitation even without specific sensory training. However, there is emerging evidence that specialized sensory interventions can result in improvement of somatosensory and motor function. Herein, we summarize the clinical presentations, examination, differential diagnoses, and therapy of sensory syndromes in stroke. PMID:22377851
Klingner, Carsten M; Witte, Otto W; Günther, Albrecht
The sensitized guinea pig was employed as a model to study the effect of immunological activation of resident mast cells on neuronal activity in the airways. The trachea was isolated with the vagus nerves and vagal sensory ganglia intact. Using conventional electrophysiological recording techniques, we noted that antigenic stimulation led to an increase in the sensitivity of sensory nerve endings
Bradley J. Undem; Margerita M. Riccio; Daniel Weinreich; James L. Ellis; Allen C. Myers
Morphological findings in sural nerves were related to nerve conduction in 12 patients with diabetic neuropathy, five with mainly sensory involvement, four with severe, symmetrical sensory-motor polyneuropathy, and three with multiple mononeuropathy. All had loss of large and small myelinated and of unmyelinated fibres, even early in the disease; segmental remyelination was the most prominent myelin alteration in teased fibres,
F Behse; F Buchthal; F Carlsen
Compared verbal and physiological reactions to sensory deprivation (SD) and extreme sensory variation (SV). 22 male undergraduates were confined to a cubicle for 8 hr. in each condition on 2 different occasions. 2 other 8-hr sessions were spent in a relatively normal, nonconfined condition. Ss found SD more boring, dislikable, and anxiety and depression provoking than SV. More unreality stress
Marvin Zuckerman; Harold Persky; Lynne Miller; Bernard Levine
Peripheral nerve trauma remains a major cause of morbidity, largely due to the death of ?40% of innervating sensory neurons, and to slow regeneration after repair. Acetyl-L-carnitine (ALCAR) is a physiological peptide that virtually eliminates sensory neuronal death, and may improve regeneration after primary nerve repair. This study determines the effect of ALCAR upon regeneration after secondary nerve repair, thereby
Andrew McKay Hart; Mikael Wiberg; Giorgio Terenghi
Nerve growth factor (NGF) is largely known as a target-derived factor responsible for the survival and maintenance of the phenotype of specific subsets of peripheral neurones and basal forebrain cholinergic nuclei during development and maturation. However, NGF also exerts a modulatory role on sensory, nociceptive nerve physiology during adulthood that appears to correlate with hyperalgesic phenomena occurring in tissue inflammation.
Rita Levi-Montalcini; Stephen D. Skaper; Roberto Dal Toso; Lucia Petrelli; Alberta Leon
We report on magnetic resonance neurography (MRN) as a supplementary diagnostic tool in sciatic nerve injection injury. The\\u000a object of the study was to test if T2-weighted (w) contrast within the sciatic nerve serves as an objective criterion for\\u000a sciatic injection injury. Three patients presented with acute sensory and\\/or motor complaints in the distribution of the sciatic\\u000a nerve after dorsogluteal
Mirko Pham; Carsten Wessig; Jörg Brinkhoff; Karlheinz Reiners; Guido Stoll; Martin Bendszus
Spina bifida aperta (SBA) is an open neural tube defect that occurs during the embryonic period. We created SBA chicks by incising the roof plate of the neural tube in the embryo. The area of the dorsal funiculus was smaller in the SBA chicks than in the normal controls. Additionally, the SBA group had fewer nerve fibres in the dorsal funiculus than the normal controls. The pathway of the ascending sensory nerves was revealed by tracing the degenerated nerve fibres using osmification. We cut the sciatic nerve (L5) of the control and SBA chicks at the central end of the dorsal root ganglion 1 day after hatching and fixed the tissue 3 days later. Degenerated sensory nerve fibres were observed in the ipsilateral dorsal funiculus in the control chicks. In contrast, degenerated sensory nerve fibres were observed in the ipsilateral and contralateral dorsal, ventral and lateral funiculi of the spinal cord in the SBA chicks. Consequently, fewer sensory nerve fibres ascended to the thoracic dorsal funiculus in the SBA chicks than in the normal controls. This is the first report of abnormal changes in the ascending sensory nerve fibres in SBA. PMID:21658418
Tsujimura, Ryusuke; Mominoki, Katsumi; Kinutani, Masae; Shimokawa, Tetsuya; Doihara, Takuya; Nabeka, Hiroaki; Wakisaka, Hiroyuki; Kobayashi, Naoto; Matsuda, Seiji
Cough is a common and protective reflex, but persistent coughing is debilitating and impairs quality of life. Antitussive treatment using opioids is limited by unacceptable side effects, and there is a great need for more effective remedies. The present study demonstrates that theobromine, a methylxanthine derivative present in cocoa, effectively inhibits citric acid- induced cough in guinea-pigs in vivo. Furthermore,
Omar S. Usmani; Maria G. Belvisi; Hema J. Patel; Natascia Crispino; Mark A. Birrell; Márta Korbonits; Peter J. Barnes
THE nature of granulomas remains uncertain. In sarcoidosis and Crohn's disease of the ileum, the aetiology is unknown. Even where a causative organism has been identified, as in tuberculosis and non-lepromatous leprosy, the role the mycobacteria play in the development of the granuloma is obscure1. There is no animal model available for the study of granulomatous hypersensitivity. But in susceptible
C. L. Crawford; P. M. D. Hardwicke; D. H. L. Evans; E. M. Evans
G protein-coupled receptors (GPCRs) are involved in a multitude of signaling processes and respond to a wide range of ligands. The activity of GPCRs is subject to three principal modes of regulation: desensitization, trafficking, and down-regulation. Desensitization is defined as a loss in the responsiveness of a signaling system. The generally established paradigm for GPCR desensitization involves receptor phosphorylation by GPCR kinases (GRKs), initiated by agonist-induced conformational changes in the receptor or by kinases activated by specific signaling pathways. GRKs have several interaction domains and may be able to contribute to receptor desensitization through mechanisms that do not involve the kinase activity of GRK. Pao and Benovic discuss some of these interactions and their relevance for the regulation of GPCR signaling.
Christina S. Pao (Thomas Jefferson University;The Kimmel Cancer Center, Department of Microbiology and Immunology REV); Jeffrey L. Benovic (Thomas Jefferson University;The Kimmel Cancer Center, Department of Microbiology and Immunology REV)
Irritation of eyes and upper airways--sensory irritation--is commonly used as a parameter for setting occupational exposure limits and is a common complaint in occupants of non-industrial buildings. Sensory irritation occurs from stimulation of receptors on trigeminal nerves. In general, chemically reactive compounds are more potent than non-reactive congeners. Animal studies allow prediction of sensory irritation effects in humans; the concentration-effect relationships are often steep. In humans, thresholds and suprathreshold effects can be obtained from short-term ( approximately seconds) exposures and from longer exposures ( approximately hours). Sensory irritation may develop over time and odour cues may influence reported sensory irritation symptoms; generally, the slope of the irritant effect is steeper than the slope of odour cues. A best available no-observed-adverse-effect level (NOAEL) should be based on a combined estimate from the three types of study. The NOAEL/5 is considered sufficient to protect individuals not especially sensitive. The present knowledge suggests that especially sensitive individuals may be protected by an additional uncertainty factor (UF) of 2, suggesting a combined UF of 10. In published studies, the combined UF is up to 300, highlighting the need of evidence-based UFs. Combined effects of sensory irritants can be considered additive as a first approximation. PMID:17241726
Nielsen, Gunnar Damgård; Wolkoff, Peder; Alarie, Yves
Autosomal dominant sensory ataxia (ADSA), a rare hereditary ataxia, is characterized by progressive dysfunction of central\\u000a sensory pathways. Its pathological features have not been previously documented. We report a case of a 61-year-old man with\\u000a ADSA who died of congestive heart failure. Autopsy specimens of brain, thoracolumbar spinal cord, peripheral nerve and skeletal\\u000a muscle were examined. There was no abnormality
Jeremy J. Moeller; Robert J. B. Macaulay; Paul N. Valdmanis; Lyle E. Weston; Guy A. Rouleau; Nicolas Dupré
Eighty-two patients with a chief complaint of plantar heel pain were evaluated for sensory abnormalities within the cutaneous distribution of both the medial calcaneal nerve and the medial plantar nerve, using quantitative neurosensory testing with a pressure-specified sensory device. The results showed that 22.68% of the patients displayed isolated abnormal sensory function within the distribution of the medial calcaneal nerve,
Jonathan D. Rose; D. Scot Malay; Dean L. Sorrento
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.
Winfried Neuhuber; Anna Mysicka
Diabetic neuropathy is the most common and debilitating complication of diabetes mellitus with over half of all patients developing altered sensation as a result of damage to peripheral sensory neurons. Hyperglycemia results in altered nerve...
Jack, Megan Marie
Vitamin D deficiency is associated with increased susceptibility to inflammatory arthritis. Sensory and sympathetic synovial nerves are critical to the development of inflammatory arthritis and spontaneously degenerate in the early phases of disease. These nerves contain vitamin D receptors and vitamin D influences nerve growth and neurotrophin expression. We therefore examined the density of synovial nerves and neurotrophin-containing cells in vitamin D-deficient rats. Seven-week-old Sprague-Dawley rats were fed either control or vitamin D-deficient diets for 4weeks. Knee synovium sections extending from the patella to the meniscus were immunostained for total nerves, myelinated and unmyelinated nerves, sympathetic nerves, peptidergic and non-peptidergic sensory nerves, and neurotrophins and immune cell markers. In control rats, intimal innervation by unmyelinated sensory fibers was denser than subintimal innervation. In contrast, sympathetic innervation was confined to the subintima. Many sensory axons contained markers for both peptidergic and non-peptidergic nerves. Nerve growth factor (NGF) was primarily expressed by intimal CD163-negative type B synoviocytes, while neurturin, a ligand selective for non-peptidergic sensory neurons, was expressed by synovial mast cells. In vitamin D-deficient rats, there were significant reductions in sensory nerves in the intima and sympathetic nerves in the subintima. While there was no significant change in NGF-immunoreactivity, the number of neurturin-expressing mast cells was significantly reduced in the intima, suggesting that intimal reductions in sensory nerves may be related to reductions in neurturin. Vitamin D deficiency therefore may increase susceptibility to inflammatory arthritis by depleting sensory and sympathetic synovial nerves as a result of reduced synovial neurotrophin content. PMID:25193239
Tague, S E; Smith, P G
by the finding that the applica- tion of 1 mM capsaicin to the tongue reversibly inhibited the neural response; extravasation; capsaicin; tongue; nociception THE SENSITIVITY OF SOME elements of the cutaneous sensory system demonstrated that irritation due to citric acid was diminished by oral desensitization by capsaicin (4
Moore, Paul A.
Capsaicin applied topically to human skin produces itching, pricking and burning sensations due to excitation of nociceptors. With repeated application, these positive sensory responses are followed by a prolonged period of hypalgesia that is usually referred to as desensitization, or nociceptor inactivation. Consequently, capsaicin has been recommended as a treatment for a variety of painful syndromes. The precise mechanisms that
Maria Nolano; Donald A Simone; Gwen Wendelschafer-Crabb; Timothy Johnson; Eric Hazen; William R Kennedy
Lipofibromatous hamartoma of the nerve is a benign tumor, which affects the major nerves and their branches in the human body. It is often found in the median nerve of the hand and is commonly associated with macrodactyly, but it is rarely found in the digital nerves at the peripheral level. This tumor is often found in young adults and may go through a self-limiting course. However, operation is indicated when the tumor size is large or when the associated nerve compressive symptoms are present. We have experienced a rare case of lipofibromatous hamartoma that symmetrically involved the volar digital nerves of both index fingers on the ulnar side. With the aid of a microscope, we dissected and removed the tumor as much as possible without sacrificing the nerve. No sensory change occurred in both fingers and no sign of recurrence was observed upon follow-up. PMID:15744823
Jung, Sung-No; Yim, Youngmin
\\u000a Together, the relationship between the mechanical response of neural tissues and the related mechanisms of injury provide\\u000a a foundation for defining relevant thresholds for injury. The nerves and nerve roots are biologic structures with specific\\u000a and important functions, and whose response to mechanical loading can have immediate, long-lasting and widespread consequences.\\u000a In particular, when nerves or nerve roots are mechanically
Kristen J. Nicholson; Beth A. Winkelstein
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
Veillona, F; Ramos-Taboada, L; Abu-Eid, M; Charpiot, A; Riehm, S
In the management of traumatic peripheral nerve injuries, the severity or degree of injury dictates the decision making between surgical management versus conservative management and serial examination. This review explores some of the recent literature, specifically addressing recent basic science advances in end-to-side and reverse end-to-side recovery, Schwann cell migration, and neuropathic pain. The management of nerve gaps, including the use of nerve conduits and acellularized nerve allografts, is examined. Current commonly performed nerve transfers are detailed with focus on both motor and sensory nerve transfers, their indications, and a basic overview of selected surgical techniques. PMID:22032591
Boyd, Kirsty U; Nimigan, André S; Mackinnon, Susan E
The neuronal mechano-gated K2P channels TREK-1 and TRAAK show pronounced desensitization within 100 ms of membrane stretch. Desensitization persists in the presence of cytoskeleton disrupting agents, upon patch excision, and when channels are expressed in membrane blebs. Mechanosensitive currents evoked with a variety of complex stimulus protocols were globally fit to a four-state cyclic kinetic model in detailed balance, without the need to introduce adaptation of the stimulus. However, we show that patch stress can be a complex function of time and stimulation history. The kinetic model couples desensitization to activation, so that gentle conditioning stimuli do not cause desensitization. Prestressing the channels with pressure, amphipaths, intracellular acidosis, or the E306A mutation reduces the peak-to-steady-state ratio by changing the preexponential terms of the rate constants, increasing the steady-state current amplitude. The mechanical responsivity can be accounted for by a change of in-plane area of ?2 nm2 between the closed and open conformations. Desensitization and its regulation by chemical messengers is predicted to condition the physiological role of K2P channels. PMID:16636285
Honore, Eric; Patel, Amanda Jane; Chemin, Jean; Suchyna, Thomas; Sachs, Frederick
Sensory innervation of the gastrointestinal (GI) tract by the vagus nerve plays important roles in regulation of GI function and feeding behavior. This innervation is composed of a large number of sensory pathways, each arising from a different population of sensory receptors. Progress in understanding the functions of these pathways has been impeded by their close association with vagal efferent,
Edward Alan Fox
Desensitization to violence is cited frequently as being an outcome of exposure to media violence and a condition that contributes to increased aggression. This article initiates the development of a conceptual model for describing possible relationships among violent video games, brain function, and desensitization by using empathy and attitudes toward violence as proxy measures of desensitization. More work is needed to understand how specific game content may affect brain activity, how brain development may be affected by heavy play at young ages, and how personality and lifestyle variables may moderate game influence. Given the current state of knowledge, recommendations are made for clinicians to help parents monitor and limit exposure to violent video games and encourage critical thinking about media violence. PMID:15936665
Funk, Jeanne B
Aim: Studies were conducted to define the kinetics of the onset of and recovery from desensitization for human ?4?2-nicotinic acetylcholine receptors (nAChR) heterologously expressed in the SH-EP1 human epithelial cell line. Methods: Whole-cell patch clamp recordings were performed to evaluate ?4?2-nAChR currents. Results: Application of 0.1 ?mol/L nicotine or 1 mmol/L acetylcholine (ACh) for 1 s or longer induced two phases, with time constants of ?70 and ?700 ms, for the onset of ?4?2-nAChR desensitization. For a given duration of agonist exposure, recovery from desensitization induced by nicotine was slower than recovery from ACh-induced desensitization. Comparisons with published reports indicate that time constants for the recovery of ?4?2-nAChRs from desensitization are smaller than those for the recovery of human muscle-type nAChRs1 from desensitization produced by the same concentrations and durations of exposure to an agonist. Moreover, the extent of human ?4?2-nAChR desensitization and rate of recovery are the same, regardless of whether they are measured using whole-cell recording or based on published findings2 using isotopic ion flux assays; this equality demonstrates the equivalent legitimacy of these techniques in the evaluation of nAChR desensitization. Perhaps most significantly, recovery from desensitization also was best fit to a biphasic process. Regardless of whether it was fit to single or double exponentials, however, half-times for recovery from desensitization grew progressively longer with an increased duration of agonist exposure during the desensitizing pulse. Conclusion: These findings indicate the existence of ?4?2-nAChRs in many distinctive states of desensitization, as well as the induction of progressively deeper states of desensitization with the increased duration of agonist exposure. PMID:19498421
Yu, Kewei D; Liu, Qiang; Wu, Jie; Lukas, Ronald J
Highly anxious self-referred snake phobics received either (a) therapist-administered desensitization, (b) self-administered desensitization with weekly therapist phone calls, (c) totally self-administered desensitization, (d) self-administered double-blind placebo control, or (e) no treatment. Pretreatment to posttreatment measures revealed…
Rosen, Gerald M.; And Others
Eye movement desensitization and reprocessing (EMDR) is a method which was initially used for the treatment of post-traumatic stress disorder. But it is now being used in different therapeutic situations. EMDR is an eight-phase treatment method. History taking, client preparation, assessment, desensitization, installation, body scan, closure and reevaluation of treatment effect are the eight phases of this treatment which are briefly described. A case report is also depicted which indicates the efficacy of EMDR. The areas where EMDR is used and the possible ways through which it is working are also described. PMID:21716864
Menon, Sukanya B; Jayan, C
Eye movement desensitization and reprocessing (EMDR) is a method which was initially used for the treatment of post-traumatic stress disorder. But it is now being used in different therapeutic situations. EMDR is an eight-phase treatment method. History taking, client preparation, assessment, desensitization, installation, body scan, closure and reevaluation of treatment effect are the eight phases of this treatment which are briefly described. A case report is also depicted which indicates the efficacy of EMDR. The areas where EMDR is used and the possible ways through which it is working are also described. PMID:21716864
Menon, Sukanya B.; Jayan, C.
The nerve growth factor protein, NGF, has been shown to play a physiologic role in the development and regeneration of the peripheral nervous system, acting on sensory and sympathetic ganglia. In the central nervous system, NGF induces choline acetyltrans...
J. R. Perez-Polo
The nerve growth factor protein, NGF, has been shown to play a physiologic role in the development and regeneration of the peripheral nervous system, acting on sensory and sympathetic ganglia. In the central nervous system, NGF induces choline acetyltrans...
J. R. Perez-Polo
The nerve growth factor protein, NGF, has been shown to play a physiologic role in the development and regeneration of the peripheral nervous system, acting on sensory and sympathetic ganglia. In the central nervous system, NGF induces choline acetyltrans...
J. R. Perez-Polo
The discussion of overdentures has been confined to their capacity to use abutment teeth to improve neuromuscular control of mandibular movement. Use of overdentures has been favored often because of their mechanical advantages, but seldom because of the sensory role of the retained abutment teeth. Even though the retained teeth may be periodontally diseased, they still may provide sufficient support for the transmission of masticatory pressures and sufficient periodontal ligament receptors to initiate a jaw opening reflex. Whereas conflicting evidence shows that the periodontal nerve receptors play a role in mandibular positional sensibility (proprioception), pressure perception by the periodontal ligament remains a primary stimulus for the jaw opening reflex. Additional investigations will be essential to a complete understanding of the role of the periodontal ligament receptors. However, recognition of the importance of the periodontal ligament receptors to the overdenture patient as a source of sensory input is vital. PMID:1066472
Kay, W D; Abes, M S
The nervus terminalis (NT; terminal nerve) was clearly identified as an additional cranial nerve in humans more than a century ago yet remains mostly undescribed in modern anatomy textbooks. The nerve is referred to as the nervus terminalis because in species initially examined its fibers were seen entering the brain in the region of the lamina terminalis. It has also been referred to as cranial nerve 0, but because there is no Roman symbol for zero, an N for the Latin word nulla is a better numerical designation. This nerve is very distinct in human fetuses and infants but also has been repeatedly identified in adult human brains. The NT fibers are unmyelinated and emanate from ganglia. The fibers pass through the cribriform plate medial to those of the olfactory nerve fila. The fibers end in the nasal mucosa and probably arise from autonomic/neuromodulatory as well as sensory neurons. The NT has been demonstrated to release luteinizing-releasing luteinizing hormone and is therefore thought to play a role in reproductive behavior. Based on the available evidence, the NT appears to be functional in adult humans and should be taught in medical schools and incorporated into anatomy/neuroanatomy textbooks. PMID:22836597
Vilensky, Joel A
Crystal structures of Gloeobacter violaceus ligand-gated ion channel (GLIC), a proton-gated prokaryotic homologue of pentameric ligand-gated ion channel (LGIC) from G. violaceus, have provided high-resolution models of the channel architecture and its role in selective ion conduction and drug binding. However, it is still unclear which functional states of the LGIC gating scheme these crystal structures represent. Much of this uncertainty arises from a lack of thorough understanding of the functional properties of these prokaryotic channels. To elucidate the molecular events that constitute gating, we have carried out an extensive characterization of GLIC function and dynamics in reconstituted proteoliposomes by patch clamp measurements and EPR spectroscopy. We find that GLIC channels show rapid activation upon jumps to acidic pH followed by a time-dependent loss of conductance because of desensitization. GLIC desensitization is strongly coupled to activation and is modulated by voltage, permeant ions, pore-blocking drugs, and membrane cholesterol. Many of these properties are parallel to functions observed in members of eukaryotic LGIC. Conformational changes in loop C, measured by site-directed spin labeling and EPR spectroscopy, reveal immobilization during desensitization analogous to changes in LGIC and acetylcholine binding protein. Together, our studies suggest conservation of mechanistic aspects of desensitization among LGICs of prokaryotic and eukaryotic origin. PMID:22474322
Velisetty, Phanindra; Chakrapani, Sudha
This study investigated the impact of group systematic desensitization (SD) on varied aspects of sexual functioning in primary and secondary nonorgasmic women. After serving as their own controls, 22 women (eight primary, 14 secondary) received 15 sessions of group SD using four common hierarchies of sexual scenes. The measures were administered to each subject and her regular sex partner at
Wayne M. Sotile; Peter R. Kilmann
Since Shapiro's introduction of Eye Movement Desensitization and Reprocessing (EMDR) in 1989, it has been a highly controversial therapeutic technique. Critical reviews of Shapiro's initial study have highlighted many methodological shortcomings in her work. And early empirical research that followed Shapiro's original study has been criticized…
Erwin, Terry McVannel
The proteasome inhibitor bortezomib has been used with variable success in the treatment of AMR following heart transplant. There is limited experience with this agent as a pretransplant desensitizing therapy. We report a case of successful HLA desensitization with a bortezomib-based protocol prior to successful heart transplantation. A nine-yr-old boy with dilated cardiomyopathy, not initially sensitized to HLA (cPRA of zero), required three days of ECMO, followed by implantation of a Heartmate II LVAD. Within six wk, the patient developed de novo class I IgG and C1q complement-fixing HLA antibodies with a cPRA of 100%. Two doses of IVIG (2 g/kg) failed to reduce antibody levels, although two courses of a novel desensitization protocol consisting of rituximab (375 mg/m(2) ), bortezomib (1.3 mg/m(2) × 5 doses), and plasmapheresis reduced his cPRA to 0% and 87% by the C1q and IgG assays, respectively. He underwent heart transplantation nearly two months later. The patient is now >one yr post-transplant, is free of both AMR and ACR, and has no detectable donor-specific antibodies by IgG or C1q. Proteasome inhibition with bortezomib and plasmapheresis may be an effective therapy for HLA desensitization pretransplant. PMID:25174602
May, Lindsay J; Yeh, Justin; Maeda, Katsuhide; Tyan, Dolly B; Chen, Sharon; Kaufman, Beth D; Bernstein, Daniel; Rosenthal, David N; Hollander, Seth A
In determining whether the technique of desensitization would reduce the initial anxiety experienced by the beginning counselor trainee, analyses of the data revealed significantly less self-reported anxiety in the experimental group. No differences were found in heart rate, skin resistance, and tape-evaluation measures. (Author/CG(
Monke, Robert H.
This study investigated the process of fear change during a course of systematic desensitization therapy. Behavioral, subjective, and physiological measures of fear were taken following each of eight therapy sessions. Changes in one fear system did not appear to be primary in initiating changes in the other fear systems. (Author)
Schroeder, Harold E.; Rich, Alex R.
Investigates the effectiveness of group systematic desensitization in reducing death anxiety. Densensitization proved to be superior with both a relaxation and test-retest group when the revised Livingston and Zimet Death Anxiety Scale was the criterion measure. Mixed results were obtained when other scales were used. (Author/JAC)
Peal, Ronald L.; And Others
The present investigation compared two prominent models of phobia treatment: the desensitization model, which emphasizes extinction of conditioned anxiety responses by exposing people to feared stimuli at low levels of anxiety arousal, and the self-efficacy model, which emphasizes building a strong sense of mastery by helping people accomplish new tasks rapidly and assuredly. Height phobics were assigned randomly to one
S. Lloyd Williams; Samuel M. Turner; David F. Peer
Eye Movement Desensitization and Reprocessing (EMDR) is a new psychological methodology that has been applied to a wide range of psychological disorders. Clinical reports over the past three years indicate that it is an important addition to the treatment of substance abuse. EMDR offers a structured, client-centered model that integrates key elements of intrapsychic, behavioral, cognitive, body-oriented, and interactional approac
Francine Shapiro; Silke Vogelmann-Sine; Larry F. Sine
The behavioral effects of nicotine and other nicotinic agonists are mediated by AChRs in the brain. The relative contribution of acute activation versus chronic desensitization of AChRs is unknown. Sustained “smoldering activation” occurs over a range of agonist concentrations at which activated and desensitized AChRs are present in equilibrium. We used a fluorescent dye sensitive to changes in membrane potential to examine the effects of acute activation and chronic desensitization by nicotinic AChR agonists on cell lines expressing human ?4?2, ?3?4 and ?7 AChRs. We examined the effects of acute and prolonged application of nicotine and the partial agonists varenicline, cytisine and sazetidine-A on these AChRs. The range of concentrations over which nicotine causes smoldering activation of ?4?2 AChRs was centered at 0.13 µM, a level found in smokers. However, nicotine produced smoldering activation of ?3?4 and ?7 AChRs at concentrations well above levels found in smokers. The ?4?2 expressing cell line contains a mixture of two stoichiometries, namely (?4?2)2?2 and (?4?2)2?4. The (?4?2)2?2 stoichiometry is more sensitive to activation by nicotine. Sazetidine-A activates and desensitizes only this stoichiometry. Varenicline, cytisine and sazetidine-A were partial agonists on this mixture of ?4?2 AChRs, but full agonists on ?3?4 and ?7 AChRs. It has been reported that cytisine and varenicline are most efficacious on the (?4?2)2?4 stoichiometry. In this study, we distinguish the dual effects of activation and desensitization of AChRs by these nicotinic agonists and define the range of concentrations over which smoldering activation can be sustained. PMID:24244538
Campling, Barbara G.; Kuryatov, Alexander; Lindstrom, Jon
Synopsis Reinnervation of a hand transplant ultimately dictates functional recovery but provides a significant regenerative challenge. The authors present a review highlighting interventions to enhance nerve regeneration through acceleration of axonal regeneration or augmentation of Schwann cell supportand discuss their relevance to composite tissue allotransplantation. Surgical techniques that may be performed at the time of transplantation to optimize intrinsic muscle recovery—including appropriate alignment of ulnar nerve motor and sensory components, transfer of the distal anterior interosseous nerve to the recurrent motor branch of the median nerve, and prophylactic release of potential nerve entrapment points—are also presented. PMID:22051390
Glaus, Simone W.; Johnson, Philip J.; Mackinnon, Susan E.
Fibre structures represent a potential class of materials for the formation of synthetic nerve conduits due to their biomimicking architecture. Although the advantages of fibres in enhancing nerve regeneration have been demonstrated, in vivo evaluation of fibre size effect on nerve regeneration remains limited. In this study, we analyzed the effects of fibre diameter of electrospun conduits on peripheral nerve regeneration across a 15-mm critical defect gap in a rat sciatic nerve injury model. By using an electrospinning technique, fibrous conduits comprised of aligned electrospun poly (?-caprolactone) (PCL) microfibers (981?±?83 nm, Microfiber) or nanofibers (251?±?32 nm, Nanofiber) were obtained. At three months post implantation, axons regenerated across the defect gap in all animals that received fibrous conduits. In contrast, complete nerve regeneration was not observed in the control group that received empty, non-porous PCL film conduits (Film). Nanofiber conduits resulted in significantly higher total number of myelinated axons and thicker myelin sheaths compared to Microfiber and Film conduits. Retrograde labeling revealed a significant increase in number of regenerated dorsal root ganglion sensory neurons in the presence of Nanofiber conduits (1.93 ± 0.71 × 10(3) vs. 0.98 ± 0.30 × 10(3) in Microfiber, p?0.01). In addition, the compound muscle action potential (CMAP) amplitudes were higher and distal motor latency values were lower in the Nanofiber conduit group compared to the Microfiber group. This study demonstrated the impact of fibre size on peripheral nerve regeneration. These results could provide useful insights for future nerve guide designs. PMID:22700359
Jiang, Xu; Mi, Ruifa; Hoke, Ahmet; Chew, Sing Yian
3 weeks following cessation of intermittent morphine administration (10 mg/kg, s.c., once daily for 14 days), [3H]dopamine and [14C]acetylcholine release induced by 10 microM N-methyl-D-aspartate (NMDA) from superfused rat striatal slices appeared to be significantly higher than the release from striatal slices from saline-treated rats. A similar adaptive increase of the NMDA-evoked release of these neurotransmitters was observed in slices of the nucleus accumbens, whereas that of [3H]noradrenaline from hippocampal slices remained unchanged. Blockade of dopamine D2 receptors by 10 microM (--)-sulpiride enhanced NMDA-induced [3H]dopamine and [14C]acetylcholine release from striatal slices from saline-treated animals, but was found to be ineffective in this respect following intermittent morphine treatment. Moreover, morphine administration appeared to cause a profound decrease in the apparent affinity of the full dopamine D2 receptor agonist LY171555 (quinpirole) for these release-inhibitory dopamine D2 receptors, indicating the occurrence of dopamine D2 receptor desensitization. It is suggested that such a desensitization of dopamine D2 receptors on dopaminergic nerve terminals as well as on cholinergic interneurons may play a pivotal role in the long-lasting nature of behavioural sensitization upon cessation of treatment with morphine and possibly other drugs of abuse. PMID:8750744
Nestby, P; Tjon, G H; Visser, D T; Drukarch, B; Leysen, J E; Mulder, A H; Schoffelmeer, A N
This is a summary of the current knowledge of sensory receptors in skin of the bill of the platypus, Ornithorhynchus anatinus, and the snout of the echidna, Tachyglossus aculeatus. Brief mention is also made of the third living member of the monotremes, the long-nosed echidna, Zaglossus bruijnii. The monotremes are the only group of mammals known to have evolved electroreception. The structures in the skin responsible for the electric sense have been identified as sensory mucous glands with an expanded epidermal portion that is innervated by large-diameter nerve fibres. Afferent recordings have shown that in both platypuses and echidnas the receptors excited by cathodal (negative) pulses and inhibited by anodal (positive) pulses. Estimates give a total of 40,000 mucous sensory glands in the upper and lower bill of the platypus, whereas there are only about 100 in the tip of the echidna snout. Recording of electroreceptor-evoked activity from the brain of the platypus have shown that the largest area dedicated to somatosensory input from the bill, S1, shows alternating rows of mechanosensory and bimodal neurons. The bimodal neurons respond to both electrosensory and mechanical inputs. In skin of the platypus bill and echidna snout, apart from the electroreceptors, there are structures called push rods, which consist of a column of compacted cells that is able to move relatively independently of adjacent regions of skin. At the base of the column are Merkel cell complexes, known to be type I slowly adapting mechanoreceptors, and lamellated corpuscles, probably vibration receptors. It has been speculated that the platypus uses its electric sense to detect the electromyographic activity from moving prey in the water and for obstacle avoidance. Mechanoreceptors signal contact with the prey. For the echidna, a role for the electrosensory system has not yet been established during normal foraging behaviour, although it has been shown that it is able to detect the presence of weak electric fields in water. Perhaps the electric sense is used to detect moving prey in moist soil. PMID:9720114
Proske, U; Gregory, J E; Iggo, A
Background: In the era of highly active antiretroviral therapy, sensory neuropathies have increased in prevalence. We have documented the frequency and profile of the two most common forms of sensory neuropathies associated with Human Immunodeficiency Virus (HIV) infection and looked into clinicoelectrophysiological correlates to differentiate the two entities. Methods: The study population comprised of all consecutive patients detected to be HIV positive and attending the Neurology outpatient department (from March 2011 to March 2012) who were aged ? 18 years and were able to give informed consent. The data were collected from the patient records (including CD4 counts and treatment details) and questionnaire based interview with each patient. All patients underwent detailed clinical examination and nerve conduction studies (NCSs). Results: Among the total study population of 50 patients, there were 31 men and 19 women. Thirty two patients were in age range of 21 - 40 years and rest were above 40 years. 25 were on antiretroviral therapy (18 on regimen containing zidovudine; seven on regimen containing stavudine). The mean duration of antiretroviral therapy was 16.6±8.4 months. Low CD4 counts (<200) were noted in 24 patients (13 of these were on antiretroviral therapy). Clinically, the patients were classified as asymptomatic (n=34) and symptomatic (n=16). Among the symptomatic patients, nine were on antiretroviral therapy since less than one year (seven of these were on regimen containing stavudine). Ten patients aged more than 40-years had symptomatic neuropathy. No significant correlation was found between low CD4 counts and symptomatic neuropathy (p=0.21). Impaired vibration (100%) and absent ankle jerks (75%) were commoner than reduced pin sensitivity (46.6%). Twenty two patients had abnormal NCS results (18 of these were on antiretroviral therapy). Axonal distal symmetrical sensory neuropathy was the commonest pattern noted in 14 patients who were receiving antiretroviral therapy. Subclinical involvement as evidenced by abnormal NCSs was noted in 5 asymptomatic patients who were all on antiretroviral therapy. Conclusion: Symptomatic neuropathy was seen predominantly in HIV patients who were on antiretroviral therapy. All patients receiving stavudine containing regimen had severe symptomatic neuropathy within 1 year. There was an increase in the likelihood of symptomatic neuropathy among patients aged > 40 years. Subclinical neuropathy was common in those on antiretroviral therapy. Axonal neuropathy was the commonest pattern noted in patients who were receiving antiretroviral therapy and demyelinating neuropathy in patients not on antiretroviral therapy. Surprisingly no significant correlation was found between low CD4 counts and symptomatic neuropathy. PMID:25177587
S, Praveen-kumar; B, Nataraju; BS, Nagaraja
Prolonged exposure of most fast neurotransmitter-operated ion channels to agonist drives the receptors into a nonfunctional, or desensitized, state. Despite extensive investigation, desensitization remains a thoroughly characterized, yet poorly understood, process. Part of the difficulty in elucidating the mechanism of desensitization has been an inability to resolve the kinetics of both agonist binding and functional desensitization in the same set of operable receptors. To overcome this limitation, we applied single oocyte 3H-ligand binding and two-electrode voltage clamp to oocytes expressing recombinant alpha1beta2gamma2 GABA receptors. Using this approach, we report several observations fundamental to the mechanism of desensitization. First, we confirm that desensitization reversibly shifts GABA receptors into a high-affinity state. For [3H]GABA binding, the half-maximal binding of the desensitized state was approximately 0.040 microm. Second, we show that, upon agonist removal, this high-affinity state disappears with a time constant of 127 +/- 12 sec (n = 4), similar to the time constant for functional recovery from desensitization of 124 +/- 26 sec (n = 5). [3H]GABA, however, dissociates fourfold faster (tau = 30 +/- 2 sec; n = 3) than functional recovery, indicating that desensitized receptors need not be bound by GABA. These data provide direct evidence for a cyclical model of receptor desensitization. PMID:12223551
Chang, Yongchang; Ghansah, Emmanuel; Chen, Yonghui; Ye, Jiawei; Weiss, David S; Chang, YongChang
We report on magnetic resonance neurography (MRN) as a supplementary diagnostic tool in sciatic nerve injection injury. The object of the study was to test if T2-weighted (w) contrast within the sciatic nerve serves as an objective criterion for sciatic injection injury. Three patients presented with acute sensory and/or motor complaints in the distribution of the sciatic nerve after dorsogluteal injection and underwent MRN covering gluteal, thigh and knee levels. Native and contrast-enhanced T1-w images were employed to identify the tibial and peroneal division of the sciatic nerve while T2-w images with fat suppression allowed visualization of the site and extent of the nerve lesion. MRN in the two patients with clinically severe sensory and motor impairment correctly depicted sciatic injury: continuity of the T2-w lesion within the nerve at the lesion site and distal to it corresponded well to severe injury confirmed by NCS/EMG as axonotmetic or neurotmetic. Topography of the T2-w lesion on cross-section corresponded to predominant peroneal involvement; moreover, associated denervation patterns of distal target muscles were revealed. One of these patients completely recovered with concomitant complete regression of MRN abnormalities on follow-up. The third patient experienced transient sensory and mild motor impairment with complete recovery after 2 weeks. In this patient, T2-w signal within the nerve and distal target muscles remained normal indicating only mild, non-axonal nerve affliction. Our case series shows that MRN can be very useful in precisely determining the site of sciatic injection injury and may provide diagnostic criteria for the assessment of lesion severity and recovery. PMID:21225276
Pham, Mirko; Wessig, Carsten; Brinkhoff, Jörg; Reiners, Karlheinz; Stoll, Guido; Bendszus, Martin
The peripheral nervous system plays an important role in motility, sensory, and autonomic functions of the human body. Preservation of peripheral nerves in surgery is essential for improving quality of life of patients. To preserve peripheral nerves, detection of ne peripheral nerves that cannot be identi ed by human eye or under white light imaging is necessary. In this study, we sought to provide a proof-of-principle demonstration of a label-free detection technique of peripheral nerve tissues against adjacent tissues that employs spontaneous Raman microspectroscopy. A line-illumination confocal Raman microscope was used for the experiment. A laser operating at the wavelength of 532 nm was used as an excitation laser light. We obtained Raman spectra of peripheral nerve, brous connective tissue, skeletal muscle, blood vessel, and adipose tissue of Wistar rats, and extracted speci c spectral features of peripheral nerves and adjacent tissues. By applying multivariate image analysis, peripheral nerves were clearly detected against adjacent tissues without any preprocessing neither xation nor staining. These results suggest the potential of the Raman spectroscopic observation for noninvasive and label-free nerve detection, and we expect this method could be a key technique for nerve-sparing surgery.
Minamikawa, Takeo; Harada, Yoshinori; Koizumi, Noriaki; Takamatsu, Tetsuro
Sensory Guillain-Barré syndrome (GBS) is an acute demyelinating neuropathy that presents clinically with involvement of the sensory peripheral nerve only. To date, <10 cases of pure sensory GBS have been reported; thus, the clinical and pathological features of sensory variant GBS are yet to be well characterized. The current study reports the case of a 43-year-old female that presented with acute, symmetric and monophasic sensory neuropathy, without motor weakness. Patient history, clinical examination, routine nerve conduction studies and sural nerve biopsy were reviewed. All the observations were consistent with a diagnosis of pure sensory GBS. In particular, the pathological features of the sural nerve biopsy revealed that the form of regenerated nerve fibers have complete structure of myelinated nerve fascicles, and these myelinated nerve fibers are thicker than other parts of the biopsy. The patient received small-dose (20 mg/day) prednisone initially, but without any benefit. Satisfactory improvements were observed with one course of intravenous immunoglobulin.
YANG, JINGJING; HUAN, MINGMING; JIANG, HUAJUN; SONG, CHUNLI; ZHONG, LIN; LIANG, ZHANHUA
In the primary olfactory center of animals, glomeruli are the relay stations where sensory neurons expressing cognate odorant receptors converge onto interneurons. In cockroaches, moths, and honeybees, sensory afferents from sensilla on the anterodorsal surface and the posteroventral surface of the flagellum form two nerves of almost equal thicknesses. In this study, double labeling of the two nerves, or proximal/distal regions of the nerves, with fluorescent dyes was used to investigate topographic organization of sensory afferents in the honeybee. The sensory neurons of ampullaceal sensilla responsive to CO2, coelocapitular sensilla responsive to hygrosensory, and thermosensory stimuli and coeloconic sensilla of unknown function were characterized with large somata and supplied thick axons exclusively to the ventral nerve. Correspondingly, all glomeruli innervated by sensory tract (T) 4 received thick axonal processes exclusively from the ventral nerve. Almost all T1-3 glomeruli received a similar number of sensory afferents from the two nerves. In the macroglomerular complexes of the drone, termination fields of afferents from the two nerves almost completely overlapped; this differs from moths and cockroaches, which show heterogeneous terminations in the glomerular complex. In T1-3 glomeruli, sensory neurons originating from more distal flagellar segments tended to terminate within the inner regions of the cortical layer. These results suggest that some degree of somatotopic organization of sensory afferents exist in T1-3 glomeruli, and part of T4 glomeruli serve for processing of hygro- and thermosensory signals. PMID:19412930
Nishino, Hiroshi; Nishikawa, Michiko; Mizunami, Makoto; Yokohari, Fumio
Relationships between short- and long-term exposure to violent video games and desensitization, as measured through components of moral evaluation, were examined. Sixty-six children aged 5–12 years old completed questionnaires assessing video game experience and preferences and empathy and attitudes toward violence. The children played a violent or nonviolent video game and then responded to vignettes about everyday occurrences. Vignette responses
Jeanne B. Funk; Debra D. Buchman; Jennifer Jenks; Heidi Bechtoldt
We treated two medical phobic subjects with eye movement desensitization (EMD). Using detailed images of fear-related events, the treatment design conformed to an additive, within-series phase change to examine enduring effects. Results indicated that both subjects' verbal reports of fear decreased substantially using the EMD procedure. There were no consistent changes in heart rate. Similarly, self-reported fear toward a simulated
Ronald A. Kleinknecht
PBX-9404 and Composition B-3 were desensitized by subjecting them to shocks in the pressure range 10 to 24 kbar. Results show that the collapse of voids, and thus the activation of hot spots by shock waves, takes time and may require more than 5 ..mu..s. This time is, in a way, a counterpart of the induction time for shock initiation of a homogeneous explosive. Gittings' data are adduced to extend the results to 100 kbar and to show that at high pressures desensitization occurs in a very brief time window. When the voids have been collapsed, the relatively homogeneous explosive is resistant to detonation through an Arrhenius type of reaction because of the lower shock temperature resulting from double shocking. This conclusion is supported by experiments on single crystals of HMX and by shock temperature calculations. The time required for desensitization of PBX-9404 is related to pressure by the expression p/sup 2.2/tau = 1150. 21 references, 5 figures, 5 tables.
Campbell, A.W.; Travis, J.R.
The objective of this appraisal is to shed light on the various approaches to screen sensory information in the human gut. Understanding and characterization of sensory symptoms in gastrointestinal disorders is poor. Experimental methods allowing the investigator to control stimulus intensity and modality, as well as using validated methods for assessing sensory response have contributed to the understanding of pain mechanisms. Mechanical stimulation based on impedance planimetry allows direct recordings of luminal cross-sectional areas, and combined with ultrasound and magnetic resonance imaging, the contribution of different gut layers can be estimated. Electrical stimulation depolarizes free nerve endings non-selectively. Consequently, the stimulation paradigm (single, train, tetanic) influences the involved sensory nerves. Visual controlled electrical stimulation combines the probes with an endoscopic approach, which allows the investigator to inspect and obtain small biopsies from the stimulation site. Thermal stimulation (cold or warm) activates selectively mucosal receptors, and chemical substances such as acid and capsaicin (either alone or in combination) are used to evoke pain and sensitization. The possibility of multimodal (e.g. mechanical, electrical, thermal and chemical) stimulation in different gut segments has developed visceral pain research. The major advantage is involvement of distinctive receptors, various sensory nerves and different pain pathways mimicking clinical pain that favors investigation of central pain mechanisms involved in allodynia, hyperalgesia and referred pain. As impairment of descending control mechanisms partly underlies the pathogenesis in chronic pain, a cold pressor test that indirectly stimulates such control mechanisms can be added. Hence, the methods undoubtedly represent a major step forward in the future characterization and treatment of patients with various diseases of the gut, which provides knowledge to clinicians about the underlying symptoms and treatment of these patients. PMID:19132764
Brock, Christina; Arendt-Nielsen, Lars; Wilder-Smith, Oliver; Drewes, Asbj?rn Mohr
Repair of peripheral nerve defects with current synthetic, tubular nerve conduits generally shows inferior recovery when compared with using nerve autografts, the current gold standard. We tested the ability of composite collagen and hyaluronan hydrogels, with and without the nerve growth factor (NGF), to stimulate neurite extension on a promising aligned, nanofiber poly-L-lactide-co-caprolactone (PLCL) scaffold. In vitro, the hydrogels significantly increased neurite extension from dorsal root ganglia explants. Consistent with these results, the addition of hydrogels as luminal fillers within aligned, nanofiber tubular PLCL conduits led to improved sensory function compared to autograft repair in a critical-size defect in the sciatic nerve in a rat model. Sensory recovery was assessed 3 and 12 weeks after repair using a withdrawal assay from thermal stimulation. The addition of hydrogel did not enhance recovery of motor function in the rat model. The NGF led to dose-dependent improvements in neurite out-growth in vitro, but did not have a significant effect in vivo. In summary, composite collagen/hyaluronan hydrogels enhanced sensory neurite outgrowth in vitro and sensory recovery in vivo. The use of such hydrogels as luminal fillers for tubular nerve conduits may therefore be useful in assisting restoration of protective sensation following peripheral nerve injury. PMID:23659607
Jin, Jenny; Limburg, Sonja; Joshi, Sunil K.; Landman, Rebeccah; Park, Michelle; Zhang, Qia; Kim, Hubert T.
Background & Objectives Nerve conduction velocity is being used as a widespread measure of diagnosis of nerve function abnormalities. Dependence of nerve conduction parameters on intrinsic factors like age and sex, as well as extrinsic factors like temperature is well known. Lateralization of various cerebral functions like speech, language, visuospatial relations, analysis of face, recognition of musical themes and use of hand for fine motor movements have also been studied. Some differences have been noted between left and right hander for nerve conduction. The aim of this study is to compare the nerve conduction velocity between left handed and right handed subjects using median nerve and find out whether there is any difference in nerve conduction velocity (motor or sensory) with handedness. Method The study was carried out in students of B J Medical College by the use of standard 2 channel physiograph. Comparison of motor and sensory nerve conduction velocity between left and right handed subjects was done under paired-t test. Results Hemispheric specialization is primarily responsible for difference of dexterity. Some skills like music, sports activities are also due to hemispheric difference. On comparison of nerve conduction velocity between left and right handed persons the study shows that there is significant difference in sensory nerve conduction velocity between left and right handed subjects. Interpretation & Conclusion From the results we can conclude that there should be different set of standards for sensory nerve conduction velocity of left and right handed subjects.
Patel, Anup; Mehta, Anju
SUMMARY The sensory branches of the trigeminal nerve encode information about facial expressions, speaking and chewing movements, and stimuli that come into contact with the orofacial tissues. Whatever the cause, damage to the inferior alveolar nerve negatively affects the quality of facial sensibility as well as the patient's ability to translate patterns of altered nerve activity into functionally meaningful motor behaviours. There is no generally accepted, standard method of estimating sensory disturbances in the distribution of the inferior alveolar nerve following injury. Assessment of sensory alterations can be conducted using three types of measures: (i) objective electrophysiological measures of nerve conduction, (ii) sensory testing (stimulus) measures and (iii) patient report. Each type of measure with advantages and disadvantages for use are reviewed. PMID:21058973
PHILLIPS, C.; ESSICK, G.
This study evaluated the effect of two desensitizers on inhibition of dentin demineralization, after immersion in artificial saliva using micro-computed tomography (?CT). Dentin blocks cut from bovine incisors were treated with deionized water (DW, a negative control) or one of three desensitizers: a fluoride varnish (Duraphat, a positive control), a calcium phosphate desensitizer (Teethmate Desensitizer), and a fluoro-alumino-calcium silicate-based desensitizer (Nanoseal). After each treatment, the specimens in Duraphat, Nanoseal, and Teethmate Desensitizer groups were pre-immersed in artificial saliva (pH 6.5) for either 1 d or 1 wk. The mineral loss of the specimens after demineralization (pH 5.0, 3 h) was evaluated by ?CT. The treated surface was investigated with scanning electron microscopy. Mineral loss in all treatment groups was significantly lower than that in DW. Duraphat was the most effective treatment against demineralization, followed by Nanoseal. Nanoseal showed significantly better reduction in mineral loss following immersion for 1 wk in artificial saliva than for 1 d. However, Teethmate Desensitizer and Duraphat did not exhibit enhanced inhibition of demineralization over a longer period of immersion in artificial saliva. Scanning electron microscopy images showed deposition of particles on the dentin in both Teethmate Desensitizer. The application of Teethmate Desensitizer and Nanoseal to the exposed dentin surface resulted in inhibition of demineralization, with Nanoseal resulting in improved inhibition after prolonged immersion in artificial saliva. PMID:25363830
Lodha, Ena; Hamba, Hidenori; Nakashima, Syozi; Sadr, Alireza; Nikaido, Toru; Tagami, Junji
To investigate the mechanisms of alpha 1-adrenergic vascular desensitization, osmotic minipumps containing either saline (n = 9) or amidephrine mesylate (AMD) (n = 9), a selective alpha 1-adrenergic receptor agonist, were implanted subcutaneously in dogs with chronically implanted arterial and right atrial pressure catheters and aortic flow probes. After chronic alpha 1-adrenergic receptor stimulation, significant physiological desensitization to acute AMD challenges was observed, i.e., pressor and vasoconstrictor responses to the alpha 1-adrenergic agonist were significantly depressed (p < 0.01) compared with responses in the same dogs studied in the conscious state before pump implantation. However, physiological desensitization to acute challenges of the neurotransmitter norepinephrine (NE) (0.1 micrograms/kg per minute) in the presence of beta-adrenergic receptor blockade was not observed for either mean arterial pressure (MAP) (30 +/- 7 versus 28 +/- 5 mm Hg) or total peripheral resistance (TPR) (29.8 +/- 4.9 versus 28.9 +/- 7.3 mm Hg/l per minute). In the presence of beta-adrenergic receptor plus ganglionic blockade after AMD pump implantation, physiological desensitization to NE was unmasked since the control responses to NE (0.1 micrograms/kg per minute) before the AMD pumps were now greater (p < 0.01) than after chronic AMD administration for both MAP (66 +/- 5 versus 32 +/- 2 mm Hg) and TPR (42.6 +/- 10.3 versus 23.9 +/- 4.4 mm Hg/l per minute). In the presence of beta-adrenergic receptor, ganglionic, plus NE-uptake blockade after AMD pump implantation, desensitization was even more apparent, since NE (0.1 micrograms/kg per minute) induced even greater differences in MAP (33 +/- 5 versus 109 +/- 6 mm Hg) and TPR (28.1 +/- 1.8 versus 111.8 +/- 14.7 mm Hg/l per minute). The maximal force of contraction induced by NE in the presence or absence of endothelium was significantly decreased (p < 0.05) in vitro in mesenteric artery rings from AMD pump dogs compared with saline control dogs. Furthermore, alpha 1-adrenergic receptor density, as determined by [3H]prazosin binding in membrane preparations from vessels in the mesentery, was decreased (8.2 +/- 1.0 versus 18.4 +/- 1.4 fmol/mg protein, p < 0.001) without any change in Kd in the AMD pump dogs compared with the saline pump dogs.(ABSTRACT TRUNCATED AT 400 WORDS).
Kiuchi, K.; Vatner, D. E.; Uemura, N.; Bigaud, M.; Hasebe, N.; Hempel, D. M.; Graham, R. M.; Vatner, S. F.
neurons and induce vasodilation by activating capsaicin-sensitive perivascular sensory nerve endings, such as capsaicin, the pungent ingredient in chili peppers, or allyl isothiocyanate (AITC), the pungent principle
The distribution and origin of nerve fibers of presumed sensory nature in the ear drum and middle-ear mucosa of the rat were studied by a retrograde tracing technique in combination with immunocytochemistry.
R. Uddman; T. Grunditz; A. Larsson; F. Sundler
We report the clinical and imaging features of a patient with transient partial trigeminal sensory neuropathy thought to have been induced by thermal injury to the tongue. Abnormal thickening and enhancement of the mandibular division of the trigeminal nerve was revealed by MR imaging. The diagnostic considerations for mass-like enlargement of the trigeminal nerve should include transient/inflammatory processes, as well as more common and sinister conditions, such as tumor. PMID:10669251
Chan, L L; DeMonte, F; Ginsberg, L E
This lesson describes the function and components of the human nervous system. It helps students understand the purpose of our brain, spinal cord, nerves and the five senses. How the nervous system is affected during spaceflight is also discussed in this lesson.
Integrated Teaching And Learning Program
Human leukocytes have been useful in studying desensitization phenomena to beta-adrenergic agonists in a number of clinical conditions. In the present in vitro study the authors have explored the mechanism for beta-adrenergic desensitization and have compared conditions for homologous and heterologous desensitization, using the intact PMN model. PMN preincubated with isoproterenol (10/sup -4/M), washed thoroughly, then restimulated, desensitized rapidly so that within 10 min 80% of control isoproterenol-induced cyclic AMP stimulation is lost. Cells washed free of isoproterenol recover full responsiveness in 1 to 2 hr. The estimated isoproterenol desensitization EC/sub 50/ in cells washed and then restimulated is 1 x 10/sup -5/M, and EC/sub 50/ in unwashed cells that are restimulated is 9 x 10/sup -8/M. Rank-order potency studies of catecholamine desensitization show isoproterenol > epinephrine > norepinephrine, a beta-2 pattern. Isoproterenol-induced desensitization results in a small reduction in (/sup 3/H)DHA binding sites, which becomes statistically significant (p < 0.05) from control values at 1 hr (67% of control) and 3 hr (64%). In the absence of GTP, isoproterenol binding is characterized by an EC/sub 50/ of 6.6 +/- 2.6 x 10/sup -/(M, which is significantly different (p < 0.05) from the EC/sub 50/ of 38.1 +/- 9.1 x 10/sup -1/M found when cells are previously desensitized with isoproterenol for 10 min. GTP does not affect the EC/sub 50/ of desensitized cells. Finally, prolonged (3 hr) isoproterenol preincubation results in a small but significant (p < 0.05) loss of cyclic AMP responsiveness to histamine (67.7% +/- 11.7 of control) and PGE/sub 1/ (59.3% +/- 7.4), suggesting heterologous desensitization. These studies suggest that the human PMN is a suitable model to study both homologous and heterologous desensitization in vitro. 22 references. 6 figures. 3 tables.
Galant, S.P.; Britt, S.
Objective Accumulation of mitochondrial DNA (mtDNA) damage has been associated with aging and abnormal oxidative metabolism. We hypothesized that in human immunodeficiency virus associated sensory neuropathy (HIV-SN), damaged mtDNA accumulates in distal nerve segments and that a spatial pattern of mitochondrial dysfunction contribute to the distal degeneration of sensory nerve fibers. Methods We measured levels of common deletion mutations in mtDNA and expression levels of mitochondrial respiratory chain complexes of matched proximal and distal nerve specimens from patients with and without HIV-SN. In mitochondria isolated from peripheral nerves of simian immunodeficiency virus (SIV) infected macaques, a model of HIV-SN, we measured mitochondrial function and generation of reactive oxygen species. Results We identified increased levels of mtDNA common deletion mutation in post-mortem sural nerves of patients with HIV-SN as compared to uninfected patients or HIV patients without sensory neuropathy. Furthermore, we found that common deletion mutation in mtDNA was more prevalent in distal sural nerves compared to dorsal root ganglia. In a primate model of HIV-SN, freshly isolated mitochondria from sural nerves of macaques infected with a neurovirulent strain of SIV showed impaired mitochondrial function compared to mitochondria from proximal nerve segments. Interpretation Our findings suggest that mtDNA damage accumulates in distal mitochondria of long axons, especially in patients with HIV-SN, and that this may lead to reduced mitochondrial function in distal nerves relative to proximal segments. Although our findings are based on HIV-SN, if confirmed in other neuropathies, these observations could explain the length-dependent nature of most axonal peripheral neuropathies. PMID:21280080
Lehmann, Helmar C.; Chen, Weiran; Borzan, Jasenka; Mankowski, Joseph; Hoke, Ahmet
Poor muscle and nerve functional recovery after nerve damage is a serious clinical problem, particularly if there is prolonged delay before nerve-muscle contact is reestablished. Our previous studies showed that sensory nerve cross-anastomosis (sensory protection) provides support to the denervated muscle. In the present study, we analyzed neurotrophic factor mRNA expression by RT-PCR in denervated rat gastrocnemius muscle receiving sensory protection with the saphenous nerve, compared to normal innervated muscle, to denervated muscle, and to denervated muscle repaired immediately with the peroneal (motor) nerve, after periods of 3 days to 3 months. No significant differences in mRNA levels of beta-actin, nerve growth factor, brain-derived neurotrophic factor or neurotrophin-3 were found between the sensory protection treatment and the denervated or the motor repair groups. However, sensory protection resulted in levels of muscle glial cell line-derived neurotrophic factor mRNA expression that were lower than in denervated muscle and higher than in muscle given immediate motor repair. These results demonstrate that glial cell line-derived neurotrophic factor mRNA is elevated following denervation but is partially down-regulated by sensory protection. Our study suggests that sensory protection provides a modified trophic environment by modulating neurotrophic factor synthesis in muscle. PMID:15672636
Zhao, Chunnian; Veltri, Karen; Li, Songlin; Bain, James R; Fahnestock, Margaret
Morphologic classifications of communication between musculocutaneous and median nerves are not based on the distribution and the function of the communicating branch. The authors report a rare case of such a communication with passage of the median nerve through the pronator teres muscle and discuss its clinical significance. The musculocutaneous nerve was divided into a lateral branch that continued to the lateral antebrachial cutaneous nerve and a medial branch that joined the median nerve in the forearm. The authors separated the nerve bundles and noted that the communicating branch derived from the sixth to seventh cervical nerves and supplied nerve fibers to the pronator teres muscle and the proper palmar digital nerve of the thumb. In addition, the median nerve penetrated the humeral head of the pronator teres muscle. Isolated musculocutaneous neuropathy with such a communication may cause unexpected symptoms such as sensory deficit in the palm and muscular weakness of the forearm and the thumb. PMID:25122101
Liu, Hong-Fu; Won, Hyung-Sun; Chung, In-Hyuk; Kim, Seung-Min; Kim, In-Beom
Recovery from peripheral nerve damage, especially for a transected nerve, is rarely complete, resulting in impaired motor function, sensory loss, and chronic pain with inappropriate autonomic responses that seriously impair quality of life. In consequence, strategies for enhancing peripheral nerve repair are of high clinical importance. Tension is a key determinant of neuronal growth and function. In vitro and in vivo experiments have shown that moderate levels of imposed tension (strain) can encourage axonal outgrowth; however, few strategies of peripheral nerve repair emphasize the mechanical environment of the injured nerve. Toward the development of more effective nerve regeneration strategies, we demonstrate the design, fabrication, and implementation of a novel, modular nerve-lengthening device, which allows the imposition of moderate tensile loads in parallel with existing scaffold-based tissue engineering strategies for nerve repair. This concept would enable nerve regeneration in two superposed regimes of nerve extension—traditional extension through axonal outgrowth into a scaffold and extension in intact regions of the proximal nerve, such as that occurring during growth or limb-lengthening. Self-sizing silicone nerve cuffs were fabricated to grip nerve stumps without slippage, and nerves were deformed by actuating a telescoping internal fixator. Poly(lactic co-glycolic) acid (PLGA) constructs mounted on the telescoping rods were apposed to the nerve stumps to guide axonal outgrowth. Neuronal cells were exposed to PLGA using direct contact and extract methods, and they exhibited no signs of cytotoxic effects in terms of cell morphology and viability. We confirmed the feasibility of implanting and actuating our device within a sciatic nerve gap and observed axonal outgrowth following device implantation. The successful fabrication and implementation of our device provides a novel method for examining mechanical influences on nerve regeneration. PMID:23102114
Chuang, Ting-Hsien; Wilson, Robin E.; Love, James M.; Fisher, John P.
In animal models of peripheral nerve injury, leukemia inhibitory factor (LIF) is normally expressed at very low levels. Following nerve injury, its expression is rapidly increased in the nerve at the injury site and promotes both sensory and motor neuron survival. Once normal nerve function is restored, LIF expression returns to negligible levels. For this reason, LIF is considered to be a peripheral nerve trauma factor. We wished to determine whether LIF is also upregulated in human nerves following trauma and whether it is expressed in neuromas of varying age. Immunohistochemical staining for the presence of LIF was performed on injured and control human nerves from a number of subjects. Results demonstrate that LIF expression is increased in nerves within hours of injury and, in the case of neuroma formation, can persist for several years. LIF immunoreactivity was consistently found in Schwann cells, in peripheral nerve axons, and, at stages when an inflammatory response was present, also in neutrophils, mast cells, macrophages, and blood vessel walls. The level of staining within the connective tissue of injured nerves was elevated compared to control nerves, which may be due to the presence of LIF bound to the soluble secreted form of the LIF receptor. Whether the continued expression of LIF is unhealed injured nerves promotes the development of neuromas remains to be resolved. PMID:11721746
Dowsing, B J; Romeo, R; Morrison, W A
Dispersed pancreatic acini were first exposed to carbamylcholine (10/sup -7/-10/sup -4/ M) for 60 min, washed, and reexposed to this same agonist (10/sup -8/-10/sup -3/ M) for 15 min. During this second incubation, the functional secretory capacity of these acini was evaluated by measuring amylase release. Acini preexposed to concentrations of carbamylcholine of 10/sup -6/ M or greater showed shifts to the right in the subsequent carbamylcholine dose-response curves of amylase release. A 3-h recovery period (without carbamylcholine) did not restore the altered carbamylcholine dose-response curve. Ca/sup 2 +/ concentrations of 10/sup -7/ M or 2.5 x 10/sup -3/ M instead of 0.5 x 10/sup -3/ M during the 60-min preincubation did not affect the desensitization process. With use of N-(/sup 3/H)methylscopolamine to evaluate muscarinic receptors, the only changes observed after desensitization were a significant decrease in the high-affinity and an equivalent increase in that of the low-affinity receptors. After cholinergic exposure amylase release stimulated by caerulein was only slightly modified, whereas amylase release in response to a phorbol ester 12-O-tetradecanoylphorbol-13-acetate and to the ionophore A23187 was not altered. These data indicate that short-term desensitization with a cholinergic agent is relatively specific to muscarinic agonists, causes changes in the muscarinic receptor high-and low-affinity concentration but does not alter intracellular steps after calcium mobilization or protein kinase C activation known to be involved in the secretion process.
Asselin, J.; Larose, L.; Morisset, J.
Hyperthermia can occur in lungs and airways during both physiological and pathophysiological conditions. A previous study carried out in our laboratory showed that hyperthermia activates and sensitizes vagal bronchopulmonary Cfiber afferents, whether this effect is through a direct action of hyperthermia on sensory nerves is not known. This dissertation study was aimed to investigate the thermal-sensitivity of pulmonary sensory neurons,
Control of hair cell excitability by vestibular primary sensory neurons Journal: Journal, utricle, voltage-gated sodium channel Themes & Topics: a. Hair celss, endorgans, and nerve Vestibular of Neuroscience 27, 13 (2007) 3503-11 #12;1 Title: Control of hair cell excitability by vestibular primary sensory
Paris-Sud XI, UniversitÃ© de
Sensory innervation of the skin influences wound healing through the release of neuropeptides from the nerve endings. The purpose of this study was to investigate the differences in the sensory innervation of the normal and the hypospadiac prepuce. The prepuce from 10 healthy children undergoing routine circumcision and 10 age-matched children undergoing hypospadias repair were submitted for immunohistochemistry, using antibodies against protein
Zafar Nazir; Rehan Masood; Resham Rehman
It is believed that repeated exposure to real-life and to entertainment violence may alter cognitive, affective, and behavioral processes, possibly leading to desensitization. The goal of the present study was to determine if there are relationships between real-life and media violence exposure and desensitization as reflected in related…
Funk, Jeanne B.; Baldacci, Heidi Bechtoldt; Pasold; Tracie; Baumgardner, Jennifer
Flooding and systematic desensitization procedures were investigated for possible interactions with subject arousal level on reduction in phobic reactions. No such interaction was found. Behaviorally and on GSR response, both flooding and systematic desensitization were effective, but only the latter was effective on subjective reports. (NG)
Suarez, Yolanda; And Others
Background: Aspirin desensitization treatment is an option to decrease disease activity and reduce the need for systemic corticosteroids in patients with aspirin-exacerbated respiratory disease (AERD). Objective: This study was designed to determine whether the clinical courses of patients with AERD improved as early as 6 months after starting aspirin desensitization and to compare this with follow-up evaluations after at least
M. Pilar Berges-Gimeno; Ronald A. Simon; Donald D. Stevenson
Sexual violence, which affects one in three women worldwide, can result in significant psychiatric morbidity and suicide. Eye movement desensitization and reprocessing (EMDR) offers health care providers the option of a brief psychiatric intervention that can result in psychiatric healing in as few as four sessions. Because health care providers often hear stories of sexual violence from their patients, they are in an ideal position to make recommendations for treatment. The purpose of this article is to introduce health care providers to the technique of EMDR, review safety and appropriateness, and discuss clinical and research implications. PMID:20623397
Posmontier, Bobbie; Dovydaitis, Tiffany; Lipman, Kenneth
Double neurotization of the deep branch of ulnar nerve (DBUN) and superficial branch of ulnar nerve using the anterior interosseous nerve (AIN) and the recurrent (thenar) branch of the median nerve was first described by Battiston and Lanzetta. This article details the postoperative results after 18months of a patient who underwent this technique using the posterior interosseous nerve (PIN) instead of the recurrent branch of the median nerve for sensory reconstruction. A 35-year-old, right-handed man suffered major trauma to his right upper limb following a serious motor vehicle accident. One year later, a pseudocystic neuroma of the ulnar nerve was evident on ultrasound examination and MRI. After the neuroma had been resected, the nerve defect was estimated at 8cm. One and a half years after the initial trauma, with the patient still at M0/S0, we transferred the AIN and PIN onto the deep and superficial branches of the ulnar nerve respectively. Nerve recovery was monitored clinically every month and by electromyography (EMG) every three months initially and then every six months. At 18months postoperative, 5th digit abduction/adduction was 28mm. Sensation was present at the base of the 5th digit. The patient was graded M3/S2. Clear re-innervation of the abductor digiti minimi was demonstrated by EMG (motor conduction velocity 50m/s). Given that the ulnar nerve could not be excited at the elbow, this re-innervation had to be the result of the double nerve transfer. Neurotization of the DBUN using the AIN produces functional results as early as 1year after surgery. Using PIN for sensory neurotization is easy to perform, has no negative consequences for the donor site, and leads to good recovery of sensation (graded as S2) after 18months. PMID:25260763
Delclaux, S; Aprédoaei, C; Mansat, P; Rongières, M; Bonnevialle, P
Nearly 100% of patients experience trauma to the trigeminal nerve during orthognathic surgery, impairing sensation and sensory function on the face. In a recent randomized clinical trial, people who performed sensory re-training exercises reported less difficulty related to residual numbness and decreased lip sensitivity than those who performed standard opening exercises only. We hypothesized that re-training reduces the impaired performance on neurosensory tests of tactile function that is commonly observed post-surgically. We analyzed thresholds for contact detection, two-point discrimination, and two-point perception, obtained during the clinical trial before and at 1, 3, and 6 months after surgery, to assess tactile detection and discriminative sensitivities, and subjective interpretation of tactile stimulation, respectively. Post-surgery, the retrained persons exhibited less impairment, on average, than non-retrained persons only in two-point perception (P < 0.025), suggesting that retrained persons experienced or interpreted the tactile stimuli differently than did non-retrained persons. PMID:17525360
Essick, G K; Phillips, C; Zuniga, J
Drug desensitization is the induction, within hours to days, of a temporary state of tolerance to a drug which the patient has developed a hypersensitivity reaction to. It may be used for IgE and non-IgE mediated allergic reactions, and certain non-allergic reactions. The indication for desensitization is where no alternative medications are available for the treatment of that condition, and where the benefits of desensitization outweigh the risks. Desensitization is a therapeutic modality for drug allergy (similar to allergen specific immunotherapy for allergic rhinitis and insect venom anaphylaxis). In contrast, the drug provocation test is a diagnostic modality used to confirm or refute the diagnosis of drug allergy. This review discusses the clinical applications of desensitization for the treatment of common infectious, metabolic and cardiovascular diseases, and oncological conditions in the Asia-Pacific region. PMID:22053290
Evidence has shown that factors other than the central pharmacological effects of nicotine are important in promoting smoking behavior. One such non-nicotine effect includes sensory stimulation, which may promote smoking by developing learned associations with nicotine's rewarding effects, or by constituting a rewarding experience independent of nicotine. The present study used internal tobacco industry documents to examine industry efforts to understand and manipulate stimulation of the sensory nerves by tobacco smoke, and the influence of sensory stimulation on smoker behavior. Research focused on sensory nerves of the head and neck, including the olfactory nerve, which carries flavor and odor, and the trigeminal nerve, which carries irritant information. The tobacco industry maintained a systematic research program designed to elucidate an understanding of responses of sensory nerves to nicotine and other components of tobacco smoke, and attempted to develop nicotine-like compounds that would enhance sensory responses in smokers. Industry research appeared intended to aid in the development of new products with greater consumer appeal. The potential influence of sensory response in enhancing nicotine dependence through an associative mechanism was acknowledged by the tobacco industry, but evidence for research in this area was limited. These findings add to evidence of industry manipulation of sensory factors to enhance smoking behavior and may have implications for development of more effective treatment strategies, including more "acceptable" nicotine replacement therapies. PMID:17978985
Megerdichian, Christine L; Rees, Vaughan W; Wayne, Geoffrey Ferris; Connolly, Gregory N
A trio of papers has resolved an outstanding controversy regarding the function of Merkel cells and their afferent nerve fiber partners. Merkel cells sense mechanical stimuli (through Piezo2), fire action potentials, and are sufficient to activate downstream sensory neurons. PMID:24937283
Vásquez, Valeria; Scherrer, Gregory; Goodman, Miriam B
Unlike other tissues in the body, peripheral nerve regeneration is slow and usually incomplete. Less than half of patients who undergo nerve repair after injury regain good to excellent motor or sensory function and current surgical techniques are similar to those described by Sunderland more than 60 years ago. Our increasing knowledge about nerve physiology and regeneration far outweighs our surgical abilities to reconstruct damaged nerves and successfully regenerate motor and sensory function. It is technically possible to reconstruct nerves at the fascicular level but not at the level of individual axons. Recent surgical options including nerve transfers demonstrate promise in improving outcomes for proximal nerve injuries and experimental molecular and bioengineering strategies are being developed to overcome biological roadblocks limiting patient recovery.
Grinsell, D.; Keating, C. P.
Catecholamines have been extensively reported to be present in most animal groups, including members of Echinodermata. In this study, we investigated the presence and distribution of catecholaminergic nerves in two members of the Holothuroidea, Holothuria glaberrima (Selenka, 1867) (Aspidochirotida, Holothuroidea) and Holothuria mexicana (Ludwig, 1875) (Aspidochirotida, Holothuroidea), by using induced fluorescence for catecholamines on tissue sections and immunohistochemistry with an antibody that recognizes tyrosine hydroxylase. The presence of a catecholaminergic nerve plexus similar in distribution and extension to those previously reported in other members of Echinodermata was observed. This plexus, composed of cells and fibers, is found in the ectoneural component of the echinoderm nervous system and is continuous with the circumoral nerve ring and the radial nerves, tentacular nerves, and esophageal plexus. In addition, fluorescent nerves in the tube feet are continuous with the catecholaminergic components of the radial nerve cords. This is the first comprehensive report on the presence and distribution of catecholamines in the nervous system of Holothuroidea. The continuity and distribution of the catecholaminergic plexus strengthen the notion that the catecholaminergic cells are interneurons, since these do not form part of the known sensory or motor circuits and the fluorescence is confined to organized nervous tissue. PMID:20827375
Diaz-Balzac, Carlos A.; Mejias, Wigberto; Jimenez, Luis B.
This paper describes a new tripolar spiral cuff electrode, composed of a thin (10 microm) and flexible polyimide insulating carrier and three circumneural platinum electrodes, suitable for stimulation of peripheral nerves. The cuffs were implanted around the sciatic nerve of two groups of ten rats each, one in which the polyimide ribbon was attached to a plastic connector to characterize the in vivo stimulating properties of the electrode, and one without a connector for testing possible mechanical nerve damage by means of functional and histological methods. The polyimide cuff electrodes induced only a very mild foreign body reaction and did not change the nerve shape over a 2-6 month implantation period. There were no changes in the motor and sensory nerve conduction tests, nociceptive responses and walking track pattern over follow-up, and no morphological evidence of axonal loss or demyelination, except in one case with partial demyelination of some large fibers after 6 months. By delivering single electrical pulses through the cuff electrodes graded recruitment curves of alpha-motor nerve fibers were obtained. Recruitment of all motor units was achieved with a mean charge density lower than 4 microC/cm(2) for a pulse width of 50 micros at the time of implantation as well as 45 days thereafter. These data indicate that the polyimide cuff electrode is a stable stimulating device, with physical properties and dimensions that avoid nerve compression or activity-induced axonal damage. PMID:10880824
Rodríguez, F J; Ceballos, D; Schüttler, M; Valero, A; Valderrama, E; Stieglitz, T; Navarro, X
Introduction Peripheral sensory neuropathy is known to be associated with several medical conditions; however, it has not been reported\\u000a in patients with cerebral palsy. Authors have observed pathological changes in the sensory nerve rootlets taken during selective\\u000a dorsal rhizotomy. This paper reports a possible novel cause of peripheral sensory neuropathy: the chronic afferent excitations\\u000a from muscle spindles.\\u000a \\u000a \\u000a \\u000a \\u000a Case report Sensory nerve rootlets
Toru Fukuhara; Yoichiro Namba; Ichiro Yamadori
Eye Movement Desensitization and Reprocessing (EMDR) is a new psychological methodology that has been applied to a wide range of psychological disorders. Clinical reports over the past three years indicate that it is an important addition to the treatment of substance abuse. EMDR offers a structured, client-centered model that integrates key elements of intrapsychic, behavioral, cognitive, body-oriented, and interactional approaches. Treatment effects are quite rapid and, during an individual session, the therapist may witness accelerated processing of information involving a shift of cognitive structures (including the assimilation of positive beliefs) along with the desensitization of attendent traumata. The application of EMDR apparently stimulates an inherent physiological processing system that allows dysfunctional information to be adaptively resolved, resulting in increased insight and more functional behavior. The judicious use of EMDR includes a comprehensive client history and extensive preparation, allowing the client to deal with the high levels of disturbance often engendered by the treatment itself. After the inauguration of a sufficient therapeutic alliance, adequately addressing potential issues of secondary gain, and appropriate client stabilization, EMDR may be used to ameliorate the effects of earlier memories that contribute to the dysfunction, potential relapse triggers, and physical cravings. In addition, EMDR is used to incorporate new coping skills and assist in learning more adaptive behaviors. Other potential targets for reprocessing include treatment noncompliance, ambivalence about abstinence, and present crises. Finally, EMDR should be used on this clinical population only by a trained clinician who is educated and experienced with this problem area. PMID:7884600
Shapiro, F; Vogelmann-Sine, S; Sine, L F
Computing targeted responses is a general problem in goal-directed behaviors. We sought the sensory template for directional turning in the predatory sea slug Pleurobranchaea californica, which calculates precise turn angles by averaging multiple stimulus sites on its chemotactile oral veil (Yafremava LS, Anthony CW, Lane L, Campbell JK, Gillette R. J Exp Biol 210: 561–569, 2007). Spiking responses to appetitive chemotactile stimulation were recorded in the two bilateral pairs of oral veil nerves, the large oral veil nerve (LOVN) and the tentacle nerve (TN). The integrative abilities of the peripheral nervous system were significant. Nerve spiking responses to punctate, one-site stimulation of the oral veil followed sigmoid relations as stimuli moved between lateral tentacle and the midline. Receptive fields of LOVN and TN were unilateral, overlapping, and oppositely weighted for responsiveness across the length of oral veil. Simultaneous two-site stimulation caused responses of amplitudes markedly smaller than the sum of corresponding one-site responses. Plots of two-site nerve responses against the summed approximate distances from midline of each site were markedly linear. Thus the sensory paths in the peripheral nervous system show reciprocal occlusion similar to lateral inhibition. This outcome suggests a novel neural function for lateral inhibitory mechanisms, distinct from simple contrast enhancement, in computation of both sensory maps and targeted motor actions. PMID:21490281
Yafremava, Liudmila S.
Background Altered sensory information arising from damaged knee joint structures has been hypothesized as a contributing factor to persistent muscle dysfunction following injury. Methods Composite femoral nerve sensory signal was measured in 24 rabbits randomly allocated (8 per group) to receive surgical anterior cruciate ligament (ACL) transection with or without autograft reconstruction or nothing (control). Two-weeks after the intervention composite afferent signals were recorded from the femoral nerve. Side-to-side ratios (surgical side vs contralateral healthy side) for peak femoral nerve afferent composite signal were used for comparison. Results Femoral nerve afferent signal ratios were significantly higher in the ACL-R (2.21?±?0.74) group when compared to the ACL-T (1.28?±?0.61, P?=?0.02) group and Control group (1.31?±?0.78, P?=?0.03). Conclusion The magnitude of sensory information recorded on the femoral nerve is increased following ACL injury and reconstruction surgery, but not after an isolated ACL injury in rabbits. PMID:24766654
In the United States more than 200,000 people are treated each year for peripheral nerve injuries that require surgery. Functional recovery of motor and sensory capability is limited following autograft, the most common ...
Harley, Brendan A. (Brendan Andrew), 1978-
In a first experiment, human subjects used a bipolar scale to rate the irritant sensation elicited by 10 sequentially repeated applications of either 3 ppm capsaicin or 250 mM citric acid on one side of the dorsal surface of the tongue, at 1 min intervals (30 s inter-stimulus interval). Citric acid-evoked irritation significantly increased across trials, consistent with sensitization. With
J.-M. Dessirier; M. O'Mahony; M. Iodi-Carstens; E. Carstens
A 58-year-old female exhibited the onset of symmetrical sensory abnormalities of the face and extremities. The neurological examination revealed normal muscle strength with abated or absent tendon reflexes. The patient experienced symmetrical glove- and stocking-type pinprick sensations in the distal extremities and a loss of temperature sensation, but had normal proprioception and vibration senses and joint topesthesia. The lumbar puncture showed protein cell separation at the fifth week after the onset of symptoms. At the same time-point, the electrophysiological examination showed demyelination changes involving the trigeminal nerve and the somatic motor nerve. Needle electromyography revealed normal results. The clinical symptoms ceased progression at the fourth week after symptom onset, and began to improve from the sixth. This case was considered to be sensory Guillain-Barré syndrome, which was characterized by its cranial nerve involvement. PMID:25371720
ZHANG, JING; LIU, NA; ZHANG, ZHE-CHENG; ZHENG, RUI-ZHI; LI, QIAN
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.
Ahmad, Imran; Akhtar, Md. Sohaib
Repairing nerve defects with large gaps remains one of the most operative challenges for surgeons. Incomplete recovery from peripheral nerve injuries can produce a diversity of negative outcomes, including numbness, impairment of sensory or motor function, possibility of developing chronic pain, and devastating permanent disability. In the last few years, numerous microsurgical techniques, such as coaptation, nerve autograft, and different biological or polymeric nerve conduits, have been developed to reconstruct a long segment of damaged peripheral nerve. A few of these techniques are promising and have become popular among surgeons. Advancements in the field of tissue engineering have led to development of synthetic nerve conduits as an alternative for the nerve autograft technique, which is the current practice to bridge nerve defects with gaps larger than 30 mm. However, to date, despite significant progress in this field, no material has been found to be an ideal alternative to the nerve autograft. This article briefly reviews major up-to-date published studies using different materials as an alternative to the nerve autograft to bridge peripheral nerve gaps in an attempt to assess their ability to support and enhance nerve regeneration and their prospective drawbacks, and also highlights the promising hope for nerve regeneration with the next generation of nerve conduits, which has been significantly enhanced with the tissue engineering approach, especially with the aid of nanotechnology in development of the three-dimensional scaffold. The goal is to determine potential alternatives for nerve regeneration and repair that are simply and directly applicable in clinical conditions. PMID:21995532
Sedaghati, Tina; Yang, Shi Yu; Mosahebi, Afshin; Alavijeh, Mohammad S; Seifalian, Alexander M
Loss of sensation and increased sensory phenomena are major expressions of varieties of diabetic polyneuropathies needing improved assessments for clinical and research purposes. We provide a neurobiological explanation for the apparent paradox between decreased sensation and increased sensory phenomena. Strongly endorsed is the use of the 10-g monofilaments for screening of feet to detect sensation loss, with the goal of improving diabetic management and prevention of foot ulcers and neurogenic arthropathy. We describe improved methods to assess for the kind, severity, and distribution of both large- and small-fiber sensory loss and which approaches and techniques may be useful for conducting therapeutic trials. The abnormality of attributes of nerve conduction may be used to validate the dysfunction of large sensory fibers. The abnormality of epidermal nerve fibers/1 mm may be used as a surrogate measure of small-fiber sensory loss but appear not to correlate closely with severity of pain. Increased sensory phenomena are recognized by the characteristic words patients use to describe them and by the severity and persistence of these symptoms. Tests of tactile and thermal hyperalgesia are additional markers of neural hyperactivity that are useful for diagnosis and disease management. PMID:24158999
Herrmann, David N.; Staff, Nathan P.; Dyck, P. James B.
Direct interfacing of transected peripheral nerves with advanced robotic prosthetic devices has been proposed as a strategy for achieving natural motor control and sensory perception of such bionic substitutes, thus fully functionally replacing missing limbs in amputees. Multi-electrode arrays placed in the brain and peripheral nerves have been used successfully to convey neural control of prosthetic devices to the user. However, reactive gliosis, micro hemorrhages, axonopathy and excessive inflammation currently limit their long-term use. Here we demonstrate that enticement of peripheral nerve regeneration through a non-obstructive multi-electrode array, after either acute or chronic nerve amputation, offers a viable alternative to obtain early neural recordings and to enhance long-term interfacing of nerve activity. Non-restrictive electrode arrays placed in the path of regenerating nerve fibers allowed the recording of action potentials as early as 8?days post-implantation with high signal-to-noise ratio, as long as 3?months in some animals, and with minimal inflammation at the nerve tissue-metal electrode interface. Our findings suggest that regenerative multi-electrode arrays of open design allow early and stable interfacing of neural activity from amputated peripheral nerves and might contribute towards conveying full neural control and sensory feedback to users of robotic prosthetic devices. PMID:19506704
Garde, Kshitija; Keefer, Edward; Botterman, Barry; Galvan, Pedro; Romero, Mario I.
The aim of this study was to clarify the distribution pattern and innervation territory of the mental nerve (MN) in the skin and mucosa by topographic examination by Sihler's staining, thereby providing reference anatomical information for surgical procedures and to enable prediction of regions of sensory disturbance following nerve damage. Ten human specimens were subjected to Sihler's staining, which is a highly accurate method for visualizing the distribution of nerve fibers without altering their topography. Each branch of the MN overlapped adjacent branches (five cases), or else they were distributed individually at the lower lip (five cases). The MN anastomosed with some branches of the facial nerve near the mental foramen. Moreover, some branches of the MN anastomosed with the buccal nerve of the trigeminal nerve, which supplies sensation to the skin and mucosa over the lateral region of the lower lip (six cases). The details of the distribution pattern and innervations territory of the MN presented herein may enable the prediction of a region of sensory disturbance following MN damage. Moreover, knowledge of the pattern of synapses with adjacent branches of other nerves, such as the facial (marginal mandibular and cervical branches) and the buccal nerves, might help to improve our understanding around incomplete anesthesia during the surgical procedures in oral & maxillofacial region. PMID:24222330
Won, Sung-Yoon; Yang, Hun-Mu; Woo, Hee-Soon; Chang, Ki-Yeon; Youn, Kwan-Hyun; Kim, Hee-Jin; Hu, Kyung-Seok
Although subclinical involvement of sensory neurons in amyotrophic lateral sclerosis (ALS) has been previously demonstrated, corneal small fiber sensory neuropathy has not been reported to-date. We examined a group of sporadic ALS patients with corneal confocal microscopy, a recently developed imaging technique allowing in vivo observation of corneal small sensory fibers. Corneal confocal microscopy (CCM) examination revealed a reduction of corneal small fiber sensory nerve number and branching in ALS patients. Quantitative analysis demonstrated an increase in tortuosity and reduction in length and fractal dimension of ALS patients’ corneal nerve fibers compared to age-matched controls. Moreover, bulbar function disability scores were significantly related to measures of corneal nerve fibers anatomical damage. Our study demonstrates for the first time a corneal small fiber sensory neuropathy in ALS patients. This finding further suggests a link between sporadic ALS and facial-onset sensory and motor neuronopathy (FOSMN) syndrome, a rare condition characterized by early sensory symptoms (with trigeminal nerve distribution), followed by wasting and weakness of bulbar and upper limb muscles. In addition, the finding supports a model of neurodegeneration in ALS as a focally advancing process. PMID:25360111
Ferrari, Giulio; Grisan, Enrico; Scarpa, Fabio; Fazio, Raffaella; Comola, Mauro; Quattrini, Angelo; Comi, Giancarlo; Rama, Paolo; Riva, Nilo
The human body has five basic sensory functions: touch, vision, hearing, taste, and smell. The effectiveness of one or more of these human sensory functions can be impaired as a result of trauma, congenital defects, or the normal ageing process. Converting one type of function into another, or translating a function to a different part of the body, could result in a better quality of life for a person with diminished sensorial capabilities.
Sensory systems detect small molecules, mechanical perturbations, or radiation via the activation of receptor proteins and downstream signaling cascades in specialized sensory cells. In vertebrates, the two principal categories of sensory receptors are ion channels, which mediate mechanosensation, thermosensation, and acid and salt taste; and G-protein-coupled receptors (GPCRs), which mediate vision, olfaction, and sweet, bitter, and umami tastes. GPCR-based signaling in rods and cones illustrates the fundamental principles of rapid activation and inactivation, signal amplification, and gain control. Channel-based sensory systems illustrate the integration of diverse modulatory signals at the receptor, as seen in the thermosensory/pain system, and the rapid response kinetics that are possible with direct mechanical gating of a channel. Comparisons of sensory receptor gene sequences reveal numerous examples in which gene duplication and sequence divergence have created novel sensory specificities. This is the evolutionary basis for the observed diversity in temperature- and ligand-dependent gating among thermosensory channels, spectral tuning among visual pigments, and odorant binding among olfactory receptors. The coding of complex external stimuli by a limited number of sensory receptor types has led to the evolution of modality-specific and species-specific patterns of retention or loss of sensory information, a filtering operation that selectively emphasizes features in the stimulus that enhance survival in a particular ecological niche. The many specialized anatomic structures, such as the eye and ear, that house primary sensory neurons further enhance the detection of relevant stimuli. PMID:22110046
Julius, David; Nathans, Jeremy
In three patients sequential studies were performed of sensory and motor conduction after complete section and suture of the median nerve at the wrist and in one patient after partial section of the nerve. The sensory potential evoked by stimuli to digits III and I and recorded proximal to the suture line at the wrist appeared after a delay of three to four months, corresponding to a growth rate of 1.5-2.0 mm per day. From early in the course of regeneration the sensory potential was dispersed in 40 components. In the adult patient the cumulative amplitude increased for two years slowly and thereafter at a two times faster rate. Amplitude and tactile sensibility were normal after 40 months, but the sensory potential was still five times more dispersed than normal. The overall increase in the amplitude of the sensory potentials in children aged 10 and 12 years was three times faster than in adults. In the adults and in the children the maximum sensory conduction velocity was 10-25% of normal. It then increased at 3% per month during the first two years, and thereafter 10 times slower. Forty months after suture in the adults and 13-19 months after suture in the children the conduction velocity had reached 65-75% of normal. The pattern of discrete electrical activity during voluntary effort and the prolonged duration of motor unit potentials indicate persistent enlargement of the reinnervated motor units by peripheral sprouting. The sensory potential recovered five times faster after a compressive nerve lesion than after section and suture as seen in another patient with an affection of the ulnar nerve at the elbow. Normal tactile sensibility was attained 10 times faster than after section and suture. Maximum sensory and motor condution velocity recovered within one year from 60-70% to 80-90% of normal. PMID:448383
Buchthal, F; Kuhl, V
Introduction The restoration of erectile function following complete transection of nerve tissue during surgery remains challenging. Recently,\\u000a graft procedures using sural nerve grafts during radical prostatectomy have had favorable outcomes, and this has rekindled\\u000a interest in the applications of neural repair in a urologic setting. Although nerve repair using autologous donor graft is\\u000a the gold standard of treatment currently, donor nerve
Stephen S. Connolly; James J. Yoo; Mohamed Abouheba; Shay Soker; W. Scott McDougal; Anthony Atala
Background It is difficult to repair nerve if proximal stump is unavailable or autogenous nerve grafts are insufficient for reconstructing\\u000a extensive nerve damage. Therefore, alternative methods have been developed, including lateral anastomosis based on axons'\\u000a ability to send out collateral sprouts into denervated nerve. The different capacity of a sensory or motor axon to send a\\u000a sprout is controversial and may
Petr Dubový; Otakar Raška; Ilona Klusáková; Lubomír Stejskal; Pavel ?elakovský; Pavel Haninec
Allopurinol, an analog of hypoxanthine has been worldwide used for the treatment of hyperuricemia and gout for over 40 years. Unfortunately some patients assuming this medication have developed hypersensitivity reactions ranging from mild cutaneous eruption to more severe clinical manifestations such as allopurinol hypersensitivity syndrome or Steven-Johnson syndrome and lethal toxic epidermal necrolysis. Various strategies of slow desensitization have been elaborated to reintroduce allopurinol in a part of these patients, mainly patients affected by mild skin reactions as fixed drug eruption or exanthema. However, several new uricosuric therapies have been recently introduced. Actually drugs as recombinant urate oxidase and febuxostat are under post-marketing surveillance to control potential adverse effects related to their immunogenicity even. PMID:23092365
Calogiuri, Gianfranco; Nettis, Eustachio; Di Leo, Elisabetta; Foti, Caterina; Ferrannini, Antonio; Butani, Lavjay
The selective reunion of motor and sensory fascicles of severed mixed nerves appears indispensible for optimal recovery of the impaired motor function. Procedures available for rapid identification of motor and sensory fascicles rendered ambiguous results. The only highly reliable and simple method marking motor fascicles, namely acetylcholinesterase histochemistry, neccessitated two operations due to its long duration (28 h). In the
M. J. Szabolcs; H. Gruben; G. E. Schaden; G. Freilinger; M. Deutinger; W. Girsch; W. Happak
Previous investigations showed that the morphological basis of the low-threshold rapidly adapting mechanoreceptors in the salamander skin is the neurite--Merkel cell complex located in the epidermis. We have now examined whether sensory nerves are required for the appearance of Merkel cells, and whether these cells act as specific targets for ingrowing sensory axons. Electronmicroscopic examination of denervated skin shows that
Sheryl A. Scott; E. Cooper; J. Diamond
We present surgicoanatomical topographic relations of nerves and plexuses in the retroperitoneal space: 1) six named parietal nerves, branches of the lumbar plexus: iliohypogastric, ilioinguinal, genitofemoral, lateral femoral cutaneous, obturator, femoral. 2) The sacral plexus is formed by the lumbosacral trunk, ventral rami of S1-S3, and part of S4; the remainder of S4 joining the coccygeal plexus. From this plexus originate the superior gluteal nerve, which passes backward through the greater sciatic foramen above the piriformis muscle; the inferior gluteal nerve also courses through the greater sciatic foramen, but below the piriformis; 3) sympathetic trunks: right and left lumbar sympathetic trunks, which comprise four interconnected ganglia, and the pelvic chains; 4) greater, lesser, and least thoracic splanchnic nerves (sympathetic), which pass the diaphragm and join celiac ganglia; 5) four lumbar splanchnic nerves (sympathetic), which arise from lumbar sympathetic ganglia; 6) pelvic splanchnic nerves (nervi erigentes), providing parasympathetic innervation to the descending colon and pelvic splanchna; and 7) autonomic (prevertebral) plexuses, formed by the vagus nerves, splanchnic nerves, and ganglia (celiac, superior mesenteric, aorticorenal). They include sympathetic, parasympathetic, and sensory (mainly pain) fibers. The autonomic plexuses comprise named parts: aortic, superior mesenteric, inferior mesenteric, superior hypogastric, and inferior hypogastric (hypogastric nerves). PMID:20349652
Mirilas, Petros; Skandalakis, John E
Background: The purpose of this article is to evaluate a new method of DIEP flap neurotization using a reliably located recipient nerve. We hypothesize that neurotization by this method (with either nerve conduit or direct nerve coaptation) will have a positive effect on sensory recovery. Methods: Fifty-seven deep inferior epigastric perforator (DIEP) flaps were performed on 35 patients. Neurotizations were performed to the third anterior intercostal nerve by directly coapting the flap donor nerve or coapting with a nerve conduit. Nine nonneurotized DIEP flaps served as controls and received no attempted neurotization. All patients were tested for breast sensibility in 9 areas of the flap skin-island and adjacent postmastectomy skin. Testing occurred at an average of 111 weeks (23–309) postoperatively. Results: At a mean of 111 weeks after breast reconstruction, neurotization of the DIEP flap resulted in recovery of sensibility that was statistically significantly better (lower threshold) in the flap skin (P < 0.01) and statistically significantly better than in the native mastectomy skin into which the DIEP flap was inserted (P < 0.01). Sensibility recovered in DIEP flaps neurotized using the nerve conduit was significantly better (lower threshold) than that in the corresponding areas of the DIEP flaps neurotized by direct coaptation (P < 0.01). Conclusion: DIEP flap neurotization using the third anterior intercostal nerve is an effective technique to provide a significant increase in sensory recovery for breast reconstruction patients, while adding minimal surgical time. Additionally, the use of a nerve conduit produces increased sensory recovery when compared direct coaptation.
Menn, Zachary K.; Eldor, Liron; Kaufman, Yoav; Dellon, A. Lee
Crocodilians hunt at night, waiting half-submerged for land-bound prey to disturb the water surface. Here I show that crocodilians have specialized sensory organs on their faces that can detect small disruptions in the surface of the surrounding water, and which are linked to a dedicated, hypertrophied nerve system. Such 'dome' pressure receptors are also evident in fossils from the Jurassic period, indicating that these semi-aquatic predators solved the problem of combining armour with tactile sensitivity many millions of years ago. PMID:12015589
This newsletter contains six articles: (1) "Early Flavor Experiences: When Do They Start?" Julie A. Mennella and Gary K. Beauchamp); (2) "Infant Massage" (Tiffany Field); (3) "The Infant's Sixth Sense: Awareness and Regulation of Bodily Processes" (Stephen W. Porges); (4) "Sensory Contributions to Action: A Sensory Integrative Approach" (Marie E.…
Zero To Three, 1993
OBJECTIVES--Both sensory and sympathetic nerve fibres are depleted in the synovium in rheumatoid arthritis (RA). The hypothesis that the induction of an inflammatory response in the synovium is capable of causing depletion of nerve fibres was tested. METHODS--To investigate this phenomenon experimental arthritis in the rat was induced by three different methods and the synovium was examined for evidence of
P I Mapp; D A Walsh; N E Garrett; B L Kidd; S C Cruwys; J M Polak; D R Blake
It is believed that repeated exposure to real-life and to entertainment violence may alter cognitive, affective, and behavioral processes, possibly leading to desensitization. The goal of the present study was to determine if there are relationships between real-life and media violence exposure and desensitization as reflected in related characteristics. One hundred fifty fourth and fifth graders completed measures of real-life
Jeanne B. Funk; Heidi Bechtoldt Baldacci; Tracie Pasold; Jennifer Baumgardner
The nicotinic acetylcholine receptor (nAChR) is a member of the important Cys-loop ligand-gated ion channel superfamily that modulates neuronal excitability. After responding to their agonists, their actions are terminated either by removal of ligand or by fast and slow desensitization, processes that play an important role in modulating the duration of conducting states and hence of integrated neuronal behavior. We monitored structural changes occurring during fast and slow desensitization in the transmembrane domain of the Torpedo nAChR using time–resolved photolabeling with the hydrophobic probe 3-(trifluoromethyl)-3-(m-iodophenyl) diazirine (TID). After channel opening, TID photolabels a residue on the ?-subunit’s M2–M3 loop and a cluster of four residues on ?M1 and ?M2, defining an open state pocket [Arevalo, E. et al. (2005) J. Biol. Chem. 280, 13631–13640]. We now find that photolabeling of this pocket persists during the transition to the fast desensitized state, decreasing only with the transition to the slow desensitized state. In contrast, photoincorporation in the channel lumen at the conserved 9? leucines on the second transmembrane helix (M2–9?) decreased successively during the resting to open and open to fast desensitized state transitions, implying that the local conformation is different in each state, a conclusion consistent with the hypothesis that there are separate gates for channel opening and desensitization. Thus, although during fast desensitization there is a conformation change in the channel lumen at the level of M2–9?, there is none in the regions of the ?-subunit’s M2–M3 loop and the interior of its M1–M4 helix bundle until slow desensitization occurs. PMID:19961216
Yamodo, Innocent H.; Chiara, David C.; Cohen, Jonathan B.; Miller, Keith W.
Epithelial Na(+) channel (ENaC)/degenerin family members are involved in mechanosensation, blood pressure control, pain sensation, and the expression of fear. Several of these channel types display a form of desensitization that allows the channel to limit Na(+) influx during prolonged stimulation. We used site-directed mutagenesis and chemical modification, functional analysis, and molecular dynamics simulations to investigate the role of the lower palm domain of the acid-sensing ion channel 1, a member of the ENaC/degenerin family. The lower palm domains of this trimeric channel are arranged around a central vestibule, at ?20 Å above the plasma membrane and are covalently linked to the transmembrane channel parts. We show that the lower palm domains approach one another during desensitization. Residues in the palm co-determine the pH dependence of desensitization, its kinetics, and the stability of the desensitized state. Mutations of palm residues impair desensitization by preventing the closing movement of the palm. Overexpression of desensitization-impaired channel mutants in central neurons allowed--in contrast to overexpression of wild type--a sustained signaling response to rapid pH fluctuations. We identify and describe here the function of an important regulatory domain that most likely has a conserved role in ENaC/degenerin channels. PMID:24018065
Roy, Sophie; Boiteux, Céline; Alijevic, Omar; Liang, Chungwen; Bernèche, Simon; Kellenberger, Stephan
Objectives: Hypersensitivity is a common clinical multietiological problem. Many desensitizing treatments are there to overcome hypersensitivity. The aim of this study was to evaluate the effect of different dentin-desensitizing treatments on the tensile bond strength of composite restoration. Materials and Methods: Twenty-four sound human molars were used. Enamel was wet abraded to expose flat dentin surfaces, polished with sandpaper. The specimens were then divided into three groups (n = 8) based on the type of dentin-desensitizing treatment given. The first group: G1 was the control group where no desensitizing agent was used. The second group: G2 was treated with desensitizing dentifrice containing a combination of potassium nitrate, triclosan, and sodium monoflorophosphate. The third group: G3 was treated with Er:YAG laser. Afterwards, the desensitized specimens were treated with one step self-etch adhesive according to manufacturer's instructions and composite microcylinders were packed. The specimens were then examined for tensile bond strength using universal tensile machine (KMITM ). Results: Statistical analysis of the data obtained revealed the mean values for the tensile bond strengths were 10.2613 MPa, 5.9400 MPa and 6.3575 MPa for groups 1, 2 and 3, respectively. These values were statistically significantly different between groups pretreated with laser or dentifrice as compared to control group. Conclusions: Dentifrice and Laser pre-treated dentin has lower tensile bond strength with resin composites as compared to dentin that is untreated.
Makkar, Sameer; Goyal, Meenu; Kaushal, Ashih; Hegde, Vivek
Activation of K(+) channels by the G protein ?? subunits is an important signaling mechanism of G-protein-coupled receptors. Typically, receptor-activated K(+) currents desensitize in the sustained presence of agonists to avoid excessive effects on cellular activity. The auxiliary GABAB receptor subunit KCTD12 induces fast and pronounced desensitization of the K(+) current response. Using proteomic and electrophysiological approaches, we now show that KCTD12-induced desensitization results from a dual interaction with the G protein: constitutive binding stabilizes the heterotrimeric G protein at the receptor, whereas dynamic binding to the receptor-activated G?? subunits induces desensitization by uncoupling G?? from the effector K(+) channel. While receptor-free KCTD12 desensitizes K(+) currents activated by other GPCRs in vitro, native KCTD12 is exclusively associated with GABAB receptors. Accordingly, genetic ablation of KCTD12 specifically alters GABAB responses in the brain. Our results show that GABAB receptors are endowed with fast and reversible desensitization by harnessing KCTD12 that intercepts G?? signaling. PMID:24836506
Turecek, Rostislav; Schwenk, Jochen; Fritzius, Thorsten; Ivankova, Klara; Zolles, Gerd; Adelfinger, Lisa; Jacquier, Valerie; Besseyrias, Valerie; Gassmann, Martin; Schulte, Uwe; Fakler, Bernd; Bettler, Bernhard
The development of dissociated cells from rat embryonic spinal ganglion after transplantation to damaged nerve of adult animals was studied using immunohistochemical differentiation markers of neural and glial cells. The cell suspension obtained after dissociation of rat embryonic spinal ganglia (embryonic day 15) was injected into the proximal segment of crushed sciatic nerve. The nerve was damaged by ligation for 40 sec. Progenitor cells were labeled with 5-bromo-2'-deoxyuridine (BrdU) before transplantation. BrdU-immunopositive cells were detected in the nerve trunks of recipients on days 1, 21, and 28 after transplantation. Dissociated cells of rat embryonic spinal ganglion (embryonic day 15) survived for at least 4 weeks after transplantation to the nerve and differentiate into NeuN-immunopositive neurons with morphological properties of sensory neurons and satellite cells containing S100 protein. PMID:25257430
Petrova, E S; Isaeva, E N; Korzhevskii, D E
The loss of a large proportion of primary sensory neurons after peripheral nerve axotomy is well documented. As a consequence of this loss, the innervation density attained on completion of regeneration will never be normal, regardless of how well the individual surviving neurons regenerate. Acetyl-l-carnitine (ALCAR), an endogenous peptide in man, has been demonstrated to protect sensory neurons, thereby avoiding
Andrew D. H Wilson; Andrew Hart; Thomas Brannstrom; Mikael Wiberg; Giorgio Terenghi
This study examines key elements of glutamatergic transmission within sensory ganglia of the rat. We show that the soma of primary sensory neurons release glutamate when depolarized. Using acute dissociated mixed neuronal/glia cultures of dorsal root ganglia (DRG) or trigeminal ganglia and a colorimetric assay, we show that when glutamate uptake by satellite glial cells (SGCs) is inhibited, KCl stimulation leads to simultaneous increase of glutamate in the culture medium. With calcium imaging we see that the soma of primary sensory neurons and SGCs respond to AMPA, NMDA, kainate and mGluR agonists, and selective antagonists block this response. Using whole cell patch-clamp technique, inward currents were recorded from small diameter (<30 µm) DRG neurons from intact DRGs (ex-vivo whole ganglion preparation) in response to local application of the above glutamate receptor agonists. Following a chronic constriction injury (CCI) of either the inferior orbital nerve or the sciatic nerve, glutamate expression increases in the trigeminal ganglia and DRG respectively. This increase occurs in neurons of all diameters and is present in the somata of neurons with injured axons as well as in somata of neighboring uninjured neurons. These data provides additional evidence that glutamate can be released within the sensory ganglion, and that the somata of primary sensory neurons as well as SGCs express functional glutamate receptors at their surface. These findings, together with our previous gene knockdown data, suggest that glutamatergic transmission within the ganglion could impact nociceptive threshold. PMID:23844184
Kung, Ling-Hsuan; Gong, Kerui; Adedoyin, Mary; Ng, Johnson; Bhargava, Aditi; Ohara, Peter T.; Jasmin, Luc
Background: Cervical Radiculopathy (CR) is a neurologic condition characterised by dysfunction of a cervical spinal nerve, the roots of the nerve, or both. Diagnostic criteria for CR are not well defined, and no universally accepted criteria for its diagnosis have been established. Clinical examination, radiological imaging and electrophysiologic evaluation are the different modalities to diagnose CR. The incidence of Cervical Spondylosis and related conditions is increasing in the present scenario and the use of radiologic examination is time consuming and uneconomical for the common Indian setup. Thus, there is a definite need to establish a cost effective, reliable, and accurate means for establishing the diagnosis of cervical radiculopathy. Electrodiagnostic tests are the closest to fulfill these criteria. Aim: To evaluate diagnostic utility of various motor and sensory nerve conduction study parameters in cervical radiculopathy. Setting and Design: It was a cross-sectional study conducted on 100 subjects of age > 40 years. Material and Methods: The consecutive patients clinically diagnosed to have cervical radiculopathy, referred from department of Orthopaedics were prospectively recruited for the motor and sensory nerve conduction study using RMS EMG EP Mark-II. Parameters studied were Compound Muscle Action Potential (CMAP), Distal Motor Latency (DML) and Conduction Velocity (CV) for motor nerves and Sensory Nerve Action Potential (SNAP) and CV for sensory nerves. Statistical Analysis: Study observations and results were analysed to find the Specificity, Sensitivity, Positive Predictive Value and Negative Predictive Value using SPSS 16.0. Results: Among various motor nerve conduction parameters CMAP was found to be more sensitive with high positive predicative value. CV was found to have greater specificity and DML had least negative predictive value. Sensory nerve conduction parameters were found to have less sensitivity but higher specificity as compared to motor parameters. Conclusion: Nerve conduction studies are useful supportive diagnostic tool for suspected cervical radiculopathy as they are found to have reliable sensitivity and specificity. PMID:24551610
Pawar, Sachin; Kashikar, Aditi; Shende, Vinod; Waghmare, Satish
Following distal nerve injury significant sensory neuronal cell death occurs in the dorsal root ganglia, while after a more proximal injury, such as brachial plexus injury, a sizeable proportion of spinal motoneurons also undergo cell death. This phenomenon has been undervalued for a long time, but it has a significant role in the lack of functional recuperation, as neuronal cells
G. Terenghi; A. Hart; M. Wiberg
The structure and function of the central nervous system strongly depend on the organization and efficacy of the incoming sensory input. A disruption of somesthetic input severely alters the metabolic activity, electrophysiological properties and even gross anatomical features of the primary somatosensory cortex. Here we examined, in the rat somatosensory cortex, the neuroprotective and therapeutic effects of artificial sensory stimulation after irreversible unilateral transection of a peripheral sensory nerve (the infraorbital branch of the trigeminal nerve). The proximal stump of the nerve was inserted into a silicon tube with stimulating electrodes, through which continuous electrical stimulation was applied for 12 h/day (square pulses of 100 ?s, 3.0 V, at 20 Hz) for 4 weeks. Deafferented animals showed significant decreases in cortical evoked potentials, cytochrome oxidase staining intensity (layers II-IV), cortical volume (layer IV) and number of parvalbumin-expressing (layers II-IV) and calbindin-D28k-expressing (layers II/III) interneurons. These deafferentation-dependent effects were largely absent in the nerve-stimulated animals. Together, these results provide evidence that chronic electrical stimulation has a neuroprotective and preservative effect on the sensory cortex, and raise the possibility that, by controlling the physical parameters of an artificial sensory input to a sectioned peripheral nerve, chronically deafferented brain regions could be maintained at near-'normal' conditions. Our findings could be important for the design of sensory neuroprostheses and for therapeutic purposes in brain lesions or neural degenerative processes. PMID:23006217
Herrera-Rincon, Celia; Torets, Carlos; Sanchez-Jimenez, Abel; Avendaño, Carlos; Panetsos, Fivos
It is more than 20 years since artificial nerve guides (or conduits) were introduced into clinical practice as a reliable\\u000a alternative to autograft. They are basically cylindrical conduits inside which a regenerating nerve stump may find protection\\u000a and guidance. Early guides were made of silicone and were not biodegradable; they were shown to support nerve regeneration\\u000a but, subsequently, were considered
A. Merolli; L. Rocchi
Hereditary sensory autonomic neuropathy type IV (HSAN -IV), also known as congenital insensitivity to pain with anhidrosis, is a very rare condition that presents in infancy with anhidrosis, absence of pain sensation and self -mutilation. Developmental delay and mental retardation are usually present. Ultrastructural study of the peripheral nerves demonstrates loss of the unmyelinated and small myelinated fibers. We here report a 8 year -old boy with HSAN IV with typical clinical features where the diagnosis was supported by nerve biopsy findings. However, our case was unusual since mental development was normal. PMID:22566729
Prashanth, G P; Kamate, Mahesh
Hereditary sensory autonomic neuropathy type IV (HSAN -IV), also known as congenital insensitivity to pain with anhidrosis, is a very rare condition that presents in infancy with anhidrosis, absence of pain sensation and self -mutilation. Developmental delay and mental retardation are usually present. Ultrastructural study of the peripheral nerves demonstrates loss of the unmyelinated and small myelinated fibers. We here report a 8 year -old boy with HSAN IV with typical clinical features where the diagnosis was supported by nerve biopsy findings. However, our case was unusual since mental development was normal. PMID:22566729
Prashanth, G. P.; Kamate, Mahesh
Objective: to establish the safety and efficacy of desensitization to co-trimoxazole in hypersensitive HIV-infected subjects. To assess if delayed hypersensitivity (type IV) to co-trimoxazole predicts those unable to be desensitized.Methods: desensitization to co-trimoxazole, comprising trimethoprim (T) 0.4 mg and sulphamethoxazole (S) 2 mg initially with doubling dose daily, full strength co-trimoxazole (T\\/S 160 mg\\/800 mg) at 10 days. Patch testing
Mark M. Gompels; Nick Simpson; Mike Snow; Gavin Spickett; Edmund Ong
Peripheral nerve injury is often followed by incomplete and unsatisfactory functional recovery and may be associated with sensory and motor impairment of the affected limb. Therefore, a novel method is needed to improve the speed of recovery and the final functional outcome after peripheral nerve injuries. This report investigates the effect of lentiviral-mediated transfer of conserved dopamine neurotrophic factor (CDNF) on regeneration of the rat peripheral nerve in a transection model in vivo. We observed notable overexpression of CDNF protein in the distal sciatic nerve after recombinant CDNF lentiviral vector application. We evaluated sciatic nerve regeneration after surgery using light and electron microscopy and the functional recovery using the sciatic functional index and target muscle weight. HE staining revealed better ordered structured in the CDNF-treated group at 8 weeks post-surgery. Quantitative analysis of immunohistochemistry of NF200 and S-100 in the CDNF group revealed significant improvement of axonal and Schwann cell regeneration compared with the control groups at 4 weeks and 8 weeks after injury. The thickness of the myelination around the axons in the CDNF group was significantly higher than in the control groups at 8 weeks post-surgery. The CDNF group displayed higher muscle weights and significantly increased sciatic nerve index values. Our findings suggest that CDNF gene therapy could provide durable and stable CDNF protein concentration and has the potential to enhance peripheral nerve regeneration, morphological and functional recovery following nerve injury, which suggests a promising strategy for peripheral nerve repair. PMID:24076387
Cheng, Lei; Liu, Yi; Zhao, Hua; Zhang, Wen; Guo, Ying-Jun; Nie, Lin
The role of neurotrophic factors in the maintenance and survival of peripheral neuronal cells has been the subject of numerous studies. Administration of exogenous neurotrophic factors after nerve injury has been shown to mimic the effect of target organ-derived trophic factors on neuronal cells. After axotomy and during peripheral nerve regeneration, the neurotrophins NGF, NT-3 and BDNF show a well defined and selective beneficial effect on the survival and phenotypic expression of primary sensory neurons in dorsal root ganglia and of motoneurons in spinal cord. Other neurotrophic factors such as CNTF, GDNF and LIF also exert a variety of actions on neuronal cells, which appear to overlap and complement those of the neurotrophins. In addition, there is an indirect contribution of GGF to nerve regeneration. GGF is produced by neurons and stimulates proliferation of Schwann cells, underlining the close interaction between neuronal and glial cells during peripheral nerve regeneration. Different possibilities have been investigated for the delivery of growth factors to the injured neurons, in search of a suitable system for clinical applications. The studies reviewed in this article show the therapeutic potential of neurotrophic factors for the treatment of peripheral nerve injury and for neuropathies. PMID:10227662
We examined the initial expression of synaptic function in the embryonic chick trigeminal nucleus using voltage-sensitive dye recording. Brainstem preparations with three trigeminal nerve afferents, the ophthalmic nerve (N.V1), maxillary nerve (N.V2) and mandibular nerve (N.V3), were dissected from 5.5- to 6.5-day-old chick embryos. In our previous study [Sato et al., 1999], we detected slow signals corresponding to glutamatergic excitatory postsynaptic potentials and identified the principal sensory nucleus of the trigeminal nerve (Pr5), spinal sensory nucleus of the trigeminal nerve (Sp5) and trigeminal motor nucleus. In this study, we examined the effects of removing Mg(2+) from the physiological solution, which enhanced N-methyl-d-aspartate receptor function in the sensory nuclei. In 6.5-day-old (St 29) embryos, the slow signal was observed in Pr5 and Sp5 only when N.V1 was stimulated, whereas it appeared in Mg(2+)-free solution with every nerve stimulation. In 6-day-old (St 28) embryos, the slow signal was observed in Sp5 with N.V1 stimulation, and the appearance of synaptic function in Mg(2+)-free solution varied, depending on the nerves and preparations used. In 5.5-day-old (St 27) embryos, synaptic function was not detected even when external Mg(2+) was removed. These results indicate that the initial expression of synaptic function in the trigeminal system occurs earlier than previously considered, and that the developmental organization of synaptic function differs among the three trigeminal nerves and between the two sensory nuclei. PMID:24769319
Momose-Sato, Yoko; Sato, Katsushige
Eye movement desensitization and reprocessing (EMDR) is an established treatment for post-traumatic stress disorder (PTSD). However, its working mechanism remains unclear. This study explored physiological correlates of eye movements during EMDR in relation to current hypotheses; distraction, conditioning, orienting response activation, and REM-like mechanisms. During EMDR therapy, fingertip temperature, heart rate, skin conductance, expiratory carbon dioxide level, and blood pulse oximeter oxygen saturation, were measured in male subjects with PTSD. The ratio between the low and high frequency components of the heart rate power spectrum (LF/HF) were computed as measures of autonomic balance. Respiratory rate was calculated from the carbon dioxide trace. Stimulation shifted the autonomic balance as indicated by decreases in heart rate, skin conductance and LF/HF-ratio, and an increased finger temperature. The breathing frequency and end-tidal carbon dioxide increased; oxygen saturation decreased during eye movements. In conclusion, eye movements during EMDR activate cholinergic and inhibit sympathetic systems. The reactivity has similarities with the pattern during REM-sleep. PMID:17604948
Elofsson, Ulf O E; von Schèele, Bo; Theorell, Töres; Söndergaard, Hans Peter
While cognitive behavior therapy is considered to be the first-line therapy for adolescent depression, there are limited data on whether other psychotherapeutic techniques are also effective in treating adolescents with depression. This report suggests the potential application of eye movement desensitization and reprocessing (EMDR) for treatment of depressive disorder related, not to trauma, but to stressful life events. At present, EMDR has only been empirically validated for only trauma-related disorders such as posttraumatic stress disorder. Two teenagers with major depressive disorder (MDD) underwent three and seven sessions of EMDR aimed at memories of stressful life events. After treatment, their depressive symptoms decreased to the level of full remission, and the therapeutic gains were maintained after two and three months of follow up. The effectiveness of EMDR for depression is explained by the model of adaptive information processing. Given the powerful effects observed within a brief period of time, the authors suggest that further investigation of EMDR for depressive disorders is warranted. PMID:20046410
Bae, Hwallip; Kim, Daeho; Park, Yong Chon
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 [Ca(2+)]i transients in unprimed cells. ET-1 induced [Ca(2+)]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 [Ca(2+)]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
Smith, Terika P; Smith, Sherika N; Sweitzer, Sarah M
Cell signaling is often mediated by the binding of multiple ligands to a multi-subunit receptor. The probabilistic nature and slow rate of binding of diffusible ligands at low concentrations can impede attempts to determine how ligand occupancy controls signaling in such protein complexes. We describe a solution to this problem that uses a photoswitched tethered ligand as a “ligand clamp” to induce rapid and stable binding and unbinding at defined subsets of subunits. We applied the approach to study gating in ionotropic glutamate receptors (iGluRs), ligand-gated ion channels that mediate excitatory neurotransmission and plasticity at glutamatergic synapses in the brain. We probed gating in two kainate-type iGluRs, GluK2 homotetramers and GluK2/GluK5 heterotetramers. Ultrafast (sub-millisecond) photoswitching of an azobenzene-based ligand on specific subunits provided a real-time measure of gating and revealed that partially occupied receptors can activate without desensitizing. The findings have implications for signaling by locally released and spillover glutamate. PMID:24561661
Reiner, Andreas; Isacoff, Ehud Y.
The primary goal was to determine agonist-specific regulation of CRF2(a) receptor function. Exposure of human retinoblastoma Y79 cells to selective (UCN2, UCN3 or stresscopins) and nonselective (UCN1 or sauvagine) agonists prominently desensitized CRF2(a) receptors in a rapid, concentration-dependent manner. A considerably slower rate and smaller magnitude of desensitization developed in response to the weak agonist CRF. CRF1 receptor desensitization stimulated by CRF, cortagine or stressin1-A had no effect on CRF2(a) receptor cyclic AMP signaling. Conversely, desensitization of CRF2(a) receptors by UCN2 or UCN3 did not cross-desensitize Gs-coupled CRF1 receptor signaling. In transfected HEK293 cells, activation of CRF2(a) receptors by UCN2, UCN3 or CRF resulted in receptor phosphorylation and internalization proportional to agonist potency. Neither protein kinase A nor casein kinases mediated CRF2(a) receptor phosphorylation or desensitization. Exposure of HEK293 or U2OS cells to UCN2 or UCN3 (100 nM) produced strong ?arrestin2 translocation and colocalization with membrane CRF2(a) receptors while CRF (1 µM) generated only weak ?arrestin2 recruitment. ?arrestin2 did not internalize with the receptor, however, indicating that transient CRF2(a) receptor-arrestin complexes dissociate at or near the cell membrane. Since deletion of the ?arrestin2 gene upregulated Gs-coupled CRF2(a) receptor signaling in MEF cells, a ?arrestin2 mechanism restrains Gs-coupled CRF2(a) receptor signaling activated by urocortins. We further conclude the rate and extent of homologous CRF2(a) receptor desensitization are governed by agonist-specific mechanisms affecting GRK phosphorylation, ?arrestin2 recruitment, and internalization thereby producing unique signal transduction profiles that differentially affect the stress response. PMID:23820308
Hauger, Richard L.; Olivares-Reyes, J. Alberto; Braun, Sandra; Hernandez-Aranda, Judith; Hudson, Christine C.; Gutknecht, Eric; Dautzenberg, Frank M.; Oakley, Robert H.
The primary goal was to determine agonist-specific regulation of CRF2(a) receptor function. Exposure of human retinoblastoma Y79 cells to selective (UCN2, UCN3 or stresscopins) and non-selective (UCN1 or sauvagine) agonists prominently desensitized CRF2(a) receptors in a rapid, concentration-dependent manner. A considerably slower rate and smaller magnitude of desensitization developed in response to the weak agonist CRF. CRF1 receptor desensitization stimulated by CRF, cortagine or stressin1-A had no effect on CRF2(a) receptor cyclic AMP signaling. Conversely, desensitization of CRF2(a) receptors by UCN2 or UCN3 did not cross-desensitize Gs-coupled CRF1 receptor signaling. In transfected HEK293 cells, activation of CRF2(a) receptors by UCN2, UCN3 or CRF resulted in receptor phosphorylation and internalization proportional to agonist potency. Neither protein kinase A nor casein kinases mediated CRF2(a) receptor phosphorylation or desensitization. Exposure of HEK293 or U2OS cells to UCN2 or UCN3 (100nM) produced strong ?arrestin2 translocation and colocalization with membrane CRF2(a) receptors while CRF (1?M) generated only weak ?arrestin2 recruitment. ?arrestin2 did not internalize with the receptor, however, indicating that transient CRF2(a) receptor-arrestin complexes dissociate at or near the cell membrane. Since deletion of the ?arrestin2 gene upregulated Gs-coupled CRF2(a) receptor signaling in MEF cells, a ?arrestin2 mechanism restrains Gs-coupled CRF2(a) receptor signaling activated by urocortins. We further conclude that the rate and extent of homologous CRF2(a) receptor desensitization are governed by agonist-specific mechanisms affecting GRK phosphorylation, ?arrestin2 recruitment, and internalization thereby producing unique signal transduction profiles that differentially affect the stress response. PMID:23820308
Hauger, Richard L; Olivares-Reyes, J Alberto; Braun, Sandra; Hernandez-Aranda, Judith; Hudson, Christine C; Gutknecht, Eric; Dautzenberg, Frank M; Oakley, Robert H
BackgroundWhile neural systems are known to respond to chemical and electrical stimulation, the effect of mechanics on these highly sensitive cells is still not well understood. The ability to examine the effects of mechanics on these cells is limited by existing approaches, although their overall response is intimately tied to cell-matrix interactions. Here, we offer a novel method, which we
Yi-Wen Lin; Chao-Min Cheng; Philip R. Leduc; Chih-Cheng Chen; Damien Keating
Injury to nerve tissue in the peripheral nervous system (PNS) results in long-term impairment of limb function, dysaesthesia and pain, often with associated psychological effects. Whilst minor injuries can be left to regenerate without intervention and short gaps up to 2 cm can be sutured, larger or more severe injuries commonly require autogenous nerve grafts harvested from elsewhere in the body (usually sensory nerves). Functional recovery is often suboptimal and associated with loss of sensation from the tissue innervated by the harvested nerve. The challenges that persist with nerve repair have resulted in development of nerve guides or conduits from non-neural biological tissues and various polymers to improve the prognosis for the repair of damaged nerves in the PNS. This study describes the design and fabrication of a multimodal controlled pore size nerve regeneration conduit using polylactic acid (PLA) and (PLA):poly(lactic-co-glycolic) acid (PLGA) fibers within a neurotrophin-enriched alginate hydrogel. The nerve repair conduit design consists of two types of PLGA fibers selected specifically for promotion of axonal outgrowth and Schwann cell growth (75:25 for axons; 85:15 for Schwann cells). These aligned fibers are contained within the lumen of a knitted PLA sheath coated with electrospun PLA nanofibers to control pore size. The PLGA guidance fibers within the nerve repair conduit lumen are supported within an alginate hydrogel impregnated with neurotrophic factors (NT-3 or BDNF with LIF, SMDF and MGF-1) to provide neuroprotection, stimulation of axonal growth and Schwann cell migration. The conduit was used to promote repair of transected sciatic nerve in rats over a period of 4 weeks. Over this period, it was observed that over-grooming and self-mutilation (autotomy) of the limb implanted with the conduit was significantly reduced in rats implanted with the full-configuration conduit compared to rats implanted with conduits containing only an alginate hydrogel. This indicates return of some feeling to the limb via the fully-configured conduit. Immunohistochemical analysis of the implanted conduits removed from the rats after the four-week implantation period confirmed the presence of myelinated axons within the conduit and distal to the site of implantation, further supporting that the conduit promoted nerve repair over this period of time. This study describes the design considerations and fabrication of a novel multicomponent, multimodal bio-engineered synthetic conduit for peripheral nerve repair.
Quigley, A. F.; Bulluss, K. J.; Kyratzis, I. L. B.; Gilmore, K.; Mysore, T.; Schirmer, K. S. U.; Kennedy, E. L.; O'Shea, M.; Truong, Y. B.; Edwards, S. L.; Peeters, G.; Herwig, P.; Razal, J. M.; Campbell, T. E.; Lowes, K. N.; Higgins, M. J.; Moulton, S. E.; Murphy, M. A.; Cook, M. J.; Clark, G. M.; Wallace, G. G.; Kapsa, R. M. I.
Injury to nerve tissue in the peripheral nervous system (PNS) results in long-term impairment of limb function, dysaesthesia and pain, often with associated psychological effects. Whilst minor injuries can be left to regenerate without intervention and short gaps up to 2 cm can be sutured, larger or more severe injuries commonly require autogenous nerve grafts harvested from elsewhere in the body (usually sensory nerves). Functional recovery is often suboptimal and associated with loss of sensation from the tissue innervated by the harvested nerve. The challenges that persist with nerve repair have resulted in development of nerve guides or conduits from non-neural biological tissues and various polymers to improve the prognosis for the repair of damaged nerves in the PNS. This study describes the design and fabrication of a multimodal controlled pore size nerve regeneration conduit using polylactic acid (PLA) and (PLA):poly(lactic-co-glycolic) acid (PLGA) fibers within a neurotrophin-enriched alginate hydrogel. The nerve repair conduit design consists of two types of PLGA fibers selected specifically for promotion of axonal outgrowth and Schwann cell growth (75:25 for axons; 85:15 for Schwann cells). These aligned fibers are contained within the lumen of a knitted PLA sheath coated with electrospun PLA nanofibers to control pore size. The PLGA guidance fibers within the nerve repair conduit lumen are supported within an alginate hydrogel impregnated with neurotrophic factors (NT-3 or BDNF with LIF, SMDF and MGF-1) to provide neuroprotection, stimulation of axonal growth and Schwann cell migration. The conduit was used to promote repair of transected sciatic nerve in rats over a period of 4 weeks. Over this period, it was observed that over-grooming and self-mutilation (autotomy) of the limb implanted with the conduit was significantly reduced in rats implanted with the full-configuration conduit compared to rats implanted with conduits containing only an alginate hydrogel. This indicates return of some feeling to the limb via the fully-configured conduit. Immunohistochemical analysis of the implanted conduits removed from the rats after the four-week implantation period confirmed the presence of myelinated axons within the conduit and distal to the site of implantation, further supporting that the conduit promoted nerve repair over this period of time. This study describes the design considerations and fabrication of a novel multicomponent, multimodal bio-engineered synthetic conduit for peripheral nerve repair. PMID:23283383
Quigley, A F; Bulluss, K J; Kyratzis, I L B; Gilmore, K; Mysore, T; Schirmer, K S U; Kennedy, E L; O'Shea, M; Truong, Y B; Edwards, S L; Peeters, G; Herwig, P; Razal, J M; Campbell, T E; Lowes, K N; Higgins, M J; Moulton, S E; Murphy, M A; Cook, M J; Clark, G M; Wallace, G G; Kapsa, R M I
Szechuan peppers contain hydroxy-?-sanshool that imparts desirable tingling, cooling, and numbing sensations. Hydroxy-?-sanshool activates a subset of sensory dorsal root ganglion (DRG) neurons by inhibiting two-pore potassium channels. We presently investigated if a tingle-evoking sanshool analog, isobutylalkenyl amide (IBA), excites rat DRG neurons and, if so, if these neurons are also activated by agonists of TRPM8, TRPA1, and/or TRPV1. Thirty-four percent of DRG neurons tested responded to IBA, with 29% of them also responding to menthol, 29% to cinnamic aldehyde, 66% to capsaicin, and subsets responding to two or more transient receptor potential (TRP) agonists. IBA-responsive cells had similar size distributions regardless of whether they responded to capsaicin or not; cells only responsive to IBA were larger. Responses to repeated application of IBA at a 5-min interstimulus interval exhibited self-desensitization (tachyphylaxis). Capsaicin did not cross-desensitize responses to IBA to any greater extent than the tachyphylaxis observed with repeated IBA applications. These findings are consistent with psychophysical observations that IBA elicits tingle sensation accompanied by pungency and cooling, with self-desensitization but little cross-desensitization by capsaicin. Intraplantar injection of IBA elicited nocifensive responses (paw licking, shaking-flinching, and guarding) in a dose-related manner similar to the effects of intraplantar capsaicin and serotonin. IBA had no effect on thermal sensitivity but enhanced mechanical sensitivity at the highest dose tested. These observations suggest that IBA elicits an unfamiliar aversive sensation that is expressed behaviorally by the limited response repertoire available to the animal. PMID:21273322
Klein, Amanda H; Sawyer, Carolyn M; Zanotto, Karen L; Ivanov, Margaret A; Cheung, Susan; Carstens, Mirela Iodi; Furrer, Stephan; Simons, Christopher T; Slack, Jay P; Carstens, E
A sensory substitution device is developed in which nonretinal stimulus is used to generate input to the brain of blind people to substitute for damage or loss of retinal input. Although the final realization of this technology (direct stimulation of the corneal nerve endings) was not addressed, a device consisting of a contact lens delivering point mechanical or electrical stimulating of the corneal nerves and a camera mounted on a spectacles frame which wirelessly transmit processed image to the contact lens, translating the visual information into tactile sensation is expected to be constructed. In order to improve the spatial resolution of the constructed image, the camera will also time multiplex, compress and encode the captured image before transmitting it to the stimulating contact lens. Preliminary devices performing tactile stimulation of the fingers and of the tongue by applying point electrical stimulations, were constructed and tested. Subjects were taught to "see" using the mechanical and the electrical tactile sensory.
Zalevsky, Zeev; Elani, Gal; Azoulay, Eli; Ilani, Dan; Beiderman, Yevgeny; Belkin, Michael
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.
Tcheng, Ping; Supplee, Frank H., Jr.; Prass, Richard L.
Background Degeneration of intraepidermal nerve fibers (IENF) is a hallmark of small fiber neuropathy of different etiology, whose clinical picture is dominated by neuropathic pain. It is unknown if critical illness can affect IENF. Methods We enrolled 14 adult neurocritical care patients with prolonged intensive care unit (ICU) stay and artificial ventilation (? 3 days), and no previous history or risk factors for neuromuscular disease. All patients underwent neurological examination including evaluation of consciousness, sensory functions, muscle strength, nerve conduction study and needle electromyography, autonomic dysfunction using the finger wrinkling test, and skin biopsy for quantification of IENF and sweat gland innervation density during ICU stay and at follow-up visit. Development of infection, sepsis and multiple organ failure was recorded throughout the ICU stay. Results Of the 14 patients recruited, 13 (93%) had infections, sepsis or multiple organ failure. All had severe and non-length dependent loss of IENF. Sweat gland innervation was reduced in all except one patient. Of the 7 patients available for follow-up visit, three complained of diffuse sensory loss and burning pain, and another three showed clinical dysautonomia. Conclusions Small fiber pathology can develop in the acute phase of critical illness and may explain chronic sensory impairment and pain in neurocritical care survivors. Its impact on long term disability warrants further studies involving also non-neurologic critical care patients. PMID:24098716
Latronico, Nicola; Filosto, Massimiliano; Fagoni, Nazzareno; Gheza, Laura; Guarneri, Bruno; Todeschini, Alice; Lombardi, Raffaella; Padovani, Alessandro; Lauria, Giuseppe
Current approaches for treating peripheral nerve injury have resulted in promising, yet insufficient functional recovery compared to the clinical standard of care, autologous nerve grafts. In order to design a construct that can match the regenerative potential of the autograft, all facets of nerve tissue must be incorporated in a combinatorial therapy. Engineered biomaterial scaffolds in the future will have to promote enhanced regeneration and appropriate reinnervation by targeting the highly sensitive response of regenerating nerves to their surrounding microenvironment. PMID:23790730
Marquardt, Laura; Sakiyama-Elbert, Shelly E.
Highlights: •CDNF was successfully transfected by a lentiviral vector into the distal sciatic nerve. •CDNF improved S-100, NF200 expression and nerve regeneration after sciatic injury. •CDNF improved the remyelination and thickness of the regenerated sciatic nerve. •CDNF improved gastrocnemius muscle weight and sciatic functional recovery. -- Abstract: Peripheral nerve injury is often followed by incomplete and unsatisfactory functional recovery and may be associated with sensory and motor impairment of the affected limb. Therefore, a novel method is needed to improve the speed of recovery and the final functional outcome after peripheral nerve injuries. This report investigates the effect of lentiviral-mediated transfer of conserved dopamine neurotrophic factor (CDNF) on regeneration of the rat peripheral nerve in a transection model in vivo. We observed notable overexpression of CDNF protein in the distal sciatic nerve after recombinant CDNF lentiviral vector application. We evaluated sciatic nerve regeneration after surgery using light and electron microscopy and the functional recovery using the sciatic functional index and target muscle weight. HE staining revealed better ordered structured in the CDNF-treated group at 8 weeks post-surgery. Quantitative analysis of immunohistochemistry of NF200 and S-100 in the CDNF group revealed significant improvement of axonal and Schwann cell regeneration compared with the control groups at 4 weeks and 8 weeks after injury. The thickness of the myelination around the axons in the CDNF group was significantly higher than in the control groups at 8 weeks post-surgery. The CDNF group displayed higher muscle weights and significantly increased sciatic nerve index values. Our findings suggest that CDNF gene therapy could provide durable and stable CDNF protein concentration and has the potential to enhance peripheral nerve regeneration, morphological and functional recovery following nerve injury, which suggests a promising strategy for peripheral nerve repair.
Cheng, Lei; Liu, Yi; Zhao, Hua; Zhang, Wen; Guo, Ying-Jun; Nie, Lin, E-mail: firstname.lastname@example.org
Objective This study was conducted to ascertain the correlation between preserved pelvic nerve networks and bladder function after laparoscopic nerve-sparing radical hysterectomy. Methods Between 2009 and 2011, 53 patients underwent total laparoscopic radical hysterectomies. They were categorized into groups A, B, and C based on the status of preserved pelvic nerve networks: complete preservation of the pelvic nerve plexus (group A, 27 cases); partial preservation (group B, 13 cases); and complete sacrifice (group C, 13 cases). To evaluate bladder function, urodynamic studies were conducted preoperatively and postoperatively at 1, 3, 6, and 12 months after surgery. Results No significant difference in sensory function was found between groups A and B. However, the sensory function of group C was significantly lower than that of the other groups. Group A had significantly better motor function than groups B and C. No significant difference in motor function was found between groups B and C. Results showed that the sensory nerve is distributed predominantly at the dorsal half of the pelvic nerve networks, but the motor nerve is predominantly distributed at the ventral half. Conclusion Various types of total laparoscopic nerve-sparing radical hysterectomies can be tailored to patients with cervical carcinomas. PMID:25045432
Fujiwara, Kazuko; Ebisawa, Keiko; Hada, Tomonori; Ota, Yoshiaki; Andou, Masaaki
OBJECTIVE This study evaluated the nerve conduction study (NCS) parameters of the most distal sensory nerves of the lower extremities—namely, the medial dorsal cutaneous (MDC), dorsal sural (DS), and medial plantar (MP) nerves—in diabetic (DM) and impaired glucose tolerance (IGT) patients who displayed normal findings on their routine NCSs. RESEARCH DESIGN AND METHODS Standard NCSs were performed on healthy control (HC), DM, and IGT groups (N = 147). The bilateral NCS parameters of the MDC, DS, and MP nerves were investigated. The Toronto Clinical Scoring System (TCSS) was assessed for the DM and IGT groups. RESULTS The mean TCSS scores of the IGT and DM groups were 2.5 ± 2.3 and 2.8 ± 2.2, respectively. No significant differences between the two groups were observed. After adjustment of age and BMI, the DM group showed significant NCS differences in DS and MDC nerves compared with the HC group (P < 0.05). These differences were also exhibited in the left DS of the IGT group (P = 0.0003). More advanced NCS findings were observed in the DM group. Bilateral abnormal NCS responses in these distal sensory nerves were found in 40 and 16% of DM and IGT patients, respectively. CONCLUSIONS These results showed that the simultaneous assessment of the most distal sensory nerves allowed the detection of early NCS changes in the IGT and DM groups, even when the routine NCS showed normal findings. PMID:22100966
Im, Sun; Kim, Sung-Rae; Park, Joo Hyun; Kim, Yang Soo; Park, Geun-Young
Surprising sensory stimuli causing arousal are known to evoke short-lasting activation of human sympathetic activity in skin but not in muscle nerves; anecdotal observations suggest that there may even be an inhibition of muscle sympathetic nerve activity (MSNA). To test this hypothesis we recorded multiunit MSNA in the peroneal nerve in 19 subjects aged 19–71 years, while sensory stimuli, consisting of either an electrical skin stimulus to a finger or a visual flash, were delivered repeatedly with intervals of approximately 20 s. The stimuli were given either 200 or 400 ms after the R wave of the electrocardiogram. Dummy stimuli, consisting of trigger pulses without sensory stimulation served as controls. Electrical skin resistance reductions were monitored from the palm of a hand as electrodermal signs of arousal-induced cutaneous sympathetic activity. On a group basis both types of sensory stimuli attenuated the amplitude of one or two bursts of MSNA, while no such effects occurred after dummy stimuli. Individually, the inhibition was evoked by at least one stimulus modality or delay in 16 subjects whereas in three subjects no significant inhibition occurred. Skin resistance responses were evoked in all subjects. Some subjects responded to one, others to both stimulus modalities, and electrical stimuli were more effective than visual stimuli in causing MSNA inhibition as well as skin resistance reduction. On the other hand, electrodermal signs of arousal were equally common in subjects with and without inhibitory responses. We suggest that the MSNA inhibition evoked by sensory stimuli is an arousal effect which varies markedly between individuals. PMID:12356899
Donadio, Vincenzo; Kallio, Mika; Karlsson, Tomas; Nordin, Magnus; Wallin, B Gunnar
Prostaglandin E1 and the beta-adrenergic hormone l-isoproterenol stimulated cyclic AMP formation in both nucleated and enucleated myeloid leukemic cells that could be induced to differentiate normally to mature cells by the macrophage- and granulocyte-inducing protein MGI (MGI+D+ cells). Enucleated as well as nucleated MGI+D+ cells also desensitized to these hormones, indicating that this desensitization is an extranuclear process. Nucleated or enucleated mutant myeloid leukemic cells that are not induced to differentiate (MGI-D- cells) were not desensitized to these hormones. The antitubulin alkaloids colchicine and vinblastine, but not the antimicrofilament compound cytochalasin B, increased the maximal hormone-induced formation of cyclic AMP in nucleated MGI+D+ cells but not in the MGI-D- cells. These alkaloids also inhibited the development of desensitization to l-isoproterenol and prostaglandin E1 in enucleated MGI+D+ cells. The results indicate that in MGI+D+ cells the cytoskeletal system puts constraints on the cells' ability to respond to these hormones and that these constraints are absent in the mutant MGI-D- cells. Because MGI+D+ but not MGI-D- cells can be induced to differentiate by the macrophage- and granulocyte-inducing protein, cytoskeletal constraints, which are also found in normal myeloid cells, may be necessary for cell competence to differentiate. The results support the suggestion that membrane cytoskeletal constraints generate may control the normal response and desensitization to membrane-mediated cell inducers. PMID:6254040
Simantov, R; Shkolnik, T; Sachs, L
Desensitization, as represented by the progressive decline in the electromotive effects of depolarizing agents at the neuromuscular junction, was studied by observing the time course of changes in effective transmembrane resistance during the prolonged application of 0.27 mM carbamylcholine to the postjunctional region of frog skeletal muscle fibers. The effective transmembrane resistance was measured by means of two intracellular microelectrodes implanted in the junctional region of single muscle fibers. When carbamylcholine was applied to the muscle there was an immediate decrease in the effective membrane resistance followed by a slower return toward control values which was identified as the phase of desensitization. When the calcium concentration was increased from 0 to 10 mM there was an approximately sevenfold increase in the rate of desensitization. On the other hand, an increase in the concentration of sodium from 28 to 120 mM caused a slowing of the rate of desensitization. Even in muscles depolarized by potassium sulfate, calcium increased the rate of desensitization while high concentrations of potassium tended to prolong the process. Some mechanisms by which calcium might exert these effects are discussed. PMID:5961360
Manthey, Arthur A.
Acetylcholine (ACh) rapidly increases cardiac K+ currents (IKACh) by activating muscarinic K+ (KACh) channels followed by a gradual amplitude decrease within seconds. This phenomenon is called short-term desensitization and its precise mechanism and physiological role are still unclear. We constructed a mathematical model for IKACh to examine the conditions required to reconstitute short-term desensitization. Two conditions were crucial: two distinct muscarinic receptors (m2Rs) with different affinities for ACh, which conferred an IKACh response over a wide range of ACh concentrations, and two distinct KACh channels with different affinities for the G-protein ?? subunits, which contributed to reconstitution of the temporal behavior of IKACh. Under these conditions, the model quantitatively reproduced several unique properties of short-term desensitization observed in myocytes: 1), the peak and quasi-steady states with 0.01–100 ?M [ACh]; 2), effects of ACh preperfusion; and 3), recovery from short-term desensitization. In the presence of 10 ?M ACh, the IKACh model conferred recurring spontaneous firing after asystole of 8.9 s and 10.7 s for the Demir and Kurata sinoatrial node models, respectively. Therefore, two different populations of KACh channels and m2Rs may participate in short-term desensitization of IKACh in native myocytes, and may be responsible for vagal escape at nodal cells. PMID:24048003
Murakami, Shingo; Inanobe, Atsushi; Kurachi, Yoshihisa
Acetylcholine (ACh) rapidly increases cardiac K(+) currents (IKACh) by activating muscarinic K(+) (KACh) channels followed by a gradual amplitude decrease within seconds. This phenomenon is called short-term desensitization and its precise mechanism and physiological role are still unclear. We constructed a mathematical model for IKACh to examine the conditions required to reconstitute short-term desensitization. Two conditions were crucial: two distinct muscarinic receptors (m2Rs) with different affinities for ACh, which conferred an IKACh response over a wide range of ACh concentrations, and two distinct KACh channels with different affinities for the G-protein ?? subunits, which contributed to reconstitution of the temporal behavior of IKACh. Under these conditions, the model quantitatively reproduced several unique properties of short-term desensitization observed in myocytes: 1), the peak and quasi-steady states with 0.01-100 ?M [ACh]; 2), effects of ACh preperfusion; and 3), recovery from short-term desensitization. In the presence of 10 ?M ACh, the IKACh model conferred recurring spontaneous firing after asystole of 8.9 s and 10.7 s for the Demir and Kurata sinoatrial node models, respectively. Therefore, two different populations of KACh channels and m2Rs may participate in short-term desensitization of IKACh in native myocytes, and may be responsible for vagal escape at nodal cells. PMID:24048003
Murakami, Shingo; Inanobe, Atsushi; Kurachi, Yoshihisa
The authors present the case of a 20-year-old man who, 3 months after his initial injury, underwent repair of a 1.7-cm defect of the ulnar nerve at the wrist; repair was performed with an acellular nerve allograft. Given the absence of clinical or electrophysiological recovery at 8 months postrepair, the patient underwent reexploration, excision of the "regenerated cable," and rerepair of the ulnar nerve with sural nerve autografts. Histology of the cable demonstrated minimal axonal regeneration at the midpoint of the repair. At the 6- and 12-month follow-ups of the sural nerve graft repair, clinical and electrophysiological evidence of both sensory and motor reinnervation of the ulnar nerve and associated hand muscles was demonstrated. In this report, the authors describe a single case of failed acellular nerve allograft and correlate the results with basic science and human studies reporting length and diameter limitations in human nerve repair utilizing grafts or conduits devoid of viable Schwann cells. PMID:23746100
Berrocal, Yerko A; Almeida, Vania W; Levi, Allan D
Adenylyl cyclase, the enzyme of synthesis of cAMP, the second messenger molecule mediating signal transduction in response to sensory, neurotransmitter and hormonal stimuli, has been localized in the sensory epithelium of the rainbow trout (Salmo gairdneri R.) saccule by cytochemical detection of enzyme activity. In the sensory receptor cell, or hair cell, reaction product has been visualized in the stereocilia in close association with the outer cell membrane and also at the apical surface of the cuticular plate. A diffuse distribution of precipitate was observed within the cytoplasm of terminal endings of nerve fibers presumed to be efferent on the basis of characteristic synaptic specializations including presynaptic vesicles and a postsynaptic cistern lying within the hair cell. Occasionally, reaction product was observed to be associated with the external cell membrane of these nerve terminals. There appeared to be little or no adenylyl cyclase activity associated with the plasma membrane at the base of the hair cell or in presumptive afferent nerve endings. However, a subpopulation of nerve fiber endings which exhibited both efferent and afferent synaptic specializations contained precipitate. A concentration of adenylyl cyclase activity in hair cell stereocilia and efferent nerve terminals in the sensory epithelium is suggestive of a role for cAMP in second messenger action at these sites, possibly related to mechanosensory transduction and efferent neuromodulation, respectively. PMID:7501269
Drescher, M J; Kern, R C; Hatfield, J S; Drescher, D G
Functional regeneration within the adult spinal cord remains a formidable task. A major barrier to regeneration of sensory axons into the spinal cord is the dorsal root entry zone. This region displays many of the inhibitory features characteristic of other central nervous system injuries. Several experimental treatments, including inactivation of inhibitory molecules (such as Nogo and chondroitin sulfate proteoglycans) or administration of neurotrophic factors (such as nerve growth factor, neurotrophin3, glial derived neurotrophic factor and artemin), have been found to promote anatomical and functional regeneration across this barrier. There have been relatively few experiments, however, to determine if regenerating axons project back to their appropriate target areas within the spinal cord. This review focuses on recent advances in sensory axon regeneration, including studies assessing the ability of sensory axons to reconnect with their original synaptic targets. PMID:22137336
Smith, George M.; Falone, Anthony E.; Frank, Eric
A 21-year-old man had progressive symmetric, distal muscle atrophy and weakness, as well as spasticity of the limbs. Histologic examination of the sural nerve disclosed swollen axons containing membranous tubular profiles, ring tubules, large mitochondria with abnormal cristae, and glycogen like granules. Peripheral sensory nerve fibers also were affected. The pathologic features of the peripheral nerves were similar to those of infantile neuroaxonal dystrophy. Sural nerve biopsy may be useful in the study of pathologic processes in spastic paraplegia. PMID:899737
Shimono, M; Ohta, M; Kuroiwa, Y
Magnetic resonance (MR) imaging of the nerves, commonly known as MR neurography is increasingly being used as noninvasive means of diagnosing peripheral nerve disease. High-resolution imaging protocols aimed at imaging the nerves of the hip, thigh, knee, leg, ankle, and foot can demonstrate traumatic or iatrogenic injury, tumorlike lesions, or entrapment of the nerves, causing a potential loss of motor and sensory function in the affected area. A thorough understanding of normal MR imaging and gross anatomy, as well as MR findings in the presence of peripheral neuropathies will aid in accurate diagnosis and ultimately help guide clinical management. PMID:24210318
Burge, Alissa J; Gold, Stephanie L; Kuong, Sharon; Potter, Hollis G
Background Anterior interosseous nerve syndrome is characterized by paralysis of the flexor digitorum profundus, the flexor pollicis\\u000a longus and the pronator quadratus muscles without sensory loss. Extended exploration of the anterior interosseous nerve is\\u000a the surgical treatment of choice. The present study evaluates the feasibility of an endoscopic approach for nerve decompression.\\u000a \\u000a \\u000a \\u000a \\u000a Methods Preparation of the anterior interosseous nerve was performed in
Doerthe Keiner; Manfred Tschabitscher; Stefan Welschehold; Joachim Oertel
Background Sensory input is generally thought to be necessary for refining and consolidating neuronal connections during brain development. We here report that cortical callosal axons in somatosensory cortex require sensory input for their target selection in contralateral cortex. Results Eliminating sensory input to either hemisphere by unilateral transection of infraorbital nerve (ION) prevents target selection of callosal axons in contralateral cortex. Strikingly, blocking sensory input bilaterally, by simultaneously transecting both IONs, results in rescued callosal projection. In contrast, non-simultaneous bilateral ION transection has the same effect as unilateral transection. Similar results are obtained by lesion of whisker hair follicles. c-Fos-positive neurons in brain slices treated with KCl is decreased more in contralateral cortex with unilateral removal of sensory input, but decreased similarly in both cortices in mice with simultaneous bilateral removal of sensory input. Frequency of sEPSC of cortical neurons is also reduced in contralateral cortex with the unilateral removal of sensory input, but equally reduced on both sides with the bilateral removal of sensory input, suggesting that unbalanced bilateral sensory input might lead to mismatched neuronal activity between the two cortices and contribute to the formation of callosal projection. Conclusion Our data demonstrate a critical role of balanced bilateral somatosensory input in the formation of callosal connections, and thus reveal a new role of sensory input in wiring brain circuits. PMID:24305168
Trauma to the optic nerve may be direct, such as from a penetrating object, or indirect, which may result despite lack of direct contact of an object with the nerve. Although indirect injury initially causes no change in the appearance of the nerve head, within a matter of weeks optic atrophy will be manifest. The pathophysiology of nerve damage is incompletely understood. Management is controversial; steroid therapy has been advocated, as has surgical decompression of the nerve. Indirect injuries affecting the optic nerve may also result from torsional rotation of the globe (avulsion) and from subdural or subarachnoid hemorrhage (Terson's syndrome). There is no treatment for optic nerve avulsion; the unaffected eye should be protected with appropriate eyewear. Hemorrhaging in the retina and vitreous in Terson's syndrome should be monitored for resolution and risk of retinal detachment. Computed tomography may be necessary if subarachnoid or intracranial hemorrhages are suspected. PMID:8268699
Dul, M W
A study involving 97 students (79 females and 18 males) at New York City Technical College was undertaken to determine the effectiveness of desensitization in reducing test anxiety and improving grade point averages (GPAs). The study compared the GPAs of students who completed workshops using the desensitization hierarchy developed by R. Strieby…
Woods, Nathaniel A.
Purpose – The purpose of this paper is to present the multi-sensory brand-experience concept in relation to the human mind and senses. It also seeks to propose a sensory marketing (SM) model of the multi-sensory brand-experience hypothesis. Design\\/methodology\\/approach – This paper applies exploratory and explanatory approaches to investigating the multi-sensory brand-experience concept within the context of discovery. The qualitative study
Background Uninjured peripheral nerves in upper-limb amputees represent attractive sites for connectivity with neuroprostheses because their predictable internal topography allows for precise sorting of motor and sensory signals. The inclusion of poly(3,4-ethylenedioxythiophene) reduces impedance and improves charge transfer at the biotic-abiotic interface. This study evaluates the in vivo performance of poly(3,4-ethylenedioxythiophene)–coated interpositional decellularized nerve grafts across a critical nerve conduction gap, and examines the long-term effects of two different poly(3,4-ethylenedioxythiophene) formulations on regenerating peripheral nerve fibers. Methods In 48 rats, a 15-mm gap in the common peroneal nerve was repaired using a nerve graft of equivalent length, including (1) decellularized nerve chemically polymerized with poly(3,4-ethylenedioxythiophene) (dry); (2) decellularized nerve electrochemically polymerized with poly(3,4-ethylenedioxythiophene) (wet); (3) intact nerve; (4) autogenous nerve graft; (5) decellularized nerve alone; and (6) unrepaired nerve gap controls. All groups underwent electrophysiologic characterization at 3 months, and nerves were harvested for histomorphometric analysis. Results Conduction velocity was significantly faster in the dry poly(3,4-ethylenedioxythiophene) group compared with the sham, decellularized nerve, and wet poly(3,4-ethylenedioxythiophene) groups. Maximum specific force for the dry poly(3,4-ethylenedioxythiophene) group was more similar to sham than were decellularized nerve controls. Evident neural regeneration was demonstrated in both dry and wet poly(3,4-ethylenedioxythiophene) groups by the presence of normal regenerating axons on histologic cross-section. Conclusions Both poly(3,4-ethylenedioxythiophene) formulations were compatible with peripheral nerve regeneration at 3 months. This study supports poly(3,4-ethylenedioxythiophene) as a promising adjunct for peripheral nerve interfaces for prosthetic control and other biomedical applications because of its recognized ionic-to-electronic coupling potential. PMID:23897336
Baghmanli, Ziya; Sugg, Kristoffer B.; Wei, Benjamin; Shim, Bong S.; Martin, David C.; Cederna, Paul S.; Urbanchek, Melanie G.
Desensitization of µ-opioid receptors (MORs) develops over 5-15 minutes after the application of some, but not all, opioid agonists and lasts for tens of minutes after agonist removal. The decrease in function is receptor selective (homologous) and could result from 1) a reduction in receptor number or 2) a decrease in receptor coupling. The present investigation used photolysis of two caged opioid ligands to examine the kinetics of MOR-induced potassium conductance before and after MOR desensitization. Photolysis of a caged antagonist, carboxynitroveratryl-naloxone (caged naloxone), blocked the current induced by a series of agonists, and the time constant of decline was significantly decreased after desensitization. The increase in the rate of current decay was not observed after partial blockade of receptors with the irreversible antagonist, ?-chlornaltrexamine (?-CNA). The time constant of current decay after desensitization was never more rapid than 1 second, suggesting an increased agonist off-rate rather than an increase in the rate of channel closure downstream of the receptor. The rate of G protein-coupled K(+) channel (GIRK) current activation was examined using photolysis of a caged agonist, carboxynitrobenzyl-tyrosine-[Leu(5)]-enkephalin. After acute desensitization or partial irreversible block of MORs with ?-CNA, there was an increase in the time it took to reach a peak current. The decrease in the rate of agonist-induced GIRK conductance was receptor selective and dependent on receptor number. The results indicate that opioid receptor desensitization reduced the number of functional receptor and that the remaining active receptors have a reduced agonist affinity. PMID:24748657
Williams, John T
Background In addition to initiating signaling events, the activation of cell surface receptors also triggers regulatory processes that restrict the duration of signaling. Acute attenuation of signaling can be accomplished either via ligand-induced internalization of receptors (endocytic downregulation) or via ligand-induced receptor desensitization. These phenomena have traditionally been viewed in the context of adaptation wherein the receptor system enters a refractory state in the presence of sustained ligand stimuli and thereby prevents the cell from over-responding to the ligand. Here we use the epidermal growth factor receptor (EGFR) and G-protein coupled receptors (GPCR) as model systems to respectively examine the effects of downregulation and desensitization on the ability of signaling receptors to decode time-varying ligand stimuli. Results Using a mathematical model, we show that downregulation and desensitization mechanisms can lead to tight and efficient input-output coupling thereby ensuring synchronous processing of ligand inputs. Frequency response analysis indicates that upstream elements of the EGFR and GPCR networks behave like low-pass filters with the system being able to faithfully transduce inputs below a critical frequency. Receptor downregulation and desensitization increase the filter bandwidth thereby enabling the receptor systems to decode inputs in a wider frequency range. Further, system-theoretic analysis reveals that the receptor systems are analogous to classical mechanical over-damped systems. This analogy enables us to metaphorically describe downregulation and desensitization as phenomena that make the systems more resilient in responding to ligand perturbations thereby improving the stability of the system resting state. Conclusion Our findings suggest that in addition to serving as mechanisms for adaptation, receptor downregulation and desensitization can play a critical role in temporal information processing. Furthermore, engineering metaphors such as the ones described here could prove to be invaluable in understanding the design principles of biological systems. PMID:17996096
Shankaran, Harish; Wiley, H Steven; Resat, Haluk
The activation of cell surface receptors in addition to initiating signaling events also triggers regulatory processes that restrict the duration of signaling. Acute attenuation of signaling can be accomplished either via ligand-induced internalization of receptors (receptor downregulation) or via ligand-induced receptor desensitization. These phenomena have traditionally been viewed in the context of “adaptation” wherein the receptor system enters a refractory state in the presence of sustained ligand stimuli and thereby prevents the cell from “over-responding” to the ligand. Here we use the epidermal growth factor receptor (EGFR) and G-protein coupled receptors (GPCR) as model systems to respectively examine the effects of downregulation and desensitization on the ability of signaling receptors to decode time-varying ligand stimuli. We show that downregulation and desensitization mechanisms can lead to tight and efficient input-output coupling thereby ensuring synchronous processing of ligand inputs. Frequency response analysis indicates that upstream elements of the EGFR and GPCR networks behave like low-pass filters. Receptor downregulation and desensitization increase the filter bandwidth thereby enabling the receptor systems to decode inputs in a wider frequency range. Further, system-theoretic analysis reveals that the receptor systems are analogous to classical mechanical over-damped oscillators. This analogy enables us to describe downregulation and desensitization as phenomena that make the systems more resilient in responding to ligand perturbations thereby improving the stability of the system resting state. We hypothesize that, in addition to serving as mechanisms for adaptation, receptor downregulation and desensitization play a critical role in temporal information processing.
Shankaran, Harish; Wiley, H. S.; Resat, Haluk
Cervicocogenic headache (CeH) is a relatively common disorder. Although on ideal treatment is available so far, blockades in different structures and nerves may be temporarily effective. We studied the effects of 1-2 mL 0.5% bupivacaine injection at the ipsilateral greater occipital nerve (GON) in 41 CeH patients. The pain is significantly reduced both immediately and as long as 7 days after the blockade. The improvement is less marked during the first two days, a phenomenon we called "tilde pattern". GON blockades may reduce the pool of exaggerated sensory input and antagonize a putative "wind-up-like effect" which may explain the headache improvement. PMID:10029873
Vincent, M B; Luna, R A; Scandiuzzi, D; Novis, S A
Women with inherited thrombophilia and recurrent miscarriage might benefit from preconceptional antiagreggation with low-dose acetylsalicylic acid (ASA), but concerns about severe adverse reactions may prevent physicians from performing this treatment in patients with ASA hypersensitivity. We report the first known case of ASA desensitization in a 41-year-old woman with inherited thrombophilia, who had homozygosity (4G/4G polymorphism) of the plasminogen activator inhibitor-1 (PAI-1) gene and first trimester recurrent miscarriage, and had previously presented with anaphylaxis to ASA. Desensitization was completed despite one self-limited adverse reaction, and the patient has maintained a daily ASA intake of 100 mg with good tolerance. PMID:23441445
Santos, N; Gaspar, A; Livramento, S; Sampaio, G; Morais-Almeida, M
Glial-derived neurotrophic factor (GDNF) promotes both sensory and motor neuron survival. The delivery of GDNF to the peripheral nervous system has been shown to enhance regeneration following injury. In this study, we evaluated the effect of affinity-based delivery of GDNF from a fibrin matrix in a nerve guidance conduit on nerve regeneration in a 13mm rat sciatic nerve defect. Seven
Matthew D. Wood; Amy M. Moore; Daniel A. Hunter; Sami Tuffaha; Gregory H. Borschel; Susan E. Mackinnon; Shelly E. Sakiyama-Elbert
This article features the National Institute of Trauma and Loss in Children (TLC), a program that has demonstrated via field testing, exploratory research, time series studies, and evidence-based research studies that its Structured Sensory Intervention for Traumatized Children, Adolescents, and Parents (SITCAP[R]) produces statistically…
Steele, William; Kuban, Caelan
Capitalizing on the resources available within a city block, this resource guide for the emotionally handicapped (K-6) describes methods and procedures for developing sensory awareness in the urban out-of-doors. Conceptual focus is on interdependency ("living things are interdependent"). Involvement in the environment (observing, thinking, doing)…
Explains the vestibular organ's role in balancing the body and stabilizing the visual world using the example of a hunter. Describes the relationship between sensory perception and learning. Recommends using optical illusions to illustrate the distinctions between external realities and internal perceptions. (Contains 13 references.) (YDS)
Ackerly, Spafford C.
Studies of the structural organization and functions of the cell body of a neuron (soma) and its surrounding satellite glial cells (SGCs) in sensory ganglia have led to the realization that SGCs actively participate in the information processing of sensory signals from afferent terminals to the spinal cord. SGCs use a variety ways to communicate with each other and with their enwrapped soma. Changes in this communication under injurious conditions often lead to abnormal pain conditions. “What are the mechanisms underlying the neuronal soma and SGC communication in sensory ganglia” and “how do tissue or nerve injuries affect the communication?” are the main questions addressed in this review. PMID:23918214
Huang, Li-Yen M.; Gu, Yanping; Chen, Yong
Axonal regeneration is one of the greatest challenges in severe injuries of peripheral nerve. To provide the bridge needed for regeneration, biological or synthetic tubular nerve constructs with aligned architecture have been developed. A key point for improving axonal regeneration is assessing the effects of substrate geometry on neuronal behavior. In the present study, we used an extracellular matrix-micropatterned substrate comprising 3 µm wide lines aimed to physically mimic the in vivo longitudinal axonal growth of mice peripheral sensory and motor neurons. Adult sensory neurons or embryonic motoneurons were seeded and processed for morphological and electrical activity analyses after two days in vitro. We show that micropattern-guided sensory neurons grow one or two axons without secondary branching. Motoneurons polarity was kept on micropattern with a long axon and small dendrites. The micro-patterned substrate maintains the growth promoting effects of conditioning injury and demonstrates, for the first time, that neurite initiation and extension could be differentially regulated by conditioning injury among DRG sensory neuron subpopulations. The micro-patterned substrate impacts the excitability of sensory neurons and promotes the apparition of firing action potentials characteristic for a subclass of mechanosensitive neurons. The line pattern is quite relevant for assessing the regenerative and developmental growth of sensory and motoneurons and offers a unique model for the analysis of the impact of geometry on the expression and the activity of mechanosensitive channels in DRG sensory neurons. PMID:25329060
Benzina, Ouafa; Cloitre, Thierry; Martin, Marta; Raoul, Cedric; Gergely, Csilla; Scamps, Frederique
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.
Dabke, Harshad V.
The axonal projection pattern of sensory neurons typically is regulated by environmental signals, but how different sensory afferents can establish distinct projections in the same environment remains largely unknown. Drosophila class IV dendrite arborization (C4da) sensory neurons project subtype-specific axonal branches in the ventral nerve cord, and we show that the Tripartite motif protein, Anomalies in sensory axon patterning (Asap) is a critical determinant of the axonal projection patterns of different C4da neurons. Asap is highly expressed in C4da neurons with both ipsilateral and contralateral axonal projections, but the Asap level is low in neurons that have only ipsilateral projections. Mutations in asap cause a specific loss of contralateral projections, whereas overexpression of Asap induces ectopic contralateral projections in C4da neurons. We also show by biochemical and genetic analysis that Asap regulates Netrin signaling, at least in part by linking the Netrin receptor Frazzled to the downstream effector Pico. In the absence of Asap, the sensory afferent connectivity within the ventral nerve cord is disrupted, resulting in specific larval behavioral deficits. These results indicate that different levels of Asap determine distinct patterns of axonal projections of C4da neurons by modulating Netrin signaling and that the Asap-mediated axonal projection is critical for assembly of a functional sensory circuit. PMID:22084112
Morikawa, Rei K.; Kanamori, Takahiro; Yasunaga, Kei-ichiro; Emoto, Kazuo
Summary Background The aim of this study was to observe the effects of autologous nerve implantation into the denervated finger flap on the regression and regeneration of sensory nerve endings and Meissner’s corpuscles. Material/Methods Bilateral nerves of fingers were separated: one was removed and the other was implanted into the denervated finger in the implantation group. In the non-implantation group, both nerves were removed. The ventral skin of fingers was collected for immunohistochemistry and electron microscopy 3, 6, 9 and 12 months after surgery. Results The nerve endings in the Meissner’s corpuscles began to degenerate 3 months after denervation. The elementary structure of Meissner’s corpuscles was not significantly altered. Nerve fibers were present around the Meissner’s corpuscles, accompanied by growing into its inward. The axons in the denervated nerve disappeared and the Meissner’s corpuscles began to atrophy at month 6. More regenerated nerve fibers were observed after nerve implantation, including intensive and thick fibers, accompanied by reinnervation of Meissner’s corpuscles. More nerve fibers and a higher proportion of myelinated nerve fibers were noted at month 9 in the implantation group, and the reinnervation was present in the majority of Meissner’s corpuscles. Naive myelinated nerve fibers appeared at the caudal end of Meissner’s corpuscles. The nerve fibers in the Meissner’s corpuscles increased to the normal level at 12 months after nerve implantation. Conclusions The implanted nerve regenerated a large amount of free nerve endings, which helped to regenerate simple Meissner’s corpuscles via governing previously degenerated corpuscles. PMID:22129896
Wang, Zhen-Xiang; Luo, Dong-Lin; Yu, Pan; Chen, Liang; Li, Zhe; Tao, Ling; Dai, Xia; Li, Yue-Jun; Li, Xue-Yong; Li, Shi-Rong
From the histologic point of view, nerves are round or flattened cords, with a complex internal structure made of myelinated\\u000a and unmyelinated nerve fibers, containing axons and Schwann cells grouped in fascicles (Fig. 4.1a) (Erickson 1997). Along the course of the nerve, fibers can traverse from one fascicle to another and fascicles can split and merge. Based\\u000a on the fascicular
Maura Valle; Maria Pia Zamorani
Persons with a suprasacral spinal cord injury cannot empty their bladder voluntarily. Bladder emptying can be restored by intermittent electrical stimulation of the sacral nerve roots (SR) to cause bladder contraction. However, this therapy requires sensory nerve transection to prevent dyssynergic contraction of the external urethral sphincter (EUS). Stimulation of the compound pudendal nerve trunk (PN) activates spinal micturition circuitry, leading to a reflex bladder contraction without a reflex EUS contraction. The present study determined if PN stimulation could produce bladder emptying without nerve transection in cats anesthetized with ?-chloralose. With all nerves intact, intermittent PN stimulation emptied the bladder (64 ± 14% of initial volume, n = 37 across six cats) more effectively than either distention-evoked micturition (40 ± 19%, p < 0.001, n = 27 across six cats) or bilateral intermittent SR stimulation (25 ± 23%, p < 0.005, n = 4 across two cats). After bilateral transection of the nerves innervating the urethral sphincter, intermittent SR stimulation voided 79 ± 17% (n = 12 across three cats), comparable to clinical results obtained with SR stimulation. Voiding via intermittent PN stimulation did not increase after neurotomy (p > 0.10), indicating that PN stimulation was not limited by bladder-sphincter dyssynergia. Intermittent PN stimulation holds promise for restoring bladder emptying following spinal injury without requiring nerve transection.
Boggs, Joseph W.; Wenzel, Brian J.; Gustafson, Kenneth J.; Grill, Warren M.
Successful injury management is often dependent upon optimal pain control. Many injuries do not require procedural sedation or systemic analgesia, and emergency clinicians have used peripheral nerve blocks for several decades for these injuries. Nerve blocks deliver anesthetic to the nerve that corresponds to the sensory innervation of the area where the wound or injury is located. In the pediatric setting, some nerve block modalities require modification to the approach and techniques commonly used in adult patients due to the age and weight of the child, the ability of the patient to cooperate, and the ability of the emergency clinician to observe pain response. Peripheral nerve blocks have a high rate of success for effective local anesthesia and a low rate of complications, making them an attractive option for analgesia in the management of some injuries. This evidence-based review summarizes the advantages and disadvantages of peripheral nerve blocks, reviews commonly used local anesthetics, describes the landmark technique for the most common nerve blocks used in pediatric emergency medicine, and presents literature on ultrasound-guided technology. PMID:24191378
Duchicela, Sacha; Lim, Anthoney
Background: Radiosurgery is a well-established treatment modality for medically refractory trigeminal neuralgia. The exact mechanism of pain relief after radiosurgery is not clearly understood. Histopathology examination of the trigeminal nerve in humans after radiosurgery is rarely performed and has produced controversial results. Case Description: We report on a 45-year-old female who received radiosurgery treatment for trigeminal neuralgia by Cyberknife. A 6-mm portion of the cisternal segment of trigeminal nerve received a dose of 60 Gy. The clinical benefit started 10 days after therapy and continued for 8 months prior to a recurrence of her previous symptoms associated with mild background pain. She underwent microvascular decompression and partial sensory root sectioning. Atrophied trigeminal nerve rootlets were grossly noted intraoperatively under surgical microscope associated with changes in trigeminal nerve color to gray. A biopsy from the inferolateral surface of the nerve proximal to the midcisternal segment showed histological changes in the form of fibrosis and axonal degeneration. Conclusion: This case study supports the evidence of histological damage of the trigeminal nerve fibers after radiosurgery therapy. Whether or not the presence and degree of nerve damage correlate with the degree of clinical benefit and side effects are not revealed by this study and need to be explored in future studies. PMID:24605252
Al-Otaibi, Faisal; Alhindi, Hindi; Alhebshi, Adnan; Albloushi, Monirah; Baeesa, Saleh; Hodaie, Mojgan
Lymphatic fluid is a plasma filtrate that can be viewed as having biological activity through the passive accumulation of molecules from the interstitial fluid. The possibility that lymphatic fluid is part of an active self-contained signaling process that parallels the endocrine system, through the activation of G-protein coupled receptors (GPCR), has remained unexplored. We show that the GPCR lysophosphatidic acid 5 (LPA5) is found in sensory nerve fibers expressing calcitonin gene-related peptide (CGRP) that innervate the lumen of lymphatic lacteals and enteric nerves. Using LPA5 as a model for nutrient-responsive GPCRs present on sensory nerves, we demonstrate that dietary protein hydrolysate (peptone) can induce c-Fos expression in enterocytes and nerves that express LPA5. Mesenteric lymphatic fluid (MLF) mobilizes intracellular calcium in cell models expressing LPA5 upon feeding in a time- and dose-dependent manner. Primary cultured neurons of the dorsal root ganglia expressing CGRP are activated by MLF, which is enhanced upon LPA5 overexpression. Activation is independent of the known LPA5 agonists, lysophosphatidic acid and farnesyl pyrophosphate. These data bring forth a pathway for the direct stimulation of sensory nerves by luminal contents and interstitial fluid. Thus, by activating LPA5 on sensory nerves, MLF provides a means for known and yet to be identified constituents of the interstitial fluid to act as signals to comprise a "neurolymphocrine" system. PMID:24578341
Poole, Daniel P; Lee, Mike; Tso, Patrick; Bunnett, Nigel W; Yo, Sek Jin; Lieu, TinaMarie; Shiu, Amy; Wang, Jen-Chywan; Nomura, Daniel K; Aponte, Gregory W
Major peripheral nerve injuries in the upper extremities can result in significant morbidity. Understanding the pathophysiology of these injuries aids in the assessment and planning of appropriate treatment. With limited nerve mobilization, tension-free repairs can often be performed using sutures, fibrin glue, or nerve connectors. Acellular allograft and autograft reconstruction are better for bridging any gaps greater than a few millimeters. Adherence to proper principles of nerve repair improves the chances of achieving a favorable result, although in general these injuries portend a guarded prognosis. PMID:23895717
Peripheral nerve injuries (PNI) are continuing to be an ever-growing socio-economic burden affecting mainly the young working population and the current clinical treatments to PNI provide a poor clinical outcome involving significant loss of sensation. Thus, our understanding of the underlying factors responsible for the extensive loss of the sensory cutaneous subpopulation in the dorsal root ganglia (DRG) that occurs following injury needs to be improved. The current investigations focus in identifying visual cues of mitochondria-related apoptotic events in the various subpopulations of sensory cutaneous neurons. Sensory neuronal subpopulations were identified using FastBlue retrograde labelling following axotomy. Specialised fluorogenic probes, MitoTracker Red and MitoTracker Orange, were employed to visualise the dynamic changes of the mitochondrial population of neurons. The results reveal a fragmented mitochondrial network in sural neurons following apoptosis, whereas a fused elongated mitochondrial population is present in sensory proprioceptive muscle neurons following tibial axotomy. We also demonstrate the neuroprotective properties of NAC and ALCAR therapy in vitro. The dynamic mitochondrial network breaks down following oxidative exposure to hydrogen peroxide (H(2)O(2)), but reinitiates fusion after NAC and ALCAR therapy. In conclusion, this study provides both qualitative and quantitative evidence of the susceptibility of sensory cutaneous sub-population in apoptosis and of the neuroprotective effects of NAC and ALCAR treatment on H(2)O(2)-challenged neurons. PMID:22923263
Englezou, Pavlos C; Esposti, Mauro Degli; Wiberg, Mikael; Reid, Adam J; Terenghi, Giorgio
The enormous popularity recently achieved by Eye Movement Desensitization and Reprocessing (EMDR) as a treatment for anxiety disorders appears to have greatly outstripped the evidence for its efficacy from controlled research studies. The disparity raises disturbing questions concerning EMDR's aggressive commercial promotion and its rapid acceptance among practitioners. In this article, we: (1) summarize the evidence concerning EMDR's efficacy; (2)
James D. Herbert; Scott O. Lilienfeld; Jeffrey M. Lohr; Robert W Montgomery; William T O'Donohue; Gerald M Rosen; David F Tolin
Past research shows that violent video game exposure increases aggressive thoughts, angry feelings, physiological arousal, aggressive behaviors, and decreases helpful behaviors. However, no research has experimentally examined violent video game effects on physiological desensitization, defined as showing less physiological arousal to violence in the real world after exposure to video game violence in the virtual world. This experiment attempts to
Nicholas L. Carnagey; Craig A. Anderson; Brad J. Bushman
Entertainment computing is central to the leisure activities of many Americans, with a remarkable array of choices now available to the average person. Video and computer games, in particular violent games, are especially popular, even with relatively young children. With this popularity, concern has been raised about possible unintended consequences of participation in interactive violence. Desensitization to violence has been
Jeanne B. Funk
Past research shows that violent video game exposure increases aggressive thoughts, angry feelings, physiological arousal, aggressive behaviors, and decreases helpful behaviors. However, no research has experimentally examined violent video game eVects on physiologi- cal desensitization, deWned as showing less physiological arousal to violence in the real world after exposure to video game violence in the virtual world. This experiment attempts
Nicholas L. Carnagey; Craig A. Anderson; Brad J. Bushman
The aim of the study was to determine the effectiveness of the recently developed Eye Movement Desensitization (EMD) procedure on traumatic memory symptomatology. Twenty-two subjects suffering from symptoms related to traumatic memories were used in the study. All had been victims of traumatic incidents concerning the Vietnam War, childhood sexual molestation, sexual or physical assault, or emotional abuse. Memories of
States that within the last six years a new therapeutic technique for the treatment of posttraumatic stress disorder, Eye Movement Desensitization and Reprocessing (EMDR), has emerged. Examines the strengths and weaknesses of published studies concerning EMDR, describes the nature of the debate about the efficacy of EMDR, and reviews implications…
MacCluskie, Kathryn C.
Eye Movement Desensitization and Reprocessing (EMDR) as a clinical technique may enhance treatment effectiveness when applied in couple therapy that is emotionally and experientially oriented. Clinical experience indicates EMDR-based interventions are useful for accessing and reprocessing intense emotions in couple interactions. EMDR can amplify…
Protinsky, Howard; Sparks, Jennifer; Flemke, Kimberly
Summary - Post-traumatic stress disorder is an exceptionally stressful syndrome that has been extremely difficult to treat. The prognosis was recently dramatically improved by the introduction of eye-movement desensitization. This paper reports, in substantial detail, a case that was precipitated by a rape 10 years earlier, describing its manifestations and various unsuccessful attempts to treat it; followed by a detailed
JOSEPH WOLPE; JANET ABRAMS
Radiation-induced segregation (RIS) in desensitized type 304 stainless steel (SS) was investigated using a combination of electrochemical potentiokinetic reactivation (EPR) test and atomic force microscopy (AFM). Desensitized type 304 SS was irradiated to 0.43 dpa (displacement per atom) using 4.8 MeV protons at 300 °C. The maximum attack in the EPR test for the irradiated desensitized SS was measured at a depth of 70 ?m from the surface. Grain boundaries and twin boundaries got attacked and pit-like features within the grains were observed after the EPR test at the depth of 70 ?m. The depth of attack, as measured by AFM, was higher at grain boundaries and pit-like features as compared to twin boundaries. It has been shown that the chromium depletion due to RIS takes place at the carbide-matrix as well as at the carbide-carbide interfaces at grain boundaries. The width of attack at grain boundaries after the EPR test of the irradiated desensitized specimen appeared larger due to the dislodgement of carbides at grain boundaries.
Ahmedabadi, Parag; Kain, V.; Arora, K.; Samajdar, I.; Sharma, S. C.; Bhagwat, P.
Scientists at the NIH have used a technique called cryo-electron microscopy to determine a molecular mechanism for the activation and desensitization of ionotropic glutamate receptors, a prominent class of neurotransmitter receptors in the brain and spinal cord that have also been implicated in some cancers.
The use of in vivo and imaginal desensitization procedures for treatment of a fear of flying in airplanes is described. The direct benefits of the program, along with the positive effects it had upon progress on a series of other, equally troublesome presenting problems is discussed. (Author)
Bernstein, Douglas A.; Beaty, William E.
Background: Aspirin-sensitive patients with asthma experience continuous inflammation of their nasal and sinus tissues, complicated by recurrent sinusitis, which frequently leads to asthma attacks. Systemic corticosteroid therapy and sinus or polyp surgery are currently required to control underlying rhinosinusitis, and bursts of corticosteroids are used for asthma control. Objective: After aspirin desensitization therapy, objective measures of respiratory disease activity, linked
Donald D. Stevenson; Marcia A. Hankammer; David A. Mathison; Sandra C. Christiansen; Ronald A. Simon
Oxaliplatin (Eloxatin ® ; Sanofi-Synthelabo Inc.; New York, NY) is a third-generation platinum agent indicated for the treatment of colorectal cancer. Severe hypersensi- tivity reactions to oxaliplatin rarely occur; however, they do represent a threat to the small number of patients that are occasionally affected. We developed a desensitization protocol and successfully applied it to a patient with severe, grade
DAVID GAMMON; PANKAJ BHARGAVA; MICHAEL J. MCCORMICKc
This paper considers the current empirical status of Eye Movement Desensitization and Reprocessing (EMDR) as a treatment method for specific phobias, along with some conceptual and practical issues in relation to its use. Both uncontrolled and controlled studies on the application of EMDR with specific phobias demonstrate that EMDR can produce significant improvements within a limited number of sessions. With
A. De Jongh; E. Ten Broeke; M. R. Renssen
Studies the effects of 3 90-minute Eye Movement Desensitization and Reprocessing (EMDR) treatment sessions on traumatic memories of 80 participants. Participants receiving EMDR showed decreases in complaints and anxiety, and increases in positive cognition. Participants in the delayed-treatment condition showed no improvement in any measures in…
Wilson, Sandra A.; And Others
A subgroup of individuals who were helped to stop smoking by hypnosis or other means returned to consuming a few cigarettes a day. A flooding and hypnotic desensitization technique assisted 4 of 7 individuals who resumed smoking in becoming and remaining abstinent for a 6- to 9-month follow-up period.
Douglas H. Powell
Cys loop receptors are pentameric arrangements of independent subunits that assemble into functional ion channels. Each subunit shows a domain architecture. Functional ion channels can be reconstituted even from independent, nonfunctional subunit domains, as shown previously for GlyR?1 receptors. Here, we demonstrate that this reconstitution is not restricted to ?1 but can be transferred to other members of the Cys loop receptor family. A nonfunctional GlyR subunit, truncated at the intracellular TM3-4 loop by a premature stop codon, can be complemented by co-expression of the missing tail portion of the receptor. Compared with ?1 subunits, rescue by domain complementation was less efficient when GlyR?3 or the GABAA/C subunit ?1 was used. If truncation disrupted an alternative splicing cassette within the intracellular TM3-4 loop of ?3 subunits, which also regulates receptor desensitization, functional rescue was not possible. When ?3 receptors were restored by complementation using domains with and without the spliced insert, no difference in desensitization was found. In contrast, desensitization properties could even be transferred between ?1/?3 receptor chimeras harboring or lacking the ?3 splice cassette proving that functional rescue depends on the integrity of the alternative splicing cassette in ?3. Thus, an intact ?3 splicing cassette in the TM3-4 loop environment is indispensable for functional rescue, and the quality of receptor restoration can be assessed from desensitization properties. PMID:25143388
Meiselbach, Heike; Vogel, Nico; Langlhofer, Georg; Stangl, Sabine; Schleyer, Barbara; Bahnassawy, Lamia'a; Sticht, Heinrich; Breitinger, Hans-Georg; Becker, Cord-Michael; Villmann, Carmen
Synesthesia, the conscious, idiosyncratic, repeatable, and involuntary sensation of one sensory modality in response to another, is a condition that has puzzled both researchers and philosophers for centuries. Much time has been spent proving the condition’s existence as well as investigating its etiology, but what can be learned from synesthesia remains a poorly discussed topic. Here, synaesthesia is presented as a possible answer rather than a question to the current gaps in our understanding of sensory perception. By first appreciating the similarities between normal sensory perception and synesthesia, one can use what is known about synaesthesia, from behavioral and imaging studies, to inform our understanding of “normal” sensory perception. In particular, in considering synesthesia, one can better understand how and where the different sensory modalities interact in the brain, how different sensory modalities can interact without confusion ? the binding problem ? as well as how sensory perception develops. PMID:23766741
Harvey, Joshua Paul
In any organism there are different kinds of sensory receptors for detecting the various, distinct stimuli through which its external environment may impinge upon it. These receptors convey these stimuli in different ways to an organism's information processing region enabling it to distinctly perceive the varied sensations and to respond to them. The behavior of cells and their response to stimuli may be captured through simple mathematical models employing regulatory feedback mechanisms. We argue that the sensory processes such as olfaction function optimally by operating in the close proximity of dynamical instabilities. In the case of coupled neurons, we point out that random disturbances and fluctuations can move their operating point close to certain dynamical instabilities triggering synchronous activity.
The prostaglandin EP4 receptor, which couples to stimulation of adenylyl cyclase, undergoes rapid agonist-induced desensitization when expressed in CHO-K1 cells.Truncation of the 488-amino acid receptor at residue 350 removes the carboxy-terminal domain and abolishes desensitization.To further delineate residues involved in desensitization, the receptor was truncated at position 408, 383 or 369. Receptors truncated at position 408 or 383 underwent PGE2-induced desensitization, whereas the receptor truncated at position 369 displayed sustained activity, indicating that the essential residues for desensitization lie between 370 and 383.The six serines in the 14-amino acid segment between residues 370 and 383 were mutated to alanine, retaining the entire C-terminal domain. Desensitization was absent in cells expressing this mutant.The results indicate involvement of serines located between 370 and 382 in rapid desensitization of the EP4 receptor. PMID:10051157
Bastepe, Murat; Ashby, Barrie
The water content of the sural nerve of diabetic patients was quantitatively defined by magnetic resonance proton imaging as a putative reflection of activity of the aldose-reductase pathway. Thirty-nine patients were evaluated, comparing group A, symptomatic diabetic men with sensory neuropathy; group B, similarly symptomatic diabetic men treated aldose-reductase inhibition; group C, neurologically asymptomatic diabetic men; and group D, control nondiabetic men. Marked increase in hydration of the sural nerve was seen in more than half of the symptomatic diabetic patients. Two of 11 neurologically asymptomatic diabetics had increased nerve hydration, suggesting a presymptomatic alteration of the nerve. Symptomatic diabetics treated with aldose-reductase inhibitors had normal nerve water levels. Increased level of peripheral nerve water represents a new finding in diabetes mellitus. It seems to be related to aldose-reductase activity, involved in the development of neuropathy, and similar to events that occur in other target tissue in human diabetes.
Griffey, R.H.; Eaton, P.; Sibbitt, R.R.; Sibbitt, W.L. Jr.; Bicknell, J.M.
Inhibition of calcium-activated neutral protease, in muscle and nerve, by the tripeptide leupeptin after median nerve transection and epineural repair in monkeys (Cebus apella) was studied. Results indicate that inhibition of the protease after nerve repair facilitates morphologic recovery in denervated thenar muscles and in distal thenar nerve branches. In addition, functional recovery was facilitated in leupeptin-treated animals after nerve repair as measured by sensory and motor conduction velocities. Toxicologic testing showed that leupeptin, administered at 18 mg/kg, intramuscularly, twice daily, for 6 months did not adversely affect hematology, clotting, or plasma complement component C3 profiles. These data indicate that leupeptin is an effective and safe adjunct to peripheral nerve repair. Images PMID:2548194
Badalamente, M A; Hurst, L C; Stracher, A
Objectives To assess and to compare the effects of Gluma® Desensitizer (GDL) with an experimental glutaraldehyde and HEMA containing fumed silica dispersion (GDG) on dentin permeability using a chemiluminous tracer penetration test. Material and Methods Twenty disc-shaped dentin specimens were dissected from extracted human third molars. The dentin specimens were mounted in a split chamber device for determination of permeability under liquid pressure using a photochemical method. Ten specimens were randomly selected and allocated to the evaluation groups Gluma® Desensitizer as aqueous solution and glutaraldehyde/HEMA as fumed silica dispersion, respectively. Dentin disc permeability was determined at two pressure levels after removal of smear with EDTA, after albumin soaking, and after application of the desensitizing agents. Two desensitizer-treated and rinsed specimens of each group were examined by scanning electron microscopy (SEM) for surface remnants. Results Comparatively large standard deviations of the mean EDTA reference and albumin soaked samples permeability values reflected the differences of the dentin substrates. The mean chemiluminescence values of specimen treated with GDL and GDG, respectively, were significantly reduced after topical application of the desensitizing agents on albumin-soaked dentin. The effects of GDL and GDG on permeability were not significantly different. Treated specimens showed no surface remnants after rinsing. Conclusions The experimental desensitizer gel formulation reduced dentin permeability as effectively as the original Gluma® Desensitizer solution. PMID:21552716
ISHIHATA, Hiroshi; FINGER, Werner J.; KANEHIRA, Masafumi; SHIMAUCHI, Hidetoshi; KOMATSU, Masashi
Target-derived influences of nerve growth factor on neuronal survival and differentiation are well documented, though effects of other neurotrophins are less clear. To examine the influence of NT-3 neurotrophin overexpression in a target tissue of sensory and sympathetic neurons, transgenic mice were isolated that overexpress NT- 3 in the epidermis. Overexpression of NT-3 led to a 42% increase in the number of dorsal root ganglia sensory neurons, a 70% increase in the number of trigeminal sensory neurons, and a 32% increase in sympathetic neurons. Elevated NT-3 also caused enlargement of touch dome mechanoreceptor units, sensory end organs innervated by slowly adapting type 1 (SA1) neurons. The enlarged touch dome units of the transgenics had an increased number of associated Merkel cells, cells at which SA1s terminate. An additional alteration of skin innervation in NT-3 transgenics was an increased density of myelinated circular endings associated with the piloneural complex. The enhancement of innervation to the skin was accompanied by a doubling in the number of sensory neurons expressing trkC. In addition, measures of nerve fibers in cross- sectional profiles of cutaneous saphenous nerves of transgenics showed a 60% increase in myelinated fibers. These results indicate that in vivo overexpression of NT-3 by the epidermis enhances the number of sensory and sympathetic neurons and the development of selected sensory endings of the skin. PMID:8707832
The genetic features of a series of 227 patients with hereditary motor and sensory neuropathy (HMSN) have been analysed. The series comprised 119 index cases from 110 families in which 108 affected relatives were identified. The cases were classified as having type I or type II HMSN on the basis of nerve conduction studies. Inheritance in the type I cases
A E Harding; P K Thomas
The extrinsic sensory innervation of the gastrointestinal tract is the conduit through which the gut and the central nervous system communicate. The hindbrain receives information directly from the bowel via the vagus nerve, while information from spinal afferents arrives in the central nervous system through the dorsal root ganglia. This review focuses on the molecular development of these vagal and
Elyanne M. Ratcliffe
To investigate whether glutamate is a neurotransmitter in vagus nerve sensory afferents terminating in the nucleus tractus solitarius, these terminals were identified by the anterograde transport and their glutamate content examined using the post-embedding immunogold technique. After injection of horseradish peroxidase into the nodose ganglion anterogradely labelled axonal boutons were visualized throughout the nucleus of the solitary tract (nTS), the
R. M. Sykes; K. M. Spyer; P. N. Izzo
Previous data suggested that somatic and vagal sensory afferent inputs may converge in the rostral ventrolateral medulla oblongata (RVLM). The aim of the present study was to establish the existence of convergence between inputs mediated via the cervical vagus and contralateral sciatic nerves using in vivo intracellular recordings. The majority of RVLM neurones that received input from the vagus or
The central projection of statocyst sensory neurons associated with the crescent hairs of the crayfish Procambarus clarkii was investigated. Cobalt fills of statocyst nerves revealed that they entered the brain as the two discrete fiber bundles and terminated in different portions of the brain. One terminates in the ipsilateral half of the brain and the other in the contralateral half.
M. Yoshino; Y. Kondoh; M. Hisada
The histochemical study examined the effects of chronic methylmercury (MeHg) intoxication on the motor and sensory innervation of extensor digitorum longus muscles. Light microscopic examination of silver-stained axons in the intramuscular nerve bundles of MeHg-treated rats showed Wallerian-like degeneration and a reduction in the number of nerve fibers. Disrupted axons were predominantly sensory because 22.2% of spindle afferents (I/sub a/) and 90.0% of Golgi tendon organ (I/sub b/) sensory fibers were completely degenerated whereas less than 1% of motor ending were totally destroyed. Partial disruption occurred in the cholinesterase and motor terminals of 13.7% of endplates. Their results demonstrated greater vulnerability of sensory nerves than of motor nerves to MeHg-induced degeneration. Thus, the abnormal reflexes, ataxia, and muscle weakness following MeHg poisoning appear related to reduction of proprioceptive feedback from muscles and tendons irradiation to the documented lesions in the central nervous system.
Yip, R.K.; Riley, D.A.
This study evaluated sensory and biomechanical assets in 2 heel pain conditions with similar symptoms, entrapment syndrome of the nerve to abductor digiti quinti and myofascial syndrome of abductor hallucis. Thirty-three patients with unilateral heel pain and 20 asymptomatic subjects underwent pressure pain threshold measurement in the painful area in site A (medial process of calcaneal tuberosity, trigger point site
Raoul Saggini; Rosa Grazia Bellomo; Giannapia Affaitati; Domenico Lapenna; Maria Adele Giamberardino
Background Hereditary spastic paraplegias (HSPs) are characterised by lower limb spasticity due to degeneration of the corticospinal tract. We set out for an electrophysiological characterisation of motor and sensory tracts in patients with HSP. Methods We clinically and electrophysiologically examined a cohort of 128 patients with genetically confirmed or clinically probable HSP. Motor evoked potentials (MEPs) to arms and legs, somato-sensory evoked potentials of median and tibial nerves, and nerve conduction studies of tibial, ulnar, sural, and radial nerves were assessed. Results Whereas all patients showed clinical signs of spastic paraparesis, MEPs were normal in 27% of patients and revealed a broad spectrum with axonal or demyelinating features in the others. This heterogeneity can at least in part be explained by different underlying genotypes, hinting for distinct pathomechanisms in HSP subtypes. In the largest subgroup, SPG4, an axonal type of damage was evident. Comprehensive electrophysiological testing disclosed a more widespread affection of long fibre tracts involving peripheral nerves and the sensory system in 40%, respectively. Electrophysiological abnormalities correlated with the severity of clinical symptoms. Conclusions Whereas HSP is primarily considered as an upper motoneuron disorder, our data suggest a more widespread affection of motor and sensory tracts in the central and peripheral nervous system as a common finding in HSP. The distribution patterns of electrophysiological abnormalities were associated with distinct HSP genotypes and could reflect different underlying pathomechanisms. Electrophysiological measures are independent of symptomatic treatment and may therefore serve as a reliable biomarker in upcoming HSP trials. PMID:24107482
Antibodies to substance P with a high titer have been produced and used in immunohistochemical studies on the peripheral and central nervous system of the rat and the cat. Evidence was obtained for the localization of substance P in a certain population of primary sensory neurons, probably small nerve cells with unmyelinated processes. Substance P or a peptide similar to
Tomas Hokfelt; Jan Olof Kellerth; Goran Nilsson; Bengt Pernow
This report summarizes our clinical experience in which the effects of both thalamic sensory relay nucleus (TSRN) and periaqueductal gray (PAG) stimulation were tested in the same series of patients with various forms of pain. The clinical data indicated that neurogenic pain due to deafferentation at the level of the peripheral nerves or the spinal cord was often controlled by
Takashi Tsubokawa; Yoichi Katayama; Takamitsu Yamamoto; Teruyasu Hirayama
Abstract Objective. To investigate the effects of four dentin desensitizers on pain reduction in hypersensitive cervical dentin lesions. Materials and methods. The trial was designed as a randomized, controlled, four-arm, single-masked study. Fifty subjects with at least one hypersensitive lesion in each of the four quadrants were allocated. The requested pre-operative pain, determined as a response to 2-s air-blast (AB) and probe scratching (PS), was ?5 on a VAS scale, 0 = no through to 10 = worst pain. Randomly each subject received each of the four treatments: MS Coat One F (MSC, Sun Medical, Japan), Nanoseal (NAN, Nishin, Japan), Teethmate Desensitizer (TMD, Kuraray Noritake, Japan) and Gluma Desensitizer PowerGel (GLU, HeraeusKulzer, Germany). The investigator assessed blindly the pain response using the two stimuli and recorded the patients' VAS scores before and immediately after application, after 1 week and after 1, 3 and 6 months. Statistical data treatment. ANOVA and post-hoc testing (p ? 0.05). Results. Forty-nine subjects completed the trial. Pre-operative dentin hypersensitivity (DH) for the groups was not significantly different. All desensitizers reduced DH significantly throughout the 6-months observation. ANOVA revealed significant differences among VAS scores, obtained with the desensitizing agents (p < 0.001). Ranking by post-hoc testing was: MSC > NAN > TMD > GLU (p < 0.05). Upon PS NAN and TMD showed slight but significant regain of sensitivity after 6 months. For GLU PS scores immediately after application and after 6 months were not significantly different, whereas recalls after 1 week, 1 month and 3 months revealed significantly lower scores. Conclusion. The calcium phosphate-based TMD and GLU proved highly effective in reducing sensitivity. PMID:24909155
Mehta, Deepak; Gowda, Vishwas S; Santosh, Ashwini; Finger, Werner J; Sasaki, Keiichi
We present a case study of a novel variation of the targeted sensory reinnervation technique that provides additional control over sensory restoration after transhumeral amputation. The use of intraoperative somatosensory evoked potentials on individual fascicles of the median and ulnar nerves allowed us to specifically target sensory fascicles to reroute to target cutaneous nerves at a distance away from anticipated motor sites in a transhumeral amputee. This resulted in restored hand maps of the median and ulnar nerve in discrete spatially separated areas. In addition, the subject was able to use native and reinnervated muscle sites to control a robotic arm while simultaneously sensing touch and force feedback from the robotic gripper in a physiologically correct manner. This proof of principle study is the first to demonstrate the ability to have simultaneous dual flow of information (motor and sensory) within the residual limb. In working towards clinical deployment of a sensory integrated prosthetic device, this surgical method addresses the important issue of restoring a usable access point to provide natural hand sensation after upper limb amputation. PMID:24760915
Hebert, Jacqueline S; Olson, Jaret L; Morhart, Michael J; Dawson, Michael R; Marasco, Paul D; Kuiken, Todd A; Chan, K Ming
Inhalation of acid aerosol or aspiration of acid solution evokes a stimulatory effect on airway C-fiber and A? 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
Lee, Lu-Yuan; Gu, Qihai; Xu, Fadi; Hong, Ju-Lun
Some syndromes are of interest to both neurologists and dermatologists, because cutaneous involvement may harbinger symptoms of a neurological disease. The aim of this review is to clarify this aspect. The skin, because of its relationships with the peripheral sensory nervous system, autonomic nervous system and central nervous system, constitutes a neuroimmunoendocrine organ. The skin contains numerous neuropeptides released from sensory nerves. Neuropeptides play a precise role in cutaneous physiology and pathophysiology, and in certain skin diseases. A complex dysregulation of neuropeptides is a feature of some diseases of both dermatological and neurological interest (e.g. cutaneous and nerve lesions following herpes zoster infection, cutaneous manifestations of carpal tunnel syndrome, trigeminal trophic syndrome). Dermatologists need to know when a patient should be referred to a neurologist and should consider this option in those presenting with syndromes of unclear etiology. PMID:24125557
Bove, D; Lupoli, A; Caccavale, S; Piccolo, V; Ruocco, E
Summary Some syndromes are of interest to both neurologists and dermatologists, because cutaneous involvement may harbinger symptoms of a neurological disease. The aim of this review is to clarify this aspect. The skin, because of its relationships with the peripheral sensory nervous system, autonomic nervous system and central nervous system, constitutes a neuroimmunoendocrine organ. The skin contains numerous neuropeptides released from sensory nerves. Neuropeptides play a precise role in cutaneous physiology and pathophysiology, and in certain skin diseases. A complex dysregulation of neuropeptides is a feature of some diseases of both dermatological and neurological interest (e.g. cutaneous and nerve lesions following herpes zoster infection, cutaneous manifestations of carpal tunnel syndrome, trigeminal trophic syndrome). Dermatologists need to know when a patient should be referred to a neurologist and should consider this option in those presenting with syndromes of unclear etiology. PMID:24125557
Bove, Domenico; Lupoli, Amalia; Caccavale, Stefano; Piccolo, Vincenzo; Ruocco, Eleonora
Perceptual consequences of disrupted auditory nerve activity were systematically studied in 21 subjects who had been clinically diagnosed with auditory neuropathy (AN), a recently defined disorder characterized by normal outer hair cell function but disrupted auditory nerve function. Neurological and electrophysical evidence suggests that disrupted auditory nerve activity is due to desynchronized or reduced neural activity or both. Psychophysical measures showed that the disrupted neural activity has minimal effects on intensity-related perception, such as loudness discrimination, pitch discrimination at high frequencies, and sound localization using interaural level differences. In contrast, the disrupted neural activity significantly impairs timing related perception, such as pitch discrimination at low frequencies, temporal integration, gap detection, temporal modulation detection, backward and forward masking, signal detection in noise, binaural beats, and sound localization using interaural time differences. These perceptual consequences are the opposite of what is typically observed in cochlear-impaired subjects who have impaired intensity perception but relatively normal temporal processing after taking their impaired intensity perception into account. These differences in perceptual consequences between auditory neuropathy and cochlear damage suggest the use of different neural codes in auditory perception: a suboptimal spike count code for intensity processing, a synchronized spike code for temporal processing, and a duplex code for frequency processing. We also proposed two underlying physiological models based on desynchronized and reduced discharge in the auditory nerve to successfully account for the observed neurological and behavioral data. These methods and measures cannot differentiate between these two AN models, but future studies using electric stimulation of the auditory nerve via a cochlear implant might. These results not only show the unique contribution of neural synchrony to sensory perception but also provide guidance for translational research in terms of better diagnosis and management of human communication disorders. PMID:15615831
Zeng, Fan-Gang; Kong, Ying-Yee; Michalewski, Henry J; Starr, Arnold
OBJECTIVE. Sensory modulation issues have a significant impact on participation in daily life. Moreover, understanding phenotypic variation in sensory modulation dysfunction is crucial for research related to defining homogeneous groups and for clinical work in guiding treatment planning. We thus evaluated the new Sensory Processing Scale (SPS) Assessment. METHOD. Research included item development, behavioral scoring system development, test administration, and item analyses to evaluate reliability and validity across sensory domains. RESULTS. Items with adequate reliability (internal reliability >.4) and discriminant validity (p < .01) were retained. Feedback from the expert panel also contributed to decisions about retaining items in the scale. CONCLUSION. The SPS Assessment appears to be a reliable and valid measure of sensory modulation (scale reliability >.90; discrimination between group effect sizes >1.00). This scale has the potential to aid in differential diagnosis of sensory modulation issues. PMID:25184464
Miller, Lucy J.; Sullivan, Jillian C.
Bronchopulmonary C fibers and acid-sensitive, capsaicin-insensitive mechanoreceptors innervating the larynx, trachea, and large bronchi regulate the cough reflex. These vagal afferent nerves may interact centrally with sensory input arising from afferent nerves innervating the intrapulmonary airways or even extrapulmonary afferents such as those innervating the nasal mucosa and esophagus to produce chronic cough or enhanced cough responsiveness. The mechanisms of cough initiation in health and in disease are briefly described. PMID:20172253
Canning, Brendan J
Clinical signs of delayed neuropathy were induced in adult white leghorn chickens given the organophosphorus ester phenyl saligenin phosphate (PSP, 2.5 mg\\/kg im) 22–24 d before assessment of nerve conduction parameters. Damage to the myelinated sensory portion of the sciatic nerve was indicated by abnormal compound action potentials in treated chickens. In particular, the amplitude of the A? response was
T. I. Lidsky; C. Manetto; M. Ehrich
Introduction Nerve injury during implant placement is a preventable, serious complication with major medico-legal implications. The incidence of implant related inferior alveolar nerve (IAN) injuries varies from 0-40%. This article presents four cases of IAN injury following mandibular implant placement with early removal, referred to the oral surgery department, King's College Hospital, London.Objectives To assess sensory disturbance and recovery in
T. Renton; N. Khawaja
Findings differ on cortical representation of fingers between human and animal studies, and on digit somatotopy among human studies. To resolve these differences, we mapped cortical sensory representation of each of the five digits and of median and ulnar nerves in three patients, using focal peripheral electrical shock stimuli. We compared locations and sizes of cortical regions among digits and nerves, using the model of a current dipole in a sphere applied to electrocorticography from subdural grids. Cortical representation was larger for the index finger than for the little finger and for the middle finger than for the ring finger, which are similar to findings in the monkey but different from Penfield's classic sensory homunculus. The thumb was larger than the middle finger, as in the homunculus. There was nonoverlapping somatotopy of all digits in each patient. These findings demonstrate a previously unrecognized similarity of cortical sensory organization of the fingers between humans and other primates. PMID:1579225
Sutherling, W W; Levesque, M F; Baumgartner, C
Diagnostic work-up of patients with peripheral nerve lesions includes a detailed evaluation of the clinical history, a thorough\\u000a search for predisposing factors and trigger events, palpation at the suspected lesion site, specific provocation maneuvers\\u000a and assessment of motor deficits (distribution, muscle power and atrophy), sensory disturbances (distribution and quality)\\u000a and autonomic impairment (sudomotor activity) — all embedded in a careful
Successful nerve regeneration after nerve trauma is not only important for the restoration of motor and sensory functions, but also to reduce the potential for abnormal sensory impulse generation that can occur following neuroma formation. Satisfying functional results after severe lesions are difficult to achieve and the development of interventional methods to achieve optimal functional recovery after peripheral nerve injury is of increasing clinical interest. Olfactory ensheathing cells (OECs) have been used to improve axonal regeneration and functional outcome in a number of studies in spinal cord injury models. The rationale is that the OECs may provide trophic support and a permissive environment for axonal regeneration. The experimental transplantation of OECs to support and enhance peripheral nerve regeneration is much more limited. This chapter reviews studies using OECs as an experimental cell therapy to improve peripheral nerve regeneration. PMID:23202929
Radtke, Christine; Kocsis, Jeffery D.
Background Approximately 12% of operations for traumatic neuropathy are for patients with segmental nerve loss and less than 50% of these injuries obtain meaningful functional recovery. Polyethylene glycol (PEG) therapy has been shown to improve functional outcomes after nerve severance and we hypothesized this therapy could also benefit nerve autografting. Methods A segmental rat sciatic nerve injury model was used, whereby a 0.5 cm defect was repaired with an autograft using microsurgery. Experimental animals were treated with solutions containing methylene blue (MB) and PEG; control animals did not receive PEG. Compound Actions Potentials (CAPs) were recorded before nerve transection, after solution therapy, and at 72 hours postoperatively. The animals underwent behavioral testing at 24 and 72 hours postoperatively. After sacrifice, nerves were fixed, sectioned, and immunostained to allow for quantitative morphometric analysis. Results The introduction of hydrophilic polymers greatly improved morphological and functional recovery of rat sciatic axons at 1–3 days following nerve autografting. PEG therapy restored CAPs in all animals and CAPs were still present 72 hours postoperatively. No CAPS were detectable in control animals. Footfall asymmetry scores and sciatic functional index scores were significantly improved for PEG therapy group at all time points (p <0.05 and p<0.001; p <0.001 and p <0.01). Sensory and motor axon counts were increased distally in nerves treated with PEG compared to control (p = 0.0189 and p = 0.0032). Conclusions PEG therapy improves early physiologic function, behavioral outcomes, and distal axonal density after nerve autografting. PMID:22521220
Sexton, Kevin W.; Pollins, Alonda C.; Cardwell, Nancy L.; Del Corral, Gabriel A.; Bittner, George D.; Shack, R. Bruce; Nanney, Lillian B.; Thayer, Wesley P.
Autologous nerve grafting is the most commocommnlynly used operative technique in delayed primary, or secondary nerve repair after the peripheral nerve injuries. The aim of this procedure is to overcome nerve gaps that results from the injury itself, fibrous and elastic retraction forces, resection of the damaged parts of the nerve, position of the articulations and mobilisation of the nerve. In this study we analyse the results of operated patients with transections and lacerations of the peripheral nerves from 1979 to 2000 year. Gunshot injuries have not been analyzed in this study. The majority of the injuries were in the upper extremity (more than 87% of cases). Donor for nerve transplantation had usually been sural nerve, and only occasionally medial cutaneous nerve of the forearm was used. In about 93% of cases we used interfascicular nerve grafting, and cable nerve grafting was performed in the rest of them. Most of the grafts were 1 do 5 cm long (70% of cases). Functional recovery was achieved in more than 86% of cases, which is similar to the results of the other authors. Follow up period was minimum 2 years. We analyzed the influence of different factors on nerve recovery after the operation: patient's age, location and the extent (total or partial) of nerve injury, the length of the nerve graft, type of the nerve, timing of surgery, presence of multiple nerve injuries and associated osseal and soft tissue injuries of the upper and lower extremities. PMID:14619715
Grujici?, D; Samardzi?, M; Rasuli?, L; Savi?, D; Cvrkota, I; Simi?, V
It is generally accepted that intestinal sensory vagal fibers are primary afferent, responding nonsynaptically to luminal stimuli. The gut also contains intrinsic primary afferent neurons (IPANs) that respond to luminal stimuli. A psychoactive Lactobacillus rhamnosus (JB-1) that affects brain function excites both vagal fibers and IPANs. We wondered whether, contrary to its primary afferent designation, the sensory vagus response to JB-1 might depend on IPAN to vagal fiber synaptic transmission. We recorded ex vivo single- and multiunit afferent action potentials from mesenteric nerves supplying mouse jejunal segments. Intramural synaptic blockade with Ca(2+) channel blockers reduced constitutive or JB-1-evoked vagal sensory discharge. Firing of 60% of spontaneously active units was reduced by synaptic blockade. Synaptic or nicotinic receptor blockade reduced firing in 60% of vagal sensory units that were stimulated by luminal JB-1. In control experiments, increasing or decreasing IPAN excitability, respectively increased or decreased nerve firing that was abolished by synaptic blockade or vagotomy. We conclude that >50% of vagal afferents function as interneurons for stimulation by JB-1, receiving input from an intramural functional "sensory synapse." This was supported by myenteric plexus nicotinic receptor immunohistochemistry. These data offer a novel therapeutic target to modify pathological gut-brain axis activity.-Perez-Burgos, A., Mao, Y.-K., Bienenstock, J., Kunze, W. A. The gut-brain axis rewired: adding a functional vagal nicotinic "sensory synapse." PMID:24719355
Perez-Burgos, Azucena; Mao, Yu-Kang; Bienenstock, John; Kunze, Wolfgang A
Patients with peripheral nerve injuries face unpredictable and often suboptimal functional outcome, even following standard microsurgical nerve repair. The challenge of improving such outcomes following nerve surgical procedures has interested many research teams, in both clinical and fundamental fields. Some innovative treatments are presently being applied to a widening range of patients, whereas others will require further development before translation to human subjects. This article presents several recent advances in emerging therapies at various stages of clinical application. Nerve transfers have been successfully used in clinical settings, but new indications are being described, enlarging the range of patients who might benefit from them. Brief direct nerve electrical stimulation has been shown to improve nerve regeneration and outcome in animal models and in a small cohort of patients. Further clinical trials are warranted to prove the efficacy of this exciting and easily applicable approach. Animal studies also suggest a tremendous potential for stem and precursor cell therapy. Further studies will lead to a better understanding of their mechanisms of action in nerve repair and potential applications for human patients. PMID:23250767
Khuong, Helene T; Midha, Rajiv
Total phallic reconstruction presents the genitourinary reconstructive surgeon with one of the most difficult surgical challenges. The development of microsurgical techniques and free tissue transfers have advanced phallic reconstruction by reducing the number of surgical procedures and by allowing more selectivity in choosing the best innervated donor tissue. During the last 5 years 16 patients underwent total phallic reconstruction using free tissue transfers from distant donor sites. The pudendal nerve was coapted routinely to the major sensory nerves of the donor free flap. The most accurate objective baseline parameters of penile sensibility are pressure and vibratory thresholds, and electrically evoked potentials. We examined 30 normal subjects and 7 patients at least 1 year postoperatively for penile (phallic) sensibility. A pressure aesthesiometer, a biothesiometer and electrodiagnostic studies were used for testing. The 7 postoperative patients (in all of whom the pudendal nerve was incorporated into the reconstruction) had an encouraging return of tactile and erogenous sensibility compared to normal subjects. This is a promising advance in phallic reconstruction. PMID:3398124
Gilbert, D A; Williams, M W; Horton, C E; Terzis, J K; Winslow, B H; Gilbert, D M; Devine, C J
The acute toxicity of five desensitized primer compounds and primer manufacturing waste effluents to three freshwater species, Daphnia magna (water flea: crustacean), Lepomis macrochirus (bluegill:fish) and Pimephales promelas (fathead minnow:fish) was de...
B. H. Sleight, K. J. Macek, R. E. Bentley
This study tests whether playing violent video games leads to desensitization and increased cardiovascular responding. In a laboratory experiment, 42 men spent 20 min playing either a high- or low-violence version of a \\
Frithjof Staude-Müller; Thomas Bliesener; Stefanie Luthman
Objective: We sought to determine lesion sites and spatial lesion patterns in spontaneous anterior interosseous nerve syndrome (AINS) with high-resolution magnetic resonance neurography (MRN). Methods: In 20 patients with AINS and 20 age- and sex-matched controls, MRN of median nerve fascicles was performed at 3T with large longitudinal anatomical coverage (upper arm/elbow/forearm): 135 contiguous axial slices (T2-weighted: echo time/repetition time 52/7,020 ms, time of acquisition: 15 minutes 48 seconds, in-plane resolution: 0.25 × 0.25 mm). Lesion classification was performed by visual inspection and by quantitative analysis of normalized T2 signal after segmentation of median nerve voxels. Results: In all patients and no controls, T2 lesions of individual fascicles were observed within upper arm median nerve trunk and strictly followed a somatotopic/internal topography: affected were those motor fascicles that will form the anterior interosseous nerve further distally while other fascicles were spared. Predominant lesion focus was at a mean distance of 14.6 ± 5.4 cm proximal to the humeroradial joint. Discriminative power of quantitative T2 signal analysis and of qualitative lesion rating was high, with 100% sensitivity and 100% specificity (p < 0.0001). Fascicular T2 lesion patterns were rated as multifocal (n = 17), monofocal (n = 2), or indeterminate (n = 1) by 2 independent observers with strong agreement (kappa = 0.83). Conclusion: It has been difficult to prove the existence of fascicular/partial nerve lesions in spontaneous neuropathies using clinical and electrophysiologic findings. With MRN, fascicular lesions with strict somatotopic organization were observed in upper arm median nerve trunks of patients with AINS. Our data strongly support that AINS in the majority of cases is not a surgically treatable entrapment neuropathy but a multifocal mononeuropathy selectively involving, within the main trunk of the median nerve, the motor fascicles that continue distally to form the anterior interosseous nerve. PMID:24415574
Baumer, Philipp; Meinck, Hans-Michael; Schiefer, Johannes; Weiler, Markus; Bendszus, Martin; Kele, Henrich
Patients with idiopathic small fibre neuropathy (ISFN) have been shown to have significant intraepidermal nerve fibre loss and an increased prevalence of impaired glucose tolerance (IGT). It has been suggested that the dysglycemia of IGT and additional metabolic risk factors may contribute to small nerve fibre damage in these patients. Twenty-five patients with ISFN and 12 aged-matched control subjects underwent a detailed evaluation of neuropathic symptoms, neurological deficits (Neuropathy deficit score (NDS); Nerve Conduction Studies (NCS); Quantitative Sensory Testing (QST) and Corneal Confocal Microscopy (CCM)) to quantify small nerve fibre pathology. Eight (32%) patients had IGT. Whilst all patients with ISFN had significant neuropathic symptoms, NDS, NCS and QST except for warm thresholds were normal. Corneal sensitivity was reduced and CCM demonstrated a significant reduction in corneal nerve fibre density (NFD) (P<0.0001), nerve branch density (NBD) (P<0.0001), nerve fibre length (NFL) (P<0.0001) and an increase in nerve fibre tortuosity (NFT) (P<0.0001). However these parameters did not differ between ISFN patients with and without IGT, nor did they correlate with BMI, lipids and blood pressure. Corneal confocal microscopy provides a sensitive non-invasive means to detect small nerve fibre damage in patients with ISFN and metabolic abnormalities do not relate to nerve damage. PMID:19748505
Tavakoli, Mitra; Marshall, Andrew; Pitceathly, Robert; Fadavi, Hassan; Gow, David; Roberts, Mark E; Efron, Nathan; Boulton, Andrew Jm; Malik, Rayaz A
During prolonged exposure of postjunctional nicotinic acetylcholine receptors (nAChR) of skeletal muscle to acetylcholine (ACh), agonist-activated nAChR (nAChRa) gradually fall into a refractory “desensitized” state (nAChRd), which no longer supports the high-conductance channel openings characteristic of the initially active nAChRa. In the present study, the possibility was examined that nAChRd, rather than simply constituting a passive “trap” for nAChRa, may
Arthur A. Manthey