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Sample records for sensory nerve function

  1. 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. PMID:8982537

  2. High Median Nerve Injury: Motor and Sensory Nerve Transfers to Restore Function.

    PubMed

    Soldado, Francisco; Bertelli, Jayme A; Ghizoni, Marcos F

    2016-05-01

    This article describes the clinically significant motor and sensory deficits that follow high median nerve injuries and addresses the indications, limitations, and outcomes of nerve transfers, when striving to overcome the deficits these patients' experiences. Preferred surgical reconstructive strategy using motor and sensory nerve transfers, and surgical techniques used to perform these transfers, are described. PMID:27094892

  3. Transient Alterations of Cutaneous Sensory Nerve Function by Noninvasive Cryolipolysis.

    PubMed

    Garibyan, Lilit; Cornelissen, Laura; Sipprell, William; Pruessner, Joachim; Elmariah, Sarina; Luo, Tuan; Lerner, Ethan A; Jung, Yookyung; Evans, Conor; Zurakowski, David; Berde, Charles B; Rox Anderson, R

    2015-11-01

    Cryolipolysis is a noninvasive, skin cooling treatment for local fat reduction that causes prolonged hypoesthesia over the treated area. We tested the hypothesis that cryolipolysis can attenuate nociception of a range of sensory stimuli, including stimuli that evoke itch. The effects of cryolipolysis on sensory phenomena were evaluated by quantitative sensory testing (QST) in 11 healthy subjects over a period of 56 days. Mechanical and thermal pain thresholds were measured on treated and contralateral untreated (control) flanks. Itch duration was evaluated following histamine iontophoresis. Unmyelinated epidermal nerve fiber and myelinated dermal nerve fiber densities were quantified in skin biopsies from six subjects. Cryolipolysis produced a marked decrease in mechanical and thermal pain sensitivity. Hyposensitivity started between two to seven days after cryolipolysis and persisted for at least thirty-five days post treatment. Skin biopsies revealed that cryolipolysis decreased epidermal nerve fiber density, as well as dermal myelinated nerve fiber density, which persisted throughout the study. In conclusion, cryolipolysis causes significant and prolonged decreases in cutaneous sensitivity. Our data suggest that controlled skin cooling to specifically target cutaneous nerve fibers has the potential to be useful for prolonged relief of cutaneous pain and might have a use as a research tool to isolate and study cutaneous itch-sensing nerves in human skin. PMID:26099028

  4. 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 function deficits, the presence of elongated nodes was inversely correlated with a number of functional and symptom related scores (P<0.023). Our findings suggest that carpal tunnel syndrome does not exclusively affect large fibres but is associated with loss of function in modalities mediated by both unmyelinated and myelinated sensory axons. We also document for the first time that entrapment neuropathies lead to a clear reduction in intraepidermal nerve fibre density, which was independent of electrodiagnostic test severity. The presence of elongated nodes in the target tissue further suggests that entrapment neuropathies affect nodal structure/myelin well beyond the focal compression site. Interestingly, nodal lengthening may be an adaptive phenomenon as it inversely correlates with symptom severity. PMID:25348629

  5. Impaired sensory function in heterozygous P0 knockout mice is associated with nodal changes in sensory nerves.

    PubMed

    Samsam, M; Frei, R; Marziniak, M; Martini, R; Sommer, C

    2002-01-15

    Mice heterozygously deficient in the major myelin component P0 are an established model of an inherited neuropathy and show signs of myelin degeneration in motor nerves. Unlike the case in patients, the sensory nerves are only mildly affected in the mouse mutants and do not show features indicative of myelin degeneration. Unexpectedly, by applying established behavioral tests, we found sensory deficits, as reflected by raised withdrawal thresholds to mechanical and thermal stimuli, whereas behavioral signs of a painful neuropathy were not detectable. By electron microscopy of longitudinal sections of sensory nerves, we found abnormalities in nodes of Ranvier comprising enlarged nodal gaps and poorly developed nodal Schwann cell microvilli. These alterations might be causally linked to the sensory deficits in the absence of profound myelin degeneration in the sensory nerves of the mutants. PMID:11782960

  6. Bladder reinnervation using a primarily motor donor nerve (femoral nerve branches) is functionally superior to using a primarily sensory donor nerve (genitofemoral nerve)

    PubMed Central

    Gomez-Amaya, Sandra M.; Barbe, Mary F.; Brown, Justin M.; Lamarre, Neil S.; Braverman, Alan S.; Massicotte, Vicky S.; Ruggieri, Michael R.

    2014-01-01

    Purpose To determine whether transfer of a primarily motor nerve (Femoral, F) to the anterior vesicle branch of the pelvic nerve (PN) allows more effective bladder reinnervation than a primarily sensory nerve (genitofemoral, GF). Methods Forty-one female mongrel hounds underwent bladder decentralization, decentralization and then bilateral nerve transfer (GFNT and FNT) or were sham/unoperated controls. Decentralization was achieved by bilateral transection of all sacral roots that induce bladder contractions upon electrical stimulation. The retrograde neuronal labeling dye fluorogold was injected into the bladder 3 weeks prior to euthanasia. Results Increased detrusor pressure after direct stimulation of the transferred nerve, lumbar spinal cord or spinal roots was observed in 12/17 GFNT dogs (mean detrusor pressure = 7.6±1.4 cmH2O) and in 9/10 FNT-V dogs (mean detrusor pressure = 11.7±3.1 cm H2O). The mean detrusor pressures after direct electrical stimulation of transferred femoral nerves were statistically significantly greater than after stimulation of the transferred genitofemoral nerves. Retrogradely labeled neurons from the bladder observed in upper lumbar cord segments after GFNT and FNT confirmed bladder reinnervation as did labeled axons at the nerve transfer site. Conclusions While transfer of either a mixed sensory and motor nerve (GFN) or a primarily motor nerve (FN) can reinnervate the bladder, using a primarily motor nerve provides greater return of nerve-evoked detrusor contraction. This surgical approach may be useful for patients with lower motor spinal cord injury to accomplish bladder emptying. PMID:25066874

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

    PubMed Central

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

    2015-01-01

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

  8. 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.

  9. Pharmacologic rescue of motor and sensory function by the neuroprotective compound P7C3 following neonatal nerve injury.

    PubMed

    Kemp, S W P; Szynkaruk, M; Stanoulis, K N; Wood, M D; Liu, E H; Willand, M P; Morlock, L; Naidoo, J; Williams, N S; Ready, J M; Mangano, T J; Beggs, S; Salter, M W; Gordon, T; Pieper, A A; Borschel, G H

    2015-01-22

    Nerve injuries cause pain, paralysis and numbness that can lead to major disability, and newborns often sustain nerve injuries during delivery that result in lifelong impairment. Without a pharmacologic agent to enhance functional recovery from these injuries, clinicians rely solely on surgery and rehabilitation to treat patients. Unfortunately, patient outcomes remain poor despite application of the most advanced microsurgical and rehabilitative techniques. We hypothesized that the detrimental effects of traumatic neonatal nerve injury could be mitigated with pharmacologic neuroprotection, and tested whether the novel neuroprotective agent P7C3 would block peripheral neuron cell death and enhance functional recovery in a rat neonatal nerve injury model. Administration of P7C3 after sciatic nerve crush injury doubled motor and sensory neuron survival, and also promoted axon regeneration in a dose-dependent manner. Treatment with P7C3 also enhanced behavioral and muscle functional recovery, and reversed pathological mobilization of spinal microglia after injury. Our findings suggest that the P7C3 family of neuroprotective compounds may provide a basis for the development of a new neuroprotective drug to enhance recovery following peripheral nerve injury. PMID:25313000

  10. Purines and sensory nerves.

    PubMed

    Burnstock, Geoffrey

    2009-01-01

    P2X and P2Y nucleotide receptors are described on sensory neurons and their peripheral and central terminals in dorsal root, nodose, trigeminal, petrosal, retinal and enteric ganglia. Peripheral terminals are activated by ATP released from local cells by mechanical deformation, hypoxia or various local agents in the carotid body, lung, gut, bladder, inner ear, eye, nasal organ, taste buds, skin, muscle and joints mediating reflex responses and nociception. Purinergic receptors on fibres in the dorsal spinal cord and brain stem are involved in reflex control of visceral and cardiovascular activity, as well as relaying nociceptive impulses to pain centres. Purinergic mechanisms are enhanced in inflammatory conditions and may be involved in migraine, pain, diseases of the special senses, bladder and gut, and the possibility that they are also implicated in arthritis, respiratory disorders and some central nervous system disorders is discussed. Finally, the development and evolution of purinergic sensory mechanisms are considered. PMID:19655112

  11. 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. PMID:24692141

  12. 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-induced chronic arthritis, they play important anti-inflammatory roles at least partially through somatostatin release. PMID:25524130

  13. 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

  14. Neuropathic Pain: Sensory Nerve Injury or Motor Nerve Injury?

    PubMed

    Liu, Xian-Guo; Pang, Rui-Ping; Zhou, Li-Jun; Wei, Xu-Hong; Zang, Ying

    2016-01-01

    Peripheral nerve injury often induces chronic neuropathic pain. Peripheral nerve is consisted of sensory fibers and motor fibers, it is questioned injury to which type of fibers is responsible for generation of neuropathic pain? Because neuropathic pain is sensory disorder, it is generally believed that the disease should be induced by injury to sensory fibers. In recent years, however, emergent evidence shows that motor fiber injury but not sensory fiber injury is necessary and sufficient for induction of neuropathic pain. Motor fiber injury leads to neuropathic pain by upregulating pro-inflammatory cytokines and brain-derived neurotrophic factor in pain pathway. PMID:26900063

  15. Natural history of sensory nerve recovery after cutaneous nerve injury following foot and ankle surgery

    PubMed Central

    Bai, Lu; Han, Yan-ni; Zhang, Wen-tao; Huang, Wei; Zhang, Hong-lei

    2015-01-01

    Cutaneous nerve injury is the most common complication following foot and ankle surgery. However, clinical studies including long-term follow-up data after cutaneous nerve injury of the foot and ankle are lacking. In the current retrospective study, we analyzed the clinical data of 279 patients who underwent foot and ankle surgery. Subjects who suffered from apparent paresthesia in the cutaneous sensory nerve area after surgery were included in the study. Patients received oral vitamin B12 and methylcobalamin. We examined final follow-up data of 17 patients, including seven with sural nerve injury, five with superficial peroneal nerve injury, and five with plantar medial cutaneous nerve injury. We assessed nerve sensory function using the Medical Research Council Scale. Follow-up immediately, at 6 weeks, 3, 6 and 9 months, and 1 year after surgery demonstrated that sensory function was gradually restored in most patients within 6 months. However, recovery was slow at 9 months. There was no significant difference in sensory function between 9 months and 1 year after surgery. Painful neuromas occurred in four patients at 9 months to 1 year. The results demonstrated that the recovery of sensory function in patients with various cutaneous nerve injuries after foot and ankle surgery required at least 6 months. PMID:25788928

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

    PubMed

    Spina, D; Page, C P

    2013-10-01

    Whilst local anaesthetics when applied directly to laryngeal nerves or topically to the lung can suppress cough, their chronic use is constrained because of dose limiting side effects. However, the effectiveness of local anaesthetics suggests that selectivity targeting nerves in the airway may provide novel approaches for the treatment of cough in the future. There is a considerable wealth of evidence showing that there are different afferent nerve subtypes in the airways. Traditionally C-fibres have been the focus of much research in the cough field since the stimulation of these afferents by capsaicin is able to elicit cough in guinea-pigs and in man, and drugs targeting various proteins expressed in these nerves (e.g. mu-opioid, NOP1, TRPV1, sodium channels) have been shown to be anti-tussive in preclinical models of cough. However, interest in Aδ fibres has increased recently in light of the discovery of a specific cough receptor in the guinea-pig that is provoked by citric acid and punctate stimulation, but not capsaicin and which has been anatomically linked to Aδ fibres. There is also some evidence that as a result of inflammation in the airways, Aδ fibres can begin to express neuropeptides and TRPV1 receptors so that they can become responsive to endogenous activators of this ion channel and to irritants like capsaicin. Consequently, there is considerable interest in targeting either one or both afferent nerve types for the treatment of chronic cough. However, to date the translation of preclinical studies into man has largely been disappointing and certainly there is a need for better preclinical models in this field. There also remain many challenges to overcome at a clinical level, such as what patient group(s) should be used to assess anti-tussive drugs and whether the use of irritants that induce cough in healthy volunteers (such as citric acid or capsaicin) is of any value in the assessment of novel anti-tussive drugs. The development of several continuous monitoring methodologies for measuring cough will hopefully allow better evaluation of treatments in patients with chronic cough. Nonetheless, cough remains a major unmet clinical need in respiratory medicine where new drugs are urgently required. PMID:23524012

  17. Role of mast cells and sensory nerves in skin inflammation.

    PubMed

    Harvima, I T; Nilsson, G; Naukkarinen, A

    2010-04-01

    Mast cells are powerful inflammatory cells which are in close functional and anatomical association with sensory nerves in the skin. During psychological stress the neuroendocrine system and peripheral sensory nerves are activated leading to release of mediators, such as neuropeptides, neurotrophins, corticotropin-releasing hormone and a-melanocyte-stimulating hormone, which are capable of activating mast cells. On the other hand, mast cell mediators released, e.g. histamine, tryptase and nerve growth factor, can in turn excite and stimulate surrounding neuropeptide-containing C-fibers possibly resulting in feedforward loop and potentiation of neurogenic inflammation. In these mechanisms, proinflammatory cytokines and chemokines are released from mast cells. In chronic skin diseases, psoriasis, atopic dermatitis and palmoplantar pustulosis, the contacts between tryptase-positive mast cells and sensory nerves are increased in number, which provides the morphological basis for increased mast cell - sensory nerve interaction in chronically inflamed skin. Hence, in this review the current understanding of the role of cutaneous mast cells and sensory nerves and their activation in psychic stress is discussed. PMID:20467393

  18. Paclitaxel alters sensory nerve biomechanical properties.

    PubMed

    Bober, Brian G; Shah, Sameer B

    2015-10-15

    Paclitaxel is an effective chemotherapeutic that, despite its common use, frequently causes debilitating peripheral sensory neuropathy. Paclitaxel binds to and stabilizes microtubules, and through unknown mechanisms, causes abnormal microtubule aggregation. Given that microtubules contribute to the mechanical properties of cells, we tested the hypothesis that paclitaxel treatment would alter the stiffness of sensory nerves. Rat sural nerves were excised and soaked in Ringer's solution with or without paclitaxel. Nerves were secured between a force transducer and actuator, and linearly strained. Stress-strain curves were generated, from which elastic moduli were calculated. Paclitaxel treated nerves exhibited significantly higher moduli in both linear and transition regions of the curve. A composite-tissue model was then generated to estimate the stiffness increase in the cellular fraction of the nerve following paclitaxel treatment. This model was supported experimentally by data on mechanical properties of sural nerves stripped of their epineurium, and area fractions of the cellular and connective tissue components of the rat sural nerve, calculated from immunohistochemical images. Model results revealed that the cellular components of the nerve must stiffen 12x to 115x, depending on the initial axonal modulus assumed, in order to achieve the observed tissue level mechanical changes. Consistent with such an increase, electron microscopy showed increased microtubule aggregation and cytoskeletal packing, suggestive of a more cross-linked cytoskeleton. Overall, our data suggests that paclitaxel treatment induces increased microtubule bundling in axons, which leads to alterations in tissue-level mechanical properties. PMID:26321364

  19. Store Operated Ca2+ Entry in Sensory Neurons: Functional Role and the Effect of Painful Nerve Injury

    PubMed Central

    Gemes, Geza; Bangaru, Madhavi Latha Yadav; Wu, Hsiang-En; Tang, Qingbo; Weihrauch, Dorothee; Koopmeiners, Andrew S.; Cruikshank, James M.; Kwok, Wai-Meng; Hogan, Quinn H.

    2011-01-01

    Painful nerve injury disrupts levels of cytoplasmic and stored Ca2+ in sensory neurons. Since influx of Ca2+ may occur through store-operated Ca2+ entry (SOCE) as well as voltage- and ligand-activated pathways, we sought confirmation of SOCE in sensory neurons from adult rats, and examined whether dysfunction of SOCE is a possible pathogenic mechanism. Dorsal root ganglion neurons displayed a fall in resting cytoplasmic Ca2+ concentration when bath Ca2+ was withdrawn, and a subsequent elevation of cytoplasmic Ca2+ concentration (40±5nM) when Ca2+ was reintroduced, which was amplified by store depletion with thapsigargin (1μM), and was significantly reduced by blockers of SOCE, but was unaffected by antagonists of voltage-gated membrane Ca2+ channels. We identified the underlying inwardly rectifying Ca2+-dependent ICRAC (Ca2+ release activated current), as well as a large thapsigargin-sensitive inward current activated by withdrawal of bath divalent cations, representing SOCE. Molecular components of SOCE, specifically STIM1 and Orai1, were confirmed in sensory neurons at both the transcript and protein levels. Axonal injury by spinal nerve ligation (SNL) elevated SOCE and ICRAC. However, SOCE was comparable in injured and control neurons when stores were maximally depleted by thapsigargin, and STIM1 and Orai1 levels were not altered by SNL, showing that upregulation of SOCE after SNL is driven by store depletion. Blockade of SOCE increased neuronal excitability in control and injured neurons, while injured neurons showed particular dependence on SOCE for maintaining levels of cytoplasmic and stored Ca2+, which indicates a compensatory role for SOCE following injury. PMID:21389210

  20. Use of the sensory nerve stimulator to accelerate healing of a venous leg ulcer with sensory nerve dysfunction: a case study.

    PubMed

    Ogrin, Rajna; Darzins, Peteris; Khalil, Zeinab

    2005-09-01

    A new therapy using sensory nerve stimulation [International Patent Application Number PCT/AU2004/001079: "nerve function and tissue healing" (Khalil, Z)] has been developed in our vascular physiology laboratory. This treatment has been found to improve the deficient sensory nerve function and associated deficient wound healing of older persons to levels seen in young people. An 82-year-old man with a small but persistent venous leg ulcer for 18 months, despite apparently appropriate wound dressings and compression therapy, was seen in a specialist wound management service. The patient's sensory and microvascular function was assessed in great detail using the vascular physiology laboratory techniques, and he was provided the sensory nerve stimulation therapy in addition to conventional therapy. His wound healed after 4 weeks. We report the case here. Prior to nerve stimulation therapy, cutaneous sensation, microvascular blood flow and oxygen tension were found to be reduced near the ulcer when compared with the opposite, non ulcerated leg. After therapy, oxygen tension and microvascular blood flow had improved. This case provides further evidence that sensory nerve stimulation therapy at the stipulated parameters improves wound healing. The observation that sensory nerve function improved provides support for the notion that improvement in healing is mediated by improved nerve function. PMID:16618329

  1. Sensory neuropeptides and airway function.

    PubMed

    Solway, J; Leff, A R

    1991-12-01

    Sensory nerves synthesize tachykinins and calcitonin-gene related peptide and package these neuropeptides together in synaptic vesicles. Stimulation of these C-fibers by a range of chemical and physical factors results in afferent neuronal conduction that elicits central parasympathetic reflexes and in antidromic conduction that results in local release of neuropeptides through the axon reflex. In the airways, sensory neuropeptides act on bronchial smooth muscle, the mucosal vasculature, and submucosal glands to promote airflow obstruction, hyperemia, microvascular hyperpermeability, and mucus hypersecretion. In addition, tachykinins potentiate cholinergic neurotransmission. Proinflammatory effects of these peptides also promote the recruitment, adherence, and activation of granulocytes that may further exacerbate neurogenic inflammation (i.e., neuropeptide-induced plasma extravasation and vasodilation). Enzymatic degradation limits the physiological effects of tachykinins but may be impaired by respiratory infection or other factors. Given their sensitivity to noxious compounds and physical stimuli and their potent effects on airway function, it is possible that neuropeptide-containing sensory nerves play an important role in mediating airway responses in human disease. Supporting this view are the striking phenomenological similarities between hyperpnea-induced bronchoconstriction (HIB) in guinea pigs and HIB in patients with exercise-induced asthma. Endogenous tachykinins released from airway sensory nerves mediate HIB in guinea pigs and also cause hyperpnea-induced bronchovascular hyperpermeability in these animals. On the basis of these observations, it is reasonable to speculate that sensory neuropeptides participate in the pathogenesis of hyperpnea-induced airflow obstruction in human asthmatic subjects as well. PMID:1663932

  2. Sensory nerve action potentials and sensory perception in women with arthritis of the hand

    PubMed Central

    2012-01-01

    Background Arthritis of the hand can limit a person’s ability to perform daily activities. Whether or not sensory deficits contribute to the disability in this population remains unknown. The primary purpose of this study was to determine if women with osteoarthritis (OA) or rheumatoid arthritis (RA) of the hand have sensory impairments. Methods Sensory function in the dominant hand of women with hand OA or RA and healthy women was evaluated by measuring sensory nerve action potentials (SNAPs) from the median, ulnar and radial nerves, sensory mapping (SM), and vibratory and current perception thresholds (VPT and CPT, respectively) of the second and fifth digits. Results All SNAP amplitudes were significantly lower for the hand OA and hand RA groups compared with the healthy group (p < 0.05). No group differences were found for SNAP conduction velocities, SM, VPT, and CPT. Discussion We propose, based on these findings, that women with hand OA or RA may have axonal loss of sensory fibers in the median, ulnar and radial nerves. Less apparent were losses in conduction speed or sensory perception. PMID:22575001

  3. Leptin-sensitive sensory nerves innervate white fat

    PubMed Central

    Murphy, Keegan T.; Schwartz, Gary J.; Nguyen, Ngoc Ly T.; Mendez, Jennifer M.; Ryu, Vitaly

    2013-01-01

    Leptin, the primary white adipose tissue (WAT) adipokine, is thought to convey lipid reserve information to the brain via the circulation. Because WAT responds to environmental/internal signals in a fat pad-specific (FPS) manner, systemic signals such as leptin would fail to communicate such distinctive information. Saturation of brain leptin transport systems also would fail to convey increased lipid levels beyond that point. WAT possesses sensory innervation exemplified by proven sensory-associated peptides in nerves within the tissue and by viral sensory nerve-specific transneuronal tract tracer, H129 strain of herpes simplex virus 1 labeling of dorsal root ganglia (DRG) pseudounipolar neurons, spinal cord and central sensory circuits. Leptin as a paracrine factor activating WAT sensory innervation could supply the brain with FPS information. Therefore, we tested for and found the presence of the long form of the leptin receptor (Ob-Rb) on DRG pseudounipolar neurons immunohistochemically labeled after injections of Fluorogold, a retrograde tract tracer, into inguinal WAT (IWAT). Intra-IWAT leptin injections (300 ng) significantly elevated IWAT nerve spike rate within 5 min and persisted for at least 30 min. Intra-IWAT leptin injections also induced significant c-Fos immunoreactivity (ir), indicating neural activation across DRG pseudounipolar sensory neurons labeled with Fluorogold IWAT injections. Intraperitoneal leptin injection did not increase c-Fos-ir in DRG or the arcuate nucleus, nor did it increase arcuate signal transducer and activator of transcription 3 phosphorylation-ir. Collectively, these results strongly suggest that endogenous leptin secreted from white adipocytes functions as a paracrine factor to activate spinal sensory nerves innervating the tissue. PMID:23612999

  4. Deep peroneal nerve transfer for established plantar sensory loss.

    PubMed

    Koshima, Isao; Nanba, Yuzaburo; Tsutsui, Tetsuya; Takahashi, Yoshio

    2003-10-01

    Patients with established or irreversible plantar sensory loss often have normal sensation on the dorsal aspect of the foot, due to an intact deep peroneal nerve. A new method of deep peroneal nerve transfer is proposed for repair of plantar sensory loss caused by extensive nerve gaps or high-level lesions of the posterior tibial nerve. Two cases in which this technique was used are described. The surgical technique is relatively easy, with a short operating time, rapid nerve regeneration after surgery, accurate sensory recovery, and minimal donor-site morbidity with sensory loss only on the first web space of the foot. PMID:14634907

  5. Study of Electrophysiological Changes in Sensory Nerves Among Diabetic Smokers

    PubMed Central

    Moinuddin, Arsalan; Ahsan, Akif; Goel, Ashish

    2016-01-01

    Introduction Neuropathy is one of the most troublesome complication affecting individuals with diabetes. The resultant loss of function in peripheral nerves causes loss of protective sensations and impairs patient’s ability to perceive incipient or even apparent ulcerations in the feet. Aim This study was undertaken to test the hypothesis of alteration in electrophysiological parameters of nerve before actual manifestations of neuropathy in type 2 diabetic patients and to analyse the effect of smoking on Sensory Nerve Conduction Velocity (SNCV) of diabetic subjects. Materials and Methods One hundred and twenty diagnosed diabetics were taken as cases while 30 healthy non diabetics were taken as control. Case group was divided into diabetic non-smoker and diabetic smoker. Diabetic smoker were further subdivided into light smoker, moderate smoker and heavy smoker according to smoking index. After detailed history and physical examination SNCV of median and ulnar nerve in upper limb and sural nerve in lower limb was performed. Results On comparison of SNCV of median and ulnar nerve of upper limb and sural nerve of lower limb between control and diabetic non-smoker only sural nerve of diabetic non smoker showed significant bilateral decrease. There was significant bilateral decrease in SNCV of median and ulnar nerve of diabetic heavy smoker when compared to control and diabetic non smoker. Similarly, SNCV of sural nerve of diabetic heavy smoker was significantly decreased when compared with control, diabetic non-smoker, diabetic light and moderate smoker. A negative and statistically significant correlation was found between SNCV and smoking index. Conclusion Present study indicates that nerves of lower limbs are more susceptible to diabetic assault as compared to upper limb suggesting that long nerves are commonly affected. Also, apart from duration and severity of diabetes, smoking itself is an independent factor for diabetic neuropathy. PMID:26894060

  6. Tissue Preparation and Immunostaining of Mouse Sensory Nerve Fibers Innervating Skin and Limb Bones

    PubMed Central

    Shepherd, Andrew J.; Mohapatra, Durga P.

    2012-01-01

    Detection and primary processing of physical, chemical and thermal sensory stimuli by peripheral sensory nerve fibers is key to sensory perception in animals and humans. These peripheral sensory nerve fibers express a plethora of receptors and ion channel proteins which detect and initiate specific sensory stimuli. Methods are available to characterize the electrical properties of peripheral sensory nerve fibers innervating the skin, which can also be utilized to identify the functional expression of specific ion channel proteins in these fibers. However, similar electrophysiological methods are not available (and are also difficult to develop) for the detection of the functional expression of receptors and ion channel proteins in peripheral sensory nerve fibers innervating other visceral organs, including the most challenging tissues such as bone. Moreover, such electrophysiological methods cannot be utilized to determine the expression of non-excitable proteins in peripheral sensory nerve fibers. Therefore, immunostaining of peripheral/visceral tissue samples for sensory nerve fivers provides the best possible way to determine the expression of specific proteins of interest in these nerve fibers. So far, most of the protein expression studies in sensory neurons have utilized immunostaining procedures in sensory ganglia, where the information is limited to the expression of specific proteins in the cell body of specific types or subsets of sensory neurons. Here we report detailed methods/protocols for the preparation of peripheral/visceral tissue samples for immunostaining of peripheral sensory nerve fibers. We specifically detail methods for the preparation of skin or plantar punch biopsy and bone (femur) sections from mice for immunostaining of peripheral sensory nerve fibers. These methods are not only key to the qualitative determination of protein expression in peripheral sensory neurons, but also provide a quantitative assay method for determining changes in protein expression levels in specific types or subsets of sensory fibers, as well as for determining the morphological and/or anatomical changes in the number and density of sensory fibers during various pathological states. Further, these methods are not confined to the staining of only sensory nerve fibers, but can also be used for staining any types of nerve fibers in the skin, bones and other visceral tissue. PMID:22314687

  7. Sural nerve defects after nerve biopsy or nerve transfer as a sensory regeneration model for peripheral nerve conduit implantation.

    PubMed

    Radtke, C; Kocsis, J D; Reimers, K; Allmeling, C; Vogt, P M

    2013-09-01

    Nerve repair after injury can be effectively accomplished by direct suture approximation of the proximal and distal segments. This is more successful if coadaptation can be achieved without tension. Currently, the gold standard repair of larger deficits is the transplantation of an autologous sensory sural nerve graft. However, a significant disadvantage of this technique is the inevitable donor morbidity (sensory loss, neuroma and scar formation) after harvesting of the sural nerve. Moreover, limitation of autologous donor nerve length and fixed diameter of the available sural nerve are major drawbacks of current autograft treatment. Another approach that was introduced for nerve repair is the implantation of alloplastic nerve tubes made of, for example, poly-L-lactide. In these, nerve stumps of the transected nerves are surgically bridged using the biosynthetic conduit. A number of experimental studies, primarily in rodents, indicate axonal regeneration and remyelination after implantation of various conduits. However, only limited clinical studies with conduit implantation have been performed in acute peripheral nerve injuries particularly on digital nerves. Clinical transfer of animal studies, which can be carefully calibrated for site and extent of injury, to humans is difficult to interpret due to the intrinsic variability in human nerve injuries. This prevents effective quantification of improvement and induces bias in the study. Therefore, standardization of lesion/repair in human studies is warranted. Here we propose to use sural nerve defects, induced due to nerve graft harvesting or from diagnostic nerve biopsies as a model site to enable standardization of nerve conduit implantation. This would help better with the characterization of the implants and its effectiveness in axonal regeneration and remyelination. Nerve regeneration can be assessed, for example, by recovery of sensation, measured non-invasively by threshold to von Frey filaments and cold allodynia. Moreover, the implantation of nerve conduits may not only serve as a model to examine nerve repair, but it could also prevent neuroma formation, which is a major morbidity of sural nerve extraction. PMID:23867139

  8. Palm to Finger Ulnar Sensory Nerve Conduction

    PubMed Central

    Davidowich, Eduardo; Orsini, Marco; Pupe, Camila; Pessoa, Bruno; Bittar, Caroline; Pires, Karina Lebeis; Bruno, Carlos; Coutinho, Bruno Mattos; de Souza, Olivia Gameiro; Ribeiro, Pedro; Velasques, Bruna; Bittencourt, Juliana; Teixeira, Silmar; Bastos, Victor Hugo

    2015-01-01

    Ulnar neuropathy at the wrist (UNW) is rare, and always challenging to localize. To increase the sensitivity and specificity of the diagnosis of UNW many authors advocate the stimulation of the ulnar nerve (UN) in the segment of the wrist and palm. The focus of this paper is to present a modified and simplified technique of sensory nerve conduction (SNC) of the UN in the wrist and palm segments and demonstrate the validity of this technique in the study of five cases of type III UNW. The SNC of UN was performed antidromically with fifth finger ring recording electrodes. The UN was stimulated 14 cm proximal to the active electrode (the standard way) and 7 cm proximal to the active electrode. The normal data from amplitude and conduction velocity (CV) ratios between the palm to finger and wrist to finger segments were obtained. Normal amplitude ratio was 1.4 to 0.76. Normal CV ratio was 0.8 to 1.23.We found evidences of abnormal SNAP amplitude ratio or substantial slowing of UN sensory fibers across the wrist in 5 of the 5 patients with electrophysiological-definite type III UNW. PMID:26788268

  9. Sensory Nerve Induced Inflammation Contributes to Heterotopic Ossification

    PubMed Central

    Salisbury, Elizabeth; Rodenberg, Eric; Sonnet, Corinne; Hipp, John; Gannon, Francis H.; Vadakkan, Tegy J.; Dickinson, Mary E.; Olmsted-Davis, Elizabeth A.; Davis, Alan R.

    2012-01-01

    Heterotopic ossification (HO), or bone formation in soft tissues, is often the result of traumatic injury. Much evidence has linked the release of BMPs (bone morphogenetic proteins) upon injury to this process. HO was once thought to be a rare occurrence, but recent statistics from the military suggest that as many as 60% of traumatic injuries, resulting from bomb blasts, have associated HO. In this study, we attempt to define the role of peripheral nerves in this process. Since BMP2 has been shown previously to induce release of the neuroinflammatory molecules, substance P (SP) and calcitonin gene related peptide (CGRP), from peripheral, sensory neurons, we examined this process in vivo. SP and CGRP are rapidly expressed upon delivery of BMP2 and remain elevated throughout bone formation. In animals lacking functional sensory neurons (TRPV1−/−), BMP2-mediated increases in SP and CGRP were suppressed as compared to the normal animals, and HO was dramatically inhibited in these deficient mice, suggesting that neuroinflammation plays a functional role. Mast cells, known to be recruited by SP and CGRP, were elevated after BMP2 induction. These mast cells were localized to the nerve structures and underwent degranulation. When degranulation was inhibited using cromolyn, HO was again reduced significantly. Immunohistochemical analysis revealed nerves expressing the stem cell markers nanog and Klf4, as well as the osteoblast marker osterix, after BMP2 induction, in mice treated with cromolyn. The data collectively suggest that BMP2 can act directly on sensory neurons to induce neurogenic inflammation, resulting in nerve remodeling and the migration/release of osteogenic and other stem cells from the nerve. Further, blocking this process significantly reduces HO, suggesting that the stem cell population contributes to bone formation. PMID:21678472

  10. Mesenteric arterial function in the rat in pregnancy: role of sympathetic and sensory-motor perivascular nerves, endothelium, smooth muscle, nitric oxide and prostaglandins.

    PubMed Central

    Ralevic, V.; Burnstock, G.

    1996-01-01

    1. The effects of pregnancy on mesenteric arterial function were examined in constantly perfused (5 ml min-1) mesenteric arterial beds isolated from 21-day pregnant rats. The function of sympathetic and sensory-motor perivascular nerves, endothelium and smooth muscle was examined. The role of nitric oxide and prostaglandins in vasoconstrictor function was tested by use of NG-nitro-L-arginine methyl ester (L-NAME; 100 microM) and indomethacin (10 microM), respectively. 2. Electrical field stimulation (EFS; 4-32 Hz, 1 ms, 90V, 30s) at basal tone elicited frequency-dependent vasoconstriction which was markedly reduced in preparations from pregnant rats at all frequencies. Vasoconstrictor responses to vasopressin and endothelin were also reduced in pregnancy and there was a trend towards a reduction in maximal responses to noradrenaline (NA). In contrast, there was no difference in vasoconstrictor responses to ATP, 5-hydroxytryptamine (5-HT) or angiotension II. 3. L-NAME (100 microM) augmented responses to EFS, NA, ATP and vasopressin in control mesenteric arterial preparations. In contrast, L-NAME augmented responses only to EFS in pregnancy, having no significant effect on responses to NA, ATP and vasopressin. 4. Indomethacin (10 microM) attenuated responses to NA and vasopressin, but not to EFS, in controls and in pregnancy. Responses to ATP were attenuated by indomethacin in controls but not in pregnancy. 5. Mesenteric preparations from pregnant rats were resistant to having tone raised by continuous perfusion with methoxamine. Despite an approximately 10 fold greater concentration of methoxamine, there was a significantly smaller increase in tone in preparations from pregnant, 34.27 +/- 4.8 mmHg (n = 11) compared to control, 65.92 +/- 5.4 mmHg (n = 11), rats. EFS (4-12 Hz, 60 V, 0.1 ms, 30s) in the presence of guanethidine (5 microM) to block sympathetic neurotransmission elicited frequency-dependent vasodilatation due to activation of sensory-motor nerves. Percentage relaxations were similar in preparations from pregnant and non-pregnant rats. 6. Dose-dependent endothelium-dependent vasodilatations to acetylcholine and ATP were similar in preparations from pregnant and non-pregnant rats. Endothelium-independent vasodilatation to sodium nitroprusside and to calcitonin gene-related peptide were also similar between the two groups. 7. There was no significant difference in the basal perfusion pressure of mesenteric arterial beds from control (21.3 +/- 1.0 mmHg, n = 24) and pregnant (20.2 +/- 1.2 mmHg, n = 23) rats. However, a step-wise increase in perfusate flow from 5 to 10, 15, 20 and 24ml min-1 produced smaller increases in perfusion pressure in pregnancy compared to the controls. L-NAME (100 microM) or indomethacin (10 microM) had no significant effect on the relationship between flow and perfusion pressure. 8. The present results show that prejunctional changes are involved in blunted sympathetic vasoconstriction of rat mesenteric arteries in pregnancy. Non-specific postjunctional changes are implicated in the reduced constrictor responses to applied methoxamine, vasopressin and endothelin, but not to ATP. In contrast, sensory-motor nerves and endothelium-dependent and -independent vasodilatation was unchanged. The decrease in receptor-mediated mesenteric arterial constrictor responsiveness in pregnancy does not appear to be due to acute modulation by NO or prostaglandins, but may involve changes in the distensibility of the bed and/or changes in wall thickness. PMID:8730740

  11. 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

  12. Facial nerve dysfunction in hereditary motor and sensory neuropathy type I and III.

    PubMed

    Glocker, F X; Rösler, K M; Linden, D; Heinen, F; Hess, C W; Lücking, C H

    1999-09-01

    Facial nerve function was studied in 19 patients with hereditary motor and sensory neuropathy type I (HMSN I) and 2 patients with hereditary motor and sensory neuropathy type III (HMSN III, Déjérine-Sottas), and compared to that in 24 patients with Guillain-Barré syndrome (GBS). The facial nerve was stimulated electrically at the stylomastoid fossa, and magnetically in its proximal intracanalicular segment. Additionally, the face-associated motor cortex was stimulated magnetically. The facial nerve motor neurography was abnormal in 17 of 19 HMSN I patients and in both HMSN III patients, revealing moderate to marked conduction slowing in both the extracranial and intracranial nerve segments, along with variable reductions of compound muscle action potential (CMAP) amplitudes. The facial nerve conduction slowing paralleled that of limb nerves, but was not associated with clinical dysfunction of facial muscles, because none of the HMSN I patients had facial palsy. Conduction slowing was most severe in the HMSN III patients, but only slight facial weakness was present. In GBS, conduction slowing was less marked, but facial weakness exceeded that in HMSN patients in all cases. We conclude that involvement of the facial nerve is common in HMSN I and HMSN III. It affects the intra- and extracranial part of the facial nerve and is mostly subclinical. PMID:10454715

  13. Tachykinins, sensory nerves, and asthma--an overview.

    PubMed

    Lundberg, J M

    1995-07-01

    Tachykinin peptides, substance P (SP) and neurokinin A (NKA), are released from airway sensory nerves upon exposure to irritant chemicals and endogenous agents including bradykinin, prostaglandins, histamine, and protons, The released neuropeptides are potent inducers of a cascade of responses, including vasodilatation, mucus secretion, plasma protein extravasation, leukocyte adhesion--activation, and bronchoconstriction. Neurokinin 1 receptors (preferably activated by SP) seem to be most important for inflammatory actions, while neurokinin 2 receptors (preferably activated by NKA) mediate bronchoconstriction. Species differences exist whereby rat and guinea-pig have a more developed neurogenic inflammation response than normal human airways. However, disease states such as inflammation or viral infections lead to enhanced peptide synthesis and (or) increased sensory nerve excitability. Together with increased neurokinin 1 receptor synthesis and loss of major tachykinin-degrading enzymes such as neutral endopeptidase in airway inflammation, this suggests that recently developed, orally active nonpeptide neurokinin receptor antagonists could have a therapeutic potential in asthmatic patients. PMID:8846429

  14. Transfer of the radial branch of the superficial radial nerve to the sensory branch of the ulnar nerve for sensory restoration after C7-T1 brachial plexus injury.

    PubMed

    Xu, Bin; Dong, Zhen; Zhang, Cheng-Gang; Gu, Yu-Dong

    2016-03-01

    Previously, we have reconstructed the motor function of patients with C7-T1 brachial plexus palsies through combined nerve and tendon transfers. However, these patients lose not only the motor function of the hand but also the sensation on the ulnar side of the hand. Without sensory recovery, the injured hand may be further damaged, particularly by burns in this contact zone. Therefore, we described a technique to restore the sensation at the ulnar aspect of the hand by performing a transfer of the radial branch of the superficial radial nerve to the sensory branch of the ulnar nerve. PMID:26626199

  15. High Ulnar Nerve Injuries: Nerve Transfers to Restore Function.

    PubMed

    Patterson, Jennifer Megan M

    2016-05-01

    Peripheral nerve injuries are challenging problems. Nerve transfers are one of many options available to surgeons caring for these patients, although they do not replace tendon transfers, nerve graft, or primary repair in all patients. Distal nerve transfers for the treatment of high ulnar nerve injuries allow for a shorter reinnervation period and improved ulnar intrinsic recovery, which are critical to function of the hand. PMID:27094893

  16. 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. PMID:27094884

  17. Uses of Skin Biopsy for Sensory and Autonomic Nerve Assessment

    PubMed Central

    Myers, M. Iliza; Peltier, Amanda C.

    2013-01-01

    Skin biopsy is a valuable diagnostic tool for small-fiber-predominant neuropathy by the quantification of intra-epidermal nerve fiber density (IENFD). It has the unique advantage of being a minimally invasive procedure with the potential for longitudinal evaluation of both sensory and autonomic fibers. Unmyelinated small fibers are not otherwise quantified objectively with such a level of sensitivity as has been reported with IENFD. Recent advances include an expansion of the skin punch biopsy technique to evaluate larger myelinated fibers and mechanoreceptors, and recent work has also focused on additional methods of quantifying dermal fibers and densely innervated autonomic structures. This review discusses current work using skin biopsy for the pathologic analysis of peripheral nerve fibers in neuropathy of various causes as well as its use in clinical trials. PMID:23250768

  18. 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

  19. Sensory conduction in medial and lateral plantar nerves.

    PubMed Central

    Ponsford, S N

    1988-01-01

    A simple and reliable method of recording medial and lateral plantar nerve sensory action potentials is described. Potentials are recorded with surface electrodes at the ankle using surface electrodes stimulating orthodromically at the sole. The normal values obtained are higher in amplitude than those obtained by the method described by Guiloff and Sherratt and are detectable in older subjects aged over 80 years. The procedure is valuable in the diagnosis of early peripheral neuropathy, mononeuritis multiplex, tarsal tunnel syndrome and in differentiation between pre and post ganglionic L5 S1 lesions. PMID:2831304

  20. Nerve repair by denatured muscle autografts promotes sustained sensory recovery in leprosy.

    PubMed

    Pereira, J H; Palande, D D; Narayanakumar, T S; Subramanian, A S; Gschmeissner, S; Wilkinson, M

    2008-02-01

    A total of 38 patients with leprosy and localised nerve damage (11 median at the wrist and 37 posterior tibial at the ankle) were treated by 48 freeze-thawed skeletal muscle autografts ranging between 2.5 cm and 14 cm in length. Sensory recovery was noted in 34 patients (89%) and was maintained during a mean period of follow-up of 12.6 years (4 to 14). After grafting the median nerve all patients remained free of ulcers and blisters, ten demonstrated perception of texture and eight recognised weighted pins. In the posterior tibial nerve group, 24 of 30 repairs (80%) resulted in improved healing of the ulcers and 26 (87%) demonstrated discrimination of texture. Quality of life and hand and foot questionnaires showed improvement; the activities of daily living scores improved in six of seven after operations on the hand, and in 14 of 22 after procedures on the foot. Another benefit was subjective improvement in the opposite limb, probably because of the protective effect of better function in the operated side. This study demonstrates that nerve/muscle interposition grafting in leprosy results in consistent sensory recovery and high levels of patient satisfaction. Ten of 11 patients with hand operations and 22 of 25 with procedures to the foot showed sensory recovery in at least one modality. PMID:18256092

  1. Altered Bone Development in a Mouse Model of Peripheral Sensory Nerve Inactivation

    PubMed Central

    Heffner, Mollie A.; Anderson, Matthew J.; Yeh, Gregory C.; Genetos, Damian C.; Christiansen, Blaine A.

    2014-01-01

    Objectives The present study sought to determine the effects of decreased peripheral sensory nerve function on skeletal development and bone metabolism in mice. Methods C57BL/6 neonatal mice were treated with capsaicin to induce peripheral sensory nerve degeneration, and compared to vehicle-treated controls at 4, 8 and 12 weeks of age. Changes in bone structure were assessed using micro-computed tomography, mechanical properties and fracture resistance were assessed using three-point bending of radii, and bone turnover was assessed using dynamic histomorphometry and serum biomarkers. Results Capsaicin treatment resulted in small but significant decreases in bone structure, particularly affecting trabecular bone. Capsaicin-treated mice exhibited lower trabecular thickness at the femoral metaphysis and L5 vertebral body compared with vehicle-treated mice. However, capsaicin- and vehicle-treated mice had similar mechanical properties and bone turnover rates. Conclusion Neonatal capsaicin treatment affected trabecular bone during development; however these small changes may not be meaningful with respect to bone strength under normal loading conditions. It is possible that capsaicin-sensitive neurons may be more important for bone under stress conditions such as increased mechanical loading or injury. Future studies will investigate this potential role of peripheral sensory nerves in bone adaptation. PMID:24583535

  2. Vascularized Nerve Bypass Graft: A Case Report of an Additional Treatment for Poor Sensory Recovery.

    PubMed

    Usami, Satoshi; Tanaka, Kentaro; Ohkubo, Alisa; Okazaki, Mutsumi

    2016-04-01

    End-to-side neurorrhaphy has proven effective in basic research and in clinical application. One of the methods of end-to-side neurorrhaphy, nerve bypass technique, has been reported and axon regeneration has been proven. In clinical application, the utility of the nerve bypass technique has been revealed in some cases; however, these bypasses were performed using nonvascularized nerves. We initially used the vascularized nerve bypass graft technique with the sural nerve as a secondary clinical procedure after median nerve injury in a 61-year-old patient and achieved motor and sensory nerve regeneration, as supported by a nerve conduction study and clinical sensory test. This technique has the potential to become one of the choices for salvage procedure of severe nerve injury. PMID:27200248

  3. 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.

  4. Noninvasive peroneal sensory and motor nerve conduction recordings in the rabbit distal hindlimb: feasibility, variability and neuropathy measure.

    PubMed

    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 models of peripheral neuropathies. PMID:24658286

  5. Sensory Recovery Outcome after Digital Nerve Repair in Relation to Different Reconstructive Techniques: Meta-Analysis and Systematic Review

    PubMed Central

    Wolf, Petra; Harder, Yves; Kern, Yasmin; Paprottka, Philipp M.; Machens, Hans-Günther; Lohmeyer, Jörn A.

    2013-01-01

    Good clinical outcome after digital nerve repair is highly relevant for proper hand function and has a significant socioeconomic impact. However, level of evidence for competing surgical techniques is low. The aim is to summarize and compare the outcomes of digital nerve repair with different methods (end-to-end and end-to-side coaptations, nerve grafts, artificial conduit-, vein-, muscle, and muscle-in-vein reconstructions, and replantations) to provide an aid for choosing an individual technique of nerve reconstruction and to create reference values of standard repair for nonrandomized clinical studies. 87 publications including 2,997 nerve repairs were suitable for a precise evaluation. For digital nerve repairs there was practically no particular technique superior to another. Only end-to-side coaptation had an inferior two-point discrimination in comparison to end-to-end coaptation or nerve grafting. Furthermore, this meta-analysis showed that youth was associated with an improved sensory recovery outcome in patients who underwent digital replantation. For end-to-end coaptations, recent publications had significantly better sensory recovery outcomes than older ones. Given minor differences in outcome, the main criteria in choosing an adequate surgical technique should be gap length and donor site morbidity caused by graft material harvesting. Our clinical experience was used to provide a decision tree for digital nerve repair. PMID:23984064

  6. Arnold's nerve cough reflex: evidence for chronic cough as a sensory vagal neuropathy.

    PubMed

    Ryan, Nicole M; Gibson, Peter G; Birring, Surinder S

    2014-10-01

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

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

    PubMed Central

    Schultz, Aimee E.; Kuiken, Todd A.

    2009-01-01

    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 pathways once serving highly functionally relevant regions of the brain. This suggests that tactile interface devices could be used to give a physiologically appropriate sense of touch to a prosthetic limb, which would likely help with better functional utilization of the prosthetic device and possibly help to more effectively integrate the device with the user's self-image. PMID:19369486

  8. Enhanced sensory recovery after median nerve repair using cortical audio-tactile interaction. A randomised multicentre study.

    PubMed

    Rosén, B; Lundborg, G

    2007-02-01

    The "Sensor Glove System" offers an alternate afferent inflow from the hand early after nerve repair in the forearm, mediated through the hearing sense, implying that deprivation of one sense can be compensated by another sense. This sensory "by-pass" was used early after repair of the median nerve with the intention of improving recovery of functional sensibility by maintaining an active sensory map of the hand in the somatosensory cortex during the deafferentation period. In a prospective multicentre clinical study, one group (n=14) started early after surgery with sensory re-education using the Sensor Glove System and the control group (n=12) received conventional sensory re-education, starting 3 months postoperatively. The patients were checked regularly during a 1-year period, with focus on recovery of tactile gnosis. After 12, months, tactile gnosis was significantly better in the Sensor Glove System group. This highlights the timing for introduction of training after nerve repair, focusing on the importance of immediate sensory re-learning. PMID:17134797

  9. Effect of long-term implanted nerve cuff electrodes on the electrophysiological properties of human sensory nerves.

    PubMed

    Slot, P J; Selmar, P; Rasmussen, A; Sinkjaer, T

    1997-03-01

    During a long-term implantation (307 days) of a tripolar split cuff electrode around the palmar digital nerve to the radial side of the left index finger, branching off the median nerve in a medullary lesioned C6 patient, the physiological state of the nerve was intensively monitored. The resulting sensory nerve action potential (SNAP) amplitude was recorded, using both near-nerve electrodes and the implanted cuff electrode. The SNAP amplitude declined within 10 days to approximately 50% of the first SNAP cuff amplitude measured on Day 2 after implantation and recovered to the initial amplitude within 3 months. The SNAP amplitude measurements made with near-nerve electrodes were consistent with the cuff results; the SNAP conduction velocity (CV) recorded by the near-nerve electrodes and the cuff electrode was constant during the whole implantation period. This is in agreement with the results from two other patients: one with a cuff implanted around the sural nerve, and the other with a cuff implanted around a branch of the tibial nerve. These results and animals studies show that the cuff electrode is an electrically stable neural-electrical transducer. PMID:9148706

  10. 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.

  11. 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

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

    PubMed

    Ryu, Seung Jun; Zhang, Ho Yeol

    2015-09-01

    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

  13. Differential Gene Expression in Motor and Sensory Schwann Cells in the Rat Femoral Nerve

    PubMed Central

    Jesuraj, Nithya J.; Nguyen, Peter K.; Wood, Matthew D.; Moore, Amy M.; Borschel, Gregory H.; Mackinnon, Susan E.; Sakiyama-Elbert, Shelly E.

    2011-01-01

    Phenotypic differences in Schwann cells (SCs) may help guide axonal regeneration down motor or sensory specific pathways following peripheral nerve injury. The goal of this study was to identify phenotypic markers for SCs harvested from the cutaneous (sensory) and quadriceps (motor) branches of the rat femoral nerve and to study the effects of expansion culture on the expression patterns of these motor or sensory phenotypic markers. RNA was extracted from SCs harvested from the motor and sensory branches of the rat femoral nerve and analyzed using Affymetrix Gene Chips© (Rat Genome 230 v2.0 Array A). Genes that were upregulated in motor SCs compared to the sensory SCs or vice versa were identified, and the results were verified for a subset of genes using quantitative real time polymerase chain reaction (qRT-PCR). The expression levels of the “phenotype-specific” genes were then evaluated in SC expansion cultures at various timepoints over 30 days by qRT-PCR to determine the effect of expansion on SC phenotype. Expression levels of the phenotype-specific genes were significantly altered after expansion culture for both the motor and sensory markers compared to fresh nerve tissue. These results indicate that both motor and sensory SC gene expression patterns are disrupted during expansion in vitro and may affect the ability of SCs to express phenotype specific genes after transplantation. PMID:21932366

  14. Documenting neuropathy of the lateral femoral cutaneous nerve using the Pressure-Specified Sensory Testing device.

    PubMed

    Coert, J Henk; Dellon, A Lee

    2003-04-01

    Entrapment of the lateral femoral cutaneous nerve has been difficult to document. The variability of the anatomic location of this nerve makes it difficult to measure with traditional electrodiagnostic studies. At the same time, anatomic variability increases the likelihood for this nerve to become entrapped within the inguinal ligament. The current study reports the ability to document the presence of this nerve entrapment in 24 patients, compared with 10 asymptomatic control subjects, by using nonpainful and noninvasive computer-assisted neurosensory testing with the Pressure-Specified Sensory Device. PMID:12671378

  15. 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

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

    PubMed Central

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

    2014-01-01

    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 cm2 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. PMID:24472004

  17. Sensory cutaneous nerve fine-needle aspiration in Hansen's disease: A retrospective analysis of our experience

    PubMed Central

    Prasoon, Dev; Mandal, Swapan Kumar; Agrawal, Parimal

    2015-01-01

    Background: Leprosy affects peripheral nerves. As Mycobacterium leprae has unique tropism for Schwann cells, thickened sensory cutaneous nerves provide an easy target for the detection of lepra bacilli and other changes associated with the disease. Materials and Methods: The data of patients with sensory cutaneous nerve involvement were retrieved from our record for the period January 2006 to December 2014. The hematoxylin and eosin (H and E)- and May-Grünwald-Giemsa (MGG)-stained slides were screened for Schwann cells, granuloma, and necrosis. Modified Ziehl-Neelsen (ZN)-stained smears were searched for lepra bacilli and globi. Morphological index was calculated in multibacillary lesions. Result: Twenty-nine sensory cutaneous nerves were aspirated in 23 patients. While 15 cases showed skin and nerve involvement, 8 cases showed only nerve involvement. Terminal cutaneous branch of the radial nerve was most often aspirated. No motor loss was observed after aspiration. Five cytologic pictures were seen — Epithelioid cell granuloma only in 6 cases, epithelioid cell granuloma with necrosis in 1 case, epithelioid cell granuloma with lepra bacilli in 3 cases, necrosis with lepra bacilli in 1 case, and only lepra bacilli in 12 cases. Morphological index ranged from 20% to 80%. Conclusion: Sensory cutaneous nerve fine-needle aspiration (FNA) is a feasible, viable, effective, and safe procedure. It adds to diagnostic FNA yield in patients with concomitant skin involvement and offers a way to evaluate patients with only nerve involvement. Calculation of morphological index allows prognostication and may have a role in assessing response to therapy and/or relapse. PMID:26729977

  18. Morphology and Nanomechanics of Sensory Neurons Growth Cones following Peripheral Nerve Injury

    PubMed Central

    Szabo, Vivien; Végh, Attila-Gergely; Lucas, Olivier; Cloitre, Thierry; Scamps, Frédérique; Gergely, Csilla

    2013-01-01

    A prior peripheral nerve injury in vivo, promotes a rapid elongated mode of sensory neurons neurite regrowth in vitro. This in vitro model of conditioned axotomy allows analysis of the cellular and molecular mechanisms leading to an improved neurite re-growth. Our differential interference contrast microscopy and immunocytochemistry results show that conditioned axotomy, induced by sciatic nerve injury, did not increase somatic size of adult lumbar sensory neurons from mice dorsal root ganglia sensory neurons but promoted the appearance of larger neurites and growth cones. Using atomic force microscopy on live neurons, we investigated whether membrane mechanical properties of growth cones of axotomized neurons were modified following sciatic nerve injury. Our data revealed that neurons having a regenerative growth were characterized by softer growth cones, compared to control neurons. The increase of the growth cone membrane elasticity suggests a modification in the ratio and the inner framework of the main structural proteins. PMID:23418549

  19. Selectivity of distal reinnervation of regenerating mixed motor and sensory nerve fibres across muscle grafts in rats.

    PubMed

    Rath, S; Green, C J

    1991-04-01

    This study investigated target specificity during axonal regeneration of a mixed motor and sensory nerve towards respective targets. The femoral nerves in rats were divided and allowed to grow across a 6 mm gap interposed with frozen and thawed muscle grafts towards their distal motor and sensory nerve stumps. Fourteen weeks later the number of motoneurons projecting axons into the motor and sensory branches were determined by retrograde axonal tracing using horse-radish peroxidase. There were significantly higher numbers of motoneurons (p = 0.0034) projecting into the motor nerve than the sensory nerve. Efferent axons of a mixed nerve selectivity grew into motor branches when allowed to regenerate across a 6 mm gap interposed with muscle grafts. It is possible that a deliberately created 'structured gap' during repair of mixed nerves could improve axonal matching by allowing expression of neurotropism. PMID:2025759

  20. 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.

  1. Nerve Transfers to Restore Shoulder Function.

    PubMed

    Leechavengvongs, Somsak; Malungpaishorpe, Kanchai; Uerpairojkit, Chairoj; Ng, Chye Yew; Witoonchart, Kiat

    2016-05-01

    The restoration of shoulder function after brachial plexus injury represents a significant challenge facing the peripheral nerve surgeons. This is owing to a combination of the complex biomechanics of the shoulder girdle, the multitude of muscles and nerves that could be potentially injured, and a limited number of donor options. In general, nerve transfer is favored over tendon transfer, because the biomechanics of the musculotendinous units are not altered. This article summarizes the surgical techniques and clinical results of nerve transfers for restoration of shoulder function. PMID:27094888

  2. 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.

  3. 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 promising strategy for peripheral nerve repair.

  4. A pilot study of sensory feedback by transcutaneous electrical nerve stimulation to improve manipulation deficit caused by severe sensory loss after stroke

    PubMed Central

    2013-01-01

    Background Sensory disturbance is common following stroke and can exacerbate functional deficits, even in patients with relatively good motor function. In particular, loss of appropriate sensory feedback in severe sensory loss impairs manipulation capability. We hypothesized that task-oriented training with sensory feedback assistance would improve manipulation capability even without sensory pathway recovery. Methods We developed a system that provides sensory feedback by transcutaneous electrical nerve stimulation (SENS) for patients with sensory loss, and investigated the feasibility of the system in a stroke patient with severe sensory impairment and mild motor deficit. The electrical current was modulated by the force exerted by the fingertips so as to allow the patient to identify the intensity. The patient had severe sensory loss due to a right thalamic hemorrhage suffered 27 months prior to participation in the study. The patient first practiced a cylindrical grasp task with SENS for 1 hour daily over 29 days. Pressure information from the affected thumb was fed back to the unaffected shoulder. The same patient practiced a tip pinch task with SENS for 1 hour daily over 4 days. Pressure information from the affected thumb and index finger was fed back to the unaffected and affected shoulders, respectively. We assessed the feasibility of SENS and examined the improvement of manipulation capability after training with SENS. Results The fluctuation in fingertip force during the cylindrical grasp task gradually decreased as the training progressed. The patient was able to maintain a stable grip force after training, even without SENS. Pressure exerted by the tip pinch of the affected hand was unstable before intervention with SENS compared with that of the unaffected hand. However, they were similar to each other immediately after SENS was initiated, suggesting that the somatosensory information improved tip pinch performance. The patient’s manipulation capability assessed by the Box and Block Test score improved through SENS intervention and was partly maintained after SENS was removed, until at least 7 months after the intervention. The sensory test score, however, showed no recovery after intervention. Conclusions We conclude that the proposed system would be useful in the rehabilitation of patients with sensory loss. PMID:23764012

  5. Capsaicin Combined with Local Anesthetics Preferentially Prolongs Sensory/Nociceptive Block in Rat Sciatic Nerve

    PubMed Central

    Binshtok, Alexander M.; Wang, Chi-Fei; Hevelone, Nathanael D.; Bean, Bruce P.; Woolf, Clifford J.; Wang, Ging Kuo

    2009-01-01

    Background Transient receptor potential vanilloid 1 channels integrate nociceptive stimuli and are predominantly expressed by unmyelinated C-fiber nociceptors, but not low-threshold mechanoreceptive sensory or motor fibers. A recent report showed that the transient receptor potential vanilloid 1 channel agonist capsaicin allows a hydrophilic quaternary ammonium derivative of lidocaine, QX-314, to selectively block C fibers without motor block. The authors tested whether a similar differential block would be produced using amphipathicN-methyl amitriptyline, amitriptyline, bupivacaine, or lidocaine, either alone or together with 0.05% capsaicin, in a rat sciatic nerve block model. Methods Rats (n = 8/group) were anesthetized with sevoflurane, and 0.2 ml of drug was injected either alone or with capsaicin (simultaneously or 10 min later) next to the sciatic nerve in the sciatic notch. Motor function was assessed by the extensor postural thrust. Nociception was evaluated by the nocifensive withdrawal reflex and vocalization evoked by pinch of a skin fold over the lateral metatarsus (cutaneous pain) with a serrated forceps. Results N-Methyl amitriptyline, amitriptyline, bupivacaine, or lidocaine, followed by injection of capsaicin 10 min later, each elicited a predominantly nociceptive-specific blockade. In comparison, simultaneous application of each local anesthetic with capsaicin did not elicit a clinically significant differential block, with the exception of N-methyl amitriptyline. Conclusions Both tertiary amine local anesthetics and their quaternary ammonium derivatives can elicit a predominantly sensory/nociceptor selective block when followed by injection of capsaicin. The combined application of transient receptor potential vanilloid 1 channel agonists and various local anesthetics or their quaternary ammonium derivatives is an appealing strategy to achieve a long-lasting differential block in regional analgesia. PMID:18946300

  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. 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. PMID:23791606

  8. Autoradiographic location of sensory nerve endings in dentin of monkey teeth

    SciTech Connect

    Byers, M.R.; Dong, W.K.

    1983-04-01

    We have used the autoradiographic method to locate trigeminal nerve endings in monkey teeth. The nerve endings were labeled in two adult female Macaca fascicularis by 20 hours of axonal transport of radioactive protein (/sup 3/H-L-proline). We found a few labeled axons in contralateral mandibular central incisors and one mandibular canine. In ipsilateral teeth, numerous myelinated and unmyelinated axons were labeled; they formed a few terminal branches in the roots but primarily branched in the crown to form the peripheral plexus of Raschkow and to terminate as free endings in the odontoblast layer, predentin, and as far as 120 micrometers into dentinal tubules. Electron microscopic autoradiography showed that the radioactive axonally transported protein was confined to sensory axons and endings; odontoblasts and dentin matrix were not significantly labeled. Labeled free nerve endings were closely apposed to odontoblasts in dentin but did not form distinctive junctions with them. Nerve endings were most numerous in the regular tubular dentin of the crown adjacent to the tip of the pulp horn, occurring in at least half of the dentinal tubules there. Our results show tha dentinal sensory nerve endings in primate teeth can be profuse, sparse, or absent depending on the location and structure of dentin and its adjacent pulp. When dentin was innervated, the tubules were straight and contained odontoblast processes, the predentin was wide, the odontoblast cell bodies were relatively columnar, and there was an adjacent cell-free zone and pulpal nerve plexus.

  9. Anatomical coupling of sensory and motor nerve trajectory via axon tracking.

    PubMed

    Wang, Liang; Klein, Rüdiger; Zheng, Binhai; Marquardt, Till

    2011-07-28

    It is a long-standing question how developing motor and sensory neuron projections cooperatively form a common principal grid of peripheral nerve pathways relaying behavioral outputs and somatosensory inputs. Here, we explored this issue through targeted cell lineage and gene manipulation in mouse, combined with in vitro live axon imaging. In the absence of motor projections, dorsal (epaxial) and ventral (hypaxial) sensory projections form in a randomized manner, while removal of EphA3/4 receptor tyrosine kinases expressed by epaxial motor axons triggers selective failure to form epaxial sensory projections. EphA3/4 act non-cell-autonomously by inducing sensory axons to track along preformed epaxial motor projections. This involves cognate ephrin-A proteins on sensory axons but is independent from EphA3/4 signaling in motor axons proper. Assembly of peripheral nerve pathways thus involves motor axon subtype-specific signals that couple sensory projections to discrete motor pathways. PMID:21791286

  10. Reappraisal of Supraorbital Sensory Nerve Conduction Recordings: Orthodromic and Antidromic Techniques

    PubMed Central

    Park, Hyeun Jun; Kim, Sung-Hoon; Lee, Se Kwang; Lee, Hang Jae

    2016-01-01

    Objective To establish a supraorbital nerve sensory conduction recording method and assess its usefulness. Methods Thirty-one healthy subjects without a history of trauma or neurological disease were recruited. For the orthodromic procedure, the recording electrode was attached immediately superior to the supraorbital notch. The stimulation electrode was placed on points along the hairline which evoked the largest sensory nerve action potentials (SNAPs). The antidromic sensory response was recorded after switching the recording and stimulating electrodes. The measured parameters were onset latency, peak latency, and baseline to peak amplitude of the SNAPs. The electrophysiological parameters of the bilateral supraorbital nerves were compared. We also recruited two patients who had sensory deficits on one side of their foreheads because of laceration injuries. Results The parameters of orthodromically recorded SNAPs were as follows: onset latency 1.21±0.22 ms (range, 0.9–1.6 ms), peak latency 1.54±0.23 ms (range, 1.2–2.2 ms), and baseline to peak amplitude 4.16±1.92 µV (range, 1.4–10 µV). Those of antidromically recorded SNAPs were onset latency 1.31±0.27 ms (range, 0.8–1.7 ms), peak latency 1.62±0.29 ms (range, 1.3–2.2 ms), and baseline to peak amplitude 4.00±1.89 µV (range, 1.5–9.0 µV). There was no statistical difference in onset latency, peak latency, or baseline to peak amplitude between the responses obtained using the orthodromic and antidromic methods, and the parameters also revealed no statistical difference between the supraorbital nerves on both sides. Conclusion We have successfully recorded supraorbital SNAPs. This conduction technique could be quite useful in evaluating patients with supraorbital nerve lesions. PMID:26949668

  11. 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.

  12. Influence of immobilization and sensory re-education on the sensory recovery after reconstruction of digital nerves with direct suture or muscle-in-vein conduits.

    PubMed

    Manoli, Theodora; Schiefer, Jennifer Lynn; Schulz, Lukas; Fuchsberger, Thomas; Schaller, Hans-Eberhard

    2016-02-01

    The influence of duration of immobilization and postoperative sensory re-education on the final outcome after reconstruction of digital nerves with direct suture or muscle-in-vein conduits was investigated. The final sensory outcome of 35 patients with 41 digital nerve injuries, who either underwent a direct suture (DS) or a nerve reconstruction with muscle-in-vein conduits (MVC), was assessed the earliest 12 months postoperatively using static and moving two-point discrimination as well as Semmes-Weinstein monofilaments. There was no significant difference in sensory recovery in cases with an immobilization of 3-7 days versus 10 days in the DS or MVC group. Moreover, no statistically significant difference in sensory recovery was found in cases receiving postoperative sensory re-education versus those not receiving in the DS or MVC group. An early mobilization does not seem to have a negative impact on the final outcome after digital nerve reconstruction. The effect of sensory re-education after digital nerve reconstruction should be reconsidered. PMID:27073390

  13. Influence of immobilization and sensory re-education on the sensory recovery after reconstruction of digital nerves with direct suture or muscle-in-vein conduits

    PubMed Central

    Manoli, Theodora; Schiefer, Jennifer Lynn; Schulz, Lukas; Fuchsberger, Thomas; Schaller, Hans-Eberhard

    2016-01-01

    The influence of duration of immobilization and postoperative sensory re-education on the final outcome after reconstruction of digital nerves with direct suture or muscle-in-vein conduits was investigated. The final sensory outcome of 35 patients with 41 digital nerve injuries, who either underwent a direct suture (DS) or a nerve reconstruction with muscle-in-vein conduits (MVC), was assessed the earliest 12 months postoperatively using static and moving two-point discrimination as well as Semmes-Weinstein monofilaments. There was no significant difference in sensory recovery in cases with an immobilization of 3–7 days versus 10 days in the DS or MVC group. Moreover, no statistically significant difference in sensory recovery was found in cases receiving postoperative sensory re-education versus those not receiving in the DS or MVC group. An early mobilization does not seem to have a negative impact on the final outcome after digital nerve reconstruction. The effect of sensory re-education after digital nerve reconstruction should be reconsidered. PMID:27073390

  14. 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

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

    PubMed Central

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

    2014-01-01

    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. PMID:25221597

  16. Osseoperception: sensory function and proprioception.

    PubMed

    Klineberg, I; Murray, G

    1999-06-01

    Tooth loss and its replacement have significant functional and psychosocial consequences. The removal of intra-dental and periodontal mechanoreception accompanying tooth loss changes the fine proprioceptive control of jaw function and influences the precision of magnitude, direction, and rate of occlusal load application. With the loss of all teeth, complete denture restoration is a compromise replacement which only partially restores function. Implant-supported prostheses restore jaw function more appropriately, with improved psychophysiological discriminatory ability and oral stereognosis. Osseoperception is defined as depending on central influences from corollary discharge from cortico-motor commands to jaw muscles, and contributions from peripheral mechanoreceptors in orofacial and temporomandibular tissues. The processing of central influences is considered with the recognition of the plasticity of neuromotor mechanisms that occurs to accommodate the loss of dental and periodontal inputs. PMID:11276734

  17. Structural and functional assessment of skin nerve fibres in small-fibre pathology.

    PubMed

    Karlsson, P; Nyengaard, J R; Polydefkis, M; Jensen, T S

    2015-09-01

    Damage to nociceptor nerve fibres may give rise to peripheral neuropathies, some of which are pain free and some are painful. A hallmark of many peripheral neuropathies is the loss of small nerve fibres in the epidermis, a condition called small-fibre neuropathy (SFN) when it is predominantly the small nerve fibres that are damaged. Historically, SFN has been very difficult to diagnose as clinical examination and nerve conduction studies mainly detect large nerve fibres, and quantitative sensory testing is not sensitive enough to detect small changes in small nerve fibres. However, taking a 3-mm punch skin biopsy from the distal leg and quantification of the nerve fibre density has proven to be a useful method to diagnose SFN. However, the correlation between the nerve fibre loss and other test results varies greatly. Recent studies have shown that it is possible not only to extract information about the nerve fibre density from the biopsies but also to get an estimation of the nerve fibre length density using stereology, quantify sweat gland innervation and detect morphological changes such as axonal swelling, all of which may be additional parameters indicating diseased small fibres relating to symptoms reported by the patients. In this review, we focus on available tests to assess structure and function of the small nerve fibres, and summarize recent advances that have provided new possibilities to more specifically relate structural findings with symptoms and function in patients with SFN. PMID:25546653

  18. Localization of NADPH Oxidase in Sympathetic and Sensory Ganglion Neurons and Perivascular Nerve Fibers

    PubMed Central

    Cao, Xian; Demel, Stacie L.; Quinn, Mark T.; Galligan, James J.; Kreulen, David L.

    2009-01-01

    Superoxide anion (O2−•) production was previously reported to be increased in celiac ganglia (CG) during DOCA-salt hypertension, possibly via activation of the reduced nicotinamide-adenine dinucleotide phosphate (NADPH) oxidase. This suggested a role for neuronal NADPH oxidase in autonomic neurovascular control. However, the expression and localization of NADPH oxidase in the peripheral neurons is not fully known. The purpose of this study was to examine the subcellular localization of NADPH oxidase in sympathetic and sensory ganglion neurons and perivascular nerve fibers. In rat CG, p22phox and neuropeptide Y (NPY) were colocalized in all neurons. P22phox was also localized to dorsal root ganglia (DRG) neurons that contain calcitonin gene related peptide (CGRP). In mesenteric arteries, p22phox and p47phox were colocalized with NPY or CGRP in perivascular nerve terminals. A similar pattern of nerve terminal staining of p22phox and p47phox was also found in cultured CG neurons and nerve growth factor (NGF)-differentiated PC12 cells. These data demonstrate a previously uncharacterized localization of NADPH oxidase in perivascular nerve fibers. The presence of a O2−• – generating enzyme in close vicinity to the sites of neurotransmitter handling in the nerve fibers suggests the possibility of novel redox-mediated mechanisms in peripheral neurovascular control. PMID:19716351

  19. A model of the electrical behaviour of myelinated sensory nerve fibres based on human data.

    PubMed

    Wesselink, W A; Holsheimer, J; Boom, H B

    1999-03-01

    Calculation of the response of human myelinated sensory nerve fibres to spinal cord stimulation initiated the development of a fibre model based on electrophysiological and morphometric data for human sensory nerve fibres. The model encompasses a mathematical description of the kinetics of the nodal membrane, and a non-linear fibre geometry. Fine tuning of only a few, not well-established parameters was performed by fitting the shape of a propagating action potential and its diameter-dependent propagation velocity. The quantitative behaviour of this model corresponds better to experimentally determined human fibre properties than other mammalian, nonhuman models do. Typical characteristics, such as the shape of the action potential, the propagation velocity and the strength-duration behaviour show a good fit with experimental data. The introduced diameter-dependent parameters did not result in a noticeable diameter dependency of action potential duration and refractory period. The presented model provides an improved tool to analyse the electrical behaviour of human myelinated sensory nerve fibres. PMID:10396827

  20. Comparison of skin sensory thresholds using pre-programmed or single-frequency transcutaneous electrical nerve stimulation

    PubMed Central

    Kang, Jong Ho

    2015-01-01

    [Purpose] The purpose of the present study was to compare the sensory thresholds of healthy subjects using pre-programmed or single-frequency transcutaneous electrical nerve stimulation. [Subjects] Ninety healthy adult subjects were randomly assigned to pre-programmed or single-frequency stimulation groups, each consisting of 45 participants. [Methods] Sensory thresholds were measured in the participants’ forearms using von Frey filaments before and after pre-programmed or single-frequency transcutaneous electrical nerve stimulation, and the result in values were analyzed. [Results] Significant increases in sensory threshold after stimulation were observed in both groups. However, there were no significant differences between the two groups in sensory thresholds after stimulation or in the magnitude of threshold increases following stimulation. [Conclusion] Our results show that there are no differences between sensory threshold increases induced by pre-programmed and single-frequency transcutaneous electrical nerve stimulation. PMID:26834358

  1. Spontaneous pain in partial nerve injury models of neuropathy and the role of nociceptive sensory cover.

    PubMed

    Koplovitch, Pini; Minert, Anne; Devor, Marshall

    2012-07-01

    Spontaneous pain is difficult to measure in animals. One proposed biomarker of spontaneous pain is autotomy, a behavior frequently observed in rats with complete hindpaw denervation (the neuroma model of neuropathic pain). A large body of evidence suggests that this behavior reflects spontaneous dysesthesic sensations akin to phantom limb pain or anesthesia dolorosa. After partial paw denervation, such as in the spared nerve injury (SNI) model of neuropathic pain, autotomy is rare. Does this mean that spontaneous pain is absent? We denervated hindpaws in two stages: SNI surgery completed 7 or 28 days later by transection of the saphenous and sural nerves (SaSu). Minimal autotomy was evoked by the first stage. But it started rapidly after SaSu surgery rendered the limb numb, much more rapidly than after denervation in a single stage (neuroma model). The acceleration was proportional to the delay between the two surgeries. This "priming" effect of the first surgery indicates that the neural substrate of autotomy, spontaneous neuropathic pain, was not initiated by the onset of numbness, but rather by the first, SNI surgery. But the animal's pain experience was occult. The saphenous and sural nerves provided nociceptive sensory cover for the paw, preventing the behavioral expression of the spontaneous pain in the form of autotomy. The results support prior observations suggesting that partial nerve injury triggers spontaneous pain as well as allodynia, and illustrate the importance of nociceptive sensory cover in the prevention of self-inflicted limb injury. PMID:22548979

  2. Functional evaluation of peripheral nerve regeneration and target reinnervation in animal models: a critical overview.

    PubMed

    Navarro, Xavier

    2016-02-01

    Peripheral nerve injuries usually lead to severe loss of motor, sensory and autonomic functions in the patients. Due to the complex requirements for adequate axonal regeneration, functional recovery is often poorly achieved. Experimental models are useful to investigate the mechanisms related to axonal regeneration and tissue reinnervation, and to test new therapeutic strategies to improve functional recovery. Therefore, objective and reliable evaluation methods should be applied for the assessment of regeneration and function restitution after nerve injury in animal models. This review gives an overview of the most useful methods to assess nerve regeneration, target reinnervation and recovery of complex sensory and motor functions, their values and limitations. The selection of methods has to be adequate to the main objective of the research study, either enhancement of axonal regeneration, improving regeneration and reinnervation of target organs by different types of nerve fibres, or increasing recovery of complex sensory and motor functions. It is generally recommended to use more than one functional method for each purpose, and also to perform morphological studies of the injured nerve and the reinnervated targets. PMID:26228942

  3. Cortical brain mapping of peripheral nerves using functional magnetic resonance imaging in a rodent model.

    PubMed

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

    2008-11-01

    The regions of the body have cortical and subcortical representation in proportion to their degree of innervation. The rat forepaw has been studied extensively in recent years using functional magnetic resonance imaging (fMRI), typically by stimulation using electrodes directly inserted into the skin of the forepaw. Here we stimulate the nerve directly using surgically implanted electrodes. A major distinction is that stimulation of the skin of the forepaw is mostly sensory, whereas direct nerve stimulation reveals not only the sensory system but also deep brain structures associated with motor activity. In this article, we seek to define both the motor and sensory cortical and subcortical representations associated with the four major nerves of the rodent upper extremity. We electrically stimulated each nerve (median, ulnar, radial, and musculocutaneous) during fMRI acquisition using a 9.4-T Bruker scanner (Bruker BioSpin, Billerica, MA). A current level of 0.5 to 1.0 mA and a frequency of 5 Hz were used while keeping the duration constant. A distinct pattern of cortical activation was found for each nerve that can be correlated with known sensorimotor afferent and efferent pathways to the rat forepaw. This direct nerve stimulation rat model can provide insight into peripheral nerve injury. PMID:18924070

  4. Sigma-1 receptor expression in sensory neurons and the effect of painful peripheral nerve injury

    PubMed Central

    2013-01-01

    Background The sigma-1 receptor (σ1R), an endoplasmic reticulum chaperone protein, is widely distributed and regulates numerous intracellular processes in neurons. Nerve injury alters the structure and function of axotomized dorsal root ganglion (DRG) neurons, contributing to the development of pain. The σ1R is enriched in the spinal cord and modulates pain after peripheral nerve injury. However, σ1R expression in the DRG has not been studied. We therefore characterized σ1R expression in DRGs at baseline and following spinal nerve ligation (SNL) in rats. Results Immunohistochemical (IHC) studies in DRG sections show σ1R in both neuronal somata and satellite glial cells. The punctate distribution of σ1R in the neuronal cytoplasm suggests expression in the endoplasmic reticulum. When classified by neuronal size, large neurons (>1300 μm) showed higher levels of σ1R staining than other groups (700-1300 μm, <700 μm). Comparing σ1R expression in neuronal groups characterized by expression of calcitonin gene-related peptide (CGRP), isolectin-B4 (IB4) and neurofilament-200 (NF-200), we found σ1R expression in all three neuronal subpopulations, with highest levels of σ1R expression in the NF-200 group. After SNL, lysates from L5 DRGs that contains axotomized neurons showed decreased σ1R protein but unaffected transcript level, compared with Control DRGs. IHC images also showed decreased σ1R protein expression, in SNL L5 DRGs, and to a lesser extent in the neighboring SNL L4 DRGs. Neurons labeled by CGRP and NF-200 showed decreased σ1R expression in L5 and, to a lesser extent, L4 DRGs. In IB4-labeled neurons, σ1R expression decreased only in axotomized L5 DRGs. Satellite cells also showed decreased σ1R expression in L5 DRGs after SNL. Conclusions Our data show that σ1R is present in both sensory neurons and satellite cells in rat DRGs. Expression of σ1R is down-regulated in axotomized neurons as well as in their accompanying satellite glial cells, while neighboring uninjured neurons show a lesser down-regulation. Therefore, elevated σ1R expression in neuropathic pain is not an explanation for pain relief after σ1R blockade. This implies that increased levels of endogenous σ1R agonists may play a role, and diminished neuroprotection from loss of glial σ1R may be a contributing factor. PMID:24015960

  5. 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.

  6. 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 nerve sprouting and formation of neuroma-like structures after inflammation/injury. Understanding the factors that drive this neuroplasticity, whether this pathologic reorganization of nerve fibers contributes to chronic joint pain, and how the phenotype of sensory and sympathetic nerves changes with age may provide pharmacologic insight and targets for better controlling aging-related joint pain. PMID:22548760

  7. Effect of Collateral Sprouting on Donor Nerve Function After Nerve Coaptation: A Study of the Brachial Plexus

    PubMed Central

    Reichert, Paweł; Kiełbowicz, Zdzisław; Dzięgiel, Piotr; Puła, Bartosz; Wrzosek, Marcin; Bocheńska, Aneta; Gosk, Jerzy

    2016-01-01

    Background The aim of the present study was to evaluate the donor nerve from the C7 spinal nerve of the rabbit brachial plexus after a coaptation procedure. Assessment was performed of avulsion of the C5 and C6 spinal nerves treated by coaptation of these nerves to the C7 spinal nerve. Material/Methods After nerve injury, fourteen rabbits were treated by end-to-side coaptation (ETS), and fourteen animals were treated by side-to-side coaptation (STS) on the right brachial plexus. Electrophysiological and histomorphometric analyses and the skin pinch test were used to evaluate the outcomes. Results There was no statistically significant difference in the G-ratio proximal and distal to the coaptation in the ETS group, but the differences in the axon, myelin sheath and fiber diameters were statistically significant. The comparison of the ETS and STS groups distal to the coaptation with the controls demonstrated statistically significant differences in the fiber, axon, and myelin sheath diameters. With respect to the G-ratio, the ETS group exhibited no significant differences relative to the control, whereas the G-ratio in the STS group and the controls differed significantly. In the electrophysiological study, the ETS and STS groups exhibited major changes in the biceps and subscapularis muscles. Conclusions The coaptation procedure affects the histological structure of the nerve donor, but it does not translate into changes in nerve conduction or the sensory function of the limb. The donor nerve lesion in the ETS group is transient and has minimal clinical relevance. PMID:26848925

  8. Effect of Collateral Sprouting on Donor Nerve Function After Nerve Coaptation: A Study of the Brachial Plexus.

    PubMed

    Reichert, Pawel; Kiełbowicz, Zdzisław; Dzięgiel, Piotr; Puła, Bartosz; Wrzosek, Marcin; Bocheńska, Aneta; Gosk, Jerzy

    2016-01-01

    BACKGROUND The aim of the present study was to evaluate the donor nerve from the C7 spinal nerve of the rabbit brachial plexus after a coaptation procedure. Assessment was performed of avulsion of the C5 and C6 spinal nerves treated by coaptation of these nerves to the C7 spinal nerve. MATERIAL AND METHODS After nerve injury, fourteen rabbits were treated by end-to-side coaptation (ETS), and fourteen animals were treated by side-to-side coaptation (STS) on the right brachial plexus. Electrophysiological and histomorphometric analyses and the skin pinch test were used to evaluate the outcomes. RESULTS There was no statistically significant difference in the G-ratio proximal and distal to the coaptation in the ETS group, but the differences in the axon, myelin sheath and fiber diameters were statistically significant. The comparison of the ETS and STS groups distal to the coaptation with the controls demonstrated statistically significant differences in the fiber, axon, and myelin sheath diameters. With respect to the G-ratio, the ETS group exhibited no significant differences relative to the control, whereas the G-ratio in the STS group and the controls differed significantly. In the electrophysiological study, the ETS and STS groups exhibited major changes in the biceps and subscapularis muscles. CONCLUSIONS The coaptation procedure affects the histological structure of the nerve donor, but it does not translate into changes in nerve conduction or the sensory function of the limb. The donor nerve lesion in the ETS group is transient and has minimal clinical relevance. PMID:26848925

  9. Sensory Sensitivities and Performance on Sensory Perceptual Tasks in High-Functioning Individuals with Autism

    ERIC Educational Resources Information Center

    Minshew, Nancy J.; Hobson, Jessica A.

    2008-01-01

    Most reports of sensory symptoms in autism are second hand or observational, and there is little evidence of a neurological basis. Sixty individuals with high-functioning autism and 61 matched typical participants were administered a sensory questionnaire and neuropsychological tests of elementary and higher cortical sensory perception. Thirty-two…

  10. Evaluation of the function status of the ulnar nerve in carpal tunnel syndrome.

    PubMed

    Zhang, J; Liu, N; Wang, Y W; Zhang, Z C; Zheng, L N; Zhu, J

    2015-01-01

    Many carpal tunnel syndrome (CTS) patients have symptoms in both the median and ulnar digits more frequently than in the median digits alone. This is possibly because of close anatomical contiguity of the carpal tunnel and Guyon's canal, and the high pressure may also affect the latter, causing indirect compression of ulnar nerve fibers. Thus, we evaluated the functional status of the ulnar nerve in patients with CTS in order to investigate the relationship between ulnar nerve impairment and sensory symptoms of the ulnar territory. Electrophysiological studies were conducted in CTS patients and healthy controls. CTS patients were divided into the mild/moderate group and severe group; they were further divided into the symptomatic and asymptomatic subgroups according to the sensory symptom of the fifth digit region. The findings suggest that CTS patients could have coexisting ulnar nerve wrist entrapments that might exacerbate the severity of CTS. Sensory impairment in the ulnar territory was observed more frequently in the mild/moderate stage of CTS, which is associated with ulnar nerve involvement. These findings also suggest that damage to the ulnar nerve fibers caused by compression forces in Guyon's canal may underlie the ulnar spread of symptoms in CTS. PMID:25966136

  11. 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

  12. Peripheral Nerve Regeneration and NGF-Dependent Neurite Outgrowth of Adult Sensory Neurons Converge on STAT3 Phosphorylation Downstream of Neuropoietic Cytokine Receptor gp130

    PubMed Central

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

    2014-01-01

    After nerve injury, adult sensory neurons can regenerate peripheral axons and reconnect with their target tissue. Initiation of outgrowth, as well as elongation of neurites over long distances, depends on the signaling of receptors for neurotrophic growth factors. Here, we investigated the importance of gp130, the signaling subunit of neuropoietic cytokine receptors in peripheral nerve regeneration. After sciatic nerve crush, functional recovery in vivo was retarded in SNS-gp130−/− mice, which specifically lack gp130 in sensory neurons. Correspondingly, a significantly reduced number of free nerve endings was detected in glabrous skin from SNS-gp130−/− compared with control mice after nerve crush. Neurite outgrowth and STAT3 activation in vitro were severely reduced in cultures in gp130-deficient cultured neurons. Surprisingly, in neurons obtained from SNS-gp130−/− mice the increase in neurite length was reduced not only in response to neuropoietic cytokine ligands of gp130 but also to nerve growth factor (NGF), which does not bind to gp130-containing receptors. Neurite outgrowth in the absence of neurotrophic factors was partially rescued in gp130-deficient neurons by leptin, which activates STAT3 downstream of leptic receptor and independent of gp130. The neurite outgrowth response of gp130-deficient neurons to NGF was fully restored in the presence of leptin. Based on these findings, gp130 signaling via STAT3 activation is suggested not only to be an important regulator of peripheral nerve regeneration in vitro and in vivo, but as determining factor for the growth promoting action of NGF in adult sensory neurons. PMID:25253866

  13. 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 Central

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

    2014-01-01

    The current use of hearing aids and artificial cochleas for deaf-mute individuals depends on their auditory nerve. Skin-hearing technology, a patented system developed by our group, uses a cutaneous sensory nerve to substitute for the auditory nerve to help deaf-mutes to hear sound. This paper introduces a new solution, multi-channel-array skin-hearing technology, to solve the problem of speech discrimination. Based on the filtering principle of hair cells, external voice signals at different frequencies are converted to current signals at corresponding frequencies using electronic multi-channel bandpass filtering technology. Different positions on the skin can be stimulated by the electrode array, allowing the perception and discrimination of external speech signals to be determined by the skin response to the current signals. Through voice frequency analysis, the frequency range of the band-pass filter can also be determined. These findings demonstrate that the sensory nerves in the skin can help to transfer the voice signal and to distinguish the speech signal, suggesting that the skin sensory nerves are good candidates for the replacement of the auditory nerve in addressing deaf-mutes’ hearing problems. Scientific hearing experiments can be more safely performed on the skin. Compared with the artificial cochlea, multi-channel-array skin-hearing aids have lower operation risk in use, are cheaper and are more easily popularized. PMID:25317171

  14. Mustard oils and cannabinoids excite sensory nerve fibres through the TRP channel ANKTM1.

    PubMed

    Jordt, Sven-Eric; Bautista, Diana M; Chuang, Huai-Hu; McKemy, David D; Zygmunt, Peter M; Högestätt, Edward D; Meng, Ian D; Julius, David

    2004-01-15

    Wasabi, horseradish and mustard owe their pungency to isothiocyanate compounds. Topical application of mustard oil (allyl isothiocyanate) to the skin activates underlying sensory nerve endings, thereby producing pain, inflammation and robust hypersensitivity to thermal and mechanical stimuli. Despite their widespread use in both the kitchen and the laboratory, the molecular mechanism through which isothiocyanates mediate their effects remains unknown. Here we show that mustard oil depolarizes a subpopulation of primary sensory neurons that are also activated by capsaicin, the pungent ingredient in chilli peppers, and by Delta(9)-tetrahydrocannabinol (THC), the psychoactive component of marijuana. Both allyl isothiocyanate and THC mediate their excitatory effects by activating ANKTM1, a member of the TRP ion channel family recently implicated in the detection of noxious cold. These findings identify a cellular and molecular target for the pungent action of mustard oils and support an emerging role for TRP channels as ionotropic cannabinoid receptors. PMID:14712238

  15. [The sensory neuropile of the nerve chain of Eurygaster integriceps P].

    PubMed

    Tysniachniuk, M S

    1986-02-01

    Structure of the sensory neuropil of the abdominal nervous chain has been studied in the Eurygaster integriceps P. by means of methylene blue and paraldehyde fuchsin with phloxin staining. The sensory neuropil consists of three parts: 1) main sensory neuropil, including terminal, T-shaped, antero- and posterconnective fibers; 2) lateral sensory neuropils of the extremities, that in the insect studied, as in the dragon-fly larva, have the form of the overturned eight; 3) system of thick T-shaped fibers getting into the first thoracic ganglion and running along the second nerves, as well as along the thoracic neuromeres of the synganglion, giving collateralies into the nuclei of the extremities and into the main neuropil and coming into both the abdominal and cranial parts. In the neuropil of the extremities certain fibers are revealed; they form collateralies in the nucleus itself and terminate in the main neuropil. Of all the insects investigated it is the Eurygaster integriceps P. that possesses the most developed sensitive nuclei in the extremities and the least developed nuclei in the wings. PMID:2423058

  16. The endogenous cannabinoid agonist, anandamide stimulates sensory nerves in guinea-pig airways

    PubMed Central

    Tucker, R C; Kagaya, M; Page, C P; Spina, D

    2001-01-01

    The endogenous cannabinoid agonist, anandamide produced a modest contractile response in guinea-pig isolated bronchus compared with the vanilloid receptor agonist capsaicin. The contractile response to both anandamide and capsaicin was inhibited by the vanilloid receptor antagonist, capsazepine. Furthermore, the NK2-selective antagonist, SR48968 but not the NK1-selective antagonist, SR140333 inhibited contractile responses to anandamide. The contractile response to anandamide was abolished in tissues desensitized by capsaicin. However, anandamide failed to cross-desensitize the contractile response to capsaicin. The contractile response to anandamide was not significantly altered in the presence of the CB1 receptor antagonist, SR141716A, nor the amidase inhibitor, phenylmethylsulphonyl fluoride (PMSF) but was significantly increased in the presence of the neutral endopeptidase inhibitor, thiorphan. The cannabinoid agonist, CP55,940 failed to significantly attenuate the excitatory non-adrenergic non-cholinergic (eNANC) response in guinea-pig airways. In contrast, the ORL1 receptor agonist, nociceptin, significantly inhibited this response. The results demonstrate that anandamide induces a modest contractile response in guinea-pig isolated bronchus that is dependent upon the activation of vanilloid receptors on airway sensory nerves. However, cannabinoid receptors do not appear to play a role in this regard, nor in regulating the release of neuropeptides from airway sensory nerves under physiological conditions. PMID:11226144

  17. 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.

  18. [Morphological and functional studies on nerve regeneration after corneal nerve injuries].

    PubMed

    Zhang, Z Q; Xie, L X; Dong, X G

    1994-07-01

    Using gold chloride impregnation of nerves and horse-radish peroxidase (HRP) axoplasma retrograde tracing technique, we monitored nerve regeneration over a period of 6 months following penetrating perilimbal incisions and penetrating keratoplasties (PKP) in rabbits. Post-operatively, at 1 month after a 180 degrees perilimbal incision, loose unconnected subepithelial plexus were present in the limbus, at 2 months 1-2 bundles of deep stromal nerve were seen in the stroma and by 6 months only a few stromal nerves regenerated. There was no difference in nerve regeneration between post-operative autograft and allograft PKP. By 6 months, the quantity of HRP-labelled cells in the trigeminal ganglia was less than the normal level. The results indicated that nerve regeneration by 6 months after corneal nerve injuries was inadequate to restore a normal corneal nerve extent and function. PMID:7843026

  19. Angiotensinergic innervation of the kidney: Localization and relationship with catecholaminergic postganglionic and sensory nerve fibers.

    PubMed

    Bohlender, Jürgen; Pfarrer, Beat; Patil, Jaspal; Nussberger, Jürg; Thalmann, Georg N; Imboden, Hans

    2012-11-01

    We describe an angiotensin (Ang) II-containing innervation of the kidney. Cryosections of rat, pig and human kidneys were investigated for the presence of Ang II-containing nerve fibers using a mouse monoclonal antibody against Ang II (4B3). Co-staining was performed with antibodies against synaptophysin, tyrosine 3-hydroxylase, and dopamine beta-hydroxylase to detect catecholaminergic efferent fibers and against calcitonin gene-related peptide to detect sensory fibers. Tagged secondary antibodies and confocal light or laser scanning microscopy were used for immunofluorescence detection. Ang II-containing nerve fibers were densely present in the renal pelvis, the subepithelial layer of the urothelium, the arterial nervous plexus, and the peritubular interstitium of the cortex and outer medulla. They were infrequent in central veins and the renal capsule and absent within glomeruli and the renal papilla. Ang II-positive fibers represented phenotypic subgroups of catecholaminergic postganglionic or sensory fibers with different morphology and intrarenal distribution compared to their Ang II-negative counterparts. The Ang II-positive postganglionic fibers were thicker, produced typically fusiform varicosities and preferentially innervated the outer medulla and periglomerular arterioles. Ang II-negative sensory fibers were highly varicose, prevailing in the pelvis and scarce in the renal periphery compared to the rarely varicose Ang II-positive fibers. Neurons within renal microganglia displayed angiotensinergic, catecholaminergic, or combined phenotypes. Our results suggest that autonomic fibers may be an independent source of intrarenal Ang II acting as a neuropeptide co-transmitter or neuromodulator. The angiotensinergic renal innervation may play a distinct role in the neuronal control of renal sodium reabsorption, vasomotion and renin secretion. PMID:23018241

  20. Changes in nerve function and nerve fibre structure induced by acute, graded compression.

    PubMed Central

    Rydevik, B; Nordborg, C

    1980-01-01

    Rabbit tibial nerves were subjected to direct, acute graded compression by means of an inflatable compression chamber. The acute and long term effects of 50, 200 and 400 mmHg applied for two hours on nerve function and nerve fibre structure were investigated. A pressure of 50 mmHg applied for two hours induced only minimal or no acute deterioration of maximal conduction velocity and nerve fibre structure. Conduction velocity was gradually reduced during compression at 200-400 mmHg pressure for two hours and in those cases the recovery of nerve conduction after pressure release was incomplete. Ultrastructural analysis revealed pronounced, early nerve fibre damage in these nerves. Three weeks after compression, nerves compressed at 50 mmHg for two hours had normal afferent and motor conduction velocity, although there were morphological signs of slight nerve fibre damage. Nerves compressed at 200 mmHg for two hours exhibited reduction of conduction velocity only at the level of compression, in contrast to the nerves compressed at 400 mmHg for two hours in which conduction velocity was reduced both at the level of compression and distal to the compressed segment. Morphologically, the nerves compressed at 200-400 mmHg for two hours showed varying degrees of demyelination and axonal degeneration three weeks after compression. Images PMID:7217952

  1. [A case of hereditary motor and sensory neuropathy with pyramidal tract sign, optic nerve atrophy and mental retardation].

    PubMed

    Adachi, T; Imaoka, K; Shirasawa, A; Yamaguchi, S; Kobayashi, S

    1998-12-01

    The patient was a 61-year-old man who suffered from gait disturbance since childhood. He also had mental retardation. Gait disturbance was slowly progressive. His mother, sister, brother and son of his sister suffered from gait disturbance. On neurological examination, he showed mental retardation, optic nerve atrophy and neural deafness. He also showed severe muscle atrophy and weakness of bilateral lower limbs associated with pes cavus. Muscle tonus of lower limbs and patellar tendon reflex were increased bilaterally. Achilles tendon reflex was absent. Babinski and Chaddock signs were positive. Superficial and deep sensations were almost normal. There were no cerebellar signs. Blood chemistry was normal. On nerve conduction studies, motor nerve conduction velocity of the upper limbs was normal and that of the posterior tibial nerve was decreased; right 36.0m/sec, left 29.7m/sec. Sensory nerve conduction velocity of the median nerve was slightly decreased; right 36.5m/sec, left 45.2m/sec and sural nerve did not respond to electric stimuli. On sural nerve biopsy, the density of myelinated fibers was severely decreased. Onion bulb formation was not observed. We classified this case as hereditary motor and sensory neuropathy (HMSN) type II based on nerve conduction studies and findings from sural nerve biopsy. HMSN with pyramidal tract sign has been classified as type V and HMSN with optic nerve atrophy as type VI. This case had characteristic symptoms as type V and VI. Histopathological findings of HMSN type V and VI have not been established yet. This case might provide an important clue for classification of HMSN. PMID:10349345

  2. [A case of hereditary motor and sensory neuropathy (HMSN type 2) with bilateral recurrent nerve palsy].

    PubMed

    Kamei, H; Nishimaru, K; Abe, H; Irie, M; Ohnishi, A

    1993-09-01

    An atypical case of hereditary motor and sensory neuropathy (HMSN) type 2 with cerebellar ataxia, hand tremor and bilateral recurrent nerve palsy was described. The patient was a 57-year-old man who complained of dyspnea, stridor , hoarseness during exercise and snored heavily during sleep since he was 20 years old. These symptoms and signs were slowly progressive. He had difficulty in breathing even at resting state when he was 54 years old and since then, he noticed muscle wasting of his hands and feet. Neurological examinations on admission revealed pes cavus, scoliosis, distal muscular atrophy in his four extremities, especially severe in bilateral lower limbs. Deep tendon reflexes were diffusely depressed. The fiberscopic examination demonstrated the limitation of bilateral vocal cord abduction and his tongue was slightly atrophic. Fine postural tremor was found in bilateral hands. Mild limb and truncal ataxias were also noted. Blood pCO2 level was elevated to 66% although FEV1.0% and vital capacity were within normal limits. Peripheral nerve conduction velocities were almost normal, though distal terminal latencies were slightly prolonged and amplitudes of evoked potentials were markedly decreased. The sural nerve biopsy studies revealed the chronic axonal or neuronal degeneration of both large and small myelinated fibers. From the clinical, electrophysiologic and histopathologic findings, the diagnosis of HMSN type 2 with bilateral recurrent nerve palsy and other atypical neurological findings was made. It is practically important to evaluate the presence or absence of vocal cord paralysis in the patients with HMSN from clinical viewpoints. PMID:8299275

  3. 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.

  4. 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

  5. Capsaicin and carbon dioxide act by distinct mechanisms on sensory nerve terminals in the cat cornea.

    PubMed

    Chen, X; Belmonte, C; Rang, H P

    1997-03-01

    The discharge of single afferent units recorded from filaments of the mixed ciliary nerve of anaesthetised cats was used to study the effects of CO2, capsaicin and the capsaicin antagonist, capsazepine, on sensory nerve terminals in the cornea. Units were selected on the basis of their sensitivity to CO2 (98.5% applied to the cornea for 30 s in a moist gas stream). Of these units, about 50% (18/38) also responded to capsaicin (0.1 microM applied as droplet and washed off after 20 s), with a discharge of similar magnitude to that produced by CO2. The other CO2-sensitive units (20/38) did not respond to capsaicin. Capsaicin-sensitive units responded more rapidly to CO2 (mean latency to first spike 0.7 +/- 0.2 s) than capsaicin-insensitive units (mean latency to first spike 5.1 +/- 1.2 s). On the basis of their conduction velocity, both the capsaicin-sensitive and the capsaicin-insensitive groups included both A- and C-fibres. Application of capsazepine (10 microM for 5-20 min) to the cornea reversibly blocked the response of the units to capsaicin without affecting responses to CO2. Units that were acutely desensitised by exposure to capsaicin (0.1 microM) for 30 s, during which time the discharge evoked by capsaicin declined to zero, still responded to CO2, though the response was reduced by 44% compared with controls. It is concluded that activation of sensory afferents in the cat cornea by capsaicin and by CO2 appear to involve distinct mechanisms, since: (a) many CO2- sensitive units are not excited by capsaicin; (b) capsazepine selectively blocks excitation by capsaicin without affecting responses to CO2; and (c) desensitisation to capsaicin impairs only partially the responsiveness to CO2. PMID:9106806

  6. Painful Peripheral Nerve Injury Decreases Calcium Current in Axotomized Sensory Neurons

    PubMed Central

    McCallum, J. Bruce; Kwok, Wai-Meng; Sapunar, Damir; Fuchs, Andreas; Hogan, Quinn H.

    2013-01-01

    Background Reports of Ca2+ current (ICa) loss after injury to peripheral sensory neurons do not discriminate between axotomized and spared neurons. The spinal nerve ligation model separates axotomized from spared neurons innervating the same site. The authors hypothesized that ICa loss is a result of neuronal injury, so they compared axotomized L5 dorsal root ganglion neurons to spared L4 neurons, as well as neurons from rats undergoing skin incision alone. Methods After behavioral testing, dissociated neurons from L4 and L5 dorsal root ganglia were studied in both current and voltage patch clamp modes. The biophysical consequence of ICa loss on the action potential was confirmed using selective ICa antagonists. Data were grouped into small, medium, and large cells for comparison. Results Reduced ICa was predominantly a consequence of axotomy (L5 after spinal nerve ligation) and was most evident in small and medium neurons. ICa losses were associated with action potential prolongation in small and medium cells, whereas the amplitude and duration of after hyperpolarization was reduced in medium and large neurons. Blockade with Ca2+ channel antagonists showed that action potential prolongation and after hyperpolarization diminution were alike, attributable to the loss of ICa. Conclusion Axotomy is required for ICa loss. ICa loss correlated with changes in the biophysical properties of sensory neuron membranes during action potential generation, which were due to ICa loss leading to decreased outward Ca2+-sensitive K+ currents. Taken together, these results suggest that neuropathic pain may be mediated, in part, by loss of ICa and the cellular processes dependent on Ca2+. PMID:16810008

  7. Calcium regulation in individual peripheral sensory nerve terminals of the rat

    PubMed Central

    Gover, Tony D; Moreira, Thaís H V; Kao, Joseph P Y; Weinreich, Daniel

    2007-01-01

    Ca2+ is vital for release of neurotransmitters and trophic factors from peripheral sensory nerve terminals (PSNTs), yet Ca2+ regulation in PSNTs remains unexplored. To elucidate the Ca2+ regulatory mechanisms in PSNTs, we determined the effects of a panel of pharmacological agents on electrically evoked Ca2+ transients in rat corneal nerve terminals (CNTs) in vitro that had been loaded with the fluorescent Ca2+ indicator, Oregon Green 488 BAPTA-1 dextran or fura-2 dextran in vivo. Inhibition of the sarco(endo)plasmic reticulum Ca2+-ATPase, disruption of mitochondrial Ca2+ uptake, or inhibition of the Na+–Ca2+ exchanger did not measurably alter the amplitude or decay kinetics of the electrically evoked Ca2+ transients in CNTs. By contrast, inhibition of the plasma membrane Ca2+-ATPase (PMCA) by increasing the pH slowed the decay of the Ca2+ transient by 2-fold. Surprisingly, the energy for ion transport across the plasma membrane of CNTs is predominantly from glycolysis rather than mitochondrial respiration, as evidenced by the observation that Ca2+ transients were suppressed by iodoacetate but unaffected by mitochondrial inhibitors. These observations indicate that, following electrical activity, the PMCA is the predominant mechanism of Ca2+ clearance from the cytosol of CNTs and glycolysis is the predominant source of energy. PMID:17095566

  8. Nerve allograft transplantation for functional restoration of the upper extremity: case series

    PubMed Central

    Elkwood, Andrew I.; Holland, Neil R.; Arbes, Spiros M.; Rose, Michael I.; Kaufman, Matthew R.; Ashinoff, Russell L.; Parikh, Mona A.; Patel, Tushar R.

    2011-01-01

    Background Major trauma to the spinal cord or upper extremity often results in severe sensory and motor disturbances from injuries to the brachial plexus and its insertion into the spinal cord. Functional restoration with nerve grafting neurotization and tendon transfers is the mainstay of treatment. Results may be incomplete due to a limited supply of autologous material for nerve grafts. The factors deemed most integral for success are early surgical intervention, reconstruction of all levels of injury, and maximization of the number of axonal conduits per nerve repair. Objective To report the second series of nerve allograft transplantation using cadaveric nerve graft and our experience with living-related nerve transplants. Participants Eight patients, seven men and one woman, average age 23 years (range 18–34), with multi-level brachial plexus injuries were selected for transplantation using either cadaveric allografts or living-related donors. Methods Grafts were harvested and preserved in the University of Wisconsin Cold Storage Solution at 5°C for up to 7 days. The immunosuppressive protocol was initiated at the time of surgery and was discontinued at approximately 1 year, or when signs of regeneration were evident. Parameters for assessment included mechanism of injury, interval between injury and treatment, level(s) of deficit, post-operative return of function, pain relief, need for revision surgery, complications, and improvement in quality of life. Results Surgery was performed using living-related donor grafts in six patients, and cadaveric grafts in two patients. Immunosuppression was tolerated for the duration of treatment in all but one patient in whom early termination occurred due to non-compliance. There were no cases of graft rejection as of most recent follow-up. Seven patients showed signs of regeneration, demonstrated by return of sensory and motor function and/or a migrating Tinel's sign. One patient was non-compliant with the post-operative regimen and experienced minimal return of function despite a reduction in pain. Conclusions Despite the small number of subjects, it appears that nerve allograft transplantation may be performed safely, permitting non-prioritized repair of long-segment peripheral nerve defects and maximizing the number of axonal conduits per nerve repair. For patients with long, multi-level brachial plexus injuries or combined upper and lower extremity nerve deficits, the use of nerve allograft allows a more complete repair that may translate into greater functional restoration than autografting alone. PMID:21675363

  9. 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

    2015-03-01

    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

  10. 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

  11. 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

  12. Timeline: exorcizing the animal spirits: Jan Swammerdam on nerve function.

    PubMed

    Cobb, M

    2002-05-01

    For more than 1,500 years, nerves were thought to function through the action of 'animal spirits'. In the seventeenth century, René Descartes conceived of these 'spirits' as liquids or gases, and used the idea to explain reflex action. But he was rapidly proven wrong by a young Dutchman, Jan Swammerdam. Swammerdam's elegant experiments pioneered the frog nerve muscle preparation and laid the foundation of our modern understanding of nerve function. PMID:11988778

  13. Bladder sensory physiology: neuroactive compounds and receptors, sensory transducers, and target-derived growth factors as targets to improve function

    PubMed Central

    Gonzalez, Eric J.; Merrill, Liana

    2014-01-01

    Urinary bladder dysfunction presents a major problem in the clinical management of patients suffering from pathological conditions and neurological injuries or disorders. Currently, the etiology underlying altered visceral sensations from the urinary bladder that accompany the chronic pain syndrome, bladder pain syndrome (BPS)/interstitial cystitis (IC), is not known. Bladder irritation and inflammation are histopathological features that may underlie BPS/IC that can change the properties of lower urinary tract sensory pathways (e.g., peripheral and central sensitization, neurochemical plasticity) and contribute to exaggerated responses of peripheral bladder sensory pathways. Among the potential mediators of peripheral nociceptor sensitization and urinary bladder dysfunction are neuroactive compounds (e.g., purinergic and neuropeptide and receptor pathways), sensory transducers (e.g., transient receptor potential channels) and target-derived growth factors (e.g., nerve growth factor). We review studies related to the organization of the afferent limb of the micturition reflex and discuss neuroplasticity in an animal model of urinary bladder inflammation to increase the understanding of functional bladder disorders and to identify potential novel targets for development of therapeutic interventions. Given the heterogeneity of BPS/IC and the lack of consistent treatment benefits, it is unlikely that a single treatment directed at a single target in micturition reflex pathways will have a mass benefit. Thus, the identification of multiple targets is a prudent approach, and use of cocktail treatments directed at multiple targets should be considered. PMID:24760999

  14. Implantable bioelectric interfaces for lost nerve functions.

    PubMed

    Heiduschka, P; Thanos, S

    1998-08-01

    Neuronal cells are unique within the organism. In addition to forming long-distance connections with other nerve cells and non-neuronal targets, they lose the ability to regenerate their neurites and to divide during maturation. Consequently, external violations like trauma or disease frequently lead to their disappearance and replacement by non-neuronal, and thus not properly functioning cells. The advent of microtechnology and construction of artificial implants prompted to create particular devices for specialised regions of the nervous system, in order to compensate for the loss of function. The scope of the present work is to review the current devices in connection with their applicability and functional perspectives. (1) Successful implants like the cochlea implant and peripherally implantable stimulators are discussed. (2) Less developed and not yet applicable devices like retinal or cortical implants are introduced, with particular emphasis given to the reasons for their failure to replace very complex functions like vision. (3) Material research is presented both from the technological aspect and from their biocompatibility as prerequisite of any implantation. (4) Finally, basic studies are presented, which deal with methods of shaping the implants, procedures of testing biocompatibility and modification of improving the interfaces between a technical device and the biological environment. The review ends by pointing to future perspectives in neuroimplantation and restoration of interrupted neuronal pathways. PMID:9670213

  15. [Joint and sensory branch block of the obturator and femoral nerves in a case of femoral head osteonecrosis and arthritis].

    PubMed

    Cortiñas-Sáenz, M; Salmerón-Velez, G; Holgado-Macho, I A

    2014-01-01

    The sensory innervation of the hip joint is complex. The joint and sensory branch block of the obturator and femoral nerves is effective for treating the pain caused due to different hip diseases. This could be an option to be considered in certain circumstances such as, being a surgical-anaesthetic high risk, or if there is significant overweight, It could also be useful on other occasions if the traumatoligist considers that it is better to delay hip replacement for a limited period. PMID:24656423

  16. Differentiation of peripheral nerve functions and properties with spectral analysis and Karnovsky-Roots staining: a preliminary study

    PubMed Central

    Xu, Qintong; Chen, Zenggan; Li, Qiong; Liu, Haifei; Zhang, Jian; Yao, Wenhua; Zhang, Ren; Li, Qingli; Liu, Hongying; Zhang, Feng; Lineaweaver, William C

    2014-01-01

    Objective: The purpose of this study was to explore the possibility for analyzing and differentiating between motor and sensory functions of peripheral nerve axons using spectral technology. Methods: 10 μm slide section of S1 anterior and posterior rabbit spinal nerve roots were made and then stained with Karnovsky-Roots method for molecular hyperspectral imaging microscopy analysis. In addition, Raman spectra data of nerve axons on each slide was collected after Karnovsky-Roots staining for 30 minutes. Results: Motor axons were differentiated from sensory axons in a nerve axon section hyperspectral image via Spectral angle mapper algorithm. Raman scatterings could be detected near 2110 cm-1, and 2155 cm-1 in motor axons after Karnvosky-Roots staining. The value of I2100/I1440 in motor axons are significantly different (P0.001) than in sensory axons after staining for 30 minutes. Conclusions: Motor and sensory nerve axons can be differentiated from their counterparts in 30 minutes by using Raman micro-spectroscopy analysis assisted with Karnovsky-Roots staining. PMID:25419356

  17. Effect of Delayed Peripheral Nerve Repair on Nerve Regeneration, Schwann Cell Function and Target Muscle Recovery

    PubMed Central

    Jonsson, Samuel; Wiberg, Rebecca; McGrath, Aleksandra M.; Novikov, Lev N.; Wiberg, Mikael; Novikova, Liudmila N.; Kingham, Paul J.

    2013-01-01

    Despite advances in surgical techniques for peripheral nerve repair, functional restitution remains incomplete. The timing of surgery is one factor influencing the extent of recovery but it is not yet clearly defined how long a delay may be tolerated before repair becomes futile. In this study, rats underwent sciatic nerve transection before immediate (0) or 1, 3, or 6 months delayed repair with a nerve graft. Regeneration of spinal motoneurons, 13 weeks after nerve repair, was assessed using retrograde labeling. Nerve tissue was also collected from the proximal and distal stumps and from the nerve graft, together with the medial gastrocnemius (MG) muscles. A dramatic decline in the number of regenerating motoneurons and myelinated axons in the distal nerve stump was observed in the 3- and 6-months delayed groups. After 3 months delay, the axonal number in the proximal stump increased 2–3 folds, accompanied by a smaller axonal area. RT-PCR of distal nerve segments revealed a decline in Schwann cells (SC) markers, most notably in the 3 and 6 month delayed repair samples. There was also a progressive increase in fibrosis and proteoglycan scar markers in the distal nerve with increased delayed repair time. The yield of SC isolated from the distal nerve segments progressively fell with increased delay in repair time but cultured SC from all groups proliferated at similar rates. MG muscle at 3- and 6-months delay repair showed a significant decline in weight (61% and 27% compared with contra-lateral side). Muscle fiber atrophy and changes to neuromuscular junctions were observed with increased delayed repair time suggestive of progressively impaired reinnervation. This study demonstrates that one of the main limiting factors for nerve regeneration after delayed repair is the distal stump. The critical time point after which the outcome of regeneration becomes too poor appears to be 3-months. PMID:23409189

  18. Mammalian nerve globins in search of functions.

    PubMed

    Ascenzi, Paolo; Gustincich, Stefano; Marino, Maria

    2014-04-01

    Nerve globins are present in nonvertebrates and vertebrates, the first nerve globin having been recognized in the nerve cord of the polychaete annelid Aphrodite aculeata in 1872. Later, in 2000, the first vertebrate nerve globin, named neuroglobin (Ngb), has been identified in neuronal tissues of humans and mice. Recently, cytoglobin, hemoglobin, and myoglobin have also been reported to be expressed in the mammalian nervous system. The concentration of mammalian nerve globins is ~1 μM, with the exception of Ngb that reaches approximately 100-200 μM only in the retina rod cells. Mammalian nerve globins have been hypothesized to be involved in the excitability of the nervous system, in the metabolism of reactive nitrogen and oxygen species, and in intracellular signaling pathways leading to the neuronal cell survival. Only in retina cells, mammalian Ngb may help to sustain O2 supply to mitochondria, thereby supporting the visual process in the eye. Here, the putative roles of mammalian nerve globins are reviewed. PMID:24753139

  19. 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

  20. Increased Nerve Growth Factor Signaling in Sensory Neurons of Early Diabetic Rats Is Corrected by Electroacupuncture

    PubMed Central

    Nori, Stefania Lucia; Rocco, Maria Luisa; Florenzano, Fulvio; Ciotti, Maria Teresa; Aloe, Luigi

    2013-01-01

    Diabetic polyneuropathy (DPN), characterized by early hyperalgesia and increased nerve growth factor (NGF), evolves in late irreversible neuropathic symptoms with reduced NGF support to sensory neurons. Electroacupuncture (EA) modulates NGF in the peripheral nervous system, being effective for the treatment of DPN symptoms. We hypothesize that NGF plays an important pathogenic role in DPN development, while EA could be useful in the therapy of DPN by modulating NGF expression/activity. Diabetes was induced in rats by streptozotocin (STZ) injection. One week after STZ, EA was started and continued for three weeks. NGF system and hyperalgesia-related mediators were analyzed in the dorsal root ganglia (DRG) and in their spinal cord and skin innervation territories. Our results show that four weeks long diabetes increased NGF and NGF receptors and deregulated intracellular signaling mediators of DRG neurons hypersensitization; EA in diabetic rats decreased NGF and NGF receptors, normalized c-Jun N-terminal and p38 kinases activation, decreased transient receptor potential vanilloid-1 ion channel, and possibly activated the nuclear factor kappa-light-chain-enhancer of activated B cells (Nf-κB). In conclusion, NGF signaling deregulation might play an important role in the development of DPN. EA represents a supportive tool to control DPN development by modulating NGF signaling in diabetes-targeted neurons. PMID:23710226

  1. Edaravone promotes functional recovery after mechanical peripheral nerve injury

    PubMed Central

    Zhang, Teng; Li, Zhengwei; Dong, Jianli; Nan, Feng; Li, Tao; Yu, Qing

    2014-01-01

    Edaravone has been shown to reduce ischemia/reperfusion-induced peripheral nerve injury. However, the therapeutic effect of edaravone on peripheral nerve injury caused by mechanical factors is unknown. In the present study, we established a peripheral nerve injury model by crushing the sciatic nerve using hemostatic forceps, and then administered edaravone 3 mg/kg intraperitoneally. The sciatic functional index and superoxide dismutase activity of the sciatic nerve were increased, and the malondialdehyde level was decreased in animals in the edaravone group compared with those in the model group. Bcl-2 expression was increased, but Bax expression was decreased in anterior horn cells of the L4-6 spinal cord segments. These results indicated that edaravone has a neuroprotective effect following peripheral nerve injury caused by mechanical factors through alleviating free radical damage to cells and inhibiting lipid peroxidation, as well as regulating apoptosis-related protein expression. PMID:25374594

  2. Luteolin improves the impaired nerve functions in diabetic neuropathy: behavioral and biochemical evidences.

    PubMed

    Li, Ming; Li, Qiang; Zhao, Qingsong; Zhang, Jinchao; Lin, Jiang

    2015-01-01

    Peripheral neuropathies are a major cause of morbidity in patients with diabetes mellitus. Up to now, drugs for improving the impaired nerve functions has been lacking for diabetic neuropathy. The antioxidant and neuroprotective effects of luteolin make it an attractive candidate for diabetic neuropathy. The present study was designed to investigate the putative beneficial effect of luteolin on diabetic neuropathy. Diabetic rats were intraperitoneally treated with daily luteolin (50 mg/kg, 100 mg/kg and 200 mg/kg) or vehicle for 3 weeks from the 28(th) day after streptozotocin injection. Behavioral, electrophysiological and biochemical studies were performed to evaluate the effect of luteolin on the impaired nerve functions in diabetic neuropathy. It was found that luteolin dose dependently alleviated abnormal sensation, improved nerve conduction velocities and nerve blood flow in diabetic rats. Biochanical analysis showed that luteolin significantly lowered the reactive oxygen species production and malondialdehyde level, as well as increased antioxidants activities in a dose dependent manner. In addition, luteolin significantly up-regulated the protein levels of nuclear factor-E2-related factor-2 (Nrf2) and heme oxygenase-1 (HO-1) in diabetic nerves. Taken together, luteolin is capable of improving diabetes-induced deficit in motor and sensory functions, which could be attributable, at least in part, to its Nrf2-dependent antioxidant capacity. The findings in the present study highlight the therapeutic value of luteolin for diabetic neuropathy. PMID:26617718

  3. Luteolin improves the impaired nerve functions in diabetic neuropathy: behavioral and biochemical evidences

    PubMed Central

    Li, Ming; Li, Qiang; Zhao, Qingsong; Zhang, Jinchao; Lin, Jiang

    2015-01-01

    Peripheral neuropathies are a major cause of morbidity in patients with diabetes mellitus. Up to now, drugs for improving the impaired nerve functions has been lacking for diabetic neuropathy. The antioxidant and neuroprotective effects of luteolin make it an attractive candidate for diabetic neuropathy. The present study was designed to investigate the putative beneficial effect of luteolin on diabetic neuropathy. Diabetic rats were intraperitoneally treated with daily luteolin (50 mg/kg, 100 mg/kg and 200 mg/kg) or vehicle for 3 weeks from the 28th day after streptozotocin injection. Behavioral, electrophysiological and biochemical studies were performed to evaluate the effect of luteolin on the impaired nerve functions in diabetic neuropathy. It was found that luteolin dose dependently alleviated abnormal sensation, improved nerve conduction velocities and nerve blood flow in diabetic rats. Biochanical analysis showed that luteolin significantly lowered the reactive oxygen species production and malondialdehyde level, as well as increased antioxidants activities in a dose dependent manner. In addition, luteolin significantly up-regulated the protein levels of nuclear factor-E2-related factor-2 (Nrf2) and heme oxygenase-1 (HO-1) in diabetic nerves. Taken together, luteolin is capable of improving diabetes-induced deficit in motor and sensory functions, which could be attributable, at least in part, to its Nrf2-dependent antioxidant capacity. The findings in the present study highlight the therapeutic value of luteolin for diabetic neuropathy. PMID:26617718

  4. Phenotyping the Function of TRPV1-Expressing Sensory Neurons by Targeted Axonal Silencing

    PubMed Central

    Brenneis, Christian; Kistner, Katrin; Puopolo, Michelino; Segal, David; Roberson, David; Sisignano, Marco; Labocha, Sandra; Ferreirós, Nerea; Strominger, Amanda; Cobos, Enrique J.; Ghasemlou, Nader; Geisslinger, Gerd; Reeh, Peter W.; Bean, Bruce P.; Woolf, Clifford J.

    2013-01-01

    Specific somatosensations may be processed by different subsets of primary afferents. C-fibers expressing heat-sensitive TRPV1 channels are proposed, for example, to be heat but not mechanical pain detectors. To phenotype in rats the sensory function of TRPV1+ afferents, we rapidly and selectively silenced only their activity, by introducing the membrane-impermeant sodium channel blocker QX-314 into these axons via the TRPV1 channel pore. Using tandem mass spectrometry we show that upon activation with capsaicin, QX-314 selectively accumulates in the cytosol only of TRPV1-expressing cells, and not in control cells. Exposure to QX-314 and capsaicin induces in small DRG neurons a robust sodium current block within 30 s. In sciatic nerves, application of extracellular QX-314 with capsaicin persistently reduces C-fiber but not A-fiber compound action potentials and this effect does not occur in TRPV1−/− mice. Behavioral phenotyping after selectively silencing TRPV1+ sciatic nerve axons by perineural injections of QX-314 and capsaicin reveals deficits in heat and mechanical pressure but not pinprick or light touch perception. The response to intraplantar capsaicin is substantially reduced, as expected. During inflammation, silencing TRPV1+ axons abolishes heat, mechanical, and cold hyperalgesia but tactile and cold allodynia remain following peripheral nerve injury. These results indicate that TRPV1-expressing sensory neurons process particular thermal and mechanical somatosensations, and that the sensory channels activated by mechanical and cold stimuli to produce pain in naive/inflamed rats differ from those in animals after peripheral nerve injury. PMID:23283344

  5. Glycomimetic functionalized collagen hydrogels for peripheral nerve repair

    NASA Astrophysics Data System (ADS)

    Masand, Shirley Narain

    Despite the innate regenerative potential of the peripheral nervous system, functional recovery is often limited. The goal of this dissertation was to develop a clinically relevant biomaterial strategy to (1) encourage the regrowth of axons and (2) direct them down their appropriate motor tracts. To this end, we use peptide mimics of two glycans, polysialic acid (PSA) and an epitope first discovered on human natural killer cells (HNK-1), to functionalize type I collagen hydrogels. Previous studies have shown that these molecules, in their glycan and glycomimetic form, are associated with acceleration of neurite outgrowth, glial cell proliferation, and motoneuron targeting. In vitro, we demonstrated the retained functionality of the peptide glycomimetics after conjugation to a type I collagen backbone. While HNK-functionalized collagen increased motor neurite outgrowth, PSA-functionalized collagen encouraged motor and sensory neurite outgrowth and Schwann cell extension and proliferation. When we introduce these glycomimetic-functionalized collagen hydrogels into a critical gap femoral nerve model, we show that both PSA and HNK-functionalized hydrogels yielded a significant increase in functional recovery when compared to saline, native and scramble-coupled hydrogels. However, there was an interesting divergence in the morphological results: PSA-functionalized hydrogels increased axon count and HNK-functionalized hydrogels increased motoneuron targeting and myelination. We believed that these differences may be attributed to distinct mechanisms by which the glycomimetics impart their benefit. Interestingly, however, we found no synergistic gain in recovery with the use of our composite hydrogels which we speculated may be due to an inadequate dose of the individual glycomimetic. To address this possibility, we show that increasing the amount of functionalized peptide functionalized in our composite hydrogels led to increases in axon count and area of regeneration, but does not affect the degree of functional recovery. Finally, in order to assess potential mechanisms by which our glycomimetics impart benefit, we describe a novel platform for studying neural cell/biomaterial interaction through the use of two types of motoneuron cultures, dissociated spinal cord neurons and organotypic spinal cord slices. We show promising evidence that this strategy can be used to probe signaling pathways potentially involved in the action of these bioactives.

  6. The structure and function of cutaneous sensory receptors.

    PubMed

    Munger, B L; Ide, C

    1988-03-01

    The present review of cutaneous sensory receptors begins with a consideration of free nerve endings (FNEs) that can be considered as sensory terminals evidencing the least structural specialization of the axon and associated cells. Using the criteria established by Kruger et al (1981), FNEs of both A delta and C fibers can be identified on the basis of ultrastructural characteristics that include an intimate relationship between axons and the associated epithelium, the lack of a complete Schwann cell investment, the accumulation of numerous vesicles and other cytoplasmic organelles, and for A delta terminals a 1:1 relationship between axon and investing Schwann cell. Using these criteria, the so-called genital end bulbs of the human glans penis are merely a skein of FNEs based on the ultrastructural study of Halata and Munger (1986). Hair follicles of most species studied to date (the exception being the rabbit and to some extent the guinea pig) are multiply innervated with lanceolate, Ruffini and FNEs. The lanceolate terminals are the rapidly adapting terminals that are numerous in guard hairs. Ruffini terminals of hairs resemble those of the periodontal ligament or joint capsules and both are remarkably similar to Golgi tendon organs in terms of ultrastructural characteristics. The key ultrastructural characteristic is the encircling of collagen bundles by axons and associated Schwann and connective tissue cells. Axons frequently enter the epidermis either to terminate as FNEs or become associated with Merkel cells in glabrous skin at the base of the papillary ridges or in clusters of Merkel cells in hairy skin in touch domes or Haarscheiben. Merkel cells have clusters of apparent secretory granules polarized toward the axon and the axon is typically a slowly adapting mechanoreceptor. The function of the granules is not known. Pacinian corpuscles are the largest of the corpuscular receptors of the dermis and are characterized by an elaborate inner core of stacks of numerous thin lamellae arranged in a bilaterally symmetrical manner. Based on the fact that the lamellae are coupled with gap junctions and the outer core lamellae isolated by numerous tight junctions, the authors have proposed that the unique ionic environment may be in part responsible for the remarkable sensitivity of Pacinian corpuscles (Munger and Ide, 1987). Meissner corpuscles are a typical corpuscular receptor of murine (Ide, 1976, 1977), marsupial and primate glabrous skin (Munger, 1971). The axons typically weave back and forth between stacks of lamellae.(ABSTRACT TRUNCATED AT 400 WORDS) PMID:3137944

  7. 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·10min(-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. PMID:26679388

  8. A comparison of nerve conduction velocities and current perception thresholds as correlates of clinical severity of diabetic sensory neuropathy.

    PubMed Central

    Rendell, M S; Katims, J J; Richter, R; Rowland, F

    1989-01-01

    Nerve conduction velocities (NCVs) are the standard measurements used to confirm the presence or absence of diabetic neuropathy. NCVs were contrasted with the newer technique of measurement of alternating current perception thresholds (CPTs) in assessing the quantitative level of correlation with severity of diabetic sensory neuropathy. A very detailed, scored neurological history (symptoms) and physical examination, emphasising sensory assessment, was conducted on 71 individuals with diabetic neuropathy of varying degrees of severity. Sensory and motor NCVs and CPTs at 5, 250, and 2000 Hz of the upper and lower extremities were determined for these individuals. In addition, vibration thresholds (VTs) were measured as a third modality. Twenty eight individuals underwent repeated evaluations at 2, 6, 10 and 12 months after the initial procedures. Using the results of 169 complete evaluations, correlations were determined between physical scores (PS) and symptoms scores (SS) and NCVs. NCV correlations with the SS were weaker than with the PS. The strongest of the correlations were found between the PS and motor NCVs of the median nerve (rho = 0.29) and the tibial nerve (rho = 0.38). Normal NCVs were present in the face of very significant historical and physical abnormality. Correlations of the SS and PS with both VTs and CPTs were higher than with the NCVs. CPTs proved the more effective as predictors of both symptomatic and physical impairment. NCVs appear to lack the resolving power necessary to evaluate subtle differences in clinical state of diabetic sensory neuropathy. The supplementary use of current perception testing may improve the quantitative assessment of this condition. PMID:2738593

  9. Differential myelinated and unmyelinated sensory and autonomic skin nerve fiber involvement in patients with ophthalmic postherpetic neuralgia

    PubMed Central

    Truini, Andrea; Haanpaa, Maija; Provitera, Vincenzo; Biasiotta, Antonella; Stancanelli, Annamaria; Caporaso, Giuseppe; Santoro, Lucio; Cruccu, Giorgio; Nolano, Maria

    2015-01-01

    Postherpetic neuralgia (PHN) is a common and exceptionally drug-resistant neuropathic pain condition. In this cross-sectional skin biopsy study, seeking information on the responsible pathophysiological mechanisms we assessed how ophthalmic PHN affects sensory and autonomic skin innervation. We took 2-mm supraorbital punch skin biopsies from the affected and unaffected sides in 10 patients with ophthalmic PHN. Using indirect immunofluorescence and a large panel of antibodies including protein gene product (PGP) 9.5 we quantified epidermal unmyelinated, dermal myelinated and autonomic nerve fibers. Although skin biopsy showed reduced epidermal and dermal myelinated fiber density in specimens from the affected side, the epidermal/dermal myelinated nerve fiber ratio was lower in the affected than in the unaffected side (p < 0.001), thus suggesting a predominant epidermal unmyelinated nerve fiber loss. Conversely, autonomic skin innervation was spared. Our study showing that ophthalmic PHN predominantly affects unmyelinated nerve fiber and spares autonomic nerve fiber might help to understand the pathophysiological mechanisms underlying this difficult-to-treat condition. PMID:26300742

  10. Nerve function in workers with long term exposure to trichloroethene.

    PubMed

    Ruijten, M W; Verberk, M M; Sallé, H J

    1991-02-01

    Certain functions of the nervous system were examined in 31 printing workers (mean age 44) exposed to trichloroethene (mean duration 16 years) and 28 controls (mean age 45). In the sural nerve the conduction velocity (SNCV), response amplitude, and refractory period (SRP) were measured. The latencies of the masseter and the blink reflex were determined to test the trigeminal nerve. In the peroneal nerve the conduction velocity of fast and slow nerve fibres, the response amplitude, and the refractory period were determined. As a measure of autonomic nerve function the response of the heart rate was determined to isometric muscle contraction and deep breathing. Individual cumulative exposure was calculated on the basis of exposure levels in the past. The mean cumulative exposure of the exposed workers was 704 ppm x years. For the assessment of the exposure effect relation a multiple linear regression model was used. A slight reduction (-1.1 m/s) in the SNCV was found and a prolongation (0.4 ms) of the SRP (mean of the controls 1.95 ms). The latency of the masseter reflex (mean 10.4 ms) had increased (0.4 ms). With respect to the blink reflex no prolongation was found. No impairment was found in the functions of motor and autonomic nerves. This study shows that the refractory period may be a sensitive indicator of preclinical toxic neuropathies. Long term exposure to trichloroethene at threshold limit values (about 35 ppm) may slightly affect the trigeminal and sural nerves. PMID:1998613

  11. Effect of remote sensory noise on hand function post stroke.

    PubMed

    Seo, Na Jin; Kosmopoulos, Marcella Lyn; Enders, Leah R; Hur, Pilwon

    2014-01-01

    Hand motor impairment persists after stroke. Sensory inputs may facilitate recovery of motor function. This pilot study tested the effectiveness of tactile sensory noise in improving hand motor function in chronic stroke survivors with tactile sensory deficits, using a repeated measures design. Sensory noise in the form of subthreshold, white noise, mechanical vibration was applied to the wrist skin during motor tasks. Hand dexterity assessed by the Nine Hole Peg Test and the Box and Block Test and pinch strength significantly improved when the sensory noise was turned on compared with when it was turned off in chronic stroke survivors. The subthreshold sensory noise to the wrist appears to induce improvements in hand motor function possibly via neuronal connections in the sensoriomotor cortex. The approach of applying concomitant, unperceivable mechanical vibration to the wrist during hand motor tasks is easily adoptable for clinic use as well as unsupervised home use. This pilot study suggests a potential for a wristband-type assistive device to complement hand rehabilitation for stroke survivors with sensorimotor deficit. PMID:25477806

  12. Effect of Remote Sensory Noise on Hand Function Post Stroke

    PubMed Central

    Seo, Na Jin; Kosmopoulos, Marcella Lyn; Enders, Leah R.; Hur, Pilwon

    2014-01-01

    Hand motor impairment persists after stroke. Sensory inputs may facilitate recovery of motor function. This pilot study tested the effectiveness of tactile sensory noise in improving hand motor function in chronic stroke survivors with tactile sensory deficits, using a repeated measures design. Sensory noise in the form of subthreshold, white noise, mechanical vibration was applied to the wrist skin during motor tasks. Hand dexterity assessed by the Nine Hole Peg Test and the Box and Block Test and pinch strength significantly improved when the sensory noise was turned on compared with when it was turned off in chronic stroke survivors. The subthreshold sensory noise to the wrist appears to induce improvements in hand motor function possibly via neuronal connections in the sensoriomotor cortex. The approach of applying concomitant, unperceivable mechanical vibration to the wrist during hand motor tasks is easily adoptable for clinic use as well as unsupervised home use. This pilot study suggests a potential for a wristband-type assistive device to complement hand rehabilitation for stroke survivors with sensorimotor deficit. PMID:25477806

  13. Degeneration of the primary snout sensory afferents in the cervical spinal cords following the infraorbital nerve transection in some mammals.

    PubMed

    Chang, C M; Kubota, K; Lee, M S; Iseki, H; Sonoda, Y; Narita, N; Shibanai, S; Nagae, K; Ohkubo, K

    1988-01-01

    To obtain the neuroanatomical information on the role of the snout sensory input in mastication, the present study was conducted on young and adult mice, young Wistar rats and adult Japanese shrew-moles. The animals were subjected to unilateral and bilateral infraorbital nerve transection. Transganglionic degeneration was studied by the Nauta method and electron microscopy including HRP application to the neck muscles. Transganglionic degeneration was found in every experimental case. 1. Transganglionic degeneration of the fibers was found not only in the main sensory nucleus and spinal tract nucleus of the trigeminal nerve but throughout the cervical and the upper part of the thoracic spinal cord. 2. These transganglionically degenerated fibers descended bilaterally through the cuneate nucleus and then caudally through the posterior funiculus at the obex level. They then entered the dorsal and ventral horns to make a synaptic contact with the degenerated synapses on the dorsal horn cells and with the multipolar cells in the ventral horns. This neuroanatomical information suggests: 1) that the trigemino-neck muscle reflex will be generated monosynaptically by the primary neurons arising from the snout sensory organs and 2) that these primary neurons may play a large role as a neuronal bridge in connecting the masticatory reflex system and the cranio-neck reflex system. PMID:3189847

  14. [Sensory functions and Alzheimer's disease: a multi-disciplinary approach].

    PubMed

    Kenigsberg, Paul-Ariel; Aquino, Jean-Pierre; Berard, Alain; Boucart, Muriel; Bouccara, Didier; Brand, Gérard; Charras, Kevin; Garcia-Larrea, Luis; Gzil, Fabrice; Krolak-Salmon, Pierre; Madjlessi, Arach; Malaquin-Pavan, Évelyne; Penicaud, Luc; Platel, Hervé; Pozzo, Thierry; Reintjens, Christophe; Salmon, Éric; Vergnon, Laurent; Robert, Philippe

    2015-09-01

    Relations between sensory functions and Alzheimer's disease are still under-explored. To understand them better, the Fondation Médéric Alzheimer has brought together a multi-disciplinary expert group. Aristote's five senses must be enhanced by today's knowledge of proprioception, motor cognition and pain perception. When cognition breaks down, the person with dementia perceives the world around her with her sensory experience, yet is unable to integrate all this information to understand the context. The treatment of multiple sensory inputs by the brain is closely linked to cognitive processes. Sensory deficits reduce considerably the autonomy of people with dementia in their daily life and their relations with others, increase their social isolation and the risk of accidents. Professionals involved with neurodegenerative diseases remain poorly aware of sensory deficits, which can bias the results of cognitive tests. However, there are simple tools to detect these deficits, notably for vision, hearing and balance disorders, which can be corrected. Many interventions for cognitive rehabilitation or quality of life improvement are based on sensory functions. The environment of people with dementia must be adapted to become understandable, comfortable, safe and eventually therapeutic. PMID:26395297

  15. Assessing nerves in leprosy.

    PubMed

    Garbino, José Antonio; Heise, Carlos Otto; Marques, Wilson

    2016-01-01

    Leprosy neuropathy is dependent on the patient's immune response and expresses itself as a focal or multifocal neuropathy with asymmetric involvement. Leprosy neuropathy evolves chronically but recurrently develops periods of exacerbation during type 1 or type 2 reactions, leading to acute neuropathy. Nerve enlargement leading to entrapment syndromes is also a common manifestation. Pain may be either of inflammatory or neuropathic origin. A thorough and detailed evaluation is mandatory for adequate patient follow-up, including nerve palpation, pain assessment, graded sensory mapping, muscle power testing, and autonomic evaluation. Nerve conduction studies are a sensitive tool for nerve dysfunction, including new lesions during reaction periods or development of entrapment syndromes. Nerve ultrasonography is also a very promising method for nerve evaluation in leprosy. The authors propose a composite nerve clinical score for nerve function assessment that can be useful for longitudinal evaluation. PMID:26773623

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

    PubMed

    Henry, F P; Farkhad, R I; Butt, F S; O'Shaughnessy, M; O'Sullivan, S T

    2012-06-01

    Post-operative immobilisation following isolated digital nerve repair remains a controversial issue amongst the microsurgical community. Protocols differ from unit to unit and even, as evidenced in our unit, may differ from consultant to consultant. We undertook a retrospective review of 46 patients who underwent isolated digital nerve repair over a 6-month period. Follow-up ranged from 6 to 18 months. Twenty-four were managed with protected active mobilisation over a 4-week period while 22 were immobilised over the same period. Outcomes such as return to work, cold intolerance, two-point discrimination and temperature differentiation were used as indicators of clinical recovery. Our results showed that there was no significant difference noted in either clinical assessment of recovery or return to work following either post-operative protocol, suggesting that either regime may be adopted, tailored to the patient's needs and resources of the unit. PMID:22147643

  17. How does the structure of extraocular muscles and their nerves affect their function?

    PubMed Central

    Bruenech, J R; Kjellevold Haugen, I B

    2015-01-01

    The sensory and motor control of human extraocular muscles (EOMs) have been subjected to considerable speculation in ophthalmic literature, often related to infranuclear structures such as the unique complement of muscle fibres and their associated sensory organs. The intrafusal fibres do not resemble their somatic counterparts and their peculiar morphology has raised questions about their proprioceptive capacity. No Golgi tendon organs have so far been observed and the myotendinous nerve endings, previously assumed to convey sensory information, have recently been argued to merely represent constituents of the efferent innervation serving the multiply innervated muscles fibres. These observations raise questions about the overall capacity to monitor the activity created by the generous efferent nerve supply observed in these muscles. Furthermore, the argued independent activity of muscular layers and compartments suggest that the required feedback must be highly structured and more specific than previously assumed. Yet, uncertainty about the source of such information remains. The purpose of this paper is to provide a short review of neuromuscular properties of human extraocular muscles. Their functional implications and the most reputable sources of proprioception will also be discussed. The promoted views are based on pertinent literature and previous research undertaken by the authors. PMID:25397785

  18. Limb immobilization alters functional electrophysiological parameters of sciatic nerve

    PubMed Central

    Alves, J.S.M.; Leal-Cardoso, J.H.; Santos-Júnior, F.F.U.; Carlos, P.S.; Silva, R.C.; Lucci, C.M.; Báo, S.N.; Ceccatto, V.M.; Barbosa, R.

    2013-01-01

    Immobilization, used in clinical practice to treat traumatologic problems, causes changes in muscle, but it is not known whether changes also occur in nerves. We investigated the effects of immobilization on excitability and compound action potential (CAP) and the ultrastructure of the rat sciatic nerve. Fourteen days after immobilization of the right leg of adult male Wistar rats (n=34), animals were killed and the right sciatic nerve was dissected and mounted in a moist chamber. Nerves were stimulated at a baseline frequency of 0.2 Hz and tested for 2 min at 20, 50, and 100 Hz. Immobilization altered nerve excitability. Rheobase and chronaxy changed from 3.13±0.05 V and 52.31±1.95 µs (control group, n=13) to 2.84±0.06 V and 59.71±2.79 µs (immobilized group, n=15), respectively. Immobilization altered the amplitude of CAP waves and decreased the conduction velocity of the first CAP wave (from 93.63±7.49 to 79.14±5.59 m/s) but not of the second wave. Transmission electron microscopy showed fragmentation of the myelin sheath of the sciatic nerve of immobilized limbs and degeneration of the axon. In conclusion, we demonstrated that long-lasting leg immobilization can induce alterations in nerve function. PMID:23969978

  19. Steady State Responses: Electrophysiological Assessment of Sensory Function in Schizophrenia

    PubMed Central

    Brenner, Colleen A.; Krishnan, Giri P.; Vohs, Jenifer L.; Ahn, Woo-Young; Hetrick, William P.; Morzorati, Sandra L.; O'Donnell, Brian F.

    2009-01-01

    Persons with schizophrenia experience subjective sensory anomalies and objective deficits on assessment of sensory function. Such deficits could be produced by abnormal signaling in the sensory pathways and sensory cortex or later stage disturbances in cognitive processing of such inputs. Steady state responses (SSRs) provide a noninvasive method to test the integrity of sensory pathways and oscillatory responses in schizophrenia with minimal task demands. SSRs are electrophysiological responses entrained to the frequency and phase of a periodic stimulus. Patients with schizophrenia exhibit pronounced auditory SSR deficits within the gamma frequency range (35–50 Hz) in response to click trains and amplitude-modulated tones. Visual SSR deficits are also observed, most prominently in the alpha and beta frequency ranges (7–30 Hz) in response to high-contrast, high-luminance stimuli. Visual SSR studies that have used the psychophysical properties of a stimulus to target specific visual pathways predominantly report magnocellular-based deficits in those with schizophrenia. Disruption of both auditory and visual SSRs in schizophrenia are consistent with neuropathological and magnetic resonance imaging evidence of anatomic abnormalities affecting the auditory and visual cortices. Computational models suggest that auditory SSR abnormalities at gamma frequencies could be secondary to γ-aminobutyric acid–mediated or N-methyl-D-aspartic acid dysregulation. The pathophysiological process in schizophrenia encompasses sensory processing that probably contributes to alterations in subsequent encoding and cognitive processing. The developmental evolution of these abnormalities remains to be characterized. PMID:19726534

  20. Enhanced early sensory outcome after nerve repair as a result of immediate post-operative re-learning: a randomized controlled trial.

    PubMed

    Rosén, B; Vikström, P; Turner, S; McGrouther, D A; Selles, R W; Schreuders, T A R; Björkman, A

    2015-07-01

    We assessed the use of guided plasticity training to improve the outcome in the first 6 months after nerve repair. In a multicentre randomized controlled trial, 37 adults with median or ulnar nerve repair at the distal forearm were randomized to intervention, starting the first week after surgery with sensory and motor re-learning using mirror visual feedback and observation of touch, or to a control group with re-learning starting when reinnervation could be detected. The primary outcome at 3 and 6 months post-operatively was discriminative touch (shape texture identification test, part of the Rosen score). At 6 months, discriminative touch was significantly better in the early intervention group. Improvement of discriminative touch between 3 and 6 months was also significantly greater in that group. There were no significant differences in motor function, pain or in the total score. We conclude that early re-learning using guided plasticity may have a potential to improve the outcomes after nerve repair. LEVEL OF EVIDENCE II. PMID:25294735

  1. 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.

  2. Gallic acid and exercise training improve motor function, nerve conduction velocity but not pain sense reflex after experimental sciatic nerve crush in male rats

    PubMed Central

    Hajimoradi, Maryam; Fazilati, Mohammad; Gharib-Naseri, Mohammad Kazem; Sarkaki, Alireza

    2015-01-01

    Objective: The aim of present study was to evaluate the effects of oral administration of gallic acid (GA) for 21 days alone and in combination with exercise on nerve conduction velocity and sensory and motor functions in rats with sciatic nerve crush. Materials and Methods: Seventy adult male Wistar rats (250-300 g) were divided randomly into 7 groups with 10 in each: 1) Control (Cont), 2) Crushed + Vehicle (Cr +Veh), 3-5) Crushed + gallic acid (Cr+GA) (50, 100, and 200 mg/kg/2 mL, orally), 6) Crushed + exercise (Cr+Exe), and 7) Crushed + exercise + effective dose of gallic acid (Cr+Exe +GA200) for 21 days. In order to establish an animal model of sciatic nerve crush, equivalent to 7 kg of force pressed on 2-3 mm of sciatic nerve for 30 s, three times with 30 s intervals. Pain sense reflex in hot plate, motor coordination in rotarod, and sciatic nerve conduction velocity (SNCV) in all groups were tested. Data were analyzed using one-way ANOVA followed by Tukey’s post hoc test and p<0.05 has assigned as the significant difference. Results: Pain threshold was increased significantly in untreated crushed rats while motor function and SNCV were decreased in all groups with nerve crush (p<0.05, p<0.01, p<0.001 vs. control). Pain reflex latency was not changed in treated groups. Motor coordination and SNCV were improved in groups Cr+GA200 and Cr+Exe + GA200 (p<0.05, p<0.01 vs. Cr+Veh). Conclusion: GA, dose-dependently, may have therapeutic potential to improve the peripheral nerve degeneration, which is most likely related, at least in part, to its antioxidant and therapeutic properties. PMID:26445710

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

    PubMed

    Stankovic, N; Johansson, O; Hildebrand, C

    1996-01-01

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

  4. Morphological and functional changes of the optic nerve following traumatic optic nerve injuries in rabbits

    PubMed Central

    XUE, FEI; WU, KUNMING; WANG, TIANYOU; CHENG, YOU; JIANG, MANJIE; JI, JUNFENG

    2016-01-01

    The aim of the present study was to investigate the morphological changes of the optic nerve following traumatic injuries and decompression at different times after injury, and to observe the changes of the visually evoked potentials, to identify the relevant associations between surgical opportunity and the clinical effect of traumatic optic nerve injuries. Rabbits were chosen as the animal model for the study. All the rabbits were randomly divided into five groups (A-E), representing the normal control, decompression in 48 h, in 1 week, in 2 weeks and non-decompression groups, respectively. The pattern reversal visual evoked potentials (P-VEP) and morphological changes of the optic nerve were observed. The P-VEP of each healthy rabbit revealed typical NPN contours, while NPN waves in the injured rabbits were low and flat. The latent period of the P-wave was lengthened and the amplitude was reduced. The differences of the latent period and amplitude pre- and post-trauma were statistically significant. The morphological changes were also assessed. In the normal control group, the astrocytes of the optic nerve exhibited a cylindrical form and were arranged evenly on the vertical section. The neural fibers were arranged neatly, were even following application of a dye, and the cross section exhibited a normal configuration of the blood vessel. For the 48-h decompression group, the arrangement of the astrocytes was even on the vertical section, and vacuoles, slight swelling of the nerve, exudation around the blood vessel and a small amount of astrocytic hyperplasia were observed in the damaged area. In the non-decompression group there were large areas of necrosis, clear nerve demyelination, serious exudation around the blood vessel and astrocytic hyperplasia were observed. In conclusion, the optic nerve decompression is beneficial to protect the visual function in indirect optic nerve injuries. Visual function may be improved by decompression in 48 h compared to 2 weeks. In order to prevent secondary axon injury and to protect visual functions, the decompression should be performed as soon as possible. PMID:26893836

  5. Putative neurotrophic factors and functional recovery from peripheral nerve damage in the rat.

    PubMed Central

    Van der Zee, C. E.; Brakkee, J. H.; Gispen, W. H.

    1991-01-01

    1. In rats, recovery of sensory-motor function following a crush lesion of the sciatic or tibial nerve was monitored by measuring foot reflex withdrawal from a local noxious stimulation of the foot sole. 2. Putative neurotrophic compounds were tested on this functional recovery model: melanocortins (peptides derived from ACTH (corticotropin) and alpha-MSH (melanotropin], gangliosides and nimodipine were effective whereas isaxonine and TRH (thyrotropin releasing hormone) were not. 3. Structure-activity studies with melanocortins revealed a similar effectiveness of alpha-MSH, [N-Leu4, D-Phe7]-alpha-MSH, desacetyl-alpha-MSH and the ACTH analogue ORG 2766, questioning the validity of the previously suggested notion that the melanotrophic properties of these peptides are responsible for their neurotrophic effect. 4. As recovery of function after peripheral nerve damage follows a similar time course in hypophysectomized (five days post operation) and sham-operated rats, effective melanocortin therapy does not mimic an endogenous peptide signal in the repair process from pituitary origin. 5. Subcutaneous treatment with ORG 2766 (7.5 micrograms kg-1 48 h-1) facilitates recovery of function following peripheral nerve damage in young (6-7 weeks old), mature (5 month old) and old (20 month old) rats. 6. In view of the diversity in structure of the effective neurotrophic factors and the complexity of nerve repair, the present data support the notion that peripheral nerve repair may be facilitated by different humoral factors likely to be active on different aspects of the recovery process. PMID:1678980

  6. Neurophysiological assessment of auditory, peripheral nerve, somatosensory, and visual system functions after developmental exposure to ethanol vapors.

    PubMed

    Boyes, William K; Degn, Laura L; Martin, Sheppard A; Lyke, Danielle F; Hamm, Charles W; Herr, David W

    2014-01-01

    Ethanol-blended gasoline entered the market in response to demand for domestic renewable energy sources, and may result in increased inhalation of ethanol vapors in combination with other volatile gasoline constituents. It is important to understand potential risks of inhalation of ethanol vapors by themselves, and also as a baseline for evaluating the risks of ethanol combined with a complex mixture of hydrocarbon vapors. Because sensory dysfunction has been reported after developmental exposure to ethanol, we evaluated the effects of developmental exposure to ethanol vapors on neurophysiological measures of sensory function as a component of a larger project evaluating developmental ethanol toxicity. Pregnant Long-Evans rats were exposed to target concentrations 0, 5000, 10,000, or 21,000 ppm ethanol vapors for 6.5h/day over GD9-GD20. Sensory evaluations of male offspring began between PND106 and PND128. Peripheral nerve function (compound action potentials, nerve conduction velocity (NCV)), somatosensory (cortical and cerebellar evoked potentials), auditory (brainstem auditory evoked responses), and visual evoked responses were assessed. Visual function assessment included pattern elicited visual evoked potentials (VEPs), VEP contrast sensitivity, and electroretinograms recorded from dark-adapted (scotopic), light-adapted (photopic) flashes, and UV flicker and green flicker. No consistent concentration-related changes were observed for any of the physiological measures. The results show that gestational exposure to ethanol vapor did not result in detectable changes in peripheral nerve, somatosensory, auditory, or visual function when the offspring were assessed as adults. PMID:24607749

  7. Influence of Breaching the Connective Sheaths of the Donor Nerve on Its Myelinated Sensory Axons and on Their Sprouting into the End-to-Side Coapted Nerve in the Rat

    PubMed Central

    Žele, Tilen; Tomšič, Martin; Sketelj, Janez; Bajrović, Fajko F.

    2012-01-01

    Abstract The influence of breaching the connective sheaths of the donor sural nerve on axonal sprouting into the end-to-side coapted peroneal nerve was examined in the rat. In parallel, the effect of these procedures on the donor nerve was assessed. The sheaths of the donor nerve at the coaptation site were either left completely intact (group A) or they were breached by epineurial sutures (group B), an epineurial window (group C), or a perineurial window (group D). In group A, the compound action potential (CAP) of sensory axons was detected in ∼10% and 40% of the recipient nerves at 4 and 8 weeks, respectively, which was significantly less frequently than in group D at both recovery periods. In addition, the number of myelinated axons in the recipient nerve was significantly larger in group D than in other groups at 4 weeks. At 8 weeks, the number of axons in group A was only ∼15% of the axon numbers in other groups (p<0.05). Focal subepineurial degenerative changes in the donor nerves were only seen after 4 weeks, but not later. The average CAP area and the total number of myelinated axons in the donor nerves were not different among the experimental groups. In conclusion, myelinated sensory axons are able to penetrate the epiperineurium of donor nerves after end-to-side nerve coaption; however, their ingrowth into recipient nerves is significantly enhanced by breaching the epiperineurial sheets at the coaptation site. Breaching does not cause permanent injury to the donor nerve. PMID:22873667

  8. Mesenchymal stem cells and their secretome partially restore nerve and urethral function in a dual muscle and nerve injury stress urinary incontinence model.

    PubMed

    Deng, Kangli; Lin, Dan Li; Hanzlicek, Brett; Balog, Brian; Penn, Marc S; Kiedrowski, Matthew J; Hu, Zhiquan; Ye, Zhangqun; Zhu, Hui; Damaser, Margot S

    2015-01-15

    Childbirth injures muscles and nerves responsible for urinary continence. Mesenchymal stem cells (MSCs) or their secretome given systemically could provide therapeutic benefit for this complex multisite injury. We investigated whether MSCs or their secretome, as collected from cell culture, facilitate recovery from simulated childbirth injury. Age-matched female Sprague-Dawley rats received pudendal nerve crush and vaginal distension (PNC+VD) and a single intravenous (iv) injection of 2 million MSCs or saline. Controls received sham injury and iv saline. Additional rats received PNC+VD and a single intraperitoneal (ip) injection of concentrated media conditioned by MSCs (CCM) or concentrated control media (CM). Controls received a sham injury and ip CM. Urethral and nerve function were assessed with leak point pressure (LPP) and pudendal nerve sensory branch potential (PNSBP) recordings 3 wk after injury. Urethral and pudendal nerve anatomy were assessed qualitatively by blinded investigators. Quantitative data were analyzed using one-way ANOVA and Holm-Sidak post hoc tests with P < 0.05 indicating significant differences. Both LPP and PNSBP were significantly decreased 3 wk after PNC+VD with saline or CM compared with sham-injured rats, but not with MSC or CCM. Elastic fiber density in the urethra increased and changed in orientation after PNC+VD, with a greater increase in elastic fibers with MSC or CCM. Pudendal nerve fascicles were less dense and irregularly shaped after PNC+VD and had reduced pathology with MSC or CCM. MSC and CCM provide similar protective effects after PNC+VD, suggesting that MSCs act via their secretions in this dual muscle and nerve injury. PMID:25377914

  9. Sensory functions of motile cilia and implication for bronchiectasis

    PubMed Central

    Jain, Raksha; Javidan-Nejad, Cylen; Alexander-Brett, Jennifer; Horani, Amjad; Cabellon, Michelle C.; Walter, Michael J.; Brody, Steven L.

    2013-01-01

    Cilia are specialized organelles that extend from the surface of cells into the local environment. Airway epithelial cell cilia are motile to provide mucociliary clearance for host defense. On other cells, solitary cilia are specialized to detect chemical or mechanosensory signals. Sensory proteins in motile cilia have recently been identified that detect shear stress, osmotic force, fluid flow, bitter taste and sex hormones. The relationship of sensory function in human motile cilia to disease is now being revealed. One example is polycystin-1 and polycystin-2. As a complex, these proteins function as a flow sensor in cilia and are mutated in autosomal dominant polycystic kidney disease (ADPKD). The polycystins are also expressed in motile cilia of the airways, potentially operating as sensors in the lung. Computed tomography studies from patients with ADPKD revealed radiographic evidence for bronchiectasis, suggesting that polycystin-1 and -2 are important in lung function. The expression of this complex and sensory channel TRPV4, and bitter taste and sex hormones receptors in motile cilia indicate that the cell is wired to interpret environmental cues to regulate cilia beat frequency and other functions. Defective signaling of sensory proteins may result in a ciliopathy that includes lung disease. PMID:22202111

  10. Assessment of recurrent laryngeal nerve function during thyroid surgery

    PubMed Central

    Douglas, J; Smith, B; Dougherty, T; Ayshford, C

    2014-01-01

    Introduction There is disparity in the reported incidence of temporary and permanent recurrent laryngeal nerve (RLN) palsy following thyroidectomy. Much of the disparity is due to the method of assessing vocal cord function. We sought to identify the incidence and natural history of temporary and permanent vocal cord palsy following thyroid surgery. The authors wanted to establish whether intraoperative nerve monitoring and stimulation aids in prognosis when managing vocal cord palsy. Methods Prospective data on consecutive thyroid operations were collected. Intraoperative nerve monitoring and stimulation, using an endotracheal tube mounted device, was performed in all cases. Endoscopic examination of the larynx was performed on the first postoperative day and at three weeks. Results Data on 102 patients and 123 nerves were collated. Temporary and permanent RLN palsy rates were 6.1% and 1.7%. Most RLN palsies were identified on the first postoperative day with all recognised at the three-week review. No preoperative clinical risk factors were identified. Although dysphonia at the three-week follow-up visit was the only significant predictor of vocal cord palsy, only two-thirds of patients with cord palsies were dysphonic. Intraoperative nerve monitoring and stimulation did not predict outcome in terms of vocal cord function. Conclusions Temporary nerve palsy rates were consistent with other series where direct laryngoscopy is used to assess laryngeal function. Direct laryngoscopy is the only reliable measure of cord function, with intraoperative monitoring being neither a reliable predictor of cord function nor a predictor of eventual laryngeal function. The fact that all temporary palsies recovered within four months has implications for staged procedures. PMID:24780671

  11. Each sensory nerve arising from the geniculate ganglion expresses a unique fingerprint of neurotrophin and neurotrophin receptor genes.

    PubMed

    Farbman, Albert I; Guagliardo, Nick; Sollars, Suzanne I; Hill, David L

    2004-12-01

    Neurons in the geniculate ganglion, like those in other sensory ganglia, are dependent on neurotrophins for survival. Most geniculate ganglion neurons innervate taste buds in two regions of the tongue and two regions of the palate; the rest are cutaneous nerves to the skin of the ear. We investigated the expression of four neurotrophins, nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), neurotrophin 3 (NT-3), and NT-4, and five neurotrophin receptors, trkA, trkB, trkC, p75, and truncated trkB (Trn-B) in single sensory neurons of the adult rat geniculate ganglion associated with the five innervation fields. For fungiform papillae, a glass pipette containing biotinylated dextran was placed over the target papilla and the tracer was iontophoresed into the target papilla. For the other target fields, Fluoro-Gold was microinjected. After 3 days, geniculate ganglia were harvested, sectioned, and treated histochemically (for biotinylated dextran) or immunohistochemically (for Fluoro-Gold) to reveal the neurons containing the tracer. Single labeled neurons were harvested from the slides and subjected to RNA amplification and RT-PCR to reveal the neurotrophin or neurotrophin receptor genes that were expressed. Neurons projecting from the geniculate ganglion to each of the five target fields had a unique expression profile of neurotrophin and neurotrophic receptor genes. Several individual neurons expressed more than one neurotrophin receptor or more than one neurotrophin gene. Although BDNF is significantly expressed in taste buds, its primary high affinity receptor, trkB, was not prominently expressed in the neurons. The results are consistent with the interpretation that at least some, perhaps most, of the trophic influence on the sensory neurons is derived from the neuronal somata, and the trophic effect is paracrine or autocrine, rather than target derived. The BDNF in the taste bud may also act in a paracrine or autocrine manner on the trkB expressed in taste buds, as shown by others. PMID:15495212

  12. Parasympathetic Functions in Children with Sensory Processing Disorder

    PubMed Central

    Schaaf, Roseann C.; Benevides, Teal; Blanche, Erna Imperatore; Brett-Green, Barbara A.; Burke, Janice P.; Cohn, Ellen S.; Koomar, Jane; Lane, Shelly J.; Miller, Lucy Jane; May-Benson, Teresa A.; Parham, Diane; Reynolds, Stacey; Schoen, Sarah A.

    2009-01-01

    The overall goal of this study was to determine if parasympathetic nervous system (PsNS) activity is a significant biomarker of sensory processing difficulties in children. Several studies have demonstrated that PsNS activity is an important regulator of reactivity in children, and thus, it is of interest to study whether PsNS activity is related to sensory reactivity in children who have a type of condition associated with sensory processing disorders termed sensory modulation dysfunction (SMD). If so, this will have important implications for understanding the mechanisms underlying sensory processing problems of children and for developing intervention strategies to address them. The primary aims of this project were: (1) to evaluate PsNS activity in children with SMD compared to typically developing (TYP) children, and (2) to determine if PsNS activity is a significant predictor of sensory behaviors and adaptive functions among children with SMD. We examine PsNS activity during the Sensory Challenge Protocol; which includes baseline, the administration of eight sequential stimuli in five sensory domains, recovery, and also evaluate response to a prolonged auditory stimulus. As a secondary aim we examined whether subgroups of children with specific physiological and behavioral sensory reactivity profiles can be identified. Results indicate that as a total group the children with severe SMD demonstrated a trend for low baseline PsNS activity, compared to TYP children, suggesting this may be a biomarker for SMD. In addition, children with SMD as a total group demonstrated significantly poorer adaptive behavior in the communication and daily living subdomains and in the overall Adaptive Behavior Composite of the Vineland than TYP children. Using latent class analysis, the subjects were grouped by severity and the severe SMD group had significantly lower PsNS activity at baseline, tones and prolonged auditory. These results provide preliminary evidence that children who demonstrate severe SMD may have physiological activity that is different from children without SMD, and that these physiological and behavioral manifestations of SMD may affect a child's ability to engage in everyday social, communication, and daily living skills. PMID:20300470

  13. Parasympathetic functions in children with sensory processing disorder.

    PubMed

    Schaaf, Roseann C; Benevides, Teal; Blanche, Erna Imperatore; Brett-Green, Barbara A; Burke, Janice P; Cohn, Ellen S; Koomar, Jane; Lane, Shelly J; Miller, Lucy Jane; May-Benson, Teresa A; Parham, Diane; Reynolds, Stacey; Schoen, Sarah A

    2010-01-01

    The overall goal of this study was to determine if parasympathetic nervous system (PsNS) activity is a significant biomarker of sensory processing difficulties in children. Several studies have demonstrated that PsNS activity is an important regulator of reactivity in children, and thus, it is of interest to study whether PsNS activity is related to sensory reactivity in children who have a type of condition associated with sensory processing disorders termed sensory modulation dysfunction (SMD). If so, this will have important implications for understanding the mechanisms underlying sensory processing problems of children and for developing intervention strategies to address them. The primary aims of this project were: (1) to evaluate PsNS activity in children with SMD compared to typically developing (TYP) children, and (2) to determine if PsNS activity is a significant predictor of sensory behaviors and adaptive functions among children with SMD. We examine PsNS activity during the Sensory Challenge Protocol; which includes baseline, the administration of eight sequential stimuli in five sensory domains, recovery, and also evaluate response to a prolonged auditory stimulus. As a secondary aim we examined whether subgroups of children with specific physiological and behavioral sensory reactivity profiles can be identified. Results indicate that as a total group the children with severe SMD demonstrated a trend for low baseline PsNS activity, compared to TYP children, suggesting this may be a biomarker for SMD. In addition, children with SMD as a total group demonstrated significantly poorer adaptive behavior in the communication and daily living subdomains and in the overall Adaptive Behavior Composite of the Vineland than TYP children. Using latent class analysis, the subjects were grouped by severity and the severe SMD group had significantly lower PsNS activity at baseline, tones and prolonged auditory. These results provide preliminary evidence that children who demonstrate severe SMD may have physiological activity that is different from children without SMD, and that these physiological and behavioral manifestations of SMD may affect a child's ability to engage in everyday social, communication, and daily living skills. PMID:20300470

  14. Microscale Electrode Implantation during Nerve Repair: Effects on Nerve Morphology, Electromyography, and Recovery of Muscle Contractile Function

    PubMed Central

    Urbanchek, Melanie G; Wei, Benjamin; Egeland, Brent M; Abidian, Mohammad R; Kipke, Daryl R; Cederna, Paul S

    2011-01-01

    Background Our goal is to develop a peripheral nerve electrode with long-term stability and fidelity for use in nerve-machine interfaces. Microelectromechanical systems (MEMS) use silicon probes that contain multi-channel actuators, sensors, and electronics. We tested the null hypothesis that implantation of MEMS probes do not have a detrimental effect on peripheral nerve function or regeneration. Methods A rat hindlimb, peroneal nerve model was utilized in all experimental groups: a) intact nerve (Control, n= 10); b) nerve division and repair (Repair, n= 9); and c) Nerve division, insertion of MEMS probe, and repair (Repair + Probe, n=9). Nerve morphology, nerve to muscle compound action potential (CMAP) studies, walking tracks, and extensor digitorum longus (EDL) muscle function tests were evaluated following an 80 day recovery. Results Repair and Repair + Probe showed no differences in axon count, axon size, percent non-neural area, CMAP amplitude, latency, muscle mass, muscle force, or walking track scores. Though there was some local fibrosis around each MEMS probe, this did not lead to measurable detrimental effects in any anatomic or functional outcome measurements. Conclusions The lack of a significant difference between Repair and Repair + Probe groups in histology, CMAP, walking tracks, and muscle force suggests that MEMS electrodes are compatible with regenerating axons and show promise for establishing chemical and electrical interfaces with peripheral nerves. PMID:21921739

  15. Rectal Mechano-sensory Function in Patients with Carcinoid Diarrhea

    PubMed Central

    Gregersen, Tine; Brock, Christina; Haase, Anne-Mette; Laurberg, Søren; Drewes, Asbjørn M; Grønbæk, Henning; Krogh, Klaus

    2016-01-01

    Background/Aims In patients with neuroendocrine tumors, excessive production of serotonin and other amines may cause the carcinoid syndrome, which is mainly characterized by diarrhea and flushing. Little is known about the pathophysiology of carcinoid diarrhea. In several other groups of patients, diarrhea may be associated with rectal hypersensitivity and increased rectal tone. Therefore, the aim of the present study was to compare rectal sensitivity and compliance in patients with carcinoid diarrhea and in healthy subjects. Methods Twelve patients (6 males, aged 54–78 years, median 65 years), with carcinoid diarrhea and 19 healthy subjects (7 males, aged 50–78 years, median 61 years) were included. Rectal mechanical and heat stimulation was used for assessment of rectal mechano-sensory properties. Results Overall, 5.3% higher temperatures were needed to elicit sensory responses in patients with carcinoid diarrhea than in healthy subjects (P = 0.015). Posthoc analyses revealed that the sensory threshold to heat was 48.1 ± 3.1°C in patients vs 44.7 ± 4.7°C in healthy subjects (P = 0.041). In contrast, patients and healthy subjects showed no overall differences in rectal sensory response to mechanical distension (P = 0.731) or rectal compliance (P = 0.990). Conclusions Patients with carcinoid diarrhea have higher sensory thresholds to heat stimulation in comparison to healthy subjects, but normal rectal sensation to mechanical distension and normal compliance. Therefore, treatment of carcinoid diarrhea should aim at prolonging gastrointestinal transit and decreasing secretion, rather than modifying rectal mechano-sensory function. PMID:26690884

  16. Sensory integration functions of children with cochlear implants.

    PubMed

    Koester, AnjaLi Carrasco; Mailloux, Zoe; Coleman, Gina Geppert; Mori, Annie Baltazar; Paul, Steven M; Blanche, Erna; Muhs, Jill A; Lim, Deborah; Cermak, Sharon A

    2014-01-01

    OBJECTIVE. We investigated sensory integration (SI) function in children with cochlear implants (CIs). METHOD. We analyzed deidentified records from 49 children ages 7 mo to 83 mo with CIs. Records included Sensory Integration and Praxis Tests (SIPT), Sensory Processing Measure (SPM), Sensory Profile (SP), Developmental Profile 3 (DP-3), and Peabody Developmental Motor Scales (PDMS), with scores depending on participants' ages. We compared scores with normative population mean scores and with previously identified patterns of SI dysfunction. RESULTS. One-sample t tests revealed significant differences between children with CIs and the normative population on the majority of the SIPT items associated with the vestibular and proprioceptive bilateral integration and sequencing (VPBIS) pattern. Available scores for children with CIs on the SPM, SP, DP-3, and PDMS indicated generally typical ratings. CONCLUSION. SIPT scores in a sample of children with CIs reflected the VPBIS pattern of SI dysfunction, demonstrating the need for further examination of SI functions in children with CIs during occupational therapy assessment and intervention planning. PMID:25184469

  17. A biomaterials approach to peripheral nerve regeneration: bridging the peripheral nerve gap and enhancing functional recovery

    PubMed Central

    Daly, W.; Yao, L.; Zeugolis, D.; Windebank, A.; Pandit, A.

    2012-01-01

    Microsurgical techniques for the treatment of large peripheral nerve injuries (such as the gold standard autograft) and its main clinically approved alternative—hollow nerve guidance conduits (NGCs)—have a number of limitations that need to be addressed. NGCs, in particular, are limited to treating a relatively short nerve gap (4 cm in length) and are often associated with poor functional recovery. Recent advances in biomaterials and tissue engineering approaches are seeking to overcome the limitations associated with these treatment methods. This review critically discusses the advances in biomaterial-based NGCs, their limitations and where future improvements may be required. Recent developments include the incorporation of topographical guidance features and/or intraluminal structures, which attempt to guide Schwann cell (SC) migration and axonal regrowth towards their distal targets. The use of such strategies requires consideration of the size and distribution of these topographical features, as well as a suitable surface for cell–material interactions. Likewise, cellular and molecular-based therapies are being considered for the creation of a more conductive nerve microenvironment. For example, hurdles associated with the short half-lives and low stability of molecular therapies are being surmounted through the use of controlled delivery systems. Similarly, cells (SCs, stem cells and genetically modified cells) are being delivered with biomaterial matrices in attempts to control their dispersion and to facilitate their incorporation within the host regeneration process. Despite recent advances in peripheral nerve repair, there are a number of key factors that need to be considered in order for these new technologies to reach the clinic. PMID:22090283

  18. Olfactory Cilia: Linking Sensory Cilia Function and Human Disease

    PubMed Central

    Jenkins, Paul M.; McEwen, Dyke P.

    2009-01-01

    The olfactory system gives us an awareness of our immediate environment by allowing us to detect airborne stimuli. The components necessary for detection of these odorants are compartmentalized in the cilia of olfactory sensory neurons. Cilia are microtubule-based organelles, which can be found projecting from the surface of almost any mammalian cell, and are critical for proper olfactory function. Mislocalization of ciliary proteins and/or the loss of cilia cause impaired olfactory function, which is now recognized as a clinical manifestation of a broad class of human diseases, termed ciliopathies. Future work investigating the mechanisms of olfactory cilia function will provide us important new information regarding the pathogenesis of human sensory perception diseases. PMID:19406873

  19. Thermographic evaluation of hind paw skin temperature and functional recovery of locomotion after sciatic nerve crush in rats

    PubMed Central

    Z. Sacharuk, Viviane; A. Lovatel, Gisele; Ilha, Jocemar; Marcuzzo, Simone; Severo do Pinho, Alexandre; L. Xavier, Léder; A. Zaro, Milton; Achaval, Matilde

    2011-01-01

    INTRODUCTION: Peripheral nerves are often damaged by direct mechanical injury, diseases, and tumors. The peripheral nerve injuries that result from these conditions can lead to a partial or complete loss of motor, sensory, and autonomic functions, which in turn are related to changes in skin temperature, in the involved segments of the body. The aim of this study was to evaluate the changes in hind paw skin temperature after sciatic nerve crush in rats in an attempt to determine whether changes in skin temperature correlate with the functional recovery of locomotion. METHODS: Wistar rats were divided into three groups: control (n = 7), sham (n = 25), and crush (n = 25). All groups were subjected to thermographic, functional, and histological assessments. RESULTS: ΔT in the crush group was different from the control and sham groups at the 1st, 3rd and 7rd postoperative days (p<0.05). The functional recovery from the crush group returned to normal values between the 3rd and 4th week post-injury, and morphological analysis of the nerve revealed incomplete regeneration at the 4th week after injury. DISCUSSION: This study is the first demonstration that sciatic nerve crush in rats induces an increase in hind paw skin temperature and that skin temperature changes do not correlate closely with functional recovery PMID:21876984

  20. Topography and ultrastructure of sensory nerve endings in the joint capsules of the Kowari (Dasyuroides byrnei), an Australian marsupial.

    PubMed

    Strasmann, T; Halata, Z; Loo, S K

    1987-01-01

    The present investigation in concerned with the topography and ultrastructure of sensory nerve endings in the joint capsules of the Kowari (Dasyuroides byrnei), an Australian marsupial. Material for light and electron microscopy was obtained from shoulder, elbow and knee joint capsules. On the basis of differences in the organization of the connective tissue belonging to the fibrous layer, 3 variants of capsule structure have been distinguished: a rigid, a flaccid and an intermediate type. Whilst the rigid type is characterized by dense connective tissue in the clearly demarcated fibrous layer, the flaccid type shows loose, irregularly arranged connective tissue in the fibrous layer which merges into the synovial layer of the joint capsule. The morphology of the intermediate type corresponds to an intermediate stage between the former two types. In the fibrous layer of the joint capsules three different types of sensory nerve endings were observed: free nerve endings, Ruffini corpuscles and lamellated corpuscles. The free nerve endings are supplied by myelinated afferent axons (1-2 microns in diameter); the terminal thickenings of which are incompletely surrounded by a terminal Schwann cell. Ruffini corpuscles are present in three different varieties: small corpuscles without a perineural capsule predominantly within the flaccid part of the capsule; slightly larger corpuscles with an incomplete perineural capsule and large corpuscles resembling Golgi tendon organs which predominantly occur in the rigid parts of the capsule. The afferent myelinated axons measure 2-4 microns in diameter. The lamellated corpuscles show two variants: small corpuscles with a 2 to 4-layered perineural capsule in the rigid parts of the joint capsules and large corpuscles with two longitudinal clefts of the inner core in the flaccid parts. Both types are supplied by myelinated axons of 3-5 microns in diameter. Thus, in the fibrous layer of the rigid type of joint capsules large Ruffini and small lamellated corpuscles predominate, whereas the fibrous layer of the flaccid type coincides with small Ruffini and large lamellated corpuscles. The present data, therefore, corroborate the concept that the morphology of mechanoreceptors depends upon the texture of the surrounding connective tissue. PMID:3605642

  1. Anorectal physiology validated: a repeatability study of the motor and sensory tests of anorectal function.

    PubMed

    Rogers, J; Laurberg, S; Misiewicz, J J; Henry, M M; Swash, M

    1989-06-01

    Sixteen subjects (mean (s.d.) age 50.7 (12.8) years, three men) were studied on two separate occasions by two experienced investigators in random order. A standard protocol of anatomical, manometric and electrophysiological assessments of anorectal motor and sensory function was followed. No significant differences were found between the results obtained by the two investigators in the measurements of perineal descent, anal canal length, and canal resting pressure and squeeze pressure, pudendal nerve terminal motor latency, single-fibre electromyography fibre density of the external anal sphincter, and thresholds of mucosal electrosensitivity. This study shows that the standard tests of anorectal sensorimotor function are repeatable by different investigators. In addition, it suggests that comparison of data obtained in different centres using these techniques is valid. PMID:2758270

  2. 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

  3. The influence of vascularization of transplanted processed allograft nerve on return of motor function in rats.

    PubMed

    Giusti, Guilherme; Lee, Joo-Yup; Kremer, Thomas; Friedrich, Patricia; Bishop, Allen T; Shin, Alexander Y

    2016-02-01

    Processed nerve allografts have become an alternative to repair segmental nerve defects, with results comparable with autografts regarding sensory recovery; however, they have failed to reproduce comparable motor recovery. The purpose of this study was to determine how revascularizaton of processed nerve allograft would affect motor recovery. Eighty-eight rats were divided in four groups of 22 animals each. A unilateral 10-mm sciatic nerve defect was repaired with allograft (group I), allograft wrapped with silicone conduit (group II), allograft augmented with vascular endothelial growth factor (group III), or autograft (group IV). Eight animals from each group were sacrificed at 3 days, and the remaining animals at 16 weeks. Revascularization was evaluated by measuring the graft capillary density at 3 days and 16 weeks. Measurements of ankle contracture, compound muscle action potential, tibialis anterior muscle weight and force, and nerve histomorphometry were performed at 16 weeks. All results were normalized to the contralateral side. The results of capillary density at 3 days were 0.99% ± 1.3% for group I, 0.33% ± 0.6% for group II, 0.05% ± 0.1% for group III, and 75.6% ± 45.7% for group IV. At 16 weeks, the results were 69.9% ± 22.4% for group I, 37.0% ± 16.6% for group II, 84.6% ± 46.6% for group III, and 108.3% ± 46.8% for group IV. The results of muscle force were 47.5% ± 14.4% for group I, 21.7% ± 13.5% for group II, 47.1% ± 7.9% for group III, and 54.4% ± 10.6% for group IV. The use of vascular endothelial growth factor in the fashion used in this study improved neither the nerve allograft short-term revascularization nor the functional motor recovery after 16 weeks. Blocking allograft vascularization from surrounding tissues was detrimental for motor recovery. The processed nerve allografts used in this study showed similar functional motor recovery compared with that of the autograft. © 2014 Wiley Periodicals, Inc. Microsurgery 36:134-143, 2016. PMID:25557845

  4. A quantitative ultrastructural study of motor and sensory lumbosacral nerve roots in the thalidomide-treated rabbit fetus.

    PubMed

    de Iongh, R U

    1990-11-01

    A quantitative electron microscopic study was conducted on the dorsal and ventral nerve roots (L7-S1) supplying the hindlimbs of control and thalidomide-treated rabbit fetuses. The ventral roots at segmental levels L7 and S1 of treated nondeformed fetuses (TND) and deformed fetuses, demonstrated significant reductions (20-30%) of four of the parameters measured; total fascicular area (TFA), myelinated axon number (AN), Schwann cell counts (SCC) and axoplasmic area. In the dorsal roots of treated animals, thalidomide affected primarily segmental level S2, where significant reductions (15-30%) were observed in three parameters (TFA, AN, SCC). The occurrence of significant reductions in these measures in TND fetuses may indicate a neurotoxic action for thalidomide in the embryo. Despite apparent reductions in Schwann cell numbers in dorsal and ventral nerve roots, analyses of axon caliber and myelin sheath thickness indicated no evidence for any effects of thalidomide on the myelination of either sensory or motor axons. The segmental distribution of the axonal lesion, being maximal at segmental levels L7 and S1 in the ventral roots and at segmental level S2 in the dorsal roots, indicates a discrete period during development when nervous tissue is susceptible to the effects of thalidomide. The results of this study suggest thalidomide may have effects on neural development as well as on limb development. PMID:2121906

  5. Axon glycoprotein routing in nerve polarity, function, and repair.

    PubMed

    Abad-Rodríguez, José; Díez-Revuelta, Natalia

    2015-07-01

    Nervous system function relies on the capacity of neurons to organize specialized domains for impulse reception or transmission. Such a polarized architecture relies on highly discriminatory and efficient mechanisms for the transport and targeting of required molecules to their functional positions. Glycans play a central role in polarized traffic based on their extraordinary capacity to encrypt bio-information. Glycan-based interactions exquisitely regulate cargo selection, trafficking, and targeting to the axon membrane. This generates segregated functional domains, where basal nerve processes such as axon growth, synaptic activity, or myelination take place. Deciphering the details of the glycan structures and carbohydrate-binding molecules that underlie these mechanisms improves our knowledge of nerve physiology and defines novel specific approaches for neurological treatments. PMID:25936977

  6. Nerve growth factor-dependence of herpes simplex virus latency in peripheral sympathetic and sensory neurons in vitro.

    PubMed

    Wilcox, C L; Smith, R L; Freed, C R; Johnson, E M

    1990-04-01

    Previously, we reported that nerve growth factor (NGF) is required to maintain herpes simplex virus (HSV) latency in cultures of rat sympathetic neurons (Wilcox and Johnson, 1987, 1988). Here, we extend these results by showing that NGF was also required to maintain HSV latency in cultures of sensory neurons obtained from dorsal root ganglia of rats, monkeys, and humans. The interruption of the neuronal supply of NGF for 1 hr reactivated HSV, indicating that the latent virus was exquisitely sensitive to perturbations in the concentration or binding of NGF. A species-specific monoclonal antibody directed against the human NGF-receptor, which blocks NGF binding, reactivated latent HSV in human, but not rat, sensory neurons. In contrast, a monoclonal antibody against the rat NGF-receptor, which binds the receptor without blocking NGF action, did not produce reactivation. These results indicate that the effects of NGF on HSV latency are mediated via NGF binding to the NGF receptor. In addition, treatments that interfere with specific steps in the transduction of the NGF signal, including treatment with 6-hydroxydopamine and colchicine, reactivated latent HSV. Further, in neurons harboring latent virus, interruption of protein synthesis or RNA transcription for 1 hr resulted in viral reactivation, suggesting that a short-lived factor may be present in neurons which represses viral reactivation. PMID:2158529

  7. A new paradigm of electrical stimulation to enhance sensory neural function.

    PubMed

    Breen, Paul P; ÓLaighin, Gearóid; McIntosh, Caroline; Dinneen, Sean F; Quinlan, Leo R; Serrador, Jorge M

    2014-08-01

    The ability to improve peripheral neural transmission would have significant therapeutic potential in medicine. A technology of this kind could be used to restore and/or enhance sensory function in individuals with depressed sensory function, such as older adults or patients with peripheral neuropathies. The goal of this study was to investigate if a new paradigm of subsensory electrical noise stimulation enhances somatosensory function. Vibration (50Hz) was applied with a Neurothesiometer to the plantar aspect of the foot in the presence or absence of subsensory electrical noise (1/f type). The noise was applied at a proximal site, on a defined region of the tibial nerve path above the ankle. Vibration perception thresholds (VPT) of younger adults were measured in control and experimental conditions, in the absence or presence of noise respectively. An improvement of ∼16% in VPT was found in the presence of noise. These are the first data to demonstrate that modulation of axonal transmission with externally applied electrical noise improves perception of tactile stimuli in humans. PMID:24894033

  8. The impact and specificity of nerve perturbation on novel vibrotactile sensory letter learning.

    PubMed

    Passmore, Steven R; Bosse, Jessica; Murphy, Bernadette; Lee, Timothy D

    2014-12-01

    The purposes of this study were to determine if induced radiating paresthesia interferes with (a) acquisition and/or (b) utilization of complex tactile information, and (c) identify whether interference reflects tactile masking or response competition. Radiating ulnar (experiment 1) and median (experiment 2) nerve paresthesia was quantified on ulnar innervated vibrotactile Morse code letter acquisition and recollection tasks. Induced paresthesia differentially impacted letter acquisition and recollection, but only when presented to the same anatomical spatial location. PMID:24844345

  9. Nerve growth factor enhances the excitability of rat sensory neurons through activation of the atypical protein kinase C isoform, PKMζ.

    PubMed

    Zhang, Y H; Kays, J; Hodgdon, K E; Sacktor, T C; Nicol, G D

    2012-01-01

    Our previous work showed that nerve growth factor (NGF) increased the excitability of small-diameter capsaicin-sensitive sensory neurons by activating the p75 neurotrophin receptor and releasing sphingolipid-derived second messengers. Whole cell patch-clamp recordings were used to establish the signaling pathways whereby NGF augments action potential (AP) firing (i.e., sensitization). Inhibition of MEK1/2 (PD-98059), PLC (U-73122, neomycin), or conventional/novel isoforms of PKC (bisindolylmaleimide I) had no effect on the sensitization produced by NGF. Pretreatment with a membrane-permeable, myristoylated pseudosubstrate inhibitor of atypical PKCs (aPKCs: PKMζ, PKCζ, and PKCλ/ι) blocked the NGF-induced increase in AP firing. Inhibitors of phosphatidylinositol 3-kinase (PI3K) also blocked the sensitization produced by NGF. Isolated sensory neurons were also treated with small interfering RNA (siRNA) targeted to PKCζ. Both Western blots and quantitative real-time PCR established that PKMζ, but neither full-length PKCζ nor PKCλ/ι, was significantly reduced after siRNA exposure. Treatment with these labeled siRNA prevented the NGF-induced enhancement of excitability. Furthermore, consistent with the high degree of catalytic homology for aPKCs, internal perfusion with active recombinant PKCζ or PKCι augmented excitability, recapitulating the sensitization produced by NGF. Internal perfusion with recombinant PKCζ suppressed the total potassium current and enhanced the tetrodotoxin-resistant sodium current. Pretreatment with the myristoylated pseudosubstrate inhibitor blocked the increased excitability produced by ceramide or internal perfusion with recombinant PKCζ. These results demonstrate that NGF leads to the activation of PKMζ that ultimately enhances the capacity of small-diameter capsaicin-sensitive sensory neurons to fire APs through a PI3K-dependent signaling cascade. PMID:21975456

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

    PubMed

    Yamada, M; Ishikawa, T; Yamanaka, A; Fujimori, A; Goto, K

    1997-10-01

    1. 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. 2. 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. 3. 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 micromol 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 ND(omega)-nitro-L-arginine methyl ester (1 micromol kg(-1) min(-1), i.v.) nor indomethacin (5 mg kg(-1), i.v.) affected the response. 4. 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). 5. 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%. 6. 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

  11. SNS/PN3 and SNS2/NaN sodium channel-like immunoreactivity in human adult and neonate injured sensory nerves.

    PubMed

    Yiangou, Y; Birch, R; Sangameswaran, L; Eglen, R; Anand, P

    2000-02-11

    Two tetrodotoxin-resistant voltage-gated sodium channels, SNS/PN3 and SNS2/NaN, have been described recently in small-diameter sensory neurones of the rat, and play a key role in neuropathic pain. Using region-specific antibodies raised against different peptide sequences of their alpha subunits, we show by Western blot evidence for the presence of these channels in human nerves and sensory ganglia. The expected fully mature 260 kDa component of SNS/PN3 was noted in all injured nerve tissues obtained from adults; however, for SNS2/NaN, smaller bands were found, most likely arising from protein degradation. There was increased intensity of the SNS/PN3 260 kDa band in nerves proximal to the site of injury, whereas it was decreased distally, suggesting accumulation at sites of injury; all adult patients had a positive Tinel's sign at the site of nerve injury, indicating mechanical hypersensitivity. Injured nerves from human neonates showed similar results for both channels, but neonate neuromas lacked the SNS2/NaN 180 kDa molecular form, which was strongly present in adult neuromas. The distribution of SNS/PN3 and SNS2/NaN sodium channels in injured human nerves indicates that they represent targets for novel analgesics, and could account for some differences in the development of neuropathic pain in infants. PMID:10675548

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

    PubMed

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

    2011-07-01

    We have recently shown that manual stimulation of target muscles promotes functional recovery after transection and surgical repair to pure motor nerves (facial: whisking and blink reflex; hypoglossal: tongue position). However, following facial nerve repair, manual stimulation is detrimental if sensory afferent input is eliminated by, e.g., infraorbital nerve extirpation. To further understand the interplay between sensory input and motor recovery, we performed simultaneous cut-and-suture lesions on both the facial and the infraorbital nerves and examined whether stimulation of the sensory afferents from the vibrissae by a forced use would improve motor recovery. The efficacy of 3 treatment paradigms was assessed: removal of the contralateral vibrissae to ensure a maximal use of the ipsilateral ones (vibrissal stimulation; Group 2), manual stimulation of the ipsilateral vibrissal muscles (Group 3), and vibrissal stimulation followed by manual stimulation (Group 4). Data were compared to controls which underwent surgery but did not receive any treatment (Group 1). Four months after surgery, all three treatments significantly improved the amplitude of vibrissal whisking to 30° versus 11° in the controls of Group 1. The three treatments also reduced the degree of polyneuronal innervation of target muscle fibers to 37% versus 58% in Group 1. These findings indicate that forced vibrissal use and manual stimulation, either alone or sequentially, reduce target muscle polyinnervation and improve recovery of whisking function when both the sensory and the motor components of the trigemino-facial system regenerate. PMID:21526334

  13. 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

  14. Semantic Relevance, Domain Specificity and the Sensory/Functional Theory of Category-Specificity

    ERIC Educational Resources Information Center

    Sartori, Giuseppe; Gnoato, Francesca; Mariani, Ilenia; Prioni, Sara; Lombardi, Luigi

    2007-01-01

    According to the sensory/functional theory of semantic memory, Living items rely more on Sensory knowledge than Non-living ones. The sensory/functional explanation of category-specificity assumes that semantic features are organised on the basis of their content. We report here a study on DAT patients with impaired performance on Living items and…

  15. 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

  16. FLRT3 is expressed in sensory neurons after peripheral nerve injury and regulates neurite outgrowth.

    PubMed

    Robinson, M; Parsons Perez, M C; Tébar, L; Palmer, J; Patel, A; Marks, D; Sheasby, A; De Felipe, C; Coffin, R; Livesey, F J; Hunt, S P

    2004-10-01

    We used a molecular screen to identify genes upregulated in regenerating adult rat dorsal root ganglion cells. FLRT3 mRNA and protein characterized by a fibronectin type III domain and a leucine-rich repeat motif was upregulated in damaged sensory neurons. The protein was then transported into their peripheral and central processes where the FLRT3 protein was localized to presynaptic axon terminals. In vitro, the FLRT3 protein was expressed at the cell surface, regulated neurite outgrowth in sensory neurons, but did not exhibit homophilic binding. FLRT3 was widely expressed in the developing embryo, particularly in the central nervous system and somites. However, in the adult, we found no evidence for accumulation or reexpression of the FLRT3 protein in damaged axons of the central nervous system. We conclude that FLRT3 codes for a putative cell surface receptor implicated in both the development of the nervous system and in the regeneration of the peripheral nervous system (PNS). PMID:15485775

  17. Skin-derived stem cells transplanted into resorbable guides provide functional nerve regeneration after sciatic nerve resection.

    PubMed

    Marchesi, C; Pluderi, M; Colleoni, F; Belicchi, M; Meregalli, M; Farini, A; Parolini, D; Draghi, L; Fruguglietti, M E; Gavina, M; Porretti, L; Cattaneo, A; Battistelli, M; Prelle, A; Moggio, M; Borsa, S; Bello, L; Spagnoli, D; Gaini, S M; Tanzi, M C; Bresolin, N; Grimoldi, N; Torrente, Y

    2007-03-01

    The regeneration in the peripheral nervous system is often incomplete and the treatment of severe lesions with nerve tissue loss is primarily aimed at recreating nerve continuity. Guide tubes of various types, filled with Schwann cells, stem cells, or nerve growth factors are attractive as an alternative therapy to nerve grafts. In this study, we evaluated whether skin-derived stem cells (SDSCs) can improve peripheral nerve regeneration after transplantation into nerve guides. We compared peripheral nerve regeneration in adult rats with sciatic nerve gaps of 16 mm after autologous transplantation of GFP-labeled SDSCs into two different types of guides: a synthetic guide, obtained by dip coating with a L-lactide and trimethylene carbonate (PLA-TMC) copolymer and a collagen-based guide. The sciatic function index and the recovery rates of the compound muscle action potential were significantly higher in the animals that received SDSCs transplantation, in particular, into the collagen guide, compared to the control guides filled only with PBS. For these guides the morphological and immunohistochemical analysis demonstrated an increased number of myelinated axons expressing S100 and Neurofilament 70, suggesting the presence of regenerating nerve fibers along the gap. GFP positive cells were found around regenerating nerve fibers and few of them were positive for the expression of glial markers as S-100 and glial fibrillary acidic protein. RT-PCR analysis confirmed the expression of S100 and myelin basic protein in the animals treated with the collagen guide filled with SDSCs. These data support the hypothesis that SDSCs could represent a tool for future cell therapy applications in peripheral nerve regeneration. PMID:17203471

  18. Endogenous Prostaglandins and Afferent Sensory Nerves in Gastroprotective Effect of Hydrogen Sulfide against Stress-Induced Gastric Lesions

    PubMed Central

    Magierowski, Marcin; Jasnos, Katarzyna; Kwiecien, Slawomir; Drozdowicz, Danuta; Surmiak, Marcin; Strzalka, Malgorzata; Ptak-Belowska, Agata; Wallace, John L.; Brzozowski, Tomasz

    2015-01-01

    Hydrogen sulfide (H2S) plays an important role in human physiology, exerting vasodilatory, neuromodulatory and anti-inflammatory effects. H2S has been implicated in the mechanism of gastrointestinal integrity but whether this gaseous mediator can affect hemorrhagic lesions induced by stress has been little elucidated. We studied the effect of the H2S precursor L-cysteine, H2S-donor NaHS, the H2S synthesizing enzyme (CSE) activity inhibitor- D,L-propargylglycine (PAG) and the gastric H2S production by CSE/CBS/3-MST activity in water immersion and restraint stress (WRS) ulcerogenesis and the accompanying changes in gastric blood flow (GBF). The role of endogenous prostaglandins (PGs) and sensory afferent nerves releasing calcitonin gene-related peptide (CGRP) in the mechanism of gastroprotection induced by H2S was examined in capsaicin-denervated rats and those pretreated with capsazepine to inhibit activity of vanilloid receptors (VR-1). Rats were pretreated with vehicle, NaHS, the donor of H2S and or L-cysteine, the H2S precursor, with or without the concurrent treatment with 1) nonselective (indomethacin) and selective cyclooxygenase (COX)-1 (SC-560) or COX-2 (rofecoxib) inhibitors. The expression of mRNA and protein for COX-1 and COX-2 were analyzed in gastric mucosa pretreated with NaHS with or without PAG. Both NaHS and L-cysteine dose-dependently attenuated severity of WRS-induced gastric lesions and significantly increased GBF. These effects were significantly reduced by pretreatment with PAG and capsaicin denervation. NaHS increased gastric H2S production via CSE/CBS but not 3-MST activity. Inhibition of COX-1 and COX-2 activity significantly diminished NaHS- and L-cysteine-induced protection and hyperemia. NaHS increased expression of COX-1, COX-2 mRNAs and proteins and raised CGRP mRNA expression. These effects of NaHS on COX-1 and COX-2 protein contents were reversed by PAG and capsaicin denervation. We conclude that H2S exerts gastroprotection against WRS-induced gastric lesions by the mechanism involving enhancement in gastric microcirculation mediated by endogenous PGs, sensory afferent nerves releasing CGRP and the activation of VR-1 receptors. PMID:25774496

  19. Functional Recovery Following an End to Side Neurorrhaphy of the Accessory Nerve to the Suprascapular Nerve: Case Report

    PubMed Central

    Ray, Wilson Z.; Kasukurthi, Rahul; Yee, Andrew

    2009-01-01

    The use of end-to-side neurrorhaphy remains a controversial topic in peripheral nerve surgery. The authors report the long-term functional outcome following a modified end-to-side motor reinnervation using the spinal accessory to innervate the suprascapular nerve following a C5 to C6 avulsion injury. Additionally, functional outcomes of an end-to-end neurotization of the triceps branch to the axillary nerve and double fascicular transfer of the ulnar and medial nerve to the biceps and brachialis are presented. Excellent functional recoveries are found in respect to shoulder abduction and flexion and elbow flexion. Electronic supplementary material The online version of this article (doi:10.1007/s11552-009-9242-3) contains supplementary material, which is available to authorized users. PMID:19902308

  20. Relationship of estimated dietary intake of n-3 polyunsaturated fatty acids from fish with peripheral nerve function after adjusting for mercury exposure

    PubMed Central

    Wang, Yi; Goodrich, Jaclyn M.; Werner, Robert; Gillespie, Brenda; Basu, Niladri; Franzblau, Alfred

    2013-01-01

    Background Some clinical studies have suggested that ingestion of n-3 polyunsaturated fatty acids (PUFA) has neuroprotective effects on peripheral nerve function. However, few epidemiological studies have examined the effect of dietary n-3 PUFA intake from fish consumption on peripheral nerve function, and none have controlled for co-occurrence of methylmercury exposure from fish consumption. Objectives We evaluated the effect of estimated dietary n-3 PUFA intake on peripheral nerve function after adjusting for biomarkers of methylmercury and elemental mercury in a convenience sample of 515 dental professionals. Methods We measured sensory nerve conduction (peak latency and amplitude) of the median, ulnar and sural nerves and total mercury concentrations in hair and urine samples. We estimated daily intake (mg/day) of the total n-3 PUFA, n-3 docosahexaenoic acid (DHA), and n-3 eicosapentaenoic acid (EPA) based on a self-administrated fish consumption frequency questionnaire. We also collected information on mercury exposure, demographics and other covariates. Results The estimated median intakes of total n-3 PUFA, n-3 EPA, and n-3 DHA were 447, 105, and 179 mg/day, respectively. The mean mercury concentrations in urine (1.05μg/L) and hair (0.49μg/g) were not significantly different from the US general population. We found no consistent association between n-3 PUFA intake and sensory nerve conduction after adjusting for mercury concentrations in hair and urine although some positive associations were observed with the sural nerve. Conclusions In a convenience sample of dental professionals, we found little evidence suggesting that dietary intake of n-3 PUFAs from fish has any impact on peripheral nerve function after adjustment for methylmercury exposure from fish and elemental mercury exposure from dental amalgam. PMID:23538138

  1. Evolutionary origins of sensation in metazoans: functional evidence for a new sensory organ in sponges

    PubMed Central

    2014-01-01

    Background One of the hallmarks of multicellular organisms is the ability of their cells to trigger responses to the environment in a coordinated manner. In recent years primary cilia have been shown to be present as ‘antennae’ on almost all animal cells, and are involved in cell-to-cell signaling in development and tissue homeostasis; how this sophisticated sensory system arose has been little-studied and its evolution is key to understanding how sensation arose in the Animal Kingdom. Sponges (Porifera), one of the earliest evolving phyla, lack conventional muscles and nerves and yet sense and respond to changes in their fluid environment. Here we demonstrate the presence of non-motile cilia in sponges and studied their role as flow sensors. Results Demosponges excrete wastes from their body with a stereotypic series of whole-body contractions using a structure called the osculum to regulate the water-flow through the body. In this study we show that short cilia line the inner epithelium of the sponge osculum. Ultrastructure of the cilia shows an absence of a central pair of microtubules and high speed imaging shows they are non-motile, suggesting they are not involved in generating flow. In other animals non-motile, ‘primary’, cilia are involved in sensation. Here we show that molecules known to block cationic ion channels in primary cilia and which inhibit sensory function in other organisms reduce or eliminate sponge contractions. Removal of the cilia using chloral hydrate, or removal of the whole osculum, also stops the contractions; in all instances the effect is reversible, suggesting that the cilia are involved in sensation. An analysis of sponge transcriptomes shows the presence of several transient receptor potential (TRP) channels including PKD channels known to be involved in sensing changes in flow in other animals. Together these data suggest that cilia in sponge oscula are involved in flow sensation and coordination of simple behaviour. Conclusions This is the first evidence of arrays of non-motile cilia in sponge oscula. Our findings provide support for the hypothesis that the cilia are sensory, and if true, the osculum may be considered a sensory organ that is used to coordinate whole animal responses in sponges. Arrays of primary cilia like these could represent the first step in the evolution of sensory and coordination systems in metazoans. PMID:24410880

  2. Effects of Local Compression on Peroneal Nerve Function in Humans

    NASA Technical Reports Server (NTRS)

    Hargens, Alan R.; Botte, Michael J.; Swenson, Michael R.; Gelberman, Richard H.; Rhoades, Charles E.; Akeson, Wayne H.

    1993-01-01

    A new apparatus was developed to compress the anterior compartment selectively and reproducibly in humans. Thirty-five normal volunteers were studied to determine short-term thresholds of local tissue pressure that produce significant neuromuscular dysfunction. Local tissue fluid pressure adjacent to the deep peroneal nerve was elevated by the compression apparatus and continuously monitored for 2-3 h by the slit catheter technique. Elevation of tissue fluid pressure to within 35-40 mm Hg of diastolic blood pressure (approx. 40 mm Hg of in situ pressure in our subjects) elicited a consistent progression of neuromuscular deterioration including, in order, (a) gradual loss of sensation, as assessed by Semmes-Weinstein monofilaments, (b) subjective complaints, (c) reduced nerve conduction velocity, (d) decreased action potential amplitude of the extensor digitorum brevis muscle, and (e) motor weakness of muscles within the anterior compartment. Generally, higher intracompartment at pressures caused more rapid deterioration of neuromuscular function. In two subjects, when in situ compression levels were 0 and 30 mm Hg, normal neuromuscular function was maintained for 3 h. Threshold pressures for significant dysfunction were not always the same for each functional parameter studied, and the magnitudes of each functional deficit did not always correlate with compression level. This variable tolerance to elevated pressure emphasizes the need to monitor clinical signs and symptoms carefully in the diagnosis of compartment syndromes. The nature of the present studies was short term; longer term compression of myoneural tissues may result in dysfunction at lower pressure thresholds.

  3. Low-Level Laser Irradiation Improves Functional Recovery and Nerve Regeneration in Sciatic Nerve Crush Rat Injury Model

    PubMed Central

    Wang, Chau-Zen; Chen, Yi-Jen; Wang, Yan-Hsiung; Yeh, Ming-Long; Huang, Mao-Hsiung; Ho, Mei-Ling; Liang, Jen-I; Chen, Chia-Hsin

    2014-01-01

    The development of noninvasive approaches to facilitate the regeneration of post-traumatic nerve injury is important for clinical rehabilitation. In this study, we investigated the effective dose of noninvasive 808-nm low-level laser therapy (LLLT) on sciatic nerve crush rat injury model. Thirty-six male Sprague Dawley rats were divided into 6 experimental groups: a normal group with or without 808-nm LLLT at 8 J/cm2 and a sciatic nerve crush injury group with or without 808-nm LLLT at 3, 8 or 15 J/cm2. Rats were given consecutive transcutaneous LLLT at the crush site and sacrificed 20 days after the crush injury. Functional assessments of nerve regeneration were analyzed using the sciatic functional index (SFI) and hindlimb range of motion (ROM). Nerve regeneration was investigated by measuring the myelin sheath thickness of the sciatic nerve using transmission electron microscopy (TEM) and by analyzing the expression of growth-associated protein 43 (GAP43) in sciatic nerve using western blot and immunofluorescence staining. We found that sciatic-injured rats that were irradiated with LLLT at both 3 and 8 J/cm2 had significantly improved SFI but that a significant improvement of ROM was only found in rats with LLLT at 8 J/cm2. Furthermore, the myelin sheath thickness and GAP43 expression levels were significantly enhanced in sciatic nerve-crushed rats receiving 808-nm LLLT at 3 and 8 J/cm2. Taken together, these results suggest that 808-nm LLLT at a low energy density (3 J/cm2 and 8 J/cm2) is capable of enhancing sciatic nerve regeneration following a crush injury. PMID:25119457

  4. 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

  5. New Chemically Functionalized Nanomaterials for Electrical Nerve Agents Sensors

    NASA Astrophysics Data System (ADS)

    Simonato, Jean-Pierre; Clavaguera, Simon; Carella, Alexandre; Delalande, Michael; Raoul, Nicolas; Lenfant, Stephane; Vuillaume, Dominique; Dubois, Emmanuel

    2011-08-01

    A chemical receptor specific to traces of organophosphorus nerve agents (OPs) has been synthesized and grafted to carbon nanotubes and silicon nanowires in order to make electrical sensors. Our results show that it is possible to detect efficiently sub-ppm traces of OPs with excellent selectivity notably with the use of silicon nanowires by monitoring the Drain-Source current of the SiNW-FET at an optimum back Gate voltage as a function of time. First developments of a prototype have also been realized.

  6. Partial Recovery of Respiratory Function and Diaphragm Reinnervation following Unilateral Vagus Nerve to Phrenic Nerve Anastomosis in Rabbits

    PubMed Central

    Li, Lijun; Sun, Guixin; Tan, Jun

    2013-01-01

    Respiratory dysfunction is the leading cause of mortality following upper cervical spinal cord injury (SCI). Reinnervation of the paralyzed diaphragm via an anastomosis between phrenic nerve and a donor nerve is a potential strategy to mitigate ventilatory deficits. In this study, anastomosis of vagus nerve (VN) to phrenic nerve (PN) in rabbits was performed to assess the potential capacity of the VN to compensate for lost PN inputs. At first, we compared spontaneous discharge pattern, nerve thickness and number of motor fibers between these nerves. The PN exhibited a highly rhythmic discharge while the VN exhibited a variable frequency discharge pattern. The rabbit VN had fewer motor axons (105.3±12.1 vs. 268.1±15.4). Nerve conduction and respiratory function were measured 20 weeks after left PN transection with or without left VN-PN anastomosis. Compared to rabbits subjected to unilateral phrenicotomy without VN-PN anastomosis, diaphragm muscle action potential (AP) amplitude was improved by 292%, distal latency by 695%, peak inspiratory flow (PIF) by 22.6%, peak expiratory flow (PRF) by 36.4%, and tidal volume by 21.8% in the anastomosis group. However, PIF recovery was only 28.0%, PEF 28.2%, and tidal volume 31.2% of Control. Our results suggested that VN-PN anastomosis is a promising therapeutic strategy for partial restoration of diaphragm reinnervation, but further modification and improvements are necessary to realize the full potential of this technique. PMID:24265777

  7. Dual Nerve Transfers for Restoration of Shoulder Function After Brachial Plexus Avulsion Injury.

    PubMed

    Chu, Bin; Wang, Huan; Chen, Liang; Gu, Yudong; Hu, Shaonan

    2016-06-01

    The purpose of this study was to investigate the effectiveness of shoulder function restoration by dual nerve transfers, spinal accessory nerve to the suprascapular nerve and 2 intercostal nerves to the anterior branch of the axillary nerve, in patients with shoulder paralysis that resulted from brachial plexus avulsion injury. It was a retrospective analysis to assess the impact of a variety of factors on reanimation of shoulder functions with dual nerve transfers. A total of 19 patients were included in this study. Most of these patients sustained avulsions of C5, C6, and C7 nerve roots (16 patients). Three of them had avulsions of C5 and C6 roots only. Through a posterior approach, direct coaptation of the intercostal nerves and the anterior branch of the axillary nerve was performed, along with accessory nerve transfer to the suprascapular nerve. Satisfactory shoulder function recovery (93.83° of shoulder abduction and 54.00° of external rotation on average) was achieved after a 62-month follow-up. This dual nerve transfer procedure provided us with a reliable and effective method for shoulder function reconstruction after brachial plexus root avulsion, especially C5/C6/C7 avulsion. The level of evidence is therapeutic IV. PMID:26835823

  8. Sensory Processing in Preterm Preschoolers and Its Association with Executive Function

    PubMed Central

    Adams, Jenna N.; Feldman, Heidi M.; Huffman, Lynne C.; Loe, Irene M.

    2015-01-01

    Background Symptoms of abnormal sensory processing have been related to preterm birth, but have not yet been studied specifically in preterm preschoolers. The degree of association between sensory processing and other domains is important for understanding the role of sensory processing symptoms in the development of preterm children. Aims To test two related hypotheses: (1) preterm preschoolers have more sensory processing symptoms than full term preschoolers and (2) sensory processing is associated with both executive function and adaptive function in preterm preschoolers. Study Design Cross-sectional study Subjects Preterm children (≤34 weeks of gestation; n = 54) and full term controls (≥37 weeks of gestation; n = 73) ages 3-5 years. Outcome Measures Sensory processing was assessed with the Short Sensory Profile. Executive function was assessed with (1) parent ratings on the Behavior Rating Inventory of Executive Function- Preschool version and (2) a performance-based battery of tasks. Adaptive function was assessed with the Vineland Adaptive Behavior Scales-II. Results Preterm preschoolers showed significantly more sensory symptoms than full term controls. A higher percentage of preterm than full term preschoolers had elevated numbers of sensory symptoms (37% vs. 12%). Sensory symptoms in preterm preschoolers were associated with scores on executive function measures, but were not significantly associated with adaptive function. Conclusions Preterm preschoolers exhibited more sensory symptoms than full term controls. Preterm preschoolers with elevated numbers of sensory symptoms also showed executive function impairment. Future research should further examine whether sensory processing and executive function should be considered independent or overlapping constructs. PMID:25706317

  9. Electrophysiological assessment of sensory and cognitive function in children exposed to lead: a review

    SciTech Connect

    Otto, D.A.

    1987-09-01

    Studies of the effects of lead absorption on sensory evoked and slow brain potentials in children are reviewed. Studies of slow-wave voltage in children during sensory conditioning indicated a linear relationship to blood lead level in two studies; an effect that could not be replicated in an independent sample of children. Results of a fourth study indicated that slow-voltage measures were more sensitive to lead during active rather than passive conditioning. Conflicting evidence of lead effects on pattern-reversal visual evoked potentials in children was found in three studies. Evidence of increased latencies of brainstorm auditory evoked potentials at blood lead levels above 25/dl were reported in two studies. Sensory evoked potentials hold considerable promise as noninvasive, clinically valid, culture-free measures of the effects of lead exposure on sensory-nerve conduction, but further study is needed in humans and animals to clarify inconsistencies in the existing literature.

  10. An Investigation of Modifying Effects of Single Nucleotide Polymorphisms in Metabolism-related Genes on the Relationship between Peripheral Nerve Function and Mercury Levels in Urine and Hair

    PubMed Central

    Wang, Yi; Goodrich, Jaclyn M.; Werner, Robert; Gillespie, Brenda; Basu, Niladri; Franzblau, Alfred

    2012-01-01

    Mercury (Hg) is a potent neurotoxicant. We hypothesized that single nucleotide polymorphisms (SNPs) in genes coding glutathione-related proteins, selenoproteins and metallothioneins may modify the relationship of mercury biomarkers with changes in peripheral nerve function. Dental professionals (n=515) were recruited in 2009 and 2010. Sensory nerve function (onset latency, peak latency and amplitude) of the median, ulnar and sural nerves were recorded. Samples of urine, hair and DNA were collected. Covariates related to demographics, nerve function and elemental and methyl- mercury exposure were also collected. Subjects included 244 dentists (47.4%) and 269 non-dentists (52.2%; mostly dental hygienists and dental assistants). The mean mercury levels in urine (1.06μg/L) and hair (0.51μg/g) were not significantly different from the US general population (0.95 μg/L and 0.47μg/g, respectively). In multivariate linear models predicting nerve function adjusting for covariates, only 3 out of a total of 504 models showed stable and statistically significant interaction of SNPs with mercury biomarkers. Overall, given the possibility of false positives, the results suggested little evidence of effect modification of the SNPs on the relationship between mercury biomarkers with peripheral nerve function at exposure levels that are relevant to the general US population. PMID:22236634

  11. Nerve Injury Diminishes Opioid Analgesia through Lysine Methyltransferase-mediated Transcriptional Repression of μ-Opioid Receptors in Primary Sensory Neurons.

    PubMed

    Zhang, Yuhao; Chen, Shao-Rui; Laumet, Geoffroy; Chen, Hong; Pan, Hui-Lin

    2016-04-15

    The μ-opioid receptor (MOR, encoded by Oprm1) agonists are the mainstay analgesics for treating moderate to severe pain. Nerve injury causes down-regulation of MORs in the dorsal root ganglion (DRG) and diminishes the opioid effect on neuropathic pain. However, the epigenetic mechanisms underlying the diminished MOR expression caused by nerve injury are not clear. G9a (encoded by Ehmt2), a histone 3 at lysine 9 methyltransferase, is a key chromatin regulator responsible for gene silencing. In this study, we determined the role of G9a in diminished MOR expression and opioid analgesic effects in animal models of neuropathic pain. We found that nerve injury in rats induced a long-lasting reduction in the expression level of MORs in the DRG but not in the spinal cord. Nerve injury consistently increased the enrichment of the G9a product histone 3 at lysine 9 dimethylation in the promoter of Oprm1 in the DRG. G9a inhibition or siRNA knockdown fully reversed MOR expression in the injured DRG and potentiated the morphine effect on pain hypersensitivity induced by nerve injury. In mice lacking Ehmt2 in DRG neurons, nerve injury failed to reduce the expression level of MORs and the morphine effect. In addition, G9a inhibition or Ehmt2 knockout in DRG neurons normalized nerve injury-induced reduction in the inhibitory effect of the opioid on synaptic glutamate release from primary afferent nerves. Our findings indicate that G9a contributes critically to transcriptional repression of MORs in primary sensory neurons in neuropathic pain. G9a inhibitors may be used to enhance the opioid analgesic effect in the treatment of chronic neuropathic pain. PMID:26917724

  12. Depletion of Calcium Stores in Injured Sensory Neurons: Anatomic and Functional Correlates

    PubMed Central

    Gemes, Geza; Rigaud, Marcel; Weyker, Paul D.; Abram, Stephen E.; Weihrauch, Dorothee; Poroli, Mark; Zoga, Vasiliki; Hogan, Quinn H.

    2010-01-01

    Background Painful nerve injury leads to disrupted Ca2+ signaling in primary sensory neurons, including decreased endoplasmic reticulum (ER) Ca2+ storage. The present study examines potential causes and functional consequences of Ca2+ store limitation after injury. Methods Neurons were dissociated from axotomized fifth lumbar (L5) and the adjacent L4 dorsal root ganglia following L5 spinal nerve ligation that produced hyperalgesia, and were compared to neurons from control animals. Intracellular Ca2+ levels were measured with Fura-2 microfluorometry, and ER was labeled with probes or antibodies. Ultrastructural morphology was analyzed by electron microscopy of nondissociated dorsal root ganglia, and intracellular electrophysiological recordings were obtained from intact ganglia. Results Live neuron staining with BODIPY FL-X thapsigargin (Invitrogen, Carlsbad, CA) revealed a 40% decrease in sarco-endoplasmic reticulum Ca2+-ATPase binding in axotomized L5 neurons and a 34% decrease in L4 neurons. Immunocytochemical labeling for the ER Ca2+-binding protein calreticulin was unaffected by injury. Total length of ER profiles in electron micrographs was reduced by 53% in small axotomized L5 neurons, but increased in L4 neurons. Cisternal stacks of ER and aggregation of ribosomes occurred less frequently in axotomized neurons. Ca2+-induced Ca2+ release, examined by microfluorometry with dantrolene, was eliminated in axotomized neurons. Pharmacologic blockade of Ca2+-induced Ca2+ release with dantrolene produced hyperexcitability in control neurons, confirming its functional importance. Conclusions After axotomy, ER Ca2+ stores are reduced by anatomic loss and possibly diminished sarco-endoplasmic reticulum Ca2+-ATPase. The resulting disruption of Ca2+-induced Ca2+ release and protein synthesis may contribute to the generation of neuropathic pain. PMID:19602957

  13. Long-Term Functional Recovery after Facial Nerve Transection and Repair in the Rat

    PubMed Central

    Banks, Caroline A.; Knox, Christopher; Hunter, Daniel A.; Mackinnon, Susan E.; Hohman, Marc H.; Hadlock, Tessa A.

    2015-01-01

    Background The rodent model is commonly used to study facial nerve injury. Because of the exceptional regenerative capacity of the rodent facial nerve, it is essential to consider the timing when studying facial nerve regeneration and functional recovery. Short-term functional recovery data following transection and repair of the facial nerve has been documented by our laboratory. However, because of the limitations of the head fixation device, there is a lack of long-term data following facial nerve injury. The objective of this study was to elucidate the long-term time course and functional deficit following facial nerve transection and repair in a rodent model. Methods Adult rats were divided into group 1 (controls) and group 2 (experimental). Group 1 animals underwent head fixation, followed by a facial nerve injury, and functional testing was performed from day 7 to day 70. Group 2 animals underwent facial nerve injury, followed by delayed head fixation, and then underwent functional testing from months 6 to 8. Results There was no statistical difference between the average whisking amplitudes in group 1 and group 2 animals. Conclusion Functional whisking recovery 6 months after facial nerve injury is comparable to recovery within 1 to 4 months of transection and repair, thus the ideal window for evaluating facial nerve recovery falls within the 4 months after injury. PMID:25629206

  14. Dissociation between biochemical and functional effects of the aldose reductase inhibitor, ponalrestat, on peripheral nerve in diabetic rats.

    PubMed Central

    Cameron, N. E.; Cotter, M. A.

    1992-01-01

    1. The aim of the study was to examine the effects in rats of two different doses of the aldose reductase inhibitor, ponalrestat, on functional measures of nerve conduction and sciatic nerve biochemistry. 2. After 1 month, streptozotocin-induced diabetes produced 22%, 23% and 15% deficits in conduction velocity of sciatic nerves supplying gastrocnemius and tibialis anterior muscles and saphenous sensory nerve respectively compared to controls. These deficits were maintained over 2 months diabetes. 3. Slower-conducting motor fibres supplying the interosseus muscles of the foot did not show a diabetic deficit compared to onset controls, however, there was a 13% reduction in conduction velocity after 2 months diabetes relative to age-matched controls, indicating a maturation deficit. 4. Resistance to hypoxic conduction failure was investigated for sciatic nerve trunks in vitro. There was an increase in the duration of hypoxia necessary for an 80% reduction in compound action potential amplitude with diabetes. This was progressive; after 1 month, hypoxia time was increased by 22% and after 2 months by 57%. 5. The effect of 1-month treatment with the aldose reductase inhibitor, ponalrestat, on the abnormalities caused by an initial month of untreated diabetes was examined. Two doses of ponalrestat were employed, 8 mg kg-1 day-1 (which is equivalent to, or greater than, the blockade employed in clinical trials), and 100 mg kg-1 day-1. 6. Sciatic nerve sorbitol content was increased 7 fold by diabetes. Both doses were effective in reducing this; 70% for 8 mg kg-1 day-1, and to within the control range for 100 mg kg-1 day-1.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1467842

  15. Chitooligosaccharide Inhibits Scar Formation and Enhances Functional Recovery in a Mouse Model of Sciatic Nerve Injury.

    PubMed

    Hou, Hongping; Zhang, Lihai; Ye, Zuguang; Li, Jianrong; Lian, Zijian; Chen, Chao; He, Rong; Peng, Bo; Xu, Qihua; Zhang, Guangping; Gan, Wenbiao; Tang, Peifu

    2016-05-01

    Chitooligosaccharide (COS) has been shown to induce fibroblast apoptosis, indicating that it could be used as a material to inhibit scar formation. In the present study, we used a mouse model of sciatic nerve injury (SNI) to determine the role of COS in scar inhibition and functional recovery. The animals were divided into three groups: SNI, SNI + vehicle, and SNI + COS group. We performed a series of functional and histological examinations at ctrl, 0 min, 14 days, and 42 days, including behavioral recovery, percentage of regenerating axons, degree of scar formation, vascular changes, type I and type III collagen ratio, and percentage of demyelinated axons. The SNI + COS group exhibited better recovery of sensory and motor function and less scar formation. Two-photon microscopy showed that the percentage of regenerating axons was highest in the SNI + COS group at 14 and 42 days. Our results suggested that COS can inhibit scar formation and enhance functional recovery by inducing fibroblast death, altering the proportion of different vascular diameters, changing the ratio of type I/type III collagen, and reducing the percentage of demyelinated axons. COS might be a useful drug in the treatment of SNI to reduce scar formation, but additional research is required to clarify the relevant molecular pathways. PMID:25972239

  16. 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

  17. CGRP-like immunoreactivity in sensory nerve endings of the Golgi tendon organ. A light- and electron-microscopic study in the grey short-tailed opossum (Monodelphis domestica).

    PubMed

    Strasmann, T; Weihe, E; Halata, Z

    1990-01-01

    Using light- and electron-microscopic immunohistochemistry, it was shown that primary sensory nerve endings in Golgi tendon organs of the grey short-tailed opossum (Monodelphis domestica) contain immunoreactivities to a polyclonal antibody directed against calcitonin gene-related peptide (CGRP). Myelinated afferent axons (6-9 microns in diameter) of the Golgi tendon organs stained moderately for CGRP. Sensory nerve endings within the sensory compartment of the Golgi tendon organs displayed electron-dense accumulations corresponding to dark-brown staining in adjacent semithin sections. On the outer surface of tendon organs C fibre bundles were observed showing CGRP-like immunoreactivity. PMID:2349873

  18. Relationship between Social Competence and Sensory Processing in Children with High Functioning Autism Spectrum Disorders

    ERIC Educational Resources Information Center

    Hilton, Claudia; Graver, Kathleen; LaVesser, Patricia

    2007-01-01

    Purpose: This study examines the relationship between social competence and sensory processing in children with high functioning autism spectrum disorders. Methodology: Children, ages 6-10 (N = 36), with high functioning autism spectrum disorders were assessed using the Social Responsiveness Scale (SRS) and the Sensory Profile (SP). A bivariate…

  19. Sensory Function: Insights From Wave 2 of the National Social Life, Health, and Aging Project

    PubMed Central

    Kern, David W.; Wroblewski, Kristen E.; Chen, Rachel C.; Schumm, L. Philip; McClintock, Martha K.

    2014-01-01

    Objectives. Sensory function, a critical component of quality of life, generally declines with age and influences health, physical activity, and social function. Sensory measures collected in Wave 2 of the National Social Life, Health, and Aging Project (NSHAP) survey focused on the personal impact of sensory function in the home environment and included: subjective assessment of vision, hearing, and touch, information on relevant home conditions and social sequelae as well as an improved objective assessment of odor detection. Method. Summary data were generated for each sensory category, stratified by age (62–90 years of age) and gender, with a focus on function in the home setting and the social consequences of sensory decrements in each modality. Results. Among both men and women, older age was associated with self-reported impairment of vision, hearing, and pleasantness of light touch. Compared with women, men reported significantly worse hearing and found light touch less appealing. There were no gender differences for vision. Overall, hearing loss seemed to have a greater impact on social function than did visual impairment. Discussion. Sensory function declines across age groups, with notable gender differences for hearing and light touch. Further analysis of sensory measures from NSHAP Wave 2 may provide important information on how sensory declines are related to health, social function, quality of life, morbidity, and mortality in this nationally representative sample of older adults. PMID:25360015

  20. 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

  1. The Mid-Term Changes of Pulmonary Function Tests After Phrenic Nerve Transfer

    PubMed Central

    Yavari, Masoud; Hassanpour, Seyed Esmail; Khodayari, Mohammad

    2016-01-01

    Background: In the restoration of elbow flexion, the phrenic nerve has proven to be a good donor, but considering the role of the phrenic nerve in respiratory function, we cannot disregard the potential dangers of this method. Objectives: In the current study, we reviewed the results of pulmonary function tests (PFT) in four patients who underwent phrenic nerve transfer. Patients and Methods: We reviewed the results of serial spirometry tests, which were performed before and after phrenic nerve transfer surgery. Results: All patients regained Biceps power to M3 strength or above. None of our patients experienced pulmonary problems or respiratory complaints, but a significant reduction of spirometric parameters occurred after surgery. Conclusions: This study highlights the close link between the role of the phrenic nerve and pulmonary function, such that the use of this nerve as a transfer donor leads to spirometric impairments. PMID:27148498

  2. Functional motor recovery is improved due to local placement of GDNF microspheres after delayed nerve repair.

    PubMed

    Wood, Matthew D; Gordon, Tessa; Kemp, Stephen W P; Liu, Edward H; Kim, Howard; Shoichet, Molly S; Borschel, Gregory H

    2013-05-01

    The majority of bioengineering strategies to promote peripheral nerve regeneration after injury have focused on therapies to bridge large nerve defects while fewer therapies are being developed to treat other nerve injuries, such as nerve transection. We constructed delivery systems using fibrin gels containing either free GDNF or polylactide-glycolic acid (PLGA) microspheres with GDNF to treat delayed nerve repair, where ELISA verified GDNF release. We determined the formulation of microspheres containing GDNF that optimized nerve regeneration and functional recovery in a rat model of delayed nerve repair. Experimental groups underwent delayed nerve repair and treatment with GDNF microspheres in fibrin glue at the repair site or control treatments (empty microspheres or free GDNF without microspheres). Contractile muscle force, muscle mass, and MUNE were measured 12 weeks following treatment, where GDNF microspheres (2 weeks formulation) were superior compared to either no GDNF or short-term release of free GDNF to nerve. Nerve histology distal to the repair site demonstrated increased axon counts and fiber diameters due to GDNF microspheres (2 weeks formulation). GDNF microspheres partially reversed the deleterious effects of chronic nerve injury, and recovery was slightly favored with the 2 weeks formulation compared to the 4 weeks formulation. PMID:23239194

  3. PARP INHIBITION ALLEVIATES DIABETES-INDUCED SYSTEMIC OXIDATIVE STRESS AND NEURAL TISSUE 4-HYDROXYNONENAL ADDUCT ACCUMULATION: CORRELATION WITH PERIPHERAL NERVE FUNCTION

    PubMed Central

    Lupachyk, Sergey; Shevalye, Hanna; Maksimchyk, Yury; Drel, Viktor R.; Obrosova, Irina G.

    2011-01-01

    This study evaluated the role of poly(ADP-ribose) polymerase in systemic oxidative stress and 4-hydoxynonenal adduct accumulation in diabetic peripheral neuropathy. Control and streptozotocin-diabetic rats were maintained with or without treatment with the PARP inhibitor, 1,5-isoquinolinediol, 3 mg kg−1d−1, for 10 weeks after initial 2 weeks. Treatment efficacy was evaluated by poly(ADP-ribosyl)ated protein content in peripheral nerve and spinal cord (Western blot analysis) and dorsal root ganglion neurons and non-neuronal cells (fluorescent immunohistochemistry), as well as by indices of peripheral nerve function. Diabetic rats displayed increased urinary isoprostane and 8-hydroxy-2'-deoxyguanosine excretion (ELISA), 4-hydroxynonenal adduct accumulation in endothelial and Schwann cells of the peripheral nerve, neurons, astrocytes, and oligodendrocytes of the spinal cord, and neurons and glial cells of the dorsal root ganglia (double-label fluorescent immunohistochemistry) as well as motor and sensory nerve conduction velocity deficits, thermal hypoalgesia, and tactile allodynia. PARP inhibition counteracted diabetes-induced systemic oxidative stress and 4-hydroxynonenal adduct accumulation in peripheral nerve and spinal cord (Western blot analysis) and dorsal root ganglion neurons (perikarya, fluorescent immunohistochemistry) which correlated with improvement of large and small nerve fiber function. The findings reveal the important role of PARP activation in systemic oxidative stress and 4-hydroxynonenal adduct accumulation in diabetic peripheral neuropathy. PMID:21300148

  4. Advances of Peripheral Nerve Repair Techniques to Improve Hand Function: A Systematic Review of Literature

    PubMed Central

    P, Mafi; S, Hindocha; M, Dhital; M, Saleh

    2012-01-01

    Concepts of neuronal damage and repair date back to ancient times. The research in this topic has been growing ever since and numerous nerve repair techniques have evolved throughout the years. Due to our greater understanding of nerve injuries and repair we now distinguish between central and peripheral nervous system. In this review, we have chosen to concentrate on peripheral nerve injuries and in particular those involving the hand. There are no reviews bringing together and summarizing the latest research evidence concerning the most up-to-date techniques used to improve hand function. Therefore, by identifying and evaluating all the published literature in this field, we have summarized all the available information about the advances in peripheral nerve techniques used to improve hand function. The most important ones are the use of resorbable poly[(R)-3-hydroxybutyrate] (PHB), epineural end-to-end suturing, graft repair, nerve transfer, side to side neurorrhaphy and end to side neurorrhaphy between median, radial and ulnar nerves, nerve transplant, nerve repair, external neurolysis and epineural sutures, adjacent neurotization without nerve suturing, Agee endoscopic operation, tourniquet induced anesthesia, toe transfer and meticulous intrinsic repair, free auto nerve grafting, use of distal based neurocutaneous flaps and tubulization. At the same time we found that the patient’s age, tension of repair, time of repair, level of injury and scar formation following surgery affect the prognosis. Despite the thorough findings of this systematic review we suggest that further research in this field is needed. PMID:22431951

  5. Fluorescently Labeled Peptide Increases Identification of Degenerated Facial Nerve Branches during Surgery and Improves Functional Outcome

    PubMed Central

    Hussain, Timon; Mastrodimos, Melina B.; Raju, Sharat C.; Glasgow, Heather L.; Whitney, Michael; Friedman, Beth; Moore, Jeffrey D.; Kleinfeld, David; Steinbach, Paul; Messer, Karen; Pu, Minya; Tsien, Roger Y.; Nguyen, Quyen T.

    2015-01-01

    Nerve degeneration after transection injury decreases intraoperative visibility under white light (WL), complicating surgical repair. We show here that the use of fluorescently labeled nerve binding probe (F-NP41) can improve intraoperative visualization of chronically (up to 9 months) denervated nerves. In a mouse model for the repair of chronically denervated facial nerves, the intraoperative use of fluorescent labeling decreased time to nerve identification by 40% compared to surgeries performed under WL alone. Cumulative functional post-operative recovery was also significantly improved in the fluorescence guided group as determined by quantitatively tracking of the recovery of whisker movement at time intervals for 6 weeks post-repair. To our knowledge, this is the first description of an injectable probe that increases visibility of chronically denervated nerves during surgical repair in live animals. Future translation of this probe may improve functional outcome for patients with chronic denervation undergoing surgical repair. PMID:25751149

  6. Sensory responsiveness as a predictor of social severity in children with high functioning autism spectrum disorders.

    PubMed

    Hilton, Claudia L; Harper, Jacquelyn D; Kueker, Rachel Holmes; Lang, Andrea Runzi; Abbacchi, Anna M; Todorov, Alexandre; LaVesser, Patricia D

    2010-08-01

    This study examines the relationship between sensory responsiveness and social severity in children with high functioning autism spectrum disorders (HFASD; N = 36) and age-matched controls (N = 26) between 6 and 10 years old. Significant relationships were found between social responsiveness scale scores and each of the six sensory profile sensory system scores for children with HFASD and controls. Multivariate regression analyses revealed atypical scores from multisensory responsiveness, and responsiveness of the proximal senses of oral sensory/olfactory and touch as the strongest predictors of greater social impairment in the participants. Findings suggest that the relationship between sensory responsiveness and other autistic traits is more important than previously recognized and addressing sensory modulation issues in children with HFASD may be more critical than previously understood. PMID:20108030

  7. Ocular Motor and Sensory Function in Parkinson Disease

    PubMed Central

    Almer, Zina; Klein, Kathyrn S.; Marsh, Laura; Gerstenhaber, Melissa; Repka, Michael X.

    2011-01-01

    Purpose To evaluate the effect of dopaminergic medication and deep brain stimulation on ocular function in Parkinson disease (PD) and to measure vision-related quality of life in subjects with PD. Design Prospective comparative case series. Participants and Controls Twenty-seven PD and 16 control subjects were recruited. Methods We measured visual acuity, ocular motor function, convergence, and vision-related quality of life using the Visual Function Questionnaire–25 (VFQ-25). Visual sensory and motor measurements were made during the “on” and “off” states of PD dopaminergic treatment. Main Outcome Measures Convergence ability and vision related quality of life. Results The PD subjects had a mean age of 58.8 years; 30% were female. Their mean duration of PD was 10.9 ± 6.8 years. The control subjects had a mean age of 61.6 years; 56% were female. There was no difference in visual acuity, contrast sensitivity or color vision of the PD subjects in their “on” state compared with controls. Convergence amplitudes measured with base-out prism were significantly poorer in PD subjects compared with controls (24.1 ± 8 Δ vs 14.8 ±10.3 Δ; P=0.003). The mean composite VFQ-25 score was significantly worse in the PD subjects compared with the controls (87.1 ± 8.69 vs 96.6 ± 3.05; P=0.0001). Comparing the PD subjects in their “on” with their “off” states, there was no difference in distance exodeviation, near exodeviation or ocular ductions. Mean convergence amplitudes and near point of convergence were better in the “on” state compared with the “off” state, 14.8±10.3 Δ vs 10.7±9.0 Δ, (P=0.0006), and 13.1±9.1 cm vs 18.1±12.2, (P=0.002), respectively. Conclusions Convergence ability is significantly poorer in PD subjects in both their “on” and “off” states compared with controls, but significantly improves with systemic dopaminergic treatment. Ocular motor function in PD subjects fluctuates in response to treatment, which complicates ophthalmic management. PD subjects have a significant reduction in vision-related quality of life, especially near activities, that is not associated with visual acuity. PMID:21959370

  8. Sensory Responsiveness as a Predictor of Social Severity in Children with High Functioning Autism Spectrum Disorders

    ERIC Educational Resources Information Center

    Hilton, Claudia L.; Harper, Jacquelyn D.; Kueker, Rachel Holmes; Lang, Andrea Runzi; Abbacchi, Anna M.; Todorov, Alexandre; LaVesser, Patricia D.

    2010-01-01

    This study examines the relationship between sensory responsiveness and social severity in children with high functioning autism spectrum disorders (HFASD; N = 36) and age-matched controls (N = 26) between 6 and 10 years old. Significant relationships were found between social responsiveness scale scores and each of the six sensory profile sensory…

  9. Relationship between sensory descriptive juiciness measurements and functionality parameters of broiler breast fillets

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Relationships between Sensory Descriptive Juiciness Measurements and Functionality Parameters of Broiler Breast Fillets H. Zhuang and E. M. Savage Quality and Safety Assessment Research Unit, ARS-USDA, Russell Research Center, P. O. Box 5677, Athens, GA 30604-5677 Sensory moisture characteristics...

  10. Biomagnetic functional localization of a peripheral nerve in man.

    PubMed Central

    Trahms, L; Erné, S N; Trontelj, Z; Curio, G; Aust, P

    1989-01-01

    The first detection of the magnetic field of a stimulated peripheral nerve in man is presented. The measurement was performed noninvasively and in vivo on a healthy subject. The spatio-temporal field distribution is utilized to calculate the location of bioelectric activity on the basis of the equivalent current dipole model. The localization of the active nerve tissue is confirmed by a computer tomography image of the upper arm cross-section. Furthermore, a calculation of the total current distribution in the nerve explains the observed morphology of the signal. Images FIGURE 5 PMID:2765652

  11. Age as a factor in sensory integration function in Taiwanese children

    PubMed Central

    Lin, Chin-Kai; Wu, Huey-Min; Wang, Hsin-Yi; Tseng, Mei-Hui; Lin, Chung-Hui

    2013-01-01

    Objective Sensory integration progresses along a normal developmental sequence. However, few studies have explored how age difference affects the way sensory integration functions in Taiwanese children as they develop. Therefore, this study aims to pinpoint the role of age in sensory integration. Method A purposive sampling plan was employed. The study population comprised 1,000 Chinese children aged 36 to 131 months (mean = 74.48 months, standard deviation = 25.69 months). Subjects were scored on seven subsets of the Test of Sensory Integration Function (TSIF). An analysis of variance (ANOVA) was used to identify differences between four age groups (ages 3–4, 5–6, 7–8, and 9–10 years), in the categories of the TSIF. Results ANOVA revealed that age is a significant factor in each of the seven tasks of sensory integration associated with various stages of development. The effect of age was significant in all four groups for the subscale of Bilateral Integration Sequences. The function of sensory integration for the children aged 5–8 years did not produce statistically significant results for the subscale of Postural Movement, Sensory Discrimination, Sensory Seeking, or Attention and Activity. For the subscale of Sensory Modulation and Emotional Behavior, the effect of age was significant in only group 1 (children aged 3–4 years) and group 2 (children aged 5–6 years). Conclusion There was significant difference between group 1 and group 2 for seven categories. Significant differences were contributed by the differences from group 1 (3–4 years) and group 4 (9–10 years) in five subscales (Postural Movement, Bilateral Integration Sequences, Sensory Discrimination, Sensory Seeking, and Attention and Activity). There were three developmental trends in the seven categories of the TSIF. PMID:23940418

  12. Presynaptic Inhibition of Olfactory Sensory Neurons: New Mechanisms and Potential Functions

    PubMed Central

    2013-01-01

    Presynaptic inhibition is the suppression of neurotransmitter release from a neuron by inhibitory input onto its presynaptic terminal. In the olfactory system, the primary sensory afferents from the olfactory neuroepithelium to the brain’s olfactory bulb are strongly modulated by a presynaptic inhibition that has been studied extensively in brain slices and in vivo. In rodents, this inhibition is mediated by γ-amino butyric acid (GABA) and dopamine released from bulbar interneurons. The specialized GABAergic circuit is now well understood to include a specific subset of GAD65-expressing periglomerular interneurons that stimulate presynaptic GABAB receptors to reduce presynaptic calcium conductance. This inhibition is organized to permit the selective modulation of neurotransmitter release from specific populations of olfactory sensory neurons based on their odorant receptor expression, includes specialized microcircuits to create a tonically active inhibition and a separate feedback inhibition evoked by sensory input, and can be modulated by centrifugal projections from other brain regions. Olfactory nerve output can also be modulated by dopaminergic circuitry, but this literature is more difficult to interpret. Presynaptic inhibition of olfactory afferents may extend their dynamic range but could also create state-dependent or odorant-specific sensory filters on primary sensory representations. New directions exploring this circuit’s role in olfactory processing are discussed. PMID:23761680

  13. Personal and workplace factors and median nerve function in a pooled study of 2396 US workers

    PubMed Central

    Rempel, David; Gerr, Fred; Harris-Adamson, Carisa; Hegmann, Kurt T; Thiese, Matthew S.; Kapellusch, Jay; Garg, Arun; Burt, Susan; Bao, Stephen; Silverstein, Barbara; Merlino, Linda; Dale, Ann Marie; Evanoff, Bradley

    2015-01-01

    Objective Evaluate associations between personal and workplace factors and median nerve conduction latency at the wrist. Methods Baseline data on workplace psychosocial and physical exposures were pooled from five prospective studies of production and service workers (N=2396). During the follow-up period, electrophysiologic measures of median nerve function were collected at regular intervals. Results Significant adjusted associations were observed between age, BMI, gender, peak hand force, duration of forceful hand exertions, TLV for HAL, forceful repetition rate, wrist extension, and decision latitude on median nerve latencies. Conclusions Occupational and non-occupational factors have adverse effects on median nerve function. Measuring median nerve function eliminates possible reporting bias that may affect symptom-based carpal tunnel syndrome (CTS) case definitions. These results suggest that previously observed associations between CTS and occupational factors are not the result of such reporting bias. PMID:25563546

  14. Effect of concurrent mental nerve reconstruction at the same time as mandibular reconstruction using a fibula osteoseptocutaneous flap.

    PubMed

    Shimizu, Fumiaki; Ooatari, Miwako; Uehara, Miyuki; Takahashi, Yoshihiro; Kawano, Kenji

    2015-09-01

    The damage of inferior alveolar nerve causes some functional problem including numbness of lower lip and drooling. During segmental mandibulectomy, inferior alveolar nerve commonly resected, therefore, it is ideal to reconstruct the nerve to get better functional result. Sensory recovery was assessed after mandibular reconstruction using free fibula osteoseptocutaneous flap in thirteen cases. In six cases, the mental nerve reconstruction was performed simultaneously, and in seven cases, the mental nerve reconstruction was not performed. In the case that the mental nerve was reconstructed simultaneously, unilateral mental nerve reconstruction was performed in five cases, and bilateral mental nerve reconstruction was performed in one cases. More than one year after the reconstruction, sensory recovery was assessed and compared between the group that the mental nerve was reconstructed and the group that was not reconstructed. Our results showed almost a normal sensory recovery of the lips on the reconstructed side more than one year after the reconstruction in reconstructed group. In contrast, sensory recovery was poor in non-reconstructed group and non-reconstructed side. These results showed that mental nerve reconstruction at the same time as mandibular reconstruction affects the postoperative mandibular function. The sural nerve can be harvested from the same donor site of the free fibula osteoseptocutaneous flap and such mental nerve reconstruction with nerve grafting can be completed within an hour. Most cases of mandibular reconstruction using a free fibula osteoseptocutaneous flap transfer can therefore be candidates for mental nerve reconstruction at the time of mandibular reconstruction. PMID:26051850

  15. Different effects of blocked potassium channels on action potentials, accommodation, adaptation and anode break excitation in human motor and sensory myelinated nerve fibres: computer simulations.

    PubMed

    Stephanova, D I; Mileva, K

    2000-08-01

    Action potentials and electrotonic responses to 300-ms depolarizing and hyperpolarizing currents for human motor and sensory myelinated nerve fibres have been simulated on the basis of double cable models. The effects of blocked nodal or internodal potassium (fast or slow) channels on the fibre action potentials, early and late adaptations to 30-ms suprathreshold slowly increasing depolarizing stimuli have been examined. The effects of the same channels on accommodation after the termination of a prolonged (100 ms) hyperpolarizing current pulse have also been investigated. By removing the nodal fast potassium conductance the action potentials of the sensory fibres are considerably broader than those of the motor neurons. For both types of fibres, the blocked nodal slow potassium channels have a substantially smaller effect on the action potential repolarization. When the suprathreshold depolarizing current intensity is increased, the onset of the spike burst occurs sooner, which is common in the behaviour of the fibres. The most striking differences in the burst activity during early adaptation have been found between the fibres when the nodal fist potassium channels are blocked. The results obtained confirm the fact that the motor fibres adapt more quickly to sustained depolarizing current pulses than the sensory ones. The results also show that normal human motor and sensory fibres cannot be excited by a 100-ms hyperpolarizing current pulse, even at the threshold level. When removing the potassium channels in the nodal or internodal axolemma, the posthyperpolarization increase in excitability is small, which is common in the behaviour of the fibres. However, anode break excitation can be simulated in the fibres with simultaneous removal of the potassium channels under the myelin sheath, and this is more pronounced in the human sensory fibres than in motor fibres. This phenomenon can also be found when the internodal and some of the nodal (fast or slow) potassium channels are simultaneously blocked. PMID:10966055

  16. Nerve Growth Factor Mediates a Switch in Intracellular Signaling for PGE2-Induced Sensitization of Sensory Neurons from Protein Kinase A to Epac

    PubMed Central

    Vasko, Michael R.; Habashy Malty, Ramy; Guo, Chunlu; Duarte, Djane B.; Zhang, Yihong; Nicol, Grant D.

    2014-01-01

    We examined whether nerve growth factor (NGF), an inflammatory mediator that contributes to chronic hypersensitivity, alters the intracellular signaling that mediates the sensitizing actions of PGE2 from activation of protein kinase A (PKA) to exchange proteins directly activated by cAMP (Epacs). When isolated sensory neurons are grown in the absence of added NGF, but not in cultures grown with 30 ng/ml NGF, inhibiting protein kinase A (PKA) activity blocks the ability of PGE2 to augment capsaicin-evoked release of the neuropeptide CGRP and to increase the number of action potentials (APs) evoked by a ramp of current. Growing sensory neurons in culture in the presence of increasing concentrations of NGF increases the expression of Epac2, but not Epac1. An intradermal injection of complete Freund's adjuvant into the rat hindpaw also increases the expression of Epac2, but not Epac1 in the dorsal root ganglia and spinal cord: an effect blocked by intraplantar administration of NGF antibodies. Treating cultures grown in the presence of 30 ng/ml NGF with Epac1siRNA significantly reduced the expression of Epac1, but not Epac2, and did not block the ability of PGE2 to augment capsaicin-evoked release of CGRP from sensory neurons. Exposing neuronal cultures grown in NGF to Epac2siRNAreduced the expression of Epac2, but not Epac1 and prevented the PGE2-induced augmentation of capsaicin and potassium-evoked CGRP release in sensory neurons and the PGE2-induced increase in the number of APs generated by a ramp of current. In neurons grown with no added NGF, Epac siRNAs did not attenuate PGE2-induced sensitization. These results demonstrate that NGF, through increasing Epac2 expression, alters the signaling cascade that mediates PGE2-induced sensitization of sensory neurons, thus providing a novel mechanism for maintaining PGE2-induced hypersensitivity during inflammation. PMID:25126967

  17. Sensory fusion in Physarum polycephalum and implementing multi-sensory functional computation.

    PubMed

    Whiting, James G H; de Lacy Costello, Ben P J; Adamatzky, Andrew

    2014-05-01

    Surface electrical potential and observational growth recordings were made of a protoplasmic tube of the slime mould Physarum polycephalum in response to a multitude of stimuli with regards to sensory fusion or multisensory integration. Each stimulus was tested alone and in combination in order to evaluate for the first time the effect that multiple stimuli have on the frequency of streaming oscillation. White light caused a decrease in frequency whilst increasing the temperature and applying a food source in the form of oat flakes both increased the frequency. Simultaneously stimulating P. polycephalum with light and oat flake produced no net change in frequency, while combined light and heat stimuli showed an increase in frequency smaller than that observed for heat alone. When the two positive stimuli, oat flakes and heat, were combined, there was a net increase in frequency similar to the cumulative increases caused by the individual stimuli. Boolean logic gates were derived from the measured frequency change. PMID:24695059

  18. 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 interactions between TRP receptors and membrane lipid raft interfaces modulate the opening properties of these channels and therefore, targeting this interaction might be a promising tool for drug developmental purposes. PMID:26238178

  19. Cochlear nerve projections to the small cell shell of the cochlear nucleus: the neuroanatomy of extremely thin sensory axons.

    PubMed

    Hurd, L B; Hutson, K A; Morest, D K

    1999-08-01

    Labeling cochlear nerve fibers in the inner ear of chinchillas with biotinylated dextran polyamine was used to trace the thin fibers (Type II), which likely innervate outer hair cells. These axons, 0. 1-0.5 microm in diameter, were distinguished from the thicker Type I, fibers innervating inner hair cells, and traced to small-cell clusters in the cochlear nucleus. This study provided two major new insights into the outer hair cell connections in the cochlear nucleus and the potential significance of very thin axons and synaptic nests, which are widespread in the CNS. 1) EM serial reconstructions of labeled and unlabeled material revealed that Type II axons rarely formed synapses with conventional features (vesicles gathered at junctions). Rather, their endings contained arrays of endoplasmic reticulum and small spherical vesicles without junctions. 2) Type II axons projected predominantly to synaptic nests, where they contacted other endings and dendrites of local interneurons (small stellate and mitt cells, but not granule cells). Synaptic nests lacked intrinsic glia and, presumably, their high-affinity amino acid transporters. As functional units, nests and their Type II inputs from outer hair cells may contribute to an analog processing mode, which is slower, more diffuse, longer-lasting, and potentially more plastic than the digital processors addressed by inner hair cells. PMID:10400889

  20. Specific α- and β-Tubulin Isotypes Optimize the Functions of Sensory Cilia in Caenorhabditis elegans

    PubMed Central

    Hurd, Daryl D.; Miller, Renee M.; Núñez, Lizbeth; Portman, Douglas S.

    2010-01-01

    Primary cilia have essential roles in transducing signals in eukaryotes. At their core is the ciliary axoneme, a microtubule-based structure that defines cilium morphology and provides a substrate for intraflagellar transport. However, the extent to which axonemal microtubules are specialized for sensory cilium function is unknown. In the nematode Caenorhabditis elegans, primary cilia are present at the dendritic ends of most sensory neurons, where they provide a specialized environment for the transduction of particular stimuli. Here, we find that three tubulin isotypes—the α-tubulins TBA-6 and TBA-9 and the β-tubulin TBB-4—are specifically expressed in overlapping sets of C. elegans sensory neurons and localize to the sensory cilia of these cells. Although cilia still form in mutants lacking tba-6, tba-9, and tbb-4, ciliary function is often compromised: these mutants exhibit a variety of sensory deficits as well as the mislocalization of signaling components. In at least one case, that of the CEM cephalic sensory neurons, cilium architecture is disrupted in mutants lacking specific ciliary tubulins. While there is likely to be some functional redundancy among C. elegans tubulin genes, our results indicate that specific tubulins optimize the functional properties of C. elegans sensory cilia. PMID:20421600

  1. Activation of extracellular signal-regulated protein kinase 5 is essential for cystitis- and nerve growth factor-induced calcitonin gene-related peptide expression in sensory neurons

    PubMed Central

    2012-01-01

    Background Cystitis causes considerable neuronal plasticity in the primary afferent pathways. The molecular mechanism and signal transduction underlying cross talk between the inflamed urinary bladder and sensory sensitization has not been investigated. Results In a rat cystitis model induced by cyclophosphamide (CYP) for 48 h, the mRNA and protein levels of the excitatory neurotransmitter calcitonin gene-related peptide (CGRP) are increased in the L6 dorsal root ganglia (DRG) in response to bladder inflammation. Cystitis-induced CGRP expression in L6 DRG is triggered by endogenous nerve growth factor (NGF) because neutralization of NGF with a specific NGF antibody reverses CGRP up-regulation during cystitis. CGRP expression in the L6 DRG neurons is also enhanced by retrograde NGF signaling when NGF is applied to the nerve terminals of the ganglion-nerve two-compartmented preparation. Characterization of the signaling pathways in cystitis- or NGF-induced CGRP expression reveals that the activation (phosphorylation) of extracellular signal-regulated protein kinase (ERK)5 but not Akt is involved. In L6 DRG during cystitis, CGRP is co-localized with phospho-ERK5 but not phospho-Akt. NGF-evoked CGRP up-regulation is also blocked by inhibition of the MEK/ERK pathway with specific MEK inhibitors U0126 and PD98059, but not by inhibition of the PI3K/Akt pathway with inhibitor LY294002. Further examination shows that cystitis-induced cAMP-responsive element binding protein (CREB) activity is expressed in CGRP bladder afferent neurons and is co-localized with phospho-ERK5 but not phospho-Akt. Blockade of NGF action in vivo reduces the number of DRG neurons co-expressing CGRP and phospho-CREB, and reverses cystitis-induced increases in micturition frequency. Conclusions A specific pathway involving NGF-ERK5-CREB axis plays an essential role in cystitis-induced sensory activation. PMID:22742729

  2. 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. PMID:24639076

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

    PubMed

    Bałkowiec, A; Kukuła, K; Szulczyk, P

    1995-03-15

    1. Single afferent fibres with receptive fields in the diaphragm (272 units) dissected from the right phrenic nerve were classified according to the following properties: reaction to contraction of the diaphragm, resting activity, conduction velocity, location and properties of receptive fields, and reaction to injection of bradykinin and lactic acid into the internal thoracic artery. Nine additional fibres dissected from the phrenic nerve had receptive fields outside the diaphragm. The experiments were performed on chloralose-anaesthetized cats. 2. Ninety-six fibres (36%) had high resting activity when unloaded by contraction of the diaphragm, had low-threshold receptive fields in the muscle and were mostly group II and III fibres. They probably innervated muscle spindles. 3. Eighty-eight fibres (32%) were vigorously activated by contraction of the diaphragm. They had low-threshold receptive fields located in the musculotendinous border and central tendon. Their conduction velocity was in the range for group II and III fibres. We infer that they may innervate tendon organs. 4. Eighty-eight fibres (32%) were slightly affected or not affected by diaphragmatic contraction. They had low- and high-threshold receptive fields located mostly in the muscular part of the diaphragm, and negligible resting activity. Most of them were group III and IV afferent fibres and were activated when bradykinin and lactic acid were applied to their receptive fields. Possibly these low- and high-threshold receptors innervated diaphragmatic ergo- and nociceptors, respectively. 5. Sensory outflow from the diaphragm was found to be somatotopically organized, so that fibres with receptive fields in the sternocostal portion were predominantly located in the upper phrenic nerve root, and those with lumbar receptive fields were in the lower root. 6. It is concluded that the phrenic nerve contains fibres from several distinct classes of sensory receptors: muscle spindles, tendon organs, ergoceptors and nociceptors. The sensory diaphragmatic outflow to the spinal cord is somatotopically organized. PMID:7776256

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

    PubMed Central

    Bałkowiec, A; Kukuła, K; Szulczyk, P

    1995-01-01

    1. Single afferent fibres with receptive fields in the diaphragm (272 units) dissected from the right phrenic nerve were classified according to the following properties: reaction to contraction of the diaphragm, resting activity, conduction velocity, location and properties of receptive fields, and reaction to injection of bradykinin and lactic acid into the internal thoracic artery. Nine additional fibres dissected from the phrenic nerve had receptive fields outside the diaphragm. The experiments were performed on chloralose-anaesthetized cats. 2. Ninety-six fibres (36%) had high resting activity when unloaded by contraction of the diaphragm, had low-threshold receptive fields in the muscle and were mostly group II and III fibres. They probably innervated muscle spindles. 3. Eighty-eight fibres (32%) were vigorously activated by contraction of the diaphragm. They had low-threshold receptive fields located in the musculotendinous border and central tendon. Their conduction velocity was in the range for group II and III fibres. We infer that they may innervate tendon organs. 4. Eighty-eight fibres (32%) were slightly affected or not affected by diaphragmatic contraction. They had low- and high-threshold receptive fields located mostly in the muscular part of the diaphragm, and negligible resting activity. Most of them were group III and IV afferent fibres and were activated when bradykinin and lactic acid were applied to their receptive fields. Possibly these low- and high-threshold receptors innervated diaphragmatic ergo- and nociceptors, respectively. 5. Sensory outflow from the diaphragm was found to be somatotopically organized, so that fibres with receptive fields in the sternocostal portion were predominantly located in the upper phrenic nerve root, and those with lumbar receptive fields were in the lower root. 6. It is concluded that the phrenic nerve contains fibres from several distinct classes of sensory receptors: muscle spindles, tendon organs, ergoceptors and nociceptors. The sensory diaphragmatic outflow to the spinal cord is somatotopically organized. PMID:7776256

  5. Expression and function of the ion channel TRPA1 in vagal afferent nerves innervating mouse lungs.

    PubMed

    Nassenstein, Christina; Kwong, Kevin; Taylor-Clark, Thomas; Kollarik, Marian; Macglashan, Donald M; Braun, Armin; Undem, Bradley J

    2008-03-15

    Transient receptor potential (TRP) A1 and TRPM8 are ion channels that have been localized to afferent nociceptive nerves. These TRP channels may be of particular relevance to respiratory nociceptors in that they can be activated by various inhaled irritants and/or cold air. We addressed the hypothesis that mouse vagal sensory nerves projecting to the airways express TRPA1 and TRPM8 and that they can be activated via these receptors. Single cell RT-PCR analysis revealed that TRPA1 mRNA, but not TRPM8, is uniformly expressed in lung-labelled TRPV1-expressing vagal sensory neurons. Neither TRPA1 nor TRPM8 mRNA was expressed in TRPV1-negative neurons. Capsaicin-sensitive, but not capsaicin-insensitive, lung-specific neurons responded to cinnamaldehyde, a TRPA1 agonist, with increases in intracellular calcium. Menthol, a TRPM8 agonist, was ineffective at increasing cellular calcium in lung-specific vagal sensory neurons. Cinnamaldehyde also induced TRPA1-like inward currents (as measured by means of whole cell patch clamp recordings) in capsaicin-sensitive neurons. In an ex vivo vagal innervated mouse lung preparation, cinnamaldehyde evoked action potential discharge in mouse vagal C-fibres with a peak frequency similar to that observed with capsaicin. Cinnamaldehyde inhalation in vivo mimicked capsaicin in eliciting strong central-reflex changes in breathing pattern. Taken together, our results support the hypothesis that TRPA1, but not TRPM8, is expressed in vagal sensory nerves innervating the airways. TRPA1 activation provides a mechanism by which certain environmental stimuli may elicit action potential discharge in airway afferent C-fibres and the consequent nocifensor reflexes. PMID:18218683

  6. Effect of skilled and unskilled training on nerve regeneration and functional recovery

    PubMed Central

    Pagnussat, A.S.; Michaelsen, S.M.; Achaval, M.; Ilha, J.; Hermel, E.E.S.; Back, F.P.; Netto, C.A.

    2012-01-01

    The most disabling aspect of human peripheral nerve injuries, the majority of which affect the upper limbs, is the loss of skilled hand movements. Activity-induced morphological and electrophysiological remodeling of the neuromuscular junction has been shown to influence nerve repair and functional recovery. In the current study, we determined the effects of two different treatments on the functional and morphological recovery after median and ulnar nerve injury. Adult Wistar male rats weighing 280 to 330?g at the time of surgery (N = 8-10 animals/group) were submitted to nerve crush and 1 week later began a 3-week course of motor rehabilitation involving either skilled (reaching for small food pellets) or unskilled (walking on a motorized treadmill) training. During this period, functional recovery was monitored weekly using staircase and cylinder tests. Histological and morphometric nerve analyses were used to assess nerve regeneration at the end of treatment. The functional evaluation demonstrated benefits of both tasks, but found no difference between them (P > 0.05). The unskilled training, however, induced a greater degree of nerve regeneration as evidenced by histological measurement (P < 0.05). These data provide evidence that both of the forelimb training tasks used in this study can accelerate functional recovery following brachial plexus injury. PMID:22584636

  7. Functional identification of sensory mechanisms required for developmental song learning

    PubMed Central

    London, Sarah E; Clayton, David F

    2008-01-01

    A young male zebra finch (Taeniopygia guttata) learns to sing by copying the vocalizations of an older tutor in a process that parallels human speech acquisition. Brain pathways that control song production are well defined, but little is known about the sites and mechanisms of tutor song memorization. Here we test the hypothesis that molecular signaling in a sensory brain area outside of the song system is required for developmental song learning. Using controlled tutoring and a pharmacological inhibitor, we transiently suppressed the extracellular signal–regulated kinase signaling pathway in a portion of the auditory forebrain specifically during tutor song exposure. On maturation, treated birds produced poor copies of tutor song, whereas controls copied the tutor song effectively. Thus the foundation of normal song learning, the formation of a sensory memory of tutor song, requires a conserved molecular pathway in a brain area that is distinct from the circuit for song motor control. PMID:18391944

  8. Nuptial gifts of male spiders function as sensory traps.

    PubMed

    Stålhandske, Pia

    2002-05-01

    While nuptial food gifts come in various forms in arthropods, their evolutionary origins are unclear. A previous study on insects has shown that such gifts may arise as a sensory trap that exploits a female's underlying motivation to feed. Here I present independent evidence of a sensory trap in spiders. In certain visually oriented spiders, I suggest that males initially exploit the maternal care instinct by producing a nuptial gift that closely resembles the female egg sac. Males of the spider Pisaura mirabilis cover their prey gift with a silk layer, transforming it into a white round object. In a laboratory experiment I tested whether the colour of the gift affected the rate that females accepted males displaying their gifts. I found that the brighter and the more alike the nuptial gift to a female's egg sac, the faster the female responded by grabbing the gift. My results support the hypothesis that the nuptial gift in P. mirabilis works as a sensory trap. PMID:12028772

  9. 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

  10. Localized and Sustained Delivery of Erythropoietin from PLGA Microspheres Promotes Functional Recovery and Nerve Regeneration in Peripheral Nerve Injury

    PubMed Central

    Zhang, Wei; Gao, Yuan; Zhou, Yan; Liu, Jianheng; Zhang, Licheng; Long, Anhua; Zhang, Lihai; Tang, Peifu

    2015-01-01

    Erythropoietin (EPO) has been demonstrated to exert neuroprotective effects on peripheral nerve injury recovery. Though daily intraperitoneal injection of EPO during a long period of time was effective, it was a tedious procedure. In addition, only limited amount of EPO could reach the injury sites by general administration, and free EPO is easily degraded in vivo. In this study, we encapsulated EPO in poly(lactide-co-glycolide) (PLGA) microspheres. Both in vitro and in vivo release assays showed that the EPO-PLGA microspheres allowed sustained release of EPO within a period of two weeks. After administration of such EPO-PLGA microspheres, the peripheral nerve injured rats had significantly better recovery compared with those which received daily intraperitoneal injection of EPO, empty PLGA microspheres, or saline treatments. This was supported by the functional, electrophysiological, and histological evaluations of the recovery done at week 8 postoperatively. We conclude that sustained delivery of EPO could be achieved by using EPO-PLGA microspheres, and such delivery method could further enhance the recovery function of EPO in nerve injury recovery. PMID:25821803

  11. A Functional Role for VEGFR1 Expressed in Peripheral Sensory Neurons in Cancer Pain

    PubMed Central

    Selvaraj, Deepitha; Gangadharan, Vijayan; Michalski, Christoph W.; Kurejova, Martina; Stösser, Sebastian; Srivastava, Kshitij; Schweizerhof, Matthias; Waltenberger, Johannes; Ferrara, Napoleone; Heppenstall, Paul; Shibuya, Masabumi; Augustin, Hellmut G.; Kuner, Rohini

    2015-01-01

    Summary Cancer pain is a debilitating disorder and a primary determinant of the poor quality of life. Here, we report a non-vascular role for ligands of the Vascular Endothelial Growth Factor (VEGF) family in cancer pain. Tumor-derived VEGF-A, PLGF-2, and VEGF-B augment pain sensitivity through selective activation of VEGF receptor 1 (VEGFR1) expressed in sensory neurons in human cancer and mouse models. Sensory-neuron-specific genetic deletion/silencing or local or systemic blockade of VEGFR1 prevented tumor-induced nerve remodeling and attenuated cancer pain in diverse mouse models in vivo. These findings identify a therapeutic potential for VEGFR1-modifying drugs in cancer pain and suggest a palliative effect for VEGF/VEGFR1-targeting anti-angiogenic tumor therapies. PMID:26058077

  12. Sphenoid sinus mucocele presenting with oculomotor nerve palsy and affecting the functions of trigeminal nerve: a case report

    PubMed Central

    Yong, Wei-Wei; Zhou, Shui-Hong; Bao, Yang-Yang

    2015-01-01

    We report a case of first-episode sphenoid mucocele successfully treated via transnasal endoscopic drainage and marsupialization of the mucocele. A 55 year-old female presented with persistent right-side facial numbness (in the areas of the first and second branches of the trigeminal nerve) and right-side ptosis. Computed tomography (CT) imaging and Magnetic resonance imaging (MRI) revealed opacification and expansion of the right-side sphenoid sinus lesion. The lesion was diagnosed as right-side sphenoid mucocele affecting the functions of the trigeminal (first and second branches), and oculomotor nerves. Transnasal endoscopic drainage and marsupialization of the mucocele result in rapid regression of these symptoms. PMID:26629234

  13. Alterations of sensori-motor functions of the digestive tract in the pathophysiology of irritable bowel syndrome.

    PubMed

    Delvaux, Michel

    2004-08-01

    Pathophysiology of irritable bowel syndrome (IBS) is based upon multiple factors that have been organised in a comprehensive model centred around the brain-gut axis. The brain-gut axis encompasses nerve pathways linking the enteric and the central nervous systems and contains a large proportion of afferent fibres. Functionally and anatomically, visceral nerves are divided in to two categories: the parasympathetic pathways distributing to the upper gut through the vagi and to the hindgut, through the pelvic and pudendal nerves, and the sympathetic pathways, arising form the spinal cord and distributing to the midgut via the paravertebral ganglia. Several abnormalities of gut sensori-motor function have been described in patients with IBS. Abnormal motility patterns have been described at the intestinal and colonic levels. Changes in colonic motility are mainly related to bowel disturbances linked to IBS but do not correlate with pain. More recently, visceral hypersensitivity has been recognised as a main characteristic of patients with IBS. It is defined by an exaggerated perception of luminal distension of various segments of the gut and related to peripheral changes in the processing of visceral sensations as well as modulation of perception by centrally acting factors including mood and stress. Viscero-visceral reflexes link the two edges of the brain-gut axis and may account for the origin of symptoms in some pathological conditions. Recent advances in the understanding of the role of myenteric plexus allowed recognition of several neurotransmitters involved at the level of both the afferent and efferent pathways. Targeting the receptors of these neurotransmitters is a promising way for development of new treatments for IBS. PMID:15324712

  14. 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 array could provide intuitive control of a virtual prosthetic hand with broad sensory feedback.

  15. Neurophysiological assessment of auditory, peripheral nerve, somatosensory, and visual system function after developmental exposure to gasoline, E15, and E85 vapors.

    PubMed

    Herr, David W; Freeborn, Danielle L; Degn, Laura; Martin, Sheppard A; Ortenzio, Jayna; Pantlin, Lara; Hamm, Charles W; Boyes, William K

    2016-01-01

    The use of gasolines blended with a range of ethanol concentrations may result in inhalation of vapors containing a variable combination of ethanol with other volatile gasoline constituents. The possibility of exposure and potential interactions between vapor constituents suggests the need to evaluate the possible risks of this complex mixture. Previously we evaluated the effects of developmental exposure to ethanol vapors on neurophysiological measures of sensory function as a component of a larger project evaluating developmental ethanol toxicity. Here we report an evaluation using the same battery of sensory function testing in offspring of pregnant dams exposed during gestation to condensed vapors of gasoline (E0), gasoline blended with 15% ethanol (E15) or gasoline blended with 85% ethanol (E85). Pregnant Long-Evans rats were exposed to target concentrations 0, 3000, 6000, or 9000ppm total hydrocarbon vapors for 6.5h/day over GD9 - GD20. Sensory evaluations of male offspring began as adults. The electrophysiological testing battery included tests of: peripheral nerve (compound action potentials, nerve conduction velocity [NCV]), somatosensory (cortical and cerebellar evoked potentials), auditory (brainstem auditory evoked responses), and visual functions. Visual function assessment included pattern elicited visual evoked potentials (VEP), VEP contrast sensitivity, dark-adapted (scotopic) electroretinograms (ERGs), light-adapted (photopic) ERGs, and green flicker ERGs. The results included sporadic statistically significant effects, but the observations were not consistently concentration-related and appeared to be statistical Type 1 errors related to multiple dependent measures evaluated. The exposure concentrations were much higher than can be reasonably expected from typical exposures to the general population during refueling or other common exposure situations. Overall the results indicate that gestational exposure of male rats to ethanol/gasoline vapor combinations did not cause detectable changes in peripheral nerve, somatosensory, auditory, or visual function when the offspring were assessed as adults. PMID:26721698

  16. Inflammatory mediator bradykinin increases population of sensory neurons expressing functional T-type Ca2+ channels

    PubMed Central

    Huang, Dongyang; Liang, Ce; Zhang, Fan; Men, Hongchao; Du, Xiaona; Gamper, Nikita; Zhang, Hailin

    2016-01-01

    T-type Ca2+ channels are important regulators of peripheral sensory neuron excitability. Accordingly, T-type Ca2+ currents are often increased in various pathological pain conditions, such as inflammation or nerve injury. Here we investigated effects of inflammation on functional expression of T-type Ca2+ channels in small-diameter cultured dorsal root ganglion (DRG) neurons. We found that overnight treatment of DRG cultures with a cocktail of inflammatory mediators bradykinin (BK), adenosine triphosphate (ATP), norepinephrine (NE) and prostaglandin E2 (PGE2) strongly increased the population size of the small-diameter neurons displaying low-voltage activated (LVA, T-type) Ca2+ currents while having no effect on the peak LVA current amplitude. When applied individually, BK and ATP also increased the population size of LVA-positive neurons while NE and PGE2 had no effect. The PLC inhibitor U-73122 and B2 receptor antagonist, Hoe-140, both abolished the increase of the population of LVA-positive DRG neurons. Inflammatory treatment did not affect CaV3.2 mRNA or protein levels in DRG cultures. Furthermore, an ubiquitination inhibitor, MG132, did not increase the population of LVA-positive neurons. Our data suggest that inflammatory mediators BK and ATP increase the abundance of LVA-positive DRG neurons in total neuronal population by stimulating the recruitment of a ‘reserve pool’ of CaV3.2 channels, particularly in neurons that do not display measurable LVA currents under control conditions. PMID:26944020

  17. Inflammatory mediator bradykinin increases population of sensory neurons expressing functional T-type Ca(2+) channels.

    PubMed

    Huang, Dongyang; Liang, Ce; Zhang, Fan; Men, Hongchao; Du, Xiaona; Gamper, Nikita; Zhang, Hailin

    2016-04-29

    T-type Ca(2+) channels are important regulators of peripheral sensory neuron excitability. Accordingly, T-type Ca(2+) currents are often increased in various pathological pain conditions, such as inflammation or nerve injury. Here we investigated effects of inflammation on functional expression of T-type Ca(2+) channels in small-diameter cultured dorsal root ganglion (DRG) neurons. We found that overnight treatment of DRG cultures with a cocktail of inflammatory mediators bradykinin (BK), adenosine triphosphate (ATP), norepinephrine (NE) and prostaglandin E2 (PGE2) strongly increased the population size of the small-diameter neurons displaying low-voltage activated (LVA, T-type) Ca(2+) currents while having no effect on the peak LVA current amplitude. When applied individually, BK and ATP also increased the population size of LVA-positive neurons while NE and PGE2 had no effect. The PLC inhibitor U-73122 and B2 receptor antagonist, Hoe-140, both abolished the increase of the population of LVA-positive DRG neurons. Inflammatory treatment did not affect CaV3.2 mRNA or protein levels in DRG cultures. Furthermore, an ubiquitination inhibitor, MG132, did not increase the population of LVA-positive neurons. Our data suggest that inflammatory mediators BK and ATP increase the abundance of LVA-positive DRG neurons in total neuronal population by stimulating the recruitment of a 'reserve pool' of CaV3.2 channels, particularly in neurons that do not display measurable LVA currents under control conditions. PMID:26944020

  18. Differential function of RNCAM isoforms in precise target selection of olfactory sensory neurons.

    PubMed

    Alenius, Mattias; Bohm, Staffan

    2003-03-01

    Olfactory sensory neurons (OSNs) are individually specified to express one odorant receptor (OR) gene among approximately 1000 different and project with precision to topographically defined convergence sites, the glomeruli, in the olfactory bulb. Although ORs partially determine the location of convergence sites, the mechanism ensuring that axons with different OR identities do not co-converge is unknown. RNCAM (OCAM, NCAM2) is assumed to regulate a broad zonal segregation of projections by virtue of being a homophilic cell adhesion molecule that is selectively expressed on axons terminating in a defined olfactory bulb region. We have identified NADPH diaphorase activity as being an independent marker for RNCAM-negative axons. Analyses of transgenic mice that ectopically express RNCAM in NADPH diaphorase-positive OSNs show that the postulated function of RNCAM in mediating zone-specific segregation of axons is unlikely. Instead, analyses of one OR-specific OSN subpopulation (P2) reveal that elevated RNCAM levels result in an increased number of P2 axons that incorrectly co-converge with axons of other OR identities. Both Gpi-anchored and transmembrane-bound RNCAM isoforms are localized on axons in the nerve layer, while the transmembrane-bound RNCAM is the predominant isoform on axon terminals within glomeruli. Overexpressing transmembrane-bound RNCAM results in co-convergence events close to the correct target glomeruli. By contrast, overexpression of Gpi-anchored RNCAM results in axons that can bypass the correct target before co-converging on glomeruli located at a distance. The phenotype specific for Gpi-anchored RNCAM is suppressed in mice overexpressing both isoforms, which suggests that two distinct RNCAM isoform-dependent activities influence segregation of OR-defined axon subclasses. PMID:12538518

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

    PubMed

    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

  20. 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

  1. Maturation of Sensori-Motor Functional Responses in the Preterm Brain

    PubMed Central

    Allievi, Alessandro G.; Arichi, Tomoki; Tusor, Nora; Kimpton, Jessica; Arulkumaran, Sophie; Counsell, Serena J.; Edwards, A. David; Burdet, Etienne

    2016-01-01

    Preterm birth engenders an increased risk of conditions like cerebral palsy and therefore this time may be crucial for the brain's developing sensori-motor system. However, little is known about how cortical sensori-motor function matures at this time, whether development is influenced by experience, and about its role in spontaneous motor behavior. We aimed to systematically characterize spatial and temporal maturation of sensori-motor functional brain activity across this period using functional MRI and a custom-made robotic stimulation device. We studied 57 infants aged from 30 + 2 to 43 + 2 weeks postmenstrual age. Following both induced and spontaneous right wrist movements, we saw consistent positive blood oxygen level–dependent functional responses in the contralateral (left) primary somatosensory and motor cortices. In addition, we saw a maturational trend toward faster, higher amplitude, and more spatially dispersed functional responses; and increasing integration of the ipsilateral hemisphere and sensori-motor associative areas. We also found that interhemispheric functional connectivity was significantly related to ex-utero exposure, suggesting the influence of experience-dependent mechanisms. At term equivalent age, we saw a decrease in both response amplitude and interhemispheric functional connectivity, and an increase in spatial specificity, culminating in the establishment of a sensori-motor functional response similar to that seen in adults. PMID:26491066

  2. On sex-related differences in auditory and visual sensory functioning.

    PubMed

    Rammsayer, Thomas H; Troche, Stefan J

    2012-06-01

    The present study was designed to elucidate sex-related differences in two basic auditory and one basic visual aspect of sensory functioning, namely sensory discrimination of pitch, loudness, and brightness. Although these three aspects of sensory functioning are of vital importance in everyday life, little is known about whether men and women differ from each other in these sensory functions. Participants were 100 male and 100 female volunteers ranging in age from 18 to 30 years. Since sensory sensitivity may be positively related to individual levels of intelligence and musical experience, measures of psychometric intelligence and musical background were also obtained. Reliably better performance for men compared to women was found for pitch and loudness, but not for brightness discrimination. Furthermore, performance on loudness discrimination was positively related to psychometric intelligence, while pitch discrimination was positively related to both psychometric intelligence and levels of musical training. Additional regression analyses revealed that each of three predictor variables (sex, psychometric intelligence, and musical training) accounted for a statistically significant portion of unique variance in pitch discrimination. With regard to loudness discrimination, regression analysis yielded a statistically significant portion of unique variance for sex as a predictor variable, whereas psychometric intelligence just failed to reach statistical significance. The potential influence of sex hormones on sex-related differences in sensory functions is discussed. PMID:22183583

  3. A hypothesis to explain how the sensory cortices respond in the appropriate sensory mode.

    PubMed

    Hocker, Geoffrey A

    2003-02-01

    How does an area of sensory cortex recognize the specific nature of the sensory mode of the stimulus that arrives from the peripheral sensory receptor, when nerve impulses are only all-or-nothing action potentials? Work in animals has shown that an area of sensory cortex can learn in which mode to respond. A period of cortical learning is required for phantom limb phenomena to develop, and for the ocular blind to dream in the visual mode. Arguing from these facts I develop the hypothesis that within the sensory cortices there are neurons that learn by neurotropic factor transport from their sensory receptors to function as surrogates for those receptors, thus enabling sensory cortical response to be modally specific. PMID:12562976

  4. Design of a robotic device for assessment and rehabilitation of hand sensory function.

    PubMed

    Lambercy, Olivier; Robles, Alejandro Juárez; Kim, Yeongmi; Gassert, Roger

    2011-01-01

    This paper presents the design and implementation of the Robotic Sensory Trainer, a robotic interface for assessment and therapy of hand sensory function. The device can provide three types of well controlled stimuli: (i) angular displacement at the metacarpophalangeal (MCP) joint using a remote-center-of-motion double-parallelogram structure, (ii) vibration stimuli at the fingertip, proximal phalange and palm, and (iii) pressure at the fingertip, while recording position, interaction force and feedback from the user over a touch screen. These stimuli offer a novel platform to investigate sensory perception in healthy subjects and patients with sensory impairments, with the potential to assess deficits and actively train detection of specific sensory cues in a standardized manner. A preliminary study with eight healthy subjects demonstrates the feasibility of using the Robotic Sensory Trainer to assess the sensory perception threshold in MCP angular position. An average just noticeable difference (JND) in the MCP joint angle of 2.46° (14.47%) was found, which is in agreement with previous perception studies. PMID:22275636

  5. Anatomical relations of the superficial sensory branches of the radial nerve: a cadaveric study with clinical implications

    PubMed Central

    2011-01-01

    Background Anatomically, it is difficult to give a systematic description of the superficial branch of the radial nerve (SBRN). Our aim was to describe the exact relationship of the SBRN to fixed bony points of radial styloid and Lister's tubercle, and to the cephalic vein. We also compared our data with other international studies. Methods The study was a descriptive anatomical study. Twenty-five forearms were dissected. Measurements were made from predefined fixed reference points. Results The mean distance to the point of emergence of the nerve from the radial styloid was 8.54 cm (SD = 1.32). The nerve branched at a mean distance of 5.57 cm (SD = 1.43) from the radial styloid. The mean distance to the point where the most medial and most lateral branches of the nerve crossing the wrist joint, measured from the Lister's tubercle were 2.51 cm (SD = 0.53) and 3.90 cm (SD = 0.64). In 17 specimens(68%) cephalic vein crossed the SBRN superficially once. Mean distance from the radial styloid to the most distal point where the vein crossed the nerve was 5.10 cm. Diffefrence between mean distance to the point of emergence and branching point, when compared with other international studies were not statistically significant. (P value > 0.05) Conclusions We recommend avoiding transverse incisions in the snuffbox region between 2.51 cm and 3.90 cm from the Listers tubercle. We also recommend avoiding cannulation of the cephalic vein in the distal forearm. PMID:22054296

  6. In vivo studies of silk based gold nano-composite conduits for functional peripheral nerve regeneration.

    PubMed

    Das, Suradip; Sharma, Manav; Saharia, Dhiren; Sarma, Kushal Konwar; Sarma, Monalisa Goswami; Borthakur, Bibhuti Bhusan; Bora, Utpal

    2015-09-01

    We report a novel silk-gold nanocomposite based nerve conduit successfully tested in a neurotmesis grade sciatic nerve injury model in rats over a period of eighteen months. The conduit was fabricated by adsorbing gold nanoparticles onto silk fibres and transforming them into a nanocomposite sheet by electrospinning which is finally given a tubular structure by rolling on a stainless steel mandrel of chosen diameter. The conduits were found to promote adhesion and proliferation of Schwann cells in vitro and did not elicit any toxic or immunogenic responses in vivo. We also report for the first time, the monitoring of muscular regeneration post nerve conduit implantation by recording motor unit potentials (MUPs) through needle electromyogram. Pre-seeding the conduits with Schwann cells enhanced myelination of the regenerated tissue. Histo-morphometric and electrophysiological studies proved that the nanocomposite based conduits pre-seeded with Schwann cells performed best in terms of structural and functional regeneration of severed sciatic nerves. The near normal values of nerve conduction velocity (50 m/sec), compound muscle action potential (29.7 mV) and motor unit potential (133 μV) exhibited by the animals implanted with Schwann cell loaded nerve conduits in the present study are superior to those observed in previous reports with synthetic materials as well as collagen based nerve conduits. Animals in this group were also able to perform complex locomotory activities like stretching and jumping with excellent sciatic function index (SFI) and led a normal life. PMID:26026910

  7. Imaging of temperature dependent hemodynamics in the rat sciatic nerve by functional photoacoustic microscopy

    PubMed Central

    2013-01-01

    Background Vascular hemodynamics is central to the regulation of neuro-metabolism and plays important roles in peripheral nerves diseases and their prevention. However, at present there are only a few techniques capable of directly measuring peripheral nerve vascular hemodynamics. Method Here, we investigate the use of dark-field functional photoacoustic microscopy (fPAM) for intrinsic visualizing of the relative hemodynamics of the rat sciatic nerve in response to localized temperature modulation (i.e., cooling and rewarming). Results and conclusion Our main results show that the relative functional total hemoglobin concentration (HbT) is more significantly correlated with localized temperature changes than the hemoglobin oxygen saturation (SO2) changes in the sciatic nerve. Our study also indicates that the relative HbT changes are better markers of neuronal activation than SO2 during nerve temperature changes. Our results show that fPAM is a promising candidate for in vivo imaging of peripheral nerve hemodynamics without the use of contrast agents. Additionally, this technique may shed light on the neuroprotective effect of hypothermia on peripheral nerves by visualizing their intrinsic hemodynamics. PMID:24245952

  8. Altered Functional Magnetic Resonance Imaging Responses to Nonpainful Sensory Stimulation in Fibromyalgia Patients

    PubMed Central

    López-Solá, Marina; Pujol, Jesus; Wager, Tor D.; Garcia-Fontanals, Alba; Blanco-Hinojo, Laura; Garcia-Blanco, Susana; Poca-Dias, Violant; Harrison, Ben J.; Contreras-Rodríguez, Oren; Monfort, Jordi; Garcia-Fructuoso, Ferran; Deus, Joan

    2015-01-01

    Objective Fibromyalgia (FM) is a disorder characterized by chronic pain and enhanced responses to acute noxious events. However, the sensory systems affected in FM may extend beyond pain itself, as FM patients show reduced tolerance to non-nociceptive sensory stimulation. Characterizing the neural substrates of multisensory hypersensitivity in FM may thus provide important clues about the underlying pathophysiology of the disorder. The aim of this study was to characterize brain responses to non-nociceptive sensory stimulation in FM patients and their relationship to subjective sensory sensitivity and clinical pain severity. Methods Functional magnetic resonance imaging (MRI) was used to assess brain response to auditory, visual, and tactile motor stimulation in 35 women with FM and 25 matched controls. Correlation and mediation analyses were performed to establish the relationship between brain responses and 3 types of outcomes: subjective hypersensitivity to daily sensory stimulation, spontaneous pain, and functional disability. Results Patients reported increased subjective sensitivity (increased unpleasantness) in response to multisensory stimulation in daily life. Functional MRI revealed that patients showed reduced task-evoked activation in primary/secondary visual and auditory areas and augmented responses in the insula and anterior lingual gyrus. Reduced responses in visual and auditory areas were correlated with subjective sensory hypersensitivity and clinical severity measures. Conclusion FM patients showed strong attenuation of brain responses to nonpainful events in early sensory cortices, accompanied by an amplified response at later stages of sensory integration in the insula. These abnormalities are associated with core FM symptoms, suggesting that they may be part of the pathophysiology of the disease. PMID:25220783

  9. Tiotropium modulates transient receptor potential V1 (TRPV1) in airway sensory nerves: A beneficial off-target effect?⋆☆

    PubMed Central

    Birrell, Mark A.; Bonvini, Sara J.; Dubuis, Eric; Maher, Sarah A.; Wortley, Michael A.; Grace, Megan S.; Raemdonck, Kristof; Adcock, John J.; Belvisi, Maria G.

    2014-01-01

    Background Recent studies have suggested that the long-acting muscarinic receptor antagonist tiotropium, a drug widely prescribed for its bronchodilator activity in patients with chronic obstructive pulmonary disease and asthma, improves symptoms and attenuates cough in preclinical and clinical tussive agent challenge studies. The mechanism by which tiotropium modifies tussive responses is not clear, but an inhibition of vagal tone and a consequent reduction in mucus production from submucosal glands and bronchodilation have been proposed. Objective The aim of this study was to investigate whether tiotropium can directly modulate airway sensory nerve activity and thereby the cough reflex. Methods We used a conscious cough model in guinea pigs, isolated vagal sensory nerve and isolated airway neuron tissue– and cell-based assays, and in vivo single-fiber recording electrophysiologic techniques. Results Inhaled tiotropium blocked cough and single C-fiber firing in the guinea pig to the transient receptor potential (TRP) V1 agonist capsaicin, a clinically relevant tussive stimulant. Tiotropium and ipratropium, a structurally similar muscarinic antagonist, inhibited capsaicin responses in isolated guinea pig vagal tissue, but glycopyrrolate and atropine did not. Tiotropium failed to modulate other TRP channel–mediated responses. Complementary data were generated in airway-specific primary ganglion neurons, demonstrating that tiotropium inhibited capsaicin-induced, but not TRPA1-induced, calcium movement and voltage changes. Conclusion For the first time, we have shown that tiotropium inhibits neuronal TRPV1-mediated effects through a mechanism unrelated to its anticholinergic activity. We speculate that some of the clinical benefit associated with taking tiotropium (eg, in symptom control) could be explained through this proposed mechanism of action. PMID:24506933

  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 descending pain system may be involved in TMD. PMID:25905862

  11. 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 descending pain system may be involved in TMD. PMID:25905862

  12. Intrinsic and therapeutic factors determining the recovery of motor function after peripheral nerve transection.

    PubMed

    Skouras, Emmanouil; Ozsoy, Umut; Sarikcioglu, Levent; Angelov, Doychin N

    2011-07-01

    Insufficient recovery after peripheral nerve injury has been attributed to (i) poor pathfinding of regrowing axons, (ii) excessive collateral axonal branching at the lesion site and (iii) polyneuronal innervation of the neuromuscular junctions (NMJ). The facial nerve transection model has been used initially to measure restoration of function after varying therapies and to examine the mechanisms underlying their effects. Since it is very difficult to control the navigation of several thousand axons, efforts concentrated on collateral branching and NMJ-polyinnervation. Treatment with antibodies against trophic factors to combat branching improved the precision of reinnervation, but had no positive effects on functional recovery. This suggested that polyneuronal reinnervation--rather than collateral branching--may be the critical limiting factor. The former could be reduced by pharmacological agents known to perturb microtubule assembly and was followed by recovery of function. Because muscle polyinnervation is activity-dependent and can be manipulated, attempts to design a clinically feasible therapy were performed by electrical stimulation or by soft tissue massage. Electrical stimulation applied to the transected facial nerve or to paralysed facial muscles did not improve vibrissal motor performance and failed to diminish polyinnervation. In contrast, gentle stroking of the paralysed muscles (vibrissal, orbicularis oculi, tongue musculature) resulted in full recovery of function. This manual stimulation was also effective after hypoglossal-facial nerve suture and after interpositional nerve grafting, but not after surgical reconstruction of the median nerve. All these findings raise hopes that clinically feasible and effective therapies could be soon designed and tested. PMID:21458252

  13. Use of Nerve Conduction Velocity to Assess Peripheral Nerve Health in Aging Mice.

    PubMed

    Walsh, Michael E; Sloane, Lauren B; Fischer, Kathleen E; Austad, Steven N; Richardson, Arlan; Van Remmen, Holly

    2015-11-01

    Nerve conduction velocity (NCV), the speed at which electrical signals propagate along peripheral nerves, is used in the clinic to evaluate nerve function in humans. A decline in peripheral nerve function is associated with a number of age-related pathologies. While several studies have shown that NCV declines with age in humans, there is little information on the effect of age on NCV in peripheral nerves in mice. In this study, we evaluated NCV in male and female C57Bl/6 mice ranging from 4 to 32 months of age. We observed a decline in NCV in both male and female mice after 20 months of age. Sex differences were detected in sensory NCV as well as the rate of decline during aging in motor nerves; female mice had slower sensory NCV and a slower age-related decline in motor nerves compared with male mice. We also tested the effect of dietary restriction on NCV in 30-month-old female mice. Dietary restriction prevented the age-related decline in sciatic NCV but not other nerves. Because NCV is clinically relevant to the assessment of nerve function, we recommend that NCV be used to evaluate healthspan in assessing genetic and pharmacological interventions that increase the life span of mice. PMID:25477428

  14. Kv7.2 regulates the function of peripheral sensory neurons

    PubMed Central

    King, Chih H.; Lancaster, Eric; Salomon, Daniela; Peles, Elior; Scherer, Steven S.

    2014-01-01

    The Kv7 (KCNQ) family of voltage-gated K+ channels regulates cellular excitability. The functional role of Kv7.2 has been hampered by the lack of a viable Kcnq2-null animal model. In this study, we generated homozygous Kcnq2-null sensory neurons using the Cre-Lox system; in these mice, Kv7.2 expression is absent in the peripheral sensory neurons, whereas the expression of other molecular components of nodes (including Kv7.3), paranodes, and juxtaparanodes is not altered. The conditional Kcnq2-null animals exhibit normal motor performance, but have increased thermal hyperalgesia and mechanical allodynia. Whole cell patch recording technique demonstrates that Kcnq2-null sensory neurons have increased excitability and reduced spike frequency adaptation. Taken together, our results suggest that the loss of Kv7.2 activity increases the excitability of primary sensory neurons. PMID:24687876

  15. 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 ?m instead of using glycerin and teasing the tissue apart as in Gairns modified gold chloride method. We attached sections directly to gelatin subbed slides after sectioning with a cryostat. The slides then were processed and coverslipped with Permount. Staining consistency was demonstrated throughout the tissue sections and neural structures were clearly identifiable. PMID:24476562

  16. Differential upregulation in DRG neurons of an α2δ-1 splice variant with a lower affinity for gabapentin after peripheral sensory nerve injury

    PubMed Central

    Lana, Beatrice; Schlick, Bettina; Martin, Stuart; Pratt, Wendy S.; Page, Karen M.; Goncalves, Leonor; Rahman, Wahida; Dickenson, Anthony H.; Bauer, Claudia S.; Dolphin, Annette C.

    2014-01-01

    The α2δ-1 protein is an auxiliary subunit of voltage-gated calcium channels, critical for neurotransmitter release. It is upregulated in dorsal root ganglion (DRG) neurons following sensory nerve injury, and is also the therapeutic target of the gabapentinoid drugs, which are efficacious in both experimental and human neuropathic pain conditions. α2δ-1 has 3 spliced regions: A, B, and C. A and C are cassette exons, whereas B is introduced via an alternative 3′ splice acceptor site. Here we have examined the presence of α2δ-1 splice variants in DRG neurons, and have found that although the main α2δ-1 splice variant in DRG is the same as that in brain (α2δ-1 ΔA+B+C), there is also another α2δ-1 splice variant (ΔA+BΔC), which is expressed in DRG neurons and is differentially upregulated compared to the main DRG splice variant α2δ-1 ΔA+B+C following spinal nerve ligation. Furthermore, this differential upregulation occurs preferentially in a small nonmyelinated DRG neuron fraction, obtained by density gradient separation. The α2δ-1 ΔA+BΔC splice variant supports CaV2 calcium currents with unaltered properties compared to α2δ-1 ΔA+B+C, but shows a significantly reduced affinity for gabapentin. This variant could therefore play a role in determining the efficacy of gabapentin in neuropathic pain. PMID:24315988

  17. 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. PMID:26332703

  18. Recovery of laryngeal function after intraoperative injury to the recurrent laryngeal nerve

    PubMed Central

    Hydman, Jonas; Svensson, Mikael

    2015-01-01

    Loss of function in the recurrent laryngeal nerve (RLN) during thyroid/parathyroid surgery, despite a macroscopically intact nerve, is a challenge which highlights the sensitivity and complexity of laryngeal innervation. Furthermore, the uncertain prognosis stresses a lack of capability to diagnose the reason behind the impaired function. There is a great deal of literature considering risk factors, surgical technique and mechanisms outside the nerve affecting the incidence of RLN paresis during surgery. To be able to prognosticate recovery in cases of laryngeal dysfunction and voice changes after thyroid surgery, the surgeon would first need to define the presence, location, and type of laryngeal nerve injury. There is little data describing the events within the nerve and the neurobiological reasons for the impaired function related to potential recovery and prognosis. In addition, very little data has been presented in order to clarify any differences between the transient and permanent injury of the RLN. This review aims, from an anatomical and neurobiological perspective, to provide an update on the current understandings of surgically-induced injury to the laryngeal nerves. PMID:25713777

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

    PubMed

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

    2014-10-01

    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 represent a promising biomaterial for use in bioengineered peripheral nerve repair. PMID:25064803

  20. 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 represent a promising biomaterial for use in bioengineered peripheral nerve repair. PMID:25064803

  1. Ciguatoxin reduces regenerative capacity of axotomized peripheral neurons and delays functional recovery in pre-exposed mice after peripheral nerve injury.

    PubMed

    Au, Ngan Pan Bennett; Kumar, Gajendra; Asthana, Pallavi; Tin, Chung; Mak, Yim Ling; Chan, Leo Lai; Lam, Paul Kwan Sing; Ma, Chi Him Eddie

    2016-01-01

    Ciguatera fish poisoning (CFP) results from consumption of tropical reef fish containing ciguatoxins (CTXs). Pacific (P)-CTX-1 is among the most potent known CTXs and the predominant source of CFP in the endemic region responsible for the majority of neurological symptoms in patients. Chronic and persistent neurological symptoms occur in some CFP patients, which often result in incomplete functional recovery for years. However, the direct effects of exposure to CTXs remain largely unknown. In present study, we exposed mice to CTX purified from ciguatera fish sourced from the Pacific region. P-CTX-1 was detected in peripheral nerves within hours and persisted for two months after exposure. P-CTX-1 inhibited axonal regrowth from axotomized peripheral neurons in culture. P-CTX-1 exposure reduced motor function in mice within the first two weeks of exposure before returning to baseline levels. These pre-exposed animals exhibited delayed sensory and motor functional recovery, and irreversible motor deficits after peripheral nerve injury in which formation of functional synapses was impaired. These findings are consistent with reduced muscle function, as assessed by electromyography recordings. Our study provides strong evidence that the persistence of P-CTX-1 in peripheral nerves reduces the intrinsic growth capacity of peripheral neurons, resulting in delayed functional recovery after injury. PMID:27229176

  2. Delayed functional expression of neuronal chemokine receptors following focal nerve demyelination in the rat: a mechanism for the development of chronic sensitization of peripheral nociceptors

    PubMed Central

    Bhangoo, Sonia; Ren, Dongjun; Miller, Richard J; Henry, Kenneth J; Lineswala, Jayana; Hamdouchi, Chafiq; Li, Baolin; Monahan, Patrick E; Chan, David M; Ripsch, Matthew S; White, Fletcher A

    2007-01-01

    Background Animal and clinical studies have revealed that focal peripheral nerve axon demyelination is accompanied by nociceptive pain behavior. C-C and C-X-C chemokines and their receptors have been strongly implicated in demyelinating polyneuropathies and persistent pain syndromes. Herein, we studied the degree to which chronic nociceptive pain behavior is correlated with the neuronal expression of chemokines and their receptors following unilateral lysophosphatidylcholine (LPC)-induced focal demyelination of the sciatic nerve in rats. Results Focal nerve demyelination increased behavioral reflex responsiveness to mechanical stimuli between postoperative day (POD) 3 and POD28 in both the hindpaw ipsilateral and contralateral to the nerve injury. This behavior was accompanied by a bilateral increase in the numbers of primary sensory neurons expressing the chemokine receptors CCR2, CCR5, and CXCR4 by POD14, with no change in the pattern of CXCR3 expression. Significant increases in the numbers of neurons expressing the chemokines monocyte chemoattractant protein-1 (MCP-1/CCL2), Regulated on Activation, Normal T Expressed and Secreted (RANTES/CCL5) and interferon γ-inducing protein-10 (IP-10/CXCL10) were also evident following nerve injury, although neuronal expression pattern of stromal cell derived factor-1α (SDF1/CXCL12) did not change. Functional studies demonstrated that acutely dissociated sensory neurons derived from LPC-injured animals responded with increased [Ca2+]i following exposure to MCP-1, IP-10, SDF1 and RANTES on POD 14 and 28, but these responses were largely absent by POD35. On days 14 and 28, rats received either saline or a CCR2 receptor antagonist isomer (CCR2 RA-[R]) or its inactive enantiomer (CCR2 RA-[S]) by intraperitoneal (i.p.) injection. CCR2 RA-[R] treatment of nerve-injured rats produced stereospecific bilateral reversal of tactile hyperalgesia. Conclusion These results suggest that the presence of chemokine signaling by both injured and adjacent, uninjured sensory neurons is correlated with the maintenance phase of a persistent pain state, suggesting that chemokine receptor antagonists may be an important therapeutic intervention for chronic pain. PMID:18076762

  3. Stem cell salvage of injured peripheral nerve.

    PubMed

    Grimoldi, Nadia; Colleoni, Federica; Tiberio, Francesca; Vetrano, Ignazio G; Cappellari, Alberto; Costa, Antonella; Belicchi, Marzia; Razini, Paola; Giordano, Rosaria; Spagnoli, Diego; Pluderi, Mauro; Gatti, Stefano; Morbin, Michela; Gaini, Sergio M; Rebulla, Paolo; Bresolin, Nereo; Torrente, Yvan

    2015-01-01

    We previously developed a collagen tube filled with autologous skin-derived stem cells (SDSCs) for bridging long rat sciatic nerve gaps. Here we present a case report describing a compassionate use of this graft for repairing the polyinjured motor and sensory nerves of the upper arms of a patient. Preclinical assessment was performed with collagen/SDSC implantation in rats after sectioning the sciatic nerve. For the patient, during the 3-year follow-up period, functional recovery of injured median and ulnar nerves was assessed by pinch gauge test and static two-point discrimination and touch test with monofilaments, along with electrophysiological and MRI examinations. Preclinical experiments in rats revealed rescue of sciatic nerve and no side effects of patient-derived SDSC transplantation (30 and 180 days of treatment). In the patient treatment, motor and sensory functions of the median nerve demonstrated ongoing recovery postimplantation during the follow-up period. The results indicate that the collagen/SDSC artificial nerve graft could be used for surgical repair of larger defects in major lesions of peripheral nerves, increasing patient quality of life by saving the upper arms from amputation. PMID:24268028

  4. Misdirection of Regenerating Axons and Functional Recovery Following Sciatic Nerve Injury in Rats

    PubMed Central

    Hamilton, Shirley K.; Hinkle, Marcus L.; Nicolini, Jennifer; Rambo, Lindsay N.; Rexwinkle, April M.; Rose, Sam J.; Sabatier, Manning J.; Backus, Deborah; English, Arthur W.

    2013-01-01

    Poor functional recovery found after peripheral nerve injury has been attributed to the misdirection of regenerating axons to reinnervate functionally inappropriate muscles. We applied brief electrical stimulation (ES) to the common fibular (CF) but not the tibial (Tib) nerve just prior to transection and repair of the entire rat sciatic nerve, to attempt to influence the misdirection of its regenerating axons. The specificity with which regenerating axons reinnervated appropriate targets was evaluated physiologically using compound muscle action potentials (M responses) evoked from stimulation of the two nerve branches above the injury site. Functional recovery was assayed using the timing of electromyography (EMG) activity recorded from the tibialis anterior (TA) and soleus (Sol) muscles during treadmill locomotion and kinematic analysis of hindlimb locomotor movements. Selective ES of the CF nerve resulted in restored M-responses at earlier times than in unstimulated controls in both TA and Sol muscles. Stimulated CF axons reinnervated inappropriate targets to a greater extent than unstimulated Tib axons. During locomotion, functional antagonist muscles, TA and Sol, were coactivated both in stimulated rats and in unstimulated but injured rats. Hindlimb kinematics in stimulated rats were comparable to untreated rats, but significantly different from intact controls. Selective ES promotes enhanced axon regeneration but does so with decreased fidelity of muscle reinnervation. Functional recovery is neither improved nor degraded, suggesting that compensatory changes in the outputs of the spinal circuits driving locomotion may occur irrespective of the extent of misdirection of regenerating axons in the periphery. PMID:21120925

  5. Immunohistochemical, Ultrastructural and Functional Analysis of Axonal Regeneration through Peripheral Nerve Grafts Containing Schwann Cells Expressing BDNF, CNTF or NT3

    PubMed Central

    Godinho, Maria João; Teh, Lip; Pollett, Margaret A.; Goodman, Douglas; Hodgetts, Stuart I.; Sweetman, Iain; Walters, Mark; Verhaagen, Joost; Plant, Giles W.; Harvey, Alan R.

    2013-01-01

    We used morphological, immunohistochemical and functional assessments to determine the impact of genetically-modified peripheral nerve (PN) grafts on axonal regeneration after injury. Grafts were assembled from acellular nerve sheaths repopulated ex vivo with Schwann cells (SCs) modified to express brain-derived neurotrophic factor (BDNF), a secretable form of ciliary neurotrophic factor (CNTF), or neurotrophin-3 (NT3). Grafts were used to repair unilateral 1 cm defects in rat peroneal nerves and 10 weeks later outcomes were compared to normal nerves and various controls: autografts, acellular grafts and grafts with unmodified SCs. The number of regenerated βIII-Tubulin positive axons was similar in all grafts with the exception of CNTF, which contained the fewest immunostained axons. There were significantly lower fiber counts in acellular, untransduced SC and NT3 groups using a PanNF antibody, suggesting a paucity of large caliber axons. In addition, NT3 grafts contained the greatest number of sensory fibres, identified with either IB4 or CGRP markers. Examination of semi- and ultra-thin sections revealed heterogeneous graft morphologies, particularly in BDNF and NT3 grafts in which the fascicular organization was pronounced. Unmyelinated axons were loosely organized in numerous Remak bundles in NT3 grafts, while the BDNF graft group displayed the lowest ratio of umyelinated to myelinated axons. Gait analysis revealed that stance width was increased in rats with CNTF and NT3 grafts, and step length involving the injured left hindlimb was significantly greater in NT3 grafted rats, suggesting enhanced sensory sensitivity in these animals. In summary, the selective expression of BDNF, CNTF or NT3 by genetically modified SCs had differential effects on PN graft morphology, the number and type of regenerating axons, myelination, and locomotor function. PMID:23950907

  6. Using multiple high-count electrode arrays in human median and ulnar nerves to restore sensorimotor function after previous transradial amputation of the hand.

    PubMed

    Clark, Gregory A; Wendelken, Suzanne; Page, David M; Davis, Tyler; Wark, Heather A C; Normann, Richard A; Warren, David J; Hutchinson, Douglas T

    2014-01-01

    Peripheral nerve interfaces that can record from and stimulate large numbers of different nerve fibers selectively and independently may help restore intuitive and effective motor and sensory function after hand amputation. To this end, and extending previous work in two subjects, two 100-electrode Utah Slanted Electrode Arrays (USEAs) were implanted for four weeks in the residual ulnar and median nerves of a 50-year-old male whose left, dominant hand had been amputated 21 years previously. Subsequent experiments involved 1) recording from USEAs for real-time control of a virtual prosthetic hand; 2) stimulation to evoke somatosensory percepts; and 3) closed-loop sensorimotor control. Overall, partial motor control and sensation were achieved using USEAs. 1) Isolated action potentials recorded from nerve motor fibers, although sparse at these distal implant sites, were activated during fictive movements of the phantom hand. Unlike in our previous two subjects, electromyographic (EMG) activity contributed to most online recordings and decodes, but was reduced in offline analyses using common average referencing. Online and offline Kalman-filter decodes of thresholded neural or EMG spikes independently controlled different digits of the virtual hand with one or two degrees of freedom. 2) Microstimulation through individual electrodes of the two USEAs evoked up to 106 different percepts, covering much of the phantom hand. The subject discriminated among five perceived stimulus locations, and between two somatosensory submodalities at a single location. 3) USEA-evoked percepts, mimicking contact with either a near or distal virtual target, were used to terminate movements of the virtual hand controlled with USEA recordings comprised wholly or mostly of EMG. These results further indicate that USEAs can help restore sensory and motor function after hand loss. PMID:25570369

  7. Time-course of Changes in Activation Among Facial Nerve Injury: A Functional Imaging Study.

    PubMed

    Xiao, Fu-Long; Gao, Pei-Yi; Sui, Bin-Bin; Wan, Hong; Lin, Yan; Xue, Jing; Zhou, Jian; Qian, Tian-Yi; Wang, Shiwei; Li, Dezhi; Liu, Song

    2015-10-01

    Patients suffering different intervals of facial nerve injury were investigated by functional magnetic resonance imaging to study changes in activation within cortex.Forty-five patients were divided into 3 groups based on intervals of facial nerve injury. Another 16 age and sex-matched healthy participants were included as a control group. Patients and healthy participants underwent task functional magnetic resonance imaging (eye blinking and lip pursing) examination.Functional reorganization after facial nerve injury is dynamic and time-dependent. Correlation between activation in sensorimotor area and intervals of facial nerve injury was significant, with a Pearson correlation coefficient of -0.951 (P < 0.001) in the left sensorimotor area and a Pearson correlation coefficient of 0.333 (P = 0.025) in the right sensorimotor area.Increased activation in integration areas, such as supramarginal gyrus and precunes lobe, could be detected in the early-middle stage of facial dysfunction compared with normal individuals. Decreased activation in sensorimotor area contralateral to facial nerve injury could be found in late stage of facial dysfunction compared with normal individuals. Dysfunction in the facial nerve has devastating effects on the activity of sensorimotor areas, whereas enhanced intensity in the sensorimotor area ipsilateral to the facial nerve injury in middle stage of facial dysfunction suggests the possible involvement of interhemispheric reorganization. Behavioral or brain stimulation technique treatment in this stage could be applied to alter reorganization within sensorimotor area in the rehabilitation of facial function, monitoring of therapeutic efficacy, and improvement in therapeutic intervention along the course of recovery. PMID:26512554

  8. In vivo characterization of regenerative peripheral nerve interface function

    NASA Astrophysics Data System (ADS)

    Ursu, Daniel C.; Urbanchek, Melanie G.; Nedic, Andrej; Cederna, Paul S.; Gillespie, R. Brent

    2016-04-01

    Objective. Regenerative peripheral nerve interfaces (RPNIs) are neurotized free autologous muscle grafts equipped with electrodes to record myoelectric signals for prosthesis control. Viability of rat RPNI constructs have been demonstrated using evoked responses. In vivo RPNI characterization is the next critical step for assessment as a control modality for prosthetic devices. Approach. Two RPNIs were created in each of two rats by grafting portions of free muscle to the ends of divided peripheral nerves (peroneal in the left and tibial in the right hind limb) and placing bipolar electrodes on the graft surface. After four months, we examined in vivo electromyographic signal activity and compared these signals to muscular electromyographic signals recorded from autologous muscles in two rats serving as controls. An additional group of two rats in which the autologous muscles were denervated served to quantify cross-talk in the electrode recordings. Recordings were made while rats walked on a treadmill and a motion capture system tracked the hind limbs. Amplitude and periodicity of signals relative to gait were quantified, correlation between electromyographic and motion recording were assessed, and a decoder was trained to predict joint motion. Main Results. Raw RPNI signals were active during walking, with amplitudes of 1 mVPP, and quiet during standing, with amplitudes less than 0.1 mVPP. RPNI signals were periodic and entrained with gait. A decoder predicted bilateral ankle motion with greater than 80% reliability. Control group signal activity agreed with literature. Denervated group signals remained quiescent throughout all evaluations. Significance. In vivo myoelectric RPNI activity encodes neural activation patterns associated with gait. Signal contamination from muscles adjacent to the RPNI is minimal, as demonstrated by the low amplitude signals obtained from the Denervated group. The periodicity and entrainment to gait of RPNI recordings suggests the transduced signals were generated via central nervous system control.

  9. Peripheral Nerve Reconstruction after Injury: A Review of Clinical and Experimental Therapies

    PubMed Central

    Grinsell, D.; Keating, C. P.

    2014-01-01

    Unlike other tissues in the body, peripheral nerve regeneration is slow and usually incomplete. Less than half of patients who undergo nerve repair after injury regain good to excellent motor or sensory function and current surgical techniques are similar to those described by Sunderland more than 60 years ago. Our increasing knowledge about nerve physiology and regeneration far outweighs our surgical abilities to reconstruct damaged nerves and successfully regenerate motor and sensory function. It is technically possible to reconstruct nerves at the fascicular level but not at the level of individual axons. Recent surgical options including nerve transfers demonstrate promise in improving outcomes for proximal nerve injuries and experimental molecular and bioengineering strategies are being developed to overcome biological roadblocks limiting patient recovery. PMID:25276813

  10. Functional and anatomical basis for brain plasticity in facial palsy rehabilitation using the masseteric nerve.

    PubMed

    Buendia, Javier; Loayza, Francis R; Luis, Elkin O; Celorrio, Marta; Pastor, Maria A; Hontanilla, Bernardo

    2016-03-01

    Several techniques have been described for smile restoration after facial nerve paralysis. When a nerve other than the contralateral facial nerve is used to restore the smile, some controversy appears because of the nonphysiological mechanism of smile recovering. Different authors have reported natural results with the masseter nerve. The physiological pathways which determine whether this is achieved continue to remain unclear. Using functional magnetic resonance imaging, brain activation pattern measuring blood-oxygen-level-dependent (BOLD) signal during smiling and jaw clenching was recorded in a group of 24 healthy subjects (11 females). Effective connectivity of premotor regions was also compared in both tasks. The brain activation pattern was similar for smile and jaw-clenching tasks. Smile activations showed topographic overlap though more extended for smile than clenching. Gender comparisons during facial movements, according to kinematics and BOLD signal, did not reveal significant differences. Effective connectivity results of psychophysiological interaction (PPI) from the same seeds located in bilateral facial premotor regions showed significant task and gender differences (p < 0.001). The hypothesis of brain plasticity between the facial nerve and masseter nerve areas is supported by the broad cortical overlap in the representation of facial and masseter muscles. PMID:26683008

  11. Importance of Tissue Morphology Relative to Patient Reports of Symptoms and Functional Limitations Resulting From Median Nerve Pathology

    PubMed Central

    Evans, Kevin D.; Li, Xiaobai; Sommerich, Carolyn M.; Case-Smith, Jane

    2013-01-01

    Significant data exist for the personal, environmental, and occupational risk factors for carpal tunnel syndrome. Few data, however, explain the interrelationship of tissue morphology to these factors among patients with clinical presentation of median nerve pathology. Therefore, our primary objective was to examine the relationship of various risk factors that may be predictive of subjective reports of symptoms or functional deficits accounting for median nerve morphology. Using diagnostic ultrasonography, we observed real-time median nerve morphology among 88 participants with varying reports of symptoms or functional limitations resulting from median nerve pathology. Body mass index, educational level, and nerve morphology were the primary predictive factors. Monitoring median nerve morphology with ultrasonography may provide valuable information for clinicians treating patients with symptoms of median nerve pathology. Sonographic measurements may be a useful clinical tool for improving treatment planning and provision, documenting patient status, or measuring clinical outcomes of prevention and rehabilitation interventions. PMID:23245784

  12. Awake vs. anesthetized: layer-specific sensory processing in visual cortex and functional connectivity between cortical areas.

    PubMed

    Sellers, Kristin K; Bennett, Davis V; Hutt, Axel; Williams, James H; Fröhlich, Flavio

    2015-06-01

    During general anesthesia, global brain activity and behavioral state are profoundly altered. Yet it remains mostly unknown how anesthetics alter sensory processing across cortical layers and modulate functional cortico-cortical connectivity. To address this gap in knowledge of the micro- and mesoscale effects of anesthetics on sensory processing in the cortical microcircuit, we recorded multiunit activity and local field potential in awake and anesthetized ferrets (Mustela putoris furo) during sensory stimulation. To understand how anesthetics alter sensory processing in a primary sensory area and the representation of sensory input in higher-order association areas, we studied the local sensory responses and long-range functional connectivity of primary visual cortex (V1) and prefrontal cortex (PFC). Isoflurane combined with xylazine provided general anesthesia for all anesthetized recordings. We found that anesthetics altered the duration of sensory-evoked responses, disrupted the response dynamics across cortical layers, suppressed both multimodal interactions in V1 and sensory responses in PFC, and reduced functional cortico-cortical connectivity between V1 and PFC. Together, the present findings demonstrate altered sensory responses and impaired functional network connectivity during anesthesia at the level of multiunit activity and local field potential across cortical layers. PMID:25833839

  13. Schwann cell-specific JAM-C-deficient mice reveal novel expression and functions for JAM-C in peripheral nerves

    PubMed Central

    Colom, Bartomeu; Poitelon, Yannick; Huang, Wenlong; Woodfin, Abigail; Averill, Sharon; Del Carro, Ubaldo; Zambroni, Desirée; Brain, Susan D.; Perretti, Mauro; Ahluwalia, Amrita; Priestley, John V.; Chavakis, Triantafyllos; Imhof, Beat A.; Feltri, M. Laura; Nourshargh, Sussan

    2012-01-01

    Junctional adhesion molecule-C (JAM-C) is an adhesion molecule expressed at junctions between adjacent endothelial and epithelial cells and implicated in multiple inflammatory and vascular responses. In addition, we recently reported on the expression of JAM-C in Schwann cells (SCs) and its importance for the integrity and function of peripheral nerves. To investigate the role of JAM-C in neuronal functions further, mice with a specific deletion of JAM-C in SCs (JAM-C SC KO) were generated. Compared to wild-type (WT) controls, JAM-C SC KO mice showed electrophysiological defects, muscular weakness, and hypersensitivity to mechanical stimuli. In addressing the underlying cause of these defects, nerves from JAM-C SC KO mice were found to have morphological defects in the paranodal region, exhibiting increased nodal length as compared to WTs. The study also reports on previously undetected expressions of JAM-C, namely on perineural cells, and in line with nociception defects of the JAM-C SC KO animals, on finely myelinated sensory nerve fibers. Collectively, the generation and characterization of JAM-C SC KO mice has provided unequivocal evidence for the involvement of SC JAM-C in the fine organization of peripheral nerves and in modulating multiple neuronal responses.—Colom, B., Poitelon, Y., Huang, W., Woodfin, A., Averill, S., Del Carro, U., Zambroni, D., Brain, S. D., Perretti, M., Ahluwalia, A., Priestley, J. V., Chavakis, T., Imhof, B. A., Feltri, M. L., Nourshargh, S. Schwann cell-specific JAM-C-deficient mice reveal novel expression and functions for JAM-C in peripheral nerves. PMID:22090315

  14. Beyond traditional approaches to understanding the functional role of neuromodulators in sensory cortices

    PubMed Central

    Edeline, Jean-Marc

    2012-01-01

    Over the last two decades, a vast literature has described the influence of neuromodulatory systems on the responses of sensory cortex neurons (review in Gu, 2002; Edeline, 2003; Weinberger, 2003; Metherate, 2004, 2011). At the single cell level, facilitation of evoked responses, increases in signal-to-noise ratio, and improved functional properties of sensory cortex neurons have been reported in the visual, auditory, and somatosensory modality. At the map level, massive cortical reorganizations have been described when repeated activation of a neuromodulatory system are associated with a particular sensory stimulus. In reviewing our knowledge concerning the way the noradrenergic and cholinergic system control sensory cortices, I will point out that the differences between the protocols used to reveal these effects most likely reflect different assumptions concerning the role of the neuromodulators. More importantly, a gap still exists between the descriptions of neuromodulatory effects and the concepts that are currently applied to decipher the neural code operating in sensory cortices. Key examples that bring this gap into focus are the concept of cell assemblies and the role played by the spike timing precision (i.e., by the temporal organization of spike trains at the millisecond time-scale) which are now recognized as essential in sensory physiology but are rarely considered in experiments describing the role of neuromodulators in sensory cortices. Thus, I will suggest that several lines of research, particularly in the field of computational neurosciences, should help us to go beyond traditional approaches and, ultimately, to understand how neuromodulators impact on the cortical mechanisms underlying our perceptual abilities. PMID:22866031

  15. Model-based analysis and design of nerve cuff electrodes for restoring bladder function by selective stimulation of the pudendal nerve

    NASA Astrophysics Data System (ADS)

    Kent, Alexander R.; Grill, Warren M.

    2013-06-01

    Objective. Electrical stimulation of the pudendal nerve (PN) is being developed as a means to restore bladder function in persons with spinal cord injury. A single nerve cuff electrode placed on the proximal PN trunk may enable selective stimulation of distinct fascicles to maintain continence or evoke micturition. The objective of this study was to design a nerve cuff that enabled selective stimulation of the PN. Approach. We evaluated the performance of both flat interface nerve electrode (FINE) cuff and round cuff designs, with a range of FINE cuff heights and number of contacts, as well as multiple contact orientations. This analysis was performed using a computational model, in which the nerve and fascicle cross-sectional positions from five human PN trunks were systematically reshaped within the nerve cuff. These cross-sections were used to create finite element models, with electric potentials calculated and applied to a cable model of a myelinated axon to evaluate stimulation selectivity for different PN targets. Subsequently, the model was coupled to a genetic algorithm (GA) to identify solutions that used multiple contact activation to maximize selectivity and minimize total stimulation voltage. Main results. Simulations did not identify any significant differences in selectivity between FINE and round cuffs, although the latter required smaller stimulation voltages for target activation due to preserved localization of targeted fascicle groups. Further, it was found that a ten contact nerve cuff generated sufficient selectivity for all PN targets, with the degree of selectivity dependent on the relative position of the target within the nerve. The GA identified solutions that increased fitness by 0.7-45.5% over single contact activation by decreasing stimulation of non-targeted fascicles. Significance. This study suggests that using an optimal nerve cuff design and multiple contact activation could enable selective stimulation of the human PN trunk for restoration of bladder function.

  16. Model-based analysis and design of nerve cuff electrodes for restoring bladder function by selective stimulation of the pudendal nerve

    PubMed Central

    Kent, Alexander R; Grill, Warren M

    2013-01-01

    Objective Electrical stimulation of the pudendal nerve (PN) is being developed as a means to restore bladder function in persons with spinal cord injury. A single nerve cuff electrode placed on the proximal PN trunk may enable selective stimulation of distinct fascicles to maintain continence or evoke micturition. The objective of this study was to design a nerve cuff that enabled selective stimulation of the PN. Approach We evaluated the performance of both flat interface nerve electrode (FINE) cuff and round cuff designs, with a range of FINE cuff heights and number of contacts, as well as multiple contact orientations. This analysis was performed using a computational model, in which the nerve and fascicle cross-sectional positions from five human PN trunks were systematically reshaped within the nerve cuff. These cross-sections were used to create finite element models, with electric potentials calculated and applied to a cable model of a myelinated axon to evaluate stimulation selectivity for different PN targets. Subsequently, the model was coupled to a genetic algorithm (GA) to identify solutions that used multiple contact activation to maximize selectivity and minimize total stimulation voltage. Main results Simulations did not identify any significant differences in selectivity between FINE and round cuffs, although the latter required smaller stimulation voltages for target activation due to preserved localization of targeted fascicle groups. Further, it was found that a 10 contact nerve cuff generated sufficient selectivity for all PN targets, with the degree of selectivity dependent on the relative position of the target within the nerve. The GA identified solutions that increased fitness by 0.7–45.5% over single contact activation by decreasing stimulation of non-targeted fascicles. Significance This study suggests that using an optimal nerve cuff design and multiple contact activation could enable selective stimulation of the human PN trunk for restoration of bladder function. PMID:23594706

  17. The effect of chronic skeletal muscle stimulation on capillary growth in the rat: are sensory nerve fibres involved?

    PubMed Central

    Hudlicka, Olga; Graciotti, Laura; Fulgenzi, Gianluca; Brown, Margaret D; Egginton, S; Milkiewicz, Malgorzata; Granata, Anna-Luisa

    2003-01-01

    Indirect chronic electrical stimulation of skeletal muscle activates not only efferent but also afferent nerve fibres. To investigate effects specific to this on capillary growth, one of the earliest changes, cell proliferation and capillary ultrastructure were studied in ankle flexors of rats with and without deafferentation of the stimulated side. Two weeks after preganglionic section of dorsal roots L4-L6, the peroneal nerve was stimulated (10 Hz, 8 h day−1) for 2 or 7 days. Proliferating nuclei labelled by bromodeoxyuridine or proliferating cell nuclear antigen staining were colocalized to alkaline phosphatase-stained capillaries (Lc) or other interstitial nuclei (Li) in frozen sections of extensor digitorum longus. Capillary fine structure was examined in extensor hallucis proprius by transmission electron microscopy. The stimulation-induced increase in capillary and interstitial proliferation (Lc 9.9 ± 1.9 %, Li 8.8 ± 2.1 % vs. Lc 2.6 ± 0.4 %, Li 1.9 ± 0.3 % in controls, P < 0.05) was depressed at 2 days by dorsal root section (Lc 4.8 ± 0.7 %, Li 3.2 ± 0.9 %, P < 0.05), an effect likely to be mainly on fibroblasts; no depression was seen at 7 days. Dorsal root section reduced stimulation-induced capillary endothelial swelling at both time points. In contralateral muscles of intact rats, stimulation increased interstitial cell proliferation and capillary swelling, both effects being eliminated by dorsal root section. Capillary growth induced by stimulation (24 % increase in capillary:fibre ratio at 7 days) was unaffected by deafferentation. The reduction in capillary ultrastructural changes and interstitial proliferation in both stimulated and contralateral muscles implies that stimulation of afferent fibres leads directly to release of humoral factors and/or activation via dorsal roots of fibres that release humoral substances. Contralateral muscles are an inadequate control for the effects of chronic stimulation in the intact animal. PMID:12563006

  18. EFFECTS OF 2,4-DITHIOBIURET ON SENSORY AND MOTOR FUNCTION

    EPA Science Inventory

    2,4-Dithiobiuret exposure causes a delayed onset muscle weakness in rats that has been attributed to depressed neuromuscular transmission. he present study compares the effects of DTB on sensory and motor function in rats. dult male Long-Evans hooded rats were exposed to saline, ...

  19. Thalamic cholinergic innervation and postural sensory integration function in Parkinson's disease.

    PubMed

    Müller, Martijn L T M; Albin, Roger L; Kotagal, Vikas; Koeppe, Robert A; Scott, Peter J H; Frey, Kirk A; Bohnen, Nicolaas I

    2013-11-01

    The pathophysiology of postural instability in Parkinson's disease remains poorly understood. Normal postural function depends in part on the ability of the postural control system to integrate visual, proprioceptive, and vestibular sensory information. Degeneration of cholinergic neurons in the brainstem pedunculopontine nucleus complex and their thalamic efferent terminals has been implicated in postural control deficits in Parkinson's disease. Our aim was to investigate the relationship of cholinergic terminal loss in thalamus and cortex, and nigrostriatal dopaminergic denervation, on postural sensory integration function in Parkinson's disease. We studied 124 subjects with Parkinson's disease (32 female/92 male; 65.5 ± 7.4 years old; 6.0 ± 4.2 years motor disease duration; modified Hoehn and Yahr mean stage 2.4 ± 0.5) and 25 control subjects (10 female/15 male, 66.8 ± 10.1 years old). All subjects underwent (11)C-dihydrotetrabenazine vesicular monoaminergic transporter type 2 and (11)C-methylpiperidin-4-yl propionate acetylcholinesterase positron emission tomography and the sensory organization test balance platform protocol. Measures of dopaminergic and cholinergic terminal integrity were obtained, i.e. striatal vesicular monoaminergic transporter type 2 binding (distribution volume ratio) and thalamic and cortical acetylcholinesterase hydrolysis rate per minute (k3), respectively. Total centre of pressure excursion (speed), a measure of total sway, and sway variability were determined for individual sensory organization test conditions. Based on normative data, principal component analysis was performed to reduce postural sensory organization functions to robust factors for regression analysis with the dopaminergic and cholinergic terminal data. Factor analysis demonstrated two factors with eigenvalues >2 that explained 52.2% of the variance, mainly reflecting postural sway during sensory organization test Conditions 1-3 and 5, respectively. Regression analysis of the Conditions 1-3 postural sway-related factor [R(2)adj = 0.123, F(5,109) = 4.2, P = 0.002] showed that decreased thalamic cholinergic innervation was associated with increased centre of pressure sway speed (β = -0.389, t = -3.4, P = 0.001) while controlling for covariate effects of cognitive capacity and parkinsonian motor impairments. There was no significant effect of cortical cholinergic terminal deficits or striatal dopaminergic terminal deficits. This effect could only be found for the subjects with Parkinson's disease. We conclude that postural sensory integration function of subjects with Parkinson's disease is modulated by pedunculopontine nucleus-thalamic but not cortical cholinergic innervation. Impaired integrity of pedunculopontine nucleus cholinergic neurons and their thalamic efferents play a role in postural control in patients with Parkinson's disease, possibly by participating in integration of multimodal sensory input information. PMID:24056537

  20. 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

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

    PubMed Central

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

    2013-01-01

    The T-junction of sensory neurons in the dorsal root ganglion (DRG) is a potential impediment to action potential (AP) propagation towards the CNS. Using intracellular recordings from rat DRG neuronal somata during stimulation of the dorsal root, we determined that the maximal rate at which all of 20 APs in a train could successfully transit the T-junction (following frequency) was lowest in C-type units, followed by A-type units with inflected descending limbs of the AP, and highest in A-type units without inflections. In C-type units, following frequency was slower than the rate at which AP trains could be produced in either dorsal root axonal segments or in the soma alone, indicating that the T-junction is a site that acts as a low-pass filter for AP propagation. Following frequency was slower for a train of 20 APs than for two, indicating that a cumulative process leads to propagation failure. Propagation failure was accompanied by diminished somatic membrane input resistance, and was enhanced when Ca2+-sensitive K+ currents were augmented or when Ca2+-sensitive Cl− currents were blocked. After peripheral nerve injury, following frequencies were increased in axotomized C-type neurons and decreased in axotomized non-inflected A-type neurons. These findings reveal that the T-junction in sensory neurons is a regulator of afferent impulse traffic. Diminished filtering of AP trains at the T-junction of C-type neurons with axotomized peripheral processes could enhance the transmission of activity that is ectopically triggered in a neuroma or the neuronal soma, possibly contributing to pain generation. PMID:23148321

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

    PubMed

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

    2013-02-15

    The T-junction of sensory neurons in the dorsal root ganglion (DRG) is a potential impediment to action potential (AP) propagation towards the CNS. Using intracellular recordings from rat DRG neuronal somata during stimulation of the dorsal root, we determined that the maximal rate at which all of 20 APs in a train could successfully transit the T-junction (following frequency) was lowest in C-type units, followed by A-type units with inflected descending limbs of the AP, and highest in A-type units without inflections. In C-type units, following frequency was slower than the rate at which AP trains could be produced in either dorsal root axonal segments or in the soma alone, indicating that the T-junction is a site that acts as a low-pass filter for AP propagation. Following frequency was slower for a train of 20 APs than for two, indicating that a cumulative process leads to propagation failure. Propagation failure was accompanied by diminished somatic membrane input resistance, and was enhanced when Ca(2+)-sensitive K(+) currents were augmented or when Ca(2+)-sensitive Cl(-) currents were blocked. After peripheral nerve injury, following frequencies were increased in axotomized C-type neurons and decreased in axotomized non-inflected A-type neurons. These findings reveal that the T-junction in sensory neurons is a regulator of afferent impulse traffic. Diminished filtering of AP trains at the T-junction of C-type neurons with axotomized peripheral processes could enhance the transmission of activity that is ectopically triggered in a neuroma or the neuronal soma, possibly contributing to pain generation. PMID:23148321

  3. Impaired endolysosomal function disrupts Notch signaling in optic nerve astrocytes

    PubMed Central

    Valapala, Mallika; Hose, Stacey; Gongora, Celine; Dong, Lijin; Wawrousek, Eric F.; Zigler, J. Samuel; Sinha, Debasish

    2013-01-01

    Astrocytes migrate from the optic nerve into the inner retina, forming a template upon which retinal vessels develop. In the Nuc1 rat, mutation in the gene encoding βA3/A1-crystallin disrupts both Notch signaling in astrocytes and formation of the astrocyte template. Here we show that loss of βA3/A1-crystallin in astrocytes does not impede Notch ligand binding or extracellular cleavages. However, it affects V-ATPase activity, thereby compromising acidification of the endolysosomal compartments, leading to reduced γ-secretase-mediated processing and release of the Notch intracellular domain (NICD). Lysosomal-mediated degradation of Notch is also impaired. These defects decrease the level of NICD in the nucleus, inhibiting expression of Notch target genes. Overexpression of βA3/A1-crystallin in those same astrocytes restored V-ATPase activity and normal endolysosomal acidification, thereby increasing the levels of γ-secretase to facilitate optimal Notch signaling. We postulate that βA3/A1-crystallin is essential for normal endolysosomal acidification, and thereby, normal activation of Notch signaling in astrocytes. PMID:23535650

  4. Sensory Aid Use and the Development of Communicative Function.

    ERIC Educational Resources Information Center

    Nicholas, Johanna Grant

    1994-01-01

    Natural language conversational samples were collected from hearing-impaired preschoolers who were either using cochlear implants, tactile aids, or hearing aids over a 33-month period. Children using cochlear implants increased their overall communicativeness, their breadth of functions, and their use of intelligible speech faster than other…

  5. Functional recovery guided by an electrospun silk fibroin conduit after sciatic nerve injury in rats.

    PubMed

    Park, Sook Young; Ki, Chang Seok; Park, Young Hwan; Lee, Kwang Gill; Kang, Seok Woo; Kweon, Hae Yong; Kim, Hyun Jeong

    2015-01-01

    The aim of this study was to evaluate the regenerative capacity of a newly developed nerve guidance conduit using electrospun silk fibroin (SFNC) implanted in a 10-mm defect of the sciatic nerve in rats. After evaluating the physical properties and cytocompatibility of SFNC in vitro, rats were randomly allocated into three groups: defect only, autograft and SFNC. To compare motor function and abnormal sensation among groups, ankle stance angle (ASA) and severity of autotomy were observed for 10 weeks after injury. Immunostaining with axonal neurofilament (NF) and myelin basic protein (MBP) antibodies were performed to investigate regenerated nerve fibres inside SFNC. ASA increased significantly in the SFNC group at 1, 7 and 10 weeks after injury compared to the defect only group (p<0.05). At one week, mean ASA of the SFNC group was significantly higher than that of the autograft group (p<0.05). Onset and severity of autotomy decreased significantly in the SFNC group compared to other groups (p<0.05). Autotomy in the SFNC group started at 4 weeks and maximally reached toe level. However, the defect only and autograft groups first showed autotomy at 2 and 1 weeks following injury, respectively, and then reached the sole level. Well myelinated nerve fibres stained with NF and MBP were found inside SFNC. In conclusion, SFNC could be helpful in restoring motor function and preventing abnormal sensations after nerve injury. PMID:23086833

  6. Reappraisal of nerve repair.

    PubMed

    Millesi, H

    1981-04-01

    In every case of acute injury involving the nerve, the surgeon must decide whether a primary repair of an elective early secondary repair is the treatment of choice. In a clean-cut nerve without defect, immediate primary repair, using trunk-to-trunk coaptation with epineurial sutures, offers an optimal solution. In the periphery of the median and the ulnar nerves, in which motor and sensory fascicles are already separated, fascicular dissection is performed, and coaptation of fascicle groups should be done. In medical centers with excellent facilities, such nerve repair will give good results even in very severe lesions. This repair can be performed also as a delayed primary procedure. If there is a nerve defect, a primary grafting procedure must be considered. We do not recommend this as a routine procedure because the nerve grafts might be lost if a complication occurs. The decision to perform a planned early secondary repair is an equally good alternative, especially in cases of a nerve defect, severe concomitant injuries, or both. In case of a combined nerve and tendon lesion in the carpal tunnel, the nerve repair can be performed at a later procedure without exposing the repaired flexor tendons, thus avoiding adhesion between tendons and nerves. If a decision is made in favor of an early secondary repair, the two stumps can be approximated by stitches to prevent retraction, if this can be achieved without tension. Approximation under tension in case of a larger defect would damage the two stumps and create an even larger defect. Marking the nerve ends by sutures is not necessary because exploration with always start in normal tissue, exposing the nerves from the proximal or the distal segments. Early secondary repair is performed during the third week, or later if this is demanded by local conditions. When indicated, plastic surgical procedures can eliminate constricting scars and provide an optimal soft tissue environment. After exploration and preparation of the two stumps, the surgeon must decide whether direct suturing or a nerve graft is indicated. If after very limited mobilization and slight flexion the nerve stumps cannot be coapted easily, a nerve graft should be used. The quality of motor recovery decreases steadily after a 6 month delay of repair. Late secondary repairs or reoperation of failure of primary repair should be performed within this time limit, although this does not mean that motor recovery cannot occur after a longer time interval. Useful motor recovery was achieved in certain cases after 18 months or more. Obviously the results might have been better if the time interval had been shorter. If a patient is seen with a nerve lesion after a long time interval, nerve repair is still indicated if sensibility is the main functional objective. In other long-standing cases, the nerve repair is combined with tendon transfer or capsulorrhaphy. After a particularly long time interval or in old patients, only palliative surgery is indicated. PMID:7233326

  7. Functional transplant of photoactivated adenylyl cyclase (PAC) into Aplysia sensory neurons.

    PubMed

    Nagahama, Tatsumi; Suzuki, Takeshi; Yoshikawa, Shinya; Iseki, Mineo

    2007-09-01

    In neural mechanisms of animal learning, intracellular cAMP has been known to play an important role. In the present experiments we attempted functional transplant of a photoactivated adenylyl cyclase (PAC) isolated from Euglena into Aplysia neurons, and explored whether PAC can produce cAMP in the neurons by light stimulation. Serotonergic modulation of mechanoafferent sensory neurons in Aplysia pleural ganglia has been reported to increase intracellular cAMP level and promotes synaptic transmission to motor neurons by increasing spike width of sensory neurons. When cAMP was directly injected into the sensory neurons, spike amplitude temporarily decreased while spike width temporarily increased. This effect was not substituted by injection of 5'AMP, and maintained longer in a bath solution containing IBMX, the phosphodiesterase inhibitor. We, therefore, explored these changes as indicators of appearance of the PAC function. PAC or the PAC expression vector (pNEX-PAC) was injected into cell bodies of sensory neurons. Spike amplitude decreased in both cases and spike width increased in the PAC injection when the neurons were stimulated with light, suggesting that the transplanted PAC works well in Aplysia neurons. These results indicate that we can control cAMP production in specific neurons with light by the functional transplant of PAC. PMID:17624456

  8. Piezoelectric materials mimic the function of the cochlear sensory epithelium

    PubMed Central

    Inaoka, Takatoshi; Shintaku, Hirofumi; Nakagawa, Takayuki; Kawano, Satoyuki; Ogita, Hideaki; Sakamoto, Tatsunori; Hamanishi, Shinji; Wada, Hiroshi; Ito, Juichi

    2011-01-01

    Cochlear hair cells convert sound vibration into electrical potential, and loss of these cells diminishes auditory function. In response to mechanical stimuli, piezoelectric materials generate electricity, suggesting that they could be used in place of hair cells to create an artificial cochlear epithelium. Here, we report that a piezoelectric membrane generated electrical potentials in response to sound stimuli that were able to induce auditory brainstem responses in deafened guinea pigs, indicating its capacity to mimic basilar membrane function. In addition, sound stimuli were transmitted through the external auditory canal to a piezoelectric membrane implanted in the cochlea, inducing it to vibrate. The application of sound to the middle ear ossicle induced voltage output from the implanted piezoelectric membrane. These findings establish the fundamental principles for the development of hearing devices using piezoelectric materials, although there are many problems to be overcome before practical application. PMID:22025702

  9. Sensory feedback in upper limb prosthetics.

    PubMed

    Antfolk, Christian; D'Alonzo, Marco; Rosén, Birgitta; Lundborg, Göran; Sebelius, Fredrik; Cipriani, Christian

    2013-01-01

    One of the challenges facing prosthetic designers and engineers is to restore the missing sensory function inherit to hand amputation. Several different techniques can be employed to provide amputees with sensory feedback: sensory substitution methods where the recorded stimulus is not only transferred to the amputee, but also translated to a different modality (modality-matched feedback), which transfers the stimulus without translation and direct neural stimulation, which interacts directly with peripheral afferent nerves. This paper presents an overview of the principal works and devices employed to provide upper limb amputees with sensory feedback. The focus is on sensory substitution and modality matched feedback; the principal features, advantages and disadvantages of the different methods are presented. PMID:23278223

  10. Nerve growth factor and neurotrophin-3 modulate the rabies infection of adult sensory neurons in primary cultures.

    PubMed

    Castellanos, J E; Martnez, M; Acosta, O; Hurtado, H

    2000-07-14

    With the aim of determining if the proportion of rabies virus (RV)-infected adult neurons from dorsal root ganglion are affected by in vitro treatment with different neurotrophins, experiments using Nerve Growth Factor (NGF), Brain Derived Neurotrophic Factor (BDNF) or Neurotrophin-3 (NT-3) as supplements for cells in culture were performed. Cultures treated with three different concentrations of each of the neurotrophins mentioned were infected with Challenge Virus Standard RV strain. An indirect immunoperoxidase technique was performed for the detection and counting of infected cells. NGF (2 ngml(-1) and 10 ngml(-1)) and NT-3 (1 ngml(-1) and 5 ngml(-1)) induced a significant reduction of infected neurons. None of the cultures treated with BDNF showed changes in the percentage of infected neurons. Likewise, the proportion of infected non-neuronal cells (Schwann cells and fibroblasts) was not altered by the treatment with neurotrophins. In addition, morphometric analysis of total and virus-immunoreactive neurons in culture were carried out, the neurotrophin treatment induced variations in the profile of neurons preferentially infected, since cell diameters in the infected cell population are different in the presence of NGF and NT-3. Data presented here could indicate a putative participation of neurotrophin receptor or biochemical modifications induced by neurotrophin treatment that affect the infection. The primary culture of dorsal root ganglion cells from adult mice is a very useful model for studying the basic phenomena of the RV-neuron interaction. PMID:10882791

  11. The effect of ubiquinone on functional recovery and morphometric indices of sciatic nerve regeneration

    PubMed Central

    Moradi, Z; Azizi, S; Hobbenaghi, R

    2014-01-01

    A common cause of peripheral nerve injury is trauma. The positive effect of antioxidants on the improvement of nerve regeneration has currently become a focus of attention. In this experiment, the effect of intraperitoneal administration of ubiquinone (CoQ10) on an acute experimentally sciatic nerve crush was studied in a rat model. Forty-five male Wistar rats, weighing between 160-180 g were used. The rats were randomly divided into two experimental groups (n=20). Each group was further subdivided into four subgroups of five animals each. Functional studies confirmed the faster recovery of regenerated axons in the treatment group compared to the un-treated group (P<0.05). Morphometric indices of the regenerated fibers showed the number and diameter of the myelinated fibers to be significantly higher in the treatment group than the un-treated group (P<0.05). Intraperitoneal administration of CoQ10 (10 mg/kg/day) in the early inflammatory stage of sciatic nerve crush was found to improve nerve regeneration.

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

    PubMed

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

    2013-05-01

    Cutaneous afferent activities recorded by a nerve cuff electrode have been used to detect the stance phase in a functional electrical stimulation system for foot drop correction. However, the implantation procedure was difficult, as the cuff electrode had to be located on the distal branches of a multi-fascicular nerve to exclude muscle afferent and efferent activities. This paper proposes a new gait phase detection scheme that can be applied to a proximal nerve root that includes cutaneous afferent fibers as well as muscle afferent and efferent fibers. To test the feasibility of this scheme, electroneurogram (ENG) signals were measured from the rat sciatic nerve during treadmill walking at several speeds, and the signal properties of the sciatic nerve were analyzed for a comparison with kinematic data from the ankle joint. On the basis of these experiments, a wavelet packet transform was tested to define a feature vector from the sciatic ENG signals according to the gait phases. We also propose a Gaussian mixture model (GMM) classifier and investigate whether it could be used successfully to discriminate feature vectors into the stance and swing phases. In spite of no significant differences in the rectified bin-integrated values between the stance and swing phases, the sciatic ENG signals could be reliably classified using the proposed wavelet packet transform and GMM classification methods. PMID:23604025

  13. 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. PMID:26296589

  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. PMID:25836703

  15. IgSF8: a developmentally and functionally regulated cell adhesion molecule in olfactory sensory neuron axons and synapses

    PubMed Central

    Ray, Arundhati; Treloar, Helen B.

    2012-01-01

    Here, we investigated an Immunoglobulin (Ig) superfamily protein IgSF8 which is abundantly expressed in olfactory sensory neuron (OSN) axons and their developing synapses. We demonstrate that expression of IgSF8 within synaptic neuropil is transitory, limited to the period of glomerular formation. Glomerular expression decreases after synaptic maturation and compartmental glomerular organization is achieved, although expression is maintained at high levels within the olfactory nerve layer (ONL). Immunoprecipitations indicate that IgSF8 interacts with tetraspanin CD9 in the olfactory bulb (OB). CD9 is a component of tetraspanin-enriched microdomains (TEMs), specialized microdomains of the plasma membrane known to regulate cell morphology, motility, invasion, fusion and signaling, in both the nervous and immune systems, as well as in tumors. In vitro, both IgSF8 and CD9 localize to puncta within axons and growth cones of OSNs, consistent with TEM localization. When the olfactory epithelium (OE) was lesioned, forcing OSN regeneration en masse, IgSF8 was once again able to be detected in OSN axons terminals as synapses were reestablished. Finally, we halted synaptic maturation within glomeruli by unilaterally blocking functional activity and found that IgSF8 did not undergo exclusion from this subcellular compartment and instead continued to be detected in adult glomeruli. These data support the hypothesis that IgSF8 facilitates OSN synapse formation. PMID:22687584

  16. Human Embryonic Stem Cell-Derived Progenitors Assist Functional Sensory Axon Regeneration after Dorsal Root Avulsion Injury

    PubMed Central

    Hoeber, Jan; Trolle, Carl; Konig, Niclas; Du, Zhongwei; Gallo, Alessandro; Hermans, Emmanuel; Aldskogius, Hakan; Shortland, Peter; Zhang, Su-Chun; Deumens, Ronald; Kozlova, Elena N.

    2015-01-01

    Dorsal root avulsion results in permanent impairment of sensory functions due to disconnection between the peripheral and central nervous system. Improved strategies are therefore needed to reconnect injured sensory neurons with their spinal cord targets in order to achieve functional repair after brachial and lumbosacral plexus avulsion injuries. Here, we show that sensory functions can be restored in the adult mouse if avulsed sensory fibers are bridged with the spinal cord by human neural progenitor (hNP) transplants. Responses to peripheral mechanical sensory stimulation were significantly improved in transplanted animals. Transganglionic tracing showed host sensory axons only in the spinal cord dorsal horn of treated animals. Immunohistochemical analysis confirmed that sensory fibers had grown through the bridge and showed robust survival and differentiation of the transplants. Section of the repaired dorsal roots distal to the transplant completely abolished the behavioral improvement. This demonstrates that hNP transplants promote recovery of sensorimotor functions after dorsal root avulsion, and that these effects are mediated by spinal ingrowth of host sensory axons. These results provide a rationale for the development of novel stem cell-based strategies for functionally useful bridging of the peripheral and central nervous system. PMID:26053681

  17. 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. PMID:25878155

  18. Redox and Nitric Oxide-Mediated Regulation of Sensory Neuron Ion Channel Function

    PubMed Central

    2015-01-01

    Abstract Significance: Reactive oxygen and nitrogen species (ROS and RNS, respectively) can intimately control neuronal excitability and synaptic strength by regulating the function of many ion channels. In peripheral sensory neurons, such regulation contributes towards the control of somatosensory processing; therefore, understanding the mechanisms of such regulation is necessary for the development of new therapeutic strategies and for the treatment of sensory dysfunctions, such as chronic pain. Recent Advances: Tremendous progress in deciphering nitric oxide (NO) and ROS signaling in the nervous system has been made in recent decades. This includes the recognition of these molecules as important second messengers and the elucidation of their metabolic pathways and cellular targets. Mounting evidence suggests that these targets include many ion channels which can be directly or indirectly modulated by ROS and NO. However, the mechanisms specific to sensory neurons are still poorly understood. This review will therefore summarize recent findings that highlight the complex nature of the signaling pathways involved in redox/NO regulation of sensory neuron ion channels and excitability; references to redox mechanisms described in other neuron types will be made where necessary. Critical Issues: The complexity and interplay within the redox, NO, and other gasotransmitter modulation of protein function are still largely unresolved. Issues of specificity and intracellular localization of these signaling cascades will also be addressed. Future Directions: Since our understanding of ROS and RNS signaling in sensory neurons is limited, there is a multitude of future directions; one of the most important issues for further study is the establishment of the exact roles that these signaling pathways play in pain processing and the translation of this understanding into new therapeutics. Antioxid. Redox Signal. 22, 486–504. PMID:24735331

  19. Functional recovery of odor representations in regenerated sensory inputs to the olfactory bulb

    PubMed Central

    Cheung, Man C.; Jang, Woochan; Schwob, James E.; Wachowiak, Matt

    2014-01-01

    The olfactory system has a unique capacity for recovery from peripheral damage. After injury to the olfactory epithelium (OE), olfactory sensory neurons (OSNs) regenerate and re-converge on target glomeruli of the olfactory bulb (OB). Thus far, this process has been described anatomically for only a few defined populations of OSNs. Here we characterize this regeneration at a functional level by assessing how odor representations carried by OSN inputs to the OB recover after massive loss and regeneration of the sensory neuron population. We used chronic imaging of mice expressing synaptopHluorin in OSNs to monitor odor representations in the dorsal OB before lesion by the olfactotoxin methyl bromide and after a 12 week recovery period. Methyl bromide eliminated functional inputs to the OB, and these inputs recovered to near-normal levels of response magnitude within 12 weeks. We also found that the functional topography of odor representations recovered after lesion, with odorants evoking OSN input to glomerular foci within the same functional domains as before lesion. At a finer spatial scale, however, we found evidence for mistargeting of regenerated OSN axons onto OB targets, with odorants evoking synaptopHluorin signals in small foci that did not conform to a typical glomerular structure but whose distribution was nonetheless odorant-specific. These results indicate that OSNs have a robust ability to reestablish functional inputs to the OB and that the mechanisms underlying the topography of bulbar reinnervation during development persist in the adult and allow primary sensory representations to be largely restored after massive sensory neuron loss. PMID:24431990

  20. A Pilot Study Examining Activity Participation, Sensory Responsiveness, and Competence in Children with High Functioning Autism Spectrum Disorder

    ERIC Educational Resources Information Center

    Reynolds, Stacey; Bendixen, Roxanna M.; Lawrence, Tami; Lane, Shelly J.

    2011-01-01

    This pilot study explored activity patterns in children with and without ASD and examined the role of sensory responsiveness in determining children's level of competence in activity performance. Twenty-six children with high functioning ASD and twenty-six typically-developing children 6-12 years old were assessed using the Sensory Profile and the…

  1. Loudness function derives from data on electrical discharge rates in auditory nerve fibers

    NASA Technical Reports Server (NTRS)

    Howes, W. L.

    1973-01-01

    Judgements of the loudness of pure-tone sound stimuli yield a loudness function which relates perceived loudness to stimulus amplitude. A loudness function is derived from physical evidence alone without regard to human judgments. The resultant loudness function is L=K(q-q0), where L is loudness, q is effective sound pressure (specifically q0 at the loudness threshold), and K is generally a weak function of the number of stimulated auditory nerve fibers. The predicted function is in agreement with loudness judgment data reported by Warren, which imply that, in the suprathreshold loudness regime, decreasing the sound-pressure level by 6 db results in halving the loudness.

  2. The rules of tool incorporation: Tool morpho-functional & sensori-motor constraints.

    PubMed

    Cardinali, L; Brozzoli, C; Finos, L; Roy, A C; Farnè, A

    2016-04-01

    Previous studies showed that using tools modifies the agent's body and space representation. However, it is still not clear which rules govern those remapping processes. Here, we studied the differential role played by the morpho-functional characteristics of a tool and the sensori-motor constraints that a tool imposes on the hand. To do so, we asked a group of participants to reach and grasp an object using, in different conditions, two different tools: Pliers, to be acted upon by the index and thumb fingertips, and Sticks, taped to the same two digits. The two tools were equivalent in terms of morpho-functional characteristics, providing index finger and thumb with the same amount of elongation. Crucially, however, they imposed different sensori-motor constraints on the acting fingers. We measured and compared the kinematic profile of free-hand movements performed before and after the use of both devices. As predicted on the basis of their equivalent morpho-functional characteristics, both tools induced similar changes in the fingers (but not the arm) kinematics compatible with the hand being represented as bigger. Furthermore, the different sensori-motor constraints imposed by Pliers and Sticks over the hand, induced differential updates of the hand representation. In particular, the Sticks selectively affected the kinematics of the two fingers they were taped on, whereas Pliers had a more global effect, affecting the kinematics of hand movements not performed during the use of the tool. These results suggest that tool-use induces a rapid update of the hand representation in the brain, not only on the basis of the morpho-functional characteristics of the tool, but also depending on the specific sensori-motor constraints imposed by the tool. PMID:26774102

  3. 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.

  4. Rootletin organizes the ciliary rootlet to achieve neuron sensory function in Drosophila

    PubMed Central

    Kao, Ling-Rong; Jana, Swadhin C.; Sivan-Loukianova, Elena; Mendonça, Susana; Cabrera, Oscar A.; Singh, Priyanka; Cabernard, Clemens; Eberl, Daniel F.; Bettencourt-Dias, Monica

    2015-01-01

    Cilia are essential for cell signaling and sensory perception. In many cell types, a cytoskeletal structure called the ciliary rootlet links the cilium to the cell body. Previous studies indicated that rootlets support the long-term stability of some cilia. Here we report that Drosophila melanogaster Rootletin (Root), the sole orthologue of the mammalian paralogs Rootletin and C-Nap1, assembles into rootlets of diverse lengths among sensory neuron subtypes. Root mutant neurons lack rootlets and have dramatically impaired sensory function, resulting in behavior defects associated with mechanosensation and chemosensation. Root is required for cohesion of basal bodies, but the cilium structure appears normal in Root mutant neurons. We show, however, that normal rootlet assembly requires centrioles. The N terminus of Root contains a conserved domain and is essential for Root function in vivo. Ectopically expressed Root resides at the base of mother centrioles in spermatocytes and localizes asymmetrically to mother centrosomes in neuroblasts, both requiring Bld10, a basal body protein with varied functions. PMID:26483560

  5. Microelectronic neural bridge for signal regeneration and function rebuilding over two separate nerves

    NASA Astrophysics Data System (ADS)

    Xiaoyan, Shen; Zhigong, Wang; Xiaoying, Lü; Shushan, Xie; Zonghao, Huang

    2011-06-01

    According to the feature of neural signals, a micro-electronic neural bridge (MENB) has been designed. It consists of two electrode arrays for neural signal detection and functional electrical stimulation (FES), and a microelectronic circuit for signal amplifying, processing, and FES driving. The core of the system is realized in 0.5-μm CMOS technology and used in animal experiments. A special experimental strategy has been designed to demonstrate the feasibility of the system. With the help of the MENB, the withdrawal reflex function of the left/right leg of one spinal toad has been rebuilt in the corresponding leg of another spinal toad. According to the coherence analysis between the source and regenerated neural signals, the controlled spinal toad's sciatic nerve signal is delayed by 0.72 ms in relation to the sciatic nerve signal of the source spinal toad and the cross-correlation function reaches a value of 0.73. This shows that the regenerated signal is correlated with the source sciatic signal significantly and the neural activities involved in reflex function have been regenerated. The experiment demonstrates that the MENB is useful in rebuilding the neural function between nerves of different bodies.

  6. Characteristics of bilateral hand function in individuals with unilateral dystonia due to perinatal stroke: sensory and motor aspects

    PubMed Central

    de Campos, Ana Carolina; Kukke, Sahana N.; Hallett, Mark; Alter, Katharine E.; Damiano, Diane L.

    2014-01-01

    We assessed bilateral motor and sensory function in individuals with upper limb dystonia due to unilateral perinatal stroke and explored interrelationships of motor function and sensory ability. Reach kinematics and tactile sensation were measured in seven participants with dystonia and nine healthy volunteers. The dystonia group had poorer motor (hold time, reach time, shoulder/elbow correlation) and sensory (spatial discrimination, stereognosis) outcomes than the control group on the non-dominant side. On the dominant side, only sensation (spatial discrimination, stereognosis) was poorer in the dystonia group compared to the control group. In the dystonia group, although sensory and motor outcomes were uncorrelated, dystonia severity was related to poorer stereognosis, longer hold and reach times, and decreased shoulder/elbow coordination. Findings of bilateral sensory deficits in dystonia may be explained by neural reorganization. Visual compensation for somatosensory changes in the non-stroke hemisphere may explain the lack of bilateral impairments in reaching. PMID:24396131

  7. Acetyl salicylic acid locally enhances functional recovery after sciatic nerve transection in rat.

    PubMed

    Mohammadi, Rahim; Amini, Keyvan; Abdollahi-Pirbazari, Mehdi; Yousefi, Alireza

    2013-01-01

    Local effect of acetyl salicylic acid (ASA) on peripheral nerve regeneration was studied using a rat sciatic nerve transection model. Forty-five male healthy White Wistar rats were divided into three experimental groups (n = 15), randomly: Sham-operation (SHAM), control (SIL), and ASA-treated (SIL/ASA) groups. In SHAM group after anesthesia left sciatic nerve was exposed through a gluteal muscle incision and after homeostasis the muscle was sutured. In SIL group the left sciatic nerve was exposed the same way and transected proximal to tibio-peroneal bifurcation leaving a 10-mm gap. Proximal and distal stumps were each inserted into a silicone tube and filled with 10 μl phosphate buffered solution. In SIL/ASA group defect was bridged using a silicone tube filled with 10 μl acetyl salisylic acid (0.1 mg/ml). Each group was subdivided into three subgroups of five animals each and were studied 4, 8, and 12 weeks after surgery. Data were analyzed statistically by factorial analysis of variance (ANOVA) and the Bonferroni test for pair-wise comparisons. Functional study confirmed faster and better recovery of regenerated axons in SIL/ASA than in SIL group (p < 0.05). Gastrocnemius muscle mass in SIL/ASA was significantly more than in SIL group. Morphometric indices of regenerated fibers showed that the number and diameter of the myelinated fibers in SIL/ASA were significantly higher than in control group. In immuohistochemistry, location of reactions to S-100 in SIL/ASA was clearly more positive than in SIL group. Response to local treatment of ASA demonstrates that it influences and improves functional recovery of peripheral nerve regeneration. PMID:24140781

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

    PubMed

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

    2013-11-01

    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-PyP(5+)) 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-PyP(5+). 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

  10. Experimental study of the functional reserve of median nerve in rats

    PubMed Central

    Cui, Jianli; Gong, Xu; Jiang, Ziping; Yu, Xin; Liu, Yuejiao; Lu, Laijin

    2015-01-01

    Objective: To study the functional changes of median nerve after removing a certain bundle of it and to explore the functional reserve of median nerves. Methods: 220 three-month old SD rats were randomly divided into experimental groups and sham groups. And the experimental group was further divided as 1/8 group, 1/4 group, 1/3 group, 1/2 group, and 2/3 group according to ratio of the resection portion, with 22 rats in each group. The section of the lowest level on median nerve trunks were exposed, and a certain portion of it were separated and resected in experimental group, while in sham groups, the nerve was only separated without resection. The general state of health of all rats were observed, and the α motor neurons in cornu anterior medullae spinalis were studied 1 week, 2 weeks and 2 months postoperatively. Neuro-electrophysiology and function of dominated muscles were studied 2 weeks, 2 months, 3 months, and 4 months postoperatively. Results: All rats survived without infection and obvious ulcer. The number of the α motor neurons in cornuanterior medullae spinalis didn’t change (P>0.05), and obvious superstructure changes were observed in early stage in 1/2 and 2/3 group, but restored after 2 months. There was no significant changes in latencies of motor neuron evoked potentials between experimental groups and sham group (P>0.05), however, there is significant difference if the 2 week group was compared with 2 month, 3 month and 4 month group (P<0.05). Moreover, there is also significant difference in terms of the wave amplitude of evoked potential of motor neurons, the maximum wave amplitude and the persistence time of its innervated muscle if the 2 week group was compared with those in 2 month, 3 month and 4 month group (P<0.05), and there is significant difference between different proportion resection groups (P<0.05). Conclusions: Median nerve has a certain amount of functional reserve, and the quantity of the functional reserve of median nerve without compromise is the 1/3 of the whole trunk. PMID:26629106

  11. Functions of adrenergic and cholinergic nerves in canine effectors of seminal emission.

    PubMed

    Arver, S; Sjöstrand, N O

    1982-05-01

    Spontaneous activity responses to acetylcholine (ACh), adrenaline (A), noradrenaline (NA) and barium chloride as well as the effects of various autonomic drugs on effects of field stimulation of nerves and muscle cells of isolated pieces or strips of cauda epididymidis, vas deferens, ampulla ductus deferentis and prostate of dog were studied. The main results and conclusions are: the muscles show little spontaneous activity but rhythmicity can easily be produced by e.g. stimulating agonists. The muscles are contracted by alpha-adrenoceptor stimulants. ACh has usually no or a very weak contractile effect in high concentrations. Muscles of young dogs are more sensitive to ACh. The excitatory innervation of the muscles is adrenergic and completely blocked by adrenergic neuron blockers as well as alpha-adrenoceptor blocking drugs. Stimulation of adrenergic nerves leads to maximum response already at low frequencies (4-6 Hz). This response is very similar to that provoked by a supramaximal dose of NA. Scopolamine enhances neurogenic contractile effects while physostigmine suppresses them. Hence cholinergic nerves may act by muscarinic prejunctional inhibition of the excitatory adrenergic neurotransmission rather than act directly upon the smooth muscle cells. Since secretory cells receive cholinergic innervation prejunctional inhibition of the adrenergic myomotor nerves may be of functional significance in at least the long copulatory events of the dog. PMID:6127870

  12. Visualization of nerve fibers and their relationship to peripheral nerve tumors by diffusion tensor imaging.

    PubMed

    Cage, Tene A; Yuh, Esther L; Hou, Stephanie W; Birk, Harjus; Simon, Neil G; Noss, Roger; Rao, Anuradha; Chin, Cynthia T; Kliot, Michel

    2015-09-01

    OBJECT The majority of growing and/or symptomatic peripheral nerve tumors are schwannomas and neurofibromas. They are almost always benign and can usually be resected while minimizing motor and sensory deficits if approached with the proper expertise and techniques. Intraoperative electrophysiological stimulation and recording techniques allow the surgeon to map the surface of the tumor in an effort to identify and thus avoid damaging functioning nerve fibers. Recently, MR diffusion tensor imaging (DTI) techniques have permitted the visualization of axons, because of their anisotropic properties, in peripheral nerves. The object of this study was to compare the distribution of nerve fibers as revealed by direct electrical stimulation with that seen on preoperative MR DTI. METHODS The authors conducted a retrospective chart review of patients with a peripheral nerve or nerve root tumor between March 2012 and January 2014. Diffusion tensor imaging and intraoperative data had been prospectively collected for patients with peripheral nerve tumors that were resected. Preoperative identification of the nerve fiber location in relation to the nerve tumor surface as seen on DTI studies was compared with the nerve fiber's intraoperative localization using electrophysiological stimulation and recordings. RESULTS In 23 patients eligible for study there was good correlation between nerve fiber location on DTI and its anatomical location seen intraoperatively. Diffusion tensor imaging demonstrated the relationship of nerve fibers relative to the tumor with 95.7% sensitivity, 66.7% specificity, 75% positive predictive value, and 93.8% negative predictive value. CONCLUSIONS Preoperative DTI techniques are useful in helping the peripheral nerve surgeon to both determine the risks involved in resecting a nerve tumor and plan the safest surgical approach. PMID:26323818

  13. Supplementary motor area deactivation impacts the recovery of hand function from severe peripheral nerve injury

    PubMed Central

    Lu, Ye-chen; Liu, Han-qiu; Hua, Xu-yun; Shen, Yun-dong; Xu, Wen-dong; Xu, Jian-guang; Gu, Yu-dong

    2016-01-01

    Although some patients have successful peripheral nerve regeneration, a poor recovery of hand function often occurs after peripheral nerve injury. It is believed that the capability of brain plasticity is crucial for the recovery of hand function. The supplementary motor area may play a key role in brain remodeling after peripheral nerve injury. In this study, we explored the activation mode of the supplementary motor area during a motor imagery task. We investigated the plasticity of the central nervous system after brachial plexus injury, using the motor imagery task. Results from functional magnetic resonance imaging showed that after brachial plexus injury, the motor imagery task for the affected limbs of the patients triggered no obvious activation of bilateral supplementary motor areas. This result indicates that it is difficult to excite the supplementary motor areas of brachial plexus injury patients during a motor imagery task, thereby impacting brain remodeling. Deactivation of the supplementary motor area is likely to be a serious problem for brachial plexus injury patients in terms of preparing, initiating and executing certain movements, which may be partly responsible for the unsatisfactory clinical recovery of hand function. PMID:27212933

  14. Assessment of canine sensory function by using sine-wave electrical stimuli paradigm.

    PubMed

    Watabiki, Tomonari; Nagakura, Yukinori; Wegner, Kirsten; Kakimoto, Shuichiro; Tozier, Nicolle A; Malkmus, Shelle A; Yaksh, Tony L

    2010-10-01

    The paradigm of sine-wave electrical stimuli has been used for sensory neurological assessment in humans. In the present study, we applied the paradigm to the dog for the quantitative assessment of sensory function. Sine-wave electrical current stimuli at frequencies of 2000, 250, and 5Hz were delivered to bipolar electrodes attached to the skin surface of the hind paws. The stimulation intensity was gradually increased, and the minimum intensity required to elicit the lifting behavior in the stimulated paw was determined as current threshold (CT) for each of the three frequencies. Dogs consistently showed the lifting behavior at CTs without showing aversive behaviors such as vocalization and wriggling. The baseline CTs (mean+/-SEM, n=12) were 4430+/-110microA for CT2000, 2215+/-173microA for CT250, and 2305+/-152microA for CT5. The CTs immediately increased after bolus intravenous injection of fentanyl at 10microg/kg, although the significant increase disappeared within 1h. The time course for the CTs was parallel to that of plasma fentanyl concentration. In conclusion, the present study applied the paradigm of transcutaneous sine-wave electrical stimuli to the dog, and used the hind paw lifting as endpoint behavior. This paradigm is simple, non-invasive, useful in the assessment of sensory function, and can be adapted to investigate the pharmacokinetics/pharmacodynamics relation of drugs. Further studies are needed to give the conclusive interpretation of the endpoint behavior. PMID:20570687

  15. Thalamic cholinergic innervation and postural sensory integration function in Parkinson’s disease

    PubMed Central

    Albin, Roger L.; Kotagal, Vikas; Koeppe, Robert A.; Scott, Peter J.H.; Frey, Kirk A.; Bohnen, Nicolaas I.

    2013-01-01

    The pathophysiology of postural instability in Parkinson’s disease remains poorly understood. Normal postural function depends in part on the ability of the postural control system to integrate visual, proprioceptive, and vestibular sensory information. Degeneration of cholinergic neurons in the brainstem pedunculopontine nucleus complex and their thalamic efferent terminals has been implicated in postural control deficits in Parkinson’s disease. Our aim was to investigate the relationship of cholinergic terminal loss in thalamus and cortex, and nigrostriatal dopaminergic denervation, on postural sensory integration function in Parkinson’s disease. We studied 124 subjects with Parkinson’s disease (32 female/92 male; 65.5 ± 7.4 years old; 6.0 ± 4.2 years motor disease duration; modified Hoehn and Yahr mean stage 2.4 ± 0.5) and 25 control subjects (10 female/15 male, 66.8 ± 10.1 years old). All subjects underwent 11C-dihydrotetrabenazine vesicular monoaminergic transporter type 2 and 11C-methylpiperidin-4-yl propionate acetylcholinesterase positron emission tomography and the sensory organization test balance platform protocol. Measures of dopaminergic and cholinergic terminal integrity were obtained, i.e. striatal vesicular monoaminergic transporter type 2 binding (distribution volume ratio) and thalamic and cortical acetylcholinesterase hydrolysis rate per minute (k3), respectively. Total centre of pressure excursion (speed), a measure of total sway, and sway variability were determined for individual sensory organization test conditions. Based on normative data, principal component analysis was performed to reduce postural sensory organization functions to robust factors for regression analysis with the dopaminergic and cholinergic terminal data. Factor analysis demonstrated two factors with eigenvalues >2 that explained 52.2% of the variance, mainly reflecting postural sway during sensory organization test Conditions 1–3 and 5, respectively. Regression analysis of the Conditions 1–3 postural sway-related factor [R2adj = 0.123, F(5,109) = 4.2, P = 0.002] showed that decreased thalamic cholinergic innervation was associated with increased centre of pressure sway speed (β = −0.389, t = −3.4, P = 0.001) while controlling for covariate effects of cognitive capacity and parkinsonian motor impairments. There was no significant effect of cortical cholinergic terminal deficits or striatal dopaminergic terminal deficits. This effect could only be found for the subjects with Parkinson’s disease. We conclude that postural sensory integration function of subjects with Parkinson’s disease is modulated by pedunculopontine nucleus-thalamic but not cortical cholinergic innervation. Impaired integrity of pedunculopontine nucleus cholinergic neurons and their thalamic efferents play a role in postural control in patients with Parkinson’s disease, possibly by participating in integration of multimodal sensory input information. PMID:24056537

  16. Outcome following Nerve Repair of High Isolated Clean Sharp Injuries of the Ulnar Nerve

    PubMed Central

    Post, René; de Boer, Kornelis S.; Malessy, Martijn J. A.

    2012-01-01

    Objective The detailed outcome of surgical repair of high isolated clean sharp (HICS) ulnar nerve lesions has become relevant in view of the recent development of distal nerve transfer. Our goal was to determine the outcome of HICS ulnar nerve repair in order to create a basis for the optimal management of these lesions. Methods High ulnar nerve lesions are defined as localized in the area ranging from the proximal forearm to the axilla just distal to the branching of the medial cord of the brachial plexus. A meta-analysis of the literature concerning high ulnar nerve injuries was performed. Additionally, a retrospective study of the outcome of nerve repair of HICS ulnar nerve injuries at our institution was performed. The Rotterdam Intrinsic Hand Myometer and the Rosén-Lundborg protocol were used. Results The literature review identified 46 papers. Many articles presented outcomes of mixed lesion groups consisting of combined ulnar and median nerves, or the outcome of high and low level injuries was pooled. In addition, outcome was expressed using different scoring systems. 40 patients with HICS ulnar nerve lesions were found with sufficient data for further analysis. In our institution, 15 patients had nerve repair with a median interval between trauma and reconstruction of 17 days (range 0–516). The mean score of the motor and sensory domain of the Rosen's Scale instrument was 58% and 38% of the unaffected arm, respectively. Two-point discrimination never reached less then 12 mm. Conclusion From the literature, it was not possible to draw a definitive conclusion on outcome of surgical repair of HICS ulnar nerve lesions. Detailed neurological function assessment of our own patients showed that some ulnar nerve function returned. Intrinsic muscle strength recovery was generally poor. Based on this study, one might cautiously argue that repair strategies of HICS ulnar nerve lesions need to be improved. PMID:23082230

  17. Glycemic responses and sensory characteristics of whole yellow pea flour added to novel functional foods.

    PubMed

    Marinangeli, Christopher P F; Kassis, Amira N; Jones, Peter J H

    2009-01-01

    A fundamental understanding regarding postprandial glycemic responses to foods containing whole yellow-pea flour (WYPF) remains unknown. This, alongside concerns that WYPF possesses unfavorable sensory characteristics has limited the incorporation of WYPF into new functional food products as a healthy novel ingredient. The objective of this study was to evaluate how WYPF modulates postprandial glycemic responses as well as sensory characteristics in novel foods. In a single-blind crossover trial, the present study assessed postprandial glycemic responses of banana bread, biscotti, and spaghetti containing either WYPF or whole wheat flour (WWF). Boiled yellow peas (BYP) and white bread (WB) were used as positive and negative controls, respectively. On day 1, subjects evaluated appearance, taste, texture, smell as well as overall acceptance of each WYPF and WWF food on a 5-point hedonic scale. WYPF banana bread (97.9 +/- 17.8 mmol x min/L) and biscotti (83 +/- 13 mmol x min/L), as well as BYP (112.3 +/- 19.9 mmol x min/L), reduced (P < 0.05) glycemic responses compared to WB (218.1 +/- 29.5 mmol x min/L). The glycemic response of WYPF pasta (160.7 +/- 19.4 mmol x min/L) was comparable to WB. WYPF biscotti produced a lower (P = 0.019) postprandial glycemic response compared to WWF biscotti (117.2 +/- 13.1 mmol x min/L). Hedonic responses between corresponding foods were similar except for the WYPF pasta (2.9 +/- 0.9) which possessed a lower sensory score (P = 0.02) for smell compared to WWF pasta (3.6 +/- 1). WYPF can be used to produce low-glycemic functional foods possessing sensory attributes that are comparable to identical food products containing WWF. PMID:20492127

  18. Bradykinin Controls Pool Size of Sensory Neurons Expressing Functional δ-Opioid Receptors

    PubMed Central

    Pettinger, Louisa; Gigout, Sylvain; Linley, John E.

    2013-01-01

    Analgesics targeting the δ-opioid receptor (DOR) may lead to fewer side effects than conventional opioid drugs, which mainly act on μ-opioid receptors (MOR), because of the less abundant expression of DOR in the CNS compared with MOR. Analgesic potential of DOR agonists increases after inflammation, an effect that may be mediated by DOR expressed in the peripheral sensory fibers. However, the expression of functional DOR at the plasma membrane of sensory neurons is controversial. Here we have used patch-clamp recordings and total internal reflection fluorescence microscopy to study the functional expression of DOR in sensory neurons from rat trigeminal (TG) and dorsal root ganglia (DRG). Real-time total internal reflection fluorescence microscopy revealed that treatment of TG and DRG cultures with the inflammatory mediator bradykinin (BK) caused robust trafficking of heterologously expressed GFP-tagged DOR to the plasma membrane. By contrast, treatment of neurons with the DOR agonist [d-Ala2, d-Leu5]-enkephalin (DADLE) caused a decrease in the membrane abundance of DOR, suggesting internalization of the receptor after agonist binding. Patch-clamp experiments revealed that DADLE inhibited voltage-gated Ca2+ channels (VGCCs) in 23% of small-diameter TG neurons. Pretreatment with BK resulted in more than twice as many DADLE responsive neurons (54%) but did not affect the efficacy of VGCC inhibition by DADLE. Our data suggest that inflammatory mediator-induced membrane insertion of DOR into the plasma membrane of peripheral sensory neurons may underlie increased DOR analgesia in inflamed tissue. Furthermore, the majority of BK-responsive TG neurons may have a potential to become responsive to DOR ligands in inflammatory conditions. PMID:23804098

  19. Esophagoprotective activity of angiotensin-(1-7) in experimental model of acute reflux esophagitis. Evidence for the role of nitric oxide, sensory nerves, hypoxia-inducible factor-1alpha and proinflammatory cytokines.

    PubMed

    Pawlik, M W; Kwiecien, S; Pajdo, R; Ptak-Belowska, A; Brzozowski, B; Krzysiek-Maczka, G; Strzalka, M; Konturek, S J; Brzozowski, T

    2014-12-01

    Gastroesophageal reflux disease (GERD) is a global disease rapidly increasing among world population. The pathogenesis of reflux esophagitis which is considered as the early stage of GERD is complex, resulting from an imbalance between aggressive factors damaging the esophagus and a number of the natural defense mechanisms. The esophageal mucosa is in a state of continuous exposure to potentially damaging endogenous and exogenous factors. Important aggressive components of gastric refluxate include acid and pepsin and also pancreatic enzymes and bile. Among aggressive factors of exogenous origin, cigarette smoking, non-steroidal anti-inflammatory drugs (NSAID), and steroids are of the utmost importance. The basic level of esophageal defense against acid-pepsin damage consists of the anti-reflux mechanisms such as the luminal acid clearance and removal of the esophageal contents and neutralization of luminal acidity. In addition the esophageal mucosal protection includes the presence of pre-epithelial, epithelial and post-epithelial cellular and functional components. Recently, the progress have been made in the understanding of role of the heptapeptide member of the renin-angiotensin system (RAS), angiotensin-(1-7) (Ang-(1-7)) in the control of gastrointestinal functions. It has been shown that all components of local RAS including Ang-(1-7) are detectable in the gastrointestinal wall including not only the stomach but also the esophagus. Previous studies revealed that Ang-(1-7), which is an important component of the RAS, exerts vasodilatory, anti-inflammatory and antioxidant activities in the stomach. Ang-(1-7) was recently implicated in gastroprotection, but its effects on esophageal mucosa in a rodent model of reflux esophagitis and in human subjects presenting GERD symptoms have not been explored. The present study was aimed to evaluate the possible protective effects of Ang-(1-7) and Mas-receptors upon esophageal mucosal damage in acute reflux esophagitis (RE) induced in anesthetized rats by ligating the pylorus and the limiting ridge (a transitional region between the forestomach and the corpus of stomach). Consequently, the total gastric reservoir to store gastric juice was greatly diminished, resulting in the reflux of this juice into the esophagus. Because Mas receptors are functionally linked to nitric oxide (NO) formation, we also studied involvement of endogenous NO in the mediation of protective and circulatory effects of exogenous Ang-(1-7). Moreover, an attempt was made to assess the possible role of sensory neurons in the modulation of the protective effects exerted by Ang-(1-7)/Mas receptor system. Six series of rats were pretreated 30 min before induction of RE with 1) vehicle (saline), 2) Ang-(1-7) (5-50 μg/kg i.p.), 3) A779 (50 μg/kg i.p.), the selective Mas receptor antagonist applied alone, 4) Ang-(1-7) (50 μg/kg i.p.) combined with A779, 5) L-NNA (20 mg/kg i.p.) administered alone, and 6) Ang-(1-7) (50 μg/kg i.p.) combined with L-NNA. In separate group of rats, capsaicin (total dosage of 125 mg/kg within three days) was administered s.c. 2 weeks before the induction of RE to induce functional ablation of sensory nerves. Rats with intact sensory nerves and those with capsaicin-induced sensory denervation received vehicle (saline) or Ang-(1-7) (50 μg/kg i.p.) to determine whether this vasoactive metabolite of angiotensin I could be also effective in rats with capsaicin-induced impairment of the synthesis and release of sensory neuropeptides such as CGRP. Four hours after induction of RE, the mucosal damage was graded with mucosal lesion index (LI) from 0 to 6, the esophageal microcirculatory blood flow (EBF) was determined by H2-gas clearance technique and plasma level of pro-inflammatory cytokines interleukin-1b (IL-1β), and tumor necrosis factor-α (TNF-α) was determined by ELISA. The expression of proinflammatory factors including COX-2, cytokine IL-1β and hypoxia inducible factor 1alpha (Hif1α) was analyzed in the esophageal mucosal biopsies. In rats with RE, the esophageal LI was significantly elevated comparing its value observed in intact rats, and the EBF was significantly decreased as compared with intact mucosa. Pretreatment with Ang-(1-7) of control rats without esophagitis induced increase in EBF by about 25% without any macroscopic changes in the esophageal mucosa or in the plasma level of cytokines. In animals with RE, pretreatment with Ang-(1-7) significantly reduced gross and histological esophageal mucosal injury and significantly increased EBF in comparison to vehicle-pretreated animals. The observed gross and histologic esophagoprotective effect of Ang-(1-7) was totally abolished by A779 so in rats with combined treatment of A779 with Ang-(1-7), the LI was identical with this observed in control RE and the EBF was decreased in these animals by about 39%. Inhibition of NO synthase by L-NNA significantly reduced the LI and the rise in EBF caused by Ang-(1-7). Similarly, the capsaicin denervation also significantly attenuated the vasodilatory and the esophagoprotective effects of Ang-(1-7). The expression of proinflammatory factors COX-2, Hif1α and IL-1β which was negligible in intact esophageal mucosa, was upregulated in esophageal mucosa of rats with RE. In contrast, the administration of Ang-(1-7) resulted in a downregulation of mRNA for COX-2, Hif1 and IL-1β in esophageal mucosa an this effect was abolished in A779-dependent manner. The Ang-(1-7) significantly decreased the RE-induced elevation of plasma levels of IL-1β and TNF-α, and this effect was also reversed by pretreatment with A779, and significantly attenuated by pretreatment with L-NNA and capsaicin-induced sensory denervation. The present study indicates that the protective effect of Ang-(1-7) observed in the esophageal mucosa during early acute stage of gastroesophageal reflux depends upon the enhancement of esophageal microcirculatory blood flow via the activation of Mas receptor possibly due to NO synthase/NO system activation, stimulation of sensory nerves, the inhibition of expression of pro-inflammatory factors including COX-2, Hif1α and IL-1β and release of proinflammatory cytokines IL-1β and TNF-α. PMID:25554985

  20. Nontubulation Repair of Peripheral Nerve Gap Using Heparin/Alginate Gel Combined with b-FGF

    PubMed Central

    Ishikawa, Namiko; Tanihara, Masao; Saito, Susumu

    2016-01-01

    Summary: All artificial nerve grafts have a tubular structure, and they guide axonal regrowth through the tube from the proximal side toward the peripheral side. Based on the results of our experimental study using animals, we used alginate gel without a tubular structure as an artificial nerve graft for digital nerve repair and evaluated peripheral nerve regeneration. In 2 patients, a gap due to digital nerve injury was bridged with controlled-release heparin/alginate gel combined with basic fibroblast growth factor, and restoration of the sensory function was serially evaluated. In both patients, Tinel’s sign appeared 3–4 weeks after the operation, and sensory recovery to the fingertip was achieved at 6 months postoperatively. Our results suggest that even gel without a tubular structure provides a site for peripheral nerve regeneration. PMID:27104099

  1. Functional and sensory properties of hen eggs with modified fatty acid compositions.

    PubMed

    Aro, H; Rokka, T; Valaja, J; Hiidenhovi, J; Huopalahti, R; Ryhänen, E-L

    2011-11-01

    Foaming, emulsifying, gelling, and sensory properties of fresh and stored hen eggs fed with a diet supplemented with flax oil (FO), rapeseed oil (RO), fish oil (FISH), and by-product from black currant processing (BC) were investigated. With these diets, the ω6/ω3 fatty acid ratio of eggs varied from 1.5 to 5.8, while the ratio for eggs in the control group was 6.2. Compared to eggs in the control group, FO supplementation in the feed had statistically significant influences on the foaming properties of the fresh eggs. Eggs stored for 21 days lost part of their foaming properties in FISH oil supplemented group, but the foaming properties in all test groups were technically acceptable. The emulsifying properties of eggs in FO and FISH supplemented feeding groups were statistically different compared to control group. In boiled eggs, flax oil and fish oil supplementation induced off flavours in eggs, but no changes between the control group and test groups were found in the sensory properties of mayonnaise preparations. These results suggest that the egg processing industry may produce egg-based products using oil-supplemented eggs without major problems in functional or sensory properties. PMID:21984041

  2. Concurrent functional magnetic resonance imaging and electroencephalography assessment of sensory gating in schizophrenia

    PubMed Central

    Bak, Nikolaj; Rostrup, Egill; Larsson, Henrik BW; Glenthøj, Birte Y; Oranje, Bob

    2014-01-01

    Schizophrenia is frequently accompanied by deficits in basic information processing, such as sensory gating. The sources behind deficient sensory gating in schizophrenia patients are, however, still largely unclear. The aim of the current study was to identify the brain structures involved in deficient sensory gating in schizophrenia patients. Twenty healthy male volunteers and 23 male schizophrenia patients were initially assessed in a somatosensory P50 suppression paradigm using concurrent electroencephalography (EEG)/functional magnetic resonance imaging (fMRI) methodology. The trials consisted of single stimuli or pairs of identical stimuli with either 500 ms or 1,000 ms interstimulus intervals. Not all subjects showed a P50 waveform as a result of the somatosensory stimuli: It was detected in 13 schizophrenia patients and 15 control subjects. Significant P50 suppression was found in the 500 ms trials in controls only. Region of interest analyses were performed for a priori chosen regions. Significant negative correlations between P50 ratios and the BOLD response were found bilaterally in the hippocampus, thalamus, anterior and posterior superior temporal gyrus (STG), and in the left inferior frontal gyrus pars opercularis. However, significant group differences were found in the hippocampus and the thalamus only. This is the first study in which P50 suppression was assessed in schizophrenia patients with concurrent fMRI/EEG methodology. The data support that the STG, thalamus, inferior frontal gyrus, and the hippocampus are involved in P50 suppression. However, of these structures only the hippocampus and thalamus appeared involved in the altered sensory processing found in schizophrenia. Hum Brain Mapp 35:3578–3587, 2014. © 2013 Wiley Periodicals, Inc. PMID:24375687

  3. Concurrent functional magnetic resonance imaging and electroencephalography assessment of sensory gating in schizophrenia.

    PubMed

    Bak, Nikolaj; Rostrup, Egill; Larsson, Henrik B W; Glenthøj, Birte Y; Oranje, Bob

    2014-08-01

    Schizophrenia is frequently accompanied by deficits in basic information processing, such as sensory gating. The sources behind deficient sensory gating in schizophrenia patients are, however, still largely unclear. The aim of the current study was to identify the brain structures involved in deficient sensory gating in schizophrenia patients. Twenty healthy male volunteers and 23 male schizophrenia patients were initially assessed in a somatosensory P50 suppression paradigm using concurrent electroencephalography (EEG)/functional magnetic resonance imaging (fMRI) methodology. The trials consisted of single stimuli or pairs of identical stimuli with either 500 ms or 1,000 ms interstimulus intervals. Not all subjects showed a P50 waveform as a result of the somatosensory stimuli: It was detected in 13 schizophrenia patients and 15 control subjects. Significant P50 suppression was found in the 500 ms trials in controls only. Region of interest analyses were performed for a priori chosen regions. Significant negative correlations between P50 ratios and the BOLD response were found bilaterally in the hippocampus, thalamus, anterior and posterior superior temporal gyrus (STG), and in the left inferior frontal gyrus pars opercularis. However, significant group differences were found in the hippocampus and the thalamus only. This is the first study in which P50 suppression was assessed in schizophrenia patients with concurrent fMRI/EEG methodology. The data support that the STG, thalamus, inferior frontal gyrus, and the hippocampus are involved in P50 suppression. However, of these structures only the hippocampus and thalamus appeared involved in the altered sensory processing found in schizophrenia. PMID:24375687

  4. Mitochondrial dysfunction in distal axons contribute to HIV sensory neuropathy

    PubMed Central

    Lehmann, Helmar C.; Chen, Weiran; Borzan, Jasenka; Mankowski, Joseph; Hke, Ahmet

    2010-01-01

    Objective Accumulation of mitochondrial DNA (mtDNA) damage has been associated with aging and abnormal oxidative metabolism. We hypothesized that in human immunodeficiency virus associated sensory neuropathy (HIV-SN), damaged mtDNA accumulates in distal nerve segments and that a spatial pattern of mitochondrial dysfunction contribute to the distal degeneration of sensory nerve fibers. Methods We measured levels of common deletion mutations in mtDNA and expression levels of mitochondrial respiratory chain complexes of matched proximal and distal nerve specimens from patients with and without HIV-SN. In mitochondria isolated from peripheral nerves of simian immunodeficiency virus (SIV) infected macaques, a model of HIV-SN, we measured mitochondrial function and generation of reactive oxygen species. Results We identified increased levels of mtDNA common deletion mutation in post-mortem sural nerves of patients with HIV-SN as compared to uninfected patients or HIV patients without sensory neuropathy. Furthermore, we found that common deletion mutation in mtDNA was more prevalent in distal sural nerves compared to dorsal root ganglia. In a primate model of HIV-SN, freshly isolated mitochondria from sural nerves of macaques infected with a neurovirulent strain of SIV showed impaired mitochondrial function compared to mitochondria from proximal nerve segments. Interpretation Our findings suggest that mtDNA damage accumulates in distal mitochondria of long axons, especially in patients with HIV-SN, and that this may lead to reduced mitochondrial function in distal nerves relative to proximal segments. Although our findings are based on HIV-SN, if confirmed in other neuropathies, these observations could explain the length-dependent nature of most axonal peripheral neuropathies. PMID:21280080

  5. Functional and anatomical characteristics of the nerve-brown adipose interaction in the rat

    NASA Technical Reports Server (NTRS)

    Flaim, K. E.; Horowitz, J. M.; Horwitz, B. A.

    1976-01-01

    Experiments were conducted on 12 male rats to study the coupling of signals from the sympathetic nervous system to the brown adipose tissue. Analysis of electron photomicrographs revealed considerable morphological heterogeneity among the nerves entering and leaving the interscapular fat pad. In response to electrical simulation of the nerves, the temperature of the brown fat increased following a rapid but transient temperature drop. Such changes were observed only on the ipsilateral side, indicating that the innervation to the interscapular brown fat of the rat is functionally bilateral rather than diffuse. The finding that brown fat is capable of responding in a graded fashion correlates well with observations suggesting that clusters of brown adipocytes may be electrically coupled.

  6. Intrinsic Functional Plasticity of the Sensory-Motor Network in Patients with Cervical Spondylotic Myelopathy

    PubMed Central

    Zhou, F. Q.; Tan, Y. M.; Wu, L.; Zhuang, Y.; He, L. C.; Gong, H. H.

    2015-01-01

    Several neuroimaging studies have suggested brain reorganisation in patients with cervical spondylotic myelopathy (CSM); however, the changes in spontaneous neuronal activity that are associated with connectedness remain largely unknown. In this study, functional connectivity strength (FCS), a data-driven degree centrality method based on a theoretical approach, was applied for the first time to investigate changes in the sensory-motor network (SMN) at the voxel level. Comparatively, CSM not only showed significantly decreased FCS in the operculum-integrated regions, which exhibited reduced resting-state functional connectivity (rsFC) around the Rolandic sulcus, but it also showed increased FCS in the premotor, primary somatosensory, and parietal-integrated areas, which primarily showed an enhanced rsFC pattern. Correlation analysis showed that altered FCS (in the left premotor-ventral/precentral-operculum, right operculum-parietale 4, and right S1) was associated with worsening Japanese Orthopaedic Association scores and that the rsFC pattern was influenced by cervical cord micro-structural damage at the C2 level. Together, these findings suggest that during myelopathy, the intrinsic functional plasticity of the SMN responds to the insufficient sensory and motor experience in CSM patients. This knowledge may improve our understanding of the comprehensive functional defects found in CSM patients and may inspire the development of new therapeutic strategies in the future. PMID:25897648

  7. Large-scale somatotopic refinement via functional synapse elimination in the sensory thalamus of developing mice.

    PubMed

    Takeuchi, Yuichi; Asano, Hidetsugu; Katayama, Yoko; Muragaki, Yoshihiro; Imoto, Keiji; Miyata, Mariko

    2014-01-22

    Functional synapse elimination and strengthening are crucial developmental processes in the formation of precise neuronal circuits in the somatosensory system, but the underlying alterations in topographical organization are not yet fully understood. To address this issue, we generated transgenic mice in which afferent fibers originating from the whisker-related brain region, called the maxillary principal trigeminal nucleus (PrV2), were selectively visualized with genetically expressed fluorescent protein. We found that functional synapse elimination drove and established large-scale somatotopic refinement even after the thalamic barreloid architecture was formed. Before functional synapse elimination, the whisker sensory thalamus was innervated by afferent fibers not only from the PrV2, but also from the brainstem nuclei representing other body parts. Most notably, only afferent fibers from PrV2 onto a whisker sensory thalamic neuron selectively survived and were strengthened, whereas other afferent fibers were preferentially eliminated via their functional synapse elimination. This large-scale somatotopic refinement was at least partially dependent on somatosensory experience. These novel results uncovered a previously unrecognized role of developmental synapse elimination in the large-scale, instead of the fine-scale, somatotopic refinement even after the initial segregation of the barreloid map. PMID:24453317

  8. Functional Self-Assembling Peptide Nanofiber Hydrogels Designed for Nerve Degeneration.

    PubMed

    Sun, Yuqiao; Li, Wen; Wu, Xiaoli; Zhang, Na; Zhang, Yongnu; Ouyang, Songying; Song, Xiyong; Fang, Xinyu; Seeram, Ramakrishna; Xue, Wei; He, Liumin; Wu, Wutian

    2016-01-27

    Self-assembling peptide (SAP) RADA16-I (Ac-(RADA)4-CONH2) has been suffering from a main drawback associated with low pH, which damages cells and host tissues upon direct exposure. In this study, we presented a strategy to prepare nanofiber hydrogels from two designer SAPs at neutral pH. RADA16-I was appended with functional motifs containing cell adhesion peptide RGD and neurite outgrowth peptide IKVAV. The two SAPs were specially designed to have opposite net charges at neutral pH, the combination of which created a nanofiber hydrogel (-IKVAV/-RGD) characterized by significantly higher G' than G″ in a viscoelasticity examination. Circular dichroism, Fourier transform infrared spectroscopy, and Raman measurements were performed to investigate the secondary structure of the designer SAPs, indicating that both the hydrophobic/hydrophilic properties and electrostatic interactions of the functional motifs play an important role in the self-assembling behavior of the designer SAPs. The neural progenitor cells (NPCs)/stem cells (NSCs) fully embedded in the 3D-IKVAV/-RGD nanofiber hydrogel survived, whereas those embedded within the RADA 16-I hydrogel hardly survived. Moreover, the -IKVAV/-RGD nanofiber hydrogel supported NPC/NSC neuron and astrocyte differentiation in a 3D environment without adding extra growth factors. Studies of three nerve injury models, including sciatic nerve defect, intracerebral hemorrhage, and spinal cord transection, indicated that the designer -IKVAV/-RGD nanofiber hydrogel provided a more permissive environment for nerve regeneration than the RADA 16-I hydrogel. Therefore, we reported a new mechanism that might be beneficial for the synthesis of SAPs for in vitro 3D cell culture and nerve regeneration. PMID:26720334

  9. The RhoGEF Trio Functions in Sculpting Class Specific Dendrite Morphogenesis in Drosophila Sensory Neurons

    PubMed Central

    Iyer, Srividya Chandramouli; Wang, Dennis; Iyer, Eswar Prasad R.; Trunnell, Sarah A.; Meduri, Ramakrishna; Shinwari, Riaz; Sulkowski, Mikolaj J.; Cox, Daniel N.

    2012-01-01

    Background As the primary sites of synaptic or sensory input in the nervous system, dendrites play an essential role in processing neuronal and sensory information. Moreover, the specification of class specific dendrite arborization is critically important in establishing neural connectivity and the formation of functional networks. Cytoskeletal modulation provides a key mechanism for establishing, as well as reorganizing, dendritic morphology among distinct neuronal subtypes. While previous studies have established differential roles for the small GTPases Rac and Rho in mediating dendrite morphogenesis, little is known regarding the direct regulators of these genes in mediating distinct dendritic architectures. Methodology/Principal Findings Here we demonstrate that the RhoGEF Trio is required for the specification of class specific dendritic morphology in dendritic arborization (da) sensory neurons of the Drosophila peripheral nervous system (PNS). Trio is expressed in all da neuron subclasses and loss-of-function analyses indicate that Trio functions cell-autonomously in promoting dendritic branching, field coverage, and refining dendritic outgrowth in various da neuron subtypes. Moreover, overexpression studies demonstrate that Trio acts to promote higher order dendritic branching, including the formation of dendritic filopodia, through Trio GEF1-dependent interactions with Rac1, whereas Trio GEF-2-dependent interactions with Rho1 serve to restrict dendritic extension and higher order branching in da neurons. Finally, we show that de novo dendritic branching, induced by the homeodomain transcription factor Cut, requires Trio activity suggesting these molecules may act in a pathway to mediate dendrite morphogenesis. Conclusions/Significance Collectively, our analyses implicate Trio as an important regulator of class specific da neuron dendrite morphogenesis via interactions with Rac1 and Rho1 and indicate that Trio is required as downstream effector in Cut-mediated regulation of dendrite branching and filopodia formation. PMID:22442703

  10. Successful tactile based visual sensory substitution use functions independently of visual pathway integrity

    PubMed Central

    Lee, Vincent K.; Nau, Amy C.; Laymon, Charles; Chan, Kevin C.; Rosario, Bedda L.; Fisher, Chris

    2014-01-01

    Purpose: Neuronal reorganization after blindness is of critical interest because it has implications for the rational prescription of artificial vision devices. The purpose of this study was to distinguish the microstructural differences between perinatally blind (PB), acquired blind (AB), and normally sighted controls (SCs) and relate these differences to performance on functional tasks using a sensory substitution device (BrainPort). Methods: We enrolled 52 subjects (PB n = 11; AB n = 35; SC n = 6). All subjects spent 15 h undergoing BrainPort device training. Outcomes of light perception, motion, direction, temporal resolution, grating, and acuity were tested at baseline and after training. Twenty-six of the subjects were scanned with a three Tesla MRI scanner for diffusion tensor imaging (DTI), and with a positron emission tomography (PET) scanner for mapping regional brain glucose consumption during sensory substitution function. Non-parametric models were used to analyze fractional anisotropy (FA; a DTI measure of microstructural integrity) of the brain via region-of-interest (ROI) analysis and tract-based spatial statistics (TBSS). Results: At baseline, all subjects performed all tasks at chance level. After training, light perception, time resolution, location and grating acuity tasks improved significantly for all subject groups. ROI and TBSS analyses of FA maps show areas of statistically significant differences (p ≤ 0.025) in the bilateral optic radiations and some visual association connections between all three groups. No relationship was found between FA and functional performance with the BrainPort. Discussion: All subjects showed performance improvements using the BrainPort irrespective of nature and duration of blindness. Definite brain areas with significant microstructural integrity changes exist among PB, AB, and NC, and these variations are most pronounced in the visual pathways. However, the use of sensory substitution devices is feasible irrespective of microstructural integrity of the primary visual pathways between the eye and the brain. Therefore, tongue based devices devices may be usable for a broad array of non-sighted patients. PMID:24860473

  11. 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

  12. Allotransplanted DRG neurons or Schwann cells affect functional recovery in a rodent model of sciatic nerve injury

    PubMed Central

    Liu, Weimin; Markman, John D.; Gelbard, Harris A.; Huang, Jason H.

    2015-01-01

    Objective In this study, the functional recoveries of Sprague-Dawley rats following repair of a complete sciatic nerve transection using allotransplanted dorsal root ganglion (DRG) neurons or Schwann cells were examined using a number of outcome measures. Methods Four groups were compared: (1) repair with a nerve guide conduit seeded with allotransplanted Schwann cells harvested from Wistar rats, (2) repair with a nerve guide conduit seeded with DRG neurons, (3) repair with solely a nerve guide conduit, and (4) sham-surgery animals where the sciatic nerve was left intact. The results corroborated our previous reported histology findings and measures of immunogenicity. Results The Wistar-DRG-treated group achieved the best recovery, significantly outperforming both the Wistar-Schwann group and the nerve guide conduit group in the Von Frey assay of touch response (P < 0.05). Additionally, Wistar-DRG and Wistar-Schwann seeded repairs showed lower frequency and severity in an autotomy measure of the self-mutilation of the injured leg because of neuralgia. Conclusion These results suggest that in complete peripheral nerve transections, surgical repair using nerve guide conduits with allotransplanted DRG and Schwann cells may improve recovery, especially DRG neurons, which elicit less of an immune response. PMID:24836462

  13. The role of adrenal nerves in the regulation of adrenocortical functions.

    PubMed

    Holzwarth, M A; Cunningham, L A; Kleitman, N

    1987-01-01

    There is now convincing evidence for the distribution of several nerve plexuses in the outer zone of the adrenal cortex. At the ultrastructural level, the close proximity of nerve boutons to cortical cells establishes the anatomical substrate for a direct neural effect on adrenal cortical cell functions. Of those neurotransmitters and neuropeptides identified to date, catecholamine, VIP, and NPY appear to be most prevalent. Importantly, the amounts of morphologically identifiable catecholamine, VIP and NPY are differentially sensitive to alteration of several physiological conditions. Furthermore, the VIP plexus appears to be intrinsic to the adrenal while the catecholamine and NPY nerve fibers enter the adrenal along blood vessels. Together, these results suggest that these multiple nerve plexuses might exert control on several adrenocortical cellular processes in addition to the regulation of adrenal blood flow. Compensatory adrenal growth, a rapid proliferative response to unilateral adrenalectomy, was previously shown to be neurally mediated. The role of the catecholamine innervation in the mediation of this process has now been demonstrated. The elimination of the sympathetic nervous system by neonatal sympathectomy inhibited the proliferative response as measured by DNA synthesis. In vivo administration of beta-adrenergic receptor blockers did not inhibit the compensatory growth response. Furthermore, the beta-adrenergic agonist isoproterenol, inhibited the rate of DNA synthesis both in vivo and in vitro. The direct action of the beta-adrenergic agonist on the adrenocortical cell DNA synthesis rate suggests that the catecholaminergic nerves tonically inhibit cell proliferation associated with compensatory growth and that the release from the beta-adrenergic inhibition is necessary for compensatory growth. Whether inhibition of the beta-adrenergic innervation is the trigger for compensatory growth or whether it is permissive to the action of a still unidentified mitogenic substance, is not yet known. The direct role of VIP and catecholamines in the regulation of steroidogenesis has been investigated in vitro using the perifused capsule-glomerulosa preparation which is representative of a normal outer zone of the adrenal and is the site of the neural plexuses and identified receptors. Both VIP and isoproterenol stimulate steroidogenesis and specifically cause a greater increase in secretion of aldosterone than corticosterone. Although the concentrations of VIP and isoproterenol required to stimulate steroidogenesis are greater than reported circulating levels, release from resident nerves could provide high local concentrations.(ABSTRACT TRUNCATED AT 400 WORDS) PMID:3126695

  14. Intramuscular nerve distribution in bladder and the relationship between intramuscular ganglia and bladder function in man and dog

    PubMed Central

    Zhao, Zeju; Xu, Qian; Lu, Li; Luo, Xu; Fu, Xiaoyun

    2014-01-01

    In clinical, the relationship between bladder intramuscular nerve and function is also elusive. This study aims to compare the bladder intramuscular nerve distribution and its characteristics and significance in human and dog. Eleven dogs’ bladders were stained by Sihler’s and HE techniques. Fifteen human bladders were adopted by Sihler’s staining, using 10% formaldehyde to fix 12 weeks, 7 by HE dyeing fixes 24 hours. Results indicated that man’s bladder was triangularpyramid-shaped. While dog’s bladder was spherical-shaped and its muscle fibers arrange were irregularly shaped. Longitudinal muscle of the outer layer is fleshy, the terminal is at the bladder neck without exception, and vesical trigone has relatively obvious three layers of structure. After dyeing dog’s bladder was transparent jelly, the nerve was purple color, enter bladder at the ureter-bladder junction with different forms. Man’s bladder nerves, no ganglion, were more trivial than that of dogs, and with smaller branches, the large nerve ganglion. The links with the nerve fibers and forms the network on the dog’s bladder wall, and the nerve fibers crosses comparatively little on both the left and right sides in the midline. The right nerve branch gains advantage on the man’s bladder wall, the situations is opposite on the dog’s. In conclusion, bladder nerves which scatter to the bladder wall have branches to lower ureter at the ureter-bladder junction, the structure and distribution of intramuscular nerves are different, the existence of intramuscular ganglia is relating to the bladder function both in man and dog. PMID:25664008

  15. Novel Roles for Osteopontin and Clusterin in Peripheral Motor and Sensory Axon Regeneration

    PubMed Central

    Mi, Ruifa; Connor, Emmalynn; Reed, Nicole; Vyas, Alka; Alspalter, Manula; Coppola, Giovanni; Geschwind, Daniel H.; Brushart, Thomas M.

    2014-01-01

    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. PMID:24478351

  16. Prospective Study of Motor, Sensory, Psychological and Autonomic Functions in Patients with Irritable Bowel Syndrome

    PubMed Central

    Camilleri, Michael; McKinzie, Sanna; Busciglio, Irene; Low, Phillip A.; Sweetser, Seth; Burton, Duane; Baxter, Kari; Ryks, Michael; Zinsmeister, Alan R.

    2008-01-01

    Background/Aim To assess pathophysiology in irritable bowel syndrome (IBS). Methods 122 IBS patients (3 male) and 41 healthy females underwent: questionnaires (symptoms, psychology), autonomic, gut transit, gastric volumes (GV), satiation, rectal compliance and sensation (thresholds and pain ratings) testing. Proportions of patients with abnormal (<10th and >90th percentiles) motor or sensory functions according to bowel symptoms [constipation (C), diarrhea (D), mixed (M)], pain/bloat and number of primary symptoms were estimated. Results IBS subgroups (C, D, M) were similar in age, gastric and small bowel transit, satiation, GV, rectal compliance, sensory thresholds or pain ratings. IBS was associated with BMI, somatic symptoms, anxiety and depression scores. Significant associations were observed with colonic transit (IBS-C [p=0.078] and IBS-D [p<0.05] at 24 h; IBS-D [p<0.01] and IBS-M [p=0.056] at 48 h): 32% IBS had abnormal colonic transit: 20.5% at 24 h and 11.5% at 48 h. Overall, 20.5% IBS patients had increased sensation to distensions: hypersensitivity (<10th percentile thresholds) in 7.6%, and hyperalgesia (pain sensation ratings to distension >90th percentile for ratings in health) in 13%. Conversely, 16.5% of IBS patients had reduced rectal sensation. Pain >6 times per year and bloating were not significantly associated with motor, satiation, or sensory functions. Endorsing 1–2 or 3–4 primary IBS symptoms were associated with abnormal transit and sensation in IBS. Conclusion In tertiary referral (predominantly female) patients with IBS, colonic transit (32%) is the most prevalent physiological abnormality; 21% had increased and 17% decreased rectal pain sensations. Comprehensive physiological assessment may help optimize management in IBS. PMID:18456567

  17. Inside-out autologous vein grafts fail to restore erectile function in a rat model of cavernous nerve crush injury after nerve-sparing prostatectomy.

    PubMed

    Bessede, T; Moszkowicz, D; Alsaid, B; Zaitouna, M; Diallo, D; Peschaud, F; Benoit, G; Droupy, S

    2015-01-01

    Some autologous tissues can restore erectile function (EF) in rats after a resection of the cavernous nerve (CN). However, a cavernous nerve crush injury (CNCI) better reproduces ED occurring after a nerve-sparing radical prostatectomy (RP). The aim was to evaluate the effect on EF of an autologous vein graft after CNCI, compared with an artificial conduit. Five groups of rats were studied: those with CN exposure, exposure+vein, crush, crush+guide and crush+vein. Four weeks after surgery, the EF of rats was assessed by electrical stimulation of the CNs. The intracavernous pressure (ICP) and mean arterial pressure (MAP) were monitored during stimulations at various frequencies. The main outcome, that is, the rigidity of the erections, was defined as the ICP/MAP ratio. At 10 Hz, the ICP/MAP ratios were 41.8%, 34.7%, 20.9%, 33.9% and 20.5%, respectively. The EF was significantly lower in rats if the CNCI was treated with a vein graft instead of an artificial guide. Contrary to cases of CN resection, autologous vein grafts did not improve EF after CNCI. In terms of clinical use, the study suggests to limit an eventual use of autologous vein grafts to non-nerve-sparing RPs. PMID:25078050

  18. Presynaptic function is altered in snake K+-depolarized motor nerve terminals containing compromised mitochondria.

    PubMed

    Calupca, M A; Prior, C; Merriam, L A; Hendricks, G M; Parsons, R L

    2001-04-01

    Presynaptic function was investigated at K+-stimulated motor nerve terminals in snake costocutaneous nerve muscle preparations exposed to carbonyl cyanide m-chlorophenylhydrazone (CCCP, 2 M), oligomycin (8 g x ml(-1)) or CCCP and oligomycin together. Miniature endplate currents (MEPCs) were recorded at -150 mV with two-electrode voltage clamp. With all three drug treatments, during stimulation by elevated K+ (35 mM), MEPC frequencies initially increased to values > 350 s(-1), but then declined. The decline occurred more rapidly in preparations treated with CCCP or CCCP and oligomycin together than in those treated with oligomycin alone. Staining with FM1-43 indicated that synaptic vesicle membrane endocytosis occurred at some CCCP- or oligomycin-treated nerve terminals after 120 or 180 min of K+ stimulation, respectively. The addition of glucose to stimulate production of ATP by glycolysis during sustained K+ stimulation attenuated the decline in MEPC frequency and increased the percentage of terminals stained by FM1-43 in preparations exposed to either CCCP or oligomycin. We propose that the decline in K+-stimulated quantal release in preparations treated with CCCP, oligomycin or CCCP and oligomycin together could result from a progressive elevation of intracellular calcium concentration ([Ca2+]i). For oligomycin-treated nerve terminals, a progressive elevation of [Ca2+]i could occur as the cytoplasmic ATP/ADP ratio decreases, causing energy-dependent Ca2+ buffering mechanisms to fail. The decline in MEPC frequency could occur more rapidly in preparations treated with CCCP or CCCP and oligomycin together because mitochondrial Ca2+ buffering and ATP production were both inhibited. Therefore, the proposed sustained elevation of [Ca2+]i could occur more rapidly. PMID:11283236

  19. Neuroprotectin D1 Restores Corneal Nerve Integrity and Function After Damage From Experimental Surgery

    PubMed Central

    Cortina, Maria Soledad; He, Jiucheng; Russ, Tiffany; Bazan, Nicolas G.; Bazan, Haydee E. P.

    2013-01-01

    Purpose. To investigate if topical treatment of neuroprotectin D1 (NPD1) increases regeneration of functional nerves after lamellar keratectomy. Methods. An 8-mm stromal dissection was performed in the left eye of each rabbit. The rabbits were treated with NPD1, pigment epithelial-derived factor (PEDF) in combination with docosahexaenoic acid (DHA) or vehicle for 6 weeks, and corneas were obtained at 8 weeks. After fixation, corneal wholemounts were stained with mouse monoclonal anti-βIII-tubulin antibody and double stained with chicken anti-calcitonin gene-related peptide (CGRP) antibody. Corneal sensitivity and tear secretion were measured using the Cochet-Bonnet esthesiometer and the Schirmer's test, respectively. Additional rabbits were treated with NPD1, PEDF+DHA, or vehicle, and corneal sections were stained with a rat monoclonal anti-neutrophil antibody. Cultures of trigeminal ganglia from 5-day-old mice were treated with NPD1, PEDF+DHA, lipoxin A4 (LXA4), 12- or 15-hydroxyeicosatetraenoic acid (12[S] or 15[S]-HETE), and nerve growth factor (NGF) as positive control. Results. NPD1 increased subepithelial corneal nerve area three times compared with vehicle-treated rabbits. The effect was similar to PEDF+DHA–treated animals. There was recovery of CGRP-positive neurons and an increase in corneal sensitivity and tear secretion in NPD1-treated animals. NPD1 decreased neutrophil infiltration after 2 and 4 days of treatment. In the in vitro cultures, NPD1 and PEDF+DHA induced a 3-fold increase in neurite outgrowth compared with cultures without supplementation. Treatments with LXA4, 12(S)-, and 15(S)- HETE did not stimulate neurite outgrowth. Conclusions. NPD1 has anti-inflammatory and nerve regenerative properties. This study demonstrates that NPD1 may offer an effective treatment for neurotrophic corneas. PMID:23702780

  20. Cavernosal nerve functionality evaluation after magnetic resonance imaging-guided transurethral ultrasound treatment of the prostate

    PubMed Central

    Sammet, Steffen; Partanen, Ari; Yousuf, Ambereen; Sammet, Christina L; Ward, Emily V; Wardrip, Craig; Niekrasz, Marek; Antic, Tatjana; Razmaria, Aria; Farahani, Keyvan; Sokka, Shunmugavelu; Karczmar, Gregory; Oto, Aytekin

    2015-01-01

    AIM: To evaluate the feasibility of using therapeutic ultrasound as an alternative treatment option for organ-confined prostate cancer. METHODS: In this study, a trans-urethral therapeutic ultrasound applicator in combination with 3T magnetic resonance imaging (MRI) guidance was used for real-time multi-planar MRI-based temperature monitoring and temperature feedback control of prostatic tissue thermal ablation in vivo. We evaluated the feasibility and safety of MRI-guided trans-urethral ultrasound to effectively and accurately ablate prostate tissue while minimizing the damage to surrounding tissues in eight canine prostates. MRI was used to plan sonications, monitor temperature changes during therapy, and to evaluate treatment outcome. Real-time temperature and thermal dose maps were calculated using the proton resonance frequency shift technique and were displayed as two-dimensional color-coded overlays on top of the anatomical images. After ultrasound treatment, an evaluation of the integrity of cavernosal nerves was performed during prostatectomy with a nerve stimulator that measured tumescence response quantitatively and indicated intact cavernous nerve functionality. Planned sonication volumes were visually correlated to MRI ablation volumes and corresponding histo-pathological sections after prostatectomy. RESULTS: A total of 16 sonications were performed in 8 canines. MR images acquired before ultrasound treatment were used to localize the prostate and to prescribe sonication targets in all canines. Temperature elevations corresponded within 1 degree of the targeted sonication angle, as well as with the width and length of the active transducer elements. The ultrasound treatment procedures were automatically interrupted when the temperature in the target zone reached 56 °C. In all canines erectile responses were evaluated with a cavernous nerve stimulator post-treatment and showed a tumescence response after stimulation with an electric current. These results indicated intact cavernous nerve functionality. In all specimens, regions of thermal ablation were limited to areas within the prostate capsule and no damage was observed in periprostatic tissues. Additionally, a visual analysis of the ablation zones on contrast-enhanced MR images acquired post ultrasound treatment correlated excellent with the ablation zones on thermal dose maps. All of the ablation zones received a consensus score of 3 (excellent) for the location and size of the correlation between the histologic ablation zone and MRI based ablation zone. During the prostatectomy and histologic examination, no damage was noted in the bladder or rectum. CONCLUSION: Trans-urethral ultrasound treatment of the prostate with MRI guidance has potential to safely, reliably, and accurately ablate prostatic regions, while minimizing the morbidities associated with conventional whole-gland resection or therapy. PMID:26753067

  1. Temporary Neurotrophin Treatment Prevents Deafness-Induced Auditory Nerve Degeneration and Preserves Function.

    PubMed

    Ramekers, Dyan; Versnel, Huib; Strahl, Stefan B; Klis, Sjaak F L; Grolman, Wilko

    2015-09-01

    After substantial loss of cochlear hair cells, exogenous neurotrophins prevent degeneration of the auditory nerve. Because cochlear implantation, the current therapy for profound sensorineural hearing loss, depends on a functional nerve, application of neurotrophins is being investigated. We addressed two questions important for fundamental insight into the effects of exogenous neurotrophins on a degenerating neural system, and for translation to the clinic. First, does temporary treatment with brain-derived neurotrophic factor (BDNF) prevent nerve degeneration on the long term? Second, how does a BDNF-treated nerve respond to electrical stimulation? Deafened guinea pigs received a cochlear implant, and their cochleas were infused with BDNF for 4 weeks. Up to 8 weeks after treatment, their cochleas were analyzed histologically. Electrically evoked compound action potentials (eCAPs) were recorded using stimulation paradigms that are informative of neural survival. Spiral ganglion cell (SGC) degeneration was prevented during BDNF treatment, resulting in 1.9 times more SGCs than in deafened untreated cochleas. Importantly, SGC survival was almost complete 8 weeks after treatment cessation, when 2.6 times more SGCs were observed. In four eCAP characteristics (three involving alteration of the interphase gap of the biphasic current pulse and one involving pulse trains), we found large and statistically significant differences between normal-hearing and deaf controls. Importantly, for BDNF-treated animals, these eCAP characteristics were near normal, suggesting healthy responsiveness of BDNF-treated SGCs. In conclusion, clinically practicable short-term neurotrophin treatment is sufficient for long-term survival of SGCs, and it can restore or preserve SGC function well beyond the treatment period. Significance statement: Successful restoration of hearing in deaf subjects by means of a cochlear implant requires a healthy spiral ganglion cell population. Deafness-induced degeneration of these cells can be averted with neurotrophic factors. In the present study in deafened guinea pigs, we investigated the long-term effects of temporary (i.e., clinically practicable) treatment with brain-derived neurotrophic factor (BDNF). We show that, after treatment cessation, the neuroprotective effect remains for at least 8 weeks. Moreover, for the first time, it is shown that the electrical responsiveness of BDNF-treated spiral ganglion cells is preserved during this period as well. These findings demonstrate that treatment of the auditory nerve with neurotrophic factors may be relevant for cochlear implant users. PMID:26354903

  2. Early interfaced neural activity from chronic amputated nerves.

    PubMed

    Garde, Kshitija; Keefer, Edward; Botterman, Barry; Galvan, Pedro; Romero, Mario I

    2009-01-01

    Direct interfacing of transected peripheral nerves with advanced robotic prosthetic devices has been proposed as a strategy for achieving natural motor control and sensory perception of such bionic substitutes, thus fully functionally replacing missing limbs in amputees. Multi-electrode arrays placed in the brain and peripheral nerves have been used successfully to convey neural control of prosthetic devices to the user. However, reactive gliosis, micro hemorrhages, axonopathy and excessive inflammation currently limit their long-term use. Here we demonstrate that enticement of peripheral nerve regeneration through a non-obstructive multi-electrode array, after either acute or chronic nerve amputation, offers a viable alternative to obtain early neural recordings and to enhance long-term interfacing of nerve activity. Non-restrictive electrode arrays placed in the path of regenerating nerve fibers allowed the recording of action potentials as early as 8 days post-implantation with high signal-to-noise ratio, as long as 3 months in some animals, and with minimal inflammation at the nerve tissue-metal electrode interface. Our findings suggest that regenerative multi-electrode arrays of open design allow early and stable interfacing of neural activity from amputated peripheral nerves and might contribute towards conveying full neural control and sensory feedback to users of robotic prosthetic devices. PMID:19506704

  3. Early Interfaced Neural Activity from Chronic Amputated Nerves

    PubMed Central

    Garde, Kshitija; Keefer, Edward; Botterman, Barry; Galvan, Pedro; Romero, Mario I.

    2009-01-01

    Direct interfacing of transected peripheral nerves with advanced robotic prosthetic devices has been proposed as a strategy for achieving natural motor control and sensory perception of such bionic substitutes, thus fully functionally replacing missing limbs in amputees. Multi-electrode arrays placed in the brain and peripheral nerves have been used successfully to convey neural control of prosthetic devices to the user. However, reactive gliosis, micro hemorrhages, axonopathy and excessive inflammation currently limit their long-term use. Here we demonstrate that enticement of peripheral nerve regeneration through a non-obstructive multi-electrode array, after either acute or chronic nerve amputation, offers a viable alternative to obtain early neural recordings and to enhance long-term interfacing of nerve activity. Non-restrictive electrode arrays placed in the path of regenerating nerve fibers allowed the recording of action potentials as early as 8 days post-implantation with high signal-to-noise ratio, as long as 3 months in some animals, and with minimal inflammation at the nerve tissue-metal electrode interface. Our findings suggest that regenerative multi-electrode arrays of open design allow early and stable interfacing of neural activity from amputated peripheral nerves and might contribute towards conveying full neural control and sensory feedback to users of robotic prosthetic devices. PMID:19506704

  4. Early auditory sensory processing deficits in mouse mutants with reduced NMDA receptor function.

    PubMed

    Bickel, Stephan; Lipp, Hans-Peter; Umbricht, Daniel

    2008-06-01

    Cognitive deficits in schizophrenia include impairments at automatic, preattentive stages of sensory information processing. These deficits are evident in the prepulse inhibition- (PPI) and habituation of the auditory startle response paradigm, the paired tone paradigm in the EEG, and the peak recovery function of auditory evoked potentials (AEP). Administration of NMDA receptor antagonists reliably disrupts PPI and habituation of the startle, but not gating of AEPs in rodents. In the peak recovery paradigm, patients with schizophrenia and primates treated with NMDA receptor antagonists show reduced maximal response at long interstimulus intervals (ISI), but normal responses at short ISIs. Thus reduced NMDA receptor signalling may underlie alterations in these paradigms observed in schizophrenia. We tested the paradigms mentioned in mouse mutants with reduced expression of the NR1 subunit of the NMDA receptor (N = 15) and their wild-type littermates (N = 16). The NR1 mutant mice showed impaired habituation and PPI of the auditory startle response, as well as impaired gating in the paired tone paradigm. Deficits between the two gating measures did not correlate, corroborating previous evidence that these paradigms measure distinct processes. In the peak recovery paradigm, the NR1 mutants showed increased responses of the AEPs P1 and N1 at short ISIs but no difference between groups were observed at long ISIs. In conclusion, the NR1 hypomorphic mice modelled sensory and sensorimotor gating and startle habituation deficits observed in schizophrenia, but failed to model alterations in the peak recovery function. PMID:17712349

  5. Set and setting: how behavioral state regulates sensory function and plasticity

    PubMed Central

    Aton, Sara J.

    2013-01-01

    Recently developed neuroimaging and electrophysiological techniques are allowing us to answer fundamental questions about how behavioral states regulate our perception of the external environment. Studies using these techniques have yielded surprising insights into how sensory processing is affected at the earliest stages by attention and motivation, and how new sensory information received during wakefulness (e.g., during learning) continues to affect sensory brain circuits (leading to plastic changes) during subsequent sleep. This review aims to describe how brain states affect sensory response properties among neurons in primary and secondary sensory cortices, and how this relates to psychophysical detection thresholds and performance on sensory discrimination tasks. This is not intended to serve as a comprehensive overview of all brain states, or all sensory systems, but instead as an illustrative description of how three specific state variables (attention, motivation, and vigilance [i.e., sleep vs. wakefulness]) affect sensory systems in which they have been best studied. PMID:23792020

  6. Treadmill exercise induced functional recovery after peripheral nerve repair is associated with increased levels of neurotrophic factors.

    PubMed

    Park, Jae-Sung; Hke, Ahmet

    2014-01-01

    Benefits of exercise on nerve regeneration and functional recovery have been reported in both central and peripheral nervous system disease models. However, underlying molecular mechanisms of enhanced regeneration and improved functional outcomes are less understood. We used a peripheral nerve regeneration model that has a good correlation between functional outcomes and number of motor axons that regenerate to evaluate the impact of treadmill exercise. In this model, the median nerve was transected and repaired while the ulnar nerve was transected and prevented from regeneration. Daily treadmill exercise resulted in faster recovery of the forelimb grip function as evaluated by grip power and inverted holding test. Daily exercise also resulted in better regeneration as evaluated by recovery of compound motor action potentials, higher number of axons in the median nerve and larger myofiber size in target muscles. Furthermore, these observations correlated with higher levels of neurotrophic factors, glial derived neurotrophic factor (GDNF), brain derived neurotrophic factor (BDNF) and insulin-like growth factor-1 (IGF-1), in serum, nerve and muscle suggesting that increase in muscle derived neurotrophic factors may be responsible for improved regeneration. PMID:24618564

  7. Roles of estrogen and progesterone in modulating renal nerve function in the rat kidney.

    PubMed

    Graceli, J B; Cicilini, M A; Bissoli, N S; Abreu, G R; Moysés, M R

    2013-06-01

    The maintenance of extracellular Na+ and Cl- concentrations in mammals depends, at least in part, on renal function. It has been shown that neural and endocrine mechanisms regulate extracellular fluid volume and transport of electrolytes along nephrons. Studies of sex hormones and renal nerves suggested that sex hormones modulate renal function, although this relationship is not well understood in the kidney. To better understand the role of these hormones on the effects that renal nerves have on Na+ and Cl- reabsorption, we studied the effects of renal denervation and oophorectomy in female rats. Oophorectomized (OVX) rats received 17β-estradiol benzoate (OVE, 2.0 mg · kg(-1) · day(-1), sc) and progesterone (OVP, 1.7 mg · kg(-1) · day(-1), sc). We assessed Na+ and Cl- fractional excretion (FENa+ and FECl- , respectively) and renal and plasma catecholamine release concentrations. FENa+ , FECl- , water intake, urinary flow, and renal and plasma catecholamine release levels increased in OVX vs control rats. These effects were reversed by 17β-estradiol benzoate but not by progesterone. Renal denervation did not alter FENa+ , FECl- , water intake, or urinary flow values vs controls. However, the renal catecholamine release level was decreased in the OVP (236.6 ± 36.1 ng/g) and denervated rat groups (D: 102.1 ± 15.7; ODE: 108.7 ± 23.2; ODP: 101.1 ± 22.1 ng/g). Furthermore, combining OVX + D (OD: 111.9 ± 25.4) decreased renal catecholamine release levels compared to either treatment alone. OVE normalized and OVP reduced renal catecholamine release levels, and the effects on plasma catecholamine release levels were reversed by ODE and ODP replacement in OD. These data suggest that progesterone may influence catecholamine release levels by renal innervation and that there are complex interactions among renal nerves, estrogen, and progesterone in the modulation of renal function. PMID:23828583

  8. Conserved Dopamine Neurotrophic Factor-Transduced Mesenchymal Stem Cells Promote Axon Regeneration and Functional Recovery of Injured Sciatic Nerve

    PubMed Central

    Liu, Yi; Nie, Lin; Zhao, Hua; Zhang, Wen; Zhang, Yuan-Qiang; Wang, Shuai-Shuai; Cheng, Lei

    2014-01-01

    Peripheral nerve injury (PNI) is a common disease that often results in axonal degeneration and the loss of neurons, ultimately leading to limited nerve regeneration and severe functional impairment. Currently, there are no effective treatments for PNI. In the present study, we transduced conserved dopamine neurotrophic factor (CDNF) into mesenchymal stem cells (MSCs) in collagen tubes to investigate their regenerative effects on rat peripheral nerves in an in vivo transection model. Scanning electron microscopy of the collagen tubes demonstrated their ability to be resorbed in vivo. We observed notable overexpression of the CDNF protein in the distal sciatic nerve after application of CDNF-MSCs. Quantitative analysis of neurofilament 200 (NF200) and S100 immunohistochemistry showed significant enhancement of axonal and Schwann cell regeneration in the group receiving CDNF-MSCs (CDNF-MSCs group) compared with the control groups. Myelination thickness, axon diameter and the axon-to fiber diameter ratio (G-ratio) were significantly higher in the CDNF-MSCs group at 8 and 12 weeks after nerve transection surgery. After surgery, the sciatic functional index, target muscle weight, wet weight ratio of gastrocnemius muscle and horseradish peroxidase (HRP) tracing demonstrated functional recovery. Light and electron microscopy confirmed successful regeneration of the sciatic nerve. The greater numbers of HRP-labeled neuron cell bodies and increased sciatic nerve index values (SFI) in the CDNF-MSCs group suggest that CDNF exerts neuroprotective effects in vivo. We also observed higher target muscle weights and a significant improvement in muscle atrophism in the CDNF-MSCs group. Collectively, these findings indicate that CDNF gene therapy delivered by MSCs is capable of promoting nerve regeneration and functional recovery, likely because of the significant neuroprotective and neurotrophic effects of CDNF and the superior environment offered by MSCs and collagen tubes. PMID:25343619

  9. Vagus Nerve Stimulation Delivered with Motor Training Enhances Recovery of Function after Traumatic Brain Injury.

    PubMed

    Pruitt, David T; Schmid, Ariel N; Kim, Lily J; Abe, Caroline M; Trieu, Jenny L; Choua, Connie; Hays, Seth A; Kilgard, Michael P; Rennaker, Robert L

    2016-05-01

    Traumatic Brain Injury (TBI) is one of the largest health problems in the United States, and affects nearly 2 million people every year. The effects of TBI, including weakness and loss of coordination, can be debilitating and last years after the initial injury. Recovery of motor function is often incomplete. We have developed a method using electrical stimulation of the vagus nerve paired with forelimb use by which we have demonstrated enhanced recovery from ischemic and hemorrhagic stroke. Here we have tested the hypothesis that vagus nerve stimulation (VNS) paired with physical rehabilitation could enhance functional recovery after TBI. We trained rats to pull on a handle to receive a food reward. Following training, they received a controlled-cortical impact (CCI) in the forelimb area of motor cortex opposite the trained forelimb, and were then randomized into two treatment groups. One group of animals received VNS paired with rehabilitative therapy, whereas another group received rehabilitative therapy without VNS. Following CCI, volitional forelimb strength and task success rate in all animals were significantly reduced. VNS paired with rehabilitative therapy over a period of 5 weeks significantly increased recovery of both forelimb strength and success rate on the isometric pull task compared with rehabilitative training without VNS. No significant improvement was observed in the Rehab group. Our findings indicate that VNS paired with rehabilitative therapy enhances functional motor recovery after TBI. PMID:26058501

  10. Sensory integration dysfunction affects efficacy of speech therapy on children with functional articulation disorders

    PubMed Central

    Tung, Li-Chen; Lin, Chin-Kai; Hsieh, Ching-Lin; Chen, Ching-Chi; Huang, Chin-Tsan; Wang, Chun-Hou

    2013-01-01

    Background Articulation disorders in young children are due to defects occurring at a certain stage in sensory and motor development. Some children with functional articulation disorders may also have sensory integration dysfunction (SID). We hypothesized that speech therapy would be less efficacious in children with SID than in those without SID. Hence, the purpose of this study was to compare the efficacy of speech therapy in two groups of children with functional articulation disorders: those without and those with SID. Method: A total of 30 young children with functional articulation disorders were divided into two groups, the no-SID group (15 children) and the SID group (15 children). The number of pronunciation mistakes was evaluated before and after speech therapy. Results: There were no statistically significant differences in age, sex, sibling order, education of parents, and pretest number of mistakes in pronunciation between the two groups (P > 0.05). The mean and standard deviation in the pre- and post-test number of mistakes in pronunciation were 10.5 ± 3.2 and 3.3 ± 3.3 in the no-SID group, and 10.1 ± 2.9 and 6.9 ± 3.5 in the SID group, respectively. Results showed great changes after speech therapy treatment (F = 70.393; P < 0.001) and interaction between the pre/post speech therapy treatment and groups (F = 11.119; P = 0.002). Conclusions: Speech therapy can improve the articulation performance of children who have functional articulation disorders whether or not they have SID, but it results in significantly greater improvement in children without SID. SID may affect the treatment efficiency of speech therapy in young children with articulation disorders. PMID:23355780

  11. Rescue of cortical neurovascular functions during the hyperacute phase of ischemia by peripheral sensory stimulation.

    PubMed

    Liao, Lun-De; Liu, Yu-Hang; Lai, Hsin-Yi; Bandla, Aishwarya; Shih, Yen-Yu Ian; Chen, You-Yin; Thakor, Nitish V

    2015-03-01

    To investigate the potential therapeutic effects of peripheral sensory stimulation during the hyperacute phase of stroke, the present study utilized electrophysiology and photoacoustic imaging techniques to evaluate neural and vascular responses of the rat cortex following ischemic insult. We employed a rat model of photothrombotic ischemia (PTI), which targeted the forelimb region of the primary somatosensory cortex (S1FL), due to its high reproducibility in creating localized ischemic injury. We also established a hybrid, dual-modality system, including six-channel electrocorticography (ECoG) and functional photoacoustic microscopy (fPAM), termed ECoG-fPAM, to image brain functional responses to peripheral sensory stimulation during the hyperacute phase of PTI. Our results showed that the evoked cerebral blood volume (CBV) and hemoglobin oxygen saturation (SO2) recovered to 84±7.4% and 79±6.2% of the baseline, respectively, when stimulation was delivered within 2.5 h following PTI induction. Moreover, neural activity significantly recovered, with 77±8.6%, 76±5.3% and 89±8.2% recovery for the resting-state inter-hemispheric coherence, alpha-to-delta ratio (ADR) and somatosensory evoked potential (SSEP), respectively. Additionally, we integrated the CBV or SO2 with ADR values as a recovery indicator (RI) to assess functional recovery after PTI. The RI indicated that 80±4.2% of neurovascular function was preserved when stimulation was delivered within 2.5h. Additionally, stimulation treatment within this optimal time window resulted in a minimal infarct volume in the ischemic hemisphere (4.6±2.1%). In contrast, the infarct volume comprised 13.7±1.7% of the ischemic hemisphere when no stimulation treatment was applied. PMID:25573087

  12. Use of Vein Conduit and Isolated Nerve Graft in Peripheral Nerve Repair: A Comparative Study

    PubMed Central

    Ahmad, Imran; Akhtar, Md. Sohaib

    2014-01-01

    Aims and Objectives. The aim of this study was to evaluate the effectiveness of vein conduit in nerve repair compared with isolated nerve graft. Materials and Methods. This retrospective study was conducted at author's centre and included a total of 40 patients. All the patients had nerve defect of more than 3 cm and underwent nerve repair using nerve graft from sural nerve. In 20 cases, vein conduit (study group) was used whereas no conduit was used in other 20 cases. Patients were followed up for 2 years at the intervals of 3 months. Results. Patients had varying degree of recovery. Sensations reached to all the digits at 1 year in study groups compared to 18 months in control group. At the end of second year, 84% patients of the study group achieved 2-point discrimination of <10 mm compared to 60% only in control group. In terms of motor recovery, 82% patients achieved satisfactory hand function in study group compared to 56% in control group (P < .05). Conclusions. It was concluded that the use of vein conduit in peripheral nerve repair is more effective method than isolated nerve graft providing good sensory and motor recovery. PMID:25405029

  13. Glaucoma progression detection using structural retinal nerve fiber layer measurements and functional visual field points.

    PubMed

    Yousefi, Siamak; Goldbaum, Michael H; Balasubramanian, Madhusudhanan; Jung, Tzyy-Ping; Weinreb, Robert N; Medeiros, Felipe A; Zangwill, Linda M; Liebmann, Jeffrey M; Girkin, Christopher A; Bowd, Christopher

    2014-04-01

    Machine learning classifiers were employed to detect glaucomatous progression using longitudinal series of structural data extracted from retinal nerve fiber layer thickness measurements and visual functional data recorded from standard automated perimetry tests. Using the collected data, a longitudinal feature vector was created for each patient's eye by computing the norm 1 difference vector of the data at the baseline and at each follow-up visit. The longitudinal features from each patient's eye were then fed to the machine learning classifier to classify each eye as stable or progressed over time. This study was performed using several machine learning classifiers including Bayesian, Lazy, Meta, and Tree, composing different families. Combinations of structural and functional features were selected and ranked to determine the relative effectiveness of each feature. Finally, the outcomes of the classifiers were assessed by several performance metrics and the effectiveness of structural and functional features were analyzed. PMID:24658239

  14. Glaucoma Progression Detection Using Structural Retinal Nerve Fiber Layer Measurements and Functional Visual Field Points

    PubMed Central

    Yousefi, Siamak; Goldbaum, Michael H.; Balasubramanian, Madhusudhanan; Jung, Tzyy-Ping; Weinreb, Robert N.; Medeiros, Felipe A.; Zangwill, Linda M.; Liebmann, Jeffrey M.; Girkin, Christopher A.

    2014-01-01

    Machine learning classifiers were employed to detect glaucomatous progression using longitudinal series of structural data extracted from retinal nerve fiber layer thickness measurements and visual functional data recorded from standard automated perimetry tests. Using the collected data, a longitudinal feature vector was created for each patient’s eye by computing the norm 1 difference vector of the data at the baseline and at each follow-up visit. The longitudinal features from each patient’s eye were then fed to the machine learning classifier to classify each eye as stable or progressed over time. This study was performed using several machine learning classifiers including Bayesian, Lazy, Meta, and Tree, composing different families. Combinations of structural and functional features were selected and ranked to determine the relative effectiveness of each feature. Finally, the outcomes of the classifiers were assessed by several performance metrics and the effectiveness of structural and functional features were analyzed. PMID:24658239

  15. Storage influence on the functional, sensory and keeping quality of quality protein maize flour.

    PubMed

    Shobha, D; Kumar, H V Dileep; Sreeramasetty, T A; Puttaramanaik; Gowda, K T Pandurange; Shivakumar, G B

    2014-11-01

    Apart from nutritional values functional and sensory properties affect the behavior of food system and its acceptability for consumption during storage. Hence keeping quality of maize flour (HQPM-7) with and without lime treatment(control) was studied in terms of functional (bulk density, pH, swelling capacity, water and oil absorption capacity, least gelation concentration, peroxide value), sensory (appearance, color, taste, texture, mouth feel and overall acceptability) and rolling parameters (water absorption by flour, rolling quality, diameter after baking ) for a period of 6 months under room temperature (25 ± 5 °C) in two types of packages viz, LDPE cover (P) and plastic box (B). Physical parameters such as length, breadth and thickness (11.26-10.52 mm, 9.67-9.14 mm, & 4.72-3.95 mm) were reduced in lime treated grains compared to control. Significant increase (p ≤ 0.05) in ash content of lime treated flour (1.67 ± 0.01 g) was observed compared to control (1.5 ± 0.02 g). Calcium content of lime treated maize flour increased significantly (p ≤ 0.05) from 48 to 136 mg. There is a significant reduction in functional properties of flour after 3 and 2 months irrespective in polyethylene cover and plastic box. The properties like rolling quality, diameter after baking and water uptake by the flour were reduced significantly (p ≤ 0.05) after 4 months of storage in treated and after 1 month in control samples. Sensory scores of roti (dry pan cake) decreased significantly after 3 months of storage with an overall acceptability score of 4.0 and 3.4. In control samples mean taste (3.6), mouth feel (3.8) as well as OAA scores (3.8) decreased after second month. Hence lime treated maize flour with added nutritional benefits is suitable for making rotis of good palatability and can be stored in LDPE covers up to 3 months. PMID:26396307

  16. Neuronal porosome - The secretory portal at the nerve terminal: Its structure-function, composition, and reconstitution

    NASA Astrophysics Data System (ADS)

    Jena, Bhanu P.

    2014-09-01

    Cup-shaped secretory portals at the cell plasma membrane called porosomes mediate secretion from cells. Membrane bound secretory vesicles transiently dock and fuse at the cytosolic compartment of the porosome base to expel intravesicular contents to the outside during cell secretion. In the past decade, the structure, isolation, composition, and functional reconstitution of the neuronal porosome complex has been accomplished providing a molecular understanding of its structure-function. Neuronal porosomes are 15 nm cup-shaped lipoprotein structures composed of nearly 40 proteins; compared to the 120 nm nuclear pore complex comprised of over 500 protein molecules composed of 30 different proteins. Being a membrane-associated supramolecular complex has precluded determination of the atomic structure of the porosome. However recent studies using small-angle X-ray solution scattering (SAXS), provide at sub-nanometer resolution, the native 3D structure of the neuronal porosome complex associated with docked synaptic vesicle at the nerve terminal. Additionally, results from the SAXS study and earlier studies using atomic force microscopy, provide the possible molecular mechanism involved in porosome-mediated neurotransmitter release at the nerve terminal.

  17. High-resolution magnetic resonance imaging of the lower extremity nerves.

    PubMed

    Burge, Alissa J; Gold, Stephanie L; Kuong, Sharon; Potter, Hollis G

    2014-02-01

    Magnetic resonance (MR) imaging of the nerves, commonly known as MR neurography is increasingly being used as noninvasive means of diagnosing peripheral nerve disease. High-resolution imaging protocols aimed at imaging the nerves of the hip, thigh, knee, leg, ankle, and foot can demonstrate traumatic or iatrogenic injury, tumorlike lesions, or entrapment of the nerves, causing a potential loss of motor and sensory function in the affected area. A thorough understanding of normal MR imaging and gross anatomy, as well as MR findings in the presence of peripheral neuropathies will aid in accurate diagnosis and ultimately help guide clinical management. PMID:24210318

  18. A comparative study evoking a sensory action potential from the medial and lateral plantar nerves using the probe and ring method of stimulation.

    PubMed

    Adam, Jamila K; Bechoo, Reneal; Rmaih, Wafaa S

    2010-01-01

    Nerve conduction studies (NCS) aid in the detection of foot nerve pathologies. However, there has been a debate on method of plantar nerves stimulation that is more effective; the ring method of stimulation or probe method of stimulation. This study aims at determining the one method that is more effective among the two methods of stimulating for eliciting proper responses. Thirty healthy adults, aged 19 to 55 years, free of any neurological disease were the subjects of the study. Values considered for determining the effectiveness of the stimulating technique were mean amplitudes of the evoked responses from medial and lateral plantar nerves. A significant increase in amplitude difference was noted in favor of the probe stimulation method. The amplitude difference noted in favor of the probe method of stimulation was double the values elicited by the ring method of stimulation in both the medial and lateral plantar nerves. Results suggest that the direct probe method of stimulation may be a more effective method of stimulating for the medial and lateral plantar nerves studies. PMID:20508349

  19. Netrin-1 overexpression in bone marrow mesenchymal stem cells promotes functional recovery in a rat model of peripheral nerve injury

    PubMed Central

    Ke, Xianjin; Li, Qian; Xu, Li; Zhang, Ying; Li, Dongmei; Ma, Jianhua; Mao, Xiaoming

    2015-01-01

    Abstract Transplantation of bone marrow mesenchymal stem cells (BMSCs) has been developed as a new method of treating diseases of the peripheral nervous system. While netrin-1 is a critical molecule for axonal path finding and nerve growth, it may also affect vascular network formation. Here, we investigated the effect of transplanting BMSCs that produce netrin-1 in a rat model of sciatic nerve crush injury. We introduced a sciatic nerve crush injury, and then injected 1×106 BMSCs infected by a recombinant adenovirus expressing netrin-1 Ad5-Netrin-1-EGFP or culture medium into the injured part in the next day. At day 7, 14 and 28 after injection, we measured motor nerve conduction and detected mRNA expressions of netrin-1 receptors UNC5B and Deleted in Colorectal Cancer (DCC), and neurotrophic factors brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) by real-time PCR. We also detected protein expressions of BDNF and NGF by Western blotting assays and examined BMSCs that incorporated into myelin and vascellum. The results showed that BMSCs infected by Ad5-Netrin-1-EGFP significantly improved the function of the sciatic nerve, and led to increased expression of BDNF and NGF (P<0.05). Moreover, 28 days after injury, more Schwann cells were found in BMSCs infected by Ad5-Netrin-1-EGFP compared to control BMSCs. In conclusion, transplantation of BMSCs that produce netrin-1 improved the function of the sciatic nerve after injury. This method may be a new treatment of nerve injury. PMID:26445571

  20. 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...

  1. Toward the functional oligomerization state of tryptophan-rich sensory proteins

    PubMed Central

    Jaremko, ?ukasz; Jaremko, Mariusz; Becker, Stefan; Zweckstetter, Markus

    2014-01-01

    A conserved family of tryptophan-rich sensory proteins (TspO) mediates the transport of heme degradation intermediates across membranes. In eukaryotes, the homologous mitochondrial translocator protein (TSPO) binds cholesterol and radioligands as monomer. On the basis of the mammalian TSPO structure, bioinformatic analysis, and a 10 resolution electron microscopy map of TspO from Rhodobacter sphaeroides, we developed a model of the tertiary and quaternary structure of TspO that is in agreement with available mutagenesis data. Our study provides insight into the conformational basis for the restricted interaction of bacterial TspO with radioligands and the functional oligomerization state of bacterial TspO proteins. PMID:24817333

  2. Anxiety dissociates the adaptive functions of sensory and motor response enhancements to social threats.

    PubMed

    El Zein, Marwa; Wyart, Valentin; Grèzes, Julie

    2015-01-01

    Efficient detection and reaction to negative signals in the environment is essential for survival. In social situations, these signals are often ambiguous and can imply different levels of threat for the observer, thereby making their recognition susceptible to contextual cues - such as gaze direction when judging facial displays of emotion. However, the mechanisms underlying such contextual effects remain poorly understood. By computational modeling of human behavior and electrical brain activity, we demonstrate that gaze direction enhances the perceptual sensitivity to threat-signaling emotions - anger paired with direct gaze, and fear paired with averted gaze. This effect arises simultaneously in ventral face-selective and dorsal motor cortices at 200 ms following face presentation, dissociates across individuals as a function of anxiety, and does not reflect increased attention to threat-signaling emotions. These findings reveal that threat tunes neural processing in fast, selective, yet attention-independent fashion in sensory and motor systems, for different adaptive purposes. PMID:26712157

  3. Evaluation of a combined index of optic nerve structure and function for glaucoma diagnosis

    PubMed Central

    2011-01-01

    Background The definitive diagnosis of glaucoma is currently based on congruent damage to both optic nerve structure and function. Given widespread quantitative assessment of both structure (imaging) and function (automated perimetry) in glaucoma, it should be possible to combine these quantitative data to diagnose disease. We have therefore defined and tested a new approach to glaucoma diagnosis by combining imaging and visual field data, using the anatomical organization of retinal ganglion cells. Methods Data from 1499 eyes of glaucoma suspects and 895 eyes with glaucoma were identified at a single glaucoma center. Each underwent Heidelberg Retinal Tomograph (HRT) imaging and standard automated perimetry. A new measure combining these two tests, the structure function index (SFI), was defined in 3 steps: 1) calculate the probability that each visual field point is abnormal, 2) calculate the probability of abnormality for each of the six HRT optic disc sectors, and 3) combine those probabilities with the probability that a field point and disc sector are linked by ganglion cell anatomy. The SFI was compared to the HRT and visual field using receiver operating characteristic (ROC) analysis. Results The SFI produced an area under the ROC curve (0.78) that was similar to that for both visual field mean deviation (0.78) and pattern standard deviation (0.80) and larger than that for a normalized measure of HRT rim area (0.66). The cases classified as glaucoma by the various tests were significantly non-overlapping. Based on the distribution of test values in the population with mild disease, the SFI may be better able to stratify this group while still clearly identifying those with severe disease. Conclusions The SFI reflects the traditional clinical diagnosis of glaucoma by combining optic nerve structure and function. In doing so, it identifies a different subset of patients than either visual field testing or optic nerve head imaging alone. Analysis of prospective data will allow us to determine whether the combined index of structure and function can provide an improved standard for glaucoma diagnosis. PMID:21314957

  4. Sensing the Underground – Ultrastructure and Function of Sensory Organs in Root-Feeding Melolontha melolontha (Coleoptera: Scarabaeinae) Larvae

    PubMed Central

    Hansson, Bill S.; Hilker, Monika; Reinecke, Andreas

    2012-01-01

    Introduction Below ground orientation in insects relies mainly on olfaction and taste. The economic impact of plant root feeding scarab beetle larvae gave rise to numerous phylogenetic and ecological studies. Detailed knowledge of the sensory capacities of these larvae is nevertheless lacking. Here, we present an atlas of the sensory organs on larval head appendages of Melolontha melolontha. Our ultrastructural and electrophysiological investigations allow annotation of functions to various sensory structures. Results Three out of 17 ascertained sensillum types have olfactory, and 7 gustatory function. These sensillum types are unevenly distributed between antennae and palps. The most prominent chemosensory organs are antennal pore plates that in total are innervated by approximately one thousand olfactory sensory neurons grouped into functional units of three-to-four. In contrast, only two olfactory sensory neurons innervate one sensillum basiconicum on each of the palps. Gustatory sensilla chaetica dominate the apices of all head appendages, while only the palps bear thermo-/hygroreceptors. Electrophysiological responses to CO2, an attractant for many root feeders, are exclusively observed in the antennae. Out of 54 relevant volatile compounds, various alcohols, acids, amines, esters, aldehydes, ketones and monoterpenes elicit responses in antennae and palps. All head appendages are characterized by distinct olfactory response profiles that are even enantiomer specific for some compounds. Conclusions Chemosensory capacities in M. melolontha larvae are as highly developed as in many adult insects. We interpret the functional sensory units underneath the antennal pore plates as cryptic sensilla placodea and suggest that these perceive a broad range of secondary plant metabolites together with CO2. Responses to olfactory stimulation of the labial and maxillary palps indicate that typical contact chemo-sensilla have a dual gustatory and olfactory function. PMID:22848471

  5. Richard P. Bunge memorial lecture. Nerve injury and repair--a challenge to the plastic brain.

    PubMed

    Lundborg, Göran

    2003-12-01

    Repair and reconstruction of major nerve trunks in the upper extremity is a very challenging surgical problem. Today, there is no surgical repair technique that can assure recovery of tactile discrimination in the hand of an adult patient following nerve repair. In contrast, young individuals usually attain a complete recovery of functional sensibility. The outcome from nerve repair depends mainly on central nervous system factors including functional cortical reorganizational processes caused by misdirection in axonal outgrowth. Deafferentation due to local anesthetic block, amputation or nerve transection in the upper extremity leads to very rapid cortical synaptic remodeling, resulting in a distorted cortical hand representation as well as in enlarged and overlapping cortical receptive fields. Sensory relearning programs are aimed at refinement of these receptive fields to normalize the distorted hand map and improve processing at a high-order cortical level in the context of the 'new language spoken by the hand'. As peripheral nerve repair techniques cannot be further refined, there is a need for new and improved strategies for sensory relearning following nerve repair. We propose the utilization of multimodal capacity of the brain, using another sense (hearing) to substitute for lost hand sensation and to provide an alternate sensory input from the hand early after transection. The purpose was to modulate cortical reorganizations due to deafferentation to preserve cortical hand representation. Preliminary results from a prospective clinical randomized study indicate that the use of a Sensor Glove System, which stereophonically transposes the friction sound elicited by active touch, results in improved recovery of tactile discrimination in the nerve-injured hand. Future strategies for treatment of nerve injuries should promote cellular methods to minimize post-traumatic nerve cell death and to improve axonal outgrowth rate and orientation, but high on the agenda are new strategies for refined sensory relearning following nerve repair. PMID:14641646

  6. A review of functional neuroimaging studies of vagus nerve stimulation (VNS).

    PubMed

    Chae, Jeong-Ho; Nahas, Ziad; Lomarev, Mikhail; Denslow, Stewart; Lorberbaum, Jeffrey P; Bohning, Daryl E; George, Mark S

    2003-01-01

    Vagus nerve stimulation (VNS) is a new method for preventing and treating seizures, and shows promise as a potential new antidepressant. The mechanisms of action of VNS are still unknown, although the afferent direct and secondary connections of the vagus nerve are well established and are the most likely route of VNS brain effects. Over the past several years, many groups have used functional brain imaging to better understand VNS effects on the brain. Since these studies differ somewhat in their methodologies, findings and conclusions, at first glance, this literature may appear inconsistent. Although disagreement exists regarding the specific locations and the direction of brain activation, the differences across studies are largely due to different methods, and the results are not entirely inconsistent. We provide an overview of these functional imaging studies of VNS. PET (positron emission tomography) and SPECT (single photon emission computed tomography) studies have implicated several brain areas affected by VNS, without being able to define the key structures consistently and immediately activated by VNS. BOLD (blood oxygen level dependent) fMRI (functional magnetic resonance imaging), with its relatively high spatio-temporal resolution, performed during VNS, can reveal the location and level of the brain's immediate response to VNS. As a whole, these studies demonstrate that VNS causes immediate and longer-term changes in brain regions with vagus innervations and which have been implicated in neuropsychiatric disorders. These include the thalamus, cerebellum, orbitofrontal cortex, limbic system, hypothalamus, and medulla. Functional neuroimaging studies have the potential to provide greater insight into the brain circuitry behind the activity of VNS. PMID:14563375

  7. Vagus Nerve Stimulation Improves Cardiac Function by Preventing Mitochondrial Dysfunction in Obese-Insulin Resistant Rats

    PubMed Central

    Samniang, Bencharunan; Shinlapawittayatorn, Krekwit; Chunchai, Titikorn; Pongkan, Wanpitak; Kumfu, Sirinart; Chattipakorn, Siriporn C.; KenKnight, Bruce H.; Chattipakorn, Nipon

    2016-01-01

    Long-term high-fat diet (HFD) consumption leads to not only obese-insulin resistance, but also impaired left ventricular (LV) function. Vagus nerve stimulation (VNS) has been shown to exert cardioprotection. However, its effects on the heart and metabolic parameters under obese-insulin resistant condition is not known. We determined the effects of VNS on metabolic parameters, heart rate variability (HRV) and LV function in obese-insulin resistant rats. Male Wistar rats were fed with HFD for 12 weeks, and were randomly divided into sham and VNS groups. VNS was applied for the next 12 weeks. Echocardiography, blood pressure and HRV were examined. Blood samples were collected for metabolic parameters. At the end, the heart was removed for determination of apoptosis, inflammation, oxidative stress, and cardiac mitochondrial function. VNS for 12 weeks significantly decreased plasma insulin, HOMA index, total cholesterol, triglyceride, LDL and visceral fat. Serum adiponectin was significantly increased in the VNS group. VNS also significantly decreased blood pressure, improved HRV and LV function, decreased cardiac MDA, TNF-α and Bax levels, and improved cardiac mitochondrial function. VNS improves metabolic and hemodynamic parameters, and the LV function via its ability against apoptosis, inflammation and oxidative stress, and preserved cardiac mitochondrial function in obese-insulin resistant rats. PMID:26830020

  8. Laryngeal Adductor Function in Experimental Models of Recurrent Laryngeal Nerve Injury

    PubMed Central

    Paniello, Randal C.; Rich, Jason T.; Debnath, Nick L.

    2014-01-01

    Objectives/Hypothesis Most patients with unilateral vocal fold paralysis experience some degree of spontaneous reinnervation, which depends upon the type and severity of recurrent laryngeal nerve (RLN) injury. After partial recovery, the paretic vocal fold may or may not adduct adequately to allow glottic closure, which in turn affects phonatory and swallowing outcomes. This process was studied in a series of canine laryngeal nerve injury models. Study Design Animal (canine) experiments. Methods Maximum stimulable laryngeal adductor pressure (LAP) was measured pre-treatment (baseline) and at 6 months following experimental RLN injuries (total n=59). The 9 study groups were designed to simulate a range of severities of RLN injury. Results The greatest LAP recovery, at 108% of original baseline, was seen in a 50% transection model; the least recovery was seen when the RLN underwent complete transection with repair, at 56% with precise alignment and 50% with alignment reversed. Intermediate models (partial RLN injuries) gave intermediate results. Crush models recovered 105% of LAP, while a half-transection, half-crush injury recovered 72% and cautery injuries recovered 61%. Controls (complete transection without repair) had no measurable recovery. Conclusions The injured RLN has a strong tendency to recover. Restoration of adductor strength, as determined by the LAP, was predictably related to the severity of RLN injury. The model RLN injuries studied provide a range of expected outcomes that can be used for future experiments exploring interventions that may improve post-injury adductor function. PMID:25283381

  9. The spinal accessory nerve plexus, the trapezius muscle, and shoulder stabilization after radical neck cancer surgery.

    PubMed Central

    Brown, H; Burns, S; Kaiser, C W

    1988-01-01

    A clinical and anatomic study of the spinal accessory, the eleventh cranial nerve, and trapezius muscle function of patients who had radical neck cancer surgery was conducted. This study was done not only to document the indispensibility of the trapezius muscle to shoulder-girdle stability, but also to clarify the role of the eleventh cranial nerve in the variable motor and sensory changes occurring after the loss of this muscle. Seventeen male patients, 49-69 years of age, (average of 60 years of age) undergoing a total of 23 radical neck dissections were examined for upper extremity function, particularly in regard to the trapezius muscle, and for subjective signs of pain. The eleventh nerve, usually regarded as the sole motor innervation to the trapezius, was cut in 17 instances because of tumor involvement. Dissection of four fresh and 30 preserved adult cadavers helped to reconcile the motor and sensory differences in patients who had undergone loss of the eleventh nerve. The dissections and clinical observations corroborate that the trapezius is a key part of a "muscle continuum" that stabilizes the shoulder. Variations in origins and insertions of the trapezius may influence its function in different individuals. As regards the spinal accessory nerve, it is concluded that varying motor and sensory connections form a plexus with the eleventh nerve, accounting, in part, for the variations in motor innervation and function of the trapezius, as well as for a variable spectrum of sensory changes when the eleventh nerve is cut. For this reason, it is suggested that the term "spinal accessory nerve plexus" be used to refer to the eleventh nerve when it is considered in the context of radical neck cancer surgery. Images Fig. 4. Fig. 6. Fig. 7. Fig. 8. PMID:3056289

  10. Local administration of icariin contributes to peripheral nerve regeneration and functional recovery.

    PubMed

    Chen, Bo; Niu, Su-Ping; Wang, Zhi-Yong; Wang, Zhen-Wei; Deng, Jiu-Xu; Zhang, Pei-Xun; Yin, Xiao-Feng; Han, Na; Kou, Yu-Hui; Jiang, Bao-Guo

    2015-01-01

    Our previous study showed that systemic administration of the traditional Chinese medicine Epimedium extract promotes peripheral nerve regeneration. Here, we sought to explore the therapeutic effects of local administration of icariin, a major component of Epimedium extract, on peripheral nerve regeneration. A poly(lactic-co-glycolic acid) biological conduit sleeve was used to bridge a 5 mm right sciatic nerve defect in rats, and physiological saline, nerve growth factor, icariin suspension, or nerve growth factor-releasing microsphere suspension was injected into the defect. Twelve weeks later, sciatic nerve conduction velocity and the number of myelinated fibers were notably greater in the rats treated with icariin suspension or nerve growth factor-releasing microspheres than those that had received nerve growth factor or physiological saline. The effects of icariin suspension were similar to those of nerve growth factor-releasing microspheres. These data suggest that icariin acts as a nerve growth factor-releasing agent, and indicate that local application of icariin after spinal injury can promote peripheral nerve regeneration. PMID:25788925

  11. Local administration of icariin contributes to peripheral nerve regeneration and functional recovery

    PubMed Central

    Chen, Bo; Niu, Su-ping; Wang, Zhi-yong; Wang, Zhen-wei; Deng, Jiu-xu; Zhang, Pei-xun; Yin, Xiao-feng; Han, Na; Kou, Yu-hui; Jiang, Bao-guo

    2015-01-01

    Our previous study showed that systemic administration of the traditional Chinese medicine Epimedium extract promotes peripheral nerve regeneration. Here, we sought to explore the therapeutic effects of local administration of icariin, a major component of Epimedium extract, on peripheral nerve regeneration. A poly(lactic-co-glycolic acid) biological conduit sleeve was used to bridge a 5 mm right sciatic nerve defect in rats, and physiological saline, nerve growth factor, icariin suspension, or nerve growth factor-releasing microsphere suspension was injected into the defect. Twelve weeks later, sciatic nerve conduction velocity and the number of myelinated fibers were notably greater in the rats treated with icariin suspension or nerve growth factor-releasing microspheres than those that had received nerve growth factor or physiological saline. The effects of icariin suspension were similar to those of nerve growth factor-releasing microspheres. These data suggest that icariin acts as a nerve growth factor-releasing agent, and indicate that local application of icariin after spinal injury can promote peripheral nerve regeneration. PMID:25788925

  12. Vascularized Thoracodorsal to Suprascapular Nerve Transfer, a Novel Technique to Restore Shoulder Function in Partial Brachial Plexopathy

    PubMed Central

    Potter, Shirley M.; Ferris, Scott I.

    2016-01-01

    We describe the clinical outcome of a novel nerve transfer to restore active shoulder motion in upper brachial plexus injury. The thoracodorsal nerve (TDN) was successfully used as a vascularized donor nerve to neurotize to the suprascapular nerve (SSN) in a patient with limited donor nerve availability. At 4 years follow-up, he had regained useful external rotation of the injured limb, with no significant donor site morbidity. Shoulder abduction return was less impressive, however, and reasons for this are discussed. We provide a comprehensive review of the literature on this topic and a subsequent discussion on the details of this novel technique. This is the first reported case of TDN to SSN transfer, and also the first reported case of a vascularized TDN transfer in the English language literature. We advocate direct thoracodorsal to SSN transfer as a valid surgical option for the restoration of shoulder function in patients with partial brachial plexus avulsion, when conventional nerve donors are unavailable. PMID:27014699

  13. Nerve growth factor alters microtubule targeting agent-induced neurotransmitter release but not MTA-induced neurite retraction in sensory neurons.

    PubMed

    Pittman, Sherry K; Gracias, Neilia G; Fehrenbacher, Jill C

    2016-05-01

    Peripheral neuropathy is a dose-limiting side effect of anticancer treatment with the microtubule-targeted agents (MTAs), paclitaxel and epothilone B (EpoB); however, the mechanisms by which the MTAs alter neuronal function and morphology are unknown. We previously demonstrated that paclitaxel alters neuronal sensitivity, in vitro, in the presence of nerve growth factor (NGF). Evidence in the literature suggests that NGF may modulate the neurotoxic effects of paclitaxel. Here, we examine whether NGF modulates changes in neuronal sensitivity and morphology induced by paclitaxel and EpoB. Neuronal sensitivity was assessed using the stimulated release of calcitonin gene-related peptide (CGRP), whereas morphology of established neurites was evaluated using a high content screening system. Dorsal root ganglion cultures, maintained in the absence or presence of NGF, were treated from day 7 to day 12 in culture with paclitaxel (300nM) or EpoB (30nM). Following treatment, the release of CGRP was stimulated using capsaicin or high extracellular potassium. In the presence of NGF, EpoB mimicked the effects of paclitaxel: capsaicin-stimulated release was attenuated, potassium-stimulated release was slightly enhanced and the total peptide content was unchanged. In the absence of NGF, both paclitaxel and EpoB decreased capsaicin- and potassium-stimulated release and the total peptide content, suggesting that NGF may reverse MTA-induced hyposensitivity. Paclitaxel and EpoB both decreased neurite length and branching, and this attenuation was unaffected by NGF in the growth media. These differential effects of NGF on neuronal sensitivity and morphology suggest that neurite retraction is not a causative factor to alter neuronal sensitivity. PMID:26883566

  14. 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; Houl, 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 4weeks 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 5mm of the lesion and their number increased 70% with exercise. Importantly propriospinal neurons in more distant regions (5-20mm 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, ?-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 this combined therapeutic intervention. PMID:26366525

  15. Cholinesterase activity in sensory-nerve endings, capillaries and motor end plates of the facial skin of the brush-tailed possum (Trichosurus vulpecula).

    PubMed

    Loo, S K; Halata, Z; Strasmann, T

    1990-01-01

    The facial skin of two adult and one 50-day-old pouch animal of the marsupial mammal Trichosurus vulpecula was removed after the animals has been suitably anesthetized and perfused for electron microscopy. Small blocks of tissue (1 x 0.5 mm) were cut and incubated in acetylthiocholine iodide substrate for cholinesterase studies. The blocks were then subsequently postfixed in osmium tetroxide. Thin sections were cut and stained with lead acetate. Specific cholinesterase was found within the nerves of both the adult and the 50-day-old pouch animal, and in the motor end plates. Nonspecific cholinesterase was present in pinocytotic vesicles and interlamellar spaces of terminal Schwann cells associated with nerve end organs in the adult, and in the same areas in Schwann cells of nonmyelinated nerves in the pouch animal. It was also present in the pinocytotic vesicles of the capillary endothelium. PMID:2075803

  16. Characterization of Neurotrophin and Trk Receptor Functions in Developing Sensory Ganglia: Direct NT-3 Activation of TrkB Neurons In Vivo

    PubMed Central

    Fariñas, Isabel; Wilkinson, George A.; Backus, Carey; Patapoutian, Ardem

    2009-01-01

    Summary Spinal sensory ganglia have been shown to contain neuronal subpopulations with different functions and neurotrophin dependencies. Neurotrophins act, in large part, through Trk receptor tyrosine kinases: nerve growth factor (NGF) via TrkA, brain-derived neurotrophic factor (BDNF) and neurotrophin-4/5 (NT-4/5) via TrkB, and neurotrophin-3 (NT-3) via TrkC. In the present paper, we use antibodies to TrkA, TrkB, and TrkC to characterize their expression patterns and to determine which subpopulations of cells are lost in mice lacking individual neurotrophins or Trk receptors. Despite previous reports of Trk receptor mRNAs in neural crest cells, we detect Trk receptor proteins only in neurons and not in neural crest cells or neuronal precursors. Comparisons of neonatal mice deficient in NT-3 or its cognate receptor TrkC have shown that there is a much greater deficiency in spinal sensory neurons in the former, suggesting that NT-3 may activate receptors in addition to TrkC. Using the same antibodies, we show that, during the major period of neurogenesis, NT-3 is required to maintain neurons that express TrkB in addition to those that express TrkC but is not essential for neurons expressing TrkA. Results also indicate that survival of cells expressing both receptors can be maintained by activation of either one alone. NT-3 can thus activate more than one Trk receptor in vivo, which when coexpressed are functionally redundant. PMID:9728914

  17. Tibial nerve dysfunction

    MedlinePlus

    ... a loss of movement or sensation in the foot from damage to the tibial nerve. ... Tibial nerve dysfunction is an unusual form of peripheral ... the calf and foot muscles. A problem in function with a single ...

  18. Effect of vitamin B12 on functional recovery and histopathologic changes of tibial nerve-crushed rats.

    PubMed

    Tamaddonfard, E; Farshid, A A; Samadi, F; Eghdami, K

    2014-09-01

    Recent studies have suggested a neuroprotective effect for vitamin B12. The present study investigated the effects of vitamin B12, diclofenac and celecoxib in separate and combined treatments on functional recovery of crushed tibial nerve in rats. In ketamine plus xylazin anesthetized rats, right tibial nerve was crushed using a small hemoatatic forceps. Footprints were recorded 1 day before and on days 7, 14 and 21 after induction of nerve injury. Tibial functional index (TFI) was used to evaluate the recovery of tibial nerve function. Histological changes of tibial nerve were investigated by light microscopy. The recovery of TFI values were significantly accelerated with 10 consecutive days treatments with 0.1 and 0.5?mg/kg of vitamin B12, 5?mg/kg of diclofenac and 1 and 5?mg/kg of celecoxib. The severity of Wallerian degeneration was reduced by above-mentioned doses of vitamin B12, diclofenac and celecoxib. Documented effects were observed when 0.1?mg/kg of vitamin B12 was concurrently used with 1?mg/kg of diclofenac and or 0.2?mg/kg of celecoxib. In the present study, vitamin B12, celecoxib and diclofenac (at a high dose) showed neuroprotective effects. Inhibition of cyclooxygenase (COX) 1 and 2 pathways may be involved in neuroprotective effect of vitamin B12. PMID:24470311

  19. Nerve Growth Factor-Regulated Emergence of Functional Delta-Opioid Receptors

    PubMed Central

    Bie, Bihua; Zhang, Zhi; Cai, You-Qing; Zhu, Wei; Zhang, Yong; Dai, Jaile; Lowenstein, Charles J.; Weinman, Edward J.; Pan, Zhizhong Z.

    2010-01-01

    Sorting of intracellular G protein-coupled receptors (GPCRs) either to lysosomes for degradation or to plasma membrane for surface insertion and functional expression is a key process regulating signaling strength of GPCRs across the plasma membrane in adult mammalian cells. However, little is known about the molecular mechanisms governing the dynamic process of receptor sorting to the plasma membrane for functional expression under normal and pathological conditions. In this study, we demonstrate that delta-opioid receptor (DOPr), a GPCR constitutively targeted to intracellular compartments, is driven to the surface membrane of central synaptic terminals and becomes functional by the neurotrophin nerve growth factor (NGF) in native brainstem neurons. The NGF-triggered DOPr translocation is predominantly mediated by the signaling pathway involving the tyrosine receptor kinase A, Ca++-mobilizing phospholipase C and Ca++/calmodulin-dependent protein kinase II. Importantly, it requires interactions with the cytoplasmic sorting protein Na+/H+ exchange regulatory factor-1 (NHERF-1) and N-Ethyl-maleimide-sensitive factor-regulated exocytosis. In addition, this NGF-mediated mechanism is likely responsible for the emergence of functional DOPr induced by chronic opioids. Thus, NGF may function as a key molecular switch that redirects the sorting of intracellularly targeted DOPr to plasma membrane, resulting in new functional DOPr on central synapses under chronic opioid conditions. PMID:20410114

  20. The sensory structures of the antennal flagellum in Hyalesthes obsoletus (Hemiptera: Fulgoromorpha: Cixiidae): a functional reduction?

    PubMed

    Romani, Roberto; Stacconi, Marco Valerio Rossi; Riolo, Paola; Isidoro, Nunzio

    2009-11-01

    Despite their relevance as harmful pests on plants of economic importance, Hemiptera Fulgoromorpha have been poorly studied as regards their antennal sensory structures. In particular, the flagellum has been neglected and, therefore, to date there are no data on its structural organization and sensory equipment. In order to fill this gap, we carried out a study on the sensillum types and distribution on the flagellum of the planthopper Hyalesthes obsoletus Signoret, an efficient vector of the stolbur phytoplasma, the cause of various crop diseases. In this cixiid species the antenna is composed of three segments, the scape, an enlarged pedicel and a long flagellum. This latter is made of a single segment and presents a basal, bulb-like enlargement from which two processes arise, a short spur and a long arista. Combining scanning electron microscopy, transmission electron microscopy and focused ion beam investigations, we discovered the presence of a total number of 6 sensilla, belonging to 4 different types: a single scolopidium extending from the bulb to the arista, three sensilla styloconica within the cuticular spur and two different sensilla coeloconica inside the bulb. As far as structural data can suggest, these sensilla might be involved in the perception of mechanical stimuli (possibly air-borne vibrations), temperature and humidity variations and CO(2) concentration. The strong reduction in sensillum number in this species is discussed as possible functional specialization of the flagellum itself. The ultrastructure of the sensilla in the flagellum of a species of Fulgoromorpha is here presented for the first time. PMID:19682602

  1. Changes in nutritional composition, functional, and sensory properties of yam flour as a result of presoaking

    PubMed Central

    Obadina, Adewale Olusegun; Babatunde, Bukunola Olaide; Olotu, Ifeoluwa

    2014-01-01

    This study investigated the effect of soaking pretreatments on some of the properties of flour obtained from two varieties of yam namely;Dioscorea alata andDioscorea rotundata with a view of providing information that will enhance their end use. The yam varieties were washed, chipped, parboiled at 50°C, soaked for different periods (0, 6, 12, and 18 h), dried at 60°C, and milled into flour. The flour samples were analyzed for their nutritional composition, pH, color, and functional properties. The flour samples were also made into pastes and were sensorially analyzed and 0 h soaked samples were used as control. The protein content of 18 h-soakedD. rotundata andD. alata flour samples was significantly different from the control and soaking had no effect (P > 0.05) on the fat and ash content but the carbohydrate content of the flour samples ranged from 83.08% to 86.13%. The 18 h-soakedD. rotundata flour sample had the lowest peak viscosity, breakdown value, and final viscosity among theD. rotundata variety samples. Pasting temperature ranged from 79.80 to 83.60°C and 6-h soakedD. alata flour sample had the lowest water absorption capacity and the highest bulk density. On the basis of sensory analysis, the panelist preferred the taste, texture, color, and appearance of paste made from the 18-h soakedD. rotundata flour to the paste of other flour samples. The results of this study show that D.rotundata should be soaked for 18 h prior to drying and milling in order to obtain a good-quality flour and paste. PMID:25493185

  2. The role of sensory cortex and cortical "hubs" in category-specific executive function.

    PubMed

    James, Thomas; Arcurio, Lindsay; Nikoulina, Anastasia

    2015-01-01

    Human executive functions are sensitive to visual cues that make up the environmental context, but there are few research programs that study this influence or study the impact of changes in sensory neural signals on frontal cortical function. In this talk, I will present findings from studies of people with alcohol use disorders (AUD) that implicate the lateral occipital cortex (LOC) and its connections with the anterior insular cortex (AIC) in impulsive decisions-to-drink when exposed to visual alcohol cues. Specifically, 31 women (15 AUD) were scanned using fMRI while performing a decisions-to-drink task. In that task, they were presented with alcohol and food cues that were normed for attractiveness/desirability. They were asked to imagine themselves in a situation where deciding to drink had a high or low probability of a negative consequence and were asked to rate their likelihood of drinking (or eating) on a 4-point scale. AUD women endorsed alcohol cues more than non-AUD, but not food cues - a category-specific effect on decision making. Differences in BOLD signal between AUD women and non-AUD for alcohol vs food cues were widespread and always greater for AUD. This finding suggests that there was no single neural system (e.g., cognitive control) that accounts for the group difference in behavior. Comparing high- to low-risk scenarios highlighted differences between AUD and non-AUD in the LOC and AIC. A task-based functional connectivity analyses provided further support for the role of LOC and AIC in AUD women producing more impulsive category-specific decisions. In conclusion, widespread differences in decision-related BOLD signal between AUD and non-AUD may originate in the visual cortex (LOC) and cascade throughout the brain by way of network "hubs" such as the AIC. These results highlight the important (but underappreciated) role of sensory cortices in decision making and other executive functions. Meeting abstract presented at VSS 2015. PMID:26326143

  3. ELECTROPHYSIOLOGICAL ASSESSMENT OF SENSORY AND COGNITIVE FUNCTION IN CHILDREN EXPOSED TO LEAD: A REVIEW

    EPA Science Inventory

    Studies of the effects of lead absorption on sensory evoked and slow brain potentials in children are reviewed. Studies of slow wave voltage in children during sensory conditioning indicated a linear relationship to blood lead level in two studies; an effect that could not be rep...

  4. Trapping of organophosphorus chemical nerve agents in water with amino acid functionalized baskets.

    PubMed

    Ruan, Yian; Dalkiliç, Erdin; Peterson, Paul W; Pandit, Aroh; Dastan, Arif; Brown, Jason D; Polen, Shane M; Hadad, Christopher M; Badjić, Jovica D

    2014-04-01

    We prepared eleven amino-acid functionalized baskets and used (1) H NMR spectroscopy to quantify their affinity for entrapping dimethyl methylphosphonate (DMMP, 118 Å(3) ) in aqueous phosphate buffer at pH=7.0±0.1; note that DMMP guest is akin in size to chemical nerve agent sarin (132 Å(3) ). The binding interaction (Ka ) was found to vary with the size of substituent groups at the basket's rim. In particular, the degree of branching at the first carbon of each substituent had the greatest effect on the host-guest interaction, as described with the Verloop's B1 steric parameter. The branching at the remote carbons, however, did not perturb the encapsulation, which is important for guiding the design of more effective hosts and catalysts in future. PMID:24616086

  5. BBS4 and BBS5 show functional redundancy in the BBSome to regulate the degradative sorting of ciliary sensory receptors

    PubMed Central

    Xu, Qingwen; Zhang, Yuxia; Wei, Qing; Huang, Yan; Li, Yan; Ling, Kun; Hu, Jinghua

    2015-01-01

    Cilia harbor sensory receptors for various signaling cascades critical for vertebrate development. However, the mechanisms underlying the ciliary homeostasis of sensory receptors remain elusive. Here, we demonstrate that BBS-4 and BBS-5, two distinct BBSome components, show unexpected functional redundancy in the context of cilia in C. elegans. BBS-4 directly interacts with BBS-5 and the interaction can be disrupted by a conserved mutation identified in human BBS4. Surprisingly, we found that BBS-4 and BBS-5 act redundantly in the BBSome to regulate the ciliary removal, rather than the ciliary entry or retrograde IFT transport, of various sensory receptors. Further analyses indicate that co-depletion of BBS-4 and BBS-5 disrupts the lysosome-targeted degradative sorting of ciliary sensory receptors. Moreover, mammalian BBS4 and BBS5 also interact directly and coordinate the ciliary removal of polycystin 2. Hence, we reveal a novel and highly conserved role for the BBSome in fine-tuning ciliary signaling by regulating the ciliary removal of sensory receptors for lysosomal degradation. PMID:26150102

  6. Molecular Evolution of the Infrared Sensory Gene TRPA1 in Snakes and Implications for Functional Studies

    PubMed Central

    Jiang, Ke; Zhang, Peng

    2011-01-01

    TRPA1 is a calcium ion channel protein recently identified as the infrared receptor in pit organ-containing snakes. Therefore, understanding the molecular evolution of TRPA1 may help to illuminate the origin of “heat vision” in snakes and reveal the molecular mechanism of infrared sensitivity for TRPA1. To this end, we sequenced the infrared sensory gene TRPA1 in 24 snake species, representing nine snake families and multiple non-snake outgroups. We found that TRPA1 is under strong positive selection in the pit-bearing snakes studied, but not in other non-pit snakes and non-snake vertebrates. As a comparison, TRPV1, a gene closely related to TRPA1, was found to be under strong purifying selection in all the species studied, with no difference in the strength of selection between pit-bearing snakes and non-pit snakes. This finding demonstrates that the adaptive evolution of TRPA1 specifically occurred within the pit-bearing snakes and may be related to the functional modification for detecting infrared radiation. In addition, by comparing the TRPA1 protein sequences, we identified 11 amino acid sites that were diverged in pit-bearing snakes but conserved in non-pit snakes and other vertebrates, 21 sites that were diverged only within pit-vipers but conserved in the remaining snakes. These specific amino acid substitutions may be potentially functional important for infrared sensing. PMID:22163322

  7. Sensory and motor function of teeth and dental implants: a basis for osseoperception.

    PubMed

    Trulsson, Mats

    2005-01-01

    1. When dental implants are loaded mechanically, a sensation, often referred to as osseoperception, is evoked. The sensory signals underlying this phenomenon are qualitatively different from the signals evoked when loading a natural tooth. In contrast with osseointegrated dental implants, natural teeth are equipped with periodontal mechanoreceptors that signal information about tooth loads. In the present review, the functional properties of human periodontal mechanoreceptors will be presented, along with a discussion about their likely functional role in the control of human jaw actions. 2. Microneurographic experiments reveal that human periodontal mechanoreceptors adapt slowly to maintained tooth loads. Populations of periodontal receptors encode information about both which teeth are loaded and the direction of forces applied to individual teeth. 3. Most receptors exhibit a markedly curved relationship between discharge rate and force amplitude, featuring the highest sensitivity to changes in tooth load at surprisingly low forces (below 1 N for anterior teeth and 4 N for posterior teeth). Accordingly, periodontal receptors efficiently encode tooth load when subjects first contact, hold and gently manipulate food by the teeth. In contrast, only a minority of receptors encodes the rapid and strong increase in force generated when biting through food. 4. It is concluded that humans use periodontal afferent signals to control jaw actions associated with intra-oral manipulation of food rather than exertion of jaw power actions. Consequently, patients who lack information from periodontal receptors show an impaired fine motor control of the mandible. PMID:15730446

  8. High lead exposure and auditory sensory-neural function in Andean children.

    PubMed Central

    Counter, S A; Vahter, M; Laurell, G; Buchanan, L H; Ortega, F; Skerfving, S

    1997-01-01

    We investigated blood lead (B-Pb) and mercury (B-Hg) levels and auditory sensory-neural function in 62 Andean school children living in a Pb-contaminated area of Ecuador and 14 children in a neighboring gold mining area with no known Pb exposure. The median B-Pb level for 62 children in the Pb-exposed group was 52.6 micrograms/dl (range 9.9-110.0 micrograms/dl) compared with 6.4 micrograms/dl (range 3.9-12.0 micrograms/dl) for the children in the non-Pb exposed group; the differences were statistically significant (p < 0.001). Auditory thresholds for the Pb-exposed group were normal at the pure tone frequencies of 0.25-8 kHz over the entire range of B-Pb levels, Auditory brain stem response tests in seven children with high B-Pb levels showed normal absolute peak and interpeak latencies. The median B-Hg levels were 0.16 micrograms/dl (range 0.04-0.58 micrograms/dl) for children in the Pb-exposed group and 0.22 micrograms/dl (range 0.1-0.44 micrograms/dl) for children in the non-Pb exposed gold mining area, and showed no significant relationship to auditory function. Images Figure 1. Figure 3. A Figure 3. B PMID:9222138

  9. Mapping a sensory-motor network onto a structural and functional ground plan in the hindbrain.

    PubMed

    Koyama, Minoru; Kinkhabwala, Amina; Satou, Chie; Higashijima, Shin-ichi; Fetcho, Joseph

    2011-01-18

    The hindbrain of larval zebrafish contains a relatively simple ground plan in which the neurons throughout it are arranged into stripes that represent broad neuronal classes that differ in transmitter identity, morphology, and transcription factor expression. Within the stripes, neurons are stacked continuously according to age as well as structural and functional properties, such as axonal extent, input resistance, and the speed at which they are recruited during movements. Here we address the question of how particular networks among the many different sensory-motor networks in hindbrain arise from such an orderly plan. We use a combination of transgenic lines and pairwise patch recording to identify excitatory and inhibitory interneurons in the hindbrain network for escape behaviors initiated by the Mauthner cell. We map this network onto the ground plan to show that an individual hindbrain network is built by drawing components in predictable ways from the underlying broad patterning of cell types stacked within stripes according to their age and structural and functional properties. Many different specialized hindbrain networks may arise similarly from a simple early patterning. PMID:21199937

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

    PubMed

    Mdol, 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. PMID:24813295

  11. Human periodontal ligament stem cells repair mental nerve injury

    PubMed Central

    Li, Bohan; Jung, Hun-Jong; Kim, Soung-Min; Kim, Myung-Jin; Jahng, Jeong Won; Lee, Jong-Ho

    2013-01-01

    Human periodontal ligament stem cells are easily accessible and can differentiate into Schwann cells. We hypothesized that human periodontal ligament stem cells can be used as an alternative source for the autologous Schwann cells in promoting the regeneration of injured peripheral nerve. To validate this hypothesis, human periodontal ligament stem cells (1 × 106) were injected into the crush-injured left mental nerve in rats. Simultaneously, autologous Schwann cells (1 × 106) and PBS were also injected as controls. Real-time reverse transcriptase polymerase chain reaction showed that at 5 days after injection, mRNA expression of low affinity nerve growth factor receptor was significantaly increased in the left trigeminal ganglion of rats with mental nerve injury. Sensory tests, histomorphometric evaluation and retrograde labeling demonstrated that at 2 and 4 weeks after injection, sensory function was significantly improved, the numbers of retrograde labeled sensory neurons and myelinated axons were significantly increased, and human periodontal ligament stem cells and autologous Schwann cells exhibited similar therapeutic effects. These findings suggest that transplantation of human periodontal ligament stem cells show a potential value in repair of mental nerve injury. PMID:25206604

  12. Interhemispheric Plasticity Protects the Deafferented Somatosensory Cortex from Functional Takeover After Nerve Injury

    PubMed Central

    Koretsky, Alan P.

    2014-01-01

    Abstract Functional changes across brain hemispheres have been reported after unilateral cortical or peripheral nerve injury. Interhemispheric callosal connections usually underlie this cortico-cortical plasticity. However, the effect of the altered callosal inputs on local cortical plasticity in the adult brain is not well studied. Ipsilateral functional magnetic resonance imaging (fMRI) activation has been reliably detected in the deafferented barrel cortex (BC) at 2 weeks after unilateral infraorbital denervation (IO) in adult rats. The ipsilateral fMRI signal relies on callosal-mediated interhemispheric plasticity. This form of interhemispheric plasticity provides a good chronic model to study the interaction between callosal inputs and local cortical plasticity. The receptive field of forepaw in the primary somatosensory cortex (S1), which is adjacent to the BC, was mapped with fMRI. The S1 receptive field expanded to take over a portion of the BC in 2 weeks after both ascending inputs and callosal inputs were removed in IO rats with ablated contralateral BC (IO+ablation). This expansion, estimated specifically by fMRI mapping, is significantly larger than what has been observed in the IO rats with intact callosal connectivity, as well as in the rats with sham surgery. This work indicates that altered callosal inputs prevent the functional takeover of the deafferented BC from adjacent cortices and may help preserve the functional identity of the BC. PMID:25117691

  13. Near infrared (NIr) light increases expression of a marker of mitochondrial function in the mouse vestibular sensory epithelium.

    PubMed

    Zhang, Lucy; Tung, Victoria W K; Mathews, Miranda; Camp, Aaron J

    2015-01-01

    Strategies for attenuating decline in balance function with increasing age are predominantly focused on physical therapies including balance tasks and exercise. However, these approaches do not address the underlying causes of balance decline. Using mice, the impact of near infrared light (NIr) on the metabolism of cells in the vestibular sensory epithelium was assessed. Data collected shows that this simple and safe intervention may protect these vulnerable cells from the deleterious effects of natural aging. mRNA was extracted from the isolated peripheral vestibular sensory epithelium (crista ampullaris and utricular macula) and subsequently transcribed into a cDNA library. This library was then probed for the expression of ubiquitous antioxidant (SOD-1). Antioxidant gene expression was then used to quantify cellular metabolism. Using transcranial delivery of NIr in young (4 weeks) and older (8-9 months) mice, and a brief treatment regime (90 sec/day for 5 days), this work suggests NIr alone may be sufficient to improve mitochondrial function in the vestibular sensory epithelium. Since there are currently no available, affordable, non-invasive methods of therapy to improve vestibular hair cell function, the application of external NIr radiation provides a potential strategy to counteract the impact of aging on cellular metabolism inthe vestibular sensory epithelium. PMID:25868009

  14. Short-term vagal nerve stimulation improves left ventricular function following chronic heart failure in rats

    PubMed Central

    LI, YAN; XUAN, YAN-HUA; LIU, SHUANG-SHUANG; DONG, JING; LUO, JIA-YING; SUN, ZHI-JUN

    2015-01-01

    Increasing numbers of animal and clinical investigations have demonstrated the effectiveness of long-term electrical vagal nerve stimulation (VNS) on chronic heart failure (CHF). The present study investigated the effects of short-term VNS on the hemodynamics of cardiac remodeling and cardiac excitation-contraction coupling (ECP) in an animal model of CHF following a large myocardial infarction. At 3 weeks subsequent to ligation of the left coronary artery, the surviving rats were randomized into vagal and sham-stimulated groups. The right vagal nerve of the CHF rats was stimulated for 72 h. The vagal nerve was stimulated with rectangular pulses of 40 ms duration at 1 Hz, 5 V. The treated rats, compared with the untreated rats, had significantly higher left ventricular ejection fraction (54.86±9.73, vs. 45.60±5.51%; P=0.025) and left ventricular fractional shortening (25.31±6.30, vs. 15.42±8.49%; P=0.013), and lower levels of brain natriuretic peptide (10.07±2.63, vs. 19.95±5.22 ng/ml; P=0.001). The improvement in cardiac pumping function was accompanied by a decrease in left ventricular end diastolic volume (1.11±0.50, vs. 1.54±0.57 cm3; P=0.032) and left ventricular end systolic volume (0.50±0.28, vs. 0.87±0.36 cm3; P=0.007). Furthermore, the expression levels of ryanodine receptor type 2 (RyR2) and sarcoplasmic reticulum calcium adenosine triphosphatase (SERCA2) were significantly higher in the treated rats compared with the untreated rats (P=0.011 and P=0.001 for RyR2 and SERCA2, respectively). Therefore, VNS was beneficial to the CHF rats through the prevention of cardiac remodeling and improvement of cardiac ECP. PMID:25873055

  15. Short‑term vagal nerve stimulation improves left ventricular function following chronic heart failure in rats.

    PubMed

    Li, Yan; Xuan, Yan-Hua; Liu, Shuang-Shuang; Dong, Jing; Luo, Jia-Ying; Sun, Zhi-Jun

    2015-08-01

    Increasing numbers of animal and clinical investigations have demonstrated the effectiveness of long-term electrical vagal nerve stimulation (VNS) on chronic heart failure (CHF). The present study investigated the effects of short-term VNS on the hemodynamics of cardiac remodeling and cardiac excitation-contraction coupling (ECP) in an animal model of CHF following a large myocardial infarction. At 3 weeks subsequent to ligation of the left coronary artery, the surviving rats were randomized into vagal and sham-stimulated groups. The right vagal nerve of the CHF rats was stimulated for 72 h. The vagal nerve was stimulated with rectangular pulses of 40 ms duration at 1 Hz, 5 V. The treated rats, compared with the untreated rats, had significantly higher left ventricular ejection fraction (54.86 ± 9.73, vs. 45.60 ± 5.51%; P=0.025) and left ventricular fractional shortening (25.31 ± 6.30, vs. 15.42 ± 8.49%; P=0.013), and lower levels of brain natriuretic peptide (10.07 ± 2.63, vs. 19.95 ± 5.22 ng/ml; P=0.001). The improvement in cardiac pumping function was accompanied by a decrease in left ventricular end diastolic volume (1.11 ± 0.50, vs. 1.54 ± 0.57 cm(3); P=0.032) and left ventricular end systolic volume (0.50 ± 0.28, vs. 0.87 ± 0.36 cm(3); P=0.007). Furthermore, the expression levels of ryanodine receptor type 2 (RyR2) and sarcoplasmic reticulum calcium adenosine triphosphatase (SERCA2) were significantly higher in the treated rats compared with the untreated rats (P=0.011 and P=0.001 for RyR2 and SERCA2, respectively). Therefore, VNS was beneficial to the CHF rats through the prevention of cardiac remodeling and improvement of cardiac ECP. PMID:25873055

  16. Transplantation of induced pluripotent stem cell-derived neurospheres for peripheral nerve repair.

    PubMed

    Uemura, Takuya; Takamatsu, Kiyohito; Ikeda, Mikinori; Okada, Mitsuhiro; Kazuki, Kenichi; Ikada, Yoshito; Nakamura, Hiroaki

    2012-03-01

    In spite of the extensive research using induced pluripotent stem (iPS) cells, the therapeutic potential of iPS cells in the treatment of peripheral nerve injury is largely unknown. In this study, we repaired peripheral nerve gaps in mice using tissue-engineered bioabsorbable nerve conduits coated with iPS cell-derived neurospheres. The secondary neurospheres derived from mouse iPS cells were suspended in each conduit (4000,000 cells per conduit) and cultured in the conduit in three-dimensional (3D) culture for 14 days. We then implanted them in the mouse sciatic nerve gaps (5 mm) (iPS group; n=10). The nerve conduit alone was implanted in the control group (n=10). After 4, 8 and 12 weeks, motor and sensory functional recovery in mice were significantly better in the iPS group. At 12 weeks, all the nerve conduits remained structurally stable without any collapse and histological analysis indicated axonal regeneration in the nerve conduits of both groups. However, the iPS group showed significantly more vigorous axonal regeneration. The bioabsorbable nerve conduits created by 3D-culture of iPS cell-derived neurospheres promoted regeneration of peripheral nerves and functional recovery in vivo. The combination of iPS cell technology and bioabsorbable nerve conduits shows potential as a future tool for the treatment of peripheral nerve defects. PMID:22333572

  17. 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.

  18. Deficiency in Monocarboxylate Transporter 1 (MCT1) in Mice Delays Regeneration of Peripheral Nerves following Sciatic Nerve Crush

    PubMed Central

    Morrison, Brett M.; Tsingalia, Akivaga; Vidensky, Svetlana; Lee, Youngjin; Jin, Lin; Farah, Mohamed H.; Lengacher, Sylvain; Magistretti, Pierre J.; Pellerin, Luc; Rothstein, Jeffrey D.

    2014-01-01

    Peripheral nerve regeneration following injury occurs spontaneously, but many of the processes require metabolic energy. The mechanism of energy supply to axons has not previously been determined. In the central nervous system, monocarboxylate transporter 1 (MCT1), expressed in oligodendroglia, is critical for supplying lactate or other energy metabolites to axons. In the current study, MCT1 is shown to localize within the peripheral nervous system to perineurial cells, dorsal root ganglion neurons, and Schwann cells by MCT1 immunofluorescence and MCT1 tdTomato BAC reporter mice. To investigate whether MCT1 is necessary for peripheral nerve regeneration, sciatic nerves in MCT1 heterozygous null mice are crushed and peripheral nerve regeneration quantified electrophysiologically and anatomically. Compound muscle action potential (CMAP) recovery is delayed from a median of 21 days in wild-type mice to greater than 38 days in MCT1 heterozygote null mice. In fact, half of the MCT1 heterozygote null mice have no recovery of CMAP at 42 days, while all of the wild-type mice recovered. In addition, muscle fibers remain 40% more atrophic and neuromuscular junctions 40% more denervated at 42 days post-crush in the MCT1 heterozygote null mice than wild-type mice. The delay in nerve regeneration is not only in motor axons, as the number of regenerated axons in the sural sensory nerve of MCT1 heterozygote null mice at 4 weeks and tibial mixed sensory and motor nerve at 3 weeks is also significantly reduced compared to wild-type mice. This delay in regeneration may be partly through failed Schwann cell function, as there is reduced early phagocytosis of myelin debris and remyelination of axon segments. These data for the first time demonstrate that MCT1 is critical for regeneration of both sensory and motor axons in mice following sciatic nerve crush. PMID:25447940

  19. Deficiency in monocarboxylate transporter 1 (MCT1) in mice delays regeneration of peripheral nerves following sciatic nerve crush.

    PubMed

    Morrison, Brett M; Tsingalia, Akivaga; Vidensky, Svetlana; Lee, Youngjin; Jin, Lin; Farah, Mohamed H; Lengacher, Sylvain; Magistretti, Pierre J; Pellerin, Luc; Rothstein, Jeffrey D

    2015-01-01

    Peripheral nerve regeneration following injury occurs spontaneously, but many of the processes require metabolic energy. The mechanism of energy supply to axons has not previously been determined. In the central nervous system, monocarboxylate transporter 1 (MCT1), expressed in oligodendroglia, is critical for supplying lactate or other energy metabolites to axons. In the current study, MCT1 is shown to localize within the peripheral nervous system to perineurial cells, dorsal root ganglion neurons, and Schwann cells by MCT1 immunofluorescence in wild-type mice and tdTomato fluorescence in MCT1 BAC reporter mice. To investigate whether MCT1 is necessary for peripheral nerve regeneration, sciatic nerves of MCT1 heterozygous null mice are crushed and peripheral nerve regeneration was quantified electrophysiologically and anatomically. Compound muscle action potential (CMAP) recovery is delayed from a median of 21 days in wild-type mice to greater than 38 days in MCT1 heterozygote null mice. In fact, half of the MCT1 heterozygote null mice have no recovery of CMAP at 42 days, while all of the wild-type mice recovered. In addition, muscle fibers remain 40% more atrophic and neuromuscular junctions 40% more denervated at 42 days post-crush in the MCT1 heterozygote null mice than wild-type mice. The delay in nerve regeneration is not only in motor axons, as the number of regenerated axons in the sural sensory nerve of MCT1 heterozygote null mice at 4 weeks and tibial mixed sensory and motor nerve at 3 weeks is also significantly reduced compared to wild-type mice. This delay in regeneration may be partly due to failed Schwann cell function, as there is reduced early phagocytosis of myelin debris and remyelination of axon segments. These data for the first time demonstrate that MCT1 is critical for regeneration of both sensory and motor axons in mice following sciatic nerve crush. PMID:25447940

  20. Channels Active in the Excitability of Nerves and Skeletal Muscles across the Neuromuscular Junction: Basic Function and Pathophysiology

    ERIC Educational Resources Information Center

    Goodman, Barbara E.

    2008-01-01

    Ion channels are essential for the basic physiological function of excitable cells such as nerve, skeletal, cardiac, and smooth muscle cells. Mutations in genes that encode ion channels have been identified to cause various diseases and disorders known as channelopathies. An understanding of how individual ion channels are involved in the

  1. Channels Active in the Excitability of Nerves and Skeletal Muscles across the Neuromuscular Junction: Basic Function and Pathophysiology

    ERIC Educational Resources Information Center

    Goodman, Barbara E.

    2008-01-01

    Ion channels are essential for the basic physiological function of excitable cells such as nerve, skeletal, cardiac, and smooth muscle cells. Mutations in genes that encode ion channels have been identified to cause various diseases and disorders known as channelopathies. An understanding of how individual ion channels are involved in the…

  2. Restoration of shoulder function and elbow flexion by nerve transfer for poliomyelitis-like paralysis caused by enterovirus 71 infection.

    PubMed

    Funahashi, S; Nagano, A; Sano, M; Ogihara, H; Omura, T

    2007-02-01

    We report the case of an eight-month-old girl who presented with a poliomyelitis-like paralysis in her left upper limb caused by enterovirus 71 infection. She recovered useful function after nerve transfers performed six months after the onset of paralysis. Early neurotisation can be used successfully in the treatment of poliomyelitis-like paralysis in children. PMID:17322446

  3. Function-Triggering Antibodies to the Adhesion Molecule L1 Enhance Recovery after Injury of the Adult Mouse Femoral Nerve

    PubMed Central

    Guseva, Daria; Loers, Gabriele; Schachner, Melitta

    2014-01-01

    L1 is among the few adhesion molecules that favors repair after trauma in the adult central nervous system of vertebrates by promoting neuritogenesis and neuronal survival, among other beneficial features. In the peripheral nervous system, L1 is up-regulated in Schwann cells and regrowing axons after nerve damage, but the functional consequences of this expression remain unclear. Our previous study of L1-deficient mice in a femoral nerve injury model showed an unexpected improved functional recovery, attenuated motoneuronal cell death, and enhanced Schwann cell proliferation, being attributed to the persistent synthesis of neurotrophic factors. On the other hand, transgenic mice over-expressing L1 in neurons led to improved remyelination, but not improved functional recovery. The present study was undertaken to investigate whether the monoclonal L1 antibody 557 that triggers beneficial L1 functions in vitro would trigger these also in femoral nerve repair. We analyzed femoral nerve regeneration in C57BL/6J mice that received this antibody in a hydrogel filled conduit connecting the cut and sutured nerve before its bifurcation, leading to short-term release of antibody by diffusion. Video-based quantitative analysis of motor functions showed improved recovery when compared to mice treated with conduits containing PBS in the hydrogel scaffold, as a vehicle control. This improved recovery was associated with attenuated motoneuron loss, remyelination and improved precision of preferential motor reinnervation. We suggest that function-triggering L1 antibodies applied to the lesion site at the time of injury over a limited time period will not only be beneficial in peripheral, but also central nervous system regeneration. PMID:25393007

  4. Senescent Cells Impair Erectile Function through Induction of Endothelial Dysfunction and Nerve Injury in Mice

    PubMed Central

    Saito, Yasuho; Niimi, Aya; Nomiya, Akira; Fukuhara, Hiroshi; Kume, Haruki; Homma, Yukio

    2015-01-01

    Erectile dysfunction (ED) is a major health problem, particularly in the elderly population, which is rapidly increasing. It is necessary to elucidate the mechanism by which ED occurs in the elderly. Cellular senescence is commonly detected in old tissues, and it is well known that senescent cells not only withdraw from the cell cycle but also remain viable and actively produce a variety of cytokines. We examined the effect of senescent cells on erectile function after injection of senescent cells into the penises of mice. Human umbilical vein endothelial cells were infected with an adenovirus expressing a constitutively active mutant of Ras to induce senescence, and were injected into the penises of nude mice. These senescent cells expressed proinflammatory cytokines such as interleukin-1β (IL-1β). Injection of senescent cells impaired erectile function, as assessed by the measurement of intracavernous pressure. Although the structure of the cavernous body did not remarkably change, expression of the catalytically active form of endothelial nitric oxide synthase and that of total neural nitric oxide synthase significantly decreased after injection. The penises injected with the senescent cells expressed human IL-1β and subsequently endogenous proinflammatory cytokines such as mouse IL-1β and tumor necrosis factor-α. These results suggested that senescent cells impaired erectile function through induction of endothelial dysfunction and nerve injury. These effects may be mediated by proinflammatory cytokines produced by senescent cells. PMID:25894557

  5. Uterine autonomic nerve innervation plays a crucial role in regulating rat uterine mast cell functions during embryo implantation.

    PubMed

    Yuan, Xue-Jun; Huang, Li-Bo; Qiao, Hui-Li; Deng, Ze-Pei; Fa, Jing-Jing

    2009-12-01

    To explore the potential mechanism of how uterine innervations would affect the uterine mast cell (MC) population and functions during the periimplantation. We herein first examined the consequence of uterine neurectomy on embryo implantation events. We observed that amputation of autonomic nerves innervating the uterus led to on-time implantation failure in rats. Exploiting MC culture and ELISA approaches, we then further analyzed the effect of neurectomy on cellular histamine levels and its release from uterine MCs, to elucidate the relation of the autonomic nerves and local cellular immunity in the uterine during early pregnancy. We observed that disconnection of autonomic nerve innervation significantly increased the population of uterine MCs. Most interestingly, these increased number of uterine MCs in neuroectomized rats contained a much reduced cellular level of histamine. Our subsequent challenge experiments revealed that uterine MCs in nerve amputated rats exhibited enhanced histamine releasing rate in response to substance P and antiIgE, suggesting loss of nerve innervation in the uterus not only increases the population of uterine MCs, but also facilitates the release of histamine from MCs, thus subsequently interfere with the normal implantation process. Collectively, our findings provide a new line of evidence supporting the concept that immune-neuro-endocrine network plays important role during pregnancy establishment and maintenance. PMID:19765668

  6. The evaluation of small fiber function-autonomic and quantitative sensory testing.

    PubMed

    Gibbons, Christopher; Freeman, Roy

    2004-08-01

    Disorders of the autonomic and small nerve fibers comprise a wide spectrum of disease states that cross a multitude of clinical specialties.The evaluation of these disorders allows the investigator to determine the presence or absence of abnormalities in the lightly myelinated and unmyelinated nerve fibers with minimal discomfort to the patient. The severity of dysfunction also can be determined to guide therapy and aid in prognostication for individual patients. PMID:15207880

  7. [Enzymatic modification of the functional, nutritional and sensorial properties of soybeans for special feeding].

    PubMed

    Calderón de la Barca, A M; Wall Medrano, A; Jara Marini, M; González Córdova, A F; Ruíz Salazar, A

    2000-03-01

    Production of new protein-based products for special nutrition such as hypoallergenic infant formulas, fortified beverages and nutraceutics, require ideal ingredients. Protein ingredients were developed by enzymatic hydrolysis and methionine synthesis of soy protein. Hydrolysis was done at 4% (w/v) using porcine pancreatic enzymes (4% w/w), 50 degrees C, 6 h and pH 8. After drying powder was resuspended (20% w/v) and incubated with 7.6% (w/w) methionine methyl-ester, 1% (w/w) chymotrypsin and 3 M glycerol, 37 degrees C, 3 h and pH 7. Hydrolysates were fractionated by ultrafiltration (UF) before and after enrichment (E): FI > 10, 10 > FII > 3 and 3 > FIII > 1 kDa. Functional properties, amino acid content, anti-physiological factor activities and antigenicity were assayed for all the UF fractions and the soybean meal. Protein quality bioassay and sensorial test of an non-enriched fraction and an enriched fraction were performed. Functional properties were positively modified by hydrolysis and synthesis by using a minimum time and methionine added for the last reaction. After UF all the fractions under 10 kDa showed 100% solubility (pH 4 and 7), good clarity, acceptable foam capacity and negligible antigenicity and antiphysiological activities. Additionally, methionine enrichment enhanced their nutritional value, upgrading sulfur amino acid requirements for infants and adults. Because functionality and nutritional value FIII-E could be used for hypoallergenic infant formulas, FII-E for fortified soluble formulas and nutraceutics and FI-E for a semi-solid baby food. PMID:11048568

  8. Signals and noise in the octavolateralis systems: what is the impact of human activities on fish sensory function?

    PubMed

    Braun, Christopher B

    2015-01-01

    The octavolateralis systems of fishes include the vestibular, auditory, lateral line and electrosensory systems. They are united by common developmental and neuro-computational features, including hair cell sensors and computations based on cross-neuron analyses of differential hair cell stimulation patterns. These systems also all use both spectral and temporal filters to separate signals from each other and from noise, and the distributed senses (lateral line and electroreception) add spatial filters as well. Like all sensory systems, these sensors must provide the animal with guidance for adaptive behavior within a sensory scene composed of multiple stimuli and varying levels of ambient noise, including that created by human activities. In the extreme, anthropogenic activities impact the octavolateralis systems by destroying or degrading the habitats that provide ecological resources and sensory inputs. At slightly lesser levels of effect, anthropogenic pollutants can be damaging to fish tissues, with sensory organs often the most vulnerable. The exposed sensory cells of the lateral line and electrosensory systems are especially sensitive to aquatic pollution. At still lesser levels of impact, anthropogenic activities can act as both acute and chronic stressors, activating hormonal changes that may affect behavioral and sensory function. Finally, human activities are now a nearly ubiquitous presence in aquatic habitats, often with no obvious effects on the animals exposed to them. Ship noise, indigenous and industrial fishing techniques, and all the ancillary noises of human civilization form a major part of the soundscape of fishes. How fish use these new sources of information about their habitat is a new and burgeoning field of study. PMID:24920543

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

    PubMed

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

    2015-11-15

    Using vagus nerve stimulation (VNS), we sought to determine the contribution of vagal afferents to efferent control of cardiac function. In anesthetized dogs, the right and left cervical vagosympathetic trunks were stimulated in the intact state, following ipsilateral or contralateral vagus nerve transection (VNTx), and then following bilateral VNTx. Stimulations were performed at currents from 0.25 to 4.0 mA, frequencies from 2 to 30 Hz, and a 500-μs pulse width. Right or left VNS evoked significantly greater current- and frequency-dependent suppression of chronotropic, inotropic, and lusitropic function subsequent to sequential VNTx. Bradycardia threshold was defined as the current first required for a 5% decrease in heart rate. The threshold for the right vs. left vagus-induced bradycardia in the intact state (2.91 ± 0.18 and 3.47 ± 0.20 mA, respectively) decreased significantly with right VNTx (1.69 ± 0.17 mA for right and 3.04 ± 0.27 mA for left) and decreased further following bilateral VNTx (1.29 ± 0.16 mA for right and 1.74 ± 0.19 mA for left). Similar effects were observed following left VNTx. The thresholds for afferent-mediated effects on cardiac parameters were 0.62 ± 0.04 and 0.65 ± 0.06 mA with right and left VNS, respectively, and were reflected primarily as augmentation. Afferent-mediated tachycardias were maintained following β-blockade but were eliminated by VNTx. The increased effectiveness and decrease in bradycardia threshold with sequential VNTx suggest that 1) vagal afferents inhibit centrally mediated parasympathetic efferent outflow and 2) the ipsilateral and contralateral vagi exert a substantial buffering capacity. The intact threshold reflects the interaction between multiple levels of the cardiac neural hierarchy. PMID:26371171

  10. 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.

  11. Effects of Polysialic Acid on Sensory Innervation of the Cornea

    PubMed Central

    Mao, Xiuli; Zhang, Yuntao; Schwend, Tyler; Conrad, Gary W.

    2014-01-01

    Sensory trigeminal growth cones innervate the cornea in a coordinated fashion during embryonic development. Polysialic acid (polySia) is known for its important roles during nerve development and regeneration. The purpose of this work is to determine whether polySia, present in developing eyefronts and on the surface of sensory nerves, may provide guidance cues to nerves during corneal innervation. Expression and localization of polySia in embryonic day (E)5-14 chick eyefronts and E9 trigeminal ganglia were identified using Western blotting and immunostaining. Effects of polySia removal on trigeminal nerve growth behavior were determined in vivo, using exogenous endoneuraminidase (endoN) treatments to remove polySia substrates during chick cornea development, and in vitro, using neuronal explant cultures. PolySia substrates, made by the physical adsorption of colominic acid to a surface coated with poly-D-lysine (PDL), were used as a model to investigate functions of the polySia expressed in axonal environments. PolySia was localized within developing eyefronts and on trigeminal sensory nerves. Distributions of PolySia in corneas and pericorneal regions are developmentally regulated. PolySia removal caused defasciculation of the limbal nerve trunk in vivo from E7 to E10. Removal of polySia on trigeminal neurites inhibited neurite outgrowth and caused axon defasciculation, but did not affect Neural Cell Adhesion Molecule (NCAM) expression or Schwann cell migration in vitro. PolySia substrates in vitro inhibited outgrowth of trigeminal neurites and promoted their fasciculation. In conclusion, polySia is localized on corneal nerves and in their targeting environment during early developing stages of chick embryos. PolySias promote fasciculation of trigeminal axons in vivo and in vitro, whereas, in contrast, their removal promotes defasciculation. PMID:25478909

  12. Influences of continuous femoral nerve block on knee function and quality of life in patients following total knee arthroplasty

    PubMed Central

    Wang, Fen; Zhou, Yingjie; Sun, Jiajun; Yang, Chunxi

    2015-01-01

    Objective: Continuous femoral nerve block (CFNB), guided by ultrasound combined nerve stimulations, offers advantages for both sides and provides effective postoperative analgesia after total knee arthroplasty (TKA). The objective of this study was to evaluate the medium-term impact of continuous femoral nerve block on knee function and quality of life in patients following TKA. Methods: This was a follow-up study. Total 168 adult patients scheduled for elective TKA were randomly allocated to receive postoperative continuous femoral nerve block guided by ultrasound combined nerve stimulator (group CFNB, n = 82) or patient-controlled epidural analgesia (group PCEA, n = 86). Quality of life, knee function, patient satisfaction, pain medication and associated adverse effects were compared at 1, 3, 6, and 12 months postoperatively. Quality of life was assessed using the Medical Outcomes Study Short Form-36 Health Survey (MOS SF-36), and clinical results were assessed using the Hospital for Special Surgery (HSS) Knee Scoring System. Patient satisfaction scores were divided into four categories. Results: A total of 162 patients completed the 12-month follow-up. The CFNB group patients had significantly improved SF-36 scores and physical function at 1 month postoperatively (P < 0.05); the remaining seven dimensions were similar between the two groups. No differences were observed at 3, 6 or 12 months. HSS scores for the four observational time points were comparable. The CFNB group patients reported less pain; improved knee function, maximum flexion and strength; less celecoxib consumption and fewer side effects at 1 month than the PCEA group patients. The satisfaction score at 12 months decreased significantly, compared with that at 1 month in both groups (3.6 to 2.95 and 3.4 to 2.45, respectively). No difference in satisfaction score was observed between the two groups. Conclusions: Continuous femoral nerve block not only could provide effective postoperative analgesia but also could improve joint function and quality of life in patients at one month postoperatively. Continuous femoral nerve block is a good choice for postoperative analgesia after TKA. PMID:26770542

  13. Functional ability loss in sensory impaired and sensory unimpaired very old adults: analyzing causal relations with positive affect across four years.

    PubMed

    Wahl, Hans-Werner; Drapaniotis, Philipp M; Heyl, Vera

    2014-11-01

    This paper focuses on the relationship between functional ability (FA) and positive affect (PA), a major component of well-being, in sensory impaired very old adults (SI) compared with sensory unimpaired individuals (UI). Previous research mostly suggests a robust causal impact of FA on PA. However, some research, drawing from Fredrickson's broaden-and-build theory, also points to the possibility of an inverse causality between FA and PA. We examine in this paper both of these causal directions in SI as well as UI individuals across a 4year observation period. Additionally, we checked for the role of negative affect (NA). The T1-T2 sample comprised 81 out of 237 SI individuals (visually or hearing impaired) assessed at T1, with a mean age at T1 of 81.8years, and 87 UI individuals out of 150 assessed at T1, with a mean age at T1 of 81.5years. Established scales were used to assess FA, PA, and NA. Using cross-lagged panel analysis to examine the direction of causality, our findings indicate that FA has significant impact on PA in both the SI and the UI group, whereas the alternative causal pathway was not confirmed. Both cross-lagged relationships between FA and NA were non-significant. No group differences in path strengths between SI and UI were present. Our study provides evidence that FA is a key competence for successful emotional aging in vulnerable groups of very old adults such as SI as well as in UI adults in advanced old age. PMID:24929008

  14. In Vivo Electrophysiological Measurements on Mouse Sciatic Nerves

    PubMed Central

    Schulz, Alexander; Walther, Christian; Morrison, Helen; Bauer, Reinhard

    2014-01-01

    Electrophysiological studies allow a rational classification of various neuromuscular diseases and are of help, together with neuropathological techniques, in the understanding of the underlying pathophysiology1. Here we describe a method to perform electrophysiological studies on mouse sciatic nerves in vivo. The animals are anesthetized with isoflurane in order to ensure analgesia for the tested mice and undisturbed working environment during the measurements that take about 30 min/animal. A constant body temperature of 37 °C is maintained by a heating plate and continuously measured by a rectal thermo probe2. Additionally, an electrocardiogram (ECG) is routinely recorded during the measurements in order to continuously monitor the physiological state of the investigated animals. Electrophysiological recordings are performed on the sciatic nerve, the largest nerve of the peripheral nervous system (PNS), supplying the mouse hind limb with both motoric and sensory fiber tracts. In our protocol, sciatic nerves remain in situ and therefore do not have to be extracted or exposed, allowing measurements without any adverse nerve irritations along with actual recordings. Using appropriate needle electrodes3 we perform both proximal and distal nerve stimulations, registering the transmitted potentials with sensing electrodes at gastrocnemius muscles. After data processing, reliable and highly consistent values for the nerve conduction velocity (NCV) and the compound motor action potential (CMAP), the key parameters for quantification of gross peripheral nerve functioning, can be achieved. PMID:24747166

  15. α2δ-1 Gene Deletion Affects Somatosensory Neuron Function and Delays Mechanical Hypersensitivity in Response to Peripheral Nerve Damage

    PubMed Central

    Patel, Ryan; Bauer, Claudia S.; Nieto-Rostro, Manuela; Margas, Wojciech; Ferron, Laurent; Chaggar, Kanchan; Crews, Kasumi; Ramirez, Juan D.; Bennett, David L. H.; Schwartz, Arnold; Dickenson, Anthony H.

    2013-01-01

    The α2δ-1 subunit of voltage-gated calcium channels is upregulated after sensory nerve injury and is also the therapeutic target of gabapentinoid drugs. It is therefore likely to play a key role in the development of neuropathic pain. In this study, we have examined mice in which α2δ-1 gene expression is disrupted, to determine whether α2δ-1 is involved in various modalities of nociception, and for the development of behavioral hypersensitivity after partial sciatic nerve ligation (PSNL). We find that naive α2δ-1−/− mice show a marked behavioral deficit in mechanical and cold sensitivity, but no change in thermal nociception threshold. The lower mechanical sensitivity is mirrored by a reduced in vivo electrophysiological response of dorsal horn wide dynamic range neurons. The CaV2.2 level is reduced in brain and spinal cord synaptosomes from α2δ-1−/− mice, and α2δ-1−/− DRG neurons exhibit lower calcium channel current density. Furthermore, a significantly smaller number of DRG neurons respond to the TRPM8 agonist menthol. After PSNL, α2δ-1−/− mice show delayed mechanical hypersensitivity, which only develops at 11 d after surgery, whereas in wild-type littermates it is maximal at the earliest time point measured (3 d). There is no compensatory upregulation of α2δ-2 or α2δ-3 after PSNL in α2δ-1−/− mice, and other transcripts, including neuropeptide Y and activating transcription factor-3, are upregulated normally. Furthermore, the ability of pregabalin to alleviate mechanical hypersensitivity is lost in PSNL α2δ-1−/− mice. Thus, α2δ-1 is essential for rapid development of mechanical hypersensitivity in a nerve injury model of neuropathic pain. PMID:24133248

  16. Effect of bleaching whey on sensory and functional properties of 80% whey protein concentrate.

    PubMed

    Jervis, S; Campbell, R; Wojciechowski, K L; Foegeding, E A; Drake, M A; Barbano, D M

    2012-06-01

    Whey is a highly functional food that has found widespread use in a variety of food and beverage applications. A large amount of the whey proteins produced in the United States is derived from annatto-colored Cheddar cheese. Color from annatto is undesirable in whey and must be bleached. The objective of this study was to compare 2 commercially approved bleaching agents, benzoyl peroxide (BP) and hydrogen peroxide (HP), and their effects on the flavor and functionality of 80% whey protein concentrate (WPC80). Colored and uncolored liquid wheys were bleached with BP or HP, and then ultrafiltered, diafiltered, and spray-dried; WPC80 from unbleached colored and uncolored Cheddar whey were manufactured as controls. All treatments were manufactured in triplicate. The WPC80 were then assessed by sensory, instrumental, functionality, color, and proximate analysis techniques. The HP-bleached WPC80 were higher in lipid oxidation compounds (specifically hexanal, heptanal, octanal, nonanal, decanal, dimethyl disulfide, and 1-octen-3-one) and had higher fatty and cardboard flavors compared with the other unbleached and BP-bleached WPC80. The WPC80 bleached with BP had lower norbixin concentrations compared with WPC80 bleached with HP. The WPC powders differed in Hunter color values (L, a, b), with bleached powders being more white, less red, and less yellow than unbleached powders. Bleaching with BP under the conditions used in this study resulted in larger reductions in yellowness of the powders made from whey with annatto color than did bleaching with HP. Functionality testing demonstrated that whey bleached with HP treatments had more soluble protein after 10 min of heating at 90°C at pH 4.6 and pH 7 than the no-bleach and BP treatments, regardless of additional color. Overall, HP bleaching caused more lipid oxidation products and subsequent off-flavors compared with BP bleaching. However, heat stability of WPC80 was enhanced by HP bleaching compared with control or BP-bleached WPC80. PMID:22612922

  17. 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 hydrogel. This indicates return of some feeling to the limb via the fully-configured conduit. Immunohistochemical analysis of the implanted conduits removed from the rats after the four-week implantation period confirmed the presence of myelinated axons within the conduit and distal to the site of implantation, further supporting that the conduit promoted nerve repair over this period of time. This study describes the design considerations and fabrication of a novel multicomponent, multimodal bio-engineered synthetic conduit for peripheral nerve repair.

  18. Electrical Stimulation to Enhance Axon Regeneration After Peripheral Nerve Injuries in Animal Models and Humans.

    PubMed

    Gordon, Tessa

    2016-04-01

    Injured peripheral nerves regenerate their lost axons but functional recovery in humans is frequently disappointing. This is so particularly when injuries require regeneration over long distances and/or over long time periods. Fat replacement of chronically denervated muscles, a commonly accepted explanation, does not account for poor functional recovery. Rather, the basis for the poor nerve regeneration is the transient expression of growth-associated genes that accounts for declining regenerative capacity of neurons and the regenerative support of Schwann cells over time. Brief low-frequency electrical stimulation accelerates motor and sensory axon outgrowth across injury sites that, even after delayed surgical repair of injured nerves in animal models and patients, enhances nerve regeneration and target reinnervation. The stimulation elevates neuronal cyclic adenosine monophosphate and, in turn, the expression of neurotrophic factors and other growth-associated genes, including cytoskeletal proteins. Electrical stimulation of denervated muscles immediately after nerve transection and surgical repair also accelerates muscle reinnervation but, at this time, how the daily requirement of long-duration electrical pulses can be delivered to muscles remains a practical issue prior to translation to patients. Finally, the technique of inserting autologous nerve grafts that bridge between a donor nerve and an adjacent recipient denervated nerve stump significantly improves nerve regeneration after delayed nerve repair, the donor nerves sustaining the capacity of the denervated Schwann cells to support nerve regeneration. These reviewed methods to promote nerve regeneration and, in turn, to enhance functional recovery after nerve injury and surgical repair are sufficiently promising for early translation to the clinic. PMID:26754579

  19. In vitro release of organophosphorus acid anhydrolase from functionalized mesoporous silica against nerve agents.

    SciTech Connect

    Chen, Baowei; Shah, Saumil S.; Shin, Yongsoon; Lei, Chenghong; Liu, Jun

    2011-10-02

    We report here that under different physiological conditions, biomolecular drugs can be stockpiled in a nanoporous support and afterward can be instantly released when needed for acute responses, and the biomolecular drug molecules can also be gradually released from the nanoporous support over a long time for a complete recovery. Organophosphorus acid anhydrolase (OPAA) was spontaneously and largely entrapped in functionalized mesoporous silica (FMS) due to the dominant electrostatic interaction. The OPAA-FMS composite exhibited a burst release in a pH 9.0 NaHCO(3)-Na(2)CO(3) buffer system and a gradual release in pH 7.4 simulated body fluid. The binding of OPAA to NH(2)-FMS can result in less tyrosinyl and tryptophanyl exposure OPAA molecules to aqueous environment. The bound OPAA in FMS displayed lower activity than the free OPAA in solution prior to the enzyme entrapment. However, the released enzyme maintained the native conformational structure and the same high enzymatic activity as that prior to the enzyme entrapment. The in vitro results in the rabbit serum demonstrate that both OPAA-FMS and the released OPAA may be used as a medical countermeasure against the organophosphorus nerve agents.

  20. Analysis of Graph Invariants in Functional Neocortical Circuitry Reveals Generalized Features Common to Three Areas of Sensory Cortex

    PubMed Central

    Gururangan, Suchin S.; Sadovsky, Alexander J.; MacLean, Jason N.

    2014-01-01

    Correlations in local neocortical spiking activity can provide insight into the underlying organization of cortical microcircuitry. However, identifying structure in patterned multi-neuronal spiking remains a daunting task due to the high dimensionality of the activity. Using two-photon imaging, we monitored spontaneous circuit dynamics in large, densely sampled neuronal populations within slices of mouse primary auditory, somatosensory, and visual cortex. Using the lagged correlation of spiking activity between neurons, we generated functional wiring diagrams to gain insight into the underlying neocortical circuitry. By establishing the presence of graph invariants, which are label-independent characteristics common to all circuit topologies, our study revealed organizational features that generalized across functionally distinct cortical regions. Regardless of sensory area, random and -nearest neighbors null graphs failed to capture the structure of experimentally derived functional circuitry. These null models indicated that despite a bias in the data towards spatially proximal functional connections, functional circuit structure is best described by non-random and occasionally distal connections. Eigenvector centrality, which quantifies the importance of a neuron in the temporal flow of circuit activity, was highly related to feedforwardness in all functional circuits. The number of nodes participating in a functional circuit did not scale with the number of neurons imaged regardless of sensory area, indicating that circuit size is not tied to the sampling of neocortex. Local circuit flow comprehensively covered angular space regardless of the spatial scale that we tested, demonstrating that circuitry itself does not bias activity flow toward pia. Finally, analysis revealed that a minimal numerical sample size of neurons was necessary to capture at least 90 percent of functional circuit topology. These data and analyses indicated that functional circuitry exhibited rules of organization which generalized across three areas of sensory neocortex. PMID:25010654

  1. Influence of putrescine and carnauba wax on functional and sensory quality of pomegranate (Punica granatum L.) fruits during storage.

    PubMed

    Barman, Kalyan; Asrey, Ram; Pal, R K; Kaur, Charanjit; Jha, S K

    2014-01-01

    Functional properties (anthocyanins, antioxidant, ascorbic acid and tannin) and sensory score were determined in pomegranate fruits at two storage temperatures (3 and 5 °C) after treatment with 2 mM putrescine and 1 : 10 carnauba wax (carnauba wax : water). The treatments (putrescine and carnauba wax) were given by immersion method followed by storage up to 60 days. Both treatments retained significantly higher anthocyanins, antioxidant, ascorbic acid, tannin and sensory qualities as compared with control fruits under both the storage conditions. Combined application of putrescine + carnauba wax showed better response in retaining functional properties than putrescine treated or nontreated fruits. The impacts of putrescine and carnauba wax treatments were found more pronounced after 30 days at 3-5 °C storage temperature in retaining functional and sensory qualities. After 60 days of storage, putrescine + carnauba wax retained about 25% higher antioxidant activity both at 3 and 5 °C storage temperatures. PMID:24426055

  2. Methyl-CpG Binding Protein 2 (Mecp2) Regulates Sensory Function Through Sema5b and Robo2

    PubMed Central

    Leong, Wan Y.; Lim, Zhi H.; Korzh, Vladimir; Pietri, Thomas; Goh, Eyleen L. K.

    2015-01-01

    Mutations in the gene encoding the MECP2 underlies Rett syndrome, a neurodevelopmental disorder in young females. Although reduced pain sensitivity in Rett syndrome patients and in partial MeCP2 deficient mice had been reported, these previous studies focused predominantly on motor impairments. Therefore, it is still unknown how MeCP2 is involved in these sensory defects. In addition, the human disease manifestations where males with mutations in MECP2 gene normally do not survive and females show typical neurological symptoms only after 18 months of age, is profoundly different in MeCP2-deficient mouse where all animals survived, and males but not females displayed Rett syndrome phenotypes at an early age. Thus, the mecp2-deficient zebrafish serves as an additional animal model to aid in deciphering the role and mechanisms of Mecp2 in neurodevelopment. Here, we used two independent methods of silencing expression of Mecp2 in zebrafish to uncover a novel role of Mecp2 in trigeminal ganglion sensory neurons during the embryonic development. mecp2-null mutation and morpholino-mediated silencing of Mecp2 in the zebrafish embryos resulted in defects in peripheral innervation of trigeminal sensory neurons and consequently affecting the sensory function. These defects were demonstrated to be dependent on the expression of Sema5b and Robo2. The expression of both proteins together could better overcome the defects caused by Mecp2 deficiency as compared to the expression of either Sema5b or Robo2 alone. Sema5b and Robo2 were downregulated upon Mecp2 silencing or in mecp2-null embryos, and Chromatin immunoprecipitation (ChIP) assay using antibody against Mecp2 was able to pull down specific regions of both Sema5b and Robo2 promoters, showing interaction between Mecp2 and the promoters of both genes. In addition, cell-specific expression of Mecp2 can overcome the innervation and sensory response defects in Mecp2 morphants indicating that these MeCP2-mediated defects are cell-autonomous. The sensory deficits caused by Mecp2 deficiency mirror the diminished sensory response observed in Rett syndrome patients. This suggests that zebrafish could be an unconventional but useful model for this disorder manifesting defects that are not easily studied in full using rodent models. PMID:26733807

  3. Rodent Facial Nerve Recovery After Selected Lesions and Repair Techniques

    PubMed Central

    Hadlock, Tessa A.; Kowaleski, Jeffrey; Lo, David; Mackinnon, Susan E.; Heaton, James T.

    2015-01-01

    Background Measuring rodent facial movements is a reliable method for studying recovery from facial nerve manipulation, and for examining the behavioral correlates of aberrant regeneration. We quantitatively compared recovery of vibrissal and ocular function following three types of clinically relevant nerve injury. Methods 178 adult rats underwent facial nerve manipulation and testing. In the experimental groups, the left facial nerve was either crushed, transected and repaired epineurially, or transected and the stumps suture-secured into a tube with a 2 mm gap between them. Facial recovery was measured for the ensuing 1–4 months. Data were analyzed for whisking recovery. Previously developed markers of co-contraction of the upper and midfacial zones (possible synkinesis markers) were also examined. Results Animals in the crush groups recovered nearly normal whisking parameters within 25 days. The distal branch crush group showed improved recovery over the main trunk crush group for several days during early recovery. By week 9, the transection/repair groups showed evidence of recovery that trended further upward throughout the study period. The entubulation groups followed a similar recovery pattern, though they did not maintain significant recovery levels by the study conclusion. Markers of potential synkinesis increased in selected groups following facial nerve injury. Conclusions Rodent vibrissial function recovers in a predictable fashion following manipulation. Generalized co-contraction of the upper and midfacial zones emerges following facial nerve manipulation, possibly related to aberrant regeneration, polyterminal axons, or hypersensitivity of the rodent to sensory stimuli following nerve manipulation. PMID:20048604

  4. The effects of sensory denervation on the responses of the rabbit eye to prostaglandin E1, bradykinin and substance P.

    PubMed Central

    Butler, J. M.; Hammond, B. R.

    1980-01-01

    1 Six to eight days after diathermic destruction of the fifth cranial nerve in the rabbit, the ocular hypertensive and miotic responses to intracameral administration of capsaicin, bradykinin, and prostaglandin E1 were greatly reduced or completely abolished. The response to substance P was not abolished. 2 A response could still be obtained to chemical irritants 36 h after coagulation of the nerve and it is deduced that manifestation of the response is dependent upon functional<