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Sample records for sensory nerve desensitization

  1. Sensory Desensitization Training for Successful Net Application and EEG/ERP Acquisition in Difficult to Test Children

    ERIC Educational Resources Information Center

    Roesler, Cynthia P.; Flax, Judy; MacRoy-Higgins, Michelle; Fermano, Zena; Morgan-Byrne, Julie; Benasich, April A.

    2013-01-01

    This study examined the effectiveness of sensory desensitization training for 12 nonverbal children with autism to facilitate participation in an electrophysiological study assessing linguistic processing. Sensory desensitization was achieved for 10 of the 12 children and thus allowed collection of usable data in a passive linguistic paradigm.…

  2. Sensory effects of capsaicin congeners. Part II: Importance of chemical structure and pungency in desensitizing activity of capsaicin-type compounds.

    PubMed

    Szolcsányi, J; Jancsó-Gábor, A

    1976-01-01

    The characteristic insensitivity of sensory nerve endings to chemically induced pain brought about by capsaicin could be reproduced on the rat's eye by pungent vanillylamides, homovanilloyl-alkylamides and piperine, while homovanilloyl-cycloalkylamides, -azacycloalkylamides, - alkylesters, -alkyl-homovanillylamides, undecenoyl-3-aminopropranololand zingerone were practically ineffective in this respect. Desensitizing potency was not parallel with the stimulating effect of the compounds, e.g. the strongly pungent homovanilloyl-octylester failed to desensitize the receptors, while the less pungent homovanilloyl-dodecylamide proved to be a more potent desensitizing agent than capsaicin itself. It is concluded that the inverse position of the acylamide linkage does not modify, while its replacement by an esteric group completely abolishes the desensitizing activity. In contrast to the stimulating effect, in desensitizing action the presence of an alkyl chain is essential and its optimal length corresponds to 10-12 C atoms. On the basis of these results the possible molecular interactions at the site of action are discussed.

  3. Sensory nerves in lung and airways.

    PubMed

    Lee, Lu-Yuan; Yu, Jerry

    2014-01-01

    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.

  4. Transient receptor potential TRPA1 channel desensitization in sensory neurons is agonist dependent and regulated by TRPV1-directed internalization.

    PubMed

    Akopian, Armen N; Ruparel, Nikita B; Jeske, Nathaniel A; Hargreaves, Kenneth M

    2007-08-15

    The pharmacological desensitization of receptors is a fundamental mechanism for regulating the activity of neuronal systems. The TRPA1 channel plays a key role in the processing of noxious information and can undergo functional desensitization by unknown mechanisms. Here we show that TRPA1 is desensitized by homologous (mustard oil; a TRPA1 agonist) and heterologous (capsaicin; a TRPV1 agonist) agonists via Ca2+-independent and Ca2+-dependent pathways, respectively, in sensory neurons. The pharmacological desensitization of TRPA1 by capsaicin and mustard oil is not influenced by activation of protein phosphatase 2B. However, it is regulated by phosphatidylinositol-4,5-bisphosphate depletion after capsaicin, but not mustard oil, application. Using a biosensor, we establish that capsaicin, unlike mustard oil, consistently activates phospholipase C in sensory neurons. We next demonstrate that TRPA1 desensitization is regulated by TRPV1, and it appears that mustard oil-induced TRPA1 internalization is prevented by coexpression with TRPV1 in a heterologous expression system and in sensory neurons. In conclusion, we propose novel mechanisms whereby TRPA1 activity undergoes pharmacological desensitization through multiple cellular pathways that are agonist dependent and modulated by TRPV1.

  5. Quantitative Sensory Testing of the Effect of Desensitizing Treatment After Dental Bleaching.

    PubMed

    Rahal, Vanessa; Gallinari, Marjorie O; Perdigão, Jorge; Cintra, Luciano T A; dos Santos, Paulo H; Briso, André L F

    2015-12-01

    The aim of this study was to quantify tooth sensitivity during bleaching and after a desensitizing treatment. Sensitivity was measured with a new device, TSA-II, which uses thermal stimuli for Quantitative Sensory Testing (QST). Ten patients underwent bleaching treatment using Whiteness HP Maxx (FGM Produtos Odontológicos Ltda) containing 35% hydrogen peroxide. After the bleaching session, the teeth were cleaned with air/water spray and the product Desensibilize KF 2% (FGM Produtos Odontológicos Ltda) was applied to the upper left teeth. Saline solution at room temperature was applied in the upper right teeth. QST was performed before bleaching, immediately after bleaching, and immediately after desensitizing treatment. In order to standardize tooth analysis, a 100% ethylene copolymer and vinyl acetate tray with circular perforations was used during measurements. Analysis of variance and the Student's t-test were used (a=0.05). Mean temperatures (SD) of cold sensation threshold for the upper right quadrant were: BB-13.898 (4.81), AB- 19.241 (3.68), AD-20.646 (3.72) and for the upper left quadrant they were: BB-14.102 (3.22), AB-19.646 (4.82), AD- 13.835 (3.63). Dental bleaching with highly concentrated peroxides changed dental cold sensation thresholds, but the topical desensitizer changed the immediate cold sensation thresholds produced by the cold stimulus.

  6. Self- and Cross-desensitization of Oral Irritation by Menthol and Cinnamaldehyde (CA) via Peripheral Interactions at Trigeminal Sensory Neurons

    PubMed Central

    Klein, Amanda H.; Zanotto, Karen L.; Sawyer, Carolyn M.; Ivanov, Margaret; Cheung, Susan

    2011-01-01

    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 μM. Menthol cross-desensitized TG cell responses to CA. CA at a concentration of 400 but not 200 μM 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

  7. Self- and cross-desensitization of oral irritation by menthol and cinnamaldehyde (CA) via peripheral interactions at trigeminal sensory neurons.

    PubMed

    Klein, Amanda H; Carstens, Mirela Iodi; Zanotto, Karen L; Sawyer, Carolyn M; Ivanov, Margaret; Cheung, Susan; Carstens, E

    2011-01-01

    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 μM. Menthol cross-desensitized TG cell responses to CA. CA at a concentration of 400 but not 200 μM 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.

  8. Activation and desensitization of TRPV1 channels in sensory neurons by the PPARα agonist palmitoylethanolamide

    PubMed Central

    Ambrosino, Paolo; Soldovieri, Maria Virginia; Russo, Claudio; Taglialatela, Maurizio

    2013-01-01

    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 PPARα 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 μM) dose-dependently increased [Ca2+]i. The TRPV1 antagonists capsazepine (1 μM) and SB-366791 (1 μM), as well as the PPARα antagonist GW-6471 (10 μM), 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 PPARα. 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 PPARα 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

  9. Functional selectivity and time-dependence of μ-opioid receptor desensitization at nerve terminals in the mouse ventral tegmental area

    PubMed Central

    Lowe, J D; Bailey, C P

    2015-01-01

    BACKGROUND AND PURPOSE The majority of studies examining desensitization of the μ-opioid receptor (MOR) have examined those located at cell bodies. However, MORs are extensively expressed at nerve terminals throughout the mammalian nervous system. This study is designed to investigate agonist-induced MOR desensitization at nerve terminals in the mouse ventral tegmental area (VTA). EXPERIMENTAL APPROACH MOR function was measured in mature mouse brain slices containing the VTA using whole-cell patch-clamp electrophysiology. Presynaptic MOR function was isolated from postsynaptic function and the functional selectivity, time-dependence and mechanisms of agonist-induced MOR desensitization were examined. KEY RESULTS MORs located at GABAergic nerve terminals in the VTA were completely resistant to rapid desensitization induced by the high-efficacy agonists DAMGO and Met-enkephalin. MORs located postsynaptically on GABAergic cell bodies readily underwent rapid desensitization in response to DAMGO. However, after prolonged (>7 h) treatment with Met-enkephalin, profound homologous MOR desensitization was observed. Morphine could induce rapid MOR desensitization at nerve terminals when PKC was activated. CONCLUSIONS AND IMPLICATIONS Agonist-induced MOR desensitization in GABAergic neurons in the VTA is compartment-selective as well as agonist-selective. When MORs are located at cell bodies, higher-efficacy agonists induce greater levels of rapid desensitization than lower-efficacy agonists. However, the converse is true at nerve terminals where agonists that induce MOR desensitization via PKC are capable of rapid agonist-induced desensitization while higher-efficacy agonists are not. MOR desensitization induced by higher-efficacy agonists at nerve terminals only takes place after prolonged receptor activation. LINKED ARTICLES This article is part of a themed section on Opioids: New Pathways to Functional Selectivity. To view the other articles in this section visit http

  10. Neonatal sensory nerve injury-induced synaptic plasticity in the trigeminal principal sensory nucleus.

    PubMed

    Lo, Fu-Sun; Erzurumlu, Reha S

    2016-01-01

    Sensory deprivation studies in neonatal mammals, such as monocular eye closure, whisker trimming, and chemical blockade of the olfactory epithelium have revealed the importance of sensory inputs in brain wiring during distinct critical periods. But very few studies have paid attention to the effects of neonatal peripheral sensory nerve damage on synaptic wiring of the central nervous system (CNS) circuits. Peripheral somatosensory nerves differ from other special sensory afferents in that they are more prone to crush or severance because of their locations in the body. Unlike the visual and auditory afferents, these nerves show regenerative capabilities after damage. Uniquely, damage to a somatosensory peripheral nerve does not only block activity incoming from the sensory receptors but also mediates injury-induced neuro- and glial chemical signals to the brain through the uninjured central axons of the primary sensory neurons. These chemical signals can have both far more and longer lasting effects than sensory blockade alone. Here we review studies which focus on the consequences of neonatal peripheral sensory nerve damage in the principal sensory nucleus of the brainstem trigeminal complex.

  11. Sensory irritation and pulmonary irritation of cumene and n-propanol: mechanisms of receptor activation and desensitization.

    PubMed

    Kristiansen, U; Hansen, L; Nielsen, G D; Holst, E

    1986-07-01

    Cumene and n-propanol, model substances for alcohols and alkylbenzenes, were investigated for sensory irritation in mice. The concentrations within the first 2 min. depressing the respiratory rate by 50% due to the effect in the upper respiratory tract were 2,058 p.p.m. and 22,080 p.p.m., respectively. Activation of the sensory irritant receptor followed the dynamics of reversible bimolecular reactions. The extrapolated maximum response and the apparent dissociation constant were 114.3% and 2,723 p.p.m. for cumene and 68.4% and 8,178 p.p.m. for propanol, respectively. Later on desensitization was observed. The effect was weak for cumene but conspicuous for propanol. For cumene desensitization had the origin in the rise of a threshold. No change in the dissociation constant or the maximum response was found. For propanol a decrease in the maximum response, which may be explained by an allosteric effect, was observed. The pulmonary irritation response was weak for cumene but was for propanol more important than sensory irritation at high concentrations. The following hypotheses are put forward: the effect of pulmonary irritation on the tidal volume is mediated via the stretch receptors while the effect on the respiratory frequency is mediated via the J-receptors.

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

    PubMed Central

    Lu, Jian

    2014-01-01

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

  13. Alteration in sensory nerve function following electrical shock.

    PubMed

    Abramov, G S; Bier, M; Capelli-Schellpfeffer, M; Lee, R C

    1996-12-01

    A study of the effects of electrical shock on peripheral nerve fibres is presented. Strength and duration of the applied shocks were similar to those encountered in a typical industrial electrical accident. The purpose of this study is: (i) to identify the electrophysiological and morphological change in nerve fibres after the application of electrical current shocks; (ii) to examine the ability of the peripheral nerve fibres to spontaneously regain function and; (iii) to demonstrate the usefulness of the sensory refractory spectrum as an additional technique in assessing the damage. Three groups of animals received twelve 4-ms electric field pulses of approximately 37 V/cm (n = 5), 75 V/cm (n = 9) and 150 V/cm (n = 6), respectively. Group 4 was a control group and received a direct application of 2 per cent lidocaine over the sciatic nerve for 30 min. Thermal effects of the shocks were negligible. The sensory refractory spectrum shows that electrical shock damage was mainly to the large, fast myelinated fibres and that higher field strengths do more damage. Also in a histological examination it was found that the more heavily shocked myelinated fibres had sustained more damage.

  14. Pre-implanted Sensory Nerve Could Enhance the Neurotization in Tissue-Engineered Bone Graft.

    PubMed

    Wu, Yan; Jing, Da; Ouyang, Hongwei; Li, Liang; Zhai, Mingming; Li, Yan; Bi, Long; Guoxian, Pei

    2015-08-01

    In our previous study, it was found that implanting the sensory nerve tract into the tissue-engineered bone to repair large bone defects can significantly result in better osteogenesis effect than tissue-engineered bone graft (TEBG) alone. To study the behavior of the preimplanted sensory nerve in the TEBG, the TEBG was constructed by seeding bone mesenchymal stem cells into β-tricalcium phosphate scaffold with (treatment group) or without (blank group) implantation of the sensory nerve. The expression of calcitonin gene-related peptide (CGRP), which helps in the healing of bone defect in the treatment group was significantly higher than the blank group at 4, 8, and 12 weeks. The expression of growth-associated protein 43 (GAP43), which might be expressed during nerve healing in the treatment group, was significantly higher than the blank group at 4 and 8 weeks. The nerve tracts of the preimplanted sensory nerve were found in the scaffold by the nerve tracing technique. The implanted sensory nerve tracts grew into the pores of scaffolds much earlier than the vascular. The implanted sensory nerve tracts traced by Dil could be observed at 4 weeks, but at the same time, no vascular was observed. In conclusion, the TEBG could be benefited from the preimplanted sensory nerve through the healing behavior of the sensory nerve. The sensory nerve fibers could grow into the pores of the TEBG rapidly, and increase the expression of CGRP, which is helpful in regulating the bone formation and the blood flow.

  15. Improved functional recovery of denervated skeletal muscle after temporary sensory nerve innervation.

    PubMed

    Bain, J R; Veltri, K L; Chamberlain, D; Fahnestock, M

    2001-01-01

    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.

  16. Comparison of the fastest regenerating motor and sensory myelinated axons in the same peripheral nerve.

    PubMed

    Moldovan, Mihai; Sørensen, Jesper; Krarup, Christian

    2006-09-01

    Functional outcome after peripheral nerve regeneration is often poor, particularly involving nerve injuries far from their targets. Comparison of sensory and motor axon regeneration before target reinnervation is not possible in the clinical setting, and previous experimental studies addressing the question of differences in growth rates of different nerve fibre populations led to conflicting results. We developed an animal model to compare growth and maturation of the fastest growing sensory and motor fibres within the same mixed nerve after Wallerian degeneration. Regeneration of cat tibial nerve after crush (n = 13) and section (n = 7) was monitored for up to 140 days, using implanted cuff electrodes placed around the sciatic and tibial nerves and wire electrodes at plantar muscles. To distinguish between sensory and motor fibres, recordings were carried out from L6-S2 spinal roots using cuff electrodes. The timing of laminectomy was based on the presence of regenerating fibres along the nerve within the tibial cuff. Stimulation of unlesioned tibial nerves (n = 6) evoked the largest motor response in S1 ventral root and the largest sensory response in L7 dorsal root. Growth rates were compared by mapping the regenerating nerve fibres within the tibial nerve cuff to all ventral or dorsal roots and, regardless of the lesion type, the fastest growth was similar in sensory and motor fibres. Maturation was assessed as recovery of the maximum motor and sensory conduction velocities (CVs) within the tibial nerve cuff. Throughout the observation period the CV was approximately 14% faster in regenerated sensory fibres than in motor fibres in accordance with the difference observed in control nerves. Recovery of amplitude was only partial after section, whereas the root distribution pattern was restored. Our data suggest that the fastest growth and maturation rates that can be achieved during regeneration are similar for motor and sensory myelinated fibres.

  17. Glial cell plasticity in sensory ganglia induced by nerve damage.

    PubMed

    Hanani, M; Huang, T Y; Cherkas, P S; Ledda, M; Pannese, E

    2002-01-01

    Numerous studies have been done on the effect of nerve injury on neurons of sensory ganglia but little is known about the contribution of satellite glial cells (SCs) in these ganglia to post-injury events. We investigated cell-to-cell coupling and ultrastructure of SCs in mouse dorsal root ganglia after nerve injury (axotomy). Under control conditions SCs were mutually coupled, but mainly to other SCs around a given neuron. After axotomy SCs became extensively coupled to SCs that enveloped other neurons, apparently by gap junctions. Serial section electron microscopy showed that after axotomy SC sheaths enveloping neighboring neurons formed connections with each other. Such connections were absent in control ganglia. The number of gap junctions between SCs increased 6.5-fold after axotomy. We propose that axotomy induces growth of perineuronal SC sheaths, leading to contacts between SCs enveloping adjacent neurons and to formation of new gap junctions between SCs. These changes may be an important mode of glial plasticity and can contribute to neuropathic pain.

  18. Photostimulation of sensory neurons of the rat vagus nerve

    NASA Astrophysics Data System (ADS)

    Rhee, Albert Y.; Li, Gong; Wells, Jonathon; Kao, Joseph P. Y.

    2008-02-01

    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-μm output of a diode laser, delivered through a 200-μm 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.

  19. Sensory nerve conduction in the upper limbs at various stages of diabetic neuropathy 1

    PubMed Central

    Noël, P.

    1973-01-01

    In 59 diabetic patients, sensory nerve potentials were recorded at various sites along the course of the median nerve. Pathological responses were characterized by reduced amplitude, desynchronization and decreased conduction velocity (CV). Four groups of patients with increasingly severe nerve dysfunction were distinguished. The presence and severity of clinical neuropathy in the upper limbs could be related to decreased maximal sensory nerve CV in the proximal segment of the limbs. When maximal sensory nerve CV was normal above the wrist, neuropathy usually remained latent. In severe cases where no sensory nerve potentials could be recorded, the cerebral evoked potentials nonetheless permitted a precise evaluation of the somatosensory conduction. In these cases, maximal sensory nerve CV was very low. In five patients with a so-called diabetic mononeuropathy, abnormal nerve potentials were recorded in the median nerve, although no clinical signs could be seen in the corresponding territory. It is proposed that the diabetic nature of a mononeuropathy can be assessed by the finding of latent abnormalities in seemingly normal nerve. PMID:4753874

  20. Clinical results and thoughts on sensory nerve repair by autologous vein graft in emergency hand reconstruction.

    PubMed

    Risitano, G; Cavallaro, G; Merrino, T; Coppolino, S; Ruggeri, F

    2002-05-01

    Lesions of the digital and other sensory nerves in the hand are common. Based on experimental studies on vein graft as a support for peripheral nerve regeneration, the Authors have been using a simple vein graft to bridge sensory nerve gaps when treating acute hand injuries. This is a retrospective study on the results of 22 sensory nerves repaired using vein grafts in cases in which primary suture was not feasible, in emergency hand reconstruction. Patients were informed that a secondary nerve graft could possibly be necessary in the future. Patients were reviewed by two independent observers at least one year after repair and evaluated using the Highest scale as modified by MacKinnon & Dellon. Evaluation chart included influence of repair on rehabilitation program and presence of painful neuromas and scars as well as patient satisfaction. Results were classified according to Sakellarides and 20/22 were classified as very good or good. Cases classified as poor were satisfied and no secondary nerve grafting has been carried out. Rehabilitation of the associated lesions (tendon lacerations or bone and soft tissue damage) was not influenced by the nerve repair and no painful neuroma was reported in the series. In conclusion, since the literature shows unsatisfactory results in repair of digital nerves with nerve grafts, since it's been demonstrated that an unrepaired sensory nerve leads to painful scar and painful neuroma and since we are reluctant to use nerve grafts in emergency procedures, we recommend this simple method because it is easy, low-cost and effective.

  1. Comparative proteomic analysis of differentially expressed proteins between peripheral sensory and motor nerves.

    PubMed

    He, Qianru; Man, Lili; Ji, Yuhua; Zhang, Shuqiang; Jiang, Maorong; Ding, Fei; Gu, Xiaosong

    2012-06-01

    Peripheral sensory and motor nerves have different functions and different approaches to regeneration, especially their distinct ability to accurately reinervate terminal nerve pathways. To understand the molecular aspects underlying these differences, the proteomics technique by coupling isobaric tags for relative and absolute quantitation (iTRAQ) with online two-dimensional liquid chromatography tandem mass spectrometry (2D LC-MS/MS) was used to investigate the protein profile of sensory and motor nerve samples from rats. A total of 1472 proteins were identified in either sensory or motor nerve. Of them, 100 proteins showed differential expressions between both nerves, and some of them were validated by quantitative real time RT-PCR, Western blot analysis, and immunohistochemistry. In the light of functional categorization, the differentially expressed proteins in sensory and motor nerves, belonging to a broad range of classes, were related to a diverse array of biological functions, which included cell adhesion, cytoskeleton, neuronal plasticity, neurotrophic activity, calcium-binding, signal transduction, transport, enzyme catalysis, lipid metabolism, DNA-binding, synaptosome function, actin-binding, ATP-binding, extracellular matrix, and commitment to other lineages. The relatively higher expressed proteins in either sensory or motor nerve were tentatively discussed in combination with their specific molecular characteristics. It is anticipated that the database generated in this study will provide a solid foundation for further comprehensive investigation of functional differences between sensory and motor nerves, including the specificity of their regeneration.

  2. Degeneration and regeneration of motor and sensory nerves: a stereological study of crush lesions in rat facial and mental nerves.

    PubMed

    Barghash, Z; Larsen, J O; Al-Bishri, A; Kahnberg, K-E

    2013-12-01

    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).

  3. Intraepithelial dendritic cells and sensory nerves are structurally associated and functional interdependent in the cornea

    PubMed Central

    Gao, Nan; Lee, Patrick; Yu, Fu-Shin

    2016-01-01

    The corneal epithelium consists of stratified epithelial cells, sparsely interspersed with dendritic cells (DCs) and a dense layer of sensory axons. We sought to assess the structural and functional correlation of DCs and sensory nerves. Two morphologically different DCs, dendriform and round-shaped, were detected in the corneal epithelium. The dendriform DCs were located at the sub-basal space where the nerve plexus resides, with DC dendrites crossing several nerve endings. The round-shaped DCs were closely associated with nerve fiber branching points, penetrating the basement membrane and reaching into the stroma. Phenotypically, the round-shaped DCs were CD86 positive. Trigeminal denervation resulted in epithelial defects with or without total tarsorrhaphy, decreased tear secretion, and the loss of dendriform DCs at the ocular surface. Local DC depletion resulted in a significant decrease in corneal sensitivity, an increase in epithelial defects, and a reduced density of nerve endings at the center of the cornea. Post-wound nerve regeneration was also delayed in the DC-depleted corneas. Taken together, our data show that DCs and sensory nerves are located in close proximity. DCs may play a role in epithelium innervation by accompanying the sensory nerve fibers in crossing the basement membrane and branching into nerve endings. PMID:27805041

  4. Identification of Changes in Gene expression of rats after Sensory and Motor Nerves Injury.

    PubMed

    Wang, Yu; Guo, Zhi-Yuan; Sun, Xun; Lu, Shi-Bi; Xu, Wen-Jing; Zhao, Qing; Peng, Jiang

    2016-06-02

    Wallerian degeneration is a sequence of events in the distal stump of axotomized nerves. Despite large numbers of researches concentrating on WD, the biological mechanism still remains unclear. Hence we constructed a rat model with both motor and sensory nerves injury and then conducted a RNA-seq analysis. Here the rats were divided into the 4 following groups: normal motor nerves (NMN), injured motor nerves (IMN), normal sensory nerves (NSN) and injured sensory nerves (ISN). The transcriptomes of rats were sequenced by the Illumina HiSeq. The differentially expressed genes (DEGs) of 4 combinations including NMN vs. IMN, NSN vs. ISN, NMN vs. NSN and IMN vs. ISN were identified respectively. For the above 4 combinations, we identified 1666, 1514, 95 and 17 DEGs. We found that NMN vs. IMN shared the most common genes with NSN vs. ISN indicating common mechanisms between motor nerves injury and sensory nerves injury. At last, we performed an enrichment analysis and observed that the DEGs of NMN vs IMN and NSN vs. ISN were significantly associated with binding and activity, immune response, biosynthesis, metabolism and development. We hope our study may shed light on the molecular mechanisms of nerves degeneration and regeneration during WD.

  5. Protein expression of sensory and motor nerves: Two-dimensional gel electrophoresis and mass spectrometry.

    PubMed

    Ren, Zhiwu; Wang, Yu; Peng, Jiang; Zhang, Li; Xu, Wenjing; Liang, Xiangdang; Zhao, Qing; Lu, Shibi

    2012-02-15

    The present study utilized samples from bilateral motor branches of the femoral nerve, as well as saphenous nerves, ventral roots, and dorsal roots of the spinal cord, to detect differential protein expression using two-dimensional gel electrophoresis and nano ultra-high performance liquid chromatography electrospray ionization mass spectrometry tandem mass spectrometry techniques. A mass spectrum was identified using the Mascot search. Results revealed differential expression of 11 proteins, including transgelin, Ig kappa chain precursor, plasma glutathione peroxidase precursor, an unnamed protein product (gi|55628), glyceraldehyde-3-phosphate dehydrogenase-like protein, lactoylglutathione lyase, adenylate kinase isozyme 1, two unnamed proteins products (gi|55628 and gi|1334163), and poly(rC)-binding protein 1 in motor and sensory nerves. Results suggested that these proteins played roles in specific nerve regeneration following peripheral nerve injury and served as specific markers for motor and sensory nerves.

  6. Motor evoked potentials enable differentiation between motor and sensory branches of peripheral nerves in animal experiments.

    PubMed

    Turkof, Edvin; Jurasch, Nikita; Knolle, Erik; Schwendenwein, Ilse; Habib, Danja; Unger, Ewald; Reichel, Martin; Losert, Udo

    2006-10-01

    Differentiation between motor and sensory fascicles is frequently necessary in reconstructive peripheral nerve surgery. The goal of this experimental study was to verify if centrally motor evoked potentials (MEP) could be implemented to differentiate sensory from motor fascicles, despite the well-known intermingling between nerve fascicles along their course to their distant periphery. This new procedure would enable surgeons to use MEP for placing nerve grafts at corresponding fascicles in the proximal and distal stumps without the need to use time-consuming staining. In ten sheep, both ulnar nerves were exposed at the terminal bifurcation between the last sensory and motor branch. Animals were then relaxed to avoid volume conduction. On central stimulation, the evoked nerve compound action potentials were simultaneously recorded from both terminal branches. In all cases, neurogenic motor nerve action potentials were recorded only from the terminal motor branch. The conclusion was that MEPs can be used for intraoperative differentiation between sensory and motor nerves. Further studies are necessary to develop this method for in situ measurements on intact nerve trunks.

  7. Sympathetic modulation of sensory nerve activity with age: human and rodent skin models.

    PubMed

    Khalil, Z; LeVasseur, S; Merhi, M; Helme, R D

    1997-11-01

    1. Sensory nerves serve an afferent role and mediate neurogenic components of inflammation and tissue repair via an axon reflex release of sensory peptides at sites of injury. Dysfunction of these nerves with age could contribute to delayed tissue healing. 2. Complementary animal and human skin models were used in the present studies to investigate changes in the modulation of sensory nerve function by sympathetic efferents during ageing. Laser Doppler flowmetry was used to monitor neurogenic skin vascular responses. 3. The animal model used skin of the hind footpad of anaesthetized rats combined with electrical stimulation of the sciatic nerve, while the human model comprised capsaicin electrophoresis to the volar surface of the forearm. Sympathetic modulation was effected by systemic phentolamine pretreatment in animals and local application in the human model. 4. The results obtained from the human model confirmed the reported decline in sensory nerve function and showed no change in sympathetic modulation with age. The results from the animal model confirm and expand results obtained from the human model. 5. The use of low (5 Hz) and high (15 Hz) frequency electrical stimulation (20 V, 2 ms for 1 min) revealed a preferential response of aged sensory nerves to low-frequency electrical stimulation parameters with differential sympathetic modulation that is dependent on the frequency of stimulation.

  8. Neurilemmoma of Deep Peroneal Nerve Sensory Branch : Thermographic Findings with Compression Test

    PubMed Central

    Ryu, Seung Jun

    2015-01-01

    We report a case of neurilemmoma of deep peroneal nerve sensory branch that triggered sensory change with compression test on lower extremity. After resection of tumor, there are evoked thermal changes on pre- and post-operative infrared (IR) thermographic images. A 52-year-old female presented with low back pain, sciatica, and sensory change on the dorsal side of the right foot and big toe that has lasted for 9 months. She also presented with right tibial mass sized 1.2 cm by 1.4 cm. Ultrasonographic imaging revealed a peripheral nerve sheath tumor arising from the peroneal nerve. IR thermographic image showed hyperthermia when the neurilemoma induced sensory change with compression test on the fibular area, dorsum of foot, and big toe. After surgery, the symptoms and thermographic changes were relieved and disappeared. The clinical, surgical, radiographic, and thermographic perspectives regarding this case are discussed. PMID:26539275

  9. Myelinated sensory and alpha motor axon regeneration in peripheral nerve neuromas

    NASA Technical Reports Server (NTRS)

    Macias, M. Y.; Lehman, C. T.; Sanger, J. R.; Riley, D. A.

    1998-01-01

    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.

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

    PubMed

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

    2015-12-01

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

  11. Evaluation of the role of g protein-coupled receptor kinase 3 in desensitization of mouse odorant receptors in a Mammalian cell line and in olfactory sensory neurons.

    PubMed

    Kato, Aya; Reisert, Johannes; Ihara, Sayoko; Yoshikawa, Keiichi; Touhara, Kazushige

    2014-11-01

    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.

  12. Evaluation of the Role of G Protein-Coupled Receptor Kinase 3 in Desensitization of Mouse Odorant Receptors in a Mammalian Cell Line and in Olfactory Sensory Neurons

    PubMed Central

    Kato, Aya; Reisert, Johannes; Ihara, Sayoko; Yoshikawa, Keiichi

    2014-01-01

    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

  13. Role of sensory nerves in gastroprotective effect of anandamide in rats.

    PubMed

    Warzecha, Z; Dembinski, A; Ceranowicz, P; Dembinski, M; Cieszkowski, J; Kownacki, P; Konturek, P C

    2011-04-01

    Previous studies have shown that stimulation of cannabinoid 1 (CB1) receptor protects the gastric mucosa against stress-induced lesion. Aim of the present study was to examine the influence of anandamide on lipid peroxidation and antioxidant defense system in gastric mucosa and the role of sensory nerves in gastroprotective effects of cannabinoids. Studies were performed on rats with intact or ablated sensory nerves (by neurotoxic doses of capsaicin). Gastric lesions were induced by water immersion and restrain stress (WRS). Anandamide was administered at the dose of 0.3, 1.5 or 3.0 μmol/kg, 30 min before exposure to WRS. CB1 receptor antagonist, AM251 (4.0 μmol/kg) was administered 40 min before WRS. WRS induced gastric lesions associated with the decrease in gastric blood flow, mucosal DNA synthesis and mucosal activity of superoxide dismutase (SOD). Serum level of interleukin-1β (IL-1β) and mucosal level of malondialdehyde (MDA) and 4-hydroxynonenal (4-HNE) were increased. Administration of anandamide reduced the ulcers area, generation of MDA+4-HNE and serum level of IL-1β, and this effect was associated with the reduction in the WRS-induced decrease in gastric mucosal blood flow, mucosal DNA synthesis and SOD activity. Ablation of sensory nerves increased the area of ulcers, serum level of IL-1β and mucosal content of MDA+4-HNE, whereas mucosal DNA synthesis, SOD activity and blood flow were additionally decreased. In rats with ablation of sensory nerves, administration of anandamide at the high doses (1.5 and 3.0 μmol/kg) partly reduced deleterious effect of WRS on gastric mucosa, but this effect was weaker than in animals with intact sensory nerves. Low dose of anandamide (0.3 μmol/kg) was ineffective in the protection of gastric mucosa against the WRS-induced lesions in rats with ablation of sensory nerves. In rats with intact sensory nerves and exposed to WRS, administration of AM251 exhibited deleterious effect. In rats with ablation of sensory

  14. Accommodation to hyperpolarizing currents: differences between motor and sensory nerves in mice.

    PubMed

    Nodera, Hiroyuki; Rutkove, Seward B

    2012-06-19

    Peripheral motor nerves have revealed variability in excitability by hyperpolarizing current at specific target response levels, likely reflecting differences in the hyperpolarization-activated current (Ih). Whether such variability in Ih exists in sensory axons is yet to be established. We performed nerve excitability testing in mouse tail motor and sensory nerves at 3 target response levels (20, 40, and 60% of the maximum amplitudes). Target-level dependent variability was present by long hyperpolarizing currents in motor and sensory nerves in which the recording at the low target level showed smaller threshold changes than at the high target level. Other excitability measures, however, showed no variability. Furthermore, the accommodation by long, strong hyperpolarization revealed smaller S3 accommodation (threshold change between the maximum and at the end of the 200 ms conditioning pulse) at the low target response level in sensory axons, but not in motor axons. Variation in the kinetics of the subtypes of the hyperpolarization-activated cyclic nucleotide-gated (HCN) channels in motor and sensory axons is the most likely explanation for these findings. The present study has proposed that nerve excitability testing may provide a non-invasive means for the assessment of the different types of Ih in neurological disorders where HCN subtypes play unique pathophysiological roles.

  15. A study of the sympathetic skin response and sensory nerve action potential after median and ulnar nerve repair.

    PubMed

    Jazayeri, M; Ghavanini, M R; Rahimi, H R; Raissi, G R

    2003-01-01

    The purpose of this study was to compare SSR with sensory nerve action potential (SNAP) responses in regeneration of injured peripheral nerves after nerve repair. We studied 10 male patients with a mean age of 26.7 years. All the patients had complete laceration of median or ulnar nerves. The patients were followed up at least for six months. SSR and SNAP assessment were performed every one to two months. Normal hands were used as controls. SSR was positive after 15.8 +/- 9.4 weeks (mean +/- 2 SD) and SNAP after 27.8 +/- 12.9 weeks (mean +/- 2 SD). The difference was statistically significant (P value < 0.001). This can be due to more rapid growth of sympathetic unmyelinated fibers relative to sensory myelinated fibers. This study also shows that recovery of the sudomotor activity following nerve repair is satisfactory in general and SSR can be used as a useful and sensitive method in the evaluation of sudomotor nerve regeneration.

  16. Inhibition of Rho-kinase differentially affects axon regeneration of peripheral motor and sensory nerves.

    PubMed

    Joshi, Abhijeet R; Bobylev, Ilja; Zhang, Gang; Sheikh, Kazim A; Lehmann, Helmar C

    2015-01-01

    The small GTPase RhoA and its down-stream effector Rho-kinase (ROCK) are important effector molecules of the neuronal cytoskeleton. Modulation of the RhoA/ROCK pathway has been shown to promote axonal regeneration, however in vitro and animal studies are inconsistent regarding the extent of axonal outgrowth induced by pharmacological inhibition of ROCK. We hypothesized that injury to sensory and motor nerves result in diverse activation levels of RhoA, which may impact the response of those nerve fiber modalities to ROCK inhibition. We therefore examined the effects of Y-27632, a chemical ROCK inhibitor, on the axonal outgrowth of peripheral sensory and motor neurons grown in the presence of growth-inhibiting chondroitin sulfate proteoglycans (CSPGs). In addition we examined the effects of three different doses of Y-27632 on nerve regeneration of motor and sensory nerves in animal models of peripheral nerve crush. In vitro, sensory neurons were less responsive to Y-27632 compared to motor neurons in a non-growth permissive environment. These differences were associated with altered expression and activation of RhoA in sensory and motor axons. In vivo, systemic treatment with high doses of Y-27632 significantly enhanced the regeneration of motor axons over short distances, while the regeneration of sensory fibers remained largely unchanged. Our results support the concept that in a growth non-permissive environment, the regenerative capacity of sensory and motor axons is differentially affected by the RhoA/ROCK pathway, with motor neurons being more responsive compared to sensory. Future treatments, that are aimed to modulate RhoA activity, should consider this functional diversity.

  17. Distribution of sensory nerve endings around the human sinus tarsi: a cadaver study.

    PubMed

    Rein, Susanne; Manthey, Suzanne; Zwipp, Hans; Witt, Andreas

    2014-04-01

    The aim of this study was to analyse the pattern of sensory nerve endings and blood vessels around the sinus tarsi. The superficial and deep parts of the fat pads at the inferior extensor retinaculum (IER) as well as the subtalar joint capsule inside the sinus tarsi from 13 cadaver feet were dissected. The distribution of the sensory nerve endings and blood vessels were analysed in the resected specimens as the number per cm(2) after staining with haematoxylin-eosin, S100 protein, low-affinity neurotrophin receptor p75, and protein gene product 9.5 using the classification of Freeman and Wyke. Free nerve endings were the predominant sensory ending (P < 0.001). Ruffini and Golgi-like endings were rarely found and no Pacini corpuscles were seen. Significantly more free nerve endings (P < 0.001) and blood vessels (P = 0.01) were observed in the subtalar joint capsule than in the superficial part of the fat pad at the IER. The deep part of the fat pad at the IER had significantly more blood vessels than the superficial part of the fat pad at the IER (P = 0.012). Significantly more blood vessels than free nerve endings were seen in all three groups (P < 0.001). No significant differences in distribution were seen in terms of right or left side, except for free nerve endings in the superficial part of the fat pad at the IER (P = 0.003). A greater number of free nerve endings correlated with a greater number of blood vessels. The presence of sensory nerve endings between individual fat cells supports the hypothesis that the fat pad has a proprioceptive role monitoring changes and that it is a source of pain in sinus tarsi syndrome due to the abundance of free nerve endings.

  18. Neuroplasticity of Sensory and Sympathetic Nerve Fibers in the Painful Arthritic Joint

    PubMed Central

    Ghilardi, Joseph R.; Freeman, Katie T.; Jimenez-Andrade, Juan M.; Coughlin, Kathleen; Kaczmarska, Magdalena J.; Castaneda-Corral, Gabriela; Bloom, Aaron P.; Kuskowski, Michael A.; Mantyh, Patrick W.

    2012-01-01

    Objective Many forms of arthritis are accompanied by significant chronic joint pain. Here we studied whether there is significant sprouting of sensory and sympathetic nerve fibers in the painful arthritic knee joint and whether nerve growth factor (NGF) drives this pathological reorganization. Methods A painful arthritic knee joint was produced by injection of complete Freund’s adjuvant (CFA) into the knee joint of young adult mice. CFA-injected mice were then treated systemically with vehicle or anti-NGF antibody. Pain behaviors were assessed and at 28 days following the initial CFA injection, the knee joints were processed for immunohistochemistry using antibodies raised against calcitonin gene-related peptide (CGRP; sensory nerve fibers), neurofilament 200 kDa (NF200; sensory nerve fibers), growth associated protein-43 (GAP43; sprouted nerve fibers), tyrosine hydroxylase (TH; sympathetic nerve fibers), CD31 (endothelial cells) or CD68 (monocytes/macrophages). Results In CFA-injected mice, but not vehicle-injected mice, there was a significant increase in the density of CD68+ macrophages, CD31+ blood vessels, CGRP+, NF200+, GAP43+, and TH+ nerve fibers in the synovium as well as joint pain-related behaviors. Administration of anti-NGF reduced these pain-related behaviors and the ectopic sprouting of nerve fibers, but had no significant effect on the increase in density of CD31+ blood vessels or CD68+ macrophages. Conclusions Ectopic sprouting of sensory and sympathetic nerve fibers occurs in the painful arthritic joint and may be involved in the generation and maintenance of arthritic pain. PMID:22246649

  19. Sensory nerve conduction and nociception in the equine lower forelimb during perineural bupivacaine infusion along the palmar nerves

    PubMed Central

    Zarucco, Laura; Driessen, Bernd; Scandella, Massimiliano; Cozzi, Francesca; Cantile, Carlo

    2010-01-01

    The purpose of this investigation was to study lateral palmar nerve (LPN) and medial palmar nerve (MPN) morphology and determine nociception and sensory nerve conduction velocity (SNCV) following placement of continuous peripheral nerve block (CPNB) catheters along LPN and MPN with subsequent bupivacaine (BUP) infusion. Myelinated nerve fiber distribution in LPN and MPN was examined after harvesting nerve specimens in 3 anesthetized horses and processing them for morphometric analysis. In 5 sedated horses, CPNB catheters were placed along each PN in both forelimbs. Horses then received in one forelimb 3 mL 0.125% BUP containing epinephrine 1:200 000 and 0.04% NaHCO3 per catheter site followed by 2 mL/h infusion over a 6-day period, while in the other forelimb equal amounts of saline (SAL) solution were administered. The hoof withdrawal response (HWR) threshold during pressure loading of the area above the dorsal coronary band was determined daily in both forelimbs. On day 6 SNCV was measured under general anesthesia of horses in each limb’s LPN and MPN to detect nerve injury, followed by CPNB catheter removal. The SNCV was also recorded in 2 anesthetized non-instrumented horses (sham controls). In both LPN and MPN myelinated fiber distributions were bimodal. The fraction of large fibers (>7 μm) was greater in the MPN than LPN (P < 0.05). Presence of CPNB catheters and SAL administration did neither affect measured HWR thresholds nor SNCVs, whereas BUP infusion suppressed HWRs. In conclusion, CPNB with 0.125% BUP provides pronounced analgesia by inhibiting sensory nerve conduction in the distal equine forelimb. PMID:21197231

  20. Effect of pulsed infrared lasers on neural conduction and axoplasmic transport in sensory nerves

    NASA Astrophysics Data System (ADS)

    Wesselmann, Ursula; Rymer, William Z.; Lin, Shien-Fong

    1990-06-01

    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.

  1. Intrafascicular stimulation of monkey arm nerves evokes coordinated grasp and sensory responses

    PubMed Central

    Ledbetter, Noah M.; Ethier, Christian; Oby, Emily R.; Hiatt, Scott D.; Wilder, Andrew M.; Ko, Jason H.; Agnew, Sonya P.; Miller, Lee E.

    2013-01-01

    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

  2. Effect of helium-neon laser irradiation on peripheral sensory nerve latency

    SciTech Connect

    Snyder-Mackler, L.; Bork, C.E.

    1988-02-01

    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.

  3. Effects of Latrodectus spider venoms on sensory and motor nerve terminals of muscle spindles.

    PubMed

    Queiroz, L S; Duchen, L W

    1982-08-23

    The effects of the venoms of the spiders Latrodectus mactans tredecimguttatus (black widow) and Latrodectus mactans hasselti (red back) on sensory nerve terminals in muscle spindles were studied in the mouse. A sublethal dose of venom was injected into tibialis anterior and extensor digitorum longus muscles of one leg. After survival from 30 minutes to 6 weeks muscles were examined in serial paraffin sections impregnated with silver or by electron microscopy. Sensory endings became swollen, some within 30 minutes, while over the next few hours there was progressive degeneration of annulospiral endings. By 24 hours every spindle identified by light or electron microscopy was devoid of sensory terminals. Degenerated nerve endings were taken up into the sarcoplasm of intrafusal muscle fibres. Regeneration of sensory axons began within 24 hours, new incomplete spirals were formed by 5 days and by 1 week annulospiral endings were almost all normal in appearance. Intrafusal motor terminals underwent similar acute degenerative and regenerative changes. These experiments show that intrafusal sensory and motor terminals are equally affected by Latrodectus venoms. Sensory nerve fibres possess a capacity for regeneration equal to that of motor fibres and reinnervate intrafusal muscle fibres close to their original sites of innervation.

  4. Serotonin and Sensory Nerves: Meeting in the Cardiovascular System

    PubMed Central

    Watts, Stephanie W.

    2014-01-01

    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

  5. Multifocal acquired demyelinating sensory and motor neuropathy presenting as a peripheral nerve tumor.

    PubMed

    Allen, David C; Smallman, Clare A; Mills, Kerry R

    2006-09-01

    A man with multifocal acquired demyelinating sensory and motor neuropathy (MADSAM), or Lewis-Sumner syndrome, presented with a progressive left lumbosacral plexus lesion resembling a neurofibroma. After 7 years he developed a left ulnar nerve lesion with conduction block in its upper segment. Treatment with intravenous immunoglobulin improved the symptoms and signs of both lesions. We conclude that inflammatory neuropathy must be considered in the differential diagnosis of peripheral nerve tumors, and that unifocal lesions may precede multifocal involvement in MADSAM by several years. In addition, we discuss the clinical features in 9 patients attending a specialist peripheral nerve clinic and review the literature.

  6. Phenotyping sensory nerve endings in vitro in the mouse

    PubMed Central

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

    2014-01-01

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

  7. NerveCheck for the Detection of Sensory Loss and Neuropathic Pain in Diabetes

    PubMed Central

    Ponirakis, Georgios; Odriozola, Maria N.; Odriozola, Samantha; Petropoulos, Ioannis N.; Azmi, Shazli; Ferdousi, Maryam; Fadavi, Hassan; Alam, Uazman; Marshall, Andrew; Jeziorska, Maria; Miro, Anthony; Kheyami, Ahmad; Tavakoli, Mitra; Al-Ahmar, Ahmed; Odriozola, Maria B.; Odriozola, Ariel

    2016-01-01

    Abstract Background: Accurate and economic detection of nerve damage in diabetes is key to more widespread diagnosis of patients with diabetic peripheral neuropathy (DPN) and painful diabetic neuropathy. This study examined the diagnostic performance of NerveCheck, an inexpensive ($500) quantitative sensory testing (QST) device. Methods: One hundred forty-four subjects (74 with and 70 without diabetes) underwent assessment with NerveCheck, neuropathy disability score (NDS), nerve conduction studies (NCS), intraepidermal and corneal nerve fiber density (IENFD and CNFD), and McGill questionnaire for neuropathic pain. Results: Of the 74 subjects with diabetes, 41 were diagnosed with DPN based on the NDS. The NerveCheck scores for vibration perception threshold (VPT), cold perception threshold (CPT), and warm perception threshold (WPT) were significantly lower (P ≤ 0.0001) in diabetic patients with DPN compared to patients without DPN. The diagnostic accuracy of VPT was high with reference to NCS (area under the curve [AUC]: 82%–84%) and moderate for IENFD, CNFD, and neuropathic pain (AUC: 60%–76%). The diagnostic accuracy of CPT and WPT was moderate with reference to NCS, IENFD, and CNFD (AUC: 69%–78%) and low for neuropathic pain (AUC: 63%–65%). Conclusions: NerveCheck is a low-cost QST device with good diagnostic utility for identifying sensory deficits, comparable to established tests of large and small fiber neuropathy and for the severity of neuropathic pain. PMID:27922760

  8. Heightened motor and sensory (mirror-touch) referral induced by nerve block or topical anesthetic.

    PubMed

    Case, Laura K; Gosavi, Radhika; Ramachandran, Vilayanur S

    2013-08-01

    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.

  9. The use of sensory action potential to evaluate inferior alveolar nerve damage after orthognathic surgery.

    PubMed

    Calabria, Francesca; Sellek, Lucy; Gugole, Fabio; Trevisiol, Lorenzo; Trevisol, Lorenzo; Bertolasi, Laura; D'Agostino, Antonio

    2013-03-01

    To assess and monitor the common event of neurosensory disturbance to the inferior alveolar nerve (IAN) after bilateral sagittal split osteotomy, we used clinical sensory tests and neurophysiologic test sensory action potentials. The diagnostic value of these tests was evaluated by comparing them with the degree of nerve damage reported by patients. Fourteen patients undergoing bilateral sagittal split osteotomy were analyzed preoperatively and 2 years postoperatively. Patients were evaluated bilaterally for positive and negative symptoms: light touch sensation, paraesthesia, hyperesthesia, and dysaesthesia; a "sensation score" was then calculated for each patient. Patients were also asked if they would be willing to repeat the procedure knowing the sensation loss they had now. Next, the right and left IAN were evaluated using sensory action potential and correlated with the other results. Before surgery, the medium latency difference between left and right was lower compared with postsurgery, with all patients having some deficit. The reduction in medium amplitude of 67% after the intervention was statistically significant. The frequency of abnormal findings in the electrophysiologic tests indicating IAN injury correlated with subjective sensory alteration. All patients said that they would repeat the surgery. Electrophysiologic testing is recommended for the evaluation of nerve dysfunction and seems a sensitive method for accurately assessing postsurgical nerve conduction.

  10. [The role of sensory nerves in the development of inflammation of oral tissues].

    PubMed

    Olgart, L

    1998-01-01

    Experimental stimulation and clinical procedures applied on the tooth crown cause vascular reactions in the dental pulp of cats and rats. These reactions depend on the activation of trigeminal afferent nerves and release of neuropeptides. A brief stimulation causes vasodilation, which is mainly mediated by calcitonin gene-related peptide (CGRP). A longer stimulation results in plasma extravasation which is mediated mainly by substance P (SP) and prostaglandins in the pulp. In adjacent oral tissues the mechanisms following stimulation or local irritation are more complex and other mediators are also involved. Nitric oxide (NO) which is instantly produced in the tissues is such a novel mediator. The chemosensitive nature of the nerves involved (capsaicin sensitive) may lead to their activation also by inflammatory mediators released in the tissues. Thus, sensory nerves may modulate the progress of inflammation. Since sensory nerves in oral tissues are often the first structures to be activated during clinical procedures, tissue reactions that occur can be assumed to be initiated and perpetuated by the sensory neuropeptides. Much work is now made to modulate the sensory nerveinduced cascade of events in oral tissues to find new treatment strategies.

  11. Painful traumatic peripheral partial nerve injury-sensory dysfunction profiles comparing outcomes of bedside examination and quantitative sensory testing.

    PubMed

    Leffler, Ann-Sofie; Hansson, Per

    2008-05-01

    The primary aim of this retrospective study was to focusing on the relationship between individual outcomes of bedside examination (BE) and quantitative testing of somatosensory functions (QST) in 32 patients with painful traumatic partial nerve injury. In addition, the potential presence of common sensory dysfunction denominators has been probed. Patients with a history of traumatic partial nerve injury and ongoing pain were included if pain was confined to the entire or part of the innervation territory of the severed nerve and a bedside titration of the neuron-anatomical borders confirmed sensory aberrations. An in-depth BE and QST was then performed in the most painful area. Categorization of normal and pathological outcome for both BE and QST was based on time honoured clinical decision-making using the healthy contralateral corresponding area as control. In patients with normal outcome or quantitative aberrations (i.e. hypo- or hyperesthesia) at BE and QST, the same individual outcome of touch sensation was reported by 48% of the patients, for cold in 54% and for warmth in 58%. The most common dysfunction found at both BE and QST was hypoesthesia, however with no common denominators in somatosensory dysfunction. In conclusion, this study demonstrated that not infrequently the individual outcome of BE and the corresponding QST measure differed, most frequently for touch sensibility. This finding is of outmost importance when QST outcomes are used to corroborate results from BE in the diagnostic situation.

  12. Patterned sensory nerve stimulation enhances the reactivity of spinal Ia inhibitory interneurons.

    PubMed

    Kubota, Shinji; Hirano, Masato; Morishita, Takuya; Uehara, Kazumasa; Funase, Kozo

    2015-03-25

    Patterned sensory nerve stimulation has been shown to induce plastic changes in the reciprocal Ia inhibitory circuit. However, the mechanisms underlying these changes have not yet been elucidated in detail. The aim of the present study was to determine whether the reactivity of Ia inhibitory interneurons could be altered by patterned sensory nerve stimulation. The degree of reciprocal Ia inhibition, the conditioning effects of transcranial magnetic stimulation (TMS) on the soleus (SOL) muscle H-reflex, and the ratio of the maximum H-reflex amplitude versus maximum M-wave (H(max)/M(max)) were examined in 10 healthy individuals. Patterned electrical nerve stimulation was applied to the common peroneal nerve every 1 s (100 Hz-5 train) at the motor threshold intensity of tibialis anterior muscle to induce activity changes in the reciprocal Ia inhibitory circuit. Reciprocal Ia inhibition, the TMS-conditioned H-reflex amplitude, and H(max)/M(max) were recorded before, immediately after, and 15 min after the electrical stimulation. The patterned electrical nerve stimulation significantly increased the degree of reciprocal Ia inhibition and decreased the amplitude of the TMS-conditioned H-reflex in the short-latency inhibition phase, which was presumably mediated by Ia inhibitory interneurons. However, it had no effect on H(max)/M(max). Our results indicated that patterned sensory nerve stimulation could modulate the activity of Ia inhibitory interneurons, and this change may have been caused by the synaptic modification of Ia inhibitory interneuron terminals. These results may lead to a clearer understanding of the spinal cord synaptic plasticity produced by repetitive sensory inputs.

  13. Recording sensory and motor information from peripheral nerves with Utah Slanted Electrode Arrays.

    PubMed

    Clark, Gregory A; Ledbetter, Noah M; Warren, David J; Harrison, Reid R

    2011-01-01

    Recording and stimulation via high-count penetrating microelectrode arrays implanted in peripheral nerves may help restore precise motor and sensory function after nervous system damage or disease. Although previous work has demonstrated safety and relatively successful stimulation for long-term implants of 100-electrode Utah Slanted Electrode Arrays (USEAs) in feline sciatic nerve [1], two major remaining challenges were 1) to maintain viable recordings of nerve action potentials long-term, and 2) to overcome contamination of unit recordings by myoelectric (EMG) activity in awake, moving animals. In conjunction with improvements to USEAs themselves, we have redesigned several aspects of our USEA containment and connector systems. Although further increases in unit yield and long-term stability remain desirable, here we report considerable progress toward meeting both of these goals: We have successfully recorded unit activity from USEAs implanted intrafascicularly in sciatic nerve for periods up to 4 months (the terminal experimental time point), and we have developed a containment system that effectively eliminates or substantially reduces EMG contamination of unit recordings in the moving animal. In addition, we used a 100-channel wireless recording integrated circuit attached to implanted USEAs to transmit broadband or spike-threshold data from nerve. Neural data thusly obtained during imposed limb movements were decoded blindly to drive a virtual prosthetic limb in real time. These results support the possibility of using USEAs in peripheral nerves to provide motor control and cutaneous or proprioceptive sensory feedback in individuals after limb loss or spinal cord injury.

  14. CAPSAICIN-SENSITIVE SENSORY NERVE FIBERS CONTRIBUTE TO THE GENERATION AND MAINTENANCE OF SKELETAL FRACTURE PAIN

    PubMed Central

    Jimenez-Andrade, Juan Miguel; Bloom, Aaron P.; Mantyh, William G.; Koewler, Nathan J.; Freeman, Katie T.; Delong, David; Ghilardi, Joseph R.; Kuskowski, Michael A.; Mantyh, Patrick W.

    2009-01-01

    Although skeletal pain can have a marked impact on a patient’s functional status and quality of life, relatively little is known about the specific populations of peripheral nerve fibers that drive non-malignant bone pain. In the present report, neonatal male Sprague Dawley rats were treated with capsaicin or vehicle and femoral fracture was produced when the animals were young adults (15–16 weeks old). Capsaicin treatment, but not vehicle, resulted in a significant (>70%) depletion in the density of calcitonin-gene related peptide positive (CGRP+) sensory nerve fibers, but not 200 kD neurofilament H positive (NF200+) sensory nerve fibers in the periosteum. The periosteum is a thin, cellular and fibrous tissue that tightly adheres to the outer surface of all but the articulated surface of bone and appears to play a pivotal role in driving fracture pain. In animals treated with capsaicin, but not vehicle, there was a 50% reduction in the severity, but no change in the time course, of fracture-induced skeletal pain related behaviors as measured by spontaneous flinching, guarding and weight bearing. These results suggest that both capsaicin-sensitive (primarily CGRP+ C-fibers) and capsaicin-insensitive (primarily NF200+ A-delta fibers) sensory nerve fibers participate in driving skeletal fracture pain. Skeletal pain can be a significant impediment to functional recovery following trauma-induced fracture, osteoporosis-induced fracture and orthopedic surgery procedures such as knee and hip replacement. Understanding the specific populations of sensory nerve fibers that need to be targeted to inhibit the generation and maintenance of skeletal pain may allow the development of more specific mechanism-based therapies that can effectively attenuate acute and chronic skeletal pain. PMID:19486928

  15. The sensory component of the facial nerve of a reptile (Lacerta viridis).

    PubMed

    Jacobs, V L

    1979-04-01

    The sensory fibers of the facial nerve in Lacerta viridis have been studied with a silver impregnation method to follow the course of axonal degeneration. Destruction of the geniculate ganglion demonstrated the degenerated sensory component of the facial nerve adjacent to the anterior vestibular root. Within the lateral vestibular area the facial sensory fibers consist of numerous rootlets separated by vestibular fibers and cells. These rootlets may join to form a main or paired sensory tract that passes through the vestibular nuclei to enter the tractus solitarius and divide into a small ascending prefacial component and a major descending prevagal division. A few fibers continue into the postvagal part of tractus solitarius and extend caudally to terminate in the nucleus commissura infima. Prefacial fibers terminate along the periventricular gray while prevagal fibers terminate within the tractus solitarius on the dendrites of cells of nucleus tractus solitarius and near the periphery of the dorsal motor nucleus of X. There was no noticeable degeneration in the descendens tractus trigemini. Terminal degeneration to descendens nucleus trigemini and motor nucleus of VII followed the tractus solitarius course. Most facial sensory fibers are probably related to taste and other visceral information.

  16. The relationship of nerve fibre pathology to sensory function in entrapment neuropathy

    PubMed Central

    Schmid, Annina B.; Bland, Jeremy D. P.; Bhat, Manzoor A.

    2014-01-01

    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 Aδ-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

  17. The relationship of nerve fibre pathology to sensory function in entrapment neuropathy.

    PubMed

    Schmid, Annina B; Bland, Jeremy D P; Bhat, Manzoor A; Bennett, David L H

    2014-12-01

    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 Aδ-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

  18. Sensory nerves and nitric oxide contribute to reflex cutaneous vasodilation in humans.

    PubMed

    Wong, Brett J

    2013-04-15

    We tested the hypothesis that inhibition of cutaneous sensory nerves would attenuate reflex cutaneous vasodilation in response to an increase in core temperature. Nine subjects were equipped with four microdialysis fibers on the forearm. Two sites were treated with topical anesthetic EMLA cream for 120 min. Sensory nerve inhibition was verified by lack of sensation to a pinprick. Microdialysis fibers were randomly assigned as 1) lactated Ringer (control); 2) 10 mM nitro-L-arginine methyl ester (L-NAME) to inhibit nitric oxide synthase; 3) EMLA + lactated Ringer; and 4) EMLA + L-NAME. Laser-Doppler flowmetry was used as an index of skin blood flow, and blood pressure was measured via brachial auscultation. Subjects wore a water-perfused suit, and oral temperature was monitored as an index of core temperature. The suit was perfused with 50°C water to initiate whole body heat stress to raise oral temperature 0.8°C above baseline. Cutaneous vascular conductance (CVC) was calculated and normalized to maximal vasodilation (%CVC(max)). There was no difference in CVC between control and EMLA sites (67 ± 5 vs. 69 ± 6% CVC(max)), but the onset of vasodilation was delayed at EMLA compared with control sites. The L-NAME site was significantly attenuated compared with control and EMLA sites (45 ± 5% CVC(max); P < 0.01). Combined EMLA + L-NAME site (25 ± 6% CVC(max)) was attenuated compared with control and EMLA (P < 0.001) and L-NAME only (P < 0.01). These data suggest cutaneous sensory nerves contribute to reflex cutaneous vasodilation during the early, but not latter, stages of heat stress, and full expression of reflex cutaneous vasodilation requires functional sensory nerves and NOS.

  19. Emerging Relationships between Exercise, Sensory Nerves, and Neuropathic Pain

    PubMed Central

    Cooper, Michael A.; Kluding, Patricia M.; Wright, Douglas E.

    2016-01-01

    The utilization of physical activity as a therapeutic tool is rapidly growing in the medical community and the role exercise may offer in the alleviation of painful disease states is an emerging research area. The development of neuropathic pain is a complex mechanism, which clinicians and researchers are continually working to better understand. The limited therapies available for alleviation of these pain states are still focused on pain abatement and as opposed to treating underlying mechanisms. The continued research into exercise and pain may address these underlying mechanisms, but the mechanisms which exercise acts through are still poorly understood. The objective of this review is to provide an overview of how the peripheral nervous system responds to exercise, the relationship of inflammation and exercise, and experimental and clinical use of exercise to treat pain. Although pain is associated with many conditions, this review highlights pain associated with diabetes as well as experimental studies on nerve damages-associated pain. Because of the global effects of exercise across multiple organ systems, exercise intervention can address multiple problems across the entire nervous system through a single intervention. This is a double-edged sword however, as the global interactions of exercise also require in depth investigations to include and identify the many changes that can occur after physical activity. A continued investment into research is necessary to advance the adoption of physical activity as a beneficial remedy for neuropathic pain. The following highlights our current understanding of how exercise alters pain, the varied pain models used to explore exercise intervention, and the molecular pathways leading to the physiological and pathological changes following exercise intervention. PMID:27601974

  20. Sensory and sympathetic nerve contributions to the cutaneous vasodilator response from a noxious heat stimulus.

    PubMed

    Carter, Stephen J; Hodges, Gary J

    2011-11-01

    We investigated the roles of sensory and noradrenergic sympathetic nerves on the cutaneous vasodilator response to a localized noxious heating stimulus. In two separate studies, four forearm skin sites were instrumented with microdialysis fibres, local heaters and laser-Doppler probes. Skin sites were locally heated from 33 to 42 °C or rapidly to 44 °C (noxious). In the first study, we tested sensory nerve involvement using EMLA cream. Treatments were as follows: (1) control 42 °C; (2) EMLA 42 °C; (3) control 44°C; and (4) EMLA 44 °C. At the EMLA-treated sites, the axon reflex was reduced compared with the control sites during heating to 42 °C (P < 0.05). There were no differences during the plateau phase (P > 0.05). At both the sites heated to 44 °C, the initial peak and nadir became indistinguishable, and the EMLA-treated sites were lower compared with the control sites during the plateau phase (P < 0.05). In the second study, we tested the involvement of noradrenergic sympathetic nerves in response to the noxious heating using bretylium tosylate (BT). Treatments were as follows: (1) control 42 °C; (2) BT 42 °C; (3) control 44 °C; and (4) BT 44 °C. Treatment with BT at the 42 °C sites resulted in a marked reduction in both the axon reflex and the secondary plateau (P < 0.05). At the 44 °C sites, there was no apparent initial peak or nadir, but the plateau phase was reduced at the BT-treated sites (P < 0.05). These data suggest that both sympathetic nerves and sensory nerves are involved during the vasodilator response to a noxious heat stimulus.

  1. Role of sensory nerves in the cutaneous vasoconstrictor response to local cooling in humans.

    PubMed

    Hodges, Gary J; Traeger, J Andrew; Tang, Tri; Kosiba, Wojciech A; Zhao, Kun; Johnson, John M

    2007-07-01

    Local cooling (LC) causes a cutaneous vasoconstriction (VC). In this study, we tested whether there is a mechanism that links LC to VC nerve function via sensory nerves. Six subjects participated. Local skin and body temperatures were controlled with Peltier probe holders and water-perfused suits, respectively. Skin blood flow at four forearm sites was monitored by laser-Doppler flowmetry with the following treatments: untreated control, pretreatment with local anesthesia (LA) blocking sensory nerve function, pretreatment with bretylium tosylate (BT) blocking VC nerve function, and pretreatment with both LA and BT. Local skin temperature was slowly reduced from 34 to 29 degrees C at all four sites. Both sites treated with LA produced an increase in cutaneous vascular conductance (CVC) early in the LC process (64 +/- 55%, LA only; 42 +/- 14% LA plus BT; P < 0.05), which was absent at the control and BT-only sites (5 +/- 8 and 6 +/- 8%, respectively; P > 0.05). As cooling continued, there were significant reductions in CVC at all sites (P < 0.05). At control and LA-only sites, CVC decreased by 39 +/- 4 and 46 +/- 8% of the original baseline values, which were significantly (P < 0.05) more than the reductions in CVC at the sites treated with BT and BT plus LA (-26 +/- 8 and -22 +/- 6%). Because LA affected only the short-term response to LC, either alone or in the presence of BT, we conclude that sensory nerves are involved early in the VC response to LC, but not for either adrenergic or nonadrenergic VC with longer term LC.

  2. Amplitude of sensory nerve action potential in early stage diabetic peripheral neuropathy: an analysis of 500 cases.

    PubMed

    Zhang, Yunqian; Li, Jintao; Wang, Tingjuan; Wang, Jianlin

    2014-07-15

    Early diagnosis of diabetic peripheral neuropathy is important for the successful treatment of diabetes mellitus. In the present study, we recruited 500 diabetic patients from the Fourth Affiliated Hospital of Kunming Medical University in China from June 2008 to September 2013: 221 cases showed symptoms of peripheral neuropathy (symptomatic group) and 279 cases had no symptoms of peripheral impairment (asymptomatic group). One hundred healthy control subjects were also recruited. Nerve conduction studies revealed that distal motor latency was longer, sensory nerve conduction velocity was slower, and sensory nerve action potential and amplitude of compound muscle action potential were significantly lower in the median, ulnar, posterior tibial and common peroneal nerve in the diabetic groups compared with control subjects. Moreover, the alterations were more obvious in patients with symptoms of peripheral neuropathy. Of the 500 diabetic patients, neural conduction abnormalities were detected in 358 cases (71.6%), among which impairment of the common peroneal nerve was most prominent. Sensory nerve abnormality was more obvious than motor nerve abnormality in the diabetic groups. The amplitude of sensory nerve action potential was the most sensitive measure of peripheral neuropathy. Our results reveal that varying degrees of nerve conduction changes are present in the early, asymptomatic stage of diabetic peripheral neuropathy.

  3. Long-Standing Motor and Sensory Recovery following Acute Fibrin Sealant Based Neonatal Sciatic Nerve Repair

    PubMed Central

    Ferreira Junior, Rui Seabra

    2016-01-01

    Brachial plexus lesion results in loss of motor and sensory function, being more harmful in the neonate. Therefore, this study evaluated neuroprotection and regeneration after neonatal peripheral nerve coaptation with fibrin sealant. Thus, P2 neonatal Lewis rats were divided into three groups: AX: sciatic nerve axotomy (SNA) without treatment; AX+FS: SNA followed by end-to-end coaptation with fibrin sealant derived from snake venom; AX+CFS: SNA followed by end-to-end coaptation with commercial fibrin sealant. Results were analyzed 4, 8, and 12 weeks after lesion. Astrogliosis, microglial reaction, and synapse preservation were evaluated by immunohistochemistry. Neuronal survival, axonal regeneration, and ultrastructural changes at ventral spinal cord were also investigated. Sensory-motor recovery was behaviorally studied. Coaptation preserved synaptic covering on lesioned motoneurons and led to neuronal survival. Reactive gliosis and microglial reaction decreased in the same groups (AX+FS, AX+CFS) at 4 weeks. Regarding axonal regeneration, coaptation allowed recovery of greater number of myelinated fibers, with improved morphometric parameters. Preservation of inhibitory synaptic terminals was accompanied by significant improvement in the motor as well as in the nociceptive recovery. Overall, the present data suggest that acute repair of neonatal peripheral nerves with fibrin sealant results in neuroprotection and regeneration of motor and sensory axons. PMID:27446617

  4. Hyperglycemia- and neuropathy-induced changes in mitochondria within sensory nerves

    PubMed Central

    Hamid, Hussein S; Mervak, Colin M; Münch, Alexandra E; Robell, Nicholas J; Hayes, John M; Porzio, Michael T; Singleton, J Robinson; Smith, A Gordon; Feldman, Eva L; Lentz, Stephen I

    2014-01-01

    Objective This study focused on altered mitochondrial dynamics as a potential mechanism for diabetic peripheral neuropathy (DPN). We employed both an in vitro sensory neuron model and an in situ analysis of human intraepidermal nerve fibers (IENFs) from cutaneous biopsies to measure alterations in the size distribution of mitochondria as a result of hyperglycemia and diabetes, respectively. Methods Neurite- and nerve-specific mitochondrial signals within cultured rodent sensory neurons and human IENFs were measured by employing a three-dimensional visualization and quantification technique. Skin biopsies from distal thigh (DT) and distal leg (DL) were analyzed from three groups of patients; patients with diabetes and no DPN, patients with diabetes and confirmed DPN, and healthy controls. Results This analysis demonstrated an increase in mitochondria distributed within the neurites of cultured sensory neurons exposed to hyperglycemic conditions. Similar changes were observed within IENFs of the DT in DPN patients compared to controls. This change was represented by a significant shift in the size frequency distribution of mitochondria toward larger mitochondria volumes within DT nerves of DPN patients. There was a length-dependent difference in mitochondria within IENFs. Distal leg IENFs from control patients had a significant shift toward larger volumes of mitochondrial signal compared to DT IENFs. Interpretation The results of this study support the hypothesis that altered mitochondrial dynamics may contribute to DPN pathogenesis. Future studies will examine the potential mechanisms that are responsible for mitochondrial changes within IENFs and its effect on DPN pathogenesis. PMID:25493271

  5. Functional coupling between motor and sensory nerves through contraction of sphincters in the pudendal area of the female cat.

    PubMed

    Lagunes-Córdoba, Roberto; Hernández, Pablo Rogelio; Raya, José Guadalupe; Muñoz-Martínez, E J

    2010-01-01

    The question of whether skin receptors might help in the perception of muscle contraction and body movement has not been settled. The present study gives direct evidence of skin receptor firing in close coincidence with the contraction of the vaginal and anal sphincters. The distal stump of the sectioned motor pudendal nerve was stimulated. Single shocks induced a wavelike increase in the lumen pressure of the distal vagina and the anal canal, as well as constriction of the vaginal introitus and the anus. The constriction pulls on and moves the surrounding skin, which was initially detected visually. In the present experiments, a thin strain gauge that pressed on the skin surface detected its displacement. Single shocks to the motor nerve induced a wave of skin movement with maximal amplitude at 5 mm from the anus and propagated with decrement beyond 35 mm. The peripheral terminals of the sensory pudendal nerve and the posterior femoral nerve supply the skin that moves. Sensory axons from both nerves fired in response to both tactile stimulation and the skin movement produced by the constriction of the orifices (motor-sensory coupling). In cats with all nerves intact, a single shock to the sensory nerves induced reflex waves of skin movement and lumen pressure (sensory-motor coupling). Both couplings provide evidence for a feedforward action that might help to maintain the female posture during mating and to the perception of muscle contraction.

  6. Complete mapping of glomeruli based on sensory nerve branching pattern in the primary olfactory center of the cockroach Periplaneta americana.

    PubMed

    Watanabe, Hidehiro; Nishino, Hiroshi; Nishikawa, Michiko; Mizunami, Makoto; Yokohari, Fumio

    2010-10-01

    Glomeruli are structural and functional units in the primary olfactory center in vertebrates and insects. In the cockroach Periplaneta americana, axons of different types of sensory neurons housed in sensilla on antennae form dorsal and ventral antennal nerves and then project to a number of glomeruli. In this study, we identified all antennal lobe (AL) glomeruli based on detailed innervation patterns of sensory tracts in addition to the shape, size, and locations in the cockroach. The number of glomeruli is approximately 205, and no sex-specific difference is observed. Anterograde dye injections into the antennal nerves revealed that axons supplying the AL are divided into 10 sensory tracts (T1-T10). Each of T1-T3 innervates small, oval glomeruli in the anteroventral region of the AL, with sensory afferents invading each glomerulus from multiple directions, whereas each of T4-T10 innervates large glomeruli with various shapes in the posterodorsal region, with a bundle of sensory afferents invading each glomerulus from one direction. The topographic branching patterns of all these tracts are conserved among individuals. Sensory afferents in a sub-tract of T10 had axon terminals in the dorsal margin of the AL and the protocerebrum, where they form numerous small glomerular structures. Sensory nerve branching pattern should reflect developmental processes to determine spatial arrangement of glomeruli, and thus the complete map of glomeruli based on sensory nerve branching pattern should provide a basis for studying the functional significance of spatial arrangement of glomeruli and its developmental basis.

  7. Evaluation of the motor and sensory components of the pudendal nerve.

    PubMed

    Loening-Baucke, V; Read, N W; Yamada, T; Barker, A T

    1994-02-01

    Extensive neurophysiological investigations consisting of different techniques to evaluate the efferents and afferents of the pudendal nerve were carried out in 27 healthy subjects. These investigations included motor evoked potential recordings from the external anal sphincter in response to magnetic stimulation of the cortex and lumbosacral roots, measurement of sacral reflex latency to magnetic and electrical stimulation, and cortical sensory evoked potential recording after stimulation of the dorso-genital nerve and anal canal. Motor latencies after transcranial magnetic stimulation to the anal sphincter were 25.1 +/- 2.9 msec at rest and 20.9 +/- 2.0 msec with voluntary sphincter contraction (facilitation). Motor latency after lumbosacral root stimulation was 3.7 +/- 1.0 msec. Mean sacral reflex latency after magnetic stimulation was 43.8 +/- 11.2 msec and was significantly longer than after electrical stimulation (37.0 +/- 7.2 msec; P < 0.05). P1 latency of the sensory evoked potentials after dorso-genital nerve stimulation was 40 +/- 3 msec and was significantly shorter than after anal stimulation 46 +/- 3 msec (P < 0.01). Evoked potential recording allows us to study both upper and lower motor neuron components to the anal sphincter. The present study paves the way for the combined application of these tests in the evaluation of disorders of the pelvic floor.

  8. Secretion of Growth Hormone in Response to Muscle Sensory Nerve Stimulation

    NASA Technical Reports Server (NTRS)

    Grindeland, Richard E.; Roy, R. R.; Edgerton, V. R.; Gosselink, K. L.; Grossman, E. J.; Sawchenko, P. E.; Wade, Charles E. (Technical Monitor)

    1994-01-01

    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.

  9. Fast-spiking GABA circuit dynamics in the auditory cortex predict recovery of sensory processing following peripheral nerve damage.

    PubMed

    Resnik, Jennifer; Polley, Daniel B

    2017-03-21

    Cortical neurons remap their receptive fields and rescale sensitivity to spared peripheral inputs following sensory nerve damage. To address how these plasticity processes are coordinated over the course of functional recovery, we tracked receptive field reorganization, spontaneous activity, and response gain from individual principal neurons in the adult mouse auditory cortex over a 50-day period surrounding either moderate or massive auditory nerve damage. We related the day-by-day recovery of sound processing to dynamic changes in the strength of intracortical inhibition from parvalbumin-expressing (PV) inhibitory neurons. Whereas the status of brainstem-evoked potentials did not predict the recovery of sensory responses to surviving nerve fibers, homeostatic adjustments in PV-mediated inhibition during the first days following injury could predict the eventual recovery of cortical sound processing weeks later. These findings underscore the potential importance of self-regulated inhibitory dynamics for the restoration of sensory processing in excitatory neurons following peripheral nerve injuries.

  10. [Should biopsy be done on the sensory branch of the radial nerve in leprosy patients? Apropos of 112 cases].

    PubMed

    Grauwin, M Y; Dieye, M; Mane, I; Cartel, J L

    1997-01-01

    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.

  11. Sensory and sympathetic nerve fibers undergo sprouting and neuroma formation in the painful arthritic joint of geriatric mice

    PubMed Central

    2012-01-01

    Introduction Although the prevalence of arthritis dramatically increases with age, the great majority of preclinical studies concerning the mechanisms that drive arthritic joint pain have been performed in young animals. One mechanism hypothesized to contribute to arthritic pain is ectopic nerve sprouting; however, neuroplasticity is generally thought to be greater in young versus old nerves. Here we explore whether sensory and sympathetic nerve fibers can undergo a significant ectopic nerve remodeling in the painful arthritic knee joint of geriatric mice. Methods Vehicle (saline) or complete Freund's adjuvant (CFA) was injected into the knee joint of 27- to 29-month-old female mice. Pain behaviors, macrophage infiltration, neovascularization, and the sprouting of sensory and sympathetic nerve fibers were then assessed 28 days later, when significant knee-joint pain was present. Knee joints were processed for immunohistochemistry by using antibodies raised against CD68 (monocytes/macrophages), PECAM (endothelial cells), calcitonin gene-related peptide (CGRP; sensory nerve fibers), neurofilament 200 kDa (NF200; sensory nerve fibers), tyrosine hydroxylase (TH; sympathetic nerve fibers), and growth-associated protein 43 (GAP43; nerve fibers undergoing sprouting). Results At 4 weeks after initial injection, CFA-injected mice displayed robust pain-related behaviors (which included flinching, guarding, impaired limb use, and reduced weight bearing), whereas animals injected with vehicle alone displayed no significant pain-related behaviors. Similarly, in the CFA-injected knee joint, but not in the vehicle-injected knee joint, a remarkable increase was noted in the number of CD68+ macrophages, density of PECAM+ blood vessels, and density and formation of neuroma-like structures by CGRP+, NF200+, and TH+ nerve fibers in the synovium and periosteum. Conclusions Sensory and sympathetic nerve fibers that innervate the aged knee joint clearly maintain the capacity for robust

  12. Immunohistochemical study of skin nerve regeneration after toe-to-finger transplantation: correlations with clinical, quantitative sensory, and electrophysiological evaluations.

    PubMed

    Hsieh, Sung-Tsang; Chu, Nai-Shin

    2004-12-01

    Cutaneous nerve regeneration following toe-to-finger transplantation was studied by immunohistochemical technique using antibody to protein gene product 9.5 (PGP 9.5) which is a specific neuronal marker. By this technique, epidermal and dermal nerves were semi-quantified and the Meissner's corpuscles were quantified. There were also quantitative sensory tests (QST) including pinprick, pressure and temperature, as well as electrophysiological studies including digital nerve sensory conduction, digital nerve somatosensory evoked potentials and sympathetic skin response at the pulp of the transplanted toes. The opposite corresponding normal finger and normal toe served as controls. Study subjects were 20 adult patients with toe-to-finger transplantation for at least one year. A score system was used to quantify the results of histochemical, psychophysiological and electrophysiological studies. Clinically 7 patients had good recovery and 13 patients had poor recovery. Cutaneous nerve regeneration in the transplanted toes was incomplete with epidermal nerve, dermal nerve and the Meissner's corpuscle significantly reduced. The nerve regeneration was correlated with clinical recovery, QST and electrophysiological data. These findings indicate that immunohischemical technique is useful to evaluate skin nerve regeneration following toe-to-finger transplantation, and that although nerve regeneration did occur, it was incomplete and correlated with the severity of hand injury.

  13. Human cutaneous reactive hyperaemia: role of BKCa channels and sensory nerves.

    PubMed

    Lorenzo, Santiago; Minson, Christopher T

    2007-11-15

    Reactive hyperaemia is the increase in blood flow following arterial occlusion. The exact mechanisms mediating this response in skin are not fully understood. The purpose of this study was to investigate the individual and combined contributions of (1) sensory nerves and large-conductance calcium activated potassium (BKCa) channels, and (2) nitric oxide (NO) and prostanoids to cutaneous reactive hyperaemia. Laser-Doppler flowmetry was used to measure skin blood flow in a total of 18 subjects. Peak blood flow (BF) was defined as the highest blood flow value after release of the pressure cuff. Total hyperaemic response was calculated by taking the area under the curve (AUC) of the hyperaemic response minus baseline. Infusates were perfused through forearm skin using microdialysis in four sites. In the sensory nerve/BKCa protocol: (1) EMLA cream (EMLA, applied topically to skin surface), (2) tetraethylammonium (TEA), (3) EMLA + TEA (Combo), and (4) Ringer solution (Control). In the prostanoid/NO protocol: (1) ketorolac (Keto), (2) NG-nitro-l-arginine methyl ester (L-NAME), (3) Keto + l-NAME (Combo), and (4) Ringer solution (Control). CVC was calculated as flux/mean arterial pressure and normalized to maximal flow. Hyperaemic responses in Control (1389 +/- 794%CVC max s) were significantly greater compared to TEA, EMLA and Combo sites (TEA, 630 +/- 512, P = 0.003; EMLA, 421 +/- 216, P < 0.001; Combo, 201 +/- 200, P < 0.001%CVC max s). Furthermore, AUC in Combo (Keto + l-NAME) site was significantly greater than Control (4109 +/- 2777 versus 1295 +/- 368%CVC max s). These data suggest (1) sensory nerves and BKCa channels play major roles in the EDHF component of reactive hyperaemia and appear to work partly independent of each other, and (2) the COX pathway does not appear to have a vasodilatory role in cutaneous reactive hyperaemia.

  14. Sensory disturbances of buccal and lingual nerve by muscle compression: A case report and review of the literature

    PubMed Central

    Alvira-González, Joaquín

    2016-01-01

    Introduction Several studies on cadavers dissection have shown that collateral branches of the trigeminal nerve cross muscle bundles on their way, being a possible etiological factor of some nerve disturbances. Case Report A 45-year-old man attended to the Temporomandibular Joint and Orofacial Pain Unit of the Master of Oral Surgery and Implantology in Hospital Odontològic of Barcelona University, referring tingling in the left hemifacial región and ipsilateral lingual side for one year, with discomfort when shaving or skin compression. Discussion Several branches of the trigeminal nerve follow a path through the masticatory muscles, being the lingual nerve and buccal nerve the most involved. The hyperactivity of the muscle bundles that are crossed by nerve structures generates a compression that could explain certain orofacial neuropathies (numbness and / or pain) in which a clear etiologic factor can not be identified. Key words:Buccal nerve, paresthesia, idiopathic trigeminal sensory neuropathy. PMID:26855715

  15. Implementation of linear sensory signaling via multiple coordinated mechanisms at central vestibular nerve synapses.

    PubMed

    McElvain, Lauren E; Faulstich, Michael; Jeanne, James M; Moore, Jeffrey D; du Lac, Sascha

    2015-03-04

    Signal transfer in neural circuits is dynamically modified by the recent history of neuronal activity. Short-term plasticity endows synapses with nonlinear transmission properties, yet synapses in sensory and motor circuits are capable of signaling linearly over a wide range of presynaptic firing rates. How do such synapses achieve rate-invariant transmission despite history-dependent nonlinearities? Here, ultrastructural, biophysical, and computational analyses demonstrate that concerted molecular, anatomical, and physiological refinements are required for central vestibular nerve synapses to linearly transmit rate-coded sensory signals. Vestibular synapses operate in a physiological regime of steady-state depression imposed by tonic firing. Rate-invariant transmission relies on brief presynaptic action potentials that delimit calcium influx, large pools of rapidly mobilized vesicles, multiple low-probability release sites, robust postsynaptic receptor sensitivity, and efficient transmitter clearance. Broadband linear synaptic filtering of head motion signals is thus achieved by coordinately tuned synaptic machinery that maintains physiological operation within inherent cell biological limitations.

  16. Sensory-motor axonal polyneuropathy involving cranial nerves: An uncommon manifestation of disulfiram toxicity.

    PubMed

    Santos, Telma; Martins Campos, António; Morais, Hugo

    2017-01-01

    Disulfiram (tetraethylthiuram disulfide) has been used for the treatment of alcohol dependence. An axonal sensory-motor polyneuropathy with involvement of cranial pairs due to disulfiram is exceedingly rare. The authors report a unique case of an extremely severe axonal polyneuropathy involving cranial nerves that developed within weeks after a regular dosage of 500mg/day disulfiram. To the authors best knowledge, such a severe and rapidly-progressive course has never been described with disulfiram dosages of only 500mg/day.

  17. A psychophysical study of the mechanisms of sensory recovery following nerve injury in humans.

    PubMed

    Van Boven, R W; Johnson, K O

    1994-02-01

    Twenty-four subjects were studied before and up to 1 year after surgery that produced injury to a major sensory branch of the trigeminal nerve. We employed a battery of 11 psychophysical tests, in which the neural mechanisms underlying performance are understood, to study the basis of recovery following nerve injury. Immediately after nerve injury, sensation was profoundly impaired in all subjects. In the following weeks and months, the recovery of performance proceeded in an orderly fashion. Although the rates of recovery varied between subjects, the order of recovery between tasks did not. The recovery rates fell into three distinct categories. Recovery in one task, brush-stroke directional discrimination, was most rapid. Two weeks after nerve injury, 52% of subjects could discriminate brush-stroke direction; by 3 months only one subject could not perform this task. The second category comprised recovery rates for pain thresholds for noxious heat, cold and mechanical stimuli, and to preinjury performance in tasks assessing touch and vibration detection, two-point discrimination, cooling detection and subjective magnitude estimation of mechanical force. The third, slowest group included recovery rates for warming detection and grating orientation discrimination. Early recovery to preinjury performance levels in the brush-stroke direction and one-point versus two-point discrimination tasks was correlated with later recovery to near normal performance in the grating orientation task. The grating orientation task was unique in providing a measure that corresponded consistently with the subjects' reports of sensory deficits. Our psychophysical findings are consistent with neurophysiological data showing that the major primary afferent fibre classes reinnervate the skin at a similar rate. A hypothesis that accounts for the psychophysical findings in this study is that differences in recovery rates between tasks is determined largely by their relative dependencies on

  18. Interaction between TRPA1 and TRPV1: Synergy on pulmonary sensory nerves.

    PubMed

    Lee, Lu-Yuan; Hsu, Chun-Chun; Lin, Yu-Jung; Lin, Ruei-Lung; Khosravi, Mehdi

    2015-12-01

    Transient receptor potential ankyrin type 1 (TRPA1) and vanilloid type 1 (TRPV1) receptors are co-expressed in vagal pulmonary C-fiber sensory nerves. Because both these ligand-gated non-selective cation channels are sensitive to a number of endogenous inflammatory mediators, it is highly probable that they can be activated simultaneously during airway inflammation. Studies were carried out to investigate whether there is an interaction between these two polymodal transducers upon simultaneous activation, and how it modulates the activity of vagal pulmonary C-fiber sensory nerves. Our studies showed a distinct potentiating effect induced abruptly by simultaneous activations of TRPA1 and TRPV1 by their respective selective agonists, allyl isothiocyanate (AITC) and capsaicin (Cap), at near-threshold concentrations. This synergistic effect was demonstrated in the studies of single-unit recording of vagal bronchopulmonary C-fiber afferents and the reflex responses elicited by activation of these afferents in intact animals, as well as in the isolated nodose and jugular bronchopulmonary sensory neurons. This potentiating effect was absent when either AITC or Cap was replaced by non-TRPA1 and non-TRPV1 chemical activators of these neurons, demonstrating the selectivity of the interaction between these two TRP channels. Furthermore, the synergism was dependent upon the extracellular Ca(2+), and the rapid onset of the action further suggests that the interaction probably occurred locally at the sites of these channels. These findings suggest that the TRPA1-TRPV1 interaction may play an important role in regulating the function and excitability of pulmonary sensory neurons during airway inflammation, but the mechanism underlying this positive interaction is not yet fully understood.

  19. Acceptable differences in sensory and motor latencies between the median and ulnar nerves.

    PubMed

    Grossart, Elizabeth A; Prahlow, Nathan D; Buschbacher, Ralph M

    2006-01-01

    The median and ulnar nerves are often studied during the same electrodiagnostic examination. The sensory and motor latencies of these nerves have been compared to detect a common electrodiagnostic entity: median neuropathy at the wrist. However, this comparison could also be used to diagnose less common ulnar pathology. For this reason, it is important to establish normal values for comparing median and ulnar sensory and motor latencies. Previous research deriving these differences in latency has had some limitations. The purpose of this study was to derive an improved normative database for the acceptable differences in latency between the median and ulnar sensory and motor nerves of the same limb. Median and ulnar sensory and motor latencies were obtained from 219 and 238 asymptomatic risk-factor-free subjects, respectively. An analysis of variance was performed to determine whether physical characteristics, specifically age, race, gender, height, or body mass index (as an indicator of obesity), correlated with differences in latency. Differences in sensory latencies were unaffected by physical characteristics. The upper limit of normal difference between median and ulnar (median longer than ulnar) onset latency was 0.5 ms (97th percentile), whereas the peak latency value was 0.4 ms (97th percentile). The upper limit of normal difference between ulnar-versus-median (ulnar longer than median) onset latency was 0.3 ms (97th percentile), whereas the peak-latency value was 0.5 ms (97th percentile). The mean difference in motor latencies correlated with age, with older subjects having a greater variability. In subjects aged 50 and over, the mean difference in median-versus-ulnar latency was 0.9 ms +/- 0.4 ms. The upper limit of normal difference (median longer than ulnar) was 1.7 ms (97th percentile). The upper limit of normal ulnar motor latency is attained if the ulnar latency comes within 0.3 ms of the median latency. In individuals less than 50 years of age, the

  20. Cutaneous sensory nerve as a substitute for auditory nerve in solving deaf-mutes' hearing problem: an innovation in multi-channel-array skin-hearing technology.

    PubMed

    Li, Jianwen; Li, Yan; Zhang, Ming; Ma, Weifang; Ma, Xuezong

    2014-08-15

    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.

  1. Antidromic effect of calcitonin gene-related peptide containing nerves on cerebral arteries in rats--a possible role of sensory nerves on cerebral circulatio.

    PubMed

    Asari, J; Suzuki, K; Matsumoto, M; Sasaki, T; Kodama, N

    2001-12-01

    It has generally been thought that the neurogenic control of cerebral circulation is decided mainly by the autonomic nervous system. Recent studies, however, indicate that sensory nerves rich in calcitonin gene-related peptide (CGRP) are also distributed on cerebral arteries. CGRP is one of neuropeptides that has strong vasodilative effect. This indicates that sensory nerves may antidromically dilate cerebral arteries mediated by CGRP. The aim of this study is to investigate the relationship between the CGRP containing nerves and cerebral circulation. Firstly, we developed a selective denervation model of CGRP containing nerves. The denervation was performed with intrathecal administration of capsaicin in rats. Secondly, we measured the change of regional cerebral blood flow (rCBF) during the occlusion of bilateral common carotid artery or systemic hypotension. CGRP immunoreactivity around cerebral arteries disappeared after capsaicin treatment. The rCBF during the occlusion of bilateral common carotid artery decreased more in the capsaicin group than in the control group. There was no significant difference in the changes of rCBF during systemic hypotension. These results showed that CGRP containing nerves would participate in the vascular response of cerebral arteries. It is likely that sensory nerves with CGRP should have antidromic effect on cerebral circulation.

  2. The functions of TRPA1 and TRPV1: moving away from sensory nerves.

    PubMed

    Fernandes, E S; Fernandes, M A; Keeble, J E

    2012-05-01

    The transient receptor potential vanilloid 1 and ankyrin 1 (TRPV1 and TRPA1, respectively) channels are members of the TRP superfamily of structurally related, non-selective cation channels. It is rapidly becoming clear that the functions of TRPV1 and TRPA1 interlink with each other to a considerable extent. This is especially clear in relation to pain and neurogenic inflammation where TRPV1 is coexpressed on the vast majority of TRPA1-expressing sensory nerves and both integrate a variety of noxious stimuli. The more recent discovery that both TRPV1 and TRPA1 are expressed on a multitude of non-neuronal sites has led to a plethora of research into possible functions of these receptors. Non-neuronal cells on which TRPV1 and TRPA1 are expressed vary from vascular smooth muscle to keratinocytes and endothelium. This review will discuss the expression, functionality and roles of these non-neuronal TRP channels away from sensory nerves to demonstrate the diverse nature of TRPV1 and TRPA1 in addition to a direct role in pain and neurogenic inflammation.

  3. Noninvasive Peroneal Sensory and Motor Nerve Conduction Recordings in the Rabbit Distal Hindlimb: Feasibility, Variability and Neuropathy Measure

    PubMed Central

    Hotson, John R.

    2014-01-01

    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 μV (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

  4. Nitro-oleic acid desensitizes TRPA1 and TRPV1 agonist responses in adult rat DRG neurons.

    PubMed

    Zhang, Xiulin; Koronowski, Kevin B; Li, Lu; Freeman, Bruce A; Woodcock, Stephen; de Groat, William C

    2014-01-01

    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 μl) 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

  5. Identifying motor and sensory myelinated axons in rabbit peripheral nerves by histochemical staining for carbonic anhydrase and cholinesterase activities

    NASA Technical Reports Server (NTRS)

    Riley, Danny A.; Sanger, James R.; Matloub, Hani S.; Yousif, N. John; Bain, James L. W.

    1988-01-01

    Carbonic anhydrase (CA) and cholinesterase (CE) histochemical staining of rabbit spinal nerve roots and dorsal root ganglia demonstrated that among the reactive myeliated axons, with minor exceptions, sensory axons were CA positive and CE negative whereas motor axons were CA negative and CE positive. The high specificity was achieved by adjusting reaction conditions to stain subpopulations of myelinated axons selectively while leaving 50 percent or so unstained. Fixation with glutaraldehyde appeared necessary for achieving selectivity. Following sciatic nerve transection, the reciprocal staining pattern persisted in damaged axons and their regenerating processes which formed neuromas within the proximal nerve stump. Within the neuromas, CA-stained sensory processes were elaborated earlier and in greater numbers than CE-stained regenerating motor processes. The present results indicate that histochemical axon typing can be exploited to reveal heterogeneous responses of motor and sensory axons to injury.

  6. Sensory capacity of reinnervated skin after redirection of amputated upper limb nerves to the chest.

    PubMed

    Marasco, Paul D; Schultz, Aimee E; Kuiken, Todd A

    2009-06-01

    Targeted reinnervation is a new neural-machine interface that has been developed to help improve the function of new-generation prosthetic limbs. Targeted reinnervation is a surgical procedure that takes the nerves that once innervated a severed limb and redirects them to proximal muscle and skin sites. The sensory afferents of the redirected nerves reinnervate the skin overlying the transfer site. This creates a sensory expression of the missing limb in the amputee's reinnervated skin. When these individuals are touched on this reinnervated skin they feel as though they are being touched on their missing limb. Targeted reinnervation takes nerves that once served the hand, a skin region of high functional importance, and redirects them to less functionally relevant skin areas adjacent to the amputation site. In an effort to better understand the sensory capacity of the reinnervated target skin following this procedure, we examined grating orientation thresholds and point localization thresholds on two amputees who had undergone the targeted reinnervation surgery. Grating orientation thresholds and point localization thresholds were also measured on the contralateral normal skin of the targeted reinnervation amputees and on analogous sites in able-bodied controls. Grating orientation thresholds for the reinnervated skin of the targeted reinnervation amputees were found to be similar to normal ranges for both the amputees' contralateral skin and also for the control population. Point localization thresholds for these amputees were found to be lower for their reinnervated skin than for their contralateral skin. Reinnervated point localization thresholds values were also lower in comparison to homologous chest sites on the control population. Mechanisms appear to be in place to maximize re-established touch input in targeted reinnervation amputees. It seems that sound sensory function is provided to the denervated skin of the residual limb when connected to afferent

  7. Somatosensory evoked potentials following nerve and segmental stimulation do not confirm cervical radiculopathy with sensory deficit.

    PubMed Central

    Schmid, U D; Hess, C W; Ludin, H P

    1988-01-01

    Twenty eight patients with unilateral cervical radiculopathy were studied by somatosensory evoked potentials (SEPs) from nerve stimulation at the wrist and from skin stimulation at the first, third or fifth finger depending on the root involved. In order to evaluate the reliability of various "radicular SEP patterns" as described in the literature, absolute latencies and side-to-side differences of the brachial plexus component from the supraclavicular fossa (N9), the medullary component (N13) from the cervical vertebra Cv7, and the primary cortical component (N20, P25) were assessed. Side-to-side differences of the amplitudes of N20/P25 and of the conduction times across the intervertebral fossa (interval N9-N13) were analysed. After nerve stimulation, 68% of the patients had false negative findings on the symptomatic, while 36% had positive findings on the asymptomatic side. After segmental stimulation, 72% of the patients had false negative findings on the symptomatic, while 22% had positive findings on the asymptomatic side. It is concluded that SEPs following nerve and segmental stimulation do not reliably confirm clear-cut already established diagnoses of unilateral radiculopathy with sensory and motor deficit. Therefore, they will not be helpful in the electrophysiological investigation of cervicobrachialgias of unknown origin. PMID:2831303

  8. Remote arteriolar dilations caused by methacholine: a role for CGRP sensory nerves?

    PubMed

    Thengchaisri, Naris; Rivers, Richard J

    2005-08-01

    Remote vasodilation caused by arteriolar microapplication of acetylcholine cannot be completely attributed to passive cell-cell communication of a hyperpolarizing signal. The present study was undertaken to ascertain whether a neural component may be involved in the remote response. In the cheek pouch of anesthetized hamsters, methacholine (100 microM) was applied to the arteriole by micropipette for 5 s, and the arteriolar responses were measured at the site of application and at remote locations: 500 and 1,000 microm upstream from the application site. Superfusion with the local anesthetic bupivacaine attenuated a local dilatory response and abolished the conducted dilation response to methacholine. Localized micropipette application of bupivacaine 300 microm from the methacholine application site also attenuated the remote dilation but did not inhibit the local dilation. Blockade of neuromuscular transmission with botulinum neurotoxin A (1 U, 3 days), micropipette application of calcitonin gene-related peptide (CGRP) receptor inhibitor CGRP-(8-37) (10 microM) 300 microm upstream from the methacholine application site, and denervation of the CGRP sensory nerve by 2 days of capsaicin treatment reduced the conducted dilation response to methacholine but did not affect the local dilatory response. Together, these data support involvement of a TTX-insensitive nerve, specifically the CGRP containing nerve, in vascular communication. Understanding the effect of regulation of a novel neural network system on the vascular network may lead to a new insight into regulation of blood flow and intraorgan blood distribution.

  9. A proposed biologic cure for recurrent genital herpes simplex through injection of neurolytic agents into cutaneous sensory nerves.

    PubMed

    Bierman, S M

    1983-01-01

    It may be possible to eliminate Herpes simplex virus (HSV) from the skin of patients with chronic recurrent genital infections through destruction of the cutaneous sensory nerves of the genitals by injecting absolute alcohol into the affected areas. In so doing the latency of the virus in the sensory ganglia may be influenced, the immediate source of reinfection suppressed, and reactivation of HSV inhibited in the skin.

  10. A Hypothesis and Pilot Study of Age-Related Sensory Innervation of the Hard Palate: Sensory Disorder After Nasopalatine Nerve Division

    PubMed Central

    Liu, Jiyuan; Li, Xiufen; Ma, Liyuan; Pan, Jian; Tang, Xiufa; Wu, Yunlong; Hua, Chengge

    2017-01-01

    Background The nasopalatine nerve may be injured during extraction of teeth embedded in the anterior hard palate. The neural recovery process and its impact on sensation in the anterior hard palatal region are controversial. In our clinical practice, we noticed a distinct recovery process in children compared with adolescents or adults after surgery. We hypothesized that the sensory innervations of the anterior palate might shift during later childhood and pre-adolescence, which is due to the development of the nasopalatine nerve along with the maxillary growth and permanent teeth eruption. Material/Method Forty patients (20 females and 20 males, mean age 11.8±2.2) with impacted supernumerary teeth in anterior palatine area were included into our study, and were divided into 3 groups according to their age. A 24-week follow-up was conducted and the sensation in the anterior hard palate region was examined at every check point. All the data were collected and analyzed by Kaplan-Meier analysis. Results Fourteen children did not complain of any numbness immediately after anesthetization, and other children with sensory disorders had shorter healing periods compared to adolescent/adult patients. Conclusions The results indicated that the dominant nerve of the anterior hard palate region was dramatically changed from the greater palatine nerve to the nasopalatine nerve, which is important in deciding when to operate and in selection of anesthesia method. PMID:28132066

  11. Self-powered sensory nerve system for civil structures using hybrid forisome actuators

    NASA Astrophysics Data System (ADS)

    Shoureshi, Rahmat A.; Shen, Amy

    2006-03-01

    In order to provide a true distributed sensor and control system for civil structures, we have developed a Structural Nervous System that mimics key attributes of a human nervous system. This nervous system is made up of building blocks that are designed based on mechanoreceptors as a fundamentally new approach for the development of a structural health monitoring and diagnostic system that utilizes the recently discovered plant-protein forisomes, a novel non-living biological material capable of sensing and actuation. In particular, our research has been focused on producing a sensory nervous system for civil structures by using forisomes as the mechanoreceptors, nerve fibers, neuronal pools, and spinocervical tract to the nodal and central processing units. This paper will present up to date results of our research, including the design and analysis of the structural nervous system.

  12. Phenotypic switching of nonpeptidergic cutaneous sensory neurons following peripheral nerve injury.

    PubMed

    Wang, Ting; Molliver, Derek C; Jing, Xiaotang; Schwartz, Erica S; Yang, Fu-Chia; Samad, Omar Abdel; Ma, Qiufu; Davis, Brian M

    2011-01-01

    In adult mammals, the phenotype of half of all pain-sensing (nociceptive) sensory neurons is tonically modulated by growth factors in the glial cell line-derived neurotrophic factor (GDNF) family that includes GDNF, artemin (ARTN) and neurturin (NRTN). Each family member binds a distinct GFRα family co-receptor, such that GDNF, NRTN and ARTN bind GFRα1, -α2, and -α3, respectively. Previous studies revealed transcriptional regulation of all three receptors in following axotomy, possibly in response to changes in growth factor availability. Here, we examined changes in the expression of GFRα1-3 in response to injury in vivo and in vitro. We found that after dissociation of adult sensory ganglia, up to 27% of neurons die within 4 days (d) in culture and this can be prevented by nerve growth factor (NGF), GDNF and ARTN, but not NRTN. Moreover, up-regulation of ATF3 (a marker of neuronal injury) in vitro could be prevented by NGF and ARTN, but not by GDNF or NRTN. The lack of NRTN efficacy was correlated with rapid and near-complete loss of GFRα2 immunoreactivity. By retrogradely-labeling cutaneous afferents in vivo prior to nerve cut, we demonstrated that GFRα2-positive neurons switch phenotype following injury and begin to express GFRα3 as well as the capsaicin receptor, transient receptor potential vanilloid 1(TRPV1), an important transducer of noxious stimuli. This switch was correlated with down-regulation of Runt-related transcription factor 1 (Runx1), a transcription factor that controls expression of GFRα2 and TRPV1 during development. These studies show that NRTN-responsive neurons are unique with respect to their plasticity and response to injury, and suggest that Runx1 plays an ongoing modulatory role in the adult.

  13. TRESK channel contribution to nociceptive sensory neurons excitability: modulation by nerve injury

    PubMed Central

    2011-01-01

    Background Neuronal hyperexcitability is a crucial phenomenon underlying spontaneous and evoked pain. In invertebrate nociceptors, the S-type leak K+ channel (analogous to TREK-1 in mammals) plays a critical role of in determining neuronal excitability following nerve injury. Few data are available on the role of leak K2P channels after peripheral axotomy in mammals. Results Here we describe that rat sciatic nerve axotomy induces hyperexcitability of L4-L5 DRG sensory neurons and decreases TRESK (K2P18.1) expression, a channel with a major contribution to total leak current in DRGs. While the expression of other channels from the same family did not significantly change, injury markers ATF3 and Cacna2d1 were highly upregulated. Similarly, acute sensory neuron dissociation (in vitro axotomy) produced marked hyperexcitability and similar total background currents compared with neurons injured in vivo. In addition, the sanshool derivative IBA, which blocked TRESK currents in transfected HEK293 cells and DRGs, increased intracellular calcium in 49% of DRG neurons in culture. Most IBA-responding neurons (71%) also responded to the TRPV1 agonist capsaicin, indicating that they were nociceptors. Additional evidence of a biological role of TRESK channels was provided by behavioral evidence of pain (flinching and licking), in vivo electrophysiological evidence of C-nociceptor activation following IBA injection in the rat hindpaw, and increased sensitivity to painful pressure after TRESK knockdown in vivo. Conclusions In summary, our results clearly support an important role of TRESK channels in determining neuronal excitability in specific DRG neurons subpopulations, and show that axonal injury down-regulates TRESK channels, therefore contributing to neuronal hyperexcitability. PMID:21527011

  14. The effect of aging on the density of the sensory nerve fiber innervation of bone and acute skeletal pain

    PubMed Central

    Jimenez-Andrade, Juan M.; Mantyh, William G.; Bloom, Aaron P.; Freeman, Katie T.; Ghilardi, Joseph R.; Kuskowski, Michael A.; Mantyh, Patrick W.

    2010-01-01

    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

  15. Implementation of linear sensory signaling via multiple coordinated mechanisms at central vestibular nerve synapses

    PubMed Central

    McElvain, Lauren E.; Faulstich, Michael; Jeanne, James M.; Moore, Jeffrey D.; du Lac, Sascha

    2015-01-01

    Summary Signal transfer in neural circuits is dynamically modified by the recent history of neuronal activity. Short-term plasticity endows synapses with nonlinear transmission properties, yet synapses in sensory and motor circuits are capable of signaling linearly over a wide range of presynaptic firing rates. How do such synapses achieve rate-invariant transmission despite history-dependent nonlinearities? Here, ultrastructural, biophysical, and computational analyses demonstrate that concerted molecular, anatomical, and physiological refinements are required for central vestibular nerve synapses to linearly transmit rate-coded sensory signals. Vestibular synapses operate in a physiological regime of steady-state depression imposed by tonic firing. Rate-invariant transmission relies on brief presynaptic action potentials that delimit calcium influx, large pools of rapidly mobilized vesicles, multiple low-probability release sites, robust postsynaptic receptor sensitivity, and efficient transmitter clearance. Broadband linear synaptic filtering of head motion signals is thus achieved by coordinately tuned synaptic machinery that maintains physiological operation within inherent cell biological limitations. PMID:25704949

  16. Variation in quantitative sensory testing and epidermal nerve fiber density in repeated measurements.

    PubMed

    Selim, Mona M; Wendelschafer-Crabb, Gwen; Hodges, James S; Simone, Donald A; Foster, Shawn X Y-L; Vanhove, Geertrui F; Kennedy, William R

    2010-12-01

    Quantitative sensory testing (QST) is commonly used to evaluate peripheral sensory function in neuropathic conditions. QST measures vary in repeated measurements of normal subjects but it is not known whether QST can reflect small changes in epidermal nerve fiber density (ENFd). This study evaluated QST measures (touch, mechanical pain, heat pain and innocuous cold sensations) for differences between genders and over time using ENFd as an objective-independent measure. QST was performed on the thighs of 36 healthy volunteers on four occasions between December and May. ENFd in skin biopsies was determined on three of those visits. Compared to men, women had a higher ENFd, a difference of 12.2 ENFs/mm. They also had lower tactile and innocuous cold thresholds, and detected mechanical pain (pinprick) at a higher frequency. Heat pain thresholds did not differ between genders. By the end of the 24-week study, men and women showed a small reduction (p<0.05) in the frequency of sharp mechanical pain evoked by pinprick whereas tactile and thermal thresholds showed no change. This coincided with a small decrease in ENFd, 4.18 ENFs/mm. Variation in measurements over time was large in a fraction of normal subjects. We conclude that most QST measures detect relatively large differences in epidermal innervation (12.2 ENFs/mm), but response to mechanical pain was the only sensory modality tested with the sensitivity to detect small changes in innervation (4.18 ENFs/mm). Since some individuals had large unsystematic variations, unexpected test results should therefore alert clinicians to test additional locations.

  17. Thyroid hormone reduces the loss of axotomized sensory neurons in dorsal root ganglia after sciatic nerve transection in adult rat.

    PubMed

    Schenker, Michel; Kraftsik, Rudolf; Glauser, Liliane; Kuntzer, Thierry; Bogousslavsky, Julien; Barakat-Walter, Ibtissam

    2003-11-01

    We have shown that a local administration of thyroid hormones (T3) at the level of transected rat sciatic nerve induced a significant increase in the number of regenerated axons. To address the question of whether local administration of T3 rescues the axotomized sensory neurons from death, in the present study we estimated the total number of surviving neurons per dorsal root ganglion (DRG) in three experimental group animals. Forty-five days following rat sciatic nerve transection, the lumbar (L4 and L5) DRG were removed from PBS-control, T3-treated as well as from unoperated rats, and serial sections (1 microm) were cut. The physical dissector method was used to estimate the total number of sensory neurons in the DRGs. Our results revealed that in PBS-control rats transection of sciatic nerve leads to a significant (P < 0.001) decrease in the mean number of sensory neurons (8743.8 +/- 748.6) compared with the number of neurons in nontransected ganglion (mean 13,293.7 +/- 1368.4). However, administration of T3 immediately after sciatic nerve transection rescues a great number of axotomized neurons so that their mean neuron number (12,045.8 +/- 929.8) is not significantly different from the mean number of neurons in the nontransected ganglion. In addition, the volume of ganglia showed a similar tendency. These results suggest that T3 rescues a high number of axotomized sensory neurons from death and allows these cells to grow new axons. We believe that the relative preservation of neurons is important in considering future therapeutic approaches of human peripheral nerve lesion and sensory neuropathy.

  18. THE MAJORITY OF MYELINATED AND UNMYELINATED SENSORY NERVE FIBERS THAT INNERVATE BONE EXPRESS THE TROPOMYOSIN RECEPTOR KINASE A

    PubMed Central

    Castañeda-Corral, Gabriela; Jimenez-Andrade, Juan M.; Bloom, Aaron P.; Taylor, Reid N.; Mantyh, William G.; Kaczmarska, Magdalena J.; Ghilardi, Joseph R.; Mantyh, Patrick W.

    2011-01-01

    Although skeletal pain is a leading cause of chronic pain and disability, relatively little is known about the specific populations of nerve fibers that innervate the skeleton. Recent studies have reported that therapies blocking nerve growth factor (NGF) or its cognate receptor, tropomyosin receptor kinase A (TrkA) are efficacious in attenuating skeletal pain. A potential factor to consider when assessing the analgesic efficacy of targeting NGF-TrkA signaling in a pain state is the fraction of NGF-responsive TrkA+ nociceptors that innervate the tissue from which the pain is arising, as this innervation and the analgesic efficacy of targeting NGF-TrkA signaling may vary considerably from tissue to tissue. To explore this in the skeleton, tissue slices and whole mount preparations of the normal, adult mouse femur were analyzed using immunohistochemistry and confocal microscopy. Analysis of these preparations revealed that 80% of the unmyelinated/thinly myelinated sensory nerve fibers that express calcitonin gene-related peptide (CGRP) and innervate the periosteum, mineralized bone and bone marrow also express TrkA. Similarly, the majority of myelinated sensory nerve fibers that express neurofilament 200 kDa (NF200) which innervate the periosteum, mineralized bone and bone marrow also co-express TrkA. In the normal femur, the relative density of CGRP+, NF200+ and TrkA+ sensory nerve fibers per unit volume is: periosteum > bone marrow > mineralized bone > cartilage with the respective relative densities being 100: 2: 0.1: 0. The observation that the majority of sensory nerve fibers innervating the skeleton express TrkA+, may in part explain why therapies that block NGF/TrkA pathway are highly efficacious in attenuating skeletal pain. PMID:21277945

  19. Fast-spiking GABA circuit dynamics in the auditory cortex predict recovery of sensory processing following peripheral nerve damage

    PubMed Central

    Resnik, Jennifer; Polley, Daniel B

    2017-01-01

    Cortical neurons remap their receptive fields and rescale sensitivity to spared peripheral inputs following sensory nerve damage. To address how these plasticity processes are coordinated over the course of functional recovery, we tracked receptive field reorganization, spontaneous activity, and response gain from individual principal neurons in the adult mouse auditory cortex over a 50-day period surrounding either moderate or massive auditory nerve damage. We related the day-by-day recovery of sound processing to dynamic changes in the strength of intracortical inhibition from parvalbumin-expressing (PV) inhibitory neurons. Whereas the status of brainstem-evoked potentials did not predict the recovery of sensory responses to surviving nerve fibers, homeostatic adjustments in PV-mediated inhibition during the first days following injury could predict the eventual recovery of cortical sound processing weeks later. These findings underscore the potential importance of self-regulated inhibitory dynamics for the restoration of sensory processing in excitatory neurons following peripheral nerve injuries. DOI: http://dx.doi.org/10.7554/eLife.21452.001 PMID:28323619

  20. Roles of Sensory Nerves in the Regulation of Radiation-Induced Structural and Functional Changes in the Heart

    SciTech Connect

    Sridharan, Vijayalakshmi; Tripathi, Preeti; Sharma, Sunil; Moros, Eduardo G.; Zheng, Junying; Hauer-Jensen, Martin; Boerma, Marjan

    2014-01-01

    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.

  1. TRPM8, a sensor for mild cooling in mammalian sensory nerve endings.

    PubMed

    Babes, Alexandru; Ciobanu, Alexandru Cristian; Neacsu, Cristian; Babes, Ramona-Madalina

    2011-01-01

    Temperature sensing is a crucial feature of the nervous system, enabling organisms to avoid physical danger and choose optimal environments for survival. TRPM8 (Transient Receptor Potential Melastatin type 8) belongs to a select group of ion channels which are gated by changes in temperature, are expressed in sensory nerves and/or skin cells and may be involved in temperature sensing. This channel is activated by a moderate decrease in temperature, with a threshold of approximately 25 °C in heterologous expression systems, and by a variety of natural and synthetic compounds, including menthol. While the physiological role of TRPM8 as a transducer of gentle cooling is widely accepted, its involvement in acute noxious cold sensing in healthy tissues is still under debate. Although accumulating evidence indicates that TRPM8 is involved in neuropathic cold allodynia, in some animal models of nerve injury peripheral and central activation of TRPM8 is followed by analgesia. A variety of inflammatory mediators, including bradykinin and prostaglandin E(2), modulate TRPM8 by inhibiting the channel and shifting its activation threshold to colder temperatures, most likely counteracting the analgesic action of TRPM8. While important progress has been made in unraveling the biophysical features of TRPM8, including the revelation of its voltage dependence, the precise mechanism involved in temperature sensing by this channel is still not completely understood. This article will review the current status of knowledge regarding the (patho)physiological role(s) of TRPM8, its modulation by inflammatory mediators, the signaling pathways involved in this regulation, and the biophysical properties of the channel.

  2. Activation of sensory nerves in guinea-pig isolated basilar artery by nicotine: evidence for inhibition of trigeminal sensory neurotransmission by sumatriptan.

    PubMed

    O'Shaughnessy, C T; Connor, H E

    1994-06-23

    Nicotine (100 microM), but not electrical field stimulation or potassium chloride (0.1-3 microM), caused capsaicin (1 microM)- and tetrodotoxin (1 microM)-sensitive relaxations of guinea-pig isolated basilar artery precontracted with prostaglandin F2 alpha. Nicotine-induced responses were blocked by the neurokinin NK1 receptor antagonist, GR82334 (10 microM), but were unaffected by the calcitonin gene-related peptide (CGRP) receptor antagonist, CGRP-(8-37) (1 microM). This suggests that nicotine activates capsaicin-sensitive sensory nerves in guinea-pig basilar artery to cause relaxation predominantly via substance P release. The vascular 5-HT1 receptor agonist, sumatriptan (0.3 and 3 microM), inhibited nicotine-induced relaxation (by 50 and 80% respectively); the inhibitory effect of sumatriptan (0.3 microM) was attenuated in the presence of the non-selective 5-HT1 receptor antagonist, methiothepin (0.1 microM). These data suggest that sumatriptan can inhibit sensory neurotransmission in guinea-pig basilar artery via activation of inhibitory prejunctional 5-HT1 receptors on sensory nerve terminals.

  3. Sensory feedback by peripheral nerve stimulation improves task performance in individuals with upper limb loss using a myoelectric prosthesis

    NASA Astrophysics Data System (ADS)

    Schiefer, Matthew; Tan, Daniel; Sidek, Steven M.; Tyler, Dustin J.

    2016-02-01

    Objective. Tactile feedback is critical to grip and object manipulation. Its absence results in reliance on visual and auditory cues. Our objective was to assess the effect of sensory feedback on task performance in individuals with limb loss. Approach. Stimulation of the peripheral nerves using implanted cuff electrodes provided two subjects with sensory feedback with intensity proportional to forces on the thumb, index, and middle fingers of their prosthetic hand during object manipulation. Both subjects perceived the sensation on their phantom hand at locations corresponding to the locations of the forces on the prosthetic hand. A bend sensor measured prosthetic hand span. Hand span modulated the intensity of sensory feedback perceived on the thenar eminence for subject 1 and the middle finger for subject 2. We performed three functional tests with the blindfolded subjects. First, the subject tried to determine whether or not a wooden block had been placed in his prosthetic hand. Second, the subject had to locate and remove magnetic blocks from a metal table. Third, the subject performed the Southampton Hand Assessment Procedure (SHAP). We also measured the subject’s sense of embodiment with a survey and his self-confidence. Main results. Blindfolded performance with sensory feedback was similar to sighted performance in the wooden block and magnetic block tasks. Performance on the SHAP, a measure of hand mechanical function and control, was similar with and without sensory feedback. An embodiment survey showed an improved sense of integration of the prosthesis in self body image with sensory feedback. Significance. Sensory feedback by peripheral nerve stimulation improved object discrimination and manipulation, embodiment, and confidence. With both forms of feedback, the blindfolded subjects tended toward results obtained with visual feedback.

  4. Alpha-Synuclein Pathology in Sensory Nerve Terminals of the Upper Aerodigestive Tract of Parkinson’s Disease Patients

    PubMed Central

    Mu, Liancai; Chen, Jingming; Sobotka, Stanislaw; Nyirenda, Themba; Benson, Brian; Gupta, Fiona; Sanders, Ira; Adler, Charles H.; Caviness, John N.; Shill, Holly A.; Sabbagh, Marwan; Samanta, Johan E.; Sue, Lucia I.; Beach, Thomas G.

    2015-01-01

    Dysphagia is common in Parkinson’s disease (PD) and causes significant morbidity and mortality. PD dysphagia has usually been explained as dysfunction of central motor control, much like other motor symptoms that are characteristic of the disease. However, PD dysphagia does not correlate with severity of motor symptoms nor does it respond to motor therapies. It is known that PD patients have sensory deficits in the pharynx, and that impaired sensation may contribute to dysphagia. However, the underlying cause of the pharyngeal sensory deficits in PD is not known. We hypothesized that PD dysphagia with sensory deficits may be due to degeneration of the sensory nerve terminals in the upper aerodigestive tract (UAT). We have previously shown that Lewy-type synucleinopathy (LTS) is present in the main pharyngeal sensory nerves of PD patients, but not in controls. In this study, the sensory terminals in UAT mucosa were studied to discern the presence and distribution of LTS. Whole-mount specimens (tongue-pharynx-larynx-upper esophagus) were obtained from 10 deceased human subjects with clinically diagnosed and neuropathologically confirmed PD (five with dysphagia and five without) and four age-matched healthy controls. Samples were taken from six sites and immunostained for phosphorylated α-synuclein (PAS). The results showed the presence of PAS-immunoreactive (PAS-ir) axons in all the PD subjects and in none of the controls. Notably, PD patients with dysphagia had more PAS-ir axons in the regions that are critical for initiating the swallowing reflex. These findings suggest that Lewy pathology affects mucosal sensory axons in specific regions of the UAT and may be related to PD dysphagia. PMID:26041249

  5. Mesenchymal stem cells in a polycaprolactone conduit promote sciatic nerve regeneration and sensory neuron survival after nerve injury.

    PubMed

    Frattini, Flávia; Lopes, Fatima Rosalina Pereira; Almeida, Fernanda Martins; Rodrigues, Rafaela Fintelman; Boldrini, Leonardo Cunha; Tomaz, Marcelo A; Baptista, Abrahão Fontes; Melo, Paulo A; Martinez, Ana Maria Blanco

    2012-10-01

    Despite the fact that the peripheral nervous system is able to regenerate after traumatic injury, the functional outcomes following damage are limited and poor. Bone marrow mesenchymal stem cells (MSCs) are multipotent cells that have been used in studies of peripheral nerve regeneration and have yielded promising results. The aim of this study was to evaluate sciatic nerve regeneration and neuronal survival in mice after nerve transection followed by MSC treatment into a polycaprolactone (PCL) nerve guide. The left sciatic nerve of C57BL/6 mice was transected and the nerve stumps were placed into a biodegradable PCL tube leaving a 3-mm gap between them; the tube was filled with MSCs obtained from GFP+ animals (MSC-treated group) or with a culture medium (Dulbecco's modified Eagle's medium group). Motor function was analyzed according to the sciatic functional index (SFI). After 6 weeks, animals were euthanized, and the regenerated sciatic nerve, the dorsal root ganglion (DRG), the spinal cord, and the gastrocnemius muscle were collected and processed for light and electron microscopy. A quantitative analysis of regenerated nerves showed a significant increase in the number of myelinated fibers in the group that received, within the nerve guide, stem cells. The number of neurons in the DRG was significantly higher in the MSC-treated group, while there was no difference in the number of motor neurons in the spinal cord. We also found higher values of trophic factors expression in MSC-treated groups, especially a nerve growth factor. The SFI revealed a significant improvement in the MSC-treated group. The gastrocnemius muscle showed an increase in weight and in the levels of creatine phosphokinase enzyme, suggesting an improvement of reinnervation and activity in animals that received MSCs. Immunohistochemistry documented that some GFP+ -transplanted cells assumed a Schwann-cell-like phenotype, as evidenced by their expression of the S-100 protein, a Schwann cell

  6. Sural sensory nerve action potential: A study in healthy Indian subjects

    PubMed Central

    Sreenivasan, Aarthika; Mansukhani, Khushnuma A; Sharma, Alika; Balakrishnan, Lajita

    2016-01-01

    Background: The sural sensory nerve action potential (SNAP) is an important electrodiagnostic study for suspected peripheral neuropathies. Incorrect technique and unavailability of reference data can lead to erroneous conclusions. Objectives: To establish reference data for sural SNAP in age-stratified healthy subjects at three sites of stimulation. Materials and Methods: A prospective study was conducted in 146 nerves from healthy subjects aged between 18 years and 90 years, stratified into six age groups (a = 18-30 years, b = 31–40 years, c = 41–50 years, d = 51–60 years, e = 61–70 years, and f >71 years). Sural SNAP was recorded antidromically, stimulating at three sites at distances of 14 cm, 12 cm, and 10 cm from the recording electrode. Mean – 2 standard deviation (SD) of the transformed data was used to generate reference values for amplitudes. Analysis of variance (ANOVA) test was used for inter-group and between three sites comparisons of amplitudes. Results: The lower limits of amplitude at 14 cm were 12.4 μV, 10.4 μV, 6.5 μV, 5.3 μV, 2.9 μV, and 1.9 μV; at 12 cm were 13.5 μV, 13.6 μV, 8.5 μV, 7.8 μV, 3.5 μV, and 2.8 μV; and at 10 cm were 16.3 μV, 16.3 μV, 11.1 μV, 10.0 μV, 4.8 μV, and 3.7 μV for groups a, b, c, d, e, and f, respectively. A statistically significant difference in amplitudes was noted from the three different sites of stimulation (P < 0.001). The amplitude differed significantly above the age of 60 years (P < 0.01) but not between groups e and f (P > 0.05). Conclusion: This study provides reference data for sural SNAP in Indian population at three different sites of stimulation along the calf in six age groups. It also shows significant variation in amplitude from the three different sites of stimulation. PMID:27570380

  7. Sensory nerves contribute to cutaneous vasodilator response to cathodal stimulation in healthy rats.

    PubMed

    Gohin, Stéphanie; Decorps, Johanna; Sigaudo-Roussel, Dominique; Fromy, Bérengère

    2015-09-01

    Cutaneous current-induced vasodilation (CIV) in response to galvanic current application is an integrative model of neurovascular interaction that relies on capsaicin-sensitive fiber activation. The upstream and downstream mechanisms related to the activation of the capsaicin-sensitive fibers involved in CIV are not elucidated. In particular, the activation of cutaneous transient receptor potential vanilloid type-1 (TRPV1) channels and/or acid-sensing ion channels (ASIC) (activators mechanisms) and the release of calcitonin gene-related peptide (CGRP) and substance P (SP) (effector mechanisms) have been tested. To assess cathodal CIV, we measured cutaneous blood flow using laser Doppler flowmetry for 20min following cathodal current application (240s, 100μA) on the skin of the thigh in anesthetized healthy rats for 20min. CIV was studied in rats treated with capsazepine and amiloride to inhibit TRPV1 and ASIC channels, respectively; CGRP8-37 and SR140333 to antagonize CGRP and neurokinin-1 (NK1) receptors, respectively; compared to their respective controls. Cathodal CIV was attenuated by capsazepine (12±2% vs 54±6%, P<0.001), amiloride (19±8% vs 61±6%, P<0.01), CGRP8-37 (15±6% vs 61±6%, P<0.001) and SR140333 (9±5% vs 54±6%, P<0.001) without changing local acidification. This is the first integrative study performed in healthy rats showing that cutaneous vasodilation in response to cathodal stimulation is initiated by activation of cutaneous TRPV1 and ASIC channels likely through local acidification. The involvement of CGRP and NK1 receptors suggests that cathodal CIV is the result of CGRP and SP released through activated capsaicin-sensitive fibers. Therefore cathodal CIV could be a valuable method to assess sensory neurovascular function in the skin, which would be particularly relevant to evaluate the presence of small nerve fiber disorders and the effectiveness of treatments.

  8. Atypical venous glomangioma causing chronic compression of the radial sensory nerve in the forearm. A case report and review of the literature.

    PubMed

    Jiga, Lucian P; Rata, Andreea; Ignatiadis, Ioannis; Geishauser, Max; Ionac, Mihai

    2012-03-01

    Extrinsic chronic nerve compression induced by nonendothelium derived vascular tumors is a rare occurrence at the forearm level. We present a case of severe chronic compression of the radial sensory nerve (RSN) caused by an undiagnosed venous glomangioma. The tumor was excised with complete symptoms relief. In the presence of severe nerve compression syndromes in young age, without predisposing comorbidities, atypical extrinsic compression due to vascular tumors should be considered.

  9. Refining the Sensory and Motor Ratunculus of the Rat Upper Extremity Using fMRI and Direct Nerve Stimulation

    PubMed Central

    Cho, Younghoon R.; Pawela, Christopher P.; Li, Rupeng; Kao, Dennis; Schulte, Marie L.; Runquist, Matthew L.; Yan, Ji-Geng; Matloub, Hani S.; Jaradeh, Safwan S.; Hudetz, Anthony G.; Hyde, James S.

    2008-01-01

    It is well understood that the different regions of the body have cortical representations in proportion to the degree of innervation. Our current understanding of the rat upper extremity has been enhanced using functional MRI (fMRI), but these studies are often limited to the rat forepaw. The purpose of this study is to describe a new technique that allows us to refine the sensory and motor representations in the cerebral cortex by surgically implanting electrodes on the major nerves of the rat upper extremity and providing direct electrical nerve stimulation while acquiring fMRI images. This technique was used to stimulate the ulnar, median, radial, and musculocutaneous nerves in the rat upper extremity using four different stimulation sequences that varied in frequency (5 Hz vs. 10 Hz) and current (0.5 mA vs. 1.0 mA). A distinct pattern of cortical activation was found for each nerve. The higher stimulation current resulted in a dramatic increase in the level of cortical activation. The higher stimulation frequency resulted in both increases and attenuation of cortical activation in different regions of the brain, depending on which nerve was stimulated. PMID:17969116

  10. Low-level laser treatment improves longstanding sensory aberrations in the inferior alveolar nerve following surgical trauma

    NASA Astrophysics Data System (ADS)

    Khullar, Shelley M.; Brodin, P.; Barkvoll, P.; Haanoes, H. R.

    1996-01-01

    The incidence of inferior alveolar nerve (IAN) damage following removal of 3rd molar teeth or saggital split osteotomy has been reported as high as up to 5.5% and 100% respectively. Sensory aberrations in the IAN persisting for longer than 6 months leave some degree of permanent defect. Low level laser treatment (LLL) has a reported beneficial effect on regeneration of traumatically injured nerves. The purpose of this double blind clinical trial was to examine the effects of LLL using a GaAlAs laser (820 nm, Ronvig, Denmark) on touch and temperature sensory perception following a longstanding post surgical IAN injury. Thirteen patients were divided into two groups, one of which received real LLL (4 by 6 J per treatment along the distribution of the IAN to a total of 20 treatments during a time period between 36 - 69 days) and the other equivalent placebo LLL. The degree of mechanoreceptor injury as assessed by Semmes Weinstein Monofilaments (North Coast Medical, USA) were comparable in the two groups prior to treatment (p equals 0.9). Subsequent to LLL the real laser treatment group showed a significant improvement in mechanoreceptor sensory testing (p equals 0.01) as manifested by a decrease in load threshold (g) necessary to elicit a response from the most damaged area. The placebo LLL group showed no significant improvement, In addition, the real LLL group reported a subjective improvement in sensory function too. The degree of thermal sensitivity disability as assessed using a thermotester (Philips, Sweden) was comparable between the two groups prior to LLL p equals 0.5). However, there was no significant improvement in thermal sensitivity post LLL for either the real or placebo laser treated groups. In conclusion, GaAlAs LLL can improve mechanoreceptor perception in longstanding sensory aberration in the IAN.

  11. Diuresis and natriuresis caused by activation of VR1-positive sensory nerves in renal pelvis of rats.

    PubMed

    Zhu, Yi; Wang, Youping; Wang, Donna H

    2005-10-01

    To test the hypothesis that activation of the vanilloid receptor 1 (VR1) expressed in sensory nerves innervating the renal pelvis leads to diuresis and natriuresis, a selective VR1 receptor agonist, capsaicin (2.4 nmol), or vehicle was perfused intravenously or into the left renal pelvis of anesthetized rats at a rate without changing renal perfusion pressure. Mean arterial pressure was not altered by capsaicin administered intravenously or into the renal pelvis. Capsaicin perfusion into the left renal pelvis but not intravenously caused significant increases in urine flow rate and urinary sodium excretion bilaterally in a dose-dependent manner, which were abolished by capsazepine, a selective VR1 receptor antagonist, given ipsilaterally to the renal pelvis or by ipsilateral renal denervation. Capsaicin given intravenously or into the left renal pelvis increased plasma calcitonin gene-related peptide levels to the same extent. Increased plasma calcitonin gene-related peptide levels induced by capsaicin (68.9+/-2.8 pg/mL) perfusion into the renal pelvis was prevented either by capsazepine (22.5+/-10.1 pg/mL) given ipsilaterally into the renal pelvis or by ipsilateral renal denervation (25.9+/-2.3 pg/mL). Taken together, our data show that unilateral activation of VR1-positive sensory nerves innervating the renal pelvis leads to bilateral diuresis and natriuresis via a mechanism that is independent of plasma calcitonin gene-related peptide levels. These data suggest that VR1-positive sensory nerves in the kidney enhance renal excretory function, a mechanism that may be critically involved in sodium and fluid homeostasis.

  12. Effect of dopamine receptor agonists on sensory nerve activity: possible therapeutic targets for the treatment of asthma and COPD

    PubMed Central

    Birrell, Mark A; Crispino, Natascia; Hele, David J; Patel, Hema J; Yacoub, Magdi H; Barnes, Peter J; Belvisi, Maria G

    2002-01-01

    Sensory nerves regulate central and local reflexes such as airway plasma leakage, and cough and their function may be enhanced during inflammation. Evidence suggests that dopamine receptor agonists may inhibit sensory nerve-mediated responses.In this study dopamine inhibited vagal sensory nerve induced microvascular leakage in the rat. In order to characterize the receptor involved rat vagus preparations were utilized. Quinagolide (D2/3 agonist), ropinirole (D2/3/4 agonist), SKF 38393 (D1/5 agonist), AR-C68397AA (Viozan™) (dual D2/B2 agonist) and dopamine inhibited hypertonic saline induced depolarization by approximately 50%. Data suggests that AR-C68397AA and quinagolide also inhibited depolarization of the human vagus.The quinagolide response was blocked by sulpiride (D2/3 antagonist) but not SCH 23390 (D1/5 antagonist); ropinirole was partially blocked by sulpiride, totally blocked by spiperone (at a concentration that blocks all dopamine receptors) but not by SCH 23390. The response to SKF 38393 was not blocked by sulpiride but was by SCH 23390. The inhibition evoked by AR-C68397AA was only partially blocked by SCH 23390 but not by sulpiride or spiperone whereas dopamine was blocked by spiperone. The effect of dopamine was not stimulus-specific as it inhibited capsaicin-induced depolarization of the rat vagus in a spiperone sensitive manner.In conclusion, dopamine receptor ligands inhibit depolarization of the rat and human vagus. These data suggest that dopamine receptor agonists may be of therapeutic benefit in the treatment of symptoms such as cough and mucus secretion which are evident in respiratory diseases such as asthma and chronic obstructive pulmonary disease. PMID:12055141

  13. Effect of dopamine receptor agonists on sensory nerve activity: possible therapeutic targets for the treatment of asthma and COPD.

    PubMed

    Birrell, Mark A; Crispino, Natascia; Hele, David J; Patel, Hema J; Yacoub, Magdi H; Barnes, Peter J; Belvisi, Maria G

    2002-06-01

    Sensory nerves regulate central and local reflexes such as airway plasma leakage, and cough and their function may be enhanced during inflammation. Evidence suggests that dopamine receptor agonists may inhibit sensory nerve-mediated responses. In this study dopamine inhibited vagal sensory nerve induced microvascular leakage in the rat. In order to characterize the receptor involved rat vagus preparations were utilized. Quinagolide (D(2/3) agonist), ropinirole (D(2/3/4) agonist), SKF 38393 (D(1/5) agonist), AR-C68397AA (Viozan) (dual D(2)/B(2) agonist) and dopamine inhibited hypertonic saline induced depolarization by approximately 50%. Data suggests that AR-C68397AA and quinagolide also inhibited depolarization of the human vagus. The quinagolide response was blocked by sulpiride (D(2/3) antagonist) but not SCH 23390 (D(1/5) antagonist); ropinirole was partially blocked by sulpiride, totally blocked by spiperone (at a concentration that blocks all dopamine receptors) but not by SCH 23390. The response to SKF 38393 was not blocked by sulpiride but was by SCH 23390. The inhibition evoked by AR-C68397AA was only partially blocked by SCH 23390 but not by sulpiride or spiperone whereas dopamine was blocked by spiperone. The effect of dopamine was not stimulus-specific as it inhibited capsaicin-induced depolarization of the rat vagus in a spiperone sensitive manner. In conclusion, dopamine receptor ligands inhibit depolarization of the rat and human vagus. These data suggest that dopamine receptor agonists may be of therapeutic benefit in the treatment of symptoms such as cough and mucus secretion which are evident in respiratory diseases such as asthma and chronic obstructive pulmonary disease.

  14. Capsaicin-sensitive sensory nerves exert complex regulatory functions in the serum-transfer mouse model of autoimmune arthritis

    PubMed Central

    Borbély, Éva; Botz, Bálint; Bölcskei, Kata; Kenyér, Tibor; Kereskai, László; Kiss, Tamás; Szolcsányi, János; Pintér, Erika; Csepregi, Janka Zsófia; Mócsai, Attila; Helyes, Zsuzsanna

    2015-01-01

    Objective The K/BxN serum-transfer arthritis is a widely-used translational mouse model of rheumatoid arthritis, in which the immunological components have thoroughly been investigated. In contrast, little is known about the role of sensory neural factors and the complexity of neuro–immune interactions. Therefore, we analyzed the involvement of capsaicin-sensitive peptidergic sensory nerves in autoantibody-induced arthritis with integrative methodology. Methods Arthritogenic K/BxN or control serum was injected to non-pretreated mice or resiniferatoxin (RTX)-pretreated animals where capsaicin-sensitive nerves were inactivated. Edema, touch sensitivity, noxious heat threshold, joint function, body weight and clinical arthritis severity scores were determined repeatedly throughout two weeks. Micro-CT and in vivo optical imaging to determine matrix-metalloproteinase (MMP) and neutrophil-derived myeloperoxidase (MPO) activities, semiquantitative histopathological scoring and radioimmunoassay to measure somatostatin in the joint homogenates were also performed. Results In RTX-pretreated mice, the autoantibody-induced joint swelling, arthritis severity score, MMP and MPO activities, as well as histopathological alterations were significantly greater compared to non-pretreated animals. Self-control quantification of the bone mass revealed decreased values in intact female mice, but significantly greater arthritis-induced pathological bone formation after RTX-pretreatment. In contrast, mechanical hyperalgesia from day 10 was smaller after inactivating capsaicin-sensitive afferents. Although thermal hyperalgesia did not develop, noxious heat threshold was significantly higher following RTX pretreatment. Somatostatin-like immunoreactivity elevated in the tibiotarsal joints in non-pretreated, which was significantly less in RTX-pretreated mice. Conclusions Although capsaicin-sensitive sensory nerves mediate mechanical hyperalgesia in the later phase of autoantibody

  15. Early sensory re-education of the hand after peripheral nerve repair based on mirror therapy: a randomized controlled trial

    PubMed Central

    Paula, Mayara H.; Barbosa, Rafael I.; Marcolino, Alexandre M.; Elui, Valéria M. C.; Rosén, Birgitta; Fonseca, Marisa C. R.

    2016-01-01

    BACKGROUND: Mirror therapy has been used as an alternative stimulus to feed the somatosensory cortex in an attempt to preserve hand cortical representation with better functional results. OBJECTIVE: To analyze the short-term functional outcome of an early re-education program using mirror therapy compared to a late classic sensory program for hand nerve repair. METHOD: This is a randomized controlled trial. We assessed 20 patients with median and ulnar nerve and flexor tendon repair using the Rosen Score combined with the DASH questionnaire. The early phase group using mirror therapy began on the first postoperative week and lasted 5 months. The control group received classic sensory re-education when the protective sensation threshold was restored. All participants received a patient education booklet and were submitted to the modified Duran protocol for flexor tendon repair. The assessments were performed by the same investigator blinded to the allocated treatment. Mann-Whitney Test and Effect Size using Cohen's d score were used for inter-group comparisons at 3 and 6 months after intervention. RESULTS: The primary outcome (Rosen score) values for the Mirror Therapy group and classic therapy control group after 3 and 6 months were 1.68 (SD=0.5); 1.96 (SD=0.56) and 1.65 (SD=0.52); 1.51 (SD=0.62), respectively. No between-group differences were observed. CONCLUSION: Although some clinical improvement was observed, mirror therapy was not shown to be more effective than late sensory re-education in an intermediate phase of nerve repair in the hand. Replication is needed to confirm these findings. PMID:26786080

  16. Differences between nerve terminal impulses of polymodal nociceptors and cold sensory receptors of the guinea-pig cornea.

    PubMed

    Brock, J A; Pianova, S; Belmonte, C

    2001-06-01

    1. Extracellular recording techniques were used to study nerve terminal impulses (NTIs) recorded from single polymodal nociceptors and cold-sensitive receptors in guinea-pig cornea isolated in vitro. 2. The amplitude and time course of NTIs recorded from polymodal nociceptors was different from those of cold-sensitive receptors. 3. Bath application of tetrodotoxin (1 microM) changed the time course of spontaneous NTIs recorded from both polymodal and cold-sensitive receptors. 4. Bath application of lignocaine (lidocaine; 1-5 mM) abolished all electrical activity. 5. Local application of lignocaine (2.5 and 20 mM) through the recording electrode changed the time course of the NTIs recorded from polymodal nociceptors but not that of NTIs recorded from cold-sensitive nerve endings. 6. It is concluded that action potentials propagate actively in the sensory nerve endings of polymodal nociceptors. In contrast, cold-sensitive receptor nerve endings appear to be passively invaded from a point more proximal in the axon where the action potential can fail or be initiated.

  17. Selective decrease of small sensory neurons in lumbar dorsal root ganglia labeled with horseradish peroxidase after ND:YAG laser irradiation of the tibial nerve in the rat

    SciTech Connect

    Wesselmann, U.; Lin, S.F.; Rymer, W.Z. )

    1991-02-01

    Recent electrophysiological evidence indicates that Q-switched Nd:YAG laser irradiation might have selective effects on neural impulse transmission in small slow conducting sensory nerve fibers as compared to large diameter afferents. In an attempt to clarify the ultimate fate of sensory neurons after laser application to their peripheral axons, we have used horseradish peroxidase (HRP) as a cell marker to retrogradely label sensory neurons innervating the distal hindlimb in the rat. Pulsed Nd:YAG laser light was applied to the tibial nerve at pulse energies of 70 or 80 mJ/pulse for 5 min in experimental rats. Seven days later HRP was applied to the left (laser-treated) and to the contralateral (untreated) tibial nerve proximal to the site of laser irradiation. In control animals the numbers of HRP-labeled dorsal root ganglion cells were not significantly different between the right and the left side. In contrast, after previous laser irradiation labeling was always less on the laser-treated side (2183 +/- 513 cells, mean +/- SEM) as compared to the untreated side (3937 +/- 225). Analysis of the dimensions of labeled cells suggested that the reduction of labeled cells on the laser-treated side was mainly due to a deficit in small sensory neurons. Since the conduction velocity of nerve fibers is related to the size of their somata, our histological data imply that laser light selectively affects retrograde transport mechanisms for HRP in slow conducting sensory nerve fibers.

  18. Dietary sodium modulates the interaction between efferent and afferent renal nerve activity by altering activation of α2-adrenoceptors on renal sensory nerves.

    PubMed

    Kopp, Ulla C; Cicha, Michael Z; Smith, Lori A; Ruohonen, Saku; Scheinin, Mika; Fritz, Nicolas; Hökfelt, Tomas

    2011-02-01

    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 α(1)-and α(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 α(2)-AR in modulating the responsiveness of renal sensory nerves during low- and high-sodium diets. Immunohistochemical analysis suggested the presence of α(2A)-AR and α(2C)-AR subtypes on renal sensory nerves. During the low-sodium diet, renal pelvic administration of the α(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 α(2)-AR contributes to the reduced interaction between ERSNA and ARNA during low-sodium intake, whereas no/minimal activation of α(2)-AR contributes to the enhanced ERSNA-ARNA interaction under conditions of high sodium intake.

  19. Dietary sodium modulates the interaction between efferent and afferent renal nerve activity by altering activation of α2-adrenoceptors on renal sensory nerves

    PubMed Central

    Cicha, Michael Z.; Smith, Lori A.; Ruohonen, Saku; Scheinin, Mika; Fritz, Nicolas; Hökfelt, Tomas

    2011-01-01

    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 α1-and α2-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 α2-AR in modulating the responsiveness of renal sensory nerves during low- and high-sodium diets. Immunohistochemical analysis suggested the presence of α2A-AR and α2C-AR subtypes on renal sensory nerves. During the low-sodium diet, renal pelvic administration of the α2-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 α2-AR contributes to the reduced interaction between ERSNA and ARNA during low-sodium intake, whereas no/minimal activation of α2-AR contributes to the enhanced ERSNA-ARNA interaction under conditions of high sodium intake. PMID:21106912

  20. The effects of juvenile capsaicin desensitization in rats: behavioral impairments.

    PubMed

    Petrovszki, Zita; Adam, Gábor; Kekesi, Gabriella; Tuboly, Gábor; Morvay, Zita; Nagy, Endre; Benedek, György; Horvath, Gyöngyi

    2014-02-10

    Capsaicin desensitization leads to behavioral changes, some of which are related to schizophrenia, but investigations into these effects have been scarce. The goal of this study was to characterize the consequences of juvenile capsaicin desensitization on different functions: acute and inflammation-induced thermal and mechanical sensitivity, urinary bladder capacity and thermoregulation, and also on the potentially schizophrenia-related impairments in sensory-motor gating, motor activity and cognitive functioning. Male Wistar rats desensitized with increasing doses of subcutaneous capsaicin after weaning were investigated. Heat and mechanical pain sensitivity did not change significantly; however, morphine produced a prolonged decrease in the nociceptive response to inflammation in desensitized animals. Ultrasound examination of the bladder revealed enhanced bladder volume in treated animals. Capsaicin-treated animals had higher body temperature at 22 °C in both dark and light periods, and they also showed prolonged hyperthermia in new environmental circumstances. Warm environment induced a profound impairment of thermoregulation in desensitized animals. The treated animals also showed higher levels of activity during the active phase and at both cool and warm temperatures. The amplitude of the responses to auditory stimuli and prepulse inhibition did not differ between the two groups, but the desensitized animals showed learning impairments in the novel object recognition test. These results suggest that juvenile capsaicin desensitization leads to sustained changes in several functions that may be related to schizophrenia. We propose that capsaicin desensitization, together with other interventions, may lead to an improved chronic animal model of schizophrenia.

  1. Role of sensory nerves in the rapid cutaneous vasodilator response to local heating in young and older endurance-trained and untrained men.

    PubMed

    Tew, Garry A; Klonizakis, Markos; Moss, James; Ruddock, Alan D; Saxton, John M; Hodges, Gary J

    2011-02-01

    The ability to increase skin blood flow (SkBF) rapidly in response to local heating is diminished with advanced age; however, the mechanisms are unclear. The primary aim of this study was to investigate the role of sensory nerves in this age-related change. A secondary aim was to investigate the effect of aerobic fitness on sensory nerve-mediated vasodilatation in young and aged skin. We measured SkBF (using laser Doppler flowmetry) in young and older endurance-trained and untrained men (n= 7 in each group) at baseline and during 35 min of local skin heating to 42°C at two sites on the ventral forearm. One site was pretreated with topical anaesthetic cream to block local sensory nerve function. Cutaneous vascular conductance (CVC) was calculated as SkBF divided by mean arterial pressure and normalized to maximal values (CVC(max)) achieved during local heating to 44°C. At the untreated site, the rapid vasodilatation during the first ~5 min of local heating (initial peak) was lower in the older untrained group (68 ± 3%CVC(max)) compared with all other groups (young trained, 76 ± 4%CVC(max); young untrained, 75 ± 5%CVC(max); and older trained, 81 ± 3%CVC(max); P < 0.05). Sensory nerve blockade abolished these differences among the groups (P > 0.05). The contribution of sensory nerve-mediated vasodilatation was lower in the older untrained group compared with all other groups (P< 0.05). Our results suggest that the age-related decline in the rapid vasodilator response to local heating in human skin is explained by diminished sensory nerve-mediated vasodilatation. These findings also indicate that this age-related change can be prevented through participation in regular aerobic exercise.

  2. Sciatic nerve injury induces apoptosis of dorsal root ganglion satellite glial cells and selectively modifies neurosteroidogenesis in sensory neurons.

    PubMed

    Schaeffer, Véronique; Meyer, Laurence; Patte-Mensah, Christine; Eckert, Anne; Mensah-Nyagan, Ayikoe G

    2010-01-15

    Neurosteroids are synthesized either by glial cells, by neurons, or within the context of neuron-glia cross-talk. Various studies suggested neurosteroid involvement in the control of neurodegeneration but there is no evidence showing that the natural protection of nerve cells against apoptosis directly depends on their own capacity to produce neuroprotective neurosteroids. Here, we investigated the interactions between neurosteroidogenesis and apoptosis occurring in sensory structures of rats subjected to neuropathic pain generated by sciatic nerve chronic constriction injury (CCI). Using the terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL), we observed no apoptotic cells in the spinal cord up to 30 days after CCI although pain symptoms such as mechano-allodynia, thermal and mechanical hyperalgesia were evidenced with the Hargreaves's behavioral and von Frey filament tests. In contrast, double-labeling experiments combining TUNEL and immunostaining with antibodies against glutamine synthetase or neuronal nuclei protein revealed apoptosis occurrence in satellite glial cells (SGC) (not in neurons) of CCI rat ipsilateral dorsal root ganglia (DRG) at day 30 after injury. Pulse-chase experiments coupled with high performance liquid chromatography and flow scintillation detection showed that, among numerous biosynthetic pathways converting [(3)H]pregnenolone into various [(3)H]neurosteroids, only [(3)H]estradiol formation was selectively modified and upregulated in DRG of CCI rats. Consistently, immunohistochemical investigations localized aromatase (estradiol-synthesizing enzyme) in DRG neurons but not in SGC. Pharmacological inhibition of aromatase caused apoptosis of CCI rat DRG neurons. Altogether, our results suggest that endogenously produced neurosteroids such as estradiol may be pivotal for the protection of DRG sensory neurons against sciatic nerve CCI-induced apoptosis.

  3. Advanced Glycation End Products in Extracellular Matrix Proteins Contribute to the Failure of Sensory Nerve Regeneration in Diabetes

    PubMed Central

    Duran-Jimenez, Beatriz; Dobler, Darin; Moffatt, Sarah; Rabbani, Naila; Streuli, Charles H.; Thornalley, Paul J.; Tomlinson, David R.; Gardiner, Natalie J.

    2009-01-01

    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 Nε-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 Nε-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

  4. Perineural Administration of Dexmedetomidine in Combination with Bupivacaine Enhances Sensory and Motor Blockade in Sciatic Nerve Block without Inducing Neurotoxicity in the Rat

    PubMed Central

    Brummett, Chad M.; Norat, Mary A.; Palmisano, John M.; Lydic, Ralph

    2008-01-01

    Background The present study was designed to test the hypothesis that high-dose dexmedetomidine added to local anesthetic would increase the duration of sensory and motor blockade in a rat model of sciatic nerve blockade without causing nerve damage. Methods Thirty-one adult Sprague Dawley rats received bilateral sciatic nerve blocks with either 0.2 ml of 0.5% bupivacaine and 0.5% bupivacaine plus 0.005% dexmedetomidine in the contralateral leg, or 0.2 ml of 0.005% dexmedetomidine and normal saline in the contralateral leg. Sensory and motor function were assessed by a blinded investigator every 30 minutes until the return of normal sensory and motor function. Sciatic nerves were harvested at either 24 hours or 14 days after injection and analyzed for perineural inflammation and nerve damage. Results High-dose dexmedetomidine added to bupivacaine significantly enhanced the duration of sensory and motor blockade. Dexmedetomidine alone did not cause significant motor or sensory block. All of the nerves analyzed had normal axons and myelin at 24 hours and 14 days. Bupivacaine plus dexmedetomidine showed less perineural inflammation at 24 hours than the bupivacaine group when compared with the saline control. Conclusion The finding that high-dose dexmedetomidine can safely improve the duration of bupivacaine-induced antinociception following sciatic nerve blockade in rats is an essential first step encouraging future studies in humans. The dose of dexmedetomidine used in this study may exceed the sedative safety threshold in humans and could cause prolonged motor blockade, therefore future work with clinically relevant doses is necessary. PMID:18719449

  5. Effect of Ranirestat on Sensory and Motor Nerve Function in Japanese Patients with Diabetic Polyneuropathy: A Randomized Double-Blind Placebo-Controlled Study

    PubMed Central

    Satoh, Jo; Kohara, Nobuo; Sekiguchi, Kenji; Yamaguchi, Yasuyuki

    2016-01-01

    We conducted a 26-week oral-administration study of ranirestat (an aldose reductase inhibitor) at a once-daily dose of 20 mg to evaluate its efficacy and safety in Japanese patients with diabetic polyneuropathy (DPN). The primary endpoint was summed change in sensory nerve conduction velocity (NCV) for the bilateral sural and proximal median sensory nerves. The sensory NCV was significantly (P = 0.006) improved by ranirestat. On clinical symptoms evaluated with the use of modified Toronto Clinical Neuropathy Score (mTCNS), obvious efficacy was not found in total score. However, improvement in the sensory test domain of the mTCNS was significant (P = 0.037) in a subgroup of patients diagnosed with neuropathy according to the TCNS severity classification. No clinically significant effects on safety parameters including hepatic and renal functions were observed. Our results indicate that ranirestat is effective on DPN (Japic CTI-121994). PMID:26881251

  6. Activin Acts with Nerve Growth Factor to Regulate Calcitonin Gene-Related Peptide mRNA in Sensory Neurons

    PubMed Central

    Xu, Pin; Hall, Alison K.

    2009-01-01

    Calcitonin Gene-Related Peptide (CGRP) increases in sensory neurons after inflammation and plays an important role in abnormal pain responses, but how this neuropeptide is regulated is not well understood. Both activin A and Nerve Growth Factor (NGF) increase in skin after inflammation and induce CGRP in neurons in vivo and in vitro. This study was designed to understand how neurons integrate these two signals to regulate the neuropeptide important for inflammatory pain. In adult dorsal root ganglion neurons, NGF but not activin alone produced a dose-dependent increase in CGRP mRNA. When added together with NGF, activin synergistically increased CGRP mRNA, indicating that sensory neurons combine these signals. Studies were then designed to learn if that combination occurred at a common receptor or shared intracellular signals. Studies with Activin IB receptor or trkA inhibitors suggested that each ligand required its cognate receptor to stimulate the neuropeptide. Further, activin did not augment NGF-initiated intracellular MAPK signals but instead stimulated Smad phosphorylation, suggesting these ligands initiated parallel signals in the cytoplasm. Activin synergy required several NGF intracellular signals to be present. Because activin did not further stimulate, but did require NGF intracellular signals, it appears that activin and NGF converge not in receptor or cytoplasmic signals, but in transcriptional mechanisms to regulate CGRP in sensory neurons after inflammation. PMID:17964731

  7. Intracerebroventricular administration of nerve growth factor induces gliogenesis in sensory ganglia, dorsal root, and within the dorsal root entry zone.

    PubMed

    Schlachetzki, Johannes C M; Pizzo, Donald P; Morrissette, Debbi A; Winkler, Jürgen

    2014-01-01

    Previous studies indicated that intracerebroventricular administration of nerve growth factor (NGF) leads to massive Schwann cell hyperplasia surrounding the medulla oblongata and spinal cord. This study was designed to characterize the proliferation of peripheral glial cells, that is, Schwann and satellite cells, in the trigeminal ganglia and dorsal root ganglia (DRG) of adult rats during two weeks of NGF infusion using bromodeoxyuridine (BrdU) to label dividing cells. The trigeminal ganglia as well as the cervical and lumbar DRG were analyzed. Along the entire neuraxis a small number of dividing cells were observed within these regions under physiological condition. NGF infusion has dramatically increased the generation of new cells in the neuronal soma and axonal compartments of sensory ganglia and along the dorsal root and the dorsal root entry zone. Quantification of BrdU positive cells within sensory ganglia revealed a 2.3- to 3-fold increase in glial cells compared to controls with a similar response to NGF for the different peripheral ganglia examined. Immunofluorescent labeling with S100β revealed that Schwann and satellite cells underwent mitosis after NGF administration. These data indicate that intracerebroventricular NGF infusion significantly induces gliogenesis in trigeminal ganglia and the spinal sensory ganglia and along the dorsal root entry zone as well as the dorsal root.

  8. Disruption and restoration of dorsal horn sensory map after peripheral nerve crush and regeneration.

    PubMed

    Sugimoto, T; Yoshida, A; Nishijima, K; Ichikawa, H

    1995-10-01

    Formalin injection into the hindpaw of rats produces many neurons with c-fos protein-like immunoreactivity (fos-neurons) in the medial 3/4 of the ipsilateral dorsal horn laminae I and II at the junction of 4th and 5th lumbar segments (the sciatic territory). The tibial nerve transection 2 or 3 days earlier resulted in almost complete elimination of stimulation-induced fos-neurons in the tibial territory (medial 1/2 of the sciatic territory). When the animals had been conditioned by crushing the tibial nerve 2 weeks before stimulation (11 or 12 days before transection), the number of fos-neurons significantly increased compared to simple transection alone. The increase (2.5-fold) was greatest in the tibial territory. Therefore, the dorsal horn neurons in the deafferented tibial territory exhibited hypersensitivity to intact peroneal primary input, and the somatotopy map was disrupted. When the nerve had been crushed 3 weeks (18 or 19 days earlier than transection) rather than 2 weeks before stimulation, however, the number and distribution of fos-neurons were not different from those without conditioning (transection alone). Regenerated tibial nerve fibers were capable of transganglionic transport of WGA-HRP from the hindpaw receptive field to the tibial territory of the dorsal horn by 3 weeks but not by 2 weeks following the nerve crush. When transection was omitted, noxious signal transmitted through the tibial nerve fibers regenerated by 3 weeks after crush was capable of inducing c-fos in the tibial territory. The injury-induced hypersensitivity of dorsal horn neurons and resulting disruption of somatotopy map were reversed by re-establishment of peripheral tissue-nerve interaction.

  9. G9a inhibits CREB-triggered expression of mu opioid receptor in primary sensory neurons following peripheral nerve injury

    PubMed Central

    Liang, Lingli; Zhao, Jian-Yuan; Gu, Xiyao; Wu, Shaogen; Mo, Kai; Xiong, Ming; Marie Lutz, Brianna; Bekker, Alex

    2016-01-01

    Neuropathic pain, a distressing and debilitating disorder, is still poorly managed in clinic. Opioids, like morphine, remain the mainstay of prescribed medications in the treatment of this disorder, but their analgesic effects are highly unsatisfactory in part due to nerve injury-induced reduction of opioid receptors in the first-order sensory neurons of dorsal root ganglia. G9a is a repressor of gene expression. We found that nerve injury-induced increases in G9a and its catalyzed repressive marker H3K9m2 are responsible for epigenetic silencing of Oprm1, Oprk1, and Oprd1 genes in the injured dorsal root ganglia. Blocking these increases rescued dorsal root ganglia Oprm1, Oprk1, and Oprd1 gene expression and morphine or loperamide analgesia and prevented the development of morphine or loperamide-induced analgesic tolerance under neuropathic pain conditions. Conversely, mimicking these increases reduced the expression of three opioid receptors and promoted the mu opioid receptor-gated release of primary afferent neurotransmitters. Mechanistically, nerve injury-induced increases in the binding activity of G9a and H3K9me2 to the Oprm1 gene were associated with the reduced binding of cyclic AMP response element binding protein to the Oprm1 gene. These findings suggest that G9a participates in the nerve injury-induced reduction of the Oprm1 gene likely through G9a-triggered blockage in the access of cyclic AMP response element binding protein to this gene. PMID:27927796

  10. Synapse formation changes the rules for desensitization of PKC translocation in Aplysia.

    PubMed

    Farah, Carole A; Naqib, Faisal; Weatherill, Daniel B; Pack, Christopher C; Sossin, Wayne S

    2015-02-01

    Protein kinase Cs (PKCs) are activated by translocating from the cytoplasm to the membrane. We have previously shown that serotonin-mediated translocation of PKC to the plasma membrane in Aplysia sensory neurons was subject to desensitization, a decrease in the ability of serotonin to induce translocation after previous application of serotonin. In Aplysia, changes in the strength of the sensory-motor neuron synapse are important for behavioral sensitization and PKC regulates a number of important aspects of this form of synaptic plasticity. We have previously suggested that the desensitization of PKC translocation in Aplysia sensory neurons may partially explain the differences between spaced and massed training, as spaced applications of serotonin, a cellular analog of spaced training, cause greater desensitization of PKC translocation than one massed application of serotonin, a cellular analog of massed training. Our previous studies were performed in isolated sensory neurons. In the present study, we monitored translocation of fluorescently-tagged PKC to the plasma membrane in living sensory neurons that were co-cultured with motor neurons to allow for synapse formation. We show that desensitization now becomes similar during spaced and massed applications of serotonin. We had previously modeled the signaling pathways that govern desensitization in isolated sensory neurons. We now modify this mathematical model to account for the changes observed in desensitization dynamics following synapse formation. Our study shows that synapse formation leads to significant changes in the molecular signaling networks that underlie desensitization of PKC translocation.

  11. G9a participates in nerve injury-induced Kcna2 downregulation in primary sensory neurons

    PubMed Central

    Liang, Lingli; Gu, Xiyao; Zhao, Jian-Yuan; Wu, Shaogen; Miao, Xuerong; Xiao, Jifang; Mo, Kai; Zhang, Jun; Lutz, Brianna Marie; Bekker, Alex; Tao, Yuan-Xiang

    2016-01-01

    Nerve injury-induced downregulation of voltage-gated potassium channel subunit Kcna2 in the dorsal root ganglion (DRG) is critical for DRG neuronal excitability and neuropathic pain genesis. However, how nerve injury causes this downregulation is still elusive. Euchromatic histone-lysine N-methyltransferase 2, also known as G9a, methylates histone H3 on lysine residue 9 to predominantly produce a dynamic histone dimethylation, resulting in condensed chromatin and gene transcriptional repression. We showed here that blocking nerve injury-induced increase in G9a rescued Kcna2 mRNA and protein expression in the axotomized DRG and attenuated the development of nerve injury-induced pain hypersensitivity. Mimicking this increase decreased Kcna2 mRNA and protein expression, reduced Kv current, and increased excitability in the DRG neurons and led to spinal cord central sensitization and neuropathic pain-like symptoms. G9a mRNA is co-localized with Kcna2 mRNA in the DRG neurons. These findings indicate that G9a contributes to neuropathic pain development through epigenetic silencing of Kcna2 in the axotomized DRG. PMID:27874088

  12. Peribulbar anesthesia for cataract surgery: Effect of lidocaine warming and alkalinization on injection pain, motor and sensory nerve blockade

    PubMed Central

    Jaichandran, Venkatakrishnan; Vijaya, Lingam; George, Ronnie Jacob; InderMohan, Bhanulakshmi

    2010-01-01

    Aim: To compare self-reported pain and efficacy of warmed, alkalinized, and warmed alkalinized lidocaine with plain 2% lidocaine at room temperature for peribulbar anesthesia in cataract surgery. Materials and Methods: Through a prospective, single-blinded, randomized, controlled clinical trial 200 patients were divided into four groups. They received either lidocaine at operating room temperature 18°C, control group (Group C), lidocaine warmed to 37°C (Group W), lidocaine alkalinized to a pH of 7.09 ± 0.10 (Group B) or lidocaine at 37°C alkalinized to a pH of 6.94 ± 0.05 (Group WB). All solutions contained Inj. Hyaluronidase 50 IU/ml. Pain was assessed using a 10-cm visual analog score scale. Time of onset of sensory and motor blockade and time to onset of postoperative pain were recorded by a blinded observer. Results: Mean pain score was significantly lower in Group B and WB compared with Group C (P < 0.001). Onset of analgesia was delayed in Group C compared with Group B (P = 0.021) and WB (P < 0.001). Mean time taken for the onset of complete akinesia and supplementation required for the block was significantly lower in Group B. Time of onset of pain after operation was significantly earlier in Group W compared with Group C (P = 0.036). Conclusion: Alkalinized lidocaine with or without warming produced less pain than lidocaine injected at room temperature. Alkalinization enhances the effect of warming for sensory nerve blockade, but warming does not enhance alkalinization, in fact it reduces the efficacy of alkalinized solution for blocking the motor nerves in the eye. PMID:20195031

  13. Nitrooleic acid, an endogenous product of nitrative stress, activates nociceptive sensory nerves via the direct activation of TRPA1.

    PubMed

    Taylor-Clark, Thomas E; Ghatta, Srinivas; Bettner, Weston; Undem, Bradley J

    2009-04-01

    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-NO(2)). Using calcium imaging and electrophysiology, we have shown that 9-OA-NO(2) activates human TRPA1 channels (EC(50), 1 microM), whereas oleic acid had no effect on TRPA1. 9-OA-NO(2) 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-NO(2) was not inhibited by the NO scavenger carboxy-PTIO. 9-OA-NO(2) had no effect on another nociceptive-specific ion channel, TRPV1. 9-OA-NO(2) 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-NO(2) failed to activate neurons derived from TRPA1(-/-) mice. The action of 9-OA-NO(2) at nociceptive nerve terminals was investigated using an ex vivo extracellular recording preparation of individual bronchopulmonary C fibers in the mouse. 9-OA-NO(2) 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.

  14. Sensory stimulation for lowering intraocular pressure, improving blood flow to the optic nerve and neuroprotection in primary open-angle glaucoma.

    PubMed

    Rom, Edith

    2013-12-01

    Primary open-angle glaucoma is a group of optic neuropathies that can lead to irreversible blindness. Sensory stimulation in the form of acupuncture or ear acupressure may contribute to protecting patients from blindness when used as a complementary method to orthodox treatment in the form of drops, laser or surgery. The objective of this article is to provide a narrative overview of the available literature up to July 2012. It summarises reported evidence on the potential beneficial effects of sensory stimulation for glaucoma. Sensory stimulation appears to significantly enhance the pressure-lowering effect of orthodox treatments. Studies suggest that it may also improve blood flow to the eye and optic nerve head. Furthermore, it may play a role in neuroprotection through regulating nerve growth factor and brain-derived neurotrophic factor and their receptors, thereby encouraging the survival pathway in contrast to the pathway to apoptosis. Blood flow and neuroprotection are areas that are not directly influenced by orthodox treatment modalities. Numerous different treatment protocols were used to investigate the effect of sensory stimulation on intraocular pressure, blood flow or neuroprotection of the retina and optic nerve in the animal model and human pilot studies. Objective outcomes were reported to have been evaluated with Goldmann tonometry, Doppler ultrasound techniques and electrophysiology (pattern electroretinography, visually evoked potentials), and supported with histological studies in the animal model. Taken together, reported evidence from these studies strongly suggests that sensory stimulation is worthy of further research.

  15. Local neurogenic regulation of rat hindlimb circulation: CO2-induced release of calcitonin gene-related peptide from sensory nerves

    PubMed Central

    Yamada, Masami; Ishikawa, Tomohisa; Yamanaka, Akihiro; Fujimori, Akira; Goto, Katsutoshi

    1997-01-01

    The mechanism of release of calcitonin gene-related peptide (CGRP) from sensory nerves in response to skeletal muscle contraction was investigated in the rat hindlimb in vivo and in vitro. In the anaesthetized rat, sciatic nerve stimulation at 10 Hz for 1 min caused a hyperaemic response in the hindlimb. During the response, partial pressure of CO2 in the venous blood effluent from the hindlimb significantly increased from 43±3 to 73±8 mmHg, whereas a small decrease in pH and no appreciable change in partial pressure of O2 were observed. An intra-arterial bolus injection of NaHCO3 (titrated to pH 7.2 with HCl), which elevated PCO2 of the venous blood, caused a sustained increase in regional blood flow of the iliac artery. Capsaicin (0.33 μmol kg−1, i.a.) and a specific calcitonin gene-related peptide (CGRP) receptor antagonist, CGRP(8–37), (100 nmol kg−1 min−1, i.v.) significantly suppressed the hyperaemic response to NaHCO3. Neither NDΩ-nitro-L-arginine methyl ester (1 μmol kg−1 min−1, i.v.) nor indomethacin (5 mg kg−1, i.v.) affected the response. The serum level of CGRP-like immunoreactivity in the venous blood was significantly increased by a bolus injection of NaHCO3 (pH=7.2) from 50±4 to 196±16 fmol ml−1. In the isolated hindlimb perfused with Krebs-Ringer solution, a bolus injection of NaHCO3 (pH=7.2) caused a decrease in perfusion pressure which was composed of two responses, i.e., an initial transient response and a slowly-developing long-lasting one. CGRP(8–37) significantly inhibited the latter response by 73%. These results suggest that CO2 liberated from exercising skeletal muscle activates capsaicin-sensitive perivascular sensory nerves locally, which results in the release of CGRP from their peripheral endings, and then the released peptide causes local vasodilatation. PMID:9375968

  16. Characterization of Thoracic Motor and Sensory Neurons and Spinal Nerve Roots in Canine Degenerative Myelopathy, a Potential Disease Model of Amyotrophic Lateral Sclerosis

    PubMed Central

    Morgan, Brandie R.; Coates, Joan R.; Johnson, Gayle C.; Shelton, G. Diane; Katz, Martin L.

    2014-01-01

    Canine Degenerative Myelopathy (DM) is a progressive adult-onset multisystem degenerative disease with many features in common with amyotrophic lateral sclerosis (ALS). As with some forms of ALS, DM is associated with mutations in superoxide dismutase 1 (SOD1). Clinical signs include general proprioceptive ataxia and spastic upper motor neuron paresis in pelvic limbs, which progress to flaccid tetraplegia and dysphagia. The purpose of this study was to characterize DM as a potential disease model for ALS. We previously reported that intercostal muscle atrophy develops in dogs with advanced stage DM. To determine if other components of the thoracic motor unit (MU) also demonstrated morphological changes consistent with dysfunction, histopathologic and morphometric analyses were conducted on thoracic spinal motor neurons (MN) and dorsal root ganglia (DRG), and in motor and sensory nerve root axons from DM-affected Boxers and Pembroke Welsh Corgis (PWCs). No alterations in MNs, or motor root axons were observed in either breed. However, advanced stage PWCs exhibited significant losses of sensory root axons, and numerous DRG sensory neurons displayed evidence of degeneration. These results indicate that intercostal muscle atrophy in DM is not preceded by physical loss of the motor neurons innervating these muscles, or of their axons. Axonal loss in thoracic sensory roots and sensory nerve death suggest sensory involvement may play an important role in DM disease progression. Further analysis of the mechanisms responsible for these morphological findings would aid in the development of therapeutic intervention for DM and some forms of ALS. PMID:24375814

  17. Peripheral nerve regeneration and NGF-dependent neurite outgrowth of adult sensory neurons converge on STAT3 phosphorylation downstream of neuropoietic cytokine receptor gp130.

    PubMed

    Quarta, Serena; Baeumer, Bastian E; Scherbakov, Nadja; Andratsch, Manfred; Rose-John, Stefan; Dechant, Georg; Bandtlow, Christine E; Kress, Michaela

    2014-09-24

    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.

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

    PubMed

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

    2009-06-01

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

  19. Selective activation of carotid nerve fibers by acetylcholine applied to the cat petrosal ganglion in vitro.

    PubMed

    Alcayaga, J; Iturriaga, R; Varas, R; Arroyo, J; Zapata, P

    1998-03-09

    The petrosal ganglion innervates carotid body chemoreceptors through the carotid (sinus) nerve. These primary sensory neurons are activated by transmitters released from receptor (glomus) cells, acetylcholine (ACh) having been proposed as one of the transmitters involved in this process. Since the perikarya of primary sensory neurons share several properties with peripheral sensory endings, we studied the electrical responses of the carotid nerve and glossopharyngeal branch to ACh locally applied to the cat petrosal ganglion superfused in vitro. Ganglionar applications of AChCl (1 microg-1 mg) generated bursts of action potentials conducted along the carotid nerve, while only a few spikes were exceptionally recorded from the glossopharyngeal branch in response to the largest doses. Carotid nerve responses to ACh were dose-dependent, the higher doses inducing transient desensitization. Application of nicotine to the petrosal ganglion also evoked dose-dependent excitatory responses in the carotid nerve. Responses to ACh were reversibly antagonized by adding hexamethonium to the superfusate, more intense and prolonged block of ACh responses being produced by mecamylamine. Ganglionar applications of gamma-amino butyric acid and serotonin, in doses of up to 5 mg, did not induce firing of action potentials in any of the branches of the glossopharyngeal nerve. Our results indicate that petrosal ganglion neurons projecting through the carotid nerve are selectively activated by ACh acting on nicotinic ACh receptors located in the somata of these neurons. Thus, cholinosensitivity would be shared by the membranes of peripheral endings and perikarya of primary sensory neurons involved in arterial chemoreception.

  20. [Thermographic quantification of sensory and sympathetic nerve lesions in mandibular fractures--a prognostic criterium?].

    PubMed

    Radtke, J; Bremerich, A; Machtens, E

    1996-01-01

    As a rule, damage to segmental afferent nerves by trauma is accompanied with local impairment of sympathic functions. Standardized quantification of subjective items concerning the deficit of sensibility is quite problematical. Investigation by electrophysiological means yield not more than qualitative issues. In contrast, changes of sympathetic status and reaction of dependent dermatomas are quantitatively measurable by thermography. -26 patients with unilateral mandibular fractures complained of different posttraumatic or postoperative sensible impairment of the third branch of the trigeminal nerve. In the course of onto 3 years area and quality of the concerned neural defect were correlated to skin temperature that was measured by contact thermography and compared to the opposite reference region.- In all cases the early posttraumatic period showed a difference in temperature of the corresponding skin areas (delta T = 0.43 +/- 0.24 C). In 20 of 26 cases a relation between the changes of temperature concerning time and area and the sensible improvement could be seen. There was an individual time-lag between these developments. Side-comparing thermography was able to forecast improvement in 17 of 26 cases. Thus, the issued device provides statements about the amount and the course of posttraumatic loss of sensibility.

  1. 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

    PubMed Central

    Herrera-Rincon, Celia; Panetsos, Fivos

    2014-01-01

    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. PMID:25452715

  2. Early Electrodiagnostic Features of Upper Extremity Sensory Nerves Can Differentiate Axonal Guillain-Barré Syndrome from Acute Inflammatory Demyelinating Polyneuropathy

    PubMed Central

    Koo, Yong Seo; Shin, Ha Young; Kim, Jong Kuk; Nam, Tai-Seung; Shin, Kyong Jin; Bae, Jong-Seok; Suh, Bum Chun; Oh, Jeeyoung; Yoon, Byeol-A

    2016-01-01

    Background and Purpose Serial nerve conduction studies (NCSs) are recommended for differentiating axonal and demyelinating Guillain-Barré syndrome (GBS), but this approach is not suitable for early diagnoses. This study was designed to identify possible NCS parameters for differentiating GBS subtypes. Methods We retrospectively reviewed the medical records of 70 patients with GBS who underwent NCS within 10 days of symptom onset. Patients with axonal GBS and acute inflammatory demyelinating polyneuropathy (AIDP) were selected based on clinical characteristics and serial NCSs. An antiganglioside antibody study was used to increase the diagnostic certainty. Results The amplitudes of median and ulnar nerve sensory nerve action potentials (SNAPs) were significantly smaller in the AIDP group than in the axonal-GBS group. Classification and regression-tree analysis revealed that the distal ulnar sensory nerve SNAP amplitude was the best predictor of axonal GBS. Conclusions Early upper extremity sensory NCS findings are helpful in differentiating axonal-GBS patients with antiganglioside antibodies from AIDP patients. PMID:27819421

  3. Evidence for an effect of sodium cromoglycate on sensory nerves in man.

    PubMed Central

    Collier, J G; Fuller, R W

    1983-01-01

    Sodium cromoglycate was given by both intravenous injection and local intra-arterial infusion to healthy volunteers. Intravenous injection of a dose of 4 mg in four subjects caused a statistically significant rise in blood pressure and pulse rate associated with a feeling of warmth in the perineum and blush areas of the face and chest. Brachial artery infusion of sodium cromoglycate at doses of 100-1000 microgram/min caused a feeling of warmth in the limb during 26 out of 30 infusions and this sensation was subject to tachyphylaxis. During eight infusions in which there was a sensation of warmth there was no change in local blood flow as measured by strain-gauge plethysmography. In a further six studies involving 12 infusions of sodium cromoglycate the feeling of warmth was not accompanied by a rise in local skin temperature. The results suggest that sodium cromoglycate may stimulate afferent nerves in man. PMID:6419758

  4. Afferent Fiber Remodeling in the Somatosensory Thalamus of Mice as a Neural Basis of Somatotopic Reorganization in the Brain and Ectopic Mechanical Hypersensitivity after Peripheral Sensory Nerve Injury

    PubMed Central

    Yagasaki, Yuki; Katayama, Yoko

    2017-01-01

    Abstract Plastic changes in the CNS in response to peripheral sensory nerve injury are a series of complex processes, ranging from local circuit remodeling to somatotopic reorganization. However, the link between circuit remodeling and somatotopic reorganization remains unclear. We have previously reported that transection of the primary whisker sensory nerve causes the abnormal rewiring of lemniscal fibers (sensory afferents) on a neuron in the mouse whisker sensory thalamus (V2 VPM). In the present study, using transgenic mice whose lemniscal fibers originate from the whisker sensory principle trigeminal nucleus (PrV2) are specifically labeled, we identified that the transection induced retraction of PrV2-originating lemniscal fibers and invasion of those not originating from PrV2 in the V2 VPM. This anatomical remodeling with somatotopic reorganization was highly correlated with the rewiring of lemniscal fibers. Origins of the non-PrV2-origin lemniscal fibers in the V2 VPM included the mandibular subregion of trigeminal nuclei and the dorsal column nuclei (DCNs), which normally represent body parts other than whiskers. The transection also resulted in ectopic receptive fields of V2 VPM neurons and extraterritorial pain behavior on the uninjured mandibular region of the face. The anatomical remodeling, emergence of ectopic receptive fields, and extraterritorial pain behavior all concomitantly developed within a week and lasted more than three months after the transection. Our findings, thus, indicate a strong linkage between these plastic changes after peripheral sensory nerve injury, which may provide a neural circuit basis underlying large-scale reorganization of somatotopic representation and abnormal ectopic sensations.

  5. Exuberant sprouting of sensory and sympathetic nerve fibers in nonhealed bone fractures and the generation and maintenance of chronic skeletal pain.

    PubMed

    Chartier, Stephane R; Thompson, Michelle L; Longo, Geraldine; Fealk, Michelle N; Majuta, Lisa A; Mantyh, Patrick W

    2014-11-01

    Skeletal injury is a leading cause of chronic pain and long-term disability worldwide. While most acute skeletal pain can be effectively managed with nonsteroidal anti-inflammatory drugs and opiates, chronic skeletal pain is more difficult to control using these same therapy regimens. One possibility as to why chronic skeletal pain is more difficult to manage over time is that there may be nerve sprouting in nonhealed areas of the skeleton that normally receive little (mineralized bone) to no (articular cartilage) innervation. If such ectopic sprouting did occur, it could result in normally nonnoxious loading of the skeleton being perceived as noxious and/or the generation of a neuropathic pain state. To explore this possibility, a mouse model of skeletal pain was generated by inducing a closed fracture of the femur. Examined animals had comminuted fractures and did not fully heal even at 90+days post fracture. In all mice with nonhealed fractures, exuberant sensory and sympathetic nerve sprouting, an increase in the density of nerve fibers, and the formation of neuroma-like structures near the fracture site were observed. Additionally, all of these animals exhibited significant pain behaviors upon palpation of the nonhealed fracture site. In contrast, sprouting of sensory and sympathetic nerve fibers or significant palpation-induced pain behaviors was never observed in naïve animals. Understanding what drives this ectopic nerve sprouting and the role it plays in skeletal pain may allow a better understanding and treatment of this currently difficult-to-control pain state.

  6. Enhanced vascular permeability in rat skin induced by sensory nerve stimulation: evaluation of the time course and appropriate stimulation parameters.

    PubMed

    Carmichael, N M E; Dostrovsky, J O; Charlton, M P

    2008-05-15

    Activation of nociceptors causes them to secrete neuropeptides. The binding of these peptides to receptors on blood vessels causes vasodilation and increased vascular permeability that allows loss of proteins and fluid (plasma extravasation, PE); this contributes to inflammation. This study defines the relationship between electrical activation of nociceptors and PE and evaluates the time course of this response in the skin of rats. We measured the time course and extent of PE by digital imaging of changes in skin reflectance caused by leakage of Evans Blue (EB) dye infused in the circulatory system before stimulation. Stimulation of the exclusively sensory saphenous nerve caused the skin to become dark blue within 2 min due to accumulation of EB. While PE is usually measured after 5-15 min of electrical stimulation, we found that stimulation for only 1 min at 4 Hz produced maximum PE. This response was dependent on the number of electrical stimuli at least for 4 Hz and 8 Hz stimulation rates. Since accumulation of EB in the skin is only slowly reversible, to determine the duration of enhanced vascular permeability we administered EB at various times after electrical stimulation of the saphenous nerve. PE was only observed when EB was infused within 5 min of electrical stimulation but could still be observed 50 min after capsaicin (1%, 25 microl) injection into the hind paw. These findings indicate that enhanced vascular permeability evoked by electrical stimulation persists only briefly after release of neuropeptides from nociceptors in the skin. Therefore, treatment of inflammation by blockade of neuropeptide release and receptors may be more effective than treatments aimed at epithelial gaps. We propose, in models of stimulation-induced inflammation, the use of a short stimulus train.

  7. Sensory perineuritis.

    PubMed Central

    Matthews, W B; Squier, M V

    1988-01-01

    A case of sensory perineuritis is described, affecting individual cutaneous nerves in the extremities and with a chronic inflammatory exudate confined to the perineurium in a sural nerve biopsy. No cause was found. The condition slowly resolved on steroid treatment. Images PMID:3379419

  8. Amplitudes of sural and radial sensory nerve action potentials in orthodromic and antidromic studies in children.

    PubMed

    Melendrez, J L; MacMillan, L J; Vajsar, J

    1998-01-01

    Several previous studies of adults have reported that the amplitudes of the sural and superficial radial nerve action potentials (SN and SRN SNAP respectively) are larger with antidromic than with orthodromic recordings. However, this difference has not been documented in children. This study evaluated the amplitudes of SN and SRN SNAPs obtained with antidromic and orthodromic recordings in children with and without neuropathy and compared these data with findings in adults. The SN or SRN or both of 10 neurologically normal children, 6 children with neuropathy and 7 healthy adults were studied with surface stimulation and recording. The position of the stimulating and recording electrodes for the orthodromic recordings was the reverse of that for the antidromic recordings. Peak-to-peak SNAP amplitudes were measured and analyzed. The mean of the SRN SNAP amplitude was significantly higher with the antidromic than the orthodromic technique for the first and third groups (p < 0.05). The mean SN SNAP amplitude was higher in the three groups, but not statistically significant when the data for the children and adult normal groups were combined and reanalyzed (p < 0.05). Consistent responses were obtained with both techniques. However, the antidromic technique was superior to the orthodromic technique because of the greater amplitude of responses. We recommend the use of the antidromic technique because of its greater amplitudes, ease of use and potential reduction of discomfort to the patient.

  9. The exceptionally high reactivity of Cys 621 is critical for electrophilic activation of the sensory nerve ion channel TRPA1.

    PubMed

    Bahia, Parmvir K; Parks, Thomas A; Stanford, Katherine R; Mitchell, David A; Varma, Sameer; Stevens, Stanley M; Taylor-Clark, Thomas E

    2016-06-01

    Activation of the sensory nerve ion channel TRPA1 by electrophiles is the key mechanism that initiates nociceptive signaling, and leads to defensive reflexes and avoidance behaviors, during oxidative stress in mammals. TRPA1 is rapidly activated by subtoxic levels of electrophiles, but it is unclear how TRPA1 outcompetes cellular antioxidants that protect cytosolic proteins from electrophiles. Here, using physiologically relevant exposures, we demonstrate that electrophiles react with cysteine residues on mammalian TRPA1 at rates that exceed the reactivity of typical cysteines by 6,000-fold and that also exceed the reactivity of antioxidant enzymes. We show that TRPA1 possesses a complex reactive cysteine profile in which C621 is necessary for electrophile-induced binding and activation. Modeling of deprotonation energies suggests that K620 contributes to C621 reactivity and mutation of K620 alone greatly reduces the effect of electrophiles on TRPA1. Nevertheless, binding of electrophiles to C621 is not sufficient for activation, which also depends on the function of another reactive cysteine (C665). Together, our results demonstrate that TRPA1 acts as an effective electrophilic sensor because of the exceptionally high reactivity of C621.

  10. The exceptionally high reactivity of Cys 621 is critical for electrophilic activation of the sensory nerve ion channel TRPA1

    PubMed Central

    Bahia, Parmvir K.; Parks, Thomas A.; Stanford, Katherine R.; Mitchell, David A.; Varma, Sameer; Stevens, Stanley M.

    2016-01-01

    Activation of the sensory nerve ion channel TRPA1 by electrophiles is the key mechanism that initiates nociceptive signaling, and leads to defensive reflexes and avoidance behaviors, during oxidative stress in mammals. TRPA1 is rapidly activated by subtoxic levels of electrophiles, but it is unclear how TRPA1 outcompetes cellular antioxidants that protect cytosolic proteins from electrophiles. Here, using physiologically relevant exposures, we demonstrate that electrophiles react with cysteine residues on mammalian TRPA1 at rates that exceed the reactivity of typical cysteines by 6,000-fold and that also exceed the reactivity of antioxidant enzymes. We show that TRPA1 possesses a complex reactive cysteine profile in which C621 is necessary for electrophile-induced binding and activation. Modeling of deprotonation energies suggests that K620 contributes to C621 reactivity and mutation of K620 alone greatly reduces the effect of electrophiles on TRPA1. Nevertheless, binding of electrophiles to C621 is not sufficient for activation, which also depends on the function of another reactive cysteine (C665). Together, our results demonstrate that TRPA1 acts as an effective electrophilic sensor because of the exceptionally high reactivity of C621. PMID:27241698

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

    PubMed

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

    2002-03-01

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

  12. Characterization of thoracic motor and sensory neurons and spinal nerve roots in canine degenerative myelopathy, a potential disease model of amyotrophic lateral sclerosis.

    PubMed

    Morgan, Brandie R; Coates, Joan R; Johnson, Gayle C; Shelton, G Diane; Katz, Martin L

    2014-04-01

    Canine degenerative myelopathy (DM) is a progressive, adult-onset, multisystem degenerative disease with many features in common with amyotrophic lateral sclerosis (ALS). As with some forms of ALS, DM is associated with mutations in superoxide dismutase 1 (SOD1). Clinical signs include general proprioceptive ataxia and spastic upper motor neuron paresis in pelvic limbs, which progress to flaccid tetraplegia and dysphagia. The purpose of this study was to characterize DM as a potential disease model for ALS. We previously reported that intercostal muscle atrophy develops in dogs with advanced-stage DM. To determine whether other components of the thoracic motor unit (MU) also demonstrated morphological changes consistent with dysfunction, histopathologic and morphometric analyses were conducted on thoracic spinal motor neurons (MNs) and dorsal root ganglia (DRG) and in motor and sensory nerve root axons from DM-affected boxers and Pembroke Welsh corgis (PWCs). No alterations in MNs or motor root axons were observed in either breed. However, advanced-stage PWCs exhibited significant losses of sensory root axons, and numerous DRG sensory neurons displayed evidence of degeneration. These results indicate that intercostal muscle atrophy in DM is not preceded by physical loss of the motor neurons innervating these muscles, nor of their axons. Axonal loss in thoracic sensory roots and sensory neuron death suggest that sensory involvement may play an important role in DM disease progression. Further analysis of the mechanisms responsible for these morphological findings would aid in the development of therapeutic intervention for DM and some forms of ALS.

  13. KW-4679-induced inhibition of tachykininergic contraction in the guinea-pig bronchi by prejunctional inhibition of peripheral sensory nerves.

    PubMed Central

    Ikemura, T.; Okarmura, K.; Sasaki, Y.; Ishi, H.; Ohmori, K.

    1996-01-01

    scyllatoxin (300 nM). Apamin or scyllatoxin per se did not influence the slow phase contractions. 7. The results suggest that KW-4679 preferentially inhibits the release of tachykinins from the bronchial sensory nerves through activation of small conductance Ca(2+)-activated K+ channels. Images Figure 4 Figure 5 PMID:8851519

  14. Release of somatostatin and its role in the mediation of the anti-inflammatory effect induced by antidromic stimulation of sensory fibres of rat sciatic nerve.

    PubMed

    Szolcsányi, J; Helyes, Z; Oroszi, G; Németh, J; Pintér, E

    1998-03-01

    1. The effect of antidromic stimulation of the sensory fibres of the sciatic nerve on inflammatory plasma extravasation in various tissues and on cutaneous vasodilatation elicited in distant parts of the body was investigated in rats pretreated with guanethidine (8 mg kg(-1), i.p.) and pipecuronium (200 microg kg(-1), i.v.). 2. Antidromic sciatic nerve stimulation with C-fibre strength (20 V, 0.5 ms) at 5 Hz for 5 min elicited neurogenic inflammation in the innervated area and inhibited by 50.3 +/- 4.67% the development of a subsequent plasma extravasation in response to similar stimulation of the contralateral sciatic nerve. Stimulation at 0.5 Hz for 1 h also evoked local plasma extravasation and inhibited the carrageenin-induced (1%, 100 microl s.c.) cutaneous inflammation by 38.5 +/- 10.0% in the contralateral paw. Excitation at 0.1 Hz for 4 h elicited no local plasma extravasation in the stimulated hindleg but still reduced the carrageenin-induced oedema by 52.1 +/- 9.7% in the paw on the contralateral side. 3. Plasma extravasation in the knee joint in response to carrageenin (2%, 200 microl intra-articular injection) was diminished by 46.1 +/- 12.69% and 40.9 +/- 4.93% when the sciatic nerve was stimulated in the contralateral leg at 0.5 Hz for 1 h or 0.1 Hz for 4 h, respectively. 4. Stimulation of the peripheral stump of the left vagal nerve (20 V, 1 ms, 8 Hz, 10 min) elicited plasma extravasation in the trachea, oesophagus and mediastinal connective tissue in rats pretreated with atropine (2 mg kg(-1), i.v.), guanethidine (8 mg kg(-1), i.p.) and pipecuronium (200 microg kg(-1), i.v.). These responses were inhibited by 37.8 +/- 5.1%, 49.7 +/- 9.9% and 37.6 +/- 4.2%, respectively by antidromic sciatic nerve excitation (5 Hz, 5 min) applied 5 min earlier. 5. Pretreatment with polyclonal somatostatin antiserum (0.5 ml/rat, i.v.) or the selective somatostatin depleting agent cysteamine (280 mg kg(-1), s.c.) prevented the anti-inflammatory effect of sciatic nerve

  15. Exuberant sprouting of sensory and sympathetic nerve fibers in nonhealed bone fractures and the generation and maintenance of chronic skeletal pain

    PubMed Central

    Chartier, Stephane R.; Thompson, Michelle L.; Longo, Geraldine; Fealk, Michelle N.; Majuta, Lisa A.; Mantyh, Patrick W.

    2014-01-01

    Skeletal injury is a leading cause of chronic pain and long-term disability worldwide. While most acute skeletal pain can be effectively managed with nonsteroidal anti-inflammatory drugs and opiates, chronic skeletal pain is more difficult to control using these same therapy regimens. One possibility as to why chronic skeletal pain is more difficult to manage over time is that there may be nerve sprouting in non-healed areas of the skeleton that normally receive little (mineralized bone) to no (articular cartilage) innervation. If such ectopic sprouting did occur, it could result in normally nonnoxious loading of the skeleton being perceived as noxious and/or the generation of a neuropathic pain state. To explore this possibility, a mouse model of skeletal pain was generated by inducing a closed fracture of the femur. Examined animals had comminuted fractures and did not fully heal even at 90+ days post fracture. In all mice with nonhealed fractures, exuberant sensory and sympathetic nerve sprouting, an increase in the density of nerve fibers, and the formation of neuroma-like structures near the fracture site were observed. Additionally, all of these animals exhibited significant pain behaviors upon palpation of the nonhealed fracture site. In contrast, sprouting of sensory and sympathetic nerve fibers or significant palpation-induced pain behaviors was never observed in naïve animals. Understanding what drives this ectopic nerve sprouting and the role it plays in skeletal pain may allow a better understanding and treatment of this currently difficult-to-control pain state. PMID:25196264

  16. The contribution of sensory nerves to the onset threshold for cutaneous vasodilatation during gradual local skin heating of the forearm and leg.

    PubMed

    Hodges, Gary J; McGarr, Gregory W; Mallette, Matthew M; Del Pozzi, Andrew T; Cheung, Stephen S

    2016-05-01

    During local skin heating, the temporal onset of vasodilatation is delayed in the leg compared to the forearm, and sensory nerve blockade abolishes these differences. However, previous work using rapid skin heating did not allow for determination of sensory nerve influences on temperature thresholds for vasodilatation. Two sites were examined on both the forearm and leg, one control (CTRL), and one treated for sensory nerve blockade (EMLA). Skin blood flux was monitored using laser-Doppler probes, with heaters controlling local skin temperature (Tloc). Tloc was increased from 32-44 °C (+1 °C·10 min(-1)). Stimulus-response curves were constructed by fitting a four-parameter logistic function. EMLA significantly increased Tloc onset in the forearm (CTRL=35.3 ± 0.4 °C; EMLA=36.8 ± 0.7 °C) and leg (CTRL=36.5 ± 0.4 °C; EMLA=38.4 ± 0.5 °C; both P<0.05). At both CTRL and EMLA, Tloc onset was higher in the leg compared to the forearm (both P<0.05). In the forearm, median effective temperature to elicit 50% vasodilatation (ET50) was similar between sites (CTRL=39.7 ± 0.3 °C; EMLA=40.2 ± 0.4 °C; P=0.09); however, in the leg, EMLA significantly increased ET50 (CTRL=40.2 ± 0.3 °C; EMLA=41.0 ± 0.3 °C)(P<0.05). At CTRL sites, no limb difference was observed for ET50 (P=0.06); however, with EMLA, ET50 was significantly higher in the leg (P<0.05). EMLA significantly increased the gain of the slope at the forearm, (CTRL=0.31 ± 0.01%CVCmax·°C(-1); EMLA=0.45 ± 0.07%CVCmax·°C(-1)), and leg (CTRL=0.37 ± 0.05%CVCmax·°C(-1); EMLA=0.54 ± 0.04%CVCmax·°C(-1))(both P<0.05). At CTRL sites, the gain was significantly higher in the leg (P<0.05); however, for EMLA, no significant limb difference existed (P=0.10). These data indicate that the onset of vasodilatation occurs at a lower temperature in the forearm than the legs, and sensory nerves play an important role in both limbs.

  17. Evidence for the role of lipid rafts and sphingomyelin in Ca2+-gating of Transient Receptor Potential channels in trigeminal sensory neurons and peripheral nerve terminals.

    PubMed

    Sághy, Éva; Szőke, Éva; Payrits, Maja; Helyes, Zsuzsanna; Börzsei, Rita; Erostyák, János; Jánosi, Tibor Zoltán; Sétáló, György; Szolcsányi, János

    2015-10-01

    Transient Receptor Potential (TRP) cation channels, such as TRP Vanilloid 1 and TRP Ankyrin repeat domain 1 (TRPV1 and TRPA1) are nocisensors playing important role to signal pain. Two "melastatin" TRP receptors, like TRPM8 and TRPM3 are also expressed in a subgroup of primary sensory neurons. These channels serve as thermosensors with unique thermal sensitivity ranges and are activated also by several exogenous and endogenous chemical ligands inducing conformational changes from various allosteric ("multisteric") sites. We analysed the role of plasma membrane microdomains of lipid rafts on isolated trigeminal (TRG) neurons and TRPV1-expressing CHO cell line by measuring agonist-induced Ca2+ transients with ratiometric technique. Stimulation-evoked calcitonin gene related peptide (CGRP) release from sensory nerve endings of the isolated rat trachea by radioimmunoassay was also measured. Lipid rafts were disrupted by cleaving sphingomyelin (SM) with sphingomyelinase (SMase), cholesterol depletion with methyl β-cyclodextrin (MCD) and ganglioside breakdown with myriocin. It has been revealed that intracellular Ca2+ increase responses evoked by the TRPV1 agonist capsaicin, the TRPA1 agonsits allyl isothiocyanate (AITC) and formaldehyde as well as the TRPM8 activator icilin were inhibited after SMase, MCD and myriocin incubation but the response to the TRPM3 agonist pregnenolon sulphate was not altered. Extracellular SMase treatment did not influence the thapsigargin-evoked Ca2+-release from intracellular stores. Besides the cell bodies, SMase also inhibited capsaicin- or AITC-evoked CGRP release from peripheral sensory nerve terminals, this provides the first evidence for the importance of lipid raft integrity in TRPV1 and TRPA1 gating on capsaicin-sensitive nerve terminals. SM metabolites, ceramide and sphingosine, did not influence TRPA1 and TRPV1 activation on TRG neurons, TRPV1-expressing CHO cell line, and nerve terminals. We suggest, that the hydrophobic

  18. Primary Sensory and Motor Cortex Excitability Are Co-Modulated in Response to Peripheral Electrical Nerve Stimulation

    PubMed Central

    Schabrun, Siobhan M.; Ridding, Michael C.; Galea, Mary P.; Hodges, Paul W.; Chipchase, Lucinda S.

    2012-01-01

    Peripheral electrical stimulation (PES) is a common clinical technique known to induce changes in corticomotor excitability; PES applied to induce a tetanic motor contraction increases, and PES at sub-motor threshold (sensory) intensities decreases, corticomotor excitability. Understanding of the mechanisms underlying these opposite changes in corticomotor excitability remains elusive. Modulation of primary sensory cortex (S1) excitability could underlie altered corticomotor excitability with PES. Here we examined whether changes in primary sensory (S1) and motor (M1) cortex excitability follow the same time-course when PES is applied using identical stimulus parameters. Corticomotor excitability was measured using transcranial magnetic stimulation (TMS) and sensory cortex excitability using somatosensory evoked potentials (SEPs) before and after 30 min of PES to right abductor pollicis brevis (APB). Two PES paradigms were tested in separate sessions; PES sufficient to induce a tetanic motor contraction (30–50 Hz; strong motor intensity) and PES at sub motor-threshold intensity (100 Hz). PES applied to induce strong activation of APB increased the size of the N20-P25 component, thought to reflect sensory processing at cortical level, and increased corticomotor excitability. PES at sensory intensity decreased the size of the P25-N33 component and reduced corticomotor excitability. A positive correlation was observed between the changes in amplitude of the cortical SEP components and corticomotor excitability following sensory and motor PES. Sensory PES also increased the sub-cortical P14-N20 SEP component. These findings provide evidence that PES results in co-modulation of S1 and M1 excitability, possibly due to cortico-cortical projections between S1 and M1. This mechanism may underpin changes in corticomotor excitability in response to afferent input generated by PES. PMID:23227260

  19. Primary sensory and motor cortex excitability are co-modulated in response to peripheral electrical nerve stimulation.

    PubMed

    Schabrun, Siobhan M; Ridding, Michael C; Galea, Mary P; Hodges, Paul W; Chipchase, Lucinda S

    2012-01-01

    Peripheral electrical stimulation (PES) is a common clinical technique known to induce changes in corticomotor excitability; PES applied to induce a tetanic motor contraction increases, and PES at sub-motor threshold (sensory) intensities decreases, corticomotor excitability. Understanding of the mechanisms underlying these opposite changes in corticomotor excitability remains elusive. Modulation of primary sensory cortex (S1) excitability could underlie altered corticomotor excitability with PES. Here we examined whether changes in primary sensory (S1) and motor (M1) cortex excitability follow the same time-course when PES is applied using identical stimulus parameters. Corticomotor excitability was measured using transcranial magnetic stimulation (TMS) and sensory cortex excitability using somatosensory evoked potentials (SEPs) before and after 30 min of PES to right abductor pollicis brevis (APB). Two PES paradigms were tested in separate sessions; PES sufficient to induce a tetanic motor contraction (30-50 Hz; strong motor intensity) and PES at sub motor-threshold intensity (100 Hz). PES applied to induce strong activation of APB increased the size of the N(20)-P(25) component, thought to reflect sensory processing at cortical level, and increased corticomotor excitability. PES at sensory intensity decreased the size of the P25-N33 component and reduced corticomotor excitability. A positive correlation was observed between the changes in amplitude of the cortical SEP components and corticomotor excitability following sensory and motor PES. Sensory PES also increased the sub-cortical P(14)-N(20) SEP component. These findings provide evidence that PES results in co-modulation of S1 and M1 excitability, possibly due to cortico-cortical projections between S1 and M1. This mechanism may underpin changes in corticomotor excitability in response to afferent input generated by PES.

  20. Capsaicin-Sensitive Sensory Nerves Mediate the Cellular and Microvascular Effects of H2S via TRPA1 Receptor Activation and Neuropeptide Release.

    PubMed

    Hajna, Zsófia; Sághy, Éva; Payrits, Maja; Aubdool, Aisah A; Szőke, Éva; Pozsgai, Gábor; Bátai, István Z; Nagy, Lívia; Filotás, Dániel; Helyes, Zsuzsanna; Brain, Susan D; Pintér, Erika

    2016-10-01

    It is supposed that TRPA1 receptor can be activated by hydrogen sulphide (H2S). Here, we have investigated the role of TRPA1 receptor in H2S-induced [Ca(2+)]i increase in trigeminal ganglia (TRG) neurons, and the involvement of capsaicin-sensitive sensory nerves in H2S-evoked cutaneous vasodilatation. [Ca(2+)]i was measured with ratiometric technique on TRG neurons of TRPA1(+/+) and TRPA1(-/-) mice after NaHS, Na2S, allylisothiocyanate (AITC) or KCl treatment. Microcirculatory changes in the ear were detected by laser Doppler imaging in response to topical NaHS, AITC, NaOH, NaSO3 or NaCl. Mice were either treated with resiniferatoxin (RTX), or CGRP antagonist BIBN4096, or NK1 receptor antagonist CP99994, or K(+) ATP channel blocker glibenclamide. Alpha-CGRP(-/-) and NK1 (-/-) mice were also investigated. NaHS and Na2S increased [Ca(2+)]i in TRG neurons derived from TRPA(+/+) but not from TRPA1(-/-) mice. NaHS increased cutaneous blood flow, while NaOH, NaSO3 and NaCl did not cause significant changes. NaHS-induced vasodilatation was reduced in RTX-treated animals, as well as by pre-treatment with BIBN4096 or CP99994 alone or in combination. NaHS-induced vasodilatation was significantly smaller in alpha-CGRP(-/-) or NK1 (-/-) mice compared to wild-types. H2S activates capsaicin-sensitive sensory nerves through TRPA1 receptors and the resultant vasodilatation is mediated by the release of vasoactive sensory neuropeptides CGRP and substance P.

  1. Desensitization to antibiotics in children.

    PubMed

    Cernadas, Josefina R

    2013-02-01

    Drug hypersensitivity reactions can occur to almost all drugs and antibiotics are among the most common cause for this kind of reactions. Drug hypersensitivity may affect any organ or system, and manifestations range widely in clinical severity from mild pruritus to anaphylaxis. In most cases, the suspected drug is avoided in the future. In case of infection, there is usually a safe antibiotic alternative. Nonetheless, in some cases, no alternative treatment exists for optimal therapy. Under these circumstances, desensitization may be performed. Drug desensitization is defined as the induction of a temporary state of tolerance to a drug which can only be maintained by continuous administration of the medication responsible for the hypersensitivity reaction. Desensitization is mainly performed in IgE-mediated reactions. Increasing doses of the implicated drug are administered over a short period of time, until the therapeutic dose is achieved and tolerated. Very few studies confined to children are found in literature. Most of them are case reports. In general, the proposed desensitization schemes are similar to those used in adults differing only in the final dose administered. The purpose of this study is to review desensitization to antibiotics in children presenting and discussing three clinical practical cases of desensitization in this age group.

  2. Desensitization properties of P2X3 receptors shaping pain signaling

    PubMed Central

    Giniatullin, Rashid; Nistri, Andrea

    2013-01-01

    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

  3. Genetics Home Reference: hereditary sensory and autonomic neuropathy type V

    MedlinePlus

    ... that primarily affects the sensory nerve cells (sensory neurons), which transmit information about sensations such as pain, ... in the development and survival of nerve cells (neurons), including sensory neurons. The NGFβ protein functions by ...

  4. Crotalphine desensitizes TRPA1 ion channels to alleviate inflammatory hyperalgesia.

    PubMed

    Bressan, Elisangela; Touska, Filip; Vetter, Irina; Kistner, Katrin; Kichko, Tatjana I; Teixeira, Nathália B; Picolo, Gisele; Cury, Yara; Lewis, Richard J; Fischer, Michael J M; Zimmermann, Katharina; Reeh, Peter W

    2016-11-01

    Crotalphine is a structural analogue to a novel analgesic peptide that was first identified in the crude venom from the South American rattlesnake Crotalus durissus terrificus. Although crotalphine's analgesic effect is well established, its direct mechanism of action remains unresolved. The aim of the present study was to investigate the effect of crotalphine on ion channels in peripheral pain pathways. We found that picomolar concentrations of crotalphine selectively activate heterologously expressed and native TRPA1 ion channels. TRPA1 activation by crotalphine required intact N-terminal cysteine residues and was followed by strong and long-lasting desensitization of the channel. Homologous desensitization of recombinant TRPA1 and heterologous desensitization in cultured dorsal root ganglia neurons was observed. Likewise, crotalphine acted on peptidergic TRPA1-expressing nerve endings ex vivo as demonstrated by suppression of calcitonin gene-related peptide release from the trachea and in vivo by inhibition of chemically induced and inflammatory hypersensitivity in mice. The crotalphine-mediated desensitizing effect was abolished by the TRPA1 blocker HC030031 and absent in TRPA1-deficient mice. Taken together, these results suggest that crotalphine is the first peptide to mediate antinociception selectively and at subnanomolar concentrations by targeting TRPA1 ion channels.

  5. Sciatic nerve injury in adult rats causes distinct changes in the central projections of sensory neurons expressing different glial cell line-derived neurotrophic factor family receptors

    PubMed Central

    Keast, Janet R.; Forrest, Shelley L.; Osborne, Peregrine B.

    2010-01-01

    Most small unmyelinated neurons in adult rat dorsal ganglia (DRG) express one or more of the co-receptors targeted by glial cell line-derived neurotrophic factor (GDNF), neurturin and artemin (GFRα1, GFRα2 and GFRα3 respectively). The function of these GDNF family ligands (GFLs) is not fully elucidated but recent evidence suggests GFLs could function in sensory neuron regeneration after nerve injury and peripheral nociceptor sensitisation. In this study, we used immunohistochemistry to determine if the DRG neurons targeted by each GFL change after sciatic nerve injury. We compared complete sciatic nerve transection and the chronic constriction model and found the pattern of changes incurred by each injury was broadly similar. In lumbar spinal cord, there was a widespread increase in neuronal GFRα1 immunoreactivity (IR) in the L1-6 dorsal horn. GFRα3-IR also increased but in a more restricted area. In contrast, GFRα2-IR decreased in patches of superficial dorsal horn and this loss was more extensive after transection injury. No change in calcitonin gene-related peptide-IR was detected after either injury. Analysis of double-immunolabelled L5 DRG sections suggested the main effect of injury on GFRα1- and GFRα3-IR was to increase expression in both myelinated and unmyelinated neurons. In contrast, no change in basal expression of GFRα2-IR was detected in DRG by analysis of fluorescence intensity and there was a small but significant reduction in GFRα2-IR neurons. Our results suggest the DRG neuronal populations targeted by GDNF, neurturin or artemin, and the effect of exogenous GFLs could change significantly after a peripheral nerve injury. PMID:20533358

  6. Motor and sensory re-innervation of the lung and heart after re-anastomosis of the cervical vagus nerve in rats

    PubMed Central

    Bregeon, Fabienne; Alliez, Jean Roch; Héry, Géraldine; Marqueste, Tanguy; Ravailhe, Sylvie; Jammes, Yves

    2007-01-01

    There is no study in the literature dealing with re-innervation of the cardiopulmonary vagus nerve after its transection followed by re-anastomosis. In the present study, we explored the bronchomotor, heart rate and respiratory responses in rats at 2, 3 and 6 months after re-anastomosis of one cervical vagus trunk. The conduction velocity of A, B and C waves was calculated in the compound vagal action potential. We searched for afferent vagal activities in phase with pulmonary inflation to assess the persistence of pulmonary stretch receptor (PSR) discharge in re-innervated lungs. In each animal, data from the stimulation or recording of one re-anastomosed vagus nerve were compared with those obtained in the contra-lateral intact one. Two and three months after surgery, the conduction velocities of A and B waves decreased, but recovery of conduction velocity was complete at 6 months. By contrast, the conduction velocity of the C wave did not change until 6 months, when it was doubled. The PSR activity was present in 50% of re-anastomosed vagus nerves at 2 and 3 months and in 75% at 6 months. Respiratory inhibition evoked by vagal stimulation was significantly weaker from the re-anastomosed than intact nerve at 2 but not 3 months. Vagal stimulation did not elicit cardiac slowing or bronchoconstriction 6 months after re-anastomosis. Our study demonstrates the capacity of pulmonary vagal sensory neurones to regenerate after axotomy followed by re-anastomosis, and the failure of the vagal efferents to re-innervate both the lungs and heart. PMID:17430986

  7. Restoring motor control and sensory feedback in people with upper extremity amputations using arrays of 96 microelectrodes implanted in the median and ulnar nerves

    NASA Astrophysics Data System (ADS)

    Davis, T. S.; Wark, H. A. C.; Hutchinson, D. T.; Warren, D. J.; O'Neill, K.; Scheinblum, T.; Clark, G. A.; Normann, R. A.; Greger, B.

    2016-06-01

    Objective. An important goal of neuroprosthetic research is to establish bidirectional communication between the user and new prosthetic limbs that are capable of controlling >20 different movements. One strategy for achieving this goal is to interface the prosthetic limb directly with efferent and afferent fibres in the peripheral nervous system using an array of intrafascicular microelectrodes. This approach would provide access to a large number of independent neural pathways for controlling high degree-of-freedom prosthetic limbs, as well as evoking multiple-complex sensory percepts. Approach. Utah Slanted Electrode Arrays (USEAs, 96 recording/stimulating electrodes) were implanted for 30 days into the median (Subject 1-M, 31 years post-amputation) or ulnar (Subject 2-U, 1.5 years post-amputation) nerves of two amputees. Neural activity was recorded during intended movements of the subject’s phantom fingers and a linear Kalman filter was used to decode the neural data. Microelectrode stimulation of varying amplitudes and frequencies was delivered via single or multiple electrodes to investigate the number, size and quality of sensory percepts that could be evoked. Device performance over time was assessed by measuring: electrode impedances, signal-to-noise ratios (SNRs), stimulation thresholds, number and stability of evoked percepts. Main results. The subjects were able to proportionally, control individual fingers of a virtual robotic hand, with 13 different movements decoded offline (r = 0.48) and two movements decoded online. Electrical stimulation across one USEA evoked >80 sensory percepts. Varying the stimulation parameters modulated percept quality. Devices remained intrafascicularly implanted for the duration of the study with no significant changes in the SNRs or percept thresholds. Significance. This study demonstrated that an array of 96 microelectrodes can be implanted into the human peripheral nervous system for up to 1 month durations. Such an

  8. Comparison of sensory tests and neuronal quantity of peripheral nerves between streptozotocin (STZ)-induced diabetic rats and paclitaxel (PAC)-treated rats.

    PubMed

    Jin, Heung Yong; Lee, Na Young; Ko, Hyun A; Lee, Kyung Ae; Park, Tae Sun

    Although diabetic peripheral neuropathy (DPN) and chemotherapy-induced peripheral neuropathy (CIPN) are different disease entities, they share similar neuropathic symptoms that impede quality of life for these patients. Despite having very similar downstream effects, there have been no direct comparisons between DPN and CIPN with respect to symptom severity and therapeutic responses. We compared peripheral nerve damage due to hyperglycemia with that caused by paclitaxel (PAC) treatment as represented by biochemical parameters, diverse sensory tests, and immunohistochemistry of cutaneous and sciatic nerves. The therapeutic effects of alpha-lipoic acid and DA-9801 were also compared in the two models. Animals were divided into seven groups (n = 7-10) as follows: normal, diabetes (DM), DM + alpha-lipoic acid 100 mg/kg (ALA), DM + DA-9801 (100 mg/kg), paclitaxel-treated rat (PAC), PAC + ALA (100 mg/kg), and PAC + DA-9801 (100 mg/kg). The sensory thresholds of animals to mechanical, heat, and pressure stimuli were altered by both hyperglycemia and PAC when compared with controls, and the responses to sensory tests were different between both groups. There were no significant differences in the biochemical markers of blood glutathione between DM and PAC groups (p > .05). Quantitative comparisons of peripheral nerves by intraepidermal nerve fiber density (IENFD) analysis indicated that the DM and PAC groups were similar (6.18 ± 1.03 vs. 5.01 ± 2.57). IENFD was significantly improved after ALA and DA-9801 treatment in diabetic animals (7.6 ± 1.28, 7.7 ± 1.28, respectively, p < .05) but did not reach significance in the PAC-treated groups (6.05 ± 1.76, 5.66 ± 1.26, respectively, p > .05). Sciatic nerves were less damaged in the PAC-treated groups compared with the DM groups with respect to axonal diameter and area (8.60 ± 1.14 μm vs. 6.66 ± 1.07 μm, and 59.04 ± 15.16 μm(2) vs. 35

  9. Dysregulation of the Descending Pain System in Temporomandibular Disorders Revealed by Low-Frequency Sensory Transcutaneous Electrical Nerve Stimulation: A Pupillometric Study

    PubMed Central

    Monaco, Annalisa; Cattaneo, Ruggero; Mesin, Luca; Ortu, Eleonora; Giannoni, Mario; Pietropaoli, Davide

    2015-01-01

    Using computerized pupillometry, our previous research established that the autonomic nervous system (ANS) is dysregulated in patients suffering from temporomandibular disorders (TMDs), suggesting a potential role for ANS dysfunction in pain modulation and the etiology of TMD. However, pain modulation hypotheses for TMD are still lacking. The periaqueductal gray (PAG) is involved in the descending modulation of defensive behavior and pain through μ, κ, and δ opioid receptors. Transcutaneous electrical nerve stimulation (TENS) has been extensively used for pain relief, as low-frequency stimulation can activate µ receptors. Our aim was to use pupillometry to evaluate the effect of low-frequency TENS stimulation of μ receptors on opioid descending pathways in TMD patients. In accordance with the Research Diagnostic Criteria for TMD, 18 females with myogenous TMD and 18 matched-controls were enrolled. All subjects underwent subsequent pupillometric evaluations under dark and light conditions before, soon after (end of stimulation) and long after (recovery period) sensorial TENS. The overall statistics derived from the darkness condition revealed no significant differences in pupil size between cases and controls; indeed, TENS stimulation significantly reduced pupil size in both groups. Controls, but not TMD patients, displayed significant differences in pupil size before compared with after TENS. Under light conditions, TMD patients presented a smaller pupil size compared with controls; the pupil size was reduced only in the controls. Pupil size differences were found before and during TENS and before and after TENS in the controls only. Pupillometry revealed that stimulating the descending opioid pathway with low-frequency sensory TENS of the fifth and seventh pairs of cranial nerves affects the peripheral target. The TMD patients exhibited a different pattern of response to TENS stimulation compared with the controls, suggesting that impaired modulation of the

  10. Dysregulation of the descending pain system in temporomandibular disorders revealed by low-frequency sensory transcutaneous electrical nerve stimulation: a pupillometric study.

    PubMed

    Monaco, Annalisa; Cattaneo, Ruggero; Mesin, Luca; Ortu, Eleonora; Giannoni, Mario; Pietropaoli, Davide

    2015-01-01

    Using computerized pupillometry, our previous research established that the autonomic nervous system (ANS) is dysregulated in patients suffering from temporomandibular disorders (TMDs), suggesting a potential role for ANS dysfunction in pain modulation and the etiology of TMD. However, pain modulation hypotheses for TMD are still lacking. The periaqueductal gray (PAG) is involved in the descending modulation of defensive behavior and pain through μ, κ, and δ opioid receptors. Transcutaneous electrical nerve stimulation (TENS) has been extensively used for pain relief, as low-frequency stimulation can activate µ receptors. Our aim was to use pupillometry to evaluate the effect of low-frequency TENS stimulation of μ receptors on opioid descending pathways in TMD patients. In accordance with the Research Diagnostic Criteria for TMD, 18 females with myogenous TMD and 18 matched-controls were enrolled. All subjects underwent subsequent pupillometric evaluations under dark and light conditions before, soon after (end of stimulation) and long after (recovery period) sensorial TENS. The overall statistics derived from the darkness condition revealed no significant differences in pupil size between cases and controls; indeed, TENS stimulation significantly reduced pupil size in both groups. Controls, but not TMD patients, displayed significant differences in pupil size before compared with after TENS. Under light conditions, TMD patients presented a smaller pupil size compared with controls; the pupil size was reduced only in the controls. Pupil size differences were found before and during TENS and before and after TENS in the controls only. Pupillometry revealed that stimulating the descending opioid pathway with low-frequency sensory TENS of the fifth and seventh pairs of cranial nerves affects the peripheral target. The TMD patients exhibited a different pattern of response to TENS stimulation compared with the controls, suggesting that impaired modulation of the

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

    PubMed

    Witherspoon, J W; Smirnova, I V; McIff, T E

    2014-07-01

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

  12. Implementing a Systematic Desensitization Laboratory.

    ERIC Educational Resources Information Center

    Ralph, David C.; Goss, Blaine

    A systematic desensitization therapy program to reduce anxiety in speakers has been developed and implemented at Michigan State University for those students in basic speech courses who have been identified by "The Personal Report of Communication Apprehension" (PRCA) as having severe speech anxiety and thus being in need of Systematic…

  13. Desensitization of metastable intermolecular composites

    SciTech Connect

    Busse, James R.; Dye, Robert C.; Foley, Timothy J.; Higa, Kelvin T.; Jorgensen, Betty S.; Sanders, Victor E.; Son, Steven F.

    2011-04-26

    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.

  14. Nerve growth factor acts through the TrkA receptor to protect sensory neurons from the damaging effects of the HIV-1 viral protein, Vpr.

    PubMed

    Webber, C A; Salame, J; Luu, G-L S; Acharjee, S; Ruangkittisakul, A; Martinez, J A; Jalali, H; Watts, R; Ballanyi, K; Guo, G F; Zochodne, D W; Power, C

    2013-11-12

    Distal sensory polyneuropathy (DSP) with associated neuropathic pain is the most common neurological disorder affecting patients with human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS). Viral protein R (Vpr) is a neurotoxic protein encoded by HIV-1 and secreted by infected macrophages. Vpr reduces neuronal viability, increases cytosolic calcium and membrane excitability of cultured dorsal root ganglion (DRG) sensory neurons, and is associated with mechanical allodynia in vivo. A clinical trial with HIV/AIDS patients demonstrated that nerve growth factor (NGF) reduced the severity of DSP-associated neuropathic pain, a problem linked to damage to small diameter, potentially NGF-responsive fibers. Herein, the actions of NGF were investigated in our Vpr model of DSP and we demonstrated that NGF significantly protected sensory neurons from the effects of Vpr. Footpads of immunodeficient Vpr transgenic (vpr/RAG1(-/-)) mice displayed allodynia (p<0.05), diminished epidermalinnervation (p<0.01) and reduced NGF mRNA expression (p<0.001) compared to immunodeficient (wildtype/RAG1(-/-)) littermate control mice. Compartmented cultures confirmed recombinant Vpr exposure to the DRG neuronal perikarya decreased distal neurite extension (p<0.01), whereas NGF exposure at these distal axons protected the DRG neurons from the Vpr-induced effect on their cell bodies. NGF prevented Vpr-induced attenuation of the phosphorylated glycogen synthase-3 axon extension pathway and tropomyosin-related kinase A (TrkA) receptor expression in DRG neurons (p<0.05) and it directly counteracted the cytosolic calcium burst caused by Vpr exposure to DRG neurons (p<0.01). TrkA receptor agonist indicated that NGFacted through the TrkA receptor to block the Vpr-mediated decrease in axon outgrowth in neonatal and adult rat and fetal human DRG neurons (p<0.05). Similarly, inhibiting the lower affinity NGF receptor, p75, blocked Vpr's effect on DRG neurons. Overall, NGF/TrkA signaling

  15. Nerve growth factor acts through the TrkA receptor to protect sensory neurons from the damaging effects of the HIV-1 viral protein, Vpr

    PubMed Central

    Webber, Christine A.; Salame, Jihan; Luu, Gia-Linh S.; Acharjee, Shaona; Ruangkittisakul, Araya; Martinez, Jose A.; Jalali, Hanieh; Watts, Russell; Ballanyi, Klaus; Guo, Gui Fang; Zochodne, Douglas W.; Power, Christopher

    2013-01-01

    Distal sensory polyneuropathy (DSP) with associated neuropathic pain is the most common neurological disorder affecting patients with human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS). Viral protein R (Vpr) is a neurotoxic protein encoded by HIV-1 and secreted by infected macrophages. Vpr reduces neuronal viability, increases cytosolic calcium and membrane excitability of cultured dorsal root ganglion (DRG) sensory neurons, and is associated with mechanical allodynia in vivo. A clinical trial with HIV/AIDS patients demonstrated that nerve growth factor (NGF) reduced the severity of DSP-associated neuropathic pain, a problem linked to damage to small diameter, potentially NGF responsive fibers. Herein, the actions of NGF were investigated in our Vpr model of DSP and we demonstrated that NGF significantly protected sensory neurons from the effects of Vpr. Footpads of immunodeficient Vpr transgenic (vpr/RAG1−/−) mice displayed allodynia (p<0.05), diminished epidermal innervation (p<0.01) and reduced NGF mRNA expression (p<0.001) compared to immunodeficient (wildtype/RAG1−/−) littermate control mice. Compartmented cultures confirmed recombinant Vpr exposure to the DRG neuronal perikarya decreased distal neurite extension (p<0.01), whereas NGF exposure at these distal axons protected the DRG neurons from the Vpr-induced effect on their cell bodies. NGF prevented Vpr-induced attenuation of the phosphorylated glycogen synthase-3 axon extension pathway and tropomyosin related kinase A (TrkA) receptor expression in DRG neurons (p<0.05) and it directly counteracted the cytosolic calcium burst caused by Vpr exposure to DRG neurons (p<0.01). TrkA receptor antagonists indicated that NGF acted through the TrkA receptor to block the Vpr-mediated decrease in axon outgrowth in neonatal and adult rat and fetal human DRG neurons (p<0.05). Similarly, inhibiting the lower affinity NGF receptor, p75, blocked Vpr’s effect on DRG neurons. Overall, NGF

  16. Importance of the pineal gland, endogenous prostaglandins and sensory nerves in the gastroprotective actions of central and peripheral melatonin against stress-induced damage.

    PubMed

    Brzozowski, Tomasz; Konturek, Peter C; Zwirska-Korczala, Krystyna; Konturek, Stanislaw J; Brzozowska, Iwona; Drozdowicz, Danuta; Sliwowski, Zbigniew; Pawlik, Michal; Pawlik, Wieslaw W; Hahn, Eckhart G

    2005-11-01

    Melatonin attenuates acute gastric lesions induced by topical strong irritants because of scavenging of free radicals, but its role in the pathogenesis of stress-induced gastric lesions has been sparingly investigated. In this study we compared the effects of intragastric (i.g.) or intracerebroventricular (i.c.v.) administration of melatonin and its precursor, L-tryptophan, with or without concurrent treatment with luzindole, a selective antagonist of melatonin MT2 receptors, on gastric lesions induced by water immersion and restraint stress (WRS). The involvement of pineal gland, endogenous prostaglandins (PG) and sensory nerves in gastroprotective action of melatonin and L-tryptophan against WRS was studied in intact or pinealectomized rats or those treated with indomethacin or rofecoxib to suppress cyclooxygenase (COX)-1 and COX-2, respectively, and with capsaicin to induce functional ablation of the sensory nerves. In addition, the influence of i.c.v. and i.g. melatonin on gastric secretion was tested in a separate group of rats equipped with gastric fistulas. At 3.5 hr after the end of WRS, the number of gastric lesions was counted, the gastric blood flow (GBF) was determined by H2-gas clearance technique and plasma melatonin and gastrin levels were measured by specific radioimmunoassay (RIA). Biopsy mucosal samples were taken for determination of expression of mRNA for COX-1 and COX-2 by reverse transcriptase-polymerase chain reaction (RT-PCR) and of the mucosal generation of prostaglandin E2 (PGE2) by RIA. Melatonin applied i.g. (1.25-10 mg/kg) or i.c.v. (1.25-10 microg/kg) dose-dependently inhibited gastric acid secretion and significantly attenuated the WRS-induced gastric damage. This protective effect of melatonin was accompanied by a significant rise in the GBF and plasma melatonin and gastrin levels and in mucosal generation of PGE2. Pinealectomy, which suppressed plasma melatonin levels, aggravated the gastric lesions induced by WRS and these effects

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

    PubMed Central

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

    2014-01-01

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

  18. Comparison of skin barrier function and sensory nerve electric current perception threshold between IgE-high extrinsic and IgE-normal intrinsic types of atopic dermatitis.

    PubMed

    Mori, T; Ishida, K; Mukumoto, S; Yamada, Y; Imokawa, G; Kabashima, K; Kobayashi, M; Bito, T; Nakamura, M; Ogasawara, K; Tokura, Y

    2010-01-01

    Background Two types of atopic dermatitis (AD) have been proposed, with different pathophysiological mechanisms underlying this seemingly heterogeneous disorder. The extrinsic type shows high IgE levels presumably as a consequence of skin barrier damage and feasible allergen permeation, whereas the intrinsic type exhibits normal IgE levels and is not mediated by allergen-specific IgE. Objectives To investigate the relationship between pruritus perception threshold and skin barrier function of patients with AD in a comparison between the extrinsic and intrinsic types. Methods Enrolled in this study were 32 patients with extrinsic AD, 17 with intrinsic AD and 24 healthy individuals. The barrier function of the stratum corneum was assessed by skin surface hydration and transepidermal water loss (TEWL), and pruritus perception was evaluated by the electric current perception threshold (CPT) of sensory nerves upon neuroselective transcutaneous electric stimulation. Results Skin surface hydration was significantly lower and TEWL was significantly higher in extrinsic AD than intrinsic AD or normal controls. Although there was no statistically significant difference in CPT among extrinsic AD, intrinsic AD and normal controls, CPT was significantly correlated with skin surface hydration and inversely with TEWL in intrinsic AD and normal controls, but not extrinsic AD. Finally, CPT was correlated with the visual analogue scale of itch in the nonlesional skin of patients with extrinsic but not intrinsic AD. Conclusions Patients with extrinsic AD have an impaired barrier, which increases the pre-existing pruritus but rather decreases sensitivity to external stimuli. In contrast, patients with intrinsic AD retain a normal barrier function and sensory reactivity to external pruritic stimuli.

  19. Nerve growth factor-tyrosine kinase A pathway is involved in thermoregulation and adaptation to stress: studies on patients with hereditary sensory and autonomic neuropathy type IV.

    PubMed

    Loewenthal, Neta; Levy, Jacov; Schreiber, Ruth; Pinsk, Vered; Perry, Zvi; Shorer, Zamir; Hershkovitz, Eli

    2005-04-01

    Hereditary sensory and autonomic neuropathy type IV (HSAN IV) is caused by mutations in the tyrosin kinase A (TrkA) gene, encoding for the high-affinity receptor of nerve growth factor (NGF). The NGF-TrkA system is expressed in many endocrine glands. We hypothesized that HSAN IV represents a natural model for impaired NGF effect on the neuroendocrine system in humans. We have documented the clinical outcome of 31 HSAN IV patients in a single medical center, and investigated their basal endocrine system status. The endocrine system response to thirst was compared between six patients and six healthy children. High rates of mortality (22%) and severe morbidity (30%) have been found in HSAN IV patients. Hypothermia was noted in 40% of the patients and unexplained fever was observed in 56%. Subnormal adrenal function was demonstrated in six (30%) of the patients studied. Furthermore, we found lower plasma norepinephrine (NE) levels in six HSAN IV patients compared with a control group after the thirst test. Our findings emphasize the importance of NGF-TrkA pathway in the physiology of the neuroendocrine system and its response to stress. Inadequate response to stress might contribute to the observed significant mortality, morbidity, and temperature instability in HSAN IV patients.

  20. Nerve growth factor derivative NGF61/100 promotes outgrowth of primary sensory neurons with reduced signs of nociceptive sensitization.

    PubMed

    Severini, C; Petrocchi Passeri, P; Ciotti, M T; Florenzano, F; Petrella, C; Malerba, F; Bruni, B; D'Onofrio, M; Arisi, I; Brandi, R; Possenti, R; Calissano, P; Cattaneo, A

    2017-02-02

    Nerve Growth Factor (NGF) is being considered as a therapeutic candidate for Alzheimer's disease. However, the development of an NGF-based therapy is limited by its potent pain activity. We have developed a "painless" derivative form of human NGF (NGF61/100), characterized by identical neurotrophic properties but a reduced nociceptive sensitization activity in vivo. Here we characterized the response of rat dorsal root ganglia neurons (DRG) to the NGF derivative NGF61/100, in comparison to that of control NGF (NGF61), analyzing the expression of noxious pro-nociceptive mediators. NGF61/100 displays a neurotrophic activity on DRG neurons comparable to that of control NGF61, despite a reduced activation of PLCγ, Akt and Erk1/2. NGF61/100 does not differ from NGF61 in its ability to up-regulate Substance P (SP) and Calcitonin Gene Related Peptide (CGRP) expression. However, upon Bradykinin (BK) stimulation, NGF61/100-treated DRG neurons release a much lower amount of SP and CGRP, compared to control NGF61 pre-treated neurons. This effect of painless NGF is explained by the reduced up-regulation of BK receptor 2 (B2R), respect to control NGF61. As a consequence, BK treatment reduced phosphorylation of the transient receptor channel subfamily V member 1 (TRPV1) in NGF61/100-treated cultures and induced a significantly lower intracellular Ca(2+) mobilization, responsible for the lower release of noxious mediators. Transcriptomic analysis of DRG neurons treated with NGF61/100 or control NGF allowed identifying a small number of nociceptive-related genes that constitute an "NGF pain fingerprint", whose differential regulation by NGF61/100 provides a strong mechanistic basis for its selective reduced pain sensitizing actions.

  1. SUSTAINED BLOCKADE OF NEUROTROPHIN RECEPTORS TrkA, TrkB AND TrkC REDUCES NON-MALIGNANT SKELETAL PAIN BUT NOT THE MAINTENANCE OF SENSORY AND SYMPATHETIC NERVE FIBERS

    PubMed Central

    Ghilardi, Joseph R.; Freeman, Katie T.; Jimenez-Andrade, Juan M.; Mantyh, William G.; Bloom, Aaron P.; Bouhana, Karyn S.; Trollinger, David; Winkler, James; Lee, Patrice; Andrews, Steven W.; Kuskowski, Michael A.; Mantyh, Patrick W.

    2010-01-01

    Current therapies for treating skeletal pain have significant limitations as available drugs (nonsteroidal anti-inflammatory drugs and opiates) have significant unwanted side effects. Targeting nerve growth factor or it's cognate receptor Tropomysin receptor kinase A (TrkA) has recently become an attractive target for inhibition of adult skeletal pain. Here we explore whether sustained administration of a selective small molecule Trk inhibitor that blocks TrkA, TrkB and TrkC kinase activity with nanomolar affinity reduces skeletal pain while allowing the maintenance of sensory and sympathetic neurons in the adult mouse. Twice-daily administration of a Trk inhibitor was begun 1 day post fracture and within 8 hours of acute administration fracture pain related behaviors were reduced by 50% without significant sedation, weight gain or inhibition of fracture healing. Following administration of the Trk inhibitor for 7 weeks, there was no significant decline in the density of unmyelinated, myelinated sensory or sympathetic nerve fibers, measures of acute thermal pain, acute mechanical pain, or general neuromuscular function. The present results suggest that sustained administration of a peripherally selective TrkA, B & C inhibitor significantly reduces skeletal pain without having any obvious detrimental effects on adult sensory and sympathetic nerve fibers or early fracture healing. As with any potential therapeutic advance, understanding whether the benefits of NGF blockade by ARRY-470 are associated with any risks or unexpected effects will be required to fully appreciate the patient populations that may benefit from this therapy. PMID:20854944

  2. Cadaveric nerve allotransplantation in the treatment of persistent thoracic neuralgia.

    PubMed

    Barbour, John R; Yee, Andrew; Moore, Amy M; Trulock, Elbert P; Buchowski, Jacob M; Mackinnon, Susan E

    2015-04-01

    When relief from neuralgia cannot be achieved with traditional methods, neurectomy may be considered to abate the stimulus, and primary opposition of the terminal nerve ending is recommended to prevent neuroma. Nerve repair with autograft is limited by autologous nerves available for large nerve defects. Cadaveric allografts provide an unlimited graft source without donor-site morbidities, but are rapidly rejected unless appropriate immunosuppression is achieved. An optimal treatment method for nerve allograft transplantation would minimize rejection while simultaneously permitting nerve regeneration. This report details a novel experience of nerve allograft transplantation using cadaveric nerve grafts to desensitize persistent postoperative thoracic neuralgia.

  3. Endogenous Opiate System and Systematic Desensitization.

    ERIC Educational Resources Information Center

    Egan, Kelly J.; And Others

    1988-01-01

    Administered intravenous infusions to phobic patients prior to systematic desensitization. Saline-infused subjects significantly demonstrated the predicted symptom decrease in response to systematic desensitization, whereas naloxone-infused subjects showed no change. Subject reports and psychophysiological measures of arousal indicated no…

  4. Guided Mastery and Performance Desensitization Treatments.

    ERIC Educational Resources Information Center

    Williams, S. Lloyd; And Others

    1985-01-01

    Compared desensitization and self-efficacy models of phobia treatment in height phobics. Self-efficacy treatment proved to be significantly more effective than desensitization treatment in restoring subjects' behavioral functioning, in raising their perceptions of self-efficacy, and in reducing their anticipated anxiety and thoughts of danger.…

  5. Potentiating potassium nitrate's desensitization with dimethyl isosorbide.

    PubMed

    Hodosh, M

    2001-01-01

    Desensitization of hypersensitive teeth by the combination of dimethyl isosorbide (DMI) and potassium nitrate (KNO3) is more effective than when KNO3 is used alone. KNO3/DMI work together to desensitize hypersensitive teeth at a higher, quicker, and more profound and lasting level.

  6. TRPA1 insensitivity of human sural nerve axons after exposure to lidocaine.

    PubMed

    Docherty, Reginald J; Ginsberg, Lionel; Jadoon, Saqiba; Orrell, Richard W; Bhattacharjee, Anupam

    2013-09-01

    TRPA1 is an ion channel of the TRP family that is expressed in some sensory neurons. TRPA1 activity provokes sensory symptoms of peripheral neuropathy, such as pain and paraesthesia. We have used a grease gap method to record axonal membrane potential and evoked compound action potentials (ECAPs) in vitro from human sural nerves and studied the effects of mustard oil (MO), a selective activator of TRPA1. Surprisingly, we failed to demonstrate any depolarizing response to MO (50, 250 μM) in any human sural nerves. There was no effect of MO on the A wave of the ECAP, but the C wave was reduced at 250 μM. In rat saphenous nerve fibres MO (50, 250 μM) depolarized axons and reduced the C wave of the ECAP but had no effect on the A wave. By contrast, both human and rat nerves were depolarized by capsaicin (0.5 to 5 μM) or nicotine (50 to 200 μM). Capsaicin caused a profound reduction in C fibre conduction in both species but had no effect on the amplitude of the A component. Lidocaine (30 mM) depolarized rat saphenous nerves acutely, and when rat nerves were pretreated with 30 mM lidocaine to mimic the exposure of human nerves to local anaesthetic during surgery, the effects of MO were abolished whilst the effects of capsaicin were unchanged. This study demonstrates that the local anaesthetic lidocaine desensitizes TRPA1 ion channels and indicates that it may have additional mechanisms for treating neuropathic pain that endure beyond simple sodium channel blockade.

  7. [Desensitization of the nicotinic acetylcholine receptor].

    PubMed

    Quiñonez, M; Rojas, L

    1994-01-01

    In biological membranes, ionic channels act speeding up ion movements. Each ionic channel is excited by a specific stimulus (i.e. electric, mechanical, chemical, etc.). Chemically activated ionic channels (CAIC), such as the nicotinic acetylcholine receptor (nAChR), suffer desensitization when the receptor site is still occupied by the agonist molecule. The desensitized CAIC is a non functional channel state regarded as a particular case of receptors rundown. CAIC desensitization only involve reduced activity and not their membrane elimination. Desensitization is important to control synaptic transmission and the development of the nervous system. In this review we discuss results related to its production, modulation and some aspects associated to models that consider it. Finally, an approach combining molecular biology and electrophysiology techniques to understand desensitization and its importance in biological systems is presented.

  8. Bioenergetic deficits in peripheral nerve sensory axons during chemotherapy-induced neuropathic pain resulting from peroxynitrite-mediated post-translational nitration of mitochondrial superoxide dismutase

    PubMed Central

    Janes, Kali; Doyle, Timothy; Bryant, Leesa; Esposito, Emanuela; Cuzzocrea, Salvatore; Ryerse, Jan; Bennett, Gary J.; Salvemini, Daniela

    2016-01-01

    Many of the widely used anticancer drugs induce dose-limiting peripheral neuropathies that undermine their therapeutic efficacy. Animal models of chemotherapy-induced painful peripheral neuropathy (CIPN) evoked by a variety of drug classes, including taxanes, vinca alkaloids, platinum-complexes, and proteasome-inhibitors, suggest that the common underlying mechanism in the development of these neuropathies is mitotoxicity in primary nerve sensory axons (PNSAs) arising from reduced mitochondrial bioenergetics [eg adenosine triphosphate (ATP) production deficits due to compromised respiratory complex I and II activity]. The causative mechanisms of this mitotoxicity remain poorly defined. However, peroxynitrite, an important pro-nociceptive agent, has been linked to mitotoxicity in several disease states and may also drive the mitotoxicity associated with CIPN. Our findings reveal that the development of mechano-hypersensitivity induced by paclitaxel, oxaliplatin, and bortezomib was prevented by administration of the peroxynitrite decomposition catalyst Mn(III) 5,10,15,20-tetrakis(N-n-hexylpyridinium-2-yl)porphyrin (MnTE-2-PyP5+) without interfering with their anti-tumor effects. Peak CIPN was associated with the nitration and inactivation of superoxide dismutase in the mitochondria, but not in the cytosol, as well as a significant decrease in ATP production within the PNSAs; all of these events were attenuated by MnTE-2-PyP5+. Our results provide continued support for the role of mitotoxicity in the development of CIPN across chemotherapeutic drug classes, and identify peroxynitrite as a key mediator in these processes, thereby providing the rationale towards development of “peroxynitrite-targeted” therapeutics for CIPN. PMID:23891899

  9. Shock desensitizing of solid explosive

    SciTech Connect

    Davis, William C

    2010-01-01

    Solid explosive can be desensitized by a shock wave too weak to initiate it promptly, and desensitized explosive does not react although its chemical composition is almost unchanged. A strong second shock does not cause reaction until it overtakes the first shock. The first shock, if it is strong enough, accelerates very slowly at first, and then more rapidly as detonation approaches. These facts suggest that there are two competing reactions. One is the usual explosive goes to products with the release of energy, and the other is explosive goes to dead explosive with no chemical change and no energy release. The first reaction rate is very sensitive to the local state, and the second is only weakly so. At low pressure very little energy is released and the change to dead explosive dominates. At high pressure, quite the other way, most of the explosive goes to products. Numerous experiments in both the initiation and the full detonation regimes are discussed and compared in testing these ideas.

  10. Shock desensitizing of solid explosives

    SciTech Connect

    Davis, William C

    2010-01-01

    Solid explosive can be desensitized by a shockwave too weak to initiate it promptly, and desensitized explosive does not react although its chemical composition is almost unchanged. A strong second shock does not cause reaction until it overtakes the first shock. The first shock, if it is strong enough, accelerates very slowly at first, and then more rapidly as detonation approaches. These facts suggest that there are two competing reactions. One is the usual explosive goes to products with the release of energy, and the other is explosive goes to dead explosive with no chemical change and no energy release. The first reaction rate is very sensitive to the local state, and the second is only weakly so. At low pressure very little energy is released and the change to dead explosive dominates. At high pressure, quite the other way, most of the explosive goes to products. Numerous experiments in both the initiation and the full detonation regimes are discussed and compared in support of these ideas.

  11. Hypothalamic thermosensitivity in capsaicin-desensitized rats.

    PubMed Central

    Cormarèche-Leydier, M; Shimada, S G; Stitt, J T

    1985-01-01

    In rats, we tested the hypothesis that capsaicin desensitization reduces hypothalamic warm thermosensitivity. We locally heated and cooled the hypothalamus using water-perfused thermodes while observing thermoregulatory variables. In untreated rats, a small dose of capsaicin had profound effects on thermoregulation. However, desensitizing rats to capsaicin had no effect on hypothalamic thermosensitivity for metabolic rate or changes in body temperature due to displacements of hypothalamic temperature. Contrary to current opinion, we conclude that capsaicin desensitization does not alter hypothalamic thermosensitivity to warm or cold. PMID:4020699

  12. [Etoposide desensitization. A case report].

    PubMed

    Alvarez Cardona, Aristóteles; Hernández Nieto, Leticia; Pérez Gómez, Martín; Pedroza Meléndez, Alvaro; Huerta López, José G

    2010-01-01

    All chemotherapeutic agents have the potential to induce hypersensitivity reactions and the repeated administration of such drugs during a cancer treatment enhances specific sensitization. Epipodophyllotoxins (etoposide and teniposide) are commonly used to treat lung, testicular, central nervous system and hematologic cancers. Hypersensitivity reactions to epipodophyllotoxins are not the most common but they have been reported. We present a case of an eight-year-old male patient, diagnosed with high risk acute lymphoblastic leukemia who received treatment with etoposide among other drugs (St. Jude XIIIB). During the first course of treatment he needed premedication to etoposide administration because of mild hypersensitivity reactions. At the beginning of a second treatment the patient presented two severe hypersensitivity reactions (acute urticaria, angioedema and hypotension) despite the use of premedication and slow infusion. We initiated a twelve steps desensitization protocol for etoposide with success in the second round allowing the administration of further doses in an ambulatory unit without hypersensitivity reactions.

  13. High-Resolution Ultrasonography of the Superficial Peroneal Motor and Sural Sensory Nerves May Be a Non-invasive Approach to the Diagnosis of Vasculitic Neuropathy

    PubMed Central

    Üçeyler, Nurcan; Schäfer, Kristina A.; Mackenrodt, Daniel; Sommer, Claudia; Müllges, Wolfgang

    2016-01-01

    High-resolution ultrasonography (HRUS) is an emerging new tool in the investigation of peripheral nerves. We set out to assess the utility of HRUS performed at lower extremity nerves in peripheral neuropathies. Nerves of 26 patients with polyneuropathies of different etiologies and 26 controls were investigated using HRUS. Patients underwent clinical, laboratory, electrophysiological assessment, and a diagnostic sural nerve biopsy as part of the routine work-up. HRUS was performed at the sural, tibial, and the common, superficial, and deep peroneal nerves. The superficial peroneal nerve longitudinal diameter (LD) distinguished best between the groups: patients with immune-mediated neuropathies (n = 13, including six with histology-proven vasculitic neuropathy) had larger LD compared to patients with non-immune-mediated neuropathies (p < 0.05) and to controls (p < 0.001). Among all subgroups, patients with vasculitic neuropathy showed the largest superficial peroneal nerve LD (p < 0.001) and had a larger sural nerve cross-sectional area when compared with disease controls (p < 0.001). Enlargement of the superficial peroneal and sural nerves as detected by HRUS may be a useful additional finding in the differential diagnosis of vasculitic and other immune-mediated neuropathies. PMID:27064457

  14. High-Resolution Ultrasonography of the Superficial Peroneal Motor and Sural Sensory Nerves May Be a Non-invasive Approach to the Diagnosis of Vasculitic Neuropathy.

    PubMed

    Üçeyler, Nurcan; Schäfer, Kristina A; Mackenrodt, Daniel; Sommer, Claudia; Müllges, Wolfgang

    2016-01-01

    High-resolution ultrasonography (HRUS) is an emerging new tool in the investigation of peripheral nerves. We set out to assess the utility of HRUS performed at lower extremity nerves in peripheral neuropathies. Nerves of 26 patients with polyneuropathies of different etiologies and 26 controls were investigated using HRUS. Patients underwent clinical, laboratory, electrophysiological assessment, and a diagnostic sural nerve biopsy as part of the routine work-up. HRUS was performed at the sural, tibial, and the common, superficial, and deep peroneal nerves. The superficial peroneal nerve longitudinal diameter (LD) distinguished best between the groups: patients with immune-mediated neuropathies (n = 13, including six with histology-proven vasculitic neuropathy) had larger LD compared to patients with non-immune-mediated neuropathies (p < 0.05) and to controls (p < 0.001). Among all subgroups, patients with vasculitic neuropathy showed the largest superficial peroneal nerve LD (p < 0.001) and had a larger sural nerve cross-sectional area when compared with disease controls (p < 0.001). Enlargement of the superficial peroneal and sural nerves as detected by HRUS may be a useful additional finding in the differential diagnosis of vasculitic and other immune-mediated neuropathies.

  15. Nerve growth factor treatment of sensory neuron primary cultures causes elevated levels of the mRNA encoding the ATP synthase beta-subunit as detected by a novel PCR-based differential cloning method.

    PubMed

    Kendall, G; Ensor, E; Crankson, H D; Latchman, D S

    1996-03-01

    The mRNA encoding the rat ATP synthase beta-subunit was rapidly induced by nerve growth factor, within 60 min, in cultured adult rat dorsal root ganglion neurons. ATP synthase beta-subunit cDNA clones were isolated from a lambda library. The library was constructed using rat dorsal root ganglion mRNA that was differentially screened with cDNA-derived probes from untreated and nerve-growth-factor-treated primary cultures of adult rat dorsal root ganglion sensory neurons. Radiolabelled probes were made from submicrogram quantities of RNA, by a novel PCR-based technique, which allows small amounts of primary tissue to be used for library screening. The use of this technique in isolating novel differentially expressed mRNAs is discussed.

  16. Inflammation of peripheral tissues and injury to peripheral nerves induce differing effects in the expression of the calcium-sensitive N-arachydonoylethanolamine-synthesizing enzyme and related molecules in rat primary sensory neurons.

    PubMed

    Sousa-Valente, João; Varga, Angelika; Torres-Perez, Jose Vicente; Jenes, Agnes; Wahba, John; Mackie, Ken; Cravatt, Benjamin; Ueda, Natsuo; Tsuboi, Kazuhito; Santha, Peter; Jancso, Gabor; Tailor, Hiren; Avelino, António; Nagy, Istvan

    2017-06-01

    Elevation of intracellular Ca(2+) concentration induces the synthesis of N-arachydonoylethanolamine (anandamide) in a subpopulation of primary sensory neurons. N-acylphosphatidylethanolamine phospholipase D (NAPE-PLD) is the only known enzyme that synthesizes anandamide in a Ca(2+) -dependent manner. NAPE-PLD mRNA as well as anandamide's main targets, the excitatory transient receptor potential vanilloid type 1 ion channel (TRPV1), the inhibitory cannabinoid type 1 (CB1) receptor, and the main anandamide-hydrolyzing enzyme fatty acid amide hydrolase (FAAH), are all expressed by subpopulations of nociceptive primary sensory neurons. Thus, NAPE-PLD, TRPV1, the CB1 receptor, and FAAH could form an autocrine signaling system that could shape the activity of a major subpopulation of nociceptive primary sensory neurons, contributing to the development of pain. Although the expression patterns of TRPV1, the CB1 receptor, and FAAH have been comprehensively elucidated, little is known about NAPE-PLD expression in primary sensory neurons under physiological and pathological conditions. This study shows that NAPE-PLD is expressed by about one-third of primary sensory neurons, the overwhelming majority of which also express nociceptive markers as well as the CB1 receptor, TRPV1, and FAAH. Inflammation of peripheral tissues and injury to peripheral nerves induce differing but concerted changes in the expression pattern of NAPE-PLD, the CB1 receptor, TRPV1, and FAAH. Together these data indicate the existence of the anatomical basis for an autocrine signaling system in a major proportion of nociceptive primary sensory neurons and that alterations in that autocrine signaling by peripheral pathologies could contribute to the development of both inflammatory and neuropathic pain.

  17. [Pathophysiology of sensory ataxic neuropathy].

    PubMed

    Sobue, G

    1996-12-01

    The main lesions of sensory ataxic neuropathy such as chronic idiopathic sensory ataxic neuropathy, (ISAN), carcinomatous neuropathy, Sjögren syndrome-associated neuropathy and acute autonomic and sensory neuropathy (AASN) are the large-diameter sensory neurons and dosal column of the spinal cord and the large myelinated fibers in the peripheral nerve trunks. In addition, afferent fibers to the Clarke's nuclei are also severely involved, suggesting Ia fibers being involved in these neuropathies. In NT-3 knockout mouse, an animal model of sensory ataxia, large-sized la neurons as well as muscle spindle and Golgi tendon organs are depleted, and are causative for sensory ataxia. Thus, the proprioceptive Ia neurons would play a role in pathogenesis of sensory ataxia in human sensory ataxic neuropathies, but the significance of dorsal column involvement in human sensory ataxia is still needed to evaluate.

  18. GABAA receptor-mediated positive inotropism in guinea-pig isolated left atria: evidence for the involvement of capsaicin-sensitive nerves.

    PubMed

    Maggi, C A; Giuliani, S; Manzini, S; Meli, A

    1989-05-01

    . After exposure to capsaicin (1 microM), no effect of GABA could be detected. 7. We conclude that, in the guinea-pig heart, GABAA receptors, presumably located on the preterminal region of capsaicin-sensitive sensory nerves, initiate a conducted impulse (since it is tetrodotoxin-sensitive) which leads to transmitter release (endogenous CGRP-like material) by activation of omega-conotoxin-sensitive, voltage-sensitive calcium channels and a functional response.

  19. Diverse mechanisms for assembly of branchiomeric nerves.

    PubMed

    Cox, Jane A; Lamora, Angela; Johnson, Stephen L; Voigt, Mark M

    2011-09-15

    The formation of branchiomeric nerves (cranial nerves V, VII, IX and X) from their sensory, motor and glial components is poorly understood. The current model for cranial nerve formation is based on the Vth nerve, in which sensory afferents are formed first and must enter the hindbrain in order for the motor efferents to exit. Using transgenic zebrafish lines to discriminate between motor neurons, sensory neurons and peripheral glia, we show that this model does not apply to the remaining three branchiomeric nerves. For these nerves, the motor efferents form prior to the sensory afferents, and their pathfinding show no dependence on sensory axons, as ablation of cranial sensory neurons by ngn1 knockdown had no effect. In contrast, the sensory limbs of the IXth and Xth nerves (but not the Vth or VIIth) were misrouted in gli1 mutants, which lack hindbrain bmn, suggesting that the motor efferents are crucial for appropriate sensory axon projection in some branchiomeric nerves. For all four nerves, peripheral glia were the intermediate component added and had a critical role in nerve integrity but not in axon guidance, as foxd3 null mutants lacking peripheral glia exhibited defasciculation of gVII, gIX, and gX axons. The bmn efferents were unaffected in these mutants. These data demonstrate that multiple mechanisms underlie formation of the four branchiomeric nerves. For the Vth, sensory axons initiate nerve formation, for the VIIth the sensory and motor limbs are independent, and for the IXth/Xth the motor axons initiate formation. In all cases the glia are patterned by the initiating set of axons and are needed to maintain axon fasciculation. These results reveal that coordinated interactions between the three neural cell types in branchiomeric nerves differ according to their axial position.

  20. Magnesium sulphate as a new desensitizing agent.

    PubMed

    Liu, G H; Morimoto, M

    1991-07-01

    Various desensitizing agents have been used in clinics to solve the problem of dentinal hypersensitivity (DH), but none of them has been shown to be consistently effective. We here introduce a new type of desensitizing agent, i.e. 4% magnesium sulphate with iontophoresis at 2mA for 3 min. These optimal conditions were determined by animal experiments, while only a minor effect on dentinal issues was observed within 4 weeks after the treatment. When this desensitizing agent was used to treat DH, the cure rate of 62.4% remained steady within the 25-week observation period, while some effect was achieved in all the subjects who participated in the study.

  1. Playing violent video games and desensitization to violence.

    PubMed

    Brockmyer, Jeanne Funk

    2015-01-01

    This article examines current research linking exposure to violent video games and desensitization to violence. Data from questionnaire, behavioral, and psychophysiologic research are reviewed to determine if exposure to violent video games is a risk factor for desensitization to violence. Real-world implications of desensitization are discussed.

  2. Exercise dependent increase in axon regeneration into peripheral nerve grafts by propriospinal but not sensory neurons after spinal cord injury is associated with modulation of regeneration-associated genes.

    PubMed

    Sachdeva, Rahul; Theisen, Catherine C; Ninan, Vinu; Twiss, Jeffery L; Houlé, John D

    2016-02-01

    Insufficient regeneration of central nervous system (CNS) axons contributes to persisting neurological dysfunction after spinal cord injury (SCI). Peripheral nerve grafts (PNGs) support regeneration by thousands of injured intraspinal axons and help them bypass some of the extracellular barriers that form after SCI. However this number represents but a small portion of the total number of axons that are injured. Here we tested if rhythmic sensory stimulation during cycling exercise would boost the intrinsic regenerative state of neurons to enhance axon regeneration into PNGs after a lower thoracic (T12) spinal transection of adult rats. Using True Blue retrograde tracing, we show that 4 weeks of cycling improves regeneration into a PNG from lumbar interneurons but not by primary sensory neurons. The majority of neurons that regenerate their axon are within 5 mm of the lesion and their number increased 70% with exercise. Importantly propriospinal neurons in more distant regions (5-20 mm from the lesion) that routinely exhibit very limited regeneration responded to exercise by increasing the number of regenerating neurons by 900%. There was no exercise-associated increase in regeneration from sensory neurons. Analyses using fluorescent in situ hybridization showed that this increase in regenerative response is associated with changes in levels of mRNAs encoding the regeneration associated genes (RAGs) GAP43, β-actin and Neuritin. While propriospinal neurons showed increased mRNA levels in response to SCI alone and then to grafting and exercise, sensory neurons did not respond to SCI, but there was a response to the presence of a PNG. Thus, exercise is a non-invasive approach to modulate gene expression in injured neurons leading to an increase in regeneration. This sets the stage for future studies to test whether exercise will promote axon outgrowth beyond the PNG and reconnection with spinal cord neurons, thereby demonstrating a potential clinical application of

  3. Desensitizing nano powders to electrostatic discharge ignition

    SciTech Connect

    Steelman, Ryan; Clark, Billy; Pantoya, Michelle L.; Heaps, Ronald J.; Daniels, Michael A.

    2015-08-01

    Electrostatic discharge (ESD) is a main cause for ignition in powder media ranging from grain silos to fireworks. Nanoscale particles are orders of magnitude more ESD ignition sensitive than their micron scale counterparts. This study shows that at least 13 vol. % carbon nanotubes (CNT) added to nano-aluminum and nano-copper oxide particles (nAl + CuO) eliminates ESD ignition sensitivity. The CNT act as a conduit for electric energy and directs electric charge through the powder to desensitize the reactive mixture to ignition. For nanoparticles, the required CNT concentration for desensitizing ESD ignition acts as a diluent to quench energy propagation.

  4. Expression changes of nerve cell adhesion molecules L1 and semaphorin 3A after peripheral nerve injury

    PubMed Central

    He, Qian-ru; Cong, Meng; Chen, Qing-zhong; Sheng, Ya-feng; Li, Jian; Zhang, Qi; Ding, Fei; Gong, Yan-pei

    2016-01-01

    The expression of nerve cell adhesion molecule L1 in the neuronal growth cone of the central nervous system is strongly associated with the direction of growth of the axon, but its role in the regeneration of the peripheral nerve is still unknown. This study explored the problem in a femoral nerve section model in rats. L1 and semaphorin 3A mRNA and protein expressions were measured over the 4-week recovery period. Quantitative polymerase chain reaction showed that nerve cell adhesion molecule L1 expression was higher in the sensory nerves than in motor nerves at 2 weeks after injury, but vice versa for the expression of semaphorin 3A. Western blot assay results demonstrated that nerve cell adhesion molecule L1 expression was higher in motor nerves than in the sensory nerves at the proximal end after injury, but its expression was greater in the sensory nerves at 2 weeks. Semaphorin 3A expression was higher in the motor nerves than in the sensory nerves at 3 days and 1 week after injury. Nerve cell adhesion molecule L1 and semaphorin 3A expressions at the distal end were higher in the motor nerves than in the sensory nerves at 3 days, 1 and 2 weeks. Immunohistochemical staining results showed that nerve cell adhesion molecule L1 expression at the proximal end was greater in the sensory nerves than in the motor nerves; semaphorin 3A expression was higher in the motor nerves than in the sensory nerves at 2 weeks after injury. Taken together, these results indicated that nerve cell adhesion molecules L1 and semaphorin 3A exhibited different expression patterns at the proximal and distal ends of sensory and motor nerves, and play a coordinating role in neural chemotaxis regeneration. PMID:28197202

  5. Use of cone-beam computed tomography in the diagnosis of sensory nerve paresthesia secondary to orthodontic tooth movement: a clinical report.

    PubMed

    Chana, Randeep S; Wiltshire, William A; Cholakis, Anastasia; Levine, Gary

    2013-08-01

    In this article, we report an incident of transient neuropathy secondary to tooth movement involving the inferior alveolar nerve. This clinical report reflects the need to thoroughly examine potentially high-risk patients for neuropathy using advanced diagnostic tools such as cone-beam computed tomography when diagnosing and planning treatment.

  6. Prevention of NKCC1 phosphorylation avoids downregulation of KCC2 in central sensory pathways and reduces neuropathic pain after peripheral nerve injury.

    PubMed

    Mòdol, Laura; Cobianchi, Stefano; Navarro, Xavier

    2014-08-01

    Neuropathic pain after peripheral nerve injury is characterized by loss of inhibition in both peripheral and central pain pathways. In the adult nervous system, the Na(+)-K(+)-2Cl(-) (NKCC1) and neuron-specific K(+)-Cl(-) (KCC2) cotransporters are involved in setting the strength and polarity of GABAergic/glycinergic transmission. After nerve injury, the balance between these cotransporters changes, leading to a decrease in the inhibitory tone. However, the role that NKCC1 and KCC2 play in pain-processing brain areas is unknown. Our goal was to study the effects of peripheral nerve injury on NKCC1 and KCC2 expression in dorsal root ganglia (DRG), spinal cord, ventral posterolateral (VPL) nucleus of the thalamus, and primary somatosensory (S1) cortex. After sciatic nerve section and suture in adult rats, assessment of mechanical and thermal pain thresholds showed evidence of hyperalgesia during the following 2 months. We also found an increase in NKCC1 expression in the DRG and a downregulation of KCC2 in spinal cord after injury, accompanied by later decrease of KCC2 levels in higher projection areas (VPL and S1) from 2 weeks postinjury, correlating with neuropathic pain signs. Administration of bumetanide (30 mg/kg) during 2 weeks following sciatic nerve lesion prevented the previously observed changes in the spinothalamic tract projecting areas and the appearance of hyperalgesia. In conclusion, the present results indicate that changes in NKCC1 and KCC2 in DRG, spinal cord, and central pain areas may contribute to development of neuropathic pain.

  7. Intravenous desensitization to beta-lactam antibiotics.

    PubMed

    Borish, L; Tamir, R; Rosenwasser, L J

    1987-09-01

    Patients allergic to penicillin (PCN) often require treatment with beta-lactam antibiotics for life-threatening bacterial infections. In this article, we review our experience with rapid intravenous desensitization for patients who gave a history of PCN allergy and who had hypersensitivity demonstrated by skin tests. Skin testing was performed with both prick and intradermal techniques and with the recommended antibiotic as well as PCN G, penicilloyl polylysine, and a minor determinant mixture. Patients were transferred to the intensive care unit, and desensitization was performed with a buret technique that required minimal preparation and was easily applied to any antibiotic. Fifteen desensitizations in 12 patients were associated with no immediate reactions. One patient developed a delayed reaction consisting of a pruritic rash and angioedema. A second patient developed a more serious delayed serum sickness-like illness with fever, rash, eosinophilia, abnormal liver function tests, and urinary abnormalities. These reactions did not necessitate stopping the antibiotic, although the latter patient required corticosteroids to suppress his symptoms. Rapid intravenous desensitization is a rapid, safe, and effective technique for patients demonstrating hypersensitivity to beta-lactam antibiotics who require therapy with these medications.

  8. Using Arrays of Microelectrodes Implanted in Residual Peripheral Nerves to Provide Dextrous Control of, and Modulated Sensory Feedback from, a Hand Prosthesis

    DTIC Science & Technology

    2015-10-01

    Design and drawings of micro-electrode arrays complete. 2 • Measure impedances on all electrodes in each array prior to sterilization, and if...allow them to compliantly move with the peripheral nerves and resist mechanical damage. Figure 1 – CAD drawings of the poly-LIFE. Top panel: A...week of implantation due to the array/ wire being crushed/broken by the patient likely during performance of their job. The second array failure

  9. Determination of Long Term Motor Control and Cutaneous Sensory Properties of a High Resolution Peripheral Nerve Interface Technology for Limb Amputees

    DTIC Science & Technology

    2012-12-01

    implant surgery , and since the nerve sizes and content vary widely by location, a “one size fits all” approach was included in the overall approach as...while larger fascicles can be readily divided into smaller fascicles during implant surgeries . In order to rigorously but fairly test the MTA approach...accomplished with available technology from advanced robotics efforts. However, if standard CMOS foundry process technology can be leveraged, then

  10. Subclinical sensory involvement in monomelic amyotrophy.

    PubMed

    Liao, Jenny P; Waclawik, Andrew J; Lotz, Barend P

    2005-12-01

    An 18-year-old woman presented with weakness and atrophy in her hand without associated sensory symptoms, preceding events, or structural abnormalities on neuroimaging. No sensory deficits were detected on neurologic examination. Electrophysiological studies showed not only the expected motor findings for monomelic amyotrophy (MA) in the affected limb, but also markedly reduced sensory nerve action potentials when compared with the unaffected side. These findings suggest that subclinical sensory involvement can exist in patients with otherwise classic presentations of MA.

  11. Genetics Home Reference: hereditary sensory and autonomic neuropathy type IE

    MedlinePlus

    ... by impaired function of nerve cells called sensory neurons, which transmit information about sensations such as pain, ... understood, the enzyme may help regulate nerve cell (neuron) maturation and specialization (differentiation), the ability of neurons ...

  12. Desensitization: Overcoming the Immunologic Barriers to Transplantation

    PubMed Central

    Choi, Jua; Vo, Ashley; Peng, Alice; Jordan, Stanley C.

    2017-01-01

    HLA (Human Leucocyte Antigen) sensitization is a significant barrier to successful kidney transplantation. It often translates into difficult crossmatch before transplant and increased risk of acute and chronic antibody mediated rejection after transplant. Over the last decade, several immunomodulatory therapies have emerged allowing for increased access to kidney transplantation for the immunologically disadvantaged group of HLA sensitized end stage kidney disease patients. These include IgG inactivating agents, anti-cytokine antibodies, costimulatory molecule blockers, complement inhibitors, and agents targeting plasma cells. In this review, we discuss currently available agents for desensitization and provide a brief analysis of data on novel biologics, which will likely improve desensitization outcomes, and have potential implications in treatment of antibody mediated rejection. PMID:28127571

  13. Morphological studies of the vestibular nerve

    NASA Technical Reports Server (NTRS)

    Bergstroem, B.

    1973-01-01

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

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

    PubMed

    Boada, M Danilo; Gutierrez, Silvia; Aschenbrenner, Carol A; Houle, Timothy T; Hayashida, Ken-Ichiro; Ririe, Douglas G; Eisenach, James C

    2015-01-01

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

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

    PubMed Central

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

    2014-01-01

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

  16. Desensitization of parathyroid hormone receptors on cultured bone cells

    SciTech Connect

    Pun, K.K.; Ho, P.W.; Nissenson, R.A.; Arnaud, C.D. )

    1990-12-01

    Administration of excessive amounts of parathyroid hormone (PTH) in the treatment of osteoporosis can reverse the beneficial effects of a low-dose, intermittent regime. To investigate the direct actions and the possible cellular mechanisms of PTH in inducing desensitization of PTH receptors, we studied the effects of desensitization on rat osteoblastic UMR-106 cells. When the osteoblasts were preincubated with bPTH-(1-34), complete refractoriness to a subsequent challenge with the hormone developed within 1 h and at hormone concentrations as low as 5 nM. When osteoblasts thus desensitized were incubated in hormone-free medium, recovery of the cAMP responses began within 2 h and reached maximum after 16 h. Cycloheximide did not affect the process of desensitization. (Nle8,Nle18,Tyr34)bPTH-(3-34)amide significantly impaired the desensitization process by PTH-(1-34) but did not have stimulatory effect on cAMP responses. No significant heterologous desensitization was obvious after preincubation with isoprenaline (50 microM), prostaglandin E1 (50 microM), or prostaglandin E2 (50 microM) for 2 h. Binding experiments with (125I)PLP-(1-36)amide after desensitization revealed that there was an approximate twofold decrease in receptor affinities as analyzed by Scatchard analysis, showing that the decrease in affinity was prominent in the process of desensitization. When the cells were treated with monensin during desensitization, PTH challenge after desensitization produced significantly lower cyclic AMP responses. Recovery after desensitization occurred over a period of 16 h. Inclusion of monensin, but not cycloheximide, impaired the recovery. The results show that homologous desensitization of rat osteoblasts to PTH is brought about by the occupancy of receptors by PTH-(1-34) but not by cAMP generation itself.

  17. Continuous Femoral Nerve Blocks: Varying Local Anesthetic Delivery Method (Bolus versus Basal) to Minimize Quadriceps Motor Block while Maintaining Sensory Block

    PubMed Central

    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.

    2011-01-01

    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

  18. The dipeptidyl peptidase IV inhibitor vildagliptin suppresses development of neuropathy in diabetic rodents: Effects on peripheral sensory nerve function, structure and molecular changes.

    PubMed

    Tsuboi, Kentaro; Mizukami, Hiroki; Inaba, Wataru; Baba, Masayuki; Yagihashi, Soroku

    2015-11-25

    Incretin-related therapy was found to be beneficial for experimental diabetic neuropathy, but its mechanism is obscure. The purpose of this study is to explore the mechanism through which dipeptidyl peptidase IV inhibitor, vildagliptin (VG), influences neuropathy in diabetic rodents. To this end, non-obese type 2 diabetic Goto-Kakizaki rats (GK) and streptozotocin (STZ)-induced diabetic mice were treated with VG orally. Neuropathy was evaluated by nerve conduction velocity (NCV) in both GK and STZ-diabetic mice, whereas calcitonin-gene-related peptide (CGRP) expressions, neuronal cell size of dorsal root ganglion (DRG) and intraepidermal nerve fiber density (IENFD) were examined in GK. DRG from GK and STZ-diabetic mice served for analyses of GLP-1 and insulin signaling. As results, VG-treatment improved glucose intolerance and increased serum insulin and GLP-1 in GK accompanied by the amelioration of delayed NCV and neuronal atrophy, reduced CGRP expressions and IENFD. Diet restriction alone did not significantly influence these measures. Impaired GLP-1 signals such as CREB, PKB/Akt and S6RP in DRG of GK were restored in VG-treated group, but the effect was equivocal in diet-treated GK. Concurrently, decreased phosphorylation of insulin receptor substrate-2 (IRS2) in GK was corrected by VG-treatment. Consistent with the effect on GK, VG-treatment improved NCV in diabetic mice without influence on hyperglycemia. DRG of VG-treated diabetic mice were characterized by correction of GLP-1 signals and IRS2 phosphorylation without effects on insulin receptor-β expression. The results suggest close association of neuropathy development with impaired signaling of insulin and GLP-1 in diabetic rodents. This article is protected by copyright. All rights reserved.

  19. Desensitization to Oxcarbazepine: Long-Term Efficacy and Tolerability

    PubMed Central

    Lee, Jiwon; Park, Eu Gene; Lee, Munhyang

    2017-01-01

    Background and Purpose Antiepileptic drug (AED)-associated cutaneous adverse drug reactions can lead to the discontinuation of medications. The aim of this study was to determine the long-term efficacy and safety of performing desensitization to oxcarbazepine. Methods This study involved 20 patients who exhibited cutaneous adverse drug reactions associated with oxcarbazepine use between July 2009 and March 2016 at Samsung Medical Center. All of the participants had to discontinue oxcarbazepine despite presenting initially positive responses. Human leukocyte antigen genotyping was performed to detect the genetic predisposition to Stevens-Johnson syndrome. The desensitization to oxcarbazepine was performed with a starting dosage of 0.1 mg/day. Efficacy was evaluated by comparing the frequency of seizures before and at 1 and 3 years after desensitization. Adverse events occurring during desensitization and the retention rate after desensitization were also investigated. Results Nineteen patients (95%) safely completed the desensitization protocol. One withdrew owing to emotional problems that appeared to be associated with oxcarbazepine. The follow-up period was 4.6±1.2 years (mean±SD), and oxcarbazepine was maintained for more than 3 years after desensitization in 15 patients (83.3%). The response rates were 84.2% and 77.8% at 1 and 3 years after desensitization, respectively. Eight patients remained seizure-free for 3 years, and two discontinued all AEDs. Transient adverse reactions such as mild rash and itching were reported by five patients during desensitization. Conclusions This study has demonstrated the long-term efficacy and safety of desensitization to oxcarbazepine in patients exhibiting cutaneous adverse drug reactions. This favorable outcome should encourage the implementation of desensitization in patients presenting with hypersensitivity to oxcarbazepine as an alternative strategy in clinical practice. PMID:27730770

  20. The ultrastructure of the sensory nerve endings in the articular capsule of the knee joint of the domestic cat (Ruffini corpuscles and Pacinian corpuscles).

    PubMed Central

    Halata, Z

    1977-01-01

    Two types of mechanoreceptor have been found in the articular capsule of the knee joint of the domestic cat--Ruffini corpuscles and Pacinian corpuscles. Ruffini corpuscles are situated in the stratum fibrosum and consist of 2 to 6 cylinders. Each cylinder is made up of an afferent axon (diameter 3-4 micrometer), its swellings and terminal processes, Schwann cells enveloping the nerve swellings and terminal processes, endoneural connective tissue and a perineural capsule. The perineural capsule is incomplete in Ruffini corpuscles. The Pacinian corpuscles are 20 to 40 micrometer wide and 150-250 micrometer long. They are situated in groups of up to five at the boundary between the stratum synoviale and the stratum fibrosum. The afferent axon is myelinated (diameter 3-5 micrometer). Its terminal portion is inside the inner bulb which is formed of modified Schwann cells. Each corpuscle is enveloped by a perineural capsule (4-8 layers). The ultrastructure of the Pacinian corpuscles is compared with the ultrastructure of the skin receptors in the cat. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 Fig. 5 Fig. 6 PMID:604339

  1. [Sensory sensitization, part II: Pathophysiology in dysfunctional disorders. Understanding the inner life of the nerve pathways may explain hitherto unexplainable symptoms].

    PubMed

    Levander, Hans

    2003-04-30

    This article is based on a vast clinical experience from patients presenting with widespread pain syndromes as well as dysfunctional symptoms from inner organs. A literature survey has been performed. Allodynia and hyperalgesia that partly explain the fibromyalgia and local myalgia syndromes seem to arise from a pathophysiological process of nociceptive sensitisation. It is proposed that the concept of "sensory sensitisation dysfunctional disorders" be applied to conditions like bronchial hyperreactivity, Da Costas syndrome, Dercum's disease (Adipositas dolorosa), dry eyes and mouth syndrome, fibromyalgia, gastralgia, globus hystericus, interstitial cystitis, chronic prostatitis, irritable bowel syndrome, photo- and phonosensitivity, rhinitis, tension headache, tinnitus, vestibulitis syndrome. These dysfunctional disorders cannot be satisfactorily explained by presently known pathophysiological models like ongoing inflammatory process, tissue degeneration, fibrosis, blood vessel diseases, tumours, immune reactions, toxic or deficiency conditions, metabolic disturbances. Neurogenic mechanisms also seem to play an important role in the pathophysiology of arthritic conditions, and might be worthwhile to include in forthcoming discussions concerning the aetiology of chronic inflammatory disease.

  2. Polymerization of actin does not regulate desensitization in human basophils

    PubMed Central

    MacGlashan, Donald; Vilariño, Natalia

    2009-01-01

    Previous studies have suggested that maintenance of IgE-mediated signaling results from regulation of the activity of signaling complexes by actin polymerization. This process is also hypothesized to be related to desensitization of basophils and mast cells. Recent studies demonstrated that any signaling process dependent on syk or PI-3K activity cannot be a mechanism of desensitization, and in this context, syk and PI-3K inhibitors were found to inhibit actin polymerization. Inhibitors of actin polymerization were tested for their effect on desensitization of human peripheral blood basophils. Latrunculin A, in particular, removed all resting and stimulated f-actin but did not inhibit desensitization. Cytochalasin D and latrunculin A also did not reverse the loss of syk phosphorylation that accompanies desensitization. These results demonstrate that desensitization mechanisms are not dependent on actin polymerization. In this context, it was also shown that progressive immobilization of FcεRI during aggregation was sensitive to syk or actin polymerization inhibition. Therefore, desensitization is also not dependent on receptor immobilization. These studies demonstrate that desensitization is not the result of two signaling pathways once considered relevant to down-regulation of IgE-mediated signaling. PMID:19150851

  3. EMG Biofeedback Training Versus Systematic Desensitization for Test Anxiety Reduction

    ERIC Educational Resources Information Center

    Romano, John L.; Cabianca, William A.

    1978-01-01

    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…

  4. Effects of Modeling and Desensitation in Reducing Dentist Phobia

    ERIC Educational Resources Information Center

    Shaw, David W.; Thoresen, Carl E.

    1974-01-01

    Many persons avoid dentists and dental work. The present study explored the effects of systematic desensitization and social-modeling treatments with placebo and assessment control groups. Modeling was more effective than desensitization as shown by the number of subjects who went to a dentist. (Author)

  5. Hypnosis Versus Systematic Desensitization in the Treatment of Test Anxiety

    ERIC Educational Resources Information Center

    Melnick, Joseph; Russell, Ronald W.

    1976-01-01

    This study compared the effectiveness of systematic desensitization and the directed experience hypnotic technique in reducing self-reported test anxiety and increasing the academic performance of test-anxious undergraduates (N=36). The results are discussed as evidence for systematic desensitization as the more effective treatment in reducing…

  6. Capsaicin desensitization and recovery on the human tongue.

    PubMed

    Karrer, T; Bartoshuk, L

    1991-04-01

    The desensitization resulting from application of 10 or 100 ppm capsaicin was investigated, using daily testing of a capsaicin series (1-1000 ppm, in log steps). The series showed a significant decrement in perceived burn following desensitization with either concentration. Perceived burn of 100 and 1000 ppm did not recover from 100 ppm desensitization in six days, and perceived burn of 1-1000 ppm did not recover from 100 ppm desensitization in six days. When single capsaicin concentrations, rather than the series, were tested at one, two, four, or six days after desensitization, 10 ppm recovered from 10 ppm desensitization in one or two days, and 100 ppm recovered from 100 ppm desensitization between two and four days. This suggests that daily testing with the capsaicin series delayed recovery from desensitization. Nontasters of 6-n-propylthiouracil rated capsaicin burn lower than did tasters. The application method of rolling capsaicin onto the tongue with a swab was found to transiently inhibit burn. Implications for ingesting capsaicin products are discussed.

  7. Galvanic Skin Response and Reported Anxiety During Systematic Desensitization

    ERIC Educational Resources Information Center

    Hyman, Edward T.; Gale, Elliot N.

    1973-01-01

    The purpose of the present study was to investigate the GSR during systematic desensitization. Three groups of females each were preselected for high snake fear. Outcome measures indicated that the desensitization group reduced phobic behavior most, followed by the relaxation group, and then the exposure groups. (Author)

  8. Identification of target areas for deep brain stimulation in human basal ganglia substructures based on median nerve sensory evoked potential criteria

    PubMed Central

    Klostermann, F; Vesper, J; Curio, G

    2003-01-01

    Objective: In the interventional treatment of movement disorders, the thalamic ventral intermediate nucleus (VIM) and the subthalamic nucleus (STN) are the most relevant electrode targets for deep brain stimulation (DBS). This study tested the value of somatosensory evoked potentials (SEP) for the functional identification of VIM and STN. Methods: Median nerve SEP were recorded from the final stimulation electrodes targeted at STN and VIM. Throughout the stereotactic procedure SEP were recorded during short electrode stops above STN/VIM and within the presumed target areas. After digital filtering, high and low frequency SEP components were analysed separately to parameterise both the 1000 Hz SEP burst and low frequency (<100 Hz) components. Results: SEP recorded in the VIM target region could unequivocally be distinguished from SEP recorded in STN. The 1000 Hz burst signal was significantly larger in VIM than in STN without any overlap of amplitude values. In the low frequency band, a primary high amplitude negativity was obtained in VIM, contrasting with a low amplitude positivity in STN. SEP waveshapes in recordings above target positions resembled SEP obtained in STN. When entering VIM, a sharp amplitude increase was observed over a few millimetres only. Conclusions: Based on SEP criteria, the VIM target but not the STN region can be identified by typical SEP configuration changes, when penetrating the target zone. The approach is independent of the patient's cooperation and vigilance and therefore feasible in general anaesthesia. It provides an easy, reliable, and robust tool for the final assessment of electrode positions at the last instance during electrode implantation when eventual electrode revisions can easily be performed. PMID:12876229

  9. Rehabilitation of the trigeminal nerve

    PubMed Central

    Iro, Heinrich; Bumm, Klaus; Waldfahrer, Frank

    2005-01-01

    When it comes to restoring impaired neural function by means of surgical reconstruction, sensory nerves have always been in the role of the neglected child when compared with motor nerves. Especially in the head and neck area, with its either sensory, motor or mixed cranial nerves, an impaired sensory function can cause severe medical conditions. When performing surgery in the head and neck area, sustaining neural function must not only be highest priority for motor but also for sensory nerves. In cases with obvious neural damage to sensory nerves, an immediate neural repair, if necessary with neural interposition grafts, is desirable. Also in cases with traumatic trigeminal damage, an immediate neural repair ought to be considered, especially since reconstructive measures at a later time mostly require for interposition grafts. In terms of the trigeminal neuralgia, commonly thought to arise from neurovascular brainstem compression, a pharmaceutical treatment is considered as the state of the art in terms of conservative therapy. A neurovascular decompression of the trigeminal root can be an alternative in some cases when surgical treatment is sought after. Besides the above mentioned therapeutic options, alternative treatments are available. PMID:22073060

  10. Association of overactive bladder and stress urinary incontinence in rats with pudendal nerve ligation injury.

    PubMed

    Furuta, Akira; Kita, Masafumi; Suzuki, Yasuyuki; Egawa, Shin; Chancellor, Michael B; de Groat, William C; Yoshimura, Naoki

    2008-05-01

    Approximately one-third of patients with stress urinary incontinence (SUI) also suffer from urgency incontinence, which is one of the major symptoms of overactive bladder (OAB) syndrome. Pudendal nerve injury has been recognized as a possible cause for both SUI and OAB. Therefore, we investigated the effects of pudendal nerve ligation (PNL) on bladder function and urinary continence in female Sprague-Dawley rats. Conscious cystometry with or without capsaicin pretreatment (125 mg/kg sc), leak point pressures (LPPs), contractile responses of bladder muscle strips to carbachol or phenylephrine, and levels of nerve growth factor (NGF) protein and mRNA in the bladder were compared in sham and PNL rats 4 wk after the injury. Urinary frequency detected by a reduction in intercontraction intervals and voided volume was observed in PNL rats compared with sham rats, but it was not seen in PNL rats with capsaicin pretreatment that desensitizes C-fiber-afferent pathways. LPPs in PNL rats were significantly decreased compared with sham rats. The contractile responses of detrusor muscle strips to phenylephrine, but not to carbachol, were significantly increased in PNL rats. The levels of NGF protein and mRNA in the bladder of PNL rats were significantly increased compared with sham rats. These results suggest that pudendal nerve neuropathy induced by PNL may be one of the potential risk factors for OAB, as well as SUI. Somato-visceral cross sensitization between somatic (pudendal) and visceral (bladder) sensory pathways that increases NGF expression and alpha(1)-adrenoceptor-mediated contractility in the bladder may be involved in this pathophysiological mechanism.

  11. Wartenberg's migrant sensory neuritis: a prospective follow-up study.

    PubMed

    Stork, Abraham C J; van der Meulen, Marjon F G; van der Pol, W-Ludo; Vrancken, Alexander F J E; Franssen, Hessel; Notermans, Nicolette C

    2010-08-01

    Migrant sensory neuropathy (Wartenberg's migrant sensory neuritis) is characterized by sudden numbness in the distribution of one or multiple cutaneous nerves. To study disease course and outcome, we prospectively followed 12 patients who presented to our tertiary referral neuromuscular outpatient clinic between January 2003 and January 2004. Medical history, neurological, laboratory and electrophysiological examinations were obtained from all patients. All patients were reviewed a second time in 2007, and five had a follow-up electrophysiological examination. At the first visit, 50% described an episode of stretching preceding the sensory complaints. All but three described pain in the affected area before or concomitant with sensory loss. At clinical examination a median of six skin areas were affected, and in 75% this could be confirmed by nerve conduction studies in at least one nerve. Forty-two percent had involvement of the trigeminal nerve. After a mean disease duration of 7.5 years, three patients reported a complete disappearance of sensory complaints and five that the pain had disappeared, but numbness remained. Three patients still had both painful and numb sensory deficits. One patient developed a distal symmetric sensory polyneuropathy. In conclusion, Wartenberg's sensory neuritis is a distinct, exclusively sensory, neuropathy, marked by pain preceding numbness in affected nerves. An episode of stretching preceding pain is not necessary for the diagnosis. Wartenberg's sensory neuritis often retains its spotty, exclusively sensory characteristics after long term follow-up.

  12. Effect of desensitizing toothpastes on dentin.

    PubMed

    Pinto, Shelon Cristina Souza; Silveira, Camila Maggi Maia; Pochapski, Márcia Thaís; Pilatt, Gibson Luiz; Santos, Fábio André

    2012-01-01

    The objective of this study was to analyze the effects of toothbrushing with desensitizing toothpastes on dentin permeability and dentinal tubule occlusion. Fifty rats provided two hundred incisor teeth divided into five groups: DW, brushed with distilled water (control); FT, brushed with fluoride toothpaste; SCT, brushed with strontium chloride toothpaste; PCT, brushed with potassium citrate toothpaste; and PNT, brushed with potassium nitrate toothpaste. Cavities were prepared to expose the dentinal tubules, and the incisor teeth were brushed using the experimental agents. After each treatment, Evans blue dye solution was applied to the teeth. Dentin permeability was analyzed using scanning electron microscopy and energy-dispersive X-rays (EDX). There were significant differences (p < 0.0001, ANOVA) among the groups regarding dentin permeability, number of dentinal tubules, diameter of dentinal tubules, and opened tubular area. In the SCT, PCT and PNT groups, opened and partially occluded tubules, deposits, and a few smear layers were observed. In the DW and FT groups, most of the dentinal tubules were open, with no deposits or smear layers on the dentin. EDX revealed peaks of calcium and phosphorus in all of the groups, as well as traces of strontium in the SCT group and of potassium in the PCT and PNT groups. Desensitizing toothpaste decreased dentin permeability, although it produced only partial dentin tubule occlusion.

  13. Desensitization of oxytocin receptors in human myometrium.

    PubMed

    Phaneuf, S; Asbóth, G; Carrasco, M P; Liñares, B R; Kimura, T; Harris, A; Bernal, A L

    1998-01-01

    In the present study, we investigated the possible mechanisms by which oxytocin might regulate oxytocin receptor (OTR) density. Exposure of cultured myometrial cells to oxytocin for a prolonged period caused desensitization: the steady-state level of oxytocin binding was 210 x 10(3) binding sites/cell, but this was time-dependently reduced to 20.1 x 10(3) sites/cell by exposing the cells to oxytocin for up to 20 h. In contrast, Western blotting data showed that the total amount of OTR protein was not affected by oxytocin treatment for up to 24 h. Flow cytometry experiments demonstrated that OTRs were not internalized during this treatment. However, RNase protection assays and Northern analysis showed that in cultured myometrial cells OTR mRNA was reduced by oxytocin treatment to reach a new low steady-state concentration. Analysis of this mRNA in myometrial biopsies from 17 patients undergoing emergency Caesarean section showed how it decreased with advancing labour. Samples obtained after 12 h of labour contained approximately 50 times less OTR mRNA than samples obtained from patients in labour for less than 12 h. We speculate that this decrease in OTR mRNA represents in-vivo OTR desensitization.

  14. Sensory development.

    PubMed

    Clark-Gambelunghe, Melinda B; Clark, David A

    2015-04-01

    Sensory development is complex, with both morphologic and neural components. Development of the senses begins in early fetal life, initially with structures and then in-utero stimulation initiates perception. After birth, environmental stimulants accelerate each sensory organ to nearly complete maturity several months after birth. Vision and hearing are the best studied senses and the most crucial for learning. This article focuses on the cranial senses of vision, hearing, smell, and taste. Sensory function, embryogenesis, external and genetic effects, and common malformations that may affect development are discussed, and the corresponding sensory organs are examined and evaluated.

  15. Dendritic cell dysfunction and diabetic sensory neuropathy in the cornea

    PubMed Central

    Gao, Nan; Yan, Chenxi; Lee, Patrick; Sun, Haijing

    2016-01-01

    Diabetic peripheral neuropathy (DPN) often leads to neurotrophic ulcerations in the cornea and skin; however, the underlying cellular mechanisms of this complication are poorly understood. Here, we used post-wound corneal sensory degeneration and regeneration as a model and tested the hypothesis that diabetes adversely affects DC populations and infiltration, resulting in disrupted DC-nerve communication and DPN. In streptozotocin-induced type 1 diabetic mice, there was a substantial reduction in sensory nerve density and the number of intraepithelial DCs in unwounded (UW) corneas. In wounded corneas, diabetes markedly delayed sensory nerve regeneration and reduced the number of infiltrating DCs, which were a major source of ciliary neurotrophic factor (CNTF) in the cornea. While CNTF neutralization retarded reinnervation in normal corneas, exogenous CNTF accelerated nerve regeneration in the wounded corneas of diabetic mice and healthy animals, in which DCs had been locally depleted. Moreover, blockade of the CNTF-specific receptor CNTFRα induced sensory nerve degeneration and retarded regeneration in normal corneas. Soluble CNTFRα also partially restored the branching of diabetes-suppressed sensory nerve endings and regeneration in the diabetic corneas. Collectively, our data show that DCs mediate sensory nerve innervation and regeneration through CNTF and that diabetes reduces DC populations in UW and wounded corneas, resulting in decreased CNTF and impaired sensory nerve innervation and regeneration. PMID:27064280

  16. Structural basis of kainate subtype glutamate receptor desensitization

    PubMed Central

    Meyerson, Joel R.; Chittori, Sagar; Merk, Alan; Rao, Prashant; Han, Tae Hee; Serpe, Mihaela; Mayer, Mark L.; Subramaniam, Sriram

    2016-01-01

    Glutamate receptors are ligand gated tetrameric ion channels that mediate synaptic transmission in the central nervous system. They are instrumental in vertebrate cognition and their dysfunction underlies diverse diseases1,2. In both the resting and desensitized states of AMPA and kainate subtype glutamate receptors the ion channels are closed while the ligand binding domain, which is physically coupled to the channel, adopts dramatically different conformations3–6. Without an atomic model for the desensitized state, it is not possible to address a central question in receptor gating: how the resting and desensitized receptor states both display closed ion channels, even though they have major differences in quaternary structure of the ligand binding domain. By determining the cryo-EM structure of the kainate receptor GluK2 subtype in its desensitized state at 3.8 Å resolution, we show that desensitization is characterized by establishment of a ring-like structure in the ligand binding domain layer of the receptor. Formation of this “desensitization ring” is mediated by staggered helix contacts between adjacent subunits, which leads to a pseudo four-fold symmetric arrangement of the ligand binding domains, illustrating subtle changes in symmetry that are at the heart of the gating mechanism. Disruption of the desensitization ring is likely the key switch that enables restoration of the receptor to its resting state, thereby completing the gating cycle. PMID:27580033

  17. Nerve root replantation.

    PubMed

    Carlstedt, Thomas

    2009-01-01

    Traumatic avulsion of nerve roots from the spinal cord is a devastating event that usually occurs in the brachial plexus of young adults following motor vehicle or sports accidents or in newborn children during difficult childbirth. A strategy to restore motor function in the affected arm by reimplanting into the spinal cord the avulsed ventral roots or autologous nerve grafts connected distally to the avulsed roots has been developed. Surgical outcome is good and useful recovery in shoulder and proximal arm muscles occurs. Pain is alleviated with motor recovery but sensory improvement is poor when only motor conduits have been reconstructed. In experimental studies, restoration of sensory connections with general improvement in the outcome from this surgery is pursued.

  18. Immediate Desensitization in Teeth Affected by Amelogenesis Imperfecta.

    PubMed

    Moreira, Rudá França; Figueiredo, Rossana Gomes; Oliveira, Henrique Eduardo; Fonseca, Ana Christina Lamosa da; Miranda, Mauro Sayão de

    2016-01-01

    The aim of this paper was to describe a clinical case of immediate dental desensitization using a self-etch adhesive system in an adolescent patient diagnosed with amelogenesis imperfecta (AI). AI was associated with severe tooth sensitivity, treated by the application of a universal adhesive system for desensitization of the teeth affected by AI. Reduction of tooth sensitivity was assessed using a visual analog scale during all reevaluations. The technique was effective for reducing tooth sensitivity. It was concluded that the adhesive system for tooth desensitization had an immediate effect and maintained its effectiveness during a 12-month follow-up period.

  19. Sensory mononeuropathies.

    PubMed

    Massey, E W

    1998-01-01

    The clinical neurologist frequently encounters patients with a variety of focal sensory symptoms and signs. This article reviews the clinical features, etiologies, laboratory findings, and management of the common sensory mononeuropathies including meralgia paresthetica, cheiralgia paresthetica, notalgia paresthetica, gonyalgia paresthetica, digitalgia paresthetica, intercostal neuropathy, and mental neuropathy.

  20. [Desensitization to darunavir in a pediatric patient].

    PubMed

    Cambray-Gutiérrez, Julio César; López-Pérez, Patricia; Chávez-García, Aurora Alejandra; Del Rivero-Hernández, Leonel Gerardo; Segura-Méndez, Nora Hilda

    2015-01-01

    Treatment of HIV infection requires the combination of multiple antiretroviral drugs, known as highly active antiretroviral therapy (HAART); however, up to 84% of patients experience adverse drug effects that lead to discontinuation within first months of treatment. Skin manifestations are reported to 22% of patients. The severity of these is variable, such as erythema multiforme, rash, hives and severe skin reactions at less than 2%. Mild rashes, usually transient and self-limiting, while severe reactions require immediately remove the drug involved to prevent progression of the reaction. Only in those cases where the offending drug does not have another alternative and documented the reaction is mediated type I hypersensitivity mechanisms, can be performed desensitization protocol.

  1. Functional gait evaluation of collagen chitosan nerve guides for sciatic nerve repair.

    PubMed

    Patel, Minal; Vandevord, Pamela J; Matthew, Howard W; Desilva, Stephen; Wu, Bin; Wooley, Paul H

    2008-12-01

    The objective of this work was to use a functional gait analysis technique to evaluate sciatic nerve repair through tissue-engineered nerve guides in a rodent animal model. The nerve guides were fabricated by blending collagen with chitosan material and evaluated over a 12-week period for motor and sensory nerve recovery assessed by gait analysis and behavioral testing. Gastrocnemius muscle weight measurements were obtained at the end of each experimental time point and correlated to motor nerve recovery. Functional gait analysis studied both the stance and swing phase angle formations during a normal gait cycle. During the stance phase, functional results revealed that blended nerve guides promoted increased motor nerve recovery than unblended chitosan nerve guides. Similar results were obtained from behavioral tests, indicating that blended nerve guides created increased sensitivity to applied stimulus compared to unblended nerve guides. Muscle strength also correlated with functional recovery and was significantly higher when compared to the unblended nerve guides. From this study, we conclude that collagen-blended chitosan nerve guides enhanced motor and sensory nerve recovery assayed through gait and behavioral testing compared to unblended nerve guides.

  2. Violent Video Games May Not 'Desensitize' Players, Brain Scans Suggest

    MedlinePlus

    ... page: https://medlineplus.gov/news/fullstory_163987.html Violent Video Games May Not 'Desensitize' Players, Brain Scans ... 8, 2017 (HealthDay News) -- Young men who play violent video games the most -- at least two hours ...

  3. Contribution of Pretesting to Several Measures of Semantic Desensitization Effectiveness

    ERIC Educational Resources Information Center

    Israel, Allen C.; And Others

    1977-01-01

    Snake- or spider-phobic subjects (N=32) were randomly assigned to one of four groups. Subjects receiving semantic desensitization therapy showed less posttest anxiety on the semantic differential than control subjects regardless of testing condition. (Author)

  4. Combining alprazolam with systematic desensitization therapy for dental injection phobia.

    PubMed

    Coldwell, Susan E; Wilhelm, Frank H; Milgrom, Peter; Prall, Christopher W; Getz, Tracy; Spadafora, Agnes; Chiu, I-Yu; Leroux, Brian G; Ramsay, Douglas S

    2007-01-01

    To determine whether a benzodiazepine facilitates systematic desensitization, 144 subjects with dental injection phobia received systematic desensitization in combination with placebo or one of two doses of alprazolam (0.5mg or 0.75mg). Systematic desensitization therapy included computer-controlled presentation of digitized video segments followed by in vivo exposure segments, culminating in an actual dental injection. Subjects advanced to the next hierarchy segment when low anxiety was reported during a segment. Alprazolam and placebo groups progressed at the same rate. The 0.75mg group had elevated heart rates while watching video segments compared with placebo. In a subsequent behavioral avoidance test (during which subjects were randomized to a new drug condition), there was no indication that state-dependent learning had occurred. Dental fear was reduced similarly in all groups for 1 year after study completion. No advantage was found to combining alprazolam with systematic desensitization for dental injection phobia.

  5. The effects of desensitizing agents on the hydraulic conductance of human dentin in vitro.

    PubMed

    Greenhill, J D; Pashley, D H

    1981-03-01

    The hydrodynamic theory of dentin sensitivity states that a stimulus applied at the orifice of exposed dentinal tubules causes movement of tubular fluid which stimulates nerve receptors. The fluid should obey principles of fluid movement through capillary tubes. Any decrease in the functional radius of the dentinal tubules should greatly reduce the rate of fluid flow, thus reducing dentinal sensitivity. The purpose of this study was to evaluate the ability of agents that have been used previously for clinical dentin desensitization to reduce the rate of fluid flow through dentin in vitro. Dentin discs prepared from extracted human third molars were treated with 50% citric acid to remove debris from tubular orifices. After placing the discs in a split chamber device, the rate at which buffer solution could filter across the dentin under 240 cm of water pressure was measured. The occlusal side of the disc was then treated with an agent thought to desensitize dentin to determine if it reduced fluid flow rate. Discs that had more than a 50% reduction in flow rate were examined by scanning electron microscopy to determine if those agents that decreased fluid flow also partially occluded tubular orifices. This in vitro model provided a useful quantitative method for screening a host of preparations that have been used in the past to decrease dentin sensitivity.

  6. Desensitization for solid organ and hematopoietic stem cell transplantation

    PubMed Central

    Zachary, Andrea A; Leffell, Mary S

    2014-01-01

    Desensitization protocols are being used worldwide to enable kidney transplantation across immunologic barriers, i.e. antibody to donor HLA or ABO antigens, which were once thought to be absolute contraindications to transplantation. Desensitization protocols are also being applied to permit transplantation of HLA mismatched hematopoietic stem cells to patients with antibody to donor HLA, to enhance the opportunity for transplantation of non-renal organs, and to treat antibody-mediated rejection. Although desensitization for organ transplantation carries an increased risk of antibody-mediated rejection, ultimately these transplants extend and enhance the quality of life for solid organ recipients, and desensitization that permits transplantation of hematopoietic stem cells is life saving for patients with limited donor options. Complex patient factors and variability in treatment protocols have made it difficult to identify, precisely, the mechanisms underlying the downregulation of donor-specific antibodies. The mechanisms underlying desensitization may differ among the various protocols in use, although there are likely to be some common features. However, it is likely that desensitization achieves a sort of immune detente by first reducing the immunologic barrier and then by creating an environment in which an autoregulatory process restricts the immune response to the allograft. PMID:24517434

  7. Meaningful power grip recovery after salvage reconstruction of a median nerve avulsion injury with a pedicled vascularized ulnar nerve

    PubMed Central

    Van Slyke, Aaron C; Jansen, Leigh A; Hynes, Sally; Hicks, Jane; Bristol, Sean; Carr, Nicholas

    2015-01-01

    In cases of median nerve injury alongside an unsalvageable ulnar nerve, a vascularized ulnar nerve graft to reconstruct the median nerve is a viable option. While restoration of median nerve sensation is consistently reported, recovery of significant motor function is less frequently observed. The authors report a case involving a previously healthy man who sustained upper arm segmental median and ulnar nerve injuries and, after failure of sural nerve grafts, was treated with a pedicled vascularized ulnar nerve graft to restore median nerve function. Long-term follow-up showed near full fist, with 12 kg of grip strength, key pinch with 1.5 kg of strength and protective sensation in the median nerve distribution. The present case demonstrates that pedicled ulnar vascularized nerve grafts can provide significant improvements to median nerve sensory and motor function in a heavily scarred environment. PMID:26665144

  8. Peripheral Nerve Injury: Stem Cell Therapy and Peripheral Nerve Transfer

    PubMed Central

    Sullivan, Robert; Dailey, Travis; Duncan, Kelsey; Abel, Naomi; Borlongan, Cesario V.

    2016-01-01

    Peripheral nerve injury can lead to great morbidity in those afflicted, ranging from sensory loss, motor loss, chronic pain, or a combination of deficits. Over time, research has investigated neuronal molecular mechanisms implicated in nerve damage, classified nerve injury, and developed surgical techniques for treatment. Despite these advancements, full functional recovery remains less than ideal. In this review, we discuss historical aspects of peripheral nerve injury and introduce nerve transfer as a therapeutic option, as well as an adjunct therapy to transplantation of Schwann cells and their stem cell derivatives for repair of the damaged nerve. This review furthermore, will provide an elaborated discussion on the sources of Schwann cells, including sites to harvest their progenitor and stem cell lines. This reflects the accessibility to an additional, concurrent treatment approach with nerve transfers that, predicated on related research, may increase the efficacy of the current approach. We then discuss the experimental and clinical investigations of both Schwann cells and nerve transfer that are underway. Lastly, we provide the necessary consideration that these two lines of therapeutic approaches should not be exclusive, but conversely, should be pursued as a combined modality given their mutual role in peripheral nerve regeneration. PMID:27983642

  9. Peripheral nerve conduits: technology update

    PubMed Central

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

    2014-01-01

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

  10. Warmth suppresses and desensitizes damage-sensing ion channel TRPA1

    PubMed Central

    2012-01-01

    Background Acute or chronic tissue damage induces an inflammatory response accompanied by pain and alterations in local tissue temperature. Recent studies revealed that the transient receptor potential A1 (TRPA1) channel is activated by a wide variety of substances that are released following tissue damage to evoke nociception and neurogenic inflammation. Although the effects of a noxious range of cold temperatures on TRPA1 have been rigorously studied, it is not known how agonist-induced activation of TRPA1 is regulated by temperature over an innocuous range centred on the normal skin surface temperature. This study investigated the effect of temperature on agonist-induced currents in human embryonic kidney (HEK) 293 cells transfected with rat or human TRPA1 and in rat sensory neurons. Results Agonist-induced TRPA1 currents in HEK293 cells were strongly suppressed by warm temperatures, and almost abolished at 39°C. Such inhibition occurred when TRPA1 was activated by either electrophilic or non-electrophilic agonists. Warming not only decreased the apparent affinity of TRPA1 for mustard oil (MO), but also greatly enhanced the desensitization and tachyphylaxis of TRPA1. Warming also attenuated MO-induced ionic currents in sensory neurons. These results suggest that the extent of agonist-induced activity of TRPA1 may depend on surrounding tissue temperature, and local hyperthermia during acute inflammation could be an endogenous negative regulatory mechanism to attenuate persistent pain at the site of injury. Conclusion These results indicate that warmth suppresses and desensitizes damage-sensing ion channel TRPA1. Such warmth-induced suppression of TRPA1 may also explain, at least in part, the mechanistic basis of heat therapy that has been widely used as a supplemental anti-nociceptive approach. PMID:22458587

  11. Peripheral nerve injury during anesthesia.

    PubMed

    Lieblich, S E

    1990-01-01

    A case is presented where a peripheral nerve injury occurred due to the pressure of a restraint buckle causing a postoperative motor and sensory deficit. Because these are iatrogenic injuries it is useful to review the mechanism of injury and means of prevention.

  12. Peripheral nerve injury during anesthesia.

    PubMed Central

    Lieblich, S. E.

    1990-01-01

    A case is presented where a peripheral nerve injury occurred due to the pressure of a restraint buckle causing a postoperative motor and sensory deficit. Because these are iatrogenic injuries it is useful to review the mechanism of injury and means of prevention. Images Figure 1 PMID:2096751

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

    PubMed Central

    2015-01-01

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

  14. Nerve biopsy

    MedlinePlus

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

  15. GABAρ1/GABAAα1 receptor chimeras to study receptor desensitization

    PubMed Central

    Martínez-Torres, Ataúlfo; Demuro, Angelo; Miledi, Ricardo

    2000-01-01

    γ-Aminobutyrate type C (GABAC) receptors are ligand-gated ion channels that are expressed preponderantly in the vertebrate retina and are characterized, among other things, by a very low rate of desensitization and resistance to the specific GABAA antagonist bicuculline. To examine which structural elements determine the nondesensitizing character of the human homomeric ρ1 receptor, we used a combination of gene chimeras and electrophysiology of receptors expressed in Xenopus oocytes. Two chimeric genes were constructed, made up of portions of the ρ1-subunit and of the α1-subunit of the GABAA receptor. When expressed in Xenopus oocytes, one chimeric gene (ρ1/α1) formed functional homooligomeric receptors that were fully resistant to bicuculline and were blocked by the specific GABAC antagonist (1,2,5,6-tetrahydropyridine-4-yl)methylphosphinic acid and by zinc. Moreover, these chimeric receptors had a fast-desensitizing component, even faster than that of heterooligomeric GABAA receptors, in striking contrast to the almost nil desensitization of wild-type ρ1 (wt ρ1) receptors. To see whether the fast-desensitizing characteristic of the chimera was determined by the amino acids forming the ion channels, we replaced the second transmembrane segment (TM2) of ρ1 by that of the α1-subunit of GABAA. Although the α1-subunit forms fast-desensitizing receptors when coexpressed with other GABAA subunits, the sole transfer of the α1TM2 segment to ρ1 was not sufficient to form desensitizing receptors. All this suggests that the slow-desensitizing trait of ρ1 receptors is determined by a combination of several interacting domains along the molecule. PMID:10725369

  16. Orofacial sensory changes and temporomandibular dysfunction.

    PubMed

    DuPont, J S; Matthews, E P

    2000-07-01

    Orofacial sensory changes are uncommon complaints that can coexist with temporomandibular dysfunction (TMD). The location, character, and intensity vary greatly with each individual and symptom fluctuation is not unusual for any patient. The etiology of orofacial sensory changes may be related to either local or systemic factors. Several investigators have reported that muscle entrapment of branches of the third division of the trigeminal nerve may result in orofacial sensory disruption. Different theories have been suggested to illustrate how TMD and trauma might be associated with these neurological changes. Additionally, several mechanisms exist to explain how muscle spasms may be responsible for nerve compression in individuals with normal anatomy and in those with anatomical variations. In this study, thirty subjects from a group of 282 TMD patients were found to have coexisting orofacial sensory disturbances and TMD. Subjects presenting with any neurological complaints should alert the clinician to the possibility that these symptoms may be the early clinical signs of serious disease.

  17. Mast cell desensitization inhibits calcium flux and aberrantly remodels actin

    PubMed Central

    Ang, W.X. Gladys; Church, Alison M.; Kulis, Mike; Choi, Hae Woong; Burks, A. Wesley

    2016-01-01

    Rush desensitization (DS) is a widely used and effective clinical strategy for the rapid inhibition of IgE-mediated anaphylactic responses. However, the cellular targets and underlying mechanisms behind this process remain unclear. Recent studies have implicated mast cells (MCs) as the primary target cells for DS. Here, we developed a murine model of passive anaphylaxis with demonstrated MC involvement and an in vitro assay to evaluate the effect of DS on MCs. In contrast with previous reports, we determined that functional IgE remains on the cell surface of desensitized MCs following DS. Despite notable reductions in MC degranulation following DS, the high-affinity IgE receptor FcεRI was still capable of transducing signals in desensitized MCs. Additionally, we found that displacement of the actin cytoskeleton and its continued association with FcεRI impede the capacity of desensitized MCs to evoke the calcium response that is essential for MC degranulation. Together, these findings suggest that reduced degranulation responses in desensitized MCs arise from aberrant actin remodeling, providing insights that may lead to improvement of DS treatments for anaphylactic responses. PMID:27669462

  18. Double peak sensory responses: effects of capsaicin.

    PubMed

    Aprile, I; Tonali, P; Stalberg, E; Di Stasio, E; Caliandro, P; Foschini, M; Vergili, G; Padua, L

    2007-10-01

    The aim of this study is to verify whether degeneration of skin receptors or intradermal nerve endings by topical application of capsaicin modifies the double peak response obtained by submaximal anodal stimulation. Five healthy volunteers topically applied capsaicin to the finger-tip of digit III (on the distal phalanx) four times daily for 4-5 weeks. Before and after local capsaicin applications, we studied the following electrophysiological findings: compound sensory action potential (CSAP), double peak response, sensory threshold and double peak stimulus intensity. Local capsaicin application causes disappearance or decrease of the second component of the double peak, which gradually increases after the suspension of capsaicin. Conversely, no significant differences were observed for CSAP, sensory threshold and double peak stimulus intensity. This study suggests that the second component of the double peak may be a diagnostic tool suitable to show an impairment of the extreme segments of sensory nerve fibres in distal sensory axonopathy in the early stages of damage, when receptors or skin nerve endings are impaired but undetectable by standard nerve conduction studies.

  19. Mechanism of action of a desensitizing fluoride toothpaste delivering calcium and phosphate ingredients in the treatment of dental hypersensitivity. Part II: comparison with a professional treatment for tooth hypersensitivity.

    PubMed

    Charig, Andrew J; Thong, Stephen; Flores, Florita; Gupta, Shivank; Major, Elizabeth; Winston, Anthony E

    2009-01-01

    Tooth hypersensitivity can occur when gum recession causes exposure of dentin. Tiny tubules, which permeate dentin, provide open passageways from the mouth to the intradental nerve in the pulpal cavity. Under such circumstances, stimuli in the mouth can cause pressure on the intradental nerve, leading to pain. Sealing the outside of the tubules with an impermeable substance can effectively treat hypersensitivity. One such clinically proven composition is a professionally applied tooth desensitizer, which has been shown to initially produce a layer of amorphous calcium phosphate (ACP) on the surface of dentin. Under the influence of fluoride, ACP reforms as hydroxyapatite (HAP), which has essentially the same composition as tooth mineral. Three fluoride toothpastes that deliver calcium and phosphate salts to the teeth also have been demonstrated in clinical trials to relieve hypersensitivity. This study compared the mechanism of action of these toothpastes to that of the professional desensitizer. A single application of the professional desensitizer or multiple applications of any of the three toothpastes was shown to reduce dentin permeability. A conventional fluoride toothpaste also was found to inhibit fluid flow through the dentin but to a lesser degree than the other toothpastes. The desensitizer and the three toothpastes were found to occlude the dentinal tubules with a layer of calcium phosphate that had a calcium-to-phosphate ratio consistent with the formation of ACP or HAP. The morphology of the coherent mineral layer formed by Arm & Hammer Enamel Care Sensitive was similar, especially to that produced by the desensitizer. In contrast, the conventional toothpaste left localized areas of surface residue composed of silica particles. The mechanism of action of the three toothpastes that deliver calcium and phosphate salts is the same as that of the professional desensitizer.

  20. Microsurgical anatomy of the trigeminal nerve.

    PubMed

    Joo, Wonil; Yoshioka, Fumitaka; Funaki, Takeshi; Mizokami, Koji; Rhoton, Albert L

    2014-01-01

    The objective of this study is to review surgical anatomy of the trigeminal nerve. We also demonstrate some pictures involving the trigeminal nerve and its surrounding connective and neurovascular structures. Ten adult cadaveric heads were studied, using a magnification ranging from 3× to 40×, after perfusion of the arteries and veins with colored latex. The trigeminal nerve is the largest and most complex of the cranial nerves. It serves as a major conduit of sensory input from the face and provides motor innervation to the muscles of mastication. Because of its size and complexity, it is essential to have thorough knowledge of the nerve before diagnoses and treatment of the pathologic processes in the orofacial, temporomandibular, infratemporal, and pterygopalatine areas. The trigeminal nerve is encountered with imaging or surgery of the skull base surgery. Thus, a comprehensive knowledge of the anatomy of the trigeminal nerve is crucial for performing the surgical procedures without significant complication.

  1. Children's exposure to violent video games and desensitization to violence.

    PubMed

    Funk, Jeanne B

    2005-07-01

    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.

  2. Mechanism of action of a desensitizing fluoride toothpaste delivering calcium and phosphate ingredients in the treatment of dental hypersensitivity. Part III: Prevention of dye penetration through dentin vs a calcium- and phosphate-free control.

    PubMed

    Winston, Anthony E; Charig, Andrew J; Thong, Stephen

    2010-01-01

    It is generally accepted that the pain of dental hypersensitivity resulting from gum recession is from the movement of fluid within the exposed tubules of dentin, causing changes in pressure on the nerve within the pulpal cavity. One method of treating hypersensitivity is to occlude the tubules, preventing fluid movement. This article discusses the use of a dye penetration technique, which establishes this mechanism of action for a desensitizing fluoride toothpaste containing calcium and phosphate. Two groups of intact teeth were perfectly sealed with enamel paint. Windows 100-micro to 200-micro deep were opened on opposite sides of each tooth at the dentin-enamel junction and briefly etched using 20% polyacrylic acid. One batch of teeth was treated eight times for 30 mins each with a 1:3 slurry of the desensitizing toothpaste and another set with a similar slurry prepared from a calcium- and phosphate-free control. A 0.85% aqueous solution of acid red fuchsin dye was applied to each window and allowed to dry. After a brief rinse, the teeth were sectioned across the windows. Almost no dye penetration was seen in teeth treated with the desensitizing toothpaste; however, extensive penetration through the dentin was visible in the control-treated teeth. The differences in dye penetration for the two sets of teeth were significant by both subjective (P < .001) and objective (P < .01) measures. Tubule occlusion because of calcium and phosphate ions from the desensitizing toothpaste accounts for its tooth desensitizing efficacy.

  3. Nerve transfers in brachial plexus birth palsies: indications, techniques, and outcomes.

    PubMed

    Kozin, Scott H

    2008-11-01

    The advent of nerve transfers has greatly increased surgical options for children who have brachial plexus birth palsies. Nerve transfers have considerable advantages, including easier surgical techniques, avoidance of neuroma resection, and direct motor and sensory reinnervation. Therefore, any functioning nerve fibers within the neuroma are preserved. Furthermore, a carefully selected donor nerve results in little or no clinical deficit. However, some disadvantages and unanswered questions remain. Because of a lack of head-to-head comparison between nerve transfers and nerve grafting, the window of opportunity for nerve grafting may be missed, which may degrade the ultimate outcome. Time will tell the ultimate role of nerve transfer or nerve grafting.

  4. Common peroneal nerve dysfunction

    MedlinePlus

    Neuropathy - common peroneal nerve; Peroneal nerve injury; Peroneal nerve palsy ... type of peripheral neuropathy (damage to nerves outside the brain ... nerve injuries. Damage to the nerve disrupts the myelin sheath ...

  5. A Controlled Study to Assess the Clinical Efficacy of Totally Self-Administered Systematic Desensitization

    ERIC Educational Resources Information Center

    Rosen, Gerald M.; And Others

    1976-01-01

    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…

  6. Evaluation Of The Shear Bond Strength Between Dentin And Dental Luting Cement Following Dentin Surface Treatment By 980 Nm Diode Laser And Desensitizing Agent

    NASA Astrophysics Data System (ADS)

    Ibrahim, T.; Gheith, M.

    2011-09-01

    Dentin hypersensitivity is described clinically as an exaggerated response to non-noxious sensory stimuli. Current treatment is concentrating on two approaches; to occlude the dentinal tubules or to block neural transmission. This is achieved through using dentin desensitizers and low power lasers. Forty eight freshly extracted human molar teeth were used in this study and divided equally into three groups. Group 1) control group, group 2) laser treated dentin surface group, and group 3) desensitizing agent dentin surface group. Scanning electron microscopic analysis of laser treated group showed melted globules, no carbonization, recrystalization and crystal growth of the apatite in some areas. In diode laser dentin surface treated group showed the highest shear bond strength mean value.

  7. [An analysis of characteristics of nerve conduction in 154 cases of amyotrophic lateral sclerosis].

    PubMed

    Ren, Y T; Cui, F; Yang, F; Chen, Z H; Ling, L; Huang, X S

    2016-10-01

    Objective: To analyze the features of nerve conduction in patients with amyotrophic lateral sclerosis (ALS), and explore the correlation between compound muscle action potential (CMAP) amplitude and disease duration and revised amyotrophic lateral sclerosis functional rating scale (ALSFRS-R). Methods: Standard motor and sensory nerve conduction studies were performed in 154 patients with ALS. The following parameters were collected including CMAP amplitude, distal motor latency (DML), motor conduction velocity, sensory conduction velocity and sensory nerve action potential amplitude. Regression study was done to explore the correlation between CMAP amplitude and disease duration and ALSFRS-R. Results: Motor nerve conduction abnormalities were presented in a majority of the patients with prolonged DML in the tibial nerve, median nerve and ulnar nerve as the most common form (61.06%-81.42%), followed by decreased CMAP amplitude (30.12%-53.98%), decreased MCV (12.05%-16.81%) and absence of CMAP (2.65%-9.73%). Sensory nerve conduction abnormalities were detected in a small proportion of patients and the decreased SCV, decreased SNAP amplitude and absence of SNAP in the sural nerve, median nerve and ulnar nerve were found in 1.22%-2.73%, 0-1.82% and 0-1.22% patients respectively. No correlation was found between CMAP of the common peroneal nerve, tibial nerve, median nerve and ulnar nerve and the disease duration (P>0.05), while significant positive correlation was established between CMAP amplitude of the median nerve and ulnar nerve and ALSFRS-R (r=0.273, P=0.016; r=0.357, P=0.001). Conclusions: Motor nerve conduction is abnormal in a majority of ALS patients with prolonged DML as the most common form, while abnormal sensory nerve conduction is only found in a few of ALS patients. CMAP amplitude of the median nerve and ulnar nerve might be of certain clinical value in evaluating the severity of ALS.

  8. Opioid receptor desensitization: mechanisms and its link to tolerance

    PubMed Central

    Allouche, Stéphane; Noble, Florence; Marie, Nicolas

    2014-01-01

    Opioid receptors (OR) are part of the class A of G-protein coupled receptors and the target of the opiates, the most powerful analgesic molecules used in clinic. During a protracted use, a tolerance to analgesic effect develops resulting in a reduction of the effectiveness. So understanding mechanisms of tolerance is a great challenge and may help to find new strategies to tackle this side effect. This review will summarize receptor-related mechanisms that could underlie tolerance especially receptor desensitization. We will focus on the latest data obtained on molecular mechanisms involved in opioid receptor desensitization: phosphorylation, receptor uncoupling, internalization, and post-endocytic fate of the receptor. PMID:25566076

  9. Eye movement desensitization and reprocessing: a conceptual framework.

    PubMed

    Menon, Sukanya B; Jayan, C

    2010-07-01

    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.

  10. [Successful drug desensitization after vemurafenib-induced rash].

    PubMed

    Klossowski, N; Kislat, A; Homey, B; Gerber, P A; Meller, S

    2015-04-01

    The BRAF inhibitor vemurafenib was approved in 2011 for the treatment of inoperable or metastatic melanoma. Vemurafenib therapy is associated with several side effects, such as arthralgia, secondary skin tumors or inflammatory rashes. In particular cutaneous toxicities represent a serious threat to patients' adherence. Here, we present the case of a successful drug desensitization in a patient that presented with a vemurafenib-induced rash. Lymphocyte activation tests failed to detect drug-specific T cells, suggesting that the development of the rash was based upon a nonallergic drug hypersensitivity reaction. A program of slow desensitization was initiated and subsequently, vemurafenib was tolerated at the full effective and recommended dosage.

  11. Exogenous nerve growth factor protects the hypoglossal nerve against crush injury

    PubMed Central

    Fan, Li-yuan; Wang, Zhong-chao; Wang, Pin; Lan, Yu-yan; Tu, Ling

    2015-01-01

    Studies have shown that sensory nerve damage can activate the p38 mitogen-activated protein kinase (MAPK) pathway, but whether the same type of nerve injury after exercise activates the p38MAPK pathway remains unclear. Several studies have demonstrated that nerve growth factor may play a role in the repair process after peripheral nerve injury, but there has been little research focusing on the hypoglossal nerve injury and repair. In this study, we designed and established rat models of hypoglossal nerve crush injury and gave intraperitoneal injections of exogenous nerve growth factor to rats for 14 days. p38MAPK activity in the damaged neurons was increased following hypoglossal nerve crush injury; exogenous nerve growth factor inhibited this increase in acitivity and increased the survival rate of motor neurons within the hypoglossal nucleus. Under transmission electron microscopy, we found that the injection of nerve growth factor contributed to the restoration of the morphology of hypoglossal nerve after crush injury. Our experimental findings indicate that exogenous nerve growth factor can protect damaged neurons and promote hypoglossal nerve regeneration following hypoglossal nerve crush injury. PMID:26889186

  12. Vascularized Nerve Grafts and Vascularized Fascia for Upper Extremity Nerve Reconstruction

    PubMed Central

    Kostopoulos, Vasileios K.

    2009-01-01

    Since 1976, experimental and clinical studies have suggested the superiority of vascularized nerve grafts. In this study, a 27-year experience of the senior author is presented regarding vascularized nerve grafts and fascia for complex upper extremity nerve reconstruction. The factors influencing outcomes as well as a comparison with conventional nerve grafts is presented. Since 1981, 21 vascularized nerve grafts, other than vascularized ulnar nerve, were used for reconstruction of nerve injuries in the upper extremity. Indications were prolonged denervation time, failure of the previously used conventional nerve grafts, and excessive scar in the recipient site. Injury was in the hand/wrist area (n = 5), in the forearm (n = 4), in the elbow (n = 2), in the arm (n = 4), or in the plexus (n = 6). Vascularized sural (n = 9), saphenous (n = 8), superficial radial (n = 3), and peroneal (superficial and deep) nerves were used. The mean follow-up was 31.4 months. Vascularized nerve grafts for upper extremity injuries provided good to excellent sensory return in severely scarred upper extremities in patients in whom conventional nerve grafts had failed. They have also provided relief of causalgia after painful neuroma resection and motor function recovery in selective cases even for above the elbow injuries. Small diameter vascularized nerve grafts should be considered for bridging long nerve gaps in regions of excessive scar or for reconstructions where conventional nerve grafts have failed. PMID:19381727

  13. Antagonist pharmacology of desensitizing and non-desensitizing nicotinic acetylcholine receptors in cockroach neurons.

    PubMed

    Salgado, Vincent L

    2016-09-01

    Two α-bungarotoxin-sensitive nicotinic acetylcholine (ACh) receptor subtypes in neurons of the American cockroach have been identified as desensitizing (nAChD) and selectively inhibitable with 100nM imidacloprid, and non-desensitizing (nAChN) and selectively inhibitable with 100pM methyllycaconitine. In this paper, the single-electrode voltage-clamp technique was used to measure concentration-response relations for the action of ACh and five antagonists on pharmacologically separated nAChD and nAChN receptors of acutely dissociated neurons from thoracic ganglia of the American cockroach. A dual bath and U-tube perfusion system was used to achieve rapid application of ACh in the continued presence of antagonists, which was essential to accurately measure inhibition by rapidly-reversible antagonists. ACh activated both receptors with an EC50 of 7μM and the antagonist potencies were (nAChD/nAChN in nM): dihydro-β-erythroidine: 1.0/5.6, d-tubocurarine: 1000/34, condelphine: 0.39/0.65, phencyclidine: 74/980 and mecamylamine 47/1150. While each of these antagonists displayed some subtype selectivity, none are selective enough to be used as subtype-selective tools. These results bring to a total of 16 the number of nicotinic compounds that have been measured on nAChD and nAChN currents. Characterization of these receptors is important for understanding the role of nAChRs in the insect nervous system and the mechanism of action of insecticides.

  14. Sensory ability in the narwhal tooth organ system.

    PubMed

    Nweeia, Martin T; Eichmiller, Frederick C; Hauschka, Peter V; Donahue, Gretchen A; Orr, Jack R; Ferguson, Steven H; Watt, Cortney A; Mead, James G; Potter, Charles W; Dietz, Rune; Giuseppetti, Anthony A; Black, Sandie R; Trachtenberg, Alexander J; Kuo, Winston P

    2014-04-01

    The erupted tusk of the narwhal exhibits sensory ability. The hypothesized sensory pathway begins with ocean water entering through cementum channels to a network of patent dentinal tubules extending from the dentinocementum junction to the inner pulpal wall. Circumpulpal sensory structures then signal pulpal nerves terminating near the base of the tusk. The maxillary division of the fifth cranial nerve then transmits this sensory information to the brain. This sensory pathway was first described in published results of patent dentinal tubules, and evidence from dissection of tusk nerve connection via the maxillary division of the fifth cranial nerve to the brain. New evidence presented here indicates that the patent dentinal tubules communicate with open channels through a porous cementum from the ocean environment. The ability of pulpal tissue to react to external stimuli is supported by immunohistochemical detection of neuronal markers in the pulp and gene expression of pulpal sensory nerve tissue. Final confirmation of sensory ability is demonstrated by significant changes in heart rate when alternating solutions of high-salt and fresh water are exposed to the external tusk surface. Additional supporting information for function includes new observations of dentinal tubule networks evident in unerupted tusks, female erupted tusks, and vestigial teeth. New findings of sexual foraging divergence documented by stable isotope and fatty acid results add to the discussion of the functional significance of the narwhal tusk. The combined evidence suggests multiple tusk functions may have driven the tooth organ system's evolutionary development and persistence.

  15. Desensitization of patients with bee sting allergy using pure bee venom.

    PubMed

    Abkiewicz, C; Lomnitzer, R; Rabson, A R

    1979-02-24

    Forty patients who had previously experienced severe systemic reactions after a bee sting were desensitized using pure bee venom. A modified 'Rush' regimen was employed whereby patients received two injections a week and reached maximal desensitization in 5 weeks. Eleven patients have subsequently been stung again and have developed no generalized reaction. Although this form of desensitization is considered to be highly effective in protecting sensitive patients, both generalized and local side-effects were frequent. Maintenance desensitizing injections are required every month for an indefinite period. It is concluded that desensitization with pure been venom should be undertaken only in highly selected sensitive patients, and should be performed under strict control.

  16. Vitamin D deficiency leads to sensory and sympathetic denervation of the rat synovium

    PubMed Central

    Tague, Sarah E.; Smith, Peter G.

    2014-01-01

    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 four weeks. Knee synovium sections extending from patella to 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. 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

  17. Cross-desensitization of responses of rat trigeminal subnucleus caudalis neurons to cinnamaldehyde and menthol

    PubMed Central

    Zanotto, Karen L.; Iodi Carstens, M.; Carstens, E.

    2008-01-01

    Most cold-sensitive subnucleus caudalis (Vc) neurons are also excited by the TRPM8 agonist menthol and the TRPA1 agonist cinnamaldehyde (CA). We investigated how interactions among menthol, CA and noxious cooling and heating of the tongue affected responses of superficial Vc units recorded in thiopental-anesthetized rats. Units responded to 1% CA which enhanced cold- and heat-evoked responses 5 min later. They responded more strongly to 10% CA which initially depressed cold responses, followed by enhancement at 5 min without affecting responses to heat. Following 10% CA, the mean response to 1% menthol was significantly lower than when menthol was tested first. After menthol, the subsequent response to CA was significantly weaker compared to the mean CA-evoked response when it was tested first. These results demonstrate mutual cross-desensitization between CA and menthol. The response to CA was enhanced following prior application of 10% ethanol (menthol vehicle). Prior application of menthol did not prevent the biphasic effect of 10% CA on cold-evoked responses, nor did prior application of CA prevent menthol enhancement of cold-evoked responses. Responses to noxious heat were unaffected by 10% CA and menthol regardless of the order of chemical presentation. These data indicate that superficial Vc neurons receive convergent input from primary afferents expressing TRPM8 and TRPA1. The mutual cross-desensitization between CA and menthol, and differential modulation of cold- vs. heat-evoked responses, suggests a direct inhibition of TRPM8 and TRPA1 expressed in peripheral nerve endings by CA and menthol, respectively, rather than a central site of interaction. PMID:18060696

  18. Plasma somatostatin-like immunoreactivity increases in the plasma of septic patients and rats with systemic inflammatory reaction: experimental evidence for its sensory origin and protective role.

    PubMed

    Suto, Balazs; Szitter, Istvan; Bagoly, Terez; Pinter, Erika; Szolcsányi, Janos; Loibl, Csaba; Nemeth, Timea; Tanczos, Krisztian; Molnar, Tihamer; Leiner, Tamas; Varnai, Bianka; Bardonicsek, Zsofia; Helyes, Zsuzsanna

    2014-04-01

    Alterations of somatostatin-like immunoreactivity (SST-LI) in the plasma of 11 systemic inflammatory response syndrome (SIRS) patients were investigated in correlation with cytokines, adhesion molecules and coagulation markers repeatedly during 4 days. The origin and role of SST were studied in the cecum ligation and puncture (CLP) rat SIRS model. Capsaicin-sensitive peptidergic sensory nerves were defunctionalized by resiniferatoxin (RTX) pretreatment 2 weeks earlier, in a separate group animals were treated with the somatostatin receptor antagonist cyclo-somatostatin (C-SOM). Plasma SST-LI significantly elevated in septic patients compared to healthy volunteers during the whole 4-day period. Significantly decreased Horowitz score showed severe lung injury, increased plasma C-reactive protein and procalcitonin confirmed SIRS. Soluble P-selectin, tissue plasminogen activator and the interleukin 8 and monocyte chemotactic protein-1 significantly increased, interleukin 6 and soluble CD40 ligand did not change, and soluble Vascular Adhesion Molecule-1 decreased. SST-LI significantly increased in rats both in the plasma and the lung 6h after CLP compared to sham-operation. After RTX pretreatment SST-LI was not altered in intact animals, but the SIRS-induced elevation was absent. Lung MPO activity significantly increased 6h following CLP compared to sham operation, which was significantly higher both after RTX-desensitization and C-SOM-treatment. Most non-pretreated operated rats survived the 6h, but 60% of the RTX-pretreated ones died showing a significantly worse survival. This is the first comprehensive study in humans and animal experiments providing evidence that SST is released from the activated peptidergic sensory nerves. It gets into the bloodstream and mediates a potent endogenous protective mechanism.

  19. Acute and chronic desensitization of penicillin-allergic patients using oral penicillin.

    PubMed

    Stark, B J; Earl, H S; Gross, G N; Lumry, W R; Goodman, E L; Sullivan, T J

    1987-03-01

    The efficacy, safety and mechanisms of penicillin desensitization were studied in 24 adults and two children with serious infections that required therapy with a beta-lactam drug. Indications for desensitization included debilitating as well as life-endangering infections. Increasing oral doses of phenoxymethyl penicillin were administered at 15-minute intervals to a cumulative dose of 1.3 million units. Parenteral therapy with the beta-lactam drug of choice was instituted at that point. Immunologic complications of desensitization or therapy, ranging from pruritus to serum sickness, occurred in 12 patients. The appearance of gradually worsening wheezing led to abandonment of the procedure in one subject with cystic fibrosis and severe pulmonary disease. The remaining 25 patients were successfully desensitized and received full-dose parenteral therapy. Chronic desensitization was maintained in seven individuals with twice daily oral penicillins for 3 weeks to more than 2 years. No allergic complications of chronic desensitization or recurrent full-dose parenteral therapy were detected. Skin test reactions to one or all penicillin determinants became negative in 11 of 15 patients retested after acute desensitization. Two desensitized patients became skin test negative, remained skin test negative after cessation of desensitization, and tolerated subsequent beta-lactam therapy without allergic reactions or resensitization. The results of this study provide new evidence that acute and chronic penicillin desensitization is useful and an acceptably safe approach and suggest that antigen-specific mast cell desensitization contributes to the protection against anaphylaxis.

  20. The sensory response to capsaicin during repeated topical exposures: differential effects on sensations of itching and pungency.

    PubMed

    Green, B G; Shaffer, G S

    1993-06-01

    Changes in sensory irritation were measured during repeated topical exposures to capsaicin over 2 days. The perceived intensities of itching and pungent sensations, predominantly burning and stinging/pricking, were assessed every 60 sec during 5 applications of capsaicin at inter-stimulus intervals (ISI) of 90 min (Exp. 1) or 15 min (Exp. 2) and in follow-up tests 24 h later. Psychophysical measurements were obtained with a hand-held dynamometer in conjunction with the method of magnitude production. When the ISI was 90 min, itching and pungency were both significantly reduced (i.e., desensitization occurred) by the fifth exposure; however, the reduction occurred more rapidly and dramatically for itching. After 24 h, desensitization remained significant only for itching. When the ISI was 15 min, the sensations on day 1 first intensified in a manner consistent with sensitization, then declined in a manner consistent with desensitization; compared to pungency, itch exhibited less sensitization and more desensitization. On day 2, overall intensity was less for both categories of sensation, primarily because of a reduction in sensitization. Marked individual differences were observed in the overall sensitivity to capsaicin, the time course of sensation, the susceptibility to capsaicin-induced itch, and the rate and duration of sensitization and desensitization. The results are discussed in terms of current hypotheses about the sensory mechanisms that underlie chemically induced itch and the use of capsaicin as a topical analgesic and antipruritic.

  1. Exposure to Violence and Children's Desensitization Attitudes in Lebanon.

    PubMed

    Tarabah, Asma; Badr, Lina Kurdahi; Usta, Jinan; Doyle, John

    2016-11-01

    Children exposed to multiple sources of violence may become desensitized, increasing the possibility of them imitating the aggressive behaviors they watch and considering such behavior as normal. The purpose of this article is to assess the association between exposure to various types of violence (including war) and desensitization in Lebanese children. A cross-sectional design with 207 school-aged children assessed exposure to violence using three surveys: (a) violence in the media (the Media Preference survey), (b) exposure to violence (the KID-SAVE survey), and (c) desensitization attitudes (the Attitude Toward Violence-Child Version). Children were between 8 and 12 years old, 56% were males, and 70%were from middle socioeconomic status (SES) backgrounds. Seventy-six percent of children reported being exposed to violence, with more exposure in males and in the lower SES group. Impact, however, was greater on girls. The predictors of attitude toward violence were "Frequency" of exposure, "Impact" of exposure, and the amount of violence viewed on television. Children are massively exposed to violence in Lebanon resulting in desensitization, which may habituate them to accept violence as normal and put them at risk for imitating violent behaviors.

  2. Systematic Desensitization of Mathematics Anxiety among Preservice Elementary Teachers.

    ERIC Educational Resources Information Center

    Olson, Alton T.; Gillingham, D. Elaine

    1980-01-01

    Systematic desensitization using deep muscle relaxation was significantly successful in the reduction of math anxiety among preservice elementary teachers, but it did not affect their enjoyment of math or their perceptions of its value. Math anxiety was shown to be related to a more globally defined notion of anxiety. (SB)

  3. Emotional Desensitization to Violence Contributes to Adolescents' Violent Behavior.

    PubMed

    Mrug, Sylvie; Madan, Anjana; Windle, Michael

    2016-01-01

    Many adolescents are exposed to violence in their schools, communities and homes. Exposure to violence at high levels or across multiple contexts has been linked with emotional desensitization, indicated by low levels of internalizing symptoms. However, the long-term consequences of such desensitization are unknown. This study examined emotional desensitization to violence, together with externalizing problems, as mediators of the relationship between exposure to violence in pre-adolescence and violent behavior in late adolescence. A community sample of youth (N = 704; 48% female; 76% African American, 22% Caucasian) reported on their exposure to violence in multiple settings at ages 11, 13 and 18. Internalizing and externalizing problems were assessed at ages 11 and 13; violent behavior was measured at age 18. Structural Equation Modeling showed that exposure to high levels of violence at age 11 was associated with lower levels of internalizing problems (quadratic effect) at age 13, as was exposure to violence across multiple contexts (linear effect). In turn, fewer internalizing problems and more externalizing problems at age 13 predicted more violent behavior at age 18. The results suggest that emotional desensitization to violence in early adolescence contributes to serious violence in late adolescence.

  4. Eye Movement Desensitization and Reprocessing: A Critical Analysis.

    ERIC Educational Resources Information Center

    Erwin, Terry McVannel

    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…

  5. Agonist mediated fetal muscle-type nicotinic acetylcholine receptor desensitization

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The exposure of a developing embryo or fetus to teratogenic alkaloids from plants has the potential to cause developmental defects in livestock due to the inhibition of fetal movement by alkaloids. The mechanism behind the inhibition of fetal movement is the desensitization of fetal muscle-type nico...

  6. Localized interstitial granuloma annulare induced by subcutaneous injections for desensitization.

    PubMed

    Spring, Philipp; Vernez, Maxime; Maniu, Christa-Maria; Hohl, Daniel

    2013-06-15

    We describe a patient with interstitial granuloma annulare associated with subcutaneous injection therapy (SIT) for desensitization to a type I allergy. Asymptomatic, erythematous, violaceous annular patches were located at the injection sites on both her arms. Medical history revealed perennial rhinoconjonctivitis treated with SIT (Phostal Stallergen® cat 100% and D. pteronyssinus/D.farinae 50%:50%).

  7. Effects of Systematic Desensitization in the Alleviation of Communication Apprehension.

    ERIC Educational Resources Information Center

    Watson, Arden K.

    A study examined stages and objectives of a systematic desensitization (SD) program and its effects on subject reported apprehension levels and perceived benefits and behavior changes toward public speaking. Subjects, 19 freshmen and sophomore university students, were administered the Personal Report of Communication Apprehension-24 (PRCA-24).…

  8. Treatment of Nightmares via Relaxation and Desensitization: A Controlled Evaluation.

    ERIC Educational Resources Information Center

    Miller, William R.; DiPilato, Marina

    1983-01-01

    Investigated the role of relaxation training as a component of desensitization to nightmares in adults (N=32). Results showed an 80 percent reduction in nightmares reported by 20 clients, of whom 12 reported total elimination of symptoms at 25-week follow-up, suggesting the effectiveness of a behavioral approach in treating nightmares. (LLL)

  9. Emotionally Numb: Desensitization to Community Violence Exposure among Urban Youth

    ERIC Educational Resources Information Center

    Kennedy, Traci M.; Ceballo, Rosario

    2016-01-01

    Community violence exposure (CVE) is associated with numerous psychosocial outcomes among youth. Although linear, cumulative effects models have typically been used to describe these relations, emerging evidence suggests the presence of curvilinear associations that may represent a pattern of emotional desensitization among youth exposed to…

  10. Emotional Desensitization to Violence Contributes to Adolescents’ Violent Behavior

    PubMed Central

    Mrug, Sylvie; Madan, Anjana; Windle, Michael

    2015-01-01

    Many adolescents are exposed to violence in their schools, communities and homes. Exposure to violence at high levels or across multiple contexts has been linked with emotional desensitization, indicated by low levels of internalizing symptoms. However, the long-term consequences of such desensitization are unknown. This study examined emotional desensitization to violence, together with externalizing problems, as mediators of the relationship between exposure to violence in pre-adolescence and violent behavior in late adolescence. A community sample of youth (N=704; 48% female; 76% African American, 22% Caucasian) reported on their exposure to violence in multiple settings at ages 11, 13 and 18. Internalizing and externalizing problems were assessed at ages 11 and 13; violent behavior was measured at age 18. Structural Equation Modeling showed that exposure to high levels of violence at age 11 was associated with lower levels of internalizing problems (quadratic effect) at age 13, as was exposure to violence across multiple contexts (linear effect). In turn, fewer internalizing problems and more externalizing problems at age 13 predicted more violent behavior at age 18. The results suggest that emotional desensitization to violence in early adolescence contributes to serious violence in late adolescence. PMID:25684447

  11. Desensitizing Children's Emotional Reactions to the Mass Media.

    ERIC Educational Resources Information Center

    Wilson, Barbara J.

    1989-01-01

    Assesses effectiveness of two desensitization strategies for reducing children's emotional reactions to mass media. Examines children having passive exposure, modeled exposure, or no exposure to lizards before watching a horror movie involving lizards. Finds that modeled exposure decreases emotional reactions and negative interpretations, whereas…

  12. Desensitization to media violence over a short period of time.

    PubMed

    Fanti, Kostas A; Vanman, Eric; Henrich, Christopher C; Avraamides, Marios N

    2009-01-01

    This study investigated the desensitization to violence over a short period of time. Participants watched nine violent movie scenes and nine comedy scenes, and reported whether they enjoyed the violent or comedy scenes and whether they felt sympathetic toward the victim of violence. Using latent growth modeling, analyses were carried out to investigate how participants responded to the different scenes across time. The findings of this study suggested that repeated exposure to media violence reduces the psychological impact of media violence in the short term, therefore desensitizing viewers to media violence. As a result, viewers tended to feel less sympathetic toward the victims of violence and actually enjoy more the violence portrayed in the media. Additionally, desensitization to media violence was better represented by a curvilinear pattern, whereas desensitization to comedy scenes was better represented by a linear pattern. Finally, trait aggression was not related to the pattern of change over time, although significant effects were found for initial reports of enjoyment and sympathy.

  13. Uncovering sensory axonal dysfunction in asymptomatic type 2 diabetic neuropathy

    PubMed Central

    Sung, Jia-Ying; Tani, Jowy; Chang, Tsui-San; Lin, Cindy Shin-Yi

    2017-01-01

    This study investigated sensory and motor nerve excitability properties to elucidate the development of diabetic neuropathy. A total of 109 type 2 diabetes patients were recruited, and 106 were analyzed. According to neuropathy severity, patients were categorized into G0, G1, and G2+3 groups using the total neuropathy score-reduced (TNSr). Patients in the G0 group were asymptomatic and had a TNSr score of 0. Sensory and motor nerve excitability data from diabetic patients were compared with data from 33 healthy controls. Clinical assessment, nerve conduction studies, and sensory and motor nerve excitability testing data were analyzed to determine axonal dysfunction in diabetic neuropathy. In the G0 group, sensory excitability testing revealed increased stimulus for the 50% sensory nerve action potential (P<0.05), shortened strength-duration time constant (P<0.01), increased superexcitability (P<0.01), decreased subexcitability (P<0.05), decreased accommodation to depolarizing current (P<0.01), and a trend of decreased accommodation to hyperpolarizing current in threshold electrotonus. All the changes progressed into G1 (TNSr 1–8) and G2+3 (TNSr 9–24) groups. In contrast, motor excitability only had significantly increased stimulus for the 50% compound motor nerve action potential (P<0.01) in the G0 group. This study revealed that the development of axonal dysfunction in sensory axons occurred prior to and in a different fashion from motor axons. Additionally, sensory nerve excitability tests can detect axonal dysfunction even in asymptomatic patients. These insights further our understanding of diabetic neuropathy and enable the early detection of sensory axonal abnormalities, which may provide a basis for neuroprotective therapeutic approaches. PMID:28182728

  14. Uncovering sensory axonal dysfunction in asymptomatic type 2 diabetic neuropathy.

    PubMed

    Sung, Jia-Ying; Tani, Jowy; Chang, Tsui-San; Lin, Cindy Shin-Yi

    2017-01-01

    This study investigated sensory and motor nerve excitability properties to elucidate the development of diabetic neuropathy. A total of 109 type 2 diabetes patients were recruited, and 106 were analyzed. According to neuropathy severity, patients were categorized into G0, G1, and G2+3 groups using the total neuropathy score-reduced (TNSr). Patients in the G0 group were asymptomatic and had a TNSr score of 0. Sensory and motor nerve excitability data from diabetic patients were compared with data from 33 healthy controls. Clinical assessment, nerve conduction studies, and sensory and motor nerve excitability testing data were analyzed to determine axonal dysfunction in diabetic neuropathy. In the G0 group, sensory excitability testing revealed increased stimulus for the 50% sensory nerve action potential (P<0.05), shortened strength-duration time constant (P<0.01), increased superexcitability (P<0.01), decreased subexcitability (P<0.05), decreased accommodation to depolarizing current (P<0.01), and a trend of decreased accommodation to hyperpolarizing current in threshold electrotonus. All the changes progressed into G1 (TNSr 1-8) and G2+3 (TNSr 9-24) groups. In contrast, motor excitability only had significantly increased stimulus for the 50% compound motor nerve action potential (P<0.01) in the G0 group. This study revealed that the development of axonal dysfunction in sensory axons occurred prior to and in a different fashion from motor axons. Additionally, sensory nerve excitability tests can detect axonal dysfunction even in asymptomatic patients. These insights further our understanding of diabetic neuropathy and enable the early detection of sensory axonal abnormalities, which may provide a basis for neuroprotective therapeutic approaches.

  15. Capsaicin Induces Degeneration of Cutaneous Autonomic Nerve Fibers

    PubMed Central

    Gibbons, Christopher H; Wang, Ningshan; Freeman, Roy

    2010-01-01

    Objective To determine the effects of topical application of capsaicin on cutaneous autonomic nerves. Methods Thirty-two healthy subjects underwent occlusive application of 0.1% capsaicin cream (or placebo) for 48 hours. Subjects were followed for 6 months with serial assessments of sudomotor, vasomotor, pilomotor and sensory function with simultaneous assessment of innervation through skin biopsies. Results There were reductions in sudomotor, vasomotor, pilomotor and sensory function in capsaicin- treated subjects (p<0.01 vs. placebo). Sensory function declined more rapidly than autonomic function; reaching a nadir by day 6 while autonomic function reached a nadir by day 16. There were reductions in sudomotor, vasomotor, pilomotor and sensory nerve fiber densities in capsaicin treated subjects (p<0.01 vs. placebo). Intra-epidermal nerve fiber density declined maximally by 6 days while autonomic nerve fiber densities reached maximal degeneration by day 16. Conversely, autonomic nerves generally regenerated more rapidly than sensory nerves, requiring 40–50 days to return to baseline levels while sensory fibers required 140–150 days to return to baseline. Interpretation Topical capsaicin leads to degeneration of sudomotor, vasomotor and pilomotor nerves accompanied by impairment of sudomotor, vasomotor and pilomotor function. These results suggest the susceptibility and/or pathophysiologic mechanisms of nerve damage may differ between autonomic and sensory nerve fibers treated with capsaicin and enhances the capsaicin model for the study of disease modifying agents. The data suggest caution should be taken when topical capsaicin is applied to skin surfaces at risk for ulceration, particularly in neuropathic conditions characterized by sensory and autonomic impairment. PMID:21061393

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

    PubMed

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

    2016-10-01

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

  17. [Trigeminal sensory involvement in Bell's palsy (author's transl)].

    PubMed

    Lapresle, J; Fernandez Manchola, I; Lasjaunias, P

    1980-01-26

    Trigeminal sensory involvement was noted in 14 out of 24 cases of Bell's palsy. The authors describe its characteristics and its chronology with regard to the facial paralysis. Then they propose a vascular mechanism for this association on the basis of two kinds of data. First it is known that there is a common arterial supply of the VIIth and Vth cranial nerves through the middle meningeal vascular system. Secondly some exceptional complications of embolisation within that system have included involvement of both VIIth and Vth sensory nerves. These facts support the vascular basis of Bell's palsy and present an example of a vascular territorial pathology in cranial nerve involvement.

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

    PubMed Central

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

    2015-01-01

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

  19. Desensitizing Addiction: Using Eye Movements to Reduce the Intensity of Substance-Related Mental Imagery and Craving

    PubMed Central

    Littel, Marianne; van den Hout, Marcel A.; Engelhard, Iris M.

    2016-01-01

    Eye movement desensitization and reprocessing (EMDR) is an effective treatment for posttraumatic stress disorder. During this treatment, patients recall traumatic memories while making horizontal eye movements (EM). Studies have shown that EM not only desensitize negative memories but also positive memories and imagined events. Substance use behavior and craving are maintained by maladaptive memory associations and visual imagery. Preliminary findings have indicated that these mental images can be desensitized by EMDR techniques. We conducted two proof-of-principle studies to investigate whether EM can reduce the sensory richness of substance-related mental representations and accompanying craving levels. We investigated the effects of EM on (1) vividness of food-related mental imagery and food craving in dieting and non-dieting students and (2) vividness of recent smoking-related memories and cigarette craving in daily smokers. In both experiments, participants recalled the images while making EM or keeping eyes stationary. Image vividness and emotionality, image-specific craving and general craving were measured before and after the intervention. As a behavioral outcome measure, participants in study 1 were offered a snack choice at the end of the experiment. Results of both experiments showed that image vividness and craving increased in the control condition but remained stable or decreased after the EM intervention. EM additionally reduced image emotionality (experiment 2) and affected behavior (experiment 1): participants in the EM condition were more inclined to choose healthy over unhealthy snack options. In conclusion, these data suggest that EM can be used to reduce intensity of substance-related imagery and craving. Although long-term effects are yet to be demonstrated, the current studies suggest that EM might be a useful technique in addiction treatment. PMID:26903888

  20. Comparative evaluation of NovaMin desensitizer and Gluma desensitizer on dentinal tubule occlusion: a scanning electron microscopic study

    PubMed Central

    Joshi, Surabhi; Gowda, Ashwini Shivananje

    2013-01-01

    Purpose In this study, the effect of calcium sodium phosphosilicate (NovaMin) desensitizing agent, which is a powder-based system, and hydroxyethyl methacrylate and glutaraldehyde (Gluma desensitizer), which is liquid-based system, on dentinal tubule occlusion was analyzed by scanning electron microscope. The effects of the above two along with one control group were compared to determine the more effective method of sealing the dentinal tubules after initial application. Methods Twenty specimens were allocated to each of 3 groups: Control, Gluma desensitizer, and NovaMin. Two additional samples were also prepared and treated with Gluma and NovaMin; these samples were longitudinally fractured. The specimens were prepared from extracted sound human premolars and were stored in 10% formalin at room temperature. The teeth were cleaned of gross debris and then sectioned to provide one to two dentin specimens. The dentin specimens were etched with 6% citric acid for 2 minutes and rinsed in distilled water. Control discs were dried, and the test discs were treated with the desensitizing agents as per the manufacturer's instructions. The discs as well as longitudinal sections were later analyzed under the scanning electron microscope. The proportions of completely occluded, partially occluded, and open tubules within each group were calculated. The ratios of completely and partially occluded tubules to the total tubules for all the groups was determined, and the data was statistically analyzed using nonparametric tests and statistical significance was calculated. Results NovaMin showed more completely occluded tubules (0.545±0.051) while Gluma desensitizer showed more partially occluded tubules (0.532±0.075). The differences among all the groups were statistically significant (P≤ 0.05). Conclusion Both materials were effective in occluding dentinal tubules but NovaMin appeared more promising in occluding tubules completely after initial application. PMID:24455439

  1. Reduced evoked motor and sensory potential amplitudes in obstructive sleep apnea patients.

    PubMed

    Mihalj, Mario; Lušić, Linda; Đogaš, Zoran

    2016-06-01

    It is unknown to what extent chronic intermittent hypoxaemia in obstructive sleep apnea causes damage to the motor and sensory peripheral nerves. It was hypothesized that patients with obstructive sleep apnea would have bilaterally significantly impaired amplitudes of both motor and sensory peripheral nerve-evoked potentials of both lower and upper limbs. An observational study was conducted on 43 patients with obstructive sleep apnea confirmed by the whole-night polysomnography, and 40 controls to assess the relationship between obstructive sleep apnea and peripheral neuropathy. All obstructive sleep apnea subjects underwent standardized electroneurographic testing, with full assessment of amplitudes of evoked compound muscle action potentials, sensory neural action potentials, motor and sensory nerve conduction velocities, and distal motor and sensory latencies of the median, ulnar, peroneal and sural nerves, bilaterally. All nerve measurements were compared with reference values, as well as between the untreated patients with obstructive sleep apnea and control subjects. Averaged compound muscle action potential and sensory nerve action potential amplitudes were significantly reduced in the nerves of both upper and lower limbs in patients with obstructive sleep apnea compared with controls (P < 0.001). These results confirmed that patients with obstructive sleep apnea had significantly lower amplitudes of evoked action potentials of both motor and sensory peripheral nerves. Clinical/subclinical axonal damage exists in patients with obstructive sleep apnea to a greater extent than previously thought.

  2. Clinical neurophysiology and quantitative sensory testing in the investigation of orofacial pain and sensory function.

    PubMed

    Jääskeläinen, Satu K

    2004-01-01

    Chronic orofacial pain represents a diagnostic and treatment challenge for the clinician. Some conditions, such as atypical facial pain, still lack proper diagnostic criteria, and their etiology is not known. The recent development of neurophysiological methods and quantitative sensory testing for the examination of the trigeminal somatosensory system offers several tools for diagnostic and etiological investigation of orofacial pain. This review presents some of these techniques and the results of their application in studies on orofacial pain and sensory dysfunction. Clinical neurophysiological investigation has greater diagnostic accuracy and sensitivity than clinical examination in the detection of the neurogenic abnormalities of either peripheral or central origin that may underlie symptoms of orofacial pain and sensory dysfunction. Neurophysiological testing may also reveal trigeminal pathology when magnetic resonance imaging has failed to detect it, so these methods should be considered complementary to each other in the investigation of orofacial pain patients. The blink reflex, corneal reflex, jaw jerk, sensory neurography of the inferior alveolar nerve, and the recording of trigeminal somatosensory-evoked potentials with near-nerve stimulation have all proved to be sensitive and reliable in the detection of dysfunction of the myelinated sensory fibers of the trigeminal nerve or its central connections within the brainstem. With appropriately small thermodes, thermal quantitative sensory testing is useful for the detection of trigeminal small-fiber dysfunction (Adelta and C). In neuropathic conditions, it is most sensitive to lesions causing axonal injury. By combining different techniques for investigation of the trigeminal system, an accurate topographical diagnosis and profile of sensory fiber pathology can be determined. Neurophysiological and quantitative sensory tests have already highlighted some similarities among various orofacial pain conditions

  3. Early compensatory sensory re-education.

    PubMed

    Daniele, Hugo R; Aguado, Leda

    2003-02-01

    After a neurorrhaphy, there will be a distal disconnection between the cortex and skin receptors, along with interruption of sensibility information. This report demonstrates the efficacy of a new sensory re-education program for achieving optimal sensation in a relatively short time. Between 1999 and 2001, in the authors' Hand Rehabilitation Department, 11 patients with previous neurorrhaphy were subjected to a program of early "compensatory sensory re-education." Lesions were caused by clean cut. There were 13 primary digital nerve procedures, 12 at the distal palmar MP level, and one at the radial dorsal branch of the index (just after emerging from the common digital nerve). The technique of compensatory sensory re-education was based on a previous, but modified, sensory re-education method. In order to evaluate the results in the compensatory sensory re-education series described, additional tests for evaluation of achieved functional sensibility were used. The authors' best results were achieved in a maximum of 8 weeks (4-8 weeks), much less time than with the original method (1-2 years). Using the British classification, it was possible to compare the achieved levels of sensibility and the time required for optimal results. The different methods of sensibility re-education may be similar, but with the authors' compensatory sensory re-education method, substantial time is saved.

  4. Novel roles for osteopontin and clusterin in peripheral motor and sensory axon regeneration.

    PubMed

    Wright, Megan C; Mi, Ruifa; Connor, Emmalynn; Reed, Nicole; Vyas, Alka; Alspalter, Manula; Coppola, Giovanni; Geschwind, Daniel H; Brushart, Thomas M; Höke, Ahmet

    2014-01-29

    Previous studies demonstrated that Schwann cells (SCs) express distinct motor and sensory phenotypes, which impact the ability of these pathways to selectively support regenerating neurons. In the present study, unbiased microarray analysis was used to examine differential gene expression in denervated motor and sensory pathways in rats. Several genes that were significantly upregulated in either denervated sensory or motor pathways were identified and two secreted factors were selected for further analysis: osteopontin (OPN) and clusterin (CLU) which were upregulated in denervated motor and sensory pathways, respectively. Sciatic nerve transection induced upregulation of OPN and CLU and expression of both returned to baseline levels with ensuing regeneration. In vitro analysis using exogenously applied OPN induced outgrowth of motor but not sensory neurons. CLU, however, induced outgrowth of sensory neurons, but not motor neurons. To assess the functional importance of OPN and CLU, peripheral nerve regeneration was examined in OPN and CLU(-/-) mice. When compared with OPN(+/+) mice, motor neuron regeneration was reduced in OPN(-/-) mice. Impaired regeneration through OPN(-/-) peripheral nerves grafted into OPN(+/+) mice indicated that loss of OPN in SCs was responsible for reduced motor regeneration. Sensory neuron regeneration was impaired in CLU(-/-) mice following sciatic nerve crush and impaired regeneration nerve fibers through CLU(-/-) nerve grafts transplanted into CLU(+/+) mice indicated that reduced sensory regeneration is likely due to SC-derived CLU. Together, these studies suggest unique roles for SC-derived OPN and CLU in regeneration of peripheral motor and sensory axons.

  5. Nicotine is highly effective at producing desensitization of rat α4β2 neuronal nicotinic receptors

    PubMed Central

    Paradiso, K G; Steinbach, Joe Henry

    2003-01-01

    We examined desensitization by acetylcholine (ACh) and nicotine at the rat α4β2 neuronal nicotinic receptor stably expressed in HEK cells. For both agonists, the decay in response due to desensitization (‘onset’) was best fitted by the sum of two exponentials with the fast component dominant at concentrations > 1 μm. The time constants for onset were similar for both agonists, and showed little concentration dependence over the range of 0.1–100 μm. Recovery from desensitization also showed two exponential components. In contrast to the similarity in onset, nicotine produced longer lasting desensitization, resulting from an increase in the proportion of receptors in the slowly recovering population and from an increase in the time constant for the slow recovery process. The proportion of receptors in the slowly recovering population increased as the duration of the desensitizing pulse increased. Desensitization was also induced by low concentrations of agonist, with no apparent macroscopic response. A 100 s application of 10 nm nicotine desensitized 70 % of the peak response, while 100 s of 10 nm ACh desensitized only 15 %. At higher concentrations of agonist, which result in a macroscopic response, desensitization in the absence of activation also can occur. Nicotine is a very potent and efficacious desensitizing agent at this neuronal nicotinic receptor. PMID:14555718

  6. Desensitization of rat renal thick ascending limb cells to vasopressin.

    PubMed Central

    Elalouf, J M; Sari, D C; Roinel, N; de Rouffignac, C

    1988-01-01

    Previous studies from this laboratory have demonstrated that vasopressin stimulates K, Mg, Ca, Cl, and Na reabsorption by the thick ascending limb of Henle's loop (TALH) of the rat kidney. Micropuncture of superficial nephrons and clearance experiments were performed to determine whether desensitization of the TALH to vasopressin may be demonstrated in vivo and whether such desensitization is specific for the effects of vasopressin (i.e., homologous) or also alters the response to the other hormones acting on the same pool of adenylate cyclase in this nephron segment. Brattleboro rats, with hereditary hypothalamic diabetes insipidus (DI), were given i.m. injections of 1-desamino-8-D-arginine-vasopressin (des-1-amino-[DArg8]VP (herein designated dDAVP); 2 micrograms/day) for 3 days. The effects of maximal physiological doses of arginine-8-vasopressin ([Arg8]VP (herein designated AVP); 20 pg/min per 100 g of body weight) were studied 2 days after the cessation of treatment, when the animals had returned to DI. The K, Mg, Ca, and, to a lesser extent, Cl and Na concentrations in the fluid leaving the TALH of superficial nephrons were higher in dDAVP-treated than in untreated rats given similar amounts of AVP during the experiments. A 50-60% desensitization of the TALH to AVP was still apparent 2 days after stopping the dDAVP injections. Desensitization is homologous, as judged from normal responses to physiological doses of glucagon and calcitonin, two hormones acting on the same cyclase pool as AVP in the rat TALH. The AVP-dependent increase of urine osmolality, however, indicated that its effects on the permeability to water of the collecting duct were scarcely affected in dDAVP-treated rats. It is concluded that (i) AVP induces homologous desensitization in the rat TALH and (ii) the TALH can be markedly desensitized to AVP when the collecting duct response to this hormone is poorly affected or even fully maintained. PMID:3353389

  7. Nerve Blocks

    MedlinePlus

    ... Sometimes the needle has to be inserted fairly deep to reach the nerve causing your problem. This ... understanding of the possible charges you will incur. Web page review process: This Web page is reviewed ...

  8. Nanofibrous nerve conduit-enhanced peripheral nerve regeneration.

    PubMed

    Jiang, Xu; Mi, Ruifa; Hoke, Ahmet; Chew, Sing Yian

    2014-05-01

    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 (ε-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.

  9. Oral rush desensitization with tomato: a case report.

    PubMed

    Nucera, E; Schiavino, D; Buonomo, A; Roncallo, C; Pollastrini, E; Lombardo, C; Alonzi, C; Pecora, V; De Pasquale, T; Patriarca, G

    2006-01-01

    Adverse food reaction in which no immunological mechanism is demonstrated should be termed nonallergic food hypersensitivity or food intolerance. We present the case of a 12-year-old girl with a clinical history of abdominal pain, nausea, and general malaise after tomato intake which completely remitted with antihistamines. The patient underwent a complete allergy evaluation: skin prick tests, serum specific IgE and IgG4 tests to tomato, and double-blind placebo-controlled food challenge. Skin prick tests and specific IgE to tomato were negative while the food challenge was positive. At the end of the workup, the patient underwent an oral rush desensitizing treatment. At the end of the treatment the patient could eat a maintenance dose of 100 g of tomato daily with no side effects at all. This successful result suggests that the oral desensitizing treatment can be used in patients with nonallergic food hypersensitivity.

  10. Effect of two desensitizing agents on dentin permeability in vitro

    PubMed Central

    ISHIHATA, Hiroshi; KANEHIRA, Masafumi; FINGER, Werner J.; TAKAHASHI, Hidekazu; TOMITA, Makoto; SASAKI, Keiichi

    2017-01-01

    Abstract Objective The aim of this in vitro study was to investigate the effect of two desensitizing agents and water on hydraulic conductance in human dentin. Material and Methods GLUMA Desensitizer PowerGel (GLU) contains glutaraldehyde (GA) and 2-hydroxyethyl methacrylate (HEMA), and Teethmate Desensitizer (TD) is a powder comprising tetracalcium phosphate (TTCP) and dicalcium phosphate anhydrous (DCPA) that is mixed with water. Deionized water was used as a negative control (CTR). Thirty discs with a thickness of 1.2 mm were cut from the coronal dentin of the third molars and cleaned with 0.5 M EDTA (pH 7.4). After being mounted in a split-chamber device, the discs were pressurized with water at 1 kPa and 3 kPa in order to measure flow rates with a highly sensitive micro-flow sensor and to calculate hydraulic conductance as a baseline value (BL). Following the application of GLU, TD, and CTR (n=10), hydraulic conductance was remeasured with intermittent storage in water after 15 min, 1 d, 1 w, and 1 m. Reduction in permeability (PR%) was calculated from hydraulic conductance. Data were statistically analyzed using nonparametric methods (α<0.05). Representative discs were inspected by SEM. Results PR% for GLU and TD were 30-50% 15 min and 1 m after their application. Post hoc tests indicated that PR% of CTR was significantly greater than those of GLU and TD at all time points tested. The PR% of GLU and TD were not significantly different. SEM examinations showed noncollapsed collagen meshes at the tubular entrances after GLU, and crystalline precipitates occluding the tubular orifices after TD, whereas CTR specimens showed typical patterns of etched dentin. Conclusions The present study on hydraulic conductance in dentin discs treated with two chemically different desensitizing agents and water as a control demonstrated that both products may be characterized as effective. PMID:28198974

  11. Differential effects of plantar desensitization on locomotion dynamics.

    PubMed

    Manor, Brad; Wolenski, Peter; Guevaro, Alvaro; Li, Li

    2009-10-01

    Reduced plantar sensation secondary to chronic diffuse polyneuropathy (PN) is believed to reduce locomotor stability, especially when walking at non-preferred speeds. However, the contribution of plantar sensation to the maintenance of locomotor stability is not entirely clear. The purpose of this study was to examine the effects of acute loss of plantar sensation on the stability-related kinematic properties of walking at different speeds. Lower-extremity joint kinematics were acquired as healthy young adults walked on a treadmill at their preferred walking speed (PWS) and three predetermined speeds (0.8, 1.0, and 1.2m/s) under both normal and desensitized conditions. Desensitization of the foot soles was induced by ice-exposure, and plantar pressure sensation was assessed by a 5.07 monofilament. The average magnitude of stride duration variability (SDvar) and lower-extremity joint angle variability (JTvar), as well as short- and long-term "finite-time" Lyapunov exponents (lambda(ST)(*), lambda(LT)(*)) associated with lower-extremity joint angles were computed. Ice-induced plantar desensitization led to increased lambda(ST)(*) ( approximately 40%) and lambda(LT)(*) (approximately 8%) values but did not affect SDvar or JTvar. Higher treadmill speed led to greater lambda(ST)(*) and lambda(LT)(*) values, but the speed effects were not influenced by plantar desensitization.While acute loss of plantar sensation does not appear to influence the magnitude of spatial or temporal variability, it did attenuate the state-space trajectory divergence caused by stride-to-stride variability (i.e., lambda(ST)( *) and lambda(LT)(*)). However, as opposed to walking at PWS, otherwise healthy locomotor systems do not appear to place increased reliance on plantar sensation when walking at non-preferred treadmill speeds.

  12. Micromorphological Evaluation of Dentin Treated with Different Desensitizing Agents

    PubMed Central

    Osmari, Deise; de Oliveira Ferreira, Ana Carolina; de Carlo Bello, Mariana; Henrique Susin, Alexandre; Cecília Correa Aranha, Ana; Marquezan, Marcela; Lopes da Silveira, Bruno

    2013-01-01

    Introduction: The purpose of a desensitizing agent is a permanent coating or filling of dentin surface. Morphological analysis in vitro of this treated surface is essential to understand the interaction between desensitizing agent and hypersensitive dentin. The aim was to evaluate the morphology of four dentin surface treated with desensitizing agents. Methods: This was an in vitro laboratory study, where fifteen specimens from extracted human premolars were obtained. The enamel was removed to expose the dentin surface, polished with silicon carbide abrasive papers and etched with 6% citric acid for 2 min.The specimens were randomly divided into 5 groups: G1 - without treatment (control) (C), G2 - fluoride varnish (FV), G3 - potassium oxalate (PO), G4 - 2-step self-etching adhesive system (AS), G5 - diode laser (DL). The specimens were cleaved in the lingual buccaldirection, prepared for analysis by Scanning Electron Microscope and the surface and interior of the dentinal tubules were observed at 1500× magnification. Results: In the control group, the dentin etching promoted smear layer removal and exposure of dentinal tubules. In the group of fluoride varnish, a film was observed on the surface, with plugs of varnish into tubules. In the group of oxalate, partial obliteration of the tubular entrances was observed. In the group of the adhesive system, the tubules were obstructed through the formation of hybrid layer and a physical barrier on the surface. In the group of the diode laser, dentin melting and solidification with partial occlusion of dentinal tubules were observed. Conclusions: All desensitizing agents evaluated demonstrated ability to modify the surface of dentin, with partial or total occlusion of dentinal tubules. Thus, it is suggested to do more clinical studies to verify the effectiveness of the findings. PMID:25606322

  13. [Acetylsalicylic acid desensitization in the new era of percutaneous coronary intervention].

    PubMed

    Fuertes Ferre, Georgina; Ferrer Gracia, Maria Cruz; Calvo Cebollero, Isabel

    2015-09-21

    Dual antiplatelet therapy is essential in patients undergoing percutaneous coronary intervention with stent implantation. Hypersensitivity to acetylsalicylic acid (ASA) limits treatment options. Desensitization to ASA has classically been studied in patients with respiratory tract disease. Over the last years, many protocols have been described about ASA desensitization in patients with ischemic heart disease, including acute coronary syndrome and the need for coronary stent implantation. It is important to know the efficacy and safety of ASA desensitization in these patients.

  14. Influence of subunit composition on desensitization of neuronal acetylcholine receptors at low concentrations of nicotine.

    PubMed

    Fenster, C P; Rains, M F; Noerager, B; Quick, M W; Lester, R A

    1997-08-01

    The influence of alpha and beta subunits on the properties of nicotine-induced activation and desensitization of neuronal nicotinic acetylcholine receptors (nAChRs) expressed in Xenopus oocytes was examined. Receptors containing alpha4 subunits were more sensitive to activation by nicotine than alpha3-containing receptors. At low concentrations of nicotine, nAChRs containing beta2 subunits reached near-maximal desensitization more rapidly than beta4-containing receptors. The concentration of nicotine producing half-maximal desensitization was influenced by the particular alpha subunit expressed; similar to results for activation, alpha4-containing receptors were more sensitive to desensitizing levels of nicotine than alpha3-containing receptors. The alpha subunit also influenced the rate of recovery from desensitization; this rate was approximately inversely proportional to the apparent nicotine affinity for the desensitized state. The homomeric alpha7 receptor showed the lowest sensitivity to nicotine for both activation and desensitization; alpha7 nAChRs also demonstrated the fastest desensitization kinetics. These subunit-dependent properties remained in the presence of external calcium, although subtle, receptor subtype-specific effects on both the apparent affinities for activation and desensitization and the desensitization kinetics were noted. These data imply that the subunit composition of various nAChRs determines the degree to which receptors are desensitized and/or activated by tobacco-related levels of nicotine. The subtype-specific balance between receptor activation and desensitization should be considered important when the cellular and behavioral actions of nicotine are interpreted.

  15. Hereditary sensory radicular neuropathy: defective neurogenic inflammation.

    PubMed

    Westerman, R A; Block, A; Nunn, A; Delaney, C A; Hahn, A; Dennett, X; Carr, R W

    1992-01-01

    Hereditary sensory radicular neuropathy exhibits autosomal dominant inheritance with complete penetrance in males and incomplete penetrance in females. Newer tests of small sensory nerve function were used in screening 8 family members aged between 14 and 66 years. All exhibited some frequent features of the disorder with an onset in the 2nd or 3rd decade, foot ulceration, foot callus, loss of pin prick, thermal and light touch sensation, and some reduction in vibration acuity and proprioception in the lower limbs. The hands were involved in 3 of 8, muscle involvement was present in 5 of 8, but deafness was not detected by audiometry. Nerve conduction velocity, sensory action potentials, latency and amplitude, thermal acuity, vibration acuity and axon reflex flares were measured in all patients. One sural nerve biopsy confirmed the presence of peripheral fibre loss in this predominantly sensory neuropathy. Chemically evoked axon reflex tests were used to evaluate the extent of primary sensory nerve fibre involvement. All patients were tested using a Moor MBF 3-D dual channel laser Doppler velocimeter. Acetylcholine or phenylephrine iontophoretically applied as 16 mC doses evoked absent or tiny axon reflexes in areas of impaired pin prick sensation. By contrast, direct microvascular dilator responses to nitroprusside (smooth muscle dependent) and acetylcholine (endothelium-dependent) were present but somewhat reduced in areas with defective neurogenic inflammation. These results differ significantly from the responses obtained in age-matched healthy controls (P < 0.05). Foot pressure analysis was performed for orthoses in 2 affected members with foot ulceration using the Musgrave Footprint system.(ABSTRACT TRUNCATED AT 250 WORDS)

  16. Optic Nerve Decompression

    MedlinePlus

    ... Nerve Decompression Dacryocystorhinostomy (DCR) Disclosure Statement Printer Friendly Optic Nerve Decompression John Lee, MD Introduction Optic nerve decompression is a surgical procedure aimed at ...

  17. Ulnar nerve dysfunction

    MedlinePlus

    Neuropathy - ulnar nerve; Ulnar nerve palsy; Mononeuropathy; Cubital tunnel syndrome ... compressed in the elbow, a problem called cubital tunnel syndrome may result. When damage destroys the nerve ...

  18. A silk sericin/silicone nerve guidance conduit promotes regeneration of a transected sciatic nerve.

    PubMed

    Xie, Hongjian; Yang, Wen; Chen, Jianghai; Zhang, Jinxiang; Lu, Xiaochen; Zhao, Xiaobo; Huang, Kun; Li, Huili; Chang, Panpan; Wang, Zheng; Wang, Lin

    2015-10-28

    Peripheral nerve gap defects lead to significant loss of sensory or motor function. Tissue engineering has become an important alternative to nerve repair. Sericin, a major component of silk, is a natural protein whose value in tissue engineering has just begun to be explored. Here, the first time use of sericin in vivo is reported as a long-term implant for peripheral nerve regeneration. A sericin nerve guidance conduit is designed and fabricated. This conduit is highly porous with mechanical strength matching peripheral nerve tissue. It supports Schwann cell proliferation and is capable of up-regulating the transcription of glial cell derived neurotrophic factor and nerve growth factor in Schwann cells. The sericin conduit wrapped with a silicone conduit (sericin/silicone double conduits) is used for bridging repair of a 5 mm gap in a rat sciatic nerve transection model. The sericin/silicone double conduits achieve functional recovery comparable to that of autologous nerve grafting as evidenced by drastically improved nerve function and morphology. Importantly, this improvement is mainly attributed to the sericin conduit as the silicone conduit alone only produces marginal functional recovery. This sericin/silicone-double-conduit strategy offers an efficient and valuable alternative to autologous nerve grafting for repairing damaged peripheral nerve.

  19. Cross-Face Nerve Grafting with Infraorbital Nerve Pathway Protection: Anatomic and Histomorphometric Feasibility Study

    PubMed Central

    Catapano, Joseph; Demsey, Daniel R.B.; Ho, Emily S.; Zuker, Ronald M.

    2016-01-01

    Smiling is an important aspect of emotional expression and social interaction, leaving facial palsy patients with impaired social functioning and decreased overall quality of life. Although there are several techniques available for facial reanimation, staged facial reanimation using donor nerve branches from the contralateral, functioning facial nerve connected to a cross-face nerve graft (CFNG) is the only technique that can reliably reproduce an emotionally spontaneous smile. Although CFNGs provide spontaneity, they typically produce less smile excursion than when the subsequent free functioning muscle flap is innervated with the motor nerve to the masseter muscle. This may be explained in part by the larger number of donor motor axons when using the masseter nerve, as studies have shown that only 20% to 50% of facial nerve donor axons successfully cross the nerve graft to innervate their targets. As demonstrated in our animal studies, increasing the number of donor axons that grow into and traverse the CFNG to innervate the free muscle transfer increases muscle movement, and this phenomenon may provide patients with the benefit of improved smile excursion. We have previously shown in animal studies that sensory nerves, when coapted to a nerve graft, improve axonal growth through the nerve graft and improve muscle excursion. Here, we describe the feasibility of and our experience in translating these results clinically by coapting the distal portion of the CFNG to branches of the infraorbital nerve. PMID:27757349

  20. Electrophysiology of corneal cold receptor nerve terminals.

    PubMed

    Carr, Richard W; Brock, James A

    2002-01-01

    The mechanisms of sensory transduction in the fine nerve terminals of free nerve endings supplied by Adelta and C sensory axons are largely a matter of speculation. This is because the nerve terminals are small and inaccessible, particularly in intact tissues like skin. However, some of the difficulties associated with investigating the physiology of fine nerve terminals have recently been overcome using an in vitro preparation of the guinea-pig cornea that allows nerve terminal impulses (NTIs) to be recorded extracellularly from single polymodal and cold receptor nerve terminals. For cold receptors, the rate of spontaneously occurring NTIs is increased during cooling and decreased during heating. In addition, heating and cooling differentially modulate the shape of the recorded NTI. At the same temperature, NTIs are larger in amplitude and faster in time course during heating than those during cooling. The differential effect of heating and cooling on NTI shape is not considered to result simply from the temperature dependence of voltage-activated conductance kinetics or activity dependent changes in membrane excitability. Instead, changes in NTI shape may reflect changes in nerve terminal membrane potential that underlie the process of thermal transduction.

  1. Multiple components of ganglion cell desensitization in response to prosthetic stimulation

    NASA Astrophysics Data System (ADS)

    Freeman, Daniel K.; Fried, Shelley I.

    2011-02-01

    Retinal prostheses aim to restore functional vision to those blinded by outer retinal diseases using electric stimulation of surviving neurons. Previous work indicates that repetitive stimulation with stimuli that activate the synaptic network reduces the sensitivity of retinal neurons to further stimulation. Such desensitization may contribute to the fading of visual percepts over time reported by human subjects. Here, we show that desensitization may be more complex than previously considered. We recorded spike trains from rabbit retinal ganglion cells and found that desensitization persists in the presence of inhibitory blockers (strychnine and picrotoxin), indicating amacrine cell inhibition is not solely responsible for reducing sensitivity in response to electric stimulation. The threshold for direct activation of the ganglion cell changes little during the simultaneous desensitization of the synaptically mediated response, indicating that desensitization likely occurs upstream of the spike generator. In addition to rapid desensitization acting over hundreds of milliseconds (τ = 176.4 ± 8.8 ms), we report the presence of slow acting desensitization with a time course of seconds (τ = 14.0 ± 1.1 s). The time courses of the two components of desensitization that we found are similar to the two phases of brightness fading seen in human subjects. This suggests that the reduction in ganglion cell firing due to desensitization may be responsible for the fading of visual percepts over time in response to prosthetic stimulation.

  2. Ulnar nerve sonography in leprosy neuropathy.

    PubMed

    Wang, Zhu; Liu, Da-Yue; Lei, Yang-Yang; Yang, Zheng; Wang, Wei

    2016-01-01

    A 23-year-old woman presented with a half-year history of right forearm sensory and motor dysfunction. Ultrasound imaging revealed definite thickening of the right ulnar nerve trunk and inner epineurium, along with heterogeneous hypoechogenicity and unclear nerve fiber bundle. Color Doppler exhibited a rich blood supply, which was clearly different from the normal ulnar nerve presentation with a scarce blood supply. The patient subsequently underwent needle aspiration of the right ulnar nerve, and histopathological examination confirmed that granulomatous nodules had formed with a large number of infiltrating lymphocytes and a plurality of epithelioid cells in the fibrous connective tissues, with visible atypical foam cells and proliferous vascularization, consistent with leprosy. Our report will familiarize readers with the characteristic sonographic features of the ulnar nerve in leprosy, particularly because of the decreasing incidence of leprosy in recent years.

  3. Mechanisms of alpha 1-adrenergic vascular desensitization in conscious dogs

    NASA Technical Reports Server (NTRS)

    Kiuchi, K.; Vatner, D. E.; Uemura, N.; Bigaud, M.; Hasebe, N.; Hempel, D. M.; Graham, R. M.; Vatner, S. F.

    1992-01-01

    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

  4. Sensory receptors in monotremes.

    PubMed

    Proske, U; Gregory, J E; Iggo, A

    1998-07-29

    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

  5. Sensory receptors in monotremes.

    PubMed Central

    Proske, U; Gregory, J E; Iggo, A

    1998-01-01

    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

  6. A bioengineered peripheral nerve construct using aligned peptide amphiphile nanofibers

    PubMed Central

    Yalom, Anisa; Berns, Eric J.; Stephanopoulos, Nicholas; McClendon, Mark T.; Segovia, Luis A.; Spigelman, Igor; Stupp, Samuel I.; Jarrahy, Reza

    2014-01-01

    Peripheral nerve injuries can result in lifelong disability. Primary coaptation is the treatment of choice when the gap between transected nerve ends is short. Long nerve gaps seen in more complex injuries often require autologous nerve grafts or nerve conduits implemented into the repair. Nerve grafts, however, cause morbidity and functional loss at donor sites, which are limited in number. Nerve conduits, in turn, lack an internal scaffold to support and guide axonal regeneration, resulting in decreased efficacy over longer nerve gap lengths. By comparison, peptide amphiphiles (PAs) are molecules that can self-assemble into nanofibers, which can be aligned to mimic the native architecture of peripheral nerve. As such, they represent a potential substrate for use in a bioengineered nerve graft substitute. To examine this, we cultured Schwann cells with bioactive PAs (RGDS-PA, IKVAV-PA) to determine their ability to attach to and proliferate within the biomaterial. Next, we devised a PA construct for use in a peripheral nerve critical sized defect model. Rat sciatic nerve defects were created and reconstructed with autologous nerve, PLGA conduits filled with various forms of aligned PAs, or left unrepaired. Motor and sensory recovery were determined and compared among groups. Our results demonstrate that Schwann cells are able to adhere to and proliferate in aligned PA gels, with greater efficacy in bioactive PAs compared to the backbone-PA alone. In vivo testing revealed recovery of motor and sensory function in animals treated with conduit/PA constructs comparable to animals treated with autologous nerve grafts. Functional recovery in conduit/PA and autologous graft groups was significantly faster than in animals treated with empty PLGA conduits. Histological examinations also demonstrated increased axonal and Schwann cell regeneration within the reconstructed nerve gap in animals treated with conduit/PA constructs. These results indicate that PA nanofibers may

  7. Raman microspectroscopy for visualization of peripheral nerves

    NASA Astrophysics Data System (ADS)

    Minamikawa, Takeo; Harada, Yoshinori; Koizumi, Noriaki; Takamatsu, Tetsuro

    2013-02-01

    The peripheral nervous system plays an important role in motility, sensory, and autonomic functions of the human body. Preservation of peripheral nerves in surgery 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.

  8. Spontaneous temporal changes and variability of peripheral nerve conduction analyzed using a random effects model.

    PubMed

    Krøigård, Thomas; Gaist, David; Otto, Marit; Højlund, Dorthe; Selmar, Peter E; Sindrup, Søren H

    2014-08-01

    The reproducibility of variables commonly included in studies of peripheral nerve conduction in healthy individuals has not previously been analyzed using a random effects regression model. We examined the temporal changes and variability of standard nerve conduction measures in the leg. Peroneal nerve distal motor latency, motor conduction velocity, and compound motor action potential amplitude; sural nerve sensory action potential amplitude and sensory conduction velocity; and tibial nerve minimal F-wave latency were examined in 51 healthy subjects, aged 40 to 67 years. They were reexamined after 2 and 26 weeks. There was no change in the variables except for a minor decrease in sural nerve sensory action potential amplitude and a minor increase in tibial nerve minimal F-wave latency. Reproducibility was best for peroneal nerve distal motor latency and motor conduction velocity, sural nerve sensory conduction velocity, and tibial nerve minimal F-wave latency. Between-subject variability was greater than within-subject variability. Sample sizes ranging from 21 to 128 would be required to show changes twice the magnitude of the spontaneous changes observed in this study. Nerve conduction studies have a high reproducibility, and variables are mainly unaltered during 6 months. This study provides a solid basis for the planning of future clinical trials assessing changes in nerve conduction.

  9. Vagus Nerve Stimulation

    MedlinePlus

    Vagus nerve stimulation Overview By Mayo Clinic Staff Vagus nerve stimulation is a procedure that involves implantation of a device that stimulates the vagus nerve with electrical impulses. There's one vagus nerve on ...

  10. Nerve biopsy (image)

    MedlinePlus

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

  11. Lumbosacral nerve root avulsion.

    PubMed

    Chin, C H; Chew, K C

    1997-01-01

    Lumbosacral nerve root avulsion is a rare clinical entity. Since the first description in 1955, only 35 cases have been reported. It is often associated with pelvic fractures and may be missed in the initial clinical examination as these patients usually present with multiple injuries. We present three such cases with clinical and radiological findings. These patients were involved in road traffic accidents. Two had fractures of the sacroiliac joint with diastasis of the symphysis pubis (Tile type C 1.2) and one had fractures of the public rami (Tile type B 2.1). All three had various degrees of sensory and motor deficit of the lower limbs. Lumbar myelogram shows characteristic pseudomeningoceles in the affected lumboscral region. Magnetic resonance (MR) imaging provides an additional non-invasive modality to diagnose this condition.

  12. Effects of clinical infrared laser on superficial radial nerve conduction

    SciTech Connect

    Greathouse, D.G.; Currier, D.P.; Gilmore, R.L.

    1985-08-01

    The purposes of this study were to demonstrate the effects of infrared laser radiation on the sensory nerve conduction of a specified peripheral nerve in man and determine temperature changes in the tissue surrounding the treated nerve. Twenty healthy adults were divided into three groups: control (n = 5); experimental (n = 10), infrared laser radiation at 20 sec/cm2; and experimental (n = 5), infrared laser radiation treatment at 120 sec/cm2. Antidromic sensory nerve conduction studies were performed on the superficial radial nerve of each subject's right forearm. The infrared laser radiation was applied at a fixed intensity for five 1-cm2 segments. Latency, amplitude, and temperature measurements were recorded pretest; posttest; and posttest intervals of 1, 3, 5, 10, and 15 minutes. An analysis of variance with repeated measures was used to examine the data. No significant change was noted in the distal sensory latency or amplitude of the evoked sensory potential in either experimental or control groups as a result of the applications of the infrared laser radiation treatment. This study demonstrates that infrared laser used at clinically applied intensities does not alter conduction of sensory nerves nor does it elevate the subcutaneous temperature.

  13. Recovery from Mu-opioid Receptor Desensitization following Chronic Treatment with Morphine and Methadone

    PubMed Central

    Quillinan, Nidia; Lau, Elaine; Virk, Michael; von Zastrow, Mark; Williams, John T

    2011-01-01

    Chronic treatment with morphine results in a decrease in mu-opioid receptor sensitivity, an increase in acute desensitization and a reduction in the recovery from acute desensitization in locus coeruleus neurons. With acute administration, morphine is unlike many other opioid agonists in that it does not mediate robust acute desensitization or induce receptor trafficking. This study compares mu-opioid receptor desensitization and trafficking in brain slices taken from rats treated for 6–7 days with a range of doses of morphine (60, 30, 15 mg/kg/day) and methadone (60, 30, 5 mg/kg/day) applied by subcutaneous implantation of osmotic mini pumps. Mice were treated with 45 mg/kg/day. In morphine treated animals, recovery from acute [Met]5enkephalin-induced desensitization and receptor recycling was diminished. In contrast, recovery and recycling were unchanged in slices from methadone treated animals. Remarkably the reduced recovery from desensitization and receptor recycling found in slices from morphine treated animals were not observed in animals lacking β-arrestin2. Further, pharmacological inhibition of GRK2, while not affecting the ability of [Met]5enkephalin to induce desensitization, acutely reversed the delay in recovery from desensitization produced by chronic morphine treatment. These results characterize a previously unidentified function of the GRK/arrestin system in mediating opioid regulation in response to chronic morphine administration. They also suggest that the GRK/arrestin system, rather then serving as a primary mediator of acute desensitization, controls recovery from desensitization by regulating receptor reinsertion to the plasma membrane after chronic treatment with morphine. The sustained GRK/arrestin dependent desensitization is another way in which morphine and methadone are distinguished. PMID:21430144

  14. Chronic citalopram administration desensitizes prefrontal cortex but not somatodendritic α2-adrenoceptors in rat brain.

    PubMed

    Fernández-Pastor, Begoña; Ortega, Jorge E; Grandoso, Laura; Castro, Elena; Ugedo, Luisa; Pazos, Ángel; Meana, J Javier

    2017-03-01

    Selective serotonin reuptake inhibitors (SSRIs) regulate brain noradrenergic neurotransmission both at somatodendritic and nerve terminal areas. Previous studies have demonstrated that noradrenaline (NA) reuptake inhibitors are able to desensitize α2-adrenoceptor-mediated responses. The present study was undertaken to elucidate the effects of repeated treatment with the SSRI citalopram on the α2-adrenoceptor sensitivity in locus coeruleus (LC) and prefrontal cortex (PFC), by using in vivo microdialysis and electrophysiological techniques, and in vitro stimulation of [(35)S]GTPγS binding autoradiography. Repeated, but not acute, treatment with citalopram (5 mg/kg, i.p., 14 days) increased extracellular NA concentration selectively in PFC. The α2-adrenoceptor agonist clonidine (0.3 mg/kg, i.p.), administered to saline-treated animals (1 ml/kg i.p., 14 days) induced NA decrease in LC (Emax = -44 ± 4%; p < 0.001) and in PFC (Emax = -61 ± 5%, p < 0.001). In citalopram chronically-treated rats, clonidine administration exerted a lower decrease of NA (Emax = -25 ± 7%; p < 0.001) in PFC whereas the effect in LC was not different to controls (Emax = -36 ± 4%). Clonidine administration (0.625-20 μg/kg, i.v.) evoked a dose-dependent decrease of the firing activity of LC noradrenergic neurons in both citalopram- (ED50 = 3.2 ± 0.4 μg/kg) and saline-treated groups (ED50 = 2.6 ± 0.5 μg/kg). No significant differences between groups were found in ED50 values. The α2-adrenoceptor agonist UK14304 stimulated specific [(35)S]GTPγS binding in brain sections containing LC (144 ± 14%) and PFC (194 ± 32%) of saline-treated animals. In citalopram-treated animals, this increase did not differ from controls in LC (146 ± 22%) but was lower in PFC (141 ± 8%; p < 0.05). Taken together, long-term citalopram treatment induces a desensitization of α2-adrenoceptors acting as axon terminal autoreceptors in PFC without changes in

  15. Cutting your nerve changes your brain.

    PubMed

    Taylor, Keri S; Anastakis, Dimitri J; Davis, Karen D

    2009-11-01

    Following upper limb peripheral nerve transection and surgical repair, some patients regain good sensorimotor function while others do not. Understanding peripheral and central mechanisms that contribute to recovery may facilitate the development of new therapeutic interventions. Plasticity following peripheral nerve transection has been demonstrated throughout the neuroaxis in animal models of nerve injury. However, the brain changes that occur following peripheral nerve transection and surgical repair in humans have not been examined. Furthermore, the extent to which peripheral nerve regeneration influences functional and structural brain changes has not been characterized. Therefore, we asked whether functional changes are accompanied by grey and/or white matter structural changes and whether these changes relate to sensory recovery? To address these key issues we (i) assessed peripheral nerve regeneration; (ii) measured functional magnetic resonance imaging brain activation (blood oxygen level dependent signal; BOLD) in response to a vibrotactile stimulus; (iii) examined grey and white matter structural brain plasticity; and (iv) correlated sensory recovery measures with grey matter changes in peripheral nerve transection and surgical repair patients. Compared to each patient's healthy contralesional nerve, transected nerves have impaired nerve conduction 1.5 years after transection and repair, conducting with decreased amplitude and increased latency. Compared to healthy controls, peripheral nerve transection and surgical repair patients had altered blood oxygen level dependent signal activity in the contralesional primary and secondary somatosensory cortices, and in a set of brain areas known as the 'task positive network'. In addition, grey matter reductions were identified in several brain areas, including the contralesional primary and secondary somatosensory cortices, in the same areas where blood oxygen level dependent signal reductions were identified

  16. Functional selectivity of kappa opioid receptor agonists in peripheral sensory neurons.

    PubMed

    Jamshidi, Raehannah J; Jacobs, Blaine A; Sullivan, Laura C; Chavera, Teresa A; Saylor, Rachel M; Prisinzano, Thomas E; Clarke, William P; Berg, Kelly A

    2015-11-01

    Activation of kappa opioid receptors (KORs) expressed by peripheral sensory neurons that respond to noxious stimuli (nociceptors) can reduce neurotransmission of pain stimuli from the periphery to the central nervous system. We have previously shown that the antinociception dose-response curve for peripherally restricted doses of the KOR agonist (-)-(trans)-3,4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl)cyclohexyl]benzeneacetamide (U50488) has an inverted U shape. Here, we found that the downward phase of the U50488 dose-response curve was blocked by an inhibitor of extracellular signal-regulated kinase (ERK) activation U0126. Local administration of the selective KOR agonist salvinorin A (Sal-A), also resulted in an inverted U-shaped curve; however, the downward phase was insensitive to U0126. By contrast, inhibition of c-Jun N-terminal kinase (JNK) partially blocked the downward phase of the dose-response curve to Sal-A, suggesting a role for JNK. In cultures of peripheral sensory neurons, U50488 and Sal-A inhibited adenylyl cyclase activity with similar efficacies; however, their ability to activate ERK and JNK differed. Whereas U50488 activated ERK but not JNK, Sal-A activated JNK but not ERK. Moreover, although both U50488 and Sal-A produced homologous desensitization, desensitization to U50488 was blocked by inhibition of ERK activation, whereas desensitization to Sal-A was blocked by inhibition of JNK. Substitution of an ethoxymethyl ether for the C2 position acetyl group of Sal-A reduced stimulation of JNK, prevented desensitization by ethoxymethyl ether for the C2 position acetyl group of Sal-A, and resulted in a monotonic antinociception dose-response curve. Collectively, these data demonstrate the functional selectivity of KOR ligands for signaling in peripheral sensory neurons, which results in differential effects on behavioral responses in vivo.

  17. Functional Selectivity of Kappa Opioid Receptor Agonists in Peripheral Sensory Neurons

    PubMed Central

    Jamshidi, Raehannah J.; Jacobs, Blaine A.; Sullivan, Laura C.; Chavera, Teresa A.; Saylor, Rachel M.; Prisinzano, Thomas E.; Clarke, William P.

    2015-01-01

    Activation of kappa opioid receptors (KORs) expressed by peripheral sensory neurons that respond to noxious stimuli (nociceptors) can reduce neurotransmission of pain stimuli from the periphery to the central nervous system. We have previously shown that the antinociception dose-response curve for peripherally restricted doses of the KOR agonist (–)-(trans)-3,4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl)cyclohexyl]benzeneacetamide (U50488) has an inverted U shape. Here, we found that the downward phase of the U50488 dose-response curve was blocked by an inhibitor of extracellular signal-regulated kinase (ERK) activation U0126. Local administration of the selective KOR agonist salvinorin A (Sal-A), also resulted in an inverted U-shaped curve; however, the downward phase was insensitive to U0126. By contrast, inhibition of c-Jun N-terminal kinase (JNK) partially blocked the downward phase of the dose-response curve to Sal-A, suggesting a role for JNK. In cultures of peripheral sensory neurons, U50488 and Sal-A inhibited adenylyl cyclase activity with similar efficacies; however, their ability to activate ERK and JNK differed. Whereas U50488 activated ERK but not JNK, Sal-A activated JNK but not ERK. Moreover, although both U50488 and Sal-A produced homologous desensitization, desensitization to U50488 was blocked by inhibition of ERK activation, whereas desensitization to Sal-A was blocked by inhibition of JNK. Substitution of an ethoxymethyl ether for the C2 position acetyl group of Sal-A reduced stimulation of JNK, prevented desensitization by ethoxymethyl ether for the C2 position acetyl group of Sal-A, and resulted in a monotonic antinociception dose-response curve. Collectively, these data demonstrate the functional selectivity of KOR ligands for signaling in peripheral sensory neurons, which results in differential effects on behavioral responses in vivo. PMID:26297384

  18. Short-term cholinergic desensitization of rat pancreatic secretory response

    SciTech Connect

    Asselin, J.; Larose, L.; Morisset, J.

    1987-03-01

    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.

  19. Flooding and Systematic Desensitization: Efficacy in Subclinical Phobics as a Function of Arousal

    ERIC Educational Resources Information Center

    Suarez, Yolanda; And Others

    1976-01-01

    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)

  20. Opioid desensitization: interactions with G-protein-coupled receptors in the locus coeruleus.

    PubMed

    Fiorillo, C D; Williams, J T

    1996-02-15

    In rat locus coeruleus (LC) neurons, alpha 2 adrenoceptors, mu-opioid and somatostatin receptors all activate the same potassium conductance. Chronic treatment with morphine causes a loss of sensitivity that is specific to the mu-opioid response, with no change in the alpha 2 adrenoceptor-mediated response. Acute desensitization induced by opioid, somatostatin, and alpha 2-adrenoceptor agonists was studied in brain slices of rat LC using intracellular recording. A supramaximal concentration of the opioid agonist Met5-enkephalin induced a profound homologous desensitization but little heterologous desensitization to an alpha 2-adrenoceptor agonist (UK 14304) or somatostatin. All desensitized currents showed partial recovery. A supramaximal concentration of UK14304 caused a relatively small amount of desensitization. Although little interaction was observed among inhibitory G-protein-coupled receptors, activation of an excitatory receptor had marked effects on inhibitory responses. Muscarinic agonists, which produce an inward current in LC neurons, reduced the magnitude of agonist-induced outward currents and increased both the rate and amount of opioid desensitization. Muscarinic activation did not alter desensitization of alpha 2-adrenoceptor responses. Acute desensitization shares several characteristics with the tolerance induced by chronic morphine treatment of animals.

  1. Substance P receptor desensitization requires receptor activation but not phospholipase C

    SciTech Connect

    Sugiya, Hiroshi; Putney, J.W. Jr. )

    1988-08-01

    Previous studies have shown that exposure of parotid acinar cells to substance P at 37{degree}C results in activation of phospholipase C, formation of ({sup 3}H)inositol 1,4,5-trisphosphate (IP{sub 3}), and persistent desensitization of the substance P response. In cells treated with antimycin in medium containing glucose, ATP was decreased to {approximately}20% of control values, IP{sub 3} formation was completely inhibited, but desensitization was unaffected. When cells were treated with antimycin in the absence of glucose, cellular ATP was decreased to {approximately}5% of control values, and both IP{sub 3} formation and desensitization were blocked. A series of substance P-related peptides increased the formation of ({sup 3}H)IP{sub 3} and induced desensitization of the substance P response with a similar rank order of potencies. The substance P antagonist, (D-Pro{sup 2}, D-Try{sup 7,9})-substance P, inhibited substance P-induced IP{sub 3} formation and desensitization but did not induce desensitization. These results suggest that the desensitization of substance P-induced IP{sub 3} formation requires agonist activation of a P-type substance P receptor, and that one or more cellular ATP-dependent processes are required for this reaction. However, activation of phospholipase C and the generation of inositol phosphates does not seem to be a prerequisite for desensitization.

  2. Violence Exposure in Real-Life, Video Games, Television, Movies, and the Internet: Is There Desensitization?

    ERIC Educational Resources Information Center

    Funk, Jeanne B.; Baldacci, Heidi Bechtoldt; Pasold; Tracie; Baumgardner, Jennifer

    2004-01-01

    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…

  3. Peripheral Nerve Repair in Rats Using Composite Hydrogel-Filled Aligned Nanofiber Conduits with Incorporated Nerve Growth Factor

    PubMed Central

    Jin, Jenny; Limburg, Sonja; Joshi, Sunil K.; Landman, Rebeccah; Park, Michelle; Zhang, Qia; Kim, Hubert T.

    2013-01-01

    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

  4. Morphology of human intracardiac nerves: an electron microscope study

    PubMed Central

    PAUZIENE, NERINGA; PAUZA, DAINIUS H.; STROPUS, RIMVYDAS

    2000-01-01

    Since many human heart diseases involve both the intrinsic cardiac neurons and nerves, their detailed normal ultrastructure was examined in material from autopsy cases without cardiac complications obtained no more than 8 h after death. Many intracardiac nerves were covered by epineurium, the thickness of which was related to nerve diameter. The perineurial sheath varied from nerve to nerve and, depending on nerve diameter, contained up to 12 layers of perineurial cells. The sheaths of the intracardiac nerves therefore become progressively attenuated during their course in the heart. The intraneural capillaries of the human heart differ from those in animals in possessing an increased number of endothelial cells. A proportion of the intraneural capillaries were fenestrated. The number of unmyelinated axons within unmyelinated nerve fibres was related to nerve diameter, thin cardiac nerves possessing fewer axons. The most distinctive feature was the presence of stacks of laminated Schwann cell processes unassociated with axons that were more frequent in older subjects. Most unmyelinated and myelinated nerve fibres showed normal ultrastructure, although a number of profiles displayed a variety of different axoplasmic contents. Collectively, the data provide baseline information on the normal structure of intracardiac nerves in healthy humans which may be useful for assessing the degree of nerve damage both in autonomic and sensory neuropathies in the human heart. PMID:11117629

  5. Altered expression of the voltage-gated calcium channel subunit α2δ-1: A comparison between two experimental models of epilepsy and a sensory nerve ligation model of neuropathic pain

    PubMed Central

    Nieto-Rostro, M.; Sandhu, G.; Bauer, C.S.; Jiruska, P.; Jefferys, J.G.R.; Dolphin, A.C.

    2014-01-01

    The auxiliary α2δ-1 subunit of voltage-gated calcium channels is up-regulated in dorsal root ganglion neurons following peripheral somatosensory nerve damage, in several animal models of neuropathic pain. The α2δ-1 protein has a mainly presynaptic localization, where it is associated with the calcium channels involved in neurotransmitter release. Relevant to the present study, α2δ-1 has been shown to be the therapeutic target of the gabapentinoid drugs in their alleviation of neuropathic pain. These drugs are also used in the treatment of certain epilepsies. In this study we therefore examined whether the level or distribution of α2δ-1 was altered in the hippocampus following experimental induction of epileptic seizures in rats, using both the kainic acid model of human temporal lobe epilepsy, in which status epilepticus is induced, and the tetanus toxin model in which status epilepticus is not involved. The main finding of this study is that we did not identify somatic overexpression of α2δ-1 in hippocampal neurons in either of the epilepsy models, unlike the upregulation of α2δ-1 that occurs following peripheral nerve damage to both somatosensory and motor neurons. However, we did observe local reorganization of α2δ-1 immunostaining in the hippocampus only in the kainic acid model, where it was associated with areas of neuronal cell loss, as indicated by absence of NeuN immunostaining, dendritic loss, as identified by areas where microtubule-associated protein-2 immunostaining was missing, and reactive gliosis, determined by regions of strong OX42 staining. PMID:24641886

  6. Surfactants and Desensitizing Wax Substitutes for TNT-Based Systems.

    DTIC Science & Technology

    1994-10-01

    Phthalimides with long-chain alkyl groups have been found to be very wax-like. They are made from phthalic anhydride and an alkyl amine. Pure N-octadecyl...Phthalate Half-Esters Phthalic anhydride (5.07 g) and 14.9 grams of Unilin 350 alcohol were charged to a container and heated with stirring for 2 hours at...With The Enthalpy Of ....... 40 Wax Desensitizers 7. DSC Of Ganex WP-660/TNT Mixture ........................ 50 8. DSC Of Solsperse 5000/TNT Mixture

  7. Sexual violence: psychiatric healing with eye movement reprocessing and desensitization.

    PubMed

    Posmontier, Bobbie; Dovydaitis, Tiffany; Lipman, Kenneth

    2010-08-01

    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.

  8. Nerve Regeneration: Understanding Biology and Its Influence on Return of Function After Nerve Transfers.

    PubMed

    Gordon, Tessa

    2016-05-01

    Poor functional outcomes are frequent after peripheral nerve injuries despite the regenerative support of Schwann cells. Motoneurons and, to a lesser extent, sensory neurons survive the injuries but outgrowth of axons across the injury site is slow. The neuronal regenerative capacity and the support of regenerating axons by the chronically denervated Schwann cells progressively declines with time and distance of the injury from the denervated targets. Strategies, including brief low-frequency electrical stimulation that accelerates target reinnervation and functional recovery, and the insertion of cross-bridges between a donor nerve and a recipient denervated nerve stump, are effective in promoting functional outcomes after complete and incomplete injuries.

  9. α-Synuclein in cutaneous autonomic nerves

    PubMed Central

    Wang, Ningshan; Gibbons, Christopher H.; Lafo, Jacob

    2013-01-01

    Objective: To develop a cutaneous biomarker for Parkinson disease (PD). Methods: Twenty patients with PD and 14 age- and sex-matched control subjects underwent examinations, autonomic testing, and skin biopsies at the distal leg, distal thigh, and proximal thigh. α-Synuclein deposition and the density of intraepidermal, sudomotor, and pilomotor nerve fibers were measured. α-Synuclein deposition was normalized to nerve fiber density (the α-synuclein ratio). Results were compared with examination scores and autonomic function testing. Results: Patients with PD had a distal sensory and autonomic neuropathy characterized by loss of intraepidermal and pilomotor fibers (p < 0.05 vs controls, all sites) and morphologic changes to sudomotor nerve fibers. Patients with PD had greater α-synuclein deposition and higher α-synuclein ratios compared with controls within pilomotor nerves and sudomotor nerves (p < 0.01, all sites) but not sensory nerves. Higher α-synuclein ratios correlated with Hoehn and Yahr scores (r = 0.58–0.71, p < 0.01), with sympathetic adrenergic function (r = −0.40 to −0.66, p < 0.01), and with parasympathetic function (r = −0.66 to −0.77, p > 0.01). Conclusions: We conclude that α-synuclein deposition is increased in cutaneous sympathetic adrenergic and sympathetic cholinergic fibers but not sensory fibers of patients with PD. Higher α-synuclein deposition is associated with greater autonomic dysfunction and more advanced PD. These data suggest that measures of α-synuclein deposition in cutaneous autonomic nerves may be a useful biomarker in patients with PD. PMID:24089386

  10. Inferior alveolar nerve injury following orthognathic surgery: a review of assessment issues

    PubMed Central

    PHILLIPS, C.; ESSICK, G.

    2011-01-01

    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

  11. Evaluation of dermal myelinated nerve fibers in diabetes mellitus.

    PubMed

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

    2013-06-01

    Skin biopsies have primarily been used to study the non-myelinated nerve fibers of the epidermis in a variety of neuropathies. In this study, we have expanded the skin biopsy technique to glabrous, non-hairy skin to evaluate myelinated nerve fibers in the most highly prevalent peripheral nerve disease, diabetic polyneuropathy (DPN). Twenty patients with DPN (Type I, n = 9; Type II, n = 11) and 16 age-matched healthy controls (age 29-73) underwent skin biopsy of the index finger, nerve conduction studies (NCS), and composite neuropathy scoring. In patients with DPN, we found a statistically significant reduction of both mechanoreceptive Meissner corpuscles (MCs) and their afferent myelinated nerve fibers (p = 0.01). This myelinated nerve fiber loss was correlated with the decreased amplitudes of sensory/motor responses in NCS. This study supports the utilization of skin biopsy to quantitatively evaluate axonal loss of myelinated nerve fibers in patients with DPN.

  12. Optic Nerve.

    PubMed

    Gordon, Lynn K

    2016-10-28

    Optic nerve diseases arise from many different etiologies including inflammatory, neoplastic, genetic, infectious, ischemic, and idiopathic. Understanding some of the characteristics of the most common optic neuropathies along with therapeutic approaches to these diseases is helpful in designing recommendations for individual patients. Although many optic neuropathies have no specific treatment, some do, and it is those potentially treatable or preventable conditions which need to be recognized in order to help patients regain their sight or develop a better understanding of their own prognosis. In this chapter several diseases are discussed including idiopathic intracranial hypertension, optic neuritis, ischemic optic neuropathies, hereditary optic neuropathies, trauma, and primary tumors of the optic nerve. For each condition there is a presentation of the signs and symptoms of the disease, in some conditions the evaluation and diagnostic criteria are highlighted, and where possible, current therapy or past trials are discussed.

  13. The Role of Peripheral Nerve Function in Age-Related Bone Loss and Changes in Bone Adaptation

    DTIC Science & Technology

    2015-12-01

    mice, despite a considerable and sustained decrease in sensory nerve activity. Physiological adaptations during development may allow mice to...Department of Anatomy, Physiology , & Cell Biology, USA Abstract Objectives: The present study sought to determine the effects of decreased peripheral...differences in bone parameters in capsaicin-treated mice, despite a considerable and sustained decrease in sensory nerve activity. Physiological

  14. Oral Food Desensitization in Children With IgE-Mediated Cow's Milk Allergy: Immunological Changes Underlying Desensitization

    PubMed Central

    Perezábad, Laura; Reche, Marta; Valbuena, Teresa; López-Fandiño, Rosina; López-Expósito, Iván

    2017-01-01

    Purpose This study aimed to evaluate the safety and efficacy to induce clinical desensitization to cow's milk (CM) of an oral immunotherapy (OIT) protocol in a pediatric population with cow's milk allergy (CMA). In addition, the immune responses against β-casein, of peripheral blood mononuclear cells (PBMCs) from CMA patients, before and after the protocol were evaluated and compared to a nonallergic population. Methods A group of 20 children with IgE-mediated CMA and 15 nonallergic children were recruited. Allergic subjects underwent an OIT protocol based on weekly doses of commercial semi-skimmed ultra-high temperature treated (UHT) CM, followed by a maintenance phase. Immune profiles and changes in all subjects were investigated by measuring Th1, Th2, and Treg cytokines, transcription factors, and specific IgE and IgG4 levels. Results The CM-OIT protocol enabled to desensitize 70% of the allergic patients. Successful OIT was accompanied by significant increases in casein-specific IgG4 levels, together with a reduction in the concentration of antigen-specific IgE and in IL-5, IL-13, and IL-10 production by β-casein-stimulated PBMCs. Baseline significant differences observed between allergic and nonallergic children in IL-13 and IL-5 levels were no longer found once the protocol had finished. Conclusions The OIT protocol was safe and effective in inducing milk desensitization in 70% of the children with CMA, leading to alterations in their immune profiles toward a nonallergic phenotype. PMID:27826960

  15. Differential fiber-specific block of nerve conduction in mammalian peripheral nerves using kilohertz electrical stimulation.

    PubMed

    Patel, Yogi A; Butera, Robert J

    2015-06-01

    Kilohertz electrical stimulation (KES) has been shown to induce repeatable and reversible nerve conduction block in animal models. In this study, we characterized the ability of KES stimuli to selectively block specific components of stimulated nerve activity using in vivo preparations of the rat sciatic and vagus nerves. KES stimuli in the frequency range of 5-70 kHz and amplitudes of 0.1-3.0 mA were applied. Compound action potentials were evoked using either electrical or sensory stimulation, and block of components was assessed through direct nerve recordings and muscle force measurements. Distinct observable components of the compound action potential had unique conduction block thresholds as a function of frequency of KES. The fast component, which includes motor activity, had a monotonically increasing block threshold as a function of the KES frequency. The slow component, which includes sensory activity, showed a nonmonotonic block threshold relationship with increasing KES frequency. The distinct trends with frequency of the two components enabled selective block of one component with an appropriate choice of frequency and amplitude. These trends in threshold of the two components were similar when studying electrical stimulation and responses of the sciatic nerve, electrical stimulation and responses of the vagus nerve, and sensorimotor stimulation and responses of the sciatic nerve. This differential blocking effect of KES on specific fibers can extend the applications of KES conduction block to selective block and stimulation of neural signals for neuromodulation as well as selective control of neural circuits underlying sensorimotor function.

  16. Immunological mechanisms for desensitization and tolerance in food allergy1

    PubMed Central

    Rachid, Rima; Umetsu, Dale T.

    2013-01-01

    Food allergy is a major public health concern in westernized countries, estimated to affect 5% of children and 3-4 % of adults. Allergen specific immunotherapy for food allergy is currently being actively evaluated, but is still experimental. The optimal protocol, in terms of the route of administration of the food, target maintenance dose, duration of maintenance therapy and the optimal patient for these procedures are still being worked out. The mechanisms underlying successful food desensitization are also unclear, in part because there is no standard immunotherapy protocol. The mechanisms involved however, may include mast cell and basophil suppression, development of food-specific IgG4 antibodies, reduction in the food specific IgE/IgG4 ratio, up-regulation and expansion of natural or inducible regulatory T cells, a skewing from a Th2 to a Th1 profile and the development of anergy and/or deletion in antigen specific cells. Additional studies are required to elucidate and understand these mechanisms by which desensitization and tolerance are achieved, and which may reveal valuable biomarkers for evaluating and following food allergic patients on immunotherapy. PMID:22821087

  17. Clinical and electrophysiological assessment of inferior alveolar nerve function after lateral nerve transposition.

    PubMed

    Nocini, P F; De Santis, D; Fracasso, E; Zanette, G

    1999-04-01

    Inferior alveolar nerve (IAN) transposition surgery may cause some degree of sensory impairment. Accurate and reproducible tests are mandatory to assess IAN conduction capacity following nerve transposition. In this study subjective (heat, pain and tactile-discriminative tests) and objective (electrophysiological) assessments were performed in 10 patients receiving IAN transposition (bilaterally in 8 cases) in order to evaluate any impairment of the involved nerves one year post-operatively. All patients reported a tingling, well-tolerated sensation in the areas supplied by the mental nerve with no anaesthesia or burning paresthesia. Tactile discrimination was affected the most (all but 1 patient). No action potential was recorded in 4 patients' sides (23.5%); 12 sides showed a decreased nerve conduction velocity (NCV) (70.5%) and 1 side normal NCV values (6%). There was no significant difference in NCV decrease between partial and total transposition sides, if examined separately. Nerve conduction findings were related 2-point discrimination scores, but not to changes in pain and heat sensitivity. These findings show that lateral nerve transposition, though resulting in a high percentage of minor IAN injuries, as determined by electrophysiological testing, provides a viable surgical procedure to allow implant placement in the posterior mandible without causing severe sensory complaints. Considering ethical and forensic implications, patients should be fully informed that a certain degree of nerve injury might be expected to occur from the procedure. Electrophysiological evaluation is a reliable way to assess the degree of IAN dysfunction, especially if combined with a clinical examination. Intraoperative monitoring of IAN conduction might help identify the pathogenetic mechanisms of nerve injury and the surgical steps that are most likely to harm nerve integrity.

  18. A novel internal fixator device for peripheral nerve regeneration.

    PubMed

    Chuang, Ting-Hsien; Wilson, Robin E; Love, James M; Fisher, John P; Shah, Sameer B

    2013-06-01

    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.

  19. Pre-differentiation of mesenchymal stromal cells in combination with a microstructured nerve guide supports peripheral nerve regeneration in the rat sciatic nerve model.

    PubMed

    Boecker, Arne Hendrik; van Neerven, Sabien Geraldine Antonia; Scheffel, Juliane; Tank, Julian; Altinova, Haktan; Seidensticker, Katrin; Deumens, Ronald; Tolba, Rene; Weis, Joachim; Brook, Gary Anthony; Pallua, Norbert; Bozkurt, Ahmet

    2016-02-01

    Many bioartificial nerve guides have been investigated pre-clinically for their nerve regeneration-supporting function, often in comparison to autologous nerve transplantation, which is still regarded as the current clinical gold standard. Enrichment of these scaffolds with cells intended to support axonal regeneration has been explored as a strategy to boost axonal regeneration across these nerve guides Ansselin et al. (1998). In the present study, 20 mm rat sciatic nerve defects were implanted with a cell-seeded microstructured collagen nerve guide (Perimaix) or an autologous nerve graft. Under the influence of seeded, pre-differentiated mesenchymal stromal cells, axons regenerated well into the Perimaix nerve guide. Myelination-related parameters, like myelin sheath thickness, benefitted from an additional seeding with pre-differentiated mesenchymal stromal cells. Furthermore, both the number of retrogradely labelled sensory neurons and the axon density within the implant were elevated in the cell-seeded scaffold group with pre-differentiated mesenchymal stromal cells. However, a pre-differentiation had no influence on functional recovery. An additional cell seeding of the Perimaix nerve guide with mesenchymal stromal cells led to an extent of functional recovery, independent of the differentiation status, similar to autologous nerve transplantation. These findings encourage further investigations on pre-differentiated mesenchymal stromal cells as a cellular support for peripheral nerve regeneration.

  20. Sensory innervation of the hairy skin (light- and electronmicroscopic study.

    PubMed

    Halata, Z

    1993-07-01

    The sense of touch develops early in phylogeny and is one of the most important senses for the survival of the animal. Touch organs of hairy skin in mammals include the so-called "Haarscheiben" (also Pinkus corpuscles) and all types of hair follicles with their nerve endings. The touch organs of the skin consist of a mechanical transducing component and the sensory component. The epithelium and its derivatives like hair follicles and sebaceous glands are the mechanical transducing component transmitting the mechanical forces like pressure or touch to the second component--the sensory nerve endings. In mammalian hairy skin all sinus and guard hairs and many vellus hairs are touch organs. The sinus hair is a typical example of a touch organ. All mammals except humans are equipped with these highly differentiated touch organs. The hair follicle is almost completely embedded in a blood sinus and equipped with more than 2,000 sensory nerve endings. All sinus and guard hairs are equipped with free nerve endings (nociceptors), Merkel nerve endings (slowly adapting [SA I] mechanoreceptor units-pressure detectors), palisades of lanceolate nerve endings (velocity detectors), and pilo-Ruffini corpuscles (tension receptors). In most of the sinus hairs lamellated corpuscles of Pacini type could be found (rapidly adapting receptors-acceleration detectors). Most vellus hairs are equipped with free and lanceolate nerve endings. Some of the vellus hairs of the upper portion of the body (head, upper extremity) are innervated by Merkel nerve endings. The presence of pilo-Ruffini nerve endings in vellus hairs is very unusual.

  1. Desensitization of α7 Nicotinic Receptor Is Governed by Coupling Strength Relative to Gate Tightness*

    PubMed Central

    Zhang, Jianliang; Xue, Fenqin; Whiteaker, Paul; Li, Chaokun; Wu, Wen; Shen, Benchang; Huang, Yao; Lukas, Ronald J.; Chang, Yongchang

    2011-01-01

    Binding of a neurotransmitter to its membrane receptor opens an integral ion conducting pore. However, prolonged exposure to the neurotransmitter drives the receptor to a refractory state termed desensitization, which plays an important role in shaping synaptic transmission. Despite intensive research in the past, the structural mechanism of desensitization is still elusive. Using mutagenesis and voltage clamp in an oocyte expression system, we provide several lines of evidence supporting a novel hypothesis that uncoupling between binding and gating machinery is the underlying mechanism for α7 nicotinic receptor (nAChR) desensitization. First, the decrease in gate tightness was highly correlated to the reduced desensitization. Second, nonfunctional mutants in three important coupling loops (loop 2, loop 7, and the M2-M3 linker) could be rescued by a gating mutant. Furthermore, the decrease in coupling strength in these rescued coupling loop mutants reversed the gating effect on desensitization. Finally, coupling between M1 and hinge region of the M2-M3 linker also influenced the receptor desensitization. Thus, the uncoupling between N-terminal domain and transmembrane domain, governed by the balance of coupling strength and gate tightness, underlies the mechanism of desensitization for the α7 nAChR. PMID:21610071

  2. Drug desensitization in the management of hypersensitivity reactions to monoclonal antibodies and chemotherapy.

    PubMed

    Mezzano, Veronica; Giavina-Bianchi, Pedro; Picard, Matthieu; Caiado, Joana; Castells, Mariana

    2014-04-01

    Hypersensitivity reactions to monoclonal antibodies and chemotherapy, which may vary in severity from mild to life-threatening, can lead to their discontinuation and replacement by alternative agents that are often less effective, more toxic, and/or more expensive. Drug desensitization has emerged as the best treatment modality capable of allowing re-introduction of the hypersensitivity reaction-inducing medication in highly sensitized patients in need of first line therapies. In recent years, the availability of new anti-neoplastic drugs and therapeutic monoclonal antibodies has increased, as has the potential for hypersensitivity reactions. Development of desensitization protocols for these new medications requires a careful assessment of the potential risks and benefits. The purposes of this review are to provide an overview of the presentation of hypersensitivity reactions amenable to desensitization and to increase awareness of the indications for and outcomes of desensitization protocols. Rapid drug desensitization has proven to be a safe and effective way of administering first line therapy to patients with hypersensitivity reactions, providing an extremely powerful treatment modality for patients for whom alternative drugs are deemed unacceptable. Rapid drug desensitization protocols should be administered only by highly trained allergists and nurses who have experience in determining which reactions are amenable to desensitization, and can identify high risk patients and provide them with appropriate care. Efforts should be made to increase awareness of the remarkable safety and efficacy of rapid drug desensitization among non-allergists, especially in the fields of oncology and rheumatology, so as to favor its universal application. Development of desensitization units to provide state-of-the-art care is possible only through coordinated teamwork.

  3. Activation and desensitization of nicotinic alpha7-type acetylcholine receptors by benzylidene anabaseines and nicotine.

    PubMed

    Papke, Roger L; Kem, William R; Soti, Ferenc; López-Hernández, Gretchen Y; Horenstein, Nicole A

    2009-05-01

    Nicotinic receptor activation is inextricably linked to desensitization. This duality affects our ability to develop useful therapeutics targeting nicotinic acetylcholine receptor (nAChR). Nicotine and some alpha7-selective experimental partial agonists produce a transient activation of alpha7 receptors followed by a period of prolonged residual inhibition or desensitization (RID). The object of the present study was to determine whether RID was primarily due to prolonged desensitization or due to channel block. To make this determination, we used agents that varied significantly in their production of RID and two alpha7-selective positive allosteric modulators (PAMs): 5-hydroxyindole (5HI), a type 1 PAM that does not prevent desensitization; and 1-(5-chloro-2,4-dimethoxy-phenyl)-3-(5-methyl-isoxanol-3-yl)-urea (PNU-120596), a type 2 PAM that reactivates desensitized receptors. The RID-producing compounds nicotine and 3-(2,4-dimethoxybenzylidene)anabaseine (diMeOBA) could obscure the potentiating effects of 5HI. However, through the use of nicotine, diMeOBA, and the RID-negative compound 3-(2,4-dihydroxybenzylidene)anabaseine (diOHBA) in combination with PNU-120596, we confirmed that diMeOBA produces short-lived channel block of alpha7 but that RID is because of the induction of a desensitized state that is stable in the absence of PNU-120596 and activated in the presence of PNU-120596. In contrast, diOHBA produced channel block but only readily reversible desensitization, whereas nicotine produced desensitization that could be converted into activation by PNU-120596 but no demonstrable channel block. Steady-state currents through receptors that would otherwise be desensitized could also be produced by the application of PNU-120596 in the presence of a physiologically relevant concentration of choline (60 microM), which may be significant for the therapeutic development of type 2 PAMs.

  4. The catecholaminergic nerve plexus of Holothuroidea

    PubMed Central

    Díaz-Balzac, Carlos A.; Mejías, Wigberto; Jiménez, Luis B.

    2010-01-01

    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

  5. Effect of Facial Sensory Re-training on Sensory Thresholds

    PubMed Central

    Essick, G.K.; Phillips, C.; Zuniga, J.

    2010-01-01

    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

  6. Excessive users of violent video games do not show emotional desensitization: an fMRI study.

    PubMed

    Szycik, Gregor R; Mohammadi, Bahram; Hake, Maria; Kneer, Jonas; Samii, Amir; Münte, Thomas F; Te Wildt, Bert T

    2016-04-16

    Playing violent video games have been linked to long-term emotional desensitization. We hypothesized that desensitization effects in excessive users of violent video games should lead to decreased brain activations to highly salient emotional pictures in emotional sensitivity brain regions. Twenty-eight male adult subjects showing excessive long-term use of violent video games and age and education matched control participants were examined in two experiments using standardized emotional pictures of positive, negative and neutral valence. No group differences were revealed even at reduced statistical thresholds which speaks against desensitization of emotion sensitive brain regions as a result of excessive use of violent video games.

  7. Nerve conduction velocity

    MedlinePlus

    ... polyneuropathy Tibial nerve dysfunction Ulnar nerve dysfunction Any peripheral neuropathy can cause abnormal results. Damage to the spinal ... Herniated disk Lambert-Eaton syndrome Mononeuropathy Multiple ... azotemia Primary amyloidosis Radial nerve dysfunction Sciatica ...

  8. Fast Synaptic Inhibition in Spinal Sensory Processing and Pain Control

    PubMed Central

    Zeilhofer, Hanns Ulrich; Wildner, Hendrik; Yevenes, Gonzalo E.

    2013-01-01

    The two amino acids γ-amino butyric acid (GABA) and glycine mediate fast inhibitory neurotransmission in different CNS areas and serve pivotal roles in the spinal sensory processing. Under healthy conditions, they limit the excitability of spinal terminals of primary sensory nerve fibers and of intrinsic dorsal horn neurons through pre- and postsynaptic mechanisms, and thereby facilitate the spatial and temporal discrimination of sensory stimuli. Removal of fast inhibition not only reduces the fidelity of normal sensory processing but also provokes symptoms very much reminiscent of pathological and chronic pain syndromes. This review summarizes our knowledge of the molecular bases of spinal inhibitory neurotransmission and its organization in dorsal horn sensory circuits. Particular emphasis is placed on the role and mechanisms of spinal inhibitory malfunction in inflammatory and neuropathic chronic pain syndromes. PMID:22298656

  9. Epilepsy and the Sensory Systems

    PubMed Central

    2016-01-01

    The relations of epilepsy and the sensory systems are bidirectional. Epilepsy may act on sensory systems by producing sensory seizure symptoms, by altering sensory performance, and by epilepsy treatment causing sensory side effects. Sensory system activity may have an important role in both generation and inhibition of seizures. PMID:27857611

  10. Pattern of sensory innervation of the perineal skin in the female rat.

    PubMed

    Cruz, Yolanda; Zempoalteca, René; Angelica Lucio, Rosa; Pacheco, Pablo; Hudson, Robyn; Martínez-Gómez, Margarita

    2004-10-22

    Here we describe the nerves innervating the perineal skin together with their sensory fields in the adult female rat. Electrophysiological recording showed that the lumbosacral and L6-S1 trunks, in part by way of the sacral plexus, transmit sensory information from the perineal skin via four nerves: the viscerocutaneous branch of the pelvic nerve innervating the skin at the midline between the vaginal opening and anus, the sensory branch of the pudendal nerve innervating the clitoral sheath, the distal perineal branch of the pudendal nerve innervating a broad area of skin adjacent to the vaginal opening and anus, and the proximal perineal branch of the sacral plexus innervating a broad area of skin adjacent to the clitoris and vaginal opening. The sensory fields of three of these nerves overlapped to some degree: the viscerocutaneous branch of the pelvic and the distal perineal branch of the pudendal nerves at the midline skin between the vaginal opening and the anus, and the distal perineal branch of the pudendal nerve and the proximal perineal branch of the sacral plexus at the skin lateral to the vaginal opening. Such overlap might provide a safeguard helping to ensure that somatosensory input from the perineal region important for triggering reproductive and nonreproductive reflexes reaches the CNS.

  11. Allopurinol hypersensitivity reactions: desensitization strategies and new therapeutic alternative molecules.

    PubMed

    Calogiuri, Gianfranco; Nettis, Eustachio; Di Leo, Elisabetta; Foti, Caterina; Ferrannini, Antonio; Butani, Lavjay

    2013-02-01

    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.

  12. Histochemical discrimination of fibers in regenerating rat infraorbital nerve

    NASA Technical Reports Server (NTRS)

    Wilke, R. A.; Riley, D. A.; Sanger, J. R.

    1992-01-01

    In rat dorsal root ganglia, histochemical staining of carbonic anhydrase (CA) and cholinesterase (CE) yields a reciprocal pattern of activity: Sensory processes are CA positive and CE negative, whereas motor processes are CA negative and CE positive. In rat infraorbital nerve (a sensory peripheral nerve), we saw extensive CA staining of nearly 100% of the myelinated axons. Although CE reactivity in myelinated axons was extremely rare, we did observe CE staining of unmyelinated autonomic fibers. Four weeks after transection of infraorbital nerves, CA-stained longitudinal sections of the proximal stump demonstrated 3 distinct morphological zones. A fraction of the viable axons retained CA activity to within 2 mm of the distal extent of the stump, and the stain is capable of resolving growth sprouts being regenerated from these fibers. Staining of unmyelinated autonomic fibers in serial sections shows that CE activity was not retained as far distally as is the CA sensory staining.

  13. Internal tobacco industry research on olfactory and trigeminal nerve response to nicotine and other smoke components.

    PubMed

    Megerdichian, Christine L; Rees, Vaughan W; Wayne, Geoffrey Ferris; Connolly, Gregory N

    2007-11-01

    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.

  14. Nerve Impulses in Plants

    ERIC Educational Resources Information Center

    Blatt, F. J.

    1974-01-01

    Summarizes research done on the resting and action potential of nerve impulses, electrical excitation of nerve cells, electrical properties of Nitella, and temperature effects on action potential. (GS)

  15. Peripheral nerve surgery--today and looking ahead.

    PubMed

    McQuarrie, I G

    1986-04-01

    The trend in peripheral nerve surgery is toward earlier definitive treatment of the lesion, based on the optimal use of preoperative and intraoperative electrodiagnostic techniques. Newer diagnostic tools include computed tomography (CT) and thermography. Knowledge is still being gained about the technology and limitations of the autogenous nerve grafts that are being used to overcome nerve gaps. The technique of nerve anastomosis is undergoing rapid improvement, and better methods have been developed for identifying motor and sensory fascicles at the time of operation. Research activity into the problem of nerve damage produced at the time of trimming nerve stumps promises to change to the technology of nerve repair in the near future. For benign nerve sheath tumors (schwannoma, neurofibroma), the trend is away from nerve excision and in the direction of tumor enucleation. Histologic methods for diagnosing malignant nerve tumors have been improved, making it possible to embark on radical excision with less hesitation. The pain syndromes (causalgia, phantom limb pain, and stump pain) that may follow nerve injury continue to present a problem in management, but steady progress is being made toward a rational program of management. A more distant prospect is for pharmacologic and electrophysiologic methods to accelerate axonal regeneration.

  16. The pattern and diagnostic criteria of sensory neuronopathy: a case–control study

    PubMed Central

    Camdessanché, Jean-Philippe; Jousserand, Guillemette; Ferraud, Karine; Vial, Christophe; Petiot, Philippe; Honnorat, Jérôme

    2009-01-01

    Acquired sensory neuronopathies encompass a group of paraneoplastic, dysimmune, toxic or idiopathic disorders characterized by degeneration of peripheral sensory neurons in dorsal root ganglia. As dorsal root ganglia cannot easily be explored, the clinical diagnosis of these disorders may be difficult. The question as to whether there exists a common clinical pattern of sensory neuronopathies, allowing the establishment of validated and easy-to-use diagnostic criteria, has not yet been addressed. In this study, logistic regression was used to construct diagnostic criteria on a retrospective study population of 78 patients with sensory neuronopathies and 56 with other sensory neuropathies. For this, sensory neuronopathy was provisionally considered as unambiguous in 44 patients with paraneoplastic disorder or cisplatin treatment and likely in 34 with a dysimmune or idiopathic setting who may theoretically have another form of neuropathy. To test the homogeneity of the sensory neuronopathy population, likely candidates were compared with unambiguous cases and then the whole population was compared with the other sensory neuropathies population. Criteria accuracy was checked on 37 prospective patients referred for diagnosis of sensory neuropathy. In the study population, sensory neuronopathy showed a common clinical and electrophysiological pattern that was independent of the underlying cause, including unusual forms with only patchy sensory loss, mild electrical motor nerve abnormalities and predominant small fibre or isolated lower limb involvement. Logistic regression allowed the construction of a set of criteria that gave fair results with the following combination: ataxia in the lower or upper limbs + asymmetrical distribution + sensory loss not restricted to the lower limbs + at least one sensory action potential absent or three sensory action potentials <30% of the lower limit of normal in the upper limbs + less than two nerves with abnormal motor nerve

  17. Injury of the Inferior Alveolar Nerve during Implant Placement: a Literature Review

    PubMed Central

    Wang, Hom-Lay; Sabalys, Gintautas

    2011-01-01

    ABSTRACT Objectives The purpose of present article was to review aetiological factors, mechanism, clinical symptoms, and diagnostic methods as well as to create treatment guidelines for the management of inferior alveolar nerve injury during dental implant placement. Material and Methods Literature was selected through a search of PubMed, Embase and Cochrane electronic databases. The keywords used for search were inferior alveolar nerve injury, inferior alveolar nerve injuries, inferior alveolar nerve injury implant, inferior alveolar nerve damage, inferior alveolar nerve paresthesia and inferior alveolar nerve repair. The search was restricted to English language articles, published from 1972 to November 2010. Additionally, a manual search in the major anatomy, dental implant, periodontal and oral surgery journals and books were performed. The publications there selected by including clinical, human anatomy and physiology studies. Results In total 136 literature sources were obtained and reviewed. Aetiological factors of inferior alveolar nerve injury, risk factors, mechanism, clinical sensory nerve examination methods, clinical symptoms and treatment were discussed. Guidelines were created to illustrate the methods used to prevent and manage inferior alveolar nerve injury before or after dental implant placement. Conclusions The damage of inferior alveolar nerve during the dental implant placement can be a serious complication. Clinician should recognise and exclude aetiological factors leading to nerve injury. Proper presurgery planning, timely diagnosis and treatment are the key to avoid nerve sensory disturbances management. PMID:24421983

  18. Nerve regeneration by human corneal stromal keratocytes and stromal fibroblasts

    PubMed Central

    Yam, Gary Hin-Fai; Williams, Geraint P.; Setiawan, Melina; Yusoff, Nur Zahirah Binte M.; Lee, Xiao-wen; Htoon, Hla Myint; Zhou, Lei; Fuest, Matthias; Mehta, Jodhbir S.

    2017-01-01

    Laser refractive surgeries reshape corneal stroma to correct refractive errors, but unavoidably affect corneal nerves. Slow nerve regeneration and atypical neurite morphology cause desensitization and neuro-epitheliopathy. Following injury, surviving corneal stromal keratocytes (CSKs) are activated to stromal fibroblasts (SFs). How these two different cell types influence nerve regeneration is elusive. Our study evaluated the neuro-regulatory effects of human SFs versus CSKs derived from the same corneal stroma using an in vitro chick dorsal root ganglion model. The neurite growth was assessed by a validated concentric circle intersection count method. Serum-free conditioned media (CM) from SFs promoted neurite growth dose-dependently, compared to that from CSKs. We detected neurotrophic and pro-inflammatory factors (interleukin-8, interleukin-15, monocyte chemoattractant protein-1, eotaxin, RANTES) in SFCM by Bio-Plex Human Cytokine assay. More than 130 proteins in SFCM and 49 in CSKCM were identified by nanoLC-MS/MS. Proteins uniquely present in SFCM had reported neuro-regulatory activities and were predicted to regulate neurogenesis, focal adhesion and wound healing. Conclusively, this was the first study showing a physiological relationship between nerve growth and the metabolically active SFs versus quiescent CSKs from the same cornea source. The dose-dependent effect on neurite growth indicated that nerve regeneration could be influenced by SF density. PMID:28349952

  19. The sensory innervation of the human pharynx: searching for mechanoreceptors.

    PubMed

    de Carlos, F; Cobo, J; Macías, E; Feito, J; Cobo, T; Calavia, M G; García-Suárez, O; Vega, J A

    2013-11-01

    The coordinate neural regulation of the upper airways muscles is basic to control airway size and resistance. The superior constrictor pharyngeal muscle (SCPM) forms the main part of the lateral and posterior walls of the pharynx and typically is devoid of muscle spindles, the main type of proprioceptor. Because proprioception arising from SCPM is potentially important in the physiology of the upper airways, we have investigated if there are mechanical sensory nerve endings substitute for the muscle spindles. Samples of human pharynx were analyzed using immunohistochemistry associated to general axonic and Schwann cells markers (NSE, PGP 9.5, RT-97, and S100P), intrafusal muscle fiber markers, and putative mechanical sense proteins (TRPV4 and ASIC2). Different kinds of sensory corpuscles were observed in the pharynx walls (Pacini-like corpuscles, Ruffini-like corpuscles, spiral-wharves nerve structures, and others) which are supplied by sensory nerves and express putative mechanoproteins. No evidence of muscle spindles was observed. The present results demonstrate the occurrence of numerous and different morphotypes of sensory corpuscles/mechanoreceptors in human pharynx that presumably detect mechanical changes in the upper airways and replace muscle spindles for proprioception. Present findings are of potential interest for the knowledge of pathologies of the upper airways with supposed sensory pathogenesis.

  20. Tyrosine phosphorylation of Kir3 following kappa-opioid receptor activation of p38 MAPK causes heterologous desensitization.

    PubMed

    Clayton, Cecilea C; Xu, Mei; Chavkin, Charles

    2009-11-13

    Prior studies showed that tyrosine 12 phosphorylation in the N-terminal, cytoplasmic domain of the G-protein-gated inwardly rectifying potassium channel, K(ir)3.1 facilitates channel deactivation by increasing intrinsic GTPase activity of the channel. Using a phosphoselective antibody directed against this residue (pY12), we now report that partial sciatic nerve ligation increased pY12-K(ir)3.1-immunoreactivity (ir) in the ipsilateral dorsal horn of wild-type mice, but not in mice lacking the kappa-opioid receptor (KOR) or lacking the G-protein receptor kinase 3 (GRK3) genes. Treatment of AtT-20 cells stably expressing KOR-GFP with the selective KOR agonist U50,488 increased both phospho-p38-ir and pY12-K(ir)3.1-ir. The U50,488-induced increase in pY12-K(ir)3.1-ir was blocked by the p38 inhibitor SB203580. Cells expressing KOR(S369A)-GFP did not increase either phospho-p38-ir or pY12-K(ir)3.1-ir following U50,488 treatment. Whole cell voltage clamp of AtT-20 cells expressing KOR-GFP demonstrated that p38 activation by U50,488 reduced somatostatin-evoked K(ir)3 currents. This heterologous desensitization was blocked by SB203580 and was not evident in cells expressing KOR(S369A)-GFP. Tyrosine phosphorylation of K(ir)3.1 was likely mediated by p38 MAPK activation of Src kinase. U50,488 also increased (pY418)Src-ir; this increase was blocked by SB203580 and not evident in KOR(S369A)-GFP expressing AtT20 cells; the Src inhibitor PP2 blocked the U50,488-induced increase in pY12-K(ir)3.1-ir; and the heterologous desensitization of K(ir)3 currents was blocked by PP2. These results suggest that KOR causes phosphorylation of Y12-K(ir)3.1 and channel inhibition through a GRK3-, p38 MAPK- and Src-dependent mechanism. Reduced inward potassium current following nerve ligation would increase dorsal horn neuronal excitability and may contribute to the neuropathic pain response.

  1. A Further Assessment of Attention-Placebo Effects and Demand Characteristics in Studies of Systematic Desensitization

    ERIC Educational Resources Information Center

    McReynolds, William T.; Tori, Christopher

    1972-01-01

    It was predicted that phobic Ss receiving systematic desensitization would show greater reductions on both fear-related behavior measures and simulated fear measures than Ss receiving relaxation treatment or no treatment at all. The prediction was confirmed. (Author)

  2. Anaphylactic reaction to polyethylene-glycol conjugated-asparaginase: premedication and desensitization may not be sufficient.

    PubMed

    Sahiner, Umit M; Yavuz, S Tolga; Gökce, Muge; Buyuktiryaki, Betul; Altan, Ilhan; Aytac, Selin; Tuncer, Murat; Tuncer, Ayfer; Sackesen, Cansin

    2013-08-01

    In hypersensitive reactions to native L-asparaginase, either premedication and desensitization or substitution with polyethylene glycol conjugated asparaginase (PEG-ASP) is preferred. Anaphylaxis with PEG-ASP is rare. An 8-year-old girl and a 2.5-year-old boy, both diagnosed as having acute lymphoblastic leukemia, presented with native L-asparaginase hypersensitivity and substitution with PEG-ASP was preferred. They received a premedication (methylprednisolone, hydroxyzine and ranitidine) followed by desensitization with PEG-ASP infusion. Both patients developed anaphylaxis with peg-asparaginase. These are the first reported cases of anaphylactic reaction to PEG-ASP, despite the application of both premedication and desensitization. Anaphylaxis with PEG-ASP is very rare and premedication and desensitization protocols may not prevent these hypersensitive reactions.

  3. Peroneal nerve palsy after compression stockings application

    PubMed Central

    Kim, Jun Hyun; Kim, Won Il; Kim, Ji Yeon; Choe, Won Joo

    2016-01-01

    Peroneal nerve palsy can be caused by various etiology. We report unilateral peroneal nerve palsy after compression stockings application. A 64-year-old man underwent off-pump coronary bypass graft. Surgeon did not use saphenous vein for the bypass graft. Sedation was stopped after 3 h postoperative. After 16 h, for prophylaxis of deep vein thrombosis, knee-high elastic stocking was applied. After 1 h, he took off right stocking because of numbness but left stocking was kept. After 24 h postoperative, (8 h after stocking application) patient complained suddenly left foot drop. Manual muscle test revealed 0/5 of ankle dorsiflexion, ankle eversion, and toe extension. Sensory was decreased to 70% in lower half of anterolateral aspect of tibia, foot dorsum, and toes. Foot drop and sensory abnormality decreased in 3 weeks. Cardiac surgery patients already have many risk factors for peripheral neuropathy. Clinicians should be careful when applying stockings on those patients. PMID:27833497

  4. Peroneal nerve palsy after compression stockings application.

    PubMed

    Kim, Jun Hyun; Kim, Won Il; Kim, Ji Yeon; Choe, Won Joo

    2016-01-01

    Peroneal nerve palsy can be caused by various etiology. We report unilateral peroneal nerve palsy after compression stockings application. A 64-year-old man underwent off-pump coronary bypass graft. Surgeon did not use saphenous vein for the bypass graft. Sedation was stopped after 3 h postoperative. After 16 h, for prophylaxis of deep vein thrombosis, knee-high elastic stocking was applied. After 1 h, he took off right stocking because of numbness but left stocking was kept. After 24 h postoperative, (8 h after stocking application) patient complained suddenly left foot drop. Manual muscle test revealed 0/5 of ankle dorsiflexion, ankle eversion, and toe extension. Sensory was decreased to 70% in lower half of anterolateral aspect of tibia, foot dorsum, and toes. Foot drop and sensory abnormality decreased in 3 weeks. Cardiac surgery patients already have many risk factors for peripheral neuropathy. Clinicians should be careful when applying stockings on those patients.

  5. Ontogeny of the cutaneous sensory organs.

    PubMed

    Saxod, R

    1996-07-01

    The ontogeny of cutaneous sensory nerve organs is described in higher vertebrates, and includes the lamellated corpuscles of Meissner, Pacini and Herbst, and the Merkel cell-neurite complex with bird Merkel and Grandry corpuscles, and mammalian Merkel cells. The main common feature is that for most corpuscles there is an inside-out order of assembly around the nerve ending which is present from the beginning of end-organ ontogeny. The exception is the mammalian Merkel cell which is present in the epidermis before the entrance of nerve fibers, and could play a promotional role in the development of skin innervation. The developmental origin of Herbst and Merkel corpuscles in birds is reported as demonstrated using embryological experiments with cell markers. Conclusions are that inner bulb cells of Herbst corpuscles and bird Merkel cells are of neural crest origin, whereas other cells (inner space and capsular cells for Herbst corpuscle and capsular cells for Merkel corpuscles) are provided by the local mesenchyme. The question of the ontogeny of mammalian Merkel cells is discussed in relation to the two debated hypothesis of epidermal and neural crest origins. Morphogenetic interactions during the development of cutaneous sensory end organs are also discussed.

  6. Pitocin and autism: An analysis of oxytocin receptor desensitization in the fetus.

    PubMed

    Gottlieb, Mark M

    2016-02-01

    The risk of Pitocin as a cause of autism attributable to oxytocin receptor desensitization in the brain of the fetus is evaluated in terms of a mathematical model. A composite unit, D, for oxytocin receptor desensitization levels is established with the form ((IU-h)/ml)E-3, where IU is the international unit for oxytocin. The desensitization values for oxytocin receptor desensitization at a concentration of 10 nmol of oxytocin per liter for 3, 4.2 and 6h corresponding to 0%, 50% and 100% desensitization are calculated to be 15 D, 21 D, and 30 D, respectively. The permeability of the blood-brain barrier in the fetus to oxytocin is discussed, and the upper limit of the concentration of Pitocin in the placenta, and its possible diffusion into the blood and brain of the fetus, is calculated for a routine dose of 6 milli U per minute of Pitocin over a 12h labor. This dose of Pitocin is shown to result in a desensitization value in units of D that is more than a factor of 10 below the 0% desensitization value of 15 D. This indicates that routine doses of Pitocin are not a significant cause of autism attributable to oxytocin receptor desensitization. This is consistent with the findings of a major epidemiological study of the association of Pitocin with autism in Denmark entitled, "Oxytocin-augmented labor and risk for males", Behavioral Brain Research, May 1, 2015; 284:207-212, which found no association between the use of Pitocin during labor and the incidence of autism for females, and a modest association for males.

  7. Candida albicans-Derived β-1,2-Linked Mannooligosaccharides Induce Desensitization of Macrophages

    PubMed Central

    Jouault, Thierry; Fradin, Chantal; Trinel, Pierre-André; Poulain, Daniel

    2000-01-01

    Candida albicans β-1,2-oligomannosides stimulate macrophage tumor necrosis factor alpha (TNF-α) but not NO release. This stimulation desensitized macrophages by altering β-1,2-oligomannoside-dependent TNF-α production and lipopolysaccharide-dependent TNF-α and NO secretion. Desensitization was not related to tyrosine phosphorylation signal transduction but was transferred by culture supernatants in which arachidonic acid derivatives were evidenced. PMID:10639473

  8. Effect of pioglitazone on nerve conduction velocity of the median nerve in the carpal tunnel in type 2 diabetes patients

    PubMed Central

    Chatterjee, Sudip; Sanyal, Debmalya; Das Choudhury, Sourav; Bandyopadhyay, Mili; Chakraborty, Suraj; Mukherjee, Arabinda

    2016-01-01

    AIM To evaluate the impact of pioglitazone pharmacotherapy in median nerve electrophysiology in the carpal tunnel among type 2 diabetes patients. METHODS The study was executed in patients with type 2 diabetes, treated with oral drugs, categorized under pioglitazone or non-pioglitazone group (14 in each group), and who received electrophysiological evaluation by nerve conduction velocity at baseline and 3 mo. RESULTS At 3 mo, pioglitazone-category had inferior amplitude in sensory median nerve [8.5 interquartile range (IQR) = 6.5 to 11.5) vs non-pioglitazone 14.5 (IQR 10.5 to 18.75)] (P = 0.002). Non-pioglitazone category displayed amelioration in amplitude in the sensory median nerve [baseline 13 (IQR = 9 to 16.25) vs 3 mo 8.5 (IQR = 6.5 to 11.5)] (P = 0.01) and amplitude in motor median nerve [baseline 9 (IQR = 4.75 to 11) vs 3 mo 6.75 (IQR = 4.75 to 10.25)] (P = 0.049); and deterioration of terminal latency of in motor ulnar nerve [baseline 2.07 (IQR = 1.92 to 2.25) vs 3 mo 2.16 (IQR = 1.97 to 2.325)] (P = 0.043). There was amelioration of terminal latency in sensory ulnar nerve [baseline 2.45 (IQR = 2.315 to 2.88) vs 3 mo 2.37 (IQR = 2.275 to 2.445) for pioglitazone group (P = 0.038). CONCLUSION Treatment with pioglitazone accentuates probability of compressive neuropathy. In spite of comparable glycemic control over 3 mo, patients treated with pioglitazone showed superior electrophysiological parameters for the ulnar nerve. Pioglitazone has favourable outcome in nerve electrophysiology which was repealed when the nerve was subjected to compressive neuropathy. PMID:27895823

  9. “Early Evaluation of Nerve Regeneration After Nerve Injury and Repair Using Functional Connectivity MRI”

    PubMed Central

    Li, Rupeng; Hettinger, Patrick C.; Liu, Xiping; Machol, Jacques; Yan, Ji-Geng; Matloub, Hani S.; Hyde, James S.

    2014-01-01

    Resting state functional connectivity magnetic resonance imaging (fcMRI) studies in rat brain show brain reorganization caused by nerve injury and repair. In this study, distinguishable differences were found in healthy, nerve transection without repair (R+) and nerve transection with repair (R−) groups in the subacute stage (two weeks after initial injury). Only forepaw on the healthy side was used to determine seed voxel regions in this study. Disturbance of neuronal network in the primary sensory region of cortex occurs within two hours after initial injury, and the network pattern was restored in R+ group in subacute stage, while the disturbed pattern remained in R− group. These are the central findings of the study. This technique provides a novel way of detecting and monitoring the effectiveness of peripheral nerve injury treatment in the early stage and potentially offers a tool for clinicians to avoid poor clinical outcomes. PMID:24515926

  10. Sensory Conversion Devices

    NASA Astrophysics Data System (ADS)

    Medelius, Pedro

    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.

  11. Signaling by Sensory Receptors

    PubMed Central

    Julius, David; Nathans, Jeremy

    2012-01-01

    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

  12. The effect of height on paclitaxel nerve damage.

    PubMed

    Openshaw, Harry; Beamon, Karen; Longmate, Jeffrey; Synold, Timothy; Slatkin, Neal E; Somlo, George

    2005-09-01

    Dying-back neuropathies result in sensory loss and motor signs in the distal distribution of the longest nerves of the body. It would be expected, therefore, that taller individuals with dying-back neuropathies would tend to have worse nerve damage than shorter individuals. This hypothesis was tested in patients receiving high dose paclitaxel. Nerve conductions and quantitative sensory tests were obtained in 21 breast cancer subjects, prior to and 20-40 days after 725 mg/m(2) paclitaxel administered intravenously over 24 h. Despite the uniform dose of paclitaxel, there was a wide variation in post minus pre-paclitaxel changes. Analysis by linear regression showed that decrease of peroneal nerve compound muscle action potential amplitude was significantly greater in taller subjects (P=0.004), and increase in cold detection threshold was greater in taller subjects (P=0.02). No correlation with height was found for paclitaxel drug clearance, maximum concentration, and area under the curve. Decrease in sural sensory nerve action potential amplitude and increase in vibration detection threshold did not correlate with height. In summary, the wide variation of changes seen in neurophysiological tests suggests that multiple factors are involved in determining the severity of neuropathy. Nerve length is probably one of these factors. To determine whether the effect of height is clinically important would require additional study with a larger number of subjects and longer clinical follow-up.

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

    PubMed

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

    2015-09-01

    Peripheral nerve injury diminishes fast conducting large myelinated afferent fibers transmission but enhances smaller pain transmitting fibers firing. This aberrant afferent neuronal behavior contributes to development of chronic post-traumatic peripheral neuropathic pain (PTP-NP). Non-invasive dynamic magnetic flux stimulation has been implicated in treating PTP-NP, a condition currently not adequately addressed by other therapies including transcutaneous electrical nerve stimulation (TENS). The current study assessed the effect of low frequency transcutaneous magnetic stimulation (LFTMS) on peripheral sensory thresholds, nerve conduction properties, and TENS induced fast afferent slowing effect as measured by motor and sensory conduction studies in the ulnar nerve. Results indicated sham LFTMS with TENS (Sham + TENS) significantly (P = 0.02 and 0.007, respectively) reduces sensory conduction velocity (CV) and increases sensory onset latency (OL), and motor peak latency (PL) whereas, real LFTMS with TENS (Real + TENS) reverses effects of TENS on sensory CV and OL, and significantly (P = 0.036) increases the sensory PL. LFTMS alone significantly (P < 0.05) elevates sensory PL and onset-to-peak latency. LFTMS appears to reverse TENS slowing effect on fast conducting fibers and casts a selective peripheral modulatory effect on slow conducting pain afferent fibers.

  14. Median and ulnar antidromic sensory studies to the fourth digit.

    PubMed

    Berkson, Andrew; Lohman, James; Buschbacher, Ralph M

    2006-01-01

    The literature documents multiple reports of neurological injury resulting from both the implantation and the removal of orthopedic devices. These injuries can be easily and objectively evaluated with nerve conduction studies. This study was undertaken to derive a normative database for median and ulnar sensory conduction studies to the fourth digit. Testing was done utilizing a 14-cm antidromic technique on 192 asymptomatic subjects with no risk factors for neuropathy. The subjects were studied bilaterally. Onset latency, peak latency, onset-to-peak amplitude, peak-to-peak amplitude, rise time, and duration were recorded. Increasing age and body mass index were associated with decreasing amplitudes and area. No other demographic factors correlated with differences in waveform measurements. Mean onset latency was 2.7 +/- 0.3 ms for the median nerve and 2.6 +/- 0.2 for the ulnar nerve. Mean peak latency was 3.4 +/- 0.3 ms for the median nerve and 3.3 +/- 0.3 ms for the ulnar nerve. Mean onset-to-peak amplitude was 21 +/- 12 muV for the median nerve and 23 +/- 12muV for the ulnar nerve. Mean peak-to-peak amplitude was 34 +/- 20 muV for the median nerve and 36 +/- 23 muV for the ulnar nerve. Mean area was 25 +/- 17 nVs for the median nerve and 28 +/- 19 nVs for the ulnar nerve. Mean rise time was 0.7 +/- 0.1 ms for the median nerve and 0.7 +/- 0.2 ms for the ulnar nerve. Mean duration was 1.9 +/- 0.4 ms for the median nerve and 1.9 +/- 0.5 ms for the ulnar nerve. The mean difference in onset and peak latency between the median and ulnar nerves (median minus ulnar) was 0.1 +/- 0.2 ms. The upper limit of normal difference of median greater than ulnar onset and peak latency was 0.5 ms. The upper limit of normal difference of ulnar greater than median onset latency was 0.2 ms (0.3 ms for peak latency). The upper limit of normal drop in median peak-to-peak amplitude from one side to the other was 56%. For the ulnar nerve this value was 73%.

  15. Hereditary sensory neuropathy type I.

    PubMed

    Auer-Grumbach, Michaela

    2008-03-18

    Hereditary sensory neuropathy type I (HSN I) is a slowly progressive neurological disorder characterised by prominent predominantly distal sensory loss, autonomic disturbances, autosomal dominant inheritance, and juvenile or adulthood disease onset. The exact prevalence is unknown, but is estimated as very low. Disease onset varies between the 2nd and 5th decade of life. The main clinical feature of HSN I is the reduction of sensation sense mainly distributed to the distal parts of the upper and lower limbs. Variable distal muscle weakness and wasting, and chronic skin ulcers are characteristic. Autonomic features (usually sweating disturbances) are invariably observed. Serious and common complications are spontaneous fractures, osteomyelitis and necrosis, as well as neuropathic arthropathy which may even necessitate amputations. Some patients suffer from severe pain attacks. Hypacusis or deafness, or cough and gastrooesophageal reflux have been observed in rare cases. HSN I is a genetically heterogenous condition with three loci and mutations in two genes (SPTLC1 and RAB7) identified so far. Diagnosis is based on the clinical observation and is supported by a family history. Nerve conduction studies confirm a sensory and motor neuropathy predominantly affecting the lower limbs. Radiological studies, including magnetic resonance imaging, are useful when bone infections or necrosis are suspected. Definitive diagnosis is based on the detection of mutations by direct sequencing of the SPTLC1 and RAB7 genes. Correct clinical assessment and genetic confirmation of the diagnosis are important for appropriate genetic counselling and prognosis. Differential diagnosis includes the other hereditary sensory and autonomic neuropathies (HSAN), especially HSAN II, as well as diabetic foot syndrome, alcoholic neuropathy, neuropathies caused by other neurotoxins/drugs, immune mediated neuropathy, amyloidosis, spinal cord diseases, tabes dorsalis, lepra neuropathy, or decaying skin

  16. Lateralization Technique and Inferior Alveolar Nerve Transposition

    PubMed Central

    Sanches, Marco Antonio; Ramalho, Gabriel Cardoso; Manzi, Marcello Roberto

    2016-01-01

    Bone resorption of the posterior mandible can result in diminished bone edge and, therefore, the installation of implants in these regions becomes a challenge, especially in the presence of the mandibular canal and its contents, the inferior alveolar nerve. Several treatment alternatives are suggested: the use of short implants, guided bone regeneration, appositional bone grafting, distraction osteogenesis, inclined implants tangential to the mandibular canal, and the lateralization of the inferior alveolar nerve. The aim was to elucidate the success rate of implants in the lateralization technique and in inferior alveolar nerve transposition and to determine the most effective sensory test. We conclude that the success rate is linked to the possibility of installing implants with long bicortical anchor which favors primary stability and biomechanics. PMID:27433360

  17. Taste placodes are primary targets of geniculate but not trigeminal sensory axons in mouse developing tongue.

    PubMed

    Mbiene, Joseph-Pascal

    2004-12-01

    Tongue embryonic taste buds begin to differentiate before the onset of gustatory papilla formation in murine. In light of this previous finding, we sought to reexamine the developing sensory innervation as it extends toward the lingual epithelium between E 11.5 and 14.5. Nerve tracings with fluorescent lipophilic dyes followed by confocal microscope examination were used to study the terminal branching of chorda tympani and lingual nerves. At E11.5, we confirmed that the chorda tympani nerve provided for most of the nerve branching in the tongue swellings. At E12.5, we show that the lingual nerve contribution to the overall innervation of the lingual swellings increased to the extent that its ramifications matched those of the chorda tympani nerve. At E13.0, the chorda tympani nerve terminal arborizations appeared more complex than those of the lingual nerve. While the chorda tympani nerve terminal branching appeared close to the lingual epithelium that of the trigeminal nerve remained rather confined to the subepithelial mesenchymal tissue. At E13.5, chorda tympani nerve terminals projected specifically to an ordered set of loci on the tongue dorsum corresponding to the epithelial placodes. In contrast, the lingual nerve terminals remained subepithelial with no branches directed towards the placodes. At E14.5, chorda tympani nerve filopodia first entered the apical epithelium of the developing fungiform papilla. The results suggest that there may be no significant delay between the differentiation of embryonic taste buds and their initial innervation.

  18. The Relationship between Nerve Conduction Study and Clinical Grading of Carpal Tunnel Syndrome

    PubMed Central

    Cheluvaiah, Janardhan D.; Agadi, Jagadish B.; Nagaraj, Karthik

    2016-01-01

    Introduction Carpal Tunnel Syndrome (CTS) is the most common nerve entrapment. Subjective sensory symptoms are common place in patients with CTS, but sometimes they are not supported by objective findings in the neurological examination. Electrodiagnostic (EDx) studies are a valid and reliable means of confirming the diagnosis. The amplitudes along with the conduction velocities of the sensory nerve action potential and motor nerve action potential reflect the functional state of axons, and are useful parameters and complement the clinical grading in the assessment of severity of CTS. Aim To conduct median nerve sensory and motor conduction studies on patients with carpal tunnel syndrome and correlate the relationship between nerve conduction study parameters and the clinical severity grading. Materials and Methods Based on clinical assessment, the study patients were divided into 03 groups with mild CTS, moderate CTS and severe CTS respectively as per Mackinnson’s classification. Median and ulnar nerve conduction studies were performed on bilateral upper limbs of 50 patients with symptoms of CTS and 50 age and sex matched healthy control subjects. The relationship between the clinical severity grade and various nerve conduction study parameters were correlated. Results In this prospective case control study, 50 patients with symptoms consistent with CTS and 50 age and sex matched healthy control subjects were examined over a 10 month period. A total of 30 patients had unilateral CTS (right upper limb in 19 and left upper limb in 11) and 20 patients had bilateral CTS. Female to male ratio was 3.54 to 1. Age ranged from 25 to 81 years. The mean age at presentation was 49.68±11.7 years. Tingling paresthesias of hand and first three fingers were the most frequent symptoms 48 (98%). Tinel’s and Phalen’s sign were positive in 36 (72%) and 44 (88%) patients respectively. The mean duration of symptoms at presentation was 52.68±99.81 weeks. 16 patients (32%) had

  19. Validation of Alexa-647-ATP as a powerful tool to study P2X receptor ligand binding and desensitization.

    PubMed

    Bhargava, Yogesh; Nicke, Annette; Rettinger, Jürgen

    2013-08-23

    Ion channel opening and desensitization is a fundamental process in neurotransmission. The ATP-gated P2X1 receptor (P2X1R) shows rapid and long-lasting desensitization upon agonist binding. This makes the electrophysiological investigation of its desensitization process, agonist unbinding, and recovery from desensitization a challenging task. Here, we show that the fluorescent agonist Alexa-647-ATP is a potent agonist at the P2X1R and a versatile tool to directly visualize agonist binding and unbinding. We demonstrate that the long-lasting desensitization of the P2X1R is due to both slow unbinding of agonist from the desensitized receptor and agonist mediated receptor internalization. Furthermore, the unbinding of the agonist Alexa-647-ATP from the desensitized receptor is accelerated in the continuous presence of competitive ligand. Modeling of our data indicates that three agonist molecules are required to drive the receptor into desensitization. Direct visualization of ligand unbinding from the desensitized receptor demonstrates the cooperativity of this process.

  20. Recombinant GABAA receptor desensitization: the role of the gamma 2 subunit and its physiological significance.

    PubMed

    Dominguez-Perrot, C; Feltz, P; Poulter, M O

    1996-11-15

    1. The purpose of these investigations was to examine the role that the gamma 2 subunit plays in human GABAA receptor desensitization. Two different recombinant GABAA receptors (alpha 1 beta 3 and alpha 1 beta 3 gamma 2) were compared by measuring the relaxation of whole-cell currents during the application of GABA, isoguvacine or taurine. 2. At concentrations which trigger a maximum response (100-500 microM GABA) the current relaxation usually fitted the sum of two exponentials. For alpha 1 beta 3 subunit receptors these values were tau 1 = 145 +/- 12 ms and tau 2 = 6.3 +/- 2.1 s (means +/- S.E.M.). Receptors consisting of alpha 1 beta 3 gamma 2 subunits desensitized faster: tau 1 = 41.6 +/- 8.3 ms and tau 2 = 2.4 +/- 0.6 s. 3. The Hill slope, determined for each receptor subunit combination, was the same and greater than 1.0, implying two binding steps in the activation of both receptor subunit combinations. 4. For alpha 1 beta 3 subunit receptors the fast desensitization rates were unaltered by reducing the GABA concentration from the EC100 (100 microM) to the approximate EC50 values (10-20 microM), whereas for alpha 1 beta 3 gamma 2 subunit receptors a significant slowing was observed. The fast desensitization disappeared at agonist concentrations below the EC50 for both subunit combinations. In contrast, the slow desensitization appeared at agonist concentrations near the EC20. This rate was dependent on agonist concentration reaching a maximum near the EC60 value of GABA. 5. The fast desensitization rates were unaltered by changing the holding potential of the cell during agonist application. However, for alpha 1 beta 3 gamma 2 subunit receptors the slow desensitization rate increased by approximately 15- to 20-fold over the range of voltages of -60 to +40 mV. This indicates that the gamma 2 subunit makes GABAA receptor desensitization voltage dependent. 6. Recovery from desensitization was also biphasic. The first recovery phase was faster for alpha 1 beta 3

  1. Neurology: an ancient sensory organ in crocodilians.

    PubMed

    Soares, Daphne

    2002-05-16

    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.

  2. End-to-side neurorrhaphy as a salvage procedure for irreparable nerve injuries. Technical note.

    PubMed

    Oğün, Tunç C; Ozdemir, Mustafa; Senaran, Hakan; Ustün, Mehmet E

    2003-07-01

    After a few reports on end-to-side nerve repair at the beginning of the last century, the technique was put aside until its recent reintroduction. The authors present their results in three patients with median nerve defects that were between 15 and 22 cm long and treated using end-to-side median-to-ulnar neurorrhaphy through an epineurial window. The follow-up times were between 32 and 38 months. Sensory evaluation involved superficial touch, pinprick, and two-point discrimination tests. Motor evaluation was completed by assessing the presence of opposition and by palpating the abductor pollicis brevis muscle. Sensory recovery was observed in all patients in the median nerve dermatome, and motor recovery was absent, except in Case 1. End-to-side nerve repair can be a viable alternative to nerve grafting in patients with long gaps between the ends of the injured nerve.

  3. IL-17 and VEGF are necessary for efficient corneal nerve regeneration

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The contribution of acute inflammation to sensory nerve regeneration was investigated in the murine cornea using a model of corneal abrasion that removes the stratified epithelium and subbasal nerve plexus. Abrasion induced accumulation of IL-17(+) CCR6(+) yo T cells, neutrophils, and platelets in t...

  4. Effects of different desensitizing treatments on root dentin permeability.

    PubMed

    Rosa, Raydsa Raíssa Moura; Calazans, Francielle Karoline Santos; Nogueira, Ruchele Dias; Lancellotti, Ailla Carla Rocha Acosta; Gonçalves, Luciano de Sousa; Geraldo-Martins, Vinícius Rangel

    2016-10-10

    The objective of this study was to evaluate the effects of diode laser and a desensitizing dentifrice on dentin permeability. Fifty-two root dentin fragments were obtained (5 × 5mm) and treated with 24% EDTA gel. The samples were divided into 4 groups (n = 13): G1, control (no treatment); G2, diode laser (λ = 908 nm, 1.5 W, continuous mode, 20s); G3, application of abrasive dentifrice for 1 minute (Elmex Sensitive Professional (International Gaba); and G4, application of abrasive dentifrice for 1 minute followed by irradiation with diode laser. Ten samples per group were immersed in 2% methylene blue solution for 4h. The specimens were washed, longitudinally sectioned, observed under optical microscopy, photographed and assessed based on the degree of dye leakage. The remaining samples were observed under scanning electron microscopy (SEM). The leakage data were subjected to ANOVA test, followed by Tukey's t-test (α = 5%). Groups 2, 3 and 4 showed less dye penetration than the control group (p < 0.05), but were similar among each other. SEM images showed that dentinal tubules were open in G1, and fused and occluded in G2. Group 3 showed dentinal tubules that were occluded by the metal ions from the toothpaste. G4 presented similar characteristics to G3, and the presence of fused dentin. The diode laser and the dentifrice were effective in reducing dentinal permeability, and the combination of the two treatments did not show better results than either one used alone.

  5. The Efficacy of Selected Desensitizing OTC Products: A Systematic Review

    PubMed Central

    Talioti, E.; Hill, R.; Gillam, D. G.

    2014-01-01

    Objectives. The aim of the present study was to review the published literature in order to identify relevant studies for inclusion and to determine whether there was any evidence on the clinical effectiveness of selected desensitizing toothpastes, calcium sodium phosphosilicate (CSPS), amorphous calcium phosphate (ACP), nanohydroxyapatite, and casein phosphopeptide-amorphous calcium phosphate (tooth mousse) on reducing dentine hypersensitivity (DH). Materials and Methods. Following a review of 593 papers identified from searching both electronic databases (PUBMED) and hand searching of relevant written journals, only 5 papers were accepted for inclusion. Results. Analysis of the included studies (3 CSPS and 2 ACP) would suggest that there may be some benefit for patients using these products for reducing DH. No direct comparative studies were available to assess all these products under the same conditions neither were there any comparative randomised controlled studies that compared at least two of these products in determining their effectiveness in treating DH. Conclusions. Due to the small number of included studies, there are limited clinical data to support any claims of clinical efficacy of these OTC products. Further studies are therefore required to determine the efficacy of these products in well-controlled RCT studies with a larger sample size. PMID:25006466

  6. Physiological correlates of eye movement desensitization and reprocessing.

    PubMed

    Elofsson, Ulf O E; von Schèele, Bo; Theorell, Töres; Söndergaard, Hans Peter

    2008-05-01

    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.

  7. Eye movement desensitization and reprocessing for adolescent depression.

    PubMed

    Bae, Hwallip; Kim, Daeho; Park, Yong Chon

    2008-03-01

    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.

  8. Eye movement desensitization and reprocessing (EMDR): a meta-analysis.

    PubMed

    Davidson, P R; Parker, K C

    2001-04-01

    Eye movement desensitization and reprocessing (EMDR), a controversial treatment suggested for posttraumatic stress disorder (PTSD) and other conditions, was evaluated in a meta-analysis of 34 studies that examined EMDR with a variety of populations and measures. Process and outcome measures were examined separately. and EMDR showed an effect on both when compared with no treatment and with therapies not using exposure to anxiety-provoking stimuli and in pre post EMDR comparisons. However, no significant effect was found when EMDR was compared with other exposure techniques. No incremental effect of eye movements was noted when EMDR was compared with the same procedure without them. R. J. DeRubeis and P. Crits-Christoph (1998) noted that EMDR is a potentially effective treatment for noncombat PTSD. but studies that examined such patient groups did not give clear support to this. In sum, EMDR appears to be no more effective than other exposure techniques, and evidence suggests that the eye movements integral to the treatment, and to its name, are unnecessary.

  9. NEUROPHYSIOLOGICAL EVALUATION OF SENSORY SYSTEMS'

    EPA Science Inventory

    Exposure to many neurotoxic compounds has been shown to produce a sensory system dysfunction. Neurophysiological assessment of sensory function in humans and animal models often uses techniques known as sensory evoked potentials. Because both humans and animals show analogous res...

  10. Influence of human skin injury on regeneration of sensory neurons.

    PubMed

    Taherzadeh, O; Otto, W R; Anand, U; Nanchahal, J; Anand, P

    2003-06-01

    The regeneration of sensory nerve fibres is regulated by trophic factors released from their target tissue, particularly the basal epidermis, and matrix molecules. Means to modulate this response may be useful for the treatment of neuromas and painful hypertrophic scars and of sensory deficits in skin grafts and flaps. We have developed an in vitro model of sensory neuron regeneration on human skin in order to study the mechanisms of sensory dysfunction in pathological conditions. Adult rat sensory neurons were co-cultured with unfixed cryosections of normal or injured (crushed) human skin for 72 h. Neurons were immunostained for growth-associated protein-43 and the neurite lengths of neuronal cell bodies situated in various skin regions were measured. Two-way analysis of variance was performed. Neurites of sensory cell bodies on epidermis of normal skin were the shortest, with a mean +/- SEM of 75+/-10 micrometer, whereas those of cells on the dermo-epidermal junction were the longest, with a mean +/- SEM of 231+/-18 micrometer. Neurons on the dermo-epidermal junction of injured skin had significantly longer neurites than those on the same region of normal skin (mean +/- SEM = 289+/-21 micrometer). Regeneration of sensory neurons may be influenced by extracellular matrix molecules, matrix-binding growth factors and trophic factors. Altered substrate or trophic factors in injured skin may explain the increase of neurite lengths. This in vitro model may be useful for studying the molecular mechanisms of sensory recovery and the development of neuropathic pain following peripheral nerve injury.

  11. Improvement of Sciatic Nerve Regeneration Using Laminin-Binding Human NGF-β

    PubMed Central

    Sun, Wenjie; Sun, Changkai; Zhao, Hui; Lin, Hang; Han, Qianqian; Wang, Jingyu; Ma, Hui; Chen, Bing; Xiao, Zhifeng; Dai, Jianwu

    2009-01-01

    Background Sciatic nerve injuries often cause partial or total loss of motor, sensory and autonomic functions due to the axon discontinuity, degeneration, and eventual death which finally result in substantial functional loss and decreased quality of life. Nerve growth factor (NGF) plays a critical role in peripheral nerve regeneration. However, the lack of efficient NGF delivery approach limits its clinical applications. We reported here by fusing with the N-terminal domain of agrin (NtA), NGF-β could target to nerve cells and improve nerve regeneration. Methods Laminin-binding assay and sustained release assay of NGF-β fused with NtA (LBD-NGF) from laminin in vitro were carried out. The bioactivity of LBD-NGF on laminin in vitro was also measured. Using the rat sciatic nerve crush injury model, the nerve repair and functional restoration by utilizing LBD-NGF were tested. Findings LBD-NGF could specifically bind to laminin and maintain NGF activity both in vitro and in vivo. In the rat sciatic nerve crush injury model, we found that LBD-NGF could be retained and concentrated at the nerve injury sites to promote nerve repair and enhance functional restoration following nerve damages. Conclusion Fused with NtA, NGF-β could bind to laminin specifically. Since laminin is the major component of nerve extracellular matrix, laminin binding NGF could target to nerve cells and improve the repair of peripheral nerve injuries. PMID:19587785

  12. Investigation of infraorbital nerve injury following zygomaticomaxillary complex fractures.

    PubMed

    Sakavicius, D; Juodzbalys, G; Kubilius, R; Sabalys, G P

    2008-12-01

    The aim of this study was to investigate the severity of infraorbital nerve injury following zygomaticomaxillary complex fractures and to estimate the treatment methods facilitating its functional recovery. A total of 478 patients with unilateral zygomaticomaxillary complex fractures were treated. Infraorbital nerve sensory disturbances were diagnosed in 64.4% of the patients. Injury of the infraorbital nerve was expressed as asymmetry index, which was calculated as a ratio between the affected side and the intact side electric pain detection thresholds at the innervation zone skin before treatment and 14 days, 1, 3, 6 and 12 months postoperatively. A mean asymmetry index of 0.6 +/- 0.03 and 1.9 +/- 0.5 was registered for 57 (11.9%) patients with hyperalgesia and for 251 (52.5%) patients with hypoalgesia, respectively. As a result of retrospective analysis of infraorbital nerve sensory disturbances and its functional recovery, infraorbital nerve injury severity was classified as mild, moderate and severe. It was found that the dynamics and outcome of the functional infraorbital nerve recovery depend on the severity of the injury and the presence of infraorbital canal damage. Function was completely recovered within 3 months after treatment in cases with mild nerve injury. In moderate cases, complete recovery was seen within 6 months and in 34.6% of the severe cases, within a 12-month period after treatment when infraorbital nerve decompression was performed according to the stated indication. Treatment based on infraorbital nerve injury classification offers a better prognosis for complete recovery of the infraorbital nerve function.

  13. Desensitization strategies in adult heart transplantation-Will persistence pay off?

    PubMed

    Chih, Sharon; Patel, Jignesh

    2016-08-01

    Strategies are needed to enable successful heart transplantation in highly sensitized patients. Immunologic challenges from sensitization to human leukocyte antigen (HLA) reduce access to compatible donors, extend waiting times to transplant, and increase the risks of antibody-mediated rejection and cardiac allograft vasculopathy after transplant. The prime goal of desensitization is to increase access to transplantation through expansion of the donor organ pool. Existing therapies are directed at key components of the humoral immune response with newer biologically based regimens able to target plasma cells as the source of antibody production, as well as complement activation that has a central role in antibody-mediated injury. Despite the emergence of early promising results for these agents, a significant knowledge gap remains with the current data for desensitization, extrapolated mostly from non-heart solid-organ transplants and small observational studies. Notably, no approach has demonstrated significant and sustainable reductions in HLA antibody pre-transplant, and the ideal desensitization strategy remains elusive. In addition, clinical tools to evaluate the humoral response and efficacy of therapy are limited, focusing almost exclusively on HLA antibody detection. Importantly, desensitization is associated with significant costs and potential risks, and overall long-term outcomes and cost-effectiveness have not been sufficiently evaluated. Investigation is ongoing into the development of a clinically effective desensitization strategy in heart transplantation.

  14. Buprenorphine is a weak partial agonist that inhibits opioid receptor desensitization

    PubMed Central

    Virk, Michael S.; Arttamangkul, Seksiri; Birdsong, William T.; Williams, John T.

    2009-01-01

    Buprenorphine is a weak partial agonist at mu-opioid receptors that is used for treatment of pain and addiction. Intracellular and whole cell recordings were made from locus coeruleus (LC) neurons in rat brain slices to characterize the actions of buprenorphine. Acute application of buprenorphine caused a hyperpolarization that was prevented by previous treatment of slices with the irreversible opioid antagonist, β-chlornaltrexamine (β-CNA), but was not reversed by a saturating concentration of naloxone. As expected for a partial agonist, sub-saturating concentrations of buprenorphine decreased the [Met]5 enkephalin (ME) induced hyperpolarization or outward current. When the ME induced current was decreased below a critical value, desensitization and internalization of μ-opioid receptors (MOR) was eliminated. The inhibition of desensitization by buprenorphine was not the result of prior desensitization, slow dissociation from the receptor, or elimination of receptor reserve. Treatment of slices with sub-saturating concentrations of etorphine, methadone, oxymorphone or β-CNA also reduced the current induced by ME but did not block ME-induced desensitization. Treatment of animals with buprenorphine for a week resulted in the inhibition of the current induced by ME and a block of desensitization that was not different from the acute application of buprenorphine to brain slices. These observations show the unique characteristics of buprenorphine and further demonstrate the range of agonist selective actions that are possible through G-protein coupled receptors. PMID:19494155

  15. Sublingual-oral rush desensitization to mixed cow and sheep milk: a case report.

    PubMed

    Nucera, E; Schiavino, D; Buonomo, A; Pollastrini, E; Altomonte, G; Pecora, V; Decinti, M; Lombardo, C; Patriarca, G

    2008-01-01

    We attempted an oral rush desensitization with mixed cow and sheep milk in a 6-year-old boy who had had adverse reactions to cow and goat milks. Skin prick tests and specific immunoglobulin (Ig) E to cow, sheep and goat milks were positive. The double-blind, placebo-controlled food challenge with cow milk was positive too. He underwent a 12-day sublingual-oral desensitization treatment with mixed cow and sheep milk. Specific IgE and IgG4 were measured. Open oral challenges with cow milk, sheep milk and sheep cheeses were also performed after the desensitization. At the end of the desensitizing treatment our patient could tolerate 120 mL of mixed milk. Specific IgE levels did not vary, whereas an increase of specific IgG4 concentrations was observed. Open oral challenges with cow and sheep milks and sheep cheeses were negative. Oral rush desensitization may represent an alternative approach to the treatment of food allergy in children.

  16. An in vitro evaluation of the effects of desensitizing agents on microleakage of Class V cavities

    PubMed Central

    Yikilgan, İhsan; Özcan, Suat; Bala, Oya; Ömürlü, Hüma

    2016-01-01

    Background The aim of this study was to evaluate the effect of a desensitizing agent on microleakage of Class V cavities. Material and Methods 72 premolar teeth were used. There were 6 groups. Class V restorations were prepared with two different restorative materials (Equia fil, GC, America and Grandio, VOCO, Germany) and two adhesive systems (Clearfil SE Bond, Kuraray, Japan and S3 Bond Plus, Kuraray, Japan) with and without desensitizing agent (Gluma Desensitizer, Heraeus Kulzer, Germany). Restorations were polished with aluminum oxide abrasive discs. Then a range of 5 - 55C thermocycling was performed 10.000 times. The microleakage of restorations was examined with dye penetration method (Basic fuchsine). Bonferroni corrections and Kruskal-Wallis test were used to determine the significance of differences in occlusal and gingival dye penetration scores between groups. Results There was no stastistical significance between the occlusal and gingival microleakage scores within the groups were shown. Conclusions It can be concluded that use of desensitizing agent under both high viscosity glass ionomer restorative materials and resin composites doesn’t affect the microleakage. Key words:High viscosity glass ionomer cement, composite resin, desensitizing agent, microleakage. PMID:26855707

  17. Rate of Homologous Desensitization and Internalization of the GLP-1 Receptor.

    PubMed

    Shaaban, Ghina; Oriowo, Mabayoje; Al-Sabah, Suleiman

    2016-12-26

    The glucagon-like peptide-1 receptor (GLP-1R) is an important target in the treatment of type 2 diabetes mellitus. The aim of this study was to compare the rate of agonist stimulated desensitization and internalization of GLP-1R. To this end, an N-terminally myc-tagged GLP-1R was stably expressed in HEK-293 cells. Homologous desensitization was assessed by measuring the cAMP response to agonist stimulation following pre-incubation with agonist for up to 120 min. Receptor internalization was monitored using an indirect ELISA-based method and confocal microscopy. Pre-incubation with GLP-1 resulted in a time-dependent loss of response to a second stimulation. Washing cells following pre-incubation failed to bring cAMP levels back to basal. Taking this into account, two desensitization rates were calculated: "apparent" (t1/2 = 19.27 min) and "net" (t1/2 = 2.99 min). Incubation of cells with GLP-1 also resulted in a time-dependent loss of receptor cell surface expression (t1/2 = 2.05 min). Rapid agonist-stimulated internalization of GLP-1R was confirmed using confocal microscopy. Stimulation of GLP-1R with GLP-1 results in rapid desensitization and internalization of the receptor. Interestingly, the rate of "net" desensitization closely matches the rate of internalization. Our results suggest that agonist-bound GLP-1R continues to generate cAMP after it has been internalized.

  18. Pattern of Peripheral Nerve Involvement in Spinocerebellar Ataxia Type 2: a Neurophysiological Assessment.

    PubMed

    Bezerra, Marcio Luiz Escorcio; Pedroso, José Luiz; Braga-Neto, Pedro; Abrahao, Agessandro; de Albuquerque, Marcus Vinicius Cristino; Borges, Franklin Roberto Pereira; Saraiva-Pereira, Maria Luiza; Jardim, Laura Bannach; de Oliveira Braga, Nadia Iandoli; Manzano, Gilberto Mastrocola; Barsottini, Orlando G P

    2016-12-01

    Peripheral neuropathy is frequent in spinocerebellar ataxia type 2 (SCA2), but the pattern and characteristics of nerve involvement are still an unsettled issue. This study aimed to evaluate the prevalence, extent, and distribution of nerve involvement in SCA2 patients through neurophysiological studies. Thirty-one SCA2 patients and 20 control subjects were enrolled in this study. All subjects were prospectively evaluated through electromyography, including nerve conduction, needle electromyography in proximal and distal muscles of the upper and lower limbs, and sural radial amplitude ratio (SRAR). We aimed to differentiate distal axonopathy from diffuse nerve commitment, characterizing neuronopathy. Nerve involvement was observed in 83.6 % (26 individuals) of SCA2 patients. Among these, 19 had diffuse sensory abnormalities on nerve conduction predominantly on the upper limbs, with diffuse chronic denervation on needle electromyography and elevated SRAR values. Four individuals had only diffuse sensory involvement, and 2 had only motor involvement on needle evaluation and normal nerve conduction. These were interpreted as neuronopathy due to the diffuse distribution of the involvement. One individual had distal sensory axonopathy, with lower limb predominance. In this study, we found neuronopathy as the main pattern of nerve involvement in SCA2 patients and that motor involvement is a frequent feature. This information brings new insights into the understanding of the pathophysiology of nerve involvement in SCA2 and sets some key points about the phenotype, which is relevant to guide the genetic/molecular diagnosis.

  19. Biomarkers of neuropathic pain in skin nerve degeneration neuropathy: contact heat-evoked potentials as a physiological signature.

    PubMed

    Wu, Shao-Wei; Wang, Yi-Chia; Hsieh, Paul-Chen; Tseng, Ming-Tsung; Chiang, Ming-Chang; Chu, Chih-Pang; Feng, Fang-Ping; Lin, Yea-Huey; Hsieh, Sung-Tsang; Chao, Chi-Chao

    2017-03-01

    Contact heat-evoked potentials (CHEPs) have become an established method of assessing small-fiber sensory nerves; however, their potential as a physiological signature of neuropathic pain symptoms has not been fully explored. To investigate the diagnostic efficacy in examining small-fiber sensory nerve degeneration, the relationship with skin innervations, and clinical correlates with sensory symptoms, we recruited 188 patients (115 men) with length-dependent sensory symptoms and reduced intraepidermal nerve fiber (IENF) density at the distal leg to perform CHEP, quantitative sensory testing, and nerve conduction study. Fifty-seven age- and sex-matched controls were enrolled for comparison of CHEP and skin innervation. Among patients with neuropathy, 144 patients had neuropathic pain and 64 cases had evoked pain. Compared with quantitative sensory testing and nerve conduction study parameters, CHEP amplitudes showed the highest sensitivity for diagnosing small-fiber sensory nerve degeneration and exhibited the strongest correlation with IENF density in multiple linear regression. Contact heat-evoked potential amplitudes were strongly correlated with the degree of skin innervation in both patients with neuropathy and controls, and the slope of the regression line between CHEP amplitude and IENF density was higher in patients with neuropathy than in controls. Patients with evoked pain had higher CHEP amplitude than those without evoked pain, independent of IENF density. Receiver operating characteristic analysis showed that CHEP had better performance in diagnosing small-fiber sensory nerve degeneration than thermal thresholds. Furthermore, CHEPs showed superior classification accuracy with respect to evoked pain. In conclusion, CHEP is a sensitive tool to evaluate pathophysiology of small-fiber sensory nerve and serves as a physiological signature of neuropathic pain symptoms.

  20. The Study of Diagnostic Efficacy of Nerve Conduction Study Parameters in Cervical Radiculopathy

    PubMed Central

    Pawar, Sachin; Kashikar, Aditi; Shende, Vinod; Waghmare, Satish

    2013-01-01

    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

  1. Pulmonary Stress Induced by Hyperthermia: Role of Airway Sensory Nerves

    DTIC Science & Technology

    2014-12-01

    96, 2013. Hsu, C.C., R.L. Lin, L.-Y. Lee and Y.S. Lin. Hydrogen sulfide induces hypersensitivity of rat lung vagal neurons: role of TRPA1 receptors...or in part by this TATRC project are included in this Annual Progress Report below: 1. Hsu CC, Lin RL, Lee LY, Lin YS. Hydrogen sulfide induces

  2. Pulmonary Stress Induced by Hyperthermia: Role of Airway Sensory Nerves

    DTIC Science & Technology

    2013-10-01

    constriction, cough , dyspnea 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF ABSTRACT 18. NUMBER OF PAGES 19a. NAME OF RESPONSIBLE PERSON...constriction, cough , etc.) in patients with allergic rhinitis. 3) To determine if thermal stress generated various airway dysfunctions in patients with...hyperventilation of humid warm air (WA) triggered cough and reflex bronchoconstriction in patients with mild asthma (Am. J. Resp. Crit. Care Med. 185:1190

  3. Pulmonary Stress Induced by Hyperthermia: Role of Airway Sensory Nerves

    DTIC Science & Technology

    2016-01-01

    selection of more suitable animal models for studying various airway diseases in humans. A continuing growth of our knowledge about the physiological and...rats, but not in control rats. Chronic airway inflammation in sensitized animals is likely a major contributing factor in causing this response. 3) A...C-fibers. 4) In an animal model of asthma (Brown-Norway rats sensitized by ovalbumin), chronic allergic inflammation sensitization increases the

  4. Pulmonary Stress Induced by Hyperthermia: Role of Airway Sensory Nerves

    DTIC Science & Technology

    2011-10-01

    cough , bronchoconstriction, and other cardiopulmonary reflex responses (1). Recent studies conducted in our lab have established the first evidence...dyspnea, airway constriction, cough , etc) in healthy volunteers, and in patients with mild asthma, allergic rhinitis and post upper respiratory...cmH2O/L/sec (P>0.05). Furthermore, increasing airway temperature also consistently elicited bouts of cough in asthmatic patients, but not in healthy

  5. Pulmonary Stress Induced by Hyperthermia: Role of Airway Sensory Nerves

    DTIC Science & Technology

    2012-10-01

    blind design was used to compare between the effects of pretreatments with ipratropium bromide and placebo aerosols on the airway responses to HA... ipratropium completely prevented the WA- induced bronchoconstriction in asthmatics. In conclusion, bronchoconstriction induced by increasing airway...patients was completely prevented by pretreatment with ipratropium aerosol, indicating an involvement of cholinergic reflex. Accompanying the

  6. A tingling sanshool derivative excites primary sensory neurons and elicits nocifensive behavior in rats

    PubMed Central

    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.

    2011-01-01

    Szechuan peppers contain hydroxy-α-sanshool that imparts desirable tingling, cooling, and numbing sensations. Hydroxy-α-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

  7. Nerve Injuries in Athletes.

    ERIC Educational Resources Information Center

    Collins, Kathryn; And Others

    1988-01-01

    Over a two-year period this study evaluated the condition of 65 athletes with nerve injuries. These injuries represent the spectrum of nerve injuries likely to be encountered in sports medicine clinics. (Author/MT)

  8. Electromechanical Nerve Stimulator

    NASA Technical Reports Server (NTRS)

    Tcheng, Ping; Supplee, Frank H., Jr.; Prass, Richard L.

    1993-01-01

    Nerve stimulator applies and/or measures precisely controlled force and/or displacement to nerve so response of nerve measured. Consists of three major components connected in tandem: miniature probe with spherical tip; transducer; and actuator. Probe applies force to nerve, transducer measures force and sends feedback signal to control circuitry, and actuator positions force transducer and probe. Separate box houses control circuits and panel. Operator uses panel to select operating mode and parameters. Stimulator used in research to characterize behavior of nerve under various conditions of temperature, anesthesia, ventilation, and prior damage to nerve. Also used clinically to assess damage to nerve from disease or accident and to monitor response of nerve during surgery.

  9. Evidence for Glutamate as a Neuroglial Transmitter within Sensory Ganglia

    PubMed Central

    Kung, Ling-Hsuan; Gong, Kerui; Adedoyin, Mary; Ng, Johnson; Bhargava, Aditi; Ohara, Peter T.; Jasmin, Luc

    2013-01-01

    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

  10. Evidence for glutamate as a neuroglial transmitter within sensory ganglia.

    PubMed

    Kung, Ling-Hsuan; Gong, Kerui; Adedoyin, Mary; Ng, Johnson; Bhargava, Aditi; Ohara, Peter T; Jasmin, Luc

    2013-01-01

    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.

  11. Establishing improved normal values for nerve conduction studies.

    PubMed

    Buschbacher, Ralph M

    2006-01-01

    Nerve conduction studies are commonly performed to diagnose injuries of the peripheral nerves. In the past, normal ranges have been derived on relatively small samples of normal subjects. These ranges were often suboptimal for clinical use. Therefore, this series of articles was created to establish an improved database of normative values. It highlights the key contributions of a number of authors. In this foreword, the contributions of the various authors to the special issue on the development of an improved database for nerve conduction studies are described. The authors are introduced, including their training, gifts, and which articles they were involved in writing. In addition, there is a brief review of each of the articles in this special supplement. The fundamentals of ulnar motor nerve conduction to the first dorsal interosseous muscle are described, as is the contribution of Nate Prahlow, MD. In addition, the median motor nerve conduction to the pronator teres muscle and flexor carpi radialis muscle is highlighted including the contributions of Brian Foley, MD. The radial sensory nerve and dorsal ulnar cutaneous sensory nerve studies are described, as well as the contributions of Van Evanoff, Jr., MD, in creating this research. Median motor conduction to the lumbrical muscles and ulnar motor conduction to the palmar interosseous muscles are described, again highlighting the contributions of Dr. Foley. In addition, medial and lateral antebrachial cutaneous nerve studies are described, along with the contributions of Dr. Nathan Prahlow. Median and ulnar sensory conduction studies recording from the fourth digit, as well as median and radial sensory conduction to the first digit, are described, as are the contributions of James Lohman, MD, and Andrew Berkson, DO. The side-to-side differences in median and ulnar sensory conduction studies and the importance of performing such studies are described, as are the contributions in this research of Dr. Nathan

  12. Physiological and Perceptual Sensory Attenuation Have Different Underlying Neurophysiological Correlates.

    PubMed

    Palmer, Clare E; Davare, Marco; Kilner, James M

    2016-10-19

    Sensory attenuation, the top-down filtering or gating of afferent information, has been extensively studied in two fields: physiological and perceptual. Physiological sensory attenuation is represented as a decrease in the amplitude of the primary and secondary components of the somatosensory evoked potential (SEP) before and during movement. Perceptual sensory attenuation, described using the analogy of a persons' inability to tickle oneself, is a reduction in the perception of the afferent input of a self-produced tactile sensation due to the central cancellation of the reafferent signal by the efference copy of the motor command to produce the action. The fields investigating these two areas have remained isolated, so the relationship between them is unclear. The current study delivered median nerve stimulation to produce SEPs during a force-matching paradigm (used to quantify perceptual sensory attenuation) in healthy human subjects to determine whether SEP gating correlated with the behavior. Our results revealed that these two forms of attenuation have dissociable neurophysiological correlates and are likely functionally distinct, which has important implications for understanding neurological disorders in which one form of sensory attenuation but not the other is impaired. Time-frequency analyses revealed a negative correlation over sensorimotor cortex between gamma-oscillatory activity and the magnitude of perceptual sensory attenuation. This finding is consistent with the hypothesis that gamma-band power is related to prediction error and that this might underlie perceptual sensory attenuation.

  13. Engineering a multimodal nerve conduit for repair of injured peripheral nerve

    NASA Astrophysics Data System (ADS)

    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.

    2013-02-01

    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

  14. Adjuvant neurotrophic factors in peripheral nerve repair with chondroitin sulfate proteoglycan-reduced acellular nerve allografts

    PubMed Central

    Boyer, Richard B.; Sexton, Kevin W.; Rodriguez-Feo, Charles L.; Nookala, Ratnam; Pollins, Alonda C.; Cardwell, Nancy L.; Tisdale, Keonna Y.; Nanney, Lillian B.; Shack, R. Bruce; Thayer, Wesley P.

    2014-01-01

    Background Acellular nerve allografts are now standard tools in peripheral nerve repair due to decreased donor site morbidity and operative time savings. Preparation of nerve allografts involves several steps of decellularization and modification of extracellular matrix to remove chondroitin sulfate proteoglycans (CSPGs), which have been shown to inhibit neurite outgrowth through a poorly understood mechanism involving RhoA and ECM-integrin interactions. Chondroitinase ABC (ChABC) is an enzyme that degrades CSPG molecules and has been shown to promote neurite outgrowth following injury of the central and peripheral nervous systems. Variable results following chondroitinase ABC treatment make it difficult to predict the effects of this drug in human nerve allografts, especially in the presence of native extracellular signaling molecules. Several studies have shown cross-talk between neurotrophic factor and CSPG signaling pathways, but their interaction remains poorly understood. In this study, we examined the adjuvant effects of nerve growth factor (NGF) and glial cell line-derived neurotrophic factor (GDNF) on neurite outgrowth post-injury in CSPG-reduced substrates and acellular nerve allografts. Materials and Methods E12 chicken DRG explants were cultured in medium containing ChABC, ChABC + NGF, ChABC + GDNF or control media. Explants were imaged at 3 d and neurite outgrowths measured. The rat sciatic nerve injury model involved a 1-cm sciatic nerve gap that was microsurgically repaired with ChABC pre-treated acellular nerve allografts. Prior to implantation, nerve allografts were incubated in NGF, GDNF or sterile water. Nerve histology was evaluated at 5d and 8wk post-injury. Results The addition of GDNF in vitro produced significant increase in sensory neurite length at 3 d compared to ChABC alone (P < 0.01), while NGF was not significantly different from control. In vivo adjuvant NGF produced increases in total myelinated axon count (P < 0.005) and motor axon

  15. Activation and Desensitization of Peripheral Muscle and Neuronal Nicotinic Acetylcholine Receptors by Selected, Naturally-Occurring Pyridine Alkaloids

    PubMed Central

    Green, Benedict T.; Lee, Stephen T.; Welch, Kevin D.; Cook, Daniel; Kem, William R.

    2016-01-01

    Teratogenic alkaloids can cause developmental defects due to the inhibition of fetal movement that results from desensitization of fetal muscle-type nicotinic acetylcholine receptors (nAChRs). We investigated the ability of two known teratogens, the piperidinyl-pyridine anabasine and its 1,2-dehydropiperidinyl analog anabaseine, to activate and desensitize peripheral nAChRs expressed in TE-671 and SH-SY5Y cells. Activation-concentration response curves for each alkaloid were obtained in the same multi-well plate. To measure rapid desensitization, cells were first exposed to five potentially-desensitizing concentrations of each alkaloid in log10 molar increments from 10 nM to 100 µM and then to a fixed concentration of acetylcholine (ACh), which alone produces near-maximal activation. The fifty percent desensitization concentration (DC50) was calculated from the alkaloid concentration-ACh response curve. Agonist fast desensitization potency was predicted by the agonist potency measured in the initial response. Anabaseine was a more potent desensitizer than anabasine. Relative to anabaseine, nicotine was more potent to autonomic nAChRs, but less potent to the fetal neuromuscular nAChRs. Our experiments have demonstrated that anabaseine is more effective at desensitizing fetal muscle-type nAChRs than anabasine or nicotine and, thus, it is predicted to be more teratogenic. PMID:27384586

  16. The Effects of Systematic Desensitization on Test-Anxious Students in an Urban Community College: Learning Theory and Applications.

    ERIC Educational Resources Information Center

    Woods, Nathaniel A.

    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…

  17. Influence of Contextual Cues on the Efficacy of Desensitization and a Credible Placebo in Alleviating Public Speaking Anxiety

    ERIC Educational Resources Information Center

    Slutsky, Jeffrey M.; Allen, George J.

    1978-01-01

    After participating in a public speaking situation that allowed collection of self-report, physiological, and behavioral manifestations of anxiety, 67 subjects were randomly assigned to either desensitization, "T scope" therapy, or no treatment. Desensitization reduced public speaking anxiety in both contexts, whereas the placebo was effective…

  18. Optic Nerve Pit

    MedlinePlus

    ... Conditions Frequently Asked Questions Español Condiciones Chinese Conditions Optic Nerve Pit What is optic nerve pit? An optic nerve pit is a ... may be seen in both eyes. How is optic pit diagnosed? If the pit is not affecting ...

  19. Unexpected motor axons in the distal superficial radial and posterior interosseous nerves: a cadaver study.

    PubMed

    Okwueze, Martina I; Cardwell, Nancy L; Wolfort, Sean L; Nanney, Lillian B

    2007-10-01

    The prevalence of motor variations in the nerves supplying muscles of the first web space was evaluated by a visual dissection and immunohistochemical analysis from 56 cadaver hands. By microscopic visualization, 30% of the superficial radial nerves (SRNs) sent branches into muscles of the first web space. Since these unexpected penetrating branches were expected to be sensory or proprioceptive, markers of sensory and motor axons were used for confirmation. Positive identifications of motor axons (as identified by positive immunostaining for choline acetyltransferase) were made in 30% of SRNs and in 28.5% of posterior interosseous nerves. Classical teachings that the SRNs and PINs are exclusively sensory have been brought into question. Our data are in agreement with the rare clinical finding that motor function occasionally persists following devastating injury to both the ulnar and median nerves. Anatomic prevalence for this variation appears much higher than previous descriptions have indicated.

  20. Neurocontrol in sensory cortex

    NASA Astrophysics Data System (ADS)

    Ritt, Jason; Nandi, Anirban; Schroeder, Joseph; Ching, Shinung

    Technology to control neural ensembles is rapidly advancing, but many important challenges remain in applications, such as design of controls (e.g. stimulation patterns) with specificity comparable to natural sensory encoding. We use the rodent whisker tactile system as a model for active touch, in which sensory information is acquired in a closed loop between feedforward encoding of sensory information and feedback guidance of sensing motions. Motivated by this system, we present optimal control strategies that are tailored for underactuation (a large ratio of neurons or degrees of freedom to stimulation channels) and limited observability (absence of direct measurement of the system state), common in available stimulation technologies for freely behaving animals. Using a control framework, we have begun to elucidate the feedback effect of sensory cortex activity on sensing in behaving animals. For example, by optogenetically perturbing primary sensory cortex (SI) activity at varied timing relative to individual whisker motions, we find that SI modulates future sensing behavior within 15 msec, on a whisk by whisk basis, changing the flow of incoming sensory information based on past experience. J.T.R. and S.C. hold Career Awards at the Scientific Interface from the Burroughs Wellcome Fund.

  1. A single mutation of the neurokinin-2 (NK2) receptor prevents agonist-induced desensitization. Divergent conformational requirements for NK2 receptor signaling and agonist-induced desensitization in Xenopus oocytes.

    PubMed

    Nemeth, K; Chollet, A

    1995-11-17

    Receptor activation and agonist-induced desensitization of the human neurokinin-2 (NK2) receptor expressed in Xenopus oocytes have been investigated. When neurokinin A (NKA) was applied repeatedly at 5-min intervals, the second and subsequent applications gave no responses. This desensitization was not observed with the specific agonists (Lys3, Gly8-R-gamma-lactam-Leu9)NKA(3-10) (GR64349) or (Nle10)-NKA(4-10). However, in the presence of the protein kinase inhibitor staurosporine, stimulation with GR64349 or (Nle10)-NKA(4-10) induced receptor desensitization. In contrast, the protein kinase C inhibitor Ro-31-8220 was not able to enhance GR64349-mediated desensitization. We created a mutation (F248S) in the third cytoplasmic loop of NK2 that impairs NKA-induced desensitization. In the presence of either staurosporine or Ro-31-8220, the mutant receptor was desensitized in response to NKA application but not to GR64349. Also, truncation mutants delta 62 and delta 87, lacking serine and threonine residues in the cytoplasmic COOH-terminal tail, were functionally active and were partially resistant to desensitization. These observations indicate that 1) there are different conformational requirements for NK2 receptor signalling and agonist-induced desensitization, 2) the third intracellular loop and the cytoplasmic tail of NK2 are functional domains important for agonist-induced desensitization, and 3) some agonists at the NK2 receptor cause much more desensitization than others and suggest that this might result from phosphorylation by receptor-specific kinases and other non-identified protein kinases.

  2. Scientific Resistance to Research, Training and Utilization of Eye Movement Desensitization and Reprocessing (EMDR) Therapy in Treating Post-War Disorders

    DTIC Science & Technology

    2008-01-01

    and utilization of eye movement desensitization and reprocessing ( EMDR ) therapy in...history: Available online 22 October 2008 Keywords: USA Resistance Zeitgeist Military Eye movement desensitization and reprocessing ( EMDR ) Post...behavioral paradigm or zeitgeist and its chief rival – eye movement desensitization and reprocessing ( EMDR ) in treating

  3. Desensitization of functional µ-opioid receptors increases agonist off-rate.

    PubMed

    Williams, John T

    2014-07-01

    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, β-chlornaltrexamine (β-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 β-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.

  4. Neurosteroid prolongs GABAA channel deactivation by altering kinetics of desensitized states.

    PubMed

    Zhu, W J; Vicini, S

    1997-06-01

    Fast applications of GABA (1 mM) to nucleated and outside-out patches excised from granule neurons in cerebellar slices from developing rats evoked currents with a double exponential time course reminiscent of that of IPSCs. A neurosteroid 3alpha, 21dihydroxy-5alpha-pregnan-20-one (THDOC) remarkably increased the slow deactivation time constant and slowed down recovery from desensitization, as estimated by paired-pulse GABA applications. THDOC also reduced the amplitude of GABA currents, whereas it failed to affect the fast deactivation component and its relative contribution to peak amplitude. The effects of THDOC on slow deactivation were greater in rats younger than postnatal day 13 (P13) as compared with rats at P30-P35. THDOC failed to alter deactivation of short responses induced by a less-potent agonist taurine at saturating doses. These responses had deactivation kinetics described by a fast single exponential decay, little desensitization, and quick recovery. However, THDOC slowed deactivation if taurine responses were long enough to allow consistent desensitization, suggesting that desensitized states are required for the neurosteroid to modulate GABA responses. In outside-out patches, just as desensitized states prolonged GABA responses by producing reopening of channels activated by brief GABA pulses, THDOC increased the channel open probability by further increasing the number of late channel openings, resulting in a prolongation of the slow deactivation. Our data suggest that neurosteroid potentiates the inhibitory postsynaptic transmission via the prolongation of the slow deactivation and that the alteration of kinetics of entry and exit from desensitized states underlies the allosteric modification of GABAA receptors by neurosteroids.

  5. Kinetic characteristics of chimeric channelrhodopsins implicate the molecular identity involved in desensitization

    PubMed Central

    Zamani, Alemeh; Sakuragi, Shigeo; Ishizuka, Toru; Yawo, Hiromu

    2017-01-01

    Channelrhodopsin (ChR)-1 and ChR2 were the first-identified members of ChRs which are a growing subfamily of microbial-type rhodopsins. Light absorption drives the generation of a photocurrent in cell membranes expressing ChR2. However, the photocurrent amplitude attenuates and becomes steady-state during prolonged irradiation. This process, called desensitization or inactivation, has been attributed to the accumulation of intermediates less conductive to cations. Here we provided evidence that the dark-adapted (DA) photocurrent before desensitization is kinetically different from the light-adapted (LA) one after desensitization, that is, the deceleration of both basal-to-conductive and conductive-to-basal transitions. When the kinetics were compared between the DA and LA photocurrents for the ChR1/2 chimeras, the transmembrane helices, TM1 and TM2, were the determinants of both basal-to-conductive and conductive-to-basal transitions, whereas TM4 may contribute to the basal-to-conductive transitions and TM5 may contribute to the conductive-to-basal transitions, respectively. The fact that the desensitization-dependent decrease of the basal-to-conductive and conductive-to-basal transitions was facilitated by the TM1 exchange from ChR2 to ChR1 and reversed by the further TM2 exchange suggests that the conformation change for the channel gating is predominantly regulated by the interaction between TM1 and TM2. Although the exchange of TM1 from ChR2 to ChR1 showed no obvious influence on the spectral sensitivity, this exchange significantly induced the desensitization-dependent blue shift. Therefore, the TM1 and 2 are the main structures involved in two features of the desensitization, the stabilization of protein conformation and the charge distribution around the retinal-Schiff base (RSB+).

  6. Sensory Substitution for Wounded Servicemembers

    DTIC Science & Technology

    2009-10-28

    traumatic brain injury (TBI) and two civilians, all with partial visual impairment , evaluated the vision sensory substitution systems. The servicemember...Mobility Augmentation; Wounded Service Members; Human-Centered Computing; Vision Augmentation, Vision , Balance and Hearing; Sensory Substitution-enabled...mitigation of vision sensory and mobility losses. 2) Improved the usefulness of available sensory substitution technologies for injured military

  7. Trk receptor signaling and sensory neuron fate are perturbed in human neuropathy caused by Gars mutations.

    PubMed

    Sleigh, James N; Dawes, John M; West, Steven J; Wei, Na; Spaulding, Emily L; Gómez-Martín, Adriana; Zhang, Qian; Burgess, Robert W; Cader, M Zameel; Talbot, Kevin; Yang, Xiang-Lei; Bennett, David L; Schiavo, Giampietro

    2017-03-28

    Charcot-Marie-Tooth disease type 2D (CMT2D) is a peripheral nerve disorder caused by dominant, toxic, gain-of-function mutations in the widely expressed, housekeeping gene, GARS The mechanisms underlying selective nerve pathology in CMT2D remain unresolved, as does the cause of the mild-to-moderate sensory involvement that distinguishes CMT2D from the allelic disorder distal spinal muscular atrophy type V. To elucidate the mechanism responsible for the underlying afferent nerve pathology, we examined the sensory nervous system of CMT2D mice. We show that the equilibrium between functional subtypes of sensory neuron in dorsal root ganglia is distorted by Gars mutations, leading to sensory defects in peripheral tissues and correlating with overall disease severity. CMT2D mice display changes in sensory behavior concordant with the afferent imbalance, which is present at birth and nonprogressive, indicating that sensory neuron identity is prenatally perturbed and that a critical developmental insult is key to the afferent pathology. Through in vitro experiments, mutant, but not wild-type, GlyRS was shown to aberrantly interact with the Trk receptors and cause misactivation of Trk signaling, which is essential for sensory neuron differentiation and development. Together, this work suggests that both neurodevelopmental and neurodegenerative mechanisms contribute to CMT2D pathogenesis, and thus has profound implications for the timing of future therapeutic treatments.

  8. Acute small fibre sensory neuropathy: another variant of Guillain-Barré syndrome?

    PubMed

    Seneviratne, U; Gunasekera, S

    2002-04-01

    Six patients who presented with acute sensory neuropathy were studied. All patients underwent detailed clinical assessment along with electrophysiological tests and relevant laboratory investigations. All patients had acute onset numbness, reaching the peak deficit within 4 weeks. Four of them had associated burning dysaesthesia. An antecedent illness was reported in four; diarrhoea in three, and urinary tract infection in one. The neurological examination disclosed normal muscle strength, symmetric glove and stocking type sensory loss for pain and temperature, normal proprioception, and vibration senses with normal or brisk tendon reflexes. Analysis of CSF demonstrated albuminocytological dissociation in all. Routine motor and sensory nerve conduction studies were normal. Sympathetic skin responses were also normal except for the lower limbs in one patient. Stool cultures for Campylobacter jejuni were negative. The outcome was favourable. Burning dysaesthesia disappeared within 4 months. Numbness and objective sensory loss tended to persist longer. The clinical features and normal routine nerve conduction studies, which assess large diameter nerve fibre function, indicate small sensory fibre dysfunction in the group. Their presentation and CSF findings would fit into the diagnosis of sensory Guillain-Barré syndrome. The current study suggests that acute small fibre sensory neuropathy (ASFSN) is another clinical entity which could perhaps be included in the heterogeneous range of Guillain-Barré syndrome.

  9. Lentiviral-mediated transfer of CDNF promotes nerve regeneration and functional recovery after sciatic nerve injury in adult rats

    SciTech Connect

    Cheng, Lei; Liu, Yi; Zhao, Hua; Zhang, Wen; Guo, Ying-Jun; Nie, Lin

    2013-10-18

    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

  10. Optic Nerve Elongation

    PubMed Central

    Alvi, Aijaz; Janecka, Ivo P.; Kapadia, Silloo; Johnson, Bruce L.; McVay, William

    1996-01-01

    The length of the optic nerves is a reflection of normal postnatal cranio-orbital development. Unilateral elongation of an optic nerve has been observed in two patients with orbital and skull base neoplasms. In the first case as compared to the patient's opposite, normal optic nerve, an elongated length of the involved optic nerve of 45 mm was present. The involved optic nerve in the second patient was 10 mm longer than the normal opposite optic nerve. The visual and extraocular function was preserved in the second patient. The first patient had only light perception in the affected eye. In this paper, the embryology, anatomy, and physiology of the optic nerve and its mechanisms of stretch and repair are discussed. ImagesFigure 1Figure 2Figure 3Figure 4Figure 5Figure 6Figure 7Figure 8Figure 9Figure 10Figure 11Figure 13 PMID:17170975

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

    PubMed Central

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

    2015-01-01

    Abstract Taste buds release ATP to activate ionotropic purinoceptors composed of P2X2 and P2X3 subunits, present on the taste nerves. Mice with genetic deletion of P2X2 and P2X3 receptors (double knockout mice) lack responses to all taste stimuli presumably due to the absence of ATP-gated receptors on the afferent nerves. Recent experiments on the double knockout mice showed, however, that their taste buds fail to release ATP, suggesting the possibility of pleiotropic deficits in these global knockouts. To test further the role of postsynaptic P2X receptors in afferent signalling, we used AF-353, a selective antagonist of P2X3-containing receptors to inhibit the receptors acutely during taste nerve recording and behaviour. The specificity of AF-353 for P2X3-containing receptors was tested by recording Ca2+ transients to exogenously applied ATP in fura-2 loaded isolated geniculate ganglion neurons from wild-type and P2X3 knockout mice. ATP responses were completely inhibited by 10 μm or 100 μm AF-353, but neither concentration blocked responses in P2X3 single knockout mice wherein the ganglion cells express only P2X2-containing receptors. Furthermore, AF-353 had no effect on taste-evoked ATP release from taste buds. In wild-type mice, i.p. injection of AF-353 or simple application of the drug directly to the tongue, inhibited taste nerve responses to all taste qualities in a dose-dependent fashion. A brief access behavioural assay confirmed the electrophysiological results and showed that preference for a synthetic sweetener, SC-45647, was abolished following i.p. injection of AF-353. These data indicate that activation of P2X3-containing receptors is required for transmission of all taste qualities. Key points Acute inhibition of purinergic receptors with a selective P2X3 antagonist prevents transmission of information from taste buds to sensory nerves. The P2X3 antagonist has no effect on taste-evoked release of ATP, confirming the effect is postsynaptic. The

  12. Electromechanical tactile stimulation system for sensory vision substitution

    NASA Astrophysics Data System (ADS)

    Zalevsky, Zeev; Elani, Gal; Azoulay, Eli; Ilani, Dan; Beiderman, Yevgeny; Belkin, Michael

    2013-02-01

    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.

  13. Pituitary adenylatecyclase-activating polypeptide-immunoreactive nerve fibers in the rat epiglottis and pharynx.

    PubMed

    Kano, Mitsuhiro; Shimizu, Yoshinaka; Suzuki, Yujiro; Furukawa, Yusuke; Ishida, Hiroko; Oikawa, Miho; Kanetaka, Hiroyasu; Ichikawa, Hiroyuki; Suzuki, Toshihiko

    2011-12-20

    The distribution of pituitary adenylatecyclase-activating polypeptide-immunoreactive (PACAP-IR) nerve fibers was studied in the rat epiglottis and pharynx. PACAP-IR nerve fibers were located beneath the mucous epithelium, and occasionally penetrated the epithelium. These nerve fibers were abundant on the laryngeal side of the epiglottis and in the dorsal and lateral border region between naso-oral and laryngeal parts of the pharynx. PACAP-IR nerve fibers were also detected in taste buds within the epiglottis and pharynx. In addition, many PACAP-IR nerve fibers were found around acinar cells and blood vessels. The double immunofluorescence method demonstrated that distribution of PACAP-IR nerve fibers was similar to that in CGRP-IR nerve fibers in the epithelium and taste bud. However, distributions of PACAP-IR and CGRP-IR nerve fibers innervating mucous glands and blood vessels were different. The retrograde tracing method also demonstrated that PACAP and CGRP were co-expressed by vagal and glossopharyngeal sensory neurons innervating the pharynx. These findings suggest that PACAP-IR nerve fibers in the epithelium and taste bud of the epiglottis and pharynx which originate from the vagal and glossopharyngeal sensory ganglia include nociceptors and chemoreceptors. The origin of PACAP-IR nerve fibers which innervate mucous glands and blood vessels may be the autonomic ganglion.

  14. Assessment of nerve morphology in nerve activation during electrical stimulation

    NASA Astrophysics Data System (ADS)

    Gomez-Tames, Jose; Yu, Wenwei

    2013-10-01

    The distance between nerve and stimulation electrode is fundamental for nerve activation in Transcutaneous Electrical Stimulation (TES). However, it is not clear the need to have an approximate representation of the morphology of peripheral nerves in simulation models and its influence in the nerve activation. In this work, depth and curvature of a nerve are investigated around the middle thigh. As preliminary result, the curvature of the nerve helps to reduce the simulation amplitude necessary for nerve activation from far field stimulation.

  15. Incidence of lingual nerve paraesthesia following mandibular third molar surgery

    PubMed Central

    Lata, Jeevan; Tiwari, Arunesh K.

    2011-01-01

    Context: The surgical removal of impacted mandibular third molar is associated with minor but expected complications like pain, swelling, bruising and trismus. The lingual nerve damage sometimes occurs after the removal of mandibular third molar producing impaired sensation or permanent sensory loss. This complication is usually unexpected and unacceptable for the patients particularly if no prior warning has been given. Aims: The aim of the present clinical prospective study was to determine the clinical incidence of lingual nerve injury following mandibular third molar removal and to analyze possible factors for the lingual nerve injury. Settings and Design: Clinical prospective study in the Department of Oral Surgery, Punjab Government Dental College and Hospital, Amritsar. Materials and Methods: Ninety patients were selected randomly, amongst the patients, who reported to our department from January 2009 to December 2009 for the surgical removal of impacted mandibular third molar. To minimize the risk of lingual nerve injury, the standard terence wards incision was made in all cases and only buccal flap was raised. Statistical Analysis: The small number of paraesthesia precluded statistical analysis. Results: Out of 90 patients, six patients were diagnosed with lingual nerve paraesthesia. The overall incidence rate of lingual nerve injury was 6.6%. Conclusions: It can be concluded that lingual nerve paraesthesia can occur with or without reflection of lingual flap in spite of all the measures taken to protect it. It may be contributed to the fact of anatomical variations of lingual nerve. PMID:22639500

  16. Nerve conduction velocities and hair concentrations of trace elements in haemodialysis patients.

    PubMed

    Sasagawa, I; Nakada, T; Sawamura, T; Kato, T; Hashimoto, T; Ishigooka, M; Izumiya, K

    1993-01-01

    Nerve conduction velocities and hair concentrations of trace elements were studied in 19 male patients with chronic renal failure undergoing haemodialysis. Both motor and sensory nerve conduction velocities were significantly lower in haemodialysis patients as compared to c