Sample records for sensory nerve desensitization

  1. 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

  2. Diagnostic value of the near-nerve needle sensory nerve conduction in sensory inflammatory demyelinating polyneuropathy.

    PubMed

    Odabasi, Zeki; Oh, Shin J

    2018-03-01

    In this study we report the diagnostic value of the near-nerve needle sensory nerve conduction study (NNN-SNCS) in sensory inflammatory demyelinating polyneuropathy (IDP) in which the routine nerve conduction study was normal or non-diagnostic. The NNN-SNCS was performed to identify demyelination in the plantar nerves in 14 patients and in the median or ulnar nerve in 2 patients with sensory IDP. In 16 patients with sensory IDP, routine NCSs were either normal or non-diagnostic for demyelination. Demyelination was identified by NNN-SNCS by dispersion and/or slow nerve conduction velocity (NCV) below the demyelination marker. Immunotherapy was initiated in 11 patients, 10 of whom improved or remained stable. NNN-SNCS played an essential role in identifying demyelinaton in 16 patients with sensory IDP, leading to proper treatment. Muscle Nerve 57: 414-418, 2018. © 2017 Wiley Periodicals, Inc.

  3. Contribution of sensory nerves to LPS-induced hyperresponsiveness of human isolated bronchi.

    PubMed

    Calzetta, Luigino; Luongo, Livio; Cazzola, Mario; Page, Clive; Rogliani, Paola; Facciolo, Francesco; Maione, Sabatino; Capuano, Annalisa; Rinaldi, Barbara; Matera, Maria Gabriella

    2015-06-15

    Bacterial lipopolysaccharide (LPS) can induce bronchial hyperresponsiveness (BHR), but the underlying mechanisms remain to be determined. Here, the possible contribution of sensory nerves to LPS-induced BHR was examined in human isolated bronchi to pharmacologically identify the mechanisms underlying this phenomenon. Human isolated bronchial tone was induced by electrical field stimulation (EFS). The responses of airways to LPS, with or without capsaicin desensitization or thiorphan treatment were studied and the transient receptor potential vanilloid type 1 (TRPV1) expression was assessed. We performed similar experiments in the presence of a TRPV1 or a neurokinin (NK) 2 receptor antagonist using SB366791 and GR159897, respectively. LPS increased (≃2.3-fold, P<0.001) the contraction induced by EFS, compared to control tissues. Acute administration of capsaicin enhanced (≃2.3-fold, P<0.001) the EFS-mediated contraction, but did not potentiate the effect of LPS. Thiorphan increased (≃1.3-fold, P<0.05) the contractile response of LPS treated tissues and, at lower frequencies, it enhanced (≃1.7-fold, P<0.001) the capsaicin-induced contraction. In capsaicin-desensitized bronchi, LPS did not modify (P>0.05) the EFS contractile response, nor after treatment with thiorphan. Capsaicin desensitization reduced (≃0.4-fold, P<0.001) the LPS-induced BHR. SB366791 and GR159897 prevented the LPS-induced BHR and the release of NKA. LPS increased (+85.3±9.5%, P<0.01) the surface membrane expression of TRPV1 in parasympathetic ganglia. Our results demonstrate the involvement of capsaicin-sensitive sensory nerves and neutral endopeptidases in LPS-induced BHR of the human bronchi, associated with an upregulation of TRPV1 and release of NKA. Copyright © 2015. Published by Elsevier Inc.

  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. Menthol Enhances the Desensitization of Human α3β4 Nicotinic Acetylcholine Receptors

    PubMed Central

    Ton, Hoai T.; Smart, Amanda E.; Aguilar, Brittany L.; Olson, Thao T.

    2015-01-01

    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 Ca2+ imaging, 86Rb+ 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 [3H]epibatidine. Taken together, these data indicate that menthol promotes desensitization of α3β4 nAChRs by an allosteric action. PMID:25964258

  6. Sensory conduction of the sural nerve in polyneuropathy.

    PubMed

    Burke, D; Skuse, N F; Lethlean, A K

    1974-06-01

    Using surface electrodes, sensory nerve action potentials (SAP) have been recorded in the proximal segment (mid-calf to lateral malleolus) and the distal segment (lateral malleolus to toe 5) of the sural nerve and in the median nerve in 79 control subjects. The values obtained for the distal segment of the sural nerve varied widely and in seven apparently normal subjects no SAP could be distinguished. In the proximal segment conduction velocities were over 40 m/s and there was no significant change with age, unlike the median nerve in which a highly significant slowing occurred with age. Comparison of the results of sural and median sensory conduction studies in 300 consecutive patients screened for sensory polyneuropathy confirms the value of sural nerve sensory studies as a routine screening test, and confirms the belief that the changes in polyneuropathy are usually more prominent in lower limb nerves. It is therefore suggested that studies of sural sensory conduction form the single most useful test in the diagnosis of sensory polyneuropathy.

  7. Prognostic factors in sensory recovery after digital nerve repair.

    PubMed

    Bulut, Tuğrul; Akgün, Ulaş; Çıtlak, Atilla; Aslan, Cihan; Şener, Ufuk; Şener, Muhittin

    2016-01-01

    The prognostic factors that affect sensory nerve recovery after digital nerve repair are variable because of nonhomogeneous data, subjective tests, and different assessment/scoring methods. The aim of this study was to evaluate the success of sensory nerve recovery after digital nerve repair and to investigate the prognostic factors in sensorial healing. Ninety-six digital nerve repairs of 63 patients were retrospectively evaluated. All nerves were repaired with end-to-end neurorraphy. The static two-point discrimination (s2PD) and Semmes Weinstein monofilament (SWM) tests were performed to evaluate sensory recovery. The association between prognostic factors such as gender, age, involved digit, time from injury to repair, length of follow-up, smoking, concomitant injuries, type of injury, and sensory recovery results were assessed. The s2PD test demonstrated excellent results in 26 nerves (27%), good results in 61 nerves (64%), and poor results in 9 nerves (9%). The results of the SWM test according to Imai classification showed that 31 nerves (32%) were normal, light touch was diminished in 38 nerves (40%), protective sensation was diminished in 17 nerves (18%), loss of protective sensation occurred in 5 nerves (5%), and 5 nerves (5%) were anesthetic. There was a negative relationship between age, smoking, concomitant injuries, and sensory recovery. Our results demonstrate that concomitant tendon, bone and vascular injuries, older age, and smoking were associated with worse sensory nerve recovery results. However, all digital nerve injuries should be repaired, regardless of these prognostic factors.

  8. End-to-side neurorrhaphy repairs peripheral nerve injury: sensory nerve induces motor nerve regeneration.

    PubMed

    Yu, Qing; Zhang, She-Hong; Wang, Tao; Peng, Feng; Han, Dong; Gu, Yu-Dong

    2017-10-01

    End-to-side neurorrhaphy is an option in the treatment of the long segment defects of a nerve. It involves suturing the distal stump of the disconnected nerve (recipient nerve) to the side of the intimate adjacent nerve (donor nerve). However, the motor-sensory specificity after end-to-side neurorrhaphy remains unclear. This study sought to evaluate whether cutaneous sensory nerve regeneration induces motor nerves after end-to-side neurorrhaphy. Thirty rats were randomized into three groups: (1) end-to-side neurorrhaphy using the ulnar nerve (mixed sensory and motor) as the donor nerve and the cutaneous antebrachii medialis nerve as the recipient nerve; (2) the sham group: ulnar nerve and cutaneous antebrachii medialis nerve were just exposed; and (3) the transected nerve group: cutaneous antebrachii medialis nerve was transected and the stumps were turned over and tied. At 5 months, acetylcholinesterase staining results showed that 34% ± 16% of the myelinated axons were stained in the end-to-side group, and none of the myelinated axons were stained in either the sham or transected nerve groups. Retrograde fluorescent tracing of spinal motor neurons and dorsal root ganglion showed the proportion of motor neurons from the cutaneous antebrachii medialis nerve of the end-to-side group was 21% ± 5%. In contrast, no motor neurons from the cutaneous antebrachii medialis nerve of the sham group and transected nerve group were found in the spinal cord segment. These results confirmed that motor neuron regeneration occurred after cutaneous nerve end-to-side neurorrhaphy.

  9. End-to-side neurorrhaphy repairs peripheral nerve injury: sensory nerve induces motor nerve regeneration

    PubMed Central

    Yu, Qing; Zhang, She-hong; Wang, Tao; Peng, Feng; Han, Dong; Gu, Yu-dong

    2017-01-01

    End-to-side neurorrhaphy is an option in the treatment of the long segment defects of a nerve. It involves suturing the distal stump of the disconnected nerve (recipient nerve) to the side of the intimate adjacent nerve (donor nerve). However, the motor-sensory specificity after end-to-side neurorrhaphy remains unclear. This study sought to evaluate whether cutaneous sensory nerve regeneration induces motor nerves after end-to-side neurorrhaphy. Thirty rats were randomized into three groups: (1) end-to-side neurorrhaphy using the ulnar nerve (mixed sensory and motor) as the donor nerve and the cutaneous antebrachii medialis nerve as the recipient nerve; (2) the sham group: ulnar nerve and cutaneous antebrachii medialis nerve were just exposed; and (3) the transected nerve group: cutaneous antebrachii medialis nerve was transected and the stumps were turned over and tied. At 5 months, acetylcholinesterase staining results showed that 34% ± 16% of the myelinated axons were stained in the end-to-side group, and none of the myelinated axons were stained in either the sham or transected nerve groups. Retrograde fluorescent tracing of spinal motor neurons and dorsal root ganglion showed the proportion of motor neurons from the cutaneous antebrachii medialis nerve of the end-to-side group was 21% ± 5%. In contrast, no motor neurons from the cutaneous antebrachii medialis nerve of the sham group and transected nerve group were found in the spinal cord segment. These results confirmed that motor neuron regeneration occurred after cutaneous nerve end-to-side neurorrhaphy. PMID:29171436

  10. The sensory-motor bridge neurorraphy: an anatomic study of feasibility between sensory branch of the musculocutaneous nerve and deep branch of the radial nerve.

    PubMed

    Goubier, Jean-Noel; Teboul, Frédéric

    2011-05-01

    Restoring elbow flexion remains the first step in the management of total palsy of the brachial plexus. Non avulsed upper roots may be grafted on the musculocutaneous nerve. When this nerve is entirely grafted, some motor fibres regenerate within the sensory fibres quota. Aiming potential utilization of these lost motor fibres, we attempted suturing the sensory branch of the musculocutaneous nerve onto the deep branch of the radial nerve. The objective of our study was to assess the anatomic feasibility of such direct suturing of the terminal sensory branch of the musculocutaneous nerve onto the deep branch of the radial nerve. The study was carried out with 10 upper limbs from fresh cadavers. The sensory branch of the musculocutaneous muscle was dissected right to its division. The motor branch of the radial nerve was identified and dissected as proximally as possible into the radial nerve. Then, the distance separating the two nerves was measured so as to assess whether direct neurorraphy of the two branches was feasible. The excessive distance between the two branches averaged 6 mm (1-13 mm). Thus, direct neurorraphy of the sensory branch of the musculocutaneous nerve and the deep branch of the radial nerve was possible. When the whole musculocutaneous nerve is grafted, some of its motor fibres are lost amongst the sensory fibres (cutaneous lateral antebrachial nerve). By suturing this sensory branch onto the deep branch of the radial nerve, "lost" fibres may be retrieved, resulting in restoration of digital extension. Copyright © 2011 Wiley-Liss, Inc.

  11. Parkinson disease affects peripheral sensory nerves in the pharynx.

    PubMed

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

    2013-07-01

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

  12. Parkinson Disease Affects Peripheral Sensory Nerves in the Pharynx

    PubMed Central

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

    2013-01-01

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

  13. Morphological differences in skeletal muscle atrophy of rats with motor nerve and/or sensory nerve injury★

    PubMed Central

    Zhao, Lei; Lv, Guangming; Jiang, Shengyang; Yan, Zhiqiang; Sun, Junming; Wang, Ling; Jiang, Donglin

    2012-01-01

    Skeletal muscle atrophy occurs after denervation. The present study dissected the rat left ventral root and dorsal root at L4-6 or the sciatic nerve to establish a model of simple motor nerve injury, sensory nerve injury or mixed nerve injury. Results showed that with prolonged denervation time, rats with simple motor nerve injury, sensory nerve injury or mixed nerve injury exhibited abnormal behavior, reduced wet weight of the left gastrocnemius muscle, decreased diameter and cross-sectional area and altered ultrastructure of muscle cells, as well as decreased cross-sectional area and increased gray scale of the gastrocnemius muscle motor end plate. Moreover, at the same time point, the pathological changes were most severe in mixed nerve injury, followed by simple motor nerve injury, and the changes in simple sensory nerve injury were the mildest. These findings indicate that normal skeletal muscle morphology is maintained by intact innervation. Motor nerve injury resulted in larger damage to skeletal muscle and more severe atrophy than sensory nerve injury. Thus, reconstruction of motor nerves should be considered first in the clinical treatment of skeletal muscle atrophy caused by denervation. PMID:25337102

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

    PubMed

    Calder, Kristina M; Martin, Alison; Lydiate, Jessica; MacDermid, Joy C; Galea, Victoria; MacIntyre, Norma J

    2012-05-10

    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. 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. 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. 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.

  15. 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

  16. Role of renal sensory nerves in physiological and pathophysiological conditions

    PubMed Central

    2014-01-01

    Whether activation of afferent renal nerves contributes to the regulation of arterial pressure and sodium balance has been long overlooked. In normotensive rats, activating renal mechanosensory nerves decrease efferent renal sympathetic nerve activity (ERSNA) and increase urinary sodium excretion, an inhibitory renorenal reflex. There is an interaction between efferent and afferent renal nerves, whereby increases in ERSNA increase afferent renal nerve activity (ARNA), leading to decreases in ERSNA by activation of the renorenal reflexes to maintain low ERSNA to minimize sodium retention. High-sodium diet enhances the responsiveness of the renal sensory nerves, while low dietary sodium reduces the responsiveness of the renal sensory nerves, thus producing physiologically appropriate responses to maintain sodium balance. Increased renal ANG II reduces the responsiveness of the renal sensory nerves in physiological and pathophysiological conditions, including hypertension, congestive heart failure, and ischemia-induced acute renal failure. Impairment of inhibitory renorenal reflexes in these pathological states would contribute to the hypertension and sodium retention. When the inhibitory renorenal reflexes are suppressed, excitatory reflexes may prevail. Renal denervation reduces arterial pressure in experimental hypertension and in treatment-resistant hypertensive patients. The fall in arterial pressure is associated with a fall in muscle sympathetic nerve activity, suggesting that increased ARNA contributes to increased arterial pressure in these patients. Although removal of both renal sympathetic and afferent renal sensory nerves most likely contributes to the arterial pressure reduction initially, additional mechanisms may be involved in long-term arterial pressure reduction since sympathetic and sensory nerves reinnervate renal tissue in a similar time-dependent fashion following renal denervation. PMID:25411364

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

    PubMed

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

    2015-08-01

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

  18. Aspirin Desensitization

    MedlinePlus

    ... Nerve Decompression Dacryocystorhinostomy (DCR) Disclosure Statement Printer Friendly Aspirin Desensitization Kevin C. Welch, MD Zara Patel, MD Introduction The term "aspirin-sensitive asthma" (also known as "aspirin triad" or " ...

  19. Differential aging of median and ulnar sensory nerve parameters.

    PubMed

    Werner, Robert A; Franzblau, Alfred; D'Arcy, Hannah J S; Evanoff, Bradley A; Tong, Henry C

    2012-01-01

    Nerve conduction velocity slows and amplitude declines with aging. Median and ulnar sensory nerves were tested at the annual meetings of the American Dental Association. Seven hundred four subjects had at least two observations. The rate of change in the nerve parameters was estimated while controlling for gender, age, change in hand temperature, baseline body mass index (BMI), and change in BMI. Amplitudes of the median sensory nerve action potentials decreased by 0.58 μV per year, whereas conduction velocity decreased at a rate of 0.41 m/s per year. Corresponding values for the ulnar nerve were 0.89 μV and 0.29 m/s per year. The rates of change in amplitudes did not differ, but the median nerve demonstrated a more rapid loss of conduction velocity. The rate of change for the median conduction velocity was higher than previously reported. The rate of change of median conduction velocity was significantly greater than for the ulnar nerve. Copyright © 2011 Wiley Periodicals, Inc.

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

    PubMed

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

    2012-06-01

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

  1. Comparison of four different nerve conduction techniques of the superficial fibular sensory nerve.

    PubMed

    Saffarian, Mathew R; Condie, Nathan C; Austin, Erica A; Mccausland, Katie E; Andary, Michael T; Sylvain, James R; Mull, Iian R; Zemper, Eric D; Jannausch, Mary L

    2017-09-01

    There are many different nerve conduction study (NCS) techniques to study the superficial fibular sensory nerve (SFSN). We present reference distal latency values and comparative data regarding 4 different NCS for the SFSN. Four different NCS techniques, Spartan technique, Izzo techniques (medial and intermediate dorsal cutaneous branches), and Daube technique, were performed on (114) healthy volunteers. A total of 108 subjects with 164 legs were included. The mean latency of the Spartan technique was longest (3.9 ± 0.3 ms) while the Daube technique was the shortest (3.6 ± 0.7 ms). The mean amplitude of the Daube technique displayed the highest (15.2 ± 8.2 μV) with the Spartan technique having the lowest (8.7 ± 4.2 μV). Among the absent sensory nerve action potentials (SNAPs), the Spartan technique was absent only twice (1.2%) and the Izzo Medial technique was absent more than the other techniques (2.9%). All 4 techniques were reliable methods for obtaining the superficial fibular nerve SNAP, present in 95% of individuals. Muscle Nerve 56: 458-462, 2017. © 2017 Wiley Periodicals, Inc.

  2. Desensitizing the posterior interosseous nerve alters wrist proprioceptive reflexes.

    PubMed

    Hagert, Elisabet; Persson, Jonas K E

    2010-07-01

    The presence of wrist proprioceptive reflexes after stimulation of the dorsal scapholunate interosseous ligament has previously been described. Because this ligament is primarily innervated by the posterior interosseous nerve (PIN) we hypothesized altered ligamento-muscular reflex patterns following desensitization of the PIN. Eight volunteers (3 women, 5 men; mean age, 26 y; range 21-28 y) participated in the study. In the first study on wrist proprioceptive reflexes (study 1), the scapholunate interosseous ligament was stimulated through a fine-wire electrode with 4 1-ms bipolar pulses at 200 Hz, 30 times consecutively, while EMG activity was recorded from the extensor carpi radialis brevis, extensor carpi ulnaris, flexor carpi radialis, and flexor carpi ulnaris, with the wrist in extension, flexion, radial deviation, and ulnar deviation. After completion of study 1, the PIN was anesthetized in the radial aspect of the fourth extensor compartment using 2-mL lidocaine (10 mg/mL) infiltration anesthesia. Ten minutes after desensitization, the experiment was repeated as in study 1. The average EMG results from the 30 consecutive stimulations were rectified and analyzed using Student's t-test. Statistically significant changes in EMG amplitude were plotted along time lines so that the results of study 1 and 2 could be compared. Dramatic alterations in reflex patterns were observed in wrist flexion, radial deviation, and ulnar deviation following desensitization of the PIN, with an average of 72% reduction in excitatory reactions. In ulnar deviation, the inhibitory reactions of the extensor carpi ulnaris were entirely eliminated. In wrist extension, no differences in the reflex patterns were observed. Wrist proprioception through the scapholunate ligament in flexion, radial deviation, and ulnar deviation depends on an intact PIN function. The unchanged reflex patterns in wrist extension suggest an alternate proprioceptive pathway for this position. Routine excision of

  3. 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.

  4. 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

  5. Oral sensory nerve damage: Causes and consequences.

    PubMed

    Snyder, Derek J; Bartoshuk, Linda M

    2016-06-01

    Oral sensations (i.e., taste, oral somatosensation, retronasal olfaction) are integrated into a composite sense of flavor, which guides dietary choices with long-term health impact. The nerves carrying this input are vulnerable to peripheral damage from multiple sources (e.g., otitis media, tonsillectomy, head injury), and this regional damage can boost sensations elsewhere in the mouth because of central interactions among nerve targets. Mutual inhibition governs this compensatory process, but individual differences lead to variation in whole-mouth outcomes: some individuals are unaffected, others experience severe loss, and some encounter sensory increases that may (if experienced early in life) elevate sweet-fat palatability and body mass. Phantom taste, touch, or pain sensations (e.g., burning mouth syndrome) may also occur, particularly in those expressing the most taste buds. To identify and treat these conditions effectively, emerging clinical tests measure regional vs. whole-mouth sensation, stimulated vs. phantom cues, and oral anatomy. Scaling methods allowing valid group comparisons have strongly aided these efforts. Overall, advances in measuring oral sensory function in health and disease show promise for understanding the varied clinical consequences of nerve damage.

  6. Oral Sensory Nerve Damage: Causes and Consequences

    PubMed Central

    Snyder, Derek J.; Bartoshuk, Linda M.

    2016-01-01

    Oral sensations (i.e., taste, oral somatosensation, retronasal olfaction) are integrated into a composite sense of flavor, which guides dietary choices with long-term health impact. The nerves carrying this input are vulnerable to peripheral damage from multiple sources (e.g., otitis media, tonsillectomy, head injury), and this regional damage can boost sensations elsewhere in the mouth because of central interactions among nerve targets. Mutual inhibition governs this compensatory process, but individual differences lead to variation in whole-mouth outcomes: some individuals are unaffected, others experience severe loss, and some encounter sensory increases that may (if experienced early in life) elevate sweet-fat palatability and body mass. Phantom taste, touch, or pain sensations (e.g., burning mouth syndrome) may also occur, particularly in those expressing the most taste buds. To identify and treat these conditions effectively, emerging clinical tests measure regional vs. whole-mouth sensation, stimulated vs. phantom cues, and oral anatomy. Scaling methods allowing valid group comparisons have strongly aided these efforts. Overall, advances in measuring oral sensory function in health and disease show promise for understanding the varied clinical consequences of nerve damage. PMID:27511471

  7. Sonoanatomy of sensory branches of the ulnar nerve below the elbow in healthy subjects.

    PubMed

    Kim, Ki Hoon; Lee, Seok Jun; Park, Byung Kyu; Kim, Dong Hwee

    2018-04-01

    We identify sensory branches of the ulnar nerve-palmar ulnar cutaneous nerve (PUCN), dorsal ulnar cutaneous nerve (DUCN), and superficial sensory branch-using ultrasonography. In 60 forearms of 30 healthy adult volunteers, the origin and size of the PUCN, DUCN, and superficial sensory branch were measured by ultrasonography. The relative pathway of the DUCN to the ulnar styloid process was also investigated. The PUCN was observed in 47 forearms (78%), and the DUCN was observed in all forearms. Average distances from the pisiform to the origin of the PUCN and DUCN were 11.9 ± 1.4 and 7.0 ± 1.0 cm, respectively. Superficial and deep divisions split 0.9 ± 0.3 cm distal to the pisiform. Cross-sectional areas of the PUCN, DUCN, and superficial sensory branch were 0.3 ± 0.1, 1.5 ± 0.5, and 3.9 ± 1.0 mm 2 , respectively. Sensory branches of the ulnar nerve can be visualized by ultrasonography, helping to differentiate ulnar nerve injury originating at either wrist or elbow. Muscle Nerve 57: 569-573, 2018. © 2017 Wiley Periodicals, Inc.

  8. Outcomes of short-gap sensory nerve injuries reconstructed with processed nerve allografts from a multicenter registry study.

    PubMed

    Rinker, Brian D; Ingari, John V; Greenberg, Jeffrey A; Thayer, Wesley P; Safa, Bauback; Buncke, Gregory M

    2015-06-01

    Short-gap digital nerve injuries are a common surgical problem, but the optimal treatment modality is unknown. A multicenter database was queried and analyzed to determine the outcomes of nerve gap reconstructions between 5 and 15 mm with processed nerve allograft. The current RANGER registry is designed to continuously monitor and compile injury, repair, safety, and outcomes data. Centers followed their own standard of care for treatment and follow-up. The database was queried for digital nerve injuries with a gap between 5 and 15 mm reporting sufficient follow-up data to complete outcomes analysis. Available quantitative outcome measures were reviewed and reported. Meaningful recovery was defined by the Medical Research Council Classification (MRCC) scale at S3-S4 for sensory function. Sufficient follow-up data were available for 24 subjects (37 repairs) in the prescribed gap range. Mean age was 43 years (range, 23-81). Mean gap was 11 ± 3 (5-15) mm. Time to repair was 13 ± 42 (0-215) days. There were 25 lacerations, 8 avulsion/amputations, 2 gunshots, 1 crush injury, and 1 injury of unknown mechanism. Meaningful recovery, defined as S3-S4 on the MRCC scales, was reported in 92% of repairs. Sensory recovery of S3+ or S4 was observed in 84% of repairs. Static 2PD was 7.1 ± 2.9 mm (n = 19). Return to light touch was observed in 23 out of 32 repairs reporting Semmes-Weinstein monofilament outcomes (SWMF). There were no reported nerve adverse events. Sensory outcomes for processed nerve allografts were equivalent to historical controls for nerve autograft and exceed those of conduit. Processed nerve allografts provide an effective solution for short-gap digital nerve reconstructions. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

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

    PubMed Central

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

    2011-01-01

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

  10. Clitoral Epidermal Inclusion Cyst Resection With Intraoperative Sensory Nerve Mapping Technique.

    PubMed

    Wu, Cindy; Damitz, Lynn; Karrat, Kimberly M; Mintz, Alice; Zolnoun, Denniz

    2016-01-01

    Despite the ever increasing popularity of labial and clitoral surgeries, the best practices and long-term effects of reconstructive procedures in these regions remain unknown. This is particularly noteworthy because the presentation of nerve-related symptoms may be delayed up to a year. Despite the convention that these surgical procedures are low risk, little is known about the best practices that may reduce the postoperative complications as a result of these reconstructive surgeries. We describe a preoperative sensory mapping technique in the context of a symptomatic inclusion cyst in the clitoral region. This technique delineates anatomical and functional regions innervated by the dorsal clitoral nerve while minimizing the vascular watershed area in the midline. A prototypical case of a patient with a clitoral mass is discussed with clinical history and surgical approach. Prior to surgical excision, the dorsal clitoral nerve distribution was mapped in order to avoid a surgical incision in this sensual zone. In our practice, preoperative sensory mapping is a clinically useful planning tool that requires minimal instrumentation and no additional operating time. Sensory mapping allows identification of the functional zone innervated by the dorsal clitoral nerve, which can aid in minimizing damage to the area.

  11. 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

  12. Immunohistochemical Mapping of Sensory Nerve Endings in the Human Triangular Fibrocartilage Complex.

    PubMed

    Rein, Susanne; Semisch, Manuel; Garcia-Elias, Marc; Lluch, Alex; Zwipp, Hans; Hagert, Elisabet

    2015-10-01

    The triangular fibrocartilage complex is the main stabilizer of the distal radioulnar joint. While static joint stability is constituted by osseous and ligamentous integrity, the dynamic aspects of joint stability chiefly concern proprioceptive control of the compressive and directional muscular forces acting on the joint. Therefore, an investigation of the pattern and types of sensory nerve endings gives more insight in dynamic distal radioulnar joint stability. We aimed to (1) analyze the general distribution of sensory nerve endings and blood vessels; (2) examine interstructural distribution of sensory nerve endings and blood vessels; (3) compare the number and types of mechanoreceptors in each part; and (4) analyze intrastructural distribution of nerve endings at different tissue depth. The subsheath of the extensor carpi ulnaris tendon sheath, the ulnocarpal meniscoid, the articular disc, the dorsal and volar radioulnar ligaments, and the ulnolunate and ulnotriquetral ligaments were dissected from 11 human cadaver wrists. Sensory nerve endings were counted in five levels per specimen as total cell amount/cm(2) after staining with low-affinity neurotrophin receptor p75, protein gene product 9.5, and S-100 protein and thereafter classified according to Freeman and Wyke. All types of sensory corpuscles were found in the various structures of the triangular fibrocartilage complex with the exception of the ulnolunate ligament, which contained only Golgi-like endings, free nerve endings, and unclassifiable corpuscles. The articular disc had only free nerve endings. Furthermore, free nerve endings were the predominant sensory nerve ending (median, 72.6/cm(2); range, 0-469.4/cm(2)) and more prevalent than all other types of mechanoreceptors: Ruffini (median, 0; range, 0-5.6/cm(2); difference of medians, 72.6; p < 0.001), Pacini (median, 0; range, 0-3.8/cm(2); difference of medians, 72.6; p < 0.001), Golgi-like (median, 0; range, 0-2.1/cm(2); difference of medians, 72

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

    PubMed

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

    2015-03-25

    Patterned sensory nerve stimulation has been shown to induce plastic changes in the reciprocal Ia inhibitory circuit. However, the mechanisms underlying these changes have not yet been elucidated in detail. The aim of the present study was to determine whether the reactivity of Ia inhibitory interneurons could be altered by patterned sensory nerve stimulation. The degree of reciprocal Ia inhibition, the conditioning effects of transcranial magnetic stimulation (TMS) on the soleus (SOL) muscle H-reflex, and the ratio of the maximum H-reflex amplitude versus maximum M-wave (H(max)/M(max)) were examined in 10 healthy individuals. Patterned electrical nerve stimulation was applied to the common peroneal nerve every 1 s (100 Hz-5 train) at the motor threshold intensity of tibialis anterior muscle to induce activity changes in the reciprocal Ia inhibitory circuit. Reciprocal Ia inhibition, the TMS-conditioned H-reflex amplitude, and H(max)/M(max) were recorded before, immediately after, and 15 min after the electrical stimulation. The patterned electrical nerve stimulation significantly increased the degree of reciprocal Ia inhibition and decreased the amplitude of the TMS-conditioned H-reflex in the short-latency inhibition phase, which was presumably mediated by Ia inhibitory interneurons. However, it had no effect on H(max)/M(max). Our results indicated that patterned sensory nerve stimulation could modulate the activity of Ia inhibitory interneurons, and this change may have been caused by the synaptic modification of Ia inhibitory interneuron terminals. These results may lead to a clearer understanding of the spinal cord synaptic plasticity produced by repetitive sensory inputs. Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.

  14. N-Glycosylation Determines Ionic Permeability and Desensitization of the TRPV1 Capsaicin Receptor*

    PubMed Central

    Veldhuis, Nicholas A.; Lew, Michael J.; Abogadie, Fe C.; Poole, Daniel P.; Jennings, Ernest A.; Ivanusic, Jason J.; Eilers, Helge; Bunnett, Nigel W.; McIntyre, Peter

    2012-01-01

    The balance of glycosylation and deglycosylation of ion channels can markedly influence their function and regulation. However, the functional importance of glycosylation of the TRPV1 receptor, a key sensor of pain-sensing nerves, is not well understood, and whether TRPV1 is glycosylated in neurons is unclear. We report that TRPV1 is N-glycosylated and that N-glycosylation is a major determinant of capsaicin-evoked desensitization and ionic permeability. Both N-glycosylated and unglycosylated TRPV1 was detected in extracts of peripheral sensory nerves by Western blotting. TRPV1 expressed in HEK-293 cells exhibited various degrees of glycosylation. A mutant of asparagine 604 (N604T) was not glycosylated but did not alter plasma membrane expression of TRPV1. Capsaicin-evoked increases in intracellular calcium ([Ca2+]i) were sustained in wild-type TRPV1 HEK-293 cells but were rapidly desensitized in N604T TRPV1 cells. There was marked cell-to-cell variability in capsaicin responses and desensitization between individual cells expressing wild-type TRPV1 but highly uniform responses in cells expressing N604T TRPV1, consistent with variable levels of glycosylation of the wild-type channel. These differences were also apparent when wild-type or N604T TRPV1-GFP fusion proteins were expressed in neurons from trpv1−/− mice. Capsaicin evoked a marked, concentration-dependent increase in uptake of the large cationic dye YO-PRO-1 in cells expressing wild-type TRPV1, indicative of loss of ion selectivity, that was completely absent in cells expressing N604T TRPV1. Thus, TRPV1 is variably N-glycosylated and glycosylation is a key determinant of capsaicin regulation of TRPV1 desensitization and permeability. Our findings suggest that physiological or pathological alterations in TRPV1 glycosylation would affect TRPV1 function and pain transmission. PMID:22570472

  15. Sensory nerves are frequently involved in the spectrum of fisher syndrome.

    PubMed

    Shahrizaila, Nortina; Goh, Khean J; Kokubun, Norito; Tan, Ai H; Tan, Cheng Y; Yuki, Nobuhiro

    2014-04-01

    Differing patterns of neurophysiological abnormalities have been reported in patients with Fisher syndrome. Fisher syndrome is rare, and few series have incorporated prospective serial studies to define the natural history of nerve conduction studies in Guillain-Barré syndrome. In an ongoing prospective study of Guillain-Barré syndrome patients, patients who presented with Fisher syndrome and its spectrum of illness were assessed through serial neurological examinations, nerve conduction studies, and serological testing of IgG against gangliosides and ganglioside complexes. Of the 36 Guillain-Barré syndrome patients identified within 2 years, 17 had features of Fisher syndrome. Serial nerve conduction studies detected significant abnormalities in sensory nerve action potential amplitude in 94% of patients associated with 2 patterns of recovery-non-demyelinating reversible distal conduction failure and axonal regeneration. Similar changes were seen in motor nerves of 5 patients. Patients with the Fisher syndrome spectrum of illness have significant sensory involvement, which may only be evident with serial neurophysiological studies. Copyright © 2013 Wiley Periodicals, Inc.

  16. 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

  17. Double peak sensory nerve action potentials to single stimuli in nerve conduction studies.

    PubMed

    Leote, Joao; Pereira, Pedro; Valls-Sole, Josep

    2017-05-01

    In humans, sensory nerve action potentials (SNAPs) can show 2 separate deflections, i.e., double peak potentials (DPp), which necessarily means that 1 peak is delayed with respect to the other. DPps may have various origins and be due to either physical or physiological properties. We review the nature of commonly encountered DPps in clinical practice, provide the most likely interpretations for their physiological origin, and assess their reproducibility and clinical utility. We classified the DPps into 3 categories: (1) simultaneous anodal and cathodal stimulation. (2) simultaneous recording from 2 different nerves at the same site, and (3) SNAP desynchronization. Although the recording of DPps is not a standardized neurophysiological method, their study brings interesting cues about the physiology of nerve stimulation and paves the way for clinical application of such an observation. Muscle Nerve 55: 619-625, 2017. © 2016 Wiley Periodicals, Inc.

  18. Reliability, reference values and predictor variables of the ulnar sensory nerve in disease free adults.

    PubMed

    Ruediger, T M; Allison, S C; Moore, J M; Wainner, R S

    2014-09-01

    The purposes of this descriptive and exploratory study were to examine electrophysiological measures of ulnar sensory nerve function in disease free adults to determine reliability, determine reference values computed with appropriate statistical methods, and examine predictive ability of anthropometric variables. Antidromic sensory nerve conduction studies of the ulnar nerve using surface electrodes were performed on 100 volunteers. Reference values were computed from optimally transformed data. Reliability was computed from 30 subjects. Multiple linear regression models were constructed from four predictor variables. Reliability was greater than 0.85 for all paired measures. Responses were elicited in all subjects; reference values for sensory nerve action potential (SNAP) amplitude from above elbow stimulation are 3.3 μV and decrement across-elbow less than 46%. No single predictor variable accounted for more than 15% of the variance in the response. Electrophysiologic measures of the ulnar sensory nerve are reliable. Absent SNAP responses are inconsistent with disease free individuals. Reference values recommended in this report are based on appropriate transformations of non-normally distributed data. No strong statistical model of prediction could be derived from the limited set of predictor variables. Reliability analyses combined with relatively low level of measurement error suggest that ulnar sensory reference values may be used with confidence. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  19. Identification of cytokine-specific sensory neural signals by decoding murine vagus nerve activity.

    PubMed

    Zanos, Theodoros P; Silverman, Harold A; Levy, Todd; Tsaava, Tea; Battinelli, Emily; Lorraine, Peter W; Ashe, Jeffrey M; Chavan, Sangeeta S; Tracey, Kevin J; Bouton, Chad E

    2018-05-22

    The nervous system maintains physiological homeostasis through reflex pathways that modulate organ function. This process begins when changes in the internal milieu (e.g., blood pressure, temperature, or pH) activate visceral sensory neurons that transmit action potentials along the vagus nerve to the brainstem. IL-1β and TNF, inflammatory cytokines produced by immune cells during infection and injury, and other inflammatory mediators have been implicated in activating sensory action potentials in the vagus nerve. However, it remains unclear whether neural responses encode cytokine-specific information. Here we develop methods to isolate and decode specific neural signals to discriminate between two different cytokines. Nerve impulses recorded from the vagus nerve of mice exposed to IL-1β and TNF were sorted into groups based on their shape and amplitude, and their respective firing rates were computed. This revealed sensory neural groups responding specifically to TNF and IL-1β in a dose-dependent manner. These cytokine-mediated responses were subsequently decoded using a Naive Bayes algorithm that discriminated between no exposure and exposures to IL-1β and TNF (mean successful identification rate 82.9 ± 17.8%, chance level 33%). Recordings obtained in IL-1 receptor-KO mice were devoid of IL-1β-related signals but retained their responses to TNF. Genetic ablation of TRPV1 neurons attenuated the vagus neural signals mediated by IL-1β, and distal lidocaine nerve block attenuated all vagus neural signals recorded. The results obtained in this study using the methodological framework suggest that cytokine-specific information is present in sensory neural signals within the vagus nerve. Copyright © 2018 the Author(s). Published by PNAS.

  20. Bladder sensory desensitization decreases urinary urgency.

    PubMed

    Silva, Carlos; Silva, João; Castro, Helder; Reis, Frederico; Dinis, Paulo; Avelino, António; Cruz, Francisco

    2007-06-11

    Bladder desensitization has been investigated as an alternative treatment for refractory detrusor overactivity. Most open and controlled clinical trials conducted with intravesical RTX showed that desensitization delays the appearance of involuntary detrusor contractions during bladder filling and decreases the number of episodes of urgency incontinence. Urgency is being recognised as the fundamental symptom of overactive bladder (OAB), a symptomatic complex which recent epidemiological studies have shown to affect more than 10% of the Western population. As anti-muscarinic drugs, the first line treatment for OAB, are far from being able to fully control urgency, the opportunity to test other therapeutic approaches is created. The present work was, therefore, designed as an exploratory investigation to evaluate the effect of bladder desensitization on urinary urgency. Twenty-three OAB patients with refractory urgency entered, after given informed consent, a 30 days run-in period in which medications influencing the bladder function were interrupted. At the end of this period patients filled a seven-day voiding chart where they scored, using a 0-4 scale, the bladder sensations felt before each voiding. Then, patients were instilled with 100 ml of 10% ethanol in saline (vehicle solution) and 30 days later a second seven-day voiding chart was collected. Finally, patients were instilled with 100 ml of 50 nM RTX in 10% ethanol in saline. At 1 and 3 months additional voiding charts were collected. At the end of the vehicle and 3 months period patients were asked to give their subjective impression about the outcome of the treatment and about the willingness to repeat the previous instillation. At the end of the run-in period the mean number of episodes of urgency per week was 71 +/- 12 (mean +/- SEM). After vehicle instillation, the mean number of episodes of urgency was 56 +/- 11, but only 4 patients (17%) considered that their urinary condition had improved enough to

  1. Restoration of Trigeminal Cutaneous Sensation with Cross-Face Sural Nerve Grafts: A Novel Approach to Facial Sensory Rehabilitation.

    PubMed

    Catapano, Joseph; Scholl, David; Ho, Emily; Zuker, Ronald M; Borschel, Gregory H

    2015-09-01

    Although treating facial palsy is considered debilitating for patients, trigeminal nerve palsy and sensory deficits of the face are overlooked components of disability. Complete anesthesia leaves patients susceptible to occult injury, and facial sensation is an important component of interaction and activities of daily living. Sensory reconstruction is well established in the restoration of hand sensation; however, only one previous report proposed a surgical strategy for sensory nerve reconstruction of the face with use of nerve transfers. Nerve transfers, when used alone, have limited application because of their restricted arc of rotation in the face; extending their arc by adding nerve grafts greatly expands their utility. The following cases demonstrate the early results after V2 and V3 reconstruction with cross-face nerve grafts in three patients with acquired trigeminal nerve palsy. Cross-face nerve grafts using the sural nerve permit more proximal reconstruction of the infraorbital and mental nerves, which allows reinnervation of their entire cutaneous distribution. All patients demonstrated improved sensation in the reconstructed dermatomes, and no patients reported donor-site abnormalities. Cross-face nerve grafts result in minimal donor-site morbidity and are promising as a surgical strategy to address sensory deficits of the face. Therapeutic, V.

  2. Patients' views on early sensory relearning following nerve repair-a Q-methodology study.

    PubMed

    Vikström, Pernilla; Carlsson, Ingela; Rosén, Birgitta; Björkman, Anders

    2017-09-26

    Descriptive study. Early sensory relearning where the dynamic capacity of the brain is used has been shown to improve sensory outcome after nerve repair. However, no previous studies have examined how patients experience early sensory relearning. To describe patient's views on early sensory relearning. Statements' scores were analyzed by factor analysis. Thirty-seven consecutive adult patients with median and/or ulnar nerve repair who completed early sensory relearning were included. Three factors were identified, explaining 45% of the variance: (1) "Believe sensory relearning is meaningful, manage to get an illusion of touch and complete the sensory relearning"; (2) "Do not get an illusion of touch easily and need support in their sensory relearning" (3) "Are not motivated, manage to get an illusion of touch but do not complete sensory relearning". Many patients succeed in implementing their sensory relearning. However, a substantial part of the patient population need more support, have difficulties to create illusion of touch, and lack motivation to complete the sensory relearning. To enhance motivation and meaningfulness by relating the training clearly to everyday occupations and to the patient's life situation is a suggested way to proceed. The three unique factors indicate motivation and sense of meaningfulness as key components which should be taken into consideration in developing programs for person-centered early sensory relearning. 3. Copyright © 2017 Hanley & Belfus. Published by Elsevier Inc. All rights reserved.

  3. Intracranial stimulation of the trigeminal nerve in man. III. Sensory potentials.

    PubMed Central

    Cruccu, G; Inghilleri, M; Manfredi, M; Meglio, M

    1987-01-01

    Percutaneous electrical stimulation of the trigeminal root was performed in 18 subjects undergoing surgery for idiopathic trigeminal neuralgia or implantation of electrodes into Meckel's cave for recording of limbic epileptic activity. All subjects had normal trigeminal reflexes and evoked potentials. Sensory action potentials were recorded antidromically from the supraorbital (V1), infraorbital (V2) and mental (V3) nerves. In the awake subject, sensory potentials were usually followed by myogenic artifacts due to direct activation of masticatory muscles or reflex activation of facial muscles. In the anaesthetised and curarised subject, sensory potentials from the three nerves showed 1.4-2.2 ms onset latency, 1.9-2.7 ms peak latency and 17-29 microV amplitude. Sensory conduction velocity was computed at the onset latency (maximum CV) and at the peak latency (peak CV). On average, maximum and peak CV were 52 and 39 m/s for V1, 54 and 42 m/s for V2 and 54 and 44 m/s for V3. There was no apparent difference in CV between subjects with trigeminal neuralgia and those with epilepsy. A significant inverse correlation was found between CV and age, the overall maximum CV declining from 59 m/s (16 years) to 49 m/s (73 years). This range of CV is compatible both with histometric data and previous electrophysiological findings on trigeminal nerve conduction. Intraoperative intracranial stimulation is also proposed as a method of monitoring trigeminal function under general anaesthesia. Images PMID:3681311

  4. Stimulus waveform determines the characteristics of sensory nerve action potentials.

    PubMed

    Pereira, Pedro; Leote, João; Cabib, Christopher; Casanova-Molla, Jordi; Valls-Sole, Josep

    2016-03-01

    In routine nerve conduction studies supramaximal electrical stimuli generate sensory nerve action potentials by depolarization of nerve fibers under the cathode. However, stimuli of submaximal intensity may give rise to action potentials generated under the anode. We tested if this phenomenon depends on the characteristics of stimulus ending. We added a circuit to our stimulation device that allowed us to modify the end of the stimulus by increasing the time constant of the decay phase. Increasing the fall time caused a reduction of anode action potential (anAP) amplitude, and eventually abolished it, in all tested subjects. We subsequently examined the stimulus waveform in a series of available electromyographs stimulators and found that the anAP could only be obtained with stimulators that issued stimuli ending sharply. Our results prove that the anAP is generated at stimulus end, and depends on the sharpness of current shut down. Electromyographs produce stimuli of varying characteristics, which limits the reproducibility of anAP results by interested researchers. The study of anodal action potentials might be a useful tool to have a quick appraisal of distal human sensory nerve excitability. Copyright © 2015 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

  5. Sensory signs in complex regional pain syndrome and peripheral nerve injury.

    PubMed

    Gierthmühlen, Janne; Maier, Christoph; Baron, Ralf; Tölle, Thomas; Treede, Rolf-Detlef; Birbaumer, Niels; Huge, Volker; Koroschetz, Jana; Krumova, Elena K; Lauchart, Meike; Maihöfner, Christian; Richter, Helmut; Westermann, Andrea

    2012-04-01

    This study determined patterns of sensory signs in complex regional pain syndrome (CRPS) type I and II and peripheral nerve injury (PNI). Patients with upper-limb CRPS-I (n=298), CRPS-II (n=46), and PNI (n=72) were examined with quantitative sensory testing according to the protocol of the German Research Network on Neuropathic Pain. The majority of patients (66%-69%) exhibited a combination of sensory loss and gain. Patients with CRPS-I had more sensory gain (heat and pressure pain) and less sensory loss than patients with PNI (thermal and mechanical detection, hypoalgesia to heat or pinprick). CRPS-II patients shared features of CRPS-I and PNI. CRPS-I and CRPS-II had almost identical somatosensory profiles, with the exception of a stronger loss of mechanical detection in CRPS-II. In CRPS-I and -II, cold hyperalgesia/allodynia (28%-31%) and dynamic mechanical allodynia (24%-28%) were less frequent than heat or pressure hyperalgesia (36%-44%, 67%-73%), and mechanical hypoesthesia (31%-55%) was more frequent than thermal hypoesthesia (30%-44%). About 82% of PNI patients had at least one type of sensory gain. QST demonstrates more sensory loss in CRPS-I than hitherto considered, suggesting either minimal nerve injury or central inhibition. Sensory profiles suggest that CRPS-I and CRPS-II may represent one disease continuum. However, in contrast to recent suggestions, small fiber deficits were less frequent than large fiber deficits. Sensory gain is highly prevalent in PNI, indicating a better similarity of animal models to human patients than previously thought. These sensory profiles should help prioritize approaches for translation between animal and human research. Copyright © 2011 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

  6. Sensory and motor peripheral nerve function and incident mobility disability.

    PubMed

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

    2014-12-01

    To assess the relationship between sensorimotor nerve function and incident mobility disability over 10 years. Prospective cohort study with longitudinal analysis. Two U.S. clinical sites. Population-based sample of community-dwelling older adults with no mobility disability at 2000/01 examination (N = 2,148 [Corrected]; mean age ± SD 76.5 ± 2.9, body mass index 27.1 ± 4.6; 50.2% female, 36.6% black, 10.7% with diabetes mellitus). Motor nerve conduction amplitude (poor <1 mV) and velocity (poor <40 m/s) were measured on the deep peroneal nerve. Sensory nerve function was measured using 10- and 1.4-g monofilaments and vibration detection threshold at the toe. Lower extremity symptoms included numbness or tingling and aching or burning pain. Incident mobility disability assessed semiannually over 8.5 years (interquartile range 4.5-9.6 years) was defined as two consecutive self-reports of a lot of difficulty or inability to walk one-quarter of a mile or climb 10 steps. Nerve impairments were detected in 55% of participants, and 30% developed mobility disability. Worse motor amplitude (HR = 1.29 per SD, 95% CI = 1.16-1.44), vibration detection threshold (HR = 1.13 per SD, 95% CI = 1.04-1.23), symptoms (HR = 1.65, 95% CI = 1.26-2.17), two motor impairments (HR = 2.10, 95% CI = 1.43-3.09), two sensory impairments (HR = 1.91, 95% CI = 1.37-2.68), and three or more nerve impairments (HR = 2.33, 95% CI = 1.54-3.53) predicted incident mobility disability after adjustment. Quadriceps strength mediated relationships between certain nerve impairments and mobility disability, although most remained significant. Poor sensorimotor nerve function independently predicted mobility disability. Future work should investigate modifiable risk factors and interventions such as strength training for preventing disability and improving function in older adults with poor nerve function. © 2014, Copyright the Authors Journal compilation © 2014, The American Geriatrics Society.

  7. Peripheral Motor and Sensory Nerve Conduction following Transplantation of Undifferentiated Autologous Adipose Tissue-Derived Stem Cells in a Biodegradable U.S. Food and Drug Administration-Approved Nerve Conduit.

    PubMed

    Klein, Silvan M; Vykoukal, Jody; Li, De-Pei; Pan, Hui-Lin; Zeitler, Katharina; Alt, Eckhard; Geis, Sebastian; Felthaus, Oliver; Prantl, Lukas

    2016-07-01

    Conduits preseeded with either Schwann cells or stem cells differentiated into Schwann cells demonstrated promising results for the outcome of nerve regeneration in nerve defects. The concept of this trial combines nerve repair by means of a commercially available nerve guidance conduit and preseeding with autologous, undifferentiated, adipose tissue-derived stem cells. Adipose tissue-derived stem cells were harvested from rats and subsequently seeded onto a U.S. Food and Drug Administration-approved type I collagen conduit. Sciatic nerve gaps 10 mm in length were created, and nerve repair was performed by the transplantation of either conduits preseeded with autologous adipose tissue-derived stem cells or acellular (control group) conduits. After 6 months, the motor and sensory nerve conduction velocity were assessed. Nerves were removed and examined by hematoxylin and eosin, van Gieson, and immunohistochemistry (S100 protein) staining for the quality of axonal regeneration. Nerve gaps treated with adipose tissue-derived stem cells showed superior nerve regeneration, reflected by higher motor and sensory nerve conduction velocity values. The motor and sensory nerve conduction velocity were significantly greater in nerves treated with conduits preseeded with adipose tissue-derived stem cells than in nerves treated with conduits alone (p < 0.05). Increased S100 immunoreactivity was detected for the adipose tissue-derived stem cell group. In this group, axon arrangement inside the conduits was more organized. Transplantation of adipose tissue-derived stem cells significantly improves motor and sensory nerve conduction velocity in peripheral nerve gaps. Preseeded conduits showed a more organized axon arrangement inside the conduit in comparison with nerve conduits alone. The approach used here could readily be translated into a clinical therapy. Therapeutic, V.

  8. Sonography-guided recording for superficial peroneal sensory nerve conduction study.

    PubMed

    Kim, Ki Hoon; Park, Byung Kyu; Kim, Dong Hwee; Kim, Yuntae

    2018-04-01

    We sought to establish the optimal recording position for antidromic conduction of the superficial peroneal nerve (SPN) by using ultrasonography (USG). The sensory nerve action potentials (SNAPs) of the intermediate dorsal cutaneous nerve (IDCN) and medial dorsal cutaneous nerve (MDCN) in 64 limbs of 32 healthy participants were recorded (nerve conduction study [NCS]-1). Both nerves were identified by using USG, and the SNAPs were obtained from the USG-guided repositioned electrodes (NCS-2). The IDCN and MDCN were located at 29.3% ± 5.1% and 43.9% ± 4.9% of the intermalleolar distance from the lateral malleolus, respectively. Significantly greater amplitude was shown for SNAPs of both nerves in NCS-2 versus NCS-1. The optimal recording position is likely to be lateral, one-third from the lateral malleolus for the IDCN, and just lateral to the midpoint of the intermalleolar line for the MDCN. When the SPN response is unexpectedly attenuated, USG-guided repositioning of the electrodes should be considered. Muscle Nerve 57: 628-633, 2018. © 2017 Wiley Periodicals, Inc.

  9. The effect of hyperbaric oxygen treatment on early regeneration of sensory axons after nerve crush in the rat.

    PubMed

    Bajrović, Fajko F; Sketelj, Janez; Jug, Marko; Gril, Iztok; Mekjavić, Igor B

    2002-09-01

    Abstract The effect of hyperbaric oxygen treatment (HBO) on sensory axon regeneration was examined in the rat. The sciatic nerve was crushed in both legs. In addition, the distal stump of the sural nerve on one side was made acellular and its blood perfusion was compromised by freezing and thawing. Two experimental groups received hyperbaric exposures (2.5 ATA) to either compressed air (pO2 = 0.5 ATA) or 100% oxygen (pO2 = 2.5 ATA) 90 minutes per day for 6 days. Sensory axon regeneration in the sural nerve was thereafter assessed by the nerve pinch test and immunohistochemical reaction to neurofilament. HBO treatment increased the distances reached by the fastest regenerating sensory axons by about 15% in the distal nerve segments with preserved and with compromised blood perfusion. There was no significant difference between the rats treated with different oxygen tensions. The total number of regenerated axons in the distal sural nerve segments after a simple crush injury was not affected, whereas in the nerve segments with compromised blood perfusion treated by the higher pO2, the axon number was about 30% lower than that in the control group. It is concluded that the beneficial effect of HBO on sensory axon regeneration is not dose-dependent between 0.5 and 2.5 ATA pO2. Although the exposure to 2.5 ATA of pO2 moderately enhanced early regeneration of the fastest sensory axons, it decreased the number of regenerating axons in the injured nerves with compromised blood perfusion of the distal nerve stump.

  10. A historical perspective on the role of sensory nerves in neurogenic inflammation.

    PubMed

    Sousa-Valente, João; Brain, Susan D

    2018-05-01

    The term 'neurogenic inflammation' is commonly used, especially with respect to the role of sensory nerves within inflammatory disease. However, despite over a century of research, we remain unclear about the role of these nerves in the vascular biology of inflammation, as compared with their interacting role in pain processing and of their potential for therapeutic manipulation. This chapter attempts to discuss the progress in understanding, from the initial discovery of sensory nerves until the present day. This covers pioneering findings that these nerves exist, are involved in vascular events and act as important sensors of environmental changes, including injury and infection. This is followed by discovery of the contents they release such as the established vasoactive neuropeptides substance P and CGRP as well as anti-inflammatory peptides such as the opioids and somatostatin. The more recent emergence of the importance of the transient receptor potential (TRP) channels has revealed some of the mechanisms by which these nerves sense environmental stimuli. This knowledge enables a platform from which to learn of the potential role of neurogenic inflammation in disease and in turn of novel therapeutic targets.

  11. 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.

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

    PubMed Central

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

    2014-01-01

    Surprisingly little is known about the impact of entrapment neuropathy on target innervation and the relationship of nerve fibre pathology to sensory symptoms and signs. Carpal tunnel syndrome is the most common entrapment neuropathy; the aim of this study was to investigate its effect on the morphology of small unmyelinated as well as myelinated sensory axons and relate such changes to somatosensory function and clinical symptoms. Thirty patients with a clinical and electrophysiological diagnosis of carpal tunnel syndrome [17 females, mean age (standard deviation) 56.4 (15.3)] and 26 age and gender matched healthy volunteers [18 females, mean age (standard deviation) 51.0 (17.3)] participated in the study. Small and large fibre function was examined with quantitative sensory testing in the median nerve territory of the hand. Vibration and mechanical detection thresholds were significantly elevated in patients with carpal tunnel syndrome (P < 0.007) confirming large fibre dysfunction and patients also presented with increased thermal detection thresholds (P < 0.0001) indicative of C and Aδ-fibre dysfunction. Mechanical and thermal pain thresholds were comparable between groups (P > 0.13). A skin biopsy was taken from a median nerve innervated area of the proximal phalanx of the index finger. Immunohistochemical staining for protein gene product 9.5 and myelin basic protein was used to evaluate morphological features of unmyelinated and myelinated axons. Evaluation of intraepidermal nerve fibre density showed a striking loss in patients (P < 0.0001) confirming a significant compromise of small fibres. The extent of Meissner corpuscles and dermal nerve bundles were comparable between groups (P > 0.07). However, patients displayed a significant increase in the percentage of elongated nodes (P < 0.0001), with altered architecture of voltage-gated sodium channel distribution. Whereas neither neurophysiology nor quantitative sensory testing correlated with patients

  13. Factors predicting sensory and motor recovery after the repair of upper limb peripheral nerve injuries

    PubMed Central

    He, Bo; Zhu, Zhaowei; Zhu, Qingtang; Zhou, Xiang; Zheng, Canbin; Li, Pengliang; Zhu, Shuang; Liu, Xiaolin; Zhu, Jiakai

    2014-01-01

    OBJECTIVE: To investigate the factors associated with sensory and motor recovery after the repair of upper limb peripheral nerve injuries. DATA SOURCES: The online PubMed database was searched for English articles describing outcomes after the repair of median, ulnar, radial, and digital nerve injuries in humans with a publication date between 1 January 1990 and 16 February 2011. STUDY SELECTION: The following types of article were selected: (1) clinical trials describing the repair of median, ulnar, radial, and digital nerve injuries published in English; and (2) studies that reported sufficient patient information, including age, mechanism of injury, nerve injured, injury location, defect length, repair time, repair method, and repair materials. SPSS 13.0 software was used to perform univariate and multivariate logistic regression analyses and to investigate the patient and intervention factors associated with outcomes. MAIN OUTCOME MEASURES: Sensory function was assessed using the Mackinnon-Dellon scale and motor function was assessed using the manual muscle test. Satisfactory motor recovery was defined as grade M4 or M5, and satisfactory sensory recovery was defined as grade S3+ or S4. RESULTS: Seventy-one articles were included in this study. Univariate and multivariate logistic regression analyses showed that repair time, repair materials, and nerve injured were independent predictors of outcome after the repair of nerve injuries (P < 0.05), and that the nerve injured was the main factor affecting the rate of good to excellent recovery. CONCLUSION: Predictors of outcome after the repair of peripheral nerve injuries include age, gender, repair time, repair materials, nerve injured, defect length, and duration of follow-up. PMID:25206870

  14. Renal sensory and sympathetic nerves reinnervate the kidney in a similar time-dependent fashion after renal denervation in rats

    PubMed Central

    Mulder, Jan; Hökfelt, Tomas; Knuepfer, Mark M.

    2013-01-01

    Efferent renal sympathetic nerves reinnervate the kidney after renal denervation in animals and humans. Therefore, the long-term reduction in arterial pressure following renal denervation in drug-resistant hypertensive patients has been attributed to lack of afferent renal sensory reinnervation. However, afferent sensory reinnervation of any organ, including the kidney, is an understudied question. Therefore, we analyzed the time course of sympathetic and sensory reinnervation at multiple time points (1, 4, and 5 days and 1, 2, 3, 4, 6, 9, and 12 wk) after renal denervation in normal Sprague-Dawley rats. Sympathetic and sensory innervation in the innervated and contralateral denervated kidney was determined as optical density (ImageJ) of the sympathetic and sensory nerves identified by immunohistochemistry using antibodies against markers for sympathetic nerves [neuropeptide Y (NPY) and tyrosine hydroxylase (TH)] and sensory nerves [substance P and calcitonin gene-related peptide (CGRP)]. In denervated kidneys, the optical density of NPY-immunoreactive (ir) fibers in the renal cortex and substance P-ir fibers in the pelvic wall was 6, 39, and 100% and 8, 47, and 100%, respectively, of that in the contralateral innervated kidney at 4 days, 4 wk, and 12 wk after denervation. Linear regression analysis of the optical density of the ratio of the denervated/innervated kidney versus time yielded similar intercept and slope values for NPY-ir, TH-ir, substance P-ir, and CGRP-ir fibers (all R2 > 0.76). In conclusion, in normotensive rats, reinnervation of the renal sensory nerves occurs over the same time course as reinnervation of the renal sympathetic nerves, both being complete at 9 to 12 wk following renal denervation. PMID:23408032

  15. 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

  16. Free flap reconstruction of the sole of the foot with or without sensory nerve coaptation.

    PubMed

    Santanelli, Fabio; Tenna, Stefania; Pace, Andrea; Scuderi, Nicolò

    2002-06-01

    The authors present a retrospective study on major plantar foot reconstruction to evaluate the role of the free fasciocutaneous flap and the importance of sensory nerve reconstruction in improving long-term results. Between 1995 and 1999, 20 patients with major defects of the sole of the foot underwent free forearm flap reconstruction performed by the senior author (F.S.). Sensory nerve reconstruction was added to this technique in 1997. The age and sex of the patients and the cause, location, and dimensions of their defects were recorded. The patients were clinically and neurophysiologically evaluated at 3, 6, and 12 months after the procedure for the following parameters: flap contour, flap stability, load capacity, walking ability, touch sensation, pain sensation, static two-point discrimination, and thermal sensibility. Dermatomic somatosensory-evoked potentials were also tested at 12 months. Follow-up ranged from 1 to 5 years. Patients were divided into two groups according to sensory nerve reconstruction. Group A consisted of 11 patients with nerve repair, and group B consisted of nine patients without nerve repair. One patient from group A who had an idiopathic neuropathy was excluded from the study because of interference with the reinnervation process. Five more patients (three from group A and two from group B) were lost at follow-up and excluded from the study. The final sample size in each group was seven. Data from both groups were compared and statistically analyzed with the Mann-Whitney test and the Fisher exact test. Long-term results confirmed in all reconstructions long-lasting stability. During the first postoperative year, patients with sensory nerve reconstruction showed better sensibility. The statistical analyses confirmed significant differences between the two groups to be dependent upon surgical technique at 3 and 6 months. Two-point discrimination and dermatomic somatosensory-evoked potentials were recorded. After 12 months, flaps without

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

    PubMed

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

    2012-05-01

    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-old) and old (36-month-old) 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 did 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. Copyright © 2012 Elsevier Inc. All rights reserved.

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

    DTIC Science & Technology

    2015-10-01

    Modulated Sensory Feedback from, a Hand Prosthesis PRINCIPAL INVESTIGATOR: Bradley Greger, PhD CONTRACTING ORGANIZATION: Arizona State University...Residual Peripheral Nerves to Provide Dextrous Control of, and Modulated Sensory Feedback from, a Hand Prosthesis 5a. CONTRACT NUMBER 5b. GRANT...Peripheral Nerve Interface, Prosthetic Hand, Neural Prosthesis , Sensory Feedback, Micro-stimulation, Electrophysiology, Action Potentials, Micro

  19. Stimulation of airway sensory nerves by cyclosporin A and FK506 in guinea-pig isolated bronchus.

    PubMed

    Harrison, S; Reddy, S; Page, C P; Spina, D

    1998-12-01

    We have investigated the contractile property of cyclosporin A and FK506 in guinea-pig isolated bronchus. Cyclosporin A (10 microM) failed to significantly attenuate the excitatory non-adrenergic non-cholinergic (eNANC) and cholinergic contractile response (per cent methacholine Emax) induced by electrical field stimulation (EFS). In contrast, eNANC responses were significantly attenuated by both the neurokinin (NK)-1 and (NK)-2 receptor antagonists, N-acetyl-L-tryptophan 3,5-bis (trifluoromethyl)-benzyl and SR48968, respectively. Cyclosporin A and FK506 caused a concentration-dependent contraction in guinea-pig isolated bronchus, which was significantly attenuated by NK-1 and NK-2 receptor antagonists. The capsaicin receptor antagonist, capsazepine (10 microM) significantly reduced the contractile response to cyclosporin A and capsaicin, but not to FK506. The N-type calcium channel blocker, omega-Conotoxin (omegaCTX: 10 nM), significantly reduced the contractile response to FK506 and the eNANC response following EFS. In contrast, omega-CTX failed to significantly reduce the contractile potency to capsaicin or cyclosporin A. In bronchial preparations desensitized by repeated application of capsaicin (1 microM), the contractile responses to both cyclosporin A (100 microM) and FK506 (100 microM), were significantly reduced. In contrast, the contractile responses to substance P and neurokinin A (10 microM) were not altered. Furthermore, repeated application of cyclosporin A (100 microM) significantly inhibited the contractile response to capsaicin (1 microM). The findings from this study would indicate that cyclosporin A and FK506 mediate contraction of guinea-pig isolated bronchus secondary to the release of neuropeptides from airway sensory nerves. However, the release of sensory neuropeptides appears to be mediated via different mechanisms for cyclosporin A and FK506, the former by stimulation of the vanilloid receptor and the latter via opening of N-type calcium

  20. Met receptor signaling is required for sensory nerve development and HGF promotes axonal growth and survival of sensory neurons

    PubMed Central

    Maina, Flavio; Hilton, Mark C.; Ponzetto, Carola; Davies, Alun M.; Klein, Rüdiger

    1997-01-01

    The development of the nervous system is a dynamic process during which factors act in an instructive fashion to direct the differentiation and survival of neurons, and to induce axonal outgrowth, guidance to, and terminal branching within the target tissue. Here we report that mice expressing signaling mutants of the hepatocyte growth factor (HGF) receptor, the Met tyrosine kinase, show a striking reduction of sensory nerves innervating the skin of the limbs and thorax, implicating the HGF/Met system in sensory neuron development. Using in vitro assays, we find that HGF cooperates with nerve growth factor (NGF) to enhance axonal outgrowth from cultured dorsal root ganglion (DRG) neurons. HGF also enhances the neurotrophic activities of NGF in vitro, and Met receptor signaling is required for the survival of a proportion of DRG neurons in vivo. This synergism is specific for NGF but not for the related neurotrophins BDNF and NT3. By using a mild signaling mutant of Met, we have demonstrated previously that Met requires signaling via the adapter molecule Grb2 to induce proliferation of myoblasts. In contrast, the actions of HGF on sensory neurons are mediated by Met effectors distinct from Grb2. Our findings demonstrate a requirement for Met signaling in neurons during development. PMID:9407027

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

    PubMed

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

    2013-12-01

    The aim of this study was to evaluate the degeneration and regeneration of a sensory nerve and a motor nerve at the histological level after a crush injury. Twenty-five female Wistar rats had their mental nerve and the buccal branch of their facial nerve compressed unilaterally against a glass rod for 30s. Specimens of the compressed nerves and the corresponding control nerves were dissected at 3, 7, and 19 days after surgery. Nerve cross-sections were stained with osmium tetroxide and toluidine blue and analysed using two-dimensional stereology. We found differences between the two nerves both in the normal anatomy and in the regenerative pattern. The mental nerve had a larger cross-sectional area including all tissue components. The mental nerve had a larger volume fraction of myelinated axons and a correspondingly smaller volume fraction of endoneurium. No differences were observed in the degenerative pattern; however, at day 19 the buccal branch had regenerated to the normal number of axons, whereas the mental nerve had only regained 50% of the normal number of axons. We conclude that the regenerative process is faster and/or more complete in the facial nerve (motor function) than it is in the mental nerve (somatosensory function). Copyright © 2013 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

  2. The effect of early relearning on sensory recovery 4 to 9 years after nerve repair: a report of a randomized controlled study.

    PubMed

    Vikström, Pernilla; Rosén, Birgitta; Carlsson, Ingela K; Björkman, Anders

    2018-01-01

    Twenty patients randomized to early sensory relearning (nine patients) or traditional relearning (11 patients) were assessed regarding sensory recovery 4 to 9 years after median or ulnar nerve repair. Outcomes were assessed with the Rosen score, questionnaires, and self-reported single-item questions regarding function and activity. The patients with early sensory relearning had significantly better sensory recovery in the sensory domain of the Rosen score, specifically, discriminative touch or tactile gnosis and dexterity. They had significantly less self-reported problems in gripping, clumsiness, and fine motor skills. No differences were found in questionnaires between the two groups. We conclude that early sensory relearning improves long-term sensory recovery following nerve repair. I.

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

    PubMed Central

    Ferreira Junior, Rui Seabra

    2016-01-01

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

  4. 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.

  5. Sensory and motor peripheral nerve function and lower-extremity quadriceps strength: the health, aging and body composition study.

    PubMed

    Strotmeyer, Elsa S; de Rekeneire, Nathalie; Schwartz, Ann V; Resnick, Helaine E; Goodpaster, Bret H; Faulkner, Kimberly A; Shorr, Ronald I; Vinik, Aaron I; Harris, Tamara B; Newman, Anne B

    2009-11-01

    To determine whether sensory and motor nerve function is associated cross-sectionally with quadriceps or ankle dorsiflexion strength in an older community-based population. Cross-sectional analyses within a longitudinal cohort study. Two U.S. clinical sites. Two thousand fifty-nine Health, Aging and Body Composition Study (Health ABC) participants (49.5% male, 36.7% black, aged 73-82) in 2000/01. Quadriceps and ankle strength were measured using an isokinetic dynamometer. Sensory and motor peripheral nerve function in the legs and feet was assessed using 10-g and 1.4-g monofilaments, vibration threshold, and peroneal motor nerve conduction amplitude and velocity. Monofilament insensitivity, poorest vibration threshold quartile (>60 mu), and poorest motor nerve conduction amplitude quartile (<1.7 mV) were associated with 11%, 7%, and 8% lower quadriceps strength (all P<.01), respectively, than in the best peripheral nerve function categories in adjusted linear regression models. Monofilament insensitivity and lowest amplitude quartile were both associated with 17% lower ankle strength (P<.01). Multivariate analyses were adjusted for demographic characteristics, diabetes mellitus, body composition, lifestyle factors, and chronic health conditions and included all peripheral nerve measures in the same model. Monofilament insensitivity (beta=-7.19), vibration threshold (beta=-0.097), and motor nerve conduction amplitude (beta=2.01) each contributed independently to lower quadriceps strength (all P<.01). Monofilament insensitivity (beta=-5.29) and amplitude (beta=1.17) each contributed independently to lower ankle strength (all P<.01). Neither diabetes mellitus status nor lean mass explained the associations between peripheral nerve function and strength. Reduced sensory and motor peripheral nerve function is related to poorer lower extremity strength in older adults, suggesting a mechanism for the relationship with lower extremity disability.

  6. Desensitization with oxaliplatin in patients intolerant of carboplatin desensitization.

    PubMed

    Rose, Peter G; Metz, Carol; Link, Nicolas

    2014-11-01

    The tolerance and efficacy of oxaliplatin desensitization in patients who were intolerant of carboplatin desensitization were determined. We retrospectively reviewed the Gynecologic Oncology patients who received carboplatin or oxaliplatin from December 2007 until August 2014. The number of treatments and number of patients of carboplatin standard infusions, carboplatin desensitizations, and oxaliplatin desensitizations were determined. Carboplatin infusions (2294) were administered to 281 patients. Twenty-eight (10%) of these patients developed carboplatin hypersensitivity and were treated with 205 carboplatin desensitizations. Nine (29%) patients were subsequently treated with 61 oxaliplatin desensitizations due to intolerance of carboplatin desensitization. Nine of the 10 patients tolerated this infusion well. Four of 9 evaluable patients had an objective response, 2 complete and 2 partial. Oxaliplatin desensitization seems well tolerated and effective in most patients who are intolerant of carboplatin desensitization.

  7. Thrombospondin-4 divergently regulates voltage-gated Ca2+ channel subtypes in sensory neurons after nerve injury.

    PubMed

    Pan, Bin; Guo, Yuan; Wu, Hsiang-En; Park, John; Trinh, Van Nancy; Luo, Z David; Hogan, Quinn H

    2016-09-01

    Loss of high-voltage-activated (HVA) calcium current (ICa) and gain of low-voltage-activated (LVA) ICa after painful peripheral nerve injury cause elevated excitability in sensory neurons. Nerve injury is also accompanied by increased expression of the extracellular matrix glycoprotein thrombospondin-4 (TSP4), and interruption of TSP4 function can reverse or prevent behavioral hypersensitivity after injury. We therefore investigated TSP4 regulation of ICa in dorsal root ganglion (DRG) neurons. During depolarization adequate to activate HVA ICa, TSP4 decreases both N- and L-type ICa and the associated intracellular calcium transient. In contrast, TSP4 increases ICa and the intracellular calcium signal after low-voltage depolarization, which we confirmed is due to ICa through T-type channels. These effects are blocked by gabapentin, which ameliorates neuropathic pain by targeting the α2δ1 calcium subunit. Injury-induced changes of HVA and LVA ICa are attenuated in TSP4 knockout mice. In the neuropathic pain model of spinal nerve ligation, TSP4 application did not further regulate ICa of injured DRG neurons. Taken together, these findings suggest that elevated TSP4 after peripheral nerve injury may contribute to hypersensitivity of peripheral sensory systems by decreasing HVA and increasing LVA in DRG neurons by targeting the α2δ1 calcium subunit. Controlling TSP4 overexpression in peripheral sensory neurons may be a target for analgesic drug development for neuropathic pain.

  8. Nerve Transfer Versus Nerve Graft for Reconstruction of High Ulnar Nerve Injuries.

    PubMed

    Sallam, Asser A; El-Deeb, Mohamed S; Imam, Mohamed A

    2017-04-01

    To assess the efficacy of nerve transfer versus nerve grafting in restoring motor and sensory hand function in patients with complete, isolated high ulnar nerve injuries. A retrospective chart review was performed, at a minimum 2 years of follow-up, of 52 patients suffering complete, isolated high ulnar nerve injury between January 2006 and June 2013 in one specialized hand surgery unit. Twenty-four patients underwent motor and sensory nerve transfers (NT group). Twenty-eight patients underwent sural nerve grafting (NG group). Motor recovery, return of sensibility and complications were examined as outcome measures. The Medical Research Council scale was applied to evaluate sensory and motor recovery. Grip and pinch strengths of the hand were measured. Twenty of 24 patients (83.33%) in the NT group regained M3 grade or greater for the adductor pollicis, the abductor digiti minimi, and the medial 2 lumbricals and interossei, compared with only 16 of 28 patients (57.14%) in the NG group. Means for percentage recovery of grip strengths compared with the other healthy hand were significantly higher for the NT group than the NG group. Sensory recovery of S3 or greater was achieved in more than half of each group with no significant difference between groups. Nerve transfer is favored over nerve grafting in managing high ulnar nerve injuries because of better improvement of motor power and better restoration of grip functions of the hand. Therapeutic IV. Copyright © 2017 American Society for Surgery of the Hand. Published by Elsevier Inc. All rights reserved.

  9. Sensation, mechanoreceptor, and nerve fiber function after nerve regeneration.

    PubMed

    Krarup, Christian; Rosén, Birgitta; Boeckstyns, Michel; Ibsen Sørensen, Allan; Lundborg, Göran; Moldovan, Mihai; Archibald, Simon J

    2017-12-01

    Sensation is essential for recovery after peripheral nerve injury. However, the relationship between sensory modalities and function of regenerated fibers is uncertain. We have investigated the relationships between touch threshold, tactile gnosis, and mechanoreceptor and sensory fiber function after nerve regeneration. Twenty-one median or ulnar nerve lesions were repaired by a collagen nerve conduit or direct suture. Quantitative sensory hand function and sensory conduction studies by near-nerve technique, including tactile stimulation of mechanoreceptors, were followed for 2 years, and results were compared to noninjured hands. At both repair methods, touch thresholds at the finger tips recovered to 81 ± 3% and tactile gnosis only to 20 ± 4% (p < 0.001) of control. The sensory nerve action potentials (SNAPs) remained dispersed and areas recovered to 23 ± 2% and the amplitudes only to 7 ± 1% (P < 0.001). The areas of SNAPs after tactile stimulation recovered to 61 ± 11% and remained slowed. Touch sensation correlated with SNAP areas (p < 0.005) and was negatively related to the prolongation of tactile latencies (p < 0.01); tactile gnosis was not related to electrophysiological parameters. The recovered function of regenerated peripheral nerve fibers and reinnervated mechanoreceptors may differentially influence recovery of sensory modalities. Touch was affected by the number and function of regenerated fibers and mechanoreceptors. In contrast, tactile gnosis depends on the input and plasticity of the central nervous system (CNS), which may explain the absence of a direct relation between electrophysiological parameters and poor recovery. Dispersed maturation of sensory nerve fibers with desynchronized inputs to the CNS also contributes to the poor recovery of tactile gnosis. Ann Neurol 2017. Ann Neurol 2017;82:940-950. © 2017 American Neurological Association.

  10. Histochemistry of nerve fibres double labelled with anti-TRPV2 antibodies and sensory nerve marker AM1-43 in the dental pulp of rat molars.

    PubMed

    Nishikawa, Sumio

    2008-09-01

    AM1-43 can label sensory nerve fibres and sensory neurons. Permeation of non-selective cation channels of the nerve cell membrane is suggested to be the mechanism responsible for labelling. To identify these channels, two candidates, TRPV1 and TRPV2 were examined by immunocytochemistry in the dental pulp and trigeminal ganglion of rats injected with AM1-43. A part of AM1-43-labelled nerve fibres was also positive for anti-TRPV2 antibody but negative for anti-TRPV1 antibody in the dental pulp. In the trigeminal ganglion, a part of the neuron showed both bright AM1-43 labelling and anti-TRPV2 immunolabelling, but neurons double labelled with AM1-43 and TRPV1 were rare. These results suggest that TRPV2 channels, but not TRPV1 channels, contribute to the fluorescent labelling of AM1-43 in the dental pulp.

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

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Sridharan, Vijayalakshmi; Tripathi, Preeti; Sharma, Sunil

    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.more » 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.« less

  12. Afferent fibers and sensory ganglion cells within the oculomotor nerve in some mammals and man. II. Electrophysiological investigations.

    PubMed

    Manni, E; Bortolami, R; Pettorossi, V E; Lucchi, M L; Callegari, E

    1978-01-01

    The main aim of the present study was to localize with electrophysiological techniques the central projections and terminations of the aberrant trigeminal fibres contained in the oculomotor nerve of the lamb. After severing a trigeminal root, single-shock electrical stimulation of the trigeminal axons present in the central stump of the ipsilateral oculomotor nerve evoked field potentials in the area of, i) the subnucleus gelatinosus of the nucleus caudalis trigemini at the level of C1-C2; ii) the main sensory trigeminal nucleus; iii) the descending trigeminal nucleus and tract; iv) the adjacent reticular formation. Units whose discharge rate was influenced by such a stimulation were also found in the same territories. These regions actually exhibited degenerations after cutting an oculomotor nerve. We conclude, therefore, that the trigeminal fibres which leave the Vth nerve at the level of the cavernous sinus and enter the brain stem through the IIIrd nerve, end in the same structures which receive the terminations of the afferent fibres entering the brain stem through the sensory trigeminal root.

  13. Sensory re-education after nerve injury of the upper limb: a systematic review.

    PubMed

    Oud, Tanja; Beelen, Anita; Eijffinger, Elianne; Nollet, Frans

    2007-06-01

    To systematically review the available evidence for the effectiveness of sensory re-education to improve the sensibility of the hand in patients with a peripheral nerve injury of the upper limb. Studies were identified by an electronic search in the databases MEDLINE, Cumulative Index to Nursing & Allied Health Literature (CINAHL), EMBASE, the Cochrane Library, the Physiotherapy Evidence Database (PEDro), and the database of the Dutch National Institute of Allied Health Professions (Doconline) and by screening the reference lists of relevant articles. Two reviewers selected studies that met the following inclusion criteria: all designs except case reports, adults with impaired sensibility of the hand due to a peripheral nerve injury of the upper limb, and sensibility and functional sensibility as outcome measures. The methodological quality of the included studies was independently assessed by two reviewers. A best-evidence synthesis was performed, based on design, methodological quality and significant findings on outcome measures. Seven studies, with sample sizes ranging from 11 to 49, were included in the systematic review and appraised for content. Five of these studies were of poor methodological quality. One uncontrolled study (N = 1 3 ) was considered to be of sufficient methodological quality, and one randomized controlled trial (N = 49) was of high methodological quality. Best-evidence synthesis showed that there is limited evidence for the effectiveness of sensory re-education, provided by a statistically significant improvement in sensibility found in one high-quality randomized controlled trial. There is a need for further well-defined clinical trials to assess the effectiveness of sensory re-education of patients with impaired sensibility of the hand due to a peripheral nerve injury.

  14. Congenital sensory neuropathy

    PubMed Central

    Barry, J. E.; Hopkins, I. J.; Neal, B. W.

    1974-01-01

    Two infants with sporadic congenital sensory neuropathy are described. The criteria of generalized lack of superficial sensory appreciation, hypotonia, areflexia, together with histological evidence of abnormalities of sensory neural structures in skin and peripheral nerves have been met. No abnormality of motor or autonomic nerves was shown. ImagesFIG. PMID:4131674

  15. 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. Copyright © 2013 Elsevier Inc. All rights reserved.

  16. 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

  17. Effect of nitric oxide synthase inhibitor on increase in nasal mucosal blood flow induced by sensory and parasympathetic nerve stimulation in rats.

    PubMed

    Ogawa, Fumio; Hanamitsu, Masakazu; Ayajiki, Kazuhide; Aimi, Yoshinari; Okamura, Tomio; Shimizu, Takeshi

    2010-06-01

    Neural control of nasal blood flow (NBF) has not been systematically investigated. The aim of the present study was to evaluate the effect of electrical stimulation of both sensory and parasympathetic nerves innervating the nasal mucosal arteries on NBF in rats. In anesthetized rats, nasociliary (sensory) nerves and postganglionic (parasympathetic) nerves derived from the right sphenopalatine ganglion were electrically stimulated. We measured NBF with a laser-Doppler flowmeter. The nerve stimulation increased NBF on both sides and increased the mean arterial blood pressure. The increase in NBF was larger on the ipsilateral side than on the contralateral side. Hexamethonium bromide, a ganglion blocker, abolished the stimulation-induced pressure effect and the increase in NBF on the contralateral side, but did not abolish the increase in NBF on the ipsilateral side. The remaining increase in NBF was abolished by N(G)-nitro-L-arginine, a nitric oxide synthase inhibitor. Histochemical analysis with nicotinamide adenine dinucleotide phosphate-diaphorase showed neuronal nitric oxide synthase-containing nerves that innervate nasal mucosal arteries. Nitric oxide released from parasympathetic nitrergic nerves may contribute to an increase in NBF in rats. The afferent impulses induced by sensory nerve stimulation may lead to an increase in mean arterial blood pressure that is partly responsible for the increase in NBF.

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

    PubMed

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

    2015-05-06

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

  19. Different Effects of Implanting Sensory Nerve or Blood Vessel on the Vascularization, Neurotization, and Osteogenesis of Tissue-Engineered Bone In Vivo

    PubMed Central

    Fan, Jun-jun; Mu, Tian-wang; Qin, Jun-jun; Bi, Long; Pei, Guo-xian

    2014-01-01

    To compare the different effects of implanting sensory nerve tracts or blood vessel on the osteogenesis, vascularization, and neurotization of the tissue-engineered bone in vivo, we constructed the tissue engineered bone and implanted the sensory nerve tracts (group SN), blood vessel (group VB), or nothing (group Blank) to the side channel of the bone graft to repair the femur defect in the rabbit. Better osteogenesis was observed in groups SN and VB than in group Blank, and no significant difference was found between groups SN and VB at 4, 8, and 12 weeks postoperatively. The neuropeptides expression and the number of new blood vessels in the bone tissues were increased at 8 weeks and then decreased at 12 weeks in all groups and were highest in group VB and lowest in group Blank at all three time points. We conclude that implanting either blood vessel or sensory nerve tract into the tissue-engineered bone can significantly enhance both the vascularization and neurotization simultaneously to get a better osteogenesis effect than TEB alone, and the method of implanting blood vessel has a little better effect of vascularization and neurotization but almost the same osteogenesis effect as implanting sensory nerve. PMID:25101279

  20. Pudendal and median nerve sensory perception threshold: a comparison between normative studies.

    PubMed

    Quaghebeur, Jörgen; Wyndaele, Jean Jacques

    2014-12-01

    For the evaluation of sensory innervation, normative data are necessary as a comparison. To compare our current perception thresholds (CPTs) with normative data from other research. Healthy volunteers were assessed for 2000, 250, and 5 Hz CPTs of the median and pudendal nerve and data were compared with other studies. Normative data in the studied group n = 41 (male: 21; female: 20) for the median nerve, 2 kHz, 250 Hz, and 5 Hz were respectively: 241.85 ± 67.72 (140-444); 106.27 ± 39.12 (45-229); 82.05 ± 43.40 (13-271). Pudendal nerve CPTs 250 Hz were: 126.44 ± 69.46 (6-333). For men 2 kHz: 349.95 ± 125.76 (100-588); 5 Hz: 132.67 ± 51.81 (59-249) and women 2 kHz:226.20 ± 119.65 (64-528); 5 Hz: 92.45 ± 44.66 (35-215). For the median nerve no statistical differences for gender were shown. For the pudendal nerve, only 250 Hz showed no difference for gender (t-test: 0.516). Comparison of our data with CPTs of other normative data showed no agreement for the pudendal nerve. For the median nerve only 2 kHz showed agreement in three studies and for 5 Hz with one study. Comparing normative data of multiple studies shows a variety of results and poor agreement. Therefore, referring to normative data of other studies should be handled with caution.

  1. 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. Copyright © 2013 Elsevier Ltd. All rights reserved.

  2. Haemangioblastoma of a cervical sensory nerve root in Von Hippel-Lindau syndrome.

    PubMed

    McEvoy, A W; Benjamin, E; Powell, M P

    2000-10-01

    Spinal haemangioblastomas are rare, accounting for only about 7% of all central nervous system cases. The case of a 40-year-old woman with a haemangioblastoma arising solely from a cervical sensory nerve root is presented. At operation via a cervical laminectomy, it was possible to resect the tumour en masse with the sensory ramus, by extending the laminectomy through the exit foramen for C6. Haemangioblastomas are commonly intramedullary, and have only been reported in this location on one previous occasion. The patient has Von Hippel-Lindau syndrome and a history of multiple solid tumours. The possible role of the Von Hippel-Lindau tumour suppressor gene in the pathogenesis of these neoplasms is discussed.

  3. Effect of walking and resting after three cryotherapy modalities on the recovery of sensory and motor nerve conduction velocity in healthy subjects.

    PubMed

    Herrera, Esperanza; Sandoval, Maria Cristina; Camargo, Diana M; Salvini, Tania F

    2011-01-01

    Different cryotherapy modalities have distinct effects on sensory and motor nerve conduction parameters. However, it is unclear how these parameters change during the post-cooling period and how the exercise carried out in this period would influence the recovery of nerve conduction velocity (NCV). To compare the effects of three cryotherapy modalities on post-cooling NCV and to analyze the effect of walking on the recovery of sensory and motor NCV. Thirty six healthy young subjects were randomly allocated into three groups: ice massage (n=12), ice pack (n=12) and cold water immersion (n=12). The modalities were applied to the right leg. The subjects of each modality group were again randomized to perform a post-cooling activity: a) 30 min rest, b) walking 15 min followed by 15 min rest. The NCV of sural (sensory) and posterior tibial (motor) nerves was evaluated. Initial (pre-cooling) and final (30 min post-cooling) NCV were compared using a paired t-test. The effects of the modalities and the post-cooling activities on NCV were evaluated by an analysis of covariance. The significance level was α=0.05. There was a significant difference between immersion and ice massage on final sensory NCV (p=0.009). Ice pack and ice massage showed similar effects (p>0.05). Walking accelerated the recovery of sensory and motor NCV, regardless of the modality previously applied (p<0.0001). Cold water immersion was the most effective modality for maintaining reduced sensory nerve conduction after cooling. Walking after cooling, with any of the three modalities, enhances the recovery of sensory and motor NCV.

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

    PubMed

    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

    2015-08-01

    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.

  5. Sensory and motor peripheral nerve function and longitudinal changes in quadriceps strength.

    PubMed

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

    2015-04-01

    Poor peripheral nerve function is common in older adults and may be a risk factor for strength decline, although this has not been assessed longitudinally. We assessed whether sensorimotor peripheral nerve function predicts strength longitudinally in 1,830 participants (age = 76.3 ± 2.8, body mass index = 27.2 ± 4.6kg/m(2), strength = 96.3 ± 34.7 Nm, 51.0% female, 34.8% black) from the Health ABC study. Isokinetic quadriceps strength was measured semiannually over 6 years. Peroneal motor nerve conduction amplitude and velocity were recorded. Sensory nerve function was assessed with 10-g and 1.4-g monofilaments and average vibration detection threshold at the toe. Lower-extremity neuropathy symptoms were self-reported. Worse vibration detection threshold predicted 2.4% lower strength in men and worse motor amplitude and two symptoms predicted 2.5% and 8.1% lower strength, respectively, in women. Initial 10-g monofilament insensitivity predicted 14.2% lower strength and faster strength decline in women and 6.6% lower strength in men (all p < .05). Poor nerve function predicted lower strength and faster strength decline. Future work should examine interventions aimed at preventing declines in strength in older adults with impaired nerve function. © The Author 2014. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  6. Ionotropic and metabotropic receptor mediated airway sensory nerve activation.

    PubMed

    Lee, Min-Goo; Kollarik, Marian; Chuaychoo, Benjamas; Undem, Bradley J

    2004-01-01

    There are several receptors capable of inducing activating generator potentials in cough-associated afferent terminals in the airways. The chemical receptors leading to generator potentials can be subclassified into ionotropic and metabotropic types. An ionotropic receptor has an agonist-binding domain, and also serves directly as an ion channel that is opened upon binding of the agonist. Examples of ionotropic receptors found in airway sensory nerve terminals include receptors for serotonin (5-HT3 receptors), ATP (P2X receptors), acetylcholine (nicotinic receptors), receptors for capsaicin and related vanilloids (TRPV1 receptors), and acid receptors (acid sensing ion channels). Afferent nerve terminals can also be depolarized via activation of metabotropic or G-protein coupled receptors (GPCRs). Among the GPCRs that can lead to activation of airway afferent fibers include bradykinin B2 and adenosine A1 receptors. The signaling events leading to GPCR-mediated membrane depolarization are more complex than that seen with ionotropic receptors. The GPCR-mediated effects are thought to occur through classical second messenger systems such as activation of phospholipase C. This may lead to membrane depolarization through interaction with specific ionotropic receptors (such as TRPV1) and/or various types of calcium activated channels.

  7. 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

  8. The vestibulocochlear nerve (VIII).

    PubMed

    Benoudiba, F; Toulgoat, F; Sarrazin, J-L

    2013-10-01

    The vestibulocochlear nerve (8th cranial nerve) is a sensory nerve. It is made up of two nerves, the cochlear, which transmits sound and the vestibular which controls balance. It is an intracranial nerve which runs from the sensory receptors in the internal ear to the brain stem nuclei and finally to the auditory areas: the post-central gyrus and superior temporal auditory cortex. The most common lesions responsible for damage to VIII are vestibular Schwannomas. This report reviews the anatomy and various investigations of the nerve. Copyright © 2013. Published by Elsevier Masson SAS.

  9. Chitin biological absorbable catheters bridging sural nerve grafts transplanted into sciatic nerve defects promote nerve regeneration.

    PubMed

    Wang, Zhi-Yong; Wang, Jian-Wei; Qin, Li-Hua; Zhang, Wei-Guang; Zhang, Pei-Xun; Jiang, Bao-Guo

    2018-06-01

    To investigate the efficacy of chitin biological absorbable catheters in a rat model of autologous nerve transplantation. A segment of sciatic nerve was removed to produce a sciatic nerve defect, and the sural nerve was cut from the ipsilateral leg and used as a graft to bridge the defect, with or without use of a chitin biological absorbable catheter surrounding the graft. The number and morphology of regenerating myelinated fibers, nerve conduction velocity, nerve function index, triceps surae muscle morphology, and sensory function were evaluated at 9 and 12 months after surgery. All of the above parameters were improved in rats in which the nerve graft was bridged with chitin biological absorbable catheters compared with rats without catheters. The results of this study indicate that use of chitin biological absorbable catheters to surround sural nerve grafts bridging sciatic nerve defects promotes recovery of structural, motor, and sensory function and improves muscle fiber morphology. © 2018 John Wiley & Sons Ltd.

  10. Parasympathetic, sympathetic, and sensory interactions in the iris: nerve growth factor regulates cholinergic ciliary ganglion innervation in vivo.

    PubMed

    Kessler, J A

    1985-10-01

    Interactions between peptidergic sensory nerves, noradrenergic sympathetic nerves, and cholinergic parasympathetic fibers were examined in the rat iris. The putative peptide neurotransmitter, substance P (SP), was used as an index of the trigeminal sensory innervation, tyrosine hydroxylase (TH) activity served to monitor the sympathetic fibers, and choline acetyltransferase (CAT) activity was used as an index of the parasympathetic innervation. Destruction of the sympathetic innervation by neonatal administration of 6-hydroxydopamine resulted in increased SP development and a smaller increase in CAT activity in the iris. Moreover, trigeminal ablation resulted in an increase in both TH and CAT activities. Finally, ciliary ganglionectomy resulted in increased SP and a smaller increase in TH activity in the iris. Administration of nerve growth factor (NGF) into the anterior chamber substantially increased both SP and TH activity in the iris and also increased CAT activity to a lesser extent. Moreover, administration of anti-NGF into the anterior chamber prevented both the sympathectomy-induced increases in SP and CAT, and the increases in TH and CAT activities after trigeminal ablation, suggesting that NGF mediated these increases. These observations suggest that the sympathetic, sensory, and parasympathetic innervations of the iris interact by altering availability of NGF elaborated by the iris. Regulation of iris CAT activity was examined in greater detail. Injection of the cholinergic toxin, AF64A, into the anterior chamber concurrently with ablation of the sympathetic and sensory innervations paradoxically increased CAT activity, whereas AF64A alone decreased CAT activity.(ABSTRACT TRUNCATED AT 250 WORDS)

  11. Bradykinin activates a cross-signaling pathway between sensory and adrenergic nerve endings in the heart: a novel mechanism of ischemic norepinephrine release?

    PubMed

    Seyedi, N; Maruyama, R; Levi, R

    1999-08-01

    We had shown that bradykinin (BK) generated by cardiac sympathetic nerve endings (i.e., synaptosomes) promotes exocytotic norepinephrine (NE) release in an autocrine mode. Because the synaptosomal preparation may include sensory C-fiber endings, which BK is known to stimulate, sensory nerves could contribute to the proadrenergic effects of BK in the heart. We report that BK is a potent releaser of NE from guinea pig heart synaptosomes (EC(50) approximately 20 nM), an effect mediated by B(2) receptors, and almost completely abolished by prior C-fiber destruction or blockade of calcitonin gene-related peptide and neurokinin-1 receptors. C-fiber destruction also greatly decreased BK-induced NE release from the intact heart, whereas tyramine-induced NE release was unaffected. Furthermore, C-fiber stimulation with capsaicin and activation of calcitonin gene-related peptide and neurokinin-1 receptors initiated NE release from cardiac synaptosomes, indicating that stimulation of sensory neurons in turn activates sympathetic nerve terminals. Thus, BK is likely to release NE in the heart in part by first liberating calcitonin gene-related peptide and Substance P from sensory nerve endings; these neuropeptides then stimulate specific receptors on sympathetic terminals. This action of BK is positively modulated by cyclooxygenase products, attenuated by activation of histamine H(3) receptors, and potentiated at a lower pH. The NE-releasing action of BK is likely to be enhanced in myocardial ischemia, when protons accumulate, C fibers become activated, and the production of prostaglandins and BK increases. Because NE is a major arrhythmogenic agent, the activation of this interneuronal signaling system between sensory and adrenergic neurons may contribute to ischemic dysrhythmias and sudden cardiac death.

  12. Influence of local noxious heat stimulation on sensory nerve activity in the feline dental pulp.

    PubMed

    Ahlberg, K F

    1978-05-01

    The present investigation was undertaken to develop an experimental model in which noxious heat stimulation was used to produce increased intradental sensory nerve activity in canine teeth of anesthetized cats. Two techniques were evaluated in which both the method of recording and the nature of the stimulus varied. Slow heating (approx 1 degree C/s) to 47 degree C of the tooth surface (combined with recording from electrodes in open dentinal cavities) did not produce any persistent nerve activity. Repeated periods of brief intense heating (approx 60 degrees C/s) (combined with recording from amalgam electrodes placed on cavity floors) resulted in an immediate response and an afterdischarge (phase 3) generally persisting for 20--60 min. Maximum phase 3 activity was characteristic for the individual cat and ranged from 0.2 to 50.2 imp/s. mean value 10.6 imp/s (S.D. +/- 9.2). A systematically higher phase 3 activity was recorded in lower compared to upper canine teeth (p less than 0.05). The maximum phase 3 response generally occurred after 3-8 stimulations; the median number of required stimuli was 3. Repeated brief heat stimulations combined with the closed cavity recording technique may be used as an experimental model by which the mechanisms behind increases in intradental sensory nerve activity associated with tissue damage can be studied.

  13. An artificial arm/hand system with a haptic sensory function using electric stimulation of peripheral sensory nerve fibers.

    PubMed

    Mabuchi, Kunihiko

    2013-01-01

    We are currently developing an artificial arm/hand system which is capable of sensing stimuli and then transferring these stimuli to users as somatic sensations. Presently, we are evoking the virtual somatic sensations by electrically stimulating a sensory nerve fiber which innervates a single mechanoreceptor unit at the target area; this is done using a tungsten microelectrode that was percutaneously inserted into the use's peripheral nerve (a microstimulation method). The artificial arm/hand system is composed of a robot hand equipped with a pressure sensor system on its fingers. The sensor system detects mechanical stimuli, which are transferred to the user by means of the microstimulation method so that the user experiences the stimuli as the corresponding somatic sensations. In trials, the system worked satisfactorily and there was a good correlation between the pressure applied to the pressure sensors on the robot fingers and the subjective intensities of the evoked pressure sensations.

  14. 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

  15. Multifocal sensory demyelinating neuropathy: Report of a case.

    PubMed

    Oh, Shin J

    2017-10-01

    Multifocal sensory demyelinating neuropathy has not been adequately reported in the literature. A 42-year-old man with numbness of the left hand for 3 years and of the right hand for 6 months had a pure multifocal sensory neuropathy involving both hands, most prominently affecting 2-point discrimination, number writing, and object recognition of the left hand. Near-nerve needle sensory and mixed nerve conduction studies were performed on the left ulnar nerve. Studies of the left ulnar nerve documented a demyelinating neuropathy characterized by temporal dispersion and marked decrease in the amplitudes of the sensory and mixed compound nerve potentials in the above-elbow-axilla segment. With intravenous immunoglobulin treatment, there was improvement in his neuropathic condition. In this study I describe a case of multifocal sensory demyelinating neuropathy as a counterpart of multifocal motor neuropathy. Muscle Nerve 56: 825-828, 2017. © 2016 Wiley Periodicals, Inc.

  16. The time course of brief and prolonged topical 8% capsaicin-induced desensitization in healthy volunteers evaluated by quantitative sensory testing and vasomotor imaging.

    PubMed

    Lo Vecchio, Silvia; Andersen, Hjalte Holm; Arendt-Nielsen, Lars

    2018-05-29

    Topically applied high-concentration capsaicin induces reversible dermo-epidermal denervation and depletion of capsaicin-sensitive nociceptors. This causes desensitization of distinct sensory modalities and is used to treat peripheral neuropathic pain and itch. For high-concentration capsaicin, the selectivity of loss of function and functional recovery rates of various afferent fibers subpopulations are unknown. This study used comprehensive quantitative sensory testing and vasomotor imaging to assess effectiveness, duration and sensory selectivity of high-concentration 8% capsaicin-ablation. Skin areas in 14 healthy volunteers were randomized to treatment with 8% capsaicin/vehicle patches for 1 and 24 h and underwent comprehensive sensory and vasomotor testing at 1, 7 and 21 days postpatch removal. Tests consisted of thermal detection and pain thresholds, tactile and vibration detection thresholds, mechanical pain threshold and mechanical pain sensitivity as well as micro-vascular and itch reactivity to histamine provocations. The 24 h capsaicin drastically inhibited warmth detection (P < 0.001), heat pain (P < 0.001) as well as histamine-induced itch (P < 0.05) and neurogenic flare (P < 0.001), but had no impact on tactile sensitivity, cold detection and cold pain. A marginal decrease in mechanical pain sensitivity was observed (P < 0.05). Capsaicin for 1 h had limited and transient sensory effects only affecting warmth and heat sensations. Time-dependent functional recovery was almost complete 21 days after the 24 h capsaicin exposure, while recovery of neurogenic inflammatory responsiveness remained partial. The psychophysically assessed sensory deficiencies induced by the used 8% capsaicin-ablation correspond well with a predominant effect on TRPV1 + -cutaneous fibers. The method is easy to apply, well tolerated, and utilizable for studies on, e.g., interactions between skin barrier, inflammation and capsaicin-sensitive afferents.

  17. Fate of combat nerve injury.

    PubMed

    Beltran, Michael J; Burns, Travis C; Eckel, Tobin T; Potter, Benjamin K; Wenke, Joseph C; Hsu, Joseph R

    2012-11-01

    Assess a cohort of combat-related type III open tibia fractures with peripheral nerve injury to determine the injury mechanism and likelihood for recovery or improvement in nerve function. Retrospective study. Three military medical centers. Out of a study cohort of 213 type III open tibia fractures, 32 fractures (in 32 patients) with a total of 43 peripheral nerve injuries (peroneal or tibial) distal to the popliteal fossa met inclusion criteria and were available for follow-up at an average of 20 months (range, 2-48 months). Clinical assessment of motor and sensory nerve improvement. There was a 22% incidence of peripheral nerve injury in the study cohort. At an average follow-up of 20 months (range, 2-48 months), 89% of injured motor nerves were functional, whereas the injured sensory nerves had function in 93%. Fifty percent and 27% of motor and sensory injuries demonstrated improvement, respectively (P = 0.043). With the numbers available, there was no difference in motor or sensory improvement based on mechanism of injury, fracture severity or location, soft tissue injury, or specific nerve injured. In the subset of patients with an initially impaired sensory examination, full improvement was related to fracture location (P = 0.0164). Type III open tibia fractures sustained in combat are associated with a 22% incidence of peripheral nerve injury, and the majority are due to multiple projectile penetrating injury. Despite the severe nature of these injuries, the vast majority of patients had a functional nerve status by an average of 2-year follow-up. Based on these findings, discussions regarding limb salvage and amputation should not be overly influenced by the patient's peripheral nerve status. Prognostic Level II. See Instructions for Authors for a complete description of levels of evidence.

  18. Increased thrombospondin-4 after nerve injury mediates disruption of intracellular calcium signaling in primary sensory neurons

    PubMed Central

    Guo, Yuan; Zhang, Zhiyong; Wu, Hsiang-en; Luo, Z. David; Hogan, Quinn H.; Pan, Bin

    2017-01-01

    Painful nerve injury disrupts Ca2+ signaling in primary sensory neurons by elevating plasma membrane Ca2+-ATPase (PMCA) function and depressing sarco-endoplasmic reticulum Ca2+-ATPase (SERCA) function, which decreases endoplasmic reticulum (ER) Ca2+ stores and stimulates store-operated Ca2+ entry (SOCE). The extracellular matrix glycoprotein thrombospondin-4 (TSP4), which is increased after painful nerve injury, decreases Ca2+ current (ICa) through high-voltage–activated Ca2+ channels and increases ICa through low-voltage–activated Ca2+ channels in dorsal root ganglion neurons, which are events similar to the effect of nerve injury. We therefore examined whether TSP4 plays a critical role in injury-induced disruption of intracellular Ca2+ signaling. We found that TSP4 increases PMCA activity, inhibits SERCA, depletes ER Ca2+ stores, and enhances store-operated Ca2+ influx. Injury-induced changes of SERCA and PMCA function are attenuated in TSP4 knock-out mice. Effects of TSP4 on intracellular Ca2+ signaling are attenuated in voltage-gated Ca2+ channel α2δ1 subunit (Cavα2δ1) conditional knock-out mice and are also Protein Kinase C (PKC) signaling dependent. These findings suggest that TSP4 elevation may contribute to the pathogenesis of chronic pain following nerve injury by disrupting intracellular Ca2+ signaling via interacting with the Cavα2δ1 and the subsequent PKC signaling pathway. Controlling TSP4 mediated intracellular Ca2+ signaling in peripheral sensory neurons may be a target for analgesic drug development for neuropathic pain. PMID:28232180

  19. 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

  20. 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

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

    PubMed

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

    2016-02-01

    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. 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. 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. 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.

  2. Anodal sensory nerve action potentials: From physiological understanding to potential clinical applicability.

    PubMed

    Leote, Joao; Pereira, Pedro; Cabib, Christopher; Cipullo, Federica; Valls-Sole, Josep

    2016-06-01

    Low-intensity electrical stimuli of digital nerves may generate a double peak potential (DPp), composed of a cathodal (caAP) and an anodal (anAP) potential in orthodromic recordings. We studied the effects on caAP and anAP of stimuli of variable intensity, duration, and frequency. We also applied a conditioning stimulus to study potential differences in recovery time. The anAP was obtained in 33 of 40 healthy subjects (82.5%) and 4 of 20 patients with various types of sensory neuropathies (20%). Changes in stimulus duration and intensity had reciprocal effects on the amplitude of the anAP and the caAP. There were significant differences in recovery time between caAP and anAP after a conditioning stimulus. The caAP and anAP are 2 interdependent waveforms generated by different effects of the same stimulus over axons at the verge of depolarization. Muscle Nerve 53: 897-905, 2016. © 2015 Wiley Periodicals, Inc.

  3. A collagen-based nerve guide conduit for peripheral nerve repair: an electrophysiological study of nerve regeneration in rodents and nonhuman primates.

    PubMed

    Archibald, S J; Krarup, C; Shefner, J; Li, S T; Madison, R D

    1991-04-22

    When a peripheral nerve is severed and left untreated, the most likely result is the formation of an endbulb neuroma; this tangled mass of disorganized nerve fibers blocks functional recovery following nerve injury. Although there are several different approaches for promoting nerve repair, which have been greatly refined over recent years, the clinical results of peripheral nerve repair remain very disappointing. In this paper we compare the results of a collagen nerve guide conduit to the more standard clinical procedure of nerve autografting to promote repair of transected peripheral nerves in rats and nonhuman primates. In rats, we tested recovery from sciatic nerve transection and repair by 1) direct microsurgical suture, 2) 4 mm autograft, or 3) entubulation repair with collagen-based nerve guide conduits. Evoked muscle action potentials (MAP) were recorded from the gastrocnemius muscle at 4 and 12 weeks following sciatic nerve transection. At 4 weeks the repair group of direct suture demonstrated a significantly greater MAP, compared to the other surgical repair groups. However, at 12 weeks all four surgical repair groups displayed similar levels of recovery of the motor response. In six adult male Macaca fascicularis monkeys the median nerve was transected 2 cm above the wrist and repaired by either a 4 mm nerve autograft or a collagen-based nerve guide conduit leaving a 4 mm gap between nerve ends. Serial studies of motor and sensory fibers were performed by recording the evoked MAP from the abductor pollicis brevis muscle (APB) and the sensory action potential (SAP) evoked by stimulation of digital nerves (digit II), respectively, up to 760 days following surgery. Evoked muscle responses returned to normal baseline levels in all cases. Statistical analysis of the motor responses, as judged by the slope of the recovery curves, indicated a significantly more rapid rate of recovery for the nerve guide repair group. The final level of recovery of the MAP

  4. CO-LOCALIZATION OF THE VANILLOID CAPSAICIN RECEPTOR AND SUBSTANCE P IN SENSORY NERVE FIBERS INNERVATING COCHLEAR AND VERTEBRO-BASILAR ARTERIES

    PubMed Central

    VASS, Z.; DAI, C. F.; STEYGER, P. S.; JANCSÓ, G.; TRUNE, D. R.; NUTTALL, A. L.

    2014-01-01

    Evidence suggests that capsaicin-sensitive substance P (SP)-containing trigeminal ganglion neurons innervate the spiral modiolar artery (SMA), radiating arterioles, and the stria vascularis of the cochlea. Antidromic electrical or chemical stimulation of trigeminal sensory nerves results in neurogenic plasma extravasation in inner ear tissues. The primary aim of this study was to reveal the possible morphological basis of cochlear vascular changes mediated by capsaicin-sensitive sensory nerves. Therefore, the distribution of SP and capsaicin receptor (transient receptor potential vanilloid type 1—TRPV1) was investigated by double immunolabeling to demonstrate the anatomical relationships between the cochlear and vertebro-basilar blood vessels and the trigeminal sensory fiber system. Extensive TRPV1 and SP expression and co-localization were observed in axons within the adventitial layer of the basilar artery, the anterior inferior cerebellar artery, the SMA, and the radiating arterioles of the cochlea. There appears to be a functional relationship between the trigeminal ganglion and the cochlear blood vessels since electrical stimulation of the trigeminal ganglion induced significant plasma extravasation from the SMA and the radiating arterioles. The findings suggest that stimulation of paravascular afferent nerves may result in permeability changes in the basilar and cochlear vascular bed and may contribute to the mechanisms of vertebro-basilar type of headache through the release of SP and stimulation of TPVR1, respectively. We propose that vertigo, tinnitus, and hearing deficits associated with migraine may arise from perturbations of capsaicin-sensitive trigeminal sensory ganglion neurons projecting to the cochlea. PMID:15026132

  5. Percutaneous freezing of sensory nerves prior to total knee arthroplasty.

    PubMed

    Dasa, Vinod; Lensing, Gabriel; Parsons, Miles; Harris, Justin; Volaufova, Julia; Bliss, Ryan

    2016-06-01

    Total knee arthroplasty (TKA) is a common procedure resulting in significant post-operative pain. Percutaneous cryoneurolysis targeting the infrapatellar branch of the saphenous nerve and anterior femoral cutaneous nerve could relieve post-operative knee pain by temporarily blocking sensory nerve conduction. A retrospective chart review of 100 patients who underwent TKA was conducted to assess the value of adding perioperative cryoneurolysis to a multimodal pain management program. The treatment group consisted of the first 50 patients consecutively treated after the practice introduced perioperative (five days prior to surgery) cryoneurolysis as part of its standard pain management protocol. The control group consisted of the 50 patients treated before cryoneurolysis was introduced. Outcomes included hospital length of stay (LOS), post-operative opioid requirements, and patient-reported outcomes of pain and function. A significantly lower proportion of patients in the treatment group had a LOS of ≥2days compared with the control group (6% vs. 67%, p<0.0001) and required 45% less opioids during the first 12weeks after surgery. The treatment group reported a statistically significant reduction in symptoms at the six- and 12-week follow-up compared with the control group and within-group significant reductions in pain intensity and pain interference at two- and six-week follow-up, respectively. Perioperative cryoneurolysis in combination with multimodal pain management may significantly improve outcomes in patients undergoing TKA. Promising results from this preliminary retrospective study warrant further investigation of this novel treatment in prospective, randomized trials. III. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

  6. The role of calcium in the desensitization of capsaicin responses in rat dorsal root ganglion neurons.

    PubMed

    Koplas, P A; Rosenberg, R L; Oxford, G S

    1997-05-15

    Capsaicin (Cap) is a pungent extract of the Capsicum pepper family, which activates nociceptive primary sensory neurons. Inward current and membrane potential responses of cultured neonatal rat dorsal root ganglion neurons to capsaicin were examined using whole-cell and perforated patch recording methods. The responses exhibited strong desensitization operationally classified as acute (diminished response during constant Cap exposure) and tachyphylaxis (diminished response to successive applications of Cap). Both acute desensitization and tachyphylaxis were greatly diminished by reductions in external Ca2+ concentration. Furthermore, chelation of intracellular Ca2+ by addition of either EGTA or bis(2-aminophenoxy)ethane-N,N,N',N'-tetra-acetic acid to the patch pipette attenuated both forms of desensitization even in normal Ca2+. Release of intracellular Ca2+ by caffeine triggered acute desensitization in the absence of extracellular Ca2+, and barium was found to effectively substitute for calcium in supporting desensitization. Cap activated inward current at an ED50 of 728 nM, exhibiting cooperativity (Hill coefficient, 2.2); however, both forms of desensitization were only weakly dependent on [Cap], suggesting a dissociation between activation of Cap-sensitive channels and desensitization. Removal of ATP and GTP from the intracellular solutions resulted in nearly complete tachyphylaxis even with intracellular Ca2+ buffered to low levels, whereas changes in nucleotide levels did not significantly alter the acute form of desensitization. These data suggest a key role for intracellular Ca2+ in desensitization of Cap responses, perhaps through Ca2+-dependent dephosphorylation at a locus that normally sustains Cap responsiveness via ATP-dependent phosphorylation. It also seems that the signaling mechanisms underlying the two forms of desensitization are not identical in detail.

  7. 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

  8. Sensory and motor neuropathy in a Border Collie.

    PubMed

    Harkin, Kenneth R; Cash, Walter C; Shelton, G Diane

    2005-10-15

    A 5-month-old female Border Collie was evaluated because of progressive hind limb ataxia. The predominant clinical findings suggested a sensory neuropathy. Sensory nerve conduction velocity was absent in the tibial, common peroneal, and radial nerves and was decreased in the ulnar nerve; motor nerve conduction velocity was decreased in the tibial, common peroneal, and ulnar nerves. Histologic examination of nerve biopsy specimens revealed considerable nerve fiber depletion; some tissue sections had myelin ovoids, foamy macrophages, and axonal degeneration in remaining fibers. Marked depletion of most myelinated fibers within the peroneal nerve (a mixed sensory and motor nerve) supported the electrodiagnostic findings indicative of sensorimotor neuropathy. Progressive deterioration in motor function occurred over the following 19 months until the dog was euthanatized. A hereditary link was not established, but a littermate was similarly affected. The hereditary characteristic of this disease requires further investigation.

  9. Peripheral ionotropic glutamate receptors contribute to Fos expression increase in the spinal cord through antidromic electrical stimulation of sensory nerves.

    PubMed

    Li, Jia-Heng; He, Pei-Yao; Fan, Dan-Ni; Alemujiang, Dilinapa; Huo, Fu-Quan; Zhao, Yan; Cao, Dong-Yuan

    2018-06-21

    Previous studies have shown that peripheral ionotropic glutamate receptors are involved in the increase in sensitivity of a cutaneous branch of spinal dorsal ramus (CBDR) through antidromic electrical stimulation (ADES) of another CBDR in the adjacent segment. CBDR in the thoracic segments run parallel to each other and no synaptic contact at the periphery is reported. The present study investigated whether the increased sensitivity of peripheral sensory nerves via ADES of a CBDR induced Fos expression changes in the adjacent segments of the spinal cord. Fos expression increased in the T8 - T12 segments of the spinal cord evoked by ADES of the T10 CBDR in rats. The increased Fos expression in the T11 and T12, but not T8 - T10 spinal cord segments, was significantly blocked by local application of either N-methyl-D-aspartate (NMDA) receptor antagonist dizocilpine maleate (MK-801) or non-NMDA receptor antagonist 6,7-dinitroquinoxaline-2,3-dione (DNQX) into the receptive field of T11 CBDR. The results suggest that endogenous glutamate released by ADES of sensory nerve may bind to peripheral ionotropic glutamate receptors and activate adjacent sensory nerve endings to increase the sensitivity of the spinal cord. These data reveal the potential mechanisms of neuron activation in the spinal cord evoked by peripheral sensitization. Copyright © 2018 Elsevier B.V. All rights reserved.

  10. Miconazole enhances nerve regeneration and functional recovery after sciatic nerve crush injury.

    PubMed

    Lin, Tao; Qiu, Shuai; Yan, Liwei; Zhu, Shuang; Zheng, Canbin; Zhu, Qingtang; Liu, Xiaolin

    2018-05-01

    Improving axonal outgrowth and remyelination is crucial for peripheral nerve regeneration. Miconazole appears to enhance remyelination in the central nervous system. In this study we assess the effect of miconazole on axonal regeneration using a sciatic nerve crush injury model in rats. Fifty Sprague-Dawley rats were divided into control and miconazole groups. Nerve regeneration and myelination were determined using histological and electrophysiological assessment. Evaluation of sensory and motor recovery was performed using the pinprick assay and sciatic functional index. The Cell Counting Kit-8 assay and Western blotting were used to assess the proliferation and neurotrophic expression of RSC 96 Schwann cells. Miconazole promoted axonal regrowth, increased myelinated nerve fibers, improved sensory recovery and walking behavior, enhanced stimulated amplitude and nerve conduction velocity, and elevated proliferation and neurotrophic expression of RSC 96 Schwann cells. Miconazole was beneficial for nerve regeneration and functional recovery after peripheral nerve injury. Muscle Nerve 57: 821-828, 2018. © 2017 Wiley Periodicals, Inc.

  11. Simultaneous Loss of NCKX4 and CNG Channel Desensitization Impairs Olfactory Sensitivity.

    PubMed

    Ferguson, Christopher H; Zhao, Haiqing

    2017-01-04

    In vertebrate olfactory sensory neurons (OSNs), Ca 2+ plays key roles in both mediating and regulating the olfactory response. Ca 2+ enters OSN cilia during the response through the olfactory cyclic nucleotide-gated (CNG) channel and stimulates a depolarizing chloride current by opening the olfactory Ca 2+ -activated chloride channel to amplify the response. Ca 2+ also exerts negative regulation on the olfactory transduction cascade, through mechanisms that include reducing the CNG current by desensitizing the CNG channel via Ca 2+ /calmodulin (CaM), to reduce the response. Ca 2+ is removed from the cilia primarily by the K + -dependent Na + /Ca 2+ exchanger 4 (NCKX4), and the removal of Ca 2+ leads to closure of the chloride channel and response termination. In this study, we investigate how two mechanisms conventionally considered negative regulatory mechanisms of olfactory transduction, Ca 2+ removal by NCKX4, and desensitization of the CNG channel by Ca 2+ /CaM, interact to regulate the olfactory response. We performed electro-olfactogram (EOG) recordings on the double-mutant mice, NCKX4 -/- ;CNGB1 ΔCaM , which are simultaneously lacking NCKX4 (NCKX4 -/- ) and Ca 2+ /CaM-mediated CNG channel desensitization (CNGB1 ΔCaM ). Despite exhibiting alterations in various response attributes, including termination kinetics and adaption properties, OSNs in either NCKX4 -/- mice or CNGB1 ΔCaM mice show normal resting sensitivity, as determined by their unchanged EOG response amplitude. We found that OSNs in NCKX4 -/- ;CNGB1 ΔCaM mice displayed markedly reduced EOG amplitude accompanied by alterations in other response attributes. This study suggests that what are conventionally considered negative regulatory mechanisms of olfactory transduction also play a role in setting the resting sensitivity in OSNs. Sensory receptor cells maintain high sensitivity at rest. Although the mechanisms responsible for setting the resting sensitivity of sensory receptor cells are not

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

    PubMed

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

    2015-03-01

    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. 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. 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. Although capsaicin-sensitive sensory nerves mediate mechanical hyperalgesia in the later phase of autoantibody-induced chronic arthritis, they play important

  13. Effects of peripheral sensory nerve stimulation plus task-oriented training on upper extremity function in patients with subacute stroke: a pilot randomized crossover trial.

    PubMed

    Ikuno, Koki; Kawaguchi, Saori; Kitabeppu, Shinsuke; Kitaura, Masaki; Tokuhisa, Kentaro; Morimoto, Shigeru; Matsuo, Atsushi; Shomoto, Koji

    2012-11-01

    To investigate the feasibility of peripheral sensory nerve stimulation combined with task-oriented training in patients with stroke during inpatient rehabilitation. A pilot randomized crossover trial. Two rehabilitation hospitals. Twenty-two patients with subacute stroke. Participants were randomly assigned to two groups and underwent two weeks of training in addition to conventional inpatient rehabilitation. The immediate group underwent peripheral sensory nerve stimulation combined with task-oriented training in the first week, followed by another week with task-oriented training alone. The delayed group underwent the same training in reverse order. Outcome measures were the level of fatigue and Wolf Motor Function Test. Patients were assessed at baseline, one and two weeks. All participants completed the study with no adverse events. There was no significant difference in level of fatigue between each treatment. From baseline to one week, the immediate group showed larger improvements than the delayed groups in the Wolf Motor Function Test (decrease in mean time (± SD) from 41.9 ± 16.2 seconds to 30.6 ± 11.4 seconds versus from 46.8 ± 19.4 seconds to 42.9 ± 14.7 seconds, respectively) but the difference did not reach significance after Bonferroni correction (P = 0.041). Within-group comparison showed significant improvements in the Wolf Motor Function Test mean time after the peripheral sensory nerve stimulation combined with task-oriented training periods in each group (P < 0.01). Peripheral sensory nerve stimulation is feasible in clinical settings and may enhance the effects of task-oriented training in patients with subacute stroke.

  14. 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

  15. Active, Passive, and Vicarious Desensitization

    ERIC Educational Resources Information Center

    Denney, Douglas R.

    1974-01-01

    Two variations of desensitization therapy for reducing test anxiety were studied, active desensitization in which the client describes his visualizations of the scenes and vicarious desensitization in which the client merely observes the desensitization treatment of another test anxious client. The relaxation treatment which emphasized application…

  16. Synaptic activation of putative sensory neurons by hexamethonium-sensitive nerve pathways in mouse colon.

    PubMed

    Hibberd, Timothy J; Travis, Lee; Wiklendt, Lukasz; Costa, Marcello; Brookes, Simon J H; Hu, Hongzhen; Keating, Damien J; Spencer, Nick J

    2018-01-01

    The gastrointestinal tract contains its own independent population of sensory neurons within the gut wall. These sensory neurons have been referred to as intrinsic primary afferent neurons (IPANs) and can be identified by immunoreactivity to calcitonin gene-related peptide (CGRP) in mice. A common feature of IPANs is a paucity of fast synaptic inputs observed during sharp microelectrode recordings. Whether this is observed using different recording techniques is of particular interest for understanding the physiology of these neurons and neural circuit modeling. Here, we imaged spontaneous and evoked activation of myenteric neurons in isolated whole preparations of mouse colon and correlated recordings with CGRP and nitric oxide synthase (NOS) immunoreactivity, post hoc. Calcium indicator fluo 4 was used for this purpose. Calcium responses were recorded in nerve cell bodies located 5-10 mm oral to transmural electrical nerve stimuli. A total of 618 recorded neurons were classified for CGRP or NOS immunoreactivity. Aboral electrical stimulation evoked short-latency calcium transients in the majority of myenteric neurons, including ~90% of CGRP-immunoreactive Dogiel type II neurons. Activation of Dogiel type II neurons had a time course consistent with fast synaptic transmission and was always abolished by hexamethonium (300 μM) and by low-calcium Krebs solution. The nicotinic receptor agonist 1,1-dimethyl-4-phenylpiperazinium iodide (during synaptic blockade) directly activated Dogiel type II neurons. The present study suggests that murine colonic Dogiel type II neurons receive prominent fast excitatory synaptic inputs from hexamethonium-sensitive neural pathways. NEW & NOTEWORTHY Myenteric neurons in isolated mouse colon were recorded using calcium imaging and then neurochemically defined. Short-latency calcium transients were detected in >90% of calcitonin gene-related peptide-immunoreactive neurons to electrical stimulation of hexamethonium-sensitive pathways

  17. Capsaicin-Sensitive Sensory Nerves Are Necessary for the Protective Effect of Ghrelin in Cerulein-Induced Acute Pancreatitis in Rats

    PubMed Central

    Bonior, Joanna; Warzecha, Zygmunt; Ceranowicz, Piotr; Gajdosz, Ryszard; Pierzchalski, Piotr; Kot, Michalina; Leja-Szpak, Anna; Nawrot-Porąbka, Katarzyna; Link-Lenczowski, Paweł; Olszanecki, Rafał; Bartuś, Krzysztof; Trąbka, Rafał; Kuśnierz-Cabala, Beata; Dembiński, Artur; Jaworek, Jolanta

    2017-01-01

    Ghrelin was shown to exhibit protective and therapeutic effect in the gut. Aim of the study was to investigate the role of sensory nerves (SN) in the protective effect of ghrelin in acute pancreatitis (AP). Studies were performed on male Wistar rats or isolated pancreatic acinar cells. After capsaicin deactivation of sensory nerves (CDSN) or treatment with saline, rats were pretreated intraperitoneally with ghrelin or saline. In those rats, AP was induced by cerulein or pancreases were used for isolation of pancreatic acinar cells. Pancreatic acinar cells were incubated in cerulein-free or cerulein containing solution. In rats with intact SN, pretreatment with ghrelin led to a reversal of the cerulein-induced increase in pancreatic weight, plasma activity of lipase and plasma concentration of tumor necrosis factor-α (TNF-α). These effects were associated with an increase in plasma interleukin-4 concentration and reduction in histological signs of pancreatic damage. CDSN tended to increase the severity of AP and abolished the protective effect of ghrelin. Exposure of pancreatic acinar cells to cerulein led to increase in cellular expression of mRNA for TNF-α and cellular synthesis of this cytokine. Pretreatment with ghrelin reduced this alteration, but this effect was only observed in acinar cells obtained from rats with intact SN. Moreover, CDSN inhibited the cerulein- and ghrelin-induced increase in gene expression and synthesis of heat shock protein 70 (HSP70) in those cells. Ghrelin exhibits the protective effect in cerulein-induced AP on the organ and pancreatic acinar cell level. Sensory nerves ablation abolishes this effect. PMID:28665321

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

    PubMed

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

    2016-01-01

    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. 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. 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. 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. 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.

  19. 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

  20. 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

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

    PubMed

    Kita, Kahori; Otaka, Yohei; Takeda, Kotaro; Sakata, Sachiko; Ushiba, Junichi; Kondo, Kunitsugu; Liu, Meigen; Osu, Rieko

    2013-06-13

    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. 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. 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

  2. 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.

  3. Sensory chronic inflammatory demyelinating polyneuropathy: an under-recognized entity?

    PubMed

    Ayrignac, Xavier; Viala, Karine; Koutlidis, Régine Morizot; Taïeb, Guillaume; Stojkovic, Tanya; Musset, Lucille; Léger, Jean-Marc; Fournier, Emmanuel; Maisonobe, Thierry; Bouche, Pierre

    2013-11-01

    Sensory chronic inflammatory demyelinating polyneuropathy (CIDP) can be difficult to diagnose. We report 22 patients with chronic sensory polyneuropathy with ≥1 clinical sign atypical for chronic idiopathic axonal polyneuropathy (CIAP) but no electrodiagnostic criteria for CIDP. Clinical signs atypical for CIAP were: sensory ataxia (59%), generalized areflexia (36%), cranial nerve involvement (32%), rapid upper limb involvement (40%), and age at onset ≤55 years (50%). Additional features were: normal sensory nerve action potentials (36%), abnormal radial/normal sural pattern (23%), abnormal somatosensory evoked potentials (SSEPs) (100%), elevated cerebrospinal fluid (CSF) protein (73%), and demyelinating features in 5/7 nerve biopsies. Over 90% of patients responded to immunotherapy. We conclude that all patients had sensory CIDP. Sensory CIDP patients can be misdiagnosed as having CIAP. If atypical clinical/electrophysiologic features are present, we recommend performing SSEPs and CSF examination. Nerve biopsy should be restricted to disabled patients if other examinations are inconclusive. Copyright © 2013 Wiley Periodicals, Inc.

  4. Axon-Sorting Multifunctional Nerve Guides: Accelerating Restoration of Nerve Function

    DTIC Science & Technology

    2014-10-01

    factor (singly & in selected combinations) in the organotypic model system for preferential sensory or motor axon extension. Use confocal microscopy to...track axon extension of labeled sensory or motor neurons from spinal cord slices (motor) or dorsal root ganglia ( DRG ) (sensory). 20 Thy1-YFP mice...RESEARCH ACCOMPLISHMENTS: • Established a system of color-coded mixed nerve tracking using GFP and RFP expressing motor and sensory neurons (Figure 1

  5. The sensory but not muscular pelvic nerve branch is necessary for parturition in the rat.

    PubMed

    Martínez-Gómez, M; Cruz, Y; Pacheco, P; Aguilar-Roblero, R; Hudson, R

    1998-03-01

    In the rat the pelvic nerve consists of a viscerocutaneous (sensory) branch which receives information from pelvic viscera and the midline perineal region, and a somatomotor (muscular) branch which innervates the ilio- and pubococcygeous muscles. To investigate the contribution of these branches to the parturition process, the length of gestation and course of delivery were closely monitored in 43 pregnant, Wistar-strain rats randomly assigned to five groups: untreated control animals, animals in which the somatomotor branch of the pelvic nerve was bilaterally sectioned on Day 14 of gestation, animals in which the viscerocutaneous branch of the pelvic nerve was bilaterally sectioned on Day 14 of gestation, animals treated similarly to the previous group but with young delivered by C-section at term, and sham-operated controls. Sectioning the viscerocutaneous branch seriously disrupted parturition and resulted in major dystocia and a high percentage of stillbirths in all females. In contrast, sectioning the somatomotor branch had no apparent effect on parturition and no significant differences were found between females of this group and sham or control dams on any of the measures recorded. It is concluded that the viscerocutaneous branch of the pelvic nerve is vital for the normal course of parturition in the rat but that the somatomotor branch plays little role, if any.

  6. [Peripheral nerve repair: 30 centuries of scientific research].

    PubMed

    Desouches, C; Alluin, O; Mutaftschiev, N; Dousset, E; Magalon, G; Boucraut, J; Feron, F; Decherchi, P

    2005-11-01

    Nerve injury compromises sensory and motor functions. Techniques of peripheral nerve repair are based on our knowledge regarding regeneration. Microsurgical techniques introduced in the late 1950s and widely developed for the past 20 years have improved repairs. However, functional recovery following a peripheral mixed nerve injury is still incomplete. Good motor and sensory function after nerve injury depends on the reinnervation of the motor end plates and sensory receptors. Nerve regeneration does not begin if the cell body has not survived the initial injury or if it is unable to initiate regeneration. The regenerated axons must reach and reinnervate the appropriate target end-organs in a timely fashion. Recovery of motor function requires a critical number of motor axons reinnervating the muscle fibers. Sensory recovery is possible if the delay in reinnervation is short. Many additional factors influence the success of nerve repair or reconstruction. The timing of the repair, the level of injury, the extent of the zone of injury, the technical skill of the surgeon, and the method of repair and reconstruction contribute to the functional outcome after nerve injury. This review presents the recent advances in understanding of neural regeneration and their application to the management of primary repairs and nerve gaps.

  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. Role of sensory C fibers in hypoxia/ reoxygenation-impaired myogenic constriction of cerebral arteries

    PubMed Central

    Xie, Hui; Ray, Patricio E.; Short, Billie Lou

    2009-01-01

    Objective Hypoxia/reoxygenation (H/R) associated with extracorporeal membrane oxygenation disrupts cerebral autoregulation. However, the underlying mechanisms remain poorly understood. The present study was designed to investigate the role of sensory C-fibers in myogenic responsiveness of cerebral arteries. Methods Arterial diameter and intraluminal pressure were simultaneously measured in vitro on rat posterior cerebral arteries. Results Cerebral arteries constricted in response to graded increase in intraluminal pressure (20–100 mmHg, in 20 mmHg increments). In vitro C-fiber desensitization with capsaicin (1 μmol/l, 20 minutes) significantly suppressed myogenic constriction by over 50%, but did not affect 5-hydroxytryptamine (0.01–10 μmol/l) and KCl (120 mmol/l)-induced constriction. Capsazepine (5 μmol/l, 30 minutes), a selective blocker of neuronal vanilloid receptor TRPV1, had similar inhibitory effect on cerebral myogenic constriction to elevated pressure. Cerebral myogenic constriction was significantly attenuated by H/R; the impairment by H/R was further enhanced after C-fiber desensitization (except at a pressure level of 100 mmHg). Discussion These findings indicate that C-fiber activity contributes to myogenic constriction of cerebral arteries under normal and H/R conditions. H/R-impaired myogenic responsiveness is exaggerated by C-fiber dysfunction. These results raise the possibility that therapeutic strategies directed toward preserving C-fiber nerve endings or supplying its constituent neuropeptides could be developed. PMID:19570322

  9. Anterograde transneuronal viral tract tracing reveals central sensory circuits from brown fat and sensory denervation alters its thermogenic responses.

    PubMed

    Vaughan, Cheryl H; Bartness, Timothy J

    2012-05-01

    Brown adipose tissue (BAT) thermogenic activity and growth are controlled by its sympathetic nervous system (SNS) innervation, but nerve fibers containing sensory-associated neuropeptides [substance P, calcitonin gene-related peptide (CGRP)] also suggest sensory innervation. The central nervous system (CNS) projections of BAT afferents are unknown. Therefore, we used the H129 strain of the herpes simplex virus-1 (HSV-1), an anterograde transneuronal viral tract tracer used to delineate sensory nerve circuits, to define these projections. HSV-1 was injected into interscapular BAT (IBAT) of Siberian hamsters and HSV-1 immunoreactivity (ir) was assessed 24, 48, 72, 96, and 114 h postinjection. The 96- and 114-h groups had the most HSV-1-ir neurons with marked infections in the hypothalamic paraventricular nucleus, periaqueductal gray, olivary areas, parabrachial nuclei, raphe nuclei, and reticular areas. These sites also are involved in sympathetic outflow to BAT suggesting possible BAT sensory-SNS thermogenesis feedback circuits. We tested the functional contribution of IBAT sensory innervation on thermogenic responses to an acute (24 h) cold exposure test by injecting the specific sensory nerve toxin capsaicin directly into IBAT pads and then measuring core (T(c)) and IBAT (T(IBAT)) temperature responses. CGRP content was significantly decreased in capsaicin-treated IBAT demonstrating successful sensory nerve destruction. T(IBAT) and T(c) were significantly decreased in capsaicin-treated hamsters compared with the saline controls at 2 h of cold exposure. Thus the central sensory circuits from IBAT have been delineated for the first time, and impairment of sensory feedback from BAT appears necessary for the appropriate, initial thermogenic response to acute cold exposure.

  10. Desensitization to rituximab in a multidisciplinary setting.

    PubMed

    Amorós-Reboredo, Patrícia; Sánchez-López, Jaime; Bastida-Fernández, Carla; do Pazo-Oubiña, Fernando; Borràs-Maixenchs, Núria; Giné, Eva; Valero, Antonio; Creus-Baró, Natàlia

    2015-10-01

    The need to offer first-line therapy to the increasing number of patients who have suffered an hypersensitivity reaction has stimulated the use of rapid desensitization protocols. To present our experience working as a multidisciplinary team using a rituximab rapid desensitization scheme. Patient demographics, allergic reaction, skin tests to rituximab, number of desensitizations, reactions during the desensitization protocol and actions taken, number of administered and completed cycles, were retrospectively collected in patients who received at least one desensitization to rituximab. Number of desensitizations successfully managed. Between 2012 and June 2013 five patients received a total of 19 desensitizations to rituximab using a 12 step rapid desensitization protocol. All patients received the scheduled chemotherapeutic cycles as inpatients, with no delay in administration dates. Three patients presented a hypersensitivity reaction during the first desensitization and in one patient the event occurred again during the second treatment cycle. All reactions occurred in the last step, when the infusion rate reached the maximum speed. The developed protocol for rapid desensitization was successful in five patients receiving rituximab. Patients could receive the full intended dose.

  11. 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)

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

    PubMed Central

    Walsh, Michael E.; Sloane, Lauren B.; Fischer, Kathleen E.; Austad, Steven N.; Richardson, Arlan

    2015-01-01

    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

  13. Evaluation of pediatric upper extremity peripheral nerve injuries.

    PubMed

    Ho, Emily S

    2015-01-01

    The evaluation of motor and sensory function of the upper extremity after a peripheral nerve injury is critical to diagnose the location and extent of nerve injury as well as document functional recovery in children. The purpose of this paper is to describe an approach to the evaluation of the pediatric upper extremity peripheral nerve injuries through a critical review of currently used tests of sensory and motor function. Outcome studies on pediatric upper extremity peripheral nerve injuries in the Medline database were reviewed. The evaluation of the outcome in children less than 10 years of age with an upper extremity peripheral nerve injury includes careful observation of preferred prehension patterns, examination of muscle atrophy and sudomotor function, provocative tests, manual muscle testing and tests of sensory threshold and tactile gnosis. The evaluation of outcome in children with upper extremity peripheral nerve injuries warrants a unique approach. Copyright © 2015 Hanley & Belfus. Published by Elsevier Inc. All rights reserved.

  14. N-cadherin expression in palisade nerve endings of rat vellus hairs.

    PubMed

    Kaidoh, Toshiyuki; Inoué, Takao

    2008-02-01

    Palisade nerve endings (PNs) are mechanoreceptors around vellus hairs of mammals. Each lanceolate nerve ending (LN) of the PN is characterized by a sensory nerve ending symmetrically sandwiched by two processes of type II terminal Schwann cells (tSCIIs). However, the molecular mechanisms underlying the structural organization of the PN are poorly understood. Electron microscopy showed that adherens junctions appeared to adhere to the sensory nerve ending and tSCII processes, so we examined the location of the N-cadherin adhesion system in PNs of rat vellus hairs by using immunoelectron microscopy. N-cadherin localized near both ends of the cell boundary between sensory nerve ending and tSCII processes, which corresponded to the sites of adherens junctions. We further found cadherin-associated proteins, alpha- and beta-catenins, at the linings of adherens junctions. Three-dimensional reconstruction of immunoelectron microscopic serial thin sections showed four linear arrays of N-cadherin arranged longitudinally along the LN beneath the four longitudinal borders of two tSCII processes. In contrast, sensory nerve fibers just proximal to the LNs formed common unmyelinated nerve fibers, in which N-cadherin was located mainly at the mesaxon of type I terminal Schwann cells (tSCIs). These results suggest that the four linear arrays of N-cadherin-mediated junctions adhere the sensory nerve ending and tSCII processes side by side to form the characteristic structure of the LN, and the structural differences between the LNs and the proximal unmyelinated nerve fibers possibly are due to the difference in the pattern of N-cadherin expression between sensory nerve endings and tSCII or tSCI processes. (c) 2007 Wiley-Liss, Inc.

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

    PubMed Central

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

    2011-01-01

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

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

    PubMed

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

    2010-12-15

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

  17. 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…

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

    PubMed

    Jääskeläinen, Satu K

    2004-01-01

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

  19. Use of sensory and motor action potentials to identify the position of trigeminal nerve divisions for radiofrequency thermocoagulation.

    PubMed

    Lin, Bo; Lu, Xuguang; Zhai, Xinli; Cai, Zhigang

    2014-12-01

    The objective of this study was to develop an electrophysiological method for intraoperative localization of the trigeminal nerve branches during radiofrequency thermocoagulation (RFTC). Twenty-three patients who were scheduled to undergo RFTC were included. The trigeminal nerve root was stimulated through the foramen ovale using the radiofrequency cannula. Antidromic responses were recorded from the target division through supraorbital, infraorbital, and mental foramina electrodes, and an additional electrode at the masseter muscle. Sensory and motor action responses, as well as verbal and masseter contraction responses, were recorded and correlated. The antidromic responses were easily recorded in the target division in all 23 patients, and they were invariably correlated with the patient's verbal responses. The potentials were recorded successively from V1 to V3. The amplitude in each division before and after RFTC showed little difference in response to electrical stimulation with the same current. The motor trigeminal nerve action potentials were recorded in 10 patients; 7 of these patients had postoperative masseter muscle weakness, while the remaining 3 had normal masseter muscle function. Potentials with low amplitudes were usually obtained from neighboring divisions, but no unexpected denervation of any branches was observed. All the patients experienced immediate pain relief after the procedure. This technique is sensitive and easy to apply. The sensory and motor potentials matched the verbal responses and the complications. Although it cannot completely substitute for the patient's verbal response, this approach is helpful in uncooperative patients, and it predicts and reduces the incidence of masseter muscle weakness. The use of these complementary techniques could increase the chances of treatment success.

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

    DOE Office of Scientific and Technical Information (OSTI.GOV)

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

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

  1. Inflammation and nerve injury induce expression of pancreatitis-associated protein-II in primary sensory neurons.

    PubMed

    He, Shao-Qiu; Yao, Jun-Ru; Zhang, Fang-Xiong; Wang, Qiong; Bao, Lan; Zhang, Xu

    2010-04-26

    Pancreatitis-associated protein (PAP)-I and -II, lectin-related secretory proteins, are members of the regenerating gene (Reg) family. Although expression of PAP-I was found in the dorsal root ganglion (DRG) neurons following peripheral nerve injury and cystitis, whether PAP-II could be expressed in DRG neurons in chronic pain models remains unclear. The present study shows an inflammation- and nerve injury-triggered expression of PAP-II in rat DRG neurons. In situ hybridization showed that only a few DRG neurons normally contained PAP-I and -II mRNAs. After peripheral inflammation, PAP-I and -II mRNAs were present in over half of small DRG neurons. Such an elevated expression of PAP-I and -II reached the peak level on the second day. Immunostaining showed that the expression of PAP-II was mostly increased in the isolectin B4-positive subset of small DRG neurons after inflammation. Furthermore, the expression of PAP-II was also induced in DRG neurons after peripheral nerve injury. Interestingly, PAP-II expression was shifted from small neurons on day 2 to large DRG neurons that expressed neuropeptide Y during the later post-injury days. These results suggest that PAP-II may play potential roles in the modulation of spinal sensory pathways in pathological pain states.

  2. The Changing Sensory and Sympathetic Innervation of the Young, Adult and Aging Mouse Femur.

    PubMed

    Chartier, Stephane R; Mitchell, Stefanie A T; Majuta, Lisa A; Mantyh, Patrick W

    2018-02-10

    Although bone is continually being remodeled and ultimately declines with aging, little is known whether similar changes occur in the sensory and sympathetic nerve fibers that innervate bone. Here, immunohistochemistry and confocal microscopy were used to examine changes in the sensory and sympathetic nerve fibers that innervate the young (10 days post-partum), adult (3 months) and aging (24 months) C57Bl/6 mouse femur. In all three ages examined, the periosteum was the most densely innervated bone compartment. With aging, the total number of sensory and sympathetic nerve fibers clearly declines as the cambium layer of the periosteum dramatically thins. Yet even in the aging femur, there remains a dense sensory and sympathetic innervation of the periosteum. In cortical bone, sensory and sympathetic nerve fibers are largely confined to vascularized Haversian canals and while there is no significant decline in the density of sensory fibers, there was a 75% reduction in sympathetic nerve fibers in the aging vs. adult cortical bone. In contrast, in the bone marrow the overall density/unit area of both sensory and sympathetic nerve fibers appeared to remain largely unchanged across the lifespan. The preferential preservation of sensory nerve fibers suggests that even as bone itself undergoes a marked decline with age, the nociceptors that detect injury and signal skeletal pain remain relatively intact. Copyright © 2018 The Author(s). Published by Elsevier Ltd.. All rights reserved.

  3. 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. © 2013 Wiley Periodicals, Inc.

  4. Which Ultrasound-Guided Sciatic Nerve Block Strategy Works Faster? Prebifurcation or Separate Tibial-Peroneal Nerve Block? A Randomized Clinical Trial.

    PubMed

    Faiz, Seyed Hamid Reza; Imani, Farnad; Rahimzadeh, Poupak; Alebouyeh, Mahmoud Reza; Entezary, Saeed Reza; Shafeinia, Amineh

    2017-08-01

    Peripheral nerve block is an accepted method in lower limb surgeries regarding its convenience and good tolerance by the patients. Quick performance and fast sensory and motor block are highly demanded in this method. The aim of the present study was to compare 2 different methods of sciatic and tibial-peroneal nerve block in lower limb surgeries in terms of block onset. In this clinical trial, 52 candidates for elective lower limb surgery were randomly divided into 2 groups: sciatic nerve block before bifurcation (SG; n = 27) and separate tibial-peroneal nerve block (TPG; n = 25) under ultrasound plus nerve stimulator guidance. The mean duration of block performance, as well as complete sensory and motor block, was recorded and compared between the groups. The mean duration of complete sensory block in the SG and TPG groups was 35.4 ± 4.1 and 24.9 ± 4.2 minutes, respectively, which was significantly lower in the TPG group (P = 0.001). The mean duration of complete motor block in the SG and TPG groups was 63.3 ± 4.4 and 48.4 ± 4.6 minutes, respectively, which was significantly lower in the TPG group (P = 0.001). No nerve injuries, paresthesia, or other possible side effects were reported in patients. According to the present study, it seems that TPG shows a faster sensory and motor block than SG.

  5. From genes to pain: nerve growth factor and hereditary sensory and autonomic neuropathy type V.

    PubMed

    Capsoni, Simona

    2014-02-01

    Hereditary sensory and autonomic neuropathy type V (HSAN V) is an autosomal recessive disorder characterized by the loss of deep pain perception. The anomalous pain and temperature sensations are due to the absence of nociceptive sensory innervation. The neurotrophin nerve growth factor (NGF), by binding to tropomyosin receptor A (TrkA) and p75NTR receptors, is essential for the development and survival of sensory neurons, and for pain perception during adulthood. Recently a homozygous missense mutation (R100W) in the NGF gene has been identified in HSAN V patients. Interestingly, alterations in NGF signalling, due to mutations in the NGF TRKA gene, have also been involved in another congenital insensitivity to pain, HSAN IV, characterized not only by absence of reaction to painful stimuli, but also anhidrosis and mental retardation. These symptoms are absent in HSAN V patients. Unravelling the mechanisms that underlie the differences between HSAN IV and V could assist in better understanding NGF biology. This review highlights the recent key findings in the understanding of HSAN V, including insights into the molecular mechanisms of the disease, derived from genetic studies of patients with this disorder. © 2014 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

  6. Chronic inflammatory pure sensory polyradiculoneuropathy: a rare CIDP variant with unusual electrophysiology.

    PubMed

    Rajabally, Yusuf A; Wong, Siew L

    2012-03-01

    We describe a patient presenting with progressive upper limb numbness and sensory ataxia of the 4 limbs. Motor nerve conduction studies were completely normal. Sensory electrophysiology showed reduced/absent upper limb sensory action potentials (SAPs). In the lower limbs, SAPs were mostly normal. Sensory conduction velocities were normal. Forearm sensory conduction blocks were present for both median nerves on antidromic testing. The maximal recordable sural SAP was preserved in comparison to maximal recordable radial SAP, consistent with an "abnormal radial normal sural" pattern. Somatosensory evoked potentials were unrecordable for tibial and median nerves. Cerebrospinal fluid protein was raised (0.99 g/L). The patient worsened on oral corticosteroids but subsequently made substantial functional recovery on intravenous immunoglobulins. This case is different to those previously reported of sensory chronic inflammatory demyelinating polyradiculoneuropathy, given its exclusive sensory electrophysiologic presentation, presence of predominant upper limb reduced sensory amplitudes, and detection of sensory conduction blocks. These electrophysiologic features were of paramount importance in establishing diagnosis and effective therapy.

  7. Effectiveness of oxaliplatin desensitization protocols.

    PubMed

    Cortijo-Cascajares, Susana; Nacle-López, Inmaculada; García-Escobar, Ignacio; Aguilella-Vizcaíno, María José; Herreros-de-Tejada, Alberto; Cortés-Funes Castro, Hernán; Calleja-Hernández, Miguel-Ángel

    2013-03-01

    Hypersensitivity reaction (HSR) to antineoplastic drugs can force doctors to stop treatment and seek other alternatives. These alternatives may be less effective, not as well tolerated and/or more expensive. Another option is to use desensitization protocols that induce a temporary state of tolerance by gradually administering small quantities of the antineoplastic drug until the therapeutic dosage is reached. The aim of this study is to assess the effectiveness of oxaliplatin desensitization protocols. A retrospective observational study was carried out between January 2006 and May 2011. The inclusion criteria were patients undergoing chemotherapy treatment with oxaliplatin who had developed an HSR to the drug and who were candidates for continuing the treatment using a desensitization protocol. The patients' clinical records were reviewed and variables were gathered relating to the patient, the treatment, the HSR, and the desensitization protocol administered. The data were analysed using version 18.0 of the statistics program SPSS. A total of 53 desensitization protocols were administered to 21 patients. In 89 % of these cases, no new reactions occurred while the drug was being administered. New reactions of mild severity only occurred in 11 % of cases, and none of these reactions were severe enough for treatment to be stopped. All patients were able to complete the desensitization protocol. This study confirms that oxaliplatin desensitization protocols are safe and effective and allow patients to continue with the treatment that initially caused an HSR.

  8. Effects of omega-conotoxin GVIA on the activation of capsaicin-sensitive afferent sensory nerves in guinea pig airway tissues.

    PubMed

    Morimoto, H; Matsuda, A; Ohori, M; Fujii, T

    1996-06-01

    We examined the effects of Ca2+ channel antagonists on various respiratory reactions induced by the activation of capsaicin-sensitive afferent sensory nerves. Intravenous (i.v.) injection of the N-type Ca2+ channel antagonist omega-conotoxin GVIA (CgTX) (1-20 micrograms/kg) dose-dependently inhibited capsaicin-induced guinea pig bronchoconstriction, whereas i.v. administration of the L-type antagonist nicardipine (100 micrograms/kg), the P-type antagonist omega-agatoxin IVA (AgaTX) (20 micrograms/kg) or the OPQ family-type antagonist omega-conotoxin MVIIC (CmTX) (20 micrograms/kg) had no effect. However, CgTX (20 micrograms/kg) failed to inhibit substance P-induced guinea pig bronchoconstriction. CgTX (20 micrograms/kg) significantly inhibited cigarette smoke-induced guinea pig tracheal plasma extravasation, but not the substance P-induced reaction. CgTX also reduced electrical field stimulation-induced guinea pig bronchial smooth muscle contraction (0.01-10 microM) and capsaicin-induced substance P-like immunoreactivity release from guinea pig lung (0.14 microM). This evidence suggests that N-type Ca2+ channels modulate tachykinin release from capsaicin-sensitive afferent sensory nerve endings in guinea pig airway tissue.

  9. Chronic Morphine Treatment Reduces Recovery from Opioid Desensitization

    PubMed Central

    Dang, Vu C.; Williams, John T.

    2013-01-01

    Tolerance and dependence result from long-term exposure to opioids, and there is growing evidence linking acute receptor desensitization to these more long-term processes. Receptor desensitization encompasses a series of events leading to the loss of receptor function and internalization. This study examines the onset and recovery from desensitization in locus ceruleus neurons recorded in brain slices taken from animals that have been chronically treated with morphine. After chronic morphine treatment, desensitization was altered as follows. First, the rate of desensitization was increased. Second, recovery from desensitization was always incomplete, even after a brief (1–2 min) exposure to agonist. This contrasts with experiments in controls in which recovery from desensitization, after a brief exposure to agonist, was complete within 25 min. Finally, morphine-6-β-D-glucuronide, a metabolite of morphine that was ineffective at causing desensitization in controls, induced significant desensitization in slices from morphine-treated animals. When brain slices from controls were treated with inhibitors of PKC or monensin, agents known to compromise G-protein-coupled receptor resensitization, desensitization was increased, and recovery was significantly reduced. These results indicate that receptor resensitization maintains signaling during periods of intense and sustained stimulation. After chronic morphine treatment, desensitization is potentiated, and receptor resensitization is compromised. PMID:15342737

  10. Chronic morphine treatment reduces recovery from opioid desensitization.

    PubMed

    Dang, Vu C; Williams, John T

    2004-09-01

    Tolerance and dependence result from long-term exposure to opioids, and there is growing evidence linking acute receptor desensitization to these more long-term processes. Receptor desensitization encompasses a series of events leading to the loss of receptor function and internalization. This study examines the onset and recovery from desensitization in locus ceruleus neurons recorded in brain slices taken from animals that have been chronically treated with morphine. After chronic morphine treatment, desensitization was altered as follows. First, the rate of desensitization was increased. Second, recovery from desensitization was always incomplete, even after a brief (1-2 min) exposure to agonist. This contrasts with experiments in controls in which recovery from desensitization, after a brief exposure to agonist, was complete within 25 min. Finally, morphine-6-beta-D-glucuronide, a metabolite of morphine that was ineffective at causing desensitization in controls, induced significant desensitization in slices from morphine-treated animals. When brain slices from controls were treated with inhibitors of PKC or monensin, agents known to compromise G-protein-coupled receptor resensitization, desensitization was increased, and recovery was significantly reduced. These results indicate that receptor resensitization maintains signaling during periods of intense and sustained stimulation. After chronic morphine treatment, desensitization is potentiated, and receptor resensitization is compromised.

  11. Nerve ultrasound shows subclinical peripheral nerve involvement in neurofibromatosis type 2.

    PubMed

    Telleman, Johan A; Stellingwerff, Menno D; Brekelmans, Geert J; Visser, Leo H

    2018-02-01

    Neurofibromatosis type 2 (NF2) is mainly associated with central nervous system (CNS) tumors. Peripheral nerve involvement is described in symptomatic patients, but evidence of subclinical peripheral nerve involvement is scarce. We conducted a cross-sectional pilot study in 2 asymptomatic and 3 minimally symptomatic patients with NF2 to detect subclinical peripheral nerve involvement. Patients underwent clinical examination, nerve conduction studies (NCS), and high-resolution ultrasonography (HRUS). A total of 30 schwannomas were found, divided over 20 nerve segments (33.9% of all investigated nerve segments). All patients had at least 1 schwannoma. Schwannomas were identified with HRUS in 37% of clinically unaffected nerve segments and 50% of nerve segments with normal NCS findings. HRUS shows frequent subclinical peripheral nerve involvement in NF2. Clinicians should consider peripheral nerve involvement as a cause of weakness and sensory loss in the extremities in patients with this disease. Muscle Nerve 57: 312-316, 2018. © 2017 Wiley Periodicals, Inc.

  12. Electrophysiology of Cranial Nerve Testing: Cranial Nerves IX and X.

    PubMed

    Martinez, Alberto R M; Martins, Melina P; Moreira, Ana Lucila; Martins, Carlos R; Kimaid, Paulo A T; França, Marcondes C

    2018-01-01

    The cranial nerves IX and X emerge from medulla oblongata and have motor, sensory, and parasympathetic functions. Some of these are amenable to neurophysiological assessment. It is often hard to separate the individual contribution of each nerve; in fact, some of the techniques are indeed a composite functional measure of both nerves. The main methods are the evaluation of the swallowing function (combined IX and X), laryngeal electromyogram (predominant motor vagal function), and heart rate variability (predominant parasympathetic vagal function). This review describes, therefore, the techniques that best evaluate the major symptoms presented in IX and X cranial nerve disturbance: dysphagia, dysphonia, and autonomic parasympathetic dysfunction.

  13. Chronic adriamycin treatment impairs CGRP-mediated functions of meningeal sensory nerves.

    PubMed

    Deák, Éva; Rosta, Judit; Boros, Krisztina; Kis, Gyöngyi; Sántha, Péter; Messlinger, Karl; Jancsó, Gábor; Dux, Mária

    2018-06-01

    Adriamycin is a potent anthracycline-type antitumor agent, but it also exerts potentially serious side effects due to its cardiotoxic and neurotoxic propensity. Multiple impairments in sensory nerve functions have been recently reported in various rat models. The present experiments were initiated in an attempt to reveal adriamycin-induced changes in sensory effector functions of chemosensitive meningeal afferents. Meningeal blood flow was measured with laser Doppler flowmetry in the parietal dura mater of adult male Wistar rats. The dura mater was repeatedly stimulated by topical applications of capsaicin, a transient receptor potential vanilloid 1 (TRPV1) receptor agonist, or acrolein, a transient receptor potential ankyrin 1 (TRPA1) receptor agonist, which induce the release of calcitonin gene-related peptide (CGRP) from meningeal afferents. The blood flow increasing effects of CGRP, histamine, acetylcholine and forskolin were also measured. Capsaicin- and acrolein-induced CGRP release was measured with enzyme-linked immunoassay in an ex vivo dura mater preparation. TRPV1 content of trigeminal ganglia and TRPV1-, CGRP- and CGRP receptor component-immunoreactive structures were examined in dura mater samples obtained from control and adriamycin-treated rats. The vasodilator effects of capsaicin, acrolein and CGRP were significantly reduced in adriamycin-treated animals while histamine-, acetylcholine- and forskolin-induced vasodilatation were unaffected. Measurements of CGRP release in an ex vivo dura mater preparation revealed an altered dynamic upon repeated stimulations of TRPV1 and TRPA1 receptors. In whole-mount dura mater preparations immunohistochemistry revealed altered CGRP receptor component protein (RCP)-immunoreactivity in adriamycin-treated animals, while CGRP receptor activity modifying protein (RAMP1)-, TRPV1- and CGRP-immunostaining were left apparently unaltered. Adriamycin-treatment slightly reduced TRPV1 protein content of trigeminal ganglia

  14. Antibiotic Desensitization Therapy in Secondary Syphilis and Listeria Infection: Case Reports and Review of Desensitization Therapy

    PubMed Central

    Magpantay, Gil; Madar, Cristian S; Hsue, Gunther; Belnap, Conrad

    2011-01-01

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

  15. Muscle Activation During Peripheral Nerve Field Stimulation Occurs Due to Recruitment of Efferent Nerve Fibers, Not Direct Muscle Activation.

    PubMed

    Frahm, Ken Steffen; Hennings, Kristian; Vera-Portocarrero, Louis; Wacnik, Paul W; Mørch, Carsten Dahl

    2016-08-01

    Peripheral nerve field stimulation (PNFS) is a potential treatment for chronic low-back pain. Pain relief using PNFS is dependent on activation of non-nociceptive Aβ-fibers. However, PNFS may also activate muscles, causing twitches and discomfort. In this study, we developed a mathematical model, to investigate the activation of sensory and motor nerves, as well as direct muscle fiber activation. The extracellular field was estimated using a finite element model based on the geometry of CT scanned lumbar vertebrae. The electrode was modeled as being implanted to a depth of 10-15 mm. Three implant directions were modeled; horizontally, vertically, and diagonally. Both single electrode and "between-lead" stimulation between contralateral electrodes were modeled. The extracellular field was combined with models of sensory Aβ-nerves, motor neurons and muscle fibers to estimate their activation thresholds. The model showed that sensory Aβ fibers could be activated with thresholds down to 0.563 V, and the lowest threshold for motor nerve activation was 7.19 V using between-lead stimulation with the cathode located closest to the nerves. All thresholds for direct muscle activation were above 500 V. The results suggest that direct muscle activation does not occur during PNFS, and concomitant motor and sensory nerve fiber activation are only likely to occur when using between-lead configuration. Thus, it may be relevant to investigate the location of the innervation zone of the low-back muscles prior to electrode implantation to avoid muscle activation. © 2016 International Neuromodulation Society.

  16. Retrograde tracing and toe spreading after experimental autologous nerve transplantation and crush injury of the sciatic nerve: a descriptive methodological study.

    PubMed

    van Neerven, Sabien Ga; Bozkurt, Ahmet; O'Dey, Dan Mon; Scheffel, Juliane; Boecker, Arne H; Stromps, Jan-Philipp; Dunda, Sebastian; Brook, Gary A; Pallua, Norbert

    2012-04-30

    Evaluation of functional and structural recovery after peripheral nerve injury is crucial to determine the therapeutic effect of a nerve repair strategy. In the present study, we examined the relationship between the structural evaluation of regeneration by means of retrograde tracing and the functional analysis of toe spreading. Two standardized rat sciatic nerve injury models were used to address this relationship. As such, animals received either a 2 cm sciatic nerve defect (neurotmesis) followed by autologous nerve transplantation (ANT animals) or a crush injury with spontaneous recovery (axonotmesis; CI animals). Functional recovery of toe spreading was observed over an observation period of 84 days. In contrast to CI animals, ANT animals did not reach pre-surgical levels of toe spreading. After the observation period, the lipophilic dye DiI was applied to label sensory and motor neurons in dorsal root ganglia (DRG; sensory neurons) and spinal cord (motor neurons), respectively. No statistical difference in motor or sensory neuron counts could be detected between ANT and CI animals.In the present study we could indicate that there was no direct relationship between functional recovery (toe spreading) measured by SSI and the number of labelled (motor and sensory) neurons evaluated by retrograde tracing. The present findings demonstrate that a multimodal approach with a variety of independent evaluation tools is essential to understand and estimate the therapeutic benefit of a nerve repair strategy.

  17. Early postnatal development of electrophysiological and histological properties of sensory sural nerves in male rats that were maternally deprived and artificially reared: Role of tactile stimulation.

    PubMed

    Zempoalteca, Rene; Porras, Mercedes G; Moreno-Pérez, Suelem; Ramirez-Funez, Gabriela; Aguirre-Benítez, Elsa L; González Del Pliego, Margarita; Mariscal-Tovar, Silvia; Mendoza-Garrido, Maria E; Hoffman, Kurt Leroy; Jiménez-Estrada, Ismael; Melo, Angel I

    2018-04-01

    Early adverse experiences disrupt brain development and behavior, but little is known about how such experiences impact on the development of the peripheral nervous system. Recently, we found alterations in the electrophysiological and histological characteristics of the sensory sural (SU) nerve in maternally deprived, artificially reared (AR) adult male rats, as compared with maternally reared (MR) control rats. In the present study, our aim was to characterize the ontogeny of these alterations. Thus, male pups of four postnatal days (PND) were (1) AR group, (2) AR and received daily tactile stimulation to the body and anogenital region (AR-Tactile group); or (3) reared by their mother (MR group). At PND 7, 14, or 21, electrophysiological properties and histological characteristics of the SU nerves were assessed. At PND 7, the electrophysiological properties and most histological parameters of the SU nerve did not differ among MR, AR, and AR-Tactile groups. By contrast, at PND 14 and/or 21, the SU nerve of AR rats showed a lower CAP amplitude and area, and a significant reduction in myelin area and myelin thickness, which were accompanied by a reduction in axon area (day 21 only) compared to the nerves of MR rats. Tactile stimulation (AR-Tactile group) partially prevented most of these alterations. These results suggest that sensory cues from the mother and/or littermates during the first 7-14 PND are relevant for the proper development and function of the adult SU nerve. © 2017 Wiley Periodicals, Inc. Develop Neurobiol 78: 351-362, 2018. © 2017 Wiley Periodicals, Inc.

  18. Raman spectroscopic detection of peripheral nerves towards nerve-sparing surgery

    NASA Astrophysics Data System (ADS)

    Minamikawa, Takeo; Harada, Yoshinori; Takamatsu, Tetsuro

    2017-02-01

    The peripheral nervous system plays an important role in motility, sensory, and autonomic functions of the human body. Preservation of peripheral nerves in surgery, namely nerve-sparing surgery, is now promising technique to avoid functional deficits of the limbs and organs following surgery as an aspect of the improvement of quality of life of patients. Detection of peripheral nerves including myelinated and unmyelinated nerves is required for the nerve-sparing surgery; however, conventional nerve identification scheme is sometimes difficult to identify peripheral nerves due to similarity of shape and color to non-nerve tissues or its limited application to only motor peripheral nerves. To overcome these issues, we proposed a label-free detection technique of peripheral nerves by means of Raman spectroscopy. We found several fingerprints of peripheral myelinated and unmyelinated nerves by employing a modified principal component analysis of typical spectra including myelinated nerve, unmyelinated nerve, and adjacent tissues. We finally realized the sensitivity of 94.2% and the selectivity of 92.0% for peripheral nerves including myelinated and unmyelinated nerves against adjacent tissues. Although further development of an intraoperative Raman spectroscopy system is required for clinical use, our proposed approach will serve as a unique and powerful tool for peripheral nerve detection for nerve-sparing surgery in the future.

  19. Selectivity and Longevity of Peripheral-Nerve and Machine Interfaces: A Review

    PubMed Central

    Ghafoor, Usman; Kim, Sohee; Hong, Keum-Shik

    2017-01-01

    For those individuals with upper-extremity amputation, a daily normal living activity is no longer possible or it requires additional effort and time. With the aim of restoring their sensory and motor functions, theoretical and technological investigations have been carried out in the field of neuroprosthetic systems. For transmission of sensory feedback, several interfacing modalities including indirect (non-invasive), direct-to-peripheral-nerve (invasive), and cortical stimulation have been applied. Peripheral nerve interfaces demonstrate an edge over the cortical interfaces due to the sensitivity in attaining cortical brain signals. The peripheral nerve interfaces are highly dependent on interface designs and are required to be biocompatible with the nerves to achieve prolonged stability and longevity. Another criterion is the selection of nerves that allows minimal invasiveness and damages as well as high selectivity for a large number of nerve fascicles. In this paper, we review the nerve-machine interface modalities noted above with more focus on peripheral nerve interfaces, which are responsible for provision of sensory feedback. The invasive interfaces for recording and stimulation of electro-neurographic signals include intra-fascicular, regenerative-type interfaces that provide multiple contact channels to a group of axons inside the nerve and the extra-neural-cuff-type interfaces that enable interaction with many axons around the periphery of the nerve. Section Current Prosthetic Technology summarizes the advancements made to date in the field of neuroprosthetics toward the achievement of a bidirectional nerve-machine interface with more focus on sensory feedback. In the Discussion section, the authors propose a hybrid interface technique for achieving better selectivity and long-term stability using the available nerve interfacing techniques. PMID:29163122

  20. Microsurgical reconstruction of large nerve defects using autologous nerve grafts.

    PubMed

    Daoutis, N K; Gerostathopoulos, N E; Efstathopoulos, D G; Misitizis, D P; Bouchlis, G N; Anagnostou, S K

    1994-01-01

    Between 1986 and 1993, 643 patients with peripheral nerve trauma were treated in our clinic. Primary neurorraphy was performed in 431 of these patients and nerve grafting in 212 patients. We present the functional results after nerve grafting in 93 patients with large nerve defects who were followed for more than 2 years. Evaluation of function was based on the Medical Research Council (MRC) classification for motor and sensory recovery. Factors affecting functional outcome, such as age of the patient, denervation time, length of the defect, and level of the injury were noted. Good results according to the MRC classification were obtained in the majority of cases, although function remained less than that of the uninjured side.

  1. Aspirin Allergy Desensitization in Cerebrovascular Disease

    PubMed Central

    Zuckerman, Scott L; Seder, David B; Tsujiura, Crystiana; Cushing, Deborah; Gallup, Holly; Mocco, J; Hanel, Richard A; Ecker, Robert D

    2014-01-01

    Summary Aspirin (ASA) is the mainstay of treatment in cerebrovascular and systemic vascular disease. ASA hypersensitivity can pose a challenge to achieving optimum medical management prior to and after neurointerventional treatment. Desensitization to ASA is well described in the allergy and cardiovascular literature, but there are no similar discussions specific to neurointervention. The purpose of our study was to describe our experience with ASA hypersensitivity management and review the relevant literature. Two cases of patients with symptomatic cerebrovascular disease requiring neurointervention who were successfully desensitized to their ASA hypersensitivity prior to treatment are described. The subsequent literature is reviewed. Several ASA desensitization protocols exist and have been proven to successfully treat ASA hypersensitivity and allow for ASA therapy to be safely initiated. We describe several previously published protocols. ASA desensitization is a safe and simple way to manage ASA hypersensitivity. We provide comprehensive management guidelines for the neurointerventionalist engaging in ASA desensitization. PMID:24556294

  2. Should sensory function after median nerve injury and repair be quantified using two-point discrimination as the critical measure?

    PubMed

    Jerosch-Herold, C

    2000-12-01

    Two-point discrimination (2PD) is widely used for evaluating outcome from peripheral nerve injury and repair. It is the only quantifiable measure used in the British Medical Research Council (MRC) classification that was developed by Highet in 1954. This paper reports the results of a study of 41 patients with complete median nerve lacerations to the wrist or forearm. Two-point discrimination thresholds were assessed together with locognosia (locognosia is the ability to localise a sensory stimulus on the body's surface), tactile gnosis, and touch threshold. Using the MRC classification 29 (71%) patients had a result of S2 or below, 11 (27%) were S3, and only one scored S3+. Patients scored much better on the other tests and showed progressive recovery. It remains too difficult for patients to obtain a measurable threshold value on 2PD and the test therefore lacks responsiveness. The rating of outcome from peripheral nerve repair should not be based solely on 2PD testing and must include other tests of tactile sensibility.

  3. In Vitro Desensitization of Human Skin Mast Cells

    PubMed Central

    Zhao, Wei; Gomez, Gregorio; Macey, Matthew; Kepley, Christopher L.

    2013-01-01

    Desensitization is a clinical procedure whereby incremental doses of a drug are administered over several hours to a sensitive patient until a therapeutic dose and clinical tolerance are achieved. Clinical tolerance may occur in part by attenuating the mast cell response. In the present study, primary human skin mast cells were used to establish and characterize an in vitro model of desensitization. Mast cells in culture were armed with allergen-specific (4-hydroxy-3-nitro-phenylacety and Der p2) and non-specific IgE antibodies, and then desensitized by incremental exposures to 4-hydroxy-3-nitrophenylacety-BSA. This desensitization procedure abrogated the subsequent degranulation response to the desensitizing allergen, to an unrelated allergen, and to IgG anti-FcεRI, but not to C5a, substance P, compound 48/80, and calcium ionophore. Desensitized cells regained their FcεRI-dependent degranulation capability by 24–48 h after free allergen had been removed. Therefore, sensitized human skin mast cells are reversibly desensitized in vitro by exposure to incremental doses of that allergen, which also cross-desensitizes them to an unrelated allergen. PMID:22009002

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

    PubMed Central

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

    2017-01-01

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

  5. Desensitization in patients with beta-lactam drug allergy.

    PubMed

    Yusin, J S; Klaustermeyer, W; Simmons, C W; Baum, M

    2013-01-01

    Patients with a history of beta-lactam antibiotic allergy are often admitted to the hospital with severe or life-threatening infections requiring beta-lactam antibiotics. Strict avoidance of beta lactams to such patients may prevent them from getting adequate coverage and can lead to an increase in the use of alternative antibiotics, which can predispose to antibiotic resistance. Past studies revealed a lower incidence of pen allergy then patients' histories suggest. Fortunately today, there are three options for patients presenting with a history of beta-lactam allergy. Penicillin skin testing, beta-lactam challenge or beta-lactam desensitization. Recently Pre Pen has been FDA re-approved and when combined with Pen G is a valid way to determine if patients are able to tolerate beta-lactam antibiotic. When these agents are not available one must decide about desensitization or challenge. When a patient has a positive penicillin skin test, desensitization or beta-lactam avoidance are the only options. This paper reviews the safety of beta-lactam desensitization. To perform a chart review on patients desensitised with beta lactam to determine if desensitizations can be performed safely without minimal complications. A retrospective chart review was performed on allergy and immunology inpatient consultations for beta-lactam desensitization between September 2003 and August 2006 at the Cedars-Sinai Medical Centre in Los Angeles. Patient data and outcomes of desensitization were analysed. A total of 13 intravenous desensitizations were performed on 12 patients. The patients consisted of eight females and four males with an average age of 65 years. Age range was 36-92 years old. All 13 intravenous desensitizations were completed without complications. No patient required a slower rate of desensitization or discontinuance of the desensitization. Patients were able to tolerate the initial therapeutic dose of their beta-lactam antibiotic and were then able to complete full

  6. Early compensatory sensory re-education.

    PubMed

    Daniele, Hugo R; Aguado, Leda

    2003-02-01

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

  7. Using humor in systematic desensitization to reduce fear.

    PubMed

    Ventis, W L; Higbee, G; Murdock, S A

    2001-04-01

    Effectiveness of systematic desensitization for fear reduction, using humorous hierarchy scenes without relaxation, was tested. Participants were 40 students highly fearful of spiders. Using a 24-item behavioral approach test with an American tarantula, participants were matched on fear level and randomly assigned to 1 of 3 treatment groups: (a) systematic desensitization, (b) humor desensitization, and (c) untreated controls. Each participant was seen for 6 sessions, including pretest and posttest. Analyses of covariance of posttest scores revealed that the 2 treatment groups showed greater reduction in fear than the controls on 3 measures but did not differ from each other. Therefore, humor in systematic desensitization reduced fear as effectively as more traditional desensitization. This finding may have therapeutic applications; however, it may also be applicable in advertising to desensitize fear of a dangerous product, such as cigarettes.

  8. [Regional nerve block in facial surgery].

    PubMed

    Gramkow, Christina; Sørensen, Jesper

    2008-02-11

    Regional nerve blocking techniques offer a suitable alternative to local infiltration anaesthesia for facial soft tissue-surgery. Moreover, they present several advantages over general anaesthesia, including smoother recovery, fewer side effects, residual analgesia into the postoperative period, earlier discharge from the recovery room and reduced costs. The branches of the trigeminal nerve and the sensory nerves originating from the upper cervical plexus can be targeted at several anatomical locations. We summarize current knowledge on facial nerve block techniques and recommend ten nerve blocks providing efficient anaesthesia for the entire head and upper-neck region.

  9. Recovery of function, peripheral sensitization and sensory neurone activation by novel pathways following axonal injury in Aplysia californica.

    PubMed

    Dulin, M F; Steffensen, I; Morris, C E; Walters, E T

    1995-10-01

    Recovery of behavioural and sensory function was examined following unilateral pedal nerve crush in Aplysia californica. Nerve crush that transected all axons connecting the tail to the central nervous system (CNS) eliminated the ipsilateral tail-evoked siphon reflex, whose sensory input travels in the crushed tail nerve (p9). The first reliable signs of recovery of this reflex were observed within 1 week, and most animals displayed tail-evoked siphon responses within 2 weeks. Wide-dynamic-range mechanosensory neurons with somata in the ventrocaudal (VC) cluster of the ipsilateral pleural ganglion exhibited a few receptive fields (RFs) on the tail 3 weeks after unilateral pedal nerve crush, indicating that the RFs had either regenerated or been reconnected to the central somata. These RFs were smaller and sensitized compared with corresponding RFs on the contralateral, uncrushed side. Centrally conducted axon responses of VC sensory neurones to electrical stimulation distal to the nerve crush site did not reappear until at least 10 days after the crush. Because the crush site was much closer to the CNS than to the tail, the failure of axon responses to be restored earlier than the behavioural responses indicates that early stages of reflex recovery are not due to regeneration of VC sensory neurone axons into the tail. Following nerve crush, VC sensory neurones often could be activated by stimulating central connectives or peripheral nerves that do not normally contain the sensory neurone's axons. These results suggest that recovery of behavioral function after nerve injury involves complex mechanisms, including regenerative growth of axotomized VC sensory neurones, sensitization of regenerating RFs and sprouting of VC sensory neurone fibres within the CNS. Furthermore, the rapidity of behavioural recovery indicates that its initial phases are mediated by additional mechanisms, perhaps centripetal regeneration of unidentified sensory neurones having peripheral

  10. 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

  11. Relaxation and Distraction in Experimental Desensitization.

    ERIC Educational Resources Information Center

    Weir, R. O.; Marshall, W. L.

    1980-01-01

    Compared experimental desensitization with a procedure that replaced relaxation with a distraction task and with an approach that combined both relaxation and distraction. Desensitization generally was more effective than the other two procedures. (Author)

  12. 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)

  13. Carboplatin hypersensitivity: evaluation and successful desensitization protocol.

    PubMed

    Bruchim, Ilan; Goldberg, Arnon; Fishman, Ami; Confino-Cohen, Ronit

    2014-01-01

    Carboplatin-induced immediate hypersensitivity reactions are relatively common among patients with gynecological malignancies. Once this occurs, the patient might be at risk for future carboplatin-induced reactions. This study evaluated the efficacy of allergic consultation, carboplatin skin testing and desensitization as a single intervention strategy in this population. Patients with a well-documented immediate reaction to carboplatin were offered allergy consultation, carboplatin skin testing and a desensitization plan in a single visit between scheduled chemotherapy sessions. Fifty-five patients with an immediate reaction were evaluated. After allergist assessment, 44 (89%) of 49 patients skin tested had a positive result. A total of 207 carboplatin desensitization cycles were administered to 49 women. Among them, 10 patients had a mild immediate hypersensitivity reaction during desensitization. Five patients subsequently tolerated carboplatin administered in the prolonged desensitization protocol. In the data presented, we propose a strategy that is both cost effective and very convenient for the patient. The diagnostic procedure, including allergist consultation and skin test, can be completed in less than 2 h. In most cases where carboplatin is indispensable, desensitization can be administered without overnight hospitalization.

  14. Depressed perivascular sensory innervation of mouse mesenteric arteries with advanced age.

    PubMed

    Boerman, Erika M; Segal, Steven S

    2016-04-15

    The dilatory role for sensory innervation of mesenteric arteries (MAs) is impaired in Old (∼24 months) versus Young (∼4 months) mice. We investigated the nature of this impairment in isolated pressurized MAs. With perivascular sensory nerve stimulation, dilatation and inhibition of sympathetic vasoconstriction observed in Young MAs were lost in Old MAs along with impaired dilatation to calcitonin gene-related peptide (CGRP). Inhibiting NO and prostaglandin synthesis increased CGRP EC50 in Young and Old MAs. Endothelial denudation attenuated dilatation to CGRP in Old MAs yet enhanced dilatation to CGRP in Young MAs while abolishing all dilatations to ACh. In Old MAs, sensory nerve density was reduced and RAMP1 (CGRP receptor component) associated with nuclear regions of endothelial cells in a manner not seen in Young MAs or in smooth muscle cells of either age. With advanced age, loss of dilatory signalling mediated through perivascular sensory nerves may compromise perfusion of visceral organs. Vascular dysfunction and sympathetic nerve activity increase with advancing age. In the gut, blood flow is governed by perivascular sensory and sympathetic nerves but little is known of how their functional role is affected by advanced age. We tested the hypothesis that functional sensory innervation of mesenteric arteries (MAs) is impaired for Old (24 months) versus Young (4 months) C57BL/6 male mice. In cannulated pressurized MAs preconstricted 50% with noradrenaline and treated with guanethidine (to inhibit sympathetic neurotransmission), perivascular nerve stimulation (PNS) evoked dilatation in Young but not Old MAs while dilatations to ACh were not different between age groups. In Young MAs, capsaicin (to inhibit sensory neurotransmission) blocked dilatation and increased constriction during PNS. With no difference in efficacy, the EC50 of CGRP as a vasodilator was ∼6-fold greater in Old versus Young MAs. Inhibiting nitric oxide (l-NAME) and prostaglandin

  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. Massive Oculomotor Nerve Enlargement: A Case of Presumed Schwannomatosis.

    PubMed

    Donaldson, Laura; Rebello, Ryan; Rodriguez, Amadeo

    2017-06-01

    A 45-year-old man presented with a slowly progressive pupil-involving third nerve palsy. Magnetic resonance imaging (MRI) revealed a tubular lesion extending from the interpeduncular cistern through the cavernous sinus and into the left orbit where it branched into a superior and an inferior division, clearly outlining the anatomy of the third cranial nerve. Multiple other, less pronounced, enlarged cranial nerves were noted. The differential diagnosis included chronic inflammatory demyelinating polyneuropathy (CIDP), hereditary motor and sensory neuropathy (HMSN), neurofibromatosis (NF), and schwannomatosis. The absence of other muscle weakness and of sensory symptoms combined with normal peripheral nerve conduction studies effectively ruled out the hypertrophic polyneuropathies and pointed to a syndromic cause of multiple benign peripheral nerve sheath tumours (PNSTs). The authors are treating this case as presumed schwannomatosis, a syndrome similar to NF2 with much lower frequency of acoustic neuromas.

  17. Endogenous Opiate System and Systematic Desensitization.

    ERIC Educational Resources Information Center

    Egan, Kelly J.; And Others

    1988-01-01

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

  18. 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.

  19. 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.

  20. The blood flow in the periodontal ligament regulated by the sympathetic and sensory nerves in the cat.

    PubMed

    Karita, K; Izumi, H; Tabata, T; Kuriwada, S; Sasano, T; Sanjo, D

    1989-01-01

    This study was carried out to investigate the nervous control of the blood flow in the periodontal ligament measured by laser Doppler flowmeter. Ten adult cats were anesthetized with pentobarbital sodium (initial dose of 30 mg/kg, i.v. and maintenance dose of 5 mg/kg, i.v.). After enucleating the left eye ball, the superior alveolar nerve was exposed. The bone overlying the labial aspect of the left maxillary canine tooth root was pared away until a transparent layer of bone was left covering the periodontal ligament. A laser light from a probe of the flowmeter fixed at the tooth was beamed through the thinned bone. Three different patterns of responses were observed following the electrical stimulation of the distal end of the cut superior alveolar nerve: an increasing, a decreasing and a biphasic change of blood flow. The application of capsaicin onto the superior alveolar nerve reduced the response of blood flow increase but had no effect on the response of blood flow decrease. On the other hand, the response of blood flow decrease was completely inhibited by the pretreatment with phentolamine while the response of blood flow increase was not affected. The present results suggest that blood flow in the periodontal ligament of cats is controlled by sympathetic alpha-adrenergic fibers for vasoconstriction and by sensory fibers for vasodilation.

  1. Sensory neuropathy in two Border collie puppies.

    PubMed

    Vermeersch, K; Van Ham, L; Braund, K G; Bhatti, S; Tshamala, M; Chiers, K; Schrauwen, E

    2005-06-01

    A peripheral sensory neuropathy was diagnosed in two Border collie puppies. Neurological, electrophysiological and histopathological examinations suggested a purely sensory neuropathy with mainly distal involvement. Urinary incontinence was observed in one of the puppies and histological examination of the vagus nerve revealed degenerative changes. An inherited disorder was suspected.

  2. Artificial sensory organs: latest progress.

    PubMed

    Nakamura, Tatsuo; Inada, Yuji; Shigeno, Keiji

    2018-03-01

    This study introduces the latest progress on the study of artificial sensory organs, with a special emphasis on the clinical results of artificial nerves and the concept of in situ tissue engineering. Peripheral nerves have a strong potential for regeneration. An artificial nerve uses this potential to recover a damaged peripheral nerve. The polyglycolic acid collagen tube (PGA-C tube) is a bio-absorbable tube stuffed with collagen of multi-chamber structure that consists of thin collagen films. The clinical application of the PGA-C tube began in 2002 in Japan. The number of PGA-C tubes used is now beyond 300, and satisfactory results have been reported on peripheral nerve repairs. This PGA-C tube is also effective for patients suffering from neuropathic pain.

  3. Agonist-Directed Desensitization of the β2-Adrenergic Receptor

    PubMed Central

    Goral, Vasiliy; Jin, Yan; Sun, Haiyan; Ferrie, Ann M.; Wu, Qi; Fang, Ye

    2011-01-01

    The β2-adrenergic receptor (β2AR) agonists with reduced tachyphylaxis may offer new therapeutic agents with improved tolerance profile. However, receptor desensitization assays are often inferred at the single signaling molecule level, thus ligand-directed desensitization is poorly understood. Here we report a label-free biosensor whole cell assay with microfluidics to determine ligand-directed desensitization of the β2AR. Together with mechanistic deconvolution using small molecule inhibitors, the receptor desensitization and resensitization patterns under the short-term agonist exposure manifested the long-acting agonism of salmeterol, and differentiated the mechanisms of agonist-directed desensitization between a full agonist epinephrine and a partial agonist pindolol. This study reveals the cellular mechanisms of agonist-selective β2AR desensitization at the whole cell level. PMID:21541288

  4. Aspirin challenge and desensitization: how, when and why.

    PubMed

    Cortellini, Gabriele; Caruso, Cristiano; Romano, Antonino

    2017-08-01

    To investigate the current approach to aspirin challenge (drug provocation) and/or desensitization in patients with histories of hypersensitivity reactions to it, particularly in those with cardiovascular diseases. The literature indicates that patients with coronary artery disease (CAD), including those with an acute coronary syndrome, may safely undergo low-dose aspirin challenge and/or desensitization. Recently, flowcharts regarding challenge/desensitization procedures with aspirin in patients with CAD and histories of aspirin hypersensitivity reactions have become available. Aspirin desensitization and continuous aspirin therapy constitute an effective option in patients with nonsteroidal anti-inflammatory drug-exacerbated respiratory diseases (NERD) who have suboptimally controlled asthma or rhinosinusitis, or require multiple revision polypectomies. The use of aspirin has proven to reduce morbidity and mortality associated with CAD. There is a general consensus on aspirin's effectiveness in secondary prevention of CAD. Therefore, aspirin desensitization is necessary in patients with CAD and histories of hypersensitivity reactions to it. The effectiveness of aspirin desensitization and continuous therapy in patients with NERD has been shown in numerous studies. However, shared selection criteria of candidates for aspirin challenge/desensitization procedures, and simple and homogeneous protocols are necessary. Moreover, preventive safety measures are still needed in order to reduce the potential risks of these procedures.

  5. 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. Copyright © 2015 Elsevier Inc. All rights reserved.

  6. "Long-term stability of stimulating spiral nerve cuff electrodes on human peripheral nerves".

    PubMed

    Christie, Breanne P; Freeberg, Max; Memberg, William D; Pinault, Gilles J C; Hoyen, Harry A; Tyler, Dustin J; Triolo, Ronald J

    2017-07-11

    Electrical stimulation of the peripheral nerves has been shown to be effective in restoring sensory and motor functions in the lower and upper extremities. This neural stimulation can be applied via non-penetrating spiral nerve cuff electrodes, though minimal information has been published regarding their long-term performance for multiple years after implantation. Since 2005, 14 human volunteers with cervical or thoracic spinal cord injuries, or upper limb amputation, were chronically implanted with a total of 50 spiral nerve cuff electrodes on 10 different nerves (mean time post-implant 6.7 ± 3.1 years). The primary outcome measures utilized in this study were muscle recruitment curves, charge thresholds, and percent overlap of recruited motor unit populations. In the eight recipients still actively involved in research studies, 44/45 of the spiral contacts were still functional. In four participants regularly studied over the course of 1 month to 10.4 years, the charge thresholds of the majority of individual contacts remained stable over time. The four participants with spiral cuffs on their femoral nerves were all able to generate sufficient moment to keep the knees locked during standing after 2-4.5 years. The dorsiflexion moment produced by all four fibular nerve cuffs in the active participants exceeded the value required to prevent foot drop, but no tibial nerve cuffs were able to meet the plantarflexion moment that occurs during push-off at a normal walking speed. The selectivity of two multi-contact spiral cuffs was examined and both were still highly selective for different motor unit populations for up to 6.3 years after implantation. The spiral nerve cuffs examined remain functional in motor and sensory neuroprostheses for 2-11 years after implantation. They exhibit stable charge thresholds, clinically relevant recruitment properties, and functional muscle selectivity. Non-penetrating spiral nerve cuff electrodes appear to be a suitable option

  7. Massive Oculomotor Nerve Enlargement: A Case of Presumed Schwannomatosis

    PubMed Central

    Donaldson, Laura; Rebello, Ryan; Rodriguez, Amadeo

    2017-01-01

    ABSTRACT A 45-year-old man presented with a slowly progressive pupil-involving third nerve palsy. Magnetic resonance imaging (MRI) revealed a tubular lesion extending from the interpeduncular cistern through the cavernous sinus and into the left orbit where it branched into a superior and an inferior division, clearly outlining the anatomy of the third cranial nerve. Multiple other, less pronounced, enlarged cranial nerves were noted. The differential diagnosis included chronic inflammatory demyelinating polyneuropathy (CIDP), hereditary motor and sensory neuropathy (HMSN), neurofibromatosis (NF), and schwannomatosis. The absence of other muscle weakness and of sensory symptoms combined with normal peripheral nerve conduction studies effectively ruled out the hypertrophic polyneuropathies and pointed to a syndromic cause of multiple benign peripheral nerve sheath tumours (PNSTs). The authors are treating this case as presumed schwannomatosis, a syndrome similar to NF2 with much lower frequency of acoustic neuromas. PMID:28512503

  8. Multiple mechanisms of serotonin 5-HT2 receptor desensitization.

    PubMed

    Rahman, S; Neuman, R S

    1993-07-20

    Desensitization of serotonin 5-HT2 receptor-mediated enhancement of the N-methyl-D-aspartate (NMDA) depolarization was studied in rat cortical neurons. Serotonin and (+/-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) induced long term desensitization. Staurosporine, a nonspecific protein kinase C inhibitor, potentiated the serotonin and DOI facilitation, suggesting acute desensitization was operative. In the case of DOI, long term desensitization was prevented by staurosporine. Activators of protein kinase C abolished the serotonin facilitation, an action prevented by staurosporine. Concanavalin A potentiated the facilitation at 100 microM, but not 30 microM serotonin, suggesting these receptors undergo dose dependent internalization. Calmodulin antagonists prevent long term desensitization induced by serotonin. The depolarization induced by NMDA alone was not altered by staurosporine, protein kinase C activators, concanavalin A or calmodulin antagonists. Serotonin at 100 microM, but not 30 microM, induced heterologous desensitization of phenylephrine and carbachol induced facilitation of the NMDA depolarization. We conclude that serotonin 5-HT2 receptors both induce and undergo several forms of desensitization.

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

    PubMed Central

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

    2013-01-01

    Background: The purpose of this article is to evaluate a new method of DIEP flap neurotization using a reliably located recipient nerve. We hypothesize that neurotization by this method (with either nerve conduit or direct nerve coaptation) will have a positive effect on sensory recovery. Methods: Fifty-seven deep inferior epigastric perforator (DIEP) flaps were performed on 35 patients. Neurotizations were performed to the third anterior intercostal nerve by directly coapting the flap donor nerve or coapting with a nerve conduit. Nine nonneurotized DIEP flaps served as controls and received no attempted neurotization. All patients were tested for breast sensibility in 9 areas of the flap skin-island and adjacent postmastectomy skin. Testing occurred at an average of 111 weeks (23–309) postoperatively. Results: At a mean of 111 weeks after breast reconstruction, neurotization of the DIEP flap resulted in recovery of sensibility that was statistically significantly better (lower threshold) in the flap skin (P < 0.01) and statistically significantly better than in the native mastectomy skin into which the DIEP flap was inserted (P < 0.01). Sensibility recovered in DIEP flaps neurotized using the nerve conduit was significantly better (lower threshold) than that in the corresponding areas of the DIEP flaps neurotized by direct coaptation (P < 0.01). Conclusion: DIEP flap neurotization using the third anterior intercostal nerve is an effective technique to provide a significant increase in sensory recovery for breast reconstruction patients, while adding minimal surgical time. Additionally, the use of a nerve conduit produces increased sensory recovery when compared direct coaptation. PMID:25289267

  10. Guided Mastery and Performance Desensitization Treatments.

    ERIC Educational Resources Information Center

    Williams, S. Lloyd; And Others

    1985-01-01

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

  11. 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

  12. Olfactory CNG channel desensitization by Ca2+/CaM via the B1b subunit affects response termination but not sensitivity to recurring stimulation.

    PubMed

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

    2008-05-08

    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, 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.

  13. 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

  14. Group Vicarious Desensitization of Test Anxiety.

    ERIC Educational Resources Information Center

    Altmaier, Elizabeth Mitchell; Woodward, Margaret

    1981-01-01

    Studied test-anxious college students (N=43) who received either vicarious desensitization, study skills training, or both treatments; there was also a no-treatment control condition. Self-report measures indicated that vicarious desensitization resulted in lower test and trait anxiety than study skills training alone or no treatment. (Author)

  15. 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. Copyright © 2014 Elsevier Inc. All rights reserved.

  16. Large Extremity Peripheral Nerve Repair

    DTIC Science & Technology

    2014-10-01

    Shahani B. Peripheral-nerve allotransplantation in rats immunosuppressed with transient or long-term FK-506. Journal of reconstructive microsurgery ...multicenter study of utilization and outcomes in sensory, mixed, and motor nerve reconstructions . Microsurgery . 2012 Jan;32(1):1-14. PubMed PMID: 22121093...PTB method can provide fixation strengths 6 approaching that of conventional microsurgery and that the PTB repair is unlikely to be disturbed in

  17. Medication Desensitization: Characterization of Outcomes and Risk Factors for Reactions.

    PubMed

    Murray, Taryn S; Rice, Todd W; Wheeler, Arthur P; Phillips, Elizabeth J; Dworski, Ryszard T; Stollings, Joanna L

    2016-03-01

    Although its mechanisms are poorly understood, desensitization has been used to induce a temporary state of immune unresponsiveness in patients who have IgE-, non-IgE-, or pharmacologically mediated reactions when a drug has no alternatives. The purpose of this study was to characterize the outcomes and identify risk factors for reactions during drug desensitization. A retrospective review of electronic medical records of adult patients undergoing drug desensitization from January 1, 2011, to December 31, 2013, was conducted in 2 intensive care units at a tertiary medical center. We used multivariate analysis to determine if specified risk factors were associated with reacting during the desensitization. Reactions were classified according to the pretest probability prior to desensitization, and then, reactions during desensitization were classified based on the occurrence of cutaneous reactions as follows: successful with no reaction, mild reaction, moderate reaction, or failed. Failure could result from any systemic allergic or cutaneous reaction resulting in procedure termination. The desensitizations were also assessed to determine if the patient required de-escalation secondary to a reaction. A total of 88 desensitizations were performed in 69 patients. Desensitization was completed with no cutaneous reaction in 85% of patients. No baseline characteristic, medication class (P = 0.46), or indication for desensitization (P = 0.59) was associated with having a reaction. Reported histories of urticaria (P < 0.0001) and labored breathing (P = 0.003) during prior exposure were significant in identifying patients who might have a reaction during desensitization. However, neither history of urticaria nor labored breathing was independently associated with having a reaction in multivariate analysis (OR = 0.979, 95% CI = 0.325-2.952, P = 0.970, and OR = 1.626, 95% CI = 0.536-4.931, P = 0.739, respectively). Drug desensitization is safe for patients who have no

  18. The visceromotor and somatic afferent nerves of the penis.

    PubMed

    Diallo, Djibril; Zaitouna, Mazen; Alsaid, Bayan; Quillard, Jeanine; Ba, Nathalie; Allodji, Rodrigue Sètchéou; Benoit, Gérard; Bedretdinova, Dina; Bessede, Thomas

    2015-05-01

    Innervation of the penis supports erectile and sensory functions. This article aims to study the efferent autonomic (visceromotor) and afferent somatic (sensory) nervous systems of the penis and to investigate how these systems relate to vascular pathways. Penises obtained from five adult cadavers were studied via computer-assisted anatomic dissection (CAAD). The number of autonomic and somatic nerve fibers was compared using the Kruskal-Wallis test. Proximally, penile innervation was mainly somatic in the extra-albugineal sector and mainly autonomic in the intracavernosal sector. Distally, both sectors were almost exclusively supplied by somatic nerve fibers, except the intrapenile vascular anastomoses that accompanied both somatic and autonomic (nitrergic) fibers. From this point, the neural immunolabeling within perivascular nerve fibers was mixed (somatic labeling and autonomic labeling). Accessory afferent, extra-albugineal pathways supplied the outer layers of the penis. There is a major change in the functional type of innervation between the proximal and distal parts of the intracavernosal sector of the penis. In addition to the pelvis and the hilum of the penis, the intrapenile neurovascular routes are the third level where the efferent autonomic (visceromotor) and the afferent somatic (sensory) penile nerve fibers are close. Intrapenile neurovascular pathways define a proximal penile segment, which guarantees erectile rigidity, and a sensory distal segment. © 2015 International Society for Sexual Medicine.

  19. Ulnar nerve entrapment in Guyon's canal due to a lipoma.

    PubMed

    Ozdemir, O; Calisaneller, T; Gerilmez, A; Gulsen, S; Altinors, N

    2010-09-01

    Guyon's canal syndrome is an ulnar nerve entrapment at the wrist or palm that can cause motor, sensory or combined motor and sensory loss due to various factors . In this report, we presented a 66-year-old man admitted to our clinic with a history of intermittent pain in the left palm and numbness in 4th and 5th finger for two years. His neurological examination revealed a sensory impairment in the right fifth finger. Also, physical examination displayed a subcutaneous mobile soft tissue in ulnar side of the wrist. Electromyographic examination confirmed the diagnosis of type-1 Guyon's canal syndrome. Under axillary blockage, a lipoma compressing the ulnar nerve was excised totally and ulnar nerve was decompressed. The symptoms were improved after the surgery and patient was symptom free on 3rd postoperative week.

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

    NASA Astrophysics Data System (ADS)

    Ibrahim, T.; Gheith, M.

    2011-09-01

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

  1. Desensitization and recovery of phototropic responsiveness in Arabidopsis thaliana

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    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 withmore » 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.« less

  2. Reliability of the nerve conduction monitor in repeated measures of median and ulnar nerve latencies

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Washington, I A

    According to the Bureau of Labor Statistics, carpal tunnel syndrome (CTS), one of the most rapidly growing work-related injuries, cost American businesses up to $10 billion dollars in medical costs each year (1992). Because conservative therapy can be implemented and CTS is more reversible in it early stages, early detection will not only save industry unnecessary health care costs, but also prevent employees from experiencing debilitating pain and unnecessary surgery. In response to the growing number of cases of CTS, many companies have introduced screening tools to detect early stages of carpal tunnel syndrome. Neurotron Medical (New Jersey) has designedmore » a portable nerve conduction monitor (Nervepace S-200) which measures motor and sensory nerve latencies. The slowing of these latencies is one diagnostic indicator of carpal tunnel syndrome. In this study, we determined the reliability of the Nervepace Monitor in measure ulnar and median nerve latencies during repeated testing. The testing was performed on 28 normal subjects between the ages of 20 and 35 who had no prior symptoms of CTS. They were tested at the same time each day for three consecutive days. Nerve latencies between different ethnic groups and genders were compared. Results show that there was no significant daily variation of the median motor and lunar sensory latencies or the median sensory latencies. No significant differences of latencies was observed among ethnic groups; however, a significant difference of latencies between male and female subjects was observed (p<0.05).« less

  3. The Trigeminal (V) and Facial (VII) Cranial Nerves

    PubMed Central

    Sanders, Richard D.

    2010-01-01

    There are close functional and anatomical relationships between cranial nerves V and VII in both their sensory and motor divisions. Sensation on the face is innervated by the trigeminal nerves (V) as are the muscles of mastication, but the muscles of facial expression are innervated mainly by the facial nerve (VII) as is the sensation of taste. This article briefly reviews the anatomy of these cranial nerves, disorders of these nerves that are of particular importance to psychiatry, and some considerations for differential diagnosis. PMID:20386632

  4. The pattern and diagnostic criteria of sensory neuronopathy: a case–control study

    PubMed Central

    Camdessanché, Jean-Philippe; Jousserand, Guillemette; Ferraud, Karine; Vial, Christophe; Petiot, Philippe; Honnorat, Jérôme

    2009-01-01

    Acquired sensory neuronopathies encompass a group of paraneoplastic, dysimmune, toxic or idiopathic disorders characterized by degeneration of peripheral sensory neurons in dorsal root ganglia. As dorsal root ganglia cannot easily be explored, the clinical diagnosis of these disorders may be difficult. The question as to whether there exists a common clinical pattern of sensory neuronopathies, allowing the establishment of validated and easy-to-use diagnostic criteria, has not yet been addressed. In this study, logistic regression was used to construct diagnostic criteria on a retrospective study population of 78 patients with sensory neuronopathies and 56 with other sensory neuropathies. For this, sensory neuronopathy was provisionally considered as unambiguous in 44 patients with paraneoplastic disorder or cisplatin treatment and likely in 34 with a dysimmune or idiopathic setting who may theoretically have another form of neuropathy. To test the homogeneity of the sensory neuronopathy population, likely candidates were compared with unambiguous cases and then the whole population was compared with the other sensory neuropathies population. Criteria accuracy was checked on 37 prospective patients referred for diagnosis of sensory neuropathy. In the study population, sensory neuronopathy showed a common clinical and electrophysiological pattern that was independent of the underlying cause, including unusual forms with only patchy sensory loss, mild electrical motor nerve abnormalities and predominant small fibre or isolated lower limb involvement. Logistic regression allowed the construction of a set of criteria that gave fair results with the following combination: ataxia in the lower or upper limbs + asymmetrical distribution + sensory loss not restricted to the lower limbs + at least one sensory action potential absent or three sensory action potentials <30% of the lower limit of normal in the upper limbs + less than two nerves with abnormal motor nerve

  5. 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)

  6. Adenosine receptor desensitization and trafficking.

    PubMed

    Mundell, Stuart; Kelly, Eamonn

    2011-05-01

    As with the majority of G-protein-coupled receptors, all four of the adenosine receptor subtypes are known to undergo agonist-induced regulation in the form of desensitization and trafficking. These processes can limit the ability of adenosine receptors to couple to intracellular signalling pathways and thus reduce the ability of adenosine receptor agonists as well as endogenous adenosine to produce cellular responses. In addition, since adenosine receptors couple to multiple signalling pathways, these pathways may desensitize differentially, while the desensitization of one pathway could even trigger signalling via another. Thus, the overall picture of adenosine receptor regulation can be complex. For all adenosine receptor subtypes, there is evidence to implicate arrestins in agonist-induced desensitization and trafficking, but there is also evidence for other possible forms of regulation, including second messenger-dependent kinase regulation, heterologous effects involving G proteins, and the involvement of non-clathrin trafficking pathways such as caveolae. In this review, the evidence implicating these mechanisms is summarized for each adenosine receptor subtype, and we also discuss those issues of adenosine receptor regulation that remain to be resolved as well as likely directions for future research in this field. Copyright © 2010 Elsevier B.V. All rights reserved.

  7. 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)

  8. 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)

  9. Assessment of nerve regeneration across nerve allografts treated with tacrolimus.

    PubMed

    Haisheng, Han; Songjie, Zuo; Xin, Li

    2008-01-01

    Although regeneration of nerve allotransplant is a major concern in the clinic, there have been few papers quantitatively assessing functional recovery of animals' nerve allografts in the long term. In this study, functional recovery, histopathological study, and immunohistochemistry changes of rat nerve allograft with FK506 were investigated up to 12 weeks without slaughtering. C57 and SD rats were used for transplantation. The donor's nerve was sliced and transplanted into the recipient. The sciatic nerve was epineurally sutured with 10-0 nylon. In total, 30 models of transplantation were performed and divided into 3 groups that were either treated with FK506 or not. Functional recovery of the grafted nerve was serially assessed by the pin click test, walking track analysis and electrophysiological evaluations. A histopathological study and immunohistochemistry study were done in the all of the models. Nerve allografts treated with FK506 have no immune rejection through 12 weeks. Sensibility had similarly improved in both isografts and allografts. There has been no difference in each graft. Walk track analysis demonstrates significant recovery of motor function of the nerve graft. No histological results of difference were found up to 12 weeks in each graft. In the rodent nerve graft model, FK506 prevented nerve allograft rejection across a major histocompatibility barrier. Sensory recovery seems to be superior to motor function. Nerve isograft and allograft treated with FK506 have no significant difference in function recovery, histopathological result, and immunohistochemistry changes.

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

    PubMed

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

    2009-06-01

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

  11. 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.

  12. Determining the functional sensibility of the hand in patients with peripheral nerve repair: Feasibility of using a novel manual tactile test for monitoring the progression of nerve regeneration.

    PubMed

    Hsu, Hsiu-Yun; Kuo, Li-Chieh; Kuan, Ta-Shen; Yang, Hsiu-Ching; Su, Fong-Chin; Chiu, Haw-Yen; Shieh, Shyh-Jou

    Case-controlled cohort study. Sensory function is difficult to observe during nerve regeneration processes. Traditional sensory tests are limited to identifying the level of functioning hand sensation for sensory stimulus is given passively to the cutaneous surface of the hand. To examine the outcome changes in the manual tactile test (MTT), Semmes-Weinstein monofilament (SWM) and 2-point discrimination (2PD) tests for patients with nerve repair and to investigate the concurrent validity of MTT by comparing it with the results of traditional tests. Fifteen patients with nerve injury of the upper limbs were recruited, along with 15 matched healthy controls. The MTT, SWM, and 2PD tests were used to examine the sensory status of the subjects. Three subtests (barognosis, roughness differentiation, and stereognosis) in MTT showed that the patients improved with time. A moderate and mild correlation was found between the MTT and 2PD results and between the barognosis and SWM results. The MTT provides practical and functional perspectives on detecting nerve progression during the courses of degeneration and regeneration. IV. Copyright © 2016 Hanley & Belfus. Published by Elsevier Inc. All rights reserved.

  13. Desensitization to clopidogrel: a tailor-made protocol.

    PubMed

    Barreira, P; Cadinha, S; Malheiro, D; Moreira da Silva, J P

    2014-01-01

    Clopidogrel is an antiplatelet drug widely used for treatment and prevention of a variety of cardiovascular diseases. We report a successful desensitization to clopidogrel in a 70-year-old Caucasian man with delayed hypersensitivity (HS) reaction. He developed lip, hand and foot swelling, erythematous papular non-pruritic lesions and arthralgias 2 weeks after starting treatment with clopidogrel 75 mg/d. A 3-hour desensitization protocol was started, achieving a cumulative dose of 154 mg without any reaction, and a daily dose of 75 mg was recommended. On the 4th day, the patient developed skin lesions similar to the previously described. He was treated with topical steroids and oral antihistamines, and the daily dose of clopidogrel was reduced to 20 mg. A new desensitization protocol was established, with a slow dose increment, according to the patient's response. It was only possible to achieve the dose of 75 mg/d after 2 months. Although well tolerated by most patients, HS reactions with clopidogrel may occur and desensitization is rising as a safe alternative in those patients. In delayed reactions with cutaneous lesions, a slower desensitization protocol may be necessary, as in this case.

  14. Is distal motor and/or sensory demyelination a distinctive feature of anti-MAG neuropathy?

    PubMed

    Lozeron, Pierre; Ribrag, Vincent; Adams, David; Brisset, Marion; Vignon, Marguerite; Baron, Marine; Malphettes, Marion; Theaudin, Marie; Arnulf, Bertrand; Kubis, Nathalie

    2016-09-01

    To report the frequency of the different patterns of sensory and motor electrophysiological demyelination distribution in patients with anti-MAG neuropathy in comparison with patients with IgM neuropathy without MAG reactivity (IgM-NP). Thirty-five anti-MAG patients at early disease stage (20.1 months) were compared to 23 patients with IgM-NP; 21 CIDP patients and 13 patients with CMT1a neuropathy were used as gold standard neuropathies with multifocal and homogeneous demyelination, respectively. In all groups, standard motor and sensory electrophysiological parameters, terminal latency index and modified F ratio were investigated. Motor electrophysiological demyelination was divided in four profiles: distal, homogeneous, proximal, and proximo-distal. Distal sensory and sensorimotor demyelination were evaluated. Anti-MAG neuropathy is a demyelinating neuropathy in 91 % of cases. In the upper limbs, reduced TLI is more frequent in anti-MAG neuropathy, compared to IgM-NP. But, predominant distal demyelination of the median nerve is encountered in only 43 % of anti-MAG neuropathy and is also common in IgM-NP (35 %). Homogeneous demyelination was the second most frequent pattern (31 %). Concordance of electrophysiological profiles across motor nerves trunks is low and median nerve is the main site of distal motor conduction slowing. Reduced sensory conduction velocities occurs in 14 % of patients without evidence of predominant distal slowing. Simultaneous sensory and motor distal slowing was more common in the median nerve of anti-MAG neuropathy than IgM-NP. Electrophysiological distal motor demyelination and sensory demyelination are not a distinctive feature of anti-MAG reactivity. In anti-MAG neuropathy it is mainly found in the median nerve suggesting a frequent nerve compression at wrist.

  15. Rituximab desensitization in three patients with severe rituximab allergy.

    PubMed

    Öztürk, Erman; Özyiğit, Leyla Pur; Öztürk, Ayşe Bilge; Akay, Meltem Olga; Çetiner, Mustafa; Ferhanoğlu, Burhan

    Rituximab is a chimeric monoclonal antibody that targets CD20 positive B cells and has a positive effect on both overall and progression-free survival in B-cell lymphoid malignancies. Combination rituximab with chemotherapy treatment provide survival improvement. Although rituximab is an important treatment option in hematological malignancies, the risk of allergic reactions is high. These reactions are usually IgE-mediated and can be varied in regard of severity from urticaria to anaphylaxis. It is an option to interrupt the treatment and ommit rituximab therapy who had allergic reactions. Drug desensitization is another option and successful results have been reported by applying desensitization to such reactions. Drug desensitization alters the immune response to induce a state of temporary clinical tolerance to the allergic drug by giving gradual increasing of doses of drug at fixed time intervals. Herein, we present 3 cases successfully treated with rituximab desensitization. The cases were using rituximab with the diagnosis of Burkitt lymphoma, follicular lymphoma, and marginal zone lymphoma, respectively. Two cases had grade 2 and 1 case had grade 3 systemic allergic reaction with rituximab. There was no known allergy history in all 3 cases. All patients tolerated the desensitization protocol. The subsequent treatments of the patients were also given by desensitization protocol. A total of 12 desensitizations were administered to 3 cases. No severe or life-threating reactions were observed in subsequent applications. To date applying desensitization protocols ensure rituximab treatment safely. Rituximab desensitization can be performed at trained allergy centers, and it may be an appropriate option for rituximab allergic patients. Copyright © 2017 Elsevier Inc. All rights reserved.

  16. A urodynamic study of surface neuromodulation versus sham in detrusor instability and sensory urgency.

    PubMed

    Bower, W F; Moore, K H; Adams, R D; Shepherd, R

    1998-12-01

    We studied the effect of surface neuromodulation on cystometric pressure and volume parameters in women with detrusor instability or sensory urgency. Electrical current was delivered to the suprapubic region and third sacral foramina via a transcutaneous electrical nerve stimulator with sham neuromodulation control. A consecutive series of women with proved detrusor instability or sensory urgency were randomized to 3 surface neuromodulation groups. Volume and pressure parameters were the main outcomes of transcutaneous electrical nerve stimulation applied during second cystometric fill. Sham transcutaneous electrical nerve stimulation did not alter the outcome measures. However, neuromodulation delivered across the suprapubic and sacral skin effected a reduction in mean maximum height of detrusor contraction. A current which inhibits motor activity was not superior to that which inhibits sensory perception in reducing detrusor pressure. Response in sensory urgency was poor. Results from our sham controlled study suggest that short-term surface neuromodulation via transcutaneous electrical nerve stimulation may have a role in the treatment of detrusor instability. Future studies must examine the clinical effect of long-term surface neuromodulation.

  17. Large Extremity Peripheral Nerve Repair

    DTIC Science & Technology

    2014-10-01

    nerve allotransplantation in rats immunosuppressed with transient or long-term FK-506. Journal of reconstructive microsurgery . 1996 Oct;12(7):451-9...outcomes in sensory, mixed, and motor nerve reconstructions . Microsurgery . 2012 Jan;32(1):1-14. PubMed PMID: 22121093. Epub 2011/11/29. eng. 12...method can provide fixation strengths 5 approaching that of conventional microsurgery and that the PTB repair is unlikely to be disturbed in vivo

  18. 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

  19. Age-dependent effects on sensory axonal excitability in normal mice.

    PubMed

    Banzrai, Chimeglkham; Nodera, Hiroyuki; Higashi, Saki; Okada, Ryo; Osaki, Yusuke; Mori, Atsuko; Kaji, Ryuji

    2016-01-12

    Serial recordings were performed to measure sensory excitability in peripheral nerves and elucidate age-dependent changes in neuronal ion currents in the peripheral sensory nervous system. The threshold tracking technique was used to measure multiple excitability indices in the tail sensory nerves of five normal male mice at four time points (6, 10, 14, and 19 weeks of age). A separate group of four mice was also measured at 43 weeks and at 60 weeks of age. Maturation was accompanied by an increase in early hyperpolarization and superexcitability at 10 weeks. At 60 weeks, the hyperpolarizing electrotonus shifted downward, while superexcitability became greater and subexcitability (double stimuli) decreased. Computer modeling showed that the most notable age-related interval changes in excitability parameters were Barrett-Barrett, H, and slow K(+) conductances. Understanding age-related changes in the excitability of sensory axons may provide a platform for understanding age-dependent sensory symptoms and developing age-specific channel-targeting therapies. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  20. Sensory neuropathy may cause central neuronal reorganization but does not respecify perceptual quality or localization of sensation.

    PubMed

    Ginanneschi, Federica; Mondelli, Mauro; Rossi, Alessandro

    2012-10-01

    Functional reorganization in the somatosensory network after peripheral nerve lesions has been suspected to modify the clinical expression of symptoms. However, no conclusive evidence exists to support this notion. We addressed this question by investigating the topographic distribution of the subjective sensory report in various chronic human mononeuropathies. We report the clinical results of 86 patients who were diagnosed with meralgia paresthetica, 86 patients with ulnar neuropathy at the elbow, and 203 patients with carpal tunnel syndrome. In the carpal tunnel syndrome group, 10% of the patients exhibited a spread of sensory symptoms beyond the innervation territory of the median nerve. As previously reported, this spread was contingent upon an indirect compressive lesion of the ulnar nerve at the wrist. In all of the patients who were affected with meralgia paresthetica or ulnar neuropathy at the elbow, the peripheral referral of sensation was always within the anatomic distribution of the affected nerve. In human neuropathies, the projected sensory symptoms are restricted to the innervation territories of the affected nerves, with no extraterritorial spread. Thus, the somatosensory localization function remains accurate, despite the central reorganization that presumably occurs after nerve injury. We conclude that reorganization of the sensory connections within the central nervous system after peripheral nerve injury in humans is a clinically silent adaptive phenomenon.

  1. Microsurgical Decompression of Inferior Alveolar Nerve After Endodontic Treatment Complications.

    PubMed

    Bianchi, Bernardo; Ferri, Andrea; Varazzani, Andrea; Bergonzani, Michela; Sesenna, Enrico

    2017-07-01

    Iatrogenic injury in oral surgery is the most frequent cause of sensory disturbance in the distribution of the inferior alveolar nerve (IAN) and mental nerve.Inferior alveolar nerve damage can occur during third molar extraction, implant location, orthognathic surgery, preprosthetic surgery, salivary gland surgery, local anesthetic injections or during the resection of benign or malignant tumors.Injuries to the IAN can be caused also by endodontic treatment of mandibular molars and premolars when filling material is forced into the tooth and mandibular canal.The sensory disturbances that could follow a damage of the IAN could be hypoesthesia, dysesthesia, hyperesthesia, anesthesia, and sometimes a painful anesthesia that strike ipsilateral lower lip, chin, and teeth. These can undermine life quality by affecting speech, chewing, and social interaction.Treatment of these complications is sometimes difficult and could consist in observation or in surgical decompression of the involved nerve to relieve the patient's symptoms and improve sensory recovery. The most debated points are the timing of intervention and the effective role of decompression in clinical outcome-improvement.The purpose of this article is to show authors' experience with 2 patients treated with microsurgical nerve decompression to remove endodontic material from the mandibular canal and providing also a comprehensive review of the literature.

  2. Effect of simvastatin on sensorial, motor, and morphological parameters in sciatic nerve crush induced-neuropathic pain in rats.

    PubMed

    Corso, Claudia Rita; Martins, Daniel Fernandes; Borges, Stephanie Carvalho; Beltrame, Olair Carlos; Telles, José Ederaldo Queiroz; Buttow, Nilza Cristina; Werner, Maria Fernanda de Paula

    2018-06-01

    The present study compares the effects of a low and high doses of simvastatin in a model of peripheral neuropathy by evaluating sensorial, motor, and morphological parameters. First, male Wistar rats were orally treated with vehicle (saline, 1 mL/kg), simvastatin (2 and 80 mg/kg) or morphine (2 mg/kg, s.c.), 1 h before 2.5% formalin injection. Neuropathic pain was induced by crushing the sciatic nerve, and mechanical and cold allodynia, nerve function, histology, MPO and NAG concentrations, as well as mevalonate induced-nociception were evaluated. Animals were orally treated with vehicle, simvastatin, or gabapentin (30 mg/kg) for 18 days. Simvastatin (2 and 80 mg/kg) reduced the inflammatory pain induced by formalin, but failed to decrease the paw edema. Mechanical allodynia was reduced by the simvastatin (2 mg/kg) until the 12th day after injury and until the 18th day by gabapentin. However, both simvastatin and gabapentin treatments failed in attenuated cold allodynia or improved motor function. Interestingly, both doses of simvastatin showed a neuroprotective effect and inhibited MPO activity without altering kidney and hepatic parameters. Additionally, only the higher dose of simvastatin reduced the cholesterol levels and the nociception induced by mevalonate. Our results reinforce the antinociceptive, antiallodynic, and anti-inflammatory effects of oral simvastatin administration, which can strongly contribute to the sciatic nerve morphology preservation. Furthermore, our data suggest that lower and higher doses of simvastatin present beneficial effects that are dependent and independent of the mevalonate pathway, respectively, without causing signs of nerve damage.

  3. Relationship Factors in Desensitization: A Persistent Trend

    ERIC Educational Resources Information Center

    Nawas, M. Mike; Pucel, John C.

    1971-01-01

    The aim of the study was to explore the relevance to the outcome of desensitization of same-sex and opposite-sex pairings of subjects and experimenters. It was concluded that desensitization is independent of the sex pairing of subject and experimenter. (Author)

  4. Improvement of hand sensibility after selective temporary anaesthesia in combination with sensory re-education.

    PubMed

    Hassan-Zadeh, Roghiyeh; Lajevardi, Laleh; Esfahani, Ahmadreza Roofigari; Kamali, Mohammad

    2009-01-01

    The results of nerve repair in adults are often poor. The study aim was to investigate the effect of repeated sessions of cutaneous forearm anaesthesia of the injured limb, in combination with sensory re-education on the recovery of the tactile discrimination and perception of touch/pressure in the injured hand after median or ulnar nerve repair. A prospective, randomized, double-blind clinical trial was designed. During a 2-week period, a topical anaesthetic cream (Lidocaine-PTC, n = 6) or placebo (n = 7) was applied repeatedly (twice a week) with occlusive bandage for 1 hour on the flexor aspect of the forearm of the same side of the nerve injury and combined with sensory re-education. Assessments of sensory function were performed prior to the experiment and after the fourth application of Lidocaine-PTC/placebo. The patients were evaluated again 4 weeks after the last Lidocaine-PTC/placebo session. Touch perception measured with Semmes-Weinstein Monofilaments (SWM), improved significantly in the Lidocaine-PTC group (p = 0.005). In placebo group, no significant changes were seen. Two{-}point discrimination improved significantly only in the Lidocaine-PTC group (p = 0.005). This finding suggests that forearm deafferentation of injured limb in combination with sensory re-education can enhance sensory recovery after nerve repair.

  5. 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

  6. Aspirin Desensitization in Patients With Coronary Artery Disease: Results of the Multicenter ADAPTED Registry (Aspirin Desensitization in Patients With Coronary Artery Disease).

    PubMed

    Rossini, Roberta; Iorio, Annamaria; Pozzi, Roberto; Bianco, Matteo; Musumeci, Giuseppe; Leonardi, Sergio; Lettieri, Corrado; Bossi, Irene; Colombo, Paola; Rigattieri, Stefano; Dossena, Cinzia; Anzuini, Angelo; Capodanno, Davide; Senni, Michele; Angiolillo, Dominick J

    2017-02-01

    There are limited data on aspirin (ASA) desensitization for patients with coronary artery disease. The aim of the present study was to assess the safety and efficacy of a standard rapid desensitization protocol in patients with ASA sensitivity undergoing coronary angiography. This is a prospective, multicenter, observational study including 7 Italian centers including patients with a history of ASA sensitivity undergoing coronary angiography with intent to undergo percutaneous coronary intervention. A total of 330 patients with history of ASA sensitivity with known/suspected stable coronary artery disease or presenting with an acute coronary syndrome, including ST-segment-elevation myocardial infarction were enrolled. Adverse effects to aspirin included urticaria (n=177, 53.6%), angioedema (n=69, 20.9%), asthma (n=65, 19.7%), and anaphylactic reaction (n=19, 5.8%). Among patients with urticaria/angioedema, 13 patients (3.9%) had a history of idiopathic chronic urticaria. All patients underwent a rapid ASA (5.5 hours) desensitization procedure. The desensitization procedure was performed before cardiac catheterization in all patients, except for those (n=78, 23.6%) presenting with ST-segment-elevation myocardial infarction who underwent the desensitization after primary percutaneous coronary intervention. Percutaneous coronary intervention was performed in 235 patients (71%) of the overall study population. The desensitization procedure was successful in 315 patients (95.4%) and in all patients with a history of anaphylactic reaction. Among the 15 patients (4.6%) who did not successfully respond to the desensitization protocol, adverse reactions were minor and responded to treatment with corticosteroids and antihistamines. Among patients with successful in-hospital ASA desensitization, 253 patients (80.3%) continued ASA for at least 12 months. Discontinuation of ASA in the 62 patients (19.7%) who had responded to the desensitization protocol was because of medical

  7. Analysis of human acellular nerve allograft reconstruction of 64 injured nerves in the hand and upper extremity: a 3 year follow-up study.

    PubMed

    Zhu, Shuang; Liu, Jianghui; Zheng, Canbin; Gu, Liqiang; Zhu, Qingtang; Xiang, Jianping; He, Bo; Zhou, Xiang; Liu, Xiaolin

    2017-08-01

    Human acellular nerve allografts have been increasingly applied in clinical practice. This study was undertaken to investigate the functional outcomes of nerve allograft reconstruction for nerve defects in the upper extremity. A total of 64 patients from 13 hospitals were available for this follow-up study after nerve repair using human acellular nerve allografts. Sensory and motor recovery was examined according to the international standards for motor and sensory nerve recovery. Subgroup analysis and logistic regression analysis were conducted to identify the relationship between the known factors and the outcomes of nerve repair. Mean follow-up time was 355 ± 158 (35-819) days; mean age was 35 ± 11 (14-68) years; average nerve gap length was 27 ± 13 (10-60) mm; no signs of infection, tissue rejection or extrusion were observed among the patients; 48/64 (75%) repaired nerves experienced meaningful recovery. Univariate analysis showed that site and gap length significantly influenced prognosis after nerve repair using nerve grafts. Delay had a marginally significant relationship with the outcome. A multivariate logistic regression model revealed that gap length was an independent predictor of nerve repair using human acellular nerve allografts. The results indicated that the human acellular nerve allograft facilitated safe and effective nerve reconstruction for nerve gaps 10-60 mm in length in the hand and upper extremity. Factors such as site and gap length had a statistically significant influence on the outcomes of nerve allograft reconstruction. Gap length was an independent predictor of nerve repair using human acellular nerve allografts. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  8. Relation between trinucleotide GAA repeat length and sensory neuropathy in Friedreich's ataxia.

    PubMed

    Santoro, L; De Michele, G; Perretti, A; Crisci, C; Cocozza, S; Cavalcanti, F; Ragno, M; Monticelli, A; Filla, A; Caruso, G

    1999-01-01

    To verify if GAA expansion size in Friedreich's ataxia could account for the severity of sensory neuropathy. Retrospective study of 56 patients with Friedreich's ataxia selected according to homozygosity for GAA expansion and availability of electrophysiological findings. Orthodromic sensory conduction velocity in the median nerve was available in all patients and that of the tibial nerve in 46 of them. Data of sural nerve biopsy and of a morphometric analysis were available in 12 of the selected patients. The sensory action potential amplitude at the wrist (wSAP) and at the medial malleolus (m mal SAP) and the percentage of myelinated fibres with diameter larger than 7, 9, and 11 microm in the sural nerve were correlated with disease duration and GAA expansion size on the shorter (GAA1) and larger (GAA2) expanded allele in each pair. Pearson's correlation test and stepwise multiple regression were used for statistical analysis. A significant inverse correlation between GAA1 size and wSAP, m mal SAP, and percentage of myelinated fibres was found. Stepwise multiple regression showed that GAA1 size significantly affects electrophysiological and morphometric data, whereas duration of disease has no effect. The data suggest that the severity of the sensory neuropathy is probably genetically determined and that it is not progressive.

  9. The neglected cranial nerve: nervus terminalis (cranial nerve N).

    PubMed

    Vilensky, Joel A

    2014-01-01

    The nervus terminalis (NT; terminal nerve) was clearly identified as an additional cranial nerve in humans more than a century ago yet remains mostly undescribed in modern anatomy textbooks. The nerve is referred to as the nervus terminalis because in species initially examined its fibers were seen entering the brain in the region of the lamina terminalis. It has also been referred to as cranial nerve 0, but because there is no Roman symbol for zero, an N for the Latin word nulla is a better numerical designation. This nerve is very distinct in human fetuses and infants but also has been repeatedly identified in adult human brains. The NT fibers are unmyelinated and emanate from ganglia. The fibers pass through the cribriform plate medial to those of the olfactory nerve fila. The fibers end in the nasal mucosa and probably arise from autonomic/neuromodulatory as well as sensory neurons. The NT has been demonstrated to release luteinizing-releasing luteinizing hormone and is therefore thought to play a role in reproductive behavior. Based on the available evidence, the NT appears to be functional in adult humans and should be taught in medical schools and incorporated into anatomy/neuroanatomy textbooks. Copyright © 2012 Wiley Periodicals, Inc., a Wiley company.

  10. Systematic Desensitization Of Test Anxiety: A Comparison Of Group And Individual Treatment

    ERIC Educational Resources Information Center

    Scissons, Edward H.; Njaa, Lloyd J.

    1973-01-01

    The results indicate the effectiveness of both individual desensitization and group desensitization in the treatment of high test anxiety. More research is needed in comparing the effectiveness of group desensitization and individual desensitization with intratreatment variables. (Author)

  11. Recovery from desensitization of IgE-dependent responses in human lung mast cells.

    PubMed

    Lewis, A; MacGlashan, D W; Suvarna, S K; Peachell, P T

    2017-08-01

    Clinical desensitization and oral food immunotherapy are therapeutic interventions that allow individuals who react adversely to an allergen (drug or food) to be made tolerant to the allergen. However, tolerance is brief, and allergen hypersensitivity can recur within days following allergen withdrawal. We hypothesize that the reason these treatments are temporary reflects rapid recovery of mast cells from a desensitized state. We sought to test this. Desensitization of IgE-mediated histamine release from human lung mast cells was explored by methods that partially replicate the pattern of treatment during clinical desensitization. Specific and non-specific desensitization and changes in surface IgE were examined following desensitization. Recovery from desensitization was also studied. Desensitization of mast cell responses was readily induced with concentrations of antigen or anti-IgE that were suboptimal for secretion. There was little or no non-specific desensitization when lung mast cells were exposed to antigens. There was no loss of cell surface IgE following desensitization. Removing the desensitizing stimulus from the media following desensitization allowed the cells to recover with half-point of recovery of ~1.5 days and complete recovery after 5 days. Both the functional response and histamine content recovered within this time frame. The recovery appeared possible because both antigens and anti-IgE dissociated rapidly from cells after washing to remove excess stimulus. Human lung mast cells readily recover from a desensitized state following removal of desensitizing antigen. This finding provides a potential explanation for the ephemeral nature of clinical desensitization. © 2017 John Wiley & Sons Ltd.

  12. N-Acetylcysteine Prevents Retrograde Motor Neuron Death after Neonatal Peripheral Nerve Injury.

    PubMed

    Catapano, Joseph; Zhang, Jennifer; Scholl, David; Chiang, Cameron; Gordon, Tessa; Borschel, Gregory H

    2017-05-01

    Neuronal death may be an overlooked and unaddressed component of disability following neonatal nerve injuries, such as obstetric brachial plexus injury. N-acetylcysteine and acetyl-L-carnitine improve survival of neurons after adult nerve injury, but it is unknown whether they improve survival after neonatal injury, when neurons are most susceptible to retrograde neuronal death. The authors' objective was to examine whether N-acetylcysteine or acetyl-L-carnitine treatment improves survival of neonatal motor or sensory neurons in a rat model of neonatal nerve injury. Rat pups received either a sciatic nerve crush or transection injury at postnatal day 3 and were then randomized to receive either intraperitoneal vehicle (5% dextrose), N-acetylcysteine (750 mg/kg), or acetyl-L-carnitine (300 mg/kg) once or twice daily. Four weeks after injury, surviving neurons were retrograde-labeled with 4% Fluoro-Gold. The lumbar spinal cord and L4/L5 dorsal root ganglia were then harvested and sectioned to count surviving motor and sensory neurons. Transection and crush injuries resulted in significant motor and sensory neuron loss, with transection injury resulting in significantly less neuron survival. High-dose N-acetylcysteine (750 mg/kg twice daily) significantly increased motor neuron survival after neonatal sciatic nerve crush and transection injury. Neither N-acetylcysteine nor acetyl-L-carnitine treatment improved sensory neuron survival. Proximal neonatal nerve injuries, such as obstetric brachial plexus injury, produce significant retrograde neuronal death after injury. High-dose N-acetylcysteine significantly increases motor neuron survival, which may improve functional outcomes after obstetrical brachial plexus injury.

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

    PubMed Central

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

    2010-01-01

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

  14. Attentional modulation of desensitization to odor.

    PubMed

    Fallon, Nicholas; Giesbrecht, Timo; Stancak, Andrej

    2018-05-22

    Subjective and behavioral responsiveness to odor diminishes during prolonged exposure. The precise mechanisms underlying olfactory desensitization are not fully understood, but previous studies indicate that the phenomenon may be modulated by central-cognitive processes. The present study investigated the effect of attention on perceived intensity during exposure to a pleasant odor. A within-subjects design was utilized with 19 participants attending 2 sessions. During each session, participants continuously rated their perceived intensity of a 10-minute exposure to a pleasant fragrance administered using an olfactometer. An auditory oddball task was implemented to manipulate the focus of attention in each session. Participants were instructed to either direct their attention toward the sounds, but still to rate odor, or to focus entirely on rating the odor. Analysis revealed three 50-second time windows with significantly lower mean intensity ratings during the distraction condition. Curve fitting of the data disclosed a linear function of desensitization in the focused attention condition compared with an exponential decay function during distraction condition, indicating an increased rate of initial desensitization when attention is distracted away from the odor. In the focused-attention condition, perceived intensity demonstrated a regular pattern of odor sensitivity occurring at approximately 1-2 minutes intervals following initial desensitization. Spectral analysis of low-frequency oscillations confirmed the presence of augmented spectral power in this frequency range during focused relative to distracted conditions. The findings demonstrate for the first time modulation of odor desensitization specifically by attentional factors, exemplifying the relevance of top-down control for ongoing perception of odor.

  15. 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…

  16. Nerve Injuries in Gynecologic Laparoscopy.

    PubMed

    Abdalmageed, Osama S; Bedaiwy, Mohamed A; Falcone, Tommaso

    2017-01-01

    Nerve injuries during gynecologic endoscopy are an infrequent but distressing complication. In benign gynecologic surgery, most of these injuries are associated with patient positioning, although some are related to port placement. Most are potentially preventable with attention to patient placement on the operating room bed and knowledge of the relative anatomy of the nerves. The highest risk group vulnerable to these injuries includes women who have extreme body mass index and those with longer surgical times in the Trendelenburg position. Upper and lower limb peripheral nerves are the most common nerves injured during gynecologic endoscopy. These injuries can result in transient or permanent sensory and motor disabilities that can interrupt patient recovery in an otherwise successful surgery. Numerous strategies are suggested to reduce the frequency of nerve injuries during gynecologic endoscopies. Proper patient positioning and proper padding of the pressure areas are mandatory to prevent malposition-related nerve injuries. Anatomic knowledge of the course of nerves, especially ilioinguinal and iliohypogastric, nerves can minimize injury. Copyright © 2016 AAGL. Published by Elsevier Inc. All rights reserved.

  17. The clinical dilemma of "silent desensitization" in aspirin-exacerbated respiratory disease.

    PubMed

    White, Andrew A; Bosso, John V; Stevenson, Donald D

    2013-01-01

    Aspirin desensitization is a treatment option for patients with aspirin-exacerbated respiratory disease (AERD). Some patients with an excellent history of aspirin or nonsteroidal anti-inflammatory drug (NSAID) reactions have negative aspirin challenges/desensitization. This study discusses the clinical entity of silent desensitization in AERD and the dilemma that this presents to the practicing allergist/immunologist. We discuss a series of patients with a strong history of NSAID reactions who initially underwent a negative challenge/silent desensitization. These patients were subsequently proven to have AERD after a second positive aspirin challenge. Silent desensitization is an uncommon but important outcome to recognize in AERD. Clinicians performing aspirin desensitization should understand that this can occur and consider a second confirmatory aspirin challenge in some patients.

  18. Sensory nerve crush and regeneration and the receptive fields and response properties of neurons in the primary somatosensory cerebral cortex of cats.

    PubMed

    Brandenberg, G A; Mann, M D

    1989-03-01

    Extracellular recordings were made of activity evoked in neurons of the forepaw focus of somatosensory cerebral cortex by electrical stimulation of each paw in control cats and cats that had undergone crush injury of all cutaneous sensory nerves to the contralateral forepaw 31 to 63 days previously. Neurons responding only to stimulation of the contralateral forepaw were classified as sa; neurons responding to stimulation of both forepaws were classified as sb; neurons responding to stimulation of both contralateral paws were classified as sc; and neurons responding to stimulation of at least three paws were classified as m. The ratio sa:sb:sc:m neurons was 46:3:0:0 in control cats and 104:15:3:26 in cats that had undergone nerve crush 1-2 months prior to study. sa neurons from experimental cats had depth distributions similar to those in controls and responded to contralateral forepaw stimulation with more spikes per discharge, longer latency, and higher threshold than sa neurons in control cats. m neurons from experimental cats were distributed deeper in the cortex than sa neurons, and, when compared to experimental sa neurons, they responded with longer latency and poorer frequency-following ability; however, the number of spikes per discharge and threshold were not significantly different. The appearance of wide-field neurons in this tissue may be explained in terms of strengthening of previously sub-threshold inputs to neurons in the somatosensory system. If the neurons in sensory cortex play a requisite role in cutaneous sensations and if changes similar to those reported here occur and persist in human cortex after nerve crush, then "complete" recovery of sensation in such patients may occur against a background of changed cortical neuronal responsiveness.

  19. 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

  20. Efficacy, outcomes, and cost-effectiveness of desensitization using IVIG and rituximab.

    PubMed

    Vo, Ashley A; Petrozzino, Jeffrey; Yeung, Kai; Sinha, Aditi; Kahwaji, Joseph; Peng, Alice; Villicana, Rafael; Mackowiak, John; Jordan, Stanley C

    2013-03-27

    Transplantation rates are very low for the broadly sensitized patient (panel reactive antibody [PRA]>80%; HS). Here, we examine the efficacy, outcomes, and cost-effectiveness of desensitization using high-dose intravenous immunoglobulin (IVIG) and rituximab to improve transplantation rates in HS patients. From July 2006 to December 2011, 207 HS (56 living donors/151 deceased donors) patients (donor-specific antibody positive, PRA>80%) were desensitized using IVIG and rituximab. After desensitization, responsive patients proceeded to transplantation with an acceptable crossmatch. Cost and outcomes of desensitization were compared with dialysis. Of the 207 treated patients, 146 (71%) were transplanted. At 48 months, patient and graft survival by Kaplan-Meier were 95% and 87.5%, respectively. The total 3-year cost for patients treated in the desensitization arm was $219,914 per patient compared with $238,667 per patient treated in the dialysis arm. Thus, each patient treated with desensitization is estimated to save the U.S. healthcare system $18,753 in 2011 USD. Overall, estimated patient survival at the end of 3 years was 96.6% for patients in the desensitization arm of the model (based on Cedars-Sinai survival rate) compared with 79.0% for an age, end-stage renal disease etiology, and PRA matched group of patients remaining on dialysis during the study period. We conclude that desensitization with IVIG+rituximab is clinically and cost-effective, with both financial savings and an estimated 17.6% greater probability of 3-year survival associated with desensitization versus dialysis alone. However, the benefits of desensitization and transplantation are limited by organ availability and allocation policies.

  1. Aspirin desensitization in aspirin-sensitive asthma: failure to maintain a desensitized state during prolonged therapy.

    PubMed

    Dankner, R E; Wedner, H J

    1983-11-01

    A patient with a history of asthma induced by acetylsalicylic acid (ASA) was found to be ASA sensitive when orally challenged with ASA. She was successfully desensitized using incremental doses of ASA given orally and maintained on ASA or other nonsteroidal antiinflammatory (NSAI) agents for the treatment of arthritis. After 6 months of uninterrupted therapy the patient developed asthmatic symptoms that were related to ASA and NSAI drug therapy. Although desensitization may be achieved in patients with ASA-sensitive asthma, sensitivity may recur despite continuous therapy.

  2. 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

  3. 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. © 2011 Peripheral Nerve Society.

  4. 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.
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  5. Hereditary sensory ataxic neuropathy associated with proximal muscle weakness in the lower extremities.

    PubMed

    Murakami, Tatsufumi; Fukai, Yuta; Rikimaru, Mitsue; Henmi, Shoji; Ohsawa, Yutaka; Sunada, Yoshihide

    2010-04-15

    We describe three patients from the same family with hereditary sensory ataxic neuropathy followed by proximal muscle weakness in the lower extremities. Sensory ataxic gait began as an initial symptom when patients were in their 50s. Mild proximal weakness in the lower extremities appeared several years later. Serum creatine kinase was mildly elevated. Nerve conduction studies revealed sensory dominant axonal neuropathy, and short sensory evoked potentials showed involvement of the sensory nerve axon, dorsal root ganglia and posterior funiculus of the spinal cord. Needle electromyography showed fibrillation, positive sharp waves, and multiple giant motor unit potentials, suggesting the involvement of anterior horn motor neurons or the anterior root. Autosomal recessive inheritance was considered, because of consanguinity. The disorder described here may be a new clinical entity with unique clinical manifestations. Copyright 2009 Elsevier B.V. All rights reserved.

  6. Relationship between Semmes-Weinstein Monofilaments perception Test and sensory nerve conduction studies in Carpal Tunnel Syndrome.

    PubMed

    Raji, Parvin; Ansari, Noureddin Nakhostin; Naghdi, Soofia; Forogh, Bijan; Hasson, Scott

    2014-01-01

    The Semmes-Weinstein Monofilament Test (SWMT) is a clinical widely used test to quantify the sensibility in patients with Carpal Tunnel Syndrome (CTS). No study has investigated the relationship between the SWMT and sensory nerve conduction studies (SNCS) in patients with CTS. To assess the relationship between the SWMT and SNCS findings in patients with CTS. This cross-sectional clinical measurement study included 35 patients with CTS (55 hands) with a mean age of 45 ± 12 years. The outcome measures were the SWMT and SNCS measures of distal latency (DLs), amplitude (AMPs), and nerve conduction velocity (NCV). The median innervated fingers were tested using SWMT and electrodiagnostic tests. The primary outcome was the correlations between the SWMTs and NCS measures. All of the patients/hands had abnormal NCS findings. When looking at the three digits of interest (thumb, index and middle), the thumb SWMTs had the highest number of abnormal findings (58.2%), with the middle digit having the lowest (45.5%). All NCS findings were statistically different between abnormal and normal thumb SWMTs and abnormal and normal total summed SWMTs. There were significant moderate correlations between thumb SWMT scores and all NCS outcomes. Although only approximately 50% of the CTS diagnosed through NCS are corroborated through SWMT; the significant associations between SWMT and NCS measures suggest that SWMT is a valid test for assessing sensations in patients with CTS.

  7. A unified model of the excitability of mouse sensory and motor axons.

    PubMed

    Makker, Preet G S; Matamala, José Manuel; Park, Susanna B; Lees, Justin G; Kiernan, Matthew C; Burke, David; Moalem-Taylor, Gila; Howells, James

    2018-06-19

    Non-invasive nerve excitability techniques have provided valuable insight into the understanding of neurological disorders. The widespread use of mice in translational research on peripheral nerve disorders and by pharmaceutical companies during drug development requires valid and reliable models that can be compared to humans. This study established a novel experimental protocol that enables comparative assessment of the excitability properties of motor and sensory axons at the same site in mouse caudal nerve, compared the mouse data to data for motor and sensory axons in human median nerve at the wrist, and constructed a mathematical model of the excitability of mouse axons. In a separate study, ischaemia was employed as an experimental manoeuvre to test the translational utility of this preparation. The patterns of mouse sensory and motor excitability were qualitatively similar to human studies under normal and ischaemic conditions. The most conspicuous differences between mouse and human studies were observed in the recovery cycle and the response to hyperpolarization. Modelling showed that an increase in temperature in mouse axons could account for most of the differences in the recovery cycle. The modelling also suggested a larger hyperpolarization-activated conductance in mouse axons. The kinetics of this conductance appeared to be much slower raising the possibility that an additional or different hyperpolarization-activated cyclic-nucleotide gated (HCN) channel isoform underlies the accommodation to hyperpolarization in mouse axons. Given a possible difference in HCN isoforms, caution should be exercised in extrapolating from studies of mouse motor and sensory axons to human nerve disorders. This article is protected by copyright. All rights reserved.

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

    PubMed

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

    2016-02-01

    Hypersensitivity reactions to chemotherapeutic agents can cause the discontinuation of first-line therapies. Chemotherapy desensitization is a safe, but labor-intensive, process to administer these important medications. A desensitization protocol can enable a patient to receive the entire target dose of a medication, even if the patient has a history of severe infusion reactions. In this article, the authors explain the pathophysiology of hypersensitivity reactions and describe the recent development of desensitization protocols in oncology. In part II of this article, which will appear in the April 2016 issue of the Clinical Journal of Oncology Nursing, the authors will give a detailed account of how a desensitization protocol is performed at an academic medical center.
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  9. Alterations in Corneal Sensory Nerves During Homeostasis, Aging, and After Injury in Mice Lacking the Heparan Sulfate Proteoglycan Syndecan-1.

    PubMed

    Pal-Ghosh, Sonali; Tadvalkar, Gauri; Stepp, Mary Ann

    2017-10-01

    To determine the impact of the loss of syndecan 1 (SDC1) on intraepithelial corneal nerves (ICNs) during homeostasis, aging, and in response to 1.5-mm trephine and debridement injury. Whole-mount corneas are used to quantify ICN density and thickness over time after birth and in response to injury in SDC1-null and wild-type (WT) mice. High-resolution three-dimensional imaging is used to visualize intraepithelial nerve terminals (INTs), axon fragments, and lysosomes in corneal epithelial cells using antibodies against growth associated protein 43 (GAP43), βIII tubulin, and LAMP1. Quantitative PCR was performed to quantify expression of SDC1, SDC2, SDC3, and SDC4 in corneal epithelial mRNA. Phagocytosis was assessed by quantifying internalization of fluorescently labeled 1-μm latex beads. Intraepithelial corneal nerves innervate the corneas of SDC1-null mice more slowly. At 8 weeks, ICN density is less but thickness is greater. Apically projecting intraepithelial nerve terminals and lysosome-associated membrane glycoprotein 1 (LAMP1) are also reduced in unwounded SDC1-null corneas. Quantitative PCR and immunofluorescence studies show that SDC3 expression and localization are increased in SDC1-null ICNs. Wild-type and SDC1-null corneas lose ICN density and thickness as they age. Recovery of axon density and thickness after trephine but not debridement wounds is slower in SDC1-null corneas compared with WT. Experiments assessing phagocytosis show reduced bead internalization by SDC1-null epithelial cells. Syndecan-1 deficiency alters ICN morphology and homeostasis during aging, reduces epithelial phagocytosis, and impairs reinnervation after trephine but not debridement injury. These data provide insight into the mechanisms used by sensory nerves to reinnervate after injury.

  10. Hereditary motor and sensory neuropathy-russe: new autosomal recessive neuropathy in Balkan Gypsies.

    PubMed

    Thomas, P K; Kalaydjieva, L; Youl, B; Rogers, T; Angelicheva, D; King, R H; Guergueltcheva, V; Colomer, J; Lupu, C; Corches, A; Popa, G; Merlini, L; Shmarov, A; Muddle, J R; Nourallah, M; Tournev, I

    2001-10-01

    A novel peripheral neuropathy of autosomal recessive inheritance has been identified in Balkan Gypsies and termed hereditary motor and sensory neuropathy-Russe (HMSN-R). We investigated 21 affected individuals from 10 families. Distal lower limb weakness began between the ages of 8 and 16 years, upper limb involvement beginning between 10 and 43 years, with an average of 22 years. This progressive disorder led to severe weakness of the lower limbs, generalized in the oldest subject (aged 57 years), and marked distal upper limb weakness. Prominent distal sensory loss involved all modalities, resulting in neuropathic joint degeneration in two instances. All patients showed foot deformity, and most showed hand deformity. Motor nerve conduction velocity was moderately reduced in the upper limbs but unobtainable in the legs. Sensory nerve action potentials were absent. There was loss of larger myelinated nerve fibers and profuse regenerative activity in the sural nerve. HMSN-R is a new form of autosomal recessive inherited HMSN caused by a single founder mutation in a 1 Mb interval on chromosome 10q.

  11. Desensitization for solid organ and hematopoietic stem cell transplantation.

    PubMed

    Zachary, Andrea A; Leffell, Mary S

    2014-03-01

    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. © 2014 The Authors. Immunological Reviews Published by John Wiley & Sons Ltd.

  12. Differential effects of myostatin deficiency on motor and sensory axons.

    PubMed

    Jones, Maria R; Villalón, Eric; Northcutt, Adam J; Calcutt, Nigel A; Garcia, Michael L

    2017-12-01

    Deletion of myostatin in mice (MSTN -/- ) alters structural properties of peripheral axons. However, properties like axon diameter and myelin thickness were analyzed in mixed nerves, so it is unclear whether loss of myostatin affects motor, sensory, or both types of axons. Using the MSTN -/- mouse model, we analyzed the effects of increasing the number of muscle fibers on axon diameter, myelin thickness, and internode length in motor and sensory axons. Axon diameter and myelin thickness were increased in motor axons of MSTN -/- mice without affecting internode length or axon number. The number of sensory axons was increased without affecting their structural properties. These results suggest that motor and sensory axons establish structural properties by independent mechanisms. Moreover, in motor axons, instructive cues from the neuromuscular junction may play a role in co-regulating axon diameter and myelin thickness, whereas internode length is established independently. Muscle Nerve 56: E100-E107, 2017. © 2017 Wiley Periodicals, Inc.

  13. 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

  14. Pre-differentiation of mesenchymal stromal cells in combination with a microstructured nerve guide supports peripheral nerve regeneration in the rat sciatic nerve model.

    PubMed

    Boecker, Arne Hendrik; van Neerven, Sabien Geraldine Antonia; Scheffel, Juliane; Tank, Julian; Altinova, Haktan; Seidensticker, Katrin; Deumens, Ronald; Tolba, Rene; Weis, Joachim; Brook, Gary Anthony; Pallua, Norbert; Bozkurt, Ahmet

    2016-02-01

    Many bioartificial nerve guides have been investigated pre-clinically for their nerve regeneration-supporting function, often in comparison to autologous nerve transplantation, which is still regarded as the current clinical gold standard. Enrichment of these scaffolds with cells intended to support axonal regeneration has been explored as a strategy to boost axonal regeneration across these nerve guides Ansselin et al. (1998). In the present study, 20 mm rat sciatic nerve defects were implanted with a cell-seeded microstructured collagen nerve guide (Perimaix) or an autologous nerve graft. Under the influence of seeded, pre-differentiated mesenchymal stromal cells, axons regenerated well into the Perimaix nerve guide. Myelination-related parameters, like myelin sheath thickness, benefitted from an additional seeding with pre-differentiated mesenchymal stromal cells. Furthermore, both the number of retrogradely labelled sensory neurons and the axon density within the implant were elevated in the cell-seeded scaffold group with pre-differentiated mesenchymal stromal cells. However, a pre-differentiation had no influence on functional recovery. An additional cell seeding of the Perimaix nerve guide with mesenchymal stromal cells led to an extent of functional recovery, independent of the differentiation status, similar to autologous nerve transplantation. These findings encourage further investigations on pre-differentiated mesenchymal stromal cells as a cellular support for peripheral nerve regeneration. © 2015 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

  15. Massed Group Desensitization in Reduction of Test-Anxiety

    ERIC Educational Resources Information Center

    Dawley, Harold H., Jr.; Wenrich, W. W.

    1973-01-01

    The results of this study of two groups of nursing students, one administered desensitization sessions, the other not, agree with earlier studies which indicate that massed group desensitization is an efficient and efficacious procedure for the reduction of anxiety-based disorders. (Author/KM)

  16. Cutaneous sensory and autonomic denervation in CADASIL.

    PubMed

    Nolano, Maria; Provitera, Vincenzo; Donadio, Vincenzo; Caporaso, Giuseppe; Stancanelli, Annamaria; Califano, Francesca; Pianese, Luigi; Liguori, Rocco; Santoro, Lucio; Ragno, Michele

    2016-03-15

    To assess the involvement of the peripheral nervous system in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) by means of immunofluorescence and confocal analysis of punch skin biopsies. We recruited 14 unrelated patients with CADASIL (M/F = 9/5; age 53.9 ± 10.5 years) and 52 healthy controls (M/F = 31/21; age 53.8 ± 9.8). Patients underwent clinical and neuroradiologic assessment. Three-millimeter punch skin biopsies were taken from the fingertip, the thigh, and the distal leg and processed using indirect immunofluorescence and a panel of primary antibodies to mark vessels and sensory and autonomic nerve fibers. Intraepidermal nerve fibers (IENF), Meissner corpuscles (MC), and sudomotor, vasomotor, and pilomotor nerves were assessed using confocal microscopy. In patients, compared to controls, we found a severe loss of IENF at the distal leg (p < 0.01), at the thigh (p < 0.01), and at the fingertip (p < 0.01) with a non-length-dependent pattern and a loss of MC (p < 0.01). A severe sudomotor, vasomotor, and pilomotor nerve fiber loss was found by semiquantitative evaluation. Along with nerve loss, a severe derangement of the vascular bed was observed. In our patient population, sensory and autonomic denervation did not correlate with age, sex, type of mutation, or MRI involvement. We found an involvement of the peripheral nervous system in patients with CADASIL through the assessment of cutaneous somatic and autonomic nerves. The neurovascular derangement observed in the skin may reflect, although to a lesser extent, what happens in the CNS. © 2016 American Academy of Neurology.

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

    PubMed

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

    2015-10-28

    Peripheral nerve gap defects lead to significant loss of sensory or motor function. Tissue engineering has become an important alternative to nerve repair. Sericin, a major component of silk, is a natural protein whose value in tissue engineering has just begun to be explored. Here, the first time use of sericin in vivo is reported as a long-term implant for peripheral nerve regeneration. A sericin nerve guidance conduit is designed and fabricated. This conduit is highly porous with mechanical strength matching peripheral nerve tissue. It supports Schwann cell proliferation and is capable of up-regulating the transcription of glial cell derived neurotrophic factor and nerve growth factor in Schwann cells. The sericin conduit wrapped with a silicone conduit (sericin/silicone double conduits) is used for bridging repair of a 5 mm gap in a rat sciatic nerve transection model. The sericin/silicone double conduits achieve functional recovery comparable to that of autologous nerve grafting as evidenced by drastically improved nerve function and morphology. Importantly, this improvement is mainly attributed to the sericin conduit as the silicone conduit alone only produces marginal functional recovery. This sericin/silicone-double-conduit strategy offers an efficient and valuable alternative to autologous nerve grafting for repairing damaged peripheral nerve. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  18. Disability following combat-sustained nerve injury of the upper limb.

    PubMed

    Rivera, J C; Glebus, G P; Cho, M S

    2014-02-01

    Injuries to the limb are the most frequent cause of permanent disability following combat wounds. We reviewed the medical records of 450 soldiers to determine the type of upper limb nerve injuries sustained, the rate of remaining motor and sensory deficits at final follow-up, and the type of Army disability ratings granted. Of 189 soldiers with an injury of the upper limb, 70 had nerve-related trauma. There were 62 men and eight women with a mean age of 25 years (18 to 49). Disabilities due to nerve injuries were associated with loss of function, neuropathic pain or both. The mean nerve-related disability was 26% (0% to 70%), accounting for over one-half of this cohort's cumulative disability. Patients injured in an explosion had higher disability ratings than those injured by gunshot. The ulnar nerve was most commonly injured, but most disability was associated with radial nerve trauma. In terms of the final outcome, at military discharge 59 subjects (84%) experienced persistent weakness, 48 (69%) had a persistent sensory deficit and 17 (24%) experienced chronic pain from scar-related or neuropathic pain. Nerve injury was the cause of frequent and substantial disability in our cohort of wounded soldiers.

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

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    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 themore » 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.« less

  20. [Features of peripheral nerve injuries in workers exposed to vibration: an analysis of 197 cases].

    PubMed

    Situ, J; Lin, C M; Qin, Z H; Zhu, D X; Lin, H; Zhang, F F; Zhang, J J

    2016-12-20

    Objective: To investigate the features of peripheral nerve injuries in workers exposed to vibration. Methods: A total of 197 male workers [median age: 34 years (21 - 50 years) ; median working years of vibration exposure: 7.3 years (1 - 20 years) ] engaged in grinding in an enterprise were enrolled. Their clinical data and electromyography results were analyzed to investigate the features of peripheral nerve impairment. Results: Of all workers, 96 (48.73%) had abnormal electromyography results. Of all workers, 88 (44.7%) had simple mild median nerve injury in the wrist, who accounted for 91.7% (88/96) of all workers with abnormal electromy-ography results. Six workers had ulnar nerve injury, superficial radial nerve injury, or/and superficial peroneal nerve injury and accounted for 6.3% of all workers with abnormal electromyography results. Of all workers, 88 had a reduced amplitude of median nerve sensory transduction, and 28 had slowed median nerve sensory transduction. A total of 46 workers were diagnosed with occupational hand-arm vibration disease and hospitalized for treatment. They were followed up for more than 4 months after leaving their jobs, and most of them showed improvements in neural electromyography results and returned to a normal state. Conclusion: Workers exposed to vibration have a high incidence rate of nerve injury in the hand, mainly sensory function impairment at the distal end of the median nerve, and all injuries are mild peripheral nerve injuries. After leaving the vibration job and being treated, most workers can achieve improvements and return to a normal state.

  1. Hereditary sensory and autonomic neuropathy type IID caused by an SCN9A mutation.

    PubMed

    Yuan, Junhui; Matsuura, Eiji; Higuchi, Yujiro; Hashiguchi, Akihiro; Nakamura, Tomonori; Nozuma, Satoshi; Sakiyama, Yusuke; Yoshimura, Akiko; Izumo, Shuji; Takashima, Hiroshi

    2013-04-30

    To identify the clinical features of Japanese patients with suspected hereditary sensory and autonomic neuropathy (HSAN) on the basis of genetic diagnoses. On the basis of clinical, in vivo electrophysiologic, and pathologic findings, 9 Japanese patients with sensory and autonomic nervous dysfunctions were selected. Eleven known HSAN disease-causing genes and 5 related genes were screened using a next-generation sequencer. A homozygous mutation, c.3993delGinsTT, was identified in exon 22 of SCN9A from 2 patients/families. The clinical phenotype was characterized by adolescent or congenital onset with loss of pain and temperature sensation, autonomic nervous dysfunctions, hearing loss, and hyposmia. Subsequently, this mutation was discovered in one of patient 1's sisters, who also exhibited sensory and autonomic nervous system dysfunctions, with recurrent fractures being the most predominant feature. Nerve conduction studies revealed definite asymmetric sensory nerve involvement in patient 1. In addition, sural nerve pathologic findings showed loss of large myelinated fibers in patient 1, whereas the younger patient showed normal sural nerve pathology. We identified a novel homozygous mutation in SCN9A from 2 Japanese families with autosomal recessive HSAN. This loss-of-function SCN9A mutation results in disturbances in the sensory, olfactory, and autonomic nervous systems. We propose that SCN9A mutation results in the new entity of HSAN type IID, with additional symptoms including hyposmia, hearing loss, bone dysplasia, and hypogeusia.

  2. Pungent products from garlic activate the sensory ion channel TRPA1

    PubMed Central

    Bautista, Diana M.; Movahed, Pouya; Hinman, Andrew; Axelsson, Helena E.; Sterner, Olov; Högestätt, Edward D.; Julius, David; Jordt, Sven-Eric; Zygmunt, Peter M.

    2005-01-01

    Garlic belongs to the Allium family of plants that produce organosulfur compounds, such as allicin and diallyl disulfide (DADS), which account for their pungency and spicy aroma. Many health benefits have been ascribed to Allium extracts, including hypotensive and vasorelaxant activities. However, the molecular mechanisms underlying these effects remain unknown. Intriguingly, allicin and DADS share structural similarities with allyl isothiocyanate, the pungent ingredient in wasabi and other mustard plants that induces pain and inflammation by activating TRPA1, an excitatory ion channel on primary sensory neurons of the pain pathway. Here we show that allicin and DADS excite an allyl isothiocyanate-sensitive subpopulation of sensory neurons and induce vasodilation by activating capsaicin-sensitive perivascular sensory nerve endings. Moreover, allicin and DADS activate the cloned TRPA1 channel when expressed in heterologous systems. These and other results suggest that garlic excites sensory neurons primarily through activation of TRPA1. Thus different plant genera, including Allium and Brassica, have developed evolutionary convergent strategies that target TRPA1 channels on sensory nerve endings to achieve chemical deterrence. PMID:16103371

  3. Inflammation role in sensory neuropathy in Chinese patients with diabetes/prediabetes.

    PubMed

    Zeng, Jing; Xu, Yalin; Shi, Yao; Jiang, Chenyin

    2018-03-01

    Prediabetes involves people with glucose-metabolism impairment, and is related to different diabetic complications, like peripheral neuropathy. We aimed to explore the relationship among inflammatory (tumor necrosis factor alpha [TNFα]) and antiinflammatory (interleukin 10 [IL10]) cytokines as well as neuropathy of very distal-sensory-nerves in Chinese patients with prediabetes/diabetes. In the present study, 55 patients having prediabetes, 55 patients having type 2 diabetes mellitus (DM), and 48 controls were included. TNFα, HbA1c, and IL10 plasma levels were measured. Electrodiagnosis was conducted on dorsal-sural/medial-plantar sensory nerve, that is most distal feet sensory-nerves. Nerve conduction test (NCT) irregularities of dorsal-sural/medial-plantar sensory nerve were considerably greater in patients with prediabetes or diabetes. The means of TNFα levels demonstrated a significant increase in patients with diabetes when compared to prediabetes patients as well as controls showed a significant decrease in patients with prediabetes and diabetes contrasted with controls. No significant contrast with respect to serum biomarkers among patients having regular as well as irregular medial-plantar/dorsal-sural NCT was noted. Critical correlationship among TNFα as well as HbA1c with symptoms severity as well as disability while negative correlations of IL10 with neuropathy severity was noted. Biomarker levels of TNFα, IL10, and HbA1c were noted to differ significantly among patients without/with neuropathy. All in all, the proinflammatory phase appears to start from initial pre-clinical phases, sometime prior to advancement of diabetes. The higher neuropathy frequency in patients with prediabetes indicates conceivable causative impact; although, the prospective part of inflammation in pathogenetics of peripheral neuropathy requires more elucidation. Copyright © 2018 Elsevier B.V. All rights reserved.

  4. Ulnar nerve sonography in leprosy neuropathy.

    PubMed

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

    2016-01-01

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

  5. Utility of nerve conduction studies for diagnosis of injury to the medial branch of the superficial radial nerve.

    PubMed

    Kon, Tomoya; Suzuki, Chieko; Hotta, Ryotaro; Funamizu, Yukihisa; Haga, Rie; Ueno, Tatsuya; Nishijima, Haruo; Arai, Akira; Nunomura, Jinichi; Nukada, Hitoshi; Tomiyama, Masahiko; Baba, Masayuki

    2017-09-01

    The clinical utility of nerve conduction study (NCS) for the distal medial branch of the superficial radial nerve (SRN) has not yet been clarified. Therefore, we investigated the clinical utility of NCS in patients with suspected SRN injury and compared the results with those in healthy control subjects. Bilateral NCS of the medial branch of the SRN was performed in two patients with suspected injury of the medial branch of the SRN, and in 20 healthy control subjects. A surface recording electrode was placed at the medial side of the metacarpophalangeal joint of the thumb. The SRN was then stimulated at a location 12 cm proximal from the recording electrode. The mean sensory nerve action potential in the two patients was significantly lower than that of the controls (6.75 ± 0.92 vs. 23.8 ± 8.2 μV, P  < 0.05). The side-to-side differences in sensory nerve action potential in the two patients were significantly higher than in the controls (55 ± 7.1 vs. 11 ± 7.8%, P  < 0.05). NCS may be useful for diagnosing injury of the medial branch of the SRN.

  6. Pilot study of intraoperative ultrasound-guided instrument placement in nerve transection surgery for peripheral nerve pain syndromes.

    PubMed

    Henning, P Troy; Wilson, Thomas J; Willsey, Matthew; John, Jessin K; Popadich, Miriana; Yang, Lynda J S

    2017-03-01

    Surgical transection of sensory nerves in the treatment of intractable neuropathic pain is a commonly performed procedure. At times these cases can be particularly challenging when encountering obese patients, when targeting deeper nerves or those with a variable branching pattern, or in the case of repeat operations. In this case series, the authors describe their experience with ultrasound-guided surgical instrument placement during transection of a saphenous nerve in the region of prior vascular surgery in 1 patient and in the lateral femoral cutaneous nerve in 2 obese patients. The authors also describe this novel technique and provide pilot data that suggests ultrasound-assisted surgery may allow for complex cases to be completed in an expedited fashion through smaller incisions.

  7. Clopidogrel (Plavix) desensitization: a case series.

    PubMed

    Camara, Miguel G; Almeda, Francis Q

    2005-08-01

    Clopidogrel (Plavix) is a thiopyridine that inhibits the ADP-dependent pathway for platelet activation and has been shown in numerous trials to be effective for a wide variety of patients with cardiovascular disease, particularly those who have undergone coronary stent implantation and who present with acute coronary syndromes. Allergic rashes are one of the common side effects of clopidogrel, which leads to its discontinuation. Type I (Gell and Combs classification) allergic reactions to drugs may be amenable to drug desensitization, allowing safe and prolonged use of the drug. This case series describes a protocol for clopidogrel desensitization over an 8-hr period using 15 doubling doses of clopidogrel given by mouth to achieve a maintenance dose of 75 mg a day. This case series suggests that patients who have had type I drug allergy to clopidogrel may be rapidly desensitized using this protocol. Further studies enrolling a larger number of patients are indicated to confirm the safety and efficacy of this regimen.

  8. The nerve supply of the lumbar intervertebral disc.

    PubMed

    Edgar, M A

    2007-09-01

    The anatomical studies, basic to our understanding of lumbar spine innervation through the sinu-vertebral nerves, are reviewed. Research in the 1980s suggested that pain sensation was conducted in part via the sympathetic system. These sensory pathways have now been clarified using sophisticated experimental and histochemical techniques confirming a dual pattern. One route enters the adjacent dorsal root segmentally, whereas the other supply is non-segmental ascending through the paravertebral sympathetic chain with re-entry through the thoracolumbar white rami communicantes. Sensory nerve endings in the degenerative lumbar disc penetrate deep into the disrupted nucleus pulposus, insensitive in the normal lumbar spine. Complex as well as free nerve endings would appear to contribute to pain transmission. The nature and mechanism of discogenic pain is still speculative but there is growing evidence to support a 'visceral pain' hypothesis, unique in the muscloskeletal system. This mechanism is open to 'peripheral sensitisation' and possibly 'central sensitisation' as a potential cause of chronic back pain.

  9. Performing Aspirin Desensitization in Aspirin-Exacerbated Respiratory Disease.

    PubMed

    Waldram, Jeremy D; Simon, Ronald A

    2016-11-01

    Aspirin-exacerbated respiratory disease (AERD) is characterized by chronic rhinosinusitis with nasal polyps, asthma, and reactions to cyclooxygenase-1-inhibiting drugs. This condition is often refractory to standard medical treatments and results in aggressive nasal polyposis that often requires multiple sinus surgeries. Aspirin desensitization followed by daily aspirin therapy is an important treatment option, and its efficacy has been validated in multiple research studies. Aspirin desensitization is not without risk, but specific protocols and recommendations exist to mitigate the risk. Most patients with AERD can undergo aspirin desensitization in an outpatient setting under the supervision of an allergist. Copyright © 2016 Elsevier Inc. All rights reserved.

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

    PubMed

    Erin, Nuray; Duymuş, Ozlem; Oztürk, Saffet; Demir, Necdet

    2012-11-10

    Chronic inflammation is involved in initiation as well as in progression of cancer. Semapimod, a tetravalent guanylhydrazon and formerly known as CNI-1493, inhibits the release of inflammatory cytokines from activated macrophages and this effect is partly mediated by the vagus nerve. Our previous findings demonstrated that inactivation of vagus nerve activity as well sensory neurons enhanced visceral metastasis of 4THM breast carcinoma. Hence semapimod by activating vagus nerve may inhibit breast cancer metastasis. Here, effects of semapimod on breast cancer metastasis, the role of vagal sensory neurons on this effect and changes in mediators of the neuroimmune connection, such as substance P (SP) as well as neprilysin-like activity, were examined. Vagotomy was performed on half of the control animals that were treated with semapimod following orthotopic injection of 4THM breast carcinoma cells. Semapimod decreased lung and liver metastases in control but not in vagotomized animals with an associated increased SP levels in sensory nerve endings. Semapimod also increased neprilysin-like activity in lung tissue of control animals but not in tumor-bearing animals. This is the first report demonstrating that semapimod enhances vagal sensory nerve activity and may have anti-tumoral effects under in-vivo conditions. Further studies, however, are required to elucidate the conditions and the mechanisms involved in anti-tumoral effects of semapimod. Copyright © 2012 Elsevier B.V. All rights reserved.

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

    PubMed

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

    2016-01-01

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

  12. Drug Hypersensitivity and Desensitizations: Mechanisms and New Approaches

    PubMed Central

    de las Vecillas Sánchez, Leticia; Alenazy, Leila A.; Garcia-Neuer, Marlene; Castells, Mariana C.

    2017-01-01

    Drug hypersensitivity reactions (HSRs) are increasing in the 21st Century with the ever expanding availability of new therapeutic agents. Patients with cancer, chronic inflammatory diseases, cystic fibrosis, or diabetes can become allergic to their first line therapy after repeated exposures or through cross reactivity with environmental allergens. Avoidance of the offending allergenic drug may impact disease management, quality of life, and life expectancy. Precision medicine provides new tools for the understanding and management of hypersensitivity reactions (HSRs), as well as a personalized treatment approach for IgE (Immunoglobuline E) and non-IgE mediated HSRs with drug desensitization (DS). DS induces a temporary hyporesponsive state by incremental escalation of sub-optimal doses of the offending drug. In vitro models have shown evidence that IgE desensitization is an antigen-specific process which blocks calcium flux, impacts antigen/IgE/FcεRI complex internalization and prevents the acute and late phase reactions as well as mast cell mediator release. Through a “bench to bedside” approach, in vitro desensitization models help elucidate the molecular pathways involved in DS, providing new insights to improved desensitization protocols for all patients. The aim of this review is to summarize up to date information on the drug HSRs, the IgE mediated mechanisms of desensitization, and their clinical applications. PMID:28632196

  13. Long-term sinonasal outcomes of aspirin desensitization in aspirin exacerbated respiratory disease.

    PubMed

    Cho, Kyu-Sup; Soudry, Ethan; Psaltis, Alkis J; Nadeau, Kari C; McGhee, Sean A; Nayak, Jayakar V; Hwang, Peter H

    2014-10-01

    This study aimed to assess sinonasal outcomes in patients with aspirin exacerbated respiratory disease (AERD) undergoing aspirin desensitization following endoscopic sinus surgery (ESS). Case series with chart review. University hospital. A retrospective review of sinonasal outcomes was conducted for 30 AERD patients undergoing aspirin desensitization and maintenance therapy following ESS. Sinonasal outcomes were prospectively assessed by the Sinonasal Outcomes Test-22 (SNOT-22) and endoscopic polyp grading system. Data were collected preoperatively, 1 and 4 weeks postsurgery (before desensitization), and 1, 6, 12, 18, 24, and 30 months after aspirin desensitization. Twenty-eight of 30 patients (93.3%) successfully completed aspirin desensitization, whereas 2 of 30 (6.7%) were unable to complete desensitization due to respiratory intolerance. Of the 21 patients who successfully completed a minimum of 24 weeks of follow-up, 20 (95.2%) patients demonstrated sustained endoscopic and symptomatic improvement for a median follow-up period of 33 months. After surgical treatment but before desensitization, patients experienced significant reductions in SNOT-22 and polyp grade scores. In the first 6 months after aspirin desensitization, patients experienced further significant reductions in SNOT-22 scores, whereas polyp grade remained stable. The improvements in symptom endoscopic scores were preserved throughout the follow-up period after desensitization. No patients required additional sinus surgery. One patient had to discontinue aspirin therapy due to gastrointestinal side effects. No other adverse reactions to aspirin were noted. Aspirin desensitization following ESS appears to be a well-tolerated and effective adjunctive therapy for long-term control of nasal polyposis in patients with AERD. © American Academy of Otolaryngology—Head and Neck Surgery Foundation 2014.

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

    PubMed Central

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

    2002-01-01

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

  15. Progress in Desensitization of the Highly HLA Sensitized Patient.

    PubMed

    Jordan, S C; Choi, J; Kahwaji, J; Vo, A

    2016-04-01

    The presence of HLA antibodies remains a significant and often impenetrable barrier to kidney transplantation, leading to increased morbidity and mortality for patients remaining on long-term dialysis. In recent years, a number of new approaches have been developed to overcome these barriers. Intravenous immunoglobulin (IVIG) remains the lynchpin of HLA desensitization therapy and has been shown in a prospective, randomized, placebo-controlled trial to improve transplantation rates. In addition, IVIG used in low doses with plasma exchange is a reliable protocol for desensitization. Another significant advancement was the addition of rituximab (anti-B-cell therapy) to IVIG and plasma exchange-based desensitization. This approach has significantly improved rates of transplantation and outcomes. There is limited experience with bortezomib (anti-plasma cell therapy) and eculizumab (complement inhibition) for desensitization. However, recent data from a completed trial of eculizumab failed to show a significant benefit for prevention of antibody-mediated rejection compared with standard therapy plus placebo, and bortezomib produced inconsistent results. There is a growing interest in developing new therapeutic agents for desensitization. Newer approaches that address antibody reduction with B-cell depletion are discussed. Copyright © 2016 Elsevier Inc. All rights reserved.

  16. Investigating the role of MRGPRC11 and capsaicin-sensitive afferent nerves in the anti-influenza effects exerted by SLIGRL-amide in murine airways.

    PubMed

    Chang, Amy Y; Mann, Tracy S; McFawn, Peter K; Han, Liang; Dong, Xinzhong; Henry, Peter J

    2016-05-23

    The hexapeptide SLIGRL-amide activates protease-activated receptor-2 (PAR-2) and mas-related G protein-coupled receptor C11 (MRGPRC11), both of which are known to be expressed on populations of sensory nerves. SLIGRL-amide has recently been reported to inhibit influenza A (IAV) infection in mice independently of PAR-2 activation, however the explicit roles of MRGPRC11 and sensory nerves in this process are unknown. Thus, the principal aim of this study was to determine whether SLIGRL-amide-induced inhibition of influenza infection is mediated by MRGPRC11 and/or by capsaicin-sensitive sensory nerves. The inhibitory effect of SLIGRL-amide on IAV infection observed in control mice in vivo was compared to effects produced in mice that did not express MRGPRC11 (mrgpr-cluster∆ (-/-) mice) or had impaired sensory nerve function (induced by chronic pre-treatment with capsaicin). Complementary mechanistic studies using both in vivo and ex vivo approaches investigated whether the anti-IAV activity of SLIGRL-amide was (1) mimicked by either activators of MRGPRC11 (BAM8-22) or by activators (acute capsaicin) or selected mediators (substance P, CGRP) of sensory nerve function, or (2) suppressed by inhibitors of sensory nerve function (e.g. NK1 receptor antagonists). SLIGRL-amide and BAM8-22 dose-dependently inhibited IAV infection in mrgpr-cluster∆ (-/-) mice that do not express MRGPRC11. In addition, SLIGRL-amide and BAM8-22 each inhibited IAV infection in capsaicin-pre-treated mice that lack functional sensory nerves. Furthermore, the anti-IAV activity of SLIGRL-amide was not mimicked by the sensory neuropeptides substance P or CGRP, nor blocked by either NK1 (L-703,606, RP67580) and CGRP receptor (CGRP8-37) antagonists. Direct stimulation of airway sensory nerves through acute exposure to the TRPV1 activator capsaicin also failed to mimic SLIGRL-amide-induced inhibition of IAV infectivity. The anti-IAV activity of SLIGRL-amide was mimicked by the purinoceptor agonist ATP

  17. Feeding-dependent activation of enteric cells and sensory neurons by lymphatic fluid: evidence for a neurolymphocrine system

    PubMed Central

    Poole, Daniel P.; Lee, Mike; Tso, Patrick; Bunnett, Nigel W.; Yo, Sek Jin; Lieu, TinaMarie; Shiu, Amy; Wang, Jen-Chywan; Nomura, Daniel K.

    2014-01-01

    Lymphatic fluid is a plasma filtrate that can be viewed as having biological activity through the passive accumulation of molecules from the interstitial fluid. The possibility that lymphatic fluid is part of an active self-contained signaling process that parallels the endocrine system, through the activation of G-protein coupled receptors (GPCR), has remained unexplored. We show that the GPCR lysophosphatidic acid 5 (LPA5) is found in sensory nerve fibers expressing calcitonin gene-related peptide (CGRP) that innervate the lumen of lymphatic lacteals and enteric nerves. Using LPA5 as a model for nutrient-responsive GPCRs present on sensory nerves, we demonstrate that dietary protein hydrolysate (peptone) can induce c-Fos expression in enterocytes and nerves that express LPA5. Mesenteric lymphatic fluid (MLF) mobilizes intracellular calcium in cell models expressing LPA5 upon feeding in a time- and dose-dependent manner. Primary cultured neurons of the dorsal root ganglia expressing CGRP are activated by MLF, which is enhanced upon LPA5 overexpression. Activation is independent of the known LPA5 agonists, lysophosphatidic acid and farnesyl pyrophosphate. These data bring forth a pathway for the direct stimulation of sensory nerves by luminal contents and interstitial fluid. Thus, by activating LPA5 on sensory nerves, MLF provides a means for known and yet to be identified constituents of the interstitial fluid to act as signals to comprise a “neurolymphocrine” system. PMID:24578341

  18. Sciatic Nerve Injury After Proximal Hamstring Avulsion and Repair.

    PubMed

    Wilson, Thomas J; Spinner, Robert J; Mohan, Rohith; Gibbs, Christopher M; Krych, Aaron J

    2017-07-01

    Muscle bellies of the hamstring muscles are intimately associated with the sciatic nerve, putting the sciatic nerve at risk of injury associated with proximal hamstring avulsion. There are few data informing the magnitude of this risk, identifying risk factors for neurologic injury, or determining neurologic outcomes in patients with distal sciatic symptoms after surgery. To characterize the frequency and nature of sciatic nerve injury and distal sciatic nerve-related symptoms after proximal hamstring avulsion and to characterize the influence of surgery on these symptoms. Cohort study; Level of evidence, 3. This was a retrospective review of patients with proximal partial or complete hamstring avulsion. The outcome of interest was neurologic symptoms referable to the sciatic nerve distribution below the knee. Neurologic symptoms in operative patients were compared pre- and postoperatively. The cohort consisted of 162 patients: 67 (41.4%) operative and 95 (58.6%) nonoperative. Sciatic nerve-related symptoms were present in 22 operative and 23 nonoperative patients, for a total of 45 (27.8%) patients (8 [4.9%] motor deficits, 11 [6.8%] sensory deficits, and 36 [22.2%] with neuropathic pain). Among the operative cohort, 3 of 3 (100.0%) patients showed improvement in their motor deficit postoperatively, 3 of 4 (75.0%) patients' sensory symptoms improved, and 17 of 19 (89.5%) patients had improvement in pain. A new or worsening deficit occurred in 5 (7.5%) patients postoperatively (2 [3.1%] motor deficits, 1 [1.5%] sensory deficit, and 3 [4.5%] with new pain). Predictors of operative intervention included lower age (odds ratio [OR], 0.952; 95% CI, 0.921-0.982; P = .001) and complete avulsion (OR, 10.292; 95% CI, 2.526-72.232; P < .001). Presence of neurologic deficit was not predictive. Sciatic nerve-related symptoms after proximal hamstring avulsion are underrecognized. Currently, neurologic symptoms are not considered when determining whether to pursue operative

  19. Effects of a sensory branch to the posterior external ear canal: coughing, pain, Ramsay Hunt's syndrome and Hitselberger's sign.

    PubMed

    Mulazimoglu, S; Flury, R; Kapila, S; Linder, T

    2017-04-01

    A distinct nerve innervating the external auditory canal can often be identified in close relation to the facial nerve when gradually thinning the posterior canal wall. This nerve has been attributed to coughing during cerumen removal, neuralgic pain, Hitselberger's sign and vesicular eruptions described in Ramsay Hunt's syndrome. This study aimed to demonstrate the origin and clinical impact of this nerve. In patients with intractable otalgia or severe coughing whilst inserting a hearing aid, who responded temporarily to local anaesthesia, the symptoms could be resolved by sectioning a sensory branch to the posterior canal. In a temporal bone specimen, it was revealed that this nerve is predominantly a continuation of Arnold's nerve, also receiving fibres from the glossopharyngeal nerve and facial nerve. Histologically, the communicating branch from the facial nerve was confirmed. Surgeons should be aware of the posterior auricular sensory branch and its clinical implications.

  20. Desensitization by noradrenaline of responses to stimulation of pre- and postsynaptic adrenoceptors

    PubMed Central

    Ball, N.; Danks, J.L.; Dorudi, S.; Nasmyth, P.A.

    1982-01-01

    1 The effect of exposing isolated preparations of rat aortic strip, rat atria and mouse vas deferens to perfusions of Krebs solution containing various concentrations of noradrenaline on their sensitivity to the drug has been determined. 2 The responses evoked by stimulation of postsynaptic adrenoceptors in all the tissues and presynaptic α-adrenoceptors in the mouse vas deferens were diminished by the perfusion of noradrenaline through the organ bath for 30 min. 3 The concentration of noradrenaline required to produce desensitization was higher in the mouse vas deferens than in the other tissues and more was required to desensitize the chronotropic responses than the inotropic responses in rat isolated atria. 4 The inclusion of cocaine (10-5 M) in the bathing solution to block uptake1 increased the sensitivity of most tissues to noradrenaline. With the possible exception of the response to stimulation of presynaptic receptors in the mouse vas deferens, desensitization was somewhat increased in its presence. 5 When uptake2 was blocked by oestradiol (10-5 M), it was not possible to desensitize the contractor responses of the aortic strip and vas deferens to exogenous noradrenaline, nor the inotropic response of the atria to the drug. However, oestradiol failed to block the desensitization of chronotropic responses and responses to stimulation of presynaptic receptors in the vas deferens. 6 Blockade of monoamine oxidase (MAO) with iproniazid (7.2 × 10-4 M) or with pargyline (5 × 10-4 M) did not affect the desensitization process in the aortic strip. 7 Blockade of catechol-O-methyltransferase (COMT) with U-0521 (5.3 × 10-5 M) greatly increased desensitization in the aortic strip and desensitization of inotropic responses in the atria. It had no effect on desensitization of chronotropic responses. Its effect on responses in the mouse vas deferens was not determined. 8 The perfusion of methoxamine at concentrations about 1000 times higher than those of noradrenaline

  1. Omalizumab facilitates rapid oral desensitization for peanut allergy

    PubMed Central

    MacGinnitie, Andrew J.; Rachid, Rima; Gragg, Hana; Little, Sara V; Lakin, Paul; Cianferoni, Antonella; Heimall, Jennifer; Makhija, Melanie; Robison, Rachel; Chinthrajah, R. Sharon; Lee, John; Lebovidge, Jennifer; Dominguez, Tina; Rooney, Courtney; Lewis, Megan Ott; Koss, Jennifer; Burke-Roberts, Elizabeth; Chin, Kimberly; Logvinenko, Tanya; Pongracic, Jacqueline A.; Umetsu, Dale T.; Spergel, Jonathan; Nadeau, Kari C.; Schneider, Lynda C.

    2017-01-01

    Background Peanut oral immunotherapy (OIT) is a promising approach to peanut allergy but reactions are frequent and some patients cannot be desensitized. The anti-IgE medication omalizumab (Xolair) may allow more rapid peanut updosing and decrease reactions. Objective To evaluate if omalizumab facilitated rapid peanut desensitization in highly allergic patients. Methods Thirty-seven subjects were randomized to omalizumab (n=29) or placebo (n=8). After 12 weeks of treatment subjects underwent a rapid one-day desensitization of up to 250 mg of peanut protein, followed by weekly increases up to 2000 mg. Omalizumab was then discontinued and subjects continued on 2000 mg of peanut protein. They underwent an open challenge to 4000 mg peanut protein twelve weeks after stopping study drug. If tolerated, subjects continued on 4000 mg of peanut protein daily. Results The median peanut dose tolerated on the initial desensitization day was 250 mg for omalizumab versus 22.5 mg for placebo treated subject. Subsequently 23 of 29 (79%) subjects randomized to omalizumab tolerated 2000 mg peanut protein 6 weeks after stopping omalizumab versus 1 of 8 (12%) receiving placebo (p<0.01). Twenty-three subjects on omalizumab versus 1 on placebo passed the 4000 mg food challenge. Overall reaction rates were not significantly lower in omalizumab versus placebo treated subjects (OR=0.57 p=0.15), although omalizumab treated subjects were exposed to much higher doses of peanut. Conclusion Omalizumab allows subjects with peanut allergy to be rapidly desensitized over as little as 8 weeks of peanut OIT. In the majority of subjects, this desensitization is sustained after omalizumab is discontinued. Additional studies will help clarify which patients would benefit most from this approach. PMID:27609658

  2. Silicone Molding and Lifetime Testing of Peripheral Nerve Interfaces for Neuroprostheses

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Gupte, Kimaya; Tolosa, Vanessa

    Implantable peripheral nerve cuffs have a large application in neuroprostheses as they can be used to restore sensation to those with upper limb amputations. Modern day prosthetics, while lessening the pain associated with phantom limb syndrome, have limited fine motor control and do not provide sensory feedback to patients. Sensory feedback with prosthetics requires communication between the nervous system and limbs, and is still a challenge to accomplish with amputees. Establishing this communication between the peripheral nerves in the arm and artificial limbs is vital as prosthetics research aims to provide sensory feedback to amputees. Peripheral nerve cuffs restore sensationmore » by electrically stimulating certain parts of the nerve in order to create feeling in the hand. Cuff electrodes have an advantage over standard electrodes as they have high selective stimulation by bringing the electrical interface close to the neural tissue in order to selectively activate targeted regions of a peripheral nerve. In order to further improve the selective stimulation of these nerve cuffs, there is need for finer spatial resolution among electrodes. One method to achieve a higher spatial resolution is to increase the electrode density on the cuff itself. Microfabrication techniques can be used to achieve this higher electrode density. Using L-Edit, a layout editor, microfabricated peripheral nerve cuffs were designed with a higher electrode density than the current model. This increase in electrode density translates to an increase in spatial resolution by at least one order of magnitude. Microfabricated devices also have two separate components that are necessary to understand before implantation: lifetime of the device and assembly to prevent nerve damage. Silicone molding procedures were optimized so that devices do not damage nerves in vivo, and lifetime testing was performed on test microfabricated devices to determine their lifetime in vivo. Future work of this

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

    PubMed Central

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

    2011-01-01

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

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

    USDA-ARS?s Scientific Manuscript database

    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...

  5. Rapid polyclonal desensitization with antibodies to IgE and FcεRIα

    PubMed Central

    Khodoun, Marat V.; Kucuk, Zeynep Yesim; Strait, Richard T.; Krishnamurthy, Durga; Janek, Kevin; Lewkowich, Ian; Morris, Suzanne C.; Finkelman, Fred D.

    2013-01-01

    Background Rapid desensitization,a procedure in which individuals allergic to an antigen are treated at short intervals with increasing doses of that antigen until they tolerate a large dose, is an effective, but risky way to induce temporary tolerance. Objective To determine whether this approach can be adapted to suppress all IgE-mediated in mice by injecting serially increasing doses of monoclonal antibodies (mAbs) to IgE or FcεRIα. Methods Active and passive models of antigen- and anti-IgE mAb-induced IgE-mediated anaphylaxis were used. Mice were desensitized with serially increasing doses of anti-IgE mAb, anti-FcεRIα mAb or antigen. Development of shock (hypothermia), histamine and mast cell protease release, cytokine secretion, calcium flux and changes in cell number and FcεRI and IgE expression were evaluated. Results Rapid desensitization with anti-IgE mAb suppressed IgE-mediated immediate hypersensitivity; however, some mice developed mild anaphylaxis during desensitization. Rapid desensitization with anti-FcεRIα mAb that only binds FcεRI that is not occupied by IgE suppressed both active and passive IgE-mediated anaphylaxis without inducing disease. It quickly, but temporarily, suppressed IgE-mediated anaphylaxis by decreasing mast cell signaling through FcεRI, then slowly slowlyinduced longer lasting mast cell unresponsiveness by removing membrane FcεRI. Rapid desensitization with anti-FcεRIα mAb was safer and longer-lasting than rapid desensitization with antigen. Conclusion A rapid desensitization approach with anti-FcεRIα mAb safely desensitizes mice to IgE-mediated anaphylaxis by inducing mast cell anergy and later, removing all mast cell IgE. Rapid desensitization with an anti-human FcεRIα mAb may be able to prevent human IgE-mediated anaphylaxis. PMID:23632296

  6. Nerve Growth Factor Inhibits Sympathetic Neurons' Response to an Injury Cytokine

    NASA Astrophysics Data System (ADS)

    Shadiack, Annette M.; Vaccariello, Stacey A.; Sun, Yi; Zigmond, Richard E.

    1998-06-01

    Axonal damage to adult peripheral neurons causes changes in neuronal gene expression. For example, axotomized sympathetic, sensory, and motor neurons begin to express galanin mRNA and protein, and recent evidence suggests that galanin plays a role in peripheral nerve regeneration. Previous studies in sympathetic and sensory neurons have established that galanin expression is triggered by two consequences of nerve transection: the induction of leukemia inhibitory factor (LIF) and the reduction in the availability of the target-derived factor, nerve growth factor. It is shown in the present study that no stimulation of galanin expression occurs following direct application of LIF to intact neurons in the superior cervical sympathetic ganglion. Injection of animals with an antiserum to nerve growth factor concomitant with the application of LIF, on the other hand, does stimulate galanin expression. The data suggest that the response of neurons to an injury factor, LIF, is affected by whether the neurons still receive trophic signals from their targets.

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

    PubMed

    Navarro, Xavier

    2016-02-01

    Peripheral nerve injuries usually lead to severe loss of motor, sensory and autonomic functions in the patients. Due to the complex requirements for adequate axonal regeneration, functional recovery is often poorly achieved. Experimental models are useful to investigate the mechanisms related to axonal regeneration and tissue reinnervation, and to test new therapeutic strategies to improve functional recovery. Therefore, objective and reliable evaluation methods should be applied for the assessment of regeneration and function restitution after nerve injury in animal models. This review gives an overview of the most useful methods to assess nerve regeneration, target reinnervation and recovery of complex sensory and motor functions, their values and limitations. The selection of methods has to be adequate to the main objective of the research study, either enhancement of axonal regeneration, improving regeneration and reinnervation of target organs by different types of nerve fibres, or increasing recovery of complex sensory and motor functions. It is generally recommended to use more than one functional method for each purpose, and also to perform morphological studies of the injured nerve and the reinnervated targets. © 2015 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

  8. Substance P-immunoreactive nerves in endobronchial biopsies in cough-variant asthma and classic asthma.

    PubMed

    Lee, Sang Yeub; Kim, Min Kyung; Shin, Chol; Shim, Jae Jeong; Kim, Han Kyeom; Kang, Kyung Ho; Yoo, Se Hwa; In, Kwang Ho

    2003-01-01

    Unlike classic asthma, cough-variant asthma does not show any evidence of airway obstruction. The main symptom is a dry cough with little known pathophysiology. Hypersensitivity of the cough receptors in cough-variant asthma and an increase in the sensory nerve density of the airway epithelium in persistent dry cough patients have been reported. Therefore, it is possible that there is a higher sensory nerve density in cough-variant asthma patients than in classic asthma patients. This study was undertaken to compare the substance P (SP)-immunoreactive nerve density in mucosal biopsies of cough-variant asthma patients, classic asthma patients, and in control subjects. Bronchoscopic biopsies were performed in 6 cough-variant asthma patients, 14 classic asthma patients, and 5 normal controls. The tissues obtained were stained immunohistochemically. The SP-immunoreactive nerve density was measured in the bronchial epithelium using a light microscope at 400 x magnification. SP- immunoreactive nerve density for the cough-variant asthma group was significantly higher than that of the classic asthma group (p = 0.001), and of the normal control group (p = 0.006). It is possible that a sensory nerve abnormality within the airway may be related to hypersensitivity of the cough receptor, and that this may be one of the pathophysiologies of cough-variant asthma. Copyright 2003 S. Karger AG, Basel

  9. Cutaneous somatic and autonomic nerve TDP-43 deposition in amyotrophic lateral sclerosis.

    PubMed

    Ren, Yuting; Liu, Wenxiu; Li, Yifan; Sun, Bo; Li, Yanran; Yang, Fei; Wang, Hongfen; Li, Mao; Cui, Fang; Huang, Xusheng

    2018-05-26

    To evaluate the involvement of the sensory and autonomic nervous system in amyotrophic lateral sclerosis (ALS) and to determine whether TDP-43/pTDP-43 deposits in skin nerve fibers signify a valuable biomarker for ALS. Eighteen patients with ALS and 18 age- and sex-matched control subjects underwent physical examinations, in addition to donating skin biopsies from the distal leg. The density of epidermal, Meissner's corpuscle (MC), sudomotor, and pilomotor nerve fibers were measured. Confocal microscopy was used to determine the cutaneous somatic and autonomic nerve fiber density and TDP-43/pTDP-43 deposition. Intraepidermal nerve fiber density (IENFD) was reduced in individuals with ALS (P < 0.001). MC density (MCD) (P = 0.001), sweat gland nerve fiber density (SGNFD) (P < 0.001), and pilomotor nerve fiber density (PNFD) (P < 0.001) were all reduced in ALS patients. The SGNFD correlated with the small-fiber neuropathy Symptoms Inventory Questionnaire (SFN-SIQ), VAS and age. The SFN-SIQ was higher in ALS with sensory symptoms than without sensory symptoms (P = 0.000). Furthermore, the SFN-SIQ was higher in ALS with autonomic symptoms than without autonomic symptoms (P = 0.002). SFN-SIQ was higher in ALS patients that were pTDP-43 positive than pTDP-43 negative (P = 0.04), respectively. We established in the peripheral nervous system that higher SFN-SIQ and VAS was involved in ALS, indicating the loss of SGNF. The deposition of TDP-43/pTDP-43 in ALS nerve fibers may indicate an important role in the underlying pathogenesis of ALS. This observation might be used as a potential biomarker for diagnosing ALS.

  10. 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

  11. Role of Netrin-1 Signaling in Nerve Regeneration

    PubMed Central

    Dun, Xin-Peng; Parkinson, David B.

    2017-01-01

    Netrin-1 was the first axon guidance molecule to be discovered in vertebrates and has a strong chemotropic function for axonal guidance, cell migration, morphogenesis and angiogenesis. It is a secreted axon guidance cue that can trigger attraction by binding to its canonical receptors Deleted in Colorectal Cancer (DCC) and Neogenin or repulsion through binding the DCC/Uncoordinated (Unc5) A–D receptor complex. The crystal structures of Netrin-1/receptor complexes have recently been revealed. These studies have provided a structure based explanation of Netrin-1 bi-functionality. Netrin-1 and its receptor are continuously expressed in the adult nervous system and are differentially regulated after nerve injury. In the adult spinal cord and optic nerve, Netrin-1 has been considered as an inhibitor that contributes to axon regeneration failure after injury. In the peripheral nervous system, Netrin-1 receptors are expressed in Schwann cells, the cell bodies of sensory neurons and the axons of both motor and sensory neurons. Netrin-1 is expressed in Schwann cells and its expression is up-regulated after peripheral nerve transection injury. Recent studies indicated that Netrin-1 plays a positive role in promoting peripheral nerve regeneration, Schwann cell proliferation and migration. Targeting of the Netrin-1 signaling pathway could develop novel therapeutic strategies to promote peripheral nerve regeneration and functional recovery. PMID:28245592

  12. Streptozocin-induced type-1 diabetes mellitus results in decreased density of CGRP sensory and TH sympathetic nerve fibers that are positively correlated with bone loss at the mouse femoral neck.

    PubMed

    Enríquez-Pérez, Iris A; Galindo-Ordoñez, Karla E; Pantoja-Ortíz, Christian E; Martínez-Martínez, Arisaí; Acosta-González, Rosa I; Muñoz-Islas, Enriqueta; Jiménez-Andrade, Juan M

    2017-08-10

    Type-1 diabetes mellitus (T1DM) results in loss of innervation in some tissues including epidermis and retina; however, the effect on bone innervation is unknown. Likewise, T1DM results in pathological bone loss and increased risk of fracture. Thus, we quantified the density of calcitonin gene-related peptide (CGRP + ) sensory and tyrosine hydroxylase (TH + ) sympathetic nerve fibers and determined the association between the innervation density and microarchitecture of trabecular bone at the mouse femoral neck. Ten weeks-old female mice received 5 daily administrations of streptozocin (i.p. 50mg/kg) or citrate (control group). Twenty weeks later, femurs were analyzed by microCT and processed for immunohistochemistry. Confocal microscopy analysis revealed that mice with T1DM had a significant loss of both CGRP + and TH + nerve fibers in the bone marrow at the femoral neck. Likewise, microCT analysis revealed a significant decrease in the trabecular bone mineral density (tBMD), bone volume/total volume ratio (BV/TB), trabecular thickness (Tb.Th), trabecular number (Tb.N) and trabecular separation (Tb.Sp) in mice with T1DM as compared to control mice. Analysis of correlation revealed a positive and significant association between density of CGRP + or TH + nerve fibers with tBMD, BV/TV, Tb.Th and Tb.Sp, but not with trabecular number (there was a positive association only for CGRP + ) and degree of anisotropy (DA). This study suggests an interaction between sensory and sympathetic nervous system and T1DM-induced bone loss. Identification of the factors involved in the loss of CGRP + sensory and TH + sympathetic fibers and how they regulate bone loss may result in new avenues to treat T1DM-related osteoporosis. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. Deficient "sensory" beta synchronization in Parkinson's disease.

    PubMed

    Degardin, A; Houdayer, E; Bourriez, J-L; Destée, A; Defebvre, L; Derambure, P; Devos, D

    2009-03-01

    Beta rhythm movement-related synchronization (beta synchronization) reflects motor cortex deactivation and sensory afference processing. In Parkinson's disease (PD), decreased beta synchronization after active movement reflects abnormal motor cortex idling and may be involved in the pathophysiology of akinesia. The objectives of the present study were to (i) compare event-related synchronization after active and passive movement and electrical nerve stimulation in PD patients and healthy, age-matched volunteers and (ii) evaluate the effect of levodopa. Using a 128-electrode EEG system, we studied beta synchronization after active and passive index finger movement and electrical median nerve stimulation in 13 patients and 12 control subjects. Patients were recorded before and after 150% of their usual morning dose of levodopa. The peak beta synchronization magnitude in the contralateral primary sensorimotor (PSM) cortex was significantly lower in PD patients after active movement, passive movement and electrical median nerve stimulation, compared with controls. Levodopa partially reversed the drop in beta synchronization after active movement but not after passive movement or electrical median nerve stimulation. If one considers that beta synchronization reflects sensory processing, our results suggest that integration of somaesthetic afferences in the PSM cortex is abnormal in PD during active and passive movement execution and after simple electrical median nerve stimulation. Better understanding of the mechanisms involved in the deficient beta synchronization observed here could prompt the development of new therapeutic approaches aimed at strengthening defective processes. The lack of full beta synchronization restoration by levodopa might be related to the involvement of non-dopaminergic pathways.

  14. Sensory Symptom Profiles and Co-Morbidities in Painful Radiculopathy

    PubMed Central

    Gockel, Ulrich; Brosz, Mathias; Freynhagen, Rainer; Tölle, Thomas R.; Baron, Ralf

    2011-01-01

    Painful radiculopathies (RAD) and classical neuropathic pain syndromes (painful diabetic polyneuropathy, postherpetic neuralgia) show differences how the patients express their sensory perceptions. Furthermore, several clinical trials with neuropathic pain medications failed in painful radiculopathy. Epidemiological and clinical data of 2094 patients with painful radiculopathy were collected within a cross sectional survey (painDETECT) to describe demographic data and co-morbidities and to detect characteristic sensory abnormalities in patients with RAD and compare them with other neuropathic pain syndromes. Common co-morbidities in neuropathic pain (depression, sleep disturbance, anxiety) do not differ considerably between the three conditions. Compared to other neuropathic pain syndromes touch-evoked allodynia and thermal hyperalgesia are relatively uncommon in RAD. One distinct sensory symptom pattern (sensory profile), i.e., severe painful attacks and pressure induced pain in combination with mild spontaneous pain, mild mechanical allodynia and thermal hyperalgesia, was found to be characteristic for RAD. Despite similarities in sensory symptoms there are two important differences between RAD and other neuropathic pain disorders: (1) The paucity of mechanical allodynia and thermal hyperalgesia might be explained by the fact that the site of the nerve lesion in RAD is often located proximal to the dorsal root ganglion. (2) The distinct sensory profile found in RAD might be explained by compression-induced ectopic discharges from a dorsal root and not necessarily by nerve damage. These differences in pathogenesis might explain why medications effective in DPN and PHN failed to demonstrate efficacy in RAD. PMID:21573064

  15. Therapist Warmth: Necessary or Sufficient Condition in Behavioral Desensitization?

    ERIC Educational Resources Information Center

    Wolowitz, Howard Martin

    1975-01-01

    Discusses the Morris and Suckerman report on experimental studies testing the Rogerian hypothesis that phobic desensitization occurs as a function of therapist warmth versus the behavioral explanation that desensitization is a function of reciprocal inhibition. Morris and Suckerman respond to the critique. (Author/EJT)

  16. Transfer, Behavioral Improvement, and Anxiety Reduction in Systematic Desensitization

    ERIC Educational Resources Information Center

    Kennedy, Thomas D.; Kimura, Harry K.

    1974-01-01

    Degree of transfer and fear change associated with four levels of desensitization, pseudodesensitization, and no treatment were assessed in snakephobic students. Desensitization subjects reported significantly less anxiety than no-treatment controls when repeating their highest pretreatment responses, but were no different from either control…

  17. 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)

  18. Safety of aspirin desensitization in patients with reported aspirin allergy and cardiovascular disease.

    PubMed

    McMullan, Kathryn L; Wedner, H James

    2013-01-01

    Aspirin (ASA) is the drug of choice in patients with coronary artery disease for primary and secondary prevention. This poses a problem for those patients reporting hypersensitivity to this drug or class of drugs. Desensitization to ASA may be carried out safely and effectively in patients with reported ASA or nonsteroidal anti-inflammatory drug (NSAID) hypersensitivity needing ASA for cardiac indications. Our 7-step protocol is one choice for a rapid desensitization protocol. A retrospective chart review was conducted evaluating ASA desensitization in patients with reported ASA or NSAID hypersensitivity and a cardiac indication for ASA. In 160 evaluations over 15 years, 89 desensitizations were performed in both the inpatient and outpatient setting with only 16 reactions (18%). Eleven of these 16 patients (68.7%) were able to take daily ASA. Twenty-six desensitization procedures were performed with our 7-step rapid desensitization protocol in 10 inpatients and 16 outpatients with 3 reactions (18.75% of reactions). Initial reaction to ASA involving angioedema and reacting to ASA within the past year increased the risk of having a reaction to desensitization. Desensitization may be safely performed in patients with reported ASA or NSAID hypersensitivity and a cardiac indication for ASA. Our 7-step rapid protocol may be used in both the inpatient and outpatient setting to desensitize these patients. Patients who had angioedema with ASA ingestion or a reaction to ASA within the past year are at higher risk for reaction during the desensitization protocol. The authors have no funding, financial relationships, or conflicts of interest to disclose. © 2012 Wiley Periodicals, Inc.

  19. Cytokine expression before and after aspirin desensitization therapy in aspirin-exacerbated respiratory disease.

    PubMed

    Aktas, Ayse; Kurt, Emel; Gulbas, Zafer

    2013-12-01

    Aspirin exacerbated respiratory disease (AERD) is induced by acetylsalicylic acid (ASA) and/or nonsteroidal antiinflammatory drugs (NSAIDs). Effects of desensitization on many mediators have been examined previously, but few studies addressed the influence of desensitization on T lymphocytes and T lymphocyte-derived cytokines. This study was performed to examine peripheral blood lymphocyte (PBL) cytokine expression in aspirin-sensitive patients who have asthma before and after aspirin desensitization. In this study, the release of interleukin-2 (IL-2), interleukin-4 (IL-4), and interferon-gamma (IFN-γ) by CD4+ T lymphocytes prior to aspirin desensitization were also measured at intracellular levels, and expression of these cytokines after 1 month aspirin desensitization was evaluated. Twelve patients with AERD were included in the study. Two different control groups were formed, one consisted of 15 healthy people and second 12 aspirin tolerant asthmatic (ATA) patients using aspirin. A blood sample was collected prior to desensitization, and the tests were repeated by taking a second blood sample 1 month after the 4-day desensitization treatment. The proportion of lymphocytes secreting IFN-γ in the study group was 15.61 ± 4.40 % before desensitization and 15.08 ± 5.89 % after desensitization. The rate of IFN-γ secreting CD4+ T lymphocytes was 20.51 ± 4.41 % in the normal control group and 16.07 ± 5.7 % in the ATA group (p = 0.021). The ratio of CD4+ T lymphocyte secreting IFN-γ was reduced in patients with AERD before desensitization compared to normal control group (p = 0.040). The levels of IL-2, IL-4, and the subsets of lymphocyte were not different before and after desensitization compared to control groups.

  20. Spinal Cord Excitability and Sprint Performance Are Enhanced by Sensory Stimulation During Cycling

    PubMed Central

    Pearcey, Gregory E. P.; Noble, Steven A.; Munro, Bridget; Zehr, E. Paul

    2017-01-01

    Spinal cord excitability, as assessed by modulation of Hoffmann (H-) reflexes, is reduced with fatiguing isometric contractions. Furthermore, spinal cord excitability is reduced during non-fatiguing arm and leg cycling. Presynaptic inhibition of Ia terminals is believed to contribute to this suppression of spinal cord excitability. Electrical stimulation to cutaneous nerves reduces Ia presynaptic inhibition, which facilitates spinal cord excitability, and this facilitation is present during arm cycling. Although it has been suggested that reducing presynaptic inhibition may prolong fatiguing contractions, it is unknown whether sensory stimulation can alter the effects of fatiguing exercise on performance or spinal cord excitability. Thus, the aim of this experiment was to determine if sensory stimulation can interfere with fatigue-related suppression of spinal cord excitability, and alter fatigue rates during cycling sprints. Thirteen participants randomly performed three experimental sessions that included: unloaded cycling with sensory stimulation (CONTROL + STIM), sprints with sensory stimulation (SPRINT + STIM) and sprints without stimulation (SPRINT). Seven participants also performed a fourth session (CONTROL), which consisted of unloaded cycling. During SPRINT and SPRINT + STIM, participants performed seven, 10 s cycling sprints interleaved with 3 min rest. For CONTROL and CONTROL + STIM, participants performed unloaded cycling for ~30 min. During SPRINT + STIM and CONTROL + STIM, participants received patterned sensory stimulation to nerves of the right foot. H-reflexes and M-waves of the right soleus were evoked by stimulation of the tibial nerve at multiple time points throughout exercise. Sensory stimulation facilitated soleus H-reflexes during unloaded cycling, whereas sprints suppressed soleus H-reflexes. While receiving sensory stimulation, there was less suppression of soleus H-reflexes and slowed reduction in average power output, compared to

  1. Spinal Cord Excitability and Sprint Performance Are Enhanced by Sensory Stimulation During Cycling.

    PubMed

    Pearcey, Gregory E P; Noble, Steven A; Munro, Bridget; Zehr, E Paul

    2017-01-01

    Spinal cord excitability, as assessed by modulation of Hoffmann (H-) reflexes, is reduced with fatiguing isometric contractions. Furthermore, spinal cord excitability is reduced during non-fatiguing arm and leg cycling. Presynaptic inhibition of Ia terminals is believed to contribute to this suppression of spinal cord excitability. Electrical stimulation to cutaneous nerves reduces Ia presynaptic inhibition, which facilitates spinal cord excitability, and this facilitation is present during arm cycling. Although it has been suggested that reducing presynaptic inhibition may prolong fatiguing contractions, it is unknown whether sensory stimulation can alter the effects of fatiguing exercise on performance or spinal cord excitability. Thus, the aim of this experiment was to determine if sensory stimulation can interfere with fatigue-related suppression of spinal cord excitability, and alter fatigue rates during cycling sprints. Thirteen participants randomly performed three experimental sessions that included: unloaded cycling with sensory stimulation ( CONTROL + STIM ), sprints with sensory stimulation ( SPRINT + STIM ) and sprints without stimulation ( SPRINT ). Seven participants also performed a fourth session ( CONTROL ), which consisted of unloaded cycling. During SPRINT and SPRINT + STIM, participants performed seven, 10 s cycling sprints interleaved with 3 min rest. For CONTROL and CONTROL + STIM , participants performed unloaded cycling for ~30 min. During SPRINT + STIM and CONTROL + STIM , participants received patterned sensory stimulation to nerves of the right foot. H-reflexes and M-waves of the right soleus were evoked by stimulation of the tibial nerve at multiple time points throughout exercise. Sensory stimulation facilitated soleus H-reflexes during unloaded cycling, whereas sprints suppressed soleus H-reflexes. While receiving sensory stimulation, there was less suppression of soleus H-reflexes and slowed reduction in average power output, compared

  2. Linezolid desensitization for a patient with multiple medication hypersensitivity reactions.

    PubMed

    Bagwell, Autumn D; Stollings, Joanna L; White, Katie D; Fadugba, Olajumoke O; Choi, Jane J

    2013-01-01

    To describe a case in which a linezolid desensitization protocol was successfully used for a polymicrobial surgical wound infection in a patient with multiple drug hypersensitivity reactions. A 24-year-old woman with vocal cord dysfunction requiring tracheostomy was admitted for a surgical wound infection following a tracheostomy fistula closure procedure. The patient reported multiple antibiotic allergies including penicillins (rash), sulfonamides (rash), vancomycin (anaphylaxis), azithromycin (rash), cephalosporins (anaphylaxis), levofloxacin (unspecified), clindamycin (unspecified), and carbapenems (unspecified). Gram stain of the purulent wound drainage demonstrated mixed gram-negative and gram-positive flora, and bacterial cultures were overgrown with Proteus mirabilis, which precluded identification of other pathogens. Following failed test doses of linezolid, tigecycline, and daptomycin, all of which resulted in hypersensitivity reactions, a 16-step linezolid desensitization protocol was developed and successfully implemented without adverse reactions. The patient completed a 2-week course of antibiotic therapy that included linezolid upon finishing the desensitization protocol. Linezolid is useful in treating complicated and uncomplicated skin and soft tissue infections caused by gram-positive bacteria. With precautions, including premedication, a monitored nursing unit, and immediate availability of an emergency anaphylaxis kit, drug desensitization allows patients the ability to safely use medications to which they may have an immediate hypersensitivity reaction. Minimal data exist on linezolid desensitization protocols. Linezolid desensitization can be a viable option in patients requiring antimicrobial therapy for complicated gram-positive skin infections.

  3. A bioinspired flexible organic artificial afferent nerve

    NASA Astrophysics Data System (ADS)

    Kim, Yeongin; Chortos, Alex; Xu, Wentao; Liu, Yuxin; Oh, Jin Young; Son, Donghee; Kang, Jiheong; Foudeh, Amir M.; Zhu, Chenxin; Lee, Yeongjun; Niu, Simiao; Liu, Jia; Pfattner, Raphael; Bao, Zhenan; Lee, Tae-Woo

    2018-06-01

    The distributed network of receptors, neurons, and synapses in the somatosensory system efficiently processes complex tactile information. We used flexible organic electronics to mimic the functions of a sensory nerve. Our artificial afferent nerve collects pressure information (1 to 80 kilopascals) from clusters of pressure sensors, converts the pressure information into action potentials (0 to 100 hertz) by using ring oscillators, and integrates the action potentials from multiple ring oscillators with a synaptic transistor. Biomimetic hierarchical structures can detect movement of an object, combine simultaneous pressure inputs, and distinguish braille characters. Furthermore, we connected our artificial afferent nerve to motor nerves to construct a hybrid bioelectronic reflex arc to actuate muscles. Our system has potential applications in neurorobotics and neuroprosthetics.

  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. Semantics Desensitization: A Paradigmatic Intervention Approach to Anxiety Disorders.

    ERIC Educational Resources Information Center

    Hekmat, Hamid; And Others

    1984-01-01

    Assigned speech-anxious clients (N=30) to one of the following treatment conditions: (1) semantic desensitization; (2) attention placebo and (3) waiting list control. Results indicated that semantic desensitization therapy reduced both the affective and behavioral components of anxiety as compared to the two controls. (LLL)

  6. [Adaptive desensitization for acetylsalicylic acid hypersensitivity: A success story?].

    PubMed

    Mühlmeier, G; Hausch, R; Maier, H

    2015-10-01

    Adaptive desensitization still remains the only causative therapy for acetylsalicylic acid (ASA) hypersensitivity and is carried out nearly worldwide. To date there are hardly any data available on disease development under current desensitization therapy and longitudinal data in particular are missing. Out of a large collective of patients with proven hypersensitivity to ASA, 194 patients with initiated desensitization treatment were observed for periods up to 5 years (average 32 months). Patients with immediate reactions to systemic challenge tests revealed a response rate of 77% after 12 months of therapy. In this period 12% reached complete remission, 38% showed a clear reduction in symptoms, 32% reached partial remission, 13% remained unchanged and 5% suffered from disease progression. Adaptive desensitization therapy for hypersensitivity to ASA has been shown to be an effective causative therapy and chronic hyperplastic sinusitis as well as bronchial asthma could be improved. For the determination of maintenance dosages and required time periods more data are needed.

  7. [Castleman's disease: Rapid desensitization for hypersensitivity reaction to rituximab].

    PubMed

    Boin, C; Lambert, S; Thomann, P; Aujoulat, O; Kieffer, P

    2016-06-01

    Rapid desensitization allows secure administration of a drug and is indicated when there is no therapeutic alternative. We report a 49-year-old patient who presented with a hypersensitivity reaction following an infusion of rituximab (375mg/m(2)) in the context of a Castleman's syndrome. After a clinical flare (splenomegaly, adenopathies) despite treatment with tocilizumab, anakinra and valganciclovir, the reintroduction of rituximab was decided, according to the rapid desensitization protocol. Four full dose desensitizations were successfully performed allowing immediate clinical improvement (apyrexia, loss of sweating and lymphadenopathy, splenomegaly partial regression) and biological (negativation of HHV8 viral load, and disappearance of neutropenia, anemia and thrombocytopenia). Rapid desensitization is a promising method for the pursuit of rituximab therapy after a hypersensitivity reaction and should be considered in patients with no acceptable therapeutic alternative. Copyright © 2015 Société Nationale Française de Médecine Interne (SNFMI). Published by Elsevier SAS. All rights reserved.

  8. Recurrent Isolated Sixth Nerve Palsy in Relapsing-Remitting Chronic Inflammatory Demyelinating Polyneuropathy.

    PubMed

    Al-Bustani, Najwa; Weiss, Michael D

    2015-09-01

    Chronic inflammatory demyelinating polyneuropathy (CIDP) is an immune-mediated sensory and motor demyelinating polyneuropathy that typically presents as a relapsing-remitting or progressive disorder. Cranial neuropathies infrequently occur in association with other more typical symptoms of CIDP. We report a case of CIDP with recurrent isolated sixth nerve palsy. Her physical examination showed a right sixth nerve palsy and absent deep tendon reflexes as the only indicator of her disease. Magnetic resonance imaging revealed thickening without enhancement of the trigeminal and sixth cranial nerves. Nerve conduction study (NCS) revealed a sensory and motor demyelinating polyneuropathy with conduction block and temporal dispersion in multiple nerves consistent with CIDP. Cerebrospinal fluid demonstrated albuminic-cytologic dissociation. She had a remarkable response to intravenous immunoglobulin and remains asymptomatic without any additional immunomodulating therapy. Isolated cranial neuropathies can rarely occur as the sole manifestation of relapsing-remitting CIDP. The profound demyelination found on NCS in this case demonstrates that there can be a dramatic discordance between the clinical and electrodiagnostic findings in some patients with this disorder.

  9. Amyotrophic lateral sclerosis with sensory neuropathy: part of a multisystem disorder?

    PubMed Central

    Isaacs, Jeremy D; Dean, Andrew F; Shaw, Christopher E; Al‐Chalabi, Ammar; Mills, Kerry R; Leigh, P Nigel

    2007-01-01

    Sensory involvement is thought not to be a feature of amyotrophic lateral sclerosis (ALS). However, in the setting of a specialist motor neuron disease clinic, we have identified five patients with sporadic ALS and a sensory neuropathy for which an alternative cause could not be identified. In three individuals, sensory nerve biopsy was performed, demonstrating axonal loss without features of an alternative aetiology. These findings support the hypothesis that ALS is a multisystem neurodegenerative disorder that may occasionally include sensory neuropathy among its non‐motor features. PMID:17575021

  10. Enhancement of acetylcholine-induced desensitization of guinea-pig ileal longitudinal muscle in Ca2+-free conditions.

    PubMed

    Horio, S; Nagare, T; Moritoki, H

    1999-10-01

    1. To determine the role of cellular Ca2+ in desensitization, acetylcholine(ACh)-induced desensitization was studied under Ca2+-free condition in guinea-pig ileal longitudinal muscle. 2. Pretreatment of the tissue with 10(-4) M ACh (desensitizing treatment) in normal Tyrode solution caused desensitization of the responses both to ACh and histamine. The desensitizing treatment performed in Ca2+-free solution enhanced desensitization of the responses to ACh and histamine significantly. 3. The desensitizing treatment with ACh caused suppression of the responses to high K+ (tonic component) and Bay K 8644. The desensitizing treatment performed in Ca2+-free solution potentiated the suppression of the responses to high K+ and Bay K 8644 significantly. 4. ACh-induced desensitization was enhanced significantly in the presence of a protein kinase C inhibitor, 1-(5-isoquinolinesulfonyl)-2-methylpiperazine(H-7, 10(-4) M) to a similar extent as desensitization obtained under Ca2+-free condition, but not in the presence of a non-specific and less potent kinase inhibitor, N-(2-guanidinoethyl)-5-isoquinolinesulfonamide hydrochloride (HA1004, 10(-4) M). 5. These results suggested that voltage-gated Ca2+ channels were involved in ACh-induced desensitization and that intracellular Ca2+, which was increased during the stimulation with ACh, inhibited desensitization through the activation of protein kinase C. This kinase could have activated or protected Ca2+ channels during the desensitization process to reduce desensitization.

  11. Interaction with Phosphoinositides Confers Adaptation onto the TRPV1 Pain Receptor

    PubMed Central

    Yao, Jing; Qin, Feng

    2009-01-01

    Adaptation is a common feature of many sensory systems. But its occurrence to pain sensation has remained elusive. Here we address the problem at the receptor level and show that the capsaicin ion channel TRPV1, which mediates nociception at the peripheral nerve terminals, possesses properties essential to the adaptation of sensory responses. Ca2+ influx following the channel opening caused a profound shift (∼14-fold) of the agonist sensitivity, but did not alter the maximum attainable current. The shift was adequate to render the channel irresponsive to normally saturating concentrations, leaving the notion that the channel became no longer functional after desensitization. By simultaneous patch-clamp recording and total internal reflection fluorescence (TIRF) imaging, it was shown that the depletion of phosphatidylinositol 4,5-bisphosphate (PIP2) induced by Ca2+ influx had a rapid time course synchronous to the desensitization of the current. The extent of the depletion was comparable to that by rapamycin-induced activation of a PIP2 5-phosphatase, which also caused a significant reduction of the agonist sensitivity without affecting the maximum response. These results support a prominent contribution of PIP2 depletion to the desensitization of TRPV1 and suggest the adaptation as a possible physiological function for the Ca2+ influx through the channel. PMID:19243225

  12. Approaches to Peripheral Nerve Repair: Generations of Biomaterial Conduits Yielding to Replacing Autologous Nerve Grafts in Craniomaxillofacial Surgery

    PubMed Central

    Knipfer, Christian; Hadlock, Tessa

    2016-01-01

    Peripheral nerve injury is a common clinical entity, which may arise due to traumatic, tumorous, or even iatrogenic injury in craniomaxillofacial surgery. Despite advances in biomaterials and techniques over the past several decades, reconstruction of nerve gaps remains a challenge. Autografts are the gold standard for nerve reconstruction. Using autografts, there is donor site morbidity, subsequent sensory deficit, and potential for neuroma development and infection. Moreover, the need for a second surgical site and limited availability of donor nerves remain a challenge. Thus, increasing efforts have been directed to develop artificial nerve guidance conduits (ANCs) as new methods to replace autografts in the future. Various synthetic conduit materials have been tested in vitro and in vivo, and several first- and second-generation conduits are FDA approved and available for purchase, while third-generation conduits still remain in experimental stages. This paper reviews the current treatment options, summarizes the published literature, and assesses future prospects for the repair of peripheral nerve injury in craniomaxillofacial surgery with a particular focus on facial nerve regeneration. PMID:27556032

  13. Dexmedetomidine Added to Local Anesthetic Mixture of Lidocaine and Ropivacaine Enhances Onset and Prolongs Duration of a Popliteal Approach to Sciatic Nerve Blockade.

    PubMed

    Hu, Xiawei; Li, Jinlei; Zhou, Riyong; Wang, Quanguang; Xia, Fangfang; Halaszynski, Thomas; Xu, Xuzhong

    2017-01-01

    A literature review of multiple clinical studies on mixing additives to improve pharmacologic limitation of local anesthetics during peripheral nerve blockade revealed inconsistency in success rates and various adverse effects. Animal research on dexmedetomidine as an adjuvant on the other hand has promising results, with evidence of minimum unwanted results. This randomized, double-blinded, contrastable observational study examined the efficacy of adding dexmedetomidine to a mixture of lidocaine plus ropivacaine during popliteal sciatic nerve blockade (PSNB). Sixty patients undergoing varicose saphenous vein resection using ultrasonography-guided PSNB along with femoral and obturator nerve blocks as surgical anesthesia were enrolled. All received standardized femoral and obturator nerve blocks, and the PSNB group was randomized to receive either 0.5 mL (50 µg) of dexmedetomidine (DL group) or 0.5 mL of saline (SL group) together with 2% lidocaine (9.5 mL) plus 0.75% ropovacaine (10 mL). Sensory onset and duration of lateral sural cutaneous nerve, sural nerve, superficial peroneal nerve, deep peroneal nerve, lateral plantar nerve, and medial plantar nerve were recorded. Motor onset and duration of tibial nerve and common peroneal nerve were also examined. Sensory onset of sural nerve, superficial peroneal nerve, lateral plantar nerve, and medial plantar nerve was significantly quicker in the DL group than in the SL group (P < 0.05). Sensory onset of lateral sural cutaneous nerve and deep peroneal nerve was not statistically different between the groups (P > 0.05). Motor onset of tibial nerve and common peroneal nerve was faster in the DL group than in in the SL group (P < 0.05). Duration of both sensory and motor blockade was significantly longer in the DL group than in the SL group (P < 0.05). Perineural dexmedetomidine added to lidocaine and ropivacaine enhanced efficacy of popliteal approach to sciatic nerve blockade with faster onset and longer duration

  14. Matrix metalloproteinase-2 is downregulated in sciatic nerve by streptozotocin induced diabetes and/or treatment with minocycline: Implications for nerve regeneration

    PubMed Central

    Ali, Sumia; Driscoll, Heather E.; Newton, Victoria L.; Gardiner, Natalie J.

    2014-01-01

    Minocycline is an inhibitor of matrix metalloproteinases (MMPs) and has been shown to have analgesic effects. Whilst increased expression of MMPs is associated with neuropathic pain, MMPs also play crucial roles in Wallerian degeneration and nerve regeneration. In this study we examined the expression of MMP-2, MMP-9 and tissue inhibitor of metalloproteinase (TIMP)-1/-2 in the sciatic nerve of control and streptozotocin-induced diabetic rats treated with either vehicle or minocycline by quantitative PCR and gelatin zymography. We assessed the effects of minocycline on nerve conduction velocity and intraepidermal nerve fibre (IENF) deficits in diabetic neuropathy and investigated the effects of minocycline or MMP-2 on neurite outgrowth from primary cultures of dissociated adult rat sensory neurons. We show that MMP-2 is expressed constitutively in the sciatic nerve in vivo and treatment with minocycline or diabetes leads to downregulation of MMP-2 expression and activity. The functional consequence of this is IENF deficits in minocycline-treated nondiabetic rats and an unsupportive microenvironment for regeneration in diabetes. Minocycline reduces levels of MMP-2 mRNA and nerve growth factor-induced neurite outgrowth. Furthermore, in vivo minocycline treatment reduces preconditioning-induced in vitro neurite outgrowth following a sciatic nerve crush. In contrast, the addition of active MMP-2 facilitates neurite outgrowth in the absence of neurotrophic support and pre-treatment of diabetic sciatic nerve substrata with active MMP-2 promotes a permissive environment for neurite outgrowth. In conclusion we suggest that MMP-2 downregulation may contribute to the regenerative deficits in diabetes. Minocycline treatment also downregulates MMP-2 activity and is associated with inhibitory effects on sensory neurons. Thus, caution should be exhibited with its use as the balance between beneficial and detrimental outcomes may be critical in assessing the benefits of using

  15. Inhibition of oxotremorine-induced desensitization of guinea-pig ileal longitudinal muscle in Ca2+-free conditions.

    PubMed

    Horio, S; Fukui, H

    2001-02-01

    The aim of this study was to investigate the differences between oxotremorine-induced and acetylcholine (ACh)-induced desensitization, particularly under Ca2+-free conditions, in guinea-pig ileal longitudinal muscle, and to elucidate the different mechanisms of desensitization that might exist between these two muscarinic agonists. Pretreatment of the tissue with 10(-7)-10(-5) M oxotremorine (desensitizing treatment) in normal Tyrode solution caused desensitization of the responses to ACh, as did the desensitizing treatment with ACh. However, Ca2+-free conditions significantly reduced oxotremorine-induced desensitization, contrary to the previous findings that Ca2+-free conditions enhanced ACh-induced desensitization. The desensitizing treatment with oxotremorine caused suppression of the responses to high K+ (tonic phase), as did the ACh treatment. Ca2+-free conditions removed this suppression, whereasthis condition enhanced ACh-induced suppression of the K+ response. A protein kinase C inhibitor, 1-(5-isoquinolinesulfonyl)-2-methylpiperazine (10(-4) M) had no effect on oxotremorine-induced desensitization of the ACh response. The results suggest that a voltage-gated Ca2+ channel was involved in oxotremorine-induced desensitization, as in ACh-induced desensitization, but that the process of inactivation of Ca2+ channels was different between oxotremorine and ACh, and that oxotremorine-induced desensitization was due not only to Ca2+ channel, but also to other unknown factors. Protein kinase C did not participate in oxotremorine-induced desensitization.

  16. The role of aspirin desensitization in patients with aspirin-exacerbated respiratory disease (AERD).

    PubMed

    Spies, Jonas Willian; Valera, Fabiana Cardoso Pereira; Cordeiro, Daniel Loiola; de Mendonça, Taís Nociti; Leite, Marcelo Gonçalves Junqueira; Tamashiro, Edwin; Arruda, Luiza Karla; Anselmo-Lima, Wilma Terezinha

    2016-01-01

    Aspirin-exacerbated respiratory disease (AERD) consists of a classic tetrad: moderate/severe asthma, chronic rhinosinusitis, nasal polyps, and intolerance to aspirin or other nonsteroidal anti-inflammatory drugs. Clinical control with drugs, surgery, and desensitization are treatment options. To evaluate the efficacy and tolerability of aspirin desensitization in patients with AERD. Periodic symptom assessment and endoscopy in patients with AERD undergoing surgery who were desensitized. Seventeen patients were desensitized. Eight patients completed the desensitization and were followed for a minimum of a one-year period (mean 3.1 years). These patients showed improvement in all symptoms. Moreover, surgical reassessment was not indicated in any of these patients and there was a decrease in costs with medication and procedures. Eight patients did not complete desensitization, mainly due to procedure intolerance and uncontrolled asthma, whereas another patient was lost to follow-up. Aspirin desensitization, when tolerated, was effective in patients with AERD and with poor clinical/surgical response. Copyright © 2015 Associação Brasileira de Otorrinolaringologia e Cirurgia Cérvico-Facial. Published by Elsevier Editora Ltda. All rights reserved.

  17. Effect of desensitizing agents on dentin permeability.

    PubMed

    Ishihata, Hiroshi; Kanehira, Masafumi; Nagai, Tomoko; Finger, Werner J; Shimauchi, Hidetoshi; Komatsu, Masashi

    2009-06-01

    To investigate the in vitro efficacy of two dentin desensitizing products at reducing liquid permeability through human dentin discs. The tested hypothesis was that the products, in spite of different chemical mechanisms were not different at reducing or eliminating flow through dentin discs. Dentin slices (1 mm thick) were prepared from 16 extracted human third molars and their permeability was indirectly recorded in a split chamber model, using a chemiluminescence technique, after EDTA treatment (control), after soaking with albumin, and after desensitizer application. Two products were studied: MS Coat, a self-curing resin-containing oxalate product, and Gluma Desensitizer, a glutaraldehyde/HEMA-based agent without initiator. The dentin slices were mounted between an upper chamber, filled with an aqueous solution of 1% potassium ferricyanide and 0.3% hydrogen peroxide, and a lower chamber filled with 1% sodium hydroxide solution and 0.02% luminol. The upper solution was pressurized, and upon contact with the luminol solution a photochemical signal was generated and recorded as a measure of permeability throughout two consecutive pressurizing cycles at 2.5 and 13 kPa (26 and 133 cm H2O), respectively. The permeability of the control and albumin-soaked samples was similarly high. After application of the desensitizing agents, dentin permeability was reduced to virtually zero at both pressure levels (P < 0.001).

  18. Nerve and muscle involvement in mitochondrial disorders: an electrophysiological study.

    PubMed

    Mancuso, Michelangelo; Piazza, Selina; Volpi, Leda; Orsucci, Daniele; Calsolaro, Valeria; Caldarazzo Ienco, Elena; Carlesi, Cecilia; Rocchi, Anna; Petrozzi, Lucia; Calabrese, Rosanna; Siciliano, Gabriele

    2012-04-01

    Involvement of the peripheral nervous system in mitochondrial disorders (MD) has been previously reported. However, the exact prevalence of peripheral neuropathy and/or myopathy in MD is still unclear. In order to evaluate the prevalence of neuropathy and myopathy in MD, we performed sensory and motor nerve conduction studies (NCS) and concentric needle electromyography (EMG) in 44 unselected MD patients. NCS were abnormal in 36.4% of cases, and were consistent with a sensori-motor axonal multineuropathy (multifocal neuropathy), mainly affecting the lower limbs. EMG evidence of myopathy was present in 54.5% of patients, again mainly affecting the lower limbs. Nerve and muscle involvement was frequently subclinical. Peripheral nerve and muscle involvement is common in MD patients. Our study supports the variability of the clinical expression of MD. Further studies are needed to better understand the molecular basis underlying the phenotypic variability among MD patients.

  19. Rapid polyclonal desensitization with antibodies to IgE and FcεRIα.

    PubMed

    Khodoun, Marat V; Kucuk, Zeynep Yesim; Strait, Richard T; Krishnamurthy, Durga; Janek, Kevin; Lewkowich, Ian; Morris, Suzanne C; Finkelman, Fred D

    2013-06-01

    Rapid desensitization, a procedure in which persons allergic to an antigen are treated at short intervals with increasing doses of that antigen until they tolerate a large dose, is an effective, but risky, way to induce temporary tolerance. We wanted to determine whether this approach can be adapted to suppress all IgE-mediated allergies in mice by injecting serially increasing doses of monoclonal antibodies (mAbs) to IgE or FcεRIα. Active and passive models of antigen- and anti-IgE mAb-induced IgE-mediated anaphylaxis were used. Mice were desensitized with serially increasing doses of anti-IgE mAb, anti-FcεRIα mAb, or antigen. Development of shock (hypothermia), histamine and mast cell protease release, cytokine secretion, calcium flux, and changes in cell number and FcεRI and IgE expression were evaluated. Rapid desensitization with anti-IgE mAb suppressed IgE-mediated immediate hypersensitivity; however, some mice developed mild anaphylaxis during desensitization. Rapid desensitization with anti-FcεRIα mAb that only binds FcεRI that is not occupied by IgE suppressed both active and passive IgE-mediated anaphylaxis without inducing disease. It quickly, but temporarily, suppressed IgE-mediated anaphylaxis by decreasing mast cell signaling through FcεRI, then slowly induced longer lasting mast cell unresponsiveness by removing membrane FcεRI. Rapid desensitization with anti-FcεRIα mAb was safer and longer lasting than rapid desensitization with antigen. A rapid desensitization approach with anti-FcεRIα mAb safely desensitizes mice to IgE-mediated anaphylaxis by inducing mast cell anergy and later removing all mast cell IgE. Rapid desensitization with an anti-human FcεRIα mAb may be able to prevent human IgE-mediated anaphylaxis. Copyright © 2013 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

  20. 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.

  1. Cranial nerves in the Australian lungfish, Neoceratodus forsteri, and in fossil relatives (Osteichthyes: Dipnoi).

    PubMed

    Kemp, A

    2017-02-01

    Three systems, two sensory and one protective, are present in the skin of the living Australian lungfish, Neoceratodus forsteri, and in fossil lungfish, and the arrangement and innervation of the sense organs is peculiar to lungfish. Peripheral branches of nerves that innervate the sense organs are slender and unprotected, and form before any skeletal structures appear. When the olfactory capsule develops, it traps some of the anterior branches of cranial nerve V, which emerged from the chondrocranium from the lateral sphenotic foramen. Cranial nerve I innervates the olfactory organ enclosed within the olfactory capsule and cranial nerve II innervates the eye. Cranial nerve V innervates the sense organs of the snout and upper lip, and, in conjunction with nerve IX and X, the sense organs of the posterior and lateral head. Cranial nerve VII is primarily a motor nerve, and a single branch innervates sense organs in the mandible. There are no connections between nerves V and VII, although both emerge from the brain close to each other. The third associated system consists of lymphatic vessels covered by an extracellular matrix of collagen, mineralised as tubules in fossils. Innervation of the sensory organs is separate from the lymphatic system and from the tubule system of fossil lungfish. Copyright © 2016 Elsevier Ltd. All rights reserved.

  2. 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.

  3. Outpatient desensitization in selected patients with platinum hypersensitivity reactions.

    PubMed

    O'Malley, David M; Vetter, Monica Hagan; Cohn, David E; Khan, Ambar; Hays, John L

    2017-06-01

    Platinum-based chemotherapies are a standard treatment for both initial and recurrent gynecologic cancers. Given this widespread use, it is important to be aware of the features of platinum hypersensitivity reactions and the subsequent treatment of these reactions. There is also increasing interest in the development of desensitization protocols to allow patients with a history of platinum hypersensitivity to receive further platinum based therapy. In this review, we describe the management of platinum hypersensitivity reactions and the desensitization protocols utilized at our institution. We also describe the clinical categorizations utilized to triage patients to appropriate desensitization protocols. Copyright © 2017 Elsevier Inc. All rights reserved.

  4. PAR-2 agonists induce contraction of murine small intestine through neurokinin receptors.

    PubMed

    Zhao, Aiping; Shea-Donohue, Terez

    2003-10-01

    Protease-activated receptor-2 (PAR-2) is a G protein-coupled receptor and is expressed throughout the gut. It is well known that PAR-2 participates in the regulation of gastrointestinal motility; however, the results are inconsistent. The present study investigated the effect and mechanism of PAR-2 activation on murine small intestinal smooth muscle function in vitro. Both trypsin and PAR-2-activating peptide SLIGRL induced a small relaxation followed by a concentration-dependent contraction. The sensitivity to trypsin was greater than that to SLIGRL (EC50 = 0.03 vs. 40 microM), but maximal responses were similar (12.3 +/- 1.6 vs. 13.7 +/- 1.3 N/cm2). Trypsin-evoked contraction (1 microM) exhibited a rapid desensitization, whereas the desensitization of response to SLIGRL was less even at high concentration (50 microM). Atropine had no effect on PAR-2 agonist-induced contractions. In contrast, TTX and capsaicin significantly attenuated those contractions, implicating a neurogenic mechanism that may involve capsaicin-sensitive sensory nerves. Furthermore, contractions induced by trypsin and SLIGRL were reduced by neurokinin receptor NK1 antagonist SR-140333 or NK2 antagonist SR-48968 alone or were further reduced by combined application of SR-140333 and SR-48968, indicating the involvement of neurokinin receptors. In addition, desensitizing neurokinin receptors with substance P and/or neurokinin A decreased the PAR-2 agonist-evoked contraction. We concluded that PAR-2 agonists induced a contraction of murine intestinal smooth muscle that was mediated by nerves. The excitatory effect is also dependent on sensory neural pathways and requires both NK1 and NK2 receptors.

  5. Omalizumab facilitates rapid oral desensitization for peanut allergy.

    PubMed

    MacGinnitie, Andrew J; Rachid, Rima; Gragg, Hana; Little, Sara V; Lakin, Paul; Cianferoni, Antonella; Heimall, Jennifer; Makhija, Melanie; Robison, Rachel; Chinthrajah, R Sharon; Lee, John; Lebovidge, Jennifer; Dominguez, Tina; Rooney, Courtney; Lewis, Megan Ott; Koss, Jennifer; Burke-Roberts, Elizabeth; Chin, Kimberly; Logvinenko, Tanya; Pongracic, Jacqueline A; Umetsu, Dale T; Spergel, Jonathan; Nadeau, Kari C; Schneider, Lynda C

    2017-03-01

    Peanut oral immunotherapy is a promising approach to peanut allergy, but reactions are frequent, and some patients cannot be desensitized. The anti-IgE medication omalizumab (Xolair; Genentech, South San Francisco, Calif) might allow more rapid peanut updosing and decrease reactions. We sought to evaluate whether omalizumab facilitated rapid peanut desensitization in highly allergic patients. Thirty-seven subjects were randomized to omalizumab (n = 29) or placebo (n = 8). After 12 weeks of treatment, subjects underwent a rapid 1-day desensitization of up to 250 mg of peanut protein, followed by weekly increases up to 2000 mg. Omalizumab was then discontinued, and subjects continued on 2000 mg of peanut protein. Subjects underwent an open challenge to 4000 mg of peanut protein 12 weeks after stopping study drug. If tolerated, subjects continued on 4000 mg of peanut protein daily. The median peanut dose tolerated on the initial desensitization day was 250 mg for omalizumab-treated subjects versus 22.5 mg for placebo-treated subject. Subsequently, 23 (79%) of 29 subjects randomized to omalizumab tolerated 2000 mg of peanut protein 6 weeks after stopping omalizumab versus 1 (12%) of 8 receiving placebo (P < .01). Twenty-three subjects receiving omalizumab versus 1 subject receiving placebo passed the 4000-mg food challenge. Overall reaction rates were not significantly lower in omalizumab-treated versus placebo-treated subjects (odds ratio, 0.57; P = .15), although omalizumab-treated subjects were exposed to much higher peanut doses. Omalizumab allows subjects with peanut allergy to be rapidly desensitized over as little as 8 weeks of peanut oral immunotherapy. In the majority of subjects, this desensitization is sustained after omalizumab is discontinued. Additional studies will help clarify which patients would benefit most from this approach. Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights

  6. Technique of the sural nerve biopsy.

    PubMed

    Bevilacqua, Nicholas J; Rogers, Lee C; Malik, Rayaz A; Armstrong, David G

    2007-01-01

    A sural nerve biopsy may be useful to enable the clinician to diagnose the etiology and underlying pathology of patients presenting with symptoms of a peripheral neuropathy, when no clear underlying cause has been determined with conventional assessment such as electrophysiology or quantitative sensory testing. Given the prevalence of lower extremity neurological pathology, it is surprising that few descriptions in the peer-reviewed medical literature exist on the rationale and technique for biopsy of the sural nerve. We review the usefulness of this procedure, describe the technique, and discuss the potential complications.

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

    PubMed Central

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

    2016-01-01

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

  8. Statin desensitization in a patient with probable familial hypercholesterolemia.

    PubMed

    Schultz, Amy E; Snider, Melissa J; Blais, Danielle M; Gulati, Martha

    2015-01-01

    With cardiovascular disease being the leading cause of morbidity and mortality in the United States, cholesterol-lowering medications have become a prominent focus of medical management and cardiovascular risk reduction, including the use of statins making them the most widely prescribed class of medications in the United States and are the cornerstone of management of hyperlipidemia. This case report describes a 29-year-old female with probable familial hypercholesterolemia (FH) who had allergic reactions to statin therapy on two separate occasions. She required statin therapy based on her elevated carotid intima media thickness test, historic LDL-C ≥ 190 mg/dL, elevated Lp(a), and family history significant for premature coronary heart disease. In this report, we document a case of successful oral desensitization to rosuvastatin and propose a replicable statin desensitization protocol. The patient was admitted for rosuvastatin desensitization following predetermined protocols, utilizing an interdisciplinary team, and monitored for 24 hours following completion of administration prior to discharge. She successfully completed desensitization to rosuvastatin 10mg by mouth daily without anaphylactic reaction. She continued to tolerate rosuvastatin 10mg daily through most recent follow-up, and with this addition, significant improvement in lipid levels was achieved. This case report presented a patient with probable FH who was previously intolerant to other statin therapies that underwent successful desensitization to rosuvastatin with subsequent achievement of therapy goals. Published by Elsevier Inc.

  9. Memantine and Ketamine Differentially Alter NMDA Receptor Desensitization

    PubMed Central

    Povysheva, Nadezhda V.; Azofeifa, Andrea M.

    2017-01-01

    Memantine and ketamine are clinically useful NMDA receptor (NMDAR) open channel blockers that inhibit NMDARs with similar potency and kinetics, but display vastly different clinical profiles. This discrepancy has been hypothesized to result from inhibition by memantine and ketamine of overlapping but distinct NMDAR subpopulations. For example, memantine but not ketamine may inhibit extrasynaptic NMDARs more effectively than synaptic NMDARs. However, the basis for preferential NMDAR inhibition depending on subcellular location has not been investigated systematically. We integrated recordings from heterologously expressed single NMDAR subtypes, kinetic modeling, and recordings of synaptically evoked NMDAR responses in acute brain slices to investigate mechanisms by which channel blockers may distinguish NMDAR subpopulations. We found that memantine and ketamine differentially alter NMDAR desensitization and that memantine stabilizes a Ca2+-dependent desensitized state. As a result, inhibition by memantine of GluN1/2A receptors in tsA201 cells and of native synaptic NMDARs in cortical pyramidal neurons from mice of either sex increased in conditions that enhanced intracellular Ca2+ accumulation. Therefore, differential inhibition by memantine and ketamine based on NMDAR location is likely to result from location dependence of the intensity and duration of NMDAR activation. Modulation of Ca2+-dependent NMDAR desensitization is an unexplored mechanism of inhibitory action with the potential to endow drugs with NMDAR selectivity that leads to superior clinical profiles. Our results suggest that designing compounds to target specific receptor states, rather than specific receptor types, may be a viable strategy for future drug development. SIGNIFICANCE STATEMENT Memantine and ketamine are NMDA receptor (NMDAR) channel-blocking drugs with divergent clinical effects. Understanding mechanistically their differential actions may advance our understanding of nervous system

  10. Memantine and Ketamine Differentially Alter NMDA Receptor Desensitization.

    PubMed

    Glasgow, Nathan G; Povysheva, Nadezhda V; Azofeifa, Andrea M; Johnson, Jon W

    2017-10-04

    Memantine and ketamine are clinically useful NMDA receptor (NMDAR) open channel blockers that inhibit NMDARs with similar potency and kinetics, but display vastly different clinical profiles. This discrepancy has been hypothesized to result from inhibition by memantine and ketamine of overlapping but distinct NMDAR subpopulations. For example, memantine but not ketamine may inhibit extrasynaptic NMDARs more effectively than synaptic NMDARs. However, the basis for preferential NMDAR inhibition depending on subcellular location has not been investigated systematically. We integrated recordings from heterologously expressed single NMDAR subtypes, kinetic modeling, and recordings of synaptically evoked NMDAR responses in acute brain slices to investigate mechanisms by which channel blockers may distinguish NMDAR subpopulations. We found that memantine and ketamine differentially alter NMDAR desensitization and that memantine stabilizes a Ca 2+ -dependent desensitized state. As a result, inhibition by memantine of GluN1/2A receptors in tsA201 cells and of native synaptic NMDARs in cortical pyramidal neurons from mice of either sex increased in conditions that enhanced intracellular Ca 2+ accumulation. Therefore, differential inhibition by memantine and ketamine based on NMDAR location is likely to result from location dependence of the intensity and duration of NMDAR activation. Modulation of Ca 2+ -dependent NMDAR desensitization is an unexplored mechanism of inhibitory action with the potential to endow drugs with NMDAR selectivity that leads to superior clinical profiles. Our results suggest that designing compounds to target specific receptor states, rather than specific receptor types, may be a viable strategy for future drug development. SIGNIFICANCE STATEMENT Memantine and ketamine are NMDA receptor (NMDAR) channel-blocking drugs with divergent clinical effects. Understanding mechanistically their differential actions may advance our understanding of nervous

  11. Nerve Conduction Study on Sural Nerve among Nepalese Tailors Using Mechanical Sewing Machine.

    PubMed

    Yadav, Prakash Kumar; Yadav, Ram Lochan; Sharma, Deepak; Shah, Dev Kumar; Thakur, Dilip; Limbu, Nirmala; Islam, Md Nazrul

    2017-03-01

    The use of new technologies and innovations are out of access for people living in a developing country like Nepal. The mechanical sewing machine is still in existence at a large scale and dominant all over the country. Tailoring is one of the major occupations adopted by skilled people with lower socioeconomic status and education level. Sural nerves of both right and left legs are exposed to strenuous and chronic stress exerted by chronic paddling of mechanical sewing machine with legs. To evaluate the influence of chronic and strenuous paddling on right and left sural nerves. The study recruited 30 healthy male tailors with median age {34(31-37.25)} years (study group), and, 30 healthy male volunteers with age {34(32-36.25)} years (control group). Anthropometric measurements (age, height, weight, BMI and length of both right and left legs) as well as cardio respiratory measurements [Systolic Blood Pressure (SBP), Dystolic Blood Pressure (DBP), Pules Rate (PR) and Respiratory Rate (RR)] were recorded for each subject. Standard nerve conduction techniques using constant measured distances were applied to evaluate sural nerve (sensory) in both legs of each individual. The differences in variables between the study and control groups were tested using Student's t-test for parametric variables and Mann-Whitney U test for nonparametric variables. A p-value of ≤ 0.05 was considered significant. Age, height, weight, body mass index and leg length were not significantly different between tailors and control groups. Cardio respiratory measurements (SBP, DBP, PR and RR) were also not significantly altered between both the groups. The sensory nerve conduction velocities (m/s) of the right {44.23(42.72-47.83) vs 50(46- 54)} and left sural nerves {45.97±5.86 vs 50.67±6.59} m/s were found significantly reduced in tailors in comparison to control group. Similarly amplitudes (μv) of right sural (20.75±5.42 vs 24.10±5.45) and left sural nerves {18.2(12.43-21.8) vs 32

  12. Nerve Conduction Study on Sural Nerve among Nepalese Tailors Using Mechanical Sewing Machine

    PubMed Central

    Yadav, Ram Lochan; Sharma, Deepak; Shah, Dev Kumar; Thakur, Dilip; Limbu, Nirmala; Islam, Md. Nazrul

    2017-01-01

    Introduction The use of new technologies and innovations are out of access for people living in a developing country like Nepal. The mechanical sewing machine is still in existence at a large scale and dominant all over the country. Tailoring is one of the major occupations adopted by skilled people with lower socioeconomic status and education level. Sural nerves of both right and left legs are exposed to strenuous and chronic stress exerted by chronic paddling of mechanical sewing machine with legs. Aim To evaluate the influence of chronic and strenuous paddling on right and left sural nerves. Materials and Methods The study recruited 30 healthy male tailors with median age {34(31-37.25)} years (study group), and, 30 healthy male volunteers with age {34(32-36.25)} years (control group). Anthropometric measurements (age, height, weight, BMI and length of both right and left legs) as well as cardio respiratory measurements [Systolic Blood Pressure (SBP), Dystolic Blood Pressure (DBP), Pules Rate (PR) and Respiratory Rate (RR)] were recorded for each subject. Standard nerve conduction techniques using constant measured distances were applied to evaluate sural nerve (sensory) in both legs of each individual. The differences in variables between the study and control groups were tested using Student’s t-test for parametric variables and Mann-Whitney U test for nonparametric variables. A p-value of ≤ 0.05 was considered significant. Results Age, height, weight, body mass index and leg length were not significantly different between tailors and control groups. Cardio respiratory measurements (SBP, DBP, PR and RR) were also not significantly altered between both the groups. The sensory nerve conduction velocities (m/s) of the right {44.23(42.72-47.83) vs 50(46- 54)} and left sural nerves {45.97±5.86 vs 50.67±6.59} m/s were found significantly reduced in tailors in comparison to control group. Similarly amplitudes (μv) of right sural (20.75±5.42 vs 24.10±5

  13. 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. © 2014 S. Karger AG, Basel.

  14. Aspirin desensitization in patients undergoing percutaneous coronary intervention: a survey of current practice.

    PubMed

    Chapman, Andrew R; Rushworth, Gordon F; Leslie, Stephen J

    2013-01-01

    Aspirin remains the mainstay of anti-platelet therapy in cardiac patients. However, if a patient is allergic to aspirin and dual anti-platelet therapy is indicated - such as with percutaneous coronary intervention (PCI), then there is no clear guidance. One possibility is aspirin desensitization. A variety of protocols exist for the rapid desensitization of patients with aspirin allergy. The aim of this survey was to assess current knowledge and practice regarding aspirin desensitization in the UK. We conducted a UK wide survey of all UK 116 PCI centers and obtained complete responses from 40 (35.4%) centers. Of these, just 7 (17.5%) centers had previously desensitised patients; 29 (87.9%) centers suggested a lack of a local protocol prevented them from desensitizing, with 10 (30.3%) unsure of how to conduct desensitization. Only 5 (12.5%) centers had a local policy for aspirin desensitization although 25 (64.1%) units had a clinical strategy for dealing with aspirin allergy; the majority (72%) giving higher doses of thienopyridine class drugs. In the UK, there appears to be no consistent approach to patients with aspirin allergy. Patients undergoing PCI benefit from dual anti-platelet therapy (including aspirin), and aspirin desensitization in those with known allergy may facilitate this. Sustained effort should be placed on encouraging UK centers to use desensitization as a treatment modality prior to PCI rather than avoiding aspirin altogether.

  15. 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

  16. A prospective, randomized comparison between single- and multiple-injection techniques for ultrasound-guided subgluteal sciatic nerve block.

    PubMed

    Yamamoto, Hiroto; Sakura, Shinichi; Wada, Minori; Shido, Akemi

    2014-12-01

    It is believed that local anesthetic injected to obtain circumferential spread around nerves produces a more rapid onset and successful blockade after some ultrasound-guided peripheral nerve blocks. However, evidence demonstrating this point is limited only to the popliteal sciatic nerve block, which is relatively easy to perform by via a high-frequency linear transducer. In the present study, we tested the hypothesis that multiple injections of local anesthetic to make circumferential spread would improve the rate of sensory and motor blocks compared with a single-injection technique for ultrasound-guided subgluteal sciatic nerve block, which is considered a relatively difficult block conducted with a low-frequency, curved-array transducer. Ninety patients undergoing knee surgery were divided randomly into 2 groups to receive the ultrasound-guided subgluteal approach to sciatic nerve block with 20 mL of 1.5% mepivacaine with epinephrine. For group M (the multiple-injection technique), the local anesthetic was injected to create circumferential spread around the sciatic nerve without limitation on the number of needle passes. For group S (the single-injection technique), the number of needle passes was limited to 1, and the local anesthetic was injected to create spread along the dorsal surface of the sciatic nerve, during which no adjustment of the needle tip was made. Sensory and motor blockade were assessed in double-blind fashion for 30 minutes after completion of the block. The primary outcome was sensory blockade of all sciatic components tested, including tibial, superficial peroneal, and sural nerves at 30 minutes after injection. Data from 86 patients (43 in each group) were analyzed. Block execution took more time for group M than group S. The proportion of patients with complete sensory blockade of all sciatic components at 30 minutes after injection was significantly larger for group M than group S (41.9% vs 16.3%, P = 0.018). Complete motor blockade of

  17. Microsurgical resection of cauda equina schwannoma with nerve root preservation.

    PubMed

    McCormick, Paul C

    2014-09-01

    The occurrence of motor deficit following resection of an intradural spinal schwannoma is an uncommon but potentially serious complication. This video illustrates the technique of microsurgical resection of an L-4 sensory nerve root schwannoma with preservation of the corresponding functional L-4 motor nerve root. The video can be found here: http://youtu.be/HrZkGj1JKd4.

  18. Sonographic assessment of volar digital nerve injury in the context of penetrating trauma.

    PubMed

    Umans, Hilary; Kessler, James; de la Lama, Mauricio; Magge, Keshav; Liebling, Ralph; Negron, Judith

    2010-05-01

    The purpose of this article was to report our experience using ultrasound to assess digital nerve integrity after penetrating hand trauma with sensory deficit. Ultrasound was performed in the long axis on 22 digital nerves in 11 patients using a 12-14-MHz linear array hockey stick transducer. Of 22 volar digital nerves evaluated by sonography, six were transected. All imaging findings were confirmed surgically. High-frequency ultrasound permits accurate imaging of intact and transected volar digital nerves.

  19. Characterization of the homologous and heterologous desensitization of rat Leydig-tumour-cell adenylate cyclase.

    PubMed

    Dix, C J; Habberfield, A D; Cooke, B A

    1984-06-15

    The homologous and heterologous desensitization of rat Leydig-tumour-cell adenylate cyclase induced by lutropin (LH) was characterized with the aid of forskolin and cholera toxin. Forskolin stimulated cyclic AMP production in a dose-dependent manner, with linear kinetics up to 2h. Forskolin also potentiated the action of LH on cyclic AMP production, but was only additive with cholera toxin. Preincubation of rat Leydig tumour cells with LH (1.0 micrograms/ml) for 1 h produced a desensitization of the subsequent LH (1.0 micrograms/ml)-stimulated cyclic AMP production, whereas the responses to cholera toxin (5.0 micrograms/ml), forskolin (100 microM), LH plus forskolin or cholera toxin plus forskolin were unaltered. In contrast, preincubation with LH for 20h produced a desensitization to all the stimuli tested. When rat Leydig tumour cells were preincubated for 1h with forskolin or dibutyryl cyclic AMP, the only subsequent response that was significantly altered was that to LH plus forskolin after preincubation with forskolin. However, preincubation for 20h with forskolin or dibutyryl cyclic AMP induced a desensitization to all stimuli subsequently tested. LH produced a rapid (0-1h) homologous desensitization, which was followed by a slower (2-8h)-onset heterologous desensitization. Forskolin and dibutyryl cyclic AMP were only able to induce heterologous desensitization. The rate of desensitization induced by either forskolin or dibutyryl cyclic AMP was similar to the rate of heterologous desensitization induced by LH. These results demonstrate that in purified rat Leydig tumour cells LH produces an initial homologous desensitization of adenylate cyclase that involves a cyclic AMP-independent lesion at or proximal to the guanine nucleotide regulatory protein (G-protein). This is followed by heterologous desensitization, which can also be induced by forskolin or dibutyryl cyclic AMP, thus indicating that LH-induced heterologous desensitization of rat Leydig

  20. Evaluation of XHVRB for Capturing Explosive Shock Desensitization

    NASA Astrophysics Data System (ADS)

    Tuttle, Leah; Schmitt, Robert; Kittell, Dave; Harstad, Eric

    2017-06-01

    Explosive shock desensitization phenomena have been recognized for some time. It has been demonstrated that pressure-based reactive flow models do not adequately capture the basic nature of the explosive behavior. Historically, replacing the local pressure with a shock captured pressure has dramatically improved the numerical modeling approaches. Models based upon shock pressure or functions of entropy have recently been developed. A pseudo-entropy based formulation using the History Variable Reactive Burn model, as proposed by Starkenberg, was implemented into the Eulerian shock physics code CTH. Improvements in the shock capturing algorithm were made. The model is demonstrated to reproduce single shock behavior consistent with published pop plot data. It is also demonstrated to capture a desensitization effect based on available literature data, and to qualitatively capture dead zones from desensitization in 2D corner turning experiments. This models shows promise for use in modeling and simulation problems that are relevant to the desensitization phenomena. Issues are identified with the current implementation and future work is proposed for improving and expanding model capabilities. Sandia National Laboratories is a multi-mission laboratory managed and operated by Sandia Corporation, a wholly owned subsidiary of Lockheed Martin Corporation, for the U.S. DOE's National Nuclear Security Administration under contract DE-AC04-94AL85000.

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

    DOE Office of Scientific and Technical Information (OSTI.GOV)

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

    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-foldmore » 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.« less

  2. Sensory Innervation of the Nonspecialized Connective Tissues in the Low Back of the Rat

    PubMed Central

    Corey, Sarah M.; Vizzard, Margaret A.; Badger, Gary J.; Langevin, Helene M.

    2011-01-01

    Chronic musculoskeletal pain, including low back pain, is a worldwide debilitating condition; however, the mechanisms that underlie its development remain poorly understood. Pathological neuroplastic changes in the sensory innervation of connective tissue may contribute to the development of nonspecific chronic low back pain. Progress in understanding such potentially important abnormalities is hampered by limited knowledge of connective tissue's normal sensory innervation. The goal of this study was to evaluate and quantify the sensory nerve fibers terminating within the nonspecialized connective tissues in the low back of the rat. With 3-dimensional reconstructions of thick (30–80 μm) tissue sections we have for the first time conclusively identified sensory nerve fiber terminations within the collagen matrix of connective tissue in the low back. Using dye labeling techniques with Fast Blue, presumptive dorsal root ganglia cells that innervate the low back were identified. Of the Fast Blue-labeled cells, 60–88% also expressed calcitonin gene-related peptide (CGRP) immunoreactivity. Based on the immunolabeling with CGRP and the approximate size of these nerve fibers (≤2 μm) we hypothesize that they are Aδ or C fibers and thus may play a role in the development of chronic pain. PMID:21411968

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

    PubMed

    Gottlieb, Mark M

    2016-02-01

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

  4. ENHANCING ADULT NERVE REGENERATION THROUGH THE KNOCKDOWN OF RETINOBLASTOMA PROTEIN

    PubMed Central

    Christie, Kimberly J.; Krishnan, Anand; Martinez, Jose A.; Purdy, Kaylynn; Singh, Bhagat; Eaton, Shane; Zochodne, Douglas

    2016-01-01

    Tumour suppressor pathways may offer novel targets capable of altering the plasticity of post-mitotic adult neurons. Here we describe a role for retinoblastoma (Rb) protein, widely expressed in adult sensory neurons and their axons, during regeneration. In adult sensory neurons, Rb siRNA knockdown or Rb1 deletion in vitro enhances neurite outgrowth and branching. Plasticity is achieved in part through upregulation of neuronal PPARγ; its antagonism inhibits Rb siRNA plasticity whereas a PPARγ agonist increases growth. In an in vivo regenerative paradigm following complete peripheral nerve trunk transection, direct delivery of Rb siRNA prompts increased outgrowth of axons from proximal stumps and entrains Schwann cells to accompany them for greater distances. Similarly Rb siRNA delivery following a nerve crush improves behavioural indices of motor and sensory recovery in mice. The overall findings indicate that inhibition of tumour suppressor molecules has a role to play in promoting adult neuron regeneration. PMID:24752312

  5. Effect of high-frequency repetitive transcranial magnetic stimulation on motor cortical excitability and sensory nerve conduction velocity in subacute-stage incomplete spinal cord injury patients.

    PubMed

    Cha, Hyun Gyu; Ji, Sang-Goo; Kim, Myoung-Kwon

    2016-07-01

    [Purpose] The aim of the present study was to determine whether repetitive transcranial magnetic stimulation can improve sensory recovery of the lower extremities in subacute-stage spinal cord injury patients. [Subjects and Methods] This study was conducted on 20 subjects with diagnosed paraplegia due to spinal cord injury. These 20 subjects were allocated to an experimental group of 10 subjects that underwent active repetitive transcranial magnetic stimulation or to a control group of 10 subjects that underwent sham repetitive transcranial magnetic stimulation. The SCI patients in the experimental group underwent active repetitive transcranial magnetic stimulation and conventional rehabilitation therapy, whereas the spinal cord injury patients in the control group underwent sham repetitive transcranial magnetic stimulation and conventional rehabilitation therapy. Participants in both groups received therapy five days per week for six-weeks. Latency, amplitude, and sensory nerve conduction velocity were assessed before and after the six week therapy period. [Results] A significant intergroup difference was observed for posttreatment velocity gains, but no significant intergroup difference was observed for amplitude or latency. [Conclusion] repetitive transcranial magnetic stimulation may be improve sensory recovery of the lower extremities in subacute-stage spinal cord injury patients.

  6. Drug desensitization in the management of hypersensitivity reactions to monoclonal antibodies and chemotherapy.

    PubMed

    Mezzano, Veronica; Giavina-Bianchi, Pedro; Picard, Matthieu; Caiado, Joana; Castells, Mariana

    2014-04-01

    Hypersensitivity reactions to monoclonal antibodies and chemotherapy, which may vary in severity from mild to life-threatening, can lead to their discontinuation and replacement by alternative agents that are often less effective, more toxic, and/or more expensive. Drug desensitization has emerged as the best treatment modality capable of allowing re-introduction of the hypersensitivity reaction-inducing medication in highly sensitized patients in need of first line therapies. In recent years, the availability of new anti-neoplastic drugs and therapeutic monoclonal antibodies has increased, as has the potential for hypersensitivity reactions. Development of desensitization protocols for these new medications requires a careful assessment of the potential risks and benefits. The purposes of this review are to provide an overview of the presentation of hypersensitivity reactions amenable to desensitization and to increase awareness of the indications for and outcomes of desensitization protocols. Rapid drug desensitization has proven to be a safe and effective way of administering first line therapy to patients with hypersensitivity reactions, providing an extremely powerful treatment modality for patients for whom alternative drugs are deemed unacceptable. Rapid drug desensitization protocols should be administered only by highly trained allergists and nurses who have experience in determining which reactions are amenable to desensitization, and can identify high risk patients and provide them with appropriate care. Efforts should be made to increase awareness of the remarkable safety and efficacy of rapid drug desensitization among non-allergists, especially in the fields of oncology and rheumatology, so as to favor its universal application. Development of desensitization units to provide state-of-the-art care is possible only through coordinated teamwork.

  7. 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…

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

    PubMed

    Taylor, Greig D; Campbell, Caroline

    2015-05-01

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

  9. Interplay between mast cells, enterochromaffin cells, and sensory signaling in the aging human bowel.

    PubMed

    Yu, Y; Daly, D M; Adam, I J; Kitsanta, P; Hill, C J; Wild, J; Shorthouse, A; Grundy, D; Jiang, W

    2016-10-01

    Advanced age is associated with a reduction in clinical visceral pain perception. However, the underlying mechanisms remain largely unknown. Previous studies have suggested that an abnormal interplay between mast cells, enterochromaffin (EC) cells, and afferent nerves contribute to nociception in gastrointestinal disorders. The aim of this study was to investigate how aging affects afferent sensitivity and neuro-immune association in the human bowel. Mechanical and chemical sensitivity of human bowel afferents were examined by ex vivo afferent nerve recordings. Age-related changes in the density of mast cells, EC cells, sensory nerve terminals, and mast cell-nerve micro-anatomical association were investigated by histological and immune staining. Human afferents could be broadly classified into subpopulations displaying mechanical and chemical sensitivity, adaptation, chemo-sensitization, and recruitment. Interestingly human bowel afferent nerve sensitivity was attenuated with age. The density of substance P-immunoreactive (SP-IR) nerve varicosities was also reduced with age. In contrast, the density of ileal and colonic mucosal mast cells was increased with age, as was ileal EC cell number. An increased proportion of mast cells was found in close apposition to SP-IR nerves. Afferent sensitivity in human bowel was reduced with advancing age. Augmentation of mast cells and EC cell numbers and the mast cell-nerve association suggest a compensatory mechanism for sensory neurodegeneration. © 2016 The Authors. Neurogastroenterology & Motility Published by John Wiley & Sons Ltd.

  10. Impaired peripheral nerve regeneration in type-2 diabetic mouse model.

    PubMed

    Pham, Vuong M; Tu, Nguyen Huu; Katano, Tayo; Matsumura, Shinji; Saito, Akira; Yamada, Akihiro; Furue, Hidemasa; Ito, Seiji

    2018-01-01

    Peripheral neuropathy is one of the most common and serious complications of type-2 diabetes. Diabetic neuropathy is characterized by a distal symmetrical sensorimotor polyneuropathy, and its incidence increases in patients 40 years of age or older. In spite of extensive research over decades, there are few effective treatments for diabetic neuropathy besides glucose control and improved lifestyle. The earliest changes in diabetic neuropathy occur in sensory nerve fibers, with initial degeneration and regeneration resulting in pain. To seek its effective treatment, here we prepared a type-2 diabetic mouse model by giving mice 2 injections of streptozotocin and nicotinamide and examining the ability for nerve regeneration by using a sciatic nerve transection-regeneration model previously established by us. Seventeen weeks after the last injection, the mice exhibited symptoms of type-2 diabetes, that is, impaired glucose tolerance, decreased insulin level, mechanical hyperalgesia, and impaired sensory nerve fibers in the plantar skin. These mice showed delayed functional recovery and nerve regeneration by 2 weeks compared with young healthy mice and by 1 week compared with age-matched non-diabetic mice after axotomy. Furthermore, type-2 diabetic mice displayed increased expression of PTEN in their DRG neurons. Administration of a PTEN inhibitor at the cutting site of the nerve for 4 weeks promoted the axonal transport and functional recovery remarkably. This study demonstrates that peripheral nerve regeneration was impaired in type-2 diabetic model and that its combination with sciatic nerve transection is suitable for the study of the pathogenesis and treatment of early diabetic neuropathy. © 2017 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

  11. 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…

  12. Chronic non-freezing cold injury results in neuropathic pain due to a sensory neuropathy

    PubMed Central

    Vale, Tom A; Symmonds, Mkael; Polydefkis, Michael; Byrnes, Kelly; Rice, Andrew S C; Themistocleous, Andreas C; Bennett, David L H

    2017-01-01

    Abstract Non-freezing cold injury develops after sustained exposure to cold temperatures, resulting in tissue cooling but not freezing. This can result in persistent sensory disturbance of the hands and feet including numbness, paraesthesia and chronic pain. Both vascular and neurological aetiologies of this pain have been suggested but remain unproven. We prospectively approached patients referred for clinical assessment of chronic pain following non-freezing cold injury between 12 February 2014 and 30 November 2016. Of 47 patients approached, 42 consented to undergo detailed neurological evaluations including: questionnaires to detail pain location and characteristics, structured neurological examination, quantitative sensory testing, nerve conduction studies and skin biopsy for intraepidermal nerve fibre assessment. Of the 42 study participants, all had experienced non-freezing cold injury while serving in the UK armed services and the majority were of African descent (76.2%) and male (95.2%). Many participants reported multiple exposures to cold. The median time between initial injury and referral was 3.72 years. Pain was principally localized to the hands and the feet, neuropathic in nature and in all study participants associated with cold hypersensitivity. Clinical examination and quantitative sensory testing were consistent with a sensory neuropathy. In all cases, large fibre nerve conduction studies were normal. The intraepidermal nerve fibre density was markedly reduced with 90.5% of participants having a count at or below the 0.05 centile of published normative controls. Using the Neuropathic Pain Special Interest Group of the International Association for the Study of Pain grading for neuropathic pain, 100% had probable and 95.2% definite neuropathic pain. Chronic non-freezing cold injury is a disabling neuropathic pain disorder due to a sensory neuropathy. Why some individuals develop an acute painful sensory neuropathy on sustained cold exposure is

  13. Progranulin overexpression in sensory neurons attenuates neuropathic pain in mice: Role of autophagy.

    PubMed

    Altmann, Christine; Hardt, Stefanie; Fischer, Caroline; Heidler, Juliana; Lim, Hee-Young; Häussler, Annett; Albuquerque, Boris; Zimmer, Béla; Möser, Christine; Behrends, Christian; Koentgen, Frank; Wittig, Ilka; Schmidt, Mirko H H; Clement, Albrecht M; Deller, Thomas; Tegeder, Irmgard

    2016-12-01

    Peripheral or central nerve injury is a frequent cause of chronic pain and the mechanisms are not fully understood. Using newly generated transgenic mice we show that progranulin overexpression in sensory neurons attenuates neuropathic pain after sciatic nerve injury and accelerates nerve healing. A yeast-2-hybrid screen revealed putative interactions of progranulin with autophagy-related proteins, ATG12 and ATG4b. This was supported by colocalization and proteomic studies showing regulations of ATG13 and ATG4b and other members of the autophagy network, lysosomal proteins and proteins involved in endocytosis. The association of progranulin with the autophagic pathway was functionally confirmed in primary sensory neurons. Autophagy and survival were impaired in progranulin-deficient neurons and improved in progranulin overexpressing neurons. Nerve injury in vivo caused an accumulation of LC3b-EGFP positive bodies in neurons of the dorsal root ganglia and nerves suggesting an impairment of autophagic flux. Overexpression of progranulin in these neurons was associated with a reduction of the stress marker ATF3, fewer protein aggregates in the injured nerve and enhanced stump healing. At the behavioral level, further inhibition of the autophagic flux by hydroxychloroquine intensified cold and heat nociception after sciatic nerve injury and offset the pain protection provided by progranulin. We infer that progranulin may assist in removal of protein waste and thereby helps to resolve neuropathic pain after nerve injury. Copyright © 2016 Elsevier Inc. All rights reserved.

  14. The sensory territory of the lateral cutaneous nerve of the thigh as determined by anatomic dissections and ultrasound-guided blocks.

    PubMed

    Corujo, Alejandro; Franco, Carlo D; Williams, James M

    2012-01-01

    A femoral block sometimes fails to provide complete sensory anesthesia of the anterior aspect of middle and distal thigh, and a block of the lateral cutaneous nerve of the thigh (LCN) is often necessary to supplement it. The goal of this study was to demonstrate, both in the anatomy laboratory and in the clinical setting, a possible contribution of the LCN to the innervation of the anterior thigh. This was a prospective, observational study, including anatomic dissections and a clinical section in which 22 patients received an ultrasound-guided block of the LCN. The resulting area of anesthesia was determined 15 minutes later using pinprick examination. In 1 of 3 thigh dissections, we found a dominant LCN innervating most of the anterior aspect of the middle and distal thigh, areas that are usually attributed to the femoral nerve. In the clinical part of the study, 10 patients (45.5%) developed an area of anesthesia that extended to the medial aspect of the thigh and distally to the patella. Our results, coming from a small sample, seem to indicate that the LCN may contribute to the innervation of the anterior thigh in some cases. A block of the LCN could be considered when a femoral block has failed to produce the expected area of anesthesia.

  15. Preferential Enhancement of Sensory and Motor Axon Regeneration by Combining Extracellular Matrix Components with Neurotrophic Factors

    PubMed Central

    Santos, Daniel; González-Pérez, Francisco; Giudetti, Guido; Micera, Silvestro; Udina, Esther; Del Valle, Jaume; Navarro, Xavier

    2016-01-01

    After peripheral nerve injury, motor and sensory axons are able to regenerate but inaccuracy of target reinnervation leads to poor functional recovery. Extracellular matrix (ECM) components and neurotrophic factors (NTFs) exert their effect on different neuronal populations creating a suitable environment to promote axonal growth. Here, we assessed in vitro and in vivo the selective effects of combining different ECM components with NTFs on motor and sensory axons regeneration and target reinnervation. Organotypic cultures with collagen, laminin and nerve growth factor (NGF)/neurotrophin-3 (NT3) or collagen, fibronectin and brain-derived neurotrophic factor (BDNF) selectively enhanced sensory neurite outgrowth of DRG neurons and motor neurite outgrowth from spinal cord slices respectively. For in vivo studies, the rat sciatic nerve was transected and repaired with a silicone tube filled with a collagen and laminin matrix with NGF/NT3 encapsulated in poly(lactic-co-glycolic acid) (PLGA) microspheres (MP) (LM + MP.NGF/NT3), or a collagen and fibronectin matrix with BDNF in PLGA MPs (FN + MP.BDNF). Retrograde labeling and functional tests showed that LM + MP.NGF/NT3 increased the number of regenerated sensory neurons and improved sensory functional recovery, whereas FN + MP.BDNF preferentially increased regenerated motoneurons and enhanced motor functional recovery. Therefore, combination of ECM molecules with NTFs may be a good approach to selectively enhance motor and sensory axons regeneration and promote appropriate target reinnervation. PMID:28036084

  16. Desensitization to Mycofenolate Mofetil: a novel 12 step protocol.

    PubMed

    Smith, M; Gonzalez-Estrada, A; Fernandez, J; Subramanian, A

    2016-07-01

    The use of MMF has become standard practice in many solid organ transplant recipients due its efficacy and favorable risk profile compared to other immunosuppressants. There has been a single case report of successful MMF desensitization. However, this protocol did not follow current Drug practice parameters. We report a successful desensitization to MMF in a double heart-kidney transplant recipient.

  17. [Two cases of hereditary motor and sensory neuropathy with proximal dominant involvement (HMSN-P)].

    PubMed

    Mori, Chiaki; Saito, Tomoko; Saito, Toshio; Fujimura, Harutoshi; Sakoda, Saburo

    2015-01-01

    We, herein, report two independent cases with hereditary motor and sensory neuropathy with proximal dominant involvement (HMSN-P) inherited in an autosomal dominant fashion. Their common clinical features are slowly progressive proximal dominant muscular atrophy, fasciculations and mild to moderate distal sensory disturbance with areflexia. Nerve conduction study revealed an absence of sensory nerve action potentials, in contrast to almost normal compound muscle action potentials. Gene analysis in both patients elucidated heterozygous mutation (c.854C>T, p.Pro285Leu) in the TFG, which is an identical mutation, already described by Ishiura et al. Okinawa and Shiga are two foci of HMSN-P in Japan. Eventually, one patient is from Okinawa and the other is from a mountain village in Shiga prefecture. When we see a patient who has symptoms suggestive of motor neuron disease with sensory neuropathy, HMSN-P should be considered as a differential diagnosis despite the patient's actual resident place.

  18. Hunting for origins of migraine pain: cluster analysis of spontaneous and capsaicin-induced firing in meningeal trigeminal nerve fibers

    PubMed Central

    Zakharov, A.; Vitale, C.; Kilinc, E.; Koroleva, K.; Fayuk, D.; Shelukhina, I.; Naumenko, N.; Skorinkin, A.; Khazipov, R.; Giniatullin, R.

    2015-01-01

    Trigeminal nerves in meninges are implicated in generation of nociceptive firing underlying migraine pain. However, the neurochemical mechanisms of nociceptive firing in meningeal trigeminal nerves are little understood. In this study, using suction electrode recordings from peripheral branches of the trigeminal nerve in isolated rat meninges, we analyzed spontaneous and capsaicin-induced orthodromic spiking activity. In control, biphasic single spikes with variable amplitude and shapes were observed. Application of the transient receptor potential vanilloid 1 (TRPV1) agonist capsaicin to meninges dramatically increased firing whereas the amplitudes and shapes of spikes remained essentially unchanged. This effect was antagonized by the specific TRPV1 antagonist capsazepine. Using the clustering approach, several groups of uniform spikes (clusters) were identified. The clustering approach combined with capsaicin application allowed us to detect and to distinguish “responder” (65%) from “non-responder” clusters (35%). Notably, responders fired spikes at frequencies exceeding 10 Hz, high enough to provide postsynaptic temporal summation of excitation at brainstem and spinal cord level. Almost all spikes were suppressed by tetrodotoxin (TTX) suggesting an involvement of the TTX-sensitive sodium channels in nociceptive signaling at the peripheral branches of trigeminal neurons. Our analysis also identified transient (desensitizing) and long-lasting (slowly desensitizing) responses to the continuous application of capsaicin. Thus, the persistent activation of nociceptors in capsaicin-sensitive nerve fibers shown here may be involved in trigeminal pain signaling and plasticity along with the release of migraine-related neuropeptides from TRPV1 positive neurons. Furthermore, cluster analysis could be widely used to characterize the temporal and neurochemical profiles of other pain transducers likely implicated in migraine. PMID:26283923

  19. Duration of Action of Bupivacaine Hydrochloride Used for Palatal Sensory Nerve Block in Infant Pigs

    PubMed Central

    Holman, Shaina Devi; Gierbolini-Norat, Estela M.; Lukasik, Stacey L.; Campbell-Malone, Regina; Ding, Peng; German, Rebecca Z.

    2015-01-01

    Summary Bupivacaine hydrochloride is frequently used in veterinary dental procedures to reduce the amount of general anesthesia needed and to reduce post-procedural pain. The aim of this study was to develop a novel method to test local anesthetic duration in mammals. Six infant pigs were placed under deep/surgical anesthesia with 3 % isoflurane and oxygen while 0.5 ml of 0.5 % bupivacaine hydrochloride was injected to block the two greater palatine and the nasopalatine nerves. They were then maintained under light anesthesia with 0.5–1.0 % isoflurane. Beginning 15-minutes after the injection, 7 sites in the oral cavity were stimulated using a pointed dental waxing instrument, including 3 sites on the hard palate. The response, or lack of response, to the stimulus was recorded on video and in written record. The bupivacaine hydrochloride injections lasted 1 to 3-hours before the animals responded to the sensory stimulation with a reflexive movement. This study provides evidence that bupivacaine used to anesthetize the hard palate has a relatively short and variable duration of action far below what is expected based on its pharmacokinetic properties. PMID:25185333

  20. A successful desensitization protocol for horse-derived antithymocyte globulin in severe aplastic anemia.

    PubMed

    Demir, Esen; Cigerci Günaydın, Nurşen; Karadaş, Nihal; Gülen, Figen; Tanac, Remziye; Yılmaz, Deniz

    2015-03-01

    Horse antithymocyte globulin (h-ATG) (ATGAM(®) ) is the first choice of treatment in very severe patients with aplastic anemia who do not have any HLA matched sibling donor. h-ATG is a heterologous serum that may cause anaphylaxis. Alternative treatment strategies must be planned in case of hypersensitivity. Desensitization must be considered in patients without an alternative treatment of choice. We aimed to present the h-ATG desensitization protocol and consider its effectiveness in patients with aplastic anemia who are hypersensitized with h-ATG and do not have an alternative treatment of choice. Skin prick tests were performed with non-diluted solution in eight very severe patients with aplastic anemia who are followed up in Ege University Children's Hospital. Although skin prick test was found negative in these eight patients, different dilution h-ATG intradermal tests were performed and found positive in all patients. h-ATG desensitization program was started to these hypersensitized patients. Desensitization program was started to six male and two female very severe patients with aplastic anemia whose ages were between seven and 19 yr (median: 12.9 yr). All of the patients completed the desensitization program. While local reaction was seen in two patients, systemic reaction was seen in one patient and late reaction was seen in one patient during and after desensitization program. A successful desensitization program with h-ATG in children with aplastic anemia is presented. Even though there is not an exposure before to such high allergy potential heterologous serum, skin tests should be performed and desensitization must be started to patients who are hypersensitized to h-ATG. As the expected effectiveness of the treatment is so much, the desensitization protocol can be carried out safely and effectively with trained stuff although allergic reactions can be seen. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  1. Anxiety Management Training and Self-Control Desensitization: 15 Months Later.

    ERIC Educational Resources Information Center

    Deffenbacher, Jerry L.; Michaels, Ann C.

    1981-01-01

    A 15-month follow-up study found that anxiety management training and self-control desensitization groups continued to report significantly less debilitating test anxiety than the control group. Anxiety management training and self-control desensitization groups also reported significantly less nontargeted anxiety than controls on both measures of…

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

    ERIC Educational Resources Information Center

    Rosen, Gerald M.; And Others

    1976-01-01

    Highly anxious self-referred snake phobics received either (a) therapist-administered desensitization, (b) self-administered desensitization with weekly therapist phone calls, (c) totally self-administered desensitization, (d) self-administered double-blind placebo control, or (e) no treatment. Pretreatment to posttreatment measures revealed…

  3. The gut-brain axis rewired: adding a functional vagal nicotinic "sensory synapse".

    PubMed

    Perez-Burgos, Azucena; Mao, Yu-Kang; Bienenstock, John; Kunze, Wolfgang A

    2014-07-01

    It is generally accepted that intestinal sensory vagal fibers are primary afferent, responding nonsynaptically to luminal stimuli. The gut also contains intrinsic primary afferent neurons (IPANs) that respond to luminal stimuli. A psychoactive Lactobacillus rhamnosus (JB-1) that affects brain function excites both vagal fibers and IPANs. We wondered whether, contrary to its primary afferent designation, the sensory vagus response to JB-1 might depend on IPAN to vagal fiber synaptic transmission. We recorded ex vivo single- and multiunit afferent action potentials from mesenteric nerves supplying mouse jejunal segments. Intramural synaptic blockade with Ca(2+) channel blockers reduced constitutive or JB-1-evoked vagal sensory discharge. Firing of 60% of spontaneously active units was reduced by synaptic blockade. Synaptic or nicotinic receptor blockade reduced firing in 60% of vagal sensory units that were stimulated by luminal JB-1. In control experiments, increasing or decreasing IPAN excitability, respectively increased or decreased nerve firing that was abolished by synaptic blockade or vagotomy. We conclude that >50% of vagal afferents function as interneurons for stimulation by JB-1, receiving input from an intramural functional "sensory synapse." This was supported by myenteric plexus nicotinic receptor immunohistochemistry. These data offer a novel therapeutic target to modify pathological gut-brain axis activity.-Perez-Burgos, A., Mao, Y.-K., Bienenstock, J., Kunze, W. A. The gut-brain axis rewired: adding a functional vagal nicotinic "sensory synapse." © FASEB.

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

    PubMed Central

    Mrug, Sylvie; Madan, Anjana; Windle, Michael

    2015-01-01

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

  5. 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.

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

    PubMed

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

    2016-11-01

    Children exposed to multiple sources of violence may become desensitized, increasing the possibility of them imitating the aggressive behaviors they watch and considering such behavior as normal. The purpose of this article is to assess the association between exposure to various types of violence (including war) and desensitization in Lebanese children. A cross-sectional design with 207 school-aged children assessed exposure to violence using three surveys: (a) violence in the media (the Media Preference survey), (b) exposure to violence (the KID-SAVE survey), and (c) desensitization attitudes (the Attitude Toward Violence-Child Version). Children were between 8 and 12 years old, 56% were males, and 70%were from middle socioeconomic status (SES) backgrounds. Seventy-six percent of children reported being exposed to violence, with more exposure in males and in the lower SES group. Impact, however, was greater on girls. The predictors of attitude toward violence were "Frequency" of exposure, "Impact" of exposure, and the amount of violence viewed on television. Children are massively exposed to violence in Lebanon resulting in desensitization, which may habituate them to accept violence as normal and put them at risk for imitating violent behaviors. © The Author(s) 2015.

  7. Effects of local anaesthetics on short-term desensitization of guinea-pig taenia caecum to histamine.

    PubMed Central

    Hishinuma, S.; Uchida, M. K.

    1987-01-01

    1 Short-term desensitization to histamine was induced by incubating guinea-pig taenia caecum with 10(-4)M histamine for 30 min (desensitizing incubation) in normal Locke-Ringer solution or Ca-free Locke-Ringer solution containing 0.2 mM EGTA. This desensitization was measured as a reduction of the maximal contractile response. 2 The effects of the presence of local anaesthetics during the desensitizing incubation were examined. Results showed that tetracaine, procaine, procainamide, oxybuprocaine and lignocaine inhibited the desensitization, whereas dibucaine, benzocaine and mepivacaine did not. 3 The inhibitory effects of these drugs on the desensitization were not correlated with their lipid solubility nor with the potency of their known effects, such as membrane stabilization, Ca channel blockade, calmodulin antagonism, or inhibition of C-kinase. 4 It is concluded that the inhibitory effects of local anaesthetics on the desensitization are not due to their non-specific membrane-stabilizing effects per se, but to some other action. PMID:3427278

  8. Neurogenin 1 Null Mutant Ears Develop Fewer, Morphologically Normal Hair Cells in Smaller Sensory Epithelia Devoid of Innervation

    PubMed Central

    Ma, Qiufu; Anderson, David J.

    2000-01-01

    The proneuronal gene neurogenin 1 (ngn1) is essential for development of the inner-ear sensory neurons that are completely absent in ngn1 null mutants. Neither afferent, efferent, nor autonomic nerve fibers were detected in the ears of ngn1 null mutants. We suggest that efferent and autonomic fibers are lost secondarily to the absence of afferents. In this article we show that ngn1 null mutants develop smaller sensory epithelia with morphologically normal hair cells. In particular, the saccule is reduced dramatically and forms only a small recess with few hair cells along a duct connecting the utricle with the cochlea. Hair cells of newborn ngn1 null mutants show no structural abnormalities, suggesting that embryonic development of hair cells is independent of innervation. However, the less regular pattern of dispersal within sensory epithelia may be caused by some effects of afferents or to the stunted growth of the sensory epithelia. Tracing of facial and stato-acoustic nerves in control and ngn1 null mutants showed that only the distal, epibranchial, placode-derived sensory neurons of the geniculate ganglion exist in mutants. Tracing further showed that these geniculate ganglion neurons project exclusively to the solitary tract. In addition to the normal complement of facial branchial and visceral motoneurons, ngn1 null mutants have some trigeminal motoneurons and contralateral inner-ear efferents projecting, at least temporarily, through the facial nerve. These data suggest that some neurons in the brainstem (e.g., inner-ear efferents, trigeminal motoneurons) require afferents to grow along and redirect to ectopic cranial nerve roots in the absence of their corresponding sensory roots. PMID:11545141

  9. Kidney transplantation after desensitization in sensitized patients: a Korean National Audit.

    PubMed

    Huh, Kyu Ha; Kim, Beom Seok; Yang, Jaeseok; Ahn, Jeongmyung; Kim, Myung-Gyu; Park, Jae Berm; Kim, Jong Man; Chung, Byung-Ha; Kim, Joong Kyung; Kong, Jin Min

    2012-10-01

    The number of end-stage renal disease (ESRD) patients with preformed antibodies waiting for a kidney transplant has been increasing lately. We conducted a nationwide study on the outcomes of kidney transplantation after desensitization in Korea. Six transplant centers have run desensitization programs. The patients who underwent living donor kidney transplantation after desensitization from 2002 to 2010 were retrospectively analyzed. A total of 86 cases were enrolled. Thirty-five of these were cases of re-transplantation (40.7 %). Indications of desensitization were positive complement-dependent cytotoxicity (CDC) cross-match responses (CDC(+), 36.0 %), positive flow-cytometric cross-match responses (FCX(+), 54.7 %), and positive donor-specific antibodies (DSA(+), 8.1 %). The desensitization protocols used pre-transplant plasmapheresis (95.3 %), intravenous immunoglobulin (62.8 %), and rituximab (67.4 %). Acute rejection occurred in 18 patients (20.9 %), graft failure occurred in 4 patients, and the 3-year graft survival rate was 93.8 %. The presence of DSA increased the acute rejection rate (P = 0.015) and decreased the 1-year post-transplant estimated glomerular filtration rate (P = 0.006). Although rejection-free survival rates did not differ significantly between the CDC(+) and FCX(+) groups, the 1-year estimated glomerular filtration rate was lower in the CDC(+) group (P = 0.010). Infectious and significant bleeding complications occurred in 15.5 % and 4.7 % of cases, respectively. Kidney transplantation after desensitization had good graft outcomes and tolerable complications in Korea, and therefore, this therapy can be recommended for sensitized ESRD patients.

  10. Acute corneal epithelial debridement unmasks the corneal stromal nerve responses to ocular stimulation in rats: implications for abnormal sensations of the eye.

    PubMed

    Hirata, Harumitsu; Mizerska, Kamila; Dallacasagrande, Valentina; Guaiquil, Victor H; Rosenblatt, Mark I

    2017-05-01

    It is widely accepted that the mechanisms for transducing sensory information reside in the nerve terminals. Occasionally, however, studies have appeared demonstrating that similar mechanisms may exist in the axon to which these terminals are connected. We examined this issue in the cornea, where nerve terminals in the epithelial cell layers are easily accessible for debridement, leaving the underlying stromal (axonal) nerves undisturbed. In isoflurane-anesthetized rats, we recorded extracellularly from single trigeminal ganglion neurons innervating the cornea that are excited by ocular dryness and cooling: low-threshold (<2°C cooling) and high-threshold (>2°C) cold-sensitive plus dry-sensitive neurons playing possible roles in tearing and ocular pain. We found that the responses in both types of neurons to dryness, wetness, and menthol stimuli were effectively abolished by the debridement, indicating that their transduction mechanisms lie in the nerve terminals. However, some responses to the cold, heat, and hyperosmolar stimuli in low-threshold cold-sensitive plus dry-sensitive neurons still remained. Surprisingly, the responses to heat in approximately half of the neurons were augmented after the debridement. We were also able to evoke these residual responses and follow the trajectory of the stromal nerves, which we subsequently confirmed histologically. The residual responses always disappeared when the stromal nerves were cut at the limbus, suggesting that the additional transduction mechanisms for these sensory modalities originated most likely in stromal nerves. The functional significance of these residual and enhanced responses from stromal nerves may be related to the abnormal sensations observed in ocular disease. NEW & NOTEWORTHY In addition to the traditional view that the sensory transduction mechanisms exist in the nerve terminals, we report here that the proximal axons (stromal nerves in the cornea from which these nerve terminals originate) may

  11. Acute corneal epithelial debridement unmasks the corneal stromal nerve responses to ocular stimulation in rats: implications for abnormal sensations of the eye

    PubMed Central

    Mizerska, Kamila; Dallacasagrande, Valentina; Guaiquil, Victor H.; Rosenblatt, Mark I.

    2017-01-01

    It is widely accepted that the mechanisms for transducing sensory information reside in the nerve terminals. Occasionally, however, studies have appeared demonstrating that similar mechanisms may exist in the axon to which these terminals are connected. We examined this issue in the cornea, where nerve terminals in the epithelial cell layers are easily accessible for debridement, leaving the underlying stromal (axonal) nerves undisturbed. In isoflurane-anesthetized rats, we recorded extracellularly from single trigeminal ganglion neurons innervating the cornea that are excited by ocular dryness and cooling: low-threshold (<2°C cooling) and high-threshold (>2°C) cold-sensitive plus dry-sensitive neurons playing possible roles in tearing and ocular pain. We found that the responses in both types of neurons to dryness, wetness, and menthol stimuli were effectively abolished by the debridement, indicating that their transduction mechanisms lie in the nerve terminals. However, some responses to the cold, heat, and hyperosmolar stimuli in low-threshold cold-sensitive plus dry-sensitive neurons still remained. Surprisingly, the responses to heat in approximately half of the neurons were augmented after the debridement. We were also able to evoke these residual responses and follow the trajectory of the stromal nerves, which we subsequently confirmed histologically. The residual responses always disappeared when the stromal nerves were cut at the limbus, suggesting that the additional transduction mechanisms for these sensory modalities originated most likely in stromal nerves. The functional significance of these residual and enhanced responses from stromal nerves may be related to the abnormal sensations observed in ocular disease. NEW & NOTEWORTHY In addition to the traditional view that the sensory transduction mechanisms exist in the nerve terminals, we report here that the proximal axons (stromal nerves in the cornea from which these nerve terminals originate) may

  12. Aging-associated sensory neuropathy alters pressure-induced vasodilation in humans.

    PubMed

    Fromy, Bérengère; Sigaudo-Roussel, Dominique; Gaubert-Dahan, Marie-Line; Rousseau, Pascal; Abraham, Pierre; Benzoni, Daniel; Berrut, Gilles; Saumet, Jean Louis

    2010-03-01

    Healthy skin is protected from pressure-induced ischemic damage because of the presence of pressure-induced vasodilation (PIV). PIV relies on small sensory nerve fibers and endothelial function. Since aging alters both nervous and vascular functions, we hypothesized that PIV is altered with aging. We compared PIV in non-neuropathic and neuropathic older subjects (60-75 years) with that of young subjects (20-35 years). Laser Doppler flowmetry was used to evaluate the cutaneous responses to local pressure application, acetylcholine, and local heating. Quantitative sensory tests were used to evaluate sensory-nerve-fiber function. The non-neuropathic older subjects had an impaired PIV (12+/-7% increase in blood flow with pressure) compared with young subjects (62+/-4%, P<0.001). In the presence of peripheral neuropathy, the older subjects were totally deprived of PIV, leading to early pressure-induced cutaneous ischemia (-31+/-10%, P<0.001). This inability of the skin to adapt to localized pressure in older subjects is related to the severity of the sensory-fiber dysfunction rather than to endothelial dysfunction, which was comparable between the non-neuropathic (141+/-19% increased blood flow with acetylcholine, P<0.05) and neuropathic older subjects (145+/-28% increase, P<0.05) compared with young subjects (234+/-25% increase).

  13. [Clinical report of hereditary motor and sensory neuropathy with proximal dominance in Shiga prefecture].

    PubMed

    Takahashi, Mitsuo; Mitsui, Yoshiyuki; Yorifuji, Shiro; Nakamura, Yuusaku; Tsukamoto, Yoshihumi; Nishimoto, Kazuhiro

    2007-09-01

    We followed eight hereditary motor and sensory neuropathy patients with proximal dominance (HMSN-P) in Shiga prefecture from 1984 to 2007. There were 4 men and 4 women from two families showing autosomal and dominant prepotency. These families were related by marriage. The average onset of disease was at 53.4 +/- 8.9 (40-68) years-old. Initial symptoms were difficulty of standing up, difficulty elevating their arms, limping, or numbness. The main feature was neurogenic muscular atrophy with proximal dominance. All deep tendon reflexes were decreased or nonexistent. Paresthesia in the hands and feet and/or decreased vibratory sense in the legs were found in six patients. High CK blood levels were recognized in three patients. EMG in four patients revealed neurogenic pattern. Nerve conduction study was conducted in two patients. MCV of the median nerve and of the tibial posterior nerve, also SCV of the median nerve and of the sural nerve were within normal range in all nerves. Amplitudes of sensory action potential or of M wave were decreased or nonexistent in five of eight nerves, and distal latency of M waves was delayed in three of four nerves. These data suggests dysfunction of distal parts of the peripheral nerve fibers and axonal degeneration of the nerve trunk. Seven patients have died, and their average death age was 69.1 +/- 8.2 (52-77) years-old. Their average affected period was 16.6 (4-30) years. Their clinical history resembles Okinawa-type HMSN-P, but without the painful muscle cramps which are distinctive Okinawa-type signs.

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

    PubMed

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

    2015-09-21

    Dual antiplatelet therapy is essential in patients undergoing percutaneous coronary intervention with stent implantation. Hypersensitivity to acetylsalicylic acid (ASA) limits treatment options. Desensitization to ASA has classically been studied in patients with respiratory tract disease. Over the last years, many protocols have been described about ASA desensitization in patients with ischemic heart disease, including acute coronary syndrome and the need for coronary stent implantation. It is important to know the efficacy and safety of ASA desensitization in these patients. Copyright © 2014 Elsevier España, S.L.U. All rights reserved.

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

    PubMed

    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 microM; 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-Galphal3 coupling after desensitization. Taken together, these results indicate that Src dynamically regulates DOR recycling and by doing so contributes to desensitization of these receptors.

  16. Biological Correlates of Cognitive, Sensory and Motor Abilities

    DTIC Science & Technology

    1975-04-01

    specialized, histologically modified ends of sensory nerve fibers. The receptors are designed to respond to a particular form of energy at a much lower...consider the comparativ ■ approach as having rich potential. It is believed to be the only currently available means of definitely establish- ing

  17. The anabolic steroid nandrolone enhances motor and sensory functional recovery in rat median nerve repair with long interpositional nerve grafts.

    PubMed

    Ghizoni, Marcos Flávio; Bertelli, Jayme Augusto; Grala, Carolina Giesel; da Silva, Rosemeri Maurici

    2013-01-01

    Recovery from peripheral nerve repair is frequently incomplete. Hence drugs that enhance nerve regeneration are needed clinically. To study the effects of nandrolone decanoate in a model of deficient reinnervation in the rat. In 40 rats, a 40-mm segment of the left median nerve was removed and interposed between the stumps of a sectioned right median nerve. Starting 7 days after nerve grafting and continuing over a 6-month period, we administered nandrolone at a dose of 5 mg/kg/wk to half the rats (n = 20). All rats were assessed behaviorally for grasp function and nociceptive recovery for up to 6 months. At final assessment, reinnervated muscles were tested electrophysiologically and weighed. Results were compared between rats that had received versus not received nandrolone and versus 20 nongrafted controls. Rats in the nandrolone group recovered finger flexion faster. At 90 days postsurgery, they had recovered 42% of normal grasp strength versus just 11% in rats grafted but not treated with nandrolone. At 180 days, the average values for grasp strength recovery in the nandrolone and no-nandrolone groups were 40% and 33% of normal values for controls, respectively. At 180 days, finger flexor muscle twitch strength was 16% higher in treated versus nontreated rats. Thresholds for nociception were not detected in either group 90 days after nerve grafting. At 180 days, nociceptive thresholds were significantly lower in the nandrolone group. Nandrolone decanoate improved functional recovery in a model of deficient reinnervation.

  18. [Herpes zoster of the trigeminal nerve: a case report and review of the literature].

    PubMed

    Carbone, V; Leonardi, A; Pavese, M; Raviola, E; Giordano, M

    2004-01-01

    Herpes zoster (shingles) is caused when the varicella zoster virus that has remained latent since an earlier varicella infection (chicken-pox) is reactivated. Herpes Zoster is a less common and endemic disease than varicella: factors causing reactivation are still not well known, but it occurs in older and/or immunocompromised individuals. Following reactivation, centrifugal migration of herpes zoster virus (HZV) occurs along sensory nerves to produce a characteristic painful cutaneous or mucocutaneous vesicular eruption that is generally limited to the single affected dermatome. Herpes zoster may affect any sensory ganglia and its cutaneous nerve: the most common sites affected are thoracic dermatomes (56%), followed by cranial nerves (13%) and lumbar (13%), cervical (11%) and sacral nerves (4%). Among cranial nerves, the trigeminal and facial nerves are the most affected due to reactivation of HZV latent in gasserian and geniculated ganglia. The 1st division of the trigeminal nerve is commonly affected, whereas the 2nd and the 3rd are rarely involved. During the prodromal stage, the only presenting symptom may be odontalgia, which may prove to be a diagnostic challenge for the dentist, since many diseases can cause orofacial pain, and the diagnosis must be established before final treatment. A literature review of herpes zoster of the trigeminal nerve is presented and the clinical presentation, differential diagnosis and treatment modalities are underlined. A case report is presented.

  19. A SAFE PROTOCOL FOR RAPID DESENSITIZATION IN PATIENTS WITH CYSTIC FIBROSIS AND ANTIBIOTIC HYPERSENSITIVITY

    PubMed Central

    Legere, Henry J.; Palis, Ross I.; Bouza, Tito Rodriguez; Uluer, Ahmet Z.; Castells, Mariana C.

    2009-01-01

    Background CF patients often demonstrate hypersensitivity to one or multiple antibiotics due to frequent and repeated exposures. Attempts at antibiotic desensitization in this population are historically complicated by higher reaction rates, failure to complete the procedure and consequent withholding of first-line therapy. This study evaluates the outcomes of a rapid desensitization protocol developed at our institution. Methods We retrospectively reviewed the medical records of 15 patients undergoing 52 rapid antibiotic desensitizations at Brigham and Women’s Hospital and Children’s Hospital Boston utilizing our protocol. Results Mean FEV1 % predicted was 44.1 (SD 16.5), with two patients at <30% and one patient desensitized during bilateral lung transplantation. Adverse reactions during desensitization occurred in 13.4%, and most were mild. 100% of patients completed the protocol and ultimately tolerated subsequent full-strength antibiotic courses. Conclusions CF patients with antibiotic hypersensitivity can safely receive first-line antibiotics via our rapid desensitization protocol, including those with severe obstructive lung disease. PMID:19740711

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

    PubMed Central

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

    2013-01-01

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

  1. Central Projections of Antennal and Labial Palp Sensory Neurons in the Migratory Armyworm Mythimna separata

    PubMed Central

    Ma, Bai-Wei; Zhao, Xin-Cheng; Berg, Bente G.; Xie, Gui-Ying; Tang, Qing-Bo; Wang, Gui-Rong

    2017-01-01

    The oriental armyworm, Mythimna separata (Walker), is a polyphagous, migratory pest relying on olfactory cues to find mates, locate nectar, and guide long-distance flight behavior. In the present study, a combination of neuroanatomical techniques were utilized on this species, including backfills, confocal microscopy, and three-dimensional reconstructions, to trace the central projections of sensory neurons from the antenna and the labial pit organ, respectively. As previously shown, the axons of the labial sensory neurons project via the ipsilateral labial nerve and terminate in three main areas of the central nervous system: (1) the labial-palp pit organ glomerulus of each antennal lobe, (2) the gnathal ganglion, and (3) the prothoracic ganglion of the ventral nerve cord. Similarly, the antennal sensory axons project to multiple areas of the central nervous system. The ipsilateral antennal nerve targets mainly the antennal lobe, the antennal mechanosensory and motor center, and the prothoracic and mesothoracic ganglia. Specific staining experiments including dye application to each of the three antennal segments indicate that the antennal lobe receives input from flagellar olfactory neurons exclusively, while the antennal mechanosensory and motor center is innervated by mechanosensory neurons from the whole antenna, comprising the flagellum, pedicle, and scape. The terminals in the mechanosensory and motor center are organized in segregated zones relating to the origin of neurons. The flagellar mechanosensory axons target anterior zones, while the pedicular and scapal axons terminate in posterior zones. In the ventral nerve cord, the processes from the antennal sensory neurons terminate in the motor area of the thoracic ganglia, suggesting a close connection with motor neurons. Taken together, the numerous neuropils innervated by axons both from the antenna and labial palp indicate the multiple roles these sensory organs serve in insect behavior. PMID:29209176

  2. Terminal changes in hereditary sensory and autonomic neuropathy: a long-term follow-up of a sporadic case.

    PubMed

    Lee, Sang-Soo; Lee, Sung-Hyun; Han, Seol-Heui

    2003-07-01

    We describe terminal changes in a long-term follow-up of a 51-year-old man with sporadic hereditary sensory and autonomic neuropathy (HSAN). From the age of 15 years onwards, he suffered from multiple painless ulcers of his feet and fingers, necessitating amputation. Neurological studies revealed almost complete sensory loss affecting all modalities in the upper and lower limbs, minimal involvement of motor fibers, and areflexia. A neurophysiological abnormality involved an absence of sensory action potentials with relatively normal motor nerve conduction velocities. Biopsy of the sural nerve showed almost total loss of myelinated fibers with a mild decrease in unmyelinated fibers. Despite the late onset of the disease, the progressive course, and the lancinating pain, the terminal features of this patient, which involved a selective loss of myelinated fibers and widespread sensory loss, seem to be symptomatic of HSAN II, the progressive form of autosomal recessive sensory neuropathy, and emphasize the clinical heterogeneity of HSAN.

  3. Desensitization of the nicotinic acetylcholine receptor by diisopropylfluorophosphate.

    PubMed

    Eldefrawi, M E; Schweizer, G; Bakry, N M; Valdes, J J

    1988-01-01

    The interaction of diisopropylfluorophosphate (DFP) with the nicotinic acetylcholine (ACh) receptor of Torpedo electric organ was studied, using [3H]-phencyclidine ([3H]-PCP) as a reporter probe. Phencyclidine binds with different kinetics to resting, activated, and desensitized receptor conformations. Although DFP did not inhibit binding of [3H]-ACh or 125I-alpha-bungarotoxin (BGT) to the receptor recognition sites and potentiated in a time-dependent manner [3H]-PCP binding to the receptor's high-affinity allosteric site, it inhibited the ACh- or carbamylcholine-stimulated [3H]-PCP binding. This suggested that DFP bound to a third kind of site on the receptor and affected receptor conformation. Preincubation of the membranes with DFP increased the receptor's affinity for carbamylcholine by eightfold and raised the pseudo-first-order rate of [3H]-PCP binding to that of an agonist-desensitized receptor. Accordingly, it is suggested that DFP induces receptor desensitization by binding to a site that is distinct from the recognition or high-affinity noncompetitive sites.

  4. Lateralization Technique and Inferior Alveolar Nerve Transposition

    PubMed Central

    Sanches, Marco Antonio; Ramalho, Gabriel Cardoso; Manzi, Marcello Roberto

    2016-01-01

    Bone resorption of the posterior mandible can result in diminished bone edge and, therefore, the installation of implants in these regions becomes a challenge, especially in the presence of the mandibular canal and its contents, the inferior alveolar nerve. Several treatment alternatives are suggested: the use of short implants, guided bone regeneration, appositional bone grafting, distraction osteogenesis, inclined implants tangential to the mandibular canal, and the lateralization of the inferior alveolar nerve. The aim was to elucidate the success rate of implants in the lateralization technique and in inferior alveolar nerve transposition and to determine the most effective sensory test. We conclude that the success rate is linked to the possibility of installing implants with long bicortical anchor which favors primary stability and biomechanics. PMID:27433360

  5. Constriction of the buccal branch of the facial nerve produces unilateral craniofacial allodynia.

    PubMed

    Lewis, Susannah S; Grace, Peter M; Hutchinson, Mark R; Maier, Steven F; Watkins, Linda R

    2017-08-01

    Despite pain being a sensory experience, studies of spinal cord ventral root damage have demonstrated that motor neuron injury can induce neuropathic pain. Whether injury of cranial motor nerves can also produce nociceptive hypersensitivity has not been addressed. Herein, we demonstrate that chronic constriction injury (CCI) of the buccal branch of the facial nerve results in long-lasting, unilateral allodynia in the rat. An anterograde and retrograde tracer (3000MW tetramethylrhodamine-conjugated dextran) was not transported to the trigeminal ganglion when applied to the injury site, but was transported to the facial nucleus, indicating that this nerve branch is not composed of trigeminal sensory neurons. Finally, intracisterna magna injection of interleukin-1 (IL-1) receptor antagonist reversed allodynia, implicating the pro-inflammatory cytokine IL-1 in the maintenance of neuropathic pain induced by facial nerve CCI. These data extend the prior evidence that selective injury to motor axons can enhance pain to supraspinal circuits by demonstrating that injury of a facial nerve with predominantly motor axons is sufficient for neuropathic pain, and that the resultant pain has a neuroimmune component. Copyright © 2016 Elsevier Inc. All rights reserved.

  6. 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…

  7. Protective effect of sensory denervation in inflammatory arthritis (evidence of regulatory neuroimmune pathways in the arthritic joint)

    PubMed Central

    Kane, D; Lockhart, J; Balint, P; Mann, C; Ferrell, W; McInnes, I

    2005-01-01

    Case report: The patient developed arthritis mutilans in all digits of both hands with the exception of the left 4th finger, which had prior sensory denervation following traumatic nerve dissection. Plain radiography, ultrasonography and nerve conduction studies of the hands confirmed the absence of articular disease and sensory innervation in the left 4th digit. Methods: This relationship between joint innervation and joint inflammation was investigated experimentally by prior surgical sensory denervation of the medial aspect of the knee in six Wistar rats in which carrageenan induced arthritis was subsequently induced. Prior sensory denervation—with preservation of muscle function—prevented the development of inflammatory arthritis in the denervated knee. Discussion: Observations in human and animal inflammatory arthritis suggest that regulatory neuroimmune pathways in the joint are an important mechanism that modulates the clinical expression of inflammatory arthritis. PMID:15155371

  8. [Prolonged desensitization pretreatment for in vitro fertilization in women with polycystic ovary].

    PubMed

    Kuczyński, W; Czech, R; Redźko, S; Wasilewski, T; Mrugacz, G; Wołczyński, S; Pietrewicz, P; Grochowski, D; Szamatowicz, M

    2000-09-01

    To analyse the outcome of intracytoplasmic sperm injection (ICSI) in women with severe polycystic ovary disease (PCD), stimulated after prolonged pituitary desensitization in comparison with regular long protocol therapy. The results of controlled ovarian hyperstimulation (COH), fertilization rate, early embryo development parameters and clinical pregnancy rates were compared depending on the duration of pituitary desensitization before gonadotropin administration. A total of 60 patients with severe PCOD were desensitized with GnRH agonist up to 30 days before COH. The results were compared with the group of 213 patients with mild PCOD treated with regular long protocol (control). We observed a slightly higher rate of mature oocytes MII as well as the number of embryos obtained in the control group, however the pregnancy rate in the group with prolonged desensitization was significantly higher (50%) in comparison to the control group (33.8%). The prolonged pituitary desensitization before controlled ovarian hyperstimulation gives better chance for obtaining pregnancy in patients with severe PCOD. It could be recommended facing previous treatment failure.

  9. PKCε phosphorylates α4β2 nicotinic ACh receptors and promotes recovery from desensitization

    PubMed Central

    Lee, A M; Wu, D-F; Dadgar, J; Wang, D; McMahon, T; Messing, R O

    2015-01-01

    Background and Purpose Nicotinic (ACh) receptor recovery from desensitization is modulated by PKC, but the PKC isozymes and the phosphorylation sites involved have not been identified. We investigated whether PKCε phosphorylation of α4β2 nAChRs regulates receptor recovery from desensitization. Experimental Approach Receptor recovery from desensitization was investigated by electrophysiological characterization of human α4β2 nAChRs. Phosphorylation of the α4 nAChR subunit was assessed by immunoblotting of mouse synaptosomes. Hypothermia induced by sazetidine-A and nicotine was measured in Prkce−/− and wild-type mice. Key Results Inhibiting PKCε impaired the magnitude of α4β2 nAChR recovery from desensitization. We identified five putative PKCε phosphorylation sites in the large intracellular loop of the α4 subunit, and mutating four sites to alanines also impaired recovery from desensitization. α4 nAChR subunit phosphorylation was reduced in synaptosomes from Prkce−/− mice. Sazetidine-A-induced hypothermia, which is mediated by α4β2 nAChR desensitization, was more severe and prolonged in Prkce−/− than in wild-type mice. Conclusions and Implications PKCε phosphorylates the α4 nAChR subunit and regulates recovery from receptor desensitization. This study illustrates the importance of phosphorylation in regulating α4β2 receptor function, and suggests that reducing phosphorylation prolongs receptor desensitization and decreases the number of receptors available for activation. PMID:26103136

  10. 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

  11. Pectoral nerves I block is associated with a significant motor blockade with no dermatomal sensory changes: a prospective volunteer randomized-controlled double-blind study.

    PubMed

    Desroches, Jean; Belliveau, Marc; Bilodeau, Carole; Landry, Michel; Roy, Maxim; Beaulieu, Pierre

    2018-03-29

    The pectoral nerves (PECS) I block, first described in 2011 for surgery involving the pectoralis muscle, has principally been used for breast cancer surgery. No formal evaluation of its differential motor- and sensory-blocking abilities has been reported. We hypothesize that the PECS I block will produce a motor block of the pectoralis muscles with diminished upper limb adduction strength as measured with a handheld dynamometer. We conducted a PECS I block in a randomized placebo-controlled trial in six healthy subjects who received 0.4 mL·kg -1 of 0.9% saline (placebo) on one side and bupivacaine (0.25% with 1:400 000 epinephrine) on the other. We measured both upper limb adduction strength with a dynamometer and sensory skin levels over the thorax. The mean (standard deviation [SD]) adductor strength evaluated before the block was 119.4 (20.7) Newtons (N). After the PECS I block with bupivacaine, the mean (SD) strength of 54.2 (16.3) N was compared with 116.0 (30.4) N in the placebo group (difference in means 61.8 N; 95% confidence interval [CI], 27.8 to 95.8 N; P = 0.005), showing a 54.6% (95% CI, 43.6 to 65.6%) reduction in adductor strength. There was no difference in dermatomal skin sensory testing between the placebo and bupivacaine sides. This study shows that a PECS I block produces motor blockade as shown by reduced upper limb adductor strength without any overlying dermatomal sensory loss. www.clinicaltrials.gov (NCT03040167) 2 February 2017.

  12. An Hourly Dose-Escalation Desensitization Protocol for Aspirin-Exacerbated Respiratory Disease.

    PubMed

    Chen, Justin R; Buchmiller, Brett L; Khan, David A

    2015-01-01

    Aspirin desensitization followed by maintenance therapy effectively improves symptom control in patients with aspirin exacerbated respiratory disease (AERD). The majority of current desensitization protocols use 3-hour dosing intervals and often require 2 to 3 days to complete. We evaluated hourly dose escalations in a subset of patients with chronic rhinosinusitis, nasal polyps, and asthma who historically reacted to aspirin within 1 hour or were avoiding aspirin with the goal of developing a safe and efficient desensitization protocol. Fifty-seven aspirin desensitizations were performed under the hourly protocol. All patients had refractory nasal polyposis as an indication for aspirin desensitization. The clinical characteristics of each subject were analyzed in relation to aspects of his or her reactions during the procedure. Ninety-eight percent of study patients were successfully treated under the hourly protocol, including those with a history of severe reactions and intubation. None required further medication than is available in an outpatient allergy clinic. A total of 96% of reactors recorded a bronchial or naso-ocular reaction within 1 hour of the preceding dose. Of the total patients on this protocol, 40% were able to complete the procedure in a single day, and 60% within 2 days. Patients with AERD who have a history of symptoms less than 1 hour after aspirin exposure can be safely desensitized with a 1-hour dose-escalation protocol that can often be completed in a single day. Copyright © 2015 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  13. Desensitization to ceftaroline in a patient with multiple medication hypersensitivity reactions.

    PubMed

    Jones, Justin M; Richter, Lisa M; Alonto, Augusto; Leedahl, David D

    2015-02-01

    The case of a patient with multiple medication hypersensitivity reactions and a methicillin-resistant Staphylococcus aureus (MRSA) infection who underwent desensitization to ceftaroline is reported. A 32-year-old Caucasian woman with asthma, gastroesophageal reflux disease, heart murmur, and major depression was admitted for MRSA cellulitis with a subcutaneous abscess along the left sternomanubrial joint and clavicular osteomyelitis secondary to port placement after gastric bypass surgery. The patient had an extensive history of hypersensitivity reactions. Pertinent documented allergies were as follows: penicillin (anaphylaxis), daptomycin (anaphylaxis), vancomycin (hives), linezolid (hives), ertapenem (rash), ciprofloxacin (rash), and tigecycline (rash). The patient also reported previous reactions to aztreonam (unknown) and gentamicin (hives). The pharmacy was consulted to develop a desensitization protocol for ceftaroline. The desensitization protocol used three serial dilutions of ceftaroline to make 14 sequential infusions with escalating doses. Intramuscular epinephrine, i.v. diphenhydramine, and i.v. methylprednisolone were ordered as needed for the development of immediate hypersensitivity reactions during or after administration of ceftaroline. The cumulative dose (574.94 mg) was administered intravenously over 225 minutes with no breakthrough symptoms reported during or after the desensitization protocol. Ceftaroline fosamil 600 mg i.v. every 12 hours was continued for six weeks. Desensitization to ceftaroline was conducted for a patient with extensive history of hypersensitivity reactions to other drugs, including penicillin-induced anaphylaxis. Desensitization and subsequent treatment with full doses of ceftaroline were accomplished without apparent adverse effects. Copyright © 2015 by the American Society of Health-System Pharmacists, Inc. All rights reserved.

  14. Anatomical organization and somatic axonal components of the lumbosacral nerves in female rabbits.

    PubMed

    Cruz, Yolanda; Hernández-Plata, Isela; Lucio, Rosa Angélica; Zempoalteca, René; Castelán, Francisco; Martínez-Gómez, Margarita

    2017-09-01

    To determine the anatomical organization and somatic axonal components of the lumbosacral nerves in female rabbits. Chinchilla adult anesthetized female rabbits were used. Anatomical, electrophysiological, and histological studies were performed. L7, S1, and some fibers from S2 and S3 form the lumbosacral trunk, which gives origin to the sciatic nerve and innervation to the gluteal region. From S2 to S3 originates the pudendal nerve, whose branches innervates the striated anal and urethra sphincters, as well as the bulbospongiosus, ischiocavernosus, and constrictor vulvae muscles. The sensory field of the pudendal nerve is ∼1800 mm 2 and is localized in the clitoral sheath and perineal and perigenital skin. The organization of the pudendal nerve varies between individuals, three patterns were identified, and one of them was present in 50% of the animals. From S3 emerge the pelvic nerve, which anastomoses to form a plexus localized between the vagina and the rectum. The innervation of the pelvic floor originates from S3 to S4 fibers. Most of the sacral spinal nerves of rabbit are mixed, carrying sensory, and motor information. Sacral nerves innervate the hind limbs, pelvic viscera, clitoris, perineal muscles, inguinal and anal glands and perineal, perigenital, and rump skin. The detailed description of the sacral nerves organization, topography, and axonal components further the knowledge of the innervation in pelvic and perinal structures of the female rabbit. This information will be useful in future studies about the physiology and physiopathology of urinary, fecal, reproductive, and sexual functions. © 2017 Wiley Periodicals, Inc.

  15. Head sensory organs of Dactylopodola baltica (Macrodasyida, Gastrotricha): a combination of transmission electron microscopical and immunocytochemical techniques.

    PubMed

    Liesenjohann, Thilo; Neuhaus, Birger; Schmidt-Rhaesa, Andreas

    2006-08-01

    The anterior and posterior head sensory organs of Dactylopodola baltica (Macrodasyida, Gastrotricha) were investigated by transmission electron microscopy (TEM). In addition, whole individuals were labeled with phalloidin to mark F-actin and with anti-alpha-tubulin antibodies to mark microtubuli and studied with confocal laser scanning microscopy. Immunocytochemistry reveals that the large number of ciliary processes in the anterior head sensory organ contain F-actin; no signal could be detected for alpha-tubulin. Labeling with anti-alpha-tubulin antibodies revealed that the anterior and posterior head sensory organs are innervated by a common stem of nerves from the lateral nerve cords just anterior of the dorsal brain commissure. TEM studies showed that the anterior head sensory organ is composed of one sheath cell and one sensory cell with a single branching cilium that possesses a basal inflated part and regularly arranged ciliary processes. Each ciliary process contains one central microtubule. The posterior head sensory organ consists of at least one pigmented sheath cell and several probably monociliary sensory cells. Each cilium branches into irregularly arranged ciliary processes. These characters are assumed to belong to the ground pattern of the Gastrotricha. Copyright 2006 Wiley-Liss, Inc.

  16. An autopsy case of minamata disease (methylmercury poisoning)--pathological viewpoints of peripheral nerves.

    PubMed

    Eto, Komyo; Tokunaga, Hidehiro; Nagashima, Kazuo; Takeuchi, Tadao

    2002-01-01

    The outbreak of methylmercury poisoning in the geographic areas around Minamata Bay, Kumamoto, Japan in the 1950s has become known as Minamata disease. Based on earlier reports and extensive pathological studies on autopsied cases at the Kumamoto University School of Medicine, destructive lesions in the anterior portion of the calcarine cortex and depletion predominantly of granular cells in the cerebellar cortex came to be recognized as the hallmark and diagnostic yardstick of methylmercury poisoning in humans. As the number of autopsy cases of Minamata disease increased, it became apparent that the cerebral lesion was not restricted to the calcarine cortex but was relatively widespread. Less severe lesions, believed to be responsible for the motor symptoms of Minamata patients, were often found in the precentral, postcentral, and lateral temporal cortices. These patients also frequently presented with signs of sensory neuropathy affecting the distal extremities. Because of few sufficiently comprehensive studies, peripheral nerve degeneration has not been universally accepted as a cause of the sensory disturbances in Minamata patients. The present paper describes both biopsy and autopsy findings of the peripheral nerves in a male fisherman who died at the age of 64 years and showed the characteristic central nervous system lesions of Minamata disease at autopsy. A sural nerve biopsy with electron microscopy performed 1 month prior to his death showed endoneurial fibrosis and regenerated myelin sheaths. At autopsy the dorsal roots and sural nerve showed endoneurial fibrosis, loss of nerve fibers, and presence of Büngner's bands. The spinal cord showed Wallerian degeneration of the fasciculus gracilis (Goll's tract) with relative preservation of neurons in sensory ganglia. These findings support the contention that there is peripheral nerve degeneration in Minamata patients due to toxic injury from methylmercury.

  17. Desensitization strategies in adult heart transplantation-Will persistence pay off?

    PubMed

    Chih, Sharon; Patel, Jignesh

    2016-08-01

    Strategies are needed to enable successful heart transplantation in highly sensitized patients. Immunologic challenges from sensitization to human leukocyte antigen (HLA) reduce access to compatible donors, extend waiting times to transplant, and increase the risks of antibody-mediated rejection and cardiac allograft vasculopathy after transplant. The prime goal of desensitization is to increase access to transplantation through expansion of the donor organ pool. Existing therapies are directed at key components of the humoral immune response with newer biologically based regimens able to target plasma cells as the source of antibody production, as well as complement activation that has a central role in antibody-mediated injury. Despite the emergence of early promising results for these agents, a significant knowledge gap remains with the current data for desensitization, extrapolated mostly from non-heart solid-organ transplants and small observational studies. Notably, no approach has demonstrated significant and sustainable reductions in HLA antibody pre-transplant, and the ideal desensitization strategy remains elusive. In addition, clinical tools to evaluate the humoral response and efficacy of therapy are limited, focusing almost exclusively on HLA antibody detection. Importantly, desensitization is associated with significant costs and potential risks, and overall long-term outcomes and cost-effectiveness have not been sufficiently evaluated. Investigation is ongoing into the development of a clinically effective desensitization strategy in heart transplantation. Copyright © 2016 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

  18. Dentin abrasivity of various desensitizing toothpastes.

    PubMed

    Arnold, W H; Gröger, Ch; Bizhang, M; Naumova, E A

    2016-04-02

    The aim of this study was to compare the abrasivity of various commercially available toothpastes that claim to reduce dentin hypersensitivity. Dentin discs were prepared from 70 human extracted molars. The discs were etched with lemon juice for 5 min, and one half of the discs were covered with aluminum tape. Following this, they were brushed with 6 different toothpastes, simulating a total brushing time of 6 months. As a negative control, discs were brushed with tap water only. The toothpastes contained pro-arginine and calcium carbonate, strontium acetate, stannous fluoride, zinc carbonate and hydroxyapatite, new silica, or tetrapotassium pyrophosphate and hydroxyapatite. After brushing, the height differences between the control halves and the brushed halves were determined with a profilometer and statistically compared using a Mann-Whitney U test for independent variables. A significant difference (p < 0.001) in height difference between the controls and the toothpaste-treated samples was found in all cases, except for the stannous fluoride-containing toothpaste (p = 0.583). The highest abrasion was found in the toothpaste containing zinc carbonate and hydroxyapatite, and the lowest was found in the toothpaste containing pro-arginine and calcium carbonate. Desensitizing toothpastes with different desensitizing ingredients have different levels of abrasivity, which may have a negative effect on their desensitizing abilities over a long period of time.

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

    PubMed

    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

    2016-02-01

    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/m), and 4 doses of bortezomib (1.3  mg/m). 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.

  20. Focal release of neurotrophic factors by biodegradable microspheres enhance motor and sensory axonal regeneration in vitro and in vivo.

    PubMed

    Santos, Daniel; Giudetti, Guido; Micera, Silvestro; Navarro, Xavier; Del Valle, Jaume

    2016-04-01

    Neurotrophic factors (NTFs) promote nerve regeneration and neuronal survival after peripheral nerve injury. However, drawbacks related with administration and bioactivity during long periods limit their therapeutic application. In this study, PLGA microspheres (MPs) were used to locally release different NTFs and evaluate whether they accelerate axonal regeneration in comparison with free NTFs or controls. ELISA, SEM, UV/visible light microscopy, organotypic cultures of DRG explants and spinal cord slices were used to characterize MP properties and the bioactivity of the released NTFs. Results of organotypic cultures showed that encapsulated NTFs maintain longer bioactivity and enhance neurite regeneration of both sensory and motor neurons compared with free NTFs. For in vivo assays, the rat sciatic nerve was transected and repaired with a silicone tube filled with collagen gel or collagen mixed with PBS encapsulated MPs (control groups) and with free or encapsulated NGF, BDNF, GDNF or FGF-2. After 20 days, a retrotracer was applied to the regenerated nerve to quantify motor and sensory axonal regeneration. NTF encapsulation in MPs improved regeneration of both motor and sensory axons, as evidenced by increased numbers of retrolabeled neurons. Hence, our results show that slow release of NTFs with PLGA MP enhance nerve regeneration. Copyright © 2016 Elsevier B.V. All rights reserved.

  1. Quantitative Sensory Testing and Current Perception Threshold Testing in Patients With Chronic Pain Following Lower Extremity Fracture.

    PubMed

    Griffioen, Mari A; Greenspan, Joel D; Johantgen, Meg; Von Rueden, Kathryn; O'Toole, Robert V; Dorsey, Susan G; Renn, Cynthia L

    2018-01-01

    Chronic pain is a significant problem for patients with lower extremity injuries. While pain hypersensitivity has been identified in many chronic pain conditions, it is not known whether patients with chronic pain following lower extremity fracture report pain hypersensitivity in the injured leg. To quantify and compare peripheral somatosensory function and sensory nerve activation thresholds in persons with chronic pain following lower extremity fractures with a cohort of persons with no history of lower extremity fractures. This was a cross-sectional study where quantitative sensory testing and current perception threshold testing were conducted on the injured and noninjured legs of cases and both legs of controls. A total of 14 cases and 28 controls participated in the study. Mean time since injury at the time of testing for cases was 22.3 (standard deviation = 12.1) months. The warmth detection threshold ( p = .024) and nerve activation thresholds at 2,000 Hz ( p < .001) and 250 Hz ( p = .002), respectively, were significantly higher in cases compared to controls. This study suggests that patients with chronic pain following lower extremity fractures may experience hypoesthesia in the injured leg, which contrasts with the finding of hyperesthesia previously observed in other chronic pain conditions but is in accord with patients with nerve injuries and surgeries. This is the first study to examine peripheral sensory nerve function at the site of injury in patients with chronic pain following lower extremity fractures using quantitative sensory testing and current perception threshold testing.

  2. 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…

  3. 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)

  4. Methods to evaluate functional nerve recovery in adult rats: walking track analysis, video analysis and the withdrawal reflex.

    PubMed

    Dijkstra, J R; Meek, M F; Robinson, P H; Gramsbergen, A

    2000-03-15

    The aim of this study was to compare different methods for the evaluation of functional nerve recovery. Three groups of adult male Wistar rats were studied. In group A, a 12-mm gap between nerve ends was bridged by an autologous nerve graft; in rats of group B we performed a crush lesion of the sciatic nerve and group C consisted of non-operated control rats. The withdrawal reflex, elicited by an electric stimulus, was used to evaluate the recovery of sensory nerve function. To investigate motor nerve recovery we analyzed the walking pattern. Three different methods were used to obtain data for footprint analysis: photographic paper with thickened film developer on the paws, normal white paper with finger paint, and video recordings. The footprints were used to calculate the sciatic function index (SFI). From the video recordings, we also analyzed stepcycles. The withdrawal reflex is a convenient and reproducible test for the evaluation of global sensory nerve recovery. Recording walking movements on video and the analysis of footplacing is a perfect although time-consuming method for the evaluation of functional aspects of motor nerve recovery.

  5. Detrimental Effects of a Self-reward Contracting Program on Subjects' Involvement in Self-administered Desensitization

    ERIC Educational Resources Information Center

    Barrera, Manuel Jr.; Rosen, Gerald M.

    1977-01-01

    Assesses a self-reward contracting procedure intended to facilitate completion of self-administered desensitization. Self-referred snake phobics received either (a) self-administered desensitization; (b) self-administered desensitization with self-reward contracting; or (c) a self-administered placebo with self-reward contracting. Results show the…

  6. Behavior Modification Through Covert Semantic Desensitization

    ERIC Educational Resources Information Center

    Hekmat, Hamid; Vanian, Daniel

    1971-01-01

    Results support the hypothesized relationship between meaning and phobia. Semantic desensitization techniques based on counter conditioning of meaning were significantly effective in altering the semantic value of the word from unpleasantness to neutrality. (Author)

  7. Desensitization to inhaled aztreonam lysine in an allergic patient with cystic fibrosis using a novel approach.

    PubMed

    Guglani, Lokesh; Abdulhamid, Ibrahim; Ditouras, Joanna; Montejo, Jenny

    2012-10-01

    To report the successful desensitization of a highly allergic patient with cystic fibrosis (CF) to inhaled aztreonam lysine using the novel approach of intravenous desensitization followed by full-dose inhaled therapy without any adverse reactions. A 19-year-old woman with CF had persistent Pseudomonas aeruginosa-positive cultures and a history of type I hypersensitivity reactions to multiple medications, including aztreonam and tobramycin (intravenous and inhaled). To start therapy with an inhaled antipseudomonal antibiotic on a chronic basis, she underwent rapid desensitization to intravenous aztreonam followed by initiation of inhaled aztreonam lysine. Following intravenous desensitization with aztreonam, there was no adverse reaction or decline in lung function noted with inhaled aztreonam lysine and the chronic therapy was continued at home, with a modified regimen to maintain desensitization. Aztreonam lysine has been used for treatment of patients with CF with chronic P. aeruginosa colonization. Previous allergic reaction to intravenous aztreonam is considered a contraindication for use of aztreonam lysine. Our patient had a history of hives and facial swelling following administration of intravenous aztreonam (type I hypersensitivity reaction) as well as hypersensitivity to tobramycin. Rapid desensitization can be done for drugs that mediate a type I hypersensitivity reaction, with mast cells and basophils being the cellular targets. There are a few case reports of desensitization to inhaled antibiotics such as tobramycin and colistin, but desensitization to aztreonam lysine has not previously been reported. Desensitization of a patient with CF who is allergic to intravenous aztreonam was successfully accomplished with the novel approach of rapid intravenous desensitization followed by inhaled therapy. As inhaled antibiotics are being increasingly used for patients with CF, this novel strategy can be used for desensitizing allergic patients with CF to

  8. Peptidomics and Secretomics of the Mammalian Peripheral Sensory-Motor System

    NASA Astrophysics Data System (ADS)

    Tillmaand, Emily G.; Yang, Ning; Kindt, Callie A. C.; Romanova, Elena V.; Rubakhin, Stanislav S.; Sweedler, Jonathan V.

    2015-12-01

    The dorsal root ganglion (DRG) and its anatomically and functionally associated spinal nerve and ventral and dorsal roots are important components of the peripheral sensory-motor system in mammals. The cells within these structures use a number of peptides as intercellular signaling molecules. We performed a variety of mass spectrometry (MS)-based characterizations of peptides contained within and secreted from these structures, and from isolated and cultured DRG cells. Liquid chromatography-Fourier transform MS was utilized in DRG and nerve peptidome analysis. In total, 2724 peptides from 296 proteins were identified in tissue extracts. Neuropeptides are among those detected, including calcitonin gene-related peptide I, little SAAS, and known hemoglobin-derived peptides. Solid phase extraction combined with direct matrix-assisted laser desorption/ionization time-of-flight MS was employed to investigate the secretome of these structures. A number of peptides were detected in the releasate from semi-intact preparations of DRGs and associated nerves, including neurofilament- and myelin basic protein-related peptides. A smaller set of analytes was observed in releasates from cultured DRG neurons. The peptide signals observed in the releasates have been mass-matched to those characterized and identified in homogenates of entire DRGs and associated nerves. This data aids our understanding of the chemical composition of the mammalian peripheral sensory-motor system, which is involved in key physiological functions such as nociception, thermoreception, itch sensation, and proprioception.

  9. Peptidomics and Secretomics of the Mammalian Peripheral Sensory-Motor System.

    PubMed

    Tillmaand, Emily G; Yang, Ning; Kindt, Callie A C; Romanova, Elena V; Rubakhin, Stanislav S; Sweedler, Jonathan V

    2015-12-01

    The dorsal root ganglion (DRG) and its anatomically and functionally associated spinal nerve and ventral and dorsal roots are important components of the peripheral sensory-motor system in mammals. The cells within these structures use a number of peptides as intercellular signaling molecules. We performed a variety of mass spectrometry (MS)-based characterizations of peptides contained within and secreted from these structures, and from isolated and cultured DRG cells. Liquid chromatography-Fourier transform MS was utilized in DRG and nerve peptidome analysis. In total, 2724 peptides from 296 proteins were identified in tissue extracts. Neuropeptides are among those detected, including calcitonin gene-related peptide I, little SAAS, and known hemoglobin-derived peptides. Solid phase extraction combined with direct matrix-assisted laser desorption/ionization time-of-flight MS was employed to investigate the secretome of these structures. A number of peptides were detected in the releasate from semi-intact preparations of DRGs and associated nerves, including neurofilament- and myelin basic protein-related peptides. A smaller set of analytes was observed in releasates from cultured DRG neurons. The peptide signals observed in the releasates have been mass-matched to those characterized and identified in homogenates of entire DRGs and associated nerves. This data aids our understanding of the chemical composition of the mammalian peripheral sensory-motor system, which is involved in key physiological functions such as nociception, thermoreception, itch sensation, and proprioception.

  10. 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.

  11. Infectious complications in living-donor kidney transplant recipients undergoing multi-modal desensitization.

    PubMed

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

    2014-06-01

    Pre-existing humoral barriers challenge the transplantation of living donor kidneys (LDK) into highly sensitized ABO- and human leukocyte antigen (HLA)-incompatible recipients. Conditioning these LDK recipients' immune systems is required before they undergo transplantation. We hypothesized that medical desensitization would yield higher post-transplantation rates of infection. We conducted a study in which matched controls consisting of non-desensitized (NDS) LDK recipients were compared with desensitized (DS) receipients. Pre-transplantation desensitization included treatment with rituximab and mycophenolate mofetil followed by intravenous immunoglobulin (IVIg) and plasmapheresis. All participants in the study underwent induction therapy and maintenance immunosuppression. Primary outcomes included infection (opportunistic, local, systemic) within 12 mo after transplantation. Twenty-five patients underwent desensitization and LDK transplantation. Graft survival in the DS and NDS groups of patients was 96% and 98%, respectively. The mean 3- and 12-mo serum creatinine concentrations in the DS and NDS groups were 1.1±0.2 mg/dL and 1.2±0.3 mg/dL and 0.95±0.4 mg/dL and 0.73±0.8 mg/dL (p=0.3 and p=0.01), respectively. Thirty-six percent of the patients in the DS group had one or more infections, vs. 28% of those in the NDS group (p=0.1). No difference was observed in the frequency of opportunistic or systemic infections in the two groups. Local infections were statistically significantly more frequent in the DS group (60% vs. 30%, respectively; p=0.02). Pre-operative desensitization in highly sensitized LDK recipients is followed by a similar incidence of opportunistic and systemic infections as in NDS patients. Local infections were significantly more frequent in the DS than in the NDS patients in the study. With careful monitoring of infectious complications, pre-transplant desensitization permits LDK transplantation into highly sensitized patients.

  12. Upper Extremity Nerve Function and Pain in Human Volunteers with Narrow versus Wide Tourniquets.

    PubMed

    Kovar, Florian; Jauregui, Julio J; Specht, Stacy C; Baker, Erin; Bhave, Anil; Herzenberg, John E

    2016-01-01

    Nerve injury is a serious potential complication associated with clinical use of tourniquets during surgery. A novel narrow, single-use silicon ring tourniquet has been introduced, which may cause less nerve compression and provide a larger field of surgical exposure than standard wide tourniquets. We investigated both types of tourniquets in the non-dominant proximal upper arm of 15 healthy human volunteers. Pain and neurological effects were assessed during 15 minute trials with each tourniquet applied 1 week apart without anesthesia according to the manufacturers' recommendations. Median nerve function was studied using the pressure-specified sensory device, an instrumented two-point discriminator, and pain was assessed by two validated instruments. Skin sores, redness, nerve damage, or neurological complications did not occur in either group. Subjects reported more pain with the narrow tourniquet; however, measurable effect on median nerve function was the same in both groups. Tourniquet application with the narrow device was more efficient, the device was easier to use, and larger surgical field exposure was obtained. We conclude that the sensory deficit with the use of narrow tourniquets is not greater than that observed with pneumatic/wide tourniquets.

  13. Nerve injuries of the upper extremity and hand

    PubMed Central

    Dahlin, Lars B.; Wiberg, Mikael

    2017-01-01

    A nerve injury has a profound impact on the patient’s daily life due to the impaired sensory and motor function, impaired dexterity, sensitivity to cold as well as eventual pain problems. To perform an appropriate treatment of nerve injuries, a correct diagnosis must be made, where the injury is properly classified, leading to an optimal surgical approach and technique, where timing of surgery is also important for the outcome. Knowledge about the nerve regeneration process, where delicate processes occur in neurons, non-neuronal cells (i.e. Schwann cells) and other cells in the peripheral as well as the central nervous systems, is crucial for the treating surgeon. The surgical decision to perform nerve repair and/or reconstruction depends on the type of injury, the condition of the wound as well as the vascularity of the wound. To reconnect injured nerve ends, various techniques can be used, which include both epineurial and fascicular nerve repair, and if a nerve defect is caused by the injury, a nerve reconstruction procedure has to be performed, including bridging the defect using nerve-grafts or nerve transfer techniques. The patients must be evaluated properly and regularly after the surgical procedure and appropriate rehabilitation programmes are useful to improve the final outcome. Cite this article: EFORT Open Rev 2017;2. DOI: 10.1302/2058-5241.2.160071. Originally published online at www.efortopenreviews.org PMID:28630754

  14. Oral desensitization for milk allergy in children: state of the art.

    PubMed

    Pajno, Giovanni B

    2011-12-01

    The purpose of this review is to research current evidence on cow's milk oral immunotherapy for the treatment of cow's milk allergy (CMA). The specific, active treatment for IgE-mediated food allergy included CMA, which is currently being investigated in human trials. Allergen-specific approaches include oral, sublingual and epicutaneous immunotherapy. Reports on oral immunotherapy (OIT) for the treatment of milk allergy have been more extensive and carried out mostly with native proteins. The aim of OIT with cow's milk is the achievement of desensitization or tolerance by patients suffering from CMA. Desensitization state can be achieved by approximately 36-92% of the children treated with specific immunotherapy; the rate of permanent tolerance is unknown. Longer duration of desensitization may result in permanent tolerance. The possibility of adverse events or reactions during OIT is quite frequent. Side-effects have been reported by patients in all published studies. OIT as an active treatment for CMA represents an emerging reality. Before this treatment can be used in clinical practice, additional studies are needed. Currently, many issues remain unanswered: severity and type of food allergy responsive to specific immunotherapy, degree of protection, 'shared schedules' of desensitization(s) in research settings and well established risk-to-benefit ratio. However the field of specific, active treatment of food allergy is poised for clinically important advances.

  15. The morphological substrate for Renal Denervation: Nerve distribution patterns and parasympathetic nerves. A post-mortem histological study.

    PubMed

    van Amsterdam, Wouter A C; Blankestijn, Peter J; Goldschmeding, Roel; Bleys, Ronald L A W

    2016-03-01

    Renal Denervation as a possible treatment for hypertension has been studied extensively, but knowledge on the distribution of nerves surrounding the renal artery is still incomplete. While sympathetic and sensory nerves have been demonstrated, there is no mention of the presence of parasympathetic nerve fibers. To provide a description of the distribution patterns of the renal nerves in man, and, in addition, provide a detailed representation of the relative contribution of the sympathetic, parasympathetic and afferent divisions of the autonomic nervous system. Renal arteries of human cadavers were each divided into four longitudinal segments and immunohistochemically stained with specific markers for afferent, parasympathetic and sympathetic nerves. Nerve fibers were semi-automatically quantified by computerized image analysis, and expressed as cross-sectional area relative to the distance to the lumen. A total of 3372 nerve segments were identified in 8 arteries of 7 cadavers. Sympathetic, parasympathetic and afferent nerves contributed for 73.5% (95% CI: 65.4-81.5%), 17.9% (10.7-25.1%) and 8.7% (5.0-12.3%) of the total cross-sectional nerve area, respectively. Nerves are closer to the lumen in more distal segments and larger bundles that presumably innervate the kidney lie at 1-3.5mm distance from the lumen. The tissue-penetration depth of the ablation required to destroy 50% of the nerve fibers is 2.37 mm in the proximal segment and 1.78 mm in the most distal segments. Sympathetic, parasympathetic and afferent nerves exist in the vicinity of the renal artery. The results warrant further investigation of the role of the parasympathetic nervous system on renal physiology, and may contribute to refinement of the procedure by focusing the ablation on the most distal segment. Copyright © 2015 Elsevier GmbH. All rights reserved.

  16. Progression from homologous to heterologous desensitization of contraction in gastric smooth muscle cells.

    PubMed

    Severi, C; Carnicelli, V; di Giulio, A; Romano, G; Bozzi, A; Oratore, A; Strom, R; delle Fave, G

    1999-02-01

    Acute desensitization of contraction and its relative mechanisms have been studied in smooth muscle cells isolated from guinea pig stomach. Desensitization was induced by pre-exposure of the cells to one of the excitatory neuropeptides linked to the phospholipase C intracellular cascade, i.e., cholecystokinin (CCK), gastrin-releasing peptide, and Substance P. Desensitization was homologous after a 30-s pre-exposure and heterologous if pre-exposure lasted for 5 min or longer. Homologous desensitization was studied in a more detailed way after pre-exposure to CCK. Preincubation with increasing concentrations of CCK (10 pM-1 microM) induced a progressive rightward shift of the dose-response curves associated with both a decrease in potency (ED50 4.5 pM-2.2 nM) and a maximum response that were not related to a modification of response kinetics. After brief pre-exposure to 1 nM CCK (Dmax), an inhibition of contraction was observed in response to an identical dose of CCK (45.1 +/- 8.6%), the decreased response being associated with an inhibition of inositol phosphates and [Ca++]i mobilization. Both inositol trisphosphate (InsP3)-induced contraction and [Ca++]i mobilization were inhibited to a lesser extent than CCK-induced responses. Any longer pre-exposure of cells to one of the above-mentioned neuropeptides caused heterologous desensitization, with an observed inhibition of contraction in response to all tested agonists (CCK, 60.3 +/- 5.9%; gastrin-releasing peptide: 56.7 +/- 3. 5%; Substance P, 60.6 +/- 6.5%). A similar decrease was observed in InsP3-induced contractions resulting in a desensitization of the InsP3 response as well. Full recovery of contractile responses appeared within 30 min from the end of preincubation, thus indicating that degradation of membrane receptors did not occur. Although pre-exposure of the cells to protein kinase C inhibitor GF109203X did not modify CCK-induced homologous desensitization, it blocked CCK-induced heterologous

  17. Desensitization: Overcoming the Immunologic Barriers to Transplantation

    PubMed Central

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

    2017-01-01

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

  18. Peripheral axotomy of the rat mandibular trigeminal nerve leads to an increase in VIP and decrease of other primary afferent neuropeptides in the spinal trigeminal nucleus.

    PubMed

    Atkinson, M E; Shehab, S A

    1986-12-01

    In the vasoactive intestinal polypeptide (VIP)-rich lumbosacral spinal cord, VIP increases at the expense of other neuropeptides after primary sensory nerve axotomy. This study was undertaken to ascertain whether similar changes occur in peripherally axotomised cranial sensory nerves. VIP immunoreactivity increased in the terminal region of the mandibular nerve in the trigeminal nucleus caudalis following unilateral section of the sensory root of the mandibular trigeminal nerve at the foramen orale. Other primary afferent neuropeptides (substance P, cholecystokinin and somatostatin) were depleted and fluoride-resistant acid phosphatase activity was abolished in the same circumscribed areas of the nucleus caudalis. The rise in VIP and depletion of other markers began 4 days postoperatively and was maximal by 10 days, these levels remaining unchanged up to 1 year postoperatively. VIP-immunoreactive cell bodies were absent from trigeminal ganglia from the unoperated side but small and medium cells stained intensely in the ganglia of the operated side after axotomy. These observations indicate that increase of VIP in sensory nerve terminals is a general phenomenon occurring in both cranial and spinal sensory terminal areas. The intense VIP immunoreactivity in axotomised trigeminal ganglia suggests that the increased levels of VIP in the nucleus caudalis are of peripheral origin, indicating a change in expression of neuropeptides within primary afferent neurons following peripheral axotomy.

  19. 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)

  20. 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.

  1. Differences in two-point discrimination and sensory threshold in the blind between braille and text reading: a pilot study.

    PubMed

    Noh, Ji-Woong; Park, Byoung-Sun; Kim, Mee-Young; Lee, Lim-Kyu; Yang, Seung-Min; Lee, Won-Deok; Shin, Yong-Sub; Kang, Ji-Hye; Kim, Ju-Hyun; Lee, Jeong-Uk; Kwak, Taek-Yong; Lee, Tae-Hyun; Kim, Ju-Young; Kim, Junghwan

    2015-06-01

    [Purpose] This study investigated two-point discrimination (TPD) and the electrical sensory threshold of the blind to define the effect of using Braille on the tactile and electrical senses. [Subjects and Methods] Twenty-eight blind participants were divided equally into a text-reading and a Braille-reading group. We measured tactile sensory and electrical thresholds using the TPD method and a transcutaneous electrical nerve stimulator. [Results] The left palm TPD values were significantly different between the groups. The values of the electrical sensory threshold in the left hand, the electrical pain threshold in the left hand, and the electrical pain threshold in the right hand were significantly lower in the Braille group than in the text group. [Conclusion] These findings make it difficult to explain the difference in tactility between groups, excluding both palms. However, our data show that using Braille can enhance development of the sensory median nerve in the blind, particularly in terms of the electrical sensory and pain thresholds.

  2. Differences in two-point discrimination and sensory threshold in the blind between braille and text reading: a pilot study

    PubMed Central

    Noh, Ji-Woong; Park, Byoung-Sun; Kim, Mee-Young; Lee, Lim-Kyu; Yang, Seung-Min; Lee, Won-Deok; Shin, Yong-Sub; Kang, Ji-Hye; Kim, Ju-Hyun; Lee, Jeong-Uk; Kwak, Taek-Yong; Lee, Tae-Hyun; Kim, Ju-Young; Kim, Junghwan

    2015-01-01

    [Purpose] This study investigated two-point discrimination (TPD) and the electrical sensory threshold of the blind to define the effect of using Braille on the tactile and electrical senses. [Subjects and Methods] Twenty-eight blind participants were divided equally into a text-reading and a Braille-reading group. We measured tactile sensory and electrical thresholds using the TPD method and a transcutaneous electrical nerve stimulator. [Results] The left palm TPD values were significantly different between the groups. The values of the electrical sensory threshold in the left hand, the electrical pain threshold in the left hand, and the electrical pain threshold in the right hand were significantly lower in the Braille group than in the text group. [Conclusion] These findings make it difficult to explain the difference in tactility between groups, excluding both palms. However, our data show that using Braille can enhance development of the sensory median nerve in the blind, particularly in terms of the electrical sensory and pain thresholds. PMID:26180348

  3. Is peroneal nerve injury associated with worse function after knee dislocation?

    PubMed

    Krych, Aaron J; Giuseffi, Steven A; Kuzma, Scott A; Stuart, Michael J; Levy, Bruce A

    2014-09-01

    Peroneal nerve palsy is a frequent and potentially disabling complication of multiligament knee dislocation, but little information exists on the degree to which patients recover motor or sensory function after this injury, and whether having this nerve injury--with or without complete recovery--is a predictor of inferior patient-reported outcome scores. The purposes of this study were to (1) report on motor and sensory recovery as well as patient-reported outcomes scores of patients with peroneal nerve injury from multiligament knee dislocation; (2) compare those endpoints between patients who had partial versus complete nerve injuries; and (3) compare patient-reported outcomes among patients who sustained peroneal nerve injuries after knee dislocation with a matched cohort of multiligament knee injuries without nerve injury. Thirty-two patients were identified, but five did not have 2-year followup and are excluded (16% lost to followup). Twenty-seven patients (24 male, three female) with peroneal nerve injury underwent multiligament knee reconstruction and were followed for 6.3 years (range, 2-18 years). Motor grades were assessed by examination and outcomes by International Knee Documentation Committee (IKDC) and Lysholm scores. Retrospectively, patients were divided into complete (n = 9) and partial nerve palsy (n = 18). Treatment for complete nerve palsy included an ankle-foot orthosis for all patients, nonoperative (one), neurolysis (two), tendon transfer (three), nerve transfer (one), and combined nerve/tendon transfer (one). Treatment for partial nerve palsy included nonoperative (12), neurolysis (four), nerve transfer (one), and combined nerve/tendon transfer (one). Furthermore, patients without nerve injury were matched by Schenck classification, age, and sex. Data were analyzed using univariate and multivariate models. Overall, 18 patients (69%) regained antigravity ankle dorsiflexion after treatment (three complete nerve palsy [38%] versus 15 partial

  4. Desensitization of Fire Bell Phobia

    ERIC Educational Resources Information Center

    O'Reilly, Patricia P.

    1971-01-01

    This case study presents an example of how one school psychologist helped a child and an entire class solve a problem. Although the techniques used are not unique to school psychological practice, the problems presented by their use are. The procedure consisted of a desensitization process lasting ten weeks. (Author)

  5. 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

  6. The subgenual organ complex in the cave cricket Troglophilus neglectus (Orthoptera: Rhaphidophoridae): comparative innervation and sensory evolution

    PubMed Central

    Strauß, Johannes; Stritih, Nataša; Lakes-Harlan, Reinhard

    2014-01-01

    Comparative studies of the organization of nervous systems and sensory organs can reveal their evolution and specific adaptations. In the forelegs of some Ensifera (including crickets and tettigoniids), tympanal hearing organs are located in close proximity to the mechanosensitive subgenual organ (SGO). In the present study, the SGO complex in the non-hearing cave cricket Troglophilus neglectus (Rhaphidophoridae) is investigated for the neuronal innervation pattern and for organs homologous to the hearing organs in related taxa. We analyse the innervation pattern of the sensory organs (SGO and intermediate organ (IO)) and its variability between individuals. In T. neglectus, the IO consists of two major groups of closely associated sensilla with different positions. While the distal-most sensilla superficially resemble tettigoniid auditory sensilla in location and orientation, the sensory innervation does not show these two groups to be distinct organs. Though variability in the number of sensory nerve branches occurs, usually either organ is supplied by a single nerve branch. Hence, no sensory elements clearly homologous to the auditory organ are evident. In contrast to other non-hearing Ensifera, the cave cricket sensory structures are relatively simple, consistent with a plesiomorphic organization resembling sensory innervation in grasshoppers and stick insects. PMID:26064547

  7. Allergy and desensitization to latex. Clinical study on 50 dentistry subjects.

    PubMed

    Vozza, I; Ranghi, G; Quaranta, A

    2005-04-01

    Nowadays latex allergy represents a relevant social and occupational problem because this substance constitutes the first material to realise many dental and non dental products; then, there is a cross-reactivity between latex allergens and proteins present in many vegetal foods. The aim of our research was to find latex allergy cases experimenting a percutaneous desensitization protocol. Among 50 examined subjects, those patients resulting positive to thiuram-mix by patch test have been submitted to desensitization after removal of all latex products and substances giving cross-allergy (kiwi, celery, chestnuts, tomato, banana etc.). Desensitization has been carried out by using latex glove from 10 s progressively to 1 h after 1-year treatment. In 7 patients out of 11 (63.6%) regression of symptoms has been verified; 2 patients (18.2%) have declined treatment and 2 patients (18.2%) have showed no regression. Apart immunotherapy and DNA-vaccines, nowadays percutaneous desensitization is the most efficacious, safe and easy treatment for latex allergic patients; it has no collateral effects during its execution and no symptoms coming back to work, but it needs further verifications.

  8. Endothelium-dependent desensitization to angiotensin II in rabbit aorta: the mechanisms involved.

    PubMed

    Jerez, S; de Bruno, M P; Coviello, A

    2001-06-01

    The aim of this study was to characterize the role of the endothelium in angiotensin II-desensitization and its mechanisms of action. Rabbit aortic rings were exposed to increasing doses of angiotensin II (Ang II, 10(-9) to 2.5 x 10(-6)) to generate two cumulative dose-response curves (CDRC I and II). A 50-min interval separated CDRC I and II. Desensitization was observed at all doses in unrubbed aortic tissue and at lower doses in rubbed aortic tissue. Tachyphylaxis was greater in arteries with endothelium. Treatment of intact rings with L-N(G)-nitroarginine methyl ester (L-NAME, 10(-4) M) did not prevent this phenomenon. However, indomethacin (10(-5) M) and miconazol (10(-6) M) attenuated Ang II-desensitization. Treatment of unrubbed rings with nifedipine (10(-6) M) and cromakalim (10(-6) M) inhibited the effect of indomethacin. To confirm the involvement of K+ channels, unrubbed and rubbed aortic rings were treated with the K(Ca2+) blockers apamin (10(-7) M), tetraethylammonium (TEA, 10(-3) M), and iberiotoxin (10(-8) M), and the K(ATP) blocker glibenclamide (10(-5) M). In both arteries apamin, TEA, and glibenclamide abolished the tachyphylaxis without changes in the maximal response. Iberiotoxin diminished Ang II-desensitization in rubbed but not unrubbed arteries. Results from this study suggest that Ang II-desensitization involves endothelium-dependent and -independent mechanisms. Endothelium-dependent desensitization could be mediated by a cyclooxygenase-cytochrome P450 product, which could act by increasing K(Ca2+) channel activity.

  9. Probing N-methyl-D-aspartate receptor desensitization with the substituted-cysteine accessibility method.

    PubMed

    Thomas, Christopher G; Krupp, Johannes J; Bagley, Elena E; Bauzon, Reginald; Heinemann, Stephen F; Vissel, Bryce; Westbrook, Gary L

    2006-04-01

    Several forms of macroscopic N-methyl-D-aspartate (NMDA) receptor desensitization affect the amplitude and duration of postsynaptic responses. In addition to its functional significance, desensitization provides one means to examine the conformational coupling of ligand binding to channel gating. Segments flanking the ligand binding domain in the extracellular N terminus of the NMDA receptor NR2 subunit influence the glycine-independent form of desensitization. The NR2A pre-M1 region, the linker between the glutamate binding domain and the channel pore, plays a critical role in desensitization. Thus, we used the substituted-cysteine accessibility method to scan the accessibility of residues in the pre-M1 region and the first transmembrane domain (M1) of NR2A. Cysteine mutants were expressed with NR1 in human embryonic kidney 293 cells and were assayed by whole-cell recording. With activation of the receptor by glutamate and glycine, only a single mutant, V557C, which is located at the beginning of M1, led to irreversible inhibition by the methanethiosulfonate derivative methanethiosulfonate ethyltrimethylammonium (MTSET). The NR2 ligand glutamate was insufficient on its own to induce modification of V557C by MTSET, suggesting that the change in accessibility required channel gating. The rate of MTSET modification of the homologous residue on NR1 (NR1-1a(L562C)/NR2A) was much slower than V557C. We also substituted cysteine in the V557 site of mutant subunits that exhibit either enhanced or reduced desensitization. Modification by MTSET correlated with the degree of desensitization for these subunits, suggesting that V557C is a sensitive detector of desensitization gating.

  10. Autosomal recessive type II hereditary motor and sensory neuropathy with acrodystrophy.

    PubMed

    Thomas, P K; Claus, D; King, R H

    1999-02-01

    A family is described with presumed autosomal recessive inheritance in which three siblings developed a progressive neuropathy that combined limb weakness and severe distal sensory loss leading to prominent mutilating changes. Electrophysiological and nerve biopsy findings indicated an axonopathy. The disorder is therefore classifiable as type II hereditary motor and sensory neuropathy (HMSN II). The clinical features differ from those reported in previously described cases of autosomal recessive HMSN II. This disorder may therefore represent a new variant.

  11. [Experience of rapid drug desensitization therapy in the treatment of mycobacterial disease].

    PubMed

    Sasaki, Yuka; Kurashima, Atsuyuki; Morimoto, Kozo; Okumura, Masao; Watanabe, Masato; Yoshiyama, Takashi; Ogata, Hideo; Gotoh, Hajime; Kudoh, Shoji; Suzuki, Hiroaki

    2014-11-01

    Drugs for tuberculosis and non-tuberculosis mycobacterial diseases are limited. In particular, no new drugs for non-tuberculosis mycobacterial disease have been developed in recent years. Antimycobacterial drugs have many adverse reactions, for which drug desensitization therapy has been used. Rapid drug desensitization (RDD) therapy, including antituberculosis drugs and clarithromycin, has been implemented in many regions in Europe and the United States. We investigated the validity of RDD therapy in Japan. We report our experience with RDD therapy in 13 patients who developed severe drug allergy to antimycobacterial treatment. The desensitization protocol reported by Holland and Cernandas was adapted. The underlying diseases were 7 cases of pulmonary Mycobacterium avium complex disease and 6 cases of pulmonary tuberculosis. Isoniazid was readministered in 2 (100%) of 2 patients; rifampicin, in 8 (67.7%) of 12 patients; ethambutol, in 4 (67.7%) of 6 patients; and clarithromycin, in 2 (100%) of 2 patients. In Japan, the desensitization therapy recommended by the Treatment Committee of the Japanese Society for Tuberculosis have been implemented generally. We think RDD therapy is effective and safe as the other desensitization therapy. We will continue to investigate the efficiency of RDD therapy in patients who had discontinued antimycobacterial treatment because of the drug allergic reaction.

  12. Grapefruit-seed extract attenuates ethanol-and stress-induced gastric lesions via activation of prostaglandin, nitric oxide and sensory nerve pathways.

    PubMed

    Brzozowski, Tomasz; Konturek, Peter C; Drozdowicz, Danuta; Konturek, Stanislaw J; Zayachivska, Oxana; Pajdo, Robert; Kwiecien, Slawomir; Pawlik, Wieslaw W; Hahn, Eckhart G

    2005-11-07

    Grapefruit-seed extract (GSE) containing flavonoids, possesses antibacterial and antioxidative properties but whether it influences the gastric defense mechanism and gastroprotection against ethanol- and stress-induced gastric lesions remains unknown. We compared the effects of GSE on gastric mucosal lesions induced in rats by topical application of 100% ethanol or 3.5 h of water immersion and restraint stress (WRS) with or without (A) inhibition of cyclooxygenase (COX)-1 activity by indomethacin and rofecoxib, the selective COX-2 inhibitor, (B) suppression of NO-synthase with L-NNA (20 mg/kg ip), and (C) inactivation by capsaicin (125 mg/kg sc) of sensory nerves with or without intragastric (ig) pretreatment with GSE applied 30 min prior to ethanol or WRS. One hour after ethanol and 3.5 h after the end of WRS, the number and area of gastric lesions were measured by planimetry, the gastric blood flow (GBF) was assessed by H2-gas clearance technique and plasma gastrin levels and the gastric mucosal generation of PGE2, superoxide dismutase (SOD) activity and malonyldialdehyde (MDA) concentration, as an index of lipid peroxidation were determined. Ethanol and WRS caused gastric lesions accompanied by the significant fall in the GBF and SOD activity and the rise in the mucosal MDA content. Pretreatment with GSE (8-64 mg/kg i g) dose-dependently attenuated gastric lesions induced by 100% ethanol and WRS; the dose reducing these lesions by 50% (ID50) was 25 and 36 mg/kg, respectively, and this protective effect was similar to that obtained with methyl PGE2 analog (5 microg/kg i g). GSE significantly raised the GBF, mucosal generation of PGE2, SOD activity and plasma gastrin levels while attenuating MDA content. Inhibition of PGE2 generation with indomethacin or rofecoxib and suppression of NO synthase by L-NNA or capsaicin denervation reversed the GSE-induced protection and the accompanying hyperemia. Co-treatment of exogenous calcitonine gene-related peptide (CGRP) with

  13. Group Desensitization of Test Anxiety.

    ERIC Educational Resources Information Center

    Cohen, Robert; Dean, Sanford J.

    Some of the specific learning and motivational variables involved in desensitization therapy were investigated. Two factors were considered: group interaction as a source of motivation and discrimination learning, and the effect of a progressive hierarchy of problem-related situations upon anxiety arousal. The design of the study involved a 2x2…

  14. 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)

  15. Subthreshold Desensitization of Human Basophils Re-capitulates the Loss of syk and FcεRI expression Characterized by Other Methods of Desensitization

    PubMed Central

    MacGlashan, Donald

    2012-01-01

    Background Clinical desensitization of patients to drugs involves progressive exposure to escalating doses of drug over a period of 24 hours. In prior studies, this method was recapitulated in vitro to also demonstrate loss of mast cell or basophil responsiveness. However, most signaling studies of human basophils have identified changes in signaling by using other methods of inducing cellular desensitization. Objective This study examined two well-described endpoints of basophil desensitization, loss of syk or FcεRI expression, under conditions of subthreshold desensitization. Methods The loss of FceRI and syk was examined in human basophils. Results It was shown that both loss of syk and FcεRI/IgE occurred during an escalating series of stimulation (anti-IgE Ab) and that expression loss occurred despite the presence of little histamine release. If basophils were first cultured for 3 days in 10 ng/ml IL-3, the concentration-dependence of histamine release shifted to 100 fold lower concentrations of stimulus. However, loss of syk did not show any change in its EC50 while loss of FcεRI also shifted 100 fold. From the perspective of early signal element activation, the marked shift in the EC50 for histamine release was not accompanied by similar shifts in the EC50s for several signaling elements. The EC50s for phospho-Src, phospho-SHIP1, phospho-Syk, or phospho-Cbl did not change while the EC50s for phospho-Erk and the cytosolic calcium response did shift 100 fold. Conclusions These studies show that under normal conditions, subthreshold desensitization leads to loss of two critical signaling molecules (FcεRI and syk) but under at least one condition, treatment with IL-3, it is possible to markedly blunt the loss of syk, but not FcεRI, while executing a proper subthreshold titration. These data also suggest that IL-3 modifies only the sensitivity of signaling elements that are downstream of syk activation. PMID:22702505

  16. Rate of Homologous Desensitization and Internalization of the GLP-1 Receptor.

    PubMed

    Shaaban, Ghina; Oriowo, Mabayoje; Al-Sabah, Suleiman

    2016-12-26

    The glucagon-like peptide-1 receptor (GLP-1R) is an important target in the treatment of type 2 diabetes mellitus. The aim of this study was to compare the rate of agonist stimulated desensitization and internalization of GLP-1R. To this end, an N-terminally myc-tagged GLP-1R was stably expressed in HEK-293 cells. Homologous desensitization was assessed by measuring the cAMP response to agonist stimulation following pre-incubation with agonist for up to 120 min. Receptor internalization was monitored using an indirect ELISA-based method and confocal microscopy. Pre-incubation with GLP-1 resulted in a time-dependent loss of response to a second stimulation. Washing cells following pre-incubation failed to bring cAMP levels back to basal. Taking this into account, two desensitization rates were calculated: "apparent" (t 1/2 = 19.27 min) and "net" (t 1/2 = 2.99 min). Incubation of cells with GLP-1 also resulted in a time-dependent loss of receptor cell surface expression (t 1/2 = 2.05 min). Rapid agonist-stimulated internalization of GLP-1R was confirmed using confocal microscopy. Stimulation of GLP-1R with GLP-1 results in rapid desensitization and internalization of the receptor. Interestingly, the rate of "net" desensitization closely matches the rate of internalization. Our results suggest that agonist-bound GLP-1R continues to generate cAMP after it has been internalized.

  17. Lentiviral-mediated transfer of CDNF promotes nerve regeneration and functional recovery after sciatic nerve injury in adult rats

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Cheng, Lei; Liu, Yi; Zhao, Hua

    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-mediatedmore » 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

  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. 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…

  20. Where are the sensory organs of Nybelinia surmenicola (Trypanorhyncha)? A comparative analysis with Parachristianella sp. and other trypanorhynchean cestodes.

    PubMed

    Biserova, Natalia M; Gordeev, Ilya I; Korneva, Janetta V

    2016-01-01

    The sensory organs in tegument of two trypanorhynchean species--Nybelinia surmenicola (plerocercoid) and adult Parachristianella sp. (Cestoda, Trypanorhyncha)--were studied with the aim of ultrastructural description and a comparative analysis. The Nybelinia surmenicola plerocercoid lacks papillae with sensory cilia on the bothria adhesive surface. We found an unciliated sensory organ within the median bothria fold. This unciliated free nerve ending contains the central electron-dense disc, three dense supporting rings, and broad root. The nerve ending locates in the basal matrix under the tegument. The tegument of N. surmenicola has a number of ultrastructural features which make it significantly different from other Trypanorhyncha: (i) the tegumental cytoplasm has a plicated constitution in a form of high apical and deep basal folds, (ii) numerous layers of the basal matrix are presented in the subtegument, and (iii) the squamiform and bristlelike microtriches N. surmenicola lack the base and the basal plate. In contrast, numerous ciliated and unciliated receptors were found in Parachristianella sp.: six types on the bothria and one type in the strobila tegument. Ultrastructural constitution of sensory organs in the form of ciliated free nerve endings as well as unciliated basal nerve endings of Parachristianella sp. has many common features inside Eucestoda. In comparison with other Trypanorhyncha, all Nybelinia species studied have less quantity of the bothrial sensory organs. This fact may reflect behavioral patterns of Nybelinia as well as phylogenetic position into Trypanorhyncha. Our observations of living animals conventionally demonstrate the ability of N. surmenicola plerocercoids to locomote in forward direction on the Petri dish surface. The participation of the bothrial microtriches in a parasite movement has been discussed.

  1. Oral desensitization to milk: how to choose the starting dose!

    PubMed Central

    Mori, Francesca; Pucci, Neri; Rossi, Maria Elisabetta; de Martino, Maurizio; Azzari, Chiara; Novembre, Elio

    2010-01-01

    Mori F, Pucci N, Rossi ME, de Martino M, Azzari C, Novembre E. Oral desensitization to milk: how to choose the starting dose! Pediatr Allergy Immunol 2010: 21: e450–e453. © 2009 John Wiley & Sons A/S A renewed interest in oral desensitization as treatment for food allergy has been observed in the last few years. We studied a novel method based on the end point skin prick test procedure to establish the starting dose for oral desensitization in a group of 30 children higly allergic to milk. The results (in terms of reactions to the first dose administered) were compared with a group of 20 children allergic to milk as well. Such control group started to swallow the same dose of 0.015 mg/ml of milk. None reacted to the first dose when administered according to the end point skin prick test. On the other side, ten out of 20 children (50%) from the control group showed mild allergic reactions to the first dose of milk. In conclusion the end point skin prick test procedure results safe and easy to be performed in each single child in order to find out the starting dose for oral desensitization to milk, also by taking into account the individual variability. PMID:19624618

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

    PubMed Central

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

    2014-01-01

    Abstract Background: Pre-existing humoral barriers challenge the transplantation of living donor kidneys (LDK) into highly sensitized ABO- and human leukocyte antigen (HLA)-incompatible recipients. Conditioning these LDK recipients' immune systems is required before they undergo transplantation. We hypothesized that medical desensitization would yield higher post-transplantation rates of infection. Methods: We conducted a study in which matched controls consisting of non-desensitized (NDS) LDK recipients were compared with desensitized (DS) receipients. Pre-transplantation desensitization included treatment with rituximab and mycophenolate mofetil followed by intravenous immunoglobulin (IVIg) and plasmapheresis. All participants in the study underwent induction therapy and maintenance immunosuppression. Primary outcomes included infection (opportunistic, local, systemic) within 12 mo after transplantation. Results: Twenty-five patients underwent desensitization and LDK transplantation. Graft survival in the DS and NDS groups of patients was 96% and 98%, respectively. The mean 3- and 12-mo serum creatinine concentrations in the DS and NDS groups were 1.1±0.2 mg/dL and 1.2±0.3 mg/dL and 0.95±0.4mg/dL and 0.73±0.8mg/dL (p=0.3 and p=0.01), respectively. Thirty-six percent of the patients in the DS group had one or more infections, vs. 28% of those in the NDS group (p=0.1). No difference was observed in the frequency of opportunistic or systemic infections in the two groups. Local infections were statistically significantly more frequent in the DS group (60% vs. 30%, respectively; p=0.02). Conclusion: Pre-operative desensitization in highly sensitized LDK recipients is followed by a similar incidence of opportunistic and systemic infections as in NDS patients. Local infections were significantly more frequent in the DS than in the NDS patients in the study. With careful monitoring of infectious complications, pre-transplant desensitization permits LDK

  3. Sensory cortex hyperexcitability predicts short survival in amyotrophic lateral sclerosis.

    PubMed

    Shimizu, Toshio; Bokuda, Kota; Kimura, Hideki; Kamiyama, Tsutomu; Nakayama, Yuki; Kawata, Akihiro; Isozaki, Eiji; Ugawa, Yoshikazu

    2018-05-01

    To investigate somatosensory cortex excitability and its relationship to survival prognosis in patients with amyotrophic lateral sclerosis (ALS). A total of 145 patients with sporadic ALS and 73 healthy control participants were studied. We recorded compound muscle action potential and sensory nerve action potential of the median nerve and the median nerve somatosensory evoked potential (SEP), and we measured parameters, including onset-to-peak amplitude of N13 and N20 and peak-to-peak amplitude between N20 and P25 (N20p-P25p). Clinical prognostic factors, including ALS Functional Rating Scale-Revised, were evaluated. We followed up patients until the endpoints (death or tracheostomy) and analyzed factors associated with survival using multivariate analysis in the Cox proportional hazard model. Compared to controls, patients with ALS showed a larger amplitude of N20p-P25p in the median nerve SEP. Median survival time after examination was shorter in patients with N20p-P25p ≥8 μV (0.82 years) than in those with N20p-P25p <8 μV (1.68 years, p = 0.0002, log-rank test). Multivariate analysis identified a larger N20p-P25p amplitude as a factor that was independently associated with shorter survival ( p = 0.002). Sensory cortex hyperexcitability predicts short survival in patients with ALS. © 2018 American Academy of Neurology.

  4. Desensitization of metastable intermolecular composites

    DOEpatents

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

    2011-04-26

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

  5. True navigation in migrating gulls requires intact olfactory nerves.

    PubMed

    Wikelski, Martin; Arriero, Elena; Gagliardo, Anna; Holland, Richard A; Huttunen, Markku J; Juvaste, Risto; Mueller, Inge; Tertitski, Grigori; Thorup, Kasper; Wild, Martin; Alanko, Markku; Bairlein, Franz; Cherenkov, Alexander; Cameron, Alison; Flatz, Reinhard; Hannila, Juhani; Hüppop, Ommo; Kangasniemi, Markku; Kranstauber, Bart; Penttinen, Maija-Liisa; Safi, Kamran; Semashko, Vladimir; Schmid, Heidi; Wistbacka, Ralf

    2015-11-24

    During migratory journeys, birds may become displaced from their normal migratory route. Experimental evidence has shown that adult birds can correct for such displacements and return to their goal. However, the nature of the cues used by migratory birds to perform long distance navigation is still debated. In this experiment we subjected adult lesser black-backed gulls migrating from their Finnish/Russian breeding grounds (from >60°N) to Africa (to < 5°N) to sensory manipulation, to determine the sensory systems required for navigation. We translocated birds westward (1080 km) or eastward (885 km) to simulate natural navigational challenges. When translocated westwards and outside their migratory corridor birds with olfactory nerve section kept a clear directional preference (southerly) but were unable to compensate for the displacement, while intact birds and gulls with the ophthalmic branch of the trigeminal nerve sectioned oriented towards their population-specific migratory corridor. Thus, air-borne olfactory information seems to be important for migrating gulls to navigate successfully in some circumstances.

  6. Parental desensitization to violence and sex in movies.

    PubMed

    Romer, Daniel; Jamieson, Patrick E; Bushman, Brad J; Bleakley, Amy; Wang, Anli; Langleben, Daniel; Jamieson, Kathleen Hall

    2014-11-01

    To assess desensitization in parents' repeated exposure to violence and sex in movies. A national US sample of 1000 parents living with at least 1 target child in 1 of 3 age groups (6 to 17 years old) viewed a random sequence of 3 pairs of short scenes with either violent or sexual content from popular movies that were unrestricted to youth audiences (rated PG-13 or unrated) or restricted to those under age 17 years without adult supervision (rated R). Parents indicated the minimum age they would consider appropriate to view each film. Predictors included order of presentation, parent and child characteristics, and parent movie viewing history. As exposure to successive clips progressed, parents supported younger ages of appropriate exposure, starting at age 16.9 years (95% confidence interval [CI], 16.8 to 17.0) for violence and age 17.2 years (95% CI, 17.0 to 17.4) for sex, and declining to age 13.9 years (95% CI, 13.7 to 14.1) for violence and 14.0 years (95% CI, 13.7 to 14.3) for sex. Parents also reported increasing willingness to allow their target child to view the movies as exposures progressed. Desensitization was observed across parent and child characteristics, violence toward both human and non-human victims, and movie rating. Those who frequently watched movies were more readily desensitized to violence. Parents become desensitized to both violence and sex in movies, which may contribute to the increasing acceptance of both types of content by both parents and the raters employed by the film industry. Copyright © 2014 by the American Academy of Pediatrics.

  7. Use of axonal projection patterns for the homologisation of cerebral nerves in Opisthobranchia, Mollusca and Gastropoda

    PubMed Central

    2013-01-01

    Introduction Gastropoda are guided by several sensory organs in the head region, referred to as cephalic sensory organs (CSOs). These CSOs are innervated by distinct nerves. This study proposes a unified terminology for the cerebral nerves and the categories of CSOs and then investigates the neuroanatomy and cellular innervation patterns of these cerebral nerves, in order to homologise them. The homologisation of the cerebral nerves in conjunction with other data, e.g. ontogenetic development or functional morphology, may then provide insights into the homology of the CSOs themselves. Results Nickel-lysine axonal tracing (“backfilling”) was used to stain the somata projecting into specific nerves in representatives of opisthobranch Gastropoda. Tracing patterns revealed the occurrence, size and relative position of somata and their axons and enabled these somata to be mapped to specific cell clusters. Assignment of cells to clusters followed a conservative approach based primarily on relative location of the cells. Each of the four investigated cerebral nerves could be uniquely identified due to a characteristic set of soma clusters projecting into the respective nerves via their axonal pathways. Conclusions As the described tracing patterns are highly conserved morphological characters, they can be used to homologise nerves within the investigated group of gastropods. The combination of adequate number of replicates and a comparative approach allows us to provide preliminary hypotheses on homologies for the cerebral nerves. Based on the hypotheses regarding cerebral nerve homology together with further data on ultrastructure and immunohistochemistry of CSOs published elsewhere, we can propose preliminary hypotheses regarding homology for the CSOs of the Opisthobranchia themselves. PMID:23597272

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

    PubMed Central

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

    2013-01-01

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

  9. Desensitization Contributes to the Synaptic Response of Gain-of-Function Mutants of the Muscle Nicotinic Receptor

    PubMed Central

    Elenes, Sergio; Ni, Ying; Cymes, Gisela D.; Grosman, Claudio

    2006-01-01

    Although the muscle nicotinic receptor (AChR) desensitizes almost completely in the steady presence of high concentrations of acetylcholine (ACh), it is well established that AChRs do not accumulate in desensitized states under normal physiological conditions of neurotransmitter release and clearance. Quantitative considerations in the framework of plausible kinetic schemes, however, lead us to predict that mutations that speed up channel opening, slow down channel closure, and/or slow down the dissociation of neurotransmitter (i.e., gain-of-function mutations) increase the extent to which AChRs desensitize upon ACh removal. In this paper, we confirm this prediction by applying high-frequency trains of brief (∼1 ms) ACh pulses to outside-out membrane patches expressing either lab-engineered or naturally occurring (disease-causing) gain-of-function mutants. Entry into desensitization was evident in our experiments as a frequency-dependent depression in the peak value of succesive macroscopic current responses, in a manner that is remarkably consistent with the theoretical expectation. We conclude that the comparatively small depression of the macroscopic currents observed upon repetitive stimulation of the wild-type AChR is due, not to desensitization being exceedingly slow but, rather, to the particular balance between gating, entry into desensitization, and ACh dissociation rate constants. Disruption of this fine balance by, for example, mutations can lead to enhanced desensitization even if the kinetics of entry into, and recovery from, desensitization themselves are not affected. It follows that accounting for the (usually overlooked) desensitization phenomenon is essential for the correct interpretation of mutagenesis-driven structure–function relationships and for the understanding of pathological synaptic transmission at the vertebrate neuromuscular junction. PMID:17074980

  10. Changes in crossed spinal reflexes after peripheral nerve injury and repair.

    PubMed

    Valero-Cabré, Antoni; Navarro, Xavier

    2002-04-01

    We investigated the changes induced in crossed extensor reflex responses after peripheral nerve injury and repair in the rat. Adults rats were submitted to non repaired sciatic nerve crush (CRH, n = 9), section repaired by either aligned epineurial suture (CS, n = 11) or silicone tube (SIL4, n = 13), and 8 mm resection repaired by tubulization (SIL8, n = 12). To assess reinnervation, the sciatic nerve was stimulated proximal to the injury site, and the evoked compound muscle action potential (M and H waves) from tibialis anterior and plantar muscles and nerve action potential (CNAP) from the tibial nerve and the 4th digital nerve were recorded at monthly intervals for 3 mo postoperation. Nociceptive reinnervation to the hindpaw was also assessed by plantar algesimetry. Crossed extensor reflexes were evoked by stimulation of the tibial nerve at the ankle and recorded from the contralateral tibialis anterior muscle. Reinnervation of the hindpaw increased progressively with time during the 3 mo after lesion. The degree of muscle and sensory target reinnervation was dependent on the severity of the injury and the nerve gap created. The crossed extensor reflex consisted of three bursts of activity (C1, C2, and C3) of gradually longer latency, lower amplitude, and higher threshold in control rats. During follow-up after sciatic nerve injury, all animals in the operated groups showed recovery of components C1 and C2 and of the reflex H wave, whereas component C3 was detected in a significantly lower proportion of animals in groups with tube repair. The maximal amplitude of components C1 and C2 recovered to values higher than preoperative values, reaching final levels between 150 and 245% at the end of the follow-up in groups CRH, CS, and SIL4. When reflex amplitude was normalized by the CNAP amplitude of the regenerated tibial nerve, components C1 (300-400%) and C2 (150-350%) showed highly increased responses, while C3 was similar to baseline levels. In conclusion

  11. Clinical Trials of Aspirin Treatment After Desensitization in Aspirin-Exacerbated Respiratory Disease.

    PubMed

    Kowalski, Marek L; Wardzyńska, Aleksandra; Makowska, Joanna S

    2016-11-01

    The clinical efficacy of aspirin treatment after desensitization in patients with respiratory disease exacerbated by nonsteroidal anti-inflammatory drugs has been documented in observational studies and in double-blind placebo-controlled trials. There is no general agreement with regard to the optimal maintenance dose or duration of treatment with acetylsalicylic acid after desensitization, thus further studies are necessary to offer clear guidelines to clinicians. This article summarizes data from noncontrolled, active-control, and placebo-controlled trials assessing clinical effectiveness and reporting on safety of treatment with acetylsalicylic acid in desensitized patients with respiratory disease exacerbated by nonsteroidal anti-inflammatory drugs. Copyright © 2016 Elsevier Inc. All rights reserved.

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

    PubMed Central

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

    1988-01-01

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

  13. Cornea nerve fiber quantification and construction of phenotypes in patients with fibromyalgia

    PubMed Central

    Oudejans, Linda; He, Xuan; Niesters, Marieke; Dahan, Albert; Brines, Michael; van Velzen, Monique

    2016-01-01

    Cornea confocal microscopy (CCM) is a novel non-invasive method to detect small nerve fiber pathology. CCM generally correlates with outcomes of skin biopsies in patients with small fiber pathology. The aim of this study was to quantify the morphology of small nerve fibers of the cornea of patients with fibromyalgia in terms of density, length and branching and further phenotype these patients using standardized quantitative sensory testing (QST). Small fiber pathology was detected in the cornea of 51% of patients: nerve fiber length was significantly decreased in 44% of patients compared to age- and sex-matched reference values; nerve fiber density and branching were significantly decreased in 10% and 28% of patients. The combination of the CCM parameters and sensory tests for central sensitization, (cold pain threshold, mechanical pain threshold, mechanical pain sensitivity, allodynia and/or windup), yielded four phenotypes of fibromyalgia patients in a subgroup analysis: one group with normal cornea morphology without and with signs of central sensitization, and a group with abnormal cornea morphology parameters without and with signs of central sensitization. In conclusion, half of the tested fibromyalgia population demonstrates signs of small fiber pathology as measured by CCM. The four distinct phenotypes suggest possible differences in disease mechanisms and may require different treatment approaches. PMID:27006259

  14. Sciatic Nerve Injury After Proximal Hamstring Avulsion and Repair

    PubMed Central

    Wilson, Thomas J.; Spinner, Robert J.; Mohan, Rohith; Gibbs, Christopher M.; Krych, Aaron J.

    2017-01-01

    Background: Muscle bellies of the hamstring muscles are intimately associated with the sciatic nerve, putting the sciatic nerve at risk of injury associated with proximal hamstring avulsion. There are few data informing the magnitude of this risk, identifying risk factors for neurologic injury, or determining neurologic outcomes in patients with distal sciatic symptoms after surgery. Purpose: To characterize the frequency and nature of sciatic nerve injury and distal sciatic nerve–related symptoms after proximal hamstring avulsion and to characterize the influence of surgery on these symptoms. Study Design: Cohort study; Level of evidence, 3. Methods: This was a retrospective review of patients with proximal partial or complete hamstring avulsion. The outcome of interest was neurologic symptoms referable to the sciatic nerve distribution below the knee. Neurologic symptoms in operative patients were compared pre- and postoperatively. Results: The cohort consisted of 162 patients: 67 (41.4%) operative and 95 (58.6%) nonoperative. Sciatic nerve–related symptoms were present in 22 operative and 23 nonoperative patients, for a total of 45 (27.8%) patients (8 [4.9%] motor deficits, 11 [6.8%] sensory deficits, and 36 [22.2%] with neuropathic pain). Among the operative cohort, 3 of 3 (100.0%) patients showed improvement in their motor deficit postoperatively, 3 of 4 (75.0%) patients’ sensory symptoms improved, and 17 of 19 (89.5%) patients had improvement in pain. A new or worsening deficit occurred in 5 (7.5%) patients postoperatively (2 [3.1%] motor deficits, 1 [1.5%] sensory deficit, and 3 [4.5%] with new pain). Predictors of operative intervention included lower age (odds ratio [OR], 0.952; 95% CI, 0.921-0.982; P = .001) and complete avulsion (OR, 10.292; 95% CI, 2.526-72.232; P < .001). Presence of neurologic deficit was not predictive. Conclusion: Sciatic nerve–related symptoms after proximal hamstring avulsion are underrecognized. Currently, neurologic

  15. Intestinal nerves and ion transport: stimuli, reflexes, and responses.

    PubMed

    Hubel, K A

    1985-03-01

    The effects of extrinsic and intrinsic nerves on ion and water transport by the intestine are considered and discussed in terms of their possible physiological function. Adrenergic nerves enter the small intestine via mesenteric nerves. Adrenergic tone is usually absent in tissues in vitro but is present in vivo. The nerves increase absorption in response to homeostatic changes associated with acute depletion of extracellular fluid. Cholinergic tone that reduces fluid absorption or causes secretion has been detected in the small intestine of humans, dogs, and cats and in the colon of humans. Extrinsic cholinergic fibers generally do not affect ion transport in small intestine but probably do so in colon. Whether peptides liberated in the mucosa affect enterocytes directly is not clear. Studies on humans and rabbits suggest that the role of substance P is minor. The physiological roles of vasoactive intestinal polypeptide (VIP) and somatostatin remain to be defined. Intraluminal factors also affect ion and water transport. Mucosal rubbing, distension, and cholera toxin cause fluid secretion; acid solutions in the duodenum cause alkaline secretion; these stimuli and hypertonic glucose liberate serotonin into the lumen, the mesenteric venous blood, or both. It has been proposed that the enterochromaffin cell is an epithelial sensory cell that responds to noxious stimuli within the lumen by liberating serotonin. The serotonin initiates a neural reflex through a nicotinic ganglion to liberate a secretagogue that acts on the enterocyte. The function of VIP in this proposed reflex is unclear. The variety of intraluminal stimuli that influence epithelial function implies that there is more than one type of epithelial sensory cell (or sensory mechanism). Prostaglandins may mediate the alkaline secretion caused by acid in the duodenum. There may be other effective substances. Although it has been known for years that intraluminal stimuli affect the coordination of smooth

  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.

    PubMed

    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

    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. 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. 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. 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

  17. 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

  18. Endemic Images and the Desensitization Process.

    ERIC Educational Resources Information Center

    Saigh, Philip A.; Antoun, Fouad T.

    1984-01-01

    Examined the effects of endemic images on levels of anxiety and achievement of 48 high school students. Results suggested that a combination of endemic images and study skills training was as effective as desensitization plus study skills training. Includes the endemic image questionnaire. (JAC)

  19. Quantitative thermal sensory testing -- value of testing for both cold and warm sensation detection in evaluation of small fiber neuropathy.

    PubMed

    Shukla, Garima; Bhatia, Manvir; Behari, Madhuri

    2005-10-01

    Small fiber neuropathy is a common neurological disorder, often missed or ignored by physicians, since examination and routine nerve conduction studies are usually normal in this condition. Many methods including quantitative thermal sensory testing are currently being used for early detection of this condition, so as to enable timely investigation and treatment. This study was conducted to assess the yield of quantitative thermal sensory testing in diagnosis of small fiber neuropathy. We included patients presenting with history suggestive of positive and/or negative sensory symptoms, with normal examination findings, clinically suggestive of small fiber neuropathy, with normal or minimally abnormal routine nerve conduction studies. These patients were subjected to quantitative thermal sensory testing using a Medoc TSA-II Neurosensory analyser at two sites and for two modalities. QST data were compared with those in 120 normal healthy controls. Twenty-five patients (16 males, 9 females) with mean age 46.8+/-16.6 years (range: 21-75 years) were included in the study. The mean duration of symptoms was 1.6+/-1.6 years (range: 3 months-6 years). Eighteen patients (72%) had abnormal thresholds in at least one modality. Thermal thresholds were normal in 7 out of the 25 patients. This study demonstrates that quantitative thermal sensory testing is a fairly sensitive method for detection of small fiber neuropathy especially in patients with normal routine nerve conduction studies.

  20. Permanent reorganization of Ia afferent synapses on motoneurons after peripheral nerve injuries

    PubMed Central

    Alvarez, Francisco J.; Bullinger, Katie L.; Titus, Haley E.; Nardelli, Paul; Cope, Timothy C.

    2010-01-01

    After peripheral nerve injuries to a motor nerve the axons of motoneurons and proprioceptors are disconnected from the periphery and monosynaptic connections from group I afferents and motoneurons become diminished in the spinal cord. Following successful reinnervation in the periphery, motor strength, proprioceptive sensory encoding, and Ia afferent synaptic transmission on motoneurons partially recover. Muscle stretch reflexes, however, never recover and motor behaviors remain uncoordinated. In this review, we summarize recent findings that suggest that lingering motor dysfunction might be in part related to decreased connectivity of Ia afferents centrally. First, sensory afferent synapses retract from lamina IX causing a permanent relocation of the inputs to more distal locations and significant disconnection from motoneurons. Second, peripheral reconnection between proprioceptive afferents and muscle spindles is imperfect. As a result, a proportion of sensory afferents that retain central connections with motoneurons might not reconnect appropriately in the periphery. A hypothetical model is proposed in which the combined effect of peripheral and central reconnection deficits might explain the failure of muscle stretch to initiate or modulate firing of many homonymous motoneurons. PMID:20536938

  1. Rapid drug desensitization for hypersensitivity reactions to chemotherapy and monoclonal antibodies in the 21st century.

    PubMed

    Castells Guitart, M C

    2014-01-01

    The frequency of hypersensitivity reactions (HSR) to drugs has risen in the last 10 years owing to increased exposure to better and more allergenic medications including monoclonal antibodies. HSRs prevent patients from using their first-line therapy, leading to decreased quality of life and life expectancy. Although premedication with antihistamines, leukotriene blockers, and corticosteroids can protect against mild-to-moderate HSR, none of these medications has provided protection against anaphylaxis. Rapid drug desensitization is a treatment option for patients with HSR to their first-line medication that protects against anaphylaxis.Although the mechanisms of drug desensitization are not completely understood, in vitro mast cell models of IgE antigen desensitization have led to the design of safe and effective in vivo protocols aimed at protecting highly sensitized patients from hypersensitivity reactions and anaphylaxis. This review provides an insight into the mechanisms of IgE/mast cell desensitization, the principles and practice of drug desensitization, and an overview of the different desensitization protocols and their safety and efficacy profiles. Drug desensitization should only be performed by allergists, trained nurses, and experienced pharmacists, since this high-risk procedure involves reintroducing allergenic medication to highly sensitized patients, with the consequent potential for severe or fatal HSRs.

  2. Electrophysiologic alterations in the excitability of the sciatic and vagus nerves during early stages of sepsis.

    PubMed

    Diniz, Lúcio Ricardo Leite; Portella, Viviane Gomes; da Silva Alves, Kerly Shamira; Araújo, Pâmella Cristina da Costa; de Albuquerque Júnior, Ricardo Luiz Cavalcanti; Cavalcante de Albuquerque, Aline Alice; Coelho-de-Souza, Andrelina Noronha; Leal-Cardoso, José Henrique

    2018-01-01

    Nonspecific and delayed diagnosis of neurologic damage contributes to the development of neuropathies in patients with severe sepsis. The present study assessed the electrophysiologic parameters related to the excitability and conductibility of sciatic and vagus nerves during early stages of sepsis. Twenty-four hours after sepsis induced by cecal ligation and puncture (CLP) model, sciatic and vagus nerves of septic (CLP group) and control (sham group) rats were removed, and selected electric stimulations were applied to measure the parameters of the first and second components of the compound action potential. The first component originated from fibers with motor and sensory functions (Types A α and A β fibers) with a large conduction velocity (70-120 m/s), and the second component originated from fibers (Type A γ ) with sensorial function. To evaluate the presence of sensorial alterations, the sensitivity to non-noxious mechanical stimuli was measured by using the von Frey test. Hematoxylin and eosin staining of the nerves was performed. We observed an increase of rheobase followed by a decrease in the first component amplitude and a higher paw withdrawal threshold in response to the application of von Frey filaments in sciatic nerves from the CLP group compared to the sham group. Differently, a decrease in rheobase and an increase in the first component amplitude of vagal C fibers from CLP group were registered. No significant morphologic alteration was observed. Our data showed that the electrophysiologic alterations in peripheral nerves vary with the fiber type and might be identified in the first 24 h of sepsis, before clinical signs of neuromuscular disorders.

  3. Cow's Milk Desensitization in Anaphylactic Patients: A New Personalized-dose Method.

    PubMed

    Babaie, Delara; Nabavi, Mohammad; Arshi, Saba; Mesdaghi, Mehrnaz; Chavoshzadeh, Zahra; Bemanian, Mohammad Hasan; Tafakori, Mitra; Amirmoini, Mehrdad; Esmailzadeh, Hosein; Molatefi, Rasoul; Rekabi, Mahsa; Akbarpour, Nadieh; Masoumi, Farimah; Fallahpour, Morteza

    2017-02-01

    Cow's milk allergy (CMA) is the most frequent food allergy in children and oral immunotherapy (OIT) is a promising approach for treatment of patients. The most challenging cases are anaphylactic with coexisting asthma and proposing safe protocols is crucial especially in high risk groups. Considering that CMA varies among patients, an individualized OIT protocol would be beneficial to achieve a safer and more efficient method of desensitization. 18 children more than 3 years of age with IgE-mediated CMA were enrolled. CMA was confirmed by positive skin prick test (SPT) and positive oral food challenge (OFC) and 60% of individuals had a convincing history of persistent asthma. SPT with milk extracts, whole fresh milk and serially diluted milk concentrations were performed.  The dilution of milk that induced 3-5 mm of wheal in each individual was selected as the starting dilution for OIT. Desensitization began by 1 drop of the defined dilution and continued increasingly. Overall, 16 out of 18 children (88.8%) achieved the daily intake of 120 mL of milk. Four out of these 16 children accomplished the protocol without any adverse allergic reactions. 12 patients experienced mild to severe reactions. Wheal and erythema in SPT (p≤0.001), and sIgE (p≤0.003) to most milk allergens were significantly decreased following desensitization. We successfully desensitized 16 of 18 children with IgE-mediated CMA by individualized desensitization protocol. Individualizing the OIT protocol would be helpful to save time and perhaps to relieve the allergic symptoms after ingesting cow's milk intake.

  4. 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)

  5. 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)

  6. Hypersensitivity and desensitization to antineoplastic agents: outcomes of 189 procedures with a new short protocol and novel diagnostic tools assessment.

    PubMed

    Madrigal-Burgaleta, R; Berges-Gimeno, M P; Angel-Pereira, D; Ferreiro-Monteagudo, R; Guillen-Ponce, C; Pueyo, C; Gomez de Salazar, E; Alvarez-Cuesta, E

    2013-07-01

    Desensitization to antineoplastic agents is becoming a standard of care. Efforts to establish and improve these techniques are being made at many institutions. Our aims are to evaluate a new rapid desensitization protocol designed to be shorter (approximately 4 h) and safer (reducing hazardous drugs exposure risks) and to assess the oxaliplatin-specific immunoglobulin E (IgE) as a novel diagnostic tool. Prospective, observational, longitudinal study with patients who, for a 1-year period, suffered reactions to antineoplastic agents and were referred to the Desensitization Program at Ramon y Cajal University Hospital (RCUH). Patients were included or excluded as desensitization candidates after anamnesis, skin testing, risk assessment, and graded challenge. Specific IgE was determined in oxaliplatin-reactive patients. Candidate patients were desensitized using the new RCUH rapid desensitization protocol. Of 189 intravenous rapid desensitizations, 188 were successfully accomplished in the 23 patients who met inclusion criteria for desensitization (of 58 referred patients). No breakthrough reactions occurred in 94% of desensitizations, and most breakthrough reactions were mild. In 10 oxaliplatin-reactive patients, 38 desensitizations were successfully accomplished. Sensitivity for oxaliplatin-specific IgE was 38% (0.35UI/l cutoff point) and 54% (0.10UI/l cutoff point); specificity was 100% for both cutoff points. In the hands of a Desensitization Program, managed by drug desensitization experts, this new protocol has proven an effective therapeutic tool for hypersensitivity to several antineoplastic agents (oxaliplatin, carboplatin, paclitaxel, docetaxel, cyclophosphamide, and rituximab); moreover, it improves safety handling of hazardous drugs. We report the first large series of oxaliplatin desensitizations. Oxaliplatin-specific IgE determination could be helpful. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  7. Local GABAergic signaling within sensory ganglia controls peripheral nociceptive transmission

    PubMed Central

    Du, Xiaona; Hao, Han; Yang, Yuehui; Huang, Sha; Wang, Caixue; Gigout, Sylvain; Ramli, Rosmaliza; Li, Xinmeng; Jaworska, Ewa; Edwards, Ian; Yanagawa, Yuchio; Qi, Jinlong; Guan, Bingcai; Jaffe, David B.; Zhang, Hailin

    2017-01-01

    The integration of somatosensory information is generally assumed to be a function of the central nervous system (CNS). Here we describe fully functional GABAergic communication within rodent peripheral sensory ganglia and show that it can modulate transmission of pain-related signals from the peripheral sensory nerves to the CNS. We found that sensory neurons express major proteins necessary for GABA synthesis and release and that sensory neurons released GABA in response to depolarization. In vivo focal infusion of GABA or GABA reuptake inhibitor to sensory ganglia dramatically reduced acute peripherally induced nociception and alleviated neuropathic and inflammatory pain. In addition, focal application of GABA receptor antagonists to sensory ganglia triggered or exacerbated peripherally induced nociception. We also demonstrated that chemogenetic or optogenetic depolarization of GABAergic dorsal root ganglion neurons in vivo reduced acute and chronic peripherally induced nociception. Mechanistically, GABA depolarized the majority of sensory neuron somata, yet produced a net inhibitory effect on the nociceptive transmission due to the filtering effect at nociceptive fiber T-junctions. Our findings indicate that peripheral somatosensory ganglia represent a hitherto underappreciated site of somatosensory signal integration and offer a potential target for therapeutic intervention. PMID:28375159

  8. Some characteristics of histamine secretion from rat peritoneal mast cells stimulated with nerve growth factor.

    PubMed Central

    Pearce, F L; Thompson, H L

    1986-01-01

    Nerve growth factor (NGF) isolated from mouse submandibular gland or from snake venom produced a dose-dependent release of histamine from isolated rat peritoneal mast cells. The response was almost totally dependent on the presence of extracellular calcium ions and on added phosphatidylserine or its lyso-derivative. At high concentrations, strontium ions could substitute for calcium. The process was non-cytotoxic, relatively slow, pH dependent and blocked by polyclonal antibodies to NGF. Binding of NGF to the mast cell was not dependent on added calcium. The release was unaffected by low molecular weight glucose polymers or specific quaternary ammonium salts and thus differed from that evoked by clinical dextran or polyamines. The release was not inhibited by soluble rat IgE or IgG and was unimpaired in mast cells recovered from specific pathogen free rats. As such it did not appear to be mediated through interaction with cell-fixed antibodies. The process further differed from anaphylactic histamine release in that there was no accompanying change in the intracellular level of adenosine 3',5'-cyclic monophosphate (cyclic AMP), the activated state induced by NGF was much more persistent than that evoked by antigen, and there was no cross-desensitization between the two latter stimuli. In total, these data suggest that NGF may induce secretion from rat mast cells by interaction with a specific receptor on the plasma membrane, possibly similar to that present on sensory and sympathetic neurones. PMID:2425086

  9. Pharmacological characterization of desensitization in scratching behavior induced by intrathecal administration of hemokinin-1 in the rat.

    PubMed

    Naono, R; Nakayama, T; Ikeda, T; Matsusima, O; Nishimori, T

    2008-02-01

    Desensitization is induced by the repeated administration of high doses of substance P (SP) or hemokinin-1 (HK-1). However, little information is available about the mechanisms involved in the induction of desensitization by these peptides. Thus, to characterize this desensitization, we examined the dose-dependent effect of these peptides, the effect of pretreatment with neurokinin 1(NK1) receptor antagonists, and the effect of pretreatment with inhibitors of protein kinases such as protein kinase A (PKA), protein kinase C (PKC), calcium/calmodulin kinase II (CaMKII) and mitogen-activated protein kinase kinase (MEK). The number of scratchings induced by 10(-3)M SP or HK-1 decreased following pretreatment with 10(-11)-10(-3)M SP or HK-1 with a marked reduction at 10(-3) and 10(-6)M SP or HK-1. The effect of NK1 receptor antagonists on desensitization induced by pretreatment with 10(-6)M SP was marked, whereas there was little effect of pretreatment with these antagonists on 10(-6)M HK-1-induced desensitization. Additionally, 10(-6)M SP- and HK-1-induced desensitization was attenuated by pretreatment with PKA, PKC and MEK inhibitors, except a CaMKII inhibitor that inhibited SP-induced desensitization. These results indicate that the receptor and kinases involved in HK-1-induced desensitization are partially different from those of SP.

  10. 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

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

    PubMed

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

    2016-01-01

    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. 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. 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

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

    PubMed

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

    2013-08-01

    In hypersensitive reactions to native L-asparaginase, either premedication and desensitization or substitution with polyethylene glycol conjugated asparaginase (PEG-ASP) is preferred. Anaphylaxis with PEG-ASP is rare. An 8-year-old girl and a 2.5-year-old boy, both diagnosed as having acute lymphoblastic leukemia, presented with native L-asparaginase hypersensitivity and substitution with PEG-ASP was preferred. They received a premedication (methylprednisolone, hydroxyzine and ranitidine) followed by desensitization with PEG-ASP infusion. Both patients developed anaphylaxis with peg-asparaginase. These are the first reported cases of anaphylactic reaction to PEG-ASP, despite the application of both premedication and desensitization. Anaphylaxis with PEG-ASP is very rare and premedication and desensitization protocols may not prevent these hypersensitive reactions. © 2013 The Authors. Pediatrics International © 2013 Japan Pediatric Society.

  13. 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…

  14. The role of sensory input of the chorda tympani nerve and the number of fungiform papillae in burning mouth syndrome.

    PubMed

    Nasri-Heir, Cibele; Gomes, Julyana; Heir, Gary M; Ananthan, Sowmya; Benoliel, Rafael; Teich, Sorin; Eliav, Eli

    2011-07-01

    The aim of this study was to evaluate patients suffering from burning mouth syndrome (BMS) and control subjects by means of sensory testing and fungiform papillae count. The left and right anterior two-thirds of the tongue of of 25 BMS subjects and 20 healthy control subjects were evaluated for electric taste and electric detection threshold. The number of fungiform papillae/cm(2) was evaluated by using close-up digital photography. The electric taste/tingling detection threshold ratio was significantly higher in BMS compared with control subjects (P = .041). No difference was found between the number of fungiform papillae/cm(2) in the BMS compared with the control subjects (P = .277). Patients suffering from BMS for a prolonged period of time presented with a significantly elevated electric taste/tingling detection threshold ratio (P = .031). BMS may be a neurodegenerative process with chorda tympani nerve hypofunction potentially playing a role in the pathophysiology of this disorder. Copyright © 2011 Mosby, Inc. All rights reserved.

  15. Nerve regeneration with aid of nanotechnology and cellular engineering.

    PubMed

    Sedaghati, Tina; Yang, Shi Yu; Mosahebi, Afshin; Alavijeh, Mohammad S; Seifalian, Alexander M

    2011-01-01

    Repairing nerve defects with large gaps remains one of the most operative challenges for surgeons. Incomplete recovery from peripheral nerve injuries can produce a diversity of negative outcomes, including numbness, impairment of sensory or motor function, possibility of developing chronic pain, and devastating permanent disability. In the last few years, numerous microsurgical techniques, such as coaptation, nerve autograft, and different biological or polymeric nerve conduits, have been developed to reconstruct a long segment of damaged peripheral nerve. A few of these techniques are promising and have become popular among surgeons. Advancements in the field of tissue engineering have led to development of synthetic nerve conduits as an alternative for the nerve autograft technique, which is the current practice to bridge nerve defects with gaps larger than 30 mm. However, to date, despite significant progress in this field, no material has been found to be an ideal alternative to the nerve autograft. This article briefly reviews major up-to-date published studies using different materials as an alternative to the nerve autograft to bridge peripheral nerve gaps in an attempt to assess their ability to support and enhance nerve regeneration and their prospective drawbacks, and also highlights the promising hope for nerve regeneration with the next generation of nerve conduits, which has been significantly enhanced with the tissue engineering approach, especially with the aid of nanotechnology in development of the three-dimensional scaffold. The goal is to determine potential alternatives for nerve regeneration and repair that are simply and directly applicable in clinical conditions. Copyright © 2011 International Union of Biochemistry and Molecular Biology, Inc.

  16. Effect of sensory denervation on the structure and physiologic responsiveness of rabbit lacrimal gland.

    PubMed

    Meneray, M A; Bennett, D J; Nguyen, D H; Beuerman, R W

    1998-01-01

    This work was conducted to determine the effects of unilateral trigeminal ganglion ablation on lacrimal gland structure and secretory activity. Adult male New Zealand rabbits underwent unilateral thermocoagulation of the ophthalmic division of the trigeminal ganglion. Sensory denervation was affirmed by anatomic inspection of the lesion and transmission electron microscopy (TEM) of the lacrimal gland innervation. Eight to 10 days after the procedure, the intraorbital lacrimal glands were removed from both sides. To compare the physiologic competence of the intact and denervated glands, freshly isolated gland fragments from the paired intact and denervated glands were stimulated with carbachol (100 microM), isoproterenol (10 microM), phorbol-12,13-dibutyrate (PDBu, 10 microM), forskolin (40 microM), or vehicle. Total secreted protein was measured at 30 or 60 min after the establishment of baseline values. Intact and denervated glands also were examined by light and TEM, and the morphologic appearance of the acinar structures as well as the appearance of nerves innervating the gland after denervation were assessed. Similar experiments were conducted with animals that underwent unilateral superior cervical ganglionectomy. Tissues from sensory denervated glands released significantly more protein than did tissues from innervated glands in response to in vitro stimulation by carbachol or isoproterenol but not in response to PDBu or forskolin. Microscopy showed that the acinar cells that had undergone sensory denervation showed a massive accumulation of secretory granules. The secretory granules filled the entire cytoplasmic space and displaced the ellipsoidal nuclei to the extreme periphery. Examination of segments of nerves revealed numerous unmyelinated axons, a few small-diameter myelinated axons, and a large amount of nerve degeneration after sensory denervation. In contrast to the effects of sensory denervation, sympathetic denervation did not alter either the

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

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Tishler, R.B.; Loeffler, J.S.; Alexander, E. III

    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 (Universitymore » 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.« less

  18. Dynamics of the sensory response to urethral flow over multiple time scales in rat

    PubMed Central

    Danziger, Zachary C; Grill, Warren M

    2015-01-01

    The pudendal nerve carries sensory information from the urethra that controls spinal reflexes necessary to maintain continence and achieve efficient micturition. Despite the key role urethral sensory feedback plays in regulation of the lower urinary tract, there is little information about the characteristics of urethral sensory responses to physiological stimuli, and the quantitative relationship between physiological stimuli and the evoked sensory activation is unknown. Such a relation is critical to understanding the neural control of the lower urinary tract and how dysfunction arises in disease states. We systematically quantified pudendal afferent responses to fluid flow in the urethra in vivo in the rat. We characterized the sensory response across a range of stimuli, and describe a previously unreported long-term neural accommodation phenomenon. We developed and validated a compact mechanistic mathematical model capable of reproducing the pudendal sensory activity in response to arbitrary profiles of urethral flows. These results describe the properties and function of urethral afferents that are necessary to understand how sensory disruption manifests in lower urinary tract pathophysiology. Key points Sensory information from the urethra is essential to maintain continence and to achieve efficient micturition and when compromised by disease or injury can lead to substantial loss of function. Despite the key role urethral sensory information plays in the lower urinary tract, the relationship between physiological urethral stimuli, such as fluid flow, and the neural sensory response is poorly understood. This work systematically quantifies pudendal afferent responses to a range of fluid flows in the urethra in vivo and describes a previously unknown long-term neural accommodation phenomenon in these afferents. We present a compact mechanistic mathematical model that reproduces the pudendal sensory activity in response to urethral flow. These results have

  19. Novel, posterior sensory organ in the trochophore larva of Phyllodoce maculata (Polychaeta).

    PubMed Central

    Nezlin, L P; Voronezhskaya, E E

    2003-01-01

    A new posterior sensory organ (PSO), located at the dorsal midline of the hyposphere, is described by immunocytochemical detection of acetylated alpha tubulin and serotonin (5-HT) in a laser-scanning microscope, as well as three-dimensional reconstructions after optical serial sectioning in the trochophore larva of the polychaete Phyllodoce maculata (Phyllodocidae). The unpaired PSO consists of five bipolar sensory cells, two of them being 5-HT immunopositive, which send axons to the cerebral ganglion and prototroch nerve. The dendrites of these cells project to the surface and bear one cilium each. A single neuronal fibre from the apical sensory organ innervates the PSO. PMID:14667369

  20. Cholesterol modulates open probability and desensitization of NMDA receptors

    PubMed Central

    Korinek, Miloslav; Vyklicky, Vojtech; Borovska, Jirina; Lichnerova, Katarina; Kaniakova, Martina; Krausova, Barbora; Krusek, Jan; Balik, Ales; Smejkalova, Tereza; Horak, Martin; Vyklicky, Ladislav

    2015-01-01

    NMDA receptors (NMDARs) are glutamate-gated ion channels that mediate excitatory neurotransmission in the CNS. Although these receptors are in direct contact with plasma membrane, lipid–NMDAR interactions are little understood. In the present study, we aimed at characterizing the effect of cholesterol on the ionotropic glutamate receptors. Whole-cell current responses induced by fast application of NMDA in cultured rat cerebellar granule cells (CGCs) were almost abolished (reduced to 3%) and the relative degree of receptor desensitization was increased (by seven-fold) after acute cholesterol depletion by methyl-β-cyclodextrin. Both of these effects were fully reversible by cholesterol repletion. By contrast, the responses mediated by AMPA/kainate receptors were not affected by cholesterol depletion. Similar results were obtained in CGCs after chronic inhibition of cholesterol biosynthesis by simvastatin and acute enzymatic cholesterol degradation to 4-cholesten-3-one by cholesterol oxidase. Fluorescence anisotropy measurements showed that membrane fluidity increased after methyl-β-cyclodextrin pretreatment. However, no change in fluidity was observed after cholesterol enzymatic degradation, suggesting that the effect of cholesterol on NMDARs is not mediated by changes in membrane fluidity. Our data show that diminution of NMDAR responses by cholesterol depletion is the result of a reduction of the open probability, whereas the increase in receptor desensitization is the result of an increase in the rate constant of entry into the desensitized state. Surface NMDAR population, agonist affinity, single-channel conductance and open time were not altered in cholesterol-depleted CGCs. The results of our experiments show that cholesterol is a strong endogenous modulator of NMDARs. Key points NMDA receptors (NMDARs) are tetrameric cation channels permeable to calcium; they mediate excitatory synaptic transmission in the CNS and their excessive activation can lead to

  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 Novel Internal Fixator Device for Peripheral Nerve Regeneration

    PubMed Central

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

    2013-01-01

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

  3. Platelet-rich plasma, an adjuvant biological therapy to assist peripheral nerve repair

    PubMed Central

    Sánchez, Mikel; Garate, Ane; Delgado, Diego; Padilla, Sabino

    2017-01-01

    Therapies such as direct tension-free microsurgical repair or transplantation of a nerve autograft, are nowadays used to treat traumatic peripheral nerve injuries (PNI), focused on the enhancement of the intrinsic regenerative potential of injured axons. However, these therapies fail to recreate the suitable cellular and molecular microenvironment of peripheral nerve repair and in some cases, the functional recovery of nerve injuries is incomplete. Thus, new biomedical engineering strategies based on tissue engineering approaches through molecular intervention and scaffolding offer promising outcomes on the field. In this sense, evidence is accumulating in both, preclinical and clinical settings, indicating that platelet-rich plasma products, and fibrin scaffold obtained from this technology, hold an important therapeutic potential as a neuroprotective, neurogenic and neuroinflammatory therapeutic modulator system, as well as enhancing the sensory and motor functional nerve muscle unit recovery. PMID:28250739

  4. Dopamine alters glutamate receptor desensitization in retinal horizontal cells of the perch (Perca fluviatilis).

    PubMed Central

    Schmidt, K F; Kruse, M; Hatt, H

    1994-01-01

    The patch-clamp technique in combination with a fast liquid filament application system was used to study the effect of dopamine on the glutamate receptor desensitization in horizontal cells of the perch (Perca fluviatilis). Kinetics of ligand-gated ion channels in fish horizontal cells are modulated by dopamine. This modulation is presumably mediated by a cAMP-dependent protein phosphorylation. Before incubation with dopamine, the glutamate receptors of horizontal cells activate and desensitize with fast time constants. In the whole-cell recording mode, fast application of the agonists L-glutamate, quisqualate, or alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid prior to the dopamine incubation gives rise to fast transient currents with peak values of about 200 pA that desensitize within 100 ms. Kainate as agonist produced higher steady-state currents but no transient currents. After incubation of the cells with dopamine for 3 min, the desensitization was significantly reduced and the agonists L-glutamate, quisqualate, or alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid induced steady-state currents with amplitudes that were similar to the previously observed transient currents. Kainate-induced currents were only slightly affected. Fast desensitizing currents upon fast application of L-glutamate were also recorded from outside-out patches that were excised from horizontal cells before incubation with dopamine. The currents from excised patches desensitized to a steady-state level of about 0.2 of the peak amplitude with time constants of less than 2 ms. When the outside-out patches were excised from cells after dopamine incubation, steady-state currents were enhanced and no transient currents were observed. The results may indicate that the dopamine-dependent modulation of glutamate-induced currents, which is presumably mediated by a protein phosphorylation, is due to an alteration of the desensitization of the glutamate receptors. PMID:7520178

  5. Recovery of C-fiber-induced extravasation following peripheral nerve injury in the rat.

    PubMed

    Bester, H; Allchorne, A J; Woolf, C J

    1998-12-01

    Peripheral nerve injury leads to substantial alterations in injured sensory neurons. These include cell death, phenotypic modifications, and regeneration. Primary sensory neurons have recently been shown not to die until a time beyond 4 months following a nerve crush or ligation and this loss is, moreover, limited to cells with unmyelinated axons, the C-fibers. The late loss of C-fibers may be due to a lack of target reinnervation during the regenerative phase. In order to investigate this, we have used a particular peripheral function, unique to C-fibers, as a measure of peripheral reinnervation: an increase in capillary permeability on antidromic activation of C-fibers, i.e., neurogenic extravasation. This was investigated in rats that had received a nerve crush injury 1 to 50 weeks earlier. Some recovery of the capacity of C-fibers to generate extravasation was detected at 8-10 weeks, which increased further at 12-14 weeks, and then plateaued at this level with no further recovery at 30 or 50 weeks. In intact and damaged sciatic nerves, A beta-fibers never induced extravasation. These findings are compatible with the hypothesis that those C-fibers which make it back to their peripheral targets do not subsequently die and those that do not, may die. Copyright 1998 Academic Press.

  6. Comparing the effectiveness of four desensitizing toothpastes on dentinal tubule occlusion: A scanning electron microscope analysis.

    PubMed

    Jena, Amit; Kala, Soumik; Shashirekha, Govind

    2017-01-01

    Dentin hypersensitivity (DH) is a sudden short sharp pain best explained by hydrodynamic theory. Several agents are available throughout the market that can treat DH either by blocking the nerves that helps in conducting pain or by blocking the open dentinal tubules. The aim of the present study was to compare the tubule occluding efficacy of four different desensitizing dentifrices under scanning electron microscope (SEM). Sixty-two dentin blocks measuring 5 mm × 5 mm × 3 mm were obtained from extracted human molar teeth and were randomly divided into five groups: Group 1 - no treatment (control, n = 2); Group 2 - Pepsodent Pro-sensitive relief and repair ( n = 15); Group 3 - Sensodyne repair and protect ( n = 15); Group 4 - Remin Pro ( n = 15); Group 5 - Test toothpaste containing 15% nano-hydroxyapatite (n-HA) crystals ( n = 15). The specimens were brushed for 2 min/day for 14 days and stored in artificial saliva. After final brushing, specimens were gold sputtered and viewed under SEM at ×2000 magnification. Results obtained were statistically analyzed using nonparametric Kruskal-Wallis test and least significant difference post hoc test. All test groups showed significant increase in dentin tubule occlusion as compared to control group. The highest percentage of tubules occluded was shown by Group 4 and Group 5 which was significantly different from other groups ( P ≤ 0.05), and there was no significant difference in tubule occlusion among them. Newer desensitizing dentifrices containing 15% n-HA and Remin Pro can provide effective tubule occlusion and thereby reduce the pain and discomfort caused by DH.

  7. Fiber diameter distributions in the chinchilla's ampullary nerves

    NASA Technical Reports Server (NTRS)

    Hoffman, Larry F.; Honrubia, Vicente

    2002-01-01

    A morphometric study of the chinchilla's ampullary nerves was conducted to produce an unbiased accounting of the diameter distribution of their constituent fibers. Diameter analyses were determined from 1 microm plastic-embedded nerve sections taken at a plane immediately proximal to the sensory epithelium. We found these nerves to be composed of 2094+/-573 fibers, having diameters that ranged from 0.5 to 8 microm. The distributions of diameters were positively skewed, where approximately 75% of the fibers were found to have diameters less than 3.5 microm. An analysis of the spatial distribution of diameters within the nerve section revealed that the lateralmost areas of the nerve contained larger fractions of fibers within the smallest diameter quintiles, and the central area harbored greater proportions of the larger diameter quintiles. However, significant fractions of all quintiles were found in all areas. These data were integrated with available data of Fernandez et al. (1998) to produce diameter estimates of calyx, dimorphic, and bouton morphology subpopulations. In view of a general relationship between diameter, innervation locus, and an afferent's physiologic characteristics, these data provide the basis for developing a perspective for the in situ distribution of afferent response dynamics.

  8. Comparison of Nerve Stimulation-guided Axillary Brachial Plexus Block, Single Injection versus Four Injections: A Prospective Randomized Double-blind Study.

    PubMed

    Badiger, Santoshi V; Desai, Sameer N

    2017-01-01

    A variety of techniques have been described for the axillary block using nerve stimulator, either with single injection, two, three, or four separate injections. Identification of all the four nerves is more difficult and time-consuming than other methods. Aim of the present study is to compare success rate, onset, and duration of sensory and motor anesthesia of axillary block using nerve stimulator, either with single injection after identification of any one of the four nerves or four separate injections following identification of each of nerve. Prospective, randomized, double-blind study. Patients undergoing forearm and hand surgeries under axillary block. One hundred patients, aged 18-75 years, were randomly allocated into two groups of 50 each. Axillary block was performed under the guidance of nerve stimulator with a mixture of 18 ml of 1.5% lignocaine and 18 ml of 0.5% bupivacaine. In the first group ( n = 50), all 36 ml of local anesthetic was injected after the identification of motor response to any one of the nerves and in Group 2, all the four nerves were identified by the motor response, and 9 ml of local anesthetic was injected at each of the nerves. The success rate of the block, onset, and duration of sensory and motor block was assessed. Categorical variables were compared using the Chi-square test, and continuous variables were compared using independent t -test. The success rate of the block with four injection technique was higher compared to single-injection technique (84% vs. 56%, P = 0.02). Four injection groups had a faster onset of sensory and motor block and prolonged duration of analgesia compared to single-injection group ( P < 0.001). There were no significant differences in the incidence of accidental arterial puncture and hemodynamic parameter between the groups. Identification of all the four nerves produced higher success rate and better quality of the block when compared to single-injection technique.

  9. Perioperative Desensitization Improves Outcomes Among Crossmatch Positive Recipients of Deceased Donor Renal Transplants.

    PubMed

    Sharma, Amit; King, Anne; Kumar, Dhiren; Behnke, Martha; McDougan, Felecia; Kimball, Pamela M

    2016-06-01

    Graft failure due to chronic rejection is greater among renal transplant patients with donor-specific antibody (DSA) than among DSA-free patients. For patients dependent on deceased donor transplantation, preoperative desensitization to eliminate DSAs may be impractical. We speculated that perioperative desensitization might eliminate preexisting DSAs and prevent de novo DSAs and improve graft outcomes. We report that brief perioperative desensitization using either intravenous immunoglobulin (IVIG) or plasmapheresis/IVIG (PP/IVIG) treatment improves clinical outcomes among patients with positive crossmatches. Immediately following deceased donor transplantation, 235 renal recipients were assigned points for PRA and flow crossmatches (FCXM): delayed graft function (DGF) ≤ 1 point received standard therapy; 2 points received high-dose IVIG; and ≥3 points received PP/IVIG. The DSAs were serially monitored by single antigen bead luminex for 1 year. Five-year clinical outcomes were determined from the chart review. All desensitized patients had preoperatively positive FCXM with DSA. Rejection was more common (P < .05) among desensitized than nonsensitized groups. However, overall graft survivals were similar between the groups (P = not significant) and superior to historic untreated patients (P < .05). Treatment with PP/IVIG more effectively eliminated preexisting DSAs (67% vs 33%, P < 0.05) than IVIG, but neither regimen prevented de novo formation of DSA (20%, P = not significant). Graft survival was >90% in all desensitizated patients with DSA elimination as well as PP/IVIG patients with residual DSA. In contrast, IVIG patients with persistent DSA had poorer graft survival (45%, P < .05). Preemptive perioperative desensitization improved overall graft survival of sensitized patients compared to historic untreated patients. Plasmapheresis/IVIG had greater impact on DSA eradication and graft survival than IVIG alone. © 2016, NATCO.

  10. Investigation into the Coating and Desensitization Effect on HNIW of Paraffin Wax/Stearic Acid Composite System

    NASA Astrophysics Data System (ADS)

    Wang, Dong-Xu; Chen, Shu-Sen; Jin, Shao-Hua; Shu, Qing-Hai; Jiang, Zhen-Ming; Shang, Feng-Qin; Li, Jin-Xin

    2016-01-01

    2,4,6,8,10,12-Hexanitro-2,4,6,8,10,12-hexaazaisowurtzitane (HNIW) was bonded by fluorine rubber and then desensitized by paraffin wax (PW), stearic acid (SA), and a PW/SA composite system using an aqueous suspension method. The coating and desensitization effects of the composite systems on HNIW and the influence of the addition of SA on the mechanical properties of the coated HNIW samples were studied. In addition, the PW/SA composite solution was simulated using a molecular dynamics method, and the relationship between the desensitization effect on HNIW and the properties of the composite solution was investigated. The results showed that the PW/SA composite system, of which the desensitization effect on HNIW was between those of the two desensitizers, could effectively coat HNIW and that the composite solution had the most stable and well-distributed state when using benzene as solvent with the mass ratio of PW/SA equal to 7/3 or 3/7, thus resulting in the best desensitization effect on HNIW. Moreover, the addition of stearic acid was successful in enhancing the mechanical properties of the coated HNIW samples.

  11. Infra Patellar Branch of Saphenous Nerve Injury during Hamstring Graft Harvest: Vertical versus Oblique Incisions.

    PubMed

    Joshi, A; Kayasth, N; Shrestha, S; Kc, B R

    2016-09-01

    Autologous hamstring grafts are commonly used for anterior cruciate ligament reconstruction. The injury of infrapatellar branch of saphenous nerve is one of the concerns leading to various pattern of sensory loss in the operated leg. An oblique incision to harvest the graft has been reported to be better than the vertical one.The aim of this study was to compare the incidence, recovery of nerve injury and final outcome in patients with hamstring harvest of vertical or oblique incision. A total of 146 patients who underwent hamstring graft harvest for anterior cruciate ligament reconstruction, were included in the study. They were randomized into two (Vertical and Oblique) groups as per the incisions used. The sensory loss along the Infra Patellar Branch of Saphenous Nerve was documented on 3rd day. Recovery of the nerve injury was monitoredat three, six and 12 months follow-ups. At final follow up Tegner Lysholm score and scale was recorded to compare between two groups. The incidence of infrapatellar branch of saphenous nerve injury was 25% in vertical group and 16.36% in oblique group. Recovery of nerve injury started earlier in oblique group compared to vertical group. The mean TegnerLyshom score was not significantly different in both the groups. Oblique incision to harvest hamstring graft has lesser incidence of infrapatellar branch of saphenous nerve injury, recovers earlier and does not have any adverse effect on final outcome compared to the vertical incision.

  12. Role of protein kinase C and μ-opioid receptor (MOPr) desensitization in tolerance to morphine in rat locus coeruleus neurons

    PubMed Central

    Bailey, C P; Llorente, J; Gabra, B H; Smith, F L; Dewey, W L; Kelly, E; Henderson, G

    2009-01-01

    In morphine tolerance a key question that remains to be answered is whether μ-opioid receptor (MOPr) desensitization contributes to morphine tolerance, and if so by what cellular mechanisms. Here we demonstrate that MOPr desensitization can be observed in single rat brainstem locus coeruleus (LC) neurons following either prolonged (> 4 h) exposure to morphine in vitro or following treatment of animals with morphine in vivo for 3 days. Analysis of receptor function by an operational model indicated that with either treatment morphine could induce a profound degree (70–80%) of loss of receptor function. Ongoing PKC activity in the MOPr-expressing neurons themselves, primarily by PKCα, was required to maintain morphine-induced MOPr desensitization, because exposure to PKC inhibitors for only the last 30–50 min of exposure to morphine reduced the MOPr desensitization that was induced both in vitro and in vivo. The presence of morphine was also required for maintenance of desensitization, as washout of morphine for > 2 h reversed MOPr desensitization. MOPr desensitization was homologous, as there was no change in α2-adrenoceptor or ORL1 receptor function. These results demonstrate that prolonged morphine treatment induces extensive homologous desensitization of MOPrs in mature neurons, that this desensitization has a significant PKC-dependent component and that this desensitization underlies the maintenance of morphine tolerance. PMID:19200236

  13. [Clinical observation on common peroneal nerve palsy treated with comprehensive therapy].

    PubMed

    Yang, Li-Juan; Liu, Ya-Li; Wang, Shu-Bin; Jin, Zhi-Gao

    2014-04-01

    To compare the difference of the clinical efficacy on common peroneal palsy between the comprehensive therapy of electroacupuncture, moxibustion and moving cupping method and western medication. Ninety cases of common peroneal nerve palsy were randomized into a comprehensive therapy group and a western medication group, 45 cases in each one. In the comprehensive therapy group, electroacupuncture was applied to Yanglingquan (GB 34), Zusanli (ST 36), Xuanzhong (GB 39), Jiexi (ST 41), Taichong (LR 3), Zulinqi (GB 41) and the others, combined with warm moxibustion and moving cupping on the lateral side of the affected leg. The comprehensive therapy was used once a day. In the western medication group, vitamin B1 , 10 mg each time, 3 times a day; and mecobalamine, 0. 5 mg each time, three times a day were prescribed for oral administration. In the two groups, 15 days made one session, and the efficacy was observed after 2 sessions treatment. The total effective rate of the improvement of sensory function and motor nerve function was 97. 8% (44/45) in the comprehensive therapy group and was 82. 2% (37/ 45) in the western medication. The efficacy in the comprehensive therapy group was better than that of the western medication (P<0. 01). The electrophysiological examination showed that the amplitude of motor conduction of deep peroneal nerve and that of sensory conduction of surficial peroneal nerve after treatment were improved remarkably as compared with those before treatment in the comprehensive therapy group (both P<0. 05). The amplitude of motor conduction of deep peroneal nerve was improved significantly in the comprehensive therapy group as compared with that in the western medication group (P<0. 05). The comprehensive therapy of electroacupuncture, moxibustion and moving cupping method achieves the significant efficacy on common peroneal nerve palsy as compared with western medication.

  14. Mass Spectrometry Imaging and GC-MS Profiling of the Mammalian Peripheral Sensory-Motor Circuit

    NASA Astrophysics Data System (ADS)

    Rubakhin, Stanislav S.; Ulanov, Alexander; Sweedler, Jonathan V.

    2015-06-01

    Matrix-assisted laser desorption/ionization (MALDI) mass spectrometry imaging (MSI) has evolved to become an effective discovery tool in science and clinical diagnostics. Here, chemical imaging approaches are applied to well-defined regions of the mammalian peripheral sensory-motor system, including the dorsal root ganglia (DRG) and adjacent nerves. By combining several MSI approaches, analyte coverage is increased and 195 distinct molecular features are observed. Principal component analysis suggests three chemically different regions within the sensory-motor system, with the DRG and adjacent nerve regions being the most distinct. Investigation of these regions using gas chromatography-mass spectrometry corroborate these findings and reveal important metabolic markers related to the observed differences. The heterogeneity of the structurally, physiologically, and functionally connected regions demonstrates the intricate chemical and spatial regulation of their chemical composition.

  15. Clinical, physiological and pathological characterisation of the sensory predominant peripheral neuropathy in copper deficiency.

    PubMed

    Taylor, Sean W; Laughlin, Ruple S; Kumar, Neeraj; Goodman, Brent; Klein, Christopher J; Dyck, Peter J; Dyck, P James B

    2017-10-01

    Myelopathy is considered the most common neurological complication of copper deficiency. Concurrent peripheral neuropathy has been recognised in association with copper deficiency but has not been well characterised. To characterise the clinical, physiological and pathological features of copper-deficient peripheral neuropathy. Patients with simultaneous copper deficiency (<0.78 μg/mL) and peripheral neuropathy seen at the Mayo Clinic from 1985 to 2005 were identified. 34 patients were identified (median age 55 years, range 36-78) including 24 women and 10 men. Myelopathy was found in 21 patients. Median serum copper level was 0.11 μg/mL (range 0-0.58). The most frequent clinical and electrophysiological pattern of neuropathy was a sensory predominant length-dependent peripheral neuropathy (71%). Somatosensory evoked potentials demonstrated central slowing supporting myelopathy (96%). Quantitative sensory testing demonstrated both small and large fibre involvement (100%). Autonomic reflex screens (77%) and thermoregulatory sweat test (67%) confirmed sudomotor dysfunction. 14 cutaneous nerve biopsies revealed loss of myelinated nerve fibres (86%), increased regenerative clusters (50%), increased rates of axonal degeneration (91%) and increased numbers of empty nerve strands (73%). 71% of biopsies demonstrated epineurial perivascular inflammation. An axonal, length-dependent sensory predominant peripheral neuropathy causing sensory ataxia is characteristic of copper deficiency usually co-occurring with myelopathy. Neurophysiological testing confirms involvement of large, greater than small fibres. The pathological findings suggest axonal degeneration and repair. Inflammatory infiltrates are common but are small and of doubtful pathological significance. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  16. Case of fibrolipomatous hamartoma of the digital nerve without macrodactyly.

    PubMed

    Nanno, Mitsuhiko; Sawaizumi, Takuya; Takai, Shinro

    2011-01-01

    Fibrolipomatous hamartoma of nerves without macrodactyly is a rare lesion characterized by fibrofatty proliferation causing epineural and perineural fibrosis with fatty infiltration around the nerve bundles. We report an unusual case of fibromatous hamartoma of the ulnar digital nerve of the thumb in a 43-year-old woman. Magnetic resonance imaging revealed a large fusiform mass along the nerve. The findings were unusual and pathognomonic and included a coaxial cable-like appearance on axial sections and a spaghettilike appearance on coronal sections on both T1- and T2-weighted images; these findings were useful for the diagnosis and preoperative evaluation of this lesion. Surgical exploration revealed a yellow, cordlike mass of the digital nerve enlarged by fat. Gross excision could not be done without extensive damage to the nerve. Therefore, a limited excision with biopsy of the fibrolipomatous tissue around the nerve bundles was performed. The histological appearance was consistent with fibrolipomatous hamartoma. There was no recurrence of the mass and no neurological deficit 3 years after surgery. Some authors have suggested that invasive excision can cause catastrophic sensory or motor deficits because of the extensive fatty infiltration of the nerve fascicles. In conclusion, the recommended treatment for this lesion is limited excision with only biopsy to confirm the diagnosis.

  17. Tenascin-C in peripheral nerve morphogenesis.

    PubMed

    Chiquet, M; Wehrle-Haller, B

    1994-01-01

    The extracellular matrix (ECM) molecule tenascin/cytotactin (TN-C) is expressed at a high level by satellite (glial precursor) cells in developing peripheral nerves of the chick embryo; synthesis of its mRNA peaks at the time period when axonal growth is maximal. When offered as a substrate in vitro, TN-C mediates neurite outgrowth by both motor and sensory neurons. The ability to grow neurites on TN-C is developmentally regulated: sensory neurons from 4-day chick embryos (the stage at which peripheral nerves start to develop) grow immediately and rapidly, whereas neurons from older embryos respond with a long delay. A TN-C domain responsible for this activity is located within the C-terminal (distal) portion of TN-C subunits. Integrin receptors seem to be involved on peripheral neurites because their growth on TN-C is completely blocked by antibodies to beta 1 integrins. In striking contrast to neuronal processes, nerve satellite cells can attach to a TN-C substrate but are completely inhibited in their migratory activity. Artificial substrate borders between tenascin and fibronectin or laminin act as selective barriers that allow neurites to pass while holding up satellite cells. The repulsive action of TN-C on satellite cells is similar to that observed for other cell types and is likely to be mediated by additional TN-C domains. In view of these data, it is surprising that mice seem to develop normally without a functional TN-C gene. TN-C is likely to be redundant, that is, its dual action on cell adhesion is shared by other molecules.(ABSTRACT TRUNCATED AT 250 WORDS)

  18. Nerve fiber layer (NFL) degeneration associated with acute q-switched laser exposure in the nonhuman primate

    NASA Astrophysics Data System (ADS)

    Zwick, Harry; Zuclich, Joseph A.; Stuck, Bruce E.; Gagliano, Donald A.; Lund, David J.; Glickman, Randolph D.

    1995-01-01

    We have evaluated acute laser retinal exposure in non-human primates using a Rodenstock scanning laser ophthalmoscope (SLO) equipped with spectral imaging laser sources at 488, 514, 633, and 780 nm. Confocal spectral imaging at each laser wavelength allowed evaluation of the image plane from deep within the retinal vascular layer to the more superficial nerve fiber layer in the presence and absence of the short wavelength absorption of the macular pigment. SLO angiography included both fluorescein and indocyanine green procedures to assess the extent of damage to the sensory retina, the retinal pigment epithelium (RPE), and the choroidal vasculature. All laser exposures in this experiment were from a Q-switched Neodymium laser source at an exposure level sufficient to produce vitreous hemorrhage. Confocal imaging of the nerve fiber layer revealed discrete optic nerve sector defects between the lesion site and the macula (retrograde degeneration) as well as between the lesion site and the optic disk (Wallerian degeneration). In multiple hemorrhagic exposures, lesions placed progressively distant from the macula or overlapping the macula formed bridging scars visible at deep retinal levels. Angiography revealed blood flow disturbance at the retina as well as at the choroidal vascular level. These data suggest that acute parafoveal laser retinal injury can involve both direct full thickness damage to the sensory and non-sensory retina and remote nerve fiber degeneration. Such injury has serious functional implications for both central and peripheral visual function.

  19. Electrophysiologic alterations in the excitability of the sciatic and vagus nerves during early stages of sepsis

    PubMed Central

    Diniz, Lúcio Ricardo Leite; Portella, Viviane Gomes; da Silva Alves, Kerly Shamira; Araújo, Pâmella Cristina da Costa; de Albuquerque Júnior, Ricardo Luiz Cavalcanti; Cavalcante de Albuquerque, Aline Alice; Coelho-de-Souza, Andrelina Noronha; Leal-Cardoso, José Henrique

    2018-01-01

    Background Nonspecific and delayed diagnosis of neurologic damage contributes to the development of neuropathies in patients with severe sepsis. The present study assessed the electrophysiologic parameters related to the excitability and conductibility of sciatic and vagus nerves during early stages of sepsis. Materials and methods Twenty-four hours after sepsis induced by cecal ligation and puncture (CLP) model, sciatic and vagus nerves of septic (CLP group) and control (sham group) rats were removed, and selected electric stimulations were applied to measure the parameters of the first and second components of the compound action potential. The first component originated from fibers with motor and sensory functions (Types Aα and Aβ fibers) with a large conduction velocity (70–120 m/s), and the second component originated from fibers (Type Aγ) with sensorial function. To evaluate the presence of sensorial alterations, the sensitivity to non-noxious mechanical stimuli was measured by using the von Frey test. Hematoxylin and eosin staining of the nerves was performed. Results We observed an increase of rheobase followed by a decrease in the first component amplitude and a higher paw withdrawal threshold in response to the application of von Frey filaments in sciatic nerves from the CLP group compared to the sham group. Differently, a decrease in rheobase and an increase in the first component amplitude of vagal C fibers from CLP group were registered. No significant morphologic alteration was observed. Conclusion Our data showed that the electrophysiologic alterations in peripheral nerves vary with the fiber type and might be identified in the first 24 h of sepsis, before clinical signs of neuromuscular disorders. PMID:29731661

  20. The central projections of the laryngeal nerves in the rat

    PubMed Central

    Pascual-Font, Arán; Hernández-Morato, Ignacio; McHanwell, Stephen; Vázquez, Teresa; Maranillo, Eva; Sañudo, Jose; Valderrama-Canales, Francisco J

    2011-01-01

    The larynx serves respiratory, protective, and phonatory functions. The motor and sensory innervation to the larynx controlling these functions is provided by the superior laryngeal nerve (SLN) and the recurrent laryngeal nerve (RLN). Classical studies state that the SLN innervates the cricothyroid muscle and provides sensory innervation to the supraglottic cavity, whereas the RLN supplies motor innervation to the remaining intrinsic laryngeal muscles and sensory innervation to the infraglottic cavity, but recent data suggest a more complex anatomical and functional organisation. The current neuroanatomical tracing study was undertaken to provide a comprehensive description of the central brainstem connections of the axons within the SLN and the RLN, including those neurons that innervate the larynx. The study has been carried out in 41 adult male Sprague–Dawley rats. The central projections of the laryngeal nerves were labelled following application of biotinylated dextran amines onto the SLN, the RLN or both. The most remarkable result of the study is that in the rat the RLN does not contain any afferent axons from the larynx, in contrast to the pattern observed in many other species including man. The RLN supplied only special visceromotor innervation to the intrinsic muscles of the larynx from motoneurons in the nucleus ambiguus (Amb). All the afferent axons innervating the larynx are contained within the SLN, and reach the nucleus of the solitary tract. The SLN also contained secretomotor efferents originating from motoneurons in the dorsal motor nucleus of the vagus, and special visceral efferent fibres from the Amb. In conclusion, the present study shows that in the rat the innervation of the larynx differs in significant ways from that described in other species. PMID:21599662