Science.gov

Sample records for sensory nerve desensitization

  1. Area of desensitization following mental nerve block in dogs.

    PubMed

    Krug, William; Losey, Jeannie

    2011-01-01

    Regional nerve blocks are commonly used to provide analgesia for dental and oral surgical procedures. The purpose of this study was to demarcate the areas of the mandible that would be desensitized by application of the mental nerve block. Seven healthy mixed-breed dogs were anesthetized for an annual dental examination and professional teeth cleaning procedure. Bupivacaine HCl (0.4 ml/ m2) was administered at one middle mental foramen based on previously described techniques for the mental nerve block. A noxious stimulus was applied at 23 predetermined ipsilateral mandibular locations using pressure from a mosquito hemostat on the mucocutaneous junction (MCJ) and a dental curette on the vestibular mucogingival line (MGL) at the incisor canine, and premolar teeth; and, the mesial and distal aspects of the first molar tooth. A thermal stimulus using a refrigerant spray on a cotton ball was applied to the ipsilateral canine, third premolar and fourth premolar teeth; and, the mesial and distal aspects of the first molar tooth. Demonstration of nociception or anesthesia was noted and the responses tabulated. The area of desensitized tissues was smaller than expected and highly variable within the study group. In conclusion, the unilateral mental nerve block does not reliably provide generalized desensitization to tissues of the incisive and rostral regions of the mandible. Although the mental nerve block is recommended, other modes of analgesia should be emphasized for surgical and dental procedures involving these areas. PMID:22206140

  2. 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

  3. Functional compartmentalization of opioid desensitization in primary sensory neurons.

    PubMed

    Samoriski, G M; Gross, R A

    2000-08-01

    The cellular correlates of desensitization or tolerance are poorly understood. To address this, we studied acute and long-term mu-opioid desensitization, with respect to Ca(2+) currents, in cultured rat dorsal root ganglion (DRG) neurons. Exposure of DRG neurons to the mu-agonist [D-Ala(2),N-MePhe(4), Gly-ol(5)]-enkephalin (DAMGO; 3 microM) reduced whole-cell currents approximately 35%, but with continued agonist application, 52% of the response was lost over 10 to 12 min. In contrast, exposure of DRG neurons to DAMGO for 24 h resulted in a nearly complete loss of Ca(2+) channel regulation after washing and re-exposure to DAMGO. Responses to the gamma-aminobutyric acid(B) agonist baclofen were not affected in these neurons. Acute desensitization preferentially affected the voltage-sensitive component of mu-opioid and gamma-aminobutyric acid(B) responses. Facilitation of both the DAMGO- and baclofen-inhibited current by a strong depolarizing prepulse was significantly attenuated in acutely desensitized neurons. Because G(betagamma)-subunits mediate neurotransmitter-induced changes in channel voltage-dependent properties, these data suggest an altered interaction of the G(betagamma)-subunit with the Ca(2+) channel. Block of N-type Ca(2+) channels with omega-conotoxin GVIA revealed a component of the opioid response that did not desensitize over 10 min. We conclude that acute and long-term mu-opioid desensitization in DRG neurons occurs by different mechanisms. Acute desensitization is heterologous and functionally compartmentalized: the pathway targeting non-N-type channels is relatively resistant to the early effects of continuous agonist exposure; the pathway targeting N-type channels in a largely voltage-insensitive manner is partially desensitized; and the pathway targeting N-type channels in a largely voltage-sensitive manner is completely desensitized. PMID:10900225

  4. 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

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

    ERIC Educational Resources Information Center

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

    2013-01-01

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

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

    ERIC Educational Resources Information Center

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

    2013-01-01

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

  7. 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

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

    PubMed

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

    2011-01-01

    Menthol and cinnamaldehyde (CA) are plant-derived spices commonly used in oral hygiene products, chewing gum, and many other applications. However, little is known regarding their sensory interactions in the oral cavity. We used a human psychophysics approach to investigate the temporal dynamics of oral irritation elicited by sequential application of menthol and/or CA, and ratiometric calcium imaging methods to investigate activation of rat trigeminal ganglion (TG) cells by these agents. Irritancy decreased significantly with sequential oral application of menthol and CA (self-desensitization). Menthol cross-desensitized irritation elicited by CA, and vice versa, over a time course of at least 60 min. Seventeen and 19% of TG cells were activated by menthol and CA, respectively, with ∼50% responding to both. TG cells exhibited significant self-desensitization to menthol applied at a 5, but not 10, min interval. They also exhibited significant self-desensitization to CA at 400 but not 200 μM. Menthol cross-desensitized TG cell responses to CA. CA at a concentration of 400 but not 200 μM also cross-desensitized menthol-evoked responses. The results support the argument that the perceived reductions in oral irritancy and cross-interactions between menthol and CA and menthol observed (at least at short interstimulus intervals) can be largely accounted for by the properties of trigeminal sensory neurons innervating the tongue. PMID:21059698

  9. Palm to Finger Ulnar Sensory Nerve Conduction.

    PubMed

    Davidowich, Eduardo; Nascimento, Osvaldo J M; 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

    2015-12-29

    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

  10. 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

  11. Patterns of slow transport in sensory nerves

    SciTech Connect

    Stromska, D.P.; Ochs, S.

    1981-09-01

    An examination of the pattern of outflow of radioactivity in sciatic nerves was made at times from 1 to 82 days in the rat and up to 132 days in the cat after injecting the L5 and L7 dorsal root ganglia, respectively, with 3H-leucine. Slow waves moving at a rate of 1-2 mm/day were looked for on the basis of their reported presence in the motor fibers of the rat. A consistent pattern of slow waves was not seen in the cat or rat sensory fibers of the sciatic nerves nor was evidence of a slow wave found in the cat dorsal columns. Irregularities in the pattern of outflow which at times appeared as waves did so in an irregular fashion, a pattern inconsistent with a steady progression of slow waves in the fibers. The decrease of radioactivity appearing first near the ganglia helps create the impression of a wave along with irregular decreases in the overall levels of radio-activity with time. The results were explained on the basis of the unitary hypothesis. The labeled components are considered to be moved down the fiber by the fast transport mechanism, those components dropping off locally in the fibers early on, constituting the slow wave. As those components turn over locally in the various organelles of fiber and are further redistributed, they may at times give rise to what appears as waves.

  12. Parkinson Disease Affects Peripheral Sensory Nerves in the Pharynx

    PubMed Central

    Mu, Liancai; Sobotka, Stanislaw; Chen, Jingming; Su, Hungxi; Sanders, Ira; Nyirenda, Themba; Adler, Charles H.; Shill, Holly A.; Caviness, John N.; Samanta, Johan E.; Sue, Lucia I.; Beach, Thomas G.

    2013-01-01

    Dysphagia is very common in patients with Parkinsons disease (PD) and often leads to aspiration pneumonia, the most common cause of death in PD. Unfortunately, current therapies are largely ineffective for dysphagia. As pharyngeal sensation normally triggers the swallowing reflex, we examined pharyngeal sensory nerves in PD for Lewy pathology. Sensory nerves supplying the pharynx were excised from autopsied pharynges obtained from patients with clinically diagnosed and neuropathologically confirmed PD (n = 10) and healthy age-matched controls (n = 4). We examined: the glossopharyngeal nerve (IX); the pharyngeal sensory branch of the vagus nerve (PSB-X); and the internal superior laryngeal nerve (ISLN) innervating the laryngopharynx. Immunohistochemistry for phosphorylated ?-synuclein was used to detect potential Lewy pathology. Axonal ?-synuclein aggregates in the pharyngeal sensory nerves were identified in all of the PD subjects but not in the controls. The density of ?-synuclein-positive lesions was significantly greater in PD subjects with documented dysphagia compared to those without dysphagia. In addition, ?-synuclein-immunoreactive nerve fibers in the ISLN were much more abundant than those in the IX and PSBX. These findings suggest that pharyngeal sensory nerves are directly affected by the pathologic process of PD. This anatomic pathology may decrease pharyngeal sensation impairing swallowing and airway protective reflexes, thereby contributing to dysphagia and aspiration. PMID:23771215

  13. 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

  14. 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

  15. 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

  16. Leptin-sensitive sensory nerves innervate white fat.

    PubMed

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

    2013-06-15

    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

  17. 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

  18. Sensory transduction in peripheral nerve axons elicits ectopic action potentials.

    PubMed

    Hoffmann, Tal; Sauer, Susanne K; Horch, Raymund E; Reeh, Peter W

    2008-06-11

    Sensory properties of unmyelinated axons in the isolated rat sciatic nerve have been revealed previously by measuring stimulated neuropeptide release in response to noxious stimuli. In addition, axonal sensitization by inflammatory mediators has been demonstrated and shown to depend on the heat- and proton-activated ion channel transient receptor potential vanilloid receptor-1. It was unclear whether this responsiveness is accompanied by ectopic generation of action potentials, which may play a crucial role in painful neuropathies. We explored this hypothesis using the isolated mouse skin-nerve preparation. This method enabled us to directly compare the sensory properties of axons in the peripheral nerve with their characterized cutaneous terminals in the receptive field using propagated action potentials as an index of axonal activation. Single-fiber recordings from 51 mechanosensitive mouse C-fibers revealed that a majority of the polymodal nociceptors responded with an encoding discharge rate to graded heating of the cutaneous receptive field (n = 38) as well as of the saphenous nerve carrying the fiber under investigation (n = 25; 66%). Axonal heat responses paralleled those of the receptive fields with regard to thresholds and discharge rates (41.5 +/- 4.3 degrees C; 7.7 +/- 9.6 spikes in a 20 s 32-48 degrees C ranged stimulation). In contrast, axonal mechanosensitivity was poor and noxious cold sensitivity more rarely encountered. In conclusion, peripheral nerve axons exhibit sensory transduction capacities similar to their nociceptive terminals in the skin with respect to noxious heat, although not to mechanical and cold sensitivity. This may become a source of ectopic discharge and pain if axonal heat threshold drops to body temperature, as may be the case during inflammation-like processes in peripheral nerves. PMID:18550771

  19. Sensory and Motor Peripheral Nerve Function and Incident Mobility Disability

    PubMed Central

    Ward, Rachel E.; Boudreau, Robert M.; Caserotti, Paolo; Harris, Tamara B.; Zivkovic, Sasa; Goodpaster, Bret H.; Satterfield, Suzanne; Kritchevsky, Stephen B.; Schwartz, Ann V.; Vinik, Aaron I.; Cauley, Jane A.; Simonsick, Eleanor M.; Newman, Anne B.; Strotmeyer, Elsa S.

    2014-01-01

    Background/Objectives Peripheral nerve impairments are highly prevalent in older adults and are associated with poor lower-extremity function. Whether sensorimotor nerve function predicts incident mobility disability has not been determined. We assessed the relationship between sensorimotor nerve function and incident mobility disability over 10 years. Design Prospective cohort study with longitudinal analysis. Setting Two U.S. clinical sites. Participants Population-based sample of community-dwelling older adults with no mobility disability at 2000/01 exam (N = 1680; mean SD: age = 76.5 2.9, BMI = 27.1 4.6; 50.2% women, 36.6% black and 10.7% with diabetes). Measurements Motor nerve conduction amplitude (poor: <1 mV) and velocity (poor: <40 m/s) were measured on the deep peroneal nerve. Sensory nerve function was measured using 10-g and 1.4-g monofilaments and vibration detection threshold at the toe. Lower-extremity symptoms included numbness or tingling and sudden stabbing, burning, pain or aches. Incident mobility disability assessed semiannually over 8.5 years (IQR: 4.59.6) was defined as two consecutive self-reports of a lot of difficulty or inability to walk mile or climb 10 steps. Results Nerve impairments were detected in 55% of participants and 30% developed mobility disability. Worse motor amplitude (HR = 1.29 per SD, 95% CI: 1.161.44), vibration detection threshold (HR = 1.13 per SD, 95% CI: 1.041.23), symptoms (HR = 1.65, 95% CI: 1.362.17), 2 motor (HR = 2.10, 95% CI: 1.433.09), 2 sensory (HR = 1.91, 95% CI: 1.372.68), and ?3 nerve impairments (HR = 2.33, 95% CI: 1.543.53) predicted incident mobility disability, after adjustment. Quadriceps strength mediated relationships between certain nerve impairments and mobility disability, although most remained significant. Conclusion Poor sensorimotor nerve function independently predicted mobility disability. Future work should investigate modifiable risk factors and interventions like strength training for preventing disability and improving function in older adults with poor nerve function. PMID:25482096

  20. Sensory outcome of fingertip replantations without nerve repair.

    PubMed

    Ozcelik, Ismail Bulent; Tuncer, Serdar; Purisa, Husrev; Sezer, Ilker; Mersa, Berkan; Kabakas, Fatih; Celikdelen, Pinar

    2008-01-01

    The sensory recovery outcomes of fingertip replantations without nerve repair were retrospectively studied. Between 2000 and 2006, 112 fingertip replantations with only arterial repair were carried out in 98 patients. About 76 of the replants survived totally, with a success rate of 67.8%. Evaluation of sensory recovery was possible in 31 patients (38 replantations). Sensory evaluation was made with Semmes-Weinstein, static and dynamic two-point discrimination, and vibration sense tests. Fingertip atrophy, nail deformities, and return to work were also evaluated. According to the Semmes-Weinstein test, 29.0% (11/38) of the fingers had normal sense, 60.5% (23/38) had diminished light touch, 7.9% (3/38) had diminished protective sensation, and 2.6% (1/38) had loss of protective sensation. Mean static and dynamic two-point discriminations were 7.2 mm (3-11 mm), and 4.60 mm (3-6 mm), respectively. Vibratory testing revealed increased vibration in 42.1% of the fingers, decreased vibration in 36.8%, and equal vibration when compared with the non-injured fingers in 21.1%. Atrophy was present in 14 (36.8%) fingers and negatively affected the results. Nail deformities, cold intolerance, return to work, and the effect of sensory education were investigated. Comparison of crush and clean cut injuries did not yield any significant difference in any of the parameters. Patients who received sensory education had significantly better results in sensory testing. The results were classified as excellent, good, and poor based on results of two-point discrimination tests. The outcome was excellent in 18 fingers and good in 20 fingers. Overall, satisfactory sensory recovery was achieved in fingertip replantations without nerve repair. PMID:18683863

  1. 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

  2. The importance of sensory nerve endings as sites of drug action.

    PubMed

    Ginzel, K H

    1975-01-01

    The role that sensory nerve endings can play in drug action and the strategy used for its experimental analysis and proof is first exemplified by three effects of nicotine which are seen when the lowest effective doses of the drug are given intravenously in the cat: (1) a vasopressor effect due to arterial chemoreceptor stimulation; (2) a triad of bradycardia, hypotension and apnea, and (3) a depressant effect upon somatic motor activity, both of which are traced to vagal afferent endings in the pulmonary circulation. While receptors in the lung are responsible at least for the initial phase of the reflex responses listed in (2) and (3), sensory endings in heart, aorta, and carotid sinus region may be recruited into action as the drug reaches them. Several of these reflex effects can also be elicited by other sensory stimulant agents such as phenyldiguanide, 5-hydroxytryptamine, and veratrum alkaloids. In the second part, a general outline is given of what may be classified as 'Afferent Pharmacology', dealing with drug action upon sensory receptors and with the resulting remote drug effects. The action upon sensory receptors can either be a direct one ('primary' drug effect) consisting of stimulation, sensitization, desensitization, depression or combinations thereof, or an indirect ('secondary') effect brought about by a variety of drug-induced changes in the tissues surrounding the receptors. Depending on the nature of the primary or secondary action, the remote drug effect can be either an initiation, modification or impairment of those reflexes which have their origin in the sensory endings acted upon. Indeed, the grossly observable pharmacological actions of 'afferent drugs' are generally those relating to the reflex response. To avoid blurring of the boundaries of afferent pharmacology, drugs acting on central synapses of reflex pathways, or on the elaborate efferent control system of afferent input, are not included. A discussion follows of the topics of investigation, the influence of experimental conditions and anesthesia, various approaches and methods, the physiological and pharmacological importance of inquiry in this area, and some of the therapeutic aspects. Finally, brief mention is made of certain features and problems which appear to be characteristic of afferent pharmacology. PMID:1099463

  3. Uses of skin biopsy for sensory and autonomic nerve assessment.

    PubMed

    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 intraepidermal 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

  4. 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

  5. Role of intact cardiac nerves and reflex mechanisms in desensitization to catecholamines in conscious dogs.

    PubMed Central

    Nejima, J; Uemura, N; Vatner, D E; Homcy, C J; Hintze, T H; Vatner, S F

    1990-01-01

    To study chronic catecholamine desensitization, mini-osmotic pumps were implanted subcutaneously to deliver NE, (0.5 micrograms/kg/min) or saline over 3-4 wk in dogs instrumented with left ventricular (LV) pressure gauges and arterial and left atrial pressure catheters. An acute challenge to NE (0.4 micrograms/kg/min) in intact, conscious dogs increased LV dP/dt by 1,531 +/- 208 mmHg/s before NE pumps, and by a similar amount, 1,340 +/- 166 mmHg/s, 3-4 wk after NE pumps. In contrast, an acute challenge to isoproterenol (ISO, 0.4 micrograms/kg/min) increased LV dP/dt by 5,344 +/- 532 mmHg/s before NE pumps, and significantly less (P less than 0.05; 2,425 +/- 175 mmHg/s) after NE pumps. In the presence of ganglionic and alpha 1-adrenergic blockades, NE (0.4 micrograms/kg/min) increased LV dP/dt by 3,656 +/- 468 mmHg/s before NE pumps and significantly less (P less than 0.01; 1,459 +/- 200 mmHg/s) after NE pumps. Confirming this, an acute challenge to NE (0.4 micrograms/kg/min) in dogs with arterial baroreceptor denervation increased LV dP/dt by 3,732 +/- 896 mmHg/s before NE pumps, and significantly less (P less than 0.05, 1,725 +/- 408 mmHg/s) after NE pumps. In addition, in cardiac denervated dogs, NE (0.4 micrograms/kg/min) increased LV dP/dt by 9,901 +/- 1,404 mmHg/s before NE pumps and significantly less (P less than 0.01, 2,690 +/- 306 mmHg/s) after NE pumps. Desensitization of heart rate responses to NE challenge was also more apparent in the absence of reflex mechanisms. Thus, neural reflex mechanisms play a major role in physiological expression of cardiac desensitization to catecholamines in conscious dogs. PMID:2254459

  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. 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-?m output of a diode laser, delivered through a 200-?m silica fiber, was used for photostimulation. Nodose neurons express the vanilloid receptor, TRPV1, which is a non-selective cation channel that opens in response to significant temperature jumps above 37 C. Opening TRPV1 channels allows entry of cations, including calcium (Ca 2+), into the cell to cause membrane depolarization. Therefore, to monitor TRPV1 activation consequent to photostimulation, we used fura-2, a fluorescent Ca 2+ indicator, to monitor the rise in intracellular Ca 2+ concentration ([Ca 2+]i). Brief trains of 2-msec IR pulses activated TRPV1 rapidly and reversibly, as evidenced by transient rises in [Ca 2+]i (referred to as Ca 2+ transients). Consistent with the Ca 2+ transients arising from influx of Ca 2+, identical photostimulation failed to evoke Ca 2+ responses in the absence of extracellular Ca 2+. Furthermore, the photo-induced Ca 2+ signals were abolished by capsazepine, a specific blocker of TRPV1, indicating that the responses were indeed mediated by TRPV1. We discuss the feasibility of using focal IR stimulation to probe neuronal circuit properties in intact neural tissue, and compare IR stimulation with another photostimulation technique-focal photolytic release of "caged" molecules.

  8. 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

  9. Changes in sensory activity of ocular surface sensory nerves during allergic keratoconjunctivitis.

    PubMed

    Acosta, M Carmen; Luna, Carolina; Quirce, Susana; Belmonte, Carlos; Gallar, Juana

    2013-11-01

    Peripheral neural mechanisms underlying the sensations of irritation, discomfort, and itch accompanying the eye allergic response have not been hitherto analyzed. We explored this question recording the changes in the electrical activity of corneoconjunctival sensory nerve fibers of the guinea pig after an ocular allergic challenge. Sensitization was produced by i.p. ovalbumin followed by repeated application in the eye of 10% ovalbumin on days 14 to 18. Blinking and tearing rate were measured. Spontaneous and stimulus-evoked (mechanical, thermal, chemical) impulse activity was recorded from mechanonociceptor, polymodal nociceptor and cold corneoscleral sensory afferent fibers. After a single (day 14) or repeated daily exposures to the allergen during the following 3 to 4days, tearing and blinking rate increased significantly. Also, sensitization was observed in mechanonociceptors (transient reduction of mechanical threshold only on day 14) and in polymodal nociceptors (sustained enhancement of the impulse response to acidic stimulation). In contrast, cold thermoreceptors showed a significant decrease in basal ongoing activity and in the response to cooling. Treatment with the TRPV1 and TRPA1 blockers capsazepine and HC-030031 reversed the augmented blinking. Only capsazepine attenuated tearing rate increase and sensitization of the polymodal nociceptors response to CO2. Capsazepine also prevented the decrease in cold thermoreceptor activity caused by the allergic challenge. We conclude that changes in nerve impulse activity accompanying the ocular allergic response, primarily mediated by activation of nociceptor's TRPV1 and to a lesser degree by activation of TRPA1 channels, explain the eye discomfort sensations accompanying allergic episodes. PMID:23867735

  10. Impaired sensory nerve function and axon morphology in mice with diabetic neuropathy

    PubMed Central

    Lennertz, Richard C.; Medler, Karen A.; Bain, James L.; Wright, Douglas E.

    2011-01-01

    Diabetes is the most prevalent metabolic disorder in the United States, and between 50% and 70% of diabetic patients suffer from diabetes-induced neuropathy. Yet our current knowledge of the functional changes in sensory nerves and their distal terminals caused by diabetes is limited. Here, we set out to investigate the functional and morphological consequences of diabetes on specific subtypes of cutaneous sensory nerves in mice. Diabetes was induced in C57Bl/6 mice by a single intraperitoneal injection of streptozotocin. After 68 wk, mice were characterized for behavioral sensitivity to mechanical and heat stimuli followed by analysis of sensory function using teased nerve fiber recordings and histological assessment of nerve fiber morphology. Diabetes produced severe functional impairment of C-fibers and rapidly adapting A?-fibers, leading to behavioral hyposensitivity to both mechanical and heat stimuli. Electron microscopy images showed that diabetic nerves have axoplasm with more concentrated organelles and frequent axon-myelin separations compared with control nerves. These changes were restricted to the distal nerve segments nearing their innervation territory. Furthermore, the relative proportion of A?-fibers was reduced in diabetic skin-nerve preparations compared with nondiabetic control mice. These data identify significant deficits in sensory nerve terminal function that are associated with distal fiber loss, morphological damage, and behavioral hyposensitivity in diabetic C57Bl/6 mice. These findings suggest that diabetes damages sensory nerves, leading to functional deficits in sensory signaling that underlie the loss of tactile acuity and pain sensation associated with insensate diabetic neuropathy. PMID:21653724

  11. Sensory outcomes of the anterior tongue after lingual nerve repair in oropharyngeal cancer.

    PubMed

    Elfring, T T; Boliek, C A; Seikaly, H; Harris, J; Rieger, J M

    2012-03-01

    Primary treatment of oropharyngeal cancer often involves surgical resection and reconstruction of the affected area. However, during base of tongue reconstruction the lingual nerve is often severed on one or both sides, affecting sensation in the preserved tissue of the anterior tongue. The loss of specific tongue sensations could negatively affect a person's oral function and quality of life. The aim of this study was to explore the effects of different types of lingual nerve intervention on sensory function for patients with base of tongue cancer as compared to healthy, age-matched adults. Subjects included 30 patients who had undergone primary oropharyngeal reconstruction with a radial forearm free-flap and 30 matched controls. Sensations tested were temperature, two-point discrimination, light touch, taste, oral stereognosis and texture on the anterior two-thirds of the tongue. Results indicated that type of surgical nerve repair may not have a significant impact on overall sensory outcomes, providing mixed results for either nerve repair technique. Sensations for the nonoperated tongue side and operated side with lingual nerve intact were comparable to matched controls, with mixed outcomes for nerve repair. The poorest sensory outcomes were observed in patients with the lingual nerve severed, while all patients with lingual nerve intervention exhibited deteriorated taste sensation on the affected tongue side. Overall, patients in this study who had undergone oropharyngeal reconstruction with lingual nerve intervention exhibited decreased levels of sensation on the operated tongue side, with minimal differences between types of lingual nerve repair. PMID:21923892

  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. 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.

  14. 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

  15. 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

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

    PubMed

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

    2015-12-01

    Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that primarily targets the motor system. Although much is known about the effects of ALS on motor neurons and glial cells, little is known about its effect on proprioceptive sensory neurons. This study examines proprioceptive sensory neurons in mice harboring mutations associated with ALS, in SOD1(G93A) and TDP43(A315T) transgenic mice. In both transgenic lines, we found fewer proprioceptive sensory neurons containing fluorescently tagged cholera toxin in their soma five days after injecting this retrograde tracer into the tibialis anterior muscle. We asked whether this is due to neuronal loss or selective degeneration of peripheral nerve endings. We found no difference in the total number and size of proprioceptive sensory neuron soma between symptomatic SOD1(G93A) and control mice. However, analysis of proprioceptive nerve endings in muscles revealed early and significant alterations at Ia/II proprioceptive nerve endings in muscle spindles before the symptomatic phase of the disease. Although these changes occur alongside those at ?-motor axons in SOD1(G93A) mice, Ia/II sensory nerve endings degenerate in the absence of obvious alterations in ?-motor axons in TDP43(A315T) transgenic mice. We next asked whether proprioceptive nerve endings are similarly affected in the spinal cord and found that nerve endings terminating on ?-motor neurons are affected during the symptomatic phase and after peripheral nerve endings begin to degenerate. Overall, we show that Ia/II proprioceptive sensory neurons are affected by ALS-causing mutations, with pathological changes starting at their peripheral nerve endings. J. Comp. Neurol. 523:2477-2494, 2015. 2015 Wiley Periodicals, Inc. PMID:26424446

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

    PubMed

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

    2015-12-01

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

  18. Loss of Corneal Sensory Nerve Fibers in SIV-Infected Macaques

    PubMed Central

    Dorsey, Jamie L.; Mangus, Lisa M.; Oakley, Jonathan D.; Beck, Sarah E.; Kelly, Kathleen M.; Queen, Suzanne E.; Metcalf Pate, Kelly A.; Adams, Robert J.; Marfurt, Carl F.; Mankowski, Joseph L.

    2015-01-01

    Peripheral neuropathy is the most frequent neurological complication of HIV infection, affecting more than one-third of infected patients, including patients treated with antiretroviral therapy. Although emerging noninvasive techniques for corneal nerve assessments are increasingly being used to diagnose and monitor peripheral neuropathies, corneal nerve alterations have not been characterized in HIV. Here, to determine whether SIV infection leads to corneal nerve fiber loss, we immunostained corneas for the nerve fiber marker ?III tubulin. We developed and applied both manual and automated methods to measure nerves in the corneal subbasal plexus. These counting methods independently indicated significantly lower subbasal corneal nerve fiber density among SIV-infected animals that rapidly progressed to AIDS compared with slow progressors. Concomitant with decreased corneal nerve fiber density, rapid progressors had increased levels of SIV RNA and CD68-positive macrophages and expression of glial fibrillary acidic protein by glial satellite cells in the trigeminal ganglia, the location of the neuronal cell bodies of corneal sensory nerve fibers. In addition, corneal nerve fiber density was directly correlated with epidermal nerve fiber length. These findings indicate that corneal nerve assessment has great potential to diagnose and monitor HIV-induced peripheral neuropathy and to set the stage for introducing noninvasive techniques to measure corneal nerve fiber density in HIV clinical settings. PMID:24828391

  19. BREAST CANCER-INDUCED BONE REMODELING, SKELETAL PAIN AND SPROUTING OF SENSORY NERVE FIBERS

    PubMed Central

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

    2011-01-01

    Breast cancer metastasis to bone is frequently accompanied by pain. What remains unclear is why this pain tends to become more severe and difficult to control with disease progression. Here we test the hypothesis that with disease progression sensory nerve fibers that innervate the breast cancer bearing bone undergo a pathological sprouting and reorganization, which in other non-malignant pathologies has been shown to generate and maintain chronic pain. Injection of human breast cancer cells (MDA-MB-231-BO) into the femoral intramedullary space of female athymic nude mice induces sprouting of calcitonin gene-related peptide (CGRP+) sensory nerve fibers. Nearly all CGRP+ nerve fibers that undergo sprouting also co-express tropomyosin receptor kinase A (TrkA+) and growth associated protein-43 (GAP43+). This ectopic sprouting occurs in periosteal sensory nerve fibers that are in close proximity to breast cancer cells, tumor-associated stromal cells and remodeled cortical bone. Therapeutic treatment with an antibody that sequesters nerve growth factor (NGF), administered when the pain and bone remodeling were first observed, blocks this ectopic sprouting and attenuates cancer pain. The present data suggest that the breast cancer cells and tumor-associated stromal cells express and release NGF, which drives bone pain and the pathological reorganization of nearby CGRP+ / TrkA+ / GAP43+ sensory nerve fibers. PMID:21497141

  20. 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

  1. 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

  2. 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 Freunds 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

  3. 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

  4. 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

  5. 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.

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

    NASA Astrophysics Data System (ADS)

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

    1990-06-01

    Over the past ten years there has been an increasing interest in the use of lasers for neurosurgical and neurological procedures. Novel recent applications range from neurosurgical procedures such as dorsal root entry zone lesions made with argon and carbon dioxide microsurgical lasers to pain relief by low power laser irradiation of the appropriate painful nerve or affected region1 '2 However, despite the widespread clinical applications of laser light, very little is known about the photobiological interactions between laser light and nervous tissue. The present studies were designed to evaluate the effects of pulsed Nd:YAG laser light on neural impulse conduction and axoplasmic transport in sensory nerves in rats and cats. Our data indicate that Q-switched Nd:YAG laser irradiation can induce a preferential impairment of (1) the synaptic effects of small afferent fibers on dorsal horn cells in the spinal cord and of (2) small slow conducting sensory nerve fibers in dorsal roots and peripheral nerves. These results imply that laser light might have selective effects on impulse conduction in slow conducting sensory nerve fibers. In agreement with our elecirophysiological observations recent histological data from our laboratory show, that axonal transport of the enzyme horseradish peroxidase is selectively impaired in small sensory nerve fibers. In summary these data indicate, that Q-switched Nd:YAG laser irradiation can selectively impair neural conduction and axoplasmic transport in small sensory nerve fibers as compared to fast conducting fibers. A selective influence of laser irradiation on slow conducting fibers could have important clinical applications, especially for the treatment of chronic pain.

  7. 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

  8. Nerve injury induces the expression of syndecan-1 heparan sulfate proteoglycan in primary sensory neurons.

    PubMed

    Murakami, K; Tanaka, T; Bando, Y; Yoshida, S

    2015-08-01

    Heparan sulfate proteoglycans (HSPGs) have important functions in development of the central nervous system; however, their functions in nerve injury are not yet fully understood. We previously reported the expression of syndecan-1, a type of HSPG, in cranial motor neurons after nerve injury, suggesting the importance of syndecan-1 in the pathology of motor nerve injury. In this study, we examined the expression of syndecan-1, a type of HSPG, in primary sensory neurons after nerve injury in mice. Sciatic nerve axotomy strongly induced the expression of syndecan-1 in a subpopulation of injured dorsal root ganglion (DRG) neurons, which were small in size and had CGRP- or isolectin B4-positive fibers. Syndecan-1 was also distributed in the dorsal horn of the spinal cord ipsilateral to the axotomy, and located on the membrane of axons in lamina II of the dorsal horn. Not only sciatic nerve axotomy, infraorbital nerve axotomy also induced the expression of syndecan-1 in trigeminal ganglion neurons. Moreover, syndecan-1 knockdown in cultured DRG neurons induced a shorter neurite extension. These results suggest that syndecan-1 expression in injured primary sensory neurons may have functional roles in nerve regeneration and synaptic plasticity, resulting in the development of neuropathic pain. PMID:26002314

  9. White adipose tissue sensory nerve denervation mimics lipectomy-induced compensatory increases in adiposity.

    PubMed

    Shi, Haifei; Bartness, Timothy J

    2005-08-01

    The sensory innervation of white adipose tissue (WAT) is indicated by the labeling of sensory bipolar neurons in the dorsal root ganglion after retrograde dye placement into WAT. In addition, immunoreactivity (ir) for sensory-associated neuropeptides such as calcitonin gene-related peptide (CGRP) and substance P in WAT pads also supports the notion of WAT sensory innervation. The function of this sensory innervation is unknown but could involve conveying the degree of adiposity to the brain. In tests of total body fat regulation, partial surgical lipectomy triggers compensatory increases in the mass of nonexcised WAT, ultimately resulting in restoration of total body fat levels in Siberian hamsters and other animals. The signal that triggers this compensation is unknown but could involve disruption of WAT sensory innervation that accompanies lipectomy. Therefore, a local and selective sensory denervation was accomplished by microinjecting the sensory nerve neurotoxin capsaicin bilaterally into epididymal WAT (EWAT) of Siberian hamsters, whereas controls received vehicle injections. Additional hamsters had bilateral EWAT lipectomy (EWATx) or sham lipectomy. As seen previously, EWATx resulted in significantly increased retroperitoneal WAT (RWAT) and inguinal WAT (IWAT) masses. Capsaicin treatment significantly decreased CGRP- but not tyrosine hydroxylase-ir, attesting to the diminished and selective sensory innervation. Capsaicin-treated hamsters also had increased RWAT and, to a lesser degree, IWAT mass largely mimicking the WAT mass increases seen after lipectomy. Collectively, these data suggest the possibility that information related to peripheral lipid stores may be conveyed to the brain via the sensory innervation of WAT. PMID:15860651

  10. 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

  11. 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 skinsaphenous 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 skinnerve recording station (few days), the preparation of the skin and the adherent saphenous nerve in the mouse (1545 min) and the isolation and recording of neurons (approximately 13 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

  12. Painful nerve injury increases plasma membrane Ca2+-ATPase activity in axotomized sensory neurons

    PubMed Central

    2012-01-01

    Background The plasma membrane Ca2+-ATPase (PMCA) is the principal means by which sensory neurons expel Ca2+ and thereby regulate the concentration of cytoplasmic Ca2+ and the processes controlled by this critical second messenger. We have previously found that painful nerve injury decreases resting cytoplasmic Ca2+ levels and activity-induced cytoplasmic Ca2+ accumulation in axotomized sensory neurons. Here we examine the contribution of PMCA after nerve injury in a rat model of neuropathic pain. Results PMCA function was isolated in dissociated sensory neurons by blocking intracellular Ca2+ sequestration with thapsigargin, and cytoplasmic Ca2+ concentration was recorded with Fura-2 fluorometry. Compared to control neurons, the rate at which depolarization-induced Ca2+ transients resolved was increased in axotomized neurons after spinal nerve ligation, indicating accelerated PMCA function. Electrophysiological recordings showed that blockade of PMCA by vanadate prolonged the action potential afterhyperpolarization, and also decreased the rate at which neurons could fire repetitively. Conclusion We found that PMCA function is elevated in axotomized sensory neurons, which contributes to neuronal hyperexcitability. Accelerated PMCA function in the primary sensory neuron may contribute to the generation of neuropathic pain, and thus its modulation could provide a new pathway for peripheral treatment of post-traumatic neuropathic pain. PMID:22713297

  13. Changes induced by peripheral nerve injury in the morphology and nanomechanics of sensory neurons

    NASA Astrophysics Data System (ADS)

    Benzina, Ouafa; Szabo, Vivien; Lucas, Olivier; Saab, Marie-belle; Cloitre, Thierry; Scamps, Frdrique; Gergely, Csilla; Martin, Marta

    2013-06-01

    Peripheral nerve injury in vivo promotes a regenerative growth in vitro characterized by an improved neurite regrowth. Knowledge of the conditioning injury effects on both morphology and mechanical properties of live sensory neurons could be instrumental to understand the cellular and molecular mechanisms leading to this regenerative growth. In the present study, we use differential interference contrast microscopy, fluorescence microscopy and atomic force microscopy (AFM) to show that conditioned axotomy, induced by sciatic nerve injury, does not increase somatic size of sensory neurons from adult mice lumbar dorsal root ganglia but promotes the appearance of longer and larger neurites and growth cones. AFM on live neurons is also employed to investigate changes in morphology and membrane mechanical properties of somas of conditioned neurons following sciatic nerve injury. Mechanical analysis of the soma allows distinguishing neurons having a regenerative growth from control ones, although they show similar shapes and sizes.

  14. Precision pinch performance in patients with sensory deficits of the median nerve at the carpal tunnel.

    PubMed

    Yen, Wei-Jang; Kuo, Yao-Lung; Kuo, Li-Chieh; Chen, Shu-Min; Kuan, Ta-Shen; Hsu, Hsiu-Yun

    2014-01-01

    To investigate how sensory symptoms impact the motor control of hands, in this study we examined the differences in conventional sensibility assessments and pinch force control in the pinch-holding-up activity (PHUA) test between carpal tunnel syndrome (CTS) patients and healthy controls. CTS patients (n = 82) with 122 affected hands and an equal number of control subjects were recruited to participate in the threshold, discrimination, and PHUA tests. The patients showed significantly poorer hand sensibility and lower efficiency of force adjustment in the PHUA test as compared with the control subjects. Baseline pinch strength and the percentage of maximal pinch strength for the PHUA were significantly higher for the subgroup of sensory nerve action potential (SNAP) of <16 ?V than for the subgroup of SNAP of ?16 ?V. Using a PHUA perspective to analyze the efficiency of force-adjustment could assist the clinical detection of sensory nerve dysfunction. PMID:24496877

  15. Electrical neurostimulation for chronic pain: On selective relay of sensory neural activities in myelinated nerve fibers.

    PubMed

    Sacre, Pierre; Sarma, Sridevi V; Yun Guan; Anderson, William S

    2015-08-01

    Chronic pain affects about 100 million adults in the US. Despite their great need, neuropharmacology and neurostimulation therapies for chronic pain have been associated with suboptimal efficacy and limited long-term success, as their mechanisms of action are unclear. Yet current computational models of pain transmission suffer from several limitations. In particular, dorsal column models do not include the fundamental underlying sensory activity traveling in these nerve fibers. We developed a (simple) simulation test bed of electrical neurostimulation of myelinated nerve fibers with underlying sensory activity. This paper reports our findings so far. Interactions between stimulation-evoked and underlying activities are mainly due to collisions of action potentials and losses of excitability due to the refractory period following an action potential. In addition, intuitively, the reliability of sensory activity decreases as the stimulation frequency increases. This first step opens the door to a better understanding of pain transmission and its modulation by neurostimulation therapies. PMID:26737344

  16. Modulation of sympathetic nerve activity by perivascular sensory nerves in the arterioles of the guinea-pig small intestine.

    PubMed

    Coffa; Kotecha

    1999-09-24

    OBJECTIVE: The aim of this study was to assess the role of perivascular sensory nerves in modulating constrictions of intestinal submucosal arterioles. METHODS: Arteriole constrictions were induced either by nerve released adenosine 5'-triphosphate (ATP) or exogenous ATP or phenylephrine (PE). Individual nerve shocks were used to elicit excitatory junction potentials (EJPs) in the arteriole smooth muscle whereas trains of stimuli were used to evoke transient constrictions of the arteriole. Effects of the sensory neurotoxin, capsaicin, were examined on constrictions and EJPs. RESULTS: Pre-treatment of the arteriole preparation with capsaicin did not cause any significant change in the amplitude of arteriole constrictions to exogenously applied ATP or PE. However, there was a significant increase in the amplitude of neurally evoked arteriole constrictions and EJPs, without a significant change in the decay time constant (tau(decay)) of the EJPs. Exogenous application of calcitonin gene related peptide (CGRP) significantly decreased tau(decay) of the EJPs without affecting their amplitude, whereas substance P (SP) significantly decreased the amplitude of EJPs without affecting tau(decay). Both, CGRP and SP, decreased the amplitude of neurally evoked and ATP induced constrictions. Whilst the inhibitory effects of CGRP on evoked and ATP induced constrictions were not significantly different, the reduction in evoked constrictions obtained with SP was significantly greater than the reduction in ATP induced constrictions. SP antagonist significantly increased the amplitude of neurally evoked constrictions. CONCLUSIONS: It is concluded that capsaicin-sensitive afferents inhibit the release of transmitter from perivascular sympathetic nerves via the prejunctional modulatory action of SP. The other putative sensory neurotransmitter, CGRP, appears to act postjunctionally on the arteriole smooth muscle. PMID:11130956

  17. 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.

  18. Menthol Enhances the Desensitization of Human α3β4 Nicotinic Acetylcholine Receptors.

    PubMed

    Ton, Hoai T; Smart, Amanda E; Aguilar, Brittany L; Olson, Thao T; Kellar, Kenneth J; Ahern, Gerard P

    2015-08-01

    The α3β4 nicotinic acetylcholine receptor (nAChR) subtype is widely expressed in the peripheral and central nervous systems, including in airway sensory nerves. The nAChR subtype transduces the irritant effects of nicotine in tobacco smoke and, in certain brain areas, may be involved in nicotine addiction and/or withdrawal. Menthol, a widely used additive in cigarettes, is a potential analgesic and/or counterirritant at sensory nerves and may also influence nicotine's actions in the brain. We examined menthol's effects on recombinant human α3β4 nAChRs and native nAChRs in mouse sensory neurons. Menthol markedly decreased nAChR activity as assessed by Ca(2+) imaging, (86)Rb(+) efflux, and voltage-clamp measurements. Coapplication of menthol with acetylcholine or nicotine increased desensitization, demonstrated by an increase in the rate and magnitude of the current decay and a reduction of the current integral. These effects increased with agonist concentration. Pretreatment with menthol followed by its washout did not affect agonist-induced desensitization, suggesting that menthol must be present during the application of agonist to augment desensitization. Notably, menthol acted in a voltage-independent manner and reduced the mean open time of single channels without affecting their conductance, arguing against a simple channel-blocking effect. Further, menthol slowed or prevented the recovery of nAChRs from desensitization, indicating that it probably stabilizes a desensitized state. Moreover, menthol at concentrations up to 1 mM did not compete for the orthosteric nAChR binding site labeled by [(3)H]epibatidine. Taken together, these data indicate that menthol promotes desensitization of α3β4 nAChRs by an allosteric action. PMID:25964258

  19. 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

  20. 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 patients 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 (1516 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

  1. Sickle cell disease in mice is associated with sensitization of sensory nerve fibers.

    PubMed

    Kenyon, Nicholas; Wang, Li; Spornick, Nicholas; Khaibullina, Alfia; Almeida, Luis Ef; Cheng, Yao; Wang, Jichuan; Guptill, Virginia; Finkel, Julia C; Quezado, Zenaide M N

    2015-01-01

    The pain phenotype in sickle cell disease (SCD) patients is highly variable. A small percentage of SCD patients experience many vaso-occlusive crises/year, 5% of patients account for over 30% of pain episodes, while 39% report few episodes of severe pain. Clearly, a better understanding of the pathobiology of SCD is needed to improve its therapy. Humanized sickle cell mice recapitulate several phenotypes of SCD patients and provide a model for the study of SCD pain. Researchers have shown that one strain of humanized SCD mice, the BERK strain, has abnormal pain phenotype. However, the nociception phenotype of another humanized SCD mouse strain, the Townes strain, has not been described. In a large cross-sectional study of BERK and Townes SCD mice, we examined thermosensory response and sensory nerve fiber function using sine-wave electrical stimulation at 2000, 250, and 5?Hz to stimulate preferentially A?, A?, and C sensory nerve fibers, respectively. We found that BERK and Townes mice, compared to respective controls, had decreases in 2000, 250, and 5?Hz current vocalization thresholds in patterns that suggest sensitization of a broad spectrum of sensory nerve fibers. In addition, the pattern of sensitization of sensory fibers varied according to strain, sex, age, and mouse genotype. In a similarly variable pattern, Townes and BERKs also had significantly altered sensitivity to noxious thermal stimuli in agreement with what has been shown by others. In summary, the analysis of somatosensory function using sine-wave electrical stimulation in humanized sickle cell mice suggests that in SCD, both myelinated and unmyelinated, fibers are sensitized. The pattern of sensory fiber sensitization is distinct from that observed in pain models of neuropathic and inflammatory pain. These findings raise the possibility that sensitization of a broad spectrum of sensory fibers might contribute to the altered and variable nociception phenotype in SCD. PMID:25070860

  2. Normal threshold values for a monofilament sensory test in sural and radial cutaneous nerves in Indian and Nepali volunteers.

    PubMed

    Wagenaar, Inge; Brandsma, Wim; Post, Erik; Richardus, Jan Hendrik

    2014-12-01

    The monofilament test (MFT) is a reliable method to assess sensory nerve function in leprosy and other neuropathies. Assessment of the radial cutaneous and sural nerves, in addition to nerves usually tested, can help improve diagnosis and monitoring of nerve function impairment (NFI). To enable the detection of impairments in leprosy patients, it is essential to know the monofilament threshold of these two nerves in normal subjects. The radial cutaneous, sural, ulnar, median and posterior tibial nerves of 245 volunteers were tested. All nerves were tested at three sites on both left and right sides. Normal monofilament thresholds were calculated per test-site and per nerve. We assessed 490 radial cutaneous and 482 sural nerves. The normal monofilament was 2 g (Filament Index Number (FIN) 4.31) for the radial cutaneous and 4 g (FIN 4.56) for the sural nerve, although heavy manual laborers demonstrated a threshold of 10 g (FIN 5.07) for the sural nerve. For median and ulnar nerves, the 200 mg (FIN 3.61) filament was confirmed as normal while the 4 g (FIN 4.56) filament was normal for the posterior tibial. Age and occupation have an effect on the mean touch sensitivity but do not affect the normal threshold for the radial cutaneous and sural nerves. The normal thresholds for the radial cutaneous and sural nerves are determined as the 2 g (FIN 4.31) and the 4 g (FIN 4.56) filaments, respectively. The addition of the radial cutaneous and sural nerve to sensory nerve assessment may improve the diagnosis of patients with impaired sensory nerve function. PMID:25675652

  3. 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

  4. 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

  5. On the identification of sensory information from mixed nerves by using single-channel cuff electrodes

    PubMed Central

    2010-01-01

    Background Several groups have shown that the performance of motor neuroprostheses can be significantly improved by detecting specific sensory events related to the ongoing motor task (e.g., the slippage of an object during grasping). Algorithms have been developed to achieve this goal by processing electroneurographic (ENG) afferent signals recorded by using single-channel cuff electrodes. However, no efforts have been made so far to understand the number and type of detectable sensory events that can be differentiated from whole nerve recordings using this approach. Methods To this aim, ENG afferent signals, evoked by different sensory stimuli were recorded using single-channel cuff electrodes placed around the sciatic nerve of anesthetized rats. The ENG signals were digitally processed and several features were extracted and used as inputs for the classification. The work was performed on integral datasets, without eliminating any noisy parts, in order to be as close as possible to real application. Results The results obtained showed that single-channel cuff electrodes are able to provide information on two to three different afferent (proprioceptive, mechanical and nociceptive) stimuli, with reasonably good discrimination ability. The classification performances are affected by the SNR of the signal, which in turn is related to the diameter of the fibers encoding a particular type of neurophysiological stimulus. Conclusions Our findings indicate that signals of acceptable SNR and corresponding to different physiological modalities (e.g. mediated by different types of nerve fibers) may be distinguished. PMID:20423488

  6. 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

  7. 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

  8. 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

  9. 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.

  10. 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

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

    PubMed

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

    2014-08-15

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

  12. 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

  13. Store-operated calcium entry in vagal sensory nerves is independent of Orai channels.

    PubMed

    Hooper, Justin Shane; Hadley, Stephen H; Mathews, Adithya; Taylor-Clark, Thomas E

    2013-03-29

    Vagal sensory nerves innervate the majority of visceral organs (e.g., heart, lungs, GI tract, etc) and their activation is critical for defensive and regulatory reflexes. Intracellular Ca(2+) is a key regulator of neuronal excitability and is largely controlled by the Ca(2+) stores of the endoplasmic reticulum. In other cell types store-operated channels (SOC) have been shown to contribute to the homeostatic control of intracellular Ca(2+). Here, using Ca(2+) imaging, we have shown that ER depletion in vagal sensory neurons (using thapsigargin or caffeine) in the absence of extracellular Ca(2+) evoked Ca(2+) influx upon re-introduction of Ca(2+) into the extracellular buffer. This store-operated Ca(2+) entry (SOCE) was observed in approximately 25-40% of vagal neurons, equally distributed among nociceptive and non-nociceptive sensory subtypes. SOCE was blocked by Gd(3+) but not by the Orai channel blocker SKF96365. We found Orai channel mRNA in extracts from whole vagal ganglia, but when using single cell RT-PCR analysis we found only 3 out of 34 neurons expressed Orai channel mRNA, indicating that Orai channel expression in the vagal ganglia was likely derived from non-neuronal cell types. Confocal microscopy of vagal neurons in 3 day cultures demonstrated rich ER tracker fluorescence throughout axonal and neurite structures and ER store depletion (thapsigargin) evoked Ca(2+) transients from these structures. However, no SOCE could be detected in the axonal/neurite structures of vagal neurons. We conclude that SOCE occurs in vagal sensory neuronal cell bodies through non-Orai mechanisms but is absent at nerve terminals. PMID:23399679

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

    PubMed

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

    2015-12-01

    Transient receptor potential ankyrin type 1 (TRPA1) and vanilloid type 1 (TRPV1) receptors are co-expressed in vagal pulmonary C-fiber sensory nerves. Because both these ligand-gated non-selective cation channels are sensitive to a number of endogenous inflammatory mediators, it is highly probable that they can be activated simultaneously during airway inflammation. Studies were carried out to investigate whether there is an interaction between these two polymodal transducers upon simultaneous activation, and how it modulates the activity of vagal pulmonary C-fiber sensory nerves. Our studies showed a distinct potentiating effect induced abruptly by simultaneous activations of TRPA1 and TRPV1 by their respective selective agonists, allyl isothiocyanate (AITC) and capsaicin (Cap), at near-threshold concentrations. This synergistic effect was demonstrated in the studies of single-unit recording of vagal bronchopulmonary C-fiber afferents and the reflex responses elicited by activation of these afferents in intact animals, as well as in the isolated nodose and jugular bronchopulmonary sensory neurons. This potentiating effect was absent when either AITC or Cap was replaced by non-TRPA1 and non-TRPV1 chemical activators of these neurons, demonstrating the selectivity of the interaction between these two TRP channels. Furthermore, the synergism was dependent upon the extracellular Ca(2+), and the rapid onset of the action further suggests that the interaction probably occurred locally at the sites of these channels. These findings suggest that the TRPA1-TRPV1 interaction may play an important role in regulating the function and excitability of pulmonary sensory neurons during airway inflammation, but the mechanism underlying this positive interaction is not yet fully understood. PMID:26283426

  15. 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.

  16. 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

  17. 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

  18. 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

  19. Mechanical sensitization of cutaneous sensory fibers in the spared nerve injury mouse model

    PubMed Central

    2013-01-01

    Background The spared nerve injury (SNI) model of neuropathic pain produces robust and reproducible behavioral mechanical hypersensitivity. Although this rodent model of neuropathic pain has been well established and widely used, peripheral mechanisms underlying this phenotype remain incompletely understood. Here we investigated the role of cutaneous sensory fibers in the maintenance of mechanical hyperalgesia in mice post-SNI. Findings SNI produced robust, long-lasting behavioral mechanical hypersensitivity compared to sham and nave controls beginning by post-operative day (POD) 1 and continuing through at least POD 180. We performed teased fiber recordings on single cutaneous fibers from the spared sural nerve using ex vivo skin-nerve preparations. Recordings were made between POD 1642 after SNI or sham surgery. A?-mechanoreceptors (AM) and C fibers, many of which are nociceptors, from SNI mice fired significantly more action potentials in response to suprathreshold mechanical stimulation than did fibers from either sham or nave control mice. However, there was no increase in spontaneous activity. Conclusions To our knowledge, this is the first study evaluating the contribution of primary afferent fibers in the SNI model. These data suggest that enhanced suprathreshold firing in AM and C fibers may play a role in the marked, persistent mechanical hypersensitivity observed in this model. These results may provide insight into mechanisms underlying neuropathic pain in humans. PMID:24286165

  20. 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.

  1. 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

  2. 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

  3. 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

  4. 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

  5. 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

  6. 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

  7. 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.

  8. A "cute" desensitization of TRPV1.

    PubMed

    Touska, Filip; Marsakova, Lenka; Teisinger, Jan; Vlachova, Viktorie

    2011-01-01

    Capsaicin and other vanilloids selectively excite and subsequently desensitize pain-conducting nerve fibers (nociceptors) and this process contributes to the analgesic (and thus therapeutically relevant) effects of these compounds. Such a desensitization process is triggered by the activation of the transient receptor potential vanilloid subtype 1 receptor channels (TRPV1) that open their cationic pores, permeable to sodium, potassium and calcium (Ca(2+)) ions. Depending on the duration of capsaicin exposure and the external calcium concentration, the Ca(2+) influx via TRPV1 channels desensitizes the channels themselves, which, from the cellular point of view, represents a feedback mechanism protecting the nociceptive neuron from toxic Ca(2+) overload. The 'acute desensitization' accounts for most of the reduction in responsiveness occurring within the first few (~20) seconds after the vanilloids are administered to the cell for the first time. Another form of desensitization is 'tachyphylaxis', which is a reduction in the response to repeated applications of vanilloid. The wealth of pathways following TRPV1 activation that lead to increased intracellular Ca(2+) levels and both forms of desensitization is huge and they might utilise just about every known type of signalling molecule. This review will not attempt to cover all historical aspects of research into all these processes. Instead, it will try to highlight some new challenging thoughts on the important phenomenon of TRPV1 desensitization and will focus on the putative mechanisms that are thought to account for the acute phase of this process. PMID:20932251

  9. Rehabilitation of peripheral nerve injuries.

    PubMed

    Frykman, G K; Waylett, J

    1981-04-01

    Rehabilitation of the patient with a peripheral nerve injury requires knowledge, understanding, and cooperation between the patient, the physician, and the therapist. Careful documentation of the patient's status prior to beginning rehabilitation and periodic follow-up assessments are of utmost importance. We have presented a detailed scheme for initial and follow-up evaluation. Prevention of unnecessary stiffness, swelling, and contractures is emphasized. Education of the patient to prevent the individual from doing further damage to the anesthetic area is important. Proper splinting techniques, from the postoperative splint and cast to splints that prevent deformities as well as overcome established contractures and improve function, will aid in the patient's recovery. Desensitization is an important aspect of sensory recovery, and sensory reeducation will aid in recovery of sensibility. Early tendon transfers are found to be particularly advantageous for high radial and median nerve palsies to gain functional recovery earlier and to allow the patient to become brace-free sooner. PMID:7243244

  10. 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 27months prior to participation in the study. The patient first practiced a cylindrical grasp task with SENS for 1hour daily over 29days. Pressure information from the affected thumb was fed back to the unaffected shoulder. The same patient practiced a tip pinch task with SENS for 1hour daily over 4days. 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 patients 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 7months 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

  11. 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.

  12. 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

  13. 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

  14. Substance P released from sensory nerve endings influences tear secretion and goblet cell function in the rat.

    PubMed

    Kovcs, Ills; Ludny, Andrea; Koszegi, Tams; Fehr, Jnos; Kovcs, Blint; Szolcsnyi, Jnos; Pintr, Erika

    2005-08-01

    The aim of this study was to present morphological and functional evidence to evaluate whether tear secretion is influenced by neuropeptides released from sensory nerve endings of the conjunctiva. Following unilateral electrical stimulation of the trigeminal ganglion, tears were collected at both sides and assessed for volume and protein concentration; as well as gel electrophoresis and luminol chemiluminescence with immunostaining to immunoglobulin A and lysozyme measurements. Goblet cell density (goblet cells/100 basal cells) was recorded during histopathological examination of removed lids. Rats were pretreated with atropine to block parasympathetic; guanethidine to block sympathetic neuronal pathways; or hexamethonium to block synaptic transmission in ganglia. Capsaicin was used to deplete neurotransmitters from sensory nerve endings or SR140333 to block substance P tachykinin NK1 receptor mediated responses. Effects of inadequate electrode position or incidental lesion of trigeminal ganglion were examined by placing the electrode in false position, or no stimulation at a correct position. Electrical stimulation resulted in 380% increase of tear secretion (p < 0.001) and 30% decrease of goblet cell density (p < 0.001) on the the stimulated side compared to the unstimulated side. Atropine, guanethidine and hexamethonium pretreatments had no effect (p > 0.05), but capsaicin and SR140333 inhibited the effect of stimulation (by 96% and 72%, respectively, p < 0.001). Inadequate stimulation did not increase the tear secretion (p < 0.05). Protein concentration decreased, whilst tear volume and total secreted protein increased (p < 0.005) after stimulation. Electrophoresis showed no difference in protein pattern between stimulated and control side and analysis of equivalent amount of tear protein with luminol chemiluminescence indicated no difference in immunoglobulin A and lysozyme ratio following stimulation (p>0.05). We conclude that antidromic electrical activation of conjunctival sensory nerve endings significantly increases water, mucus and protein phases of tear. It is suggested that the sensory neuropeptide substance P plays a pivotal role in this neurogenic regulatory mechanism. PMID:15992924

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

    PubMed

    Gohin, Stphanie; Decorps, Johanna; Sigaudo-Roussel, Dominique; Fromy, Brengre

    2015-09-01

    Cutaneous current-induced vasodilation (CIV) in response to galvanic current application is an integrative model of neurovascular interaction that relies on capsaicin-sensitive fiber activation. The upstream and downstream mechanisms related to the activation of the capsaicin-sensitive fibers involved in CIV are not elucidated. In particular, the activation of cutaneous transient receptor potential vanilloid type-1 (TRPV1) channels and/or acid-sensing ion channels (ASIC) (activators mechanisms) and the release of calcitonin gene-related peptide (CGRP) and substance P (SP) (effector mechanisms) have been tested. To assess cathodal CIV, we measured cutaneous blood flow using laser Doppler flowmetry for 20min following cathodal current application (240s, 100?A) on the skin of the thigh in anesthetized healthy rats for 20min. CIV was studied in rats treated with capsazepine and amiloride to inhibit TRPV1 and ASIC channels, respectively; CGRP8-37 and SR140333 to antagonize CGRP and neurokinin-1 (NK1) receptors, respectively; compared to their respective controls. Cathodal CIV was attenuated by capsazepine (122% vs 546%, P<0.001), amiloride (198% vs 616%, P<0.01), CGRP8-37 (156% vs 616%, P<0.001) and SR140333 (95% vs 546%, P<0.001) without changing local acidification. This is the first integrative study performed in healthy rats showing that cutaneous vasodilation in response to cathodal stimulation is initiated by activation of cutaneous TRPV1 and ASIC channels likely through local acidification. The involvement of CGRP and NK1 receptors suggests that cathodal CIV is the result of CGRP and SP released through activated capsaicin-sensitive fibers. Therefore cathodal CIV could be a valuable method to assess sensory neurovascular function in the skin, which would be particularly relevant to evaluate the presence of small nerve fiber disorders and the effectiveness of treatments. PMID:26205659

  16. 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

  17. Motor and sensory conduction velocities and amplitude of nerve or muscle potentials in the normal rat according to age.

    PubMed

    Hort-Legrand, C; Lestrade, R; Behar, A

    2001-01-01

    The relative changes in sensory and motor nerve conductions and SNAP and CMAP amplitudes were studied on the sural and tibial posterior nerves in anesthetized male rats, between the 1st and the 23rd month. Neural growth was controlled with the measure of the nerve path length on the skin, between stimulating and recording cathodes for the sural nerve and proximal and distal stimulating cathodes for the tibial posterior nerve. The sural SCV and SNAP amplitude are consistent with a more accurate method than the H-reflex one. Similar changes were observed in both parameters. During the maturation of the peripheral nervous system, between the 1st and the 5th month, parameters rapidly increased. Over 14 months old, parameters decrease: the diminution of SNAP and CMAP amplitudes is characteristic of aging. The results were analyzed through quadratic and linear regression and were similar to those in young and elderly human patients. Parabola curves fitted the best way to represent the evolution of parameters. Moreover, the linear regression permitted to divide the rat life in 3 parts and to distinguish a period between the 6th and 13th months during which studied parameters are considered as constant. SCV, MCV, SNAP and CMAP amplitudes from the 1st to the 5th, from 6th to 13th and over the 14th month, could be used as reference. PMID:12162582

  18. Inhibitory activity of the novel CB2 receptor agonist, GW833972A, on guinea-pig and human sensory nerve function in the airways

    PubMed Central

    Belvisi, M G; Patel, H J; Freund-Michel, V; Hele, D J; Crispino, N; Birrell, M A

    2008-01-01

    Background and purpose: Sensory nerves regulate central and local reflexes such as airway plasma protein leakage, bronchoconstriction and cough. Sensory nerve activity may be enhanced during inflammation such that these protective effects become exacerbated and deleterious. Cannabinoids are known to inhibit airway sensory nerve function. However, there is still controversy surrounding which receptor is involved in eliciting these effects. Experimental approach: We have adopted a pharmacological approach, including using a novel, more selective CB2 receptor agonist, GW 833972A (1000-fold selective CB2/CB1), and receptor selective antagonists to investigate the inhibitory activity of cannabinoids on sensory nerve activity in vitro and in vivo in guinea-pig models of cough and plasma extravasation. Key results: GW 833972A inhibited capsaicin-induced depolarization of the human and guinea-pig and prostaglandin E2 (PGE2) and hypertonic saline-induced depolarization of the guinea-pig isolated vagus nerve in vitro. GW 833972A also inhibited citric acid-induced cough but not plasma extravasation in the guinea-pig and this effect was blocked by a CB2 receptor antagonist. Conclusions and implications: This confirms and extends previous studies highlighting the role of CB2 receptors in the modulation of sensory nerve activity elicited both by the exogenous ligands capsaicin and hypertonic saline but also by endogenous modulators such as PGE2 and low pH stimuli. These data establish the CB2 receptor as an interesting target for the treatment of chronic cough. PMID:18695648

  19. 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.

  20. Continuous Femoral Nerve Blocks: The Impact of Catheter Tip Location Relative to the Femoral Nerve (Anterior Versus Posterior) on Quadriceps Weakness and Cutaneous Sensory Block

    PubMed Central

    Ilfeld, Brian M.; Loland, Vanessa J.; Sandhu, NavParkash S.; Suresh, Preetham J.; Bishop, Michael J.; Donohue, Michael C.; Ferguson, Eliza J.; Madison, Sarah J.

    2012-01-01

    Background During a continuous femoral nerve block, the influence of catheter tip position relative to the femoral nerve on infusion characteristics remains unknown. Methods We inserted bilateral femoral perineural catheters in volunteers (ultrasound-guided, needle in-plane). Subjects dominant side was randomized to have the catheter tip placed either anterior or posterior to the femoral nerve. The contralateral limb received the alternative position. Ropivacaine 0.1% was administered through both catheters concurrently for 6 hours (4 mL/h). Outcome measures included the maximum voluntary isometric contraction (MVIC) of the quadriceps femoris muscle and tolerance to cutaneous electrical current over to the distal quadriceps tendon. Measurements were performed at Hour 0 (baseline), and on the hour until Hour 9, as well as Hour 22. The primary endpoint was the MVIC of the quadriceps at Hour 6. Results As a percentage of the baseline measurement, quadriceps MVIC for limbs with anterior (n=16) and posterior (n=16) catheter tip placement did not differ to a statistically significant degree at Hour 6 (mean [SD] 29% [26] vs. 30% [28], respectively; 95% CI: ?22% to 20%; p=0.931), or at any other time point. However, the maximum tolerance to cutaneous electrical current was higher in limbs with anterior compared to posterior catheter tip placement at Hour 6 (20 [23] vs. 6 [4] mA, respectively; 95% CI: 1 mA to 27 mA; p=0.035), as well as at Hours 1, 7, 8, and 9 (p<0.04). Conclusions This study documents the significant (7080%) quadriceps femoris weakness induced by a continuous femoral nerve block infusion at a relatively low dose of ropivacaine (4 mg/h) delivered through a perineural catheter located both anterior and posterior to the femoral nerve. In contrast, an anterior placement increases cutaneous sensory block compared with a posterior insertion, without a concurrent relative increase in motor block. PMID:22745116

  1. Sensory Neuron Downregulation of the Kv9.1 Potassium Channel Subunit Mediates Neuropathic Pain following Nerve Injury

    PubMed Central

    Tsantoulas, Christoforos; Zhu, Lan; Shaifta, Yasin; Grist, John; Ward, Jeremy P. T.; Raouf, Ramin; Michael, Gregory J.; McMahon, Stephen B.

    2013-01-01

    Chronic neuropathic pain affects millions of individuals worldwide, is typically long-lasting, and remains poorly treated with existing therapies. Neuropathic pain arising from peripheral nerve lesions is known to be dependent on the emergence of spontaneous and evoked hyperexcitability in damaged nerves. Here, we report that the potassium channel subunit Kv9.1 is expressed in myelinated sensory neurons, but is absent from small unmyelinated neurons. Kv9.1 expression was strongly and rapidly downregulated following axotomy, with a time course that matches the development of spontaneous activity and pain hypersensitivity in animal models. Interestingly, siRNA-mediated knock-down of Kv9.1 in naive rats led to neuropathic pain behaviors. Diminished Kv9.1 function also augmented myelinated sensory neuron excitability, manifested as spontaneous firing, hyper-responsiveness to stimulation, and persistent after-discharge. Intracellular recordings from ex vivo dorsal root ganglion preparations revealed that Kv9.1 knock-down was linked to lowered firing thresholds and increased firing rates under physiologically relevant conditions of extracellular potassium accumulation during prolonged activity. Similar neurophysiological changes were detected in animals subjected to traumatic nerve injury and provide an explanation for neuropathic pain symptoms, including poorly understood conditions such as hyperpathia and paresthesias. In summary, our results demonstrate that Kv9.1 dysfunction leads to spontaneous and evoked neuronal hyperexcitability in myelinated fibers, coupled with development of neuropathic pain behaviors. PMID:23197740

  2. 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

  3. 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

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

    PubMed Central

    Borbly, va; Botz, Blint; Blcskei, Kata; Kenyr, Tibor; Kereskai, Lszl; Kiss, Tams; Szolcsnyi, Jnos; Pintr, Erika; Csepregi, Janka Zsfia; Mcsai, 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 neuroimmune 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

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

    PubMed

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

    2001-06-01

    1. Extracellular recording techniques were used to study nerve terminal impulses (NTIs) recorded from single polymodal nociceptors and cold-sensitive receptors in guinea-pig cornea isolated in vitro. 2. The amplitude and time course of NTIs recorded from polymodal nociceptors was different from those of cold-sensitive receptors. 3. Bath application of tetrodotoxin (1 microM) changed the time course of spontaneous NTIs recorded from both polymodal and cold-sensitive receptors. 4. Bath application of lignocaine (lidocaine; 1-5 mM) abolished all electrical activity. 5. Local application of lignocaine (2.5 and 20 mM) through the recording electrode changed the time course of the NTIs recorded from polymodal nociceptors but not that of NTIs recorded from cold-sensitive nerve endings. 6. It is concluded that action potentials propagate actively in the sensory nerve endings of polymodal nociceptors. In contrast, cold-sensitive receptor nerve endings appear to be passively invaded from a point more proximal in the axon where the action potential can fail or be initiated. PMID:11389207

  6. Loss of corneal sensory nerve fibers in SIV-infected macaques: an alternate approach to investigate HIV-induced PNS damage.

    PubMed

    Dorsey, Jamie L; Mangus, Lisa M; Oakley, Jonathan D; Beck, Sarah E; Kelly, Kathleen M; Queen, Suzanne E; Metcalf Pate, Kelly A; Adams, Robert J; Marfurt, Carl F; Mankowski, Joseph L

    2014-06-01

    Peripheral neuropathy is the most frequent neurological complication of HIV infection, affecting more than one-third of infected patients, including patients treated with antiretroviral therapy. Although emerging noninvasive techniques for corneal nerve assessments are increasingly being used to diagnose and monitor peripheral neuropathies, corneal nerve alterations have not been characterized in HIV. Here, to determine whether SIV infection leads to corneal nerve fiber loss, we immunostained corneas for the nerve fiber marker ?III tubulin. We developed and applied both manual and automated methods to measure nerves in the corneal subbasal plexus. These counting methods independently indicated significantly lower subbasal corneal nerve fiber density among SIV-infected animals that rapidly progressed to AIDS compared with slow progressors. Concomitant with decreased corneal nerve fiber density, rapid progressors had increased levels of SIV RNA and CD68-positive macrophages and expression of glial fibrillary acidic protein by glial satellite cells in the trigeminal ganglia, the location of the neuronal cell bodies of corneal sensory nerve fibers. In addition, corneal nerve fiber density was directly correlated with epidermal nerve fiber length. These findings indicate that corneal nerve assessment has great potential to diagnose and monitor HIV-induced peripheral neuropathy and to set the stage for introducing noninvasive techniques to measure corneal nerve fiber density in HIV clinical settings. PMID:24828391

  7. 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.

  8. Differential motor and sensory functional recovery in male but not female adult rats is associated with remyelination rather than axon regeneration after sciatic nerve crush.

    PubMed

    Tong, Ling-Ling; Ding, You-Quan; Jing, Hong-Bo; Li, Xuan-Yang; Qi, Jian-Guo

    2015-05-01

    Peripheral nerve functional recovery after injuries relies on both axon regeneration and remyelination. Both axon regeneration and remyelination require intimate interactions between regenerating neurons and their accompanying Schwann cells. Previous studies have shown that motor and sensory neurons are intrinsically different in their regeneration potentials. Moreover, denervated Schwann cells accompanying myelinated motor and sensory axons have distinct gene expression profiles for regeneration-associated growth factors. However, it is unknown whether differential motor and sensory functional recovery exists. If so, the particular one among axon regeneration and remyelination responsible for this difference remains unclear. Here, we aimed to establish an adult rat sciatic nerve crush model with the nonserrated microneedle holders and measured rat motor and sensory functions during regeneration. Furthermore, axon regeneration and remyelination was evaluated by morphometric analysis of electron microscopic images on the basis of nerve fiber classification. Our results showed that A? fiber-mediated motor function was successfully recovered in both male and female rats. A? fiber-mediated sensory function was partially restored in male rats, but completely recovered in female littermates. For both male and female rats, the numbers of regenerated motor and sensory axons were quite comparable. However, remyelination was diverse among myelinated motor and sensory nerve fibers. In detail, A? and A? fibers incompletely remyelinated in male, but not female rats, whereas A? fibers fully remyelinated in both sexes. Our result indicated that differential motor and sensory functional recovery in male but not female adult rats is associated with remyelination rather than axon regeneration after sciatic nerve crush. PMID:25830493

  9. 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

  10. 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

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

    PubMed

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

    2014-01-01

    Previous studies indicated that intracerebroventricular administration of nerve growth factor (NGF) leads to massive Schwann cell hyperplasia surrounding the medulla oblongata and spinal cord. This study was designed to characterize the proliferation of peripheral glial cells, that is, Schwann and satellite cells, in the trigeminal ganglia and dorsal root ganglia (DRG) of adult rats during two weeks of NGF infusion using bromodeoxyuridine (BrdU) to label dividing cells. The trigeminal ganglia as well as the cervical and lumbar DRG were analyzed. Along the entire neuraxis a small number of dividing cells were observed within these regions under physiological condition. NGF infusion has dramatically increased the generation of new cells in the neuronal soma and axonal compartments of sensory ganglia and along the dorsal root and the dorsal root entry zone. Quantification of BrdU positive cells within sensory ganglia revealed a 2.3- to 3-fold increase in glial cells compared to controls with a similar response to NGF for the different peripheral ganglia examined. Immunofluorescent labeling with S100? revealed that Schwann and satellite cells underwent mitosis after NGF administration. These data indicate that intracerebroventricular NGF infusion significantly induces gliogenesis in trigeminal ganglia and the spinal sensory ganglia and along the dorsal root entry zone as well as the dorsal root. PMID:24738070

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

    PubMed Central

    Xu, Pin; Hall, Alison K.

    2009-01-01

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

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

    PubMed

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

    2014-02-10

    Capsaicin desensitization leads to behavioral changes, some of which are related to schizophrenia, but investigations into these effects have been scarce. The goal of this study was to characterize the consequences of juvenile capsaicin desensitization on different functions: acute and inflammation-induced thermal and mechanical sensitivity, urinary bladder capacity and thermoregulation, and also on the potentially schizophrenia-related impairments in sensory-motor gating, motor activity and cognitive functioning. Male Wistar rats desensitized with increasing doses of subcutaneous capsaicin after weaning were investigated. Heat and mechanical pain sensitivity did not change significantly; however, morphine produced a prolonged decrease in the nociceptive response to inflammation in desensitized animals. Ultrasound examination of the bladder revealed enhanced bladder volume in treated animals. Capsaicin-treated animals had higher body temperature at 22 °C in both dark and light periods, and they also showed prolonged hyperthermia in new environmental circumstances. Warm environment induced a profound impairment of thermoregulation in desensitized animals. The treated animals also showed higher levels of activity during the active phase and at both cool and warm temperatures. The amplitude of the responses to auditory stimuli and prepulse inhibition did not differ between the two groups, but the desensitized animals showed learning impairments in the novel object recognition test. These results suggest that juvenile capsaicin desensitization leads to sustained changes in several functions that may be related to schizophrenia. We propose that capsaicin desensitization, together with other interventions, may lead to an improved chronic animal model of schizophrenia. PMID:24291382

  15. Sensory nerve recording for closed-loop control to restore motor functions.

    PubMed

    Popovi?, D B; Stein, R B; Jovanovi?, K L; Dai, R; Kostov, A; Armstrong, W W

    1993-10-01

    A method is developed for using neural recordings to control functional electrical stimulation (FES) to nerves and muscles. Experiments were done in chronic cats with a goal of designing a rule-based controller to generate rhythmic movements of the ankle joint during treadmill locomotion. Neural signals from the tibial and superficial peroneal nerves were recorded with cuff electrodes and processed simultaneously with muscular signals from ankle flexors and extensors in the cat's hind limb. Cuff electrodes are an effective method for long-term chronic recording in peripheral nerves without causing discomfort or damage to the nerve. For real-time operation we designed a low-noise amplifier with a blanking circuit to minimize stimulation artifacts. We used threshold detection to design a simple rule-based control and compared its output to the pattern determined using adaptive neural networks. Both the threshold detection and adaptive networks are robust enough to accommodate the variability in neural recordings. The adaptive logic network used for this study is effective in mapping transfer functions and therefore applicable for determination of gait invariants to be used for closed-loop control in an FES system. Simple rule-bases will probably be chosen for initial applications to human patients. However, more complex FES applications require more complex rule-bases and better mapping of continuous neural recordings and muscular activity. Adaptive neural networks have promise for these more complex applications. PMID:8294127

  16. Neurotrophin and GDNF family ligand receptor expression in vagal sensory nerve subtypes innervating the adult guinea pig respiratory tract

    PubMed Central

    Lieu, TinaMarie; Kollarik, Marian; Myers, Allen C.

    2011-01-01

    We combined retrograde tracing techniques with single-neuron RT-PCR to compare the expression of neurotrophic factor receptors in nodose vs. jugular vagal sensory neurons. The neurons were further categorized based on location of their terminals (tracheal or lungs) and based on expression of the ionotropic capsaicin receptor TRPV1. Consistent with functional studies, nearly all jugular neurons innervating the trachea and lungs expressed TRPV1. With respect to the neurotrophin receptors, the TRPV1-expressing jugular C-fiber neurons innervating both the trachea and lung compartments preferentially expressed tropomyosin-receptor kinase A (TrkA), with only a minority of neurons expressing TrkB or TrkC. The nodose neurons that express TRPV1 (presumed nodose C-fibers) innervate mainly intrapulmonary structures. These neurons preferentially expressed TrkB, with only a minority expressing TrkA or TrkC. The expression pattern in tracheal TRPV1-negative neurons, nodose tracheal presumed A?-fiber neurons as well as the intrapulmonary TRPV1-negative presumed A?-fiber neurons, was similar to that observed in the nodose C-fiber neurons. We also evaluated the expression of GFR? receptors and RET (receptors for the GDNF family ligands). Virtually all vagal sensory neurons innervating the respiratory tract expressed RET and GFR?1. The jugular neurons also categorically expressed GFR?3, as well as ?50% of the nodose neurons. GFR?2 was expressed in ?50% of the neurons irrespective of subtype. The results reveal that Trk receptor expression in vagal afferent neurons innervating the adult respiratory tract depends more on the location of the cell bodies (jugular vs. nodose ganglion) than either the location of the terminals or the functional phenotype of the nerve. The data also reveal that in addition to neurotrophins, the GDNF family ligands may be important neuromodulators of vagal afferent nerves innervating the adult respiratory tract. PMID:21335521

  17. Antinociceptive desensitizing actions of TRPV1 receptor agonists capsaicin, resiniferatoxin and N-oleoyldopamine as measured by determination of the noxious heat and cold thresholds in the rat.

    PubMed

    Blcskei, Kata; Tkus, Valria; Dzsi, Lszl; Szolcsnyi, Jnos; Petho, Gbor

    2010-05-01

    Agonists of the TRPV1 receptor excite TRPV1-expressing polymodal nociceptors that is followed after higher doses by a state of diminished responsiveness called desensitization which ensues at two levels: (i) diminished responsiveness of the ion channel (TRPV1 receptor desensitization); (ii) diminished responsiveness of the nerve endings to all stimuli including noxious heat. The aim was to compare these desensitizing actions of TRPV1 agonists in the rat by measuring with an incremental hot/cold plate the noxious heat and cold thresholds, i.e. the lowest hot and highest cold plate temperature, respectively, that evokes nocifensive behaviour. Capsaicin (3.3-1000 nmol) or resiniferatoxin (0.016-0.5 nmol) applied intraplantarly evoked a sustained dose-dependent elevation of the noxious heat threshold lasting for 2-11 days. N-oleoyldopamine failed to elevate the heat threshold. The noxious cold threshold was decreased by capsaicin or resiniferatoxin with a recovery within 2-4 days. The diminished acute nocifensive and heat threshold-lowering effects of resiniferatoxin or N-oleoyldopamine by pretreatment with doses that failed to elevate the heat threshold and to alter the nocifensive action of the TRPA1 activator formaldehyde, were taken as indication of TRPV1 receptor desensitization. In conclusion, using measurement of threshold temperatures eliciting nocifensive reactions in rats both in the hot and cold range revealed that capsaicin and RTX impair thermosensation in both noxious ranges due to a functional desensitization of peripheral terminals of TRPV1-expressing sensory neurons responsible for noxious heat and cold responsiveness. This could be differentiated from desensitization of TRPV1 receptor evoked by lower doses of resiniferatoxin or N-oleoyldopamine. PMID:19800272

  18. 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

  19. Nerve growth factor enhances the excitability of rat sensory neurons through activation of the atypical protein kinase C isoform, PKM?

    PubMed Central

    Zhang, Y. H.; Kays, J.; Hodgdon, K. E.; Sacktor, T. C.

    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: PKM?, PKC?, and PKC?/?) 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 PKC?. Both Western blots and quantitative real-time PCR established that PKM?, but neither full-length PKC? nor PKC?/?, 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 PKC? or PKC? augmented excitability, recapitulating the sensitization produced by NGF. Internal perfusion with recombinant PKC? 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 PKC?. These results demonstrate that NGF leads to the activation of PKM? that ultimately enhances the capacity of small-diameter capsaicin-sensitive sensory neurons to fire APs through a PI3K-dependent signaling cascade. PMID:21975456

  20. 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

  1. 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

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

    PubMed

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

    2014-09-24

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

  3. p75 and TrkA neurotrophin receptors in human skin after spinal cord and peripheral nerve injury, with special reference to sensory corpuscles.

    PubMed

    Lpez, S M; Prez-Prez, M; Mrquez, J M; Naves, F J; Represa, J; Vega, J A

    1998-07-01

    Human skin, including nerves and sensory corpuscles, displays immunoreactivity (IR) for low- (p75) and high-affinity (TrkA-like) receptors for nerve growth factor (NGF), the best characterized member of the family of neurotrophins. This study was designed to analyze the changes induced by spinal cord and peripheral nerve injuries in the expression of neurotrophin receptors in digital skin, with special reference to nerves and sensory corpuscles. Skin biopsy samples were obtained from 1) the hand and toes of normal subjects, 2) below the level of the lesion of patients with spinal cord injury affecting dorsal and lateral funiculi, 3) the cutaneous territory of entrapped peripheral nerves (median and ulnar nerves), and 4) the cutaneous territory of sectioned and grafted nerves (median nerve). The pieces were formalin-fixed and paraffin-embedded, cut in serial sections, and processed for immunohistochemistry using antibodies against human p75 and TrkA proteins. The percentage of sensory corpuscles displaying IR for p75 and TrkA-like, as well as the intensity of IR developed within them, was assessed using quantitative image analysis. Spinal cord severance causes a decrease in p75 IR in Meissner and Pacinian corpuscles, whereas TrkA-like IR did not vary. In other nonnervous tissues (i.e., epidermis, sweat glands), both p75 and TrkA-like IR was diminished or even absent. Similar but more severe changes were encountered in the skin from the territory of entrapped nerves. Finally, in subjects with sectioned-grafted nerves, p75 IR was found close to controls in nerves, reduced in Meissner corpuscles, and absent in the inner core of the Pacinian ones; TrkA-like IR was in the perineurium, a small percentage of Meissner corpuscles (about 7%), and the outer core and capsule of the Pacinan corpuscles. In the nonnervous tissues, p75 IR was practically absent, whereas TrkA-like IR did not change. No changes in the expression of neurotrophin receptors were observed in Merkel cells of the different groups. Present results show the following: 1) expression of nerve p75 IR in human cutaneous sensory corpuscles is sensitive to central deafferentation, to blockade or difficulty in axonal transport, and to disruption of axonal continuity independently of possible restoration of axonal integrity due to grafts; 2) expression of TrkA-like IR in nerves and sensory corpuscles is sensitive only to nerve transection; 3) the corpuscular Schwann-related cells are the only cells involved in the above modifications, the perineurial cells remaining unchanged; 4) the expression of p75 and TrkA-like IR by Merkel cells is independent of normal innervation; 5) an adequate innervation of the skin seems to be necessary for the expression of p75 but not TrkA-like in nonneuronal cells, especially in the epidermis. A role for NGF in the maintenance of epidermis integrity is discussed. PMID:9669765

  4. 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

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

    PubMed

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

    2014-11-01

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

  6. 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

  7. Endogenous prostaglandins and afferent sensory nerves in gastroprotective effect of hydrogen sulfide against stress-induced gastric lesions.

    PubMed

    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

  8. Camphor activates and strongly desensitizes the transient receptor potential vanilloid subtype 1 channel in a vanilloid-independent mechanism.

    PubMed

    Xu, Haoxing; Blair, Nathaniel T; Clapham, David E

    2005-09-28

    Camphor is a naturally occurring compound that is used as a major active ingredient of balms and liniments supplied as topical analgesics. Despite its long history of common medical use, the underlying molecular mechanism of camphor action is not understood. Capsaicin and menthol, two other topically applied agents widely used for similar purposes, are known to excite and desensitize sensory nerves by acting on two members of transient receptor potential (TRP) channel superfamily: heat-sensitive TRP vanilloid subtype 1 (TRPV1) and cold-sensitive TRP channel M8, respectively. Camphor has recently been shown to activate TRPV3, and here we show that camphor also activates heterologously expressed TRPV1, requiring higher concentrations than capsaicin. Activation was enhanced by phospholipase C-coupled receptor stimulation mimicking inflamed conditions. Similar camphor-activated TRPV1-like currents were observed in isolated rat DRG neurons and were strongly potentiated after activation of protein kinase C with phorbol-12-myristate-13-acetate. Camphor activation of rat TRPV1 was mediated by distinct channel regions from capsaicin, as indicated by camphor activation in the presence of the competitive inhibitor capsazepine and in a capsaicin-insensitive point mutant. Camphor did not activate the capsaicin-insensitive chicken TRPV1. TRPV1 desensitization is believed to contribute to the analgesic actions of capsaicin. We found that, although camphor activates TRPV1 less effectively, camphor application desensitized TRPV1 more rapidly and completely than capsaicin. Conversely, TRPV3 current sensitized after repeated camphor applications, which is inconsistent with the analgesic role of camphor. We also found that camphor inhibited several other related TRP channels, including ankyrin-repeat TRP 1 (TRPA1). The camphor-induced desensitization of TRPV1 and block of TRPA1 may underlie the analgesic effects of camphor. PMID:16192383

  9. Divergent effects of painful nerve injury on mitochondrial Ca(2+) buffering in axotomized and adjacent sensory neurons.

    PubMed

    Hogan, Quinn H; Sprick, Chelsea; Guo, Yuan; Mueller, Samantha; Bienengraeber, Martin; Pan, Bin; Wu, Hsiang-En

    2014-11-17

    Mitochondria critically regulate cytoplasmic Ca(2+) concentration ([Ca(2+)]c), but the effects of sensory neuron injury have not been examined. Using FCCP (1M) to eliminate mitochondrial Ca(2+) uptake combined with oligomycin (10M) to prevent ATP depletion, we first identified features of depolarization-induced neuronal [Ca(2+)]c transients that are sensitive to blockade of mitochondrial Ca(2+) buffering in order to assess mitochondrial contributions to [Ca(2+)]c regulation. This established the loss of a shoulder during the recovery of the depolarization (K(+))-induced transient, increased transient peak and area, and elevated shoulder level as evidence of diminished mitochondrial Ca(2+) buffering. We then examined transients in Control neurons and neurons from the 4th lumbar (L4) and 5th lumbar (L5) dorsal root ganglia after L5 spinal nerve ligation (SNL). The SNL L4 neurons showed decreased transient peak and area compared to control neurons, while the SNL L5 neurons showed increased shoulder level. Additionally, SNL L4 neurons developed shoulders following transients with lower peaks than Control neurons. Application of FCCP plus oligomycin elevated resting [Ca(2+)]c in SNL L4 neurons more than in Control neurons. Whereas application of FCCP plus oligomycin 2s after neuronal depolarization initiated mitochondrial Ca(2+) release in most Control and SNL L4 neurons, this usually failed to release mitochondrial Ca(2+) from SNL L5 neurons. For comparable cytoplasmic Ca(2+) loads, the releasable mitochondrial Ca(2+) in SNL L5 neurons was less than Control while it was increased in SNL L4 neurons. These findings show diminished mitochondrial Ca(2+) buffering in axotomized SNL L5 neurons but enhanced Ca(2+) buffering by neurons in adjacent SNL L4 neurons. PMID:25251590

  10. Sensory and autonomic nerve changes in the monosodium glutamate-treated rat: a model of type II diabetes.

    PubMed

    Morrison, John F B; Shehab, Safa; Sheen, Rajan; Dhanasekaran, Subramanian; Shaffiullah, Mohammed; Mensah-Brown, Eric

    2008-02-01

    Rats that had been injected with monosodium glutamate (MSG) neonatally were studied for up to 70 weeks and compared with age-matched control rats to study changes in glucose tolerance and in sympathetic and sensory nerves. At 61 and 65 weeks of age, there were significant differences in glucose tolerance between the MSG and control groups, and the MSG group had raised fasting blood glucose. These changes were not associated with changes in the number of beta-cells in the islets of Langerhans. In addition, the diabetic MSG-treated rats had central obesity and cataracts. Hypoalgesia to thermal stimuli was present in MSG-treated rats as early as 6 weeks and persisted at 70 weeks. However, no differences were observed in the distribution of substance P, the neurokinin-1 receptor or calcitonin gene-related peptide in the dorsal horn of L3-L5 at this age (70 weeks). Diabetic MSG-treated animals at 65 and 70 weeks of age had significantly reduced noradrenaline concentrations in the heart, tail artery and ileum, while concentrations in the adrenal gland and corpus cavernosum were significantly increased. There was also a significant increase in adrenal adrenaline, dopamine and serotonin, largely attributable to changes in weight of the adrenal gland in the MSG-treated animals. The results indicate that MSG-treated animals develop a form of type II diabetes by about 60 weeks of age, and that there are significant changes in amine levels in various tissues associated with these developments. PMID:17911358

  11. 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 nave 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

  12. The effect of treatment with BRX-220, a co-inducer of heat shock proteins, on sensory fibers of the rat following peripheral nerve injury.

    PubMed

    Kalmar, B; Greensmith, L; Malcangio, M; McMahon, S B; Csermely, P; Burnstock, G

    2003-12-01

    In this study, we examined the effect BRX-220, a co-inducer of heat shock proteins, in injury-induced peripheral neuropathy. Following sciatic nerve injury in adult rats and treatment with BRX-220, the following features of the sensory system were studied: (a) expression of calcitonin gene-related peptide (CGRP); (b) binding of isolectin B4 (IB4) in dorsal root ganglia (DRG) and spinal cord; (c) stimulation-evoked release of substance P (SP) in an in vitro spinal cord preparation and (d) nociceptive responses of partially denervated rats. BRX-220 partially reverses axotomy-induced changes in the sensory system. In vehicle-treated rats there is a decrease in IB4 binding and CGRP expression in injured neurones, while in BRX-220-treated rats these markers were better preserved. Thus, 7.0 +/- 0.6% of injured DRG neurones bound IB4 in vehicle-treated rats compared to 14.4 +/- 0.9% in BRX-220-treated animals. Similarly, 4.5 +/- 0.5% of DRG neurones expressed CGRP in the vehicle-treated group, whereas 9.0 +/- 0.3% were positive in the BRX-220-treated group. BRX-220 also partially restored SP release from spinal cord sections to electrical stimulation of primary sensory neurones. Behavioural tests carried out on partially denervated animals showed that BRX-220 treatment did not prevent the emergence of mechanical or thermal hyperalgesia. However, oral treatment for 4 weeks lead to reduced pain-related behaviour suggesting either slowly developing analgesic actions or enhancement of recovery processes. Thus, the morphological improvement seen in sensory neurone markers was accompanied by restored functional activity. Therefore, treatment with BRX-220 promotes restoration of morphological and functional properties in the sensory system following peripheral nerve injury. PMID:14769355

  13. 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

  14. Modified oral metronidazole desensitization protocol.

    PubMed

    Gendelman, Samantha R; Pien, Lily C; Gutta, Ravi C; Abouhassan, Susan R

    2014-03-01

    The Center for Disease Control guidelines recommend desensitization to metronidazole in patients with trichomoniasis and hypersensitivity to metronidazole. There is only one published oral metronidazole desensitization protocol. The purpose of this study was to design a new, more gradual oral desensitization protocol to decrease systemic reactions that may occur when using the previously published protocol. We present two patients with presumed IgE-mediated allergy to metronidazole who underwent oral desensitization using our modified protocol. Case 1 was a 65-year-old woman with trichomoniasis who presented for metronidazole desensitization with a history of intraoperative anaphylaxis and positive skin tests to metronidazole. The patient tolerated six doses of the modified desensitization but developed systemic symptoms of nasal congestion and diffuse pruritus after the 25- and 100-mg doses. Both reactions were treated with intravenous (i.v.) antihistamines. Because of gastrointestinal irritation, the desensitization was completed at a dose of 250 mg orally every 6 hours. Case 2 was a 42-year-old woman with trichomoniasis and a history of hives immediately after administration of i.v. metronidazole who presented for desensitization. The patient had negative skin-prick and intradermal testing to metronidazole. She developed lip tingling and pruritus on her arms 15 minutes after the 10-mg dose. Fexofenadine at 180 mg was given orally and symptoms resolved. She tolerated the rest of the protocol without reaction and received a total dose of 2 g of metronidazole. Our oral metronidazole desensitization for presumed IgE-mediated reactions offers a second option for physicians wishing to use a more gradual escalation in dose. PMID:24612959

  15. Stimuli of Sensory-Motor Nerves Terminate Arterial Contractile Effects of Endothelin-1 by CGRP and Dissociation of ET-1/ETA-Receptor Complexes

    PubMed Central

    Meens, Merlijn J. P. M. T.; Compeer, Matthijs G.; Hackeng, Tilman M.; van Zandvoort, Marc A.; Janssen, Ben J. A.; De Mey, Jo G. R.

    2010-01-01

    Background Endothelin-1 (ET-1), a long-acting paracrine mediator, is implicated in cardiovascular diseases but clinical trials with ET-receptor antagonists were not successful in some areas. We tested whether the quasi-irreversible receptor-binding of ET-1 (i) limits reversing effects of the antagonists and (ii) can be selectively dissociated by an endogenous counterbalancing mechanism. Methodology/Principal findings In isolated rat mesenteric resistance arteries, ETA-antagonists, endothelium-derived relaxing factors and synthetic vasodilators transiently reduced contractile effects of ET-1 but did not prevent persistent effects of the peptide. Stimuli of peri-vascular vasodilator sensory-motor nerves such as capsaicin not only reduced but also terminated long-lasting effects of ET-1. This was prevented by CGRP-receptor antagonists and was mimicked by exogenous calcitonin gene-related peptide (CGRP). Using 2-photon laser scanning microscopy in vital intact arteries, capsaicin and CGRP, but not ETA-antagonism, were observed to promote dissociation of pre-existing ET-1/ETA-receptor complexes. Conclusions Irreversible binding and activation of ETA-receptors by ET-1 (i) occur at an antagonist-insensitive site of the receptor and (ii) are selectively terminated by endogenously released CGRP. Hence, natural stimuli of sensory-motor nerves that stimulate release of endogenous CGRP can be considered for therapy of diseases involving ET-1. PMID:20532232

  16. 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

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

    PubMed

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

    2015-10-01

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

  18. 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

  19. 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

  20. 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 ?, ?, and ? opioid receptors. Transcutaneous electrical nerve stimulation (TENS) has been extensively used for pain relief, as low-frequency stimulation can activate receptors. Our aim was to use pupillometry to evaluate the effect of low-frequency TENS stimulation of ? 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

  1. Relaxation as a Factor in Semantic Desensitization

    ERIC Educational Resources Information Center

    Bechtel, James E.; McNamara, J. Regis

    1975-01-01

    Relaxation and semantic desensitization were used to alleviate the fear of phobic females. Results showed that semantic desensitization, alone or in combination with relaxation, failed to modify the evaluative meanings evoked by the feared object. (SE)

  2. 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

  3. Differential upregulation in DRG neurons of an ?2?-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 ?2?-1 protein is an auxiliary subunit of voltage-gated calcium channels, critical for neurotransmitter release. It is upregulated in dorsal root ganglion (DRG) neurons following sensory nerve injury, and is also the therapeutic target of the gabapentinoid drugs, which are efficacious in both experimental and human neuropathic pain conditions. ?2?-1 has 3 spliced regions: A, B, and C. A and C are cassette exons, whereas B is introduced via an alternative 3? splice acceptor site. Here we have examined the presence of ?2?-1 splice variants in DRG neurons, and have found that although the main ?2?-1 splice variant in DRG is the same as that in brain (?2?-1 ?A+B+C), there is also another ?2?-1 splice variant (?A+B?C), which is expressed in DRG neurons and is differentially upregulated compared to the main DRG splice variant ?2?-1 ?A+B+C following spinal nerve ligation. Furthermore, this differential upregulation occurs preferentially in a small nonmyelinated DRG neuron fraction, obtained by density gradient separation. The ?2?-1 ?A+B?C splice variant supports CaV2 calcium currents with unaltered properties compared to ?2?-1 ?A+B+C, but shows a significantly reduced affinity for gabapentin. This variant could therefore play a role in determining the efficacy of gabapentin in neuropathic pain. PMID:24315988

  4. Changes of cutaneous sensory thresholds induced by non-painful transcutaneous electrical nerve stimulation in normal subjects and in subjects with chronic pain.

    PubMed Central

    Zoppi, M; Francini, F; Maresca, M; Procacci, P

    1981-01-01

    Transcutaneous electrical nerve stimulation (TENS) of the nervi cutaneus surae medialis was applied to 59 healthy subjects and 30 patients suffering from chronic myofascial pain in one lower limb, with an intensity of current that induced a well tolerated tingling sensation. Each period of stimulation lasted 24 minutes. The thresholds of the tactile, tingling and painful sensations were tested at fixed intervals before, during and after stimulation. Trains of constant current square waves in the distribution area of the stimulated nerve (local thresholds) and in other areas (general thresholds) were used. In all subjects repeated changes of the current were necessary in order to maintain constant tingling during the first period of TENS (changing phase); after that few if any changes of the current were necessary (steady phase). There were changes in thresholds within the territory of the electrically stimulated nerve, and marked changes elsewhere and generally in the body. In healthy subjects local thresholds increased during both phases of TENS; general thresholds decreased during the changing phase and increased during the steady phase. After TENS, thresholds showed the same trend as during the steady phase. Trends of the sensory thresholds during and after TENS differed in different subjects according to their thresholds before TENS. Thresholds did not return to normal for more than 20 minutes after TENS. In the group of 30 patients there was a significant difference between thresholds on the two sides of the body. The difference between the two sides was reduced by TENS. Pain relief induced by TENS may be related to this fact. PMID:6975355

  5. Nerve growth factor-induced synapse-like structures in contralateral sensory ganglia contribute to chronic mirror-image pain.

    PubMed

    Cheng, Chau-Fu; Cheng, Jen-Kun; Chen, Chih-Yang; Rau, Ruey-Horng; Chang, Yu-Cheng; Tsaur, Meei-Ling

    2015-11-01

    Elevated nerve growth factor (NGF) in the contralateral dorsal root ganglion (DRG) mediates mirror-image pain after peripheral nerve injury, but the underlying mechanism remains unclear. Using intrathecal injection of NGF antibodies, we found that NGF is required for the development of intra-DRG synapse-like structures made by neurite sprouts of calcitonin gene-related peptide (CGRP(+)) nociceptors and sympathetic axons onto neurite sprouts of Kv4.3(+) nociceptors. These synapse-like structures are formed near NGF-releasing satellite glia surrounding large DRG neurons. Downregulation of the postsynaptic protein PSD95 with a specific shRNA largely eliminates these synapse-like structures, suppresses activities of Kv4.3(+) but not CGRP(+) nociceptors, and attenuates mirror-image pain. Furthermore, neutralizing the neurotransmitter norepinephrine or CGRP in the synapse-like structures by antibodies has similar analgesic effect. Thus, elevated NGF after peripheral nerve injury induces neurite sprouting and the formation of synapse-like structures within the contralateral DRG, leading to the development of chronic mirror-image pain. PMID:26121254

  6. Desensitization of metastable intermolecular composites

    DOEpatents

    Busse, James R. (South Fork, CO); Dye, Robert C. (Los Alamos, NM); Foley, Timothy J. (Los Alamos, NM); Higa, Kelvin T. (Ridgecrest, CA); Jorgensen, Betty S. (Jemez Springs, NM); Sanders, Victor E. (White Rock, NM); Son, Steven F. (Los Alamos, NM)

    2011-04-26

    A method to substantially desensitize a metastable intermolecular composite material to electrostatic discharge and friction comprising mixing the composite material with an organic diluent and removing enough organic diluent from the mixture to form a mixture with a substantially putty-like consistency, as well as a concomitant method of recovering the metastable intermolecular composite material.

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

    PubMed

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

    2013-11-12

    Distal sensory polyneuropathy (DSP) with associated neuropathic pain is the most common neurological disorder affecting patients with human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS). Viral protein R (Vpr) is a neurotoxic protein encoded by HIV-1 and secreted by infected macrophages. Vpr reduces neuronal viability, increases cytosolic calcium and membrane excitability of cultured dorsal root ganglion (DRG) sensory neurons, and is associated with mechanical allodynia in vivo. A clinical trial with HIV/AIDS patients demonstrated that nerve growth factor (NGF) reduced the severity of DSP-associated neuropathic pain, a problem linked to damage to small diameter, potentially NGF-responsive fibers. Herein, the actions of NGF were investigated in our Vpr model of DSP and we demonstrated that NGF significantly protected sensory neurons from the effects of Vpr. Footpads of immunodeficient Vpr transgenic (vpr/RAG1(-/-)) mice displayed allodynia (p<0.05), diminished epidermalinnervation (p<0.01) and reduced NGF mRNA expression (p<0.001) compared to immunodeficient (wildtype/RAG1(-/-)) littermate control mice. Compartmented cultures confirmed recombinant Vpr exposure to the DRG neuronal perikarya decreased distal neurite extension (p<0.01), whereas NGF exposure at these distal axons protected the DRG neurons from the Vpr-induced effect on their cell bodies. NGF prevented Vpr-induced attenuation of the phosphorylated glycogen synthase-3 axon extension pathway and tropomyosin-related kinase A (TrkA) receptor expression in DRG neurons (p<0.05) and it directly counteracted the cytosolic calcium burst caused by Vpr exposure to DRG neurons (p<0.01). TrkA receptor agonist indicated that NGFacted through the TrkA receptor to block the Vpr-mediated decrease in axon outgrowth in neonatal and adult rat and fetal human DRG neurons (p<0.05). Similarly, inhibiting the lower affinity NGF receptor, p75, blocked Vpr's effect on DRG neurons. Overall, NGF/TrkA signaling or p75 receptor inhibition protects somatic sensory neurons exposed to Vpr, thus laying the groundwork for potential therapeutic options for HIV/AIDS patients suffering from DSP. PMID:23912036

  8. 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

  9. 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

  10. 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

  11. 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

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

    PubMed

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

    2015-04-01

    When relief from neuralgia cannot be achieved with traditional methods, neurectomy may be considered to abate the stimulus, and primary opposition of the terminal nerve ending is recommended to prevent neuroma. Nerve repair with autograft is limited by autologous nerves available for large nerve defects. Cadaveric allograftsprovide an unlimited graft source without donor-site morbidities, but are rapidly rejected unless appropriate immunosuppression is achieved. An optimal treatment method for nerve allograft transplantation would minimize rejection while simultaneously permitting nerve regeneration. This report details a novel experience of nerve allograft transplantation using cadaveric nerve grafts to desensitize persistent postoperative thoracic neuralgia. PMID:25841822

  13. Etodolac activates and desensitizes transient receptor potential ankyrin 1.

    PubMed

    Wang, Shenglan; Dai, Yi; Kogure, Yoko; Yamamoto, Satoshi; Zhang, Wensheng; Noguchi, Koichi

    2013-12-01

    The transient receptor potential ankyrin 1 (TRPA1) channel is well known as a sensor to environmental irritant compounds, cold, and endogenous proalgesic agents. TRPA1 is expressed on sensory neurons and is involved in pain modulation. Etodolac is a cyclooxygenase (COX)-2 inhibitor that belongs to the class of nonsteroidal anti-inflammatory drugs (NSAIDs). A recent study indicates that etodolac inhibits allyl isothiocyanate (AITC)-induced calcium influx in heterologous HEK293 cells and sensory neurons. To examine whether and how etodolac modulates the TRPA1 channels, we applied etodolac to TRPA1-transfected HEK293 cells or rat dorsal root ganglion (DRG) neurons and recorded the currents using the whole-cell patch clamp technique. We found that etodolac at higher doses could activate and then desensitize TRPA1 channels in heterologous expressing HEK293 cells as well as in DRG neurons. The etodolac-induced currents were significantly attenuated in cysteine residues mutated human TRPA1-transfected HEK293 cells. Interestingly, application of etodolac at drug plasma levels in clinical usage did not induce significant TRPA1 currents but reduced the subsequent AITC-induced currents to 25% in HEK293 cells expressing TRPA1. Moreover, no modulatory effect of etodolac on TRPA1 was detected in the cysteine mutant cells. These data indicate a novel mechanism of the anti-inflammatory and analgesic clinical effects of etodolac, which may be involved with its direct activation and the subsequent desensitization of TRPA1 through the covalent modification of cysteine residues. PMID:24027177

  14. Sensory regulation of swallowing and airway protection: a role for the internal superior laryngeal nerve in humans

    PubMed Central

    Jafari, Samah; Prince, Rebecca A; Kim, Daniel Y; Paydarfar, David

    2003-01-01

    During swallowing, the airway is protected from aspiration of ingested material by brief closure of the larynx and cessation of breathing. Mechanoreceptors innervated by the internal branch of the superior laryngeal nerve (ISLN) are activated by swallowing, and connect to central neurones that generate swallowing, laryngeal closure and respiratory rhythm. This study was designed to evaluate the hypothesis that the ISLN afferent signal is necessary for normal deglutition and airway protection in humans. In 21 healthy adults, we recorded submental electromyograms, videofluoroscopic images of the upper airway, oronasal airflow and respiratory inductance plethysmography. In six subjects we also recorded pressures in the hypopharynx and upper oesophagus. We analysed swallows that followed a brief infusion (45 ml) of liquid barium onto the tongue, or a sip (118 ml) from a cup. In 16 subjects, the ISLN was anaesthetised by transcutaneous injection of bupivacaine into the paraglottic compartment. Saline injections using the identical procedure were performed in six subjects. Endoscopy was used to evaluate upper airway anatomy, to confirm ISLN anaesthesia, and to visualise vocal cord movement and laryngeal closure. Comparisons of swallowing and breathing were made within subjects (anaesthetic or saline injection vs. control, i.e. no injection) and between subjects (anaesthetic injection vs. saline injection). In the non-anaesthetised condition (saline injection, 174 swallows in six subjects; no injection, 522 swallows in 20 subjects), laryngeal penetration during swallowing was rare (1.4 %) and tracheal aspiration was never observed. During ISLN anaesthesia (16 subjects, 396 swallows), all subjects experienced effortful swallowing and an illusory globus sensation in the throat, and 15 subjects exhibited penetration of fluid into the larynx during swallowing. The incidence of laryngeal penetration in the anaesthetised condition was 43 % (P < 0.01, compared with either saline or no injection) and of these penetrations, 56 % led to tracheal aspiration (without adverse effects). We further analysed the swallow cycle to evaluate the mechanism(s) by which fluid entered the larynx. Laryngeal penetration was not caused by premature spillage of oral fluid into the hypopharynx, delayed clearance of fluid from the hypopharynx, or excessive hypopharyngeal pressure generated by swallowing. Furthermore, there was no impairment in the ability of swallowing to halt respiratory airflow during the period of pharyngeal bolus flow. Rather, our observations suggest that loss of airway protection was due to incomplete closure of the larynx during the pharyngeal phase of swallowing. In contrast to the insufficient closure during swallowing, laryngeal closure was robust during voluntary challenges with the Valsalva, Mller and cough manoeuvres under ISLN anaesthesia. We suggest that an afferent signal arising from the ISLN receptor field is necessary for normal deglutition, especially for providing feedback to central neural circuits that facilitate laryngeal closure during swallowing. The ISLN afferent signal is not essential for initiating and sequencing the swallow cycle, for co-ordinating swallowing with breathing, or for closing the larynx during voluntary manoeuvres. PMID:12754311

  15. Investigations on neurotoxicity of chemical substances at the workplace. V. Determination of the motor and sensory nerve conduction velocity in persons occupationally exposed to lead.

    PubMed

    Triebig, G; Weltle, D; Valentin, H

    1984-01-01

    A cross-sectional study was performed in order to investigate the influence of chronic lead-exposure on the peripheral nervous system. We examined 148 male workers of a storage battery manufacturing plant, who had been exposed to lead metal and inorganic lead compounds for 1 to 28 years (mean 11 years). Fifteen workers with non-occupational risks of peripheral neuropathy (former diseases, alcohol abuse, medication) were excluded from the study. The investigation program comprised: case history, physical examination, analyses of blood- and urine-samples and determination of maximal motor, mixed and sensory conduction velocity (NCV) of the ulnar and median nerve of the right forearm. Objectively no worker showed any signs of health effects related to lead exposure. The "Biological Monitoring" included the determination of (1) Blood-lead level (Pb-B), (2) Free erythrocyte porphyrins (FEP), (3) delta-Aminolevulinic acid dehydratase (ALA-D) and (4) delta-Aminolevulinic acid in urine (ALA-U). Further "time-weighted-average (TWA)"-values of Pb-B were calculated on the basis of several determinations over the period 1975-1981. The following "actual" ("TWA") median values resulted: Pb-B 53 micrograms/dl (54 micrograms/dl), ALA-U 5.6 mg/l (8.4 mg/l), FEP 2.0 mg/l (2.0 mg/l). The "Biologischer Arbeitsstoff Toleranz Wert (BAT)" of 70 micrograms/dl for Pb-B was exceeded in 15 workers (11%), and of 15 mg/l for ALA-U in 30 cases (23%). In comparison with age-matched controls, the lead workers showed a mild slowing of NCV with mean values between 0.8 and 2.0 m/s. Multiple stepwise regression analyses revealed statistically significant correlations between the four NCV and age as well as Pb-B. There were better correlations by using "TWA" than "actual" data of Pb-B. Consideration of the results of the regression analyses, together with an evaluation of the individual neurophysiological status as a function of internal lead exposure, a "dose-effect-relationship" was found only in the case of Pb-B exceeding 70 micrograms/dl. From our study it is concluded that chronic lead exposure resulting in blood-lead levels of below 70 micrograms/dl is no occupational risk causing a functionally significant slowing of nerve conduction velocities. PMID:6323322

  16. Peripheral nerve blocks for distal extremity surgery.

    PubMed

    Offierski, Chris

    2013-10-01

    Peripheral nerve block is well suited for distal extremity surgery. Blocking the nerves at the distal extremity is easily done. It does not require ultrasound or stimulators to identify the nerve. Blocking nerves in the distal extremity is safe with low risk of toxicity. The effect of the nerve block is limited to the distribution of the nerve. The distal nerves in the lower extremity are sensory branches of the sciatic nerve. This provides a sensory block only. This has the advantage of allowing the patient to actively contract tendons in the foot and ambulate more quickly after surgery. PMID:24093651

  17. Endogenous Opiate System and Systematic Desensitization.

    ERIC Educational Resources Information Center

    Egan, Kelly J.; And Others

    1988-01-01

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

  18. Endogenous Opiate System and Systematic Desensitization.

    ERIC Educational Resources Information Center

    Egan, Kelly J.; And Others

    1988-01-01

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

  19. [Desensitization of the nicotinic acetylcholine receptor].

    PubMed

    Quionez, M; Rojas, L

    1994-01-01

    In biological membranes, ionic channels act speeding up ion movements. Each ionic channel is excited by a specific stimulus (i.e. electric, mechanical, chemical, etc.). Chemically activated ionic channels (CAIC), such as the nicotinic acetylcholine receptor (nAChR), suffer desensitization when the receptor site is still occupied by the agonist molecule. The desensitized CAIC is a non functional channel state regarded as a particular case of receptors rundown. CAIC desensitization only involve reduced activity and not their membrane elimination. Desensitization is important to control synaptic transmission and the development of the nervous system. In this review we discuss results related to its production, modulation and some aspects associated to models that consider it. Finally, an approach combining molecular biology and electrophysiology techniques to understand desensitization and its importance in biological systems is presented. PMID:8525756

  20. 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

  1. Shock desensitizing of solid explosive

    SciTech Connect

    Davis, William C

    2010-01-01

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

  2. Shock desensitizing of solid explosives

    SciTech Connect

    Davis, William C

    2010-01-01

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

  3. [Etoposide desensitization. A case report].

    PubMed

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

    2010-01-01

    All chemotherapeutic agents have the potential to induce hypersensitivity reactions and the repeated administration of such drugs during a cancer treatment enhances specific sensitization. Epipodophyllotoxins (etoposide and teniposide) are commonly used to treat lung, testicular, central nervous system and hematologic cancers. Hypersensitivity reactions to epipodophyllotoxins are not the most common but they have been reported. We present a case of an eight-year-old male patient, diagnosed with high risk acute lymphoblastic leukemia who received treatment with etoposide among other drugs (St. Jude XIIIB). During the first course of treatment he needed premedication to etoposide administration because of mild hypersensitivity reactions. At the beginning of a second treatment the patient presented two severe hypersensitivity reactions (acute urticaria, angioedema and hypotension) despite the use of premedication and slow infusion. We initiated a twelve steps desensitization protocol for etoposide with success in the second round allowing the administration of further doses in an ambulatory unit without hypersensitivity reactions. PMID:20857627

  4. Antibiotic desensitization therapy in secondary syphilis and Listeria infection: case reports and review of desensitization therapy.

    PubMed

    Magpantay, Gil; Cardile, Anthony P; Madar, Cristian S; Hsue, Gunther; Belnap, Conrad

    2011-12-01

    Two adult cases, one of secondary syphilis and one of Listeria monocytogenes bacteremia, in which antibiotic desensitization therapy was utilized to assist treatment of active infection in the face of severe penicillin allergy. Clinical considerations are discussed that led to the decision to employ a formal desensitization procedure. Antibiotic desensitization protocols can facilitate optimal and safe antibiotic therapy in the appropriate clinical setting. PMID:22187514

  5. Systematic Desensitization: A Technique Worth Trying

    ERIC Educational Resources Information Center

    Bugg, Charles A.

    1972-01-01

    The author relates his experiences in using a modified form of systematic desensitization in a public school setting with counselees whose success and development are hampered by test anxiety and fear of public speaking. (Author)

  6. A pharmacological approach to elucidation of the role of different nerve fibres and receptor endings in mediation of pain.

    PubMed

    Szolcsnyi, J

    1977-09-01

    Capsaicin, after initial stimulation, induced a long-lasting insensitivity to chemical pain stimuli without reducing the sensitivity to mechanical pain. The effect was peripheral as shown by recording action potentials from sensory nerves. In order to throw light on the receptors responsible for chemogenic pain, the specificity of the capsaicin effect was analysed. 1. In cats, capsaicin given in close arterial injection excited the slowest conducting C2 fibres as measured by the collision technique on the saphenous nerve. In rats, the frequency of action potentials evoked by s.c. injection of capsaicin was sensitized by rapid warming of the skin area, while sudden cooling had a blocking effect. On the human skin, the threshold of thermal pain was shifted from 45 degrees C to 30-31 degrees C; below this skin temperature, the burning pain and hyperalgesia induced by capsaicin treatment disappeared and cold sensation remained unimpaired. 2. On the human tongue, local capsaicin desensitization resulted in an elevated threshold of warm discrimination, while gustatory sensitivity as well as the capacity for discriminating cold or tactile stimuli remained unimpaired. 3. It is concluded that capsaicin is a selective sensory blocking agent which acts by stimulation and subsequent sensory blockage of polymodal nociceptors and warm receptors. PMID:926026

  7. PP2B/calcineurin-mediated desensitization of TRPV1 does not require AKAP150

    PubMed Central

    Por, Elaine D.; Samelson, Bret K.; Belugin, Sergei; Akopian, Armen N.; Scott, John D.; Jeske, Nathaniel A.

    2011-01-01

    Activation of protein kinases and phosphatases at the plasma membrane often initiates agonist-dependent signalling events. In sensory neurons, AKAP150 (A-kinase-anchoring protein 150) orientates PKA (protein kinase A), PKC (protein kinase C) and the Ca2+/calmodulin-dependent PP2B (protein phosphatase 2B, also known as calcineurin) towards membrane-associated substrates. Recent evidence indicates that AKAP150-anchored PKA and PKC phosphorylate and sensitize the TRPV1 (transient receptor potential subfamily V type 1 channel, also known as the capsaicin receptor). In the present study, we explore the hypothesis that an AKAP150-associated pool of PP2B catalyses the dephosphorylation and desensitization of TRPV1. Biochemical, electrophysiological and cell-based experiments indicate that PP2B associates with AKAP150 and TRPV1 in cultured TG (trigeminal ganglia) neurons. Gene silencing of AKAP150 reduces basal phosphorylation of TRPV1. However, functional studies in neurons isolated from AKAP150?/? mice indicate that the anchoring protein is not required for pharmacological desensitization of TRPV1. Behavioural analysis of AKAP150?/? mice further support this notion, demonstrating that agonist-stimulated desensitization of TRPV1 is sensitive to PP2B inhibition and does not rely on AKAP150. These findings allow us to conclude that pharmacological desensitization of TRPV1 by PP2B may involve additional regulatory components. PMID:20883208

  8. Peripheral nerve lengthening as a regenerative strategy

    PubMed Central

    Vaz, Kenneth M.; Brown, Justin M.; Shah, Sameer B.

    2014-01-01

    Peripheral nerve injury impairs motor, sensory, and autonomic function, incurring substantial financial costs and diminished quality of life. For large nerve gaps, proximal lesions, or chronic nerve injury, the prognosis for recovery is particularly poor, even with autografts, the current gold standard for treating small to moderate nerve gaps. In vivo elongation of intact proximal stumps towards the injured distal stumps of severed peripheral nerves may offer a promising new strategy to treat nerve injury. This review describes several nerve lengthening strategies, including a novel internal fixator device that enables rapid and distal reconnection of proximal and distal nerve stumps. PMID:25317163

  9. Subjective olfactory desensitization and recovery in humans.

    PubMed

    Stuck, Boris A; Fadel, Victor; Hummel, Thomas; Sommer, J Ulrich

    2014-02-01

    Adaptation to smells is a well-known phenomenon and appears to be one of the major characteristics of olfaction. However, no standardized protocols for the psychophysical measurement of olfactory adaptation and recovery are available to date. Twenty normosmic participants were included. Hydrogen sulfide (H2S) and phenylethyl alcohol were used in different concentrations based on air dilution olfactometry. Volunteers were exposed to a constant flow of odorous air until perception disappeared completely. For testing recovery, the volunteers were exposed to a reference stimulus following complete self-desensitization with the same odor. The subjects were then again exposed to the same odorant after recovery periods of different lengths and instructed to rate stimulus intensity. The time to complete desensitization increased with increasing stimulus concentration for both odorants. Subjects desensitized more rapidly using H2S. Olfactory adaptation led to a reduction in stimulus intensity for the subsequent identical stimulation. Longer recovery periods resulted in increased intensity of the subsequent stimulus independent of the stimulus used. The results confirm current knowledge regarding the dynamics of olfactory adaptation and demonstrate differences in olfactory desensitization between the 2 odorants used. Olfactory recovery was independent of the odorant used, indicating that olfactory recovery after complete desensitization may be a uniform process. PMID:24293565

  10. 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

  11. The generalizability of capsaicin sensitization and desensitization.

    PubMed

    Prescott, J

    1999-07-01

    Studies using capsaicin-saturated filter papers have shown that the intensity of oral irritation tends to grow over successive samples, a phenomenon known as sensitization. If a hiatus of 5-15 min is then introduced, the intensity of irritation produced by a subsequent capsaicin stimulus is much reduced, and desensitization is said to have occurred. The use of other methodologies such as whole-mouth rinses, either with capsaicin or the irritants menthol or zingerone, have not consistently shown this response pattern, casting doubt on the extent to which sensitization and desensitization are general phenomena. Experiment 1 addressed this issue by comparing responses to whole-mouth rinses of 0.6 and 3 ppm capsaicin with those to 3 ppm capsaicin filter papers. Over an initial series of 10 samples, sensitization was evident but only for the 3 ppm capsaicin stimuli. Following a 10-min hiatus, desensitization was observed for all stimulus types. An examination of the data of individual subjects revealed considerable variability in response patterns over the initial 10 samples between subjects and, within subjects, between the filter paper and rinse stimuli, and between the test replications. Desensitization to the posthiatus stimuli was more consistent. A second experiment examined whether the capsaicin sensitization and desensitization shown by stimulation with filter papers or solutions also occurred in the context of the consumption of foods containing capsaicin. Two foods--soup and chili con carne--were consumed under conditions in which the rate of consumption was timed, as in Experiment 1, or was self-paced. In neither of the two conditions or foods was there strong evidence of sensitization, although, again, desensitization following a hiatus was evident. Substantial individual variability in response patterns was again apparent. There is thus no evidence for sensitization occurring during normal food consumption. PMID:10405101

  12. Playing violent video games and desensitization to violence.

    PubMed

    Brockmyer, Jeanne Funk

    2015-01-01

    This article examines current research linking exposure to violent video games and desensitization to violence. Data from questionnaire, behavioral, and psychophysiologic research are reviewed to determine if exposure to violent video games is a risk factor for desensitization to violence. Real-world implications of desensitization are discussed. PMID:25455576

  13. Desensitizing nano powders to electrostatic discharge ignition

    SciTech Connect

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

    2015-08-01

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

  14. 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

  15. A theoretical experimental method to determine the locus of desensitization.

    PubMed

    Buchman, E; Parnas, H

    1999-09-01

    Consider a ligand-gated channel with n agonist binding sites which can undergo desensitization. We present a theoretical experimental procedure for pinpointing the principal receptor state from which there is a transition to the desensitized state. The method is based on the observation that the dependence of the slope of the time constant of desensitization vs agonist concentration, at low concentrations, represents the state from which desensitization occurs. In those receptors where desensitization occurs from the open state (or the one immediately preceding it), the method also enables us to determine the number of binding sites. PMID:17886752

  16. Desensitization and recovery of metastable intermolecular composites

    DOEpatents

    Busse, James R. (South Fork, CO); Dye, Robert C. (Los Alamos, NM); Foley, Timothy J. (Los Alamos, NM); Higa, Kelvin T. (Ridgecrest, CA); Jorgensen, Betty S. (Jemez Springs, NM); Sanders, Victor E. (White Rock, NM); Son, Steven F. (Los Alamos, NM)

    2010-09-07

    A method to substantially desensitize a metastable intermolecular composite material to electrostatic discharge and friction comprising mixing the composite material with an organic diluent and removing enough organic diluent from the mixture to form a mixture with a substantially putty-like consistency, as well as a concomitant method of recovering the metastable intermolecular composite material.

  17. 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.

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

    PubMed

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

    2015-01-01

    Chronic pain after nerve injury is often accompanied by hypersensitivity to mechanical stimuli, yet whether this reflects altered input, altered processing, or both remains unclear. Spinal nerve ligation or transection results in hypersensitivity to mechanical stimuli in skin innervated by adjacent dorsal root ganglia, but no previous study has quantified the changes in receptive field properties of these neurons in vivo. To address this, we recorded intracellularly from L4 dorsal root ganglion neurons of anesthetized young adult rats, 1 wk after L5 partial spinal nerve ligation (pSNL) or sham surgery. One week after pSNL, hindpaw mechanical withdrawal threshold in awake, freely behaving animals was decreased in the L4 distribution on the nerve-injured side compared with sham controls. Electrophysiology revealed that high-threshold mechanoreceptive cells of A-fiber conduction velocity in L4 were sensitized, with a seven-fold reduction in mechanical threshold, a seven-fold increase in receptive field area, and doubling of maximum instantaneous frequency in response to peripheral stimuli, accompanied by reductions in after-hyperpolarization amplitude and duration. Only a reduction in mechanical threshold (minimum von Frey hair producing neuronal activity) was observed in C-fiber conduction velocity high-threshold mechanoreceptive cells. In contrast, low-threshold mechanoreceptive cells were desensitized, with a 13-fold increase in mechanical threshold, a 60% reduction in receptive field area, and a 40% reduction in instantaneous frequency to stimulation. No spontaneous activity was observed in L4 ganglia, and the likelihood of recording from neurons without a mechanical receptive field was increased after pSNL. These data suggest massively altered input from undamaged sensory afferents innervating areas of hypersensitivity after nerve injury, with reduced tactile and increased nociceptive afferent response. These findings differ importantly from previous preclinical studies, but are consistent with clinical findings in most patients with chronic neuropathic pain. PMID:25274350

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

    PubMed Central

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

    2014-01-01

    Chronic pain after nerve injury is often accompanied by hypersensitivity to mechanical stimuli, yet whether this reflects altered input, altered processing, or both remains unclear. Spinal nerve ligation or transection results in hypersensitivity to mechanical stimuli in skin innervated by adjacent dorsal root ganglia, but no previous study has quantified the changes in receptive field properties of these neurons in vivo. To address this, we recorded intracellularly from L4 dorsal root ganglion neurons of anesthetized young adult rats, 1 wk after L5 partial spinal nerve ligation (pSNL) or sham surgery. One week after pSNL, hindpaw mechanical withdrawal threshold in awake, freely behaving animals was decreased in the L4 distribution on the nerve-injured side compared with sham controls. Electrophysiology revealed that high-threshold mechanoreceptive cells of A-fiber conduction velocity in L4 were sensitized, with a seven-fold reduction in mechanical threshold, a seven-fold increase in receptive field area, and doubling of maximum instantaneous frequency in response to peripheral stimuli, accompanied by reductions in after-hyperpolarization amplitude and duration. Only a reduction in mechanical threshold (minimum von Frey hair producing neuronal activity) was observed in C-fiber conduction velocity high-threshold mechanoreceptive cells. In contrast, low-threshold mechanoreceptive cells were desensitized, with a 13-fold increase in mechanical threshold, a 60% reduction in receptive field area, and a 40% reduction in instantaneous frequency to stimulation. No spontaneous activity was observed in L4 ganglia, and the likelihood of recording from neurons without a mechanical receptive field was increased after pSNL. These data suggest massively altered input from undamaged sensory afferents innervating areas of hypersensitivity after nerve injury, with reduced tactile and increased nociceptive afferent response. These findings differ importantly from previous preclinical studies, but are consistent with clinical findings in most patients with chronic neuropathic pain. PMID:25274350

  20. Sensory nerve fibers containing calcitonin gene-related peptide in gastrocnemius, latissimus dorsi and erector spinae muscles and thoracolumbar fascia in mice.

    PubMed

    Barry, C M; Kestell, G; Gillan, M; Haberberger, R V; Gibbins, I L

    2015-04-16

    Chronic pain is a significant burden and much is attributed to back muscles. Back muscles and their associated fasciae make important and distinct contributions to back pain. Peptidergic nociceptors innervating these structures contribute to central transmission and pain modulation by peripheral and central actions. Plastic changes that augment and prolong pain are exhibited by neurons containing calcitonin gene-related peptide (CGRP) following muscle injury. Subpopulations of neurons containing this peptide have been identified in dorsal root ganglia but the distribution of their fibers in skeletal muscles and associated fasciae has not been fully documented. This study used multiple-labeling immunofluorescence and retrograde axonal tracing to identify dorsal root ganglion cells associated with muscle, and to characterize the distribution and density of their nerve fibers in mouse gastrocnemius and back muscles and in the thoracolumbar fascia. Most nerve fibers in these tissues contained CGRP and two major subpopulations of neurons were found: those containing CGRP and substance P (SP) and those containing CGRP but not SP. Innervation density was three times higher in the thoracolumbar fascia than in muscles of the back. These studies show mouse back and leg muscles are predominantly innervated by neurons containing CGRP, an important modulator of pain signal transmission. There are two distinct populations of neurons containing this peptide and their fibers were three times more densely distributed in the thoracolumbar fascia than back muscles. PMID:25681518

  1. Homologous desensitization to prostaglandins in rabbit ileum

    SciTech Connect

    Musch, M.W.; Field, M.; Miller, R.J.; Stoff, J.S.

    1987-01-01

    Prostaglandins (PG's) increase short-circuit current (I/sub sc/), inhibit NaCl absorption, and stimulate Cl secretion in rabbit ileum. These changes occur with the following PGs; E/sub 3/, E/sub 1/, nitrilo-I/sub 2/ and, to a lesser extent, with A/sub 2/, D/sub 2/, and F/sub 2..cap alpha../. Arachidonic acid (AA) also stimulates secretion. The PG- or AA-stimulated I/sub sc/ does not persist, however, and on prolonged exposure tachyphylaxis develops. Resensitization of the I/sub sc/ response to PGE/sub 2/ is rapid, being essentially complete in 15 min after the PG is removed. Desensitization to AA is not reflected by diminished PG generation. PGE/sub 2/ release from the mucosa after AA addition is constant, although the AA-stimulated I/sub sc/ decreases. I/sub sc/ measurements indicate that PGE/sub 2/ at slightly below its EC/sub 50/ partially desensitizes and a near-maximal concentration completely desensitizes to PGE/sub 2/ but does not, however, inhibit the subsequent change in I/sub sc/ caused by theophylline or vasoactive intestinal peptide (VIP). Adenosine 3',5'-cyclic monophosphate (cAMP) measurements suggest that desensitization applies to cAMP production. PGE/sub 2/ (10/sup -5/ M) increases mucosal cAMP three- to sevenfold, but this elevation is transient; a second challenge dose, which fails to elicit a I/sub sc/ change, also fails to increase mucosal cAMP. Adenylate cyclase measurements from untreated and PGE/sub 2/-treated enterocytes demonstrate a decrease in stimulation by PGE/sub 2/ but not in stimulation by VIP, fluoride, or 5-guanylylimidodiphosphate.

  2. Desensitization protocol for rituximab-induced serum sickness.

    PubMed

    Fajt, Merritt L; Petrov, Andrej A

    2014-01-01

    Rituximab, a chimeric anti-CD20 monoclonal antibody, is used to treat rheumatologic and hematologic diseases. Serum sickness, a Type III delayed hypersensitivity reaction, has been reported with rituximab treatment. Traditionally, drug desensitization has been used to treat Type I IgE-mediated hypersensitivity reactions. We report the first case of successful drug desensitization to rituximab in a patient with medication-induced serum sickness. In our case, a 37-year-old woman with Sjogren's syndrome and papillary thyroid carcinoma developed serum sickness 72 hours following rituximab infusion for gastric mucosal associated lymphoma tissue (MALT). Her MALT progressed after stopping rituximab. She underwent a rapid 12-step intravenous rituximab desensitization without recurrence of serum sickness. Following the completion of 4 rituximab desensitizations, she had gastric MALT remission. She received 25 maintenance rituximab doses using this desensitization protocol quarterly without complications. This is the first report documenting rituximab desensitization for the treatment of delayed drug reactions like serum sickness. PMID:24861993

  3. Electrophysiological evaluation of nerve function in inferior alveolar nerve injury: relationship between nerve action potentials and histomorphometric observations.

    PubMed

    Murayama, M; Sasaki, K; Shibahara, T

    2015-12-01

    The objective of this study was to improve the accuracy of diagnosis of inferior alveolar nerve (IAN) injury by determining degrees of nerve disturbance using the sensory nerve action potential (SNAP) and sensory nerve conduction velocity (SCV). Crush and partial and complete nerve amputation injuries were applied to the IAN of rabbits, then SNAPs and histomorphometric observations were recorded at 1, 5, and 10 weeks. For crush injury, most nerves were smaller in diameter at 5 weeks than at 1 week, however after 10 weeks, extensive nerve regeneration was observed. The SNAP showed a decrease in SCV at weeks 1 and 5, followed by an increase at week 10. For partial nerve amputation, small to medium-sized nerve fibres were observed at weeks 1 and 5, then larger nerves were seen at week 10. Minimal changes in SCV were observed at weeks 1 and 5, however SCV increased at week 10. For complete nerve amputation, nerve fibres were sparse at week 1, but gradual nerve regeneration was observed at weeks 5 and 10. SNAPs were detectable from week 10, however the SCV was extremely low. This study showed SCV to be an effective factor in the evaluation of nerve injury and regeneration. PMID:26433750

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

    PubMed Central

    Charous, Matthew T.; Madison, Sarah J.; Suresh, J.; Sandhu, NavParkash S.; Loland, Vanessa J.; Mariano, Edward R.; Donohue, Michael C.; Dutton, Pascual H.; Ferguson, Eliza J.; Ilfeld, Brian M.

    2011-01-01

    Background Whether the method of local anesthetic administration for continuous femoral nerve blocks basal infusion versus repeated hourly bolus doses influences block effects remains unknown. Methods Bilateral femoral perineural catheters were inserted in volunteers (n = 11). Ropivacaine 0.1% was administered through both catheters concurrently: a 6-h continuous 5 ml/h basal infusion on one side and 6 hourly bolus doses on the contralateral side. The primary endpoint was the maximum voluntary isometric contraction (MVIC) of the quadriceps femoris muscle at Hour 6. Secondary end points included quadriceps MVIC at other time points, hip adductor MVIC, and cutaneous sensation 2 cm medial to the distal quadriceps tendon in the 22 h following local anesthetic administration initiation. Results Quadriceps MVIC for limbs receiving 0.1% ropivacaine as a basal infusion declined by a mean (SD) of 84% (19) compared with 83% (24) for limbs receiving 0.1% ropivacaine as repeated bolus doses between baseline and Hour 6 (paired t test P = 0.91). Intrasubject comparisons (left vs. right) reflected a lack of difference as well: the mean basal-bolus difference in quadriceps MVIC at Hour 6 was ?1.1% (95% CI ?22.0 to 19.8%). The similarity did not reach our a priori threshold for concluding equivalence, which was the 95% CI falling within 20%. There were similar minimal differences in the secondary endpoints during local anesthetic administration. Conclusions This study did not find evidence to support the hypothesis that varying the method of local anesthetic administration basal infusion versus repeated bolus doses influences continuous femoral nerve block effects to a clinically significant degree. PMID:21394001

  5. Desensitization of parathyroid hormone receptors on cultured bone cells

    SciTech Connect

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

    1990-12-01

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

  6. Nursing Care of Patients Undergoing Chemotherapy Desensitization: Part II.

    PubMed

    Jakel, Patricia; Carsten, Cynthia; Carino, Arvie; Braskett, Melinda

    2016-04-01

    Chemotherapy desensitization protocols are safe, but labor-intensive, processes that allow patients with cancer to receive medications even if they initially experienced severe hypersensitivity reactions. Part I of this column discussed the pathophysiology of hypersensitivity reactions and described the development of desensitization protocols in oncology settings. Part II incorporates the experiences of an academic medical center and provides a practical guide for the nursing care of patients undergoing chemotherapy desensitization.
. PMID:26991706

  7. 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

  8. Desensitization and recovery of phototropic responsiveness in Arabidopsis thaliana

    NASA Technical Reports Server (NTRS)

    Janoudi, A. K.; Poff, K. L.

    1993-01-01

    Phototropism is induced by blue light, which also induces desensitization, a partial or total loss of phototropic responsiveness. The fluence and fluence-rate dependence of desensitization and recovery from desensitization have been measured for etiolated and red light (669-nm) preirradiated Arabidopsis thaliana seedlings. The extent of desensitization increased as the fluence of the desensitizing 450-nm light was increased from 0.3 to 60 micromoles m-2 s-1. At equal fluences, blue light caused more desensitization when given at a fluence rate of 1.0 micromole m-2 s-1 than at 0.3 micromole m-2 s-1. In addition, seedlings irradiated with blue light at the higher fluence rate required a longer recovery time than seedlings irradiated at the lower fluence rate. A red light preirradiation, probably mediated via phytochrome, decreased the time required for recovery from desensitization. The minimum time for detectable recovery was about 65 s, and the maximum time observed was about 10 min. It is proposed that the descending arm of the fluence-response relationship for first positive phototropism is a consequence of desensitization, and that the time threshold for second positive phototropism establishes a period during which recovery from desensitization occurs.

  9. Nerve biopsy

    MedlinePLUS

    ... myelin sheath covering the nerve) Inflammatory nerve conditions (neuropathies) Additional conditions under which the test may be performed: Alcoholic neuropathy Axillary nerve dysfunction Brachial plexopathy Charcot-Marie-Tooth ...

  10. Nerve grafting in the repair of complicated peripheral nerve trauma.

    PubMed

    Walton, R; Finseth, F

    1977-10-01

    Peripheral nerve trauma has been a challenge to surgeons, with significant advances in the surgery of repair occurring in major wars. The standard method of treatment involving wide mobilization and end-to-end suture to close traumatic gaps in peripheral nerves has not produced consistently acceptable results, particularly with large gaps. However, with the recent development of microsurgical techniques and instrumentation, the method of interfascicular nerve grafting has been applied to selected patients with trauma problems of the peripheral nerve, by resecting and autogenous nerve grafting at staggered levels to distribute scar formation, followed by plaster immobilization for 3 weeks. Ten patients are reported, with motor nerve recovery ranging from M2 to M4 and sensory recovery, S2-S4 (See Table I), based on Seddon's classification (11). PMID:909120

  11. Complete sciatic nerve transection induces increase of neuropeptide Y-like immunoreactivity in primary sensory neurons and spinal cord of frogs.

    PubMed

    Guedes, Renata P; Marchi, Melina I; Achaval, Matilde; Partata, Wania A

    2004-12-01

    Neuropeptide Y (NPY) was immunohistochemically investigated in the frog spinal cord and dorsal root ganglia after axotomy. In normal ganglia, moderate NPY-like immunoreactivity (NPY-IR) prevailed in large and medium cells. In the spinal cord, the NPY-IR was densest in the dorsal part of the lateral funiculus. Other fibers and neurons NPY-IR were observed in the dorsal and ventral terminal fields and mediolateral band. NPY-IR fibers were also found in the ventral horn and in the ventral and lateral funiculi. The sciatic nerve transection increased the NPY-IR in large and medium neurons of the ipsilateral and contralateral dorsal root ganglia at 3 and 7 days, but no clear change was found at 15 days. In the spinal cord, there was a bilateral increase in the NPY-IR of the dorsal part of the lateral funiculus. In the ipsilateral side, the NPY-IR was increased at 3 and 7 days but was decreased at 15 days. In the contralateral side, a significant reduction at 15 days occurred. These findings seem to favor the role of NPY in the modulation of pain-related information in frogs, suggesting that this role of NPY may have appeared early in vertebrate evolution. PMID:15596391

  12. Internalization and desensitization of adenosine receptors

    PubMed Central

    Klaasse, Elisabeth C.; de Grip, Willem J.; Beukers, Margot W.

    2007-01-01

    Until now, more than 800 distinct G protein-coupled receptors (GPCRs) have been identified in the human genome. The four subtypes of the adenosine receptor (A1, A2A, A2B and A3 receptor) belong to this large family of GPCRs that represent the most widely targeted pharmacological protein class. Since adenosine receptors are widespread throughout the body and involved in a variety of physiological processes and diseases, there is great interest in understanding how the different subtypes are regulated, as a basis for designing therapeutic drugs that either avoid or make use of this regulation. The major GPCR regulatory pathway involves phosphorylation of activated receptors by G protein-coupled receptor kinases (GRKs), a process that is followed by binding of arrestin proteins. This prevents receptors from activating downstream heterotrimeric G protein pathways, but at the same time allows activation of arrestin-dependent signalling pathways. Upon agonist treatment, adenosine receptor subtypes are differently regulated. For instance, the A1Rs are not (readily) phosphorylated and internalize slowly, showing a typical half-life of several hours, whereas the A2AR and A2BR undergo much faster downregulation, usually shorter than 1h. The A3R is subject to even faster downregulation, often a matter of minutes. The fast desensitization of the A3R after agonist exposure may be therapeutically equivalent to antagonist occupancy of the receptor. This review describes the process of desensitization and internalization of the different adenosine subtypes in cell systems, tissues and in vivo studies. In addition, molecular mechanisms involved in adenosine receptor desensitization are discussed. PMID:18368531

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

    ERIC Educational Resources Information Center

    Romano, John L.; Cabianca, William A.

    1978-01-01

    Biofeedback training to reduce test anxiety among university students was investigated. Biofeedback training with systematic desensitization was compared to an automated systematic desensitization program not using EMG feedback. Biofeedback training is a useful technique for reducing test anxiety, but not necessarily more effective than systematic

  14. Desensitization and recovery of phototropic responsiveness in Arabidopsis thaliana

    SciTech Connect

    Janoudi, A.K.; Poff, K.L. )

    1993-04-01

    Phototropism is induced by blue light, which also induces desensitization, a partial or total loss of phototropic responsiveness. The fluence and fluence-rate dependence of densensitization and recovery from desensitization have been measured for etiolated and red light (669-nm) preirradiated Arabidopsis thaliana seedlings. The extent of desensitization increased as the fluence of the desensitizing 450-nm light was increased from 0.3 to 60 [mu]mol m[sup [minus]2] s[sup [minus]1]. At equal fluences, blue light caused more desensitization when given at a fluence rate of 1.0 [mu]mol m[sup [minus]2] s[sup [minus]1] than at 0.3 [mu]mol m[sup [minus]2] s[sup [minus]1]. In addition, seedlings irradiated with blue light at the higher fluence rate required a longer recovery time than seedlings irradiated at the lower fluence rate. A red light preirradiation, probably mediated via phytochrome, decreased the time required for recovery from desensitization. The minimum time for detectable recovery was about 65 s, and the maximum time observed was about 10 min. It is proposed that the descending arm of the fluence-response relationship for first positive phototropism is a consequence of desensitization, and that the time threshold for second positive phototropism establishes a period during which recovery from desensitization occurs. 11 refs., 6 figs.

  15. Evidence that removal of capsaicin accelerates desensitization on the tongue.

    PubMed

    Green, B G

    1993-02-01

    It has previously been shown that repeated presentations of a moderate concentration of capsaicin could either sensitize or desensitize the tongue, depending upon the temporal pattern of stimulation. Only when stimulation was halted for 5 min or longer did sensitization begin to give way to desensitization. The apparent necessity of a hiatus in stimulation led to the hypothesis that desensitization involved an inability to re-excite quiescent fibers rather than a progressive suppression of stimulated fibers. This hypothesis was tested in the present study by measuring the perceptual response to a non-desensitizing irritant, zingerone, when it was presented at the rate of l/min following a series of capsaicin conditioning stimuli. After an initial, brief period of cross-hyper-sensitization, cross-desensitization developed at a rate equivalent to that observed when no stimulus was presented. Thus, the results disproved the hypothesis that desensitization cannot occur if capsaicin-sensitive fibers continue to be stimulated, and suggested that after an initial period of excitation, the removal of capsaicin accelerates the desensitization process. This seeming paradox is discussed in terms of the neural mechanisms that may underlie capsaicin desensitization. PMID:8469401

  16. The desensitization gate of inhibitory Cys-loop receptors

    NASA Astrophysics Data System (ADS)

    Gielen, Marc; Thomas, Philip; Smart, Trevor G.

    2015-04-01

    Cys-loop neurotransmitter-gated ion channels are vital for communication throughout the nervous system. Following activation, these receptors enter into a desensitized state in which the ion channel shuts even though the neurotransmitter molecules remain bound. To date, the molecular determinants underlying this most fundamental property of Cys-loop receptors have remained elusive. Here we present a generic mechanism for the desensitization of Cys-loop GABAA (GABAARs) and glycine receptors (GlyRs), which both mediate fast inhibitory synaptic transmission. Desensitization is regulated by interactions between the second and third transmembrane segments, which affect the ion channel lumen near its intracellular end. The GABAAR and GlyR pore blocker picrotoxin prevented desensitization, consistent with its deep channel-binding site overlapping a physical desensitization gate.

  17. Sural and Radial Sensory Responses in Patients with Sensory Polyneuropathy

    PubMed Central

    Guo, Ying; Palmer, J. Lynn; Brown, Xun S.; Fu, Jack B.

    2016-01-01

    Introduction The sural/radial nerve amplitude ratio (SRAR) is the quotient of the sensory nerve action potential (SNAP) amplitudes (Amp) of the sural and the superficial radial nerve. It has been hypothesized that this ratio can be used for the detection of early axonal loss, because the sural SNAP amplitude will decrease first, thereby also decreasing the SRAR value. Objectives To determine the sensitivity and specificity of SRAR, age-adjusted sural and radial SNAP Amp in the diagnosis of axonal sensory polyneuropathy in cancer patients. Design Retrospective review. Setting Comprehensive cancer center. Patients One hundred and ninety one EMG reports from January 2001 to December 2005. Methods The independent variable is the diagnosis of axonal sensory polyneuropathy in the EMG reports that is based on multiple tests. Main Outcome Measurements We assessed the agreement between classifications of axonal sensory polyneuropathy made using the current ‘gold standard’ and the proposed method that is based on patients’ age-adjusted radial and sural SNAP amplitude; an SRAR being above or below the normal value (0.21). Results We found that the sensitivities for age-adjusted radial SNAP Amp, age-adjusted sural SNAP Amp, and SRAR were 33%, 64%, 56% respectively; the specificities were 85%, 70%, 77% respectively. Conclusions SRAR is neither the most sensitive, nor the most specific in the diagnosis of axonal sensory polyneuropathy.

  18. Pharmacist-managed allergy desensitization program.

    PubMed

    Almond, S N; Caiola, S M; Huff, P S

    1982-02-01

    A pharmacist-managed immunotherapy program for ambulatory atopic patients is described. Pharmacists in a network of three health centers recommended that they assume management of the allergy desensitization program when they recognized problems with the existing program. Guidelines for the immunotherapy service were developed and approved by the pharmacy, therapeutics, and standing orders committee. Patients, already tested by an allergist, are referred to the pharmacists for the administration of their immunotherapy. Under the guidelines for the program, pharmacists collect and record the patients' history, assess the patients' knowledge of allergy desensitization, administer the allergens, examine the injection site, question the patients about symptoms, and initiate treatment of local and systemic reactions. A physician is available for consultation and for treatment of life-threatened adverse reactions. Following any reaction, the pharmacist adjusts the next antigen dose accordingly. Typical charges for these services are $10-15 for the first visit, and $3.50 for subsequent visits. The pharmacists spend about 30 minutes of their time for the initial visits, and 10 minutes for subsequent visits. The time spent by physicians is negligible, and there is no charge for their consultations. Patients under the care of the pharmacists rarely wait more than 15 minutes for an appointment. This service has been well accepted by patients, physicians, and mid-level practitioners. Pharmacists are using their knowledge and skills to provide a direct patient-care service, and they are being reimbursed for a nondispensing activity. PMID:7058798

  19. μ-Opioid receptor desensitization: homologous or heterologous?

    PubMed

    Llorente, Javier; Lowe, Janet D; Sanderson, Helen S; Tsisanova, Elena; Kelly, Eamonn; Henderson, Graeme; Bailey, Chris P

    2012-12-01

    There is considerable controversy over whether μ-opioid receptor (MOPr) desensitization is homologous or heterologous and over the mechanisms underlying such desensitization. In different cell types MOPr desensitization has been reported to involve receptor phosphorylation by various kinases, including G-protein-coupled receptor kinases (GRKs), second messenger and other kinases as well as perturbation of the MOPr effector pathway by GRK sequestration of G protein βγ subunits or ion channel modulation. Here we report that in brainstem locus coeruleus (LC) neurons prepared from relatively mature rats (5-8 weeks old) rapid MOPr desensitization induced by the high-efficacy opioid peptides methionine enkephalin and DAMGO was homologous and not heterologous to α(2)-adrenoceptors and somatostatin SST(2) receptors. Given that these receptors all couple through G proteins to the same set of G-protein inwardly rectifying (GIRK) channels it is unlikely therefore that in mature neurons MOPr desensitization involves G protein βγ subunit sequestration or ion channel modulation. In contrast, in slices from immature animals (less than postnatal day 20), MOPr desensitization was observed to be heterologous and could be downstream of the receptor. Heterologous MOPr desensitization was not dependent on protein kinase C or c-Jun N-terminal kinase activity, but the change from heterologous to homologous desensitization with age was correlated with a decrease in the expression levels of GRK2 in the LC and other brain regions. The observation that the mechanisms underlying MOPr desensitization change with neuronal development is important when extrapolating to the mature brain results obtained from experiments on expression systems, cell lines and immature neuronal preparations. PMID:23002724

  20. Rapid recovery from capsaicin desensitization during recurrent stimulation.

    PubMed

    Green, B G

    1996-12-01

    Topical desensitization of the tongue was assessed during multiple bouts of exposure to capsaicin. In the first experiment subjects rated perceived irritation as 30 capsaicin stimuli (33 microM) were applied to the tongue tip in three blocks of 10, with 15 min breaks between blocks. Significant desensitization was measured at the beginning of the second and third blocks within each session. However, as stimulation continued within those blocks sensations of irritation grew toward undesensitized levels ('stimulus-induced recovery' (SIR)). Desensitization did not extend across days. The second experiment employed a 10-fold higher concentration of capsaicin (330 microM) to determine if SIR was limited to low levels of desensitization. SIR occurred as before within sessions, and the higher concentration produced desensitization across days that also exhibited recovery during the first block of stimuli on days 2 and 3. The third experiment included piperine, zingerone and citric acid as stimuli to determine if SIR was specific to capsaicin. Piperine produced SIR under conditions of both self- and cross-desensitization with capsaicin, whereas recovery failed to materialize with zingerone. Citric acid was not significantly cross-desensitized by capsaicin, so recovery could not be measured. Overall the results demonstrate that desensitization of the tongue produced by either capsaicin or piperine can be temporarily reversed if stimulation with either chemical is resumed for only a few minutes. The implications these findings may have for hypotheses about the mechanisms of capsaicin desensitization and sensitization as well as for clinical applications of capsaicin as a topical analgesic are discussed. PMID:9121811

  1. Painful channels in sensory neurons.

    PubMed

    Lee, Yunjong; Lee, Chang-Hun; Oh, Uhtaek

    2005-12-31

    Pain is an unpleasant sensation experienced when tissues are damaged. Thus, pain sensation in some way protects body from imminent threat or injury. Peripheral sensory nerves innervated to peripheral tissues initially respond to multiple forms of noxious or strong stimuli, such as heat, mechanical and chemical stimuli. In response to these stimuli, electrical signals for conducting the nociceptive neural signals through axons are generated. These action potentials are then conveyed to specific areas in the spinal cord and in the brain. Sensory afferent fibers are heterogeneous in many aspects. For example, sensory nerves are classified as Aa, -b, -d and C-fibers according to their diameter and degree of myelination. It is widely accepted that small sensory fibers tend to respond to vigorous or noxious stimuli and related to nociception. Thus these fibers are specifically called nociceptors. Most of nociceptors respond to noxious mechanical stimuli and heat. In addition, these sensory fibers also respond to chemical stimuli [Davis et al. (1993)] such as capsaicin. Thus, nociceptors are considered polymodal. Recent advance in research on ion channels in sensory neurons reveals molecular mechanisms underlying how various types of stimuli can be transduced to neural signals transmitted to the brain for pain perception. In particular, electrophysiological studies on ion channels characterize biophysical properties of ion channels in sensory neurons. Furthermore, molecular biology leads to identification of genetic structures as well as molecular properties of ion channels in sensory neurons. These ion channels are expressed in axon terminals as well as in cell soma. When these channels are activated, inward currents or outward currents are generated, which will lead to depolarization or hyperpolarization of the membrane causing increased or decreased excitability of sensory neurons. In order to depolarize the membrane of nerve terminals, either inward currents should be generated or outward currents should be inhibited. So far, many cationic channels that are responsible for the excitation of sensory neurons are introduced recently. Activation of these channels in sensory neurons is evidently critical to the generation of nociceptive signals. The main channels responsible for inward membrane currents in nociceptors are voltage-activated sodium and calcium channels, while outward current is carried mainly by potassium ions. In addition, activation of non-selective cation channels is also responsible for the excitation of sensory neurons. Thus, excitability of neurons can be controlled by regulating expression or by modulating activity of these channels. PMID:16404144

  2. Forty years in capsaicin research for sensory pharmacology and physiology.

    PubMed

    Szolcsnyi, Jnos

    2004-12-01

    Capsaicin, the pungent ingredient of chilli peppers has become a "hot" topic in neuroscience with yearly publications over half thousand papers. It is outlined in this survey how this exciting Hungarian research field emerged from almost complete ignorance. From the initial observation of the phenomenon of "capsaicin desensitization", a long-lasting chemoanalgesia and impairment in thermoregulation against heat, the chain of new discoveries which led to the formulation of the existence of a "capsaicin receptor" on C-polymodal nociceptors is briefly summarized. Neurogenic inflammation is mediated by these C-afferents which are supplied by the putative capsaicin receptor and were termed as "capsaicin sensitive" chemoceptive afferents. They opened new avenues in local peptidergic regulation in peripheral tissues. It has been suggested that in contrast to the classical axon reflex theory, the capsaicin-sensitive sensory system subserves a "dual sensory-efferent" function whereby initiation of afferent signals and neuropeptide release are coupled at the same nerve endings. Furthermore, in the skin at threshold stimuli which do not evoke sensation elicit already maximum efferent response as enhanced microcirculation. In isolated organ preparations large scale of new type of peptidergic capsaicin-sensitive neurogenic smooth muscle responses were revealed after the first one was described by ourselves on the guinea-pig ileum in 1978. Recently the "capsaicin receptor" has been cloned and it is now named as the "transient receptor potential vanilloid 1" (TRPV1). Hence, capsaicin research led to the discovery of the first temperature-gated ion channel gated by noxious heat, protons, vanilloids and endogenous ligands as anandamide, N-oleoyldopamine and lipoxygenase products. Another recent achievement is the discovery of a novel "unorthodox" neurohumoral regulatory mechanism mediated by somatostatin. Somatostatin released from the TRPV1-expressing nerve endings reaches the circulation and elicits systemic antiinflammatory and analgesic "sensocrine" functions with counter-regulatory influence e.g. in Freund's adjuvant-induced chronic arthritis. Nociceptors supplied by TRPV1 and sst4 somatostatin receptors has become nowadays promising targets for drug development. PMID:15567473

  3. Peripheral nerve conduits: technology update

    PubMed Central

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

    2014-01-01

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

  4. A clinical guide to needle desensitization for the paediatric patient.

    PubMed

    Taylor, Greig D; Campbell, Caroline

    2015-05-01

    Needle phobia is a common problem encountered by dental practitioners and it can pose a challenge, especially in the paediatric patient. Needle desensitization can be used for patients who have needle fear or phobia and help them overcome this by repeated, non-threatening and controlled contacts. This paper will describe an accepted technique of needle desensitization and work through the steps required to achieve a successful outcome of local anaesthesia being delivered in a calm, safe and controlled manner. Clinical Relevance: Needle desensitization is an effective technique which can be used to enable a needle phobic patient to receive a dental injection. PMID:26062263

  5. 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

  6. Fascial entrapment of the sural nerve and its clinical relevance

    PubMed Central

    Natsis, Konstantinos; Tzika, Maria; Ioannidis, Orestis

    2014-01-01

    Sural nerve presents great topographic variability and it is responsible for sensory innervation of the posterolateral side of the distal third of the leg and lateral aspect of the foot. Entrapment of the nerve could be caused by compression due to fascial thickening, while the symptomatology includes sensory alterations and deficits at the nerve distribution area. We report a cadaveric case of a variant sural nerve that presented a distinct entrapment site. A supernumerary sensory branch was encountered originating from the common peroneal nerve, while the peroneal component of the sural nerve was observed to take a course within a fibrous fascial tunnel 3.1 cm in length that caused nerve fixation and flattening. The tension applied to the aforementioned branch was shown to worsen during passive forcible foot plantaflexion and inversion. The etiology, diagnosis and the treatment options are discussed comprehensively. PMID:24987554

  7. Injection nerve palsy

    PubMed Central

    Kakati, Arindhom; Bhat, Dhananjaya; Devi, Bhagavathula Indira; Shukla, Dhaval

    2013-01-01

    Objective: To study the clinical profile and outcome of surgery for injection nerve palsies. Materials and Methods: This is a retrospective study of patients with INP who were treated at our institute during May 2000 to May 2009. Clinical, electroneuromyography (ENMG), and operative findings were noted. Intraoperative nerve action potential monitoring was not used in any case. Outcome of patients who were followed was reviewed. Results: INP comprised 92 (11%) of 837 nerve injury patients. Seventy one patients were children less than 16 years. The nerves involved were sciatic in 80 patients, radial in 8, and others in four. Fifty seven patients had power, grade 0/5. ENMG studies revealed absent compound muscle action potential in 64 and absent sensory nerve action potential in 67 patients. Thirty nine (42.3%) of 92 patients underwent surgery. The mean duration since injury in these patients was 5.2 months (3 months to 11 months). All underwent neurolysis. Only 18 patients who underwent surgery had a follow up of more than 3 months. Ten (55.5%) patients had good or fair outcome after surgery. Except for grade of motor deficit prior to surgery, none of the variables were found to significantly affect the outcome. Conclusion: The outcome of INP is generally good and many patients recover spontaneously. The outcome of surgery is dependent on preoperative motor power. PMID:23546341

  8. 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

  9. Nursing Care of Patients Undergoing Chemotherapy Desensitization: Part I.

    PubMed

    Jakel, Patricia; Carsten, Cynthia; Braskett, Melinda; Carino, Arvie

    2016-02-01

    Hypersensitivity reactions to chemotherapeutic agents can cause the discontinuation of first-line therapies. Chemotherapy desensitization is a safe, but labor-intensive, process to administer these important medications. A desensitization protocol can enable a patient to receive the entire target dose of a medication, even if the patient has a history of severe infusion reactions. In this article, the authors explain the pathophysiology of hypersensitivity reactions and describe the recent development of desensitization protocols in oncology. In part II of this article, which will appear in the April 2016 issue of the Clinical Journal of Oncology Nursing, the authors will give a detailed account of how a desensitization protocol is performed at an academic medical center.?. PMID:26800403

  10. The epidermis: a sensory tissue.

    PubMed

    Boulais, Nicholas; Misery, Laurent

    2008-01-01

    The skin is an efficient barrier which protects our bodies from the external environment but it is also an important site for the perception of various stimuli. Sensory neurones of the peripheral nervous system send many primary afferent fibres to the skin. They pass through the dermis and penetrate the basement membrane to innervate epidermal cells or remain as free endings. Nerve fibres are clearly involved in somatosensation. However, they are not always so numerous, for example in distal parts of the limbs, and some kinds of sensors can be at a distance of hundreds of micrometers from each other. The skin can detect patterns at a very fine and smaller scale, which suggests that nerve terminals are helped by epidermal sensors. All epidermal cells (keratinocytes, melanocytes, Langerhans cells and Merkel cells) express sensor proteins and neuropeptides regulating the neuro-immuno-cutaneous system. Hence, they must play a part in the epidermal sensory system. This review will consider the epidermal components of this forefront sensory system and the stimulations they perceive. The epidermis can be considered a true sensory tissue where sensor proteins and neurone-like properties enable epidermal cells to participate in the skin surface perception through interactions with nerve fibres. PMID:18424369

  11. Desensitization for solid organ and hematopoietic stem cell transplantation

    PubMed Central

    Zachary, Andrea A; Leffell, Mary S

    2014-01-01

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

  12. Nerve coaptation studies with and without a gap in rabbits.

    PubMed

    Hasegawa, J; Shibata, M; Takahashi, H

    1996-03-01

    Appropriate matching of proximal and distal fibers is a major objective when suturing a lacerated nerve. Recent studies suggest that neurotropic factors may influence motor/sensory specificity and affect the functional outcome. This was studied in animal models by direct coaptation of cut nerve ends inside a 5-mm collagen tube with and without appropriate sensory/motor alignment, as well as in models where the cut nerve ends were placed in a 10-mm collagen tube with a 5-mm gap, with and without appropriate sensory/motor alignment. The radial nerve of 49 New Zealand white rabbits was chosen because it has distinct motor and sensory divisions. The animals were killed at 24 weeks and electrophysiologic, histologic, and muscle contraction studies were performed. Axon counts and diameters were measured from the distal motor and sensory stumps. Nerve conduction velocity, dry muscle weight, and motor axon counts were not statistically different between the groups. The malaligned group without a gap had better regeneration in sensory nerves than other groups. The muscle contraction force of the malaligned group without a gap was significantly less than the other groups. The malaligned group with a 5-mm gap had the same muscle contraction force as the aligned group without a gap. In this study, a short nerve gap lessened the misdirection of motor fibers after nerve-end coaptation. PMID:8683059

  13. Ulnar nerve reconstruction with an expanded polytetrafluoroethylene conduit.

    PubMed

    Stanec, S; Stanec, Z

    1998-12-01

    The ulnar nerve of a 22-year-old woman was reconstructed by expanded polytetrafluoroethylene (ePTFE) conduit, 141 days after nerve transection at the distal forearm level. A 2.9 cm nerve gap was bridged by a corrugated, 3.9 cm long, 6 mm diameter ePTFE tube. At final evaluation 3 years later the patient achieved excellent motor and sensory recovery. Exploration of the tube, at that time, showed macroscopically normal nerve inside the conduit. PMID:10209470

  14. Therapy of vaginismus by hypnotic desensitization.

    PubMed

    Fuchs, K

    1980-05-01

    Fear and anxiety are of tremendous importance in the production and maintenance of a symptom. Vaginismus, as a reaction of avoidance of an anxiety-producing situation, is readily amenable to treatment by systematic desensitization. This may proceed mainly in two ways: "in vitro" or "in vivo." In order to strengthen and speed up the densensitization process, we used hypnotic techniques in a dynamic approach. The "in vitro" treatment proceeds with imagery, under hypnosis, of an "anxiety hierarchy" of increasingly erotic and sexually intimate situations which will be reproduced at home with the partner, until sexual intercourse is achieved. In the "in vivo" method the patient learns self-hypnosis and then inserts in the vagina first a finger, and then Hegar dilators of gradually increasing sizes. The partner, the patient, and the physician will then successively proceed to insertion, forming a team-referred work situation. This continues until the "female superior position," practiced first with the largest dilator, is reproduced at home by intercourse. Between 1965 and 1974 we treated 71 women with this method. Good results were obtained in 16 of 18 by the "in vitro" technique and in 53 of 54 by the "in vivo" technique. One patient was referred from the "in vitro" group to the "in vivo" group. In follow-up of 2 to 5 years there was no relapse or symptom substitution. PMID:6102843

  15. 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

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

    PubMed Central

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

    2015-01-01

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

  17. On the mechanism of desensitization in quisqualate-type glutamate channels.

    PubMed

    Tour, O; Parnas, H; Parnas, I

    2000-07-01

    Desensitization of crayfish glutamate channels was studied in outside-out patches employing an improved fast drug-application technique. Low concentrations of glutamate produced substantial desensitization without correlation with the detected number of open channels. The desensitization time constant (tau(D)) was found to be independent of glutamate concentration (0.3-20 mM). These results suggest that in addition to desensitization from a state of fully liganded channels, a substantial fraction of desensitization occurs also from channels in a partly-liganded state. A kinetic model was developed. The model accounts for the multifaceted behavior of desensitization as well as for resensitization. PMID:10899178

  18. GABArho 1/GABAAalpha 1 receptor chimeras to study receptor desensitization.

    PubMed

    Martnez-Torres, A; Demuro, A; Miledi, R

    2000-03-28

    gamma-Aminobutyrate type C (GABA(C)) receptors are ligand-gated ion channels that are expressed preponderantly in the vertebrate retina and are characterized, among other things, by a very low rate of desensitization and resistance to the specific GABA(A) antagonist bicuculline. To examine which structural elements determine the nondesensitizing character of the human homomeric rho1 receptor, we used a combination of gene chimeras and electrophysiology of receptors expressed in Xenopus oocytes. Two chimeric genes were constructed, made up of portions of the rho1-subunit and of the alpha1-subunit of the GABA(A) receptor. When expressed in Xenopus oocytes, one chimeric gene (rho1/alpha1) formed functional homooligomeric receptors that were fully resistant to bicuculline and were blocked by the specific GABA(C) antagonist (1,2,5, 6-tetrahydropyridine-4-yl)methylphosphinic acid and by zinc. Moreover, these chimeric receptors had a fast-desensitizing component, even faster than that of heterooligomeric GABA(A) receptors, in striking contrast to the almost nil desensitization of wild-type rho1 (wt rho1) receptors. To see whether the fast-desensitizing characteristic of the chimera was determined by the amino acids forming the ion channels, we replaced the second transmembrane segment (TM2) of rho1 by that of the alpha1-subunit of GABA(A). Although the alpha1-subunit forms fast-desensitizing receptors when coexpressed with other GABA(A) subunits, the sole transfer of the alpha1TM2 segment to rho1 was not sufficient to form desensitizing receptors. All this suggests that the slow-desensitizing trait of rho1 receptors is determined by a combination of several interacting domains along the molecule. PMID:10725369

  19. Desensitization to oral zingerone irritation: effects of stimulus parameters.

    PubMed

    Prescott, J; Stevenson, R J

    1996-12-01

    In humans, repeated oral stimulation with the irritant capsaicin produces sensitization or desensitization, depending on the temporal relationship and, to a lesser extent, the intensity of the stimuli. We have previously shown that zingerone, an irritant present in ginger, shows only desensitization across repeated samples, as well as following a hiatus in stimulation. Because the time-course of zingerone irritation differs from that of capsaicin, it is likely that optimal temporal and other stimulation parameters may also be different. In Experiment 1, we examined the effects of stimulus intensity (0.5%, 1.0%, 2.0% zingerone) and the number of successive stimuli in a series on psychophysical responses to zingerone irritation within the series and following a 5-min hiatus. Experiment 2 examined the effect of the duration of this hiatus on desensitization and recovery. Desensitization was apparent across the initial series of stimuli in both experiments and, irrespective of zingerone concentration, in Experiment 1. Desensitization also occurred following the 5-min hiatus, evident primarily at the higher concentrations. Preceding the hiatus with 5 or 10 stimuli produced the greatest posthiatus desensitization, but a decrease in rated intensity was also evident following a single stimulus. Experiment 2 showed that the optimal hiatus for demonstrating desensitization was 5 min and that, by 15 min, recovery had begun. In both experiments, individual differences in response were marked, with some subjects showing sensitization and others little change in response across repeated zingerone stimuli. The origin of these differences is unclear but were shown to be relatively stable across multiple sessions. PMID:8946493

  20. The migrant sensory neuritis of Wartenberg.

    PubMed Central

    Matthews, W B; Esiri, M

    1983-01-01

    Six cases are reported that conform to Wartenberg's description of migrant sensory neuritis. This is a benign relapsing and remitting condition in which pain and subsequent loss of sensation in the distribution of individual cutaneous nerves is induced by movement of the limbs inducing stretch. Sural nerve biopsy in one case showed loss of large myelinated fibres, axonal sprouting and some changes suggestive of ischaemia. Images PMID:6842194

  1. Nerve conduction study among healthy malays. The influence of age, height and body mass index on median, ulnar, common peroneal and sural nerves.

    PubMed

    Awang, Mohamed Saufi; Abdullah, Jafri Malin; Abdullah, Mohd Rusli; Tharakan, John; Prasad, Atul; Husin, Zabidi Azhar; Hussin, Ahmad Munawir; Tahir, Adnan; Razak, Salmi Abdul

    2006-07-01

    Nerve conduction study is essential in the diagnosis of focal neuropathies and diffuse polyneuropathies. Age, height and body mass index (BMI) can affect nerve velocities as reported by previous studies. We studied the effect of these factors on median, ulnar, common peroneal and sural nerves among healthy Malay subjects. We observed slowing of nerve conduction velocities (NCVs) with increasing age and BMI (except ulnar sensory velocities). No demonstrable trend can be seen across different height groups except in common peroneal nerve. PMID:22589600

  2. Nerve Conduction Study Among Healthy Malays. The Influence of Age, Height and Body Mass Index on Median, Ulnar, Common Peroneal and Sural Nerves

    PubMed Central

    Awang, Mohamed Saufi; Abdullah, Jafri Malin; Abdullah, Mohd Rusli; Tharakan, John; Prasad, Atul; Husin, Zabidi Azhar; Hussin, Ahmad Munawir; Tahir, Adnan; Razak, Salmi Abdul

    2006-01-01

    Nerve conduction study is essential in the diagnosis of focal neuropathies and diffuse polyneuropathies. Age, height and body mass index (BMI) can affect nerve velocities as reported by previous studies. We studied the effect of these factors on median, ulnar, common peroneal and sural nerves among healthy Malay subjects. We observed slowing of nerve conduction velocities (NCVs) with increasing age and BMI (except ulnar sensory velocities). No demonstrable trend can be seen across different height groups except in common peroneal nerve. PMID:22589600

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

    PubMed

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

    2009-01-01

    Tooth hypersensitivity can occur when gum recession causes exposure of dentin. Tiny tubules, which permeate dentin, provide open passageways from the mouth to the intradental nerve in the pulpal cavity. Under such circumstances, stimuli in the mouth can cause pressure on the intradental nerve, leading to pain. Sealing the outside of the tubules with an impermeable substance can effectively treat hypersensitivity. One such clinically proven composition is a professionally applied tooth desensitizer, which has been shown to initially produce a layer of amorphous calcium phosphate (ACP) on the surface of dentin. Under the influence of fluoride, ACP reforms as hydroxyapatite (HAP), which has essentially the same composition as tooth mineral. Three fluoride toothpastes that deliver calcium and phosphate salts to the teeth also have been demonstrated in clinical trials to relieve hypersensitivity. This study compared the mechanism of action of these toothpastes to that of the professional desensitizer. A single application of the professional desensitizer or multiple applications of any of the three toothpastes was shown to reduce dentin permeability. A conventional fluoride toothpaste also was found to inhibit fluid flow through the dentin but to a lesser degree than the other toothpastes. The desensitizer and the three toothpastes were found to occlude the dentinal tubules with a layer of calcium phosphate that had a calcium-to-phosphate ratio consistent with the formation of ACP or HAP. The morphology of the coherent mineral layer formed by Arm & Hammer Enamel Care Sensitive was similar, especially to that produced by the desensitizer. In contrast, the conventional toothpaste left localized areas of surface residue composed of silica particles. The mechanism of action of the three toothpastes that deliver calcium and phosphate salts is the same as that of the professional desensitizer. PMID:19998729

  4. 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 4050 days to return to baseline levels while sensory fibers required 140150 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

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

    PubMed

    Funk, Jeanne B

    2005-07-01

    Desensitization to violence is cited frequently as being an outcome of exposure to media violence and a condition that contributes to increased aggression. This article initiates the development of a conceptual model for describing possible relationships among violent video games, brain function, and desensitization by using empathy and attitudes toward violence as proxy measures of desensitization. More work is needed to understand how specific game content may affect brain activity, how brain development may be affected by heavy play at young ages, and how personality and lifestyle variables may moderate game influence. Given the current state of knowledge, recommendations are made for clinicians to help parents monitor and limit exposure to violent video games and encourage critical thinking about media violence. PMID:15936665

  6. Sciatic Nerve Injury Associated with Acetabular Fractures

    PubMed Central

    Helfet, David L.

    2008-01-01

    Sciatic nerve injuries associated with acetabular fractures may be a result of the initial trauma or injury at the time of surgical reconstruction. Patients may present with a broad range of symptoms ranging from radiculopathy to foot drop. There are several posttraumatic, perioperative, and postoperative causes for sciatic nerve palsy including fracturedislocation of the hip joint, excessive tension or inappropriate placement of retractors, instrument- or implant-related complications, heterotopic ossification, hematoma, and scarring. Natural history studies suggest that nerve recovery depends on several factors. Prevention requires attention to intraoperative limb positioning, retractor placement, and instrumentation. Somatosensory evoked potentials and spontaneous electromyography may help minimize iatrogenic nerve injury. Heterotopic ossification prophylaxis can help reduce delayed sciatic nerve entrapment. Reports on sciatic nerve decompression are not uniformly consistent but appear to have better outcomes for sensory than motor neuropathy. PMID:19089496

  7. Spontaneous intraneural hematoma of the sural nerve.

    PubMed

    Richardson, Shawn S; McLawhorn, Alexander S; Mintz, Douglas N; DiCarlo, Edward F; Weiland, Andrew J

    2015-04-01

    Symptomatic intraneural hemorrhage occurs rarely. It presents with pain and/or weakness in the distribution following the anatomic innervation pattern of the involved nerve. When a purely sensory nerve is affected, the symptoms can be subtle. We present a previously healthy 36-year-old female who developed an atraumatic, spontaneous intraneural hematoma of her sural nerve. Sural dysfunction was elicited from the patient's history and physical examination. The diagnosis was confirmed with magnetic resonance imaging, and surgical decompression provided successful resolution of her preoperative symptoms. To our knowledge, this entity has not been reported previously. Our case highlights the importance of having a high index of suspicion for nerve injury or compression in patients whose complaints follow a typical peripheral nerve distribution. Prior studies have shown that the formation of intraneural hematoma and associated compression of nerve fibers result in axonal degeneration, and surgical decompression decreases axonal degeneration and aids functional recovery. PMID:25311865

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

    PubMed

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

    2010-01-01

    It is generally accepted that the pain of dental hypersensitivity resulting from gum recession is from the movement of fluid within the exposed tubules of dentin, causing changes in pressure on the nerve within the pulpal cavity. One method of treating hypersensitivity is to occlude the tubules, preventing fluid movement. This article discusses the use of a dye penetration technique, which establishes this mechanism of action for a desensitizing fluoride toothpaste containing calcium and phosphate. Two groups of intact teeth were perfectly sealed with enamel paint. Windows 100-micro to 200-micro deep were opened on opposite sides of each tooth at the dentin-enamel junction and briefly etched using 20% polyacrylic acid. One batch of teeth was treated eight times for 30 mins each with a 1:3 slurry of the desensitizing toothpaste and another set with a similar slurry prepared from a calcium- and phosphate-free control. A 0.85% aqueous solution of acid red fuchsin dye was applied to each window and allowed to dry. After a brief rinse, the teeth were sectioned across the windows. Almost no dye penetration was seen in teeth treated with the desensitizing toothpaste; however, extensive penetration through the dentin was visible in the control-treated teeth. The differences in dye penetration for the two sets of teeth were significant by both subjective (P < .001) and objective (P < .01) measures. Tubule occlusion because of calcium and phosphate ions from the desensitizing toothpaste accounts for its tooth desensitizing efficacy. PMID:20158016

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

    PubMed Central

    Allouche, Stéphane; Noble, Florence; Marie, Nicolas

    2014-01-01

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

  10. 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

  11. 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

  12. 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

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

    PubMed Central

    Tague, Sarah E.; Smith, Peter G.

    2014-01-01

    Vitamin D deficiency is associated with increased susceptibility to inflammatory arthritis. Sensory and sympathetic synovial nerves are critical to the development of inflammatory arthritis and spontaneously degenerate in the early phases of disease. These nerves contain vitamin D receptors and vitamin D influences nerve growth and neurotrophin expression. We therefore examined the density of synovial nerves and neurotrophin-containing cells in vitamin D deficient rats. Seven week old Sprague Dawley rats were fed either control or vitamin D deficient diets for four weeks. Knee synovium sections extending from patella to meniscus were immunostained for total nerves, myelinated and unmyelinated nerves, sympathetic nerves, peptidergic and non-peptidergic sensory nerves, and neurotrophins and immune cell markers. In control rats, intimal innervation by unmyelinated sensory fibers was denser than subintimal innervation. In contrast, sympathetic innervation was confined to the subintima. Many sensory axons contained markers for both peptidergic and non-peptidergic nerves. NGF was primarily expressed by intimal CD163-negative type B synoviocytes, while neurturin, a ligand selective for non-peptidergic sensory neurons, was expressed by synovial mast cells. In vitamin D deficient rats, there were significant reductions in sensory nerves in the intima and sympathetic nerves in the subintima. While there was no significant change in NGF-immunoreactivity, the number of neurturin-expressing mast cells was significantly reduced in the intima, suggesting that intimal reductions in sensory nerves may be related to reductions in neurturin. Vitamin D deficiency therefore may increase susceptibility to inflammatory arthritis by depleting sensory and sympathetic synovial nerves as a result of reduced synovial neurotrophin content. PMID:25193239

  14. 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

  15. Implications of Sensory Stimulation in Self-Destructive Behavior.

    ERIC Educational Resources Information Center

    Edelson, Stephen M.

    1984-01-01

    The author extends the self stimulatory theory of self destructive behavior in autistic, schizophrenic, and mentally retarded individuals to suggest that damage of the skin's nerve structure lowers the tactile sensory threshold for physical input and enables individuals to obtain sensory stimulation by repeatedly depressing the damaged area. (CL)

  16. Nerve Blocks

    MedlinePLUS

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

  17. Sensory analysis

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Sensory evaluation can answer questions about a product that instruments cannot. The human subject is the instrument, and data can provide a wealth of information for a product developer, or results can be very variable and erroneous if all the precautions to minimize bias and external noise are no...

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

    ERIC Educational Resources Information Center

    Erwin, Terry McVannel

    Since Shapiro's introduction of Eye Movement Desensitization and Reprocessing (EMDR) in 1989, it has been a highly controversial therapeutic technique. Critical reviews of Shapiro's initial study have highlighted many methodological shortcomings in her work. And early empirical research that followed Shapiro's original study has been criticized…

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

    PubMed

    Mrug, Sylvie; Madan, Anjana; Windle, Michael

    2016-01-01

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

  20. Visualization, Systematic Desensitization, and Rational Emotive Therapy: A Comparative Evaluation.

    ERIC Educational Resources Information Center

    Ayers, Joe; Hopf, Theodore S.

    1987-01-01

    Compares the effectiveness of systematic desensitization (SD), rational emotive therapy (RET), and visualization (VIS) in reducing communication apprehension (CA). Concludes that, while all treatment modes reduce CA, no significant differences were found in their effectiveness. Emphasizes that VIS is a relatively simple technique that can be used

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

    ERIC Educational Resources Information Center

    Wilson, Barbara J.

    1989-01-01

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

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

    ERIC Educational Resources Information Center

    Wilson, Barbara J.

    1989-01-01

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

  3. The consistent presence of the human accessory deep peroneal nerve.

    PubMed

    Kudoh, H; Sakai, T; Horiguchi, M

    1999-01-01

    Twenty-four human legs were dissected macroscopically to study the morphological details of the accessory deep peroneal nerve. This nerve arose from the superficial peroneal nerve and descended in the lateral compartment of the leg, deep to peroneus longus along the posterior border of peroneus brevis. Approaching the ankle joint, this nerve passed through the peroneal tunnels to wind around the lateral malleolus; it then crossed beneath the peroneus brevis tendon anteriorly to reach the dorsum of the foot. The accessory deep peroneal nerve was found in every case examined and constantly gave off muscular branches to peroneus brevis and sensory branches to the ankle region. In addition, this nerve occasionally had muscular branches to peroneus longus and extensor digitorum brevis, and sensory branches to the fibula and the foot. The anomalous muscles around the lateral malleolus were also innervated by this nerve. Neither cutaneous branches nor communicating branches with other nerves were found. The present study reveals that the accessory deep peroneal nerve is consistently present and possesses a proper motor and sensory distribution in the lateral region of the leg and ankle. It is not an anomalous nerve as has previously been suggested. PMID:10227671

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

    PubMed

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

    1987-03-01

    The efficacy, safety and mechanisms of penicillin desensitization were studied in 24 adults and two children with serious infections that required therapy with a beta-lactam drug. Indications for desensitization included debilitating as well as life-endangering infections. Increasing oral doses of phenoxymethyl penicillin were administered at 15-minute intervals to a cumulative dose of 1.3 million units. Parenteral therapy with the beta-lactam drug of choice was instituted at that point. Immunologic complications of desensitization or therapy, ranging from pruritus to serum sickness, occurred in 12 patients. The appearance of gradually worsening wheezing led to abandonment of the procedure in one subject with cystic fibrosis and severe pulmonary disease. The remaining 25 patients were successfully desensitized and received full-dose parenteral therapy. Chronic desensitization was maintained in seven individuals with twice daily oral penicillins for 3 weeks to more than 2 years. No allergic complications of chronic desensitization or recurrent full-dose parenteral therapy were detected. Skin test reactions to one or all penicillin determinants became negative in 11 of 15 patients retested after acute desensitization. Two desensitized patients became skin test negative, remained skin test negative after cessation of desensitization, and tolerated subsequent beta-lactam therapy without allergic reactions or resensitization. The results of this study provide new evidence that acute and chronic penicillin desensitization is useful and an acceptably safe approach and suggest that antigen-specific mast cell desensitization contributes to the protection against anaphylaxis. PMID:3819232

  5. 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

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

    PubMed

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

    2016-01-01

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

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed Central

    Joshi, Surabhi; Gowda, Ashwini Shivananje

    2013-01-01

    Purpose In this study, the effect of calcium sodium phosphosilicate (NovaMin) desensitizing agent, which is a powder-based system, and hydroxyethyl methacrylate and glutaraldehyde (Gluma desensitizer), which is liquid-based system, on dentinal tubule occlusion was analyzed by scanning electron microscope. The effects of the above two along with one control group were compared to determine the more effective method of sealing the dentinal tubules after initial application. Methods Twenty specimens were allocated to each of 3 groups: Control, Gluma desensitizer, and NovaMin. Two additional samples were also prepared and treated with Gluma and NovaMin; these samples were longitudinally fractured. The specimens were prepared from extracted sound human premolars and were stored in 10% formalin at room temperature. The teeth were cleaned of gross debris and then sectioned to provide one to two dentin specimens. The dentin specimens were etched with 6% citric acid for 2 minutes and rinsed in distilled water. Control discs were dried, and the test discs were treated with the desensitizing agents as per the manufacturer's instructions. The discs as well as longitudinal sections were later analyzed under the scanning electron microscope. The proportions of completely occluded, partially occluded, and open tubules within each group were calculated. The ratios of completely and partially occluded tubules to the total tubules for all the groups was determined, and the data was statistically analyzed using nonparametric tests and statistical significance was calculated. Results NovaMin showed more completely occluded tubules (0.5450.051) while Gluma desensitizer showed more partially occluded tubules (0.5320.075). The differences among all the groups were statistically significant (P? 0.05). Conclusion Both materials were effective in occluding dentinal tubules but NovaMin appeared more promising in occluding tubules completely after initial application. PMID:24455439

  9. Evaluation of dermal myelinated nerve fibers in diabetes mellitus

    PubMed Central

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

    2013-01-01

    Skin biopsies have primarily been used to study the non-myelinated nerve fibers of the epidermis in a variety of neuropathies. In the present study, we have expanded the skin biopsy technique to glabrous, non-hairy skin to evaluate myelinated nerve fibers in the most highly prevalent peripheral nerve disease, diabetic polyneuropathy (DPN). Twenty patients with DPN (Type I, n=9; Type II, n=11) and sixteen age-matched healthy controls (ages 2973) underwent skin biopsy of the index finger, nerve conduction studies, and composite neuropathy scoring. In patients with DPN, we found a statistically significant reduction of both mechanoreceptive Meissner corpuscles (MC) and their afferent myelinated nerve fibers (p=0.01). This myelinated nerve fiber loss was correlated with the decreased amplitudes of sensory/motor responses in nerve conduction studies. This study supports the utilization of skin biopsy to quantitatively evaluate axonal loss of myelinated nerve fibers in patients with DPN. PMID:23781963

  10. Ulnar nerve sonography in leprosy neuropathy.

    PubMed

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

    2016-01-01

    A 23-year-old woman presented with a half-year history of rightforearmsensory and motordysfunction. Ultrasound imaging revealed definite thickening of the right ulnar nerve trunk and inner epineurium, along with heterogeneous hypoechogenicity and unclear nerve fiber bundle. Color Doppler exhibited a rich blood supply, which was clearly different from the normal ulnar nerve presentation with a scarce blood supply. The patient subsequently underwent needle aspiration of the right ulnar nerve, and histopathological examination confirmed that granulomatousnoduleshad formed with a large numberof infiltrating lymphocytes anda plurality of epithelioidcells in the fibrous connectivetissues,with visible atypicalfoam cells and proliferous vascularization, consistent withleprosy. Our report will familiarize readers with the characteristic sonographic features of the ulnar nerve in leprosy, particularly because of the decreasing incidence of leprosy inrecent years. PMID:26703181

  11. 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

  12. 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

  13. 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.

  14. Peripheral Nerve Disorders

    MedlinePLUS

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

  15. Medial Plantar Nerve Entrapment

    MedlinePLUS

    ... Fibromatosis Medial and lateral plantar nerve entrapment is compression of nerve branches at the inner heel (the ... nerve or surgery to free the nerve from compression may help relieve pain. Foot Problems Overview of ...

  16. Structural mechanism of glutamate receptor activation and desensitization

    PubMed Central

    Meyerson, Joel R.; Kumar, Janesh; Chittori, Sagar; Rao, Prashant; Pierson, Jason; Bartesaghi, Alberto; Mayer, Mark L.; Subramaniam, Sriram

    2014-01-01

    Ionotropic glutamate receptors are ligand-gated ion channels that mediate excitatory synaptic transmission in the vertebrate brain. To better understand how structural changes gate ion flux across the membrane, we trapped AMPA and kainate receptor subtypes in their major functional states and analyzed the resulting structures using cryo-electron microscopy. We show that transition to the active state involves a corkscrew motion of the receptor assembly, driven by closure of the ligand binding domain. Desensitization is accompanied by disruption of the amino terminal domain tetramer in AMPA, but not kainate receptors, with a 2-fold to 4-fold symmetry transition in the ligand binding domains in both subtypes. The 7.6 structure of a desensitized kainate receptor shows how these changes accommodate channel closing. These findings integrate previous physiological, biochemical, and structural analyses of glutamate receptors and provide a molecular explanation for key steps in receptor gating. PMID:25119039

  17. Psychodynamic Emotional Regulation in View of Wolpe's Desensitization Model.

    PubMed

    Rabinovich, Merav

    2016-01-01

    The current research belongs to the stream of theoretical integration and establishes a theoretical platform for integrative psychotherapy in anxiety disorders. Qualitative metasynthesis procedures were applied to 40 peer-reviewed psychoanalytic articles involving emotional regulation. The concept of psychodynamic emotional regulation was found to be connected with the categories of desensitization, gradual exposure, containment, and transference. This article presents a model according to which psychoanalytic psychotherapy allows anxiety to be tolerated while following the core principles of systematic desensitization. It is shown that despite the antiresearch image of psychoanalytic psychotherapy, its foundations obey evidence-based principles. The findings imply that anxiety tolerance might be a key goal in which the cumulative wisdom of the different therapies can be used to optimize psychotherapy outcomes. PMID:27029107

  18. Explosives malfunction from sympathetic detonation to shock desensitization

    SciTech Connect

    Katsabanis, P.D.; Yeung, C.; Fitz, G.; Heater, R.

    1994-12-31

    Explosives malfunction due to shock waves is a serious concern for successful blasting results. Malfunction can range from sympathetic detonation to desensitization and modification of firing times of conventional pyrotechnic detonators. Decked charges consisting of commercial emulsion explosives having a detonator and a primer were placed in 10cm diameter blastholes and their performance was recorded. Due to the limited length of the holes the events were mainly sympathetic detonations although desensitization was also recorded. Pressure measurements along the stemming column showed that shock waves produced by an explosive have a significant amplitude even at relatively large distances away from the detonating explosive. It was found that 2m away from a detonating charge the pressures in the stemming material were above 0.1 GPa indicating that there is potential for primers and detonators to malfunction. Parallel charges consisting of a commercial emulsion explosive with a diameter of 32mm were confined in 2mm thick steel tubes and initiation was attempted using detonators having a delay interval of 25ms. The charges were placed in sand and the velocity of detonation of the acceptor charge was recorded using a continuous resistance probe system. Carbon resistors were also placed in the same position as the acceptor charge to examine the dynamic pressures that were applied to the charge. Sympathetic detonation, complete desensitization, partial desensitization and properly sequenced detonations were observed as the distance between charges was increased from 76 mm to 305 mm. Delay detonators were also tested in a similar to the last configuration. Modification of firing times was observed at distances between 150 and 360 mm.

  19. Nonverbal patient with autism spectrum disorder and obstructive sleep apnea: use of desensitization to acclimatize to a dental appliance.

    PubMed

    Fetner, Maggie; Cascio, Carissa J; Essick, Gregory

    2014-01-01

    Patients with autism spectrum disorders (ASDs) may have difficulty tolerating conventional dental treatment due to aberrant sensory responsiveness. The purpose of this report was to describe the successful treatment of obstructive sleep apnea (OSA) in a nonverbal 20-year-old male patient with ASD using a dental appliance. A series of appointments prepared the patient for the required treatment procedures and desensitized him for use of the final appliance. The final appliance improved outcomes of a post-treatment sleep study, indicating successful treatment of OSA. Understanding the specific challenges of patients with ASD and the patience and foresight of providers in approaching these challenges, in collaboration with caregivers, can contribute to improved health outcomes for these patients. PMID:25514080

  20. 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

  1. 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

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

    PubMed

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

    2015-09-21

    Dual antiplatelet therapy is essential in patients undergoing percutaneous coronary intervention with stent implantation. Hypersensitivity to acetylsalicylic acid (ASA) limits treatment options. Desensitization to ASA has classically been studied in patients with respiratory tract disease. Over the last years, many protocols have been described about ASA desensitization in patients with ischemic heart disease, including acute coronary syndrome and the need for coronary stent implantation. It is important to know the efficacy and safety of ASA desensitization in these patients. PMID:25577589

  3. Peripheral Nerve Repair in Rats Using Composite Hydrogel-Filled Aligned Nanofiber Conduits with Incorporated Nerve Growth Factor

    PubMed Central

    Jin, Jenny; Limburg, Sonja; Joshi, Sunil K.; Landman, Rebeccah; Park, Michelle; Zhang, Qia; Kim, Hubert T.

    2013-01-01

    Repair of peripheral nerve defects with current synthetic, tubular nerve conduits generally shows inferior recovery when compared with using nerve autografts, the current gold standard. We tested the ability of composite collagen and hyaluronan hydrogels, with and without the nerve growth factor (NGF), to stimulate neurite extension on a promising aligned, nanofiber poly-L-lactide-co-caprolactone (PLCL) scaffold. In vitro, the hydrogels significantly increased neurite extension from dorsal root ganglia explants. Consistent with these results, the addition of hydrogels as luminal fillers within aligned, nanofiber tubular PLCL conduits led to improved sensory function compared to autograft repair in a critical-size defect in the sciatic nerve in a rat model. Sensory recovery was assessed 3 and 12 weeks after repair using a withdrawal assay from thermal stimulation. The addition of hydrogel did not enhance recovery of motor function in the rat model. The NGF led to dose-dependent improvements in neurite out-growth in vitro, but did not have a significant effect in vivo. In summary, composite collagen/hyaluronan hydrogels enhanced sensory neurite outgrowth in vitro and sensory recovery in vivo. The use of such hydrogels as luminal fillers for tubular nerve conduits may therefore be useful in assisting restoration of protective sensation following peripheral nerve injury. PMID:23659607

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

    NASA Technical Reports Server (NTRS)

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

    1992-01-01

    To investigate the mechanisms of alpha 1-adrenergic vascular desensitization, osmotic minipumps containing either saline (n = 9) or amidephrine mesylate (AMD) (n = 9), a selective alpha 1-adrenergic receptor agonist, were implanted subcutaneously in dogs with chronically implanted arterial and right atrial pressure catheters and aortic flow probes. After chronic alpha 1-adrenergic receptor stimulation, significant physiological desensitization to acute AMD challenges was observed, i.e., pressor and vasoconstrictor responses to the alpha 1-adrenergic agonist were significantly depressed (p < 0.01) compared with responses in the same dogs studied in the conscious state before pump implantation. However, physiological desensitization to acute challenges of the neurotransmitter norepinephrine (NE) (0.1 micrograms/kg per minute) in the presence of beta-adrenergic receptor blockade was not observed for either mean arterial pressure (MAP) (30 +/- 7 versus 28 +/- 5 mm Hg) or total peripheral resistance (TPR) (29.8 +/- 4.9 versus 28.9 +/- 7.3 mm Hg/l per minute). In the presence of beta-adrenergic receptor plus ganglionic blockade after AMD pump implantation, physiological desensitization to NE was unmasked since the control responses to NE (0.1 micrograms/kg per minute) before the AMD pumps were now greater (p < 0.01) than after chronic AMD administration for both MAP (66 +/- 5 versus 32 +/- 2 mm Hg) and TPR (42.6 +/- 10.3 versus 23.9 +/- 4.4 mm Hg/l per minute). In the presence of beta-adrenergic receptor, ganglionic, plus NE-uptake blockade after AMD pump implantation, desensitization was even more apparent, since NE (0.1 micrograms/kg per minute) induced even greater differences in MAP (33 +/- 5 versus 109 +/- 6 mm Hg) and TPR (28.1 +/- 1.8 versus 111.8 +/- 14.7 mm Hg/l per minute). The maximal force of contraction induced by NE in the presence or absence of endothelium was significantly decreased (p < 0.05) in vitro in mesenteric artery rings from AMD pump dogs compared with saline control dogs. Furthermore, alpha 1-adrenergic receptor density, as determined by [3H]prazosin binding in membrane preparations from vessels in the mesentery, was decreased (8.2 +/- 1.0 versus 18.4 +/- 1.4 fmol/mg protein, p < 0.001) without any change in Kd in the AMD pump dogs compared with the saline pump dogs.(ABSTRACT TRUNCATED AT 400 WORDS).

  5. Positive allosteric modulators of AMPA receptors reduce proton-induced receptor desensitization in rat hippocampal neurons.

    PubMed

    Lei, S; Orser, B A; Thatcher, G R; Reynolds, J N; MacDonald, J F

    2001-05-01

    Whole-cell or outside-out patch recordings were used to investigate the effects of protons and positive modulators of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors on the desensitization of glutamate-evoked AMPA receptor currents in isolated hippocampal CA1 neurons. Protons inhibited glutamate-evoked currents (IC(50) of 6.2 pH units) but also enhanced the apparent rate and extent of AMPA receptor desensitization. The proton-induced enhancement of desensitization could not be attributed to a reduction in the rate of recovery from desensitization or to a change in the kinetics of deactivation. Non-stationary variance analysis indicated that protons reduced maximum open probability without changing the conductance of AMPA channels. The positive modulators of AMPA receptor desensitization, cyclothiazide and GT-21-005 (an organic nitrate), reduced the proton sensitivity of AMPA receptor desensitization, which suggests that they interact with protons to diminish desensitization. In contrast, the effects of wheat germ agglutinin and aniracetam on AMPA receptor desensitization were independent of pH. These results demonstrate that a reduction in the proton sensitivity of receptor desensitization contributes to the mechanism of action of some positive modulators of AMPA receptors. PMID:11353019

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

    NASA Astrophysics Data System (ADS)

    Freeman, Daniel K.; Fried, Shelley I.

    2011-02-01

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

  7. Effect of different desensitizers on inhibition of bovine dentin demineralization: micro-computed tomography assessment.

    PubMed

    Lodha, Ena; Hamba, Hidenori; Nakashima, Syozi; Sadr, Alireza; Nikaido, Toru; Tagami, Junji

    2014-12-01

    This study evaluated the effect of two desensitizers on inhibition of dentin demineralization, after immersion in artificial saliva using micro-computed tomography (?CT). Dentin blocks cut from bovine incisors were treated with deionized water (DW, a negative control) or one of three desensitizers: a fluoride varnish (Duraphat, a positive control), a calcium phosphate desensitizer (Teethmate Desensitizer), and a fluoro-alumino-calcium silicate-based desensitizer (Nanoseal). After each treatment, the specimens in Duraphat, Nanoseal, and Teethmate Desensitizer groups were pre-immersed in artificial saliva (pH 6.5) for either 1 d or 1 wk. The mineral loss of the specimens after demineralization (pH 5.0, 3 h) was evaluated by ?CT. The treated surface was investigated with scanning electron microscopy. Mineral loss in all treatment groups was significantly lower than that in DW. Duraphat was the most effective treatment against demineralization, followed by Nanoseal. Nanoseal showed significantly better reduction in mineral loss following immersion for 1 wk in artificial saliva than for 1 d. However, Teethmate Desensitizer and Duraphat did not exhibit enhanced inhibition of demineralization over a longer period of immersion in artificial saliva. Scanning electron microscopy images showed deposition of particles on the dentin in both Teethmate Desensitizer. The application of Teethmate Desensitizer and Nanoseal to the exposed dentin surface resulted in inhibition of demineralization, with Nanoseal resulting in improved inhibition after prolonged immersion in artificial saliva. PMID:25363830

  8. Agonist-induced desensitization of adenylyl cyclase in Y1 adrenocortical tumor cells

    SciTech Connect

    Olson, M.F.; Tsao, J.; Pon, D.J.; Schimmer, B.P. )

    1991-01-01

    Y1 adrenocortical tumor cells (Y1DS) and Y1 mutants resistant to ACTH-induced desensitization of adenylyl cyclase (Y1DR) were transfected with a gene encoding the mouse beta 2-adrenergic receptor (beta 2-AR). Transfectants expressed beta 2-ARs that were able to stimulate adenylyl cyclase activity and steroid biosynthesis. These transfectants were used to explore the basis for the DR mutation in Y1 cells. The authors demonstrate that beta-adrenergic agonists desensitize the adenylyl cyclase system in transfected Y1DS cells whereas transfected Y1DR cells are resistant to desensitization by beta-adrenergic agonists. The fate of the beta 2-ARs during desensitization was evaluated by photoaffinity labelling with (125I)iodocyanopindolol diazerine. Desensitization of Y1DS transfectants was accompanied by a modest loss in receptor density that was insufficient to account for the complete loss of responsiveness to beta-adrenergic agonists. The extent of receptor loss induced by beta-adrenergic agonists in Y1DR transfectants exceeded that in the Y1DS transfectants indicating that the mutation which protects Y1DR cells from agonist-induced desensitization is prior to receptor down-regulation in the desensitization pathway. From these results we infer that ACTH and isoproterenol desensitize adenylyl cyclase by a common pathway and that receptor loss is not a major component of the desensitization process in these cells.

  9. 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

  10. 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

  11. A Novel Internal Fixator Device for Peripheral Nerve Regeneration

    PubMed Central

    Chuang, Ting-Hsien; Wilson, Robin E.; Love, James M.; Fisher, John P.

    2013-01-01

    Recovery from peripheral nerve damage, especially for a transected nerve, is rarely complete, resulting in impaired motor function, sensory loss, and chronic pain with inappropriate autonomic responses that seriously impair quality of life. In consequence, strategies for enhancing peripheral nerve repair are of high clinical importance. Tension is a key determinant of neuronal growth and function. In vitro and in vivo experiments have shown that moderate levels of imposed tension (strain) can encourage axonal outgrowth; however, few strategies of peripheral nerve repair emphasize the mechanical environment of the injured nerve. Toward the development of more effective nerve regeneration strategies, we demonstrate the design, fabrication, and implementation of a novel, modular nerve-lengthening device, which allows the imposition of moderate tensile loads in parallel with existing scaffold-based tissue engineering strategies for nerve repair. This concept would enable nerve regeneration in two superposed regimes of nerve extensiontraditional extension through axonal outgrowth into a scaffold and extension in intact regions of the proximal nerve, such as that occurring during growth or limb-lengthening. Self-sizing silicone nerve cuffs were fabricated to grip nerve stumps without slippage, and nerves were deformed by actuating a telescoping internal fixator. Poly(lactic co-glycolic) acid (PLGA) constructs mounted on the telescoping rods were apposed to the nerve stumps to guide axonal outgrowth. Neuronal cells were exposed to PLGA using direct contact and extract methods, and they exhibited no signs of cytotoxic effects in terms of cell morphology and viability. We confirmed the feasibility of implanting and actuating our device within a sciatic nerve gap and observed axonal outgrowth following device implantation. The successful fabrication and implementation of our device provides a novel method for examining mechanical influences on nerve regeneration. PMID:23102114

  12. Neuromodulation of the suprascapular nerve.

    PubMed

    Elahi, Foad; Reddy, Chandan G

    2014-01-01

    The shoulder joint is an enarthrodial or ball-and-socket joint. A complex network of anatomic structures endows the human shoulder with tremendous mobility, greater than any other joint in the body. Many pathologies can been found in those patients with chronic shoulder pain. The painful limitation of shoulder motion affects hand and arm motion as well; therefore, it significantly influences work performance and everyday activities as well as the quality of life. Therefore, the treatment of patients with chronic shoulder pain has major social and health economic implications. In this article we present a patient with a complex history of shoulder pathology including 7 surgeries that left the patient with chronic debilitating shoulder pain. She was suffering from chronic pain and limited mobility of the shoulder joint due to adhesive shoulder capsulitis. She was treated with a multimodality approach with the goals of increasing shoulder range of motion and decreasing her pain. This did not provide significant improvement. The suprascapular nerve supplies motor and sensory innervation to the shoulder, and can be easily accessible in the supraspinatus fossa. A suprascapular nerve block dramatically decreased her pain. This clinical observation along with confirmatory nerve block play an important role during the decision-making process for a trial period of electrical neuromodulation. She was followed for 3 months after the permanent implantation of a suprascapular nerve stimulator. Her pain and shoulder range of motion in all planes improved dramatically. Peripheral nerve stimulation (PNS) of the suprascapular nerve, in addition to multimodality pain management, is one approach to the difficult task of treating adhesive capsulitis with accompanying pain and the inability to move the shoulder. We conducted a literature review on PubMed and found no case describing a similar patient to our knowledge. PMID:25415792

  13. Expression of leukemia inhibitory factor in human nerve following injury.

    PubMed

    Dowsing, B J; Romeo, R; Morrison, W A

    2001-11-01

    In animal models of peripheral nerve injury, leukemia inhibitory factor (LIF) is normally expressed at very low levels. Following nerve injury, its expression is rapidly increased in the nerve at the injury site and promotes both sensory and motor neuron survival. Once normal nerve function is restored, LIF expression returns to negligible levels. For this reason, LIF is considered to be a peripheral nerve trauma factor. We wished to determine whether LIF is also upregulated in human nerves following trauma and whether it is expressed in neuromas of varying age. Immunohistochemical staining for the presence of LIF was performed on injured and control human nerves from a number of subjects. Results demonstrate that LIF expression is increased in nerves within hours of injury and, in the case of neuroma formation, can persist for several years. LIF immunoreactivity was consistently found in Schwann cells, in peripheral nerve axons, and, at stages when an inflammatory response was present, also in neutrophils, mast cells, macrophages, and blood vessel walls. The level of staining within the connective tissue of injured nerves was elevated compared to control nerves, which may be due to the presence of LIF bound to the soluble secreted form of the LIF receptor. Whether the continued expression of LIF is unhealed injured nerves promotes the development of neuromas remains to be resolved. PMID:11721746

  14. 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

  15. Ultrasound imaging accurately identifies the intercostobrachial nerve

    PubMed Central

    Thallaj, Ahmed K.; Harbi, Mohammad K. Al; Alzahrani, Tariq A.; El-Tallawy, Salah N.; Alsaif, Abdulaziz A.; Alnajjar, Mohannad

    2015-01-01

    Objectives: To test the hypothesis that identification and blockade of the intercostobrachial nerve (ICBN) can be achieved under ultrasound (US) guidance using a small volume of local anesthetic. Methods: Twenty-eight adult male volunteers were examined at King Khalid University Hospital, Riyadh, Kingdom of Saudi Arabia from November 2012 to September 2013. Intercostobrachial nerve blockade was performed using one ml of 2% lidocaine under US guidance. A sensory map of the blocked area was developed relative to the medial aspect of the humeral head. Results: The ICBN appears as a hyper-echoic structure. The nerve diameter was 2.30.28 mm, and the depth was 90.28 mm. The measurements of the sensory-blocked area relative to the medial aspect of the humeral head were as follows: 6.31.6 cm anteriorly; 6.22.9 cm posteriorly; 9.42.9 cm proximally; and 9.24.4 cm distally. Intercostobrachial nerve blockade using one ml of local anesthetic was successful in all cases. Conclusion: The present study described the sonographic anatomical details of the ICBN and its sensory distribution to successfully perform selective US-guided ICBN blockade. PMID:26446339

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

    SciTech Connect

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

    1987-03-01

    Dispersed pancreatic acini were first exposed to carbamylcholine (10/sup -7/-10/sup -4/ M) for 60 min, washed, and reexposed to this same agonist (10/sup -8/-10/sup -3/ M) for 15 min. During this second incubation, the functional secretory capacity of these acini was evaluated by measuring amylase release. Acini preexposed to concentrations of carbamylcholine of 10/sup -6/ M or greater showed shifts to the right in the subsequent carbamylcholine dose-response curves of amylase release. A 3-h recovery period (without carbamylcholine) did not restore the altered carbamylcholine dose-response curve. Ca/sup 2 +/ concentrations of 10/sup -7/ M or 2.5 x 10/sup -3/ M instead of 0.5 x 10/sup -3/ M during the 60-min preincubation did not affect the desensitization process. With use of N-(/sup 3/H)methylscopolamine to evaluate muscarinic receptors, the only changes observed after desensitization were a significant decrease in the high-affinity and an equivalent increase in that of the low-affinity receptors. After cholinergic exposure amylase release stimulated by caerulein was only slightly modified, whereas amylase release in response to a phorbol ester 12-O-tetradecanoylphorbol-13-acetate and to the ionophore A23187 was not altered. These data indicate that short-term desensitization with a cholinergic agent is relatively specific to muscarinic agonists, causes changes in the muscarinic receptor high-and low-affinity concentration but does not alter intracellular steps after calcium mobilization or protein kinase C activation known to be involved in the secretion process.

  17. Chronic norepinephrine elicits desensitization by uncoupling the beta-receptor.

    PubMed Central

    Vatner, D E; Vatner, S F; Nejima, J; Uemura, N; Susanni, E E; Hintze, T H; Homcy, C J

    1989-01-01

    The goal of this study was to determine the mechanism of beta-adrenergic receptor desensitization after chronic elevation of circulating NE levels. Osmotic minipumps containing either NE or saline were implanted subcutaneously in dogs for 3-4 wk. Physiologic desensitization to isoproterenol was confirmed in conscious dogs, i.e., left ventricular dP/dt increased in response to isoproterenol (0.4 micrograms/kg per min) by 5,625 +/- 731 mmHg/s in control dogs with saline pumps, and significantly less, P less than 0.01, by 2,093 +/- 263 mmHg/s in dogs with NE pumps. Myocardial beta-adrenergic receptor density as determined with 125I-cyanopindolol binding was 49% higher (p less than 0.05) in the NE pump group. However, beta-adrenergic receptor agonist binding with isoproterenol demonstrated a significant shift into the low affinity state for the animals with NE pumps. Basal, GTP plus isoproterenol, 5'-guanylylimidodiphosphate, sodium fluoride, and forskolin-stimulated adenylate cyclase activity in the NE pump group were significantly depressed (P less than 0.05) by amounts ranging from 20 to 40%. The functional activity of the guanine nucleotide binding protein Gs was also reduced (P less than 0.05) in animals with NE pumps. Thus, the process of desensitization in response to chronic elevation of NE levels in intact, normal dogs does not involve a decrease in beta-adrenergic receptor density. Rather, it is characterized by reduced adenylate cyclase activation and uncoupling of the beta-adrenergic receptor in association with decreased activity of the GTP-coupling protein Gs. PMID:2556443

  18. Altered expression of the voltage-gated calcium channel subunit ?2?-1: A comparison between two experimental models of epilepsy and a sensory nerve ligation model of neuropathic pain

    PubMed Central

    Nieto-Rostro, M.; Sandhu, G.; Bauer, C.S.; Jiruska, P.; Jefferys, J.G.R.; Dolphin, A.C.

    2014-01-01

    The auxiliary ?2?-1 subunit of voltage-gated calcium channels is up-regulated in dorsal root ganglion neurons following peripheral somatosensory nerve damage, in several animal models of neuropathic pain. The ?2?-1 protein has a mainly presynaptic localization, where it is associated with the calcium channels involved in neurotransmitter release. Relevant to the present study, ?2?-1 has been shown to be the therapeutic target of the gabapentinoid drugs in their alleviation of neuropathic pain. These drugs are also used in the treatment of certain epilepsies. In this study we therefore examined whether the level or distribution of ?2?-1 was altered in the hippocampus following experimental induction of epileptic seizures in rats, using both the kainic acid model of human temporal lobe epilepsy, in which status epilepticus is induced, and the tetanus toxin model in which status epilepticus is not involved. The main finding of this study is that we did not identify somatic overexpression of ?2?-1 in hippocampal neurons in either of the epilepsy models, unlike the upregulation of ?2?-1 that occurs following peripheral nerve damage to both somatosensory and motor neurons. However, we did observe local reorganization of ?2?-1 immunostaining in the hippocampus only in the kainic acid model, where it was associated with areas of neuronal cell loss, as indicated by absence of NeuN immunostaining, dendritic loss, as identified by areas where microtubule-associated protein-2 immunostaining was missing, and reactive gliosis, determined by regions of strong OX42 staining. PMID:24641886

  19. Median and ulnar nerve injuries; what causes different repair outcomes?

    PubMed Central

    Nouraei, Mohammad Hadi; Hosseini, Alireza; Salek, Shadi; Nouraei, Farhad; Bina, Roya

    2015-01-01

    Background: Peripheral nerve injuries have significant effects on patients life quality. To make patients therapeutic expectations more realistic, prediction of repair outcome has significant importance. Materials and Methods: Totally, 74 patients with 94 nerve injuries (44 median and 50 ulnar nerves) were evaluated and followed up for 5 years between 2008 and 2013 in two main university hospitals of Isfahan. Patients age was 664 years. 24 nerves were excluded from the study and among the remaining; 53 nerves were repaired primarily and 17 nerves secondarily. 42 nerves were injured at a low-level, 17 nerves at intermediate and 11 at a high one. Medical Research Council Scale used for sensory and motor assessment. S3+ and S4 scores for sensory recovery and M4 and M5 scores for motor recovery were considered as favorable results. The follow-up time was between 8 and 24 months. Results: There was no significant difference between favorable sensory outcomes of median and ulnar nerves. The difference between favorable motor outcomes of the median nerve was higher than ulnar nerve (P = 0.03, odds ratio = 2.9). More favorable results were seen in high-level injuries repair than low ones (P = 0.035), and also cases followed more than 18 months compared to less than 12 months (P = 0.041), respectively. The favorable outcomes for patients younger than 16 were more than 40 and older, however, their difference was not significant (P = 0.059). The difference between primary and secondary repair favorable outcomes was not significant (P = 0.37). Conclusion: In patients older than 40 or injured at a high-level, there is a high possibility of repetitive operations and reconstructive measures. The necessity for long-term follow-up and careful attentions during a postoperative period should be pointed to all patients. PMID:26605244

  20. Self-Desensitization and Meditation in the Reduction of Public Speaking Anxiety.

    ERIC Educational Resources Information Center

    Kirsch, Irving; Henry, David

    1979-01-01

    Speech-anxious students were assigned to self-administered treatment conditions: (1) systematic desensitization, (2) desensitization with meditation replacing progressive relaxation, and (3) meditation only. Treatment manuals included coping-skill instructions. Treatments were equally effective in reducing anxiety and produced a greater reduction

  1. Substance P receptor desensitization requires receptor activation but not phospholipase C

    SciTech Connect

    Sugiya, Hiroshi; Putney, J.W. Jr. )

    1988-08-01

    Previous studies have shown that exposure of parotid acinar cells to substance P at 37{degree}C results in activation of phospholipase C, formation of ({sup 3}H)inositol 1,4,5-trisphosphate (IP{sub 3}), and persistent desensitization of the substance P response. In cells treated with antimycin in medium containing glucose, ATP was decreased to {approximately}20% of control values, IP{sub 3} formation was completely inhibited, but desensitization was unaffected. When cells were treated with antimycin in the absence of glucose, cellular ATP was decreased to {approximately}5% of control values, and both IP{sub 3} formation and desensitization were blocked. A series of substance P-related peptides increased the formation of ({sup 3}H)IP{sub 3} and induced desensitization of the substance P response with a similar rank order of potencies. The substance P antagonist, (D-Pro{sup 2}, D-Try{sup 7,9})-substance P, inhibited substance P-induced IP{sub 3} formation and desensitization but did not induce desensitization. These results suggest that the desensitization of substance P-induced IP{sub 3} formation requires agonist activation of a P-type substance P receptor, and that one or more cellular ATP-dependent processes are required for this reaction. However, activation of phospholipase C and the generation of inositol phosphates does not seem to be a prerequisite for desensitization.

  2. Violence Exposure in Real-Life, Video Games, Television, Movies, and the Internet: Is There Desensitization?

    ERIC Educational Resources Information Center

    Funk, Jeanne B.; Baldacci, Heidi Bechtoldt; Pasold; Tracie; Baumgardner, Jennifer

    2004-01-01

    It is believed that repeated exposure to real-life and to entertainment violence may alter cognitive, affective, and behavioral processes, possibly leading to desensitization. The goal of the present study was to determine if there are relationships between real-life and media violence exposure and desensitization as reflected in related…

  3. A practical and successful desensitization protocol for immediate hypersensitivity reactions to iron salts.

    PubMed

    Demir, Semra; Olgac, Muge; Unal, Derya; Gelincik, Asli; Colakoglu, Bahauddin; Buyukozturk, Suna

    2014-01-01

    Orally administered iron salts (OAS) are widely used in the management of iron deficiency anemia and hypersensitivity reactions to OAS are not common. If an offending drug is the sole option or is significantly more effective than its alternatives, it can be readministered by desensitization. The oral desensitization protocols for iron published so far concern either desensitization that was completed only over a long period or did not attain the recommended therapeutic dose. We aimed to develop a more effective protocol. We report here on 2 patients who experienced hypersensitivity reactions to OAS. After confirming the diagnosis, both patients were desensitized to oral ferrous (II) glycine sulfate complex according to a 2-day desensitization protocol. A commercial suspension of oral ferrous glycine sulfate, which contains 4 mg of elemental iron in 1 ml, was preferred. We started with a dose as low as 0.1 ml from a 1/100 dilution (0.004 mg elemental iron) of the original suspension and reached the maximum effective dose in 2 days. Both patients were successfully desensitized and they went on to complete the 6-month iron treatment without any adverse effects. Although hypersensitvity reactions to iron are not common, there is no alternative for iron administration. Therefore, desensitization has to be the choice. This easy desensitization protocol seems to be a promising option. PMID:25402762

  4. Violence Exposure in Real-Life, Video Games, Television, Movies, and the Internet: Is There Desensitization?

    ERIC Educational Resources Information Center

    Funk, Jeanne B.; Baldacci, Heidi Bechtoldt; Pasold; Tracie; Baumgardner, Jennifer

    2004-01-01

    It is believed that repeated exposure to real-life and to entertainment violence may alter cognitive, affective, and behavioral processes, possibly leading to desensitization. The goal of the present study was to determine if there are relationships between real-life and media violence exposure and desensitization as reflected in related

  5. Comparison of Anxiety Management Training and Desensitization in Reducing Test and Other Anxieties.

    ERIC Educational Resources Information Center

    Deffenbacher, Jerry L.; Shelton, John L.

    1978-01-01

    Effects of systematic desensitization and anxiety management training in reducing test anxiety and generalizing to other anxieties were compared. Both desensitization and anxiety management training produced significant reduction of text anxiety, but by follow-up, anxiety management training produced significantly more test-anxiety reduction on

  6. Nerve conduction velocity

    MedlinePLUS

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

  7. Infraorbital nerve transpositioning into orbital floor: a modified technique to minimize nerve injury following zygomaticomaxillary complex fractures

    PubMed Central

    Kotrashetti, Sharadindu Mahadevappa; Kale, Tejraj Pundalik; Bhandage, Supriya

    2015-01-01

    Objectives Transpositioning of the inferior alveolar nerve to prevent injury in lower jaw has been advocated for orthognathic, pre-prosthetic and for implant placement procedures. However, the concept of infra-orbital nerve repositioning in cases of mid-face fractures remains unexplored. The infraorbital nerve may be involved in trauma to the zygomatic complex which often results in sensory disturbance of the area innervated by it. Ten patients with infraorbital nerve entrapment were treated in similar way at our maxillofacial surgery centre. Materials and Methods In this article we are reporting three cases of zygomatico-maxillary complex fracture in which intra-operative repositioning of infra-orbital nerve into the orbital floor was done. This was done to release the nerve from fractured segments and to reduce the postoperative neural complications, to gain better access to fracture site and ease in plate fixation. This procedure also decompresses the nerve which releases it off the soft tissue entrapment caused due to trauma and the organized clot at the fractured site. Results There was no evidence of sensory disturbance during their three month follow-up in any of the patient. Conclusion Infraorbital nerve transposition is very effective in preventing paresthesia in patients which fracture line involving the infraorbital nerve. PMID:25922818

  8. Sensory testing of the human gastrointestinal tract

    PubMed Central

    Brock, Christina; Arendt-Nielsen, Lars; Wilder-Smith, Oliver; Drewes, Asbjrn Mohr

    2009-01-01

    The objective of this appraisal is to shed light on the various approaches to screen sensory information in the human gut. Understanding and characterization of sensory symptoms in gastrointestinal disorders is poor. Experimental methods allowing the investigator to control stimulus intensity and modality, as well as using validated methods for assessing sensory response have contributed to the understanding of pain mechanisms. Mechanical stimulation based on impedance planimetry allows direct recordings of luminal cross-sectional areas, and combined with ultrasound and magnetic resonance imaging, the contribution of different gut layers can be estimated. Electrical stimulation depolarizes free nerve endings non-selectively. Consequently, the stimulation paradigm (single, train, tetanic) influences the involved sensory nerves. Visual controlled electrical stimulation combines the probes with an endoscopic approach, which allows the investigator to inspect and obtain small biopsies from the stimulation site. Thermal stimulation (cold or warm) activates selectively mucosal receptors, and chemical substances such as acid and capsaicin (either alone or in combination) are used to evoke pain and sensitization. The possibility of multimodal (e.g. mechanical, electrical, thermal and chemical) stimulation in different gut segments has developed visceral pain research. The major advantage is involvement of distinctive receptors, various sensory nerves and different pain pathways mimicking clinical pain that favors investigation of central pain mechanisms involved in allodynia, hyperalgesia and referred pain. As impairment of descending control mechanisms partly underlies the pathogenesis in chronic pain, a cold pressor test that indirectly stimulates such control mechanisms can be added. Hence, the methods undoubtedly represent a major step forward in the future characterization and treatment of patients with various diseases of the gut, which provides knowledge to clinicians about the underlying symptoms and treatment of these patients. PMID:19132764

  9. Homologous and Heterologous Desensitization of Capsaicin and Mustard Oil Responses Utilize Different Cellular Pathways in Nociceptors

    PubMed Central

    Ruparel, Nikita B.; Patwardhan, Amol M.; Akopian, Armen N.; Hargreaves, Kenneth M.

    2008-01-01

    The Transient Receptor Potential channel subtypes V1 (TRPV1) and A1 (TRPA1) play a critical role in the development of hyperalgesia in inflammatory pain models. Although several studies in animals and humans have demonstrated that capsaicin (CAP), a TRPV1-specific agonist, and mustard oil (MO), a TRPA1 agonist, evoke responses that undergo functional cross-desensitization in various models, the mechanisms mediating this phenomenon are largely unknown. In the present study, we evaluated the mechanisms underlying homologous and heterologous desensitization between CAP and MO responses in peripheral nociceptors using an in vitro neuropeptide release assay from acutely isolated rat hindpaw skin preparation and in vivo behavioral assessments. The pretreatment with CAP or MO significantly inhibited (5060%) both CAP- and MO-evoked CGRP release indicating homologous and heterologous desensitization using this assay. Further studies evaluating the requirement of calcium in these phenomena revealed that homologous desensitization of CAP responses was calcium-dependent while homologous desensitization of MO responses was calcium-independent. Moreover, heterologous desensitization of both CAP and MO responses was calcium-dependent. Further studies evaluating the role of calcineurin demonstrated that heterologous desensitization of CAP responses was calcineurin-dependent while heterologous desensitization of MO responses was calcineurin-independent. Homologous and heterologous desensitization of CAP and MO was also demonstrated using in vivo behavioral nocifensive assays. Taken together, these results indicate that TRPV1 and TRPA1 could be involved in a functional interaction that is regulated via different cellular pathways. The heterologous desensitization of these receptors and corresponding inhibition of nociceptor activity might have potential application as a therapeutic target for developing novel analgesics. PMID:17590514

  10. Nerve Impulses in Plants

    ERIC Educational Resources Information Center

    Blatt, F. J.

    1974-01-01

    Summarizes research done on the resting and action potential of nerve impulses, electrical excitation of nerve cells, electrical properties of Nitella, and temperature effects on action potential. (GS)

  11. Femoral nerve dysfunction

    MedlinePLUS

    Neuropathy - femoral nerve; Femoral neuropathy ... Felice, KJ. Focal neuropathies of the femoral, obturator, lateral femoral cutaneous and other nerves of the thigh and pelvis. In: Bromberg MB, Smith ...

  12. 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

  13. Immunological mechanisms for desensitization and tolerance in food allergy1

    PubMed Central

    Rachid, Rima; Umetsu, Dale T.

    2013-01-01

    Food allergy is a major public health concern in westernized countries, estimated to affect 5% of children and 3-4 % of adults. Allergen specific immunotherapy for food allergy is currently being actively evaluated, but is still experimental. The optimal protocol, in terms of the route of administration of the food, target maintenance dose, duration of maintenance therapy and the optimal patient for these procedures are still being worked out. The mechanisms underlying successful food desensitization are also unclear, in part because there is no standard immunotherapy protocol. The mechanisms involved however, may include mast cell and basophil suppression, development of food-specific IgG4 antibodies, reduction in the food specific IgE/IgG4 ratio, up-regulation and expansion of natural or inducible regulatory T cells, a skewing from a Th2 to a Th1 profile and the development of anergy and/or deletion in antigen specific cells. Additional studies are required to elucidate and understand these mechanisms by which desensitization and tolerance are achieved, and which may reveal valuable biomarkers for evaluating and following food allergic patients on immunotherapy. PMID:22821087

  14. 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

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

    PubMed

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

    2015-11-01

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

  16. Histochemical discrimination of fibers in regenerating rat infraorbital nerve

    NASA Technical Reports Server (NTRS)

    Wilke, R. A.; Riley, D. A.; Sanger, J. R.

    1992-01-01

    In rat dorsal root ganglia, histochemical staining of carbonic anhydrase (CA) and cholinesterase (CE) yields a reciprocal pattern of activity: Sensory processes are CA positive and CE negative, whereas motor processes are CA negative and CE positive. In rat infraorbital nerve (a sensory peripheral nerve), we saw extensive CA staining of nearly 100% of the myelinated axons. Although CE reactivity in myelinated axons was extremely rare, we did observe CE staining of unmyelinated autonomic fibers. Four weeks after transection of infraorbital nerves, CA-stained longitudinal sections of the proximal stump demonstrated 3 distinct morphological zones. A fraction of the viable axons retained CA activity to within 2 mm of the distal extent of the stump, and the stain is capable of resolving growth sprouts being regenerated from these fibers. Staining of unmyelinated autonomic fibers in serial sections shows that CE activity was not retained as far distally as is the CA sensory staining.

  17. Internal tobacco industry research on olfactory and trigeminal nerve response to nicotine and other smoke components.

    PubMed

    Megerdichian, Christine L; Rees, Vaughan W; Wayne, Geoffrey Ferris; Connolly, Gregory N

    2007-11-01

    Evidence has shown that factors other than the central pharmacological effects of nicotine are important in promoting smoking behavior. One such non-nicotine effect includes sensory stimulation, which may promote smoking by developing learned associations with nicotine's rewarding effects, or by constituting a rewarding experience independent of nicotine. The present study used internal tobacco industry documents to examine industry efforts to understand and manipulate stimulation of the sensory nerves by tobacco smoke, and the influence of sensory stimulation on smoker behavior. Research focused on sensory nerves of the head and neck, including the olfactory nerve, which carries flavor and odor, and the trigeminal nerve, which carries irritant information. The tobacco industry maintained a systematic research program designed to elucidate an understanding of responses of sensory nerves to nicotine and other components of tobacco smoke, and attempted to develop nicotine-like compounds that would enhance sensory responses in smokers. Industry research appeared intended to aid in the development of new products with greater consumer appeal. The potential influence of sensory response in enhancing nicotine dependence through an associative mechanism was acknowledged by the tobacco industry, but evidence for research in this area was limited. These findings add to evidence of industry manipulation of sensory factors to enhance smoking behavior and may have implications for development of more effective treatment strategies, including more "acceptable" nicotine replacement therapies. PMID:17978985

  18. Injury of the Inferior Alveolar Nerve during Implant Placement: a Literature Review

    PubMed Central

    Wang, Hom-Lay; Sabalys, Gintautas

    2011-01-01

    ABSTRACT Objectives The purpose of present article was to review aetiological factors, mechanism, clinical symptoms, and diagnostic methods as well as to create treatment guidelines for the management of inferior alveolar nerve injury during dental implant placement. Material and Methods Literature was selected through a search of PubMed, Embase and Cochrane electronic databases. The keywords used for search were inferior alveolar nerve injury, inferior alveolar nerve injuries, inferior alveolar nerve injury implant, inferior alveolar nerve damage, inferior alveolar nerve paresthesia and inferior alveolar nerve repair. The search was restricted to English language articles, published from 1972 to November 2010. Additionally, a manual search in the major anatomy, dental implant, periodontal and oral surgery journals and books were performed. The publications there selected by including clinical, human anatomy and physiology studies. Results In total 136 literature sources were obtained and reviewed. Aetiological factors of inferior alveolar nerve injury, risk factors, mechanism, clinical sensory nerve examination methods, clinical symptoms and treatment were discussed. Guidelines were created to illustrate the methods used to prevent and manage inferior alveolar nerve injury before or after dental implant placement. Conclusions The damage of inferior alveolar nerve during the dental implant placement can be a serious complication. Clinician should recognise and exclude aetiological factors leading to nerve injury. Proper presurgery planning, timely diagnosis and treatment are the key to avoid nerve sensory disturbances management. PMID:24421983

  19. 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

  20. 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

  1. Blockade by the local anaesthetic, tetracaine, of desensitization of Ca-induced Ca release after muscarinic stimulation in smooth muscle.

    PubMed Central

    Hishinuma, S.; Uchida, M. K.

    1991-01-01

    1. Desensitization of contractile responses dependent on release of intracellularly stored Ca elicited by carbachol, histamine or caffeine was measured after desensitizing treatment with carbachol or histamine in the presence or absence of local anaesthetics in Ca-free solution containing 2 mM EGTA in the smooth muscle of guinea-pig taenia caecum. 2. Histamine-induced homologous desensitization was inhibited by tetracaine and procainamide. Dibucaine did not exert an inhibitory effect on the desensitization. This is consistent with our previous findings concerning the effects of local anaesthetics on the desensitization of histamine H1-receptors measured under normal physiological conditions. 3. Carbachol induced a functional change of intracellular Ca stores which resulted in heterologous desensitization. Tetracaine completely blocked carbachol-induced desensitization of the caffeine-elicited contraction, but in the case of carbachol-induced desensitization of carbachol- and histamine-elicited contractions, this blocking effect of tetracaine was very weak and absent, respectively. The other local anaesthetics used did not affect the desensitization. These results suggest that the Ca-induced and inositol trisphosphate-induced Ca release mechanisms were both desensitized by carbachol and that the desensitization of the Ca-induced Ca release mechanism was selectively blocked by tetracaine. PMID:1884098

  2. In vivo desensitization of glycogenolysis to Ca2+-mobilizing hormones in rat liver cells.

    PubMed Central

    Tsujimoto, G; Tsujimoto, A; Kato, K; Hashimoto, K

    1988-01-01

    Rat hepatocytes contain several types of Ca2+-linked receptors, all of which stimulate glycogen breakdown by increasing cytosolic free Ca2+ concentration [( Ca2+]c). In vivo desensitization of this Ca2+ messenger system was studied in hepatocytes isolated from either pheochromocytoma (PHEO)-harboring and chronically norepinephrine (NE)-infused rats. Homologous desensitization for alpha 1-adrenergic receptor-mediated phosphorylase activation developed in the early stage of PHEO rats (3-4 wk after implantation), whereas, in the later stage of tumor development or in the NE-infused rats, phosphorylase responses to all Ca2+-mobilizing stimulations were subsensitive (heterologous desensitization). In the homologous desensitization, the [Ca2+]c response to alpha 1-adrenergic stimulation was selectively reduced. We found, using the phenoxybenzamine inactivation method, that there was a linear relationship between alpha 1 receptor density and the [Ca2+]c response; consequently, the blunted [Ca2+]c response to alpha 1-adrenergic stimulation could not be explained by the 34% downregulation of alpha 1 receptors seen in these rats. These results indicated that uncoupling at a step proximal to alpha 1 receptor-stimulated [Ca2+]c increase is also of primary importance in homologous desensitization of phosphorylase activation. On the other hand, heterologous desensitization also involved alteration(s) at steps distal to the rise in [Ca2+]c. Our data demonstrate that prolonged exposure to catecholamines results in desensitization of the [Ca2+]c mobilization pathway and may involve multiple mechanisms. PMID:2848864

  3. Desensitization of. gamma. -aminobutyric acid receptor from rat brain: two distinguishable receptors on the same membrane

    SciTech Connect

    Cash, D.J.; Subbarao, K.

    1987-12-01

    Transmembrane chloride flux mediated by ..gamma..-aminobutyric acid (GABA) receptor can be measured with a mammalian brain homogenate preparation containing sealed membrane vesicles. The preparation can be mixed rapidly with solutions of defined composition. Influx of /sup 36/Cl/sup -/ tracer initiated by mixing with GABA was rapidly terminated by mixing with bicuculline methiodide. The decrease in the isotope influx measurement due to prior incubation of the vesicle preparation with GABA, which increased with preincubation time and GABA concentration, was attributed to desensitization of the GABA receptor. By varying the time of preincubation with GABA between 10 ms and 50 s with quench-flow technique, the desensitization rates could be measured over their whole time course independently of the chloride ion flux rate. Most of the receptor activity decreased in a fast phase of desensitization complete in 200 ms at saturation with GABA. Remaining activity was desensitized in a few seconds. These two phases of desensitization were each kinetically first order and were shown to correspond with two distinguishable GABA receptors on the same membrane. The receptor activities could be estimated, and the faster desensitizing receptor was the predominant one, giving on average ca. 80% of the total activity. The half-response concentrations were similar, 150 and 114 ..mu..M for the major and minor receptors, respectively. The dependence on GABA concentration indicated that desensitization is mediated by two GABA binding sites. The fast desensitization rate was approximately 20-fold faster than previously reported rates while the slower desensitization rate was slightly faster than previously reported rates.

  4. Clinical observations on sensory effects of trigeminal dorsal root section1

    PubMed Central

    Ley, Adolfo; Guitart, Jos Ma.

    1971-01-01

    Further clinical and operative support is presented for Dandy's discovery in 1929 of the presence of accessory sensory fibres of the fifth cranial nerve, running a separate course from the main sensory root at its exit from the pons. The advantages are stressed of Dandy's subcerebellar approach in selected cases for sparing those fibres as well as the motor root. Images PMID:5571312

  5. Surgical anatomy of the retroperitoneal spaces, Part IV: retroperitoneal nerves.

    PubMed

    Mirilas, Petros; Skandalakis, John E

    2010-03-01

    We present surgicoanatomical topographic relations of nerves and plexuses in the retroperitoneal space: 1) six named parietal nerves, branches of the lumbar plexus: iliohypogastric, ilioinguinal, genitofemoral, lateral femoral cutaneous, obturator, femoral. 2) The sacral plexus is formed by the lumbosacral trunk, ventral rami of S1-S3, and part of S4; the remainder of S4 joining the coccygeal plexus. From this plexus originate the superior gluteal nerve, which passes backward through the greater sciatic foramen above the piriformis muscle; the inferior gluteal nerve also courses through the greater sciatic foramen, but below the piriformis; 3) sympathetic trunks: right and left lumbar sympathetic trunks, which comprise four interconnected ganglia, and the pelvic chains; 4) greater, lesser, and least thoracic splanchnic nerves (sympathetic), which pass the diaphragm and join celiac ganglia; 5) four lumbar splanchnic nerves (sympathetic), which arise from lumbar sympathetic ganglia; 6) pelvic splanchnic nerves (nervi erigentes), providing parasympathetic innervation to the descending colon and pelvic splanchna; and 7) autonomic (prevertebral) plexuses, formed by the vagus nerves, splanchnic nerves, and ganglia (celiac, superior mesenteric, aorticorenal). They include sympathetic, parasympathetic, and sensory (mainly pain) fibers. The autonomic plexuses comprise named parts: aortic, superior mesenteric, inferior mesenteric, superior hypogastric, and inferior hypogastric (hypogastric nerves). PMID:20349652

  6. Allopurinol hypersensitivity reactions: desensitization strategies and new therapeutic alternative molecules.

    PubMed

    Calogiuri, Gianfranco; Nettis, Eustachio; Di Leo, Elisabetta; Foti, Caterina; Ferrannini, Antonio; Butani, Lavjay

    2013-02-01

    Allopurinol, an analog of hypoxanthine has been worldwide used for the treatment of hyperuricemia and gout for over 40 years. Unfortunately some patients assuming this medication have developed hypersensitivity reactions ranging from mild cutaneous eruption to more severe clinical manifestations such as allopurinol hypersensitivity syndrome or Steven-Johnson syndrome and lethal toxic epidermal necrolysis. Various strategies of slow desensitization have been elaborated to reintroduce allopurinol in a part of these patients, mainly patients affected by mild skin reactions as fixed drug eruption or exanthema. However, several new uricosuric therapies have been recently introduced. Actually drugs as recombinant urate oxidase and febuxostat are under post-marketing surveillance to control potential adverse effects related to their immunogenicity even. PMID:23092365

  7. Sensory preconditioning in honeybees.

    PubMed

    Müller, D; Gerber, B; Hellstern, F; Hammer, M; Menzel, R

    2000-04-01

    Sensory preconditioning means that reinforcement of stimulus A after unreinforced exposure to a compound AB also leads to responses to stimulus B. Here, we describe and analyze sensory preconditioning in an insect, the honeybee Apis mellifera. Using two-element odorant compounds in classical conditioning of the proboscis extension reflex, we found (i) that sensory preconditioning is not due to stimulus generalization, (ii) that paired, but not unpaired, presentation of elements supports sensory preconditioning, (iii) that simultaneous, but not sequential, exposure to the elements of the compound supports sensory preconditioning and (iv) that a single presentation of the compound yields maximal sensory preconditioning. The results are discussed with respect to configural and chain-like associative explanations for sensory preconditioning. We suggest an experience-dependent step of compound processing, establishing configural units, as an additional explanation for sensory preconditioning. PMID:10729283

  8. Beyond Desensitization: Physiological Relevance of Arrestin-Dependent Signaling

    PubMed Central

    Luttrell, Louis M.

    2010-01-01

    Heptahelical G protein-coupled receptors are the most diverse and therapeutically important family of receptors in the human genome. Ligand binding activates heterotrimeric G proteins that transmit intracellular signals by regulating effector enzymes or ion channels. G protein signaling is terminated, in large part, by arrestin binding, which uncouples the receptor and G protein and targets the receptor for internalization. It is clear, however, that heptahelical receptor signaling does not end with desensitization. Arrestins bind a host of catalytically active proteins and serve as ligand-regulated scaffolds that recruit protein and lipid kinase, phosphatase, phosphodiesterase, and ubiquitin ligase activity into the receptor-arrestin complex. Although many of these arrestin-bound effectors serve to modulate G protein signaling, degrading second messengers and regulating endocytosis and trafficking, other signals seem to extend beyond the receptor-arrestin complex to regulate such processes as protein translation and gene transcription. Although these findings have led to a re-envisioning of heptahelical receptor signaling, little is known about the physiological roles of arrestin-dependent signaling. In vivo, the duality of arrestin function makes it difficult to dissociate the consequences of arrestin-dependent desensitization from those that might be ascribed to arrestin-mediated signaling. Nonetheless, recent evidence generated using arrestin knockouts, G protein-uncoupled receptor mutants, and arrestin pathway-selective “biased agonists” is beginning to reveal that arrestin signaling plays important roles in the retina, central nervous system, cardiovascular system, bone remodeling, immune system, and cancer. Understanding the signaling roles of arrestins may foster the development of pathway-selective drugs that exploit these pathways for therapeutic benefit. PMID:20427692

  9. Fast Synaptic Inhibition in Spinal Sensory Processing and Pain Control

    PubMed Central

    Zeilhofer, Hanns Ulrich; Wildner, Hendrik; Yevenes, Gonzalo E.

    2013-01-01

    The two amino acids ?-amino butyric acid (GABA) and glycine mediate fast inhibitory neurotransmission in different CNS areas and serve pivotal roles in the spinal sensory processing. Under healthy conditions, they limit the excitability of spinal terminals of primary sensory nerve fibers and of intrinsic dorsal horn neurons through pre- and postsynaptic mechanisms, and thereby facilitate the spatial and temporal discrimination of sensory stimuli. Removal of fast inhibition not only reduces the fidelity of normal sensory processing but also provokes symptoms very much reminiscent of pathological and chronic pain syndromes. This review summarizes our knowledge of the molecular bases of spinal inhibitory neurotransmission and its organization in dorsal horn sensory circuits. Particular emphasis is placed on the role and mechanisms of spinal inhibitory malfunction in inflammatory and neuropathic chronic pain syndromes. PMID:22298656

  10. Breast Reinnervation: DIEP Neurotization Using the Third Anterior Intercostal Nerve

    PubMed Central

    Menn, Zachary K.; Eldor, Liron; Kaufman, Yoav; Dellon, A. Lee

    2013-01-01

    Background: The purpose of this article is to evaluate a new method of DIEP flap neurotization using a reliably located recipient nerve. We hypothesize that neurotization by this method (with either nerve conduit or direct nerve coaptation) will have a positive effect on sensory recovery. Methods: Fifty-seven deep inferior epigastric perforator (DIEP) flaps were performed on 35 patients. Neurotizations were performed to the third anterior intercostal nerve by directly coapting the flap donor nerve or coapting with a nerve conduit. Nine nonneurotized DIEP flaps served as controls and received no attempted neurotization. All patients were tested for breast sensibility in 9 areas of the flap skin-island and adjacent postmastectomy skin. Testing occurred at an average of 111 weeks (23309) postoperatively. Results: At a mean of 111 weeks after breast reconstruction, neurotization of the DIEP flap resulted in recovery of sensibility that was statistically significantly better (lower threshold) in the flap skin (P < 0.01) and statistically significantly better than in the native mastectomy skin into which the DIEP flap was inserted (P < 0.01). Sensibility recovered in DIEP flaps neurotized using the nerve conduit was significantly better (lower threshold) than that in the corresponding areas of the DIEP flaps neurotized by direct coaptation (P < 0.01). Conclusion: DIEP flap neurotization using the third anterior intercostal nerve is an effective technique to provide a significant increase in sensory recovery for breast reconstruction patients, while adding minimal surgical time. Additionally, the use of a nerve conduit produces increased sensory recovery when compared direct coaptation. PMID:25289267

  11. Malignant lymphoma presented as recurrent multiple cranial nerve palsy after spontaneous regression of oculomotor nerve palsy: A case report.

    PubMed

    Hirose, Takahiko; Nakajima, Hideto; Shigekiyo, Tarou; Yokote, Taiji; Ishida, Shimon; Kimura, Fumiharu

    2016-01-29

    We report the case of a 62-year-old man who presented with malignant lymphoma as recurrent multiple cranial nerve palsy after spontaneous regression of oculomotor nerve palsy. He developed ptosis and diplopia due to right oculomotor nerve palsy. Brain MRI/MRA showed no abnormality, and he recovered with conservative medical management. Three months later, he showed diplopia due to right abducens nerve palsy and facial pain and trigeminal sensory loss. Neurological examination revealed multiple cranial nerve palsy involved cranial nerve III, V, IX, and X of the right side. Serum soluble interleukin-2 receptor levels were normal, and cerebrospinal fluid examination was unremarkable. Steroid and subsequent intravenous immunoglobulin therapy didn't improve his symptoms. Six weeks after his admission, he showed rapid enlargement of the cervical lymph node and the right tonsil, and post-contrast T1-weighted MRI showed enlargement and enhancement of the left infraorbital nerve, the bilateral cavernous sinus, the bilateral facial nerves, and the left trigeminal nerve. The histopathologic examination of the tonsil biopsy revealed diffuse large B cell lymphoma. The cause of these symptoms was thought to be infiltrating the cavernous sinus, and adjacent nerves. Spontaneous regression of malignant lymphoma is an exceptional event, but this possibility should be considered so as to the correct diagnosis and proper treatment. PMID:26616489

  12. 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

  13. Sensory response following knee joint damage in rabbits

    PubMed Central

    2014-01-01

    Background Altered sensory information arising from damaged knee joint structures has been hypothesized as a contributing factor to persistent muscle dysfunction following injury. Methods Composite femoral nerve sensory signal was measured in 24 rabbits randomly allocated (8 per group) to receive surgical anterior cruciate ligament (ACL) transection with or without autograft reconstruction or nothing (control). Two-weeks after the intervention composite afferent signals were recorded from the femoral nerve. Side-to-side ratios (surgical side vs contralateral healthy side) for peak femoral nerve afferent composite signal were used for comparison. Results Femoral nerve afferent signal ratios were significantly higher in the ACL-R (2.21??0.74) group when compared to the ACL-T (1.28??0.61, P?=?0.02) group and Control group (1.31??0.78, P?=?0.03). Conclusion The magnitude of sensory information recorded on the femoral nerve is increased following ACL injury and reconstruction surgery, but not after an isolated ACL injury in rabbits. PMID:24766654

  14. IL-17 and VEGF are necessary for efficient corneal nerve regeneration

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The contribution of acute inflammation to sensory nerve regeneration was investigated in the murine cornea using a model of corneal abrasion that removes the stratified epithelium and subbasal nerve plexus. Abrasion induced accumulation of IL-17(+) CCR6(+) yo T cells, neutrophils, and platelets in t...

  15. The sensory innervation of the human pharynx: searching for mechanoreceptors.

    PubMed

    de Carlos, F; Cobo, J; Macías, E; Feito, J; Cobo, T; Calavia, M G; García-Suárez, O; Vega, J A

    2013-11-01

    The coordinate neural regulation of the upper airways muscles is basic to control airway size and resistance. The superior constrictor pharyngeal muscle (SCPM) forms the main part of the lateral and posterior walls of the pharynx and typically is devoid of muscle spindles, the main type of proprioceptor. Because proprioception arising from SCPM is potentially important in the physiology of the upper airways, we have investigated if there are mechanical sensory nerve endings substitute for the muscle spindles. Samples of human pharynx were analyzed using immunohistochemistry associated to general axonic and Schwann cells markers (NSE, PGP 9.5, RT-97, and S100P), intrafusal muscle fiber markers, and putative mechanical sense proteins (TRPV4 and ASIC2). Different kinds of sensory corpuscles were observed in the pharynx walls (Pacini-like corpuscles, Ruffini-like corpuscles, spiral-wharves nerve structures, and others) which are supplied by sensory nerves and express putative mechanoproteins. No evidence of muscle spindles was observed. The present results demonstrate the occurrence of numerous and different morphotypes of sensory corpuscles/mechanoreceptors in human pharynx that presumably detect mechanical changes in the upper airways and replace muscle spindles for proprioception. Present findings are of potential interest for the knowledge of pathologies of the upper airways with supposed sensory pathogenesis. PMID:24123994

  16. Anaphylactic reaction to polyethylene-glycol conjugated-asparaginase: premedication and desensitization may not be sufficient.

    PubMed

    Sahiner, Umit M; Yavuz, S Tolga; Gkce, Muge; Buyuktiryaki, Betul; Altan, Ilhan; Aytac, Selin; Tuncer, Murat; Tuncer, Ayfer; Sackesen, Cansin

    2013-08-01

    In hypersensitive reactions to native L-asparaginase, either premedication and desensitization or substitution with polyethylene glycol conjugated asparaginase (PEG-ASP) is preferred. Anaphylaxis with PEG-ASP is rare. An 8-year-old girl and a 2.5-year-old boy, both diagnosed as having acute lymphoblastic leukemia, presented with native L-asparaginase hypersensitivity and substitution with PEG-ASP was preferred. They received a premedication (methylprednisolone, hydroxyzine and ranitidine) followed by desensitization with PEG-ASP infusion. Both patients developed anaphylaxis with peg-asparaginase. These are the first reported cases of anaphylactic reaction to PEG-ASP, despite the application of both premedication and desensitization. Anaphylaxis with PEG-ASP is very rare and premedication and desensitization protocols may not prevent these hypersensitive reactions. PMID:23910807

  17. Voltage clamp analysis of acetylcholine receptor desensitization in isolated mollusc neurones.

    PubMed Central

    Bregestovksi, P D; Bukharaeva, E A; Iljin, V I

    1979-01-01

    1. Desensitization produced by acetylcholine (ACh) in completely isolated Limnaea stagnalis neurones with chloride-selective membrane channels was studied using a voltage-clamp technique. 2. A difference in the time course of the neurone responses to ACh, depending on whether the measured parameter was voltage or current, was observed and explained on the basis of an equivalent electric scheme of the neurone soma membrane. 3. Desensitization onset was shown not to depend on membrane potential in the range of -30 to -120 mV. 4. Variation of external Ca2+, Na+ and Cl- concentrations over a wide range had little influence on the onset of desensitization and recovery from it. 5. An obvious difference is shown to exist between features of desensitization in mollusc neurone and frog muscle end-plate ACh receptors. PMID:536923

  18. Lymphocyte-mediated regulation of platelet activation during desensitization in patients with hymenoptera venom hypersensitivity.

    PubMed Central

    Ledru, E; Pestel, J; Tsicopoulos, A; Joseph, M; Wallaert, B; Tonnel, A B; Capron, A

    1988-01-01

    T cells from peripheral blood of hymenoptera sensitive patients were studied before and after venom desensitization. Before treatment, T cells showed a variable but higher proliferative response to allergen than T cells of treated patients or controls. While before desensitization, T cell products, specifically released after in vitro allergen stimulation, were able to amplify the IgE-dependent platelet activity, we showed that after treatment of the same patients, T cell products strongly reduced platelet activation. Considering the modifications in platelet activation previously observed in patients treated by specific immunotherapy, the present results suggest that, through a modification of T cell reactivity to allergen, T cell functions are modulated by desensitization, and emphasize the involvement of T cell products in the desensitization mechanisms. PMID:3263227

  19. Gangliosides and chondroitin sulfate desensitize and internalize B2 bradykinin receptors.

    PubMed

    Shimazaki, Ayaka; Nakagawa, Tetsuto; Mitoma, Junya; Higashi, Hideyoshi

    2012-03-30

    Prolonged or repeated agonist activation of G-protein-coupled receptors (GPCRs) initiates their desensitization and internalization, rendering them unresponsive to agonist activation. We analyzed how gangliosides and chondroitin sulfate affect B2 bradykinin (BK) receptors (B2Rs). Gangliosides and chondroitin sulfate did not stimulate intracellular Ca(2+) release from B2R-expressing CHO-K1 cells, but repeated exposure desensitized B2Rs to BK stimulation. Microscopic observation of DsRed-fused B2Rs revealed that several gangliosides and chondroitin sulfate C (CSC) effectively internalized B2Rs. Ganglioside-CSC treatment of B2R mutant-expressing cells failed to desensitize and internalize the mutant receptors. As this mutant lacks the first extracellular domain and cannot activate GPCR kinase (GRK), gangliosides and CSC likely initiate B2R desensitization and endocytosis through GRK-mediated B2R phosphorylation. PMID:22409970

  20. Respiratory peripheral sensory irritation and hypersensitivity studies with glutaraldehyde vapor.

    PubMed

    Werley, M S; Burleigh-Flayer, H D; Ballantyne, B

    1995-01-01

    Overexposure to glutaraldehyde (GA) vapor (CAS No. 111-30-8) is known to cause peripheral sensory irritant effects in humans. Respiratory sensory irritation was investigated in male ND4 Swiss Webster mice to quantify the effect, and also as a preliminary to a study of the respiratory sensitizing potential of GA. For the irritation study, groups of four mice were exposed to seven different GA vapor concentrations in the range of 1.6 to 36.7 ppm, while respiratory rate (RR) was measured by plethysmography. Concentration-related decreases in RR were measured, with a maximum decrease at 3 to 20 min, which was sustained, indicating an absence of desensitization. The 50% decrease in RR (RD50) was calculated to be 13.9 ppm, which accords with the known sensory irritancy of GA and other aliphatic aldehydes. In a separate study, the respiratory sensitizing potential of GA vapor was studied in male Hartley guinea pigs, who were exposed for one hour per day for five consecutive days to an inducing GA vapor concentration of 13.9 ppm. Subsequent challenge exposures to 4.4 ppm at 14, 21, and 35 days after the final induction exposure did not produce any evidence of respiratory sensitization. The above findings confirm that GA vapor is a moderately potent peripheral sensory irritant, and does not produce respiratory sensitization in the guinea pig at the concentrations tested. PMID:8677514

  1. Nonadaptive Fluctuation in an Adaptive Sensory System: Bacterial Chemoreceptor

    PubMed Central

    Nishikawa, Masatoshi; Shibata, Tatsuo

    2010-01-01

    Background Sensory systems often exhibit an adaptation or desensitization after a transient response, making the system ready to receive a new signal over a wide range of backgrounds. Because of the strong influence of thermal stochastic fluctuations on the biomolecules responsible for the adaptation, such as many membrane receptors and channels, their response is inherently noisy, and the adaptive property is achieved as a statistical average. Methodology/Principal Findings Here, we study a simple kinetic model characterizing the essential aspects of these adaptive molecular systems and show theoretically that, while such an adaptive sensory system exhibits a perfect adaptation property on average, its temporal stochastic fluctuations are able to be sensitive to the environmental conditions. Among the adaptive sensory systems, an extensively studied model system is the bacterial receptor responsible for chemotaxis. The model exhibits a nonadaptive fluctuation sensitive to the environmental ligand concentration, while perfect adaptation is achieved on average. Furthermore, we found that such nonadaptive fluctuation makes the bacterial behavior dependent on the environmental chemoattractant concentrations, which enhances the chemotactic performance. Conclusions/Significance This result indicates that adaptive sensory systems can make use of such stochastic fluctuation to carry environmental information, which is not possible by means of the average, while keeping responsive to the changing stimulus. PMID:20613875

  2. Opposite Effects of KCTD Subunit Domains on GABAB Receptor-mediated Desensitization*

    PubMed Central

    Seddik, Riad; Jungblut, Stefan P.; Silander, Olin K.; Rajalu, Mathieu; Fritzius, Thorsten; Besseyrias, Valrie; Jacquier, Valrie; Fakler, Bernd; Gassmann, Martin; Bettler, Bernhard

    2012-01-01

    GABAB receptors assemble from principle and auxiliary subunits. The principle subunits GABAB1 and GABAB2 form functional heteromeric GABAB(1,2) receptors that associate with homotetramers of auxiliary KCTD8, -12, -12b, or -16 (named after their K+ channel tetramerization domain) subunits. These auxiliary subunits constitute receptor subtypes with distinct functional properties. KCTD12 and -12b generate desensitizing receptor responses while KCTD8 and -16 generate largely non-desensitizing receptor responses. The structural elements of the KCTDs underlying these differences in desensitization are unknown. KCTDs are modular proteins comprising a T1 tetramerization domain, which binds to GABAB2, and a H1 homology domain. KCTD8 and -16 contain an additional C-terminal H2 homology domain that is not sequence-related to the H1 domains. No functions are known for the H1 and H2 domains. Here we addressed which domains and sequence motifs in KCTD proteins regulate desensitization of the receptor response. We found that the H1 domains in KCTD12 and -12b mediate desensitization through a particular sequence motif, T/NFLEQ, which is not present in the H1 domains of KCTD8 and -16. In addition, the H2 domains in KCTD8 and -16 inhibit desensitization when expressed C-terminal to the H1 domains but not when expressed as a separate protein in trans. Intriguingly, the inhibitory effect of the H2 domain is sequence-independent, suggesting that the H2 domain sterically hinders desensitization by the H1 domain. Evolutionary analysis supports that KCTD12 and -12b evolved desensitizing properties by liberating their H1 domains from antagonistic H2 domains and acquisition of the T/NFLEQ motif. PMID:23035119

  3. Pitocin and autism: An analysis of oxytocin receptor desensitization in the fetus.

    PubMed

    Gottlieb, Mark M

    2016-02-01

    The risk of Pitocin as a cause of autism attributable to oxytocin receptor desensitization in the brain of the fetus is evaluated in terms of a mathematical model. A composite unit, D, for oxytocin receptor desensitization levels is established with the form ((IU-h)/ml)E-3, where IU is the international unit for oxytocin. The desensitization values for oxytocin receptor desensitization at a concentration of 10nmol of oxytocin per liter for 3, 4.2 and 6h corresponding to 0%, 50% and 100% desensitization are calculated to be 15 D, 21 D, and 30 D, respectively. The permeability of the blood-brain barrier in the fetus to oxytocin is discussed, and the upper limit of the concentration of Pitocin in the placenta, and its possible diffusion into the blood and brain of the fetus, is calculated for a routine dose of 6milliU per minute of Pitocin over a 12h labor. This dose of Pitocin is shown to result in a desensitization value in units of D that is more than a factor of 10 below the 0% desensitization value of 15 D. This indicates that routine doses of Pitocin are not a significant cause of autism attributable to oxytocin receptor desensitization. This is consistent with the findings of a major epidemiological study of the association of Pitocin with autism in Denmark entitled, "Oxytocin-augmented labor and risk for males", Behavioral Brain Research, May 1, 2015; 284:207-212, which found no association between the use of Pitocin during labor and the incidence of autism for females, and a modest association for males. PMID:26545832

  4. Desensitization of homomeric alpha1 glycine receptor increases with receptor density.

    PubMed

    Legendre, Pascal; Muller, Emilie; Badiu, Carmen Ionela; Meier, Jochen; Vannier, Christian; Triller, Antoine

    2002-10-01

    Variations in the number of receptors at glycinergic synapses are now established and are believed to contribute to inhibitory synaptic plasticity. However, the relation between glycine receptor (GlyR) kinetics and density is still unclear. We used outside-out patch-clamp recordings and fast-flow application techniques to resolve fast homomeric GlyRalpha1 kinetics and to determine how the functional properties of these receptors depend on their density and on the presence of the anchoring protein gephyrin. The expression of GlyRs in human embryonic kidney cells increased with time and was correlated with an increase in GlyR desensitization at 2 days after transfection. Cotransfection of homomeric GlyRalpha1 bearing the gephyrin-binding site with gephyrin also increased desensitization but at 1 day after transfection compared with transfections of homomeric GlyRalpha1 without gephyrin. This increase results from the occurrence of a fast desensitization component and short applications of a saturating concentration of glycine suffice to promote a rapidly entered desensitized closed state. The level of desensitization changed neither the EC(50) value nor the Hill coefficient of the glycine dose-response curves because the amplitude of the current was measured at the peak of the responses. These results demonstrate that variations in GlyR density during cluster formation result from a change in GlyR efficiency due to modifications in their desensitization properties. PMID:12237328

  5. Mechanisms of fast desensitization of GABA(B) receptor-gated currents.

    PubMed

    Raveh, Adi; Turecek, Rostislav; Bettler, Bernhard

    2015-01-01

    GABA(B) receptors (GABA(B)Rs) regulate the excitability of most neurons in the central nervous system by modulating the activity of enzymes and ion channels. In the sustained presence of the neurotransmitter γ-aminobutyric acid, GABA(B)Rs exhibit a time-dependent decrease in the receptor response-a phenomenon referred to as homologous desensitization. Desensitization prevents excessive receptor influences on neuronal activity. Much work focused on the mechanisms of GABA(B)R desensitization that operate at the receptor and control receptor expression at the plasma membrane. Over the past few years, it became apparent that GABA(B)Rs additionally evolved mechanisms for faster desensitization. These mechanisms operate at the G protein rather than at the receptor and inhibit G protein signaling within seconds of agonist exposure. The mechanisms for fast desensitization are ideally suited to regulate receptor-activated ion channel responses, which influence neuronal activity on a faster timescale than effector enzymes. Here, we provide an update on the mechanisms for fast desensitization of GABA(B)R responses and discuss physiological and pathophysiological implications. PMID:25637440

  6. Effect of desensitizing treatments on bond strength of resin composites to dentin an in vitro study

    PubMed Central

    Makkar, Sameer; Goyal, Meenu; Kaushal, Ashih; Hegde, Vivek

    2014-01-01

    Objectives: Hypersensitivity is a common clinical multietiological problem. Many desensitizing treatments are there to overcome hypersensitivity. The aim of this study was to evaluate the effect of different dentin-desensitizing treatments on the tensile bond strength of composite restoration. Materials and Methods: Twenty-four sound human molars were used. Enamel was wet abraded to expose flat dentin surfaces, polished with sandpaper. The specimens were then divided into three groups (n = 8) based on the type of dentin-desensitizing treatment given. The first group: G1 was the control group where no desensitizing agent was used. The second group: G2 was treated with desensitizing dentifrice containing a combination of potassium nitrate, triclosan, and sodium monoflorophosphate. The third group: G3 was treated with Er:YAG laser. Afterwards, the desensitized specimens were treated with one step self-etch adhesive according to manufacturer's instructions and composite microcylinders were packed. The specimens were then examined for tensile bond strength using universal tensile machine (KMITM ). Results: Statistical analysis of the data obtained revealed the mean values for the tensile bond strengths were 10.2613 MPa, 5.9400 MPa and 6.3575 MPa for groups 1, 2 and 3, respectively. These values were statistically significantly different between groups pretreated with laser or dentifrice as compared to control group. Conclusions: Dentifrice and Laser pre-treated dentin has lower tensile bond strength with resin composites as compared to dentin that is untreated. PMID:25298648

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

    PubMed

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

    2015-09-01

    Peripheral nerve injury diminishes fast conducting large myelinated afferent fibers transmission but enhances smaller pain transmitting fibers firing. This aberrant afferent neuronal behavior contributes to development of chronic post-traumatic peripheral neuropathic pain (PTP-NP). Non-invasive dynamic magnetic flux stimulation has been implicated in treating PTP-NP, a condition currently not adequately addressed by other therapies including transcutaneous electrical nerve stimulation (TENS). The current study assessed the effect of low frequency transcutaneous magnetic stimulation (LFTMS) on peripheral sensory thresholds, nerve conduction properties, and TENS induced fast afferent slowing effect as measured by motor and sensory conduction studies in the ulnar nerve. Results indicated sham LFTMS with TENS (Sham?+?TENS) significantly (P?=?0.02 and 0.007, respectively) reduces sensory conduction velocity (CV) and increases sensory onset latency (OL), and motor peak latency (PL) whereas, real LFTMS with TENS (Real?+?TENS) reverses effects of TENS on sensory CV and OL, and significantly (P?=?0.036) increases the sensory PL. LFTMS alone significantly (P?sensory PL and onset-to-peak latency. LFTMS appears to reverse TENS slowing effect on fast conducting fibers and casts a selective peripheral modulatory effect on slow conducting pain afferent fibers. PMID:25989482

  8. Ulnar nerve damage (image)

    MedlinePLUS

    ... arm. The nerve is commonly injured at the elbow because of elbow fracture or dislocation. The ulnar nerve is near ... surface of the body where it crosses the elbow, so prolonged pressure on the elbow or entrapment ...

  9. Electromechanical Nerve Stimulator

    NASA Technical Reports Server (NTRS)

    Tcheng, Ping; Supplee, Frank H., Jr.; Prass, Richard L.

    1993-01-01

    Nerve stimulator applies and/or measures precisely controlled force and/or displacement to nerve so response of nerve measured. Consists of three major components connected in tandem: miniature probe with spherical tip; transducer; and actuator. Probe applies force to nerve, transducer measures force and sends feedback signal to control circuitry, and actuator positions force transducer and probe. Separate box houses control circuits and panel. Operator uses panel to select operating mode and parameters. Stimulator used in research to characterize behavior of nerve under various conditions of temperature, anesthesia, ventilation, and prior damage to nerve. Also used clinically to assess damage to nerve from disease or accident and to monitor response of nerve during surgery.

  10. Nerve Injuries in Athletes.

    ERIC Educational Resources Information Center

    Collins, Kathryn; And Others

    1988-01-01

    Over a two-year period this study evaluated the condition of 65 athletes with nerve injuries. These injuries represent the spectrum of nerve injuries likely to be encountered in sports medicine clinics. (Author/MT)

  11. Optic Nerve Decompression

    MedlinePLUS

    ... this delicate surgery without any cuts to the face. In the following sections, we will review the indications, risks and benefits of endoscopic optic nerve decompression. Indications The reasons for optic nerve decompression usually ...

  12. Peripheral nerve regeneration and neurotrophic factors

    PubMed Central

    TERENGHI, GIORGIO

    1999-01-01

    The role of neurotrophic factors in the maintenance and survival of peripheral neuronal cells has been the subject of numerous studies. Administration of exogenous neurotrophic factors after nerve injury has been shown to mimic the effect of target organ-derived trophic factors on neuronal cells. After axotomy and during peripheral nerve regeneration, the neurotrophins NGF, NT-3 and BDNF show a well defined and selective beneficial effect on the survival and phenotypic expression of primary sensory neurons in dorsal root ganglia and of motoneurons in spinal cord. Other neurotrophic factors such as CNTF, GDNF and LIF also exert a variety of actions on neuronal cells, which appear to overlap and complement those of the neurotrophins. In addition, there is an indirect contribution of GGF to nerve regeneration. GGF is produced by neurons and stimulates proliferation of Schwann cells, underlining the close interaction between neuronal and glial cells during peripheral nerve regeneration. Different possibilities have been investigated for the delivery of growth factors to the injured neurons, in search of a suitable system for clinical applications. The studies reviewed in this article show the therapeutic potential of neurotrophic factors for the treatment of peripheral nerve injury and for neuropathies. PMID:10227662

  13. Assessing Decreased Sensation and Increased Sensory Phenomena in Diabetic Polyneuropathies

    PubMed Central

    Herrmann, David N.; Staff, Nathan P.; Dyck, P. James B.

    2013-01-01

    Loss of sensation and increased sensory phenomena are major expressions of varieties of diabetic polyneuropathies needing improved assessments for clinical and research purposes. We provide a neurobiological explanation for the apparent paradox between decreased sensation and increased sensory phenomena. Strongly endorsed is the use of the 10-g monofilaments for screening of feet to detect sensation loss, with the goal of improving diabetic management and prevention of foot ulcers and neurogenic arthropathy. We describe improved methods to assess for the kind, severity, and distribution of both large- and small-fiber sensory loss and which approaches and techniques may be useful for conducting therapeutic trials. The abnormality of attributes of nerve conduction may be used to validate the dysfunction of large sensory fibers. The abnormality of epidermal nerve fibers/1 mm may be used as a surrogate measure of small-fiber sensory loss but appear not to correlate closely with severity of pain. Increased sensory phenomena are recognized by the characteristic words patients use to describe them and by the severity and persistence of these symptoms. Tests of tactile and thermal hyperalgesia are additional markers of neural hyperactivity that are useful for diagnosis and disease management. PMID:24158999

  14. Engineering Peripheral Nerve Repair

    PubMed Central

    Marquardt, Laura; Sakiyama-Elbert, Shelly E.

    2013-01-01

    Current approaches for treating peripheral nerve injury have resulted in promising, yet insufficient functional recovery compared to the clinical standard of care, autologous nerve grafts. In order to design a construct that can match the regenerative potential of the autograft, all facets of nerve tissue must be incorporated in a combinatorial therapy. Engineered biomaterial scaffolds in the future will have to promote enhanced regeneration and appropriate reinnervation by targeting the highly sensitive response of regenerating nerves to their surrounding microenvironment. PMID:23790730

  15. 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

  16. Optic Nerve Pit

    MedlinePLUS

    ... Conditions Frequently Asked Questions Español Condiciones Chinese Conditions Optic Nerve Pit What is optic nerve pit? An optic nerve pit is a ... may be seen in both eyes. How is optic pit diagnosed? If the pit is not affecting ...

  17. 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

  18. 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.

  19. Engineering a multimodal nerve conduit for repair of injured peripheral nerve.

    PubMed

    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 2cm can be sutured, larger or more severe injuries commonly require autogenous nerve grafts harvested from elsewhere in the body (usually sensory nerves). Functional recovery is often suboptimal and associated with loss of sensation from the tissue innervated by the harvested nerve. The challenges that persist with nerve repair have resulted in development of nerve guides or conduits from non-neural biological tissues and various polymers to improve the prognosis for the repair of damaged nerves in the PNS. This study describes the design and fabrication of a multimodal controlled pore size nerve regeneration conduit using polylactic acid (PLA) and (PLA):poly(lactic-co-glycolic) acid (PLGA) fibers within a neurotrophin-enriched alginate hydrogel. The nerve repair conduit design consists of two types of PLGA fibers selected specifically for promotion of axonal outgrowth and Schwann cell growth (75:25 for axons; 85:15 for Schwann cells). These aligned fibers are contained within the lumen of a knitted PLA sheath coated with electrospun PLA nanofibers to control pore size. The PLGA guidance fibers within the nerve repair conduit lumen are supported within an alginate hydrogel impregnated with neurotrophic factors (NT-3 or BDNF with LIF, SMDF and MGF-1) to provide neuroprotection, stimulation of axonal growth and Schwann cell migration. The conduit was used to promote repair of transected sciatic nerve in rats over a period of 4 weeks. Over this period, it was observed that over-grooming and self-mutilation (autotomy) of the limb implanted with the conduit was significantly reduced in rats implanted with the full-configuration conduit compared to rats implanted with conduits containing only an alginate hydrogel. This indicates return of some feeling to the limb via the fully-configured conduit. Immunohistochemical analysis of the implanted conduits removed from the rats after the four-week implantation period confirmed the presence of myelinated axons within the conduit and distal to the site of implantation, further supporting that the conduit promoted nerve repair over this period of time. This study describes the design considerations and fabrication of a novel multicomponent, multimodal bio-engineered synthetic conduit for peripheral nerve repair. PMID:23283383

  20. Tethered ligands reveal glutamate receptor desensitization depends on subunit occupancy

    PubMed Central

    Reiner, Andreas; Isacoff, Ehud Y.

    2014-01-01

    Cell signaling is often mediated by the binding of multiple ligands to a multi-subunit receptor. The probabilistic nature and slow rate of binding of diffusible ligands at low concentrations can impede attempts to determine how ligand occupancy controls signaling in such protein complexes. We describe a solution to this problem that uses a photoswitched tethered ligand as a ligand clamp to induce rapid and stable binding and unbinding at defined subsets of subunits. We applied the approach to study gating in ionotropic glutamate receptors (iGluRs), ligand-gated ion channels that mediate excitatory neurotransmission and plasticity at glutamatergic synapses in the brain. We probed gating in two kainate-type iGluRs, GluK2 homotetramers and GluK2/GluK5 heterotetramers. Ultrafast (sub-millisecond) photoswitching of an azobenzene-based ligand on specific subunits provided a real-time measure of gating and revealed that partially occupied receptors can activate without desensitizing. The findings have implications for signaling by locally released and spillover glutamate. PMID:24561661

  1. The Efficacy of Selected Desensitizing OTC Products: A Systematic Review

    PubMed Central

    Talioti, E.; Hill, R.; Gillam, D. G.

    2014-01-01

    Objectives. The aim of the present study was to review the published literature in order to identify relevant studies for inclusion and to determine whether there was any evidence on the clinical effectiveness of selected desensitizing toothpastes, calcium sodium phosphosilicate (CSPS), amorphous calcium phosphate (ACP), nanohydroxyapatite, and casein phosphopeptide-amorphous calcium phosphate (tooth mousse) on reducing dentine hypersensitivity (DH). Materials and Methods. Following a review of 593 papers identified from searching both electronic databases (PUBMED) and hand searching of relevant written journals, only 5 papers were accepted for inclusion. Results. Analysis of the included studies (3 CSPS and 2 ACP) would suggest that there may be some benefit for patients using these products for reducing DH. No direct comparative studies were available to assess all these products under the same conditions neither were there any comparative randomised controlled studies that compared at least two of these products in determining their effectiveness in treating DH. Conclusions. Due to the small number of included studies, there are limited clinical data to support any claims of clinical efficacy of these OTC products. Further studies are therefore required to determine the efficacy of these products in well-controlled RCT studies with a larger sample size. PMID:25006466

  2. Unexpected motor axons in the distal superficial radial and posterior interosseous nerves: a cadaver study.

    PubMed

    Okwueze, Martina I; Cardwell, Nancy L; Wolfort, Sean L; Nanney, Lillian B

    2007-10-01

    The prevalence of motor variations in the nerves supplying muscles of the first web space was evaluated by a visual dissection and immunohistochemical analysis from 56 cadaver hands. By microscopic visualization, 30% of the superficial radial nerves (SRNs) sent branches into muscles of the first web space. Since these unexpected penetrating branches were expected to be sensory or proprioceptive, markers of sensory and motor axons were used for confirmation. Positive identifications of motor axons (as identified by positive immunostaining for choline acetyltransferase) were made in 30% of SRNs and in 28.5% of posterior interosseous nerves. Classical teachings that the SRNs and PINs are exclusively sensory have been brought into question. Our data are in agreement with the rare clinical finding that motor function occasionally persists following devastating injury to both the ulnar and median nerves. Anatomic prevalence for this variation appears much higher than previous descriptions have indicated. PMID:17708562

  3. Evaluation of Nerve Conduction Studies in Obese Children With Insulin Resistance or Impaired Glucose Tolerance.

    PubMed

    Ince, Hülya; Taşdemir, Haydar Ali; Aydin, Murat; Ozyürek, Hamit; Tilki, Hacer Erdem

    2015-07-01

    The aim of the study was to investigate nerve conduction studies in terms of neuropathic characteristics in obese patients who were in prediabetes stage and also to determine the abnormal findings. The study included 69 obese adolescent patients between April 2009 and December 2010. All patients and control group underwent motor (median, ulnar, tibial, and peroneal) and sensory (median, ulnar, sural, and medial plantar) nerve conduction studies and sympathetic skin response test. Sensory response amplitude of the medial plantar nerve was significantly lower in the patients with impaired glucose tolerance and insulin resistance. To our knowledge, the present study is the first study demonstrating the development of sensory and autonomic neuropathy due to metabolic complications of obesity in adolescent children even in the period without development of diabetes mellitus. We recommend that routine electrophysiological examinations be performed, using medial plantar nerve conduction studies and sympathetic skin response test. PMID:25342307

  4. 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.

  5. Evodiamine suppresses capsaicin-induced thermal hyperalgesia through activation and subsequent desensitization of the transient receptor potential V1 channels.

    PubMed

    Iwaoka, Emiko; Wang, Shenglan; Matsuyoshi, Nobuyuki; Kogure, Yoko; Aoki, Shunji; Yamamoto, Satoshi; Noguchi, Koichi; Dai, Yi

    2016-01-01

    Evodiae fructus (EF), a fruit of Evodia rutaecarpa Bentham, has long been used as an analgesic drug in traditional Chinese and Japanese medicine. However, the underlying molecular mechanism of its pharmacological action is unclear. Here, using calcium imaging, whole-cell patch-clamp recording, and behavioral analysis, we investigated the pharmacological action of EF and its principal compound, evodiamine, on the transient receptor potential (TRP) V1 channels. Dorsal root ganglion (DRG) neurons and TRPV1- or TRPA1-transfected human embryonic kidney-derived (HEK) 293 cells were used for calcium imaging or whole-cell patch-clamp recording. Twenty male adult Sprague-Dawley rats were used for the capsaicin-induced thermal hyperalgesia behavioral analyses. We found that evodiamine induced significant increases in intracellular calcium and robust inward currents in a subpopulation of isolated rat DRG neurons, most of which were also sensitive to capsaicin. The effect of evodiamine was completely blocked by capsazepine, a competitive antagonist of TRPV1. Evodiamine induced significant inward currents in TRPV1-, but not TRPA1-transfected HEK293 cells. Pretreatment with evodiamine reduced capsaicin-induced currents significantly. Furthermore, the in vivo pre-treatment of evodiamine suppressed thermal hyperalgesia induced by intraplantar injection of capsaicin in rats. These results identify that the analgesic effect of EF and evodiamine may be due to the activation and subsequent desensitization of TRPV1 in sensory neurons. PMID:26188960

  6. The non-linear relationship between nerve conduction velocity and skin temperature.

    PubMed Central

    Todnem, K; Knudsen, G; Riise, T; Nyland, H; Aarli, J A

    1989-01-01

    Median motor and sensory nerves were examined in 20 healthy subjects. Superficial stimulating and recording electrodes were used, and the nerves were examined at natural skin temperature, after cooling and after heating of the arm. The conduction velocity for the fastest and slow conducting sensory fibres (temperature range 17-37 degrees C), and for the fastest conducting motor fibres (temperature range 19-38 degrees C) increased non-linearly with increase in skin temperature. Similarly, distal motor latencies increased non-linearly with decrease in skin temperature. The effect of temperature was most pronounced in the low temperature range, and change in conduction velocity per degree centigrade was reduced toward higher skin temperature. Sensory nerve response duration increased linearly with decline in skin temperature. Sensory and motor amplitude did not show any significant relation to skin temperature. PMID:2738592

  7. A desensitization-selective potentiator of AMPA-type glutamate receptors.

    PubMed

    Sekiguchi, Masayuki; Nishikawa, Kaori; Aoki, Shunsuke; Wada, Keiji

    2002-08-01

    1: We examined the effects of PEPA, an allosteric potentiator of AMPA receptors, on AMPA receptor kinetics. 2: PEPA did not affect the deactivation of glutamate responses but potently attenuated the extent of receptor desensitization without slowing the onset of desensitization in most of the recombinant AMPA receptors (GluR1-flip, GluR1-flop, GluR3-flip, GluR3-flip+GluR2-flip, and GluR3-flop+GluR2-flop) expressed in Xenopus oocytes. For the GluR3-flop subunit, PEPA attenuated the extent of desensitization and only weakly prolonged deactivation (1.3 fold). 3: PEPA did not significantly affect recovery from desensitization in oocytes expressing GluR3-flip, GluR1-flop, and GluR1-flop, but weakly accelerated (2.6 fold) recovery from desensitization in oocytes expressing GluR3-flop. 4: PEPA's effect on desensitization of GluR3-flop-containing receptors is unique in that onset is very slow. 5: Simulation studies using simplified kinetic models for AMPA receptors are utilized to explore the differential effects of PEPA on GluR3-flip and -flop. It is possible to simulate the action on GluR3-flip by modulating two rate constants in a 12-state kinetic model. For simulation of the action on GluR3-flop, the 12-state kinetic model is not enough, and it is necessary to invoke a 13th state, a PEPA-bound receptor to which glutamate cannot bind. 6: These results suggest that attenuation of extent of desensitization represents the principal mechanism underlying the potentiation of AMPA receptors by PEPA, and that PEPA exhibits different mechanisms with respect to GluR3-flip and GluR3-flop. PMID:12145103

  8. Src promotes delta opioid receptor (DOR) desensitization by interfering with receptor recycling

    PubMed Central

    Archer-Lahlou, Elodie; Audet, Nicolas; Amraei, Mohammad Gholi; Huard, Karine; Paquin-Gobeil, Mélanie; Pineyro, Graciela

    2009-01-01

    Abstract An important limitation in the clinical use of opiates is progressive loss of analgesic efficacy over time. Development of analgesic tolerance is tightly linked to receptor desensitization. In the case of delta opioid receptors (DOR), desensitization is especially swift because receptors are rapidly internalized and are poorly recycled to the membrane. In the present study, we investigated whether Src activity contributed to this sorting pattern and to functional desensitization of DORs. A first series of experiments demonstrated that agonist binding activates Src and destabilizes a constitutive complex formed by the spontaneous association of DORs with the kinase. Src contribution to DOR desensitization was then established by showing that pre-treatment with Src inhibitor PP2 (20 μM; 1 hr) or transfection of a dominant negative Src mutant preserved DOR signalling following sustained exposure to an agonist. This protection was afforded without interfering with endocytosis, but suboptimal internalization interfered with PP2 ability to preserve DOR signalling, suggesting a post-endocytic site of action for the kinase. This assumption was confirmed by demonstrating that Src inhibition by PP2 or its silencing by siRNA increased membrane recovery of internalized DORs and was further corroborated by showing that inhibition of recycling by monensin or dominant negative Rab11 (Rab11S25N) abolished the ability of Src blockers to prevent desensitization. Finally, Src inhibitors accelerated recovery of DOR-Gαl3 coupling after desensitization. Taken together, these results indicate that Src dynamically regulates DOR recycling and by doing so contributes to desensitization of these receptors. PMID:18363847

  9. Does PKC activation increase the homologous desensitization of μ opioid receptors?

    PubMed Central

    Arttamangkul, Seksiri; Birdsong, William; Williams, John T

    2015-01-01

    BACKGROUND AND PURPOSE This study examined the role of agents known to activate PKC on morphine-induced desensitization of μ-opioid receptors (MOP receptors) in brain slices containing locus coeruleus neurons. EXPERIMENTAL APPROACH Intracellular recordings were obtained from rat locus coeruleus neurons. Two measurements were used to characterize desensitization, the decline in hyperpolarization induced by application of a saturating concentration of agonist (acute desensitization) and the decrease in hyperpolarization induced by a subsaturating concentration of [Met]5enkephalin (ME) following washout of the saturating concentration (sustained desensitization). Internalization of MOP receptors was studied in brain slices prepared from transgenic mice expressing Flag-MOP receptors. The subcellular distribution of activated PKC was examined using a novel fluorescent sensor of PKC in HEK293 cells. KEY RESULTS The phorbol esters (PMA and PDBu) and muscarine increased acute desensitization induced by a saturating concentration of morphine and ME. These effects were not sensitive to staurosporine. Staurosporine did not block the decline in hyperpolarization induced by muscarine. PDBu and muscarine did not affect sustained desensitization induced by ME nor did phorbol esters or muscarine change the trafficking of MOP receptors induced by morphine or ME. The distribution of activated PKC measured in HEK293 cells differed depending on which phorbol ester was applied. CONCLUSIONS AND IMPLICATIONS This study demonstrates a distinct difference in two measurements that are often used to evaluate desensitization. The measure of decline correlated well with the reduction in peak amplitudes caused by PKC activators implicating the modification of other factors rather than MOP receptors. LINKED ARTICLES This article is part of a themed section on Opioids: New Pathways to Functional Selectivity. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2015.172.issue-2 PMID:24697621

  10. Infectious Complications in Living-Donor Kidney Transplant Recipients Undergoing Multi-Modal Desensitization

    PubMed Central

    Shafique, Michael; Lobo, Peter I.; Sawyer, Robert G.; Keith, Douglas S.; Brayman, Kenneth L.; Agarwal, Avinash

    2014-01-01

    Abstract Background: Pre-existing humoral barriers challenge the transplantation of living donor kidneys (LDK) into highly sensitized ABO- and human leukocyte antigen (HLA)-incompatible recipients. Conditioning these LDK recipients' immune systems is required before they undergo transplantation. We hypothesized that medical desensitization would yield higher post-transplantation rates of infection. Methods: We conducted a study in which matched controls consisting of non-desensitized (NDS) LDK recipients were compared with desensitized (DS) receipients. Pre-transplantation desensitization included treatment with rituximab and mycophenolate mofetil followed by intravenous immunoglobulin (IVIg) and plasmapheresis. All participants in the study underwent induction therapy and maintenance immunosuppression. Primary outcomes included infection (opportunistic, local, systemic) within 12 mo after transplantation. Results: Twenty-five patients underwent desensitization and LDK transplantation. Graft survival in the DS and NDS groups of patients was 96% and 98%, respectively. The mean 3- and 12-mo serum creatinine concentrations in the DS and NDS groups were 1.10.2?mg/dL and 1.20.3?mg/dL and 0.950.4mg/dL and 0.730.8mg/dL (p=0.3 and p=0.01), respectively. Thirty-six percent of the patients in the DS group had one or more infections, vs. 28% of those in the NDS group (p=0.1). No difference was observed in the frequency of opportunistic or systemic infections in the two groups. Local infections were statistically significantly more frequent in the DS group (60% vs. 30%, respectively; p=0.02). Conclusion: Pre-operative desensitization in highly sensitized LDK recipients is followed by a similar incidence of opportunistic and systemic infections as in NDS patients. Local infections were significantly more frequent in the DS than in the NDS patients in the study. With careful monitoring of infectious complications, pre-transplant desensitization permits LDK transplantation into highly sensitized patients. PMID:24773230

  11. Signaling by Sensory Receptors

    PubMed Central

    Julius, David; Nathans, Jeremy

    2012-01-01

    Sensory systems detect small molecules, mechanical perturbations, or radiation via the activation of receptor proteins and downstream signaling cascades in specialized sensory cells. In vertebrates, the two principal categories of sensory receptors are ion channels, which mediate mechanosensation, thermosensation, and acid and salt taste; and G-protein-coupled receptors (GPCRs), which mediate vision, olfaction, and sweet, bitter, and umami tastes. GPCR-based signaling in rods and cones illustrates the fundamental principles of rapid activation and inactivation, signal amplification, and gain control. Channel-based sensory systems illustrate the integration of diverse modulatory signals at the receptor, as seen in the thermosensory/pain system, and the rapid response kinetics that are possible with direct mechanical gating of a channel. Comparisons of sensory receptor gene sequences reveal numerous examples in which gene duplication and sequence divergence have created novel sensory specificities. This is the evolutionary basis for the observed diversity in temperature- and ligand-dependent gating among thermosensory channels, spectral tuning among visual pigments, and odorant binding among olfactory receptors. The coding of complex external stimuli by a limited number of sensory receptor types has led to the evolution of modality-specific and species-specific patterns of retention or loss of sensory information, a filtering operation that selectively emphasizes features in the stimulus that enhance survival in a particular ecological niche. The many specialized anatomic structures, such as the eye and ear, that house primary sensory neurons further enhance the detection of relevant stimuli. PMID:22110046

  12. Hereditary sensory neuropathy type I.

    PubMed

    Auer-Grumbach, Michaela

    2008-01-01

    Hereditary sensory neuropathy type I (HSN I) is a slowly progressive neurological disorder characterised by prominent predominantly distal sensory loss, autonomic disturbances, autosomal dominant inheritance, and juvenile or adulthood disease onset. The exact prevalence is unknown, but is estimated as very low. Disease onset varies between the 2nd and 5th decade of life. The main clinical feature of HSN I is the reduction of sensation sense mainly distributed to the distal parts of the upper and lower limbs. Variable distal muscle weakness and wasting, and chronic skin ulcers are characteristic. Autonomic features (usually sweating disturbances) are invariably observed. Serious and common complications are spontaneous fractures, osteomyelitis and necrosis, as well as neuropathic arthropathy which may even necessitate amputations. Some patients suffer from severe pain attacks. Hypacusis or deafness, or cough and gastrooesophageal reflux have been observed in rare cases. HSN I is a genetically heterogenous condition with three loci and mutations in two genes (SPTLC1 and RAB7) identified so far. Diagnosis is based on the clinical observation and is supported by a family history. Nerve conduction studies confirm a sensory and motor neuropathy predominantly affecting the lower limbs. Radiological studies, including magnetic resonance imaging, are useful when bone infections or necrosis are suspected. Definitive diagnosis is based on the detection of mutations by direct sequencing of the SPTLC1 and RAB7 genes. Correct clinical assessment and genetic confirmation of the diagnosis are important for appropriate genetic counselling and prognosis. Differential diagnosis includes the other hereditary sensory and autonomic neuropathies (HSAN), especially HSAN II, as well as diabetic foot syndrome, alcoholic neuropathy, neuropathies caused by other neurotoxins/drugs, immune mediated neuropathy, amyloidosis, spinal cord diseases, tabes dorsalis, lepra neuropathy, or decaying skin tumours like amelanotic melanoma. Management of HSN I follows the guidelines given for diabetic foot care (removal of pressure to the ulcer and eradication of infection, followed by the use of specific protective footwear) and starts with early and accurate counselling of patients about risk factors for developing foot ulcerations. The disorder is slowly progressive and does not influence life expectancy but is often severely disabling after a long duration of the disease. PMID:18348718

  13. Neurology: an ancient sensory organ in crocodilians.

    PubMed

    Soares, Daphne

    2002-05-16

    Crocodilians hunt at night, waiting half-submerged for land-bound prey to disturb the water surface. Here I show that crocodilians have specialized sensory organs on their faces that can detect small disruptions in the surface of the surrounding water, and which are linked to a dedicated, hypertrophied nerve system. Such 'dome' pressure receptors are also evident in fossils from the Jurassic period, indicating that these semi-aquatic predators solved the problem of combining armour with tactile sensitivity many millions of years ago. PMID:12015589

  14. 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.

  15. Optic Nerve Elongation

    PubMed Central

    Alvi, Aijaz; Janecka, Ivo P.; Kapadia, Silloo; Johnson, Bruce L.; McVay, William

    1996-01-01

    The length of the optic nerves is a reflection of normal postnatal cranio-orbital development. Unilateral elongation of an optic nerve has been observed in two patients with orbital and skull base neoplasms. In the first case as compared to the patient's opposite, normal optic nerve, an elongated length of the involved optic nerve of 45 mm was present. The involved optic nerve in the second patient was 10 mm longer than the normal opposite optic nerve. The visual and extraocular function was preserved in the second patient. The first patient had only light perception in the affected eye. In this paper, the embryology, anatomy, and physiology of the optic nerve and its mechanisms of stretch and repair are discussed. ImagesFigure 1Figure 2Figure 3Figure 4Figure 5Figure 6Figure 7Figure 8Figure 9Figure 10Figure 11Figure 13 PMID:17170975

  16. In vivo electrophysiological measurements on mouse sciatic nerves.

    PubMed

    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 pathophysiology(1). 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 probe(2). 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 electrodes(3) 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

  17. Effects of lead acetate on guinea pig - cochear microphonics, action potential, and motor nerve conduction velocity

    SciTech Connect

    Yamamura, K.; Maehara, N.; Terayama, K.; Ueno, N.; Kohyama, A.; Sawada, Y.; Kishi, R.

    1987-04-01

    Segmental demyelination and axonal degeneration of motor nerves induced by lead exposure is well known in man, and animals. The effect of lead acetate exposure to man may involve the cranial nerves, since vertigo and sensory neuronal deafness have been reported among lead workers. However, there are few reports concerning the dose-effects of lead acetate both to the peripheral nerve and the cranial VII nerve with measurement of blood lead concentration. The authors investigated the effects of lead acetate to the cochlea and the VIII nerve using CM (cochlear microphonics) and AP (action potential) of the guinea pigs. The effects of lead acetate to the sciatic nerve were measured by MCV of the sciatic nerve with measurement of blood lead concentration.

  18. Neural stem/progenitor cell properties of glial cells in the adult mouse auditory nerve.

    PubMed

    Lang, Hainan; Xing, Yazhi; Brown, LaShardai N; Samuvel, Devadoss J; Panganiban, Clarisse H; Havens, Luke T; Balasubramanian, Sundaravadivel; Wegner, Michael; Krug, Edward L; Barth, Jeremy L

    2015-01-01

    The auditory nerve is the primary conveyor of hearing information from sensory hair cells to the brain. It has been believed that loss of the auditory nerve is irreversible in the adult mammalian ear, resulting in sensorineural hearing loss. We examined the regenerative potential of the auditory nerve in a mouse model of auditory neuropathy. Following neuronal degeneration, quiescent glial cells converted to an activated state showing a decrease in nuclear chromatin condensation, altered histone deacetylase expression and up-regulation of numerous genes associated with neurogenesis or development. Neurosphere formation assays showed that adult auditory nerves contain neural stem/progenitor cells (NSPs) that were within a Sox2-positive glial population. Production of neurospheres from auditory nerve cells was stimulated by acute neuronal injury and hypoxic conditioning. These results demonstrate that a subset of glial cells in the adult auditory nerve exhibit several characteristics of NSPs and are therefore potential targets for promoting auditory nerve regeneration. PMID:26307538

  19. Neural stem/progenitor cell properties of glial cells in the adult mouse auditory nerve

    PubMed Central

    Lang, Hainan; Xing, Yazhi; Brown, LaShardai N.; Samuvel, Devadoss J.; Panganiban, Clarisse H.; Havens, Luke T.; Balasubramanian, Sundaravadivel; Wegner, Michael; Krug, Edward L.; Barth, Jeremy L.

    2015-01-01

    The auditory nerve is the primary conveyor of hearing information from sensory hair cells to the brain. It has been believed that loss of the auditory nerve is irreversible in the adult mammalian ear, resulting in sensorineural hearing loss. We examined the regenerative potential of the auditory nerve in a mouse model of auditory neuropathy. Following neuronal degeneration, quiescent glial cells converted to an activated state showing a decrease in nuclear chromatin condensation, altered histone deacetylase expression and up-regulation of numerous genes associated with neurogenesis or development. Neurosphere formation assays showed that adult auditory nerves contain neural stem/progenitor cells (NSPs) that were within a Sox2-positive glial population. Production of neurospheres from auditory nerve cells was stimulated by acute neuronal injury and hypoxic conditioning. These results demonstrate that a subset of glial cells in the adult auditory nerve exhibit several characteristics of NSPs and are therefore potential targets for promoting auditory nerve regeneration. PMID:26307538

  20. Diacetyl Increases Sensory Innervation and Substance P Production in Rat Trachea

    PubMed Central

    Goravanahally, Madhusudan P.; Hubbs, Ann F.; Fedan, Jeffery S.; Kashon, Michael L.; Battelli, Lori A.; Mercer, Robert R.; Goldsmith, W. Travis; Jackson, Mark C.; Cumpston, Amy; Frazer, David G.; Dey, Richard D.

    2015-01-01

    Inhalation of diacetyl, a butter flavoring, causes airway responses potentially mediated by sensory nerves. This study examines diacetyl-induced changes in sensory nerves of tracheal epithelium. Rats (n = 6/group) inhaled 0-, 25-, 249-, or 346-ppm diacetyl for 6 hr. Tracheas and vagal ganglia were removed 1-day postexposure and labeled for substance P (SP) or protein gene product 9.5 (PGP9.5). Vagal ganglia neurons projecting to airway epithelium were identified by axonal transport of fluorescent microspheres intratracheally instilled 14 days before diacetyl inhalation. End points were SP and PGP9.5 nerve fiber density (NFD) in tracheal epithelium and SP-positive neurons projecting to the trachea. PGP9.5-immunoreactive NFD decreased in foci with denuded epithelium, suggesting loss of airway sensory innervation. However, in the intact epithelium adjacent to denuded foci, SP-immunoreactive NFD increased from 0.01 0.002 in controls to 0.05 0.01 after exposure to 346-ppm diacetyl. In vagal ganglia, SP-positive airway neurons increased from 3.3 3.0% in controls to 25.5 6.6% after inhaling 346-ppm diacetyl. Thus, diacetyl inhalation increases SP levels in sensory nerves of airway epithelium. Because SP release in airways promotes inflammation and activation of sensory nerves mediates reflexes, neural changes may contribute to flavorings-related lung disease pathogenesis. PMID:23847039

  1. Temporal mismatch between pain behaviour, skin Nerve Growth Factor and intra-epidermal nerve fibre density in trigeminal neuropathic pain

    PubMed Central

    2014-01-01

    Background The neurotrophin Nerve Growth factor (NGF) is known to influence the phenotype of mature nociceptors, for example by altering synthesis of neuropeptides, and changes in NGF levels have been implicated in the pathophysiology of chronic pain conditions such as neuropathic pain. We have tested the hypothesis that after partial nerve injury, NGF accumulates within the skin and causes pro-nociceptive phenotypic changes in the remaining population of sensory nerve fibres, which could underpin the development of neuropathic pain. Results Eleven days after chronic constriction injury of the rat mental nerve the intra-epidermal nerve fibre density of the chin skin from had reduced from 11.6??4.9 fibres/mm to 1.0??0.4 fibres/mm; this slowly recovered to 2.4??2.0 fibres/mm on day 14 and 4.0??0.8 fibres/mm on day 21. Cold hyperalgesia in the ipsilateral lower lip was detectable 11days after chronic constriction injury, although at this time skin [NGF] did not differ between sides. At 14days post-injury, there was a significantly greater [NGF] ipsilaterally compared to contralaterally (ipsilateral?=?111??23pg/mg, contralateral?=?69??13pg/mg), but there was no behavioural evidence of neuropathic pain at this time-point. By 21days post-injury, skin [NGF] was elevated bilaterally and there was a significant increase in the proportion of TrkA-positive (the high-affinity NGF receptor) intra-epidermal nerve fibres that were immunolabelled for the neuropeptide Calcitonin Gene-related peptide. Conclusions The temporal mismatch in behaviour, skin [NGF] and phenotypic changes in sensory nerve fibres indicate that increased [NGF] does not cause hyperalgesia after partial mental nerve injury, although it may contribute to the altered neurochemistry of cutaneous nerve fibres. PMID:24380503

  2. Effect of combined nicotine and shrapnel exposure on pain measures and gait after nerve injury.

    PubMed

    Rittenhouse, Bradley; Hill-Pryor, Crystal D; McConathy, Adam; Parker, Peter; Franco, Nelson; Toussaint, Esra; Barker, Darrell; Prasad, Balakrishna; Pizarro, Jose M

    2011-11-01

    A significant fraction of military soldiers sustain nerve injury and use tobacco or nicotine containing products. Healing of nerve injuries is influenced by many factors, such as degree of original injury, healing potential of the nerve, and general health of patient. However, recently, it has been demonstrated that the presence of retained insoluble metal fragments decreases healing. The effects of systemic nicotine administration, with or without metal fragments at the site of nerve injury, were evaluated. Both the nicotine-administered groups (nicotine, nicotine + shrapnel) showed significant increase in the peroneal function compared with untreated controls, as assessed by paw area (p < 0.05). Furthermore, to test possible role of altered sensory function, we used the hot plate assay. Latency to withdraw paw from a hot plate was significantly shorter in nicotine groups (p < 0.05). These data indicate that nicotine improves sensory and motor aspects of nerve function, in the presence or absence of shrapnel. PMID:22165666

  3. Buprenorphine is a weak partial agonist that inhibits opioid receptor desensitization.

    PubMed

    Virk, Michael S; Arttamangkul, Seksiri; Birdsong, William T; Williams, John T

    2009-06-01

    Buprenorphine is a weak partial agonist at mu-opioid receptors that is used for treatment of pain and addiction. Intracellular and whole-cell recordings were made from locus ceruleus neurons in rat brain slices to characterize the actions of buprenorphine. Acute application of buprenorphine caused a hyperpolarization that was prevented by previous treatment of slices with the irreversible opioid antagonist beta-chlornaltrexamine (beta-CNA) but was not reversed by a saturating concentration of naloxone. As expected for a partial agonist, subsaturating concentrations of buprenorphine decreased the [Met](5)enkephalin (ME)-induced hyperpolarization or outward current. When the ME-induced current was decreased below a critical value, desensitization and internalization of mu-opioid receptors was eliminated. The inhibition of desensitization by buprenorphine was not the result of previous desensitization, slow dissociation from the receptor, or elimination of receptor reserve. Treatment of slices with subsaturating concentrations of etorphine, methadone, oxymorphone, or beta-CNA also reduced the current induced by ME but did not block ME-induced desensitization. Treatment of animals with buprenorphine for 1 week resulted in the inhibition of the current induced by ME and a block of desensitization that was not different from the acute application of buprenorphine to brain slices. These observations show the unique characteristics of buprenorphine and further demonstrate the range of agonist-selective actions that are possible through G-protein-coupled receptors. PMID:19494155

  4. Short-Term Desensitization of Muscarinic K+ Current in the Heart

    PubMed Central

    Murakami, Shingo; Inanobe, Atsushi; Kurachi, Yoshihisa

    2013-01-01

    Acetylcholine (ACh) rapidly increases cardiac K+ currents (IKACh) by activating muscarinic K+ (KACh) channels followed by a gradual amplitude decrease within seconds. This phenomenon is called short-term desensitization and its precise mechanism and physiological role are still unclear. We constructed a mathematical model for IKACh to examine the conditions required to reconstitute short-term desensitization. Two conditions were crucial: two distinct muscarinic receptors (m2Rs) with different affinities for ACh, which conferred an IKACh response over a wide range of ACh concentrations, and two distinct KACh channels with different affinities for the G-protein ?? subunits, which contributed to reconstitution of the temporal behavior of IKACh. Under these conditions, the model quantitatively reproduced several unique properties of short-term desensitization observed in myocytes: 1), the peak and quasi-steady states with 0.01100 ?M [ACh]; 2), effects of ACh preperfusion; and 3), recovery from short-term desensitization. In the presence of 10 ?M ACh, the IKACh model conferred recurring spontaneous firing after asystole of 8.9s and 10.7s for the Demir and Kurata sinoatrial node models, respectively. Therefore, two different populations of KACh channels and m2Rs may participate in short-term desensitization of IKACh in native myocytes, and may be responsible for vagal escape at nodal cells. PMID:24048003

  5. An in vitro evaluation of the effects of desensitizing agents on microleakage of Class V cavities

    PubMed Central

    Yikilgan, İhsan; Özcan, Suat; Bala, Oya; Ömürlü, Hüma

    2016-01-01

    Background The aim of this study was to evaluate the effect of a desensitizing agent on microleakage of Class V cavities. Material and Methods 72 premolar teeth were used. There were 6 groups. Class V restorations were prepared with two different restorative materials (Equia fil, GC, America and Grandio, VOCO, Germany) and two adhesive systems (Clearfil SE Bond, Kuraray, Japan and S3 Bond Plus, Kuraray, Japan) with and without desensitizing agent (Gluma Desensitizer, Heraeus Kulzer, Germany). Restorations were polished with aluminum oxide abrasive discs. Then a range of 5 - 55C thermocycling was performed 10.000 times. The microleakage of restorations was examined with dye penetration method (Basic fuchsine). Bonferroni corrections and Kruskal-Wallis test were used to determine the significance of differences in occlusal and gingival dye penetration scores between groups. Results There was no stastistical significance between the occlusal and gingival microleakage scores within the groups were shown. Conclusions It can be concluded that use of desensitizing agent under both high viscosity glass ionomer restorative materials and resin composites doesn’t affect the microleakage. Key words:High viscosity glass ionomer cement, composite resin, desensitizing agent, microleakage. PMID:26855707

  6. Successful desensitization of a patient with aplastic anemia to antithymocyte globulin.

    PubMed

    Wolanin, Stephanie A; Demain, Jeffrey G; Meier, Eric A

    2015-01-01

    Antithymocyte globulin (ATG) is a polyclonal gamma immunoglobulin derived from either rabbit or equine serum that serves as therapy for aplastic anemia; however, ATG causes serum sickness in up to 70% and anaphylaxis in up to 5% of recipients. Intradermal (ID) skin testing has been the primary technique used to evaluate for a preexisting Gell and Coombs type I hypersensitivity reaction to ATG. There are no data reporting the predictive value of delayed reactions to ID testing on the risk of serum sickness. This study was designed to establish the importance of epicutaneous and ID skin testing before the administration of ATG through a case report and literature discussion. We report a patient with severe aplastic anemia that was successfully desensitized to ATG after a negative epicutaneous skin test and positive ID skin test. The patient had neither systemic nor localized reactions during the desensitization. Desensitization to ATG in patients with positive epicutaneous skin testing has been shown to be associated with serious and potentially life-threatening complications and should only be considered when the benefits outweigh the risks. Epicutaneous skin testing should be considered in conjunction with ID skin testing when screening for potential sensitivity to ATG. Because of the serious risk of anaphylaxis, desensitization should be performed in an intensive care unit setting in conjunction with a physician familiar with drug desensitization and the management of anaphylaxis. PMID:25730287

  7. Mutations in the channel domain alter desensitization of a neuronal nicotinic receptor.

    PubMed

    Revah, F; Bertrand, D; Galzi, J L; Devillers-Thiéry, A; Mulle, C; Hussy, N; Bertrand, S; Ballivet, M; Changeux, J P

    1991-10-31

    A variety of ligand-gated ion channels undergo a fast activation process after the rapid application of agonist and also a slower transition towards desensitized or inactivated closed channel states when exposure to agonist is prolonged. Desensitization involves at least two distinct closed states in the acetylcholine receptor, each with an affinity for agonists higher than those of the resting or active conformations. Here we investigate how structural elements could be involved in the desensitization of the acetylcholine-gated ion channel from the chick brain alpha-bungarotoxin sensitive homo-oligomeric alpha 7 receptor, using site-directed mutagenesis and expression in Xenopus oocytes. Mutations of the highly conserved leucine 247 residue from the uncharged MII segment of alpha 7 suppress inhibition by the open-channel blocker QX-222, indicating that this residue, like others from MII, faces the lumen of the channel. But, unexpectedly, the same mutations decrease the rate of desensitization of the response, increase the apparent affinity for acetylcholine and abolish current rectification. Moreover, unlike wild-type alpha 7, which has channels with a single conductance level, the leucine-to-threonine mutant has an additional conducting state active at low acetylcholine concentrations. It is possible that mutation of Leu 247 renders conductive one of the high-affinity desensitized states of the receptor. PMID:1719423

  8. Albuterol-induced downregulation of Gs? accounts for pulmonary ?2-adrenoceptor desensitization in vivo

    PubMed Central

    Finney, Paul A.; Belvisi, Maria G.; Donnelly, Louise E.; Chuang, Tsu-Tshen; Mak, Judith C.W.; Scorer, Carol; Barnes, Peter J.; Adcock, Ian M.; Giembycz, Mark A.

    2000-01-01

    The aim of the present study was to develop a chronic in vivo model of pulmonary ?2-adrenoceptor desensitization and to elucidate the nature and molecular basis of this state. Subcutaneous infusion of rats with albuterol for 7 days compromised the ability of albuterol, given acutely, to protect against acetylcholine-induced bronchoconstriction. The bronchoprotective effect of prostaglandin E2, but not forskolin, was also impaired, indicating that the desensitization was heterologous and that the primary defect in signaling was upstream of adenylyl cyclase. ?2-Adrenoceptor density was reduced in lung membranes harvested from albuterol-treated animals, and this was associated with impaired albuterol-induced cyclic adenosine monophosphate (cAMP) accumulation and activation of cAMP-dependent protein kinase ex vivo. Gs? expression was reduced in the lung and tracheae of albuterol-treated rats, and cholera toxininduced cAMP accumulation was blunted. Chronic treatment of rats with albuterol also increased cAMP phosphodiesterase activity and G proteincoupled receptor kinase-2, but the extent to which these events contributed to ?2-adrenoceptor desensitization was unclear given that forskolin was active in both groups of animals and that desensitization was heterologous. Collectively, these results indicate that albuterol effects heterologous desensitization of pulmonary Gs-coupled receptors in this model, with downregulation of Gs? representing a primary molecular etiology. PMID:10880056

  9. Increased nicotinic receptor desensitization in hypoglossal motor neurons following chronic developmental nicotine exposure.

    PubMed

    Pilarski, Jason Q; Wakefield, Hilary E; Fuglevand, Andrew J; Levine, Richard B; Fregosi, Ralph F

    2012-01-01

    Neuronal nicotinic acetylcholine receptors (nAChRs) are expressed on hypoglossal motor neurons (XII MNs) that innervate muscles of the tongue. Activation of XII MN nAChRs evokes depolarizing currents, which are important for regulating the size and stiffness of the upper airway. Although data show that chronic developmental nicotine exposure (DNE) blunts cholinergic neurotransmission in the XII motor nucleus, it is unclear how nAChRs are involved. Therefore, XII MN nAChR desensitization and recovery were examined in tissues from DNE or control pups using a medullary slice preparation and tight-seal whole cell patch-clamp recordings. nAChR-mediated inward currents were evoked by brief pressure pulses of nicotine or the ?4?2 nAChR agonist RJR-2403. We found that, regardless of treatment, activatable nAChRs underwent desensitization, but, following DNE, nAChRs exhibited increased desensitization and delayed recovery. Similar results were produced using RJR-2403, showing that DNE influences primarily the ?4?2 nAChR subtype. These results show that while some nAChRs preserve their responsiveness to acute nicotine following DNE, they more readily desensitize and recover more slowly from the desensitized state. These data provide new evidence that chronic DNE modulates XII MN nAChR function, and suggests an explanation for the association between DNE and the incidence of central and obstructive apneas. PMID:22013232

  10. Measurement of Conformational Changes Accompanying Desensitization in an Ionotropic Glutamate Receptor

    SciTech Connect

    Armstrong,N.; Jasti, J.; Beich-Frandsen, M.; Gouaux, E.

    2006-01-01

    The canonical conformational states occupied by most ligand-gated ion channels, and many cell-surface receptors, are the resting, activated, and desensitized states. While the resting and activated states of multiple receptors are well characterized, elaboration of the structural properties of the desensitized state, a state that is by definition inactive, has proven difficult. Here we use electrical, chemical, and crystallographic experiments on the AMPA-sensitive GluR2 receptor, defining the conformational rearrangements of the agonist binding cores that occur upon desensitization of this ligand-gated ion channel. These studies demonstrate that desensitization involves the rupture of an extensive interface between domain 1 of 2-fold related glutamate-binding core subunits, compensating for the ca. 21{sup o} of domain closure induced by glutamate binding. The rupture of the domain 1 interface allows the ion channel to close and thereby provides a simple explanation to the long-standing question of how agonist binding is decoupled from ion channel gating upon receptor desensitization.

  11. Successful desensitization of a patient with aplastic anemia to antithymocyte globulin

    PubMed Central

    Wolanin, Stephanie A.; Meier, Eric A.

    2015-01-01

    Antithymocyte globulin (ATG) is a polyclonal gamma immunoglobulin derived from either rabbit or equine serum that serves as therapy for aplastic anemia; however, ATG causes serum sickness in up to 70% and anaphylaxis in up to 5% of recipients. Intradermal (ID) skin testing has been the primary technique used to evaluate for a preexisting Gell and Coombs type I hypersensitivity reaction to ATG. There are no data reporting the predictive value of delayed reactions to ID testing on the risk of serum sickness. This study was designed to establish the importance of epicutaneous and ID skin testing before the administration of ATG through a case report and literature discussion. We report a patient with severe aplastic anemia that was successfully desensitized to ATG after a negative epicutaneous skin test and positive ID skin test. The patient had neither systemic nor localized reactions during the desensitization. Desensitization to ATG in patients with positive epicutaneous skin testing has been shown to be associated with serious and potentially life-threatening complications and should only be considered when the benefits outweigh the risks. Epicutaneous skin testing should be considered in conjunction with ID skin testing when screening for potential sensitivity to ATG. Because of the serious risk of anaphylaxis, desensitization should be performed in an intensive care unit setting in conjunction with a physician familiar with drug desensitization and the management of anaphylaxis. PMID:25730287

  12. beta. -Adrenergic receptor desensitization of wild-type but not cyc lymphoma cells unmasked by submillimolar Mg/sup 2 +/

    SciTech Connect

    Clark, R.B.; Friedman, J.; Johnson, J.A.; Kunkel, M.W.

    1987-10-01

    Treatment with low physiological concentrations of epinephrine (5-50 nM) rapidly desensitizes ..beta..-adrenergic stimulation of cAMP formation in S49 wild-type (WT) lymphoma cells. Previous attempts to detect this early phase desensitization in cell free assays of adenylate cyclase after intact cell treatment were unsuccessful. The authors have now found that reducing the Mg/sup 2 +/ concentrations in the adenylate cyclase assays to < 1.0 mM unmasked this rapid phase of desensitization of the WT cells, and that high Mg/sup 2 +/ concentrations (5-10 mM) largely obscured the desensitization. Submillimolar Mg/sup 2 +/ conditions also revealed a two-to-threefold decrease in the affinity of epinephrine to the ..beta..-adrenergic receptor after desensitization with 20 nM epinephrine. Detection of 4..beta..-phorbol 12-myristate 13-acetate (PMA) desensitization of the WT ..beta..-adrenergic receptor was also dependent on low Mg/sup 2 +/ as measured either by the decrease in epinephrine stimulation of adenylate cyclase or by the reduction in the affinity of epinephrine binding. Unexpectedly, when cyc/sup -/ cells were pretreated with 50 nM epinephrine, the ..beta..-adrenergic stimulation of reconstituted adenylate cyclase was not desensitized. The characteristics of the Mg/sup 2 +/ effect on epinephrine- and PMA-induced desensitizations suggest a similar mechanism of action with the most likely events being phosphorylations of the ..beta..-adrenergic receptors. Their data indicate that cAMP dependent protein kinase may play a role in the desensitization caused by low epinephrine concentrations inasmuch as this phase of desensitization did not occur in the cyc/sup -/. For the PMA-induced desensitization, the phosphorylation may be mediated by protein kinase C.

  13. Sensory Correlations in Autism

    ERIC Educational Resources Information Center

    Kern, Janet K.; Trivedi, Madhukar H.; Grannemann, Bruce D.; Garver, Carolyn R.; Johnson, Danny G.; Andrews, Alonzo A.; Savla, Jayshree S.; Mehta, Jyutika A.; Schroeder, Jennifer L.

    2007-01-01

    This study examined the relationship between auditory, visual, touch, and oral sensory dysfunction in autism and their relationship to multisensory dysfunction and severity of autism. The Sensory Profile was completed on 104 persons with a diagnosis of autism, 3 to 56 years of age. Analysis showed a significant correlation between the different

  14. [Sensory Systems of Infants.

    ERIC Educational Resources Information Center

    Zero To Three, 1993

    1993-01-01

    This newsletter contains six articles: (1) "Early Flavor Experiences: When Do They Start?" Julie A. Mennella and Gary K. Beauchamp); (2) "Infant Massage" (Tiffany Field); (3) "The Infant's Sixth Sense: Awareness and Regulation of Bodily Processes" (Stephen W. Porges); (4) "Sensory Contributions to Action: A Sensory Integrative Approach" (Marie E.

  15. An animal model of peripheral nerve regeneration after the application of a collagen-polyvinyl alcohol scaffold and mesenchymal stem cells.

    PubMed

    Marinescu, Silviu Adrian; Z?rnescu, Otilia; Mihai, Ioana Ruxandra; Giuglea, Carmen; Sinescu, Ruxandra Diana

    2014-01-01

    Extensive nerve injuries often leading to nerve gaps can benefit, besides the gold standard represented by autologous nerve grafts, by the inciting field of tissue engineering. To enhance the role of biomaterials in nerve regeneration, the nerve conduits are associated with Schwann or Schwann-like cells. In this study, we evaluated rat sciatic nerve regeneration, by using a biodegradable nerve guide composed of Collagen (COL) and Polyvinyl Alcohol (PVA), associated with mesenchymal stem cells (MSC). After the exposure of the rat sciatic nerve, a nerve gap was created by excising 1 cm of the nerve. Three experimental groups were used for nerve gap bridging: autografts, nerve conduits filled with medium culture and nerve conduits filled with MSC. The methods of sensory and motor assessment consisted of the functional evaluation of sciatic nerve recovery - toe-spread, pinprick tests and gastrocnemius muscle index (GMI). The histological and immunocytochemical analysis of the probes that were harvested from the repair site was performed at 12 weeks. Successful nerve regeneration was noted in all three groups at the end of the 12th week. The functional and immunocytochemical results suggested that COL-PVA tubes supported with mesenchymal stem cells could be considered similar to autologous nerve grafts in peripheral nerve regeneration, without the drawbacks of the last ones. The functional results were better for the autografts and the ultrastructural data were better for the nerve conduits, but there were not noticed any statistical differences. PMID:25329117

  16. 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...

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

    PubMed Central

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

    2015-01-01

    Abstract Taste buds release ATP to activate ionotropic purinoceptors composed of P2X2 and P2X3 subunits, present on the taste nerves. Mice with genetic deletion of P2X2 and P2X3 receptors (double knockout mice) lack responses to all taste stimuli presumably due to the absence of ATP-gated receptors on the afferent nerves. Recent experiments on the double knockout mice showed, however, that their taste buds fail to release ATP, suggesting the possibility of pleiotropic deficits in these global knockouts. To test further the role of postsynaptic P2X receptors in afferent signalling, we used AF-353, a selective antagonist of P2X3-containing receptors to inhibit the receptors acutely during taste nerve recording and behaviour. The specificity of AF-353 for P2X3-containing receptors was tested by recording Ca2+ transients to exogenously applied ATP in fura-2 loaded isolated geniculate ganglion neurons from wild-type and P2X3 knockout mice. ATP responses were completely inhibited by 10 μm or 100 μm AF-353, but neither concentration blocked responses in P2X3 single knockout mice wherein the ganglion cells express only P2X2-containing receptors. Furthermore, AF-353 had no effect on taste-evoked ATP release from taste buds. In wild-type mice, i.p. injection of AF-353 or simple application of the drug directly to the tongue, inhibited taste nerve responses to all taste qualities in a dose-dependent fashion. A brief access behavioural assay confirmed the electrophysiological results and showed that preference for a synthetic sweetener, SC-45647, was abolished following i.p. injection of AF-353. These data indicate that activation of P2X3-containing receptors is required for transmission of all taste qualities. Key points Acute inhibition of purinergic receptors with a selective P2X3 antagonist prevents transmission of information from taste buds to sensory nerves. The P2X3 antagonist has no effect on taste-evoked release of ATP, confirming the effect is postsynaptic. The results confirm previous results with P2X2/3 double knockout mice that ATP is required for transmission of all taste qualities, including sour and salty. Previously, ATP was confirmed to be required for bitter, sweet and umami tastes, but was questioned for salty and sour tastes due to pleomorphic deficits in the double knockout mice. The geniculate ganglion in mouse contains two populations of ganglion cells with different subunit composition of P2X2 and P2X3 receptors making them differently susceptible to pharmacological block and, presumably, desensitization. PMID:25524179

  18. 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

  19. Chinese Medicine in Diabetic Peripheral Neuropathy: Experimental Research on Nerve Repair and Regeneration

    PubMed Central

    Piao, Yuanlin; Liang, Xiaochun

    2012-01-01

    Diabetic peripheral neuropathy (DPN) is one of the most common complications of chronic diabetes mellitus. Pathological characteristics of DPN include axonal atrophy, nerve demyelination, and delayed regeneration of peripheral sensory nerve fibers. The goal of treatment in DPN is not only to ameliorate neurological symptoms but also to slow or reverse the underlying neurodegenerative process. Schwann cells and neurotrophic factors play important roles in the repair and regeneration of peripheral nerves. The present paper reviews current studies and evidence regarding the neurological effects of traditional Chinese medicine, with an emphasis on recent developments in the area of nerve repair and regeneration in DPN. PMID:22927874

  20. Ultrasonography of MADSAM neuropathy: focal nerve enlargements at sites of existing and resolved conduction blocks.

    PubMed

    Scheidl, Erika; Bhm, Josef; Sim, Magdolna; Rzsa, Csilla; Bereznai, Benjamin; Kovcs, Tibor; Arnyi, Zsuzsanna

    2012-07-01

    Using the emerging technique of peripheral nerve ultrasonography, multiple focal nerve swellings corresponding to sites of existing conduction blocks have been described in demyelinating polyneuropathies. We report two cases of multifocal acquired demyelinating sensory and motor neuropathy (MADSAM). In the first, multiple focal nerve enlargements were detected by ultrasound at sites of previous conduction blocks, well after complete clinical and electrophysiological resolution. In the second case, existing proximal conduction blocks could be localized by ultrasound. Our cases highlight the importance of nerve ultrasound in identifying conduction blocks and demonstrate that ultrasonographic morphological changes may outlast functional recovery in demyelinating neuropathies. PMID:22513319

  1. Biological and Electrophysiologic Effects of Poly(3,4-ethylenedioxythiophene) on Regenerating Peripheral Nerve Fibers

    PubMed Central

    Baghmanli, Ziya; Sugg, Kristoffer B.; Wei, Benjamin; Shim, Bong S.; Martin, David C.; Cederna, Paul S.; Urbanchek, Melanie G.

    2014-01-01

    Background Uninjured peripheral nerves in upper-limb amputees represent attractive sites for connectivity with neuroprostheses because their predictable internal topography allows for precise sorting of motor and sensory signals. The inclusion of poly(3,4-ethylenedioxythiophene) reduces impedance and improves charge transfer at the biotic-abiotic interface. This study evaluates the in vivo performance of poly(3,4-ethylenedioxythiophene)coated interpositional decellularized nerve grafts across a critical nerve conduction gap, and examines the long-term effects of two different poly(3,4-ethylenedioxythiophene) formulations on regenerating peripheral nerve fibers. Methods In 48 rats, a 15-mm gap in the common peroneal nerve was repaired using a nerve graft of equivalent length, including (1) decellularized nerve chemically polymerized with poly(3,4-ethylenedioxythiophene) (dry); (2) decellularized nerve electrochemically polymerized with poly(3,4-ethylenedioxythiophene) (wet); (3) intact nerve; (4) autogenous nerve graft; (5) decellularized nerve alone; and (6) unrepaired nerve gap controls. All groups underwent electrophysiologic characterization at 3 months, and nerves were harvested for histomorphometric analysis. Results Conduction velocity was significantly faster in the dry poly(3,4-ethylenedioxythiophene) group compared with the sham, decellularized nerve, and wet poly(3,4-ethylenedioxythiophene) groups. Maximum specific force for the dry poly(3,4-ethylenedioxythiophene) group was more similar to sham than were decellularized nerve controls. Evident neural regeneration was demonstrated in both dry and wet poly(3,4-ethylenedioxythiophene) groups by the presence of normal regenerating axons on histologic cross-section. Conclusions Both poly(3,4-ethylenedioxythiophene) formulations were compatible with peripheral nerve regeneration at 3 months. This study supports poly(3,4-ethylenedioxythiophene) as a promising adjunct for peripheral nerve interfaces for prosthetic control and other biomedical applications because of its recognized ionic-to-electronic coupling potential. PMID:23897336

  2. Successful desensitization to imiglucerase of an adult patient diagnosed with type I Gaucher disease.

    PubMed

    Erdo?du, Derya; Gelincik, Asl?; Canbaz, Blent; Colako?lu, Bahattin; Bykztrk, Suna; Tanakol, Refik

    2013-01-01

    Gaucher disease is the most common lysosomal storage disorder, and enzyme replacement therapy, such as administration of imiglucerase, is the standard therapy. Anaphylaxis to imiglucerase is rarely reported. Here, we report a 26-year-old female who was diagnosed with type 1 Gaucher disease and referred to our Allergy Outpatient Clinic because of an anaphylactic reaction due to imiglucerase enzyme therapy. A desensitization protocol was administered with two different dilutions with an increasing rate of administration delivered in 10 consecutive steps by intravenous infusion in an intensive care setting. No reactions occurred during the procedure, and the total final dose of 2,000 U was successfully administered. To our knowledge, this is the first adult case with successful desensitization to imiglucerase. Desensitization protocols to drugs in chronic disease patients for whom no alternative therapies are available can be lifesaving. PMID:23018845

  3. Unusually large quiescent ancient schwannoma of hypoglossal nerve.

    PubMed

    Wanjari, Sangeeta P; Wanjari, Panjab V; Parwani, Rajkumar N; Tekade, Satyajitraje A

    2013-01-01

    Ancient schwannoma is considered as a variant of schwannoma, comprising about 10% of all schwanommas. Schwannoma is a benign neoplasm derived from the nerve sheath of peripheral motor, sensory and sympathetic nerves and from the cranial nerve pairs. It usually presents as a solitary soft-tissue lesion which is slow growing, encapsulated and is often associated with nerve attached peripherally. Diagnosis is often confirmed with the microscopic examination. The long standing schwannoma attributes to degenerative changes and is termed "ancient" schwannoma. Present case is of a 68-year-old female patient who reported with an asymptomatic large swelling below mandible on the left side since last 23 years. The lesion was surgically excised under general anesthesia. PMID:24552945

  4. Spinal nerve root stimulation.

    PubMed

    Kellner, Christopher P; Kellner, Michael A; Winfree, Christopher J

    2011-01-01

    Spinal nerve root stimulation (SNRS) is a neuromodulation technique that is used to treat chronic pain. This modality places stimulator electrode array(s) along the spinal nerve roots, creating stimulation paresthesias within the distribution of the target nerve root(s), thereby treating pain in that same distribution. There are several different forms of spinal nerve root stimulation, depending upon the exact electrode positioning along the nerve roots. SNRS combines the minimally invasive nature, central location, and ease of placement of spinal cord stimulation with the focal targeting of stimulation paresthesias of peripheral nerve stimulation. This hybrid technique may be an effective alternative for patients in whom other forms of neurostimulation are either ineffective or inappropriate. PMID:21422788

  5. Probable trigeminal nerve schwannoma in a dog.

    PubMed

    Saunders, J H; Poncelet, L; Clercx, C; Snaps, F R; Flandroy, P; Capasso, P; Dondelinger, R F

    1998-01-01

    A 7-year-old male Husky dog developed atrophy of the right masseter muscle and pruritus of the right side of the face. A myogenic origin was excluded using muscular biopsy. Electrophysiologically, there was involvement of the motor and sensory fibers of the trigeminal nerve, suggesting a lesion located between the brainstem and the trigeminal ganglion. On MRI examination, a nodular mass was detected in the right caudal fossa. This mass was characterized by intense enhancement after injection of contrast medium. Because of the progressive clinical signs, electrophysiology, and MRI results, a presumptive diagnosis of a trigeminal nerve schwannoma was made. The animal's condition improved slightly with corticosteroids. The dog underwent euthanasia 3 months after initial presentation. Necropsy was not performed. PMID:9845193

  6. The Effects of Systematic Desensitization on Test-Anxious Students in an Urban Community College: Learning Theory and Applications.

    ERIC Educational Resources Information Center

    Woods, Nathaniel A.

    A study involving 97 students (79 females and 18 males) at New York City Technical College was undertaken to determine the effectiveness of desensitization in reducing test anxiety and improving grade point averages (GPAs). The study compared the GPAs of students who completed workshops using the desensitization hierarchy developed by R. Strieby…

  7. An Evaluation of in Vivo Desensitization and Video Modeling to Increase Compliance with Dental Procedures in Persons with Mental Retardation

    ERIC Educational Resources Information Center

    Conyers, Carole; Miltenberger, Raymond G.; Peterson, Blake; Gubin, Amber; Jurgens, Mandy; Selders, Andrew; Dickinson, Jessica; Barenz, Rebecca

    2004-01-01

    Fear of dental procedures deters many individuals with mental retardation from accepting dental treatment. This study was conducted to assess the effectiveness of two procedures, in vivo desensitization and video modeling, for increasing compliance with dental procedures in participants with severe or profound mental retardation. Desensitization

  8. Activin is a nerve cell survival molecule.

    PubMed

    Schubert, D; Kimura, H; LaCorbiere, M; Vaughan, J; Karr, D; Fischer, W H

    1990-04-26

    The structures of five neurotrophic molecules have so far been published. Nerve growth factor, fibroblast growth factor and purpurin, have been identified as nerve-cell survival molecules. More recently, brain-derived neurotrophic factor (BDNF) and ciliary neurotrophic factor have been cloned and sequenced. As all these proteins stimulate the survival of ciliary or sensory neurons, a new cell survival assay is required if novel neurotrophic molecules are to be discovered. P19 teratoma cells differentiate to nerve-like cells in the presence of 5 x 10(-7) M retinoic acid (RA). But when P19 cells are plated in N2 synthetic medium without being exposed to RA, they die within 48 h. In an attempt to identify a molecule(s) that can substitute for RA in promoting P19 survival, we assayed serum-free growth-conditioned media for their ability to promote P19 survival. One cell line from the rat eye secreted a molecule that promoted the survival of P19 cells and some types of nerve cell. We identified this molecule as activin, better known for its role in hormone secretion. PMID:2330043

  9. Two-component desensitization of nicotinic receptors induced by acetylcholine agonists in Lymnaea stagnalis neurones.

    PubMed Central

    Andreev, A A; Veprintsev, B N; Vulfius, C A

    1984-01-01

    The kinetics of desensitization induced by different agonists of acetylcholine (ACh) as well as the kinetics of recovery from densensitization, have been studied using the voltage-clamp technique in isolated, identified Lymnaea stagnalis neurones. Desensitization follows the sum of two exponentials: one fast and one slow. The time constant of the fast desensitization component (tau Ids) under ACh application is in the range of seconds at room temperature (18-23 degrees C). It increases upon cooling (Q10 = 2.8 +/- 0.9), decreases with increasing ACh concentration and is independent of membrane voltage. The time constant of the slow component of densensitization (tau Ids) is in the range of tens of seconds. It decreases with increasing drug concentration and is weakly dependent upon temperature (Q10 = 1.3 +/- 0.4). The relative amplitude of the fast component, estimated by back extrapolation to the position of the peak current, increases with agonist concentration and decreases upon cooling. Recovery from desensitization follows the sum of two exponentials with time constants (tau Ir and tau IIr) of the order of seconds and minutes, respectively. Cooling prolongs the slow component (Q10 of tau IIr is approx. 3) and reduces its contribution during recovery. A comparison of the desensitization induced by various agonists indicates that for the small monoquaternary agonists the onset and recovery of desensitization resemble the onset and recovery observed with ACh. For more bulky agonists, like ethoxysebacylcholine, sebacylcholine and suberylcholine, the decay of the response during prolonged application of the agonist may involve an additional blocking process. PMID:6481626

  10. Receptor downregulation and desensitization enhance the information processing ability of signaling receptors

    SciTech Connect

    Shankaran, Harish; Wiley, H. S.; Resat, Haluk

    2007-11-09

    The activation of cell surface receptors in addition to initiating signaling events also triggers regulatory processes that restrict the duration of signaling. Acute attenuation of signaling can be accomplished either via ligand-induced internalization of receptors (receptor downregulation) or via ligand-induced receptor desensitization. These phenomena have traditionally been viewed in the context of adaptation wherein the receptor system enters a refractory state in the presence of sustained ligand stimuli and thereby prevents the cell from over-responding to the ligand. Here we use the epidermal growth factor receptor (EGFR) and G-protein coupled receptors (GPCR) as model systems to respectively examine the effects of downregulation and desensitization on the ability of signaling receptors to decode time-varying ligand stimuli. We show that downregulation and desensitization mechanisms can lead to tight and efficient input-output coupling thereby ensuring synchronous processing of ligand inputs. Frequency response analysis indicates that upstream elements of the EGFR and GPCR networks behave like low-pass filters. Receptor downregulation and desensitization increase the filter bandwidth thereby enabling the receptor systems to decode inputs in a wider frequency range. Further, system-theoretic analysis reveals that the receptor systems are analogous to classical mechanical over-damped oscillators. This analogy enables us to describe downregulation and desensitization as phenomena that make the systems more resilient in responding to ligand perturbations thereby improving the stability of the system resting state. We hypothesize that, in addition to serving as mechanisms for adaptation, receptor downregulation and desensitization play a critical role in temporal information processing.

  11. Neurotoxicity of perineural vs intraneural-extrafascicular injection of liposomal bupivacaine in the porcine model of sciatic nerve block.

    PubMed

    Damjanovska, M; Cvetko, E; Hadzic, A; Seliskar, A; Plavec, T; Mis, K; Vuckovic Hasanbegovic, I; Stopar Pintaric, T

    2015-12-01

    Liposomal bupivacaine is a prolonged-release local anaesthetic, the neurotoxicity of which has not yet been determined. We used quantitative histomorphometric and immunohistochemical analyses to evaluate the neurotoxic effect of liposomal bupivacaine after perineural and intraneural (extrafascicular) injection of the sciatic nerve in pigs. In this double-blind prospective randomised trial, 4 ml liposomal bupivacaine 1.3% was injected either perineurally (n = 5) or intraneurally extrafascicularly (n = 5). Intraneural-extrafascicular injection of saline (n = 5) was used as a control. After emergence from anaesthesia, neurological examinations were conducted over two weeks. After harvesting the sciatic nerves, no changes in nerve fibre density or myelin width indicative of nerve injury were observed in any of the groups. Intraneural injections resulted in longer sensory blockade than perineural (p < 0.003) without persistent motor or sensory deficit. Sciatic nerve block with liposomal bupivacaine in pigs did not result in histological evidence of nerve injury. PMID:26338496

  12. Overview of the Cranial Nerves

    MedlinePLUS

    ... nervesthe cranial nerveslead directly from the brain to various parts of the head, neck, and trunk. Some of the cranial nerves are ... cranial nerves emerge from the underside of the brain, pass through ... to parts of the head, neck, and trunk. The nerves are named and numbered, ...

  13. Homologous desensitization of HEL cell thrombin receptors. Distinguishable roles for proteolysis and phosphorylation.

    PubMed

    Brass, L F

    1992-03-25

    Loss of sensitivity to thrombin following an initial response is characteristic of a number of cell types, including platelets. It has recently been proposed that thrombin receptors resemble other G protein-coupled receptors, but that activation involves a novel mechanism in which thrombin cleaves the receptor, exposing a new N terminus that serves as the ligand for the receptor. Based upon this model, we have examined the mechanism of thrombin receptor desensitization by comparing the effects of thrombin with those of a peptide corresponding to the N-terminal sequence of the receptor following proteolysis by thrombin: SFLLRNPNDKYEPF or TRP42/55. Like thrombin, TRP42/55 stimulated pertussis toxin-sensitive inositol 1,4,5-trisphosphate formation, raised cytosolic Ca2+, and inhibited cAMP formation in the megakaryoblastic HEL cell line. Exposure to either thrombin or TRP42/55 desensitized the cells to both, but not to a third agonist, neuropeptide Y. The rate of recovery after desensitization depended upon the order of agonist addition. Resensitization of the cell to thrombin following a brief exposure to thrombin required up to 24 h and could be inhibited with cycloheximide. Resensitization to TRP42/55 after exposure to thrombin, or to thrombin after exposure to TRP42/55, on the other hand, was detectable within 30 min and could be inhibited by serine/threonine phosphatase inhibitors, but not by cycloheximide. Loss of responsiveness to thrombin and TRP42/55 was also observed following addition of the phorbol ester, 12-O-tetradecanoylphorbol-13-acetate (TPA). However, while the protein kinase inhibitor staurosporine completely prevented the desensitization caused by TPA, it had only a limited effect on the desensitization caused by TRP42/55. These results demonstrate that the G protein-mediated effects of thrombin can be reproduced by a receptor-derived peptide and suggest that desensitization occurs by at least two mechanisms. The first, which is seen with thrombin, but not TRP42/55, involves proteolysis and requires protein synthesis for recovery. The second, which occurs with TRP42/55 and TPA, as well as with thrombin, involves phosphorylation, possibly of the receptor itself. Although protien kinase C is activated by thrombin and is presumably responsible for the desensitization caused by TPA, it does not appear to play a major role in receptor desensitization caused by thrombin and TRP42/55. This suggests that other kinases, such as those which inactivate adrenergic receptors and rhodopsin, are involved in the down-regulation of thrombin receptor function. PMID:1313426

  14. Laryngeal and tracheal afferent nerve stimulation evokes swallowing in anaesthetized guinea pigs

    PubMed Central

    Tsujimura, Takanori; Udemgba, Chioma; Inoue, Makoto; Canning, Brendan J

    2013-01-01

    We describe swallowing reflexes evoked by laryngeal and tracheal vagal afferent nerve stimulation in anaesthetized guinea pigs. The swallowing reflexes evoked by laryngeal citric acid challenges were abolished by recurrent laryngeal nerve (RLN) transection and mimicked by electrical stimulation of the central cut ends of an RLN. By contrast, the number of swallows evoked by upper airway/pharyngeal distensions was not significantly reduced by RLN transection but they were virtually abolished by superior laryngeal nerve transection. Laryngeal citric acid-evoked swallowing was mimicked by laryngeal capsaicin challenges, implicating transient receptor potential vanilloid 1 (TRPV1)-expressing laryngeal afferent nerves arising from the jugular ganglia. The swallowing evoked by citric acid and capsaicin and evoked by electrical stimulation of either the tracheal or the laryngeal mucosa occurred at stimulation intensities that were typically subthreshold for evoking cough in these animals. Swallowing evoked by airway afferent nerve stimulation also desensitized at a much slower rate than cough. We speculate that swallowing is an essential component of airway protection from aspiration associated with laryngeal and tracheal afferent nerve activation. PMID:23858010

  15. Laryngeal and tracheal afferent nerve stimulation evokes swallowing in anaesthetized guinea pigs.

    PubMed

    Tsujimura, Takanori; Udemgba, Chioma; Inoue, Makoto; Canning, Brendan J

    2013-09-15

    ? We describe swallowing reflexes evoked by laryngeal and tracheal vagal afferent nerve stimulation in anaesthetized guinea pigs. The swallowing reflexes evoked by laryngeal citric acid challenges were abolished by recurrent laryngeal nerve (RLN) transection and mimicked by electrical stimulation of the central cut ends of an RLN. By contrast, the number of swallows evoked by upper airway/pharyngeal distensions was not significantly reduced by RLN transection but they were virtually abolished by superior laryngeal nerve transection. Laryngeal citric acid-evoked swallowing was mimicked by laryngeal capsaicin challenges, implicating transient receptor potential vanilloid 1 (TRPV1)-expressing laryngeal afferent nerves arising from the jugular ganglia. The swallowing evoked by citric acid and capsaicin and evoked by electrical stimulation of either the tracheal or the laryngeal mucosa occurred at stimulation intensities that were typically subthreshold for evoking cough in these animals. Swallowing evoked by airway afferent nerve stimulation also desensitized at a much slower rate than cough. We speculate that swallowing is an essential component of airway protection from aspiration associated with laryngeal and tracheal afferent nerve activation. PMID:23858010

  16. Human sensory subsystems emulator.

    PubMed

    Frenger, P

    2001-01-01

    Last year this author presented his design for a computerized human nervous system function emulator for use in an android robot. This paper describes that emulator's sensory subsystems in more detail and adds new functions. Topics covered include sensor types, signal conditioning, data handling in the afferent pathways and interpretation of sensory information. Physiological sensory modalities (including: temperature, pressure, acceleration, humidity, sound and light stimuli) as well as nonphysiological (including: magnetic, radio, infrared, ultrasound and satellite GPS) are elucidated. The relationship of a primitive stimulus (i.e.: heat) to a high level sensation (i.e.: pain) is explored. PMID:11347421

  17. Effects of Acute Organophosphorus Poisoning on Function of Peripheral Nerves: A Cohort Study

    PubMed Central

    Jayasinghe, Sudheera S.; Pathirana, Kithsiri D.; Buckley, Nick A.

    2012-01-01

    Background Following acute organophosphorus (OP) poisoning patients complain of numbness without objective sensory abnormalities or other features of OP induced delayed polyneuropathy. The aim of this study was to measure peripheral nerve function after acute exposure to OP. Methods A cohort study was conducted with age, gender and occupation matched controls. Motor nerve conduction velocity (MNCV), amplitude and area of compound muscle action potential (CMAP), sensory nerve conduction velocity (SNCV), F- waves and electromyography (EMG) on the deltoid and the first dorsal interosseous muscles on the dominant side were performed, following acute OP poisoning. All neurophysiological assessments except EMG were performed on the controls. Assessments were performed on the day of discharge from the hospital (the first assessment) and six weeks (the second assessment) after the exposure. The controls were assessed only once. Results There were 70 patients (50 males) and 70 controls. Fifty-three patients attended for the second assessment. In the first assessment MNCV of all the motor nerves examined, CMAP amplitude and SNCV of ulnar nerve, median and ulnar F-wave occurrence in the patients were significantly reduced compared to the controls. In the second assessment significant reduction was found in SNCV of both sensory nerves examined, MNCV of ulnar nerve, CMAP amplitude of common peroneal nerve, F-wave occurrence of median and ulnar nerves. No abnormalities were detected in the patients when compared to the standard cut-off values of nerve conduction studies except F-wave occurrence. EMG studies did not show any abnormality. Conclusion There was no strong evidence of irreversible peripheral nerve damage following acute OP poisoning, however further studies are required. PMID:23185328

  18. Electromechanical tactile stimulation system for sensory vision substitution

    NASA Astrophysics Data System (ADS)

    Zalevsky, Zeev; Elani, Gal; Azoulay, Eli; Ilani, Dan; Beiderman, Yevgeny; Belkin, Michael

    2013-02-01

    A sensory substitution device is developed in which nonretinal stimulus is used to generate input to the brain of blind people to substitute for damage or loss of retinal input. Although the final realization of this technology (direct stimulation of the corneal nerve endings) was not addressed, a device consisting of a contact lens delivering point mechanical or electrical stimulating of the corneal nerves and a camera mounted on a spectacles frame which wirelessly transmit processed image to the contact lens, translating the visual information into tactile sensation is expected to be constructed. In order to improve the spatial resolution of the constructed image, the camera will also time multiplex, compress and encode the captured image before transmitting it to the stimulating contact lens. Preliminary devices performing tactile stimulation of the fingers and of the tongue by applying point electrical stimulations, were constructed and tested. Subjects were taught to "see" using the mechanical and the electrical tactile sensory.

  19. Bladder emptying by intermittent electrical stimulation of the pudendal nerve

    NASA Astrophysics Data System (ADS)

    Boggs, Joseph W.; Wenzel, Brian J.; Gustafson, Kenneth J.; Grill, Warren M.

    2006-03-01

    Persons with a suprasacral spinal cord injury cannot empty their bladder voluntarily. Bladder emptying can be restored by intermittent electrical stimulation of the sacral nerve roots (SR) to cause bladder contraction. However, this therapy requires sensory nerve transection to prevent dyssynergic contraction of the external urethral sphincter (EUS). Stimulation of the compound pudendal nerve trunk (PN) activates spinal micturition circuitry, leading to a reflex bladder contraction without a reflex EUS contraction. The present study determined if PN stimulation could produce bladder emptying without nerve transection in cats anesthetized with ?-chloralose. With all nerves intact, intermittent PN stimulation emptied the bladder (64 14% of initial volume, n = 37 across six cats) more effectively than either distention-evoked micturition (40 19%, p < 0.001, n = 27 across six cats) or bilateral intermittent SR stimulation (25 23%, p < 0.005, n = 4 across two cats). After bilateral transection of the nerves innervating the urethral sphincter, intermittent SR stimulation voided 79 17% (n = 12 across three cats), comparable to clinical results obtained with SR stimulation. Voiding via intermittent PN stimulation did not increase after neurotomy (p > 0.10), indicating that PN stimulation was not limited by bladder-sphincter dyssynergia. Intermittent PN stimulation holds promise for restoring bladder emptying following spinal injury without requiring nerve transection.

  20. 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

  1. Histopathological effects of radiosurgery on a human trigeminal nerve

    PubMed Central

    Al-Otaibi, Faisal; Alhindi, Hindi; Alhebshi, Adnan; Albloushi, Monirah; Baeesa, Saleh; Hodaie, Mojgan

    2013-01-01

    Background: Radiosurgery is a well-established treatment modality for medically refractory trigeminal neuralgia. The exact mechanism of pain relief after radiosurgery is not clearly understood. Histopathology examination of the trigeminal nerve in humans after radiosurgery is rarely performed and has produced controversial results. Case Description: We report on a 45-year-old female who received radiosurgery treatment for trigeminal neuralgia by Cyberknife. A 6-mm portion of the cisternal segment of trigeminal nerve received a dose of 60 Gy. The clinical benefit started 10 days after therapy and continued for 8 months prior to a recurrence of her previous symptoms associated with mild background pain. She underwent microvascular decompression and partial sensory root sectioning. Atrophied trigeminal nerve rootlets were grossly noted intraoperatively under surgical microscope associated with changes in trigeminal nerve color to gray. A biopsy from the inferolateral surface of the nerve proximal to the midcisternal segment showed histological changes in the form of fibrosis and axonal degeneration. Conclusion: This case study supports the evidence of histological damage of the trigeminal nerve fibers after radiosurgery therapy. Whether or not the presence and degree of nerve damage correlate with the degree of clinical benefit and side effects are not revealed by this study and need to be explored in future studies. PMID:24605252

  2. Bupivacaine and ropivacaine: comparative effects on nerve conduction block.

    PubMed

    Bariskaner, H; Ayaz, M; Guney, F B; Dalkilic, N; Guney, O

    2007-06-01

    Unlike other drugs which act in the region of the synapse, local anesthetics are agents that reversibly block the generation and conduction of nerve impulses along a nerve fiber. This study aims to investigate the comparative inhibitions of bupivacaine and ropivacaine on the frog sciatic nerve. Isolated nerves were transferred to the nerve chamber which includes Ringer's solution. The nerves were stimulated by standard square wave pulse protocols and the responses were recorded with conventional systems. Bupivacaine (n = 8) and ropivacaine (n = 8) were administered in the nerve chamber bath with cumulative concentrations (10(-9) to 10(-3) M) and the effects were monitored for variable time periods (5, 10 and 15 min). Both bupivacaine and ropivacaine significantly depressed the compound action potential (CAP) parameters in a dose-dependent (p < 0.05) and reversible manner. Difference in the effects of these two drugs was detectable only when the dose (> or =10(-5) M) and exposure time (15 min) were increased. Percent inhibitions in maximum derivatives and latency-period measurements have shown that ropivacaine is not only fast but also much more powerful in conduction block for longer and higher doses. Bupivacaine, on the other hand, is effective in the group of fibers with relatively slower conduction velocity for all the measured doses and time periods. In conclusion, ropivacaine has a sensory specific side of action, when compared with the bupivacaine. PMID:17805435

  3. The importance of pelvic nerve fibers in endometriosis.

    PubMed

    Miller, Emily J; Fraser, Ian S

    2015-08-01

    Several lines of recent evidence suggest that pelvic innervation is altered in endometriosis-affected women, and there is a strong presumption that nerve fibers demonstrated in eutopic endometrium (of women with endometriosis) and in endometriotic lesions play roles in the generation of chronic pelvic pain. The recent observation of sensory C, sensory A-delta, sympathetic and parasympathetic nerve fibers in the functional layer of endometrium of most women affected by endometriosis, but not demonstrated in most women who do not have endometriosis, was a surprise. Nerve fiber densities were also greatly increased in myometrium of women with endometriosis and in endometriotic lesions compared with normal peritoneum. Chronic pelvic pain is complex, and endometriosis is only one condition which contributes to this pain. The relationship between the presence of certain nerve fibers and the potential for local pain generation requires much future research. This paper reviews current knowledge concerning nerve fibers in endometrium, myometrium and endometriotic lesions, and discusses avenues of research that may improve our knowledge and lead to enriched understanding and management of endometriotic pain symptoms. PMID:26314611

  4. Comparative study of peripheral neuropathy and nerve regeneration in NOD and ICR diabetic mice.

    PubMed

    Homs, Judit; Ariza, Lorena; Pagès, Gemma; Verdú, Enrique; Casals, Laura; Udina, Esther; Chillón, Miguel; Bosch, Assumpció; Navarro, Xavier

    2011-09-01

    The non-obese diabetic (NOD) mouse was suggested as an adequate model for diabetic autonomic neuropathy. We evaluated sensory-motor neuropathy and nerve regeneration following sciatic nerve crush in NOD males rendered diabetic by multiple low doses of streptozotocin, in comparison with similarly treated Institute for Cancer Research (ICR) mice, a widely used model for type I diabetes. Neurophysiological values for both strains showed a decline in motor and sensory nerve conduction velocity at 7 and 8 weeks after induction of diabetes in the intact hindlimb. However, amplitudes of compound muscle and sensory action potentials (CMAPs and CNAPs) were significantly reduced in NOD but not in ICR diabetic mice. Morphometrical analysis showed myelinated fiber loss in highly hyperglycemic NOD mice, but no significant changes in fiber size. There was a reduction of intraepidermal nerve fibers, more pronounced in NOD than in ICR diabetic mice. Interestingly, aldose reductase and poly(ADP-ribose) polymerase (PARP) activities were increased already at 1 week of hyperglycemia, persisting until the end of the experiment in both strains. Muscle and nerve reinnervation was delayed in diabetic mice following sciatic nerve crush, being more marked in NOD mice. Thus, diabetes of mid-duration induces more severe peripheral neuropathy and slower nerve regeneration in NOD than in ICR mice. PMID:22003936

  5. 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

  6. Spatial and Functional Selectivity of Peripheral Nerve Signal Recording With the Transversal Intrafascicular Multichannel Electrode (TIME).

    PubMed

    Badia, Jordi; Raspopovic, Stanisa; Carpaneto, Jacopo; Micera, Silvestro; Navarro, Xavier

    2016-01-01

    The selection of suitable peripheral nerve electrodes for biomedical applications implies a trade-off between invasiveness and selectivity. The optimal design should provide the highest selectivity for targeting a large number of nerve fascicles with the least invasiveness and potential damage to the nerve. The transverse intrafascicular multichannel electrode (TIME), transversally inserted in the peripheral nerve, has been shown to be useful for the selective activation of subsets of axons, both at inter- and intra-fascicular levels, in the small sciatic nerve of the rat. In this study we assessed the capabilities of TIME for the selective recording of neural activity, considering the topographical selectivity and the distinction of neural signals corresponding to different sensory types. Topographical recording selectivity was proved by the differential recording of CNAPs from different subsets of nerve fibers, such as those innervating toes 2 and 4 of the hindpaw of the rat. Neural signals elicited by sensory stimuli applied to the rat paw were successfully recorded. Signal processing allowed distinguishing three different types of sensory stimuli such as tactile, proprioceptive and nociceptive ones with high performance. These findings further support the suitability of TIMEs for neuroprosthetic applications, by exploiting the transversal topographical structure of the peripheral nerves. PMID:26087496

  7. 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

  8. [Sciatic nerve intraneural perineurioma].

    PubMed

    Bonhomme, Benjamin; Poussange, Nicolas; Le Collen, Philippe; Fabre, Thierry; Vital, Anne; Lepreux, Sbastien

    2015-12-01

    Intraneural perineurioma is a benign tumor developed from the perineurium and responsible for localized nerve hypertrophy. This uncommon tumor is characterized by a proliferation of perineural cells with a "pseudo-onion bulb" pattern. We report a sciatic nerve intraneural perineurioma in a 39-year-old patient. PMID:26586011

  9. Axillary nerve dysfunction

    MedlinePLUS

    ... muscle of the shoulder may show signs of muscle atrophy . Tests that may be used to check axillary nerve dysfunction include: EMG and nerve conduction tests, will be ... the injury or symptoms start MRI or x-rays of the shoulder

  10. Imaging the hypoglossal nerve.

    PubMed

    Alves, Pedro

    2010-05-01

    The hypoglossal nerve is a pure motor nerve. It provides motor control to the intrinsic and extrinsic tongue muscles thus being essential for normal tongue movement and coordination. In order to design a useful imaging approach and a working differential diagnosis in cases of hypoglossal nerve damage one has to have a good knowledge of the normal anatomy of the nerve trunk and its main branches. A successful imaging evaluation to hypoglossal diseases always requires high resolution studies due to the small size of the structures being studied. MRI is the preferred modality to directly visualize the nerve, while CT is superior in displaying the bony anatomy of the neurovascular foramina of the skull base. Also, while CT is only able to detect nerve pathology by indirect signs, such as bony expansion of the hypoglossal canal, MRI is able to visualize directly the causative pathological process as in the case of small tumors, or infectious/inflammatory processes affecting the nerve. The easiest way to approach the study of the hypoglossal nerve is to divide it in its main segments: intra-axial, cisternal, skull base and extracranial segment, tailoring the imaging technique to each anatomical area while bearing in mind the main disease entities affecting each segment. PMID:20347541

  11. Examining Sensory Quadrants in Autism

    ERIC Educational Resources Information Center

    Kern, Janet K.; Garver, Carolyn R.; Carmody, Thomas; Andrews, Alonzo A.; Trivedi, Madhukar H.; Mehta, Jyutika A.

    2007-01-01

    The purpose of this study was to examine sensory quadrants in autism based on Dunn's Theory of Sensory Processing. The data for this study was collected as part of a cross-sectional study that examined sensory processing (using the Sensory Profile) in 103 persons with autism, 3-43 years of age, compared to 103 age- and gender-matched community

  12. An hereditary sensory and autonomic neuropathy transmitted as an X-linked recessive trait.

    PubMed Central

    Jestico, J V; Urry, P A; Efphimiou, J

    1985-01-01

    Five members of a single family presented with neuropathic deformities and ulceration of the feet developing in the first and second decades of life, and progressed slowly over many years. In this form of hereditary sensory and autonomic neuropathy, there was minimal tendon reflex impairment, cutaneous sensory impairment was restricted to the feet, and there was no autonomic dysfunction. The only neurophysiological abnormality was that of reduced or absent sural nerve sensory action potentials. Sural nerve biopsies taken from two affected family members showed changes of a chronic neuropathy with loss of myelinated fibres, particularly affecting those of small diameter. Unmyelinated fibres were present in normal numbers. This condition differed from other forms of hereditary sensory and autonomic neuropathy having an X-linked recessive mode of inheritance. Images PMID:3866836

  13. Peripheral nerve stimulation: definition.

    PubMed

    Abejn, David; Prez-Cajaraville, Juan

    2011-01-01

    Recently, there has been a tremendous evolution in the field of neurostimulation, both from the technological point of view and from development of the new and different indications. In some areas, such as peripheral nerve stimulation, there has been a boom in recent years due to the variations in the surgical technique and the improved results documented by in multiple published papers. All this makes imperative the need to classify and define the different types of stimulation that are used today. The confusion arises when attempting to describe peripheral nerve stimulation and subcutaneous stimulation. Peripheral nerve stimulation, in its pure definition, involves implanting a lead on a nerve, with the aim to produce paresthesia along the entire trajectory of the stimulated nerve. PMID:21422790

  14. Preoperative transcutaneous electrical nerve stimulation for localizing superficial nerve paths.

    PubMed

    Natori, Yuhei; Yoshizawa, Hidekazu; Mizuno, Hiroshi; Hayashi, Ayato

    2015-12-01

    During surgery, peripheral nerves are often seen to follow unpredictable paths because of previous surgeries and/or compression caused by a tumor. Iatrogenic nerve injury is a serious complication that must be avoided, and preoperative evaluation of nerve paths is important for preventing it. In this study, transcutaneous electrical nerve stimulation (TENS) was used for an in-depth analysis of peripheral nerve paths. This study included 27 patients who underwent the TENS procedure to evaluate the peripheral nerve path (17 males and 10 females; mean age: 59.9 years, range: 18-83 years) of each patient preoperatively. An electrode pen coupled to an electrical nerve stimulator was used for superficial nerve mapping. The TENS procedure was performed on patients' major peripheral nerves that passed close to the surgical field of tumor resection or trauma surgery, and intraoperative damage to those nerves was apprehensive. The paths of the target nerve were detected in most patients preoperatively. The nerve paths of 26 patients were precisely under the markings drawn preoperatively. The nerve path of one patient substantially differed from the preoperative markings with numbness at the surgical region. During surgery, the nerve paths could be accurately mapped preoperatively using the TENS procedure as confirmed by direct visualization of the nerve. This stimulation device is easy to use and offers highly accurate mapping of nerves for surgical planning without major complications. The authors conclude that TENS is a useful tool for noninvasive nerve localization and makes tumor resection a safe and smooth procedure. PMID:26420473

  15. 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

  16. Comparative Psychotherapy: Rational-Emotive Therapy Versus Systematic Desensitization in the Treatment of Stuttering

    ERIC Educational Resources Information Center

    Moleski, Richard; Tosi, Donald J.

    1976-01-01

    The present study examined the efficacy of rational-emotive psychotherapy and systematic desensitization in the treatment of stuttering. Both therapies, making extensive use of in vivo behavioral assignments, were examined under the presence and absence of in vivo tasks. Results show that rational-emotive therapy was more effective in reducing…

  17. Eye Movement Desensitization and Reprocessing (EMDR) Treatment for Psychologically Traumatized Individuals.

    ERIC Educational Resources Information Center

    Wilson, Sandra A.; And Others

    1995-01-01

    Studies the effects of 3 90-minute Eye Movement Desensitization and Reprocessing (EMDR) treatment sessions on traumatic memories of 80 participants. Participants receiving EMDR showed decreases in complaints and anxiety, and increases in positive cognition. Participants in the delayed-treatment condition showed no improvement in any measures in

  18. Using Eye Movement Desensitization and Reprocessing To Enhance Treatment of Couples.

    ERIC Educational Resources Information Center

    Protinsky, Howard; Sparks, Jennifer; Flemke, Kimberly

    2001-01-01

    Eye Movement Desensitization and Reprocessing (EMDR) as a clinical technique may enhance treatment effectiveness when applied in couple therapy that is emotionally and experientially oriented. Clinical experience indicates EMDR-based interventions are useful for accessing and reprocessing intense emotions in couple interactions. EMDR can amplify

  19. Single expressed glycine receptor domains reconstitute functional ion channels without subunit-specific desensitization behavior.

    PubMed

    Meiselbach, Heike; Vogel, Nico; Langlhofer, Georg; Stangl, Sabine; Schleyer, Barbara; Bahnassawy, Lamia'a; Sticht, Heinrich; Breitinger, Hans-Georg; Becker, Cord-Michael; Villmann, Carmen

    2014-10-17

    Cys loop receptors are pentameric arrangements of independent subunits that assemble into functional ion channels. Each subunit shows a domain architecture. Functional ion channels can be reconstituted even from independent, nonfunctional subunit domains, as shown previously for GlyR?1 receptors. Here, we demonstrate that this reconstitution is not restricted to ?1 but can be transferred to other members of the Cys loop receptor family. A nonfunctional GlyR subunit, truncated at the intracellular TM3-4 loop by a premature stop codon, can be complemented by co-expression of the missing tail portion of the receptor. Compared with ?1 subunits, rescue by domain complementation was less efficient when GlyR?3 or the GABAA/C subunit ?1 was used. If truncation disrupted an alternative splicing cassette within the intracellular TM3-4 loop of ?3 subunits, which also regulates receptor desensitization, functional rescue was not possible. When ?3 receptors were restored by complementation using domains with and without the spliced insert, no difference in desensitization was found. In contrast, desensitization properties could even be transferred between ?1/?3 receptor chimeras harboring or lacking the ?3 splice cassette proving that functional rescue depends on the integrity of the alternative splicing cassette in ?3. Thus, an intact ?3 splicing cassette in the TM3-4 loop environment is indispensable for functional rescue, and the quality of receptor restoration can be assessed from desensitization properties. PMID:25143388

  20. Single Expressed Glycine Receptor Domains Reconstitute Functional Ion Channels without Subunit-specific Desensitization Behavior*

    PubMed Central

    Meiselbach, Heike; Vogel, Nico; Langlhofer, Georg; Stangl, Sabine; Schleyer, Barbara; Bahnassawy, Lamia'a; Sticht, Heinrich; Breitinger, Hans-Georg; Becker, Cord-Michael; Villmann, Carmen

    2014-01-01

    Cys loop receptors are pentameric arrangements of independent subunits that assemble into functional ion channels. Each subunit shows a domain architecture. Functional ion channels can be reconstituted even from independent, nonfunctional subunit domains, as shown previously for GlyR?1 receptors. Here, we demonstrate that this reconstitution is not restricted to ?1 but can be transferred to other members of the Cys loop receptor family. A nonfunctional GlyR subunit, truncated at the intracellular TM34 loop by a premature stop codon, can be complemented by co-expression of the missing tail portion of the receptor. Compared with ?1 subunits, rescue by domain complementation was less efficient when GlyR?3 or the GABAA/C subunit ?1 was used. If truncation disrupted an alternative splicing cassette within the intracellular TM34 loop of ?3 subunits, which also regulates receptor desensitization, functional rescue was not possible. When ?3 receptors were restored by complementation using domains with and without the spliced insert, no difference in desensitization was found. In contrast, desensitization properties could even be transferred between ?1/?3 receptor chimeras harboring or lacking the ?3 splice cassette proving that functional rescue depends on the integrity of the alternative splicing cassette in ?3. Thus, an intact ?3 splicing cassette in the TM34 loop environment is indispensable for functional rescue, and the quality of receptor restoration can be assessed from desensitization properties. PMID:25143388

  1. Clinical trial of tooth desensitization prior to in-office bleaching.

    PubMed

    Mehta, Deepak; Venkata, Suresh; Naganath, Meena; LingaReddy, Usha; Ishihata, Hiroshi; Finger, Werner J

    2013-10-01

    The aim of this clinical trial was to compare tooth sensitivity during and after bleaching with hydrogen peroxide gel following application of GLUMA Desensitizer PowerGel or placebo. Forty-six subjects with sound maxillary incisors and canines were enrolled. Tooth shades were determined by comparison with a Vitapan Classic Shade guide. GLUMA Desensitizer PowerGel and placebo were randomly applied to the labial surfaces of the left or right anterior teeth for 1 min, which were then rinsed and dried. Then, Opalescence Boost PF 40% gel was applied onto labial enamel for 15 min. Sensitivity scores [recorded on a 10-point visual-analog scale (VAS)] were determined before, at 5, 10, and 15 min during, and 1, 24, 48 h and 1 wk after, the bleaching treatment. Shades were determined postbleaching and after 1 wk. Prebleaching application of GLUMA Desensitizer PowerGel significantly reduced tooth sensitivity during and after bleaching when compared with treatment with placebo. The whitening effects immediately and 1 wk after bleaching were significant when compared with the prebleaching shades. In conclusion, tooth pretreatment with GLUMA Desensitizer PowerGel for 1 min prior to 15 min of in-office bleaching with 40% hydrogen peroxide gel was highly effective in reducing tooth sensitivity during and after bleaching. PMID:24028597

  2. Reducing Student Anxiety toward Introductory Chemistry by Use of Systematic Desensitization.

    ERIC Educational Resources Information Center

    Rasor, Richard A.; Engel, Dominique

    A study was conducted at American River College during Spring 1981 to assess the effectiveness of a systematic desensitization program in reducing student anxiety toward chemistry and in improving student performance in chemistry courses. During the study, students in two sections of an introductory chemistry course were administered three tests

  3. Diffusion of peroxides through dentine in vitro with and without prior use of a desensitizing varnish.

    PubMed

    Hannig, Christian; Weinhold, Hans Christian; Becker, Klaus; Attin, Thomas

    2011-12-01

    Different bleaching regimens are used in dentistry possibly penetrating the dentine and affecting the pulp. The aim of the present study was to investigate peroxide diffusion through dentine pre-treated with a desensitizing varnish (Vivasens) in a standardized in vitro setup during application of different bleaching materials. The penetration was tested using 1.3-mm-thick bovine dentine slabs. The following bleaching materials were tested with and without prior application of the desensitizing varnish on the external side of the dentine slabs: Vivastyle, Whitestrips, Simply White, Opalescence (external bleaching), and sodium perborate (internal bleaching, only tested without varnish; n?=?8 samples per subgroup). The penetration of peroxides was measured photometrically using 4-aminoantipyrin as a substrate, the penetration of peroxides was monitored over 240min. All bleaching agents yielded a diffusion of peroxides through the dentine, the kinetics of penetration were approximately linear for all materials tested. The significantly highest diffusion of peroxides was observed with Opalescence, the lowest with sodium perborate. The adoption of the desensitizing varnish reduced the diffusion of peroxides significantly for all external bleaching materials. Peroxides penetrated the dentine during application of bleaching materials; the penetration of peroxides can be reduced by application of a desensitizing agent. PMID:20697758

  4. ?-Arrestin-2 Desensitizes the Transient Receptor Potential Vanilloid 1 (TRPV1) Channel*

    PubMed Central

    Por, Elaine D.; Bierbower, Sonya M.; Berg, Kelly A.; Gomez, Ruben; Akopian, Armen N.; Wetsel, William C.; Jeske, Nathaniel A.

    2012-01-01

    Transient receptor potential vanilloid 1 (TRPV1) is a nonselective cation channel activated by multiple stimuli and is implicated in a variety of pain disorders. Dynamic sensitization of TRPV1 activity by A-kinase anchoring protein 150 demonstrates a critical role for scaffolding proteins in nociception, yet few studies have investigated scaffolding proteins capable of mediating receptor desensitization. In this study, we identify ?-arrestin-2 as a scaffolding protein that regulates TRPV1 receptor activity. We report ?-arrestin-2 association with TRPV1 in multiple cell models. Moreover, siRNA-mediated knockdown of ?-arrestin-2 in primary cultures resulted in a significant increase in both initial and repeated responses to capsaicin. Electrophysiological analysis further revealed significant deficits in TRPV1 desensitization in primary cultures from ?-arrestin-2 knock-out mice compared with wild type. In addition, we found that ?-arrestin-2 scaffolding of phosphodiesterase PDE4D5 to the plasma membrane was required for TRPV1 desensitization. Importantly, inhibition of PDE4D5 activity reversed ?-arrestin-2 desensitization of TRPV1. Together, these results identify a new endogenous scaffolding mechanism that regulates TRPV1 ligand binding and activation. PMID:22952227

  5. Phorbol ester, but not endotoxin, desensitizes mannan-induced glycogenolysis in the perfused rat liver.

    PubMed

    Kimura, K; Hamada, M; Moriyama, M; Kannan, Y; Shiota, M; Sakurada, K; Musashi, M; Sugano, T

    1996-09-01

    Mannan, a ligand for the mannose/N-acetylglucosamine (GlcNAc) receptor, induces suppression of oxygen consumption and increases glucose production in the perfused rat liver, and repeated infusion of mannan causes desensitization of the responses. In this study, we examined whether activation of Kupffer cells by endotoxin and phorbol ester alters the glycogenolytic responses to mannan. Infusion of lipopolysaccharide (LPS, 10 micrograms/ ml) in the perfusate failed to inhibit the responses to mannan. Intravenous administration of LPS (1 mg/kg) 6 and 24 h before perfusion did not desensitize the responses to mannan, suggesting that the responses through mannose/GlcNAc receptors in the liver are retained even after activation of Kupffer cells by LPS. In contrast, prior infusion of phorbol 12-myristate 13-acetate (PMA, 100 nM) in vitro abolished the glycogenolytic responses to subsequently infused mannan, but not that to norepinephrine (100 nM), while prior infusions of 4-alpha-phorbol 12,13-didecanoate (100 nM), A23187 (50 nM), or forskolin (1 microM) had no effect on the mannan-induced responses. H-7, an inhibitor of protein kinase C, reduced the glycogenolytic responses to mannan, while it failed to restore the desensitization. These results suggest that protein kinase C may be involved in the process of glycogenolysis by mannan, but is unlikely to be involved in the homologous desensitization of the responses. PMID:8902610

  6. Eye Movement Desensitization and Reprocessing (EMDR) Treatment for Psychologically Traumatized Individuals.

    ERIC Educational Resources Information Center

    Wilson, Sandra A.; And Others

    1995-01-01

    Studies the effects of 3 90-minute Eye Movement Desensitization and Reprocessing (EMDR) treatment sessions on traumatic memories of 80 participants. Participants receiving EMDR showed decreases in complaints and anxiety, and increases in positive cognition. Participants in the delayed-treatment condition showed no improvement in any measures in…

  7. A Review of Eye Movement Desensitization and Reprocessing (EMDR): Research Findings and Implications for Counsellors.

    ERIC Educational Resources Information Center

    MacCluskie, Kathryn C.

    1998-01-01

    States that within the last six years a new therapeutic technique for the treatment of posttraumatic stress disorder, Eye Movement Desensitization and Reprocessing (EMDR), has emerged. Examines the strengths and weaknesses of published studies concerning EMDR, describes the nature of the debate about the efficacy of EMDR, and reviews implications…

  8. Using Eye Movement Desensitization and Reprocessing To Enhance Treatment of Couples.

    ERIC Educational Resources Information Center

    Protinsky, Howard; Sparks, Jennifer; Flemke, Kimberly

    2001-01-01

    Eye Movement Desensitization and Reprocessing (EMDR) as a clinical technique may enhance treatment effectiveness when applied in couple therapy that is emotionally and experientially oriented. Clinical experience indicates EMDR-based interventions are useful for accessing and reprocessing intense emotions in couple interactions. EMDR can amplify…

  9. Neuroepithelial circuit formed by innervation of sensory enteroendocrine cells

    PubMed Central

    Bohrquez, Diego V.; Shahid, Rafiq A.; Erdmann, Alan; Kreger, Alex M.; Wang, Yu; Calakos, Nicole; Wang, Fan; Liddle, Rodger A.

    2015-01-01

    Satiety and other core physiological functions are modulated by sensory signals arising from the surface of the gut. Luminal nutrients and bacteria stimulate epithelial biosensors called enteroendocrine cells. Despite being electrically excitable, enteroendocrine cells are generally thought to communicate indirectly with nerves through hormone secretion and not through direct cell-nerve contact. However, we recently uncovered in intestinal enteroendocrine cells a cytoplasmic process that we named neuropod. Here, we determined that neuropods provide a direct connection between enteroendocrine cells and neurons innervating the small intestine and colon. Using cell-specific transgenic mice to study neural circuits, we found that enteroendocrine cells have the necessary elements for neurotransmission, including expression of genes that encode pre-, post-, and transsynaptic proteins. This neuroepithelial circuit was reconstituted in vitro by coculturing single enteroendocrine cells with sensory neurons. We used a monosynaptic rabies virus to define the circuits functional connectivity in vivo and determined that delivery of this neurotropic virus into the colon lumen resulted in the infection of mucosal nerves through enteroendocrine cells. This neuroepithelial circuit can serve as both a sensory conduit for food and gut microbes to interact with the nervous system and a portal for viruses to enter the enteric and central nervous systems. PMID:25555217

  10. Natural history and biomarkers in hereditary sensory neuropathy type 1

    PubMed Central

    Fridman, Vera; Oaklander, Anne louise; David, William S; Johnson, Elise A; Pan, Jessica; Novak, Peter; Brown, Robert H; Eichler, Florian S

    2015-01-01

    Introduction: Hereditary sensory and autonomic neuropathy type 1 (HSAN1) is most commonly caused by missense mutations in SPTLC1. In this study we mapped symptom progression and compared the utility of outcomes. Methods: We administered retrospective surveys of symptoms and analyzed results of nerve conduction, autonomic function testing (AFT), and PGP9.5-immunolabeled skin biopsies. Results: The first symptoms were universally sensory and occurred at a median age of 20 years (range 1454 years). The onset of weakness, ulcers, pain, and balance problems followed sequentially. Skin biopsies revealed universally absent epidermal innervation at the distal leg with relative preservation in the thigh. Neurite density was highly correlated with total Charcot-Marie-Tooth Examination Score (CMTES; r2?=??0.8) and median motor amplitude (r2?=??0.75). Conclusions: These results confirm sensory loss as the initial symptom of HSAN1 and suggest that skin biopsy may be the most promising biomarker for future clinical trials. Muscle Nerve, 2015 Muscle Nerve 51: 489495, 2015 PMID:25042817

  11. Diabetic neuropathy: structural analysis of nerve hydration by Magnetic Resonance Spectroscopy

    SciTech Connect

    Griffey, R.H.; Eaton, P.; Sibbitt, R.R.; Sibbitt, W.L. Jr.; Bicknell, J.M.

    1988-11-18

    The water content of the sural nerve of diabetic patients was quantitatively defined by magnetic resonance proton imaging as a putative reflection of activity of the aldose-reductase pathway. Thirty-nine patients were evaluated, comparing group A, symptomatic diabetic men with sensory neuropathy; group B, similarly symptomatic diabetic men treated aldose-reductase inhibition; group C, neurologically asymptomatic diabetic men; and group D, control nondiabetic men. Marked increase in hydration of the sural nerve was seen in more than half of the symptomatic diabetic patients. Two of 11 neurologically asymptomatic diabetics had increased nerve hydration, suggesting a presymptomatic alteration of the nerve. Symptomatic diabetics treated with aldose-reductase inhibitors had normal nerve water levels. Increased level of peripheral nerve water represents a new finding in diabetes mellitus. It seems to be related to aldose-reductase activity, involved in the development of neuropathy, and similar to events that occur in other target tissue in human diabetes.

  12. The beta-adrenergic receptor kinase: role in homologous desensitization in S49 lymphoma cells.

    PubMed

    Strasser, R H; Benovic, J L; Lefkowitz, R J; Caron, M G

    1988-01-01

    Phosphorylation of the beta-adrenergic receptor (beta AR) is closely associated with homologous desensitization of the beta-adrenergic receptor-coupled adenylate cyclase system. Homologous desensitization and receptor phosphorylation also occur in cell mutants which are deficient in their cAMP-dependent protein kinase (kin- mutant of S49 lymphoma cells). beta AR phosphorylation is mediated by a cAMP-independent protein kinase which phosphorylates the receptor only when it is occupied by a beta-agonist. During the time course of desensitization the beta AR kinase (beta ARK) activity is translocated from a cytoplasmic to a plasma membrane location. beta ARK translocation can also be effected by prostaglandin E1 (PGE1) suggesting that this beta ARK may represent a more general enzyme capable of phosphorylating other adenylate cyclase-coupled receptors. Thus, beta ARK may play a key role in the process of homologous desensitization of adenylate cyclase coupled receptors. Extracellular hormones interact with specific receptors at the outer surface of the plasma membrane and thus initiate a cellular response. One of the best studied transmembrane signalling systems known to be coupled to the occupancy of cell surface receptors is adenylate cyclase. The adenylate cyclase system is composed of various components all of which have been purified to homogeneity (Shorr et al., 1982; Homcy et al., 1983; Benovic et al., 1984; Codina et al., 1984; Northup et al., 1980; Sternweis et al., 1981; Bokoch et al., 1984; Pfeuffer et al., 1985). Initially, agonist binding to the receptor promotes coupling of the occupied receptor to one of the guanine nucleotide binding regulatory proteins. These proteins are members of a family of heterotrimeric proteins consisting of alpha, beta and gamma subunits. Stimulatory receptors like the beta-adrenergic (Cerione et al., 1984) or glucagon (Iyengar et al., 1979) receptors couple to the stimulatory regulatory protein Ns (or Gs) whereas inhibitory receptors like the alpha 2-adrenergic (Jacobs et al., 1976) or M2-muscarinic (Harden et al., 1982) receptors couple to the inhibitory regulatory protein Ni (or Gi). Prolonged exposure to agonist hormones, either stimulatory or inhibitory, results in an attenuation of the response to the hormonal activation, a phenomenon called tachyphylaxis or desensitization (Harden, 1983; Sibley and Lefkowitz, 1985; Sharma et al., 1975). One of the best studied models for desensitization is the beta-adrenergic receptor-coupled adenylate cyclase system. In this system two different forms of desensitization have been characterized.(ABSTRACT TRUNCATED AT 400 WORDS) PMID:2843012

  13. GLIAL RESPONSES AFTER CHORDA TYMPANI NERVE INJURY

    PubMed Central

    Bartel, Dianna L.

    2013-01-01

    The chorda tympani (CT) nerve innervates lingual taste buds and is susceptible to damage during dental and inner ear procedures. Interruption of the CT results in a disappearance of taste buds, which can be accompanied by taste disturbances. Because the CT usually regenerates to reinnervate taste buds successfully in a few weeks, a persistence of taste disturbances may indicate alterations in central nervous function. Peripheral injury to other sensory nerves leads to glial responses at central terminals, which actively contribute to abnormal sensations arising from nerve damage. Therefore, the current study examined microglial and astrocytic responses in the first central gustatory relay -the nucleus of the solitary tract (nTS)- after transection of the CT. Damage to the CT resulted in significant microglial responses in terms of morphological reactivity and an increased density of microglial cells from 2-20 days after injury. This increased microglial population primarily resulted from microglial proliferation from 1.5-3 days, which was supplemented by microglial migration within sub-divisions of the nTS between days 2-3. Unlike other nerve injuries, CT injury did not result in recruitment of bone marrow-derived precursors. Astrocytes also reacted in the nTS with increased levels of GFAP by 3 days, although none showed evidence of cell division. GFAP levels remained increased at 30 days by which time microglial responses had resolved. These results show that nerve damage to the CT results in central glial responses, which may participate in long lasting taste alterations following CT lesion. PMID:22315167

  14. Alkaline phosphatase relieves desensitization of adenylate cyclase-coupled beta-adrenergic receptors in avian erythrocyte membranes

    SciTech Connect

    Stadel, J.M.; Rebar, R.; Crooke, S.T.

    1987-05-01

    Desensitization of adenylate cyclase-coupled ..beta..-adrenergic receptors in avian erythrocytes results in 40-65% decrease in agonist-stimulated adenylate cyclase activity and correlates with increased phosphorylation of ..beta..-adrenergic receptors. To assess the role of phosphorylation in desensitization, membranes from isoproterenol- and cAMP-desensitized turkey erythrocytes were incubated with alkaline phosphatase for 30 min at 37/sup 0/C, pH = 8.0. In both cases alkaline phosphatase treatment significantly reduced desensitization of agonist-stimulated adenylate cyclase activity by 40-60%. Similar results were obtained following alkaline phosphatase treatment of membranes from isoproterenol- and cAMP-desensitized duck erythrocytes. In addition, alkaline phosphatase treatment of membranes from duck erythrocytes desensitized with phorbol 12-mystrate 13-acetate returned adenylate cyclase activity to near control values. In all experiments inclusion of 20 mM NaPO/sub 4/ to inhibit alkaline phosphatase during treatment of membranes blocked the enzyme's effect on agonist-stimulated adenylate cyclase activity. These results demonstrate a role for phosphorylation in desensitization of adenylate cyclase-coupled ..beta..-adrenergic receptors in avian erythrocytes.

  15. Cellular mechanism of action of resiniferatoxin: a potent sensory neuron excitotoxin.

    PubMed

    Winter, J; Dray, A; Wood, J N; Yeats, J C; Bevan, S

    1990-06-18

    The mechanism of activation of sensory neurons by the potent irritant resiniferatoxin (RTX) was compared with that of the pungent compound, capsaicin. RTX and capsaicin evoked an inward, depolarising current associated with an increase in membrane conductance in a subpopulation of dissociated cultured neurons from rat dorsal root ganglia. RTX also evoked an uptake of 45Ca into and an efflux of [14C]guanidinium and of 86Rb from these cells but was at least 100-fold more potent than capsaicin. The levels of cGMP, but not cAMP were elevated by RTX. Prolonged exposure to RTX damaged DRG neurons by a predominantly osmotic process. RTX-sensitive cells were identified by a cobalt-staining method; neurofilament-containing DRG neurons were RTX-insensitive as were all sympathetic neurons and non-neuronal cells. Cultured DRG neurons from chick embryos were also unaffected by RTX. In a neonatal rat spinal cord-tail preparation in vitro, RTX activated capsaicin-sensitive peripheral nociceptive fibres and caused a subsequent spinal cord depolarization measured in the ventral spinal roots. Neither prolonged exposure to a phorbol ester, to desensitize/down-regulate protein kinase C, nor inhibition of protein kinase C by staurosporine affected responses produced by RTX or capsaicin. The effects of capsaicin were abolished when preparations were exposed to desensitizing concentrations of RTX. RTX therefore acts as a highly potent capsaicin analogue to activate a subpopulation of rat sensory neurons. PMID:2169951

  16. Tolerance of cranial nerves of the cavernous sinus to radiosurgery

    SciTech Connect

    Tishler, R.B.; Loeffler, J.S.; Alexander, E. III; Kooy, H.M. ); Lunsford, L.D.; Duma, C.; Flickinger, J.C. )

    1993-09-20

    Stereotactic radiosurgery is becoming a more accepted treatment option for benign, deep seated intracranial lesions. However, little is known about the effects of large single fractions of radiation on cranial nerves. This study was undertaken to assess the effect of radiosurgery on the cranial nerves of the cavernous sinus. The authors examined the tolerance of cranial nerves (II-VI) following radiosurgery for 62 patients (42/62 with meningiomas) treated for lesions within or near the cavernous sinus. Twenty-nine patients were treated with a modified 6 MV linear accelerator (Joint Center for Radiation Therapy) and 33 were treated with the Gamma Knife (University of Pittsburgh). Three-dimensional treatment plans were retrospectively reviewed and maximum doses were calculated for the cavernous sinus and the optic nerve and chiasm. Median follow-up was 19 months (range 3-49). New cranial neuropathies developed in 12 patients from 3-41 months following radiosurgery. Four of these complications involved injury to the optic system and 8 (3/8 transient) were the result of injury to the sensory or motor nerves of the cavernous sinus. There was no clear relationship between the maximum dose to the cavernous sinus and the development of complications for cranial nerves III-VI over the dose range used (1000-4000 cGy). For the optic apparatus, there was a significantly increased incidence of complications with dose. Four of 17 patients (24%) receiving greater than 800 cGy to any part of the optic apparatus developed visual complications compared with 0/35 who received less than 800 cGy (p = 0.009). Radiosurgery using tumor-controlling doses of up to 4000 cGy appears to be a relatively safe technique in treating lesions within or near the sensory and motor nerves (III-VI) of the cavernous sinus. The dose to the optic apparatus should be limited to under 800 cGy. 21 refs., 4 tabs.

  17. Peripheral nerve tumours: 30-year experience in the surgical treatment.

    PubMed

    Gosk, Jerzy; Gutkowska, Olga; Mazurek, Piotr; Koszewicz, Magdalena; Zi?kowski, Piotr

    2015-07-01

    Peripheral nerve tumours are relatively rare type of soft tissue tumours. The aim of this work is to present our experience with surgical treatment of this type of lesions. Clinical material consists of 94 patients (56 females, 38 males), in whom 101 tumours deriving from peripheral nervous system were removed. The patients underwent surgical treatment between 1983 and 2012. Tumours occurred mainly in the upper extremity (72 tumours), less often in the lower extremity (25 tumours). Lesions developed in major peripheral nerves (51 tumours) and small nerve branches (50 tumours). The most common symptoms reported before surgery included presence of tumour mass (100 %), positive Hoffmann-Tinel sign (95.6 %) and paraesthesia (93.4 %). Less often sensory deficit (89.1 %) and pain (71.7 %) were observed. Motor deficit was the least common manifestation (41.3 %). Benign tumours prevailed in presented material (94 tumours). In 7 cases, malignant peripheral nerve sheath tumour (MPNST) was identified. As a result of surgical treatment in the group of tumours deriving from major peripheral nerves, in 87.8 % of the patients, pain relief was achieved; in 84 %, Hoffmann-Tinel sign was negative; and in 79 %, paraesthesia resolved. Sensory function improvement was observed in 51.2 % of the patients while motor function improved in 26.3 % of the patients. None of the patients experienced tumour relapse. In the group of tumours deriving from small nerve branches, 47 patients had no signs of tumour recurrence. One female patient diagnosed with MPNST suffered a relapse. Obtaining satisfactory results of peripheral nerve tumour treatment requires both careful differential diagnosis and well thought-out strategy at every stage of therapeutic management. PMID:25727458

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

    PubMed Central

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

    2009-01-01

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

  19. Outcome after Desensitization in HLA or ABO-Incompatible Kidney Transplant Recipients: A Single Center Experience

    PubMed Central

    Kauke, Teresa; Klimaschewski, Sandra; Schoenermarck, Ulf; Fischereder, Michael; Dick, Andrea; Guba, Markus; Stangl, Manfred; Werner, Jens; Meiser, Bruno; Habicht, Antje

    2016-01-01

    Background The shortage of deceased donors led to an increase of living donor kidney (LDK) transplantations performed in the presence of donor-specific antibodies (DSA) or ABO incompatibility (ABOi) using various desensitization protocols. Methods We herein analyzed 26 ABOi and 8 Luminex positive DSA patients who were successfully desensitized by anti-CD20, antigen-specific immunoadsorption and/or plasmapheresis to receive an LDK transplant. Twenty LDK recipients with non-donor-specific HLA-antibodies (low risk) and 32 without anti-HLA antibodies (no risk) served as control groups. Results 1-year graft survival rate and renal function was similar in all 4 groups (creatinine: 1.63 ± 0.5 vs 1.78 ± 0.6 vs 1.64 ± 0.5 vs 1.6 ± 0.3 mg/dl in ABOi, DSA, low risk and no risk group). The incidence of acute T-cell mediated rejections did not differ between the 4 groups (15% vs 12, 5% vs 15% vs 22% in ABOi, DSA, low risk and no risk), while antibody-mediated rejections were only found in the DSA (25%) and ABOi (7.5%) groups. Incidence of BK nephropathy (BKVN) was significantly more frequent after desensitization as compared to controls (5/34 vs 0/52, p = 0.03). Conclusion We demonstrate favorable short-term allograft outcome in LDK transplant recipients after desensitization. However, the desensitization was associated with an increased risk of BKVN. PMID:26730981

  20. Benzoquinone reveals a cysteine-dependent desensitization mechanism of TRPA1.

    PubMed

    Ibarra, Yessenia; Blair, Nathaniel T

    2013-05-01

    The transient receptor potential ankyrin 1 (TRPA1) nonselective cation channel has a conserved function as a noxious chemical sensor throughout much of Metazoa. Electrophilic chemicals activate both insect and vertebrate TRPA1 via covalent modification of cysteine residues in the amino-terminal region. Although naturally occurring electrophilic plant compounds, such as mustard oil and cinnamaldehyde, are TRPA1 agonists, it is unknown whether arthropod-produced electrophiles activate mammalian TRPA1. We characterized the effects of the electrophilic arthropod defensive compound para-benzoquinone (pBQN) on the human TRPA1 channel. We used whole-cell recordings of human embryonic kidney cells heterologously expressing either wild-type TRPA1 or TRPA1 with three serine-substituted cysteines crucial for electrophile activation (C621S, C641S, C665S). We found that pBQN activates TRPA1 starting at 10 nM and peaking at 300 nM; higher concentrations caused rapid activation followed by a fast decline. Activation by pBQN required reactivity with cysteine residues, but ones that are distinct from those previously reported to be the key targets of electrophiles. The current reduction we found at higher pBQN concentrations was a cysteine-dependent desensitization of TRPA1, and did not require prior activation. The cysteines required for desensitization are not accessible to all electrophiles as iodoacetamide and internally applied 2-(trimethylammonium)ethyl methanesulfonate failed to cause desensitization (despite large activation). Interestingly, following pBQN desensitization, wild-type TRPA1 had dramatically reduced response to the nonelectrophile agonist carvacrol, whereas the triple cysteine mutant TRPA1 retained its full response. Our results suggest that modification of multiple cysteine residues by electrophilic compounds can generate both activation and desensitization of the TRPA1 channel. PMID:23478802

  1. Benzoquinone Reveals a Cysteine-Dependent Desensitization Mechanism of TRPA1

    PubMed Central

    Ibarra, Yessenia

    2013-01-01

    The transient receptor potential ankyrin 1 (TRPA1) nonselective cation channel has a conserved function as a noxious chemical sensor throughout much of Metazoa. Electrophilic chemicals activate both insect and vertebrate TRPA1 via covalent modification of cysteine residues in the amino-terminal region. Although naturally occurring electrophilic plant compounds, such as mustard oil and cinnamaldehyde, are TRPA1 agonists, it is unknown whether arthropod-produced electrophiles activate mammalian TRPA1. We characterized the effects of the electrophilic arthropod defensive compound para-benzoquinone (pBQN) on the human TRPA1 channel. We used whole-cell recordings of human embryonic kidney cells heterologously expressing either wild-type TRPA1 or TRPA1 with three serine-substituted cysteines crucial for electrophile activation (C621S, C641S, C665S). We found that pBQN activates TRPA1 starting at 10 nM and peaking at 300 nM; higher concentrations caused rapid activation followed by a fast decline. Activation by pBQN required reactivity with cysteine residues, but ones that are distinct from those previously reported to be the key targets of electrophiles. The current reduction we found at higher pBQN concentrations was a cysteine-dependent desensitization of TRPA1, and did not require prior activation. The cysteines required for desensitization are not accessible to all electrophiles as iodoacetamide and internally applied 2-(trimethylammonium)ethyl methanesulfonate failed to cause desensitization (despite large activation). Interestingly, following pBQN desensitization, wild-type TRPA1 had dramatically reduced response to the nonelectrophile agonist carvacrol, whereas the triple cysteine mutant TRPA1 retained its full response. Our results suggest that modification of multiple cysteine residues by electrophilic compounds can generate both activation and desensitization of the TRPA1 channel. PMID:23478802

  2. Desensitization of ETA endothelin receptor-mediated negative chronotropic response in right atriaspecies difference and intracellular mechanisms

    PubMed Central

    Ono, Kageyoshi; Sakamoto, Aiji; Masaki, Tomoh; Satake, Motoyoshi

    1998-01-01

    Desensitization of ETA endothelin receptor (ETAR) was compared between the rat and guinea-pig with regard to negative chronotropic response (NC) in the right atria (RA).ET-1 (100?nM) produced distinct NC in the presence of BQ788 (300?nM), and positive chronotropic response (PC) in the presence of BQ123 (1??M) in both species, showing that ETAR and ETB endothelin receptor (ETBR) mediate NC and PC, respectively.Repetitive applications of ET-1 (50?nM) desensitized PC, and the second application only induced a strong NC in both species. Later applications of ET-1 produced virtually no response in the rat RA, whereas they produced BQ123-sensitive NCs repetitively in guinea-pig RA, exhibiting marked species difference in desensitization of ETAR-mediated NC.Pretreatment with staurosporine (100?nM) prevented desensitization of ETAR in the rat RA altogether. However, phorbol 12-myristate 13-acetate (PMA, 300?nM) failed to induce, but rather hampered, desensitization of ETAR.Partial amino acid sequencing of ETARs, spanning from the 2nd through the 4th intracellular loops, revealed that all the potential Ser/Thr phosphorylation sites, including a protein kinase C (PKC) site, are conserved among guinea-pigs, rats, rabbits, bovines and humans.In guinea pig RA, pretreatment with okadaic acid (1??g?ml?1) and PMA did not facilitate desensitization of ETAR whereas these agents successfully desensitized ETAR during combined stimulation of ?-adrenoceptor and ETAR by isoproterenol (300?nM) and ET-1 (100?nM).These results suggest that species differences in desensitization of ETAR are not caused by differences in the site(s) of, but caused by differences in the environment for phosphorylation of the receptor. Desensitization of ETAR appears to require phosphorylation of the receptor by PKC as well as a kinase stimulated by ?-adrenoceptor activation. PMID:9831916

  3. A direct role for arrestins in desensitization of the luteinizing hormone/choriogonadotropin receptor in porcine ovarian follicular membranes

    PubMed Central

    Mukherjee, Sutapa; Palczewski, Krzysztof; Gurevich, Vsevolod; Benovic, Jeffrey L.; Banga, J. Paul; Hunzicker-Dunn, Mary

    1999-01-01

    The luteinizing hormone/choriogonadotropin (LH/CG) receptor (R) is a heptahelical R that, upon agonist binding, activates the stimulatory guanine nucleotide-binding protein (Gs) and the downstream effector adenylyl cyclase (AC). Like other G protein-coupled Rs, the LH/CG R subsequently exhibits reduced agonist-dependent effector activity, or desensitization, in response to saturating agonist. Unlike desensitization of many other G protein-coupled Rs, the in vivo desensitization response of LH/CG R-stimulated AC activity of ovarian follicles to the preovulatory surge of LH can be mimicked under cell-free conditions. Based on evidence that porcine ovarian follicular membranes unexpectedly contained ?-arrestin-1, the role of arrestins in desensitization of the LH/CG R was investigated. Results showed that neutralizing arrestin antibodies blocked the development of desensitization and that desensitization was rescued with a synthetic peptide corresponding to the antibody-binding epitope on ?-arrestin-1. These results suggest that endogenous ?-arrestin-1 participates in agonist-dependent desensitization of the LH/CG R. Addition of recombinant purified ?-arrestin-1 mimicked human chorionic gonadotrophin to promote desensitization of human chorionic gonadotrophin-stimulated AC activity, in the presence of the ATP phosphorylation antagonist adenylyl-imidodiphosphate, with an ED50 of ?0.1 nM. Increased levels of an 87-kDa protein reactive with glycoprotein hormone R-reactive antibody, consistent with the LH/CG R, coimmunoprecipitated with follicular membrane ?-arrestin-1 in response to LH/CG R activation compared with unactivated R. Taken together, these results show that ovarian follicles contain membrane-associated ?-arrestin-1, that ?-arrestin-1 participates in agonist-dependent desensitization of the LH/CG R, and that the trigger for ?-arrestin-1 binding to the LH/CG R appears to be R activation. PMID:9892661

  4. Anterior interosseous nerve syndrome

    PubMed Central

    Bumer, Philipp; Meinck, Hans-Michael; Schiefer, Johannes; Weiler, Markus; Bendszus, Martin; Kele, Henrich

    2014-01-01

    Objective: We sought to determine lesion sites and spatial lesion patterns in spontaneous anterior interosseous nerve syndrome (AINS) with high-resolution magnetic resonance neurography (MRN). Methods: In 20 patients with AINS and 20 age- and sex-matched controls, MRN of median nerve fascicles was performed at 3T with large longitudinal anatomical coverage (upper arm/elbow/forearm): 135 contiguous axial slices (T2-weighted: echo time/repetition time 52/7,020 ms, time of acquisition: 15 minutes 48 seconds, in-plane resolution: 0.25 0.25 mm). Lesion classification was performed by visual inspection and by quantitative analysis of normalized T2 signal after segmentation of median nerve voxels. Results: In all patients and no controls, T2 lesions of individual fascicles were observed within upper arm median nerve trunk and strictly followed a somatotopic/internal topography: affected were those motor fascicles that will form the anterior interosseous nerve further distally while other fascicles were spared. Predominant lesion focus was at a mean distance of 14.6 5.4 cm proximal to the humeroradial joint. Discriminative power of quantitative T2 signal analysis and of qualitative lesion rating was high, with 100% sensitivity and 100% specificity (p < 0.0001). Fascicular T2 lesion patterns were rated as multifocal (n = 17), monofocal (n = 2), or indeterminate (n = 1) by 2 independent observers with strong agreement (kappa = 0.83). Conclusion: It has been difficult to prove the existence of fascicular/partial nerve lesions in spontaneous neuropathies using clinical and electrophysiologic findings. With MRN, fascicular lesions with strict somatotopic organization were observed in upper arm median nerve trunks of patients with AINS. Our data strongly support that AINS in the majority of cases is not a surgically treatable entrapment neuropathy but a multifocal mononeuropathy selectively involving, within the main trunk of the median nerve, the motor fascicles that continue distally to form the anterior interosseous nerve. PMID:24415574

  5. Carboxyl-terminal Domain of Transient Receptor Potential Vanilloid 1 Contains Distinct Segments Differentially Involved in Capsaicin- and Heat-induced Desensitization*

    PubMed Central

    Joseph, John; Wang, Sen; Lee, Jongseok; Ro, Jin Y.; Chung, Man-Kyo

    2013-01-01

    Multiple Ca2+-dependent processes are involved in capsaicin-induced desensitization of transient receptor potential vanilloid 1 (TRPV1), but desensitization of TRPV1 by heat occurs even in the absence of extracellular Ca2+, although the mechanisms are unknown. In this study, we tested the hypothesis that capsaicin and heat desensitize TRPV1 through distinct mechanisms involving distinct structural segments of TRPV1. In HEK293 cells that heterologously express TRPV1, we found that heat-induced desensitization was not affected by the inclusion of intracellular ATP or alanine mutation of Lys155, both of which attenuate capsaicin-induced desensitization, suggesting that heat-induced desensitization occurs through mechanisms distinct from capsaicin-induced desensitization. To determine protein domains involved in heat-induced desensitization, we generated chimeric proteins between TRPV1 and TRPV3, a heat-gated channel lacking heat-induced desensitization. We found that TRPV1 with the carboxyl-terminal domain (CTD) of TRPV3 retained heat activation but was impaired in heat-induced desensitization. Further experiments using chimeric or deletion mutants within TRPV1 CTD indicated that the distal half of CTD regulates the activation and desensitization of TRPV1 in modality-specific manners. Within the distal CTD, we identified two segments that distinctly regulated capsaicin- and heat-induced desensitization. The results suggest that the activation and desensitization of TRPV1 by capsaicin and heat can be modulated differentially and disproportionally through different regions of TRPV1 CTD. Identifying the domains involved in thermal regulation of TRPV1 may facilitate the development of novel anti-hyperalgesic approaches aimed at attenuating activation and enhancing desensitization of TRPV1 by thermal stimuli. PMID:24174527

  6. Dermatological and immunological conditions due to nerve lesions

    PubMed Central

    Bove, Domenico; Lupoli, Amalia; Caccavale, Stefano; Piccolo, Vincenzo; Ruocco, Eleonora

    2013-01-01

    Summary Some syndromes are of interest to both neurologists and dermatologists, because cutaneous involvement may harbinger symptoms of a neurological disease. The aim of this review is to clarify this aspect. The skin, because of its relationships with the peripheral sensory nervous system, autonomic nervous system and central nervous system, constitutes a neuroimmunoendocrine organ. The skin contains numerous neuropeptides released from sensory nerves. Neuropeptides play a precise role in cutaneous physiology and pathophysiology, and in certain skin diseases. A complex dysregulation of neuropeptides is a feature of some diseases of both dermatological and neurological interest (e.g. cutaneous and nerve lesions following herpes zoster infection, cutaneous manifestations of carpal tunnel syndrome, trigeminal trophic syndrome). Dermatologists need to know when a patient should be referred to a neurologist and should consider this option in those presenting with syndromes of unclear etiology. PMID:24125557

  7. A new type of functional chemical sensitizer {MgH}2 for improving pressure desensitization resistance of emulsion explosives

    NASA Astrophysics Data System (ADS)

    Cheng, Y. F.; Yan, S. L.; Ma, H. H.; Shen, Z. W.; Liu, R.

    2015-07-01

    In millisecond-delay blasting and deep water blasting projects, traditional emulsion explosives sensitized by the chemical sensitizer NaNO2 often encounter incomplete explosion or misfire problems because of the "pressure desensitization" phenomenon, which seriously affects blasting safety and construction progress. A MgH2 -sensitized emulsion explosive was invented to solve these problems. Experimental results show that MgH2 can effectively reduce the problem of pressure desensitization. In this paper, the factors which influence the pressure desensitization of two types of emulsion explosives are studied, and resistance to this phenomenon of MgH2 -sensitized emulsion explosives is discussed.

  8. Suprascapular nerve entrapment.

    PubMed

    Cor, L; Azuelos, A; Alexandre, A

    2005-01-01

    It is important to be aware of neuropathy involving the suprascapular nerve. While direct trauma to the suprascapular nerve is the usual cause (direct blow to the base of the neck or posterior shoulder, shoulder dislocation or fracture), the problem may result from overuse injuries (such as repetitive tennis serving or spiking of a volley ball), excessive horizontal adduction, weight lifting, backpacking or no apparent reason. These last three years we have operated 8 cases of suprascapular nerve neurolysis at the level of suprascapular incision, and section of the transverse scapular ligament through the back supraspinal approach. PMID:15830964

  9. Accelerating axonal growth promotes motor recovery after peripheral nerve injury in mice

    PubMed Central

    Ma, Chi Him Eddie; Omura, Takao; Cobos, Enrique J.; Latrmolire, Alban; Ghasemlou, Nader; Brenner, Gary J.; van Veen, Ed; Barrett, Lee; Sawada, Tomokazu; Gao, Fuying; Coppola, Giovanni; Gertler, Frank; Costigan, Michael; Geschwind, Dan; Woolf, Clifford J.

    2011-01-01

    Although peripheral nerves can regenerate after injury, proximal nerve injury in humans results in minimal restoration of motor function. One possible explanation for this is that injury-induced axonal growth is too slow. Heat shock protein 27 (Hsp27) is a regeneration-associated protein that accelerates axonal growth in vitro. Here, we have shown that it can also do this in mice after peripheral nerve injury. While rapid motor and sensory recovery occurred in mice after a sciatic nerve crush injury, there was little return of motor function after sciatic nerve transection, because of the delay in motor axons reaching their target. This was not due to a failure of axonal growth, because injured motor axons eventually fully re-extended into muscles and sensory function returned; rather, it resulted from a lack of motor end plate reinnervation. Tg mice expressing high levels of Hsp27 demonstrated enhanced restoration of motor function after nerve transection/resuture by enabling motor synapse reinnervation, but only within 5 weeks of injury. In humans with peripheral nerve injuries, shorter wait times to decompression surgery led to improved functional recovery, and, while a return of sensation occurred in all patients, motor recovery was limited. Thus, absence of motor recovery after nerve damage may result from a failure of synapse reformation after prolonged denervation rather than a failure of axonal growth. PMID:21965333

  10. Distinct signaling of Drosophila chemoreceptors in olfactory sensory neurons.

    PubMed

    Cao, Li-Hui; Jing, Bi-Yang; Yang, Dong; Zeng, Xiankun; Shen, Ying; Tu, Yuhai; Luo, Dong-Gen

    2016-02-16

    In Drosophila, olfactory sensory neurons (OSNs) rely primarily on two types of chemoreceptors, odorant receptors (Ors) and ionotropic receptors (Irs), to convert odor stimuli into neural activity. The cellular signaling of these receptors in their native OSNs remains unclear because of the difficulty of obtaining intracellular recordings from Drosophila OSNs. Here, we developed an antennal preparation that enabled the first recordings (to our knowledge) from targeted Drosophila OSNs through a patch-clamp technique. We found that brief odor pulses triggered graded inward receptor currents with distinct response kinetics and current-voltage relationships between Or- and Ir-driven responses. When stimulated with long-step odors, the receptor current of Ir-expressing OSNs did not adapt. In contrast, Or-expressing OSNs showed a strong Ca(2+)-dependent adaptation. The adaptation-induced changes in odor sensitivity obeyed the Weber-Fechner relation; however, surprisingly, the incremental sensitivity was reduced at low odor backgrounds but increased at high odor backgrounds. Our model for odor adaptation revealed two opposing effects of adaptation, desensitization and prevention of saturation, in dynamically adjusting odor sensitivity and extending the sensory operating range. PMID:26831094

  11. Vagus Nerve and Vagus Nerve Stimulation, a Comprehensive Review: Part I.

    PubMed

    Yuan, Hsiangkuo; Silberstein, Stephen D

    2016-01-01

    The vagus nerve (VN), the "great wondering protector" of the body, comprises an intricate neuro-endocrine-immune network that maintains homeostasis. With reciprocal neural connections to multiple brain regions, the VN serves as a control center that integrates interoceptive information and responds with appropriate adaptive modulatory feedbacks. While most VN fibers are unmyelinated C-fibers from the visceral organs, myelinated A- and B-fiber play an important role in somatic sensory, motor, and parasympathetic innervation. VN fibers are primarily cholinergic but other noncholinergic nonadrenergic neurotransmitters are also involved. VN has four vagal nuclei that provide critical controls to the cardiovascular, respiratory, and alimentary systems. Latest studies revealed that VN is also involved in inflammation, mood, and pain regulation, all of which can be potentially modulated by vagus nerve stimulation (VNS). With a broad vagal neural network, VNS may exert a neuromodulatory effect to activate certain innate "protective" pathways for restoring health. PMID:26364692

  12. Activation of vagus nerve by semapimod alters substance P levels and decreases breast cancer metastasis.

    PubMed

    Erin, Nuray; Duymu?, Ozlem; Oztrk, Saffet; Demir, Necdet

    2012-11-10

    Chronic inflammation is involved in initiation as well as in progression of cancer. Semapimod, a tetravalent guanylhydrazon and formerly known as CNI-1493, inhibits the release of inflammatory cytokines from activated macrophages and this effect is partly mediated by the vagus nerve. Our previous findings demonstrated that inactivation of vagus nerve activity as well sensory neurons enhanced visceral metastasis of 4THM breast carcinoma. Hence semapimod by activating vagus nerve may inhibit breast cancer metastasis. Here, effects of semapimod on breast cancer metastasis, the role of vagal sensory neurons on this effect and changes in mediators of the neuroimmune connection, such as substance P (SP) as well as neprilysin-like activity, were examined. Vagotomy was performed on half of the control animals that were treated with semapimod following orthotopic injection of 4THM breast carcinoma cells. Semapimod decreased lung and liver metastases in control but not in vagotomized animals with an associated increased SP levels in sensory nerve endings. Semapimod also increased neprilysin-like activity in lung tissue of control animals but not in tumor-bearing animals. This is the first report demonstrating that semapimod enhances vagal sensory nerve activity and may have anti-tumoral effects under in-vivo conditions. Further studies, however, are required to elucidate the conditions and the mechanisms involved in anti-tumoral effects of semapimod. PMID:22982142

  13. Capsaicin and sensory neurones: a historical perspective.

    PubMed

    Szolcsnyi, Jnos

    2014-01-01

    Capsaicin, the pungent ingredient of red pepper has become not only a "hot" topic in neuroscience but its new target-related unique actions have opened the door for the drug industry to introduce a new chapter of analgesics. After several lines of translational efforts with over 1,000 patents and clinical trials, the 8% capsaicin dermal patch reached the market and its long-lasting local analgesic effect in some severe neuropathic pain states is now well established. This introductory chapter outlines on one hand the historical background based on the author's 50 years of experience in this field and on the other hand emphasizes new scopes, fascinating perspectives in pharmaco-physiology, and molecular pharmacology of nociceptive sensory neurons. Evidence for the effect of capsaicin on C-polymodal nociceptors (CMH), C-mechanoinsensitive (CHMi), and silent C-nociceptors are listed and the features of the capsaicin-induced blocking effects of nociceptors are demonstrated. Common and different characteristics of nociceptor-blocking actions after systemic, perineural, local, intrathecal, and in vitro treatments are summarized. Evidence for the misleading conclusions drawn from neonatal capsaicin pretreatment is presented. Perspectives opened from cloning the capsaicin receptor "Transient Receptor Potential Vanilloid 1" (TRPV1) are outlined and potential molecular mechanisms behind the long-lasting functional, ultrastructural, and nerve terminal-damaging effects of capsaicin and other TRPV1 agonists are summarized. Neurogenic inflammation and the long-list of "capsaicin-sensitive" tissue responses are mediated by an unorthodox dual sensory-efferent function of peptidergic TRPV1-expressing nerve terminals which differ from the classical efferent and sensory nerve endings that have a unidirectional role in neuroregulation. Thermoregulatory effects of capsaicin are discussed in detail. It is suggested that since hyperthermia and burn risk due to enhanced noxious heat threshold are the major obstacles of some TRPV1 antagonists, they could be overcome. The special "multisteric" gating function of the TRPV1 cation channel provides the structural ground for blocking chemical activation of TRPV1 without affecting its responsiveness to physical stimuli. A new chapter of potential analgesics targeting nociceptors is now already supported for pain relief in persistent pathological pain states. PMID:24941663

  14. 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

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

    PubMed

    Reichert, Pawel; Kie?bowicz, Zdzis?aw; Dzi?giel, Piotr; Pu?a, Bartosz; Wrzosek, Marcin; Boche?ska, 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

  16. Degenerative Nerve Diseases

    MedlinePLUS

    Degenerative nerve diseases affect many of your body's activities, such as balance, movement, talking, breathing, and heart function. Many of these diseases are genetic. Sometimes the cause is a medical ...

  17. Tibial nerve dysfunction

    MedlinePLUS

    ... and successfully treated. Some people may have a partial or complete loss of movement or sensation. Nerve ... mild to severe) Movement loss in the toes (partial or complete) Repeated or unnoticed injury to the ...

  18. Vagus Nerve Stimulation

    PubMed Central

    Howland, Robert H.

    2014-01-01

    The vagus nerve is a major component of the autonomic nervous system, has an important role in the regulation of metabolic homeostasis, and plays a key role in the neuroendocrine-immune axis to maintain homeostasis through its afferent and efferent pathways. Vagus nerve stimulation (VNS) refers to any technique that stimulates the vagus nerve, including manual or electrical stimulation. Left cervical VNS is an approved therapy for refractory epilepsy and for treatment resistant depression. Right cervical VNS is effective for treating heart failure in preclinical studies and a phase II clinical trial. The effectiveness of various forms of non-invasive transcutaneous VNS for epilepsy, depression, primary headaches, and other conditions has not been investigated beyond small pilot studies. The relationship between depression, inflammation, metabolic syndrome, and heart disease might be mediated by the vagus nerve. VNS deserves further study for its potentially favorable effects on cardiovascular, cerebrovascular, metabolic, and other physiological biomarkers associated with depression morbidity and mortality. PMID:24834378

  19. Diabetic Nerve Problems

    MedlinePLUS

    ... the wrong times. This damage is called diabetic neuropathy. Over half of people with diabetes get it. ... change positions quickly Your doctor will diagnose diabetic neuropathy with a physical exam and nerve tests. Controlling ...

  20. [Optic nerve disc drusen].

    PubMed

    Samoil?, O; C?lug?ru, D; C?lug?ru, M; Emese, Kaucsar

    2006-01-01

    Optic nerve head drusen represents a frequent condition, with unknown pathogenesis, mostly asymptomatic. Here, we present a patient with visual impairment, who has reacted well to anti-inflammatory and vasodilator treatment. PMID:16927754

  1. [Nerve injuries and posttraumatic therapy].

    PubMed

    Radtke, C; Vogt, P M

    2014-06-01

    Peripheral nerve injuries are a common clinical problem and can represent a major challenge, especially after trauma. In order to achieve optimal therapy, an early and adequate diagnosis with subsequent therapy is critical for functional preservation and restoration. Especially after complete severance of a peripheral nerve, the surgical techniques for nerve coaptation are an important prerequisite for peripheral nerve regeneration. The importance and necessity of adequate nerve coaptation and nerve transplantation are presented in detail. In addition, the types of primary and secondary nerve reconstruction procedures are described as well as the optimal time point of nerve repair. This article provides a comprehensive overview of the possibilities for diagnosis and intervention after nerve injury, additionally including an algorithm for surgical intervention. Furthermore, possible pitfalls and factors for improving the functional outcome are presented to optimize results with trauma-related nerve injury. PMID:24903504

  2. Small nerve fiber involvement in CMT1A

    PubMed Central

    Manganelli, Fiore; Provitera, Vincenzo; Pisciotta, Chiara; Stancanelli, Annamaria; Caporaso, Giuseppe; Iodice, Rosa; Shy, Michael E.; Santoro, Lucio

    2015-01-01

    Objective: To assess the involvement of small nerve fibers in Charcot-Marie-Tooth type 1A (CMT1A). Methods: We used indirect immunofluorescence and confocal microscopy on punch biopsies from glabrous (fingertip) and hairy (thigh and leg) skin of 20 unrelated patients with CMT1A to quantify somatic and autonomic nerve fibers. In particular, we quantified epidermal nerve fibers (ENF), Meissner corpuscles (MC), intrapapillary myelinated endings (IME), and sudomotor nerves. We correlated morphologic data with findings from quantitative sensory testing, sudomotor output, sympathetic skin response, and cardiovascular reflexes. A control population of healthy age- and sex-matched controls was included with a matching ratio of 1:2. Results: We found a length-dependent loss of ENFs that worsened with aging. We also observed a loss of MCs, IMEs, and sudomotor nerves. The loss of ENF at distal leg correlated with the increase in heat-pain thresholds (p < 0.05) and with tactile thresholds (p < 0.05). Sudomotor nerve fiber loss correlated with ENF density (p < 0.05) and sweating output (p < 0.001). Conclusions: We demonstrated through morphologic, physical, and psychophysical testing that small somatic and autonomic fibers are abnormal and cause symptoms in patients with CMT1A. Awareness of such symptoms by the clinician could lead to better treatment. PMID:25540311

  3. Brain mass and cranial nerve size in shrews and moles.

    PubMed

    Leitch, Duncan B; Sarko, Diana K; Catania, Kenneth C

    2014-01-01

    We investigated the relationship between body size, brain size, and fibers in selected cranial nerves in shrews and moles. Species include tiny masked shrews (S. cinereus) weighing only a few grams and much larger mole species weighing up to 90 grams. It also includes closely related species with very different sensory specializations - such as the star-nosed mole and the common, eastern mole. We found that moles and shrews have tiny optic nerves with fiber counts not correlated with body or brain size. Auditory nerves were similarly small but increased in fiber number with increasing brain and body size. Trigeminal nerve number was by far the largest and also increased with increasing brain and body size. The star-nosed mole was an outlier, with more than twice the number of trigeminal nerve fibers than any other species. Despite this hypertrophied cranial nerve, star-nosed mole brains were not larger than predicted from body size, suggesting that magnification of their somatosensory systems does not result in greater overall CNS size. PMID:25174995

  4. Brain Mass and Cranial Nerve Size in Shrews and Moles