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Sample records for sensory nerve desensitization

  1. 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

  2. Systemic Chemical Desensitization of Peptidergic Sensory Neurons with Resiniferatoxin Inhibits Experimental Periodontitis

    PubMed Central

    Breivik, Torbjørn; Gundersen, Yngvar; Gjermo, Per; Fristad, Inge; Opstad, Per Kristian

    2011-01-01

    Background and objective: The immune system is an important player in the pathophysiology of periodontitis. The brain controls immune responses via neural and hormonal pathways, and brain-neuro-endocrine dysregulation may be a central determinant for pathogenesis. Our current knowledge also emphasizes the central role of sensory nerves. In line with this, we wanted to investigate how desensitization of peptidergic sensory neurons influences the progression of ligature-induced periodontitis, and, furthermore, how selected cytokine and stress hormone responses to Gram-negative bacterial lipopolysaccharide (LPS) stimulation are affected. Material and methods: Resiniferatoxin (RTX; 50 μg/kg) or vehicle was injected subcutaneously on days 1, 2, and 3 in stress high responding and periodontitis-susceptible Fischer 344 rats. Periodontitis was induced 2 days thereafter. Progression of the disease was assessed after the ligatures had been in place for 20 days. Two h before decapitation all rats received LPS (150 μg/kg i.p.) to induce a robust immune and stress response. Results: Desensitization with RTX significantly reduced bone loss as measured by digital X-rays. LPS provoked a significantly higher increase in serum levels of the pro-inflammatory cytokine tumour necrosis factor (TNF)-α, but lower serum levels of the anti-inflammatory cytokine interleukin (IL)-10 and the stress hormone corticosterone. Conclusions: In this model RTX-induced chemical desensitization of sensory peptidergic neurons attenuated ligature-induced periodontitis and promoted a shift towards stronger pro-inflammatory cytokine and weaker stress hormone responses to LPS. The results may partly be explained by the attenuated transmission of immuno-inflammatory signals to the brain. In turn, this may weaken the anti-inflammatory brain-derived pathways. PMID:21339860

  3. 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

  4. 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.…

  5. 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

  6. Sensory nerves in lung and airways.

    PubMed

    Lee, Lu-Yuan; Yu, Jerry

    2014-01-01

    Sensory nerves innervating the lung and airways play an important role in regulating various cardiopulmonary functions and maintaining homeostasis under both healthy and disease conditions. Their activities conducted by both vagal and sympathetic afferents are also responsible for eliciting important defense reflexes that protect the lung and body from potential health-hazardous effects of airborne particulates and chemical irritants. This article reviews the morphology, transduction properties, reflex functions, and respiratory sensations of these receptors, focusing primarily on recent findings derived from using new technologies such as neural immunochemistry, isolated airway-nerve preparation, cultured airway neurons, patch-clamp electrophysiology, transgenic mice, and other cellular and molecular approaches. Studies of the signal transduction of mechanosensitive afferents have revealed a new concept of sensory unit and cellular mechanism of activation, and identified additional types of sensory receptors in the lung. Chemosensitive properties of these lung afferents are further characterized by the expression of specific ligand-gated ion channels on nerve terminals, ganglion origin, and responses to the action of various inflammatory cells, mediators, and cytokines during acute and chronic airway inflammation and injuries. Increasing interest and extensive investigations have been focused on uncovering the mechanisms underlying hypersensitivity of these airway afferents, and their role in the manifestation of various symptoms under pathophysiological conditions. Several important and challenging questions regarding these sensory nerves are discussed. Searching for these answers will be a critical step in developing the translational research and effective treatments of airway diseases. PMID:24692141

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

    PubMed

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

    2003-10-01

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

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

    PubMed

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

    2013-09-01

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

  9. 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

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

    PubMed

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

    2016-05-01

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

  11. 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

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

    PubMed Central

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

    2001-01-01

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

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

    PubMed Central

    Lowe, J D; Bailey, C P

    2015-01-01

    BACKGROUND AND PURPOSE The majority of studies examining desensitization of the μ-opioid receptor (MOR) have examined those located at cell bodies. However, MORs are extensively expressed at nerve terminals throughout the mammalian nervous system. This study is designed to investigate agonist-induced MOR desensitization at nerve terminals in the mouse ventral tegmental area (VTA). EXPERIMENTAL APPROACH MOR function was measured in mature mouse brain slices containing the VTA using whole-cell patch-clamp electrophysiology. Presynaptic MOR function was isolated from postsynaptic function and the functional selectivity, time-dependence and mechanisms of agonist-induced MOR desensitization were examined. KEY RESULTS MORs located at GABAergic nerve terminals in the VTA were completely resistant to rapid desensitization induced by the high-efficacy agonists DAMGO and Met-enkephalin. MORs located postsynaptically on GABAergic cell bodies readily underwent rapid desensitization in response to DAMGO. However, after prolonged (>7 h) treatment with Met-enkephalin, profound homologous MOR desensitization was observed. Morphine could induce rapid MOR desensitization at nerve terminals when PKC was activated. CONCLUSIONS AND IMPLICATIONS Agonist-induced MOR desensitization in GABAergic neurons in the VTA is compartment-selective as well as agonist-selective. When MORs are located at cell bodies, higher-efficacy agonists induce greater levels of rapid desensitization than lower-efficacy agonists. However, the converse is true at nerve terminals where agonists that induce MOR desensitization via PKC are capable of rapid agonist-induced desensitization while higher-efficacy agonists are not. MOR desensitization induced by higher-efficacy agonists at nerve terminals only takes place after prolonged receptor activation. LINKED ARTICLES This article is part of a themed section on Opioids: New Pathways to Functional Selectivity. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2015.172.issue-2 PMID:24467517

  14. 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

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

    PubMed Central

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

    2015-01-01

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

  16. 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

  17. Leptin-sensitive sensory nerves innervate white fat

    PubMed Central

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

    2013-01-01

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

  18. 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

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

    PubMed Central

    2012-01-01

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

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

    PubMed

    Lundberg, J M

    1995-07-01

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

  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. Alteration in sensory nerve function following electrical shock.

    PubMed

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

    1996-12-01

    A study of the effects of electrical shock on peripheral nerve fibres is presented. Strength and duration of the applied shocks were similar to those encountered in a typical industrial electrical accident. The purpose of this study is: (i) to identify the electrophysiological and morphological change in nerve fibres after the application of electrical current shocks; (ii) to examine the ability of the peripheral nerve fibres to spontaneously regain function and; (iii) to demonstrate the usefulness of the sensory refractory spectrum as an additional technique in assessing the damage. Three groups of animals received twelve 4-ms electric field pulses of approximately 37 V/cm (n = 5), 75 V/cm (n = 9) and 150 V/cm (n = 6), respectively. Group 4 was a control group and received a direct application of 2 per cent lidocaine over the sciatic nerve for 30 min. Thermal effects of the shocks were negligible. The sensory refractory spectrum shows that electrical shock damage was mainly to the large, fast myelinated fibres and that higher field strengths do more damage. Also in a histological examination it was found that the more heavily shocked myelinated fibres had sustained more damage. PMID:8982537

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

    PubMed Central

    Myers, M. Iliza; Peltier, Amanda C.

    2013-01-01

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

  4. Sensory conduction in medial and lateral plantar nerves.

    PubMed Central

    Ponsford, S N

    1988-01-01

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

  5. 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

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

    PubMed

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

    2002-01-15

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

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

    PubMed Central

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

    2014-01-01

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

  8. 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

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

    PubMed

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

    2016-04-01

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

  10. Photostimulation of sensory neurons of the rat vagus nerve

    NASA Astrophysics Data System (ADS)

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

    2008-02-01

    We studied the effect of infrared (IR) stimulation on rat sensory neurons. Primary sensory neurons were prepared by enzymatic dissociation of the inferior (or "nodose") ganglia from the vagus nerves of rats. The 1.85-μm output of a diode laser, delivered through a 200-μm silica fiber, was used for photostimulation. Nodose neurons express the vanilloid receptor, TRPV1, which is a non-selective cation channel that opens in response to significant temperature jumps above 37 C. Opening TRPV1 channels allows entry of cations, including calcium (Ca 2+), into the cell to cause membrane depolarization. Therefore, to monitor TRPV1 activation consequent to photostimulation, we used fura-2, a fluorescent Ca 2+ indicator, to monitor the rise in intracellular Ca 2+ concentration ([Ca 2+]i). Brief trains of 2-msec IR pulses activated TRPV1 rapidly and reversibly, as evidenced by transient rises in [Ca 2+]i (referred to as Ca 2+ transients). Consistent with the Ca 2+ transients arising from influx of Ca 2+, identical photostimulation failed to evoke Ca 2+ responses in the absence of extracellular Ca 2+. Furthermore, the photo-induced Ca 2+ signals were abolished by capsazepine, a specific blocker of TRPV1, indicating that the responses were indeed mediated by TRPV1. We discuss the feasibility of using focal IR stimulation to probe neuronal circuit properties in intact neural tissue, and compare IR stimulation with another photostimulation technique-focal photolytic release of "caged" molecules.

  11. 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

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

    PubMed

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

    1997-03-01

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

  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. 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

  16. 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

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

    PubMed

    Coert, J Henk; Dellon, A Lee

    2003-04-01

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

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

    PubMed Central

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

    2012-01-01

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

  19. 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

  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. 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

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

    PubMed

    Rath, S; Green, C J

    1991-04-01

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

  3. 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.

  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. 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

  6. Phenotyping sensory nerve endings in vitro in the mouse

    PubMed Central

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

    2014-01-01

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

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

    PubMed Central

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

    2014-01-01

    Thousands of odors are sensed and discriminated by G protein-coupled odorant receptors (ORs) expressed in olfactory sensory neurons (OSNs). G protein-coupled receptor kinases (GRKs) may have a role in desensitization of ORs. However, whether ORs are susceptible to agonist-dependent desensitization and whether GRKs affect odorant responsiveness of OSNs are currently unknown. Here we show that GRK3 attenuated the agonist responsiveness of a specific mouse odorant receptor for eugenol (mOR-EG) upon agonist pretreatment in HEK293 cells, but GRK3 did not affect the response amplitude or the recovery kinetics upon repeated agonist stimulation. We performed electrophysiological recordings of single OSNs which expressed mOR-EG and green fluorescent protein (GFP) in the presence or absence of GRK3. The kinetics and amplitude of agonist responsiveness of individual GFP-labeled mOR-EG neurons were not significantly affected by the absence of GRK3. These results indicate that the role of GRK3 in attenuating ORs responsiveness in OSNs may have been overestimated. PMID:25313015

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

    PubMed

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

    2013-08-01

    Mirror neurons allow us to covertly simulate the sensation and movement of others. If mirror neurons are sensory and motor neurons, why do we not actually feel this simulation- like "mirror-touch synesthetes"? Might afferent sensation normally inhibit mirror representations from reaching consciousness? We and others have reported heightened sensory referral to phantom limbs and temporarily anesthetized arms. These patients, however, had experienced illness or injury of the deafferented limb. In the current study we observe heightened sensory and motor referral to the face after unilateral nerve block for routine dental procedures. We also obtain double-blind, quantitative evidence of heightened sensory referral in healthy participants completing a mirror-touch confusion task after topical anesthetic cream is applied. We suggest that sensory and motor feedback exist in dynamic equilibrium with mirror representations; as feedback is reduced, the brain draws more upon visual information to determine- perhaps in a Bayesian manner- what to feel. PMID:23791606

  9. 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.

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

    PubMed

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

    2011-07-28

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

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

    PubMed

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

    2008-02-01

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

  12. 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

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

    PubMed Central

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

    2009-01-01

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

  14. Ca2+/calmodulin-mediated fast desensitization by the B1b subunit of the CNG channel affects response termination but not sensitivity to recurring stimulation in olfactory sensory neurons

    PubMed Central

    Song, Yijun; Cygnar, Katherine D.; Sagdullaev, Botir; Valley, Matthew; Hirsh, Sarah; Stephan, Aaron; Reisert, Johannes; Zhao, Haiqing

    2008-01-01

    Summary Ca2+/calmodulin-mediated negative feedback is a prototypical regulatory mechanism for Ca2+ permeable ion channels. In olfactory sensory neurons (OSNs) such regulation on the cyclic nucleotide-gated (CNG) channel is considered a major mechanism of OSN adaptation. To determine the role of Ca2+/calmodulin desensitization of the olfactory CNG channel, we introduced a mutation in the channel subunit CNGB1b in mice that rendered the channel resistant to fast desensitization by Ca2+/calmodulin. Contrary to expectations, mutant OSNs showed normal receptor current adaptation to repeated stimulation. Rather, they displayed slower response termination and consequently, a reduced ability to transmit olfactory information to the olfactory bulb. They also displayed reduced response decline during sustained odorant exposure. These results suggest that Ca2+/calmodulin-mediated CNG channel fast desensitization is less important in regulating the sensitivity to recurring stimulation than previously thought and instead functions primarily to terminate OSN responses. PMID:18466748

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

    PubMed

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

    2016-02-01

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

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

    PubMed Central

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

    2016-01-01

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

  17. 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

  18. 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

  19. 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

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

    PubMed Central

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

    2009-01-01

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

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

    PubMed

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

    1999-03-01

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

  2. 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

  3. 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

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

    PubMed

    Koplovitch, Pini; Minert, Anne; Devor, Marshall

    2012-07-01

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

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

    PubMed

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

    2016-03-01

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

  6. 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.

  7. 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

  8. 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

  9. 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

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

    PubMed

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

    2004-01-15

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

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

    PubMed

    Tysniachniuk, M S

    1986-02-01

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

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

    PubMed

    Hotson, John R

    2014-01-01

    The peroneal nerve anatomy of the rabbit distal hindlimb is similar to humans, but reports of distal peroneal nerve conduction studies were not identified with a literature search. Distal sensorimotor recordings may be useful for studying rabbit models of length-dependent peripheral neuropathy. Surface electrodes were adhered to the dorsal rabbit foot overlying the extensor digitorum brevis muscle and the superficial peroneal nerve. The deep and superficial peroneal nerves were stimulated above the ankle and the common peroneal nerve was stimulated at the knee. The nerve conduction studies were repeated twice with a one-week intertest interval to determine measurement variability. Intravenous vincristine was used to produce a peripheral neuropathy. Repeat recordings measured the response to vincristine. A compound muscle action potential and a sensory nerve action potential were evoked in all rabbits. The compound muscle action potential mean amplitude was 0.29 mV (SD ± 0.12) and the fibula head to ankle mean motor conduction velocity was 46.5 m/s (SD ± 2.9). The sensory nerve action potential mean amplitude was 22.8 μV (SD ± 2.8) and the distal sensory conduction velocity was 38.8 m/s (SD ± 2.2). Sensorimotor latencies and velocities were least variable between two test sessions (coefficient of variation  =  2.6-5.9%), sensory potential amplitudes were intermediate (coefficient of variation  =  11.1%) and compound potential amplitudes were the most variable (coefficient of variation  = 19.3%). Vincristine abolished compound muscle action potentials and reduced sensory nerve action potential amplitudes by 42-57% while having little effect on velocity. Rabbit distal hindlimb nerve conduction studies are feasible with surface recordings and stimulation. The evoked distal sensory potentials have amplitudes, configurations and recording techniques that are similar to humans and may be valuable for measuring large sensory fiber function in chronic models of peripheral neuropathies. PMID:24658286

  13. 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.

  14. 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

  15. INCREASED CARDIAC SYMPATHETIC NERVE ACTIVITY IN HEART FAILURE IS NOT DUE TO DESENSITIZATION OF THE ARTERIAL BAROREFLEX

    PubMed Central

    Watson, A.M.D.; Hood, S.G.; Ramchandra, R.; McAllen, R.M.; May, C.N.

    2007-01-01

    Increased sympathetic drive to the heart worsens prognosis in heart failure, but the level of cardiac sympathetic nerve activity (CSNA) has been assessed only by indirect methods, which do not permit testing whether its control by arterial baroreceptors is defective. To do this, CSNA was measured directly in 16 female sheep, 8 of which had been ventricularly paced at 200–220 beats/min for 4–6 weeks, until their ejection fraction fell to between 35 and 40%. Recording electrodes were surgically implanted in the cardiac sympathetic nerves and after 3 days’ recovery, responses to intravenous phenylephrine and nitroprusside infusions were measured in conscious sheep. Electrophysiological recordings showed that resting CSNA (bursts/100 heart beats) was significantly elevated in heart failure sheep (89±3) compared with normal animals (46±6, P<0.001). This increased CSNA was not accompanied by any increase in the low frequency power of heart rate variability. The baroreceptor- heart rate reflex was significantly depressed in heart failure (maximum gain −3.29±0.56 vs. −5.34±0.66 beats/min/mmHg in normal animals), confirming published findings. In contrast, the baroreflex control of CSNA was undiminished (maximum gain in heart failure −6.33±1.06, vs. −6.03±0.95 %/mmHg in normal sheep). Direct recordings in a sheep model of heart failure thus show that resting CSNA is strikingly increased, but this is not due to defective control by arterial baroreceptors. PMID:17434976

  16. 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

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

    PubMed

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

    1998-12-01

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

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

    PubMed

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

    1993-09-01

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

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

    PubMed Central

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

    2015-01-01

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

  1. 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.

  2. 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

  3. 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

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

    PubMed Central

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

    2009-01-01

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

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

    PubMed Central

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

    2013-01-01

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

  6. 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

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

    PubMed Central

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

    2007-01-01

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

  8. 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

  9. 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

  10. 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

  11. 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.

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

    PubMed

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

    2014-01-01

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

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

    PubMed Central

    2013-01-01

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

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

    PubMed Central

    2013-01-01

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

  15. 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

  16. 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.

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

    PubMed Central

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

    2013-01-01

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

  18. 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

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

    PubMed Central

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

    1989-01-01

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

  20. 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

  1. 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.

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed Central

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

    2015-01-01

    Objective The K/BxN serum-transfer arthritis is a widely-used translational mouse model of rheumatoid arthritis, in which the immunological components have thoroughly been investigated. In contrast, little is known about the role of sensory neural factors and the complexity of neuro–immune interactions. Therefore, we analyzed the involvement of capsaicin-sensitive peptidergic sensory nerves in autoantibody-induced arthritis with integrative methodology. Methods Arthritogenic K/BxN or control serum was injected to non-pretreated mice or resiniferatoxin (RTX)-pretreated animals where capsaicin-sensitive nerves were inactivated. Edema, touch sensitivity, noxious heat threshold, joint function, body weight and clinical arthritis severity scores were determined repeatedly throughout two weeks. Micro-CT and in vivo optical imaging to determine matrix-metalloproteinase (MMP) and neutrophil-derived myeloperoxidase (MPO) activities, semiquantitative histopathological scoring and radioimmunoassay to measure somatostatin in the joint homogenates were also performed. Results In RTX-pretreated mice, the autoantibody-induced joint swelling, arthritis severity score, MMP and MPO activities, as well as histopathological alterations were significantly greater compared to non-pretreated animals. Self-control quantification of the bone mass revealed decreased values in intact female mice, but significantly greater arthritis-induced pathological bone formation after RTX-pretreatment. In contrast, mechanical hyperalgesia from day 10 was smaller after inactivating capsaicin-sensitive afferents. Although thermal hyperalgesia did not develop, noxious heat threshold was significantly higher following RTX pretreatment. Somatostatin-like immunoreactivity elevated in the tibiotarsal joints in non-pretreated, which was significantly less in RTX-pretreated mice. Conclusions Although capsaicin-sensitive sensory nerves mediate mechanical hyperalgesia in the later phase of autoantibody-induced chronic arthritis, they play important anti-inflammatory roles at least partially through somatostatin release. PMID:25524130

  6. 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.

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

    PubMed

    Stankovic, N; Johansson, O; Hildebrand, C

    1996-01-01

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

  8. 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

  9. 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

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

    PubMed Central

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

    2011-01-01

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

  11. 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

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

    PubMed

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

    1987-01-01

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

  13. 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

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

    PubMed

    de Iongh, R U

    1990-11-01

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

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

    PubMed

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

    1990-04-01

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

  16. 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

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

    PubMed

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

    2012-01-01

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

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

    PubMed

    Spina, D; Page, C P

    2013-10-01

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

  19. 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

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

    PubMed

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

    2000-02-11

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

  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 Central

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

    2014-01-01

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

  3. 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

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

    PubMed

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

    2004-10-01

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

  5. 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

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

    PubMed

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

    2016-04-15

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

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed

    Strasmann, T; Weihe, E; Halata, Z

    1990-01-01

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

  9. 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

  10. 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

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

    PubMed Central

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

    2014-01-01

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

  12. 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

  13. 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

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

    PubMed

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

    2015-07-01

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

  15. Systematic Desensitization and the Reduction of Anxiety.

    ERIC Educational Resources Information Center

    Deffenbacher, Jerry L.; Suinn, Richard M.

    1988-01-01

    Provides detailed information on systematic desensitization, describing in detail the procedures of imaginal desensitization. Briefly describes variants of group, in vivo, massed, and self-administered desensitization. Outlines guidelines for appropriate selection and use of desensitization and presents sampling of research findings with diversity…

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

    NASA Astrophysics Data System (ADS)

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

    2016-06-01

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

  17. Hydrogen sulphide–mediated vasodilatation involves the release of neurotransmitters from sensory nerves in pressurized mesenteric small arteries isolated from rats

    PubMed Central

    White, Benjamin J O; Smith, Paul A; Dunn, William R

    2013-01-01

    Background and Purpose Hydrogen sulphide (H2S) is a gas that has recently been shown to have biological activity. In the majority of blood vessels studied so far, H2S has been shown to cause vasorelaxation, although contractile responses have been reported. In the present study, we have made a pharmacological assessment of the effects of H2S in mesenteric small arteries isolated from rats. Experimental Approach Rat mesenteric small arteries were studied using pressure myography. In pressurised arteries, responses were obtained to the H2S donor, sodium hydrogen sulphide (NaHS), in the absence and presence of the NOS inhibitor L-NAME, raised extracellular potassium, the KATP channel inhibitor glibenclamide, the Cl– channel blockers DIDS, NPPB and A9C, the TRPV1 receptor desensitizing agent, capsaicin, the CGRP antagonist, olcegepant, the TRPV1 channel blocker capsazepine and the TRPA1 channel blocker HC-030031. Key Results NaHS produced a vasodilator response in rat mesenteric small arteries held at 90 mmHg. Responses to NaHS were not reproducible. Neither, glibenclamide nor, L-NAME inhibited responses to NaHS. DIDS abolished vasodilator responses to NaHS, but these were unaffected by the chloride channel blockers, NPPB and A9C. Responses to NaHS were attenuated after capsaicin pre-treatment, by a CGRP receptor antagonist and an inhibitor of TRPA1 channels. Conclusions and Implications In small arteries isolated from the rat mesentery, NaHS caused a vasodilatation. This response was not reproducible in vitro, since it was mediated by the release of sensory neurotransmitters in a capsaicin-like action. This release was mediated by a H2S-induced activation of TRPA1 channels. PMID:22928888

  18. Modified oral metronidazole desensitization protocol

    PubMed Central

    Pien, Lily C.; Gutta, Ravi C.; Abouhassan, Susan R.

    2014-01-01

    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

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed

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

    2015-01-01

    Using computerized pupillometry, our previous research established that the autonomic nervous system (ANS) is dysregulated in patients suffering from temporomandibular disorders (TMDs), suggesting a potential role for ANS dysfunction in pain modulation and the etiology of TMD. However, pain modulation hypotheses for TMD are still lacking. The periaqueductal gray (PAG) is involved in the descending modulation of defensive behavior and pain through μ, κ, and δ opioid receptors. Transcutaneous electrical nerve stimulation (TENS) has been extensively used for pain relief, as low-frequency stimulation can activate µ receptors. Our aim was to use pupillometry to evaluate the effect of low-frequency TENS stimulation of μ receptors on opioid descending pathways in TMD patients. In accordance with the Research Diagnostic Criteria for TMD, 18 females with myogenous TMD and 18 matched-controls were enrolled. All subjects underwent subsequent pupillometric evaluations under dark and light conditions before, soon after (end of stimulation) and long after (recovery period) sensorial TENS. The overall statistics derived from the darkness condition revealed no significant differences in pupil size between cases and controls; indeed, TENS stimulation significantly reduced pupil size in both groups. Controls, but not TMD patients, displayed significant differences in pupil size before compared with after TENS. Under light conditions, TMD patients presented a smaller pupil size compared with controls; the pupil size was reduced only in the controls. Pupil size differences were found before and during TENS and before and after TENS in the controls only. Pupillometry revealed that stimulating the descending opioid pathway with low-frequency sensory TENS of the fifth and seventh pairs of cranial nerves affects the peripheral target. The TMD patients exhibited a different pattern of response to TENS stimulation compared with the controls, suggesting that impaired modulation of the descending pain system may be involved in TMD. PMID:25905862

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

    PubMed Central

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

    2015-01-01

    Using computerized pupillometry, our previous research established that the autonomic nervous system (ANS) is dysregulated in patients suffering from temporomandibular disorders (TMDs), suggesting a potential role for ANS dysfunction in pain modulation and the etiology of TMD. However, pain modulation hypotheses for TMD are still lacking. The periaqueductal gray (PAG) is involved in the descending modulation of defensive behavior and pain through μ, κ, and δ opioid receptors. Transcutaneous electrical nerve stimulation (TENS) has been extensively used for pain relief, as low-frequency stimulation can activate µ receptors. Our aim was to use pupillometry to evaluate the effect of low-frequency TENS stimulation of μ receptors on opioid descending pathways in TMD patients. In accordance with the Research Diagnostic Criteria for TMD, 18 females with myogenous TMD and 18 matched-controls were enrolled. All subjects underwent subsequent pupillometric evaluations under dark and light conditions before, soon after (end of stimulation) and long after (recovery period) sensorial TENS. The overall statistics derived from the darkness condition revealed no significant differences in pupil size between cases and controls; indeed, TENS stimulation significantly reduced pupil size in both groups. Controls, but not TMD patients, displayed significant differences in pupil size before compared with after TENS. Under light conditions, TMD patients presented a smaller pupil size compared with controls; the pupil size was reduced only in the controls. Pupil size differences were found before and during TENS and before and after TENS in the controls only. Pupillometry revealed that stimulating the descending opioid pathway with low-frequency sensory TENS of the fifth and seventh pairs of cranial nerves affects the peripheral target. The TMD patients exhibited a different pattern of response to TENS stimulation compared with the controls, suggesting that impaired modulation of the descending pain system may be involved in TMD. PMID:25905862

  3. 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

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed Central

    Ralevic, V.; Burnstock, G.

    1996-01-01

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

  6. 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)

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

    PubMed Central

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

    2003-01-01

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

  8. Pharmacologic desensitization for dental phobias: clinical observations.

    PubMed Central

    Moore, P. A.; Peskin, R. M.; Pierce, C. J.

    1990-01-01

    The elimination of the extreme fear reported by dental phobic patients traditionally involves psychologic interventions such as systematic desensitization. Observations resulting from a conscious sedation approach, as outlined in two case histories, suggest that a desensitization phenomena is occurring. This pharmacologic desensitization appears to mimic elements of systematic desensitization. Optimal management of fearful patients may sometimes require conjunctive support from both dental behavioral scientists and dental anesthesiologists. PMID:1982984

  9. 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

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

    PubMed

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

    2013-02-15

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

  11. 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

  12. 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

  13. 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

  14. Desensitization of metastable intermolecular composites

    SciTech Connect

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

    2011-04-26

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

  15. Implementing a Systematic Desensitization Laboratory.

    ERIC Educational Resources Information Center

    Ralph, David C.; Goss, Blaine

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

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2013-11-01

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

  18. 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

  19. Desensitization of Mouse Nicotinic Acetylcholine Receptor Channels

    PubMed Central

    Auerbach, Anthony; Akk, Gustav

    1998-01-01

    The rate constants of acetylcholine receptor channels (AChR) desensitization and recovery were estimated from the durations and frequencies of clusters of single-channel currents. Diliganded-open AChR desensitize much faster than either unliganded- or diliganded-closed AChR, which indicates that the desensitization rate constant depends on the status of the activation gate rather than the occupancy of the transmitter binding sites. The desensitization rate constant does not change with the nature of the agonist, the membrane potential, the species of permeant cation, channel block by ACh, the subunit composition (ε or γ), or several mutations that are near the transmitter binding sites. The results are discussed in terms of cyclic models of AChR activation, desensitization, and recovery. In particular, a mechanism by which activation and desensitization are mediated by two distinct, but interrelated, gates in the ion permeation pathway is proposed. PMID:9689026

  20. Systematic Desensitization in Group Counseling Settings: An Overview

    ERIC Educational Resources Information Center

    Mayton, Daniel M., II; Atkinson, Donald R.

    1974-01-01

    This article summarizes research on systematic desensitization applied in group settings. Guidelines for use of group desensitization by college counselors are developed, and relevant sources regarding procedural variations cited. The need for research on group desensitization parameters is discussed. (Author)

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

    PubMed Central

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

    2016-01-01

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

  2. Comment on the Status of Systematic Desensitization

    ERIC Educational Resources Information Center

    McGlynn, F. Dudley; Smitherman, Todd A.; Gothard, Kelly D.

    2004-01-01

    Articles about systematic desensitization that appeared in mainstream behavior therapy journals between the years 1970 and 2002 were counted. Graphic displays of the data point to a sudden and lasting decline of interest in systematic desensitization among academics and researchers. A questionnaire concerning clinical use of orthodox systematic…

  3. Endogenous Opiate System and Systematic Desensitization.

    ERIC Educational Resources Information Center

    Egan, Kelly J.; And Others

    1988-01-01

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

  4. 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.

  5. 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.

  6. A comparative study evoking a sensory action potential from the medial and lateral plantar nerves using the probe and ring method of stimulation.

    PubMed

    Adam, Jamila K; Bechoo, Reneal; Rmaih, Wafaa S

    2010-01-01

    Nerve conduction studies (NCS) aid in the detection of foot nerve pathologies. However, there has been a debate on method of plantar nerves stimulation that is more effective; the ring method of stimulation or probe method of stimulation. This study aims at determining the one method that is more effective among the two methods of stimulating for eliciting proper responses. Thirty healthy adults, aged 19 to 55 years, free of any neurological disease were the subjects of the study. Values considered for determining the effectiveness of the stimulating technique were mean amplitudes of the evoked responses from medial and lateral plantar nerves. A significant increase in amplitude difference was noted in favor of the probe stimulation method. The amplitude difference noted in favor of the probe method of stimulation was double the values elicited by the ring method of stimulation in both the medial and lateral plantar nerves. Results suggest that the direct probe method of stimulation may be a more effective method of stimulating for the medial and lateral plantar nerves studies. PMID:20508349

  7. 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

  8. M2 receptors exert analgesic action on DRG sensory neurons by negatively modulating VR1 activity.

    PubMed

    De Angelis, Federica; Marinelli, Sara; Fioretti, Bernard; Catacuzzeno, Luigi; Franciolini, Fabio; Pavone, Flaminia; Tata, Ada Maria

    2014-06-01

    The peripheral application of the M2 cholinergic agonist arecaidine on sensory nerve endings shows anti-nociceptive properties. In this work, we analyze in vitro, the mechanisms downstream M2 receptor activation causing the analgesic effects, and in vivo the effects produced by M2 agonist arecaidine administration on nociceptive responses in a murine model of nerve growth factor (NGF)-induced pain. Cultured DRG neurons treated with arecaidine showed a decreased level of VR1 and SP transcripts. Conversely, we found an increased expression of VR1 and SP transcripts in DRG from M2/M4(-/-) mice compared to WT and M1(-/-) mice, confirming the inhibitory effect in particular of M2 receptors on SP and VR1 expression. Patch-clamp experiments in the whole-cell configuration showed that arecaidine treatment caused a reduction of the fraction of capsaicin-responsive cells, without altering the mean capsaicin-activated current in responsive cells. We also demonstrated that arecaidine prevents PKCϵ translocation to the plasma membrane after inflammatory agent stimulation, mainly in medium-small sensory neurons. Finally, in mice, we have observed that intraperitoneal injection of arecaidine reduces VR1 expression blocking hyperalgesia and allodynia caused by NGF intraplantar administration. In conclusion, our data demonstrate that in vivo M2 receptor activation induces desensitization to mechanical and heat stimuli by a down-regulation of VR1 expression and by the inhibition of PKCϵ activity hindering its translocation to the plasma membrane, as suggested by in vitro experiments. PMID:24166293

  9. [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

  10. Desensitization of Children to Television Violence

    ERIC Educational Resources Information Center

    Cline, Victor B.; And Others

    1973-01-01

    To find if children do become desensitized to violence, a test for a measurable physiological difference in emotional response to filmed violence was administered to children who are high exposure and low exposure television viewers. (Author/KM)

  11. 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)

  12. 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

  13. Cholinesterase activity in sensory-nerve endings, capillaries and motor end plates of the facial skin of the brush-tailed possum (Trichosurus vulpecula).

    PubMed

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

    1990-01-01

    The facial skin of two adult and one 50-day-old pouch animal of the marsupial mammal Trichosurus vulpecula was removed after the animals has been suitably anesthetized and perfused for electron microscopy. Small blocks of tissue (1 x 0.5 mm) were cut and incubated in acetylthiocholine iodide substrate for cholinesterase studies. The blocks were then subsequently postfixed in osmium tetroxide. Thin sections were cut and stained with lead acetate. Specific cholinesterase was found within the nerves of both the adult and the 50-day-old pouch animal, and in the motor end plates. Nonspecific cholinesterase was present in pinocytotic vesicles and interlamellar spaces of terminal Schwann cells associated with nerve end organs in the adult, and in the same areas in Schwann cells of nonmyelinated nerves in the pouch animal. It was also present in the pinocytotic vesicles of the capillary endothelium. PMID:2075803

  14. In Vivo Desensitization: An Alternative to Systematic Desensitization with College Students

    ERIC Educational Resources Information Center

    Atkinson, Donald R.

    1973-01-01

    It is the thesis of this article that college counselors would make more economical and efficacious use of their time and would greatly reduce the risk of turning off'' students if they employed in vivo desensitization rather than systematic desensitization when dealing with anxious clients. (Author)

  15. 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

  16. Morphological studies of the vestibular nerve

    NASA Technical Reports Server (NTRS)

    Bergstroem, B.

    1973-01-01

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

  17. 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

  18. Systematic Desensitization as Training in Self-Control

    ERIC Educational Resources Information Center

    Goldfried, Marvin R.

    1971-01-01

    A description of a mediational model to explain the effectiveness of desensitization and a discussion of the available corroborative research findings for this alternative explanation are given. Also, specific procedural modifications for systematic desensitization are suggested. (Author)

  19. Decoupling control of a multivariable system with a desensitizer

    SciTech Connect

    Wenteng Wu; Jingwei Ko; Hsingwo Lee . Dept. of Chemical Engineering)

    1993-11-01

    Decoupling control of a multivariable system with a desensitizer has been proposed. Interactions between control loops were decoupled by means of a desensitizer and a two-way decoupler. The objective of the desensitizer was to reduce the decoupler sensitivity while the two-way decoupler was for actually decoupling control loops. The proposed control structure was verified on models of a highly interacting system and a distillation column. The control system with desensitizer significantly enhanced the robustness of the decoupling control system.

  20. Involvement of capsaicin-sensitive nerves in the bronchomotor effects of arachidonic acid and melittin: a possible role for lipoxin A4.

    PubMed Central

    Manzini, S.; Meini, S.

    1991-01-01

    1. Functional studies have been performed to evaluate the potential involvement of capsaicin-sensitive nerves in the bronchomotor responses evoked by lipid mediators produced from the metabolic breakdown of arachidonic acid (AA) in the guinea-pig bronchus. 2. In the presence of indomethacin, the exogenous administration of AA (0.01-1 mM) produced a concentration-dependent contractile response in guinea-pig isolated bronchial rings. AA-induced contractions were augmented by epithelium-removal and by thiorphan (10 microM), an inhibitor of tachykinin breakdown. A sustained downward and rightward displacement of the complete concentration-response curve to AA was observed after in vitro capsaicin desensitization. 3. BWA4C (1 microM), a selective inhibitor of 5-lipoxygenase, shifted the AA concentration-response curve to the right. In the presence of this inhibitor, capsaicin desensitization did not have any further inhibitory action. 4. A potent, concentration-dependent and capsaicin-sensitive bronchoconstrictor effect was also observed with the polypeptide, melittin (10 nM-1 microM), an activator of phospholipase A2, which therefore should generate endogenous AA. 5. In vitro capsaicin-desensitization produced a significant reduction of the bronchomotor responses evoked by lipoxin A4 (1-6 microM), but not of those elicited by other lipoxygenases products such as leukotriene D4 (1-100 nM) or by 15-hydroxyeicosatetraenoic acid (15-HETE, 1-6 microM). 6. These findings indicate that lipoxin A4 but not leukotriene D4 or 15-HETE, might be one of the lipoxygenase mediators of excitatory effects of AA on capsaicin-sensitive sensory nerves. PMID:1908731

  1. Playing violent video games and desensitization to violence.

    PubMed

    Brockmyer, Jeanne Funk

    2015-01-01

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

  2. 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

  3. Desensitizing nano powders to electrostatic discharge ignition

    SciTech Connect

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

    2015-08-01

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

  4. 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

  5. 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

  6. Desensitization and recovery of metastable intermolecular composites

    DOEpatents

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

    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.

  7. Systematic Desensitization as an Instructional Module

    ERIC Educational Resources Information Center

    Horan, John J.; And Others

    1976-01-01

    This article reports on the development and evaluation of an instructional module for teaching systematic desensitization. Physiological and self-report data reflecting changes in client fear levels were gathered in an attempt to determine whether the instructional module is effective. (Author)

  8. An Aversion-Desensitization Treatment for Alcoholism

    ERIC Educational Resources Information Center

    Primo, Richard V.; And Others

    1972-01-01

    A six-to nine-month interview follow-up showed that five of the seven traceable Ss given the interpersonal aversion-systematic desensitization treatment had been abstinent, compared with only one of seven treated by the interpersonal aversion-control procedure. (Author)

  9. Rehabilitation of the trigeminal nerve

    PubMed Central

    Iro, Heinrich; Bumm, Klaus; Waldfahrer, Frank

    2005-01-01

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

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

    PubMed

    Levander, Hans

    2003-04-30

    This article is based on a vast clinical experience from patients presenting with widespread pain syndromes as well as dysfunctional symptoms from inner organs. A literature survey has been performed. Allodynia and hyperalgesia that partly explain the fibromyalgia and local myalgia syndromes seem to arise from a pathophysiological process of nociceptive sensitisation. It is proposed that the concept of "sensory sensitisation dysfunctional disorders" be applied to conditions like bronchial hyperreactivity, Da Costas syndrome, Dercum's disease (Adipositas dolorosa), dry eyes and mouth syndrome, fibromyalgia, gastralgia, globus hystericus, interstitial cystitis, chronic prostatitis, irritable bowel syndrome, photo- and phonosensitivity, rhinitis, tension headache, tinnitus, vestibulitis syndrome. These dysfunctional disorders cannot be satisfactorily explained by presently known pathophysiological models like ongoing inflammatory process, tissue degeneration, fibrosis, blood vessel diseases, tumours, immune reactions, toxic or deficiency conditions, metabolic disturbances. Neurogenic mechanisms also seem to play an important role in the pathophysiology of arthritic conditions, and might be worthwhile to include in forthcoming discussions concerning the aetiology of chronic inflammatory disease. PMID:12789809

  11. Nerve growth factor alters microtubule targeting agent-induced neurotransmitter release but not MTA-induced neurite retraction in sensory neurons.

    PubMed

    Pittman, Sherry K; Gracias, Neilia G; Fehrenbacher, Jill C

    2016-05-01

    Peripheral neuropathy is a dose-limiting side effect of anticancer treatment with the microtubule-targeted agents (MTAs), paclitaxel and epothilone B (EpoB); however, the mechanisms by which the MTAs alter neuronal function and morphology are unknown. We previously demonstrated that paclitaxel alters neuronal sensitivity, in vitro, in the presence of nerve growth factor (NGF). Evidence in the literature suggests that NGF may modulate the neurotoxic effects of paclitaxel. Here, we examine whether NGF modulates changes in neuronal sensitivity and morphology induced by paclitaxel and EpoB. Neuronal sensitivity was assessed using the stimulated release of calcitonin gene-related peptide (CGRP), whereas morphology of established neurites was evaluated using a high content screening system. Dorsal root ganglion cultures, maintained in the absence or presence of NGF, were treated from day 7 to day 12 in culture with paclitaxel (300nM) or EpoB (30nM). Following treatment, the release of CGRP was stimulated using capsaicin or high extracellular potassium. In the presence of NGF, EpoB mimicked the effects of paclitaxel: capsaicin-stimulated release was attenuated, potassium-stimulated release was slightly enhanced and the total peptide content was unchanged. In the absence of NGF, both paclitaxel and EpoB decreased capsaicin- and potassium-stimulated release and the total peptide content, suggesting that NGF may reverse MTA-induced hyposensitivity. Paclitaxel and EpoB both decreased neurite length and branching, and this attenuation was unaffected by NGF in the growth media. These differential effects of NGF on neuronal sensitivity and morphology suggest that neurite retraction is not a causative factor to alter neuronal sensitivity. PMID:26883566

  12. 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

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

    PubMed

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

    2014-12-01

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

  14. 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

  15. 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.

  16. 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.

  17. Sensory neuropeptides and airway function.

    PubMed

    Solway, J; Leff, A R

    1991-12-01

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

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

    PubMed

    Gao, Nan; Yan, Chenxi; Lee, Patrick; Sun, Haijing; Yu, Fu-Shin

    2016-05-01

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

  19. Protein kinase C-mediated mu-opioid receptor phosphorylation and desensitization in rats, and its prevention during early diabetes.

    PubMed

    Mousa, Shaaban A; Shaqura, Mohammed; Winkler, Jens; Khalefa, Baled I; Al-Madol, Mohammed A; Shakibaei, Mehdi; Schulz, Stefan; Schäfer, Michael

    2016-04-01

    Painful diabetic neuropathy is associated with impaired opioid analgesia; however, the precise mechanism in sensory neurons remains unclear. This study aimed to identify putative mechanisms involved in modified opioid responsiveness during early streptozotocin-induced diabetes in rats. In this study, we demonstrate that in diabetic animals, impaired peripheral opioid analgesia is associated with a reduction in functional mu-opioid receptor (MOR) G protein coupling. Mu-opioid receptor immunoreactive neurons colocalized with activated forms of protein kinase C (PKC) and with the receptor for advanced glycation end products (RAGE) during streptozotocin-induced diabetes. Moreover, MOR phosphorylation at Thr370 in sensory neurons of diabetic rats, and thus desensitization, was due to RAGE-dependent PKC activation. Importantly, blocking PKC activation using PKC selective inhibitor, silencing RAGE with intrathecal RAGE siRNA, or inhibiting advanced glycation end product (AGE) formation prevented sensory neuron MOR phosphorylation and, consequently, restored MOR G protein coupling and analgesic efficacy. Thus, our findings give the first in vivo evidence of a RAGE-dependent PKC-mediated heterologous MOR phosphorylation and desensitization in sensory neurons under pathological conditions such as diabetic neuropathy. This may unravel putative mechanisms and suggest possible prevention strategies of impaired opioid responsiveness. PMID:26713421

  20. 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

  1. 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

  2. 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…

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

    ERIC Educational Resources Information Center

    Melnick, Joseph; Russell, Ronald W.

    1976-01-01

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

  4. Galvanic Skin Response and Reported Anxiety During Systematic Desensitization

    ERIC Educational Resources Information Center

    Hyman, Edward T.; Gale, Elliot N.

    1973-01-01

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

  5. Effects of Modeling and Desensitation in Reducing Dentist Phobia

    ERIC Educational Resources Information Center

    Shaw, David W.; Thoresen, Carl E.

    1974-01-01

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

  6. 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.

  7. 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

  8. Pinched Nerve

    MedlinePlus

    ... people recover from pinched nerve. However, in some cases, the damage is irreversible. What research is being done? Within the NINDS research programs, pinched nerves are addressed primarily through studies associated with pain research. NINDS vigorously pursues a ...

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

    PubMed Central

    2015-01-01

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

  10. 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.

  11. 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

  12. 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

  13. 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

  14. Sensory mononeuropathies.

    PubMed

    Massey, E W

    1998-01-01

    The clinical neurologist frequently encounters patients with a variety of focal sensory symptoms and signs. This article reviews the clinical features, etiologies, laboratory findings, and management of the common sensory mononeuropathies including meralgia paresthetica, cheiralgia paresthetica, notalgia paresthetica, gonyalgia paresthetica, digitalgia paresthetica, intercostal neuropathy, and mental neuropathy. PMID:9608615

  15. 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

  16. 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

  17. Desensitization of diliganded mouse muscle nicotinic acetylcholine receptor channels

    PubMed Central

    Elenes, Sergio; Auerbach, Anthony

    2002-01-01

    Nicotinic ACh receptor channels (AChRs) exposed to high concentrations of ACh adopt ‘desensitized’ conformations that have a high affinity for the transmitter and no measurable ion conductance. Single-channel currents elicited by 0.1 or 1 mmACh were recorded from human embryonic kidney (HEK) cells that had been transiently transfected with mouse α, β, δ, and ε subunits. On the time scale of ∼0.1 ms to ∼1 h, apparent open intervals are described by a single exponential component, and shut intervals associated with desensitization are described by the sum of four or five exponential components. The kinetic behaviour appeared to be stationary and homogeneous. Desensitization rate constants were estimated by kinetic modelling of currents from cell-attached and outside-out patches (where the number of channels in the patch was measured). A single AChR recovered from the longest-lived desensitized state only after ∼5 min. The occupancy of an AChR for each of the desensitized states was calculated as a function of time after the continuous application of a pulse of saturating ACh. The longest-lived desensitized state accounted for 90 % of the total only after several seconds. The fractional recovery from desensitization (during a 200 ms wash period) decreased as the duration of the desensitizing pulse increased, suggesting that recovery is slower from the longer-lived desensitized states. The free energy landscape for the AChR desensitization reaction in cell-attached patches exhibited an initial destabilization, followed by a plateau region of gradually increasing stability, followed by a deep well. PMID:12042345

  18. 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

  19. 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

  20. 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

  1. Autograft Substitutes: Conduits and Processed Nerve Allografts.

    PubMed

    Safa, Bauback; Buncke, Gregory

    2016-05-01

    Manufactured conduits and allografts are viable alternatives to direct suture repair and nerve autograft. Manufactured tubes should have gaps less than 10 mm, and ideally should be considered as an aid to the coaptation. Processed nerve allograft has utility as a substitute for either conduit or autograft in sensory nerve repairs. There is also a growing body of evidence supporting their utility in major peripheral nerve repairs, gap repairs up to 70 mm in length, as an alternative source of tissue to bolster the diameter of a cable graft, and for the management of neuromas in non-reconstructable injuries. PMID:27094886

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

    PubMed

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

    2015-01-01

    Treatment of HIV infection requires the combination of multiple antiretroviral drugs, known as highly active antiretroviral therapy (HAART); however, up to 84% of patients experience adverse drug effects that lead to discontinuation within first months of treatment. Skin manifestations are reported to 22% of patients. The severity of these is variable, such as erythema multiforme, rash, hives and severe skin reactions at less than 2%. Mild rashes, usually transient and self-limiting, while severe reactions require immediately remove the drug involved to prevent progression of the reaction. Only in those cases where the offending drug does not have another alternative and documented the reaction is mediated type I hypersensitivity mechanisms, can be performed desensitization protocol. PMID:26239335

  3. Systematic Desensitization: An Effective Technique for Clinical Practice

    ERIC Educational Resources Information Center

    Fischer, Joel

    1973-01-01

    This article describes the basic procedures of the technique of systematic desensitization, and suggests that social welfare practitioners make use of this extensively tested approach to dysfunctional behavior. (ST)

  4. A Comparison of Traditional and Self-Control Desensitization.

    ERIC Educational Resources Information Center

    Deffenbacher, Jerry L.; Parks, Donald H.

    1979-01-01

    Compared effectiveness of counterconditioning and self-control models of systematic desensitization in reducing targeted and nontargeted anxieties. Treatments were equally effective in reducing and maintaining reduction of targeted anxiety, debilitating test anxiety. (Author)

  5. Hierarchies for Desensitization of Test and Speech Anxieties

    ERIC Educational Resources Information Center

    Deffenbacher, Jerry L.

    1974-01-01

    Systematic desensitization is described as an effective method for reducing test and speech anxieties in college students. Two standardized hierarchies, one for test anxiety, are presented to minimize problems in hierarchy construction. (Author)

  6. Systematic Versus Semantic Desensitization and Implosive Therapy: A Comparative Study

    ERIC Educational Resources Information Center

    Hekmat, Hamid

    1973-01-01

    In this study, both the semantic and systematic desensitization methods were found to be significantly more effective than the implosive therapy and the control treatments in the modification of phobic behavior among the college student population. (Author)

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

    PubMed

    Hocker, Geoffrey A

    2003-02-01

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

  8. 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

  9. 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

  10. Capsaicin Induces Degeneration of Cutaneous Autonomic Nerve Fibers

    PubMed Central

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

    2010-01-01

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

  11. 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

  12. 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

  13. 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

  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. 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

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

    PubMed Central

    Tague, Sarah E.; Smith, Peter G.

    2014-01-01

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

  17. Sensory Dysfunction

    MedlinePlus

    ... to Web version Sensory Dysfunction Overview Why are smell and taste important? Your senses of smell and taste let you fully enjoy the scents ... bitter and sour. Flavor involves both taste and smell. For example, because a person is able to ...

  18. 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...

  19. 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)

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

    PubMed

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

    2015-11-01

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

  1. Sensory feedback in upper limb prosthetics.

    PubMed

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

    2013-01-01

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

  2. Achieving incompatible transplantation through desensitization: current perspectives and future directions.

    PubMed

    Jordan, Stanley C; Choi, Jua; Vo, Ashley

    2015-01-01

    The application of life-saving transplantation is severely limited by the shortage of organs, and histoincompatibility. To increase transplant rates in sensitized patients, new protocols for HLA and blood type incompatible (ABOi) desensitization have emerged. These approaches require significant desensitization using intravenous immunoglobulin, rituximab and plasma exchange. In addition, the development of donor-specific antibody responses post transplant is the major cause of allograft failure with return to dialysis. This increases patient morbidity/mortality and cost. Immunotherapeutic agents used for desensitization evolved from drug development in oncology and autoimmune diseases. Currently, there is a renaissance in development of novel drugs likely to improve antibody reduction in transplantation. These include agents that inactivate IgG molecules, anticytokine antibodies, costimulatory molecule blockade, anticomplement agents and therapies aimed at the plasma cell. PMID:25917629

  3. 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

  4. Systematic Desensitization and Relaxation of High Test Anxious Secondary School Students.

    ERIC Educational Resources Information Center

    Laxer, Robert M.; And Others

    This study was designed to answer two questions: (1) Is the systematic desensitization of test anxiety effective with secondary school students?; (2) Is relaxation per se as useful a technique as systematic desensitization? High test anxious secondary-school students were assigned to one of two experimental conditions, desensitization or…

  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. 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

  7. Raman microspectroscopy for visualization of peripheral nerves

    NASA Astrophysics Data System (ADS)

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

    2013-02-01

    The peripheral nervous system plays an important role in motility, sensory, and autonomic functions of the human body. Preservation of peripheral nerves in surgery is essential for improving quality of life of patients. To preserve peripheral nerves, detection of ne peripheral nerves that cannot be identi ed by human eye or under white light imaging is necessary. In this study, we sought to provide a proof-of-principle demonstration of a label-free detection technique of peripheral nerve tissues against adjacent tissues that employs spontaneous Raman microspectroscopy. A line-illumination confocal Raman microscope was used for the experiment. A laser operating at the wavelength of 532 nm was used as an excitation laser light. We obtained Raman spectra of peripheral nerve, brous connective tissue, skeletal muscle, blood vessel, and adipose tissue of Wistar rats, and extracted speci c spectral features of peripheral nerves and adjacent tissues. By applying multivariate image analysis, peripheral nerves were clearly detected against adjacent tissues without any preprocessing neither xation nor staining. These results suggest the potential of the Raman spectroscopic observation for noninvasive and label-free nerve detection, and we expect this method could be a key technique for nerve-sparing surgery.

  8. 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. ...

  9. 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

  10. 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

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

    PubMed

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

    2014-08-01

    The reproducibility of variables commonly included in studies of peripheral nerve conduction in healthy individuals has not previously been analyzed using a random effects regression model. We examined the temporal changes and variability of standard nerve conduction measures in the leg. Peroneal nerve distal motor latency, motor conduction velocity, and compound motor action potential amplitude; sural nerve sensory action potential amplitude and sensory conduction velocity; and tibial nerve minimal F-wave latency were examined in 51 healthy subjects, aged 40 to 67 years. They were reexamined after 2 and 26 weeks. There was no change in the variables except for a minor decrease in sural nerve sensory action potential amplitude and a minor increase in tibial nerve minimal F-wave latency. Reproducibility was best for peroneal nerve distal motor latency and motor conduction velocity, sural nerve sensory conduction velocity, and tibial nerve minimal F-wave latency. Between-subject variability was greater than within-subject variability. Sample sizes ranging from 21 to 128 would be required to show changes twice the magnitude of the spontaneous changes observed in this study. Nerve conduction studies have a high reproducibility, and variables are mainly unaltered during 6 months. This study provides a solid basis for the planning of future clinical trials assessing changes in nerve conduction. PMID:25083853

  12. 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

  13. Effects Of Desensitization Treatment On Core-Condition Training

    ERIC Educational Resources Information Center

    Fry, P. S.

    1973-01-01

    Pre- and posttest ratings on measures of helping skills such as empathy, respect, concreteness, and genuineness were obtained in the preliminary and advanced training. A significant training effect was obtained for both groups. Desensitization treatment was a significant source of variance for the experimental subjects in training. (Author/LA)

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

    ERIC Educational Resources Information Center

    Miller, William R.; DiPilato, Marina

    1983-01-01

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

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

    PubMed

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

    2013-06-01

    We describe a patient with interstitial granuloma annulare associated with subcutaneous injection therapy (SIT) for desensitization to a type I allergy. Asymptomatic, erythematous, violaceous annular patches were located at the injection sites on both her arms. Medical history revealed perennial rhinoconjonctivitis treated with SIT (Phostal Stallergen® cat 100% and D. pteronyssinus/D.farinae 50%:50%). PMID:24011321

  16. Behavioral Support for Systematic Desensitization for Communication Apprehension

    ERIC Educational Resources Information Center

    And Others; Goss, Blaine

    1978-01-01

    Reports two experiments designed to further understanding of the effects of systematic desensitization (SD) training on college students and presents experimental test results indicating that students in SD do not differ significantly from those who choose not to join SD. (MH)

  17. Counterconditioning versus Relaxation in the Desensitization of Test Anxiety

    ERIC Educational Resources Information Center

    Laxer, R. M.; Walker, Keith

    1970-01-01

    Hypotheses that efficacy of systematic desensitization could be attributed to anxlety reduction as a result of relaxation training, to extinction of nonreinforced fear responses, or to operation of placebo factors were tested as alternatives to counterconditioning hypothesis. Test anxiety reduction was found only for subjects given relaxation…

  18. The Effectiveness of a Generic Computer Program for Systematic Desensitization.

    ERIC Educational Resources Information Center

    Chandler, Gerald M.; And Others

    1988-01-01

    Discussion of applications of computer technology in the mental health field focuses on the design, implementation, and effectiveness of an interactive generic computer program for the systematic desensitization of phobias. Guidelines for developing the program are presented; Goal Attainment Scaling is discussed; and suggestions for future…

  19. The Process of Fear Reduction Through Systematic Desensitization

    ERIC Educational Resources Information Center

    Schroeder, Harold E.; Rich, Alex R.

    1976-01-01

    This study investigated the process of fear change during a course of systematic desensitization therapy. Behavioral, subjective, and physiological measures of fear were taken following each of eight therapy sessions. Changes in one fear system did not appear to be primary in initiating changes in the other fear systems. (Author)

  20. A Group Desensitization Procedure for the Reduction of Death Anxiety.

    ERIC Educational Resources Information Center

    Peal, Ronald L.; And Others

    1981-01-01

    Investigates the effectiveness of group systematic desensitization in reducing death anxiety. Densensitization proved to be superior with both a relaxation and test-retest group when the revised Livingston and Zimet Death Anxiety Scale was the criterion measure. Mixed results were obtained when other scales were used. (Author/JAC)

  1. 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…

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

    ERIC Educational Resources Information Center

    Olson, Alton T.; Gillingham, D. Elaine

    1980-01-01

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

  3. 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

  4. 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

  5. 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…

  6. 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…

  7. 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

  8. 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

  9. 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

  10. The ring nerve of the box jellyfish Tripedalia cystophora.

    PubMed

    Garm, A; Poussart, Y; Parkefelt, L; Ekström, P; Nilsson, D-E

    2007-07-01

    Box jellyfish have the most elaborate sensory system and behavioural repertoire of all cnidarians. Sensory input largely comes from 24 eyes situated on four club-shaped sensory structures, the rhopalia, and behaviour includes obstacle avoidance, light shaft attractance and mating. To process the sensory input and convert it into the appropriate behaviour, the box jellyfish have a central nervous system (CNS) but this is still poorly understood. The CNS has two major components: the rhopalial nervous system and the ring nerve. The rhopalial nervous system is situated within the rhopalia in close connection with the eyes, whereas the ring nerve encircles the bell. We describe the morphology of the ring nerve of the box jellyfish Tripedalia cystophora as ascertained by normal histological techniques, immunohistochemistry and transmission electron microscopy. By light microscopy, we have estimated the number of cells in the ring nerve by counting their nuclei. In cross sections at the ultrastructural level, the ring nerve appears to have three types of neurites: (1) small "normal"-looking neurites, (2) medium-sized neurites almost completely filled by electron-lucent vacuoles and (3) giant neurites. In general, only one giant neurite is seen on each section; this type displays the most synapses. Epithelial cells divide the ring nerve into compartments, each having a tendency to contain neurites of similar morphology. The number and arrangement of the compartments vary along the length of the ring nerve. PMID:17340150

  11. 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

  12. 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

  13. Nerve Regeneration: Understanding Biology and Its Influence on Return of Function After Nerve Transfers.

    PubMed

    Gordon, Tessa

    2016-05-01

    Poor functional outcomes are frequent after peripheral nerve injuries despite the regenerative support of Schwann cells. Motoneurons and, to a lesser extent, sensory neurons survive the injuries but outgrowth of axons across the injury site is slow. The neuronal regenerative capacity and the support of regenerating axons by the chronically denervated Schwann cells progressively declines with time and distance of the injury from the denervated targets. Strategies, including brief low-frequency electrical stimulation that accelerates target reinnervation and functional recovery, and the insertion of cross-bridges between a donor nerve and a recipient denervated nerve stump, are effective in promoting functional outcomes after complete and incomplete injuries. PMID:27094884

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

    PubMed Central

    Paradiso, K G; Steinbach, Joe Henry

    2003-01-01

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

  15. Differential fiber-specific block of nerve conduction in mammalian peripheral nerves using kilohertz electrical stimulation.

    PubMed

    Patel, Yogi A; Butera, Robert J

    2015-06-01

    Kilohertz electrical stimulation (KES) has been shown to induce repeatable and reversible nerve conduction block in animal models. In this study, we characterized the ability of KES stimuli to selectively block specific components of stimulated nerve activity using in vivo preparations of the rat sciatic and vagus nerves. KES stimuli in the frequency range of 5-70 kHz and amplitudes of 0.1-3.0 mA were applied. Compound action potentials were evoked using either electrical or sensory stimulation, and block of components was assessed through direct nerve recordings and muscle force measurements. Distinct observable components of the compound action potential had unique conduction block thresholds as a function of frequency of KES. The fast component, which includes motor activity, had a monotonically increasing block threshold as a function of the KES frequency. The slow component, which includes sensory activity, showed a nonmonotonic block threshold relationship with increasing KES frequency. The distinct trends with frequency of the two components enabled selective block of one component with an appropriate choice of frequency and amplitude. These trends in threshold of the two components were similar when studying electrical stimulation and responses of the sciatic nerve, electrical stimulation and responses of the vagus nerve, and sensorimotor stimulation and responses of the sciatic nerve. This differential blocking effect of KES on specific fibers can extend the applications of KES conduction block to selective block and stimulation of neural signals for neuromodulation as well as selective control of neural circuits underlying sensorimotor function. PMID:25878155

  16. Morphometric nerve fiber analysis and aging process of the human inferior alveolar nerve.

    PubMed

    Sagara, N; Moriyama, H; Miyauchi, Y; Tani, H; Goto, N

    2001-08-01

    We studied morphometric nerve fiber analysis and the aging process of the inferior alveolar nerve (IAN). Human IANs were resected at the mandibular foramen. The preparation of sections involved fixation, washing, dehydration, embedding, sectioning and staining as described in our previous reports. We estimated the total number of myelinated axons in the IAN being average 26,200, the transverse area of those being average 37.1 microns 2, the average perimeter of those being 23.0 microns, the average circularity ratio of those being 0.85, respectively. According to these results, the IAN did not demonstrate notable age-relation change in any measured item. The IAN differed from not only our previous data on the human motor peripheral nerves but also those on the human sensory peripheral nerves. With regard to the aging process, the IAN indicated morphological features compared with other peripheral nerves. PMID:11732205

  17. 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

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

    PubMed Central

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

    1988-01-01

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

  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. 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

  1. Emotionally numb: Desensitization to community violence exposure among urban youth.

    PubMed

    Kennedy, Traci M; Ceballo, Rosario

    2016-05-01

    Community violence exposure (CVE) is associated with numerous psychosocial outcomes among youth. Although linear, cumulative effects models have typically been used to describe these relations, emerging evidence suggests the presence of curvilinear associations that may represent a pattern of emotional desensitization among youth exposed to chronic community violence. This study uses longitudinal data to investigate relations between CVE and both internalizing and externalizing symptoms among 3,480 youth ages 3 to 12 at baseline and 9 to 18 at outcome. Results support desensitization models, as evidenced by longitudinal quadratic associations between Wave 2 CVE and Wave 3 anxiety/depressive symptoms, alongside cross-sectional linear associations between Wave 3 CVE and Wave 3 aggression. Neither age nor gender moderated the associations between CVE and well-being. (PsycINFO Database Record PMID:26986229

  2. 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 Å 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

  3. 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

  4. Altered expression of the voltage-gated calcium channel subunit α2δ-1: A comparison between two experimental models of epilepsy and a sensory nerve ligation model of neuropathic pain

    PubMed Central

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

    2014-01-01

    The auxiliary α2δ-1 subunit of voltage-gated calcium channels is up-regulated in dorsal root ganglion neurons following peripheral somatosensory nerve damage, in several animal models of neuropathic pain. The α2δ-1 protein has a mainly presynaptic localization, where it is associated with the calcium channels involved in neurotransmitter release. Relevant to the present study, α2δ-1 has been shown to be the therapeutic target of the gabapentinoid drugs in their alleviation of neuropathic pain. These drugs are also used in the treatment of certain epilepsies. In this study we therefore examined whether the level or distribution of α2δ-1 was altered in the hippocampus following experimental induction of epileptic seizures in rats, using both the kainic acid model of human temporal lobe epilepsy, in which status epilepticus is induced, and the tetanus toxin model in which status epilepticus is not involved. The main finding of this study is that we did not identify somatic overexpression of α2δ-1 in hippocampal neurons in either of the epilepsy models, unlike the upregulation of α2δ-1 that occurs following peripheral nerve damage to both somatosensory and motor neurons. However, we did observe local reorganization of α2δ-1 immunostaining in the hippocampus only in the kainic acid model, where it was associated with areas of neuronal cell loss, as indicated by absence of NeuN immunostaining, dendritic loss, as identified by areas where microtubule-associated protein-2 immunostaining was missing, and reactive gliosis, determined by regions of strong OX42 staining. PMID:24641886

  5. Pure sensory Guillain-Barré syndrome: A case report and review of the literature

    PubMed Central

    YANG, JINGJING; HUAN, MINGMING; JIANG, HUAJUN; SONG, CHUNLI; ZHONG, LIN; LIANG, ZHANHUA

    2014-01-01

    Sensory Guillain-Barré syndrome (GBS) is an acute demyelinating neuropathy that presents clinically with involvement of the sensory peripheral nerve only. To date, <10 cases of pure sensory GBS have been reported; thus, the clinical and pathological features of sensory variant GBS are yet to be well characterized. The current study reports the case of a 43-year-old female that presented with acute, symmetric and monophasic sensory neuropathy, without motor weakness. Patient history, clinical examination, routine nerve conduction studies and sural nerve biopsy were reviewed. All the observations were consistent with a diagnosis of pure sensory GBS. In particular, the pathological features of the sural nerve biopsy revealed that the form of regenerated nerve fibers have complete structure of myelinated nerve fascicles, and these myelinated nerve fibers are thicker than other parts of the biopsy. The patient received small-dose (20 mg/day) prednisone initially, but without any benefit. Satisfactory improvements were observed with one course of intravenous immunoglobulin. PMID:25289029

  6. Optic Nerve Imaging

    MedlinePlus

    ... is a special laser that produces a three-dimensional high-resolution image of the optic nerve. This ... the nerve fiber layer and create a three dimensional representation of the optic nerve. Last reviewed on ...

  7. 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 ...

  8. The distribution of nerves in human deciduous and permanent teeth.

    PubMed

    Itoh, K

    1976-11-01

    Human permanent teeth without caries, obtained from 10-16 year old males and females and noncarious human deciduous teeth in which roots remained intact or were only poorly resorbed, were studied histologically. The distribution of sensory nerves in deciduous teeth were compared with that in permanent teeth by means of the silver-nitrate technique. 1. In radicular pulp, the sensory nerve fiber bundles accompany blood vessels in the axial area and several nerve single-fibers occur in the peripheral area of the pulp. 2. The subodontoblastic nerve plexus is formed in or beneath the cell-rich zone of the coronal pulp, and further, the marginal nerve plexus is built up near the pulpo-predentinal border. 3. The nerve fibers entering the predentin can be classified into 3 types by their courses. In the first type, nerve fibers pass directly toward the calcification front along the dentinal tubules in the predentin. In the second type, nerve fibers run obliquely or transversely in the predentin. The transversal fibers form a plexus-like structure by dividing and interlacing at various levels of predentin. The third type nerve fibers pass along the dentinal tubules in the predentin and, after reaching the predentino-dentinal border, reverse the odontoblast layer, thus forming a looped course. 4. There is no essential difference between the nerve supply in the deciduous and in the permanent teeth, but the nerves in the deciduous teeth are less dense in distribution and lower in amount than in the permanent teeth. Moreover, a typical marginal nerve plexus, which occurs constantly in the permanent teeth, is only occasionally found in the deciduous teeth; and no nerve fiber was observed to penetrate into the calcified dentin in the deciduous teeth. This finding seems to account for the fact that the deciduous teeth are less sensitive than their permanent successors. PMID:798562

  9. Fiber composition of the rat sciatic nerve.

    PubMed

    Schmalbruch, H

    1986-05-01

    The rat sciatic nerve originates from the spinal segments L4-L6. It is unifascicular at the trochanter; 5-7 mm distally, the nerve splits into two and then into four fascicles. The tibial portion gives rise to the tibial and the sural nerves, and the peroneal portion gives rise to the peroneal nerve and a cutaneous branch that perforates the lateral hamstring muscles to innervate the proximolateral face of the calf. The number and type of the axons in these branches were determined in light and electron micrographs of normal nerves, and after de-efferentation or sympathectomy. Deafferentation was technically not feasible because spinal ganglia and ventral roots were supplied by the same vascular plexus. The tibial nerve contained 1,000 motor and 3,500 myelinated afferent axons, 3,700 sympathetic axons, and 5,400 unmyelinated afferent axons. The peroneal nerve contained 600 motor and 1,300 myelinated afferent axons, 1,100 sympathetic axons and 3,000 unmyelinated afferent axons. The sural nerve contained 1,100 myelinated and 2,800 unmyelinated afferent axons; in addition, there were 1,500 unmyelinated sympathetic axons. The cutaneous branch consisted of 400 myelinated and 1,800 unmyelinated afferent axons. Thus, the entire sciatic nerve at midthigh is composed of about 27,000 axons; 6% are myelinated motor axons, 23% and 48% are myelinated and unmyelinated sensory axons, respectively, and 23% are unmyelinated sympathetic axons. The techniques used did not demonstrate sympathetic axons in the cutaneous branch and did not reveal the few motor axons contained in the sural nerve. PMID:3706794

  10. 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.

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

    NASA Astrophysics Data System (ADS)

    Freeman, Daniel K.; Fried, Shelley I.

    2011-02-01

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

  12. Pilot Study on the Effectiveness of Systematic Desensitization with Neurologically Impaired Children with Phobic Disorders

    ERIC Educational Resources Information Center

    Obler, Martin; Terwilliger, Robert F.

    1970-01-01

    A modified version of Wolpe's systematic desensitization therapy involving direct confrontation with the fear inducing stimulus was attempted with neurologically impaired children with phobic symptoms. (Author)

  13. 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 (μCT). 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 μCT. 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

  14. 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

  15. Interaction of myenteric neurons and extrinsic nerves in the intestinal inhibitory response induced by mesenteric nerve stimulation.

    PubMed

    Yamasato, T; Nakayama, S

    1991-04-01

    Effects of the mesenteric nerve stimulation (MNS) on the twitch contraction induced by field stimulation were investigated regarding the relationship between myenteric neurons and extrinsic cholinergic nerves in the guinea-pig mesenteric nerve-ileal preparation. The twitch contraction was inhibited after MNS. The inhibition of the twitch contraction after MNS was induced twice, just after MNS (1st inhibition) and 2-3 min later (2nd inhibition) (type I), or once, just after MNS (1st inhibition) (type II), in recovery course of twitch contraction for 6-8 min. The 1st inhibition was slightly decreased by guanethidine and hexamethonium. The inhibitory response (1st inhibition) in both types I and II was recovered to the control level by pretreatment with naloxone (recovered twitch contraction), but the late inhibitory response (2nd inhibition) was markedly observed after 2-3 min in types I and II. Either the 1st or the 2nd inhibition was not altered by capsaicin, desensitization to calcitonin gene-related polypeptide (CGRP), vasoactive intestinal polypeptide (VIP), somatostatin, or galanin. The recovered twitch contraction in types I and II was decreased by CGRP-desensitization, or capsaicin. These results suggest that the first inhibitory response was induced by enteric opioid neurons connected with extrinsic cholinergic nerves, but the 2nd inhibition was induced by unknown substances other than CGRP, VIP, somatostatin, and galanin. The twitch contraction may partly be induced by endogenous neurokinin-like substances. And, some CGRP containing neurons, which connect with extrinsic cholinergic nerves, probably activate the intrinsic excitatory neurons. PMID:1678243

  16. 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).

  17. 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 ...

  18. 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

  19. Ultrasound-guided Lateral Femoral Cutaneous Nerve Block in Meralgia Paresthetica.

    PubMed

    Kim, Jeong Eun; Lee, Sang Gon; Kim, Eun Ju; Min, Byung Woo; Ban, Jong Suk; Lee, Ji Hyang

    2011-06-01

    Meralgia paresthetica is a rarely encountered sensory mononeuropathy characterized by paresthesia, pain or sensory impairment along the distribution of the lateral femoral cutaneous nerve (LFCN) caused by entrapment or compression of the nerve as it crossed the anterior superior iliac spine and runs beneath the inguinal ligament. There is great variability regarding the area where the nerve pierces the inguinal ligament, which makes it difficult to perform blind anesthetic blocks. Ultrasound has developed into a powerful tool for the visualization of peripheral nerves including very small nerves such as accessory and sural nerves. The LFCN can be located successfully, and local anesthetic solution distribution around the nerve can be observed with ultrasound guidance. Our successfully performed ultrasound-guided blockade of the LFCN in meralgia paresthetica suggests that this technique is a safe way to increase the success rate. PMID:21716611

  20. Ultrasound-guided Lateral Femoral Cutaneous Nerve Block in Meralgia Paresthetica

    PubMed Central

    Kim, Jeong Eun; Kim, Eun Ju; Min, Byung Woo; Ban, Jong Suk; Lee, Ji Hyang

    2011-01-01

    Meralgia paresthetica is a rarely encountered sensory mononeuropathy characterized by paresthesia, pain or sensory impairment along the distribution of the lateral femoral cutaneous nerve (LFCN) caused by entrapment or compression of the nerve as it crossed the anterior superior iliac spine and runs beneath the inguinal ligament. There is great variability regarding the area where the nerve pierces the inguinal ligament, which makes it difficult to perform blind anesthetic blocks. Ultrasound has developed into a powerful tool for the visualization of peripheral nerves including very small nerves such as accessory and sural nerves. The LFCN can be located successfully, and local anesthetic solution distribution around the nerve can be observed with ultrasound guidance. Our successfully performed ultrasound-guided blockade of the LFCN in meralgia paresthetica suggests that this technique is a safe way to increase the success rate. PMID:21716611

  1. 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

  2. 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.

  3. 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

  4. 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

  5. The Anatomy and Morphology of the Superficial Peroneal Nerve.

    PubMed

    Ribak, Samuel; Fonseca, Juliano R; Tietzmann, Alexandre; Gama, Sérgio A M; Hirata, Helton H

    2016-05-01

    Background Knowledge on the anatomical and morphological characteristics of the superficial peroneal nerve is amenable to further refinement. This cadaveric study aimed to further evaluate anatomical and morphological characteristics of the superficial peroneal nerve. Methods In this study, 10 lower limbs from five fresh cadavers were dissected. The anatomical characteristics of the superficial peroneal nerve were identified. Nerve segments were submitted for histological and morphometric analyses, and nerve thicknesses and number of fascicles were assessed. Results Regarding the superficial peroneal nerve's bifurcation, 80% of the terminal branches were distal to the point of emergence from the fascia. In 90% limbs, two sensory branches were observed immediately after the distal bifurcation of the superficial peroneal nerve. The mean distance from the fibular head to the superficial peroneal nerve's emergence from the fascia was 24.6 cm and mean nerve thickness at this point was 0.3 cm. The mean distance between the lateral malleolus and the main nerve trunk at the ankle was 4.68 cm. The mean distance from the motor branch of the peroneus brevis to the lateral malleolus was 29.3 cm. Morphometric analyses revealed an average five nerve bundles at the broadest nerve diameter (2.6 mm). Conclusion The anatomical and morphometrical characteristics of the superficial peroneal nerve indicate that it may be a safe and useful donor for autologous graft treatment of peripheral nerve injuries. Our morphological study shows a median of five fascicles, and that the thickest diameter of the nerve was 2.6 mm at the emergence from the deep to the superficial compartment. PMID:26676677

  6. The effect of omega conotoxin GVIA, a peptide modulator of the N-type voltage sensitive calcium channels, on motor responses produced by activation of efferent and sensory nerves in mammalian smooth muscle.

    PubMed

    Maggi, C A; Patacchini, R; Santicioli, P; Lippe, I T; Giuliani, S; Geppetti, P; Del Bianco, E; Selleri, S; Meli, A

    1988-08-01

    1. The effect of omega-conotoxin (CTX) GVIA, a peptide which blocks neuronal calcium channels, were investigated on nerve-mediated motor responses in a variety of isolated smooth muscle preparations from rats and guinea-pigs. 2. In the rat or guinea-pig isolated vas deferens CTX (1 nM-1 microM) produced a concentration and time-related inhibition of the response to field stimulation, while the responses to KCl, noradrenaline or adenosine triphosphate were unaffected. In the presence of CTX a series of tetrodotoxin-resistant contractions could be elicited by field stimulation by increasing pulse width and/or voltage. 3. In the rat or guinea-pig isolated urinary bladder, CTX produced a concentration and time-dependent inhibition of twitch responses to field stimulation without affecting the response to exogenous acetylcholine. In the rat bladder the maximal effect did not exceed 25% inhibition while a much larger fraction of the response (about 70%) was inhibited in the guinea-pig bladder. The CTX-resistant response was abolished, in both tissues, by tetrodotoxin. 4. The effects of CTX in the rat bladder were also studied with a whole range of frequencies of field stimulation (0.1-50 Hz). Maximal inhibition was observed toward contractions elicited at frequencies of 2-5 Hz. At low frequencies the inhibitory effects of CTX and atropine were almost additive while at high frequencies of stimulation a large component of the atropine-sensitive response was CTX-resistant. 5. In the rat isolated proximal duodenum, field stimulation in the presence of atropine and guanethidine produced a primary relaxation followed by a rebound contraction.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:2460772

  7. 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

  8. Early interfaced neural activity from chronic amputated nerves.

    PubMed

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

    2009-01-01

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

  9. 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

  10. 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.

  11. Comparison of Three Methods of Reducing Test Anxiety: Systematic Desensitization, Implosive Therapy, and Study Counseling

    ERIC Educational Resources Information Center

    Cornish, Richard D.; Dilley, Josiah S.

    1973-01-01

    Systematic desensitization, implosive therapy, and study counseling have all been effective in reducing test anxiety. In addition, systematic desensitization has been compared to study counseling for effectiveness. This study compares all three methods and suggests that systematic desentization is more effective than the others, and that implosive…

  12. The Role of Attention-Placebo Influences in the Efficacy of Systematic Desensitization

    ERIC Educational Resources Information Center

    McReynolds, William T.; And Others

    1973-01-01

    Systematic desensitization was compared with two attention-placebo control treatments--one taken from Paul and one currently devised as an elaborate, highly impressive therapeutic'' experience--and no treatment. It was hypothesized that (a) fear reductions following desensitization would be no greater than those associated with an equally…

  13. Desensitization And Study-Skills Training As Treatment For Two Types of Test-Anxious Students

    ERIC Educational Resources Information Center

    Osterhouse, Robert A.

    1972-01-01

    This study compared the effectiveness of systematic desensitization and training in efficient study methods for reducing test anxiety among subjects selected on the basis of two types of self reported anxiety. Desensitization offered more promise as a treatment method for test anxiety than did training in study skills. (Author)

  14. Cognitive Modification and Systematic Desensitization with Test Anxious High School Students.

    ERIC Educational Resources Information Center

    Leal, Lois L.; And Others

    1981-01-01

    Compares the relative effectiveness of cognitive modification and systematic desensitization with test anxious high school students (N=30). The systematic desensitization treatment appeared to be significantly more effective on the performance measure while cognitive modification was more effective on one of the self-report measures. (Author/JAC)

  15. Group Systematic Desensitization Versus Covert Positive Reinforcement in the Reduction of Test Anxiety

    ERIC Educational Resources Information Center

    Kostka, Marion P.; Galassi, John P.

    1974-01-01

    The study compared modified versions of systematic desensitization and covert positive reinforcement to a no-treatment control condition in the reduction of test anxiety. On an anagrams performance test, the covert reinforcement and control groups were superior to the desensitization group. (Author)

  16. Effects of Two Short-Term Desensitization Methods in the Treatment of Test Anxiety

    ERIC Educational Resources Information Center

    Richardson, Frank C.; Suinn, Richard M.

    1974-01-01

    Accelerated massed desensitization and anxiety management training were compared with standard systematic desensitization in terms of reducing self-reported test anxiety in high test-anxious college students. All three treatments significantly reduced test anxiety as compared with a waiting list control group. (Author)

  17. 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…

  18. Systematic Desensitization as a Method of Teaching a General Anxiety-Reducing Skill

    ERIC Educational Resources Information Center

    Zemore, Robert

    1975-01-01

    College students were treated with either a standard or modified version of systematic desensitization. Relative to a no-treatment control group, both treatment methods produced significant reductions in both the treated and untreated fears. The implications these findings have for two alternative conceptions of systematic desensitization are…

  19. 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…

  20. Effectiveness of Structured Psychodrama and Systematic Desensitization in Reducing Test Anxiety.

    ERIC Educational Resources Information Center

    Kipper, David A.; Giladi, Daniel

    1978-01-01

    Students with examination anxiety took part in study of effectiveness of two kinds of treatment, structured psychodrama and systematic desensitization, in reducing test anxiety. Results showed that subjects in both treatment groups significantly reduced test-anxiety scores. Structured psychodrama is as effective as systematic desensitization in…

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

    ERIC Educational Resources Information Center

    Suarez, Yolanda; And Others

    1976-01-01

    Flooding and systematic desensitization procedures were investigated for possible interactions with subject arousal level on reduction in phobic reactions. No such interaction was found. Behaviorally and on GSR response, both flooding and systematic desensitization were effective, but only the latter was effective on subjective reports. (NG)

  2. 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

  3. 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…

  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. The Role of Relaxation in the Desensitization Process: Guidelines and Precautions.

    ERIC Educational Resources Information Center

    Seamons, Terry R.

    The theoretical basis for Wolpe's systematic desensitization, with its principle of reciprocal inhibition and its emphasis on the role of physiological relaxation, is explained. The author examines the literature relevant to the effectiveness of desensitization with, and without, relaxation, as well as the effectiveness of relaxation alone. All 3…

  6. Too much experience: a desensitization bias in emotional perspective taking.

    PubMed

    Campbell, Troy; O'Brien, Ed; Van Boven, Leaf; Schwarz, Norbert; Ubel, Peter

    2014-02-01

    People often use their own feelings as a basis to predict others' feelings. For example, when trying to gauge how much someone else enjoys a television show, people might think "How much do I enjoy it?" and use this answer as basis for estimating others' reactions. Although personal experience (such as actually watching the show oneself) often improves empathic accuracy, we found that gaining too much experience can impair it. Five experiments highlight a desensitization bias in emotional perspective taking, with consequences for social prediction, social judgment, and social behavior. Participants who viewed thrilling or shocking images many times predicted first-time viewers would react less intensely (Experiments 1 and 2); participants who heard the same funny joke or annoying noise many times estimated less intense reactions of first-time listeners (Experiments 3 and 4); and further, participants were less likely to actually share good jokes and felt less bad about blasting others with annoying noise after they themselves became desensitized to those events (Experiments 3-5). These effects were mediated by participants' own attenuated reactions. Moreover, observers failed to anticipate this bias, believing that overexposed participants (i.e., repeatedly exposed participants who became desensitized) would make better decisions on their behalf (Experiment 5). Taken together, these findings reveal a novel paradox in emotional perspective taking: If people experience an evocative event many times, they may not become wiser companions but worse, unable to disentangle self-change from other-oriented thinking. Just as lacking exposure to others' experiences can create gaps in empathy and understanding, so may gaining too much. PMID:24467422

  7. 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.

  8. Increased Numbers of Thoracic Dorsal Root Axons in Rats Given Antibodies to Nerve Growth Factor

    NASA Astrophysics Data System (ADS)

    Hulsebosch, C. E.; Coggeshall, R. E.; Perez-Polo, J. R.

    1984-08-01

    Sensory axons were counted in untreated 1-month-old rats and in littermates that were injected with antibodies to nerve growth factor. There were 45 percent more unmyelinated and 17 percent more myelinated axons in dorsal roots of the fifth thoracic spinal segment in treated rats. This suggests that the number of sensory axons can be changed by postnatal inactivation of nerve growth factor.

  9. Chronic fatigue syndrome from vagus nerve infection: a psychoneuroimmunological hypothesis.

    PubMed

    VanElzakker, Michael B

    2013-09-01

    Chronic fatigue syndrome (CFS) is an often-debilitating condition of unknown origin. There is a general consensus among CFS researchers that the symptoms seem to reflect an ongoing immune response, perhaps due to viral infection. Thus, most CFS research has focused upon trying to uncover that putative immune system dysfunction or specific pathogenic agent. However, no single causative agent has been found. In this speculative article, I describe a new hypothesis for the etiology of CFS: infection of the vagus nerve. When immune cells of otherwise healthy individuals detect any peripheral infection, they release proinflammatory cytokines. Chemoreceptors of the sensory vagus nerve detect these localized proinflammatory cytokines, and send a signal to the brain to initiate sickness behavior. Sickness behavior is an involuntary response that includes fatigue, fever, myalgia, depression, and other symptoms that overlap with CFS. The vagus nerve infection hypothesis of CFS contends that CFS symptoms are a pathologically exaggerated version of normal sickness behavior that can occur when sensory vagal ganglia or paraganglia are themselves infected with any virus or bacteria. Drawing upon relevant findings from the neuropathic pain literature, I explain how pathogen-activated glial cells can bombard the sensory vagus nerve with proinflammatory cytokines and other neuroexcitatory substances, initiating an exaggerated and intractable sickness behavior signal. According to this hypothesis, any pathogenic infection of the vagus nerve can cause CFS, which resolves the ongoing controversy about finding a single pathogen. The vagus nerve infection hypothesis offers testable hypotheses for researchers, animal models, and specific treatment strategies. PMID:23790471

  10. 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

  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. 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

  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. Structural mechanism of glutamate receptor activation and desensitization.

    PubMed

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

    2014-10-16

    Ionotropic glutamate receptors are ligand-gated ion channels that mediate excitatory synaptic transmission in the vertebrate brain. To gain a better understanding of how structural changes gate ion flux across the membrane, we trapped rat AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid) and kainate receptor subtypes in their major functional states and analysed 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 two-fold to four-fold symmetry transition in the ligand-binding domains in both subtypes. The 7.6 Å 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

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

    PubMed Central

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

    2014-01-01

    Previous studies demonstrated that Schwann cells (SCs) express distinct motor and sensory phenotypes, which impact the ability of these pathways to selectively support regenerating neurons. In the present study, unbiased microarray analysis was used to examine differential gene expression in denervated motor and sensory pathways in rats. Several genes that were significantly upregulated in either denervated sensory or motor pathways were identified and two secreted factors were selected for further analysis: osteopontin (OPN) and clusterin (CLU) which were upregulated in denervated motor and sensory pathways, respectively. Sciatic nerve transection induced upregulation of OPN and CLU and expression of both returned to baseline levels with ensuing regeneration. In vitro analysis using exogenously applied OPN induced outgrowth of motor but not sensory neurons. CLU, however, induced outgrowth of sensory neurons, but not motor neurons. To assess the functional importance of OPN and CLU, peripheral nerve regeneration was examined in OPN and CLU−/− mice. When compared with OPN+/+ mice, motor neuron regeneration was reduced in OPN−/− mice. Impaired regeneration through OPN−/− peripheral nerves grafted into OPN+/+ mice indicated that loss of OPN in SCs was responsible for reduced motor regeneration. Sensory neuron regeneration was impaired in CLU−/− mice following sciatic nerve crush and impaired regeneration nerve fibers through CLU−/− nerve grafts transplanted into CLU+/+ mice indicated that reduced sensory regeneration is likely due to SC-derived CLU. Together, these studies suggest unique roles for SC-derived OPN and CLU in regeneration of peripheral motor and sensory axons. PMID:24478351

  16. The sensory ending of duck muscle spindles.

    PubMed Central

    Adal, M N; Chew Cheng, S B

    1980-01-01

    Thin and thick types of muscle spindles have been demonstrated from the extensor pollicis (EP) and the extensor digitorum communis (EDC) wing muscles of the duck. The thin type shows a smaller capsule, innervated by a long and narrow sensory ending; the thick type consists of a larger capsule innervated by a truncated and wide sensory ending. Each spindle receives an afferent nerve fibre within the range of 2.1-8.4 microns diameter and the ratio between fibre and sensory ending is always 1:1. There is no secondary sensory ending in duck spindles. By electron microscopy, sensory terminals of different sizes may be seen to lie in depressions of various depths on intrafusal muscle fibres, usually without disturbing the external contour of the muscle fibre, and are covered externally by a rather thick layer of basement membrane. Images Fig. 1 Fig. 2 Fig. 3 Figs. 4-5 Fig. 6 Fig. 7 Fig. 8 Fig. 9 Fig. 10 PMID:6452432

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

    PubMed Central

    Ishikawa, Namiko; Tanihara, Masao; Saito, Susumu

    2016-01-01

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

  18. 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...

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

    PubMed

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

    2013-11-01

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

  20. 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

  1. 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

  2. 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

  3. Desensitization of mammalian. beta. -adrenergic receptors: receptor sequestration vs. receptor function

    SciTech Connect

    Kassis, S.; Olasmaa, M.; Fishman, P.H.

    1986-05-01

    Human A431 and rat glioma C6 cells exposed to isoproterenol (ISO) underwent a time and dose dependent loss of ISO-stimulated adenylate cyclase (AC) activity (desensitization). In addition, ..beta..-adrenergic receptors (..beta..AR) became less accessible to the hydrophilic antagonist (/sup 3/H)CGP-12177 and redistributed from the heavier density plasma membrane fraction to a lighter density membrane fraction (sequestration). Pretreatment of the cells with Concanavalin A (Con A) or phenylarsine oxide blocked sequestration but not desensitization. ..beta..AR of membranes prepared from Con A-pretreated cells exhibited a reduced affinity for ISO after desensitization as measured by the half-maximal concentration of ISO required to stimulate AC (Kact) and to compete for antagonist binding (IC50). Membranes were exposed to alkali to inactivate AC and ..beta..AR was transferred to a foreign AC by membrane fusion with polyethylene glycol. ..beta..AR from desensitized cells exhibited a reduced affinity for ISO (both Kact and IC50) and a reduced ability to stimulate the foreign AC. In addition, ..beta..AR from desensitized cells remained accessible to (/sup 3/H)CGP-12177 in the fused membranes. The authors conclude that the primary, essential step in desensitization is a reduction in ..beta..AR function. In contrast, ..beta..AR sequestration is not a prerequisite but a secondary event in the desensitization process.

  4. 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

  5. [Surgery-induced abdominal wall nerve entrapment: do not overlook intensive postoperative pain].

    PubMed

    Tuuliranta, Mikko

    2016-01-01

    The most common cause of persistent postoperative pain after inguinal hernia repair is entrapment of a sensory nerve in the wound closure, The pain may be triggered by touching the skin, and the pain is relieved after a nerve block. In two patient cases, division of the nerve immediately terminated the pain, and the relief seemed to be permanent. Pains are common in inguinal hernia scars, but also after an appendectomy operation and Pfannenstiel's incision. PMID:27044184

  6. Mucosal sensory threshold of urinary bladder and urethra measured electrically.

    PubMed

    Kiesswetter, H

    1977-01-01

    Urodynamic investigation consists of evaluation of detrusor stretch responses, muscle strength and motor activities. The electrosensitivity test is the only method to evaluate mucosal sensory threshold of exteroceptive receptors in urinary bladder and posterior urethra thus checking integrity of sensory reflex arcs. A constant current square wave pulse of 0.5 msec duration and 10 msec interval is used with increasing amplitude from 0 to 25 mA until the patient registers sensation. Skin electrosensitivity is tested to start with, then perception threshold of urinary bladder and posterior urethra is recorded. Sensory deficits after segmental sacral nerve lesions or after peripheral nerve injuries postoperatively can be quantitated in terms of milliamperes. The urgency syndrome in adult women is characterized by a low perception threshold in the posterior urethra (below 1 mA) while the bladder electrosensitivity is within normal range (3--10 mA). PMID:610035

  7. Comparison of Automated versus Traditional Nerve Conduction Study Methods for Median Nerve Testing in a General Worker Population

    PubMed Central

    Dale, Ann Marie; Agboola, Folasade; Yun, Amber; Zeringue, Angelique; Al-Lozi, Muhammed T.; Evanoff, Bradley

    2014-01-01

    Objective To investigate the validity of automated nerve conduction studies compared to traditional electrodiagnostic studies (EDS) for testing median nerve abnormalities in a working population. Design Agreement study and sensitivity investigation from two devices Setting Field research testing lab Participants Active workers from several industries participating in a longitudinal study of CTS. Methods Sixty-two subjects received bilateral median and ulnar nerve conduction testing across the wrist with a traditional device and the NC-stat automated device. We compared intermethod agreement of analogous measurements. Main outcome measurement Nerve conduction study parameters Results Median motor and sensory latency comparisons showed excellent agreement (intra-class correlation 0.85 and 0.80 respectively). Areas under the receiver operator characteristic curves were 0.97 and 0.96 respectively, using the optimal thresholds of 4.4ms median motor latency (sensitivity 100%, specificity 86%) and 3.9ms median sensory latency (sensitivity 100%, specificity 87%). Ulnar nerve testing results were less favorable. Conclusion The automated NC-stat device showed excellent agreement with traditional EDS for detecting median nerve conduction abnormalities in a general population of workers, suggesting that this automated nerve conduction device can be used to ascertain research case definitions of CTS in population health studies. Further study is needed to determine optimal thresholds for defining median conduction abnormalities in populations that are not seeking clinical care. PMID:25463687

  8. 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)

  9. 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 ...

  10. 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.

  11. Distal median nerve dysfunction

    MedlinePlus

    ... affect nerves. Medical conditions such as diabetes and kidney disease can damage nerves. In these cases, treatment is directed at the medical condition. Physical therapy exercises may help some peoplemaintain muscle strength. Orthopedic ...

  12. Tibial nerve dysfunction

    MedlinePlus

    ... a loss of movement or sensation in the foot from damage to the tibial nerve. ... Tibial nerve dysfunction is an unusual form of peripheral ... the calf and foot muscles. A problem in function with a single ...

  13. Ontogeny of beta-adrenoceptor/adenylyl cyclase desensitization mechanisms: the role of neonatal innervation.

    PubMed

    Slotkin, T A; Saleh, J L; Zhang, J; Seidler, F J

    1996-12-01

    The ability of adrenergic stimulation to elicit desensitization of the beta-receptor/adenylyl cyclase signaling cascade is not an inherent property of cells but rather is acquired during the period in which sympathetic innervation develops. This study examines whether innervation provides the signal that enables target cardiac and hepatic cells to learn to desensitize their responses. Neonatal rats were sympathectomized with 6-OHDA on postnatal day 1 and were treated at various ages with a regimen of isoproterenol known to elicit desensitization in adults. In control rats, desensitization first appeared between days 6 and 15. Desensitization was heterologous, involving changes in the efficiency of G-protein coupling, as there were parallel decreases in isoproterenol-stimulated adenylyl cyclase activity, basal activity and fluoride-stimulated activity (maximal G-protein activation) without changes in forskolin-Mn2+-stimulated activity (total cyclase catalytic activity). The lesioned animals showed a delay in the onset of desensitization as isoproterenol did not evoke decreased responsiveness until day 25 in the heart; the liver did not display agonist-induced desensitization even at day 25. The effects of lesioning on development of desensitization were entirely separable from those on regulation of beta-receptors themselves: agonist-induced decreases in receptor binding appeared by day 15 in both control and lesioned animals. Uniquely in the youngest animals (6 days old), isoproterenol treatment produced heterologous sensitization of adenylyl cyclase responses rather than desensitization, with a parallel increase in basal, isoproterenol-, fluoride- and forskolin-Mn2+-stimulated activity; the latter indicates induction of total catalytic activity as the primary mechanism of sensitization. The lesioned neonates did not show sensitization, despite the fact that during this period, sympathetic pathways are not functionally competent. Our results indicate that innervation provides a timing signal for the onset of desensitization capabilities of sympathetic target cells, but is not absolutely required for the cells to learn how to desensitize. Prior to the onset of desensitization, agonists induce sensitization that may be important in preserving physiological responsiveness during ontogenetic surges of adrenergic activity. The absence of sensitization in lesioned animals implies that, before physiological function is completely established, early pioneer synapses provide a trophic signal that enables cells to increase their sensitivity to stimulation during the perinatal transition period. PMID:9117411

  14. Time-varying pulse trains limit retinal desensitization caused by continuous electrical stimulation.

    PubMed

    Davuluri, Navya S; Weiland, James D

    2014-01-01

    An epiretinal prosthesis aims to restore functional vision in patients suffering from retinal degeneration caused by diseases such as Retinitis Pigmentosa (RP) and Age-Related Macular Degeneration (AMD). These diseases result in the loss of photoreceptors but bipolar, amacrine and ganglion cells survive at high rates and can be electrically activate to produce the sensation of light. Continuous application of biphasic stimulus pulses results in desensitization of the retina. In humans, this manifests as decreased brightness and increased stimulus thresholds. This study presents an in vivo model of retinal desensitization caused by continuous electrical stimulation and describes a novel stimulation pattern that limit desensitization. PMID:25569984

  15. 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

  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. Human periodontal ligament stem cells repair mental nerve injury

    PubMed Central

    Li, Bohan; Jung, Hun-Jong; Kim, Soung-Min; Kim, Myung-Jin; Jahng, Jeong Won; Lee, Jong-Ho

    2013-01-01

    Human periodontal ligament stem cells are easily accessible and can differentiate into Schwann cells. We hypothesized that human periodontal ligament stem cells can be used as an alternative source for the autologous Schwann cells in promoting the regeneration of injured peripheral nerve. To validate this hypothesis, human periodontal ligament stem cells (1 × 106) were injected into the crush-injured left mental nerve in rats. Simultaneously, autologous Schwann cells (1 × 106) and PBS were also injected as controls. Real-time reverse transcriptase polymerase chain reaction showed that at 5 days after injection, mRNA expression of low affinity nerve growth factor receptor was significantaly increased in the left trigeminal ganglion of rats with mental nerve injury. Sensory tests, histomorphometric evaluation and retrograde labeling demonstrated that at 2 and 4 weeks after injection, sensory function was significantly improved, the numbers of retrograde labeled sensory neurons and myelinated axons were significantly increased, and human periodontal ligament stem cells and autologous Schwann cells exhibited similar therapeutic effects. These findings suggest that transplantation of human periodontal ligament stem cells show a potential value in repair of mental nerve injury. PMID:25206604

  18. 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

  19. 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.

  20. 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

  1. Deficiency in Monocarboxylate Transporter 1 (MCT1) in Mice Delays Regeneration of Peripheral Nerves following Sciatic Nerve Crush

    PubMed Central

    Morrison, Brett M.; Tsingalia, Akivaga; Vidensky, Svetlana; Lee, Youngjin; Jin, Lin; Farah, Mohamed H.; Lengacher, Sylvain; Magistretti, Pierre J.; Pellerin, Luc; Rothstein, Jeffrey D.

    2014-01-01

    Peripheral nerve regeneration following injury occurs spontaneously, but many of the processes require metabolic energy. The mechanism of energy supply to axons has not previously been determined. In the central nervous system, monocarboxylate transporter 1 (MCT1), expressed in oligodendroglia, is critical for supplying lactate or other energy metabolites to axons. In the current study, MCT1 is shown to localize within the peripheral nervous system to perineurial cells, dorsal root ganglion neurons, and Schwann cells by MCT1 immunofluorescence and MCT1 tdTomato BAC reporter mice. To investigate whether MCT1 is necessary for peripheral nerve regeneration, sciatic nerves in MCT1 heterozygous null mice are crushed and peripheral nerve regeneration quantified electrophysiologically and anatomically. Compound muscle action potential (CMAP) recovery is delayed from a median of 21 days in wild-type mice to greater than 38 days in MCT1 heterozygote null mice. In fact, half of the MCT1 heterozygote null mice have no recovery of CMAP at 42 days, while all of the wild-type mice recovered. In addition, muscle fibers remain 40% more atrophic and neuromuscular junctions 40% more denervated at 42 days post-crush in the MCT1 heterozygote null mice than wild-type mice. The delay in nerve regeneration is not only in motor axons, as the number of regenerated axons in the sural sensory nerve of MCT1 heterozygote null mice at 4 weeks and tibial mixed sensory and motor nerve at 3 weeks is also significantly reduced compared to wild-type mice. This delay in regeneration may be partly through failed Schwann cell function, as there is reduced early phagocytosis of myelin debris and remyelination of axon segments. These data for the first time demonstrate that MCT1 is critical for regeneration of both sensory and motor axons in mice following sciatic nerve crush. PMID:25447940

  2. 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

  3. 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

  4. 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

  5. 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.

  6. 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

  7. A Further Assessment of Attention-Placebo Effects and Demand Characteristics in Studies of Systematic Desensitization

    ERIC Educational Resources Information Center

    McReynolds, William T.; Tori, Christopher

    1972-01-01

    It was predicted that phobic Ss receiving systematic desensitization would show greater reductions on both fear-related behavior measures and simulated fear measures than Ss receiving relaxation treatment or no treatment at all. The prediction was confirmed. (Author)

  8. Inducing Assertive Behavior in Chronic Schizophrenics: A Comparison of Socioenvironmental Desensitization, and Relaxation Therapies

    ERIC Educational Resources Information Center

    Weinman, Bernard; And Others

    1972-01-01

    It is concluded that systematic desensitization or relaxation therapy is not effective in inducing assertive behavior in the male chronic schizophrenic. The treatment of choice for the older chronic male schizophrenic remains socioenvironmental therapy. (Author)

  9. Rational-Emotive Therapy versus Systematic Desensitization: A Comment on Moleski and Tosi.

    ERIC Educational Resources Information Center

    Atkinson, Leslie

    1983-01-01

    Questioned the statistical analyses of the Moleski and Tosi investigation of rational-emotive therapy versus systematic desensitization. Suggested means for lowering the error rate through a more efficient experimental design. Recommended a reanalysis of the original data. (LLL)

  10. Quantifying Hierarchy Stimuli in Systematic Desensitization Via GSR: A Preliminary Investigation

    ERIC Educational Resources Information Center

    Barabasz, Arreed F.

    1974-01-01

    The aim of the method for quantifying hierarchy stimuli by Galvanic Skin Resistance recordings is to improve the results of systematic desensitization by attenuating the subjective influences in hierarchy construction which are common in traditional procedures. (Author/CS)

  11. 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

  12. 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

  13. 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.

  14. 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

  15. Fast desensitization of the nicotinic receptor at the mouse neuromuscular junction

    PubMed Central

    Pennefather, P.; Quastel, D.M.J.

    1982-01-01

    1 When low concentrations of carbachol (2-20 μM) were applied by local superfusion to mouse diaphragm endplates, there occurred a rapid decrease (within seconds) in the height of miniature endplate currents (m.e.p.cs) in addition to the increase of muscle membrane conductance. 2 With 2, 5, 10 and 20 μM carbachol, m.e.p.c. heights were diminished by 5, 10, 30 and 50% respectively. A subsequent slow decrease in height took place at a rate corresponding to that reported for the slow desensitization produced by bath-applied carbachol (see Adams, 1975). 3 The effect of carbachol on m.e.p.c. height was not affected by poisoning of acetylcholinesterase (AChE). After poisoning of AChE, 4 μM acetylcholine (ACh) depressed m.e.p.c. height by 23%. 4 At 20 μM carbachol, both the onset and offset of the effect on m.e.p.c. height lagged behind the subsynaptic conductance change, and the calculated change of subsynaptic agonist concentration, by about 3 s; the onset rate was at least ten times faster than expected for slow desensitization. 5 When the conductance responses produced by carbachol were corrected for fast desensitization, the slope of the log-response log-dose line (Hill coefficient) was increased from 1.7 to 2.0. 6 The Hill coefficient for fast desensitization was 1.4. The data were compatible with a cyclic model for fast desensitization, with receptor activation not a prerequisite for desensitization of receptors. 7 The failure of AChE poisoning to affect m.e.p.c. height during desensitization suggests that desensitized receptor associated with exogenous agonist can continue to bind quantal ACh. PMID:7139194

  16. Immune Profiles to Predict Response to Desensitization Therapy in Highly HLA-Sensitized Kidney Transplant Candidates

    PubMed Central

    Yabu, Julie M.; Siebert, Janet C.; Maecker, Holden T.

    2016-01-01

    Background Kidney transplantation is the most effective treatment for end-stage kidney disease. Sensitization, the formation of human leukocyte antigen (HLA) antibodies, remains a major barrier to successful kidney transplantation. Despite the implementation of desensitization strategies, many candidates fail to respond. Current progress is hindered by the lack of biomarkers to predict response and to guide therapy. Our objective was to determine whether differences in immune and gene profiles may help identify which candidates will respond to desensitization therapy. Methods and Findings Single-cell mass cytometry by time-of-flight (CyTOF) phenotyping, gene arrays, and phosphoepitope flow cytometry were performed in a study of 20 highly sensitized kidney transplant candidates undergoing desensitization therapy. Responders to desensitization therapy were defined as 5% or greater decrease in cumulative calculated panel reactive antibody (cPRA) levels, and non-responders had 0% decrease in cPRA. Using a decision tree analysis, we found that a combination of transitional B cell and regulatory T cell (Treg) frequencies at baseline before initiation of desensitization therapy could distinguish responders from non-responders. Using a support vector machine (SVM) and longitudinal data, TRAF3IP3 transcripts and HLA-DR-CD38+CD4+ T cells could also distinguish responders from non-responders. Combining all assays in a multivariate analysis and elastic net regression model with 72 analytes, we identified seven that were highly interrelated and eleven that predicted response to desensitization therapy. Conclusions Measuring baseline and longitudinal immune and gene profiles could provide a useful strategy to distinguish responders from non-responders to desensitization therapy. This study presents the integration of novel translational studies including CyTOF immunophenotyping in a multivariate analysis model that has potential applications to predict response to desensitization, select candidates, and personalize medicine to ultimately improve overall outcomes in highly sensitized kidney transplant candidates. PMID:27078882

  17. 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

  18. Acute Alcohol Action and Desensitization of Ligand-Gated Ion Channels

    PubMed Central

    Dopico, Alex M.; Lovinger, David M.

    2009-01-01

    Ethanol exerts its biological actions through multiple receptors, including ion channels. Ion channels that are sensitive to pharmacologically relevant ethanol concentrations constitute a heterogeneous set, including structurally unrelated proteins solely sharing the property that their gating is regulated by a ligand(s). Receptor desensitization is almost universal among these channels, and its modulation by ethanol may be a crucial aspect of alcohol pharmacology and effects in the body. We review the evidence documenting interactions between ethanol and ionotropic receptor desensitization, and the contribution of this interaction to overall ethanol action on channel function. In some cases, such as type 3 serotonin, nicotinic acetylcholine, GABA-A, and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionate receptors, ethanol actions on apparent desensitization play a significant role in acute drug action on receptor function. In a few cases, mutagenesis helped to identify different areas within a receptor protein that differentially sense n-alcohols, resulting in differential modulation of receptor desensitization. However, desensitization of a receptor is linked to a variety of biochemical processes that may alter protein conformation, such as the lipid microenvironment, post-translational channel modification, and channel subunit composition, the relative contribution of these processes to ethanol interactions with channel desensitization remains unclear. Understanding interactions between ethanol and ionotropic receptor desensitization may help to explain different ethanol actions 1) when ethanol is evaluated in vitro on cloned channel proteins, 2) under physiological or pathological conditions or in distinct cell domains with modified ligand concentration and/or receptor conformation. Finally, receptor desensitization is likely to participate in molecular and, possibly, behavioral tolerance to ethanol, which is thought to contribute to the risk of alcoholism. PMID:19270242

  19. 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

  20. In Vivo Electrophysiological Measurements on Mouse Sciatic Nerves

    PubMed Central

    Schulz, Alexander; Walther, Christian; Morrison, Helen; Bauer, Reinhard

    2014-01-01

    Electrophysiological studies allow a rational classification of various neuromuscular diseases and are of help, together with neuropathological techniques, in the understanding of the underlying pathophysiology1. Here we describe a method to perform electrophysiological studies on mouse sciatic nerves in vivo. The animals are anesthetized with isoflurane in order to ensure analgesia for the tested mice and undisturbed working environment during the measurements that take about 30 min/animal. A constant body temperature of 37 °C is maintained by a heating plate and continuously measured by a rectal thermo probe2. Additionally, an electrocardiogram (ECG) is routinely recorded during the measurements in order to continuously monitor the physiological state of the investigated animals. Electrophysiological recordings are performed on the sciatic nerve, the largest nerve of the peripheral nervous system (PNS), supplying the mouse hind limb with both motoric and sensory fiber tracts. In our protocol, sciatic nerves remain in situ and therefore do not have to be extracted or exposed, allowing measurements without any adverse nerve irritations along with actual recordings. Using appropriate needle electrodes3 we perform both proximal and distal nerve stimulations, registering the transmitted potentials with sensing electrodes at gastrocnemius muscles. After data processing, reliable and highly consistent values for the nerve conduction velocity (NCV) and the compound motor action potential (CMAP), the key parameters for quantification of gross peripheral nerve functioning, can be achieved. PMID:24747166

  1. The Proximal Medial Sural Nerve Biopsy Model: A Standardised and Reproducible Baseline Clinical Model for the Translational Evaluation of Bioengineered Nerve Guides

    PubMed Central

    van Neerven, Sabien G. A.; Claeys, Kristl G.; O'Dey, Dan mon; Brook, Gary A.; Sellhaus, Bernd; Schulz, Jörg B.; Weis, Joachim; Pallua, Norbert

    2014-01-01

    Autologous nerve transplantation (ANT) is the clinical gold standard for the reconstruction of peripheral nerve defects. A large number of bioengineered nerve guides have been tested under laboratory conditions as an alternative to the ANT. The step from experimental studies to the implementation of the device in the clinical setting is often substantial and the outcome is unpredictable. This is mainly linked to the heterogeneity of clinical peripheral nerve injuries, which is very different from standardized animal studies. In search of a reproducible human model for the implantation of bioengineered nerve guides, we propose the reconstruction of sural nerve defects after routine nerve biopsy as a first or baseline study. Our concept uses the medial sural nerve of patients undergoing diagnostic nerve biopsy (≥2 cm). The biopsy-induced nerve gap was immediately reconstructed by implantation of the novel microstructured nerve guide, Neuromaix, as part of an ongoing first-in-human study. Here we present (i) a detailed list of inclusion and exclusion criteria, (ii) a detailed description of the surgical procedure, and (iii) a follow-up concept with multimodal sensory evaluation techniques. The proximal medial sural nerve biopsy model can serve as a preliminarynature of the injuries or baseline nerve lesion model. In a subsequent step, newly developed nerve guides could be tested in more unpredictable and challenging clinical peripheral nerve lesions (e.g., following trauma) which have reduced comparability due to the different nature of the injuries (e.g., site of injury and length of nerve gap). PMID:25006574

  2. 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

  3. 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

  4. 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.

  5. 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...

  6. 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

  7. 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

  8. Lumbar plexus nerve entrapment syndromes as a cause of groin pain in athletes.

    PubMed

    Rassner, Leslie

    2011-01-01

    In athletes, groin pain is not uncommon and can be severe and activity-limiting. Nerve entrapment syndromes of the lumbar plexus are a rare but important etiology that should be considered when evaluating athletes. Diagnosis can be made based on patterns of pain and hypoesthesia following the sensory distribution of the involved nerve and by pain relief with nerve block. Conservative therapies, including nerve blocks, neurodestructive procedures, and medications, may provide long-term pain relief. If nonsurgical therapies fail, referral should be made for surgical exploration and neurectomy. PMID:21623294

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

    PubMed

    Burge, Alissa J; Gold, Stephanie L; Kuong, Sharon; Potter, Hollis G

    2014-02-01

    Magnetic resonance (MR) imaging of the nerves, commonly known as MR neurography is increasingly being used as noninvasive means of diagnosing peripheral nerve disease. High-resolution imaging protocols aimed at imaging the nerves of the hip, thigh, knee, leg, ankle, and foot can demonstrate traumatic or iatrogenic injury, tumorlike lesions, or entrapment of the nerves, causing a potential loss of motor and sensory function in the affected area. A thorough understanding of normal MR imaging and gross anatomy, as well as MR findings in the presence of peripheral neuropathies will aid in accurate diagnosis and ultimately help guide clinical management. PMID:24210318

  10. Processing of nerve biopsies: A practical guide for neuropathologists

    PubMed Central

    Weis, Joachim; Brandner, Sebastian; Lammens, Martin; Sommer, Claudia; Vallat, Jean-Michel

    2012-01-01

    Nerve biopsy is a valuable tool in the diagnostic work-up of peripheral neuropathies. Currently, major indications include interstitial pathologies such as suspected vasculitis and amyloidosis, atypical cases of inflammatory neuropathy and the differential diagnosis of hereditary neuropathies that cannot be specified otherwise. However, surgical removal of a piece of nerve causes a sensory deficit and – in some cases – chronic pain. Therefore, a nerve biopsy is usually performed only when other clinical, laboratory and electrophysiological methods have failed to clarify the cause of disease. The neuropathological work-up should include at least paraffin and resin semithin histology using a panel of conventional and immunohistochemical stains. Cryostat section staining, teased fiber preparations, electron microscopy and molecular genetic analyses are potentially useful additional methods in a subset of cases. Being performed, processed and read by experienced physicians and technicians nerve biopsies can provide important information relevant for clinical management. PMID:22192700

  11. Evidence for Glutamate as a Neuroglial Transmitter within Sensory Ganglia

    PubMed Central

    Kung, Ling-Hsuan; Gong, Kerui; Adedoyin, Mary; Ng, Johnson; Bhargava, Aditi; Ohara, Peter T.; Jasmin, Luc

    2013-01-01

    This study examines key elements of glutamatergic transmission within sensory ganglia of the rat. We show that the soma of primary sensory neurons release glutamate when depolarized. Using acute dissociated mixed neuronal/glia cultures of dorsal root ganglia (DRG) or trigeminal ganglia and a colorimetric assay, we show that when glutamate uptake by satellite glial cells (SGCs) is inhibited, KCl stimulation leads to simultaneous increase of glutamate in the culture medium. With calcium imaging we see that the soma of primary sensory neurons and SGCs respond to AMPA, NMDA, kainate and mGluR agonists, and selective antagonists block this response. Using whole cell patch-clamp technique, inward currents were recorded from small diameter (<30 µm) DRG neurons from intact DRGs (ex-vivo whole ganglion preparation) in response to local application of the above glutamate receptor agonists. Following a chronic constriction injury (CCI) of either the inferior orbital nerve or the sciatic nerve, glutamate expression increases in the trigeminal ganglia and DRG respectively. This increase occurs in neurons of all diameters and is present in the somata of neurons with injured axons as well as in somata of neighboring uninjured neurons. These data provides additional evidence that glutamate can be released within the sensory ganglion, and that the somata of primary sensory neurons as well as SGCs express functional glutamate receptors at their surface. These findings, together with our previous gene knockdown data, suggest that glutamatergic transmission within the ganglion could impact nociceptive threshold. PMID:23844184

  12. 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

  13. CONDUCTION IN NERVE FIBRES

    PubMed Central

    Blair, H. A.

    1934-01-01

    Data by E. A. Blair and Erlanger on the voltage-capacity curves and the nerve impulse velocities of each of several fibres in the same nerve trunk are related to Rashevsky's equation for the velocity of transmission in nerve. The results lend support to Rashevsky's analysis. Other empirical relations between the velocity and the parameters of the excitation equations indicate the correctness of the hypothesis that the action current is the primary factor in transmission, which process is carried on by the electrical excitation of successive regions of the nerve fibre by means of its action current according to the ordinary laws of electrical excitation. PMID:19872822

  14. Three-dimensional reconstruction and visualization of the median nerve from serial tissue sections.

    PubMed

    Sun, Kuo; Zhang, Jian; Chen, Tongyi; Chen, Zhongwei; Chen, Zenggan; Li, Zhi; Li, Hua; Hu, Ping

    2009-01-01

    The purpose of this study was to definitively implement the three-dimensional visualization of sensory and motor fascicles in the human median nerve by means of acetylcholinesterase (AChe) histochemical staining and under the assistance of the computer technology. One fresh human median nerve was harvested from a male adult cadaver. The median nerve was fixed at a special holder. Then, the whole holder was embedded and rapidly frozen in the liquid nitrogen. The processed median nerve was then cut coronally every 100 microm at a 20 microm thickness along its long axis in a sliding freezing microtome. The total number of sections was 4,650 slices. All sections were stained with the AChe histochemical method. The stained sections were scanned and saved as Joint Photographic Experts Group files. These images with positively and negatively stained sections were acquired to an Intel dual Pentium computer. The Adobe Photoshop CS2 software was used to compare the reference points of images before and after staining. The two-dimensional intraneural microstructure database of median nerve was then acquired. A software of 3D nerve visualization system was developed. With the 3D nerve visualization system, the 3D visualization result of intraneural microstructure of median nerve was created. The findings may provide more accurate and detailed anatomic information for nerve repairs, specifically for the fascicular nerve repairs. The 3D nerve visualization technique may have potential for future studies of topography of peripheral nerve. (c) 2009 Wiley-Liss, Inc. Microsurgery, 2009. PMID:19308949

  15. Cross-face nerve transfer for established trigeminal branch II palsy.

    PubMed

    Koshima, Isao; Narushima, Mitsunaga; Mihara, Makoto; Uchida, Gentaro; Nakagawa, Masahiro

    2009-12-01

    Reconstruction for trigeminal nerve II palsy is challenging. Cross-face nerve transfer from the contralateral trigeminal nerve facilitates this reconstruction. However, the microanatomy and techniques required for nerve sutures cause problems for many surgeons. Following the recent development of supramicrosurgical techniques appropriate for the microanatomy of peripheral nerves, a new method of intraoral "cross-face nerve transfer" was successfully used for repairing trigeminal nerve II palsy. Two cases of trigeminal nerve II palsy were repaired with contralateral trigeminal nerve transfer without any nerve graft. Affected upper labial sensory recovery was 1.65 to 2.44 (Semmes-Weinstein values) and 15 to 30 mm (moving 2-point discriminations) at 1 to 1 1/2 years after surgery. The advantages of this method are excellent nerve regeneration and the lack of donor site morbidity. It is a brief and simple operation in comparison to free nerve grafts. The disadvantage is a need for a supramicrosurgical technique, using a needle less than 80 microm wide. PMID:19934846

  16. Fiber components of the recurrent laryngeal nerve in the cat.

    PubMed

    Gacek, R R; Lyon, M J

    1976-01-01

    Experimental neuroanatomical methods were employed in 21 adult cats to determine 1) the number and size of myelinated motor and sensory fibers in the recurrent laryngeal nerve (RLN), and 2) the fiber components originating in the nucleus ambiguus (NA) and retrofacial nucleus (RFN) of the brain stem. Intracranial transection of the X and XI cranial nerves and selective destruction of the NA or RFN were the experimental lesions inflicted in order to obtain the following results. About 55% (312) of the right RLN (565 fibers) is composed of myelinated motor nerve fibers which measure 4 mu - 9 mu in diameter. Nine percent come from the RFN and are smaller (4-6 mu) than the 46% which emanate from the NA and measure 6-9 mu in diameter. The remaining 45% of the RLN is made up of sensory neurons which can be divided into three groups. 1) The largest numerical group (32%) is very small in caliber (1-3 mu) and supplies extralaryngeal regions (trachea, esophagus). 2) The intermediate size fiber group (4-9 mu) comprises 11% of the RLN and probably supplies the subglottic mucosa. 3) The smallest group (2%) of sensory fibers is the largest in diameter (10-15 mu) and may represent either the innervation of muscle spindles or afferents from the superior laryngeal nerve coursing down into the chest. PMID:949153

  17. 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

  18. Desensitization of histamine H1 receptor-mediated inositol phosphate production in HeLa cells.

    PubMed Central

    Bristow, D. R.; Zamani, M. R.

    1993-01-01

    1. Histamine stimulated the accumulation of total [3H]-inositol phosphates (IPn) in control HeLa cells with an EC50 of 3.7 +/- 0.7 microM in the presence of 10 mM LiCl. The maximum response to histamine after 15 min incubation was 43 +/- 5% over basal accumulation and occurred at a concentration of 1 mM histamine. 2. The histamine-induced IPn production in HeLa cells was confirmed as H1 receptor-mediated, since the H1 antagonist mepyramine (10(-6) M) inhibited the histamine response (10(-4) M) by 83 +/- 7%, whereas the H2 antagonist, ranitidine (10(-4) M), and H3 antagonist, thioperamide (10(-6) M), were ineffective. 3. Histamine (10(-4) M) pretreatment of HeLa cells for 30 min desensitized the subsequent histamine-induced IPn accumulation. The desensitized cells accumulated IPn in response to histamine with an EC50 of 1.7 +/- 0.7 microM after 15 min incubation. The maximum histamine-induced IPn accumulation at 10(-4) M was 19 +/- 5% over basal and was significantly lower (P < 0.03) than the maximum response in control cells. 4. The desensitization of histamine-induced IPn accumulation was time-dependent and, at a desensitizing histamine concentration of 10(-4) M, the half-maximal attenuation occurred after approximately 9 min and maximum desensitization was achieved by 15-20 min. The desensitization of the IPn accumulation was a reversible phenomenon and full recovery of the response occurred 150 min after the removal of the desensitizing histamine-containing medium. The half-time for the recovery of the histamine-induced response was estimated at 120 min.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:8358540

  19. 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

  20. 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

  1. Physiological correlates of eye movement desensitization and reprocessing.

    PubMed

    Elofsson, Ulf O E; von Schèele, Bo; Theorell, Töres; Söndergaard, Hans Peter

    2008-05-01

    Eye movement desensitization and reprocessing (EMDR) is an established treatment for post-traumatic stress disorder (PTSD). However, its working mechanism remains unclear. This study explored physiological correlates of eye movements during EMDR in relation to current hypotheses; distraction, conditioning, orienting response activation, and REM-like mechanisms. During EMDR therapy, fingertip temperature, heart rate, skin conductance, expiratory carbon dioxide level, and blood pulse oximeter oxygen saturation, were measured in male subjects with PTSD. The ratio between the low and high frequency components of the heart rate power spectrum (LF/HF) were computed as measures of autonomic balance. Respiratory rate was calculated from the carbon dioxide trace. Stimulation shifted the autonomic balance as indicated by decreases in heart rate, skin conductance and LF/HF-ratio, and an increased finger temperature. The breathing frequency and end-tidal carbon dioxide increased; oxygen saturation decreased during eye movements. In conclusion, eye movements during EMDR activate cholinergic and inhibit sympathetic systems. The reactivity has similarities with the pattern during REM-sleep. PMID:17604948

  2. Endothelin-1 induced desensitization in primary afferent neurons

    PubMed Central

    Smith, Terika P.; Smith, Sherika N.; Sweitzer, Sarah M.

    2014-01-01

    Endothelin-1 (ET-1) is a known algogen that causes acute pain and sensitization in humans and spontaneous nociceptive behaviors when injected into the periphery in rats, and is elevated during vaso-occlusive episodes (VOEs) in sickle cell disease (SCD) patients. Previously, our lab has shown that a priming dose of ET-1 produces sensitization to capsaicin-induce secondary hyperalgesia. The goal of this study was to determine if the sensitization induced by ET-1 priming is occurring at the level of the primary afferent neuron. Calcium imaging in cultured dorsal root ganglion (DRG) neurons was utilized to examine the effects of ET-1 on primary afferent neurons. ET-1 induces [Ca2+]i transients in unprimed cells. ET-1 induced [Ca2+]i transients are attenuated by priming with ET-1. This priming effect occurs whether the priming dose is given 0-4 days prior to the challenge dose. Similarly, ET-1 priming decreases capsaicin-induced [Ca2+]i transients. At the level of the primary afferent neuron, ET-1 priming has a desensitizing effect on challenge exposures to ET-1 and capsaicin. PMID:25220703

  3. 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

  4. Mitotoxicity in distal symmetrical sensory peripheral neuropathies

    PubMed Central

    Bennett, Gary J.; Doyle, Timothy; Salvemini, Daniela

    2016-01-01

    Chronic distal symmetrical sensory peripheral neuropathy is a common neurological complication of cancer chemotherapy, HIV treatment and diabetes. Although aetiology-specific differences in presentation are evident, the clinical signs and symptoms of these neuropathies are clearly similar. Data from animal models of neuropathic pain suggest that the similarities have a common cause: mitochondrial dysfunction in primary afferent sensory neurons. Mitochondrial dysfunction is caused by mitotoxic effects of cancer chemotherapeutic drugs of several chemical classes, HIV-associated viral proteins, and nucleoside reverse transcriptase inhibitor treatment, as well as the (possibly both direct and indirect) effects of excess glucose. The mitochondrial injury results in a chronic neuronal energy deficit, which gives rise to spontaneous nerve impulses and a compartmental neuronal degeneration that is first apparent in the terminal receptor arbor—that is, intraepidermal nerve fibres—of cutaneous afferent neurons. Preliminary data suggest that drugs that prevent mitochondrial injury or improve mitochondrial function could be useful in the treatment of these conditions. PMID:24840972

  5. 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

  6. Electroneurography of right median and ulnar nerves in diabetic patients with and without retinopathy.

    PubMed

    Tupković, Emir; Pavljesević, Suzana; Nisić, Mediha; Salihović, Samiha

    2007-08-01

    In this study we examined motor and sensory conduction velocities in right median and ulnar nerves in diabetic patients. Control group consisted of 25 healthy volunteers (13 males) with average age of 52 years. The first examined group consisted of 25 diabetic patients (13 males) without retinal changes, 59,6 years old on average, and the second group consisted of 40 patients (15 males) 59,4 years old on average: 22 of them with type 1, and 18 with type 2 retinal changes. The motor and sensory conduction velocities in right median nerve in the control group were significantly higher than those measured in the first group (p<0,0005 for motor, and p=0,0027 for sensory velocity), and the second group (p<0,0001 for motor, and p=0,0001 for sensory velocity). Significantly higher conduction velocities in sensory median nerve were compared between the examined groups (p<0,001), but motor conduction velocity was not significantly higher (p=0,09). The motor conduction velocity in ulnar nerve in the control group was significantly higher in comparison with the patients of first (p=0,0027) and second examined group (p=0,0001). The sensory conduction velocity in ulnar nerve was not significantly higher compared with the first (p=0,081), and significantly higher compared with the second examined group (p<0,0001). The sensory conduction velocity of ulnar nerve was significantly higher (p=0,019) in diabetic patients without retinopathy compared with patients with retinopathy. Diabetic patients with retinal changes have higher risk of developing more severe neurophysiologic signs of neuropathy. So, simple observation with ophthalmoscope may be useful diagnostic tool in its determination and may be the target of further therapeutic strategy. PMID:17848148

  7. Musculocutaneous nerve injury after simulated freefall in a vertical wind-tunnel: a case report.

    PubMed

    Mautner, Kenneth; Keel, John C

    2007-03-01

    We report a case of a skydiver with isolated musculocutaneous nerve injury, which occurred after prolonged positioning of the arm during simulated freefall in a vertical wind-tunnel. Musculocutaneous nerve injury is rare, and the mechanism of isolated injury to this nerve is not entirely understood. Isolated peripheral nerve injuries such as this easily mimic other injuries and can be difficult to diagnose. The skydiver complained of right arm weakness and numbness that began after training in a vertical wind-tunnel. Exam revealed weakness in right elbow flexion and forearm supination, and diminished sensation in the right lateral forearm. Electrodiagnostic testing revealed a decreased amplitude in the right lateral antebrachial cutaneous nerve sensory nerve action potential, and fibrillations and positive sharp waves in the biceps and brachialis muscles. By 5 months, the subject reported complete sensory and motor recovery. Physical and electrodiagnostic findings corresponded to the distribution of the musculocutaneous nerve. The mechanism of injury was likely the prolonged abducted, extended, and externally rotated position of the shoulder during simulated freefall. Although isolated nerve injuries are uncommon, unusual activities and physiologic demands of athletes can result in such injuries. It is important to be aware of peripheral nerve injuries to facilitate proper diagnosis and management. PMID:17321836

  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. 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

  10. 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

  11. Desensitization Using Bortezomib and High-dose Immunoglobulin Increases Rate of Deceased Donor Kidney Transplantation

    PubMed Central

    Jeong, Jong Cheol; Jambaldorj, Enkthuya; Kwon, Hyuk Yong; Kim, Myung-Gyu; Im, Hye Jin; Jeon, Hee Jung; In, Ji Won; Han, Miyeun; Koo, Tai Yeon; Chung, Junho; Song, Eun Young; Ahn, Curie; Yang, Jaeseok

    2016-01-01

    Abstract Combination therapy of intravenous immunoglobulin (IVIG) and rituximab showed a good transplant rate in highly sensitized wait-listed patients for deceased donor kidney transplantation (DDKT), but carried the risk of antibody-mediated rejection. The authors investigated the impact of a new combination therapy of bortezomib, IVIG, and rituximab on transplantation rate. This study was a prospective, open-labeled clinical trial. The desensitization regimen consisted of 2 doses of IVIG (2 g/kg), a single dose of rituximab (375 mg/m2), and 4 doses of bortezomib (1.3 mg/m2). The transplant rate was analyzed. Anti-Human leukocyte antigen (HLA) DRB antibodies were determined by a Luminex solid-phase bead assay at baseline and after 2, 3, and 6 months in the desensitized patients. There were 19 highly sensitized patients who received desensitization and 17 patients in the control group. Baseline values of class I and II panel reactive antibody (%, peak mean fluorescence intensity) were 83 ± 16.0 (14952 ± 5820) and 63 ± 36.0 (10321 ± 7421), respectively. Deceased donor kidney transplantation was successfully performed in 8 patients (42.1%) in the desensitization group versus 4 (23.5%) in the control group. Multivariate time-varying covariate Cox regression analysis showed that desensitization increased the probability of DDKT (hazard ratio, 46.895; 95% confidence interval, 3.468–634.132; P = 0.004). Desensitization decreased mean fluorescence intensity values of class I panel reactive antibody by 15.5% (20.8%) at 2 months. In addition, a liberal mismatch strategy in post hoc analysis increased the benefit of desensitization in donor-specific antibody reduction. Desensitization was well tolerated, and acute rejection occurred only in the control group. In conclusion, a desensitization protocol using bortezomib, high-dose IVIG, and rituximab increased the DDKT rate in highly sensitized, wait-listed patients. PMID:26844479

  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. Neuromorphic sensory systems.

    PubMed

    Liu, Shih-Chii; Delbruck, Tobi

    2010-06-01

    Biology provides examples of efficient machines which greatly outperform conventional technology. Designers in neuromorphic engineering aim to construct electronic systems with the same efficient style of computation. This task requires a melding of novel engineering principles with knowledge gleaned from neuroscience. We discuss recent progress in realizing neuromorphic sensory systems which mimic the biological retina and cochlea, and subsequent sensor processing. The main trends are the increasing number of sensors and sensory systems that communicate through asynchronous digital signals analogous to neural spikes; the improved performance and usability of these sensors; and novel sensory processing methods which capitalize on the timing of spikes from these sensors. Experiments using these sensors can impact how we think the brain processes sensory information. PMID:20493680

  14. 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.

  15. 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

  16. 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

  17. 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.

  18. Shear bond strengths of two dentin bonding agents with two desensitizers: An in vitro study

    PubMed Central

    Ravikumar, N; Shankar, P; Indira, R

    2011-01-01

    Aim: The aim of this in vitro study was to compare the shear bond strengths of two different dentin bonding agents with two different desensitizers. Materials and Methods: Eighty molars were taken which were ground to expose the dentin. The teeth were divided into two major groups. Each major group was subdivided into four subgroups of 10 samples each. Groups Ia and IIa were treated as dry bonding groups, groups Ib and IIb were treated as a moist bonding groups, groups Ic and IIc were rewetted with Gluma desensitizer, and groups Id and IId were rewetted with vivasens desensitizer. Major group I was treated with Gluma comfort bond and Charisma. Major group II was treated Prime and Bond NT and TPH. The samples were thermo cycled and shear bond test was performed using an Instron machine. The data were analyzed using one-way analysis of variance and Tukey's Honestly significant different test. Results: The results revealed that the specimens rewetted with Gluma desensitizer showed the highest shear bond strength compared to all other groups, irrespective of the bonding agent or composite resin used. Conclusions: It can be concluded that rewetting with desensitizer provided better bond strength than the other groups. PMID:22025827

  19. 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

  20. 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

  1. 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

  2. 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

  3. Motor nerve conduction velocity is affected in segmental vitiligo lesional limbs.

    PubMed

    Zhou, Jun; Zhong, Zhenyu; Li, Jian; Fu, Wenwen

    2016-06-01

    To evaluate the effects of segmental vitiligo (SV) on nerve conduction velocity (NCV) in different nerves, we compared the patient's lesional side of their body to the contralateral normal side. The 106 participants were selected from outpatients visiting the dermatological clinics of Huashan Hospital, Fudan University, from November 2011 to March 2014. NCVs were measured on the limbs and the face, including both motor and sensory nerves. The parameters for NCVs included motor nerve conduction velocity (MCV) and its distal conduction latency, sensory nerve conduction velocity, sensory nerve action potentials amplitude, and compound muscle action potential amplitude. MCV on the limbs was compromised by SV state, which was significantly slower on the lesional side of the body compared with the normal contralateral side (P = 0.006). Furthermore, SV at the stable stage significantly impaired MCV compared with the SV at progressive stage. There was no significant difference in the other parameters of NCV between lesional and normal sides of the body. Compound muscle action potentials in the face did not differ between lesional and healthy sides. Motor nerves in the limbs were compromised by SV, particularly when the disease was at the stable stage. PMID:26916936

  4. 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

  5. Neurocontrol in sensory cortex

    NASA Astrophysics Data System (ADS)

    Ritt, Jason; Nandi, Anirban; Schroeder, Joseph; Ching, Shinung

    Technology to control neural ensembles is rapidly advancing, but many important challenges remain in applications, such as design of controls (e.g. stimulation patterns) with specificity comparable to natural sensory encoding. We use the rodent whisker tactile system as a model for active touch, in which sensory information is acquired in a closed loop between feedforward encoding of sensory information and feedback guidance of sensing motions. Motivated by this system, we present optimal control strategies that are tailored for underactuation (a large ratio of neurons or degrees of freedom to stimulation channels) and limited observability (absence of direct measurement of the system state), common in available stimulation technologies for freely behaving animals. Using a control framework, we have begun to elucidate the feedback effect of sensory cortex activity on sensing in behaving animals. For example, by optogenetically perturbing primary sensory cortex (SI) activity at varied timing relative to individual whisker motions, we find that SI modulates future sensing behavior within 15 msec, on a whisk by whisk basis, changing the flow of incoming sensory information based on past experience. J.T.R. and S.C. hold Career Awards at the Scientific Interface from the Burroughs Wellcome Fund.

  6. 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…

  7. 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

  8. Low-intensity pulsed ultrasound accelerates nerve regeneration following inferior alveolar nerve transection in rats.

    PubMed

    Sato, Mai; Motoyoshi, Mitsuru; Shinoda, Masamichi; Iwata, Koichi; Shimizu, Noriyoshi

    2016-06-01

    Inferior alveolar nerve (IAN) injury, which is frequently caused by orofacial surgery or trauma, induces sensory loss in orofacial regions innervated by the IAN. However, no effective treatment for orofacial sensory loss currently exists. We determined whether sensory loss in facial skin above the mental foramen following IAN transection was recovered by exposure of the transected IAN to low-intensity pulsed ultrasound (LIPUS). Inferior alveolar nerve transection (IANX) was performed in 7-wk-old male Sprague-Dawley rats. On day 7 after IANX, the effect of daily LIPUS (from day 0) on the transected IAN, in terms of sensitivity to mechanical stimulation of the facial skin above the mental foramen, was examined. Moreover, the number of trigeminal ganglion (TG) neurons innervating the facial skin above the mental foramen of rats with IANX treated daily with LIPUS was counted using the retrograde neurotracing technique. Daily exposure of the transected IAN to LIPUS significantly promoted recovery of the head-withdrawal threshold in response to mechanical stimulation of the facial skin above the mental foramen, and the number of TG neurons innervating the facial skin above mental foramen was significantly increased in rats with IANX treated daily with LIPUS compared with sham or LIPUS-unexposed rats. Daily treatment of stumps of the transected IAN with LIPUS facilitated morphological and functional regeneration, suggesting that LIPUS is an effective and novel therapy for IAN injury. PMID:27058986

  9. Nerve Growth Factor: A Focus on Neuroscience and Therapy

    PubMed Central

    Aloe, Luigi; Rocco, Maria Luisa; Omar Balzamino, Bijorn; Micera, Alessandra

    2015-01-01

    Nerve growth factor (NGF) is the firstly discovered and best characterized neurotrophic factor, known to play a critical protective role in the development and survival of sympathetic, sensory and forebrain cholinergic neurons. NGF promotes neuritis outgrowth both in vivo and in vitro and nerve cell recovery after ischemic, surgical or chemical injuries. Recently, the therapeutic property of NGF has been demonstrated on human cutaneous and corneal ulcers, pressure ulcer, glaucoma, maculopathy and retinitis pigmentosa. NGF eye drops administration is well tolerated, with no detectable clinical evidence of systemic or local adverse effects. The aim of this review is to summarize these biological properties and the potential clinical development of NGF. PMID:26411962

  10. Lentivirus vector-mediated Rho guanine nucleotide dissociation inhibitor 2 induces beta-2 adrenergic receptor desensitization in β2AR desensitization mice model

    PubMed Central

    Ni, Songshi; Zhao, Jing; Fu, Zhenxue

    2014-01-01

    Background It is well-known that chronic administration of β2AR agonists can induce β2AR desensitization. Our previous study showed that Rho guanine nucleotide dissociation inhibitor 2 (RhoGDI2) overexpression induced beta-2 adrenergic receptor (β2AR) desensitization in airway smooth muscle cells. The purpose of this study was to further study the function of RhoGDI2 in β2AR desensitization by β2AR desensitization mouse model. Methods Studies were performed using a β2AR desensitization mice model induced by salbutamol. The mice were randomly divided into five groups (n=45): RhoGDI2 overexpression group (n=10); RhoGDI2 siRNA group (n=10); empty viral vector group (n=10); experimental control group (n=10); blank control group—without any drug treatment (n=5). The first four groups were used the same methods and the same dose to establish β2AR desensitization mice model by salbutamol. The first three groups that salbutamol-treated were used for intratracheal delivery of lentiviral vectors. Airway hyperreactivity was measured through a whole-body plethysmograph system. RhoGDI2, β2AR, GRK2 mRNA and protein expression levels were then detected by RT-PCR and western blot analyses in fresh lung tissues. As well as the activity of GRK was assessed by light-dependent phosphorylation of rhodopsin. Results We successfully constructed β2AR desensitization mouse model. As expected, airway responsiveness after inhaling acetylcholine chloride (Ach) was markedly increased in the RhoGDI2 overexpression group compared to experimental control group and blank control group when concentrations of Ach was 45 mg/mL (all P<0.05), while, it was markedly decreased in the RhoGDI2 siRNA group compared to experimental control group (P<0.05). RhoGDI2, GRK2 expressions and GRK enzymatic activity were significantly increased in RhoGDI2 overexpression group compared to experimental control group and blank control group (all P<0.05). RhoGDI2, GRK2 expressions and GRK enzymatic activity were significantly decreased in RhoGDI2 siRNA group compared to experimental control group and blank control group (all P<0.05). Conversely, β2AR expression were significantly lower in RhoGDI2 overexpression group compared to experimental control group and blank control group (all P<0.05), exhibiting an inverse correlation with RhoGDI2 expression. Conclusions To sum up, our present studies found that RhoGDI2 might induce β2AR desensitization and GRK2 might take part in RhoGDI2-mediated β2AR desensitization. PMID:24605225

  11. 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

  12. Transplantation of induced pluripotent stem cell-derived neurospheres for peripheral nerve repair.

    PubMed

    Uemura, Takuya; Takamatsu, Kiyohito; Ikeda, Mikinori; Okada, Mitsuhiro; Kazuki, Kenichi; Ikada, Yoshito; Nakamura, Hiroaki

    2012-03-01

    In spite of the extensive research using induced pluripotent stem (iPS) cells, the therapeutic potential of iPS cells in the treatment of peripheral nerve injury is largely unknown. In this study, we repaired peripheral nerve gaps in mice using tissue-engineered bioabsorbable nerve conduits coated with iPS cell-derived neurospheres. The secondary neurospheres derived from mouse iPS cells were suspended in each conduit (4000,000 cells per conduit) and cultured in the conduit in three-dimensional (3D) culture for 14 days. We then implanted them in the mouse sciatic nerve gaps (5 mm) (iPS group; n=10). The nerve conduit alone was implanted in the control group (n=10). After 4, 8 and 12 weeks, motor and sensory functional recovery in mice were significantly better in the iPS group. At 12 weeks, all the nerve conduits remained structurally stable without any collapse and histological analysis indicated axonal regeneration in the nerve conduits of both groups. However, the iPS group showed significantly more vigorous axonal regeneration. The bioabsorbable nerve conduits created by 3D-culture of iPS cell-derived neurospheres promoted regeneration of peripheral nerves and functional recovery in vivo. The combination of iPS cell technology and bioabsorbable nerve conduits shows potential as a future tool for the treatment of peripheral nerve defects. PMID:22333572

  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. 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

  15. 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…

  16. 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.

  17. [Ultrasound-guided peripheral nerve block--evidence based medicine and future trends].

    PubMed

    Fujiwara, Yoshihiro; Ito, Hiroshi; Shibata, Yasuyuki; Komatsu, Toru

    2008-05-01

    Ultrasound-guided peripheral nerve block has been gaining popularity in the community of anesthesiologists. Despite its well-known clinical benefits, inconsistent success in block has been one of the major limita- tions of conventional peripheral nerve block. Recent development in ultrasound technology enables us to see nerves, needles and surrounding structures in real-time. We expect that ultrasound imaging may overcome the shortcoming of conventional technique. In this article, we introduce some evidences that support the clinical benefits of ultrasound-guided peripheral nerve block, including performance time, quality, onset and duration of sensory blockade, cost analysis and patient satisfaction. However, ultrasound-guidance may be even more dangerous without appropriate imaging of target nerve and surrounding structures, accurate localization of needle tip and assessment of local anesthetic spread around the target nerve. These problems will be solved by future guidelines, teaching program and further advancement in ultrasound technology. PMID:18516880

  18. The sensory innervation of the shoulder joint of the mouse.

    PubMed

    Backenköhler, U; Halata, Z; Strasmann, T J

    1996-04-01

    The ultrastructure and location of sensory nerve endings in the shoulder-joint capsule, its tendinous reinforcements and in the periarticular connective and muscle tissue have been studied by means of light and electron microscopy in adult female white NMRI-F2 laboratory mice, aged 2.5-13 months. Most of the sensory nerve endings were detected in the fibrous layer of the joint capsule or in the inserting tendons. The identified lamellated corpuscles of the Pacini type are small and sometimes associated with Golgi tendon-organs. Large Vater-Pacini corpuscles were not detected. Ruffini corpuscles are found in small numbers only in the moderately dense connective tissue of the joint capsule. Golgi tendon organs were found mainly at the muscle-tendon junction of the muscles surrounding the joint. Muscle spindles have been identified mainly in periarticular muscles close to the muscle-tendon junctions. The number and distribution of the different types of mechanoreceptors investigated in the present study suggest that periarticular corpuscular sensory nerve endings play an important role in shoulder-joint control and mobility. The occurrence of small uniformly shaped lamellated corpuscles of the Pacini type in qualitatively different areas of surrounding tissue implies that they are susceptible to different kinds of mechanical stimuli. PMID:8638772

  19. Neuroepithelial circuit formed by innervation of sensory enteroendocrine cells.

    PubMed

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

    2015-02-01

    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 circuit's 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

  20. Neuroepithelial circuit formed by innervation of sensory enteroendocrine cells

    PubMed Central

    Bohórquez, 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 circuit’s 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

  1. 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

  2. [Neuralgias of the lower cranial nerves: microsurgical posterior fossa exploration].

    PubMed

    Antić, B; Perić, P; Ivanović, S; Spaić, M

    2004-01-01

    Neuralgias of the lower cranial nerves are trigeminal neuralgia (TN), glossopharingeal neuralgia (GphN), and geniculate neuralgia (GN). Microsurgical posterior fossa exploration with its variations microvascular decompression (MVD), partial sensory rhisotomy (PSR), and total sensory rhisotomy (TSR) is one of the most efficient ways of treating these neuralgias. It was performed 130 operations in 125 patients with TN, 3 in GphN patients, 1 in GN patient, 1 in GN/TN patients, 1 in GphN/GN patient, and 2 in GN/hemifacial spasm patients. Of total of 125 patients with TN, MVD was performed in 63, PSR in 18, and MVD+PSR in 44 cases. In 5 patients with recidivate TN PSR was performed. Of total 3 patients with GphN MVD was performed in 2 cases, and extirpation of a small meningeoma in 1 case (it was not seen on CT). In the patients with GN TSR of intermediate nerve was performed, in GN/TN patients TSR of intermediate nerve and PSR of trigeminal nerve was performed, in the GN/GphN patients MVD of glossopharingeal and TSR of intermediate nerve were performed, and in the GN/hemifacial spasm patients TSR of intermediate and MVD of facial nerve were performed. The results of TN patients are: excellent in 82.4%, good in 12%, and poor in 5.6% of patients. There is no difference in complete pain relief, rate of recurrence, and complications between MVD, MVD+PSR and PSR operative groups (p0.05). Among patients with other neuralgias the following results are noted: excellent in 4, good in 3, and poor in 1 patient. Microsurgical posterior fossa exploration is the method of choice in the treatment of the neuralgias of the lower cranial nerves. PMID:16018407

  3. 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.

  4. Anterior interosseous nerve syndrome

    PubMed Central

    Bäumer, 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. Desensitization of Functional µ-Opioid Receptors Increases Agonist Off-Rate

    PubMed Central

    2014-01-01

    Desensitization of µ-opioid receptors (MORs) develops over 5–15 minutes after the application of some, but not all, opioid agonists and lasts for tens of minutes after agonist removal. The decrease in function is receptor selective (homologous) and could result from 1) a reduction in receptor number or 2) a decrease in receptor coupling. The present investigation used photolysis of two caged opioid ligands to examine the kinetics of MOR-induced potassium conductance before and after MOR desensitization. Photolysis of a caged antagonist, carboxynitroveratryl-naloxone (caged naloxone), blocked the current induced by a series of agonists, and the time constant of decline was significantly decreased after desensitization. The increase in the rate of current decay was not observed after partial blockade of receptors with the irreversible antagonist, β-chlornaltrexamine (β-CNA). The time constant of current decay after desensitization was never more rapid than 1 second, suggesting an increased agonist off-rate rather than an increase in the rate of channel closure downstream of the receptor. The rate of G protein–coupled K+ channel (GIRK) current activation was examined using photolysis of a caged agonist, carboxynitrobenzyl-tyrosine-[Leu5]-enkephalin. After acute desensitization or partial irreversible block of MORs with β-CNA, there was an increase in the time it took to reach a peak current. The decrease in the rate of agonist-induced GIRK conductance was receptor selective and dependent on receptor number. The results indicate that opioid receptor desensitization reduced the number of functional receptor and that the remaining active receptors have a reduced agonist affinity. PMID:24748657

  6. 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

  7. Receptor downregulation and desensitization enhance the information processing ability of signalling receptors

    PubMed Central

    Shankaran, Harish; Wiley, H Steven; Resat, Haluk

    2007-01-01

    Background In addition to initiating signaling events, the activation of cell surface receptors also triggers regulatory processes that restrict the duration of signaling. Acute attenuation of signaling can be accomplished either via ligand-induced internalization of receptors (endocytic downregulation) or via ligand-induced receptor desensitization. These phenomena have traditionally been viewed in the context of adaptation wherein the receptor system enters a refractory state in the presence of sustained ligand stimuli and thereby prevents the cell from over-responding to the ligand. Here we use the epidermal growth factor receptor (EGFR) and G-protein coupled receptors (GPCR) as model systems to respectively examine the effects of downregulation and desensitization on the ability of signaling receptors to decode time-varying ligand stimuli. Results Using a mathematical model, we show that downregulation and desensitization mechanisms can lead to tight and efficient input-output coupling thereby ensuring synchronous processing of ligand inputs. Frequency response analysis indicates that upstream elements of the EGFR and GPCR networks behave like low-pass filters with the system being able to faithfully transduce inputs below a critical frequency. Receptor downregulation and desensitization increase the filter bandwidth thereby enabling the receptor systems to decode inputs in a wider frequency range. Further, system-theoretic analysis reveals that the receptor systems are analogous to classical mechanical over-damped systems. This analogy enables us to metaphorically describe downregulation and desensitization as phenomena that make the systems more resilient in responding to ligand perturbations thereby improving the stability of the system resting state. Conclusion Our findings suggest that in addition to serving as mechanisms for adaptation, receptor downregulation and desensitization can play a critical role in temporal information processing. Furthermore, engineering metaphors such as the ones described here could prove to be invaluable in understanding the design principles of biological systems. PMID:17996096

  8. 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.

  9. Nerve conduction in relation to vibration exposure - a non-positive cohort study

    PubMed Central

    2010-01-01

    Background Peripheral neuropathy is one of the principal clinical disorders in workers with hand-arm vibration syndrome. Electrophysiological studies aimed at defining the nature of the injury have provided conflicting results. One reason for this lack of consistency might be the sparsity of published longitudinal etiological studies with both good assessment of exposure and a well-defined measure of disease. Against this background we measured conduction velocities in the hand after having assessed vibration exposure over 21 years in a cohort of manual workers. Methods The study group consisted of 155 male office and manual workers at an engineering plant that manufactured pulp and paper machinery. The study has a longitudinal design regarding exposure assessment and a cross-sectional design regarding the outcome of nerve conduction. Hand-arm vibration dose was calculated as the product of self-reported occupational exposure, collected by questionnaire and interviews, and the measured or estimated hand-arm vibration exposure in 1987, 1992, 1997, 2002, and 2008. Distal motor latencies in median and ulnar nerves and sensory nerve conduction over the carpal tunnel and the finger-palm segments in the median nerve were measured in 2008. Before the nerve conduction measurement, the subjects were systemically warmed by a bicycle ergometer test. Results There were no differences in distal latencies between subjects exposed to hand-arm vibration and unexposed subjects, neither in the sensory conduction latencies of the median nerve, nor in the motor conduction latencies of the median and ulnar nerves. Seven subjects (9%) in the exposed group and three subjects (12%) in the unexposed group had both pathological sensory nerve conduction at the wrist and symptoms suggestive of carpal tunnel syndrome. Conclusion Nerve conduction measurements of peripheral hand nerves revealed no exposure-response association between hand-arm vibration exposure and distal neuropathy of the large myelinated fibers in a cohort of male office and manual workers. PMID:20642848

  10. 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

  11. 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

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

    PubMed

    Patterson, Jennifer Megan M

    2016-05-01

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

  13. 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

  14. 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 ...

  15. Ulnar nerve dysfunction

    MedlinePlus

    ... surface of the body where it crosses the elbow. The damage destroys the nerve covering ( myelin sheath) ... be caused by: Long-term pressure on the elbow An elbow fracture or dislocation Temporary pain and ...

  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. 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

  18. Sensory innervation of the temporomandibular joint in the mouse.

    PubMed

    Dreessen, D; Halata, Z; Strasmann, T

    1990-01-01

    The sensory innervation of the temporomandibular joints (TMJs) of 8 STR/IN mice was investigated by means of light and electron microscopy. Through the cutting of complete semithin sections in series it was possible to investigate the joints thoroughly. Additionally, one joint with its nerve supply was reconstructed three-dimensionally with a computerized three-dimensional programme. The reconstruction was based on one complete semithin section series. The joint's nerve supply originates from the nervus auriculotemporalis and additionally from motor branches of the n. mandibularis: n. massetericus, n. pterygoideus lateralis and the nn. temporales posteriores. The greatest number of nerve fibres and endings is located in the dorsolateral part of the joint capsule. They lie only in the stratum fibrosum and subsynovially. Neither the stratum synoviale nor the discus articularis contain any nerve fibres or endings, whereas the peri-articular loose connective tissue is richly innervated. The only type of nerve ending observed within the joint was the free nerve ending, which is assumed to serve not only as a nociceptor but also as a polymodal mechanoreceptor. Merely within the insertion of the musculus pterygoideus lateralis at the collum mandibulae single stretch receptors of the Ruffini type were observed. Ultrastructurally, they correspond to those described in the cat's knee joint. Neither lamellated nor nerve endings of the Golgi or Pacini type were observed in the joint or in the peri-articular connective tissue. The unexpected paucity of nerve fibres and endings in the TMJ itself of the mouse suggests that the afferent information from the joint is less important for position sense and movement than the afferent information from muscles, tendons and periodontal ligaments. PMID:2288202

  19. Cranial Nerve VIII

    PubMed Central

    Sanders, Richard D

    2010-01-01

    Cranial nerve VIII brings sound and information about one's position and movement in space into the brain. The auditory and vestibular systems subserve several functions basic to clinical medicine and to psychiatry. This article covers the basics of cranial nerve VIII, hearing and vestibular systems, including common problems with hearing and balance, problems with hearing and balance that tend to be found in psychiatric patients, and some simple assessments of value in clinical practice. PMID:20436771

  20. 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

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

    PubMed

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

    2016-01-01

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

  2. Optic nerve aspergillosis.

    PubMed

    Yuan, Lisi; Prayson, Richard A

    2015-07-01

    We report a 55-year-old woman with optic nerve Aspergillosis. Aspergillus is an ubiquitous airborne saprophytic fungus. Inhaled Aspergillus conidia are normally eliminated in the immunocompetent host by innate immune mechanisms; however, in immunosuppressed patients, they can cause disease. The woman had a past medical history of hypertension and migraines. She presented 1 year prior to death with a new onset headache behind the left eye and later developed blurred vision and scotoma. A left temporal artery biopsy was negative for giant cell arteritis. One month prior to the current admission, she had an MRI showing optic nerve thickening with no other findings. Because of the visual loss and a positive antinuclear antibody test, she was given a trial of high dose steroids and while it significantly improved her headache, her vision did not improve. At autopsy, the left optic nerve at the level of the cavernous sinus and extending into the optic chiasm was enlarged in diameter and there was a 1.3 cm firm nodule surrounding the left optic nerve. Histologically, an abscess surrounded and involved the left optic nerve. Acute angle branching, angioinvasive fungal hyphae were identified on Grocott's methenamine silver stained sections, consistent with Aspergillus spp. No gross or microscopic evidence of systemic vasculitis or infection was identified in the body. The literature on optic nerve Aspergillosis is reviewed. PMID:25861888

  3. 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

  4. Brain Mass and Cranial Nerve Size in Shrews and Moles

    PubMed Central

    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

  5. Sensory activity affects sensory axon development in C. elegans.

    PubMed

    Peckol, E L; Zallen, J A; Yarrow, J C; Bargmann, C I

    1999-05-01

    The simple nervous system of the nematode C. elegans consists of 302 neurons with highly reproducible morphologies, suggesting a hard-wired program of axon guidance. Surprisingly, we show here that sensory activity shapes sensory axon morphology in C. elegans. A class of mutants with deformed sensory cilia at their dendrite endings have extra axon branches, suggesting that sensory deprivation disrupts axon outgrowth. Mutations that alter calcium channels or membrane potential cause similar defects. Cell-specific perturbations of sensory activity can cause cell-autonomous changes in axon morphology. Although the sensory axons initially reach their targets in the embryo, the mutations that alter sensory activity cause extra axon growth late in development. Thus, perturbations of activity affect the maintenance of sensory axon morphology after an initial pattern of innervation is established. This system provides a genetically tractable model for identifying molecular mechanisms linking neuronal activity to nervous system structure. PMID:10101123

  6. Laminin-based Nanomaterials for Peripheral Nerve Tissue Engineering

    NASA Astrophysics Data System (ADS)

    Neal, Rebekah Anne

    Peripheral nerve transection occurs commonly in traumatic injury, causing motor and sensory deficits distal to the site of injury. One option for surgical repair is the nerve conduit. Conduits currently on the market are hollow tubes into which the nerve ends are sutured. Although these conduits fill the gap, they often fail due to the slow rate of regeneration over long gaps. To facilitate increased speed of regeneration and greater potential for functional recovery, the ideal conduit should provide biochemically relevant signals and physical guidance cues, thus playing an active role in peripheral nerve regeneration. In this dissertation, I fabricated laminin-1 and laminin-polycaprolactone (PCL) blend nanofibers that mimic the geometry and functionality of the peripheral nerve basement membrane. These fibers resist hydration in aqueous media and require no harsh chemical crosslinkers. Adhesion and differentiation of both neuron-like and neuroprogenitor cells is improved on laminin nanofibrous meshes over two-dimensional laminin substrates. Blend meshes with varying laminin content were characterized for composition, tensile properties, degradation rates, and bioactivity in terms of cell attachment and axonal elongation. I have established that 10% (wt) laminin content is sufficient to retain the significant neurite-promoting effects of laminin critical in peripheral nerve repair. In addition, I utilized modified collector plate design to manipulate electric field gradients during electrospinning for the fabrication of aligned nanofibers. These aligned substrates provide enhanced directional guidance cues to the regenerating axons. Finally, I replicated the clinical problem of peripheral nerve transection using a rat tibial nerve defect model for conduit implantation. When the lumens of conduits were filled with nanofiber meshes of varying laminin content and alignment, I observed significant recovery of sensory and motor function over six weeks. This recovery was supported by nerve conduction studies and electromyography which described impulse transmission, muscle stimulation, and foot twitch through the region of regeneration. These studies provide a firm foundation for the use of natural-synthetic blend electrospun nanofibers to enhance existing hollow nerve guidance conduits. The similarity in surgical technique and obvious benefit to the patient should lead to rapid translation into clinical application.

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

    PubMed

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

    2015-01-01

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

  8. Electrical Stimulation to Enhance Axon Regeneration After Peripheral Nerve Injuries in Animal Models and Humans.

    PubMed

    Gordon, Tessa

    2016-04-01

    Injured peripheral nerves regenerate their lost axons but functional recovery in humans is frequently disappointing. This is so particularly when injuries require regeneration over long distances and/or over long time periods. Fat replacement of chronically denervated muscles, a commonly accepted explanation, does not account for poor functional recovery. Rather, the basis for the poor nerve regeneration is the transient expression of growth-associated genes that accounts for declining regenerative capacity of neurons and the regenerative support of Schwann cells over time. Brief low-frequency electrical stimulation accelerates motor and sensory axon outgrowth across injury sites that, even after delayed surgical repair of injured nerves in animal models and patients, enhances nerve regeneration and target reinnervation. The stimulation elevates neuronal cyclic adenosine monophosphate and, in turn, the expression of neurotrophic factors and other growth-associated genes, including cytoskeletal proteins. Electrical stimulation of denervated muscles immediately after nerve transection and surgical repair also accelerates muscle reinnervation but, at this time, how the daily requirement of long-duration electrical pulses can be delivered to muscles remains a practical issue prior to translation to patients. Finally, the technique of inserting autologous nerve grafts that bridge between a donor nerve and an adjacent recipient denervated nerve stump significantly improves nerve regeneration after delayed nerve repair, the donor nerves sustaining the capacity of the denervated Schwann cells to support nerve regeneration. These reviewed methods to promote nerve regeneration and, in turn, to enhance functional recovery after nerve injury and surgical repair are sufficiently promising for early translation to the clinic. PMID:26754579

  9. Chemotherapy-induced bone marrow nerve injury impairs hematopoietic regeneration

    PubMed Central

    Lucas, Daniel; Scheiermann, Christoph; Chow, Andrew; Kunisaki, Yuya; Bruns, Ingmar; Barrick, Colleen; Tessarollo, Lino; Frenette, Paul S.

    2013-01-01

    Anti-cancer chemotherapy drugs challenge hematopoietic tissues to regenerate, but commonly produce long-term sequelae. Deficits in hematopoietic stem or stromal cell function have been described, but the mechanisms mediating chemotherapy-induced hematopoietic dysfunction remain unclear. Administration of multiple cycles of cisplatin chemotherapy causes significant sensory neuropathy. Here, we demonstrate that chemotherapy-induced nerve injury in the bone marrow is a critical lesion impairing hematopoietic regeneration. We show using various pharmacological and genetic models that the selective loss of adrenergic innervation in the BM alters its regeneration following genotoxic insult. Sympathetic nerves in the marrow promote the survival of stem cell niche constituents that initiate recovery. Neuroprotection by deletion of Trp53 in sympathetic neurons or neuro-regeneration using 4-methylcatechol or glial-derived neurotrophic factor (GDNF) administration can restore hematopoietic recovery. Thus, these results shed light on the potential benefit of adrenergic nerve protection to shield hematopoietic niches from injury. PMID:23644514

  10. The effects of sensory denervation on the responses of the rabbit eye to prostaglandin E1, bradykinin and substance P.

    PubMed Central

    Butler, J. M.; Hammond, B. R.

    1980-01-01

    1 Six to eight days after diathermic destruction of the fifth cranial nerve in the rabbit, the ocular hypertensive and miotic responses to intracameral administration of capsaicin, bradykinin, and prostaglandin E1 were greatly reduced or completely abolished. The response to substance P was not abolished. 2 A response could still be obtained to chemical irritants 36 h after coagulation of the nerve and it is deduced that manifestation of the response is dependent upon functional sensory nerve terminals, and is independent of central connections. 3 It is suggested that prostaglandin E1 and bradykinin act directly upon the sensory nerve endings and that propagation of the response is augmented by axon reflex. 4 In view of the ability of substance P to induce miosis in the denervated eyes, it is presumed that its actions are not mediated via sensory nerves. 5 It is considered possible that the mediator(s) released from sensory nerve endings after chemical irritation or antidromic stimulation may act in the same way as substance P with regard to the miotic effect. 6 Synthetic substance P will only produce ocular hypertension in doses which induce a maximal miotic response. This may either be a question of access or a partial resemblance to the endogenous mediator. PMID:6156734

  11. Facilitating and Debilitating Test Anxiety Among College Students and Volunteers for Desensitization Workshops

    ERIC Educational Resources Information Center

    Hudesman, John; Wiesner, Ezra

    1978-01-01

    Examines whether the degree of facilitating and debilitating test anxiety is different for students who volunteer for test anxiety desensitization workshops than it is for the general college population, whether test anxiety in urban community college students is correlated, and whether either or both of the AAT scales are predictive of student…

  12. The Systematic Desensitization of High Debilitating Test Anxious College Students by Relaxation and Assertion.

    ERIC Educational Resources Information Center

    Parker, Paul J.

    The present study compared the effects of assertion with that of progressive relaxation training in systematic desensitization. Nineteen Ss were selected on the basis of exemplifying high debilitating test anxiety according to Alpert and Haber's (1960) Achievement Anxiety Test. Results showed that test anxious Ss who received either relaxation or…

  13. 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…

  14. Systematic Desensitization as a Model for Dealing with the Reticent Student.

    ERIC Educational Resources Information Center

    Pedersen, Douglas J.

    1980-01-01

    Describes systematic desensitization as a form of behavior therapy for reducing anxiety. Examines its rationale and clinical practice and explores two features of the technique (relaxation and anxiety hierarchy) as they may be applied to classroom speech instruction for reticent students. (JMF)

  15. Expectancy, False Galvanic Skin Response Feedback, and Systematic Desensitization in the Modification of Phobic Behavior

    ERIC Educational Resources Information Center

    Lick, John

    1975-01-01

    This study compared systematic desensitization and two pseudotherapy manipulations with and without false galvanic skin response feedback after every session suggesting improvement in the modification of intense snake and spider fear. The results indicated no consistent differences between the three treatment groups. (Author)

  16. Treatment of Speech Anxiety by Cue-Controlled Relaxation and Desensitization with Professional and Paraprofessional Counselors

    ERIC Educational Resources Information Center

    Russell, Richard K.; Wise, Fred

    1976-01-01

    This investigation compared the relative effectiveness of group-administered cue-controlled relaxation and group systematic desensitization in the treatment of speech anxiety. Also examined was the role of professional versus paraprofessional counselors in implementing the treatment program. A description of the cue-controlled relaxation technique…

  17. Treatment of Test Anxiety by Cue-Controlled Relaxation and Systematic Desensitization

    ERIC Educational Resources Information Center

    Russell, Richard K.; And Others

    1976-01-01

    Test-anxious subjects (N=19) participated in an outcome study comparing systematic desensitization, cue-controlled relaxation, and no treatment. The treatment groups demonstrated significant improvement on the self-report measures of test and state anxiety but not on the behavioral indices. The potential advantages of this technique over…

  18. Cue-Controlled Relaxation and Systematic Desensitization versus Nonspecific Factors in Treating Test Anxiety.

    ERIC Educational Resources Information Center

    Russell, Richard K.; Lent, Robert W.

    1982-01-01

    Compared the efficacy of two behavioral anxiety reduction techniques against "subconscious reconditioning," an empirically derived placebo method. Examination of within-group changes showed systematic desensitization produced significant reductions in test and trait anxiety, and remaining treatments and the placebo demonstrated significant…

  19. Implementation of a Systematic Desensitization Program and Classroom Instruction to Reduce Communication Apprehension in Pharmacy Students.

    ERIC Educational Resources Information Center

    Berger, Bruce A.

    1982-01-01

    Since research shows the proportion of pharmacy students with high communication apprehension greater than in the general population, a formal program to combine systematic desensitization and cognitive restructuring with classroom instruction was developed. Results indicate substantial reductions in communication apprehension. (Author/MSE)

  20. Overcoming Math Anxiety: A Comparison of Stress Inoculation Training and Systematic Desensitization.

    ERIC Educational Resources Information Center

    Schneider, Walter J.; Nevid, Jeffrey S.

    1993-01-01

    Stress inoculation training and systematic desensitization treatment provided to 45 college students resulted in significantly lower mathematics anxiety ratings and less subjective distress reported prior to a mathematics aptitude test, with no significant changes found in a delayed treatment control. No treatment group differences were found for…

  1. A Sexual-Enchantment Workshop: Beyond Group Systematic Desensitization for Women's Sexual Anxiety

    ERIC Educational Resources Information Center

    Sotile, Wayne M.; And Others

    1977-01-01

    This study investigates whether six women who previously had received 15 sessions of group systematic desensitization (SD) for their sexual anxiety would report additional treatment gains from participation in a sexual-enchantment workshop with their partners. The women reported a significant decrease in sexual anxiety. (Author)

  2. 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…

  3. A Comparison of Systematic Desensitization and Conditioned Relaxation in Reducing Speech Anxiety.

    ERIC Educational Resources Information Center

    Heald, Gary R.

    Speech and communication departments at several universities currently offer behavioral training programs aimed at reducing communication-related anxiety. Traditionally, these programs involve the use of a "systematic desensitization" training method. An alternative behavioral training method is found in "conditioned relaxation." This paper…

  4. Vicarious Desensitization of Test Anxiety Through Observation of Video-taped Treatment

    ERIC Educational Resources Information Center

    Mann, Jay

    1972-01-01

    Procedural variations were compared for a vicarious group treatment of test anxiety involving observation of videotapes depicting systematic desensitization of a model. The theoretical implications of the present study and the feasibility of using videotaped materials to treat test anxiety and other avoidance responses in school settings are…

  5. A Self-Control Versus a Counterconditioning Paradigm for Systematic Desensitization: An Experimental Comparison

    ERIC Educational Resources Information Center

    Spiegler, Michael D.; And Others

    1976-01-01

    A comparison was made between the traditional counterconditioning paradigm and a self-control paradigm of systematic desensitization. College students reporting high test anxiety and indicating interest in receiving treatment were assigned to counterconditioning, self-control, or wait-list control conditions. As predicted, self-control procedures…

  6. 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 240 min. 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

  7. Heme-assisted S-Nitrosation Desensitizes Ferric Soluble Guanylate Cyclase to Nitric Oxide*

    PubMed Central

    Fernhoff, Nathaniel B.; Derbyshire, Emily R.; Underbakke, Eric S.; Marletta, Michael A.

    2012-01-01

    Nitric oxide (NO) signaling regulates key processes in cardiovascular physiology, specifically vasodilation, platelet aggregation, and leukocyte rolling. Soluble guanylate cyclase (sGC), the mammalian NO sensor, transduces an NO signal into the classical second messenger cyclic GMP (cGMP). NO binds to the ferrous (Fe2+) oxidation state of the sGC heme cofactor and stimulates formation of cGMP several hundred-fold. Oxidation of the sGC heme to the ferric (Fe3+) state desensitizes the enzyme to NO. The heme-oxidized state of sGC has emerged as a potential therapeutic target in the treatment of cardiovascular disease. Here, we investigate the molecular mechanism of NO desensitization and find that sGC undergoes a reductive nitrosylation reaction that is coupled to the S-nitrosation of sGC cysteines. We further characterize the kinetics of NO desensitization and find that heme-assisted nitrosothiol formation of β1Cys-78 and β1Cys-122 causes the NO desensitization of ferric sGC. Finally, we provide evidence that the mechanism of reductive nitrosylation is gated by a conformational change of the protein. These results yield insights into the function and dysfunction of sGC in cardiovascular disease. PMID:23093402

  8. Ethanol increases desensitization of recombinant GluR-D AMPA receptor and TARP combinations

    PubMed Central

    Möykkynen, Tommi P.; Coleman, Sarah K.; Keinänen, Kari; Lovinger, David M.; Korpi, Esa R.

    2009-01-01

    Glutamate receptors are important target molecules of the acute effect of ethanol. We studied ethanol sensitivity of homomeric GluR-D receptors expressed in HEK293 cells, and examined whether recently discovered transmembrane AMPA receptor regulatory proteins (TARPs) affect ethanol sensitivity. Co-expression of the TARPs, stargazin and γ4, increased the time constant (τ-value) of current decay in the presence of agonist, thus slowing the onset of desensitization and increasing the steady-state current. Ethanol produced less inhibition of the peak current than the steady-state current for all types of the GluR-D receptors. In addition, ethanol concentration-dependently accelerated the rate of desensitization, measured as the τ-value of fast decay of peak current. This effect was enhanced with co-expression of TARPs. The recovery from desensitization was slowed down by co-expression of γ4, but ethanol did not affect this process in any GluR-D combination. The results support the idea that increased desensitization is an important mechanism in the ethanol inhibition of AMPA receptors, and indicate that co-expression of TARPs can alter this effect of ethanol. PMID:19560629

  9. 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…

  10. 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…

  11. 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…

  12. 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 GlyRα1 receptors. Here, we demonstrate that this reconstitution is not restricted to α1 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 α1 subunits, rescue by domain complementation was less efficient when GlyRα3 or the GABAA/C subunit ρ1 was used. If truncation disrupted an alternative splicing cassette within the intracellular TM3–4 loop of α3 subunits, which also regulates receptor desensitization, functional rescue was not possible. When α3 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 α1/α3 receptor chimeras harboring or lacking the α3 splice cassette proving that functional rescue depends on the integrity of the alternative splicing cassette in α3. Thus, an intact α3 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

  13. 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 GlyRα1 receptors. Here, we demonstrate that this reconstitution is not restricted to α1 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 α1 subunits, rescue by domain complementation was less efficient when GlyRα3 or the GABAA/C subunit ρ1 was used. If truncation disrupted an alternative splicing cassette within the intracellular TM3-4 loop of α3 subunits, which also regulates receptor desensitization, functional rescue was not possible. When α3 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 α1/α3 receptor chimeras harboring or lacking the α3 splice cassette proving that functional rescue depends on