We have investigated the possible roles of NGF, and of im- pulse activity, in the regeneration of sensory nerves. Un- expectedly, the ability of crushed axons to regrow and to restore functional recovery of three sensory modalities in adult rat skin (Aa-mediated touch, A&mediated mechano- nociception, and C-fiber-mediated heat nociception) was totally unaffected by anti-NGF treatment. This finding ap- plied
Jack Diamond; Anne Foerster; Michael Holmes; Michael Coughlin
The neuralb pathways that relay information from cutaneous receptors to the cortex provide the somatic sensory information needed for cortical function. The last sensory relay neurons in this pathway have cell bodies in the thalamus and axons that synapse on neurons in the somatosensory cortex. After cortical lesions that damage mature thalamocortical fibers in the somatosensory cortex, we have attempted to reestablish somatosensory cortical function by grafting embryonic neocortical cells into the lesioned area. Such grafts survive in adult host animals but are not innervated by thalamic neurons, and consequently the grafted neurons show little if any spontaneous activity and no responses to cutaneous stimuli. We have reported that transection of peripheral sensory nerves prior to grafting ``conditions'' or ``primes'' the thalamic neurons in the ventrobasal complex so that they extend axons into grafts subsequently placed in the cortical domain of the cut nerve. In this report we present evidence that the ingrowth of ventrobasal fibers leads to graft neurons that become functionally integrated into the sensory circuitry of the host brain. Specifically, the conditioning lesions made prior to grafting produce graft neurons that are spontaneously active and can be driven by natural activation of cutaneous receptors or electrical stimulation of the transected nerve after it regenerates. Furthermore, oxidative metabolism in these grafts reaches levels that are comparable to normal cortex, whereas without prior nerve cut, oxidative metabolism is abnormally low in neocortical grafts. We conclude that damage to the sensory periphery transsynaptically stimulates reorganization of sensory pathways through mechanisms that include axonal elongation and functional synaptogenesis.
Ebner, Ford F.; Erzurumlu, Reha S.; Lee, Stefan M.
Restoration of the voluntary use of paralyzed limbs using functional neuromuscular stimulation (FNS) is limited by complex muscle properties and unpredictable load behaviors; closed-loop control of FNS would improve performance but requires reliable sensory feedback modalities. Sensory nerve signals recorded by cuff electrodes provide accurate information about forces acting on the skin in anesthetized animals; however, nerve cuff signals are
Morten K. Haugland; J. Andy Hoffer
\\u000a This chapter reviews the expression and regulation of opioid receptors in sensory neurons and the interactions of these receptors\\u000a with endogenous and exogenous opioid ligands. Inflammation of peripheral tissues leads to increased synthesis and axonal transport\\u000a of opioid receptors in dorsal root ganglion neurons. This results in opioid receptor upregulation and enhanced G protein coupling\\u000a at peripheral sensory nerve terminals.
Christoph Stein; Christian Zöllner
We have recently shown in rat that daily manual stimulation (MS) of vibrissal muscles promotes recovery of whisking and reduces polyinnervation of muscle fibers following repair of the facial nerve (facial-facial anastomosis, FFA). Here, we examined whether these positive effects were: (1) correlated with alterations of the afferent connections of regenerated facial motoneurons, and (2) whether they were achieved by enhanced sensory input through the intact trigeminal nerve. First, we quantified the extent of total synaptic input to motoneurons in the facial nucleus using synaptophysin immunocytochemistry following FFA with and without subsequent MS. We found that, without MS, this input was reduced compared to intact animals. The number of synaptophysin-positive terminals returned to normal values following MS. Thus, MS appears to counteract the deafferentation of regenerated facial motoneurons. Second, we performed FFA and, in addition, eliminated the trigeminal sensory input to facial motoneurons by extirpation of the ipsilateral infraorbital nerve (IONex). In this paradigm, without MS, vibrissal motor performance and pattern of end-plate reinnervation were as aberrant as after FFA without MS. MS did not influence the reinnervation pattern after IONex and functional recovery was even worse than after IONex without MS. Thus, when the sensory system is intact, MS restores normal vibrissal function and reduces the degree of polyinnervation. When afferent inputs are abolished, these effects are eliminated or even reversed. We conclude that rehabilitation strategies must be carefully designed to take into account the extent of motor and/or sensory damage. PMID:18381213
Pavlov, Stoyan P; Grosheva, Maria; Streppel, Michael; Guntinas-Lichius, Orlando; Irintchev, Andrey; Skouras, Emmanouil; Angelova, Srebrina K; Kuerten, Stefanie; Sinis, Nektarios; Dunlop, Sarah A; Angelov, Doychin N
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. PMID:24110391
Asthmatic subjects cough and bronchoconstrict to various agents known to stimulate sensory nerves. A population of sensory nerves, the C fibres, contain the neuropeptides substance P, neurokinin A (NKA), and calcitonin gene-related peptide (CGRP). Capsaicin, the principal ingredient of hot peppers, selectively stimulates C fibre afferents resulting in the release of these proinflammatory peptides. An upregulation in the function of sensory nerves may lead to augmented afferent and efferent function which, in asthma, could contribute to bronchial hyper-responsiveness, inflammation, and remodelling of the airway wall. Drugs specifically designed to attenuate the function of airway sensory nerves may prove useful in the treatment of asthma. Images
Objectives: Sensory nerves play an important role in mediating neurogenic inflammation and subsequent tissue healing. A decrease in sensory nerve function with increasing age has been reported to correlate with poor tissue healing. Sympathetic nerves are known to modulate sensory nerve function, and changes in this modulation could also have important implications with ageing. The aims of this study were
M. Merhi; R. D. Helme; Z. Khalil
We have used a self-curling nerve cuff electrode to record sensory information from a cutaneous nerve. This type of cuffs has previously been used only for stimulation, but its mechanical properties could make it very suitable for recording also, since it can be fitted closer to the nerve than traditional cuffs without compromising the nerve. In this study we show
T. Sinjar; B. Hinge; A. Jorgensen; M. L. Jensen; M. Haugland
Background and purpose: Sensory nerves regulate central and local reflexes such as airway plasma protein leakage, bronchoconstriction and cough. Sensory nerve activity may be enhanced during inflammation such that these protective effects become exacerbated and deleterious. Cannabinoids are known to inhibit airway sensory nerve function. However, there is still controversy surrounding which receptor is involved in eliciting these effects. Experimental approach: We have adopted a pharmacological approach, including using a novel, more selective CB2 receptor agonist, GW 833972A (1000-fold selective CB2/CB1), and receptor selective antagonists to investigate the inhibitory activity of cannabinoids on sensory nerve activity in vitro and in vivo in guinea-pig models of cough and plasma extravasation. Key results: GW 833972A inhibited capsaicin-induced depolarization of the human and guinea-pig and prostaglandin E2 (PGE2) and hypertonic saline-induced depolarization of the guinea-pig isolated vagus nerve in vitro. GW 833972A also inhibited citric acid-induced cough but not plasma extravasation in the guinea-pig and this effect was blocked by a CB2 receptor antagonist. Conclusions and implications: This confirms and extends previous studies highlighting the role of CB2 receptors in the modulation of sensory nerve activity elicited both by the exogenous ligands capsaicin and hypertonic saline but also by endogenous modulators such as PGE2 and low pH stimuli. These data establish the CB2 receptor as an interesting target for the treatment of chronic cough.
Belvisi, M G; Patel, H J; Freund-Michel, V; Hele, D J; Crispino, N; Birrell, M A
1. Chemical responses of skin and tongue, recorded in vivo from intact and self-regenerated cutaneous or lingual nerves, were compared to responses from cutaneous nerves cross-united with distal stumps of lingual nerves. Cross-innervated tongue grafts were also studied. 2. In contrast to normal tongue—nerve preparations, skin preparations usually showed responses to chemical stimulation with longer latency, higher threshold, and less variation of temporal pattern with diverse stimuli. These characteristics were similar when the nerve, having been cut, had regenerated. 3. On chemical stimulation of the tongue, cutaneous nerves cross-innervating the tongue often yielded records which were `gustatory' by all criteria. Some responses with low threshold and short latency were also obtained from dorsal cutaneous nerves innervating tongue grafts. 4. Thus, cutaneous nerves can serve the same role as gustatory nerves. The functional characteristics of these sensory neurones are not predetermined and must depend on the environment of the nerve endings.
Objectives: Spinally elicited peripheral nerve responses, commonly called neurogenic motor evoked potentials (NMEPs), are widely used to monitor spinal cord motor function during surgery. However, numerous evidence suggests that these responses are primarily sensory rather than motor. The collision technique was utilized to address this issue.Methods: Collision studies were performed in 7 patients during surgery. An ascending volley of sensory
J. R Toleikis; J. P Skelly; A. O Carlvin; J. K Burkus
Purpose: Our purpose was to study the recovery of sensory nerve function after treatment of traumatic peripheral nerve lesions with a biodegradable poly(DL-lactide--caprolactone) Neurolac nerve guide (Polyganics B.V., Groningen, the Netherlands) versus the current standard reconstruc- tion techniques. Methods: Thirty patients with 34 nerve lesions were included in this randomized, multicenter trial. Results: Both groups were comparable considering their demographics.
Mariëtta J. O. E. Bertleff; Marcel F. Meek; Jean-Phillipe A. Nicolai
Capsaicin-sensitive sensory neurons are stimulated by noxious stimuli, and may be activated in endotoxaemia. The present study investigated the acute and chronic effects of lipopolysaccharide upon the efferent function of these nerves. Conscious rats received infusion (i.v.) of lipopolysaccharide (150 microg kg(-1) h(-1)) or saline for 2 or 24 h. Following infusion, animals were killed and the mesenteric arterial bed isolated and perfused with Krebs' solution. Electrical field stimulation of capsaicin-sensitive sensory nerves was investigated. Postjunctional mechanisms of sensory neurotransmission were examined using calcitonin gene-related peptide, and endothelial and smooth muscle function assessed using acetylcholine and sodium nitroprusside, respectively. All preparations exhibited dose dependency to the agonists, and frequency dependency to electrical field stimulation. No significant differences were observed between the four groups (2-h saline, 24-h saline, 2-h lipopolysaccharide and 24-h lipopolysaccharide) with regard to responses to electrical field stimulation, acetylcholine, sodium nitroprusside or calcitonin gene-related peptide. Thus, the efferent function of capsaicin-sensitive sensory nerves is unaltered in the isolated mesenteric arterial bed prepared ex vivo from rats receiving lipopolysaccharide, either acutely (2 h) or chronically (24 h). PMID:12963421
Farmer, Matthew R; Gardiner, Sheila M; Ralevic, Vera
Sensory-selective local anesthesia has long been a key goal in local anesthetic development. For example, it allows women to be pain-free during labor without compromising their ability to push. Here we show that prolonged sensory-selective nerve block can be produced by specific concentrations of surfactants—such as are used to enhance drug flux across skin—in combination with QX-314, a lidocaine derivative that has relative difficulty penetrating nerves. For example, injection of 25 mM QX-314 in 30 mM octyltrimethylammonium bromide (OTAB) lasted up to 7 h. Sensory selectivity was imparted to varying degrees by cationic, neutral, and anionic surfactants, and also was achieved with another lidocaine derivative, QX-222. Simultaneous injection of OTAB at a s.c. injection site remote from the sciatic nerve did not result in prolonged sensory-specific nerve blockade from QX-314, suggesting that the observed effect is due to a local interaction between the surfactant and the lidocaine derivative, not a systemic effect.
Sagie, Itay; Kohane, Daniel S.
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.
Patients with established or irreversible plantar sensory loss often have normal sensation on the dorsal aspect of the foot, due to an intact deep peroneal nerve. A new method of deep peroneal nerve transfer is proposed for repair of plantar sensory loss caused by extensive nerve gaps or high-level lesions of the posterior tibial nerve. Two cases in which this technique was used are described. The surgical technique is relatively easy, with a short operating time, rapid nerve regeneration after surgery, accurate sensory recovery, and minimal donor-site morbidity with sensory loss only on the first web space of the foot. PMID:14634907
Koshima, Isao; Nanba, Yuzaburo; Tsutsui, Tetsuya; Takahashi, Yoshio
The recovery of functional sensibility after nerve transection and repair is often disappointing. Here we address the timing of sensory re-education that aims at re-learning and modulating the changed sensory code from the hand after such an injury. Such training utilises the capacity for cortical functional re-modelling which characterises the young as well as the adult brain. Sensory re-education is traditionally not introduced until there is reinnervation in the hand, and such a late onset of training may be one explanatory factor for the poor functional results after nerve repair. Since functional reorganisation changes of the cortex occurring after changes in peripheral input are very fast processes, we suggest that this specific intervention should be introduced very early in the rehabilitation phase--already in the initial phase after nerve repair when no axons have yet arrived to the asensible hand. The goal is to avoid, minimise and modulate the central functional re-organisation which follows the de-afferentiation associated with nerve injury and repair. This early intervention can be done with the use of artificial sensibility the first post-operative day. According to this technique, based on sense substitution and utilising the multimodal capacity of the brain, miniature microphones on the fingertips of the asensible hand pick up the friction sound generated by active touch. The vibro-tactile signals are stereophonically transposed to vibro-acoustic signals, thereby providing an alternate feed-back which hypothetically helps to maintain or re-establish the cortical hand map. PMID:15083384
Rosén, B; Lundborg, G
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 ?-synuclein was used to detect Lewy pathology. Axonal ?-synuclein aggregates in the pharyngeal sensory nerves were identified in all of the PD subjects but not in the controls. The density of ?-synuclein-positive lesions was greater in PD patients with dysphagia versus those without dysphagia. In addition, ?-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. PMID:23771215
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
Mitochondrial dysfunction and subsequent oxidative stress has been reported for a variety of cell types in inflammatory diseases. Given the abundance of mitochondria at the peripheral terminals of sensory nerves and the sensitivity of transient receptor potential (TRP) ankyrin 1 (A1) and TRP vanilloid 1 (V1) to reactive oxygen species (ROS) and their downstream products of lipid peroxidation, we investigated the effect of nerve terminal mitochondrial dysfunction on airway sensory nerve excitability. Here we show that mitochondrial dysfunction evoked by acute treatment with antimycin A (mitochondrial complex III Qi site inhibitor) preferentially activated TRPA1-expressing "nociceptor-like" mouse bronchopulmonary C-fibers. Action potential discharge was reduced by the TRPA1 antagonist HC-030031. Inhibition of TRPV1 further reduced C-fiber activation. In mouse dissociated vagal neurons, antimycin A induced Ca(2+) influx that was significantly reduced by pharmacological inhibition or genetic knockout of either TRPA1 or TRPV1. Inhibition of both TRPA1 and TRPV1 was required to abolish antimycin A-induced Ca(2+) influx in vagal neurons. Using an HEK293 cell expression system, antimycin A induced concentration-dependent activation of both hTRPA1 and hTRPV1 but failed to activate nontransfected cells. Myxothiazol (complex III Qo site inhibitor) inhibited antimycin A-induced TRPA1 activation, as did the reducing agent dithiothreitol. Scavenging of both superoxide and hydrogen peroxide inhibited TRPA1 activation following mitochondrial modulation. In conclusion, we present evidence that acute mitochondrial dysfunction activates airway sensory nerves preferentially via TRPA1 through the actions of mitochondrially-derived ROS. This represents a novel mechanism by which inflammation may be transduced into nociceptive electrical signaling. PMID:23444014
Nesuashvili, Lika; Hadley, Stephen H; Bahia, Parmvir K; Taylor-Clark, Thomas E
Targeted reinnervation is a new neural-machine interface that has been developed to help improve the function of new- generation prosthetic limbs. Targeted reinnervation is a surgical procedure that takes the nerves that once innervated a severed limb and redirects them to proximal muscle and skin sites. The sensory afferents of the redirected nerves reinnervate the skin overlying the transfer site.
Paul D. Marasco; Aimee E. Schultz; Todd A. Kuiken
fibers and the subepidermal neural plexus in capsaicin-treated skin, as indicated by the loss of immunoreactivity for PGP 9.5 and CGRP. The effect of capsaicin on dermal nerve fibers immunoreactive for SP was less obvious. Capsaicin decreased sensitivity to pain produced by sharp mechanical stimuli and nearly eliminated heat-evoked pain within the injected area. Limited reinnervation of the epidermis and
Donald A. Simone; Maria Nolano; Timothy Johnson; Gwen Wendelschafer-Crabb; William R. Kennedy
Bilateral injuries of the sensory branch of the radial nerve (SBRN) usually occur as a result of tight-handcuff neuropathy. In this case we aimed to present bilateral isolated cut of SBRN resulting an injury mechanism that has not been reported in the literature previously. A male twenty-four years old, a worker in a glass factory, presented to our clinic. The dorsolateral skin of his wrists were cut by breaking of the glass as a result of occupational accident and was primarily sutured in a healthcare center. The patient sought additional care after a month because of lingering numbness and pain, and surgery was planned. During surgery, scar tissue and neuroma at the cut ends of SBRN were excised, and bilateral SBRN cuts were repaired. Four weeks after operation, mild sensory deficit on the dorsal side of bilateral thumbs, and left first web space and flexion limitation on the right wrist were detected. At the 3rd month postoperative, right wrist joint range of motion was full, and sensory deficits, and hyperesthesia were decreased. The SBRN elicits the sensory innervation of the thumb dorsum and its injury does not cause important functional deficit. However because of susceptibility of SBRN to develop painful neuroma, diagnosis, treatment and follow up of isolated SBRN injury would be worthwhile for prevention of possible painful neuropathy disturbing quality of life. PMID:23599208
Akkaya, Nuray; Özcan, Hakan Ramazan; Gökalan Kara, Inci; Sahin, Füsun
The use of superficial fibular nerve (Sfn) as a potential donor nerve in nerve grafting has been introduced. The limited availability of donor nerves has paved the way for nerve allografting. We studied the sensory portion of Sfn in 60 limbs from 30 fetuses. Three distinct patterns of the nerve were designated as Types 1, 2, and 3 by us. Type 1 (66.67%) comprised Sfn piercing fascia cruris then branching into Mdn and Idn. Type 2 (21.67%) was a pattern where Sfn penetrated deep fascia then continued undivided over the dorsum of foot. Type 3 (11.67%) was where Mdn and Idn penetrated deep fascia independently. The study provided quantitative measurement data of the sensory portion of Sfn and its branching nerves with respect to osseous landmarks like the head of fibula and the malleoli. Such data may be of help in defining nerve segments suitable for harvesting in nerve grafts from fetuses. PMID:20564350
Wahee, Pratima; Aggarwal, Anjali; Harjeet, K; Sahni, Daisy
The effects of extreme cold on sensory nerves are discussed and a clinical application of these effects is proposed. The structural changes observed following the freezing of sensory nerves in the rat are described and correlated with the clinical results in patients with chronic facial pain treated by cryogenic peripheral nerve blockade. It is suggested that this technique offers features which are not shown by any other method for interrupting peripheral pain pathways and provides a useful alternative to existing methods of treatment for chronic pain. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 Fig. 5 Fig. 6 Fig. 7
In this study, we have characterized the phenotype of mast cells in rat dura mater and their topological and functional relationships with C-fibers in normal and inflammatory conditions. Three mast cell populations with different size, morphology and localization were characterized by their content of specific neutral serine proteases. They showed immunoreactivity corresponding to rat mast cell protease I, rat mast
V Dimitriadou; A Rouleau; M. D Trung Tuong; G. J. F Newlands; H. R. P Miller; G Luffau; J.-C Schwartz; M Garbarg
AIM: Cardiovascular autonomic and peripheral sensory neuropathy is a known complication of chronic alcoholic and non-alcoholic liver diseases. We aimed to assess the prevalence and risk factors for peripheral sensory nerve and autonomic dysfunction using sensitive methods in patients with primary biliary cirrhosis (PBC). METHODS: Twenty-four AMA M2 positive female patients with clinical, biochemical and histological evidence of PBC and
Katalin Keresztes; Ildikó Istenes; Aniko Folhoffer; Peter L Lakatos; Andrea Horvath; Timea Csak; Peter Varga; Peter Kempler; Ferenc Szalay; Lakatos PL
High-count microelectrode arrays implanted in peripheral nerves could restore motor function after spinal cord injury or sensory function after limb loss. In this study, we implanted Utah Slanted Electrode Arrays (USEAs) intrafascicularly at the elbow or shoulder in arm nerves of rhesus monkeys (n = 4) under isoflurane anesthesia. Input-output curves indicated that pulse-width-modulated single-electrode stimulation in each arm nerve could recruit single muscles with little or no recruitment of other muscles. Stimulus trains evoked specific, natural, hand movements, which could be combined via multielectrode stimulation to elicit coordinated power or pinch grasp. Stimulation also elicited short-latency evoked potentials (EPs) in primary somatosensory cortex, which might be used to provide sensory feedback from a prosthetic limb. These results demonstrate a high-resolution, high-channel-count interface to the peripheral nervous system for restoring hand function after neural injury or disruption or for examining nerve structure. PMID:23076108
Ledbetter, Noah M; Ethier, Christian; Oby, Emily R; Hiatt, Scott D; Wilder, Andrew M; Ko, Jason H; Agnew, Sonya P; Miller, Lee E; Clark, Gregory A
Complete loss of median nerve motor function is a rare but devastating injury. Loss of median motor hand function and upper-extremity pronation can significantly impact a patient's ability to perform many activities of daily living independently. The authors report the long-term follow-up in a case of median nerve motor fiber transection that occurred during an arthroscopic elbow procedure, which was then treated with multiple nerve transfers. Motor reconstruction used the nerves to the supinator and extensor carpi radialis brevis to transfer to the anterior interosseous nerve and pronator. Sensory sensation was restored using the lateral antebrachial cutaneous (LABC) nerve to transfer to a portion of the sensory component of the median nerve, and a second cable of LABC nerve as a direct median nerve sensory graft. The patient ultimately recovered near normal motor function of the median nerve, but had persistent pain symptoms 4 years postinjury. PMID:22978538
Murphy, Rory K J; Ray, Wilson Z; Mackinnon, Susan E
Purpose: This prospective study reports the rate and factors influencing sensory impairment of the inferior alveolar and lingual nerves after the removal of impacted mandibular third molars under local anesthesia. Patients and Methods: There were 741 patients with 741 mandibular third molars removed under local anesthesia during a 3-year period from 1994 to 1997. Standardized data collection included the patient's
Anwar B Bataineh
Recording and stimulation via high-count penetrating microelectrode arrays implanted in peripheral nerves may help restore precise motor and sensory function after nervous system damage or disease. Although previous work has demonstrated safety and relatively successful stimulation for long-term implants of 100-electrode Utah Slanted Electrode Arrays (USEAs) in feline sciatic nerve , two major remaining challenges were 1) to maintain viable
Gregory A. Clark; Noah M. Ledbetter; David J. Warren; Reid R. Harrison
In the diagnosis of functional weakness and sensory disturbance, positive physical signs are as important as absence of signs of disease. Motor signs, particularly Hoover's sign, are more reliable than sensory signs, but none should be used in isolation and must be interpreted in the overall context of the presentation. It should be borne in mind that a patient may have both a functional and an organic disorder.
Stone, J; Zeman, A; Sharpe, M
TRANSECTION of a sensory nerve in adults results in profound abnormalities in sensory perception, even if the severed nerve is surgically repaired to facilitate accurate nerve regeneration. In marked contrast, fewer perceptual errors follow nerve transection and surgical repair in children1-3. The basis for this superior recovery in children was unknown. Here we show that there is little or no
Sherre L. Florence; Neeraj Jain; Marcie W. Pospichal; Pam D. Beck; D. Lewis Sly; Jon H. Kaas
Auxiliary structures of the cutaneous sensory nerve formations (SNF) are dependent on sensory innervation during their critical period of development. Denervation of mature cutaneous corpuscles results in survival of the terminal Schwann cells and the capsular structures which are probably responsible for successful reinnervation of the cutaneous SNF. In addition, the basal lamina tubes of Schwann cells are connected with the terminal Schwann cells and play an important role in the guidance of regrowing axons to their original targets. Long-lasting denervation causes atrophic changes of the terminal Schwann cells and alterations of their molecular equipment. These atrophic changes in the terminal Schwann cells may be responsible for erroneous reinnervation of cutaneous SNF. A population of the cutaneous Merkel cells surviving denervation may also serve as targets for regrowing sensory axons. The basal laminae of terminal Schwann cells are produced under control of the sensory terminals during maturation of cutaneous SNF. In adult animals, the basal laminae are capable of stimulating differentiation of migrated Schwann cells to the terminal Schwann cells without the presence of the sensory terminals. Nonspecific cholinesterase (nChE) is secreted by the terminal Schwann cells and is attached to their extracellular matrix. The synthesis of these molecules in adult animals is not influenced by the sensory terminals. However, the presence of nChE molecules is associated with living terminal Schwann cells. Fetal orthotopically grafted dorsal root ganglion (DRG) neurons have the ability to reinnervate cutaneous SNF of adult hosts. When cutaneous areas are denervated, axons from adjacent sensory nerves may extend collateral branches into this area. The capacity for such extension is dependent on: (1) type of sensory nerve ending, C and A delta fibers having significantly greater capacity than sensory axons of larger caliber; (2) age of the animal, immature animals generally showing a greater capacity for collateral sprouting; (3) the state of the adjacent axons, those already in a growth mode being more capable than "resting" ones; and (4) the regional and mechanical conditions at the site of denervation, hindpaw skin being much less extensively reinnervated by collateral fibers than that of the trunk. PMID:8807619
Dubový, P; Aldskogius, H
The growth/differentiation factor-15, GDF-15, has been found to be secreted by Schwann cells in the lesioned peripheral nervous system. To investigate whether GDF-15 plays a role in peripheral nerve regeneration, we substituted exogenous GDF-15 into 10-mm sciatic nerve gaps in adult rats and compared functional and morphological regeneration to a vehicle control group. Over a period of 11 weeks, multiple functional assessments, including evaluation of pinch reflexes, the Static Sciatic Index and of electrophysiological parameters, were performed. Regenerated nerves were then morphometrically analyzed for the number and quality of regenerated myelinated axons. Substitution of GDF-15 significantly accelerated sensory recovery while the effects on motor recovery were less strong. Although the number of regenerated myelinated axons was significantly reduced after GDF-15 treatment, the regenerated axons displayed advanced maturation corroborating the results of the functional assessments. Our results suggest that GDF-15 is involved in the complex orchestration of peripheral nerve regeneration after lesion. PMID:22955564
Mensching, Leonore; Börger, Ann-Kathrin; Wang, Xialong; Charalambous, Petar; Unsicker, Klaus; Haastert-Talini, Kirsten
The contribution of collateral sprouting to the sensory and sudomotor recovery was studied in 52 patients aged 3-66 years (mean 35.5 years) from 2 to 9 years following nerve injury and repair. The study included three groups of patients: (1) patients with complete division of median and ulnar nerves (skin reinnervation exclusively due to axon regeneration), (2) patients with isolated division of ulnar or median nerve (skin reinnervation due to axon regeneration and possible collateral sprouting), and (3) patients in whom injured axons failed to regenerate (skin reinnervation exclusively due to collateral sprouting). The end stage of sensory and sudomotor recovery was studied by: clinical methods, sensory nerve action potential (SNAP) measurements, sympathetic skin response (SSR) and the ninhydrin test. We found that recovery of sensory and sudomotor function in groups 1 and 2 was similar. End-stage sudomotor and sensory recovery within the autonomous area of the nerve did not depend on possible collateral reinnervation. Collateral reinnervation from the uninjured nerve was limited to the border innervation area of the palm and ring finger. Adjacent uninjured nerve may contribute to sprouting of nociceptive axons providing a protective function. PMID:9849363
Ahcan, U; Arn?z, Z M; Bajrovi?, F; Janko, M
Regenerating sensory axons of each receptor class make new connections with similar denervated receptors. This study investigates to what extent these axons return to their original receptive field. The lateral cutaneous nerves of the thigh in rats were divided and allowed to regenerate across a 6 mm. gap interposed with frozen and thawed muscle graft towards their original distal nerve stump and a "foreign" sensory nerve, the saphenous nerve. 16 weeks later, myelinated axon counts of 26 pairs of distal nerves showed no preferential growth towards the original receptive field. Lack of topographic specificity during sensory nerve regeneration may explain the faulty localisation of sensation after nerve repair in clinical practice. Following sensory nerve regeneration, the somatosensory cortex receives accurate afferent information but from disparate skin sites; this probably alters the relationship of overlapping sensory fields and may be the cause of distorted pattern recognition. PMID:1791364
Rath, S; Green, C J
1. The chorda tympani nerve, which innervates the front of the rat tongue, was found to be much less responsive to tongue cooling than the IXth nerve, which innervates the back of the tongue. The two nerves also differed in their relative responsiveness to various taste chemicals. 2. Through cross-union the IXth nerve was made to innervate the front of the tongue, and in other rats the chorda tympani nerve the back of the tongue. 3. After an average of 15 post-operative weeks, electrophysiological recordings of whole nerve action potential discharges were made from normal, control regenerated, and cross-regenerated nerves. Cooling, and chemical and mechanical stimulation of the tongue demonstrated that the control regenerated and cross-regenerated nerves had established functional connexions. 4. Neither the response to cooling nor the relative taste responses were altered by either of two types of control chorda tympani nerve regeneration. 5. In contrast, the cross-regenerated chorda increased its responsiveness to tongue cooling and the cross-regenerated IXthe nerve lost much of its responsiveness to cooling. 6. Cross-regeneration also caused the relative taste responses to change and appear quite similar to the responses obtained from the nerve which normally innervated that tongue region (e.g. the cross-regenerated IXth nerve responded like a chorda tympani nerve). 7. It is suggested that the sensory response evoked in the chorda tympani and IXth nerves by tongue cooling or taste stimulation is at least partially dependent upon the character of the tongue tissue in which the nerve terminates—the epithelium at the front differs from that at the back of the rat tongue. 8. These results rule out the following two hypotheses: (a) that the nerve ending itself functions as a taste receptor in direct contact with applied chemicals and yet is uninfluenced by the character of the tissue in which it terminates, (b) that assuming the taste bud cells are an integral part of the receptive process, the taste nerve ending determines the chemical specificity of the taste cell which it induces, without any previous modification of the nerve by the tissue in which it terminates.
Skin biopsy is a valuable diagnostic tool for small-fiber-predominant neuropathy by the quantification of intra-epidermal nerve fiber density (IENFD). It has the unique advantage of being a minimally invasive procedure with the potential for longitudinal evaluation of both sensory and autonomic fibers. Unmyelinated small fibers are not otherwise quantified objectively with such a level of sensitivity as has been reported with IENFD. Recent advances include an expansion of the skin punch biopsy technique to evaluate larger myelinated fibers and mechanoreceptors, and recent work has also focused on additional methods of quantifying dermal fibers and densely innervated autonomic structures. This review discusses current work using skin biopsy for the pathologic analysis of peripheral nerve fibers in neuropathy of various causes as well as its use in clinical trials.
Myers, M. Iliza; Peltier, Amanda C.
Skin biopsy is a valuable diagnostic tool for small-fiber-predominant neuropathy by the quantification of intraepidermal nerve fiber density (IENFD). It has the unique advantage of being a minimally invasive procedure with the potential for longitudinal evaluation of both sensory and autonomic fibers. Unmyelinated small fibers are not otherwise quantified objectively with such a level of sensitivity as has been reported with IENFD. Recent advances include an expansion of the skin punch biopsy technique to evaluate larger myelinated fibers and mechanoreceptors, and recent work has also focused on additional methods of quantifying dermal fibers and densely innervated autonomic structures. This review discusses current work using skin biopsy for the pathologic analysis of peripheral nerve fibers in neuropathy of various causes as well as its use in clinical trials. PMID:23250768
Myers, M Iliza; Peltier, Amanda C
|Discusses renal neuroanatomy, renal vasculature, renal tubules, renin secretion, renorenal reflexes, and hypertension as related to renal nerve functions. Indicates that high intensitites of renal nerve stimulation have produced alterations in several renal functions. (A chart with various stimulations and resultant renal functions and 10-item,…
Koepke, John P.; DiBona, Gerald F.
A total of 37 patients with traumatic transection of median or ulnar nerves at the wrist (total 41 nerves) were examined clinically and electrophysiologically 4–59 months after primary or secondary suture or grafting. There was a significant increase of cumulative amplitude with the time after suture, whereas maximum sensory nerve conduction velocity and maximum amplitude of nerve action potentials did
W. Tackmann; J. Brennwald; H. Nigst
The effect of 1 mW helium neon continuous-wave (0.633 microns) laser irradiation on superficial radical sensory and median sensory nerve function was examined in a double-blind, controlled study involving 40 volunteers. No differences in action potential amplitudes, distal latencies, or forearm skin temperatures were found between the treated and control groups either at the time of irradiation or at subsequent evaluations 15 and 30 minutes later. As a result, we are unable to confirm reports that low-energy lasers of this power and wavelength alter nerve function.
Basford, J.R.; Daube, J.R.; Hallman, H.O.; Millard, T.L.; Moyer, S.K. (Mayo Clinic and Foundation, Rochester, MN (USA))
Purinoceptors are present in the cell bodies as well as in both peripheral and central terminals of many sensory neurons, where they may play a role in sensory transmission, including pain. After peripheral nerve injury at the spinal nerve level, some axotomized afferent neurons develop ongoing discharges (ectopic discharges) that originate in the dorsal root ganglion (DRG). In the present
Junli Zhou; Kyungsoon Chung; Jin Mo Chung
We tested the hypothesis that inhibition of cutaneous sensory nerves would attenuate reflex cutaneous vasodilation in response to an increase in core temperature. Nine subjects were equipped with four microdialysis fibers on the forearm. Two sites were treated with topical anesthetic EMLA cream for 120 min. Sensory nerve inhibition was verified by lack of sensation to a pinprick. Microdialysis fibers were randomly assigned as 1) lactated Ringer (control); 2) 10 mM nitro-L-arginine methyl ester (L-NAME) to inhibit nitric oxide synthase; 3) EMLA + lactated Ringer; and 4) EMLA + L-NAME. Laser-Doppler flowmetry was used as an index of skin blood flow, and blood pressure was measured via brachial auscultation. Subjects wore a water-perfused suit, and oral temperature was monitored as an index of core temperature. The suit was perfused with 50°C water to initiate whole body heat stress to raise oral temperature 0.8°C above baseline. Cutaneous vascular conductance (CVC) was calculated and normalized to maximal vasodilation (%CVC(max)). There was no difference in CVC between control and EMLA sites (67 ± 5 vs. 69 ± 6% CVC(max)), but the onset of vasodilation was delayed at EMLA compared with control sites. The L-NAME site was significantly attenuated compared with control and EMLA sites (45 ± 5% CVC(max); P < 0.01). Combined EMLA + L-NAME site (25 ± 6% CVC(max)) was attenuated compared with control and EMLA (P < 0.001) and L-NAME only (P < 0.01). These data suggest cutaneous sensory nerves contribute to reflex cutaneous vasodilation during the early, but not latter, stages of heat stress, and full expression of reflex cutaneous vasodilation requires functional sensory nerves and NOS. PMID:23408029
Wong, Brett J
Late and ultralate cerebral potentials in response to cutaneous heat (CO2 laser pulses) and electrical nerve stimuli were studied in a patient with hereditary motor and sensory neuropathy type I who showed severe impairment of myelinated nerve fibre function. Cerebral potentials in response to electrical stimuli were absent (tibial nerve) or small (median nerve). With the laser pulses applied to
J Lankers; A Frieling; K Kunze; B Bromm
A choclear apical turn taken from a 66-year-old woman showed an area with marked decrease in number of the inner sensory cells. After observation by scanning electron microscope, the same specimen was thin-sectioned tangentially to the osseous spiral lamina. Numbers of myelinated nerve fibers were counted and the thickness of the fiber was measured by computed measuring equipment. Compared to the area with inner sensory cells intact, the area without inner sensory cells showed a 70% decrease in number of myelinated fibers. These degenerated fibers might have had intimate relationship with the inner sensory cells, probably being the afferent nerve supply to the inner sensory cells. PMID:475658
Hoshino, T; Kodama, A
Artificial sensibility based on use of a "tactile glove" which substitutes for lack of sensory afferent inflow with acoustic feedback, was used early after repair of the median and ulnar nerves in a 21-year-old man. After six and 12 months the functional outcome exceeded what is expected in adults, and analysis with calculations for the minimal detectable change (MDC) in tactile gnosis showed a true change. This case highlights the timing of sensory re-education after nerve repair and also emphasises the importance of early restitution of afferent inflow from a denervated hand during rehabilitation. PMID:12625396
Rosén, Birgitta; Lundborg, Göran
We studied the effect of infrared (IR) stimulation on rat sensory neurons. Primary sensory neurons were prepared by enzymatic dissociation of the inferior (or "nodose") ganglia from the vagus nerves of rats. The 1.85-?m output of a diode laser, delivered through a 200-?m silica fiber, was used for photostimulation. Nodose neurons express the vanilloid receptor, TRPV1, which is a non-selective cation channel that opens in response to significant temperature jumps above 37 C. Opening TRPV1 channels allows entry of cations, including calcium (Ca2+), into the cell to cause membrane depolarization. Therefore, to monitor TRPV1 activation consequent to photostimulation, we used fura-2, a fluorescent Ca2+ indicator, to monitor the rise in intracellular Ca2+ concentration ([Ca2+]i). Brief trains of 2-msec IR pulses activated TRPV1 rapidly and reversibly, as evidenced by transient rises in [Ca2+]i (referred to as Ca2+ transients). Consistent with the Ca2+ transients arising from influx of Ca2+, identical photostimulation failed to evoke Ca2+ responses in the absence of extracellular Ca2+. Furthermore, the photo-induced Ca2+ signals were abolished by capsazepine, a specific blocker of TRPV1, indicating that the responses were indeed mediated by TRPV1. We discuss the feasibility of using focal IR stimulation to probe neuronal circuit properties in intact neural tissue, and compare IR stimulation with another photostimulation technique-focal photolytic release of "caged" molecules.
Rhee, Albert Y.; Li, Gong; Wells, Jonathon; Kao, Joseph P. Y.
We used immunohistochemical techniques and monoclonal antibodies to localize two basement membrane components (laminin and type IV collagen) in the nerves and sensory nerve formations, or corpuscles, supplying human digital skin. Furthermore, neurofilament proteins, S-100 protein and epithelial membrane antigen were studied in parallel. In dermal nerve trunks, immunostaining for laminin and type IV collagen was found to be co-localized
J. A. Vega; I. Esteban; F. J. Naves; M. E. Valle; L. Malinovsky
Peripheral neural mechanisms underlying the sensations of irritation, discomfort, and itch accompanying the eye allergic response have not been hitherto analyzed. We explored this question recording the changes in the electrical activity of corneoconjunctival sensory nerve fibers of the guinea pig after an ocular allergic challenge. Sensitization was produced by i.p. ovalbumin followed by repeated application in the eye of 10% ovalbumin on days 14 to 18. Blinking and tearing rate were measured. Spontaneous and stimulus-evoked (mechanical, thermal, chemical) impulse activity was recorded from mechanonociceptor, polymodal nociceptor and cold corneoscleral sensory afferent fibers. After a single (day 14) or repeated daily exposures to the allergen during the following 3 to 4days, tearing and blinking rate increased significantly. Also, sensitization was observed in mechanonociceptors (transient reduction of mechanical threshold only on day 14) and in polymodal nociceptors (sustained enhancement of the impulse response to acidic stimulation). In contrast, cold thermoreceptors showed a significant decrease in basal ongoing activity and in the response to cooling. Treatment with the TRPV1 and TRPA1 blockers capsazepine and HC-030031 reversed the augmented blinking. Only capsazepine attenuated tearing rate increase and sensitization of the polymodal nociceptors response to CO2. Capsazepine also prevented the decrease in cold thermoreceptor activity caused by the allergic challenge. We conclude that changes in nerve impulse activity accompanying the ocular allergic response, primarily mediated by activation of nociceptor's TRPV1 and to a lesser degree by activation of TRPA1 channels, explain the eye discomfort sensations accompanying allergic episodes. PMID:23867735
Acosta, M Carmen; Luna, Carolina; Quirce, Susana; Belmonte, Carlos; Gallar, Juana
Introduction: This study evaluated whether Schwann cells (SCs) from different nerve sources transplanted into cold-preserved acellular nerve grafts (CP-ANGs) would improve functional regeneration compared to nerve isografts. Methods: SCs isolated and expanded from motor and sensory branches of rat femoral and sciatic nerves were seeded into 14mm CP-ANGs. Growth factor expression, axonal regeneration, and functional recovery were evaluated in a14 mm rat sciatic injury model and compared to isografts. Results: At 14 days, motor or sensory-derived SCs increased expression of growth factors in CP-ANGs versus isografts. After 42 days, histomorphometric analysis found CP-ANGs with SCs and isografts had similar numbers of regenerating nerve fibers. At 84 days, muscle force generation was similar for CP-ANGs with SCs and isografts. SC source did not affect nerve fiber counts or muscle force generation. Discussion: SCs transplanted into CP-ANGs increase functional regeneration to isograft levels; however SC nerve source did not have an effect. © 2013 Wiley Periodicals, Inc. PMID:23625513
Jesuraj, Nithya J; Santosa, Katherine B; Macewan, Matthew R; Moore, Amy M; Kasukurthi, Rahul; Ray, Wilson Z; Flagg, Eric R; Hunter, Daniel A; Borschel, Gregory H; Johnson, Philip J; Mackinnon, Susan E; Sakiyama-Elbert, Shelly E
Motor dominance is well established, but sensory dominance is much less clear. We therefore studied the cortical evoked magnetic fields using magnetoencephalography (MEG) in a group of 20 healthy right handed subjects in order to examine whether standard electrical stimulation of the median and ulnar nerve demonstrated sensory lateralization. The global field power (GFP) curves, as an indication of cortical activation, did not depict sensory lateralization to the dominant left hemisphere. Comparison of the M20, M30, and M70 peak latencies and GFP values exhibited no statistical differences between the hemispheres, indicating no sensory hemispherical dominance at these latencies for each nerve. Field maps at these latencies presented a first and second polarity reversal for both median and ulnar stimulation. Spatial dipole position parameters did not reveal statistical left-right differences at the M20, M30 and M70 peaks for both nerves. Neither did the dipolar strengths at M20, M30 and M70 show a statistical left-right difference for both nerves. Finally, the Laterality Indices of the M20, M30 and M70 strengths did not indicate complete lateralization to one of the hemispheres. After electrical median and ulnar nerve stimulation no evidence was found for sensory hand dominance in brain responses of either hand, as measured by MEG. The results can provide a new assessment of patients with sensory dysfunctions or perceptual distortion when sensory dominance occurs way beyond the estimated norm. PMID:22080222
Chen, Andrew C N; Theuvenet, Peter J; de Munck, Jan C; Peters, Maria J; van Ree, Jan M; Lopes da Silva, Fernando L
We studied orthodromic sensory conduction velocity along the distal and proximal segments of the median and ulnar nerves by tactile stimulation of the distal phalanx of the 3rd and 5th digits in 44 healthy subjects divided into 2 age groups: from 16 to 35 years and from 63 to 81 years. In the same nerves, we used selective electrical stimulation of the corresponding digital nerves to obtain sensory potentials. In both groups, responses to tactile stimuli had a longer latency and smaller amplitude than those to electrical stimulation, and they were distributed in a series of 6-7 main deflections, apparently regardless of whether the recording site was distal or proximal. Moreover, irrespective of the nerve and of subject age, conduction velocity along both the digit-wrist and the wrist-elbow nerve segments was significantly slower with tactile stimuli than with electrical stimuli. However, independently of the stimulus used, conduction velocity along the proximal nerve segment was significantly faster than that measured along the digit-wrist nerve segment. In both the median and ulnar nerves, maximum potential amplitude, cumulative area and conduction velocity were significantly reduced in the older age group. This finding could reflect the smaller number of Meissner's corpuscles in older subjects, and the loss of large nerve fibres in individuals over 60. PMID:7507425
Caruso, G; Nilsson, J; Crisci, C; Nolano, M; Massini, R; Lullo, F
Regenerating sensory axons of each receptor class make new connections with similar denervated receptors. This study investigates to what extent these axons return to their original receptive field. The lateral cutaneous nerves of the thigh in rats were divided and allowed to regenerate across a 6 mm. gap interposed with frozen and thawed muscle graft towards their original distal nerve
S. RATH; C. J. GREEN
Peripheral nerves show spontaneous regenerative responses, but recovery after injury or peripheral neuropathies (toxic, diabetic, or chronic inflammatory demyelinating polyneuropathy syndromes) is slow and often incomplete, and at present no efficient treatment is available. Using well-defined peripheral nerve lesion paradigms, we assessed the therapeutic usefulness of etifoxine, recently identified as a ligand of the translocator protein (18 kDa) (TSPO), to promote axonal regeneration, modulate inflammatory responses, and improve functional recovery. We found by histologic analysis that etifoxine therapy promoted the regeneration of axons in and downstream of the lesion after freeze injury and increased axonal growth into a silicone guide tube by a factor of 2 after nerve transection. Etifoxine also stimulated neurite outgrowth in PC12 cells, and the effect was even stronger than for specific TSPO ligands. Etifoxine treatment caused a marked reduction in the number of macrophages after cryolesion within the nerve stumps, which was rapid in the proximal and delayed in the distal nerve stumps. Functional tests revealed accelerated and improved recovery of locomotion, motor coordination, and sensory functions in response to etifoxine. This work demonstrates that etifoxine, a clinically approved drug already used for the treatment of anxiety disorders, is remarkably efficient in promoting acceleration of peripheral nerve regeneration and functional recovery. Its possible mechanism of action is discussed, with reference to the neurosteroid concept. This molecule, which easily enters nerve tissues and regulates multiple functions in a concerted manner, offers promise for the treatment of peripheral nerve injuries and axonal neuropathies.
Girard, Christelle; Liu, Song; Cadepond, Francoise; Adams, David; Lacroix, Catherine; Verleye, Marc; Gillardin, Jean-Marie; Baulieu, Etienne-Emile; Schumacher, Michael; Schweizer-Groyer, Ghislaine
The overall goals of this research project are to longitudinally quantify deficits in the maintenance of dynamic stability during locomotion and in sensory motor functions of individuals following a concussion and to establish recovery curves of these mea...
L. S. Chou P. van Donkelaar L. Osternig
This report reviews presentations at the symposium on Drugs and Sensory Functions, held 23-24 Mar 1966 at the Royal College of Physicians, London, which was supported by six British and two international scientific organizations. Approximately 250 attende...
C. H. Miller
The distribution of sensory nerve endings in the labial mucosa of the mouse was investigated by the vital methylene blue staining method. Encapsulated corpuscles were distributed uniformly throughout the mucosa, whereas bush-like nerve endings were localized in the area along the median line where the mucosal epithelium showed a considerable thickness. The number of the encapsulated corpuscles per individual was 72-133, and that of the bush-like nerve endings was 131-248. PMID:7336425
Yamamoto, T; Sakada, S
Thirty nine patients with unilateral lumbar nerve root compression at one level were examined with quantitative sensory testing immediately before microdiscectomy and at six weeks, four months, and 12 months after surgery. Twenty one healthy volounteers were used as controls. The patients were classified as having a good or a poor result at the one year follow up. The improvement
Ř P Nygaard; R Kloster; S I Mellgren
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.
Bloom, Aaron P.; Jimenez-Andrade, Juan M.; Taylor, Reid N.; Castaneda-Corral, Gabriela; Kaczmarska, Magdalena J.; Freeman, Katie T.; Coughlin, Kathleen A.; Ghilardi, Joseph R.; Kuskowski, Michael A.; Mantyh, Patrick W.
In this study, we extracted gait-phase information from natural sensory nerve signals of primarily cutaneous origin recorded in the forelimbs of cats during walking on a motorized treadmill. Nerve signals were recorded in seven cats using nerve cuff or patch electrodes chronically implanted on the median, ulnar, and\\/or radial nerves. Features in the electroneurograms that were related to paw contact
K. D. Strange; J. A. Hoffer; J. B. Wagenaar
BACKGROUND: Sensory disturbance is common following stroke and can exacerbate functional deficits, even in patients with relatively good motor function. In particular, loss of appropriate sensory feedback in severe sensory loss impairs manipulation capability. We hypothesized that task-oriented training with sensory feedback assistance would improve manipulation capability even without sensory pathway recovery. METHODS: We developed a system that provides sensory feedback by transcutaneous electrical nerve stimulation (SENS) for patients with sensory loss, and investigated the feasibility of the system in a stroke patient with severe sensory impairment and mild motor deficit. The electrical current was modulated by the force exerted by the fingertips so as to allow the patient to identify the intensity. The patient had severe sensory loss due to a right thalamic hemorrhage suffered 27 months prior to participation in the study. The patient first practiced a cylindrical grasp task with SENS for 1 hour daily over 29 days. Pressure information from the affected thumb was fed back to the unaffected shoulder. The same patient practiced a tip pinch task with SENS for 1 hour daily over 4 days. Pressure information from the affected thumb and index finger was fed back to the unaffected and affected shoulders, respectively. We assessed the feasibility of SENS and examined the improvement of manipulation capability after training with SENS. RESULTS: The fluctuation in fingertip force during the cylindrical grasp task gradually decreased as the training progressed. The patient was able to maintain a stable grip force after training, even without SENS. Pressure exerted by the tip pinch of the affected hand was unstable before intervention with SENS compared with that of the unaffected hand. However, they were similar to each other immediately after SENS was initiated, suggesting that the somatosensory information improved tip pinch performance. The patient's manipulation capability assessed by the Box and Block Test score improved through SENS intervention and was partly maintained after SENS was removed, until at least 7 months after the intervention. The sensory test score, however, showed no recovery after intervention. CONCLUSIONS: We conclude that the proposed system would be useful in the rehabilitation of patients with sensory loss. PMID:23764012
Kita, Kahori; Otaka, Yohei; Takeda, Kotaro; Sakata, Sachiko; Ushiba, Junichi; Kondo, Kunitsugu; Liu, Meigen; Osu, Rieko
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
Martin, Marta; Benzina, Ouafa; Szabo, Vivien; Végh, Attila-Gergely; Lucas, Olivier; Cloitre, Thierry; Scamps, Frédérique; Gergely, Csilla
The normal postganglionic adrenergic innervation of the nictitating membrane of the cat was replaced by sensory fibers pertaining to the central root of the vagal nodose ganglion. Under these conditions stimulation of the vagal trunk resulted in a contrac...
C. L. Vera J. V. Luco
The neurotransmitters\\/modulators involved in the interaction between pulmonary neuroepithelial bodies (NEBs) and the va- gal sensory component of their innervation have not yet been elucidated. Because P2X 3 purinoreceptors are known to be strongly expressed in peripheral sensory neurons, the aim of the present study was to examine the localization of nerve endings expressing P2X 3 purinoreceptors in the rat
Inge Brouns; Dirk Adriaensen; Geoff Burnstock; Jean-Pierre Timmermans
This article aims to provide an overview of all clinical studies reporting sensory outcome as measured by two-point discrimination after digital nerve repair in the hand using resorbable Food and Drug Administration (FDA)- and CE-approved nerve conduits. The minimum follow-up for inclusion in this review was 11 months. In total, 235 nerve reconstructions could be classified. A total of 169 (72%) nerve reconstructions with a synthetic polyester-based nerve conduit were included; the other 66 nerves were reconstructed with collagen-based nerve conduits. To obtain the most reliable and comparable data, outcomes of each study were reclassified in the classification system as was used in the first two prospective randomised multicentre studies on the use of resorbable nerve conduits for repair of digital nerve gaps in the hand. Of the 235 nerve reconstructions, 171 (73%) nerve reconstructions showed good to excellent functional outcome. As many as 64 (27%) of the nerve reconstructions had a poor outcome. Based on the available data in this article at this moment, we conclude that digital nerve gaps up to 4 cm can be bridged by resorbable nerve conduits with a sensory outcome that can be qualified as good to excellent in almost 75% of cases after 11 months. Differences between FDA- and CE-approved nerve conduits could not be detected, apart from the rates of protrusion that were not observed using collagen-based nerve conduits. PMID:23827446
Meek, Marcel F; Coert, J Henk
The purpose of this randomized, double-blind study was to determine the effect of a helium-neon (He-Ne) laser on latency of peripheral sensory nerve. Forty healthy subjects with no history of right upper extremity pathological conditions were assigned to either a Laser or a Placebo Group. Six 1-cm2 blocks along a 12-cm segment of the subjects' right superficial radial nerve received 20-second applications of either the He-Ne laser or a placebo. We assessed differences between pretest and posttest latencies with t tests for correlated and independent samples. The Laser Group showed a statistically significant increase in latency that corresponded to a decrease in sensory nerve conduction velocity. Short-duration He-Ne laser application significantly increased the distal latency of the superficial radial nerve. This finding provides information about the mechanism of the reported pain-relieving effect of the He-Ne laser.
Snyder-Mackler, L.; Bork, C.E.
The purpose of this investigation was to study lateral palmar nerve (LPN) and medial palmar nerve (MPN) morphology and determine nociception and sensory nerve conduction velocity (SNCV) following placement of continuous peripheral nerve block (CPNB) catheters along LPN and MPN with subsequent bupivacaine (BUP) infusion. Myelinated nerve fiber distribution in LPN and MPN was examined after harvesting nerve specimens in 3 anesthetized horses and processing them for morphometric analysis. In 5 sedated horses, CPNB catheters were placed along each PN in both forelimbs. Horses then received in one forelimb 3 mL 0.125% BUP containing epinephrine 1:200 000 and 0.04% NaHCO3 per catheter site followed by 2 mL/h infusion over a 6-day period, while in the other forelimb equal amounts of saline (SAL) solution were administered. The hoof withdrawal response (HWR) threshold during pressure loading of the area above the dorsal coronary band was determined daily in both forelimbs. On day 6 SNCV was measured under general anesthesia of horses in each limb’s LPN and MPN to detect nerve injury, followed by CPNB catheter removal. The SNCV was also recorded in 2 anesthetized non-instrumented horses (sham controls). In both LPN and MPN myelinated fiber distributions were bimodal. The fraction of large fibers (>7 ?m) was greater in the MPN than LPN (P < 0.05). Presence of CPNB catheters and SAL administration did neither affect measured HWR thresholds nor SNCVs, whereas BUP infusion suppressed HWRs. In conclusion, CPNB with 0.125% BUP provides pronounced analgesia by inhibiting sensory nerve conduction in the distal equine forelimb.
Zarucco, Laura; Driessen, Bernd; Scandella, Massimiliano; Cozzi, Francesca; Cantile, Carlo
A prospective study was conducted to evaluate patient outcomes following sensory nerve transfer. Twenty patients with irreparable ulnar or median nerve lesions underwent the procedure. Nerve involvement was bilateral in 5 cases. The mean age of the patients at the time of surgery was 29 years. The mean paralysis time and the average length of follow-up were 59 and 78
Türker Özkan; Ka?an Özer; Ayan Gülgönen
Several hundred thousand peripheral nerve injuries occur each year in Europe alone. Largely due to the death of around 40%\\u000a of primary sensory neurons, sensory outcome remains disappointingly poor despite considerable advances in surgical technique;\\u000a yet no clinical therapies currently exist to prevent this neuronal death. Acetyl-l-carnitine (ALCAR) is a physiological peptide with roles in mitochondrial bioenergetic function, which may
Andrew McKay Hart; Mikael Wiberg; Mike Youle; Giorgio Terenghi
Background Transient receptor potential vanilloid 1 channels integrate nociceptive stimuli and are predominantly expressed by unmyelinated C-fiber nociceptors, but not low-threshold mechanoreceptive sensory or motor fibers. A recent report showed that the transient receptor potential vanilloid 1 channel agonist capsaicin allows a hydrophilic quaternary ammonium derivative of lidocaine, QX-314, to selectively block C fibers without motor block. The authors tested whether a similar differential block would be produced using amphipathicN-methyl amitriptyline, amitriptyline, bupivacaine, or lidocaine, either alone or together with 0.05% capsaicin, in a rat sciatic nerve block model. Methods Rats (n = 8/group) were anesthetized with sevoflurane, and 0.2 ml of drug was injected either alone or with capsaicin (simultaneously or 10 min later) next to the sciatic nerve in the sciatic notch. Motor function was assessed by the extensor postural thrust. Nociception was evaluated by the nocifensive withdrawal reflex and vocalization evoked by pinch of a skin fold over the lateral metatarsus (cutaneous pain) with a serrated forceps. Results N-Methyl amitriptyline, amitriptyline, bupivacaine, or lidocaine, followed by injection of capsaicin 10 min later, each elicited a predominantly nociceptive-specific blockade. In comparison, simultaneous application of each local anesthetic with capsaicin did not elicit a clinically significant differential block, with the exception of N-methyl amitriptyline. Conclusions Both tertiary amine local anesthetics and their quaternary ammonium derivatives can elicit a predominantly sensory/nociceptor selective block when followed by injection of capsaicin. The combined application of transient receptor potential vanilloid 1 channel agonists and various local anesthetics or their quaternary ammonium derivatives is an appealing strategy to achieve a long-lasting differential block in regional analgesia.
Binshtok, Alexander M.; Wang, Chi-Fei; Hevelone, Nathanael D.; Bean, Bruce P.; Woolf, Clifford J.; Wang, Ging Kuo
This study analyzed the relationship between the density of intraepidermal nerve fibers (IENF) and the characteristics of either nociceptive laser-evoked potentials (LEPs) or contact heat-evoked potentials (CHEPs) in patients with painful sensory polyneuropathy with the aim to determine which parameters of LEPs and CHEPs more reliably reflect IENF loss. A total of 96 patients and 35 healthy volunteers took part
Jordi Casanova-Molla; Josep Maria Grau-Junyent; Merche Morales; Josep Valls-Solé
Background: It has recently been suggested that regular treatment with racemic ?2-adrenoceptor agonists might result in bronchial hyperresponsiveness (BHR) to a range of spasmogens, and this might be due to adverse effects of the distomer. Objective: We sought to determine whether BHR induced by means of continuous exposure to racemic and S-albuterol was mediated by sensory nerves. Methods: Naive or
Sandra Keir; Clive Page; Domenico Spina
Computerized detection method (CDM) software programs have been extensively developed in the field of astronomy to process and analyze images from nearby bright stars to tiny galaxies at the edge of the Universe. These object-recognition algorithms have potentially broader applications, including the detection and quantification of cutaneous small sensory nerve fibers (SSNFs) found in the dermal and epidermal layers, and
Kazuyuki Tamura; Violet A. Mager; Lindsey A. Burnett; John H. Olson; Jeremy B. Brower; Ashley R. Casano; Debra P. Baluch; Jerome H. Targovnik; Rogier A. Windhorst; Richard M. Herman
Although neuropathies of the infrapatellar nerve (infrapatellar branch of the saphenous nerve, IPBSN) have been reported clinically, no electrophysiological method has been defined to evaluate IPBSN conduction. We therefore studied a total of 60 saphenous nerves and 60 IPBSNs from 36 volunteers. The IPBSN was stimulated medially with a surface electrode 2 cm below the patella. The response was recorded with a needle electrode located close to the nerve 1 cm lateral to the femoral artery in the inguinal region. Sensory nerve action potentials were obtained from each subject; mean latency of the first positive peak was 8.1 +/- 0.9 ms, conduction velocity was 54 +/- 4.4 m/s, and response amplitude was 1.3 +/- 1.1 microV. The method that we describe may be an easy and useful electrophysiological test for neuropathies of the IPBSN. PMID:17068766
Bademkiran, Fikret; Obay, Basra; Aydogdu, Ibrahim; Ertekin, Cumhur
Injured adult mammalian axons are unable to regenerate spontaneously in the central nervous tissue. This study investigated in two adult rat models the effects of nerve growth factor (NGF) on the capacity of central primary sensory axons to regenerate back into the spinal cord. Sensory fibers were conditioned by transection of the peripheral nerve 1 week prior to the experiment and identified by anterograde tracing with cholera toxin B subunit injected in the sciatic nerve. In the first model, a predegenerated autologous peripheral nerve graft was implanted as a bridge for the transected sensory fibers into a resection gap in the dorsal columns at the tenth thoracic (T10) spinal cord segment. Vehicle or vehicle with purified mouse or recombinant human NGF was continuously infused for 2 weeks directly into the dorsal column at T9, 3 mm from the rostral border of the nerve graft. With vehicle infusion many ascending sensory axons had grown across the nerve bridge, but essentially none had grown back into the rostral cord. In sharp contrast, NGF promoted the reentry into the denervated dorsal columns of 51% of the sensory axons that had reached the rostral level of the nerve graft. Twenty-six percent had grown 2 mm into the spinal tissue and 10% had reached the NGF-infusion site at 3 mm from the nerve graft. A few fibers were found circling around, but not beyond, the infusion site, perhaps due to the chemoattractant action of NGF. In a second model, the fourth lumbar (L4) dorsal root was crushed 2 mm from its insertion point into the spinal cord and the dorsal roots L2, L3, L5, and L6 were transected. Vehicle or vehicle with purified mouse NGF was infused for 2 weeks directly into the lumbar spinal cord, 2.5 mm rostral to the transition zone of the crushed L4 root. With vehicle, only 6% of the regenerating fibers at the transition zone had crossed the root-spinal cord barrier, but not farther than 0.5 mm into the spinal tissue. With NGF, 18% of the fibers at the transition zone were found at 0.5 mm, 9% at 1.5 mm, and 5% at 2.5 mm (the infusion site) from the transition zone. The present results demonstrate that NGF can promote the regeneration of adult sensory fibers into the otherwise nonpermissive spinal cord white matter. PMID:8690064
Oudega, M; Hagg, T
Indirect immunofluorescence technique was used to study the occurrence and distribution of CGRP immunoreactivity in the submandibular gland of normal rats and after unilateral sensory and sympathetic denervations. In normal rats, CGRP-immunoreactive nerve fibers and nerve trunks were seen around or in close contact with interlobular salivary ducts as well as around small blood vessels of the gland. Occasionally, CGRP-immunoreactive nerve fibers were also detected between or around the acini of the gland. The submandibular ganglia contained CGRP-immunoreactive nerve fibers, but the ganglion cells were not immunoreactive for CGRP. The trigeminal ganglion contained a population of CGRP-immunoreactive, mainly small sized ganglion cells and nerve fibers distributed throughout the ganglion. Unilateral electrocoagulation of the trigeminal nerve caused a significant reduction in the number of immunoreactive nerve fibers in the gland, although some fibers still were present in the ipsilateral glandular tissue. Unilateral superior cervical ganglionectomy caused no detectable effect on the number of CGRP-immunoreactive nerve fibers in the gland. The present results suggest that the rat submandibular gland contains CGRP-immunoreactive nerve fibers both around blood vessels and in glandular secretory elements. Denervation experiments support the view that the majority, but perhaps not all of them originate from the trigeminal ganglion. PMID:2670843
Soinila, J; Salo, A; Uusitalo, H; Yanaihara, N; Häppölä, O
In this article, a new electrodiagnostic approach is described for patients with Morton's neuroma. The new method is based on the anatomic fact that the two branches of the common plantar interdigital nerves innervate the lateral side of one toe and the medial side the next one. This study included 20 normal subjects (aged 28-58 years, 10 men and 10 women) and 4 patients with Morton's neuroma (aged 44-52 years, 4 women). The branches of adjacent common plantar interdigital nerves that innerve one toe were stimulated superficially and separately with half of one toe covered with a piece of medical tape. The recordings were obtained on the posterior tibial nerve at the medial malleolus with needle electrodes. Thus, the difference in latencies of obtained sensory nerve action potentials on the posterior tibial nerve with needle electrode was measured. From normal subjects' data, it was determined that a latency difference value of above 0.17 milliseconds (mean +/- 2.5 SD) in one toe was abnormal. All of the patients with Morton's neuroma showed abnormal interlatency difference values. This new method, which we have developed, is more sensitive, simple to use, does not require extra equipment, and does not cause excessive pain. We suggest that interlatency difference between branches of the common plantar interdigital nerves is a useful and sensitive method for the diagnosis of Morton's neuroma. PMID:20479659
Uludag, Burhanettin; Tataroglu, Cengiz; Bademkiran, Fikret; Uludag, Irem Fatma; Ertekin, Cumhur
ABSTRACT. Peripheral nerve injury in vivo promotes a regenerative growth in vitro characterized by an improved neurite regrowth. Knowledge of the conditioning injury effects on both morphology and mechanical properties of live sensory neurons could be instrumental to understand the cellular and molecular mechanisms leading to this regenerative growth. In the present study, we use differential interference contrast microscopy, fluorescence microscopy, and atomic force microscopy (AFM) to show that conditioned axotomy, induced by sciatic nerve injury, does not increase somatic size of sensory neurons from adult mice lumbar dorsal root ganglia but promotes the appearance of longer and larger neurites and growth cones. AFM on live neurons is also employed to investigate changes in morphology and membrane mechanical properties of somas of conditioned neurons following sciatic nerve injury. Mechanical analysis of the soma allows distinguishing neurons having a regenerative growth from control ones, although they show similar shapes and sizes. PMID:24165740
Benzina, Ouafa; Szabo, Vivien; Lucas, Olivier; Saab, Mari-Belle; Cloitre, Thierry; Scamps, Frédérique; Gergely, Csilla; Martin, Marta
It is a long-standing question how developing motor and sensory neuron projections cooperatively form a common principal grid of peripheral nerve pathways relaying behavioral outputs and somatosensory inputs. Here, we explored this issue through targeted cell lineage and gene manipulation in mouse, combined with in vitro live axon imaging. In the absence of motor projections, dorsal (epaxial) and ventral (hypaxial) sensory projections form in a randomized manner, while removal of EphA3/4 receptor tyrosine kinases expressed by epaxial motor axons triggers selective failure to form epaxial sensory projections. EphA3/4 act non-cell-autonomously by inducing sensory axons to track along preformed epaxial motor projections. This involves cognate ephrin-A proteins on sensory axons but is independent from EphA3/4 signaling in motor axons proper. Assembly of peripheral nerve pathways thus involves motor axon subtype-specific signals that couple sensory projections to discrete motor pathways. PMID:21791286
Wang, Liang; Klein, Rüdiger; Zheng, Binhai; Marquardt, Till
Most reports of sensory symptoms in autism are second hand or observational, and there is little evidence of a neurological\\u000a basis. Sixty individuals with high-functioning autism and 61 matched typical participants were administered a sensory questionnaire\\u000a and neuropsychological tests of elementary and higher cortical sensory perception. Thirty-two percent of autism participants\\u000a endorsed more sensory sensitivity items than any control participants.
Nancy J. Minshew; Jessica A. Hobson
The peripheral taste system remains plastic during adulthood. Sectioning the chorda tympani (CT) nerve, which sends sensory information from the anterior tongue to the central nervous system, causes degeneration of distal fibers and target taste buds. However, taste function is restored after about 40 days in young adult rodents. We tested whether aging impacts the reappearance of neural responses after unilateral CT nerve injury. Taste bud regeneration was minimal at day 50-65 after denervation, and most aged animals died before functional recovery could be assessed. A subset (n=3/5) of old rats exhibited normal CT responses at day 85 postsectioning, suggesting the potential for efficient recovery. The aged taste system is fairly resilient to sensory receptor loss and major functional changes in normal aging. However, injury to the taste system reveals a surprising vulnerability in old rodents. The gustatory system provides an excellent model to study mechanisms underlying delayed recovery from peripheral nerve injury. Strategies to accelerate recovery and restore normal function will be of interest, as the elderly population continues to grow. PMID:22387273
He, L; Yadgarov, A; Sharif, S; McCluskey, L P
The incidence of inferior alveolar nerve (IAN) damage following removal of 3rd molar teeth or saggital split osteotomy has been reported as high as up to 5.5% and 100% respectively. Sensory aberrations in the IAN persisting for longer than 6 months leave some degree of permanent defect. Low level laser treatment (LLL) has a reported beneficial effect on regeneration of traumatically injured nerves. The purpose of this double blind clinical trial was to examine the effects of LLL using a GaAlAs laser (820 nm, Ronvig, Denmark) on touch and temperature sensory perception following a longstanding post surgical IAN injury. Thirteen patients were divided into two groups, one of which received real LLL (4 by 6 J per treatment along the distribution of the IAN to a total of 20 treatments during a time period between 36 - 69 days) and the other equivalent placebo LLL. The degree of mechanoreceptor injury as assessed by Semmes Weinstein Monofilaments (North Coast Medical, USA) were comparable in the two groups prior to treatment (p equals 0.9). Subsequent to LLL the real laser treatment group showed a significant improvement in mechanoreceptor sensory testing (p equals 0.01) as manifested by a decrease in load threshold (g) necessary to elicit a response from the most damaged area. The placebo LLL group showed no significant improvement, In addition, the real LLL group reported a subjective improvement in sensory function too. The degree of thermal sensitivity disability as assessed using a thermotester (Philips, Sweden) was comparable between the two groups prior to LLL p equals 0.5). However, there was no significant improvement in thermal sensitivity post LLL for either the real or placebo laser treated groups. In conclusion, GaAlAs LLL can improve mechanoreceptor perception in longstanding sensory aberration in the IAN.
Khullar, Shelley M.; Brodin, P.; Barkvoll, P.; Haanoes, H. R.
It is well understood that the different regions of the body have cortical representations in proportion to the degree of innervation. Our current understanding of the rat upper extremity has been enhanced using functional MRI (fMRI), but these studies are often limited to the rat forepaw. The purpose of this study is to describe a new technique that allows us to refine the sensory and motor representations in the cerebral cortex by surgically implanting electrodes on the major nerves of the rat upper extremity and providing direct electrical nerve stimulation while acquiring fMRI images. This technique was used to stimulate the ulnar, median, radial, and musculocutaneous nerves in the rat upper extremity using four different stimulation sequences that varied in frequency (5 Hz vs. 10 Hz) and current (0.5 mA vs. 1.0 mA). A distinct pattern of cortical activation was found for each nerve. The higher stimulation current resulted in a dramatic increase in the level of cortical activation. The higher stimulation frequency resulted in both increases and attenuation of cortical activation in different regions of the brain, depending on which nerve was stimulated.
Cho, Younghoon R.; Pawela, Christopher P.; Li, Rupeng; Kao, Dennis; Schulte, Marie L.; Runquist, Matthew L.; Yan, Ji-Geng; Matloub, Hani S.; Jaradeh, Safwan S.; Hudetz, Anthony G.; Hyde, James S.
Summary Nerve growth factor receptor immunoreactivity (NGFR-IR) in sensory nerves and somatosensory receptors of adult rat dental and periodontal tissue was analysed using a monoclonal antibody (192-IgG) and electron microscopy. In dental and periodontal nerves, the unmyelinated axons and their Schwann cells had occasional labelling of their cell membranes, and myelinated axons had none. Dental free nerve endings in predentin
M. R. Byers
Dorsal root injury results in substantial and often irreversible loss of sensory functions as a result of the limited regenerative capacity of sensory axons and the inhibitory barriers that prevent both axonal entry into and regeneration in the spinal cord. Here, we describe previously unknown effects of the growth factor artemin after crush injury of the dorsal spinal nerve roots in rats. Artemin not only promoted re-entry of multiple classes of sensory fibers into the spinal cord and re-establishment of synaptic function and simple behavior, but it also, surprisingly, promoted the recovery of complex behavior. These effects occurred after a 2-week schedule of intermittent, systemic administration of artemin and persisted for at least 6 months following treatment, suggesting a substantial translational advantage. Systemic artemin administration produced essentially complete and persistent restoration of nociceptive and sensorimotor functions, and could represent a promising therapy that may effectively promote sensory neuronal regeneration and functional recovery after injury.
Wang, Ruizhong; King, Tamara; Ossipov, Michael H; Rossomando, Anthony J; Vanderah, Todd W; Harvey, Pamela; Cariani, Peter; Frank, Eric; Sah, Dinah W Y; Porreca, Frank
Summary The reaction of dorsal root ganglia (DRG) neurons to axotomy and its alteration by locally supplied nerve growth factor (NGF) were examined in adult rats. Surgically implanted silicone chambers attached to the severed tip of the sciatic nerve acted as reservoirs capable of providing prolonged access of NGF to the site of injury. The time course of NGF activity
Keith M. Rich; Jack R. Luszczynski; Patricia A. Osborne; Eugene M. Johnson
In this study, we aimed to determine whether there is a correlation between the electrodiagnostic findings and the functional status, muscle strength and sensibility in patients with traumatic nerve injury to the wrists. We assessed 50 patients at a mean of 11.6 months (SD 5.85) (range 6-25) after nerve injury. Sensibility was assessed by monofilament testing. Motor function was evaluated by assessing the manual muscle grade of the abductor pollicis brevis and abductor digiti minimi muscles. Function was evaluated by the Sollerman Hand Function Test. The amplitudes of the compound muscle action potential and the sensory nerve action potential were determined by electroneuromyography. While the compound muscle action potential and sensory nerve action potential amplitudes had significant correlation with muscle grade and Semmes Weinstein Monofilament tests, there was no correlation with the functional scores. PMID:23456925
Sahin, F; Atalay, N S; Akkaya, N; Ercidogan, O; Basakçi, B; Kuran, B
Chronic neuropathic pain affects millions of individuals worldwide, is typically long-lasting, and remains poorly treated with existing therapies. Neuropathic pain arising from peripheral nerve lesions is known to be dependent on the emergence of spontaneous and evoked hyperexcitability in damaged nerves. Here, we report that the potassium channel subunit Kv9.1 is expressed in myelinated sensory neurons, but is absent from small unmyelinated neurons. Kv9.1 expression was strongly and rapidly downregulated following axotomy, with a time course that matches the development of spontaneous activity and pain hypersensitivity in animal models. Interestingly, siRNA-mediated knock-down of Kv9.1 in naive rats led to neuropathic pain behaviors. Diminished Kv9.1 function also augmented myelinated sensory neuron excitability, manifested as spontaneous firing, hyper-responsiveness to stimulation, and persistent after-discharge. Intracellular recordings from ex vivo dorsal root ganglion preparations revealed that Kv9.1 knock-down was linked to lowered firing thresholds and increased firing rates under physiologically relevant conditions of extracellular potassium accumulation during prolonged activity. Similar neurophysiological changes were detected in animals subjected to traumatic nerve injury and provide an explanation for neuropathic pain symptoms, including poorly understood conditions such as hyperpathia and paresthesias. In summary, our results demonstrate that Kv9.1 dysfunction leads to spontaneous and evoked neuronal hyperexcitability in myelinated fibers, coupled with development of neuropathic pain behaviors.
Tsantoulas, Christoforos; Zhu, Lan; Shaifta, Yasin; Grist, John; Ward, Jeremy P. T.; Raouf, Ramin; Michael, Gregory J.; McMahon, Stephen B.
Cough is a persistent symptom of many inflammatory airways' diseases. Cough is mediated by receptors sited on sensory nerves\\u000a and then through vagal afferent pathways, which terminate in the brainstem respiratory centre. Cough is often described as\\u000a an unmet clinical need. Opioids are the only prescription-based anti-tussives currently available in the UK. They possess\\u000a limited efficacy and exhibit serious unwanted
M. G. Belvisi; D. J. Hele
Sensory nerve biopsy specimens from patients with Guillain Barré syndrome (GBS), chronic inflammatory demyelinating polyneuropathy\\u000a (CIDP), and controls consisting of other neuropathies, were examined in order to characterise the nature and intensity of\\u000a any inflammatory infiltrate. In order to establish whether ?? T cells were present in these infiltrates we examined the expression\\u000a of ?? and ?? T cell receptors
John Winer; Sharon Hughes; Joanne Cooper; Anne Ben-Smith; Caroline Savage
The objective of this study was to determine if a recently developed human Ranvier node model, which is based on a modified\\u000a version of the Hodgkin–Huxley model, could predict the excitability behaviour in human peripheral sensory nerve fibres with\\u000a diameters ranging from 5.0 to 15.0 ?m. The Ranvier node model was extended to include a persistent sodium current and was
Jacoba E. Smit; Tania Hanekom; Johan J. Hanekom
Regeneration of axons into inappropriate distal nerve branches may adversely affect functional recovery after pe- ripheral nerve suture. The degree to which motor axons rein- nervate sensory nerves, and vice versa, has not been de- termined. In these experiments, HRP is used to quantify the sensory and motor neurons that reinnervate sensory and motor branches of the rat femoral nerve
Thomas M. E. Brushart
We investigated the roles of sensory and noradrenergic sympathetic nerves on the cutaneous vasodilator response to a localized noxious heating stimulus. In two separate studies, four forearm skin sites were instrumented with microdialysis fibres, local heaters and laser-Doppler probes. Skin sites were locally heated from 33 to 42 °C or rapidly to 44 °C (noxious). In the first study, we tested sensory nerve involvement using EMLA cream. Treatments were as follows: (1) control 42 °C; (2) EMLA 42 °C; (3) control 44°C; and (4) EMLA 44 °C. At the EMLA-treated sites, the axon reflex was reduced compared with the control sites during heating to 42 °C (P < 0.05). There were no differences during the plateau phase (P > 0.05). At both the sites heated to 44 °C, the initial peak and nadir became indistinguishable, and the EMLA-treated sites were lower compared with the control sites during the plateau phase (P < 0.05). In the second study, we tested the involvement of noradrenergic sympathetic nerves in response to the noxious heating using bretylium tosylate (BT). Treatments were as follows: (1) control 42 °C; (2) BT 42 °C; (3) control 44 °C; and (4) BT 44 °C. Treatment with BT at the 42 °C sites resulted in a marked reduction in both the axon reflex and the secondary plateau (P < 0.05). At the 44 °C sites, there was no apparent initial peak or nadir, but the plateau phase was reduced at the BT-treated sites (P < 0.05). These data suggest that both sympathetic nerves and sensory nerves are involved during the vasodilator response to a noxious heat stimulus. PMID:21890519
Carter, Stephen J; Hodges, Gary J
Superoxide anion (O2?•) production was previously reported to be increased in celiac ganglia (CG) during DOCA-salt hypertension, possibly via activation of the reduced nicotinamide-adenine dinucleotide phosphate (NADPH) oxidase. This suggested a role for neuronal NADPH oxidase in autonomic neurovascular control. However, the expression and localization of NADPH oxidase in the peripheral neurons is not fully known. The purpose of this study was to examine the subcellular localization of NADPH oxidase in sympathetic and sensory ganglion neurons and perivascular nerve fibers. In rat CG, p22phox and neuropeptide Y (NPY) were colocalized in all neurons. P22phox was also localized to dorsal root ganglia (DRG) neurons that contain calcitonin gene related peptide (CGRP). In mesenteric arteries, p22phox and p47phox were colocalized with NPY or CGRP in perivascular nerve terminals. A similar pattern of nerve terminal staining of p22phox and p47phox was also found in cultured CG neurons and nerve growth factor (NGF)-differentiated PC12 cells. These data demonstrate a previously uncharacterized localization of NADPH oxidase in perivascular nerve fibers. The presence of a O2?• – generating enzyme in close vicinity to the sites of neurotransmitter handling in the nerve fibers suggests the possibility of novel redox-mediated mechanisms in peripheral neurovascular control.
Cao, Xian; Demel, Stacie L.; Quinn, Mark T.; Galligan, James J.; Kreulen, David L.
We investigated the molecular determinants of Ca(2+)-activated chloride current (CaCC) expressed in adult sensory neurons after a nerve injury. Dorsal root ganglia express the transcripts of three gene families known to induce CaCCs in heterologous systems: bestrophin, tweety, and TMEM16. We found with quantitative transcriptional analysis and in situ hybridization that nerve injury induced upregulation of solely bestrophin-1 transcripts in sensory neurons. Gene screening with RNA interference in single neurons demonstrated that mouse Best1 is required for the expression of CaCC in injured sensory neurons. Transfecting injured sensory neurons with bestrophin-1 mutants inhibited endogenous CaCC. Exogenous expression of the fusion protein green fluorescent protein-Bestrophin-1 in naive neurons demonstrated a plasma membrane localization of the protein that generates a CaCC with biophysical and pharmacological properties similar to endogenous CaCC. Our data suggest that Best1 belongs to a group of genes upregulated by nerve injury and supports functional CaCC expression in injured sensory neurons. PMID:19675239
Boudes, Mathieu; Sar, Chamroeun; Menigoz, Aurélie; Hilaire, Cécile; Péquignot, Marie O; Kozlenkov, Alexei; Marmorstein, Alan; Carroll, Patrick; Valmier, Jean; Scamps, Frédérique
Despite the fact that the peripheral nervous system is able to regenerate after traumatic injury, the functional outcomes following damage are limited and poor. Bone marrow mesenchymal stem cells (MSCs) are multipotent cells that have been used in studies of peripheral nerve regeneration and have yielded promising results. The aim of this study was to evaluate sciatic nerve regeneration and neuronal survival in mice after nerve transection followed by MSC treatment into a polycaprolactone (PCL) nerve guide. The left sciatic nerve of C57BL/6 mice was transected and the nerve stumps were placed into a biodegradable PCL tube leaving a 3-mm gap between them; the tube was filled with MSCs obtained from GFP+ animals (MSC-treated group) or with a culture medium (Dulbecco's modified Eagle's medium group). Motor function was analyzed according to the sciatic functional index (SFI). After 6 weeks, animals were euthanized, and the regenerated sciatic nerve, the dorsal root ganglion (DRG), the spinal cord, and the gastrocnemius muscle were collected and processed for light and electron microscopy. A quantitative analysis of regenerated nerves showed a significant increase in the number of myelinated fibers in the group that received, within the nerve guide, stem cells. The number of neurons in the DRG was significantly higher in the MSC-treated group, while there was no difference in the number of motor neurons in the spinal cord. We also found higher values of trophic factors expression in MSC-treated groups, especially a nerve growth factor. The SFI revealed a significant improvement in the MSC-treated group. The gastrocnemius muscle showed an increase in weight and in the levels of creatine phosphokinase enzyme, suggesting an improvement of reinnervation and activity in animals that received MSCs. Immunohistochemistry documented that some GFP+ -transplanted cells assumed a Schwann-cell-like phenotype, as evidenced by their expression of the S-100 protein, a Schwann cell marker. Our findings suggest that using a PCL tube filled with MSCs is a good strategy to improve nerve regeneration after a nerve transection in mice. PMID:22646222
Frattini, Flávia; Lopes, Fatima Rosalina Pereira; Almeida, Fernanda Martins; Rodrigues, Rafaela Fintelman; Boldrini, Leonardo Cunha; Tomaz, Marcelo A; Baptista, Abrahăo Fontes; Melo, Paulo A; Martinez, Ana Maria Blanco
Primary sensory neurones in cranial and dorsal root ganglia (DRG) of adult animals are generally thought to be maintained through connections with their peripheral (but not central) targets by trophic factor(s) other than nerve growth factor (NGF)1. Damage to the peripheral process of sensory neurones results in a dramatic response or even death of the neurones, whereas axotomy (cutting) of
Eugene M. Johnson; Henry K. Yip
Recent studies suggest that nitric oxide (NO) may act as a chemical messenger in the nervous system. Since neurotransmitters are considered necessary for the sensory function of the carotid body, and molecular O2 is a co-factor for NO synthesis, we examined whether (a) chemoreceptor tissue also synthesizes NO and if so, (b) does endogenous NO affect chemosensory activity. Experiments were performed on carotid bodies obtained from anesthetized cats (n = 20). Distribution of nitric oxide synthase (NOS), an enzyme that catalyzes the formation of NO was examined using NADPH-diaphorase histochemistry. Many nerve plexuses innervating the chemoreceptor tissue were positive for NADPH-diaphorase, indicating that the nerve fibers are the primary source of NO production in the carotid body. Radiometric analysis of NOS activity of the chemoreceptor tissue averaged 1.94 pmol [3H]citrulline/min/mg protein. NOS activity was significantly less in low pO2 reaction medium than in room air controls. Chemosensory activity in vitro increased in a dose-dependent manner in response to L-omega-nitro arginine (L-NNA), an inhibitor of NOS activity. The effects of NOS inhibitor were enantiomer selective as evidenced by reversal of the responses by L- but not D-arginine. These observations imply that endogenous NO is inhibitory to carotid body sensory activity. cGMP levels of L-NNA-treated carotid bodies were significantly less than untreated controls, suggesting that the actions of NO are coupled to the cGMP second messenger system, as elsewhere in the nervous system.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7694772
Prabhakar, N R; Kumar, G K; Chang, C H; Agani, F H; Haxhiu, M A
This study examined C1 spinal nerve roots and their anastomotic connections with the spinal accessory nerve for histological evidence of sensory neurons in adult humans. C1 spinal nerves and roots with the adjacent segments of the spinal accessory nerve and the spinal cord were dissected en bloc from cadaveric specimens, and prepared for histological study. Results show that in 39.3% of specimens studied, no sensory component to the C1 spinal nerve could be identified. The C1 dorsal root was present 35.7% of the time, and when present it always contained neuronal cell bodies. In the remaining specimens, the sensory contribution to the C1 spinal nerve came through an anastomotic connection with the spinal accessory nerve. The investigators were able to identify clusters of neuronal cell bodies along the spinal accessory nerve at the level of C1 in 100% of the specimens examined. Anat Rec, 296:1588-1593, 2013. © 2013 Wiley Periodicals, Inc. PMID:23929774
Hovorka, Michelle S; Uray, Nandor J
This paper examines conditions that have variously been called sensory integration disorder, sensory processing disorder,\\u000a and sensory modulation disorder (SID\\/SPD\\/SMD). As these conditions lack readily and consistently agreed-upon operational definitions,\\u000a there has been confusion as to how these disorders are conceptualized. Rather than addressing various diagnostic controversies,\\u000a we will instead focus upon explaining the symptoms that are believed to characterize
Leonard F. Koziol; Deborah Ely Budding; Dana Chidekel
Background Following acute organophosphorus (OP) poisoning patients complain of numbness without objective sensory abnormalities or other features of OP induced delayed polyneuropathy. The aim of this study was to measure peripheral nerve function after acute exposure to OP. Methods A cohort study was conducted with age, gender and occupation matched controls. Motor nerve conduction velocity (MNCV), amplitude and area of compound muscle action potential (CMAP), sensory nerve conduction velocity (SNCV), F- waves and electromyography (EMG) on the deltoid and the first dorsal interosseous muscles on the dominant side were performed, following acute OP poisoning. All neurophysiological assessments except EMG were performed on the controls. Assessments were performed on the day of discharge from the hospital (the first assessment) and six weeks (the second assessment) after the exposure. The controls were assessed only once. Results There were 70 patients (50 males) and 70 controls. Fifty-three patients attended for the second assessment. In the first assessment MNCV of all the motor nerves examined, CMAP amplitude and SNCV of ulnar nerve, median and ulnar F-wave occurrence in the patients were significantly reduced compared to the controls. In the second assessment significant reduction was found in SNCV of both sensory nerves examined, MNCV of ulnar nerve, CMAP amplitude of common peroneal nerve, F-wave occurrence of median and ulnar nerves. No abnormalities were detected in the patients when compared to the standard cut-off values of nerve conduction studies except F-wave occurrence. EMG studies did not show any abnormality. Conclusion There was no strong evidence of irreversible peripheral nerve damage following acute OP poisoning, however further studies are required.
Jayasinghe, Sudheera S.; Pathirana, Kithsiri D.; Buckley, Nick A.
We have recently shown that manual stimulation of target muscles promotes functional recovery after transection and surgical\\u000a repair to pure motor nerves (facial: whisking and blink reflex; hypoglossal: tongue position). However, following facial nerve\\u000a repair, manual stimulation is detrimental if sensory afferent input is eliminated by, e.g., infraorbital nerve extirpation.\\u000a To further understand the interplay between sensory input and motor
H. Bendella; S. P. Pavlov; M. Grosheva; A. Irintchev; S. K. Angelova; D. Merkel; N. Sinis; K. Kaidoglou; E. Skouras; S. A. Dunlop; Doychin N. Angelov
One of the major consequences of neonatal infraorbital nerve damage is irreversible morphological reorganization in the principal sensory nucleus (PrV) of the trigeminal nerve in the brainstem. We used the voltage-clamp technique to study synaptic transmission in the normal and the denervated PrV of neonatal rats in an in vitro brainstem preparation. Most of the synapses in the PrV are already functional at birth. Three days after peripheral deafferentation, functional synapses become silent, lacking AMPA receptor-mediated currents. Without sensory inputs from the whiskers, silent synapses persist through the second postnatal week, indicating that the maintenance of AMPA receptor function depends on sensory inputs. High-frequency (50 Hz) electrical stimulation of the afferent pathway, which mimics sensory input, restores synaptic function, whereas low-frequency (1 Hz) stimulation has no effect. Application of glycine, which promotes AMPA receptor exocytosis, also restores synaptic function. Therefore, normal synaptic function in the developing PrV requires incoming activity via sensory afferents and/or enhanced AMPA receptor exocytosis. Sensory deprivation most likely results in AMPA receptor endocytosis and/or lateral diffusion to the extrasynaptic membrane. PMID:17475801
Lo, Fu-Sun; Erzurumlu, Reha S
Vagal sensory nerves innervate the majority of visceral organs (e.g., heart, lungs, GI tract, etc) and their activation is critical for defensive and regulatory reflexes. Intracellular Ca(2+) is a key regulator of neuronal excitability and is largely controlled by the Ca(2+) stores of the endoplasmic reticulum. In other cell types store-operated channels (SOC) have been shown to contribute to the homeostatic control of intracellular Ca(2+). Here, using Ca(2+) imaging, we have shown that ER depletion in vagal sensory neurons (using thapsigargin or caffeine) in the absence of extracellular Ca(2+) evoked Ca(2+) influx upon re-introduction of Ca(2+) into the extracellular buffer. This store-operated Ca(2+) entry (SOCE) was observed in approximately 25-40% of vagal neurons, equally distributed among nociceptive and non-nociceptive sensory subtypes. SOCE was blocked by Gd(3+) but not by the Orai channel blocker SKF96365. We found Orai channel mRNA in extracts from whole vagal ganglia, but when using single cell RT-PCR analysis we found only 3 out of 34 neurons expressed Orai channel mRNA, indicating that Orai channel expression in the vagal ganglia was likely derived from non-neuronal cell types. Confocal microscopy of vagal neurons in 3 day cultures demonstrated rich ER tracker fluorescence throughout axonal and neurite structures and ER store depletion (thapsigargin) evoked Ca(2+) transients from these structures. However, no SOCE could be detected in the axonal/neurite structures of vagal neurons. We conclude that SOCE occurs in vagal sensory neuronal cell bodies through non-Orai mechanisms but is absent at nerve terminals. PMID:23399679
Hooper, Justin Shane; Hadley, Stephen H; Mathews, Adithya; Taylor-Clark, Thomas E
Opioid peptides are endogenous neuromodulators that play a major role in the nociceptive pathway by interacting with opioid receptors. So far, four opioid receptors (micro-, delta-, kappa-, orphan-receptor) have been cloned with a wide distribution in the central and peripheral nervous system. In the present study, we give first evidence for the presence of the micro-opioid receptor (MOR) isoform 1A in nerve fibers of human skin. Immunohistochemical analysis revealed MOR immunoreactivity to be present in dermal and epidermal nerve fibers. Double-immunofluorescence staining revealed that MOR is present on calcitonin gene-related protein (CGRP)-positive sensory nerve fibers, while autonomic nerves of blood vessels, hair follicles, or skin glands were negative. In diseased skin such as psoriasis vulgaris, atopic dermatitis, and prurigo nodularis, distribution of MOR 1A immunoreactivity was similar to that of normal skin. These findings expand our knowledge about a direct regulatory role of cutaneous opioid receptors in the skin. Thus, peripheral cutaneous opioid receptors may be involved in the transmission of pain and pruritus, respectively. This is supported by previous observation that opioid receptor antagonists may significantly diminish experimentally evoked histamine-induced itch of the skin. Together, our findings contribute to the understanding of the high antipruritic potency of opioid receptor antagonists in various skin and systemic diseases. PMID:12468112
Ständer, Sonja; Gunzer, Matthias; Metze, Dieter; Luger, Thomas; Steinhoff, Martin
This study analyzed the relationship between the density of intraepidermal nerve fibers (IENF) and the characteristics of either nociceptive laser-evoked potentials (LEPs) or contact heat-evoked potentials (CHEPs) in patients with painful sensory polyneuropathy with the aim to determine which parameters of LEPs and CHEPs more reliably reflect IENF loss. A total of 96 patients and 35 healthy volunteers took part in the study. Based on clinical examination, nerve conduction tests, and quantitative sensory testing, we identified 52 patients with small-fiber neuropathy (SFN), 40 with mixed (small-fiber and large-fiber) neuropathy (MFN), and 4 who were excluded from the analysis because of no evidence of involvement of small fibers. The latency of the N2 was delayed for both LEPs and CHEPs in patients with MFN and for CHEPs only in patients with SFN. The amplitude of the vertex N2/P2 potential was similarly reduced in both types of neuropathy, but LEPs were more frequently absent than CHEPs in MFN patients (68% vs 40%). In general, latency and amplitude of LEPs and CHEPs were well correlated with IENF density. SFN patients were characterized by abnormal EPs and slightly decreased but morphologically abnormal IENF. MFN patients were characterized by frequently absent LEPs and CHEPs and a rather severe IENF loss. The correlation between nociceptive evoked potentials (laser-evoked potentials and contact heat-evoked potentials) and skin biopsy aids in the diagnosis of painful neuropathies. PMID:21185650
Casanova-Molla, Jordi; Grau-Junyent, Josep Maria; Morales, Merche; Valls-Solé, Josep
Peripheral nerve regeneration after traumatic injury and standard repair with a nerve autograft is usually incomplete. This study tested the influence of graft vascularity and pharmacological intervention with GM-1 ganglioside on nerve regeneration in a rat sciatic nerve model. Controls included an unoperated contralateral side and sham-operated groups either with or without the GM-1. During the 5 months of recovery, locomotion was tested by the sciatic function index (SFI). At killing, anesthetized animals were prepared for nerve conduction velocity (NCV) studies, followed by the wet weight of the gastrocnemius muscle (expression of atrophy), toe-chewing (expression of lesion severity and sensory loss), and histological examination of the nerve segments. The SFI showed a slight but significant recovery for both the vascular and avascular groups (34% at 20 weeks), but when GM-1 ganglioside treatment was included, the SFI was poor throughout (20-33%). The average NCV of the graft groups without GM-1 was 46% to 57% of the normal nerve (52.7 m/s), whereas for the groups treated with GM-1, it was 63% to 64% of normal; treatment of the non-vascular graft group significantly improved recovery. A uniformly poor recovery from muscle atrophy was seen for all nerve graft groups (62-67%) compared with normal controls. The mean number of toes per foot chewed was 1.9 and 2.4 in graft groups without GM-1 treatment and 0.9 and 1.3 in graft groups treated with GM-1. This treatment significantly reduced both the extent and the number of animals exhibiting autotomy. The qualitative microscopic appearance of the distal nerve segment in all surgical groups was similar. We conclude that the systemic addition of GM-1 ganglioside enhances only some aspects of regeneration in grafted nerves, possibly with a preferential effect on sensory nerve regeneration and functional recovery. PMID:11372071
Sobeski, J K; Kerns, J M; Safanda, J F; Shott, S; Gonzalez, M H
Background Standard tibial motor nerve conduction measures are established with recording from the abductor hallucis. This technique is often technically challenging and clinicians have difficulty interpreting the information particularly in the short segment needed to assess focal tibial nerve entrapment at the medial ankle as occurs in posterior tarsal tunnel syndrome. The flexor hallucis brevis (FHB) has been described as an alternative site for recording tibial nerve function in those with posterior tarsal tunnel syndrome. Normative data has not been established for this technique. This pilot study describes the technique in detail. In addition we provide reference values for medial and lateral plantar orthodromic sensory measures and assessed intrarater reliability for all measures. Methods Eighty healthy female participants took part, and 39 returned for serial testing at 4 time points. Mean values ± SD were recorded for nerve conduction measures, and coefficient of variation as well as intraclass correlation coefficients (ICC) were calculated. Results Motor latency, amplitude and velocity values for the FHB were 4.1 ± 0.9 msec, 8.0 ± 3.0 mV and 45.6 ± 3.4 m/s, respectively. Sensory latencies, amplitudes, and velocities, respectively, were 2.8 ± 0.3 msec, 26.7 ± 10.1 ?V, and 41.4 ± 3.5 m/s for the medial plantar nerve and 3.2 ± 0.5 msec, 13.3 ± 4.7 ?V, and 44.3 ± 4.0 msec for the lateral plantar nerve. All values demonstrated significant ICC values (P ? 0.007). Conclusion Motor recording from the FHB provides technically clear waveforms that allow for an improved ability to assess tibial nerve function in the short segments used to assess tarsal tunnel syndrome. The reported means will begin to establish normal values for this technique.
Background Clinical tests to assess peripheral nerve disorders can be classified into two categories: tests for afferent/efferent nerve function such as nerve conduction (bedside neurological examination) and tests for increased mechanosensitivity (e.g. upper limb neurodynamic tests (ULNTs) and nerve palpation). Reliability reports of nerve palpation and the interpretation of neurodynamic tests are scarce. This study therefore investigated the intertester reliability of nerve palpation and ULNTs. ULNTs were interpreted based on symptom reproduction and structural differentiation. To put the reliability of these tests in perspective, a comparison with the reliability of clinical tests for nerve function was made. Methods Two experienced clinicians examined 31 patients with unilateral arm and/or neck pain. The examination included clinical tests for nerve function (sensory testing, reflexes and manual muscle testing (MMT)) and mechanosensitivity (ULNTs and palpation of the median, radial and ulnar nerve). Kappa statistics were calculated to evaluate intertester reliability. A meta-analysis determined an overall kappa for the domains with multiple kappa values (MMT, ULNT, palpation). We then compared the difference in reliability between the tests of mechanosensitivity and nerve function using a one-sample t-test. Results We observed moderate to substantial reliability for the tests for afferent/efferent nerve function (sensory testing: kappa = 0.53; MMT: kappa = 0.68; no kappa was calculated for reflexes due to a lack of variation). Tests to investigate mechanosensitivity demonstrated moderate reliability (ULNT: kappa = 0.45; palpation: kappa = 0.59). When compared statistically, there was no difference in reliability for tests for nerve function and mechanosensitivity (p = 0.06). Conclusion This study demonstrates that clinical tests which evaluate increased nerve mechanosensitivity and afferent/efferent nerve function have comparable moderate to substantial reliability. To further investigate the clinometric properties of these tests, more studies are needed to evaluate their validity.
Schmid, Annina B; Brunner, Florian; Luomajoki, Hannu; Held, Ulrike; Bachmann, Lucas M; Kunzer, Sabine; Coppieters, Michel W
Sensory organs are composed of neurons, which convert environmental stimuli to electrical signals, and glia-like cells, whose functions are not well-understood. To decipher glial roles in sensory organs, we ablated the sheath glial cell of the major sensory organ of Caenorhabditis elegans. We found that glia-ablated animals exhibit profound sensory deficits and that glia provide activities that affect neuronal morphology, behavior generation, and neuronal uptake of lipophilic dyes. To understand the molecular bases of these activities, we identified 298 genes whose mRNAs are glia-enriched. One gene, fig-1, encodes a labile protein with conserved thrombospondin TSP1 domains. FIG-1 protein functions extracellularly, is essential for neuronal dye uptake, and also affects behavior. Our results suggest that glia are required for multiple aspects of sensory organ function.
Bacaj, Taulant; Tevlin, Maya; Lu, Yun; Shaham, Shai
Twenty eight patients with unilateral cervical radiculopathy were studied by somatosensory evoked potentials (SEPs) from nerve stimulation at the wrist and from skin stimulation at the first, third or fifth finger depending on the root involved. In order to evaluate the reliability of various "radicular SEP patterns" as described in the literature, absolute latencies and side-to-side differences of the brachial plexus component from the supraclavicular fossa (N9), the medullary component (N13) from the cervical vertebra Cv7, and the primary cortical component (N20, P25) were assessed. Side-to-side differences of the amplitudes of N20/P25 and of the conduction times across the intervertebral fossa (interval N9-N13) were analysed. After nerve stimulation, 68% of the patients had false negative findings on the symptomatic, while 36% had positive findings on the asymptomatic side. After segmental stimulation, 72% of the patients had false negative findings on the symptomatic, while 22% had positive findings on the asymptomatic side. It is concluded that SEPs following nerve and segmental stimulation do not reliably confirm clear-cut already established diagnoses of unilateral radiculopathy with sensory and motor deficit. Therefore, they will not be helpful in the electrophysiological investigation of cervicobrachialgias of unknown origin.
Schmid, U D; Hess, C W; Ludin, H P
While there is general agreement that vision and audition decline with aging, observations for the somatosensory senses and taste are less clear. The purpose of this study was to assess age differences in multimodal sensory perception in healthy, community-dwelling participants. Participants (100 females and 78 males aged 20-89 years) judged the magnitudes of sensations associated with graded levels of thermal, tactile, and taste stimuli in separate testing sessions using a cross-modality matching (CMM) procedure. During each testing session, participants also rated words that describe magnitudes of percepts associated with differing-level sensory stimuli. The words provided contextual anchors for the sensory ratings, and the word-rating task served as a control for the CMM. The mean sensory ratings were used as dependent variables in a MANOVA for each sensory domain, with age and sex as between-subject variables. These analyses were repeated with the grand means for the word ratings as a covariate to control for the rating task. The results of this study suggest that there are modest age differences for somatosensory and taste domains. While the magnitudes of these differences are mediated somewhat by age differences in the rating task, differences in warm temperature, tactile, and salty taste persist. PMID:23625154
Heft, Marc W; Robinson, Michael E
A fine branch of the median nerve innervates the periosteum and medullary cavity of the cat humerus. After branching to innervate the periosteum on the medial surface of the humerus, the nerve enters and supplies the medullary cavity via a nutrient foramen, accompanied by a small artery and vein. The composition of the fibres in the nerve was examined using electron microscopy. Myelinated fibres with diameters of 0.8–6.6 µm and unmyelinated fibres with diameters of 0.1–1.4 µm were observed. These diameters indicate that afferent fibres of this nerve are confined within the Group III and IV categories, and may therefore be nociceptive or mechanoreceptive in function. In addition, autonomic efferent fibres may also be present in these fibre groups. As no fibre diameters greater than 7 µm were noted, it appears that Group I and II fibres are absent in this nerve. The fibre distribution suggests that the principal role of this nerve is to relay bone-related nociceptive or mechanoreceptive information to the central nervous system and to provide autonomic regulatory influences on the bone.
Ivanusic, Jason J; Mahns, David A; Sahai, Vineet; Rowe, Mark J
The functional source separation procedure (FSS) was applied to identify the activities of the primary sensorimotor areas (SM1) devoted to hand control. FSS adds a functional constraint to the cost function of the basic independent component analysis, and obtains source activity all along different processing states. Magnetoencephalographic signals from the left SM1 were recorded in 14 healthy subjects during a simple sensorimotor paradigm--galvanic right median nerve stimuli intermingled with submaximal isometric thumb opposition. Two functional sources related to the sensory flow in the primary cortex were extracted requiring maximal responsiveness to the nerve stimulation at around 20 and 30 ms (S1a, S1b). Maximal cortico-muscular coherence was required for the extraction of the motor source (M1). Sources were multiplied by the Euclidean norm of their corresponding weight vectors, allowing amplitude comparisons among sources in a fixed position. In all subjects, S1a, S1b, M1 were successfully obtained, positioned consistently with the SM1 organization, and behaved as physiologically expected during the movement and processing of the sensory stimuli. The M1 source reacted to the nerve stimulation with higher intensity at latencies around 30 ms than around 20 ms. The FSS method was demonstrated to be able to obtain the dynamics of different primary cortical network activities, two devoted mainly to sensory inflow, and the other to the motor control of the contralateral hand. It was possible to observe each source both during pure sensory processing and during motor tasks. In all conditions, a direct comparison of source intensities can be achieved. PMID:17318837
Porcaro, Camillo; Barbati, Giulia; Zappasodi, Filippo; Rossini, Paolo M; Tecchio, Franca
The primal need for nutrients is satisfied by mechanisms for sensing internal stores and detecting food; ATP is the most primitive\\u000a signal. With increasing density of sensory neurons and glia (the primordial brain) and the emergence of autonomic neural activity\\u000a throughout the endoderm, transmitters and other signaling molecules enable alimentation before the appearance of innate storage\\u000a functions. Memory and, ultimately,
John G. Kral; Wencesley Paez; Bruce M. Wolfe
Successful assessing intestinal lumen content with ultrasound signals might lay a strong basis for the development of the artificial anal sphincter. In the present study, we utilized a modified MLU02-212 ultrasonic gas bubble detector to test the distal part of proximal colon in each rabbit, for the group of twenty healthy New Zealand rabbits. Voltage signals of solid, liquid, gas and empty content of the lumen were collected and compared. The results indicated that there were significant differences among the voltage signals in the 4 conditions (P = 0.000), respectively. Multiple comparison showed significant differences existed in any pair of the four conditions (P = 0.000). Three signal non-overlapping regions existed in these 4 conditions. Thus it seemed that ultrasound could be utilized to distinguish various contents inside the intestinal lumen and could act as "artificial sensory nerve". PMID:22616169
Li, Jianguo; Huang, Zonghai; Shi, Fujun; Chen, Fei; Zhang, Quanan
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. PMID:20947214
Jimenez-Andrade, Juan M; Mantyh, William G; Bloom, Aaron P; Freeman, Katie T; Ghilardi, Joseph R; Kuskowski, Michael A; Mantyh, Patrick W
Background Neuronal hyperexcitability is a crucial phenomenon underlying spontaneous and evoked pain. In invertebrate nociceptors, the S-type leak K+ channel (analogous to TREK-1 in mammals) plays a critical role of in determining neuronal excitability following nerve injury. Few data are available on the role of leak K2P channels after peripheral axotomy in mammals. Results Here we describe that rat sciatic nerve axotomy induces hyperexcitability of L4-L5 DRG sensory neurons and decreases TRESK (K2P18.1) expression, a channel with a major contribution to total leak current in DRGs. While the expression of other channels from the same family did not significantly change, injury markers ATF3 and Cacna2d1 were highly upregulated. Similarly, acute sensory neuron dissociation (in vitro axotomy) produced marked hyperexcitability and similar total background currents compared with neurons injured in vivo. In addition, the sanshool derivative IBA, which blocked TRESK currents in transfected HEK293 cells and DRGs, increased intracellular calcium in 49% of DRG neurons in culture. Most IBA-responding neurons (71%) also responded to the TRPV1 agonist capsaicin, indicating that they were nociceptors. Additional evidence of a biological role of TRESK channels was provided by behavioral evidence of pain (flinching and licking), in vivo electrophysiological evidence of C-nociceptor activation following IBA injection in the rat hindpaw, and increased sensitivity to painful pressure after TRESK knockdown in vivo. Conclusions In summary, our results clearly support an important role of TRESK channels in determining neuronal excitability in specific DRG neurons subpopulations, and show that axonal injury down-regulates TRESK channels, therefore contributing to neuronal hyperexcitability.
Functional role of lingual nerve in breastfeeding was investigated in rat pups during the suckling period. DiI, a postmortem neuronal tracer, was used to confirm the immature lingual nerve (LN) responsible for tongue sensation and resulted in successful fiber labeling anterogradely to the tongue, which showed different distribution patterns from fiber labeling derived from the hypoglossal nerve. Unilaterally LN-injured pups did not show suckling disturbance with absence of any shortening (P11 pups: 559+/-16s; 105% of the control value) in nipple attachment time and the survival rate remained high (P11: 100%). Bilaterally LN-injured pups showed suckling disturbance with marked shortening (P11 pups: 220+/-54 s; 42% of the control value) in nipple attachment time and a low survival rate (P1: 33%; P11: 41%). Bilaterally infraorbital nerve-injured or bilaterally bulbectomized pups did not show any nipple attachment at all and there were no survivors, confirming the crucial roles of upper lip sensation and olfaction in suckling. Based on these findings, we conclude that tongue sensation is very important, but not essential for suckling. PMID:17275242
Yokouchi, Kumiko; Fukushima, Nanae; Kakegawa, Akira; Kawagishi, Kyutaro; Fukuyama, Tetsuhiro; Moriizumi, Tetsuji
Dental treatments sometimes cause sensory impairment, especially in the region innervated by the third division of the trigeminal nerve. The most frequent symptoms are loss of sensation and abnormal sensation. Although most studies have addressed the neuropathic symptom "allodynia" using experimental animal models of the infraorbital nerve, there is little information regarding the sensory impairment that frequently occurs clinically. Therefore, different experimental models are required to clarify the mechanisms of the clinical effects, and previous experimental models have been limited to rats. Here, we report a sensory impairment model in mice whose mechanical touch threshold increased after tight ligation of the mental nerve. Habituation before surgery by mechanical touching of the face enabled us to observe the long-term chronological changes in sensation. The mechanical touch thresholds within the mental nerve region were measured for 70 postoperative (PO) days. Changes in the distribution of substance P (SP) were evaluated by immunohistochemistry to clarify the involvement of axonal flow in the sensory impairment and its recovery. The mechanical touch thresholds transiently increased by PO days 2-3, but decreased to the preoperative levels at around PO day 14. Apparent SP immunoreactivity was recognizable on the medial side to the ligation at PO days 2-3 and disappeared at PO day 7. These behavioural and immunohistochemical changes appeared to exhibit similar time courses, suggesting a possible relationship between them. Therefore, we suggest that our experimental mouse model could represent a new model for clarifying the mechanism of the sensory impairment caused by peripheral nerve injury. PMID:19409417
Seino, Hiroyuki; Seo, Kenji; Maeda, Takeyasu; Someya, Genji
Although skeletal pain is a leading cause of chronic pain and disability, relatively little is known about the specific populations of nerve fibers that innervate the skeleton. Recent studies have reported that therapies blocking nerve growth factor (NGF) or its cognate receptor, tropomyosin receptor kinase A (TrkA) are efficacious in attenuating skeletal pain. A potential factor to consider when assessing the analgesic efficacy of targeting NGF-TrkA signaling in a pain state is the fraction of NGF-responsive TrkA+ nociceptors that innervate the tissue from which the pain is arising, as this innervation and the analgesic efficacy of targeting NGF-TrkA signaling may vary considerably from tissue to tissue. To explore this in the skeleton, tissue slices and whole mount preparations of the normal, adult mouse femur were analyzed using immunohistochemistry and confocal microscopy. Analysis of these preparations revealed that 80% of the unmyelinated/thinly myelinated sensory nerve fibers that express calcitonin gene-related peptide (CGRP) and innervate the periosteum, mineralized bone and bone marrow also express TrkA. Similarly, the majority of myelinated sensory nerve fibers that express neurofilament 200 kDa (NF200) which innervate the periosteum, mineralized bone and bone marrow also co-express TrkA. In the normal femur, the relative density of CGRP+, NF200+ and TrkA+ sensory nerve fibers per unit volume is: periosteum > bone marrow > mineralized bone > cartilage with the respective relative densities being 100: 2: 0.1: 0. The observation that the majority of sensory nerve fibers innervating the skeleton express TrkA+, may in part explain why therapies that block NGF/TrkA pathway are highly efficacious in attenuating skeletal pain.
Castaneda-Corral, Gabriela; Jimenez-Andrade, Juan M.; Bloom, Aaron P.; Taylor, Reid N.; Mantyh, William G.; Kaczmarska, Magdalena J.; Ghilardi, Joseph R.; Mantyh, Patrick W.
One of the important goals of peripheral nerve electrode development is to design an electrode for selective recruitment of the different functions of a common nerve trunk. A challenging task is gaining selective access to central axon populations. In this paper, a simple electrode that takes advantage of the neural plasticity to reshape the nerve is presented. The flat interface
Dustin J. Tyler; Dominique M. Durand
Purpose The aim of this study was to evaluate the effect of adhesiolysis followed by the injection of steroid and local anesthetic\\u000a during epiduroscopy on sensory nerve function, pain, and functional disability in patients with chronic sciatica.\\u000a \\u000a \\u000a \\u000a Methods Epidural adhesiolysis, using epiduroscopy, followed by the injection of steroid and local anesthetic, was scheduled in 19\\u000a patients with chronic sciatica refractory to lumbar
Tetsuya Sakai; Hiroshi Aoki; Minoru Hojo; Masafumi Takada; Hiroaki Murata; Koji Sumikawa
Objectives: Individuals who use manual wheelchairs are at high risk for median nerve injury and subsequent carpal tunnel syndrome (CTS). To gain a better understanding of the mechanism behind CTS in manual wheelchair users, this study examined the relation between (1) pushrim biomechanics and function of the median nerve, (2) pushrim biomechanics and subject characteristics, and (3) median nerve function
Michael L. Boninger; Rory A. Cooper; Mark A. Baldwin; Sean D. Shimada; Alicia Koontz
The aim of the present study was to define the age-related changes in sensory and secretomotor nerve endings in the larynx of F344/N rats. For this purpose, laryngeal tissue sections obtained from 12-, 24- and 35-month-old F344/N rats were compared with respect to the density, distribution and morphology of various types of sensory and secretomotor nerve endings immunoreactive for protein gene product 9.5 (PGP 9.5), calcitonin gene-related peptide (CGRP) and substance P (SP). Two distinct forms of PGP 9.5-immunoreactive motor end-plates were noted; the large sized motor end-plates localized in thyroarytenoid and cricoarytenoid muscles were degenerated in aged rats, while the small sized motor end-plates, localized predominantly in vocal muscles, did not show any age-related changes. CGRP- and SP-immunoreactive nerve fibres of the laryngeal glands did not show any age-related changes. Subepithelial laminar nerve endings immunoreactive to PGP 9.5 showed degeneration with ageing. Aggregates of terminal arborisations in the subepithelial region were smaller in aged animals. PGP 9.5-immunostained taste cells and well-developed subgemmal network were abundant in 12- and 24-month-old rats, but only a few were noted in aged rats. The total number of taste buds decreased significantly with ageing. CGRP- and SP-immunostained taste bud-nerve endings were noted in 12- and 24-month-old rats, but only rarely in 35-month-old rats. The laryngeal epithelium contained PGP 9.5-, CGRP- and SP-immunoreactive thin free nerve endings with many varicosities; their number and distribution were similar between 12- and 24-month-old rats, while only a few endings were observed in 35-month-old rats. Our results indicated that ageing is associated with the reduction of laryngeal sensory and secretomotor nerve endings. PMID:12849090
Yamamoto, Yoshio; Tanaka, Shin; Tsubone, Hirokazu; Atoji, Yasuro; Suzuki, Yoshitaka
A mathematical model of nerve-cell functioning is described. This model is embodied in digital-computer programs which simulate the behavior of nerve cells, their interconnecting fibers, and extrinsic sources of impulses. The simulation utilizes a contino...
D. H. Perkel
As part of the Medical Research Council prospective study of the neurological complications of HIV infection, neurophysiological tests of spinal cord and peripheral nerve function were recorded in a cohort of homosexual or bisexual men. The studies included motor and sensory nerve conduction studies, vibration perception thresholds, somatosensory evoked potentials and motor evoked potentials elicited by magnetic stimulation. The results
S. Connolly; H. Manji; R. H. McAllister; G. B. Griffin; C. Loveday; C. Kirkis; B. Sweeney; O. Sartawi; P. Durrance; M. Fell; M. Boland; C. J. Fowler; S. P. Newman; I. V. D. Weller; M. J. G. Harrison
Background In the developing vertebrate peripheral nervous system, the survival of sympathetic neurons and the majority of sensory neurons depends on a supply of nerve growth factor (NGF) from tissues they innervate. Although neurotrophic theory presupposes, and the available evidence suggests, that the level of NGF expression is completely independent of innervation, the possibility that innervation may regulate the timing or level of NGF expression has not been rigorously investigated in a sufficiently well-characterized developing system. Results To address this important question, we studied the influence of innervation on the regulation of NGF mRNA expression in the embryonic mouse maxillary process in vitro and in vivo. The maxillary process receives its innervation from predominantly NGF-dependent sensory neurons of the trigeminal ganglion and is the most densely innervated cutaneous territory with the highest levels of NGF in the embryo. When early, uninnervated maxillary processes were cultured alone, the level of NGF mRNA rose more slowly than in maxillary processes cultured with attached trigeminal ganglia. In contrast to the positive influence of early innervation on NGF mRNA expression, the levels of brain-derived neurotrophic factor (BDNF) mRNA and neurotrophin-3 (NT3) mRNA rose to the same extent in early maxillary processes grown with and without trigeminal ganglia. The level of NGF mRNA, but not BDNF mRNA or NT3 mRNA, was also significantly lower in the maxillary processes of erbB3-/- mice, which have substantially fewer trigeminal neurons than wild-type mice. Conclusions This selective effect of initial innervation on target field NGF mRNA expression provokes a re-evaluation of a key assertion of neurotrophic theory that the level of NGF expression is independent of innervation.
Alterations of nerve growth factor (NGF) expression have been demonstrated during peripheral nerve disease and the impaired expression or synthesis and transportation of NGF has been correlated with the pathogenesis of several peripheral neuropathies. Since exogenous NGF administration seems to cause undesired side-effects, therapeutical strategies based on the regulation of endogenous synthesis of NGF could prove useful in the clinical treatment of these disorders. The aim of the present study was to analyse the effects of exogenous peripheral administration of the neuropeptide cholecystokinin-8 (CCK-8) on endogenous NGF synthesis, NGF mRNA and distribution of peripheral neuropeptides which are known to be regulated by this neurotrophin. To address these questions we studied the effects of capsaicin (CAPS) before and after the administration of CCK-8 on NGF levels, NGF mRNA expression and localization, and the concentration of substance P (SP) and calcitonin gene-related peptide (CGRP) in peripheral tissue These studies demonstrate that administration of the CCK-8 induces an increase of NGF protein and mRNA in peripheral tissue. NGF level in paw skin of CAPS/CCK-8-treated mice is 3 fold higher than in controls (1241±110?pg?gr?1 of tissue wet weight versus 414±110?pg?gr?1 of controls) and nearly 6 fold higher than in CAPS-treated mice (1241±110?pg?gr?1 versus 248±27?pg?gr?1). The increase of NGF is correlated with the recovery of impaired nocifensive behaviour and with an overexpression of SP and CGRP. The evidence that CCK-8 promotes the recovery of sensory deficits suggests a potential clinical use for this neuropeptide in peripheral neuropathies.
Manni, Luigi; Lundeberg, Thomas; Tirassa, Paola; Aloe, Luigi
Purpose: This study tests the hypothesis that major peripheral nerves serve as important routes for adrenergic neural fibers and therefore peripheral nerve injury affects cutaneous perfusion within the nerve's sensory innervation territory. The specific aim of the study was to determine whether an acute isolated peripheral nerve injury would result in alteration of blood flow to a specific digit, digital
David S. Ruch; Jeff Vallee; Zhongyu Li; Beth Paterson Smith; Martha Holden; L. Andrew Koman
Early experience considerably modulates the organization and function of all sensory systems. In the mammalian olfactory system, deprivation of the sensory inputs via neonatal, unilateral naris closure has been shown to induce structural, molecular, and functional changes from the olfactory epithelium to the olfactory bulb and cortex. However, it remains unknown how early experience shapes functional properties of individual olfactory sensory neurons (OSNs), the primary odor detectors in the nose. To address this question, we examined odorant response properties of mouse OSNs in both the closed and open nostril after four weeks of unilateral naris closure with age-matched untreated animals as control. Using patch-clamp technique on genetically-tagged OSNs with defined odorant receptors (ORs), we found that sensory deprivation increased the sensitivity of MOR23 neurons in the closed side while overexposure caused the opposite effect in the open side. We next analyzed the response properties including rise time, decay time, and adaptation induced by repeated stimulation in MOR23 and M71 neurons. Even though these two types of neurons showed distinct properties in dynamic range and response kinetics, sensory deprivation significantly slowed down the decay phase of odorant-induced transduction events in both types. Using western blotting and antibody staining, we confirmed upregulation of several signaling proteins in the closed side as compared with the open side. This study suggests that early experience modulates functional properties of OSNs, probably via modifying the signal transduction cascade.
He, Jiwei; Tian, Huikai; Lee, Anderson C.; Ma, Minghong
Persons with schizophrenia experience subjective sensory anomalies and objective deficits on assessment of sensory function. Such deficits could be produced by abnormal signaling in the sensory pathways and sensory cortex or later stage disturbances in cognitive processing of such inputs. Steady state responses (SSRs) provide a noninvasive method to test the integrity of sensory pathways and oscillatory responses in schizophrenia with minimal task demands. SSRs are electrophysiological responses entrained to the frequency and phase of a periodic stimulus. Patients with schizophrenia exhibit pronounced auditory SSR deficits within the gamma frequency range (35–50 Hz) in response to click trains and amplitude-modulated tones. Visual SSR deficits are also observed, most prominently in the alpha and beta frequency ranges (7–30 Hz) in response to high-contrast, high-luminance stimuli. Visual SSR studies that have used the psychophysical properties of a stimulus to target specific visual pathways predominantly report magnocellular-based deficits in those with schizophrenia. Disruption of both auditory and visual SSRs in schizophrenia are consistent with neuropathological and magnetic resonance imaging evidence of anatomic abnormalities affecting the auditory and visual cortices. Computational models suggest that auditory SSR abnormalities at gamma frequencies could be secondary to ?-aminobutyric acid–mediated or N-methyl-D-aspartic acid dysregulation. The pathophysiological process in schizophrenia encompasses sensory processing that probably contributes to alterations in subsequent encoding and cognitive processing. The developmental evolution of these abnormalities remains to be characterized.
Brenner, Colleen A.; Krishnan, Giri P.; Vohs, Jenifer L.; Ahn, Woo-Young; Hetrick, William P.; Morzorati, Sandra L.; O'Donnell, Brian F.
Computerized detection method (CDM) software programs have been extensively developed in the field of astronomy to process and analyze images from nearby bright stars to tiny galaxies at the edge of the Universe. These object-recognition algorithms have potentially broader applications, including the detection and quantification of cutaneous small sensory nerve fibers (SSNFs) found in the dermal and epidermal layers, and in the intervening basement membrane of a skin punch biopsy. Here, we report the use of astronomical software adapted as a semi-automated method to perform density measurements of SSNFs in skin-biopsies imaged by Laser Scanning Confocal Microscopy (LSCM). In the first half of the paper, we present a detailed description of how the CDM is applied to analyze the images of skin punch biopsies. We compare the CDM results to the visual classification results in the second half of the paper. Abbreviations used in the paper, description of each astronomical tools, and their basic settings and how-tos are described in the appendices. Comparison between the normalized CDM and the visual classification results on identical images demonstrates that the two density measurements are comparable. The CDM therefore can be used - at a relatively low cost - as a quick (a few hours for entire processing of a single biopsy with 8-10 scans) and reliable (high-repeatability with minimum user-dependence) method to determine the densities of SSNFs. PMID:19852982
Tamura, Kazuyuki; Mager, Violet A; Burnett, Lindsey A; Olson, John H; Brower, Jeremy B; Casano, Ashley R; Baluch, Debra P; Targovnik, Jerome H; Windhorst, Rogier A; Herman, Richard M
... HSAN IE is characterized by impaired function of nerve cells called sensory neurons, which transmit information about sensations ... not well understood, the enzyme may help regulate nerve cell (neuron) maturation and specialization (differentiation), the ability of ...
The L5 dorsal root ganglion (DRG) cells and L5 anterior horn (AH) cells of rats were studied and examined immunocytochemically after transection of the sciatic nerve to find out whether there would be time-dependent differences in the increase of growth-associated protein (GAP-43) expression between sensory neurons and motoneurons. On the seventh day after transection at mid-thigh level, the levels of GAP-43 in the DRG cells significantly increased, while those in the AH cells began to increase gradually from the 14th day onward. Transection at the piriform muscle level induced a significant increase in immunoreactivity of GAP-43 on the third day in the DRG cells, and on the seventh day in the AH cells. These results showed that sensory neurons expressed GAP-43 immunoreactivity earlier than motoneurons after peripheral nerve transection regardless of the site, suggesting that sensory neurons might start to produce cytoskeletons for axonal elongation earlier than motoneurons after nerve transection. PMID:10505438
Matsuura, Y; Ochi, M; Uchio, Y; Suzuki, G; Iwata, A
We compared the characteristics of near-nerve recorded sensory potentials elicited in response to electrical stimulation of digital nerves versus tactile stimulation of the digital skin in 17 healthy subjects with a mean age of 26 years. We also calculated the density of Meissner's corpuscles in the distal and proximal phalanx of digit III of 6 males who had suffered a violent death, but were free from diseases of the peripheral nerve system. Responses to tactile stimulation had a longer latency and lower amplitude than responses to electrical stimulation. Unlike electrically elicited responses, responses to tactile stimulation, which consisted of six or seven main spike components plus several minor components, were similar in recordings from the wrist and elbow. However, with proximal stimulation the electrically evoked responses were more compact and had a higher amplitude and area, whereas the tactile evoked potential became significantly reduced in maximum amplitude and cumulative area. The differences in sensory conduction between distal and proximal could reflect activation of a larger number of nerve fibers when electrical stimuli are used and a smaller amount of mechanoreceptors when tactile stimuli are used. PMID:8107703
Caruso, G; Nolano, M; Lullo, F; Crisci, C; Nilsson, J; Massini, R
Following proximal peripheral nerve injury, motor recovery is often poor due to prolonged muscle denervation and loss of regenerative potential. The transfer of a sensory nerve to denervated muscle results in improved functional recovery in experimental models. The authors here report the first clinical case of sensory protection. Following a total hip arthroplasty, this patient experienced a complete sciatic nerve palsy with no recovery at 3 months postsurgery and profound denervation confirmed electrodiagnostically. He underwent simultaneous neurolysis of the sciatic nerve and saphenous nerve transfers to the tibialis anterior branch of the peroneal nerve and gastrocnemius branch from the tibial nerve. He noted an early proprioceptive response. Electromyography demonstrated initially selective amelioration of denervation potentials followed by improved motor recovery in sensory protected muscles only. The patient reported clinically significant functional improvements in activities of daily living. The authors hypothesize that the presence of a sensory nerve during muscle denervation can improve functional motor recovery.
Bain, James R.; Hason, Yaniv; Veltri, Karen; Fahnestock, Margaret; Quartly, Caroline
The different applications of natural sensors for feedback in rehabilitation systems using functional electrical stimulation (FES) require specialised and optimised designs of nerve cuff electrodes for recording of the sensory information. This paper describes a simple artificial nerve fiber for evaluation of nerve cuff electrode designs, cuff recording configurations and noise reduction methods in a controlled environment. The idea is
Lotte N. S. Andreasen; Johannes J. Struijk; Morten Haugland
Gastric microcirculation plays an important role in the maintenance of the mucosal gastric integrity and the mechanism of injury as well as providing protection to the gastric mucosa. Disturbances in the blood perfusion, through the microcapillaries within the gastric mucosa may result in the formation of mucosal damage. Acute gastric mucosal lesions constitute an important clinical problem. Originally, one of the essential component of maintaining the gastric mucosal integrity was the biosynthesis of prostaglandins (PGs), an issue that has captured the attention of numerous investigations. PGs form due to the activity of cyclooxygenase (COX), an enzyme which is divided into 2 isoforms: constitutive (COX-1) and inducible (COX-2) ones. The inhibition of COX-1 by SC-560, or COX-2 by rofecoxib, reduces gastric blood flow (GBF) and impairs gastric mucosal integrity. Another detrimental effect on the gastric mucosal barrier results from the ablation of sensory afferent nerves by neurotoxic doses of capsaicin. Functional ablation of the sensory afferent nerves by capsaicin attenuates GBF and also renders the gastric mucosa more susceptible to gastric mucosal damage induced by ethanol, aspirin and stress. However, the role of reactive oxygen species (ROS) in the interaction between COX specific inhibitors and afferent sensory nerves has not been extensively studied. The aim of our present study was to determine the participation of ROS in pathogenesis of stress-induced gastric lesions in rats administered with SC-560 or rofecoxib, with or without ablation of the sensory afferent nerves. ROS were estimated by measuring the gastric mucosal tissue level of MDA and 4-HNE, the products of lipid peroxidation by ROS as well as the SOD activity and reduced glutathione (GSH) levels, both considered to be scavengers of ROS. It was demonstrated that exposure to 3.5 h of WRS resulted in gastric lesions, causing a significant increase of MDA and 4-HNE in the gastric mucosa, accompanied by a decrease of SOD activity and mucosal GSH level. Pretreatment with COX-1 and COX-2 inhibitors (SC-560 and rofecoxib, respectively) aggravated the number of gastric lesions, decreased GBF, attenuated GSH level without further significant changes in MDA and 4-HNE tissue levels and SOD activity. Furthermore, the capsaicin--nactivation of sensory nerves resulted in exaggeration of gastric mucosal damage induced by WRS and this was further augmented by rofecoxib. We conclude that oxidative stress, as reflected by an increase of MDA and 4-HNE tissue concentrations (an index of lipid peroxidation), as well as decrease of SOD activity and the fall in GSH tissue level, may play an important role in the mechanism of interaction between the inhibition of COX activity and afferent sensory nerves releasing vasoactive neuropeptides. This is supported by the fact that the addition of specific COX-1 or COX-2 inhibitors to animals with capsaicin denervation led to exacerbation of gastric lesions, and further fall in the antioxidizing status of gastric mucosa exposed to stress. PMID:22653901
Kwiecien, S; Konturek, P C; Sliwowski, Z; Mitis-Musiol, M; Pawlik, M W; Brzozowski, B; Jasnos, K; Magierowski, M; Konturek, S J; Brzozowski, T
It is commonly believed that the cell bodies of mammalian sensory neurons are contained within spinal and cranial sensory ganglia associated with the central nervous system or within the central nervous system itself. However, strong circumstantial evidence implies that some sensory neurons are contained entirely within the gastrointestinal tract.1,8,13 We have investigated this possibility by using intracellular methods to record
W. A. A. Kunze; J. C. Bornstein; J. B. Furness
Transcutaneous electrical nerve stimulation decreased early and late somatosensory evoked potential amplitudes and stimulus intensity ratings, and elevated sensory detection threshold, in normal subjects. Effects on pain threshold depended on pre-treatment threshold. These findings are relevant to treatment of clinical pain by transcutaneous electrical nerve stimulation.
Golding, J F; Ashton, H; Marsh, R; Thompson, J W
Nerve conduction velocities (NCVs) are the standard measurements used to confirm the presence or absence of diabetic neuropathy. NCVs were contrasted with the newer technique of measurement of alternating current perception thresholds (CPTs) in assessing the quantitative level of correlation with severity of diabetic sensory neuropathy. A very detailed, scored neurological history (symptoms) and physical examination, emphasising sensory assessment, was conducted on 71 individuals with diabetic neuropathy of varying degrees of severity. Sensory and motor NCVs and CPTs at 5, 250, and 2000 Hz of the upper and lower extremities were determined for these individuals. In addition, vibration thresholds (VTs) were measured as a third modality. Twenty eight individuals underwent repeated evaluations at 2, 6, 10 and 12 months after the initial procedures. Using the results of 169 complete evaluations, correlations were determined between physical scores (PS) and symptoms scores (SS) and NCVs. NCV correlations with the SS were weaker than with the PS. The strongest of the correlations were found between the PS and motor NCVs of the median nerve (rho = 0.29) and the tibial nerve (rho = 0.38). Normal NCVs were present in the face of very significant historical and physical abnormality. Correlations of the SS and PS with both VTs and CPTs were higher than with the NCVs. CPTs proved the more effective as predictors of both symptomatic and physical impairment. NCVs appear to lack the resolving power necessary to evaluate subtle differences in clinical state of diabetic sensory neuropathy. The supplementary use of current perception testing may improve the quantitative assessment of this condition.
Rendell, M S; Katims, J J; Richter, R; Rowland, F
The overall goal of this study was to determine if parasympathetic nervous system (PsNS) activity is a significant biomarker of sensory processing difficulties in children. Several studies have demonstrated that PsNS activity is an important regulator of reactivity in children, and thus, it is of interest to study whether PsNS activity is related to sensory reactivity in children who have a type of condition associated with sensory processing disorders termed sensory modulation dysfunction (SMD). If so, this will have important implications for understanding the mechanisms underlying sensory processing problems of children and for developing intervention strategies to address them. The primary aims of this project were: (1) to evaluate PsNS activity in children with SMD compared to typically developing (TYP) children, and (2) to determine if PsNS activity is a significant predictor of sensory behaviors and adaptive functions among children with SMD. We examine PsNS activity during the Sensory Challenge Protocol; which includes baseline, the administration of eight sequential stimuli in five sensory domains, recovery, and also evaluate response to a prolonged auditory stimulus. As a secondary aim we examined whether subgroups of children with specific physiological and behavioral sensory reactivity profiles can be identified. Results indicate that as a total group the children with severe SMD demonstrated a trend for low baseline PsNS activity, compared to TYP children, suggesting this may be a biomarker for SMD. In addition, children with SMD as a total group demonstrated significantly poorer adaptive behavior in the communication and daily living subdomains and in the overall Adaptive Behavior Composite of the Vineland than TYP children. Using latent class analysis, the subjects were grouped by severity and the severe SMD group had significantly lower PsNS activity at baseline, tones and prolonged auditory. These results provide preliminary evidence that children who demonstrate severe SMD may have physiological activity that is different from children without SMD, and that these physiological and behavioral manifestations of SMD may affect a child's ability to engage in everyday social, communication, and daily living skills.
Schaaf, Roseann C.; Benevides, Teal; Blanche, Erna Imperatore; Brett-Green, Barbara A.; Burke, Janice P.; Cohn, Ellen S.; Koomar, Jane; Lane, Shelly J.; Miller, Lucy Jane; May-Benson, Teresa A.; Parham, Diane; Reynolds, Stacey; Schoen, Sarah A.
A key characteristic of mast cells appears to be an ability to span the division between nervous and immune system. Indeed, much of our understanding of the bi-directional relationship between the nervous and immune systems has come from the study of mast cell-nerve interaction. Although differences in species have been reported, morphologic as well as functional associations between mast cell and nerves are found in most tissues in many mammalian species, including humans. These interactions are involved in the regulation of physiologic homeostatic processes as well as in disease mechanisms. Here we discuss the influence of cholinergic and sensory neurons on mast cells as well as the importance of mast cell nerve interactions at specific tissue sites, including the brain. PMID:22767065
Forsythe, Paul; Bienenstock, John
Background: Autonomic control on cardiovascular activity is modified with age. Impaired autonomic nerve functions are common features of patients suffering from cardiovascular diseases particularly in old age. Objective: To observe the influence of aging process on parasympathetic nerve function. Study design: This observational study was conducted in the Department of Physiology, BSMMU, Dhaka during the period of July 2005 to
Islam T; Begum N; Begum S; Ferdousi S; Ali T
Angiotensin II (Ang II) and its type-1 receptor (AT1) occur in neurons at multiple locations within the organism, but the basic biology of the receptor in the nervous system remains incompletely understood. We previously observed abundant AT1–like binding sites and intense expression of AT1 immunoreactivity in perikarya of the dorsal root ganglion and ventral horn of the rat spinal cord. We have now examined the receptor in rat sciatic nerve, including the dynamics of its axonal transport. Ligand-binding autoradiography of resting nerve showed “hot spots” of 125I-Ang II binding that could be specifically blocked by the AT1 antagonist, losartan. Immunohistochemistry with an AT1-antibody validated by Western blots also showed patches of AT1-reactivity in nerve. These patches were localized around large myelinated axons with faint immunoreactivity in their lumens. Sixteen hr after nerve ligation there was no change in the patches or hot spots, but luminal AT1-reactivity increased dramatically in a narrow zone immediately above the ligature. With double ligation there was a pronounced accumulation of AT1 immunoreactivity proximal to the upstream ligature and a very slight accumulation distal to the second ligature. This asymmetric pattern of accumulation, confirmed by quantitative receptor binding autoradiography, probably reflected axonal transport rather than local production of receptor. Retrograde tracing and stereological analysis to determine the source of transported AT1 indicated that many AT1-positive fibers arise in the ventral horn, and a larger number arise in dorsal root ganglia. A corresponding result was obtained with double-label immunohistochemistry of ligated nerve, which showed AT1 accumulations in both motor and sensory fibers. We conclude that somatic sensory and motor neurons of the rat export substantial quantities of AT1 into axons, which transport them to the periphery. The physiologic implications of this finding require further investigation.
Tang, Hui; Pavel, Jaroslav; Saavedra, Juan; Brimijoin, Stephen
[A case of acute autonomic, sensory and motor neuropathy with swelling and gadolinium enhancement of bilateral trigeminal nerve on MRI and dissociation between superficial and deep sensation disturbance].
We report a case of a 46-year old man with acute autonomic, sensory and motor neuropathy (AASMN). He developed severe orthostatic hypotension, anuria,anhydrosis, tonic pupil with dysarthria, dysphagia, jaw claudication, and dysesthesia and sharp pain several days after symptom of upper respiratory infection. Neurological examination revealed severely decreased superficial sensation with normal deep sensation. Brain MRI findings showed bilateral trigeminal nerve swelling with gadolinium (Gd) enhancement. His motor and sensory symptoms and MRI abnormality were improved after the administration of intravenous immunoglobulin and intravenous methylprednisolone therapy; however his autonomic symptoms scarcely reacted to these immunotherapies. As long as we investigated in AASMN cases, bilateral trigeminal nerve swelling with Gd enhancement and dissociation between superficial and deep sensation disturbance have not reported, suggesting that the present case mainly disrupted C nerve fibers distributing postganglionic autonomic and temperature-pain sensory nerves. PMID:23470893
Naito, Hiroyuki; Doi, Hikaru; Inamizu, Saeko; Ito, Hijiri; Araki, Takehisa
This review of the past year's literature on neurophysiology of muscles and peripheral nerves emphasizes areas with direct clinical interest. The subject is diversified but will be discussed under the following major headings: nerve conduction studies, electromyography, magnetic motor evoked potentials, quantitative sensory testing, assessment of peripheral pain fibers, and autonomic function assessment. PMID:8293143
Jamal, G A; Mann, C
Although a variety of industrial chemicals, as well as several chemotherapeutic agents used to treat cancer or HIV, preferentially induce a peripheral sensory neuropathy what remains unclear is why these agents induce a sensory vs. a motor or mixed neuropathy. Previous studies have shown that the endothelial cells that vascularize the dorsal root ganglion (DRG), which houses the primary afferent sensory neurons, are unique in that they have large fenestrations and are permeable to a variety of low and high molecular weight agents. In the present report we used whole-mount preparations, immunohistochemistry, and confocal laser scanning microscopy to show that the cell body-rich area of the L4 mouse DRG has a 7 fold higher density of CD31+ capillaries than cell fiber rich area of the DRG or the distal or proximal aspect of the sciatic nerve. This dense vascularization, coupled with the high permeability of these capillaries, may synergistically contribute, and in part explain, why many potentially neurotoxic agents preferentially accumulate and injure cells within the DRG. Currently, cancer survivors and HIV patients constitute the largest and most rapidly expanding groups that have chemically induced peripheral sensory neuropathy. Understanding the unique aspects of the vascularization of the DRG and closing the endothelial fenestrations of the rich vascular bed of capillaries that vascularize the DRG before intravenous administration of anti-neoplastic or anti-HIV therapies, may offer a mechanism based approach to attenuate these chemically induced peripheral neuropathies in these patients.
Jimenez-Andrade, Juan M; Herrera, Monica B; Ghilardi, Joseph R; Vardanyan, Marina; Melemedjian, Ohannes K; Mantyh, Patrick W
This report describes the waveform and properties of somatosensory evoked potentials recorded from various levels of the human spinal cord, with electrodes inserted into the epidural space and the stimulus delivered to the posterior tibial nerve at the knee. The object was to provide a means of monitoring spinal cord function during surgery for the correction of spinal deformities. The responses could be resolved into at least three components with different activation thresholds and different conduction velocities within the spinal cord (45-80 m/s approximately). The findings are in accord with recent studies, suggesting that the fast activity may be conducted in the dorsal spinocerebellar tract and the slower waves in the posterior columns.
Jones, S J; Edgar, M A; Ransford, A O
Nerve growth factor (NGF) promotes the survival of embryonic sensory neurons and maintains the phenotypic characteristics of primary nociceptive neurons postnatally. NGF also contributes to nociceptor activation and hyperalgesia during inflammatory pain states. The purpose of this study was to determine whether NGF might have an additional pronociceptive action by interfering with opioid-mediated analgesia in primary nociceptive neurons. Sensory neurons were isolated from the dorsal root ganglia of weanling rats and kept in standard culture conditions either with or without exogenous NGF (50 ng/ml). Currents through voltage-gated calcium channels were recorded from individual neurons using the whole cell patch clamp technique with Ba(2+) as the charge carrier (I(Ba)). The micro-opioid agonist fentanyl (1 microM) and the GABA(B) agonist baclofen (50 microM) were used to test G protein-dependent inhibition of I(Ba). Fentanyl inhibited I(Ba) by an average of 38+/-4% in untreated cells vs. 25+/-2% in NGF-treated cells (P<0.01). NGF had no effect on I(Ba) current magnitude or kinetics. The NGF-induced attenuation of opioid action was observed as early as 4 h after exposure, but was not seen when NGF was applied by bath perfusion for up to 40 min, suggesting that the effect was not mediated by a rapid phosphorylation event. The effect of NGF was prevented by K-252a (100 nM), an inhibitor of TrkA autophosphorylation. Baclofen-induced inhibition of I(Ba), on the other hand, was not affected by NGF treatment, suggesting that NGF modulation of opioid-mediated inhibition occurred upstream from the G protein. This was supported by the finding that GTP-gamma-S, an agonist independent G protein activator, inhibited I(Ba) similarly in both untreated and NGF treated cells. The results show that NGF selectively attenuated opioid-mediated inhibition of I(Ba) via TrkA receptor activation, possibly by altering opioid receptor function. PMID:15120862
McDowell, T S
Background During a continuous femoral nerve block, the influence of catheter tip position relative to the femoral nerve on infusion characteristics remains unknown. Methods We inserted bilateral femoral perineural catheters in volunteers (ultrasound-guided, needle in-plane). Subjects’ dominant side was randomized to have the catheter tip placed either anterior or posterior to the femoral nerve. The contralateral limb received the alternative position. Ropivacaine 0.1% was administered through both catheters concurrently for 6 hours (4 mL/h). Outcome measures included the maximum voluntary isometric contraction (MVIC) of the quadriceps femoris muscle and tolerance to cutaneous electrical current over to the distal quadriceps tendon. Measurements were performed at Hour 0 (baseline), and on the hour until Hour 9, as well as Hour 22. The primary endpoint was the MVIC of the quadriceps at Hour 6. Results As a percentage of the baseline measurement, quadriceps MVIC for limbs with anterior (n=16) and posterior (n=16) catheter tip placement did not differ to a statistically significant degree at Hour 6 (mean [SD] 29%  vs. 30% , respectively; 95% CI: ?22% to 20%; p=0.931), or at any other time point. However, the maximum tolerance to cutaneous electrical current was higher in limbs with anterior compared to posterior catheter tip placement at Hour 6 (20  vs. 6  mA, respectively; 95% CI: 1 mA to 27 mA; p=0.035), as well as at Hours 1, 7, 8, and 9 (p<0.04). Conclusions This study documents the significant (70–80%) quadriceps femoris weakness induced by a continuous femoral nerve block infusion at a relatively low dose of ropivacaine (4 mg/h) delivered through a perineural catheter located both anterior and posterior to the femoral nerve. In contrast, an anterior placement increases cutaneous sensory block compared with a posterior insertion, without a concurrent relative increase in motor block.
Ilfeld, Brian M.; Loland, Vanessa J.; Sandhu, NavParkash S.; Suresh, Preetham J.; Bishop, Michael J.; Donohue, Michael C.; Ferguson, Eliza J.; Madison, Sarah J.
Nerve conduit provides a promising strategy for nerve regeneration, and the proper microenvironment in the lumen could improve the regeneration. Our previous work had demonstrated that linear ordered collagen scaffold (LOCS) could effectively guide the oriented growth of axons. Laminin is known as an important nerve growth promoting factor and can facilitate the growth cone formation. In addition, ciliary neurotrophic factor (CNTF) and brain-derived neurotrophic factor (BDNF) can effectively improve the nerve regeneration after nerve injuries. However, in practice, diffusion caused by the body fluids is the major obstacle in their applications. To retain CNTF or BDNF on the scaffolds, we produced collagen binding CNTF (CBD-CNTF), collagen binding BDNF (CBD-BDNF) and laminin binding CNTF (LBD-CNTF), laminin binding BDNF (LBD-BDNF) respectively. In this work, we developed laminin modified LOCS fibers (L × LOCS) by chemical cross-linking LOCS fibers with laminin. Collagen binding or laminin binding neurotrophic factors were combined with LOCS or L × LOCS, and then filled them into the collagen nerve conduit. They were found to guide the ordered growth of axons, and improve the nerve functional recovery in the rat facial nerve transection model. The combination of CNTF and BDNF greatly enhanced the facial nerve regeneration and functional recovery. PMID:23122676
Cao, Jiani; Xiao, Zhifeng; Jin, Wei; Chen, Bing; Meng, Danqing; Ding, Wenyong; Han, Sufang; Hou, Xiaoshan; Zhu, Tiansheng; Yuan, Baoyu; Wang, Jing; Liang, Weibang; Dai, Jianwu
The clinical features of idiopathic polyneuritis in 22 patients admitted to the University of Kentucky Medical Center between July 1965 and June 1970 are described. Serial studies of peripheral nerve function in 12 patients followed to clinical recovery showed changes in nerve conduction velocity, distal motor latency, and\\/or muscle action potential amplitude. Six children and one adult, showing a change
Michael P. McQuillen
Recent electrophysiological evidence indicates that Q-switched Nd:YAG laser irradiation might have selective effects on neural impulse transmission in small slow conducting sensory nerve fibers as compared to large diameter afferents. In an attempt to clarify the ultimate fate of sensory neurons after laser application to their peripheral axons, we have used horseradish peroxidase (HRP) as a cell marker to retrogradely label sensory neurons innervating the distal hindlimb in the rat. Pulsed Nd:YAG laser light was applied to the tibial nerve at pulse energies of 70 or 80 mJ/pulse for 5 min in experimental rats. Seven days later HRP was applied to the left (laser-treated) and to the contralateral (untreated) tibial nerve proximal to the site of laser irradiation. In control animals the numbers of HRP-labeled dorsal root ganglion cells were not significantly different between the right and the left side. In contrast, after previous laser irradiation labeling was always less on the laser-treated side (2183 +/- 513 cells, mean +/- SEM) as compared to the untreated side (3937 +/- 225). Analysis of the dimensions of labeled cells suggested that the reduction of labeled cells on the laser-treated side was mainly due to a deficit in small sensory neurons. Since the conduction velocity of nerve fibers is related to the size of their somata, our histological data imply that laser light selectively affects retrograde transport mechanisms for HRP in slow conducting sensory nerve fibers.
Wesselmann, U.; Lin, S.F.; Rymer, W.Z. (Northwestern Univ. Medical School, Chicago, IL (USA))
The vanilloid receptor subtype 1 (VR1)/(TRPV1), binding capsaicin, is a non-selective cation channel that recently has been shown in human keratinocytes in vitro and in vivo. However, a description of VR1 localization in other cutaneous compartments in particular cutaneous nerve fibers is still lacking. We therefore investigated VR1 immunoreactivity as well as mRNA and protein expression in a series (n = 26) of normal (n = 7), diseased (n = 13) [prurigo nodularis (PN) (n = 10), generalized pruritus (n = 1), and mastocytosis (n = 2)], and capsaicin-treated human skin (n = 6). VR1 immunoreactivity could be observed in cutaneous sensory nerve fibers, mast cells, epidermal keratinocytes, dermal blood vessels, the inner root sheet and the infundibulum of hair follicles, differentiated sebocytes, sweat gland ducts, and the secretory portion of eccrine sweat glands. Upon reverse transcriptase-polymerase chain reaction and Western blot analysis, VR1 was detected in mast cells and keratinocytes from human skin. In pruritic skin of PN, VR1 expression was highly increased in epidermal keratinocytes and nerve fibers, which was normalized after capsaicin application. During capsaicin therapy, a reduction of neuropeptides (substance P, calcitonin gene-related peptide) was observed. After cessation of capsaicin therapy, neuropeptides re-accumulated in skin nerves. In conclusion, VR1 is widely distributed in the skin, suggesting a major role for this receptor, e.g. in nociception and neurogenic inflammation. PMID:14987252
Ständer, Sonja; Moormann, Corinna; Schumacher, Mark; Buddenkotte, Jörg; Artuc, Metin; Shpacovitch, Victoria; Brzoska, Thomas; Lippert, Undine; Henz, Beate M; Luger, Thomas A; Metze, Dieter; Steinhoff, Martin
1. Extracellular recording techniques were used to study nerve terminal impulses (NTIs) recorded from single polymodal nociceptors and cold-sensitive receptors in guinea-pig cornea isolated in vitro. 2. The amplitude and time course of NTIs recorded from polymodal nociceptors was different from those of cold-sensitive receptors. 3. Bath application of tetrodotoxin (1 microM) changed the time course of spontaneous NTIs recorded from both polymodal and cold-sensitive receptors. 4. Bath application of lignocaine (lidocaine; 1-5 mM) abolished all electrical activity. 5. Local application of lignocaine (2.5 and 20 mM) through the recording electrode changed the time course of the NTIs recorded from polymodal nociceptors but not that of NTIs recorded from cold-sensitive nerve endings. 6. It is concluded that action potentials propagate actively in the sensory nerve endings of polymodal nociceptors. In contrast, cold-sensitive receptor nerve endings appear to be passively invaded from a point more proximal in the axon where the action potential can fail or be initiated. PMID:11389207
Brock, J A; Pianova, S; Belmonte, C
Irvine, California 92664 The nervous systeni of polyclad flatworn-is is comprised of a number of nerve tracts which radiate outwards from at-i anterior ganglionic mass often called the brain. These nerve tracts branch and anastomose repeatedly to form a network of strands. Two such networks have beet-i recognized, ( 1) a ventral network of coarse nerves with a meshwork of
Sensory sensitivity is typically measured using behavioural techniques (psychophysics), which rely on observers responding to very large numbers of stimulus presentations. Psychophysics can be problematic when working with special populations, such as children or clinical patients who may lack the compliance or cognitive skills to perform the behavioural tasks. We used an auditory gap-detection paradigm to develop an accurate measure of sensory threshold derived from passively-recorded magnetoencephalographic (MEG) data. Auditory evoked responses were elicited by silent gaps of varying durations in an on-going noise stimulus. Source modelling was used to spatially filter the MEG data and sigmoidal 'cortical psychometric functions' relating response amplitude to gap duration were obtained for each individual participant. Fitting the functions with a curve and estimating the gap duration at which the amplitude of the evoked response exceeded one standard deviation of the prestimulus brain activity provided an excellent prediction of psychophysical threshold. Accurate sensory thresholds can therefore be reliably extracted from MEG data recorded while participants listen passively to a stimulus. Because our paradigm required no behavioural task, the method is suitable for studies of populations where variations in cognitive skills or vigilance make traditional psychophysics unsuitable. PMID:22902921
Witton, C; Patel, T; Furlong, P L; Henning, G B; Worthen, S F; Talcott, J B
Neuronal oscillations appear throughout the nervous system, in structures as diverse as the cerebral cortex, hippocampus, subcortical nuclei and sense organs. Whether neural rhythms contribute to normal function, are merely epiphenomena, or even interfere with physiological processing are topics of vigorous debate. Sensory pathways are ideal for investigation of oscillatory activity because their inputs can be defined. Thus, we will focus on sensory systems as we ask how neural oscillations arise and how they might encode information about the stimulus. We will highlight recent work in the early visual pathway that shows how oscillations can multiplex different types of signals to increase the amount of information that spike trains encode and transmit. Last, we will describe oscillation-based models of visual processing and explore how they might guide further research.
Koepsell, Kilian; Wang, Xin; Hirsch, Judith A.; Sommer, Friedrich T.
The loss of sensation is not an uncommon associated finding after injury to the peripheral nerves and the spinal cord. However, the sensory examination is prone to the influence of nonphysiologic factors, and one cannot use it to determine whether functional sensory loss reflects unconscious or intentional symptom production. This distinction has important implications for differential diagnosis and for decision making in the context of workers' compensation claims and personal injury litigation. We present 3 cases of patients with chronic pain and nondermatomal patterns of loss of fine-touch sensation, whose sensory loss was examined by a sensory forced-choice symptom validity test. Their below-chance scores showed intentionally produced sensory symptoms. The use of this methodology in differential diagnosis is discussed. PMID:12917866
Greve, Kevin W; Bianchini, Kevin J; Ameduri, Clifford J
The present review gives a survey of rehabilitative measures for disorders of the motor function of the mimetic muscles (facial nerve), and muscles innervated by the spinal accessory and hypoglossal nerves. The dysfunction can present either as paralysis or hyperkinesis (hyperkinesia). Conservative and surgical treatment options aimed at restoring normal motor function and correcting the movement disorders are described. Static reanimation techniques are not dealt with. The final section describes the use of botulinum toxin in the therapy of dysphagia.
Laskawi, R.; Rohrbach, S.
The pro-inflammatory mediator bradykinin plays an important role in hyperalgesia during inflammatory conditions. Here, we used unilateral ligation of the sciatic nerve to investigate whether the expression of bradykinin binding sites in isolated rat dorsal root ganglion neurons is changed following nerve injury. Under control conditions, the percentage of neurons expressing bradykinin binding sites increased from 52% at day 0.8
M Petersen; A. S Eckert; G Segond von Banchet; B Heppelmann; A Klusch; K.-D Kniffki
Serial electron microscope reconstructions were used to examine the organization and cell types of the nerve plexus that surrounds the mouth in amphioxus larvae. The plexus is involved in a rejection response that occurs during feeding: a number of oral spines project across the mouth, and debris impinging on them triggers a contraction of the gill slit and pharyngeal musculature that forces water through the mouth, dislodging the debris. The oral spine cells are secondary sense cells that synapse with neurites belonging to a class of peripheral interneurons intrinsic to the oral nerve plexus. These in turn synapse with a second class of peripheral neurons with large axons that we interpret as sensory cells and which probably transmit signals to the nerve cord. The intrinsic cells also appear to synapse with each other, implying that local integrative activities of some complexity occur in the oral plexus. In comparative terms, the intrinsic neurons most closely resemble the Merkel-like accessory cells of vertebrate taste buds, and we postulate a homology between oral spine cells and taste buds, despite differences in function. There are also similarities between the amphioxus oral plexus and adoral nerves and ganglia of echinoderm larvae, suggesting homology of both the oral nerve plexus and the mouth itself between lower deuterostome phyla and chordates.
C.Lacalli, T.; J.Gilmour, T. H.; J.Kelly, S.
|According to the sensory/functional theory of semantic memory, Living items rely more on Sensory knowledge than Non-living ones. The sensory/functional explanation of category-specificity assumes that semantic features are organised on the basis of their content. We report here a study on DAT patients with impaired performance on Living items and…
Sartori, Giuseppe; Gnoato, Francesca; Mariani, Ilenia; Prioni, Sara; Lombardi, Luigi
A contribution to a handbook on psychonomy relating to sensory functions is presented. The properties of the human eye are described, including optical image formation, image quality, the retina, photometry, light and dark adaptation, and color vision.
J. J. Vos
Activation of efferent renal sympathetic nerve activity (ERSNA) increases afferent renal nerve activity (ARNA), which then reflexively decreases ERSNA via activation of the renorenal reflexes to maintain low ERSNA. The ERSNA-ARNA interaction is mediated by norepinephrine (NE) that increases and decreases ARNA by activation of renal ?(1)-and ?(2)-adrenoceptors (AR), respectively. The ERSNA-induced increases in ARNA are suppressed during a low-sodium (2,470 ± 770% s) and enhanced during a high-sodium diet (5,670 ± 1,260% s). We examined the role of ?(2)-AR in modulating the responsiveness of renal sensory nerves during low- and high-sodium diets. Immunohistochemical analysis suggested the presence of ?(2A)-AR and ?(2C)-AR subtypes on renal sensory nerves. During the low-sodium diet, renal pelvic administration of the ?(2)-AR antagonist rauwolscine or the AT1 receptor antagonist losartan alone failed to alter the ARNA responses to reflex increases in ERSNA. Likewise, renal pelvic release of substance P produced by 250 pM NE (from 8.0 ± 1.3 to 8.5 ± 1.6 pg/min) was not affected by rauwolscine or losartan alone. However, rauwolscine+losartan enhanced the ARNA responses to reflex increases in ERSNA (4,680 ± 1,240%·s), and renal pelvic release of substance P by 250 pM NE, from 8.3 ± 0.6 to 14.2 ± 0.8 pg/min. During a high-sodium diet, rauwolscine had no effect on the ARNA response to reflex increases in ERSNA or renal pelvic release of substance P produced by NE. Losartan was not examined because of low endogenous ANG II levels in renal pelvic tissue during a high-sodium diet. Increased activation of ?(2)-AR contributes to the reduced interaction between ERSNA and ARNA during low-sodium intake, whereas no/minimal activation of ?(2)-AR contributes to the enhanced ERSNA-ARNA interaction under conditions of high sodium intake. PMID:21106912
Kopp, Ulla C; Cicha, Michael Z; Smith, Lori A; Ruohonen, Saku; Scheinin, Mika; Fritz, Nicolas; Hökfelt, Tomas
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. PMID:16266014
Harkin, Kenneth R; Cash, Walter C; Shelton, G Diane
OBJECTIVE The goal of this study was to characterize glycation adducts formed in both in vivo extracellular matrix (ECM) proteins of endoneurium from streptozotocin (STZ)-induced diabetic rats and in vitro by glycation of laminin and fibronectin with methylglyoxal and glucose. We also investigated the impact of advanced glycation end product (AGE) residue content of ECM on neurite outgrowth from sensory neurons. RESEARCH DESIGN AND METHODS Glycation, oxidation, and nitration adducts of ECM proteins extracted from the endoneurium of control and STZ-induced diabetic rat sciatic nerve (3–24 weeks post-STZ) and of laminin and fibronectin that had been glycated using glucose or methylglyoxal were examined by liquid chromatography with tandem mass spectrometry. Methylglyoxal-glycated or unmodified ECM proteins were used as substrata for dissociated rat sensory neurons as in vitro models of regeneration. RESULTS STZ-induced diabetes produced a significant increase in early glycation N?-fructosyl-lysine and AGE residue contents of endoneurial ECM. Glycation of laminin and fibronectin by methylglyoxal and glucose increased glycation adduct residue contents with methylglyoxal-derived hydroimidazolone and N?-fructosyl-lysine, respectively, of greatest quantitative importance. Glycation of laminin caused a significant decrease in both neurotrophin-stimulated and preconditioned sensory neurite outgrowth. This decrease was prevented by aminoguanidine. Glycation of fibronectin also decreased preconditioned neurite outgrowth, which was prevented by aminoguanidine and nerve growth factor. CONCLUSIONS Early glycation and AGE residue content of endoneurial ECM proteins increase markedly in STZ-induced diabetes. Glycation of laminin and fibronectin causes a reduction in neurotrophin-stimulated neurite outgrowth and preconditioned neurite outgrowth. This may provide a mechanism for the failure of collateral sprouting and axonal regeneration in diabetic neuropathy.
Duran-Jimenez, Beatriz; Dobler, Darin; Moffatt, Sarah; Rabbani, Naila; Streuli, Charles H.; Thornalley, Paul J.; Tomlinson, David R.; Gardiner, Natalie J.
Certain functions of the nervous system were examined in 31 printing workers (mean age 44) exposed to trichloroethene (mean duration 16 years) and 28 controls (mean age 45). In the sural nerve the conduction velocity (SNCV), response amplitude, and refractory period (SRP) were measured. The latencies of the masseter and the blink reflex were determined to test the trigeminal nerve. In the peroneal nerve the conduction velocity of fast and slow nerve fibres, the response amplitude, and the refractory period were determined. As a measure of autonomic nerve function the response of the heart rate was determined to isometric muscle contraction and deep breathing. Individual cumulative exposure was calculated on the basis of exposure levels in the past. The mean cumulative exposure of the exposed workers was 704 ppm x years. For the assessment of the exposure effect relation a multiple linear regression model was used. A slight reduction (-1.1 m/s) in the SNCV was found and a prolongation (0.4 ms) of the SRP (mean of the controls 1.95 ms). The latency of the masseter reflex (mean 10.4 ms) had increased (0.4 ms). With respect to the blink reflex no prolongation was found. No impairment was found in the functions of motor and autonomic nerves. This study shows that the refractory period may be a sensitive indicator of preclinical toxic neuropathies. Long term exposure to trichloroethene at threshold limit values (about 35 ppm) may slightly affect the trigeminal and sural nerves.
Ruijten, M W; Verberk, M M; Salle, H J
Neuregulin 1 (NRG1) and epidermal growth factor receptor (ErbB) signaling pathways control Schwann cells during axonal regeneration\\u000a in an injured peripheral nervous system. We investigated whether a persistent supply of recombinant NRG1 to the injury site\\u000a could improve axonal growth and recovery of sensory and motor functions in rats during nerve regeneration. We generated a\\u000a recombinant adenovirus expressing a secreted
Insil Joung; Minjoo Yoo; Ji Hyoun Woo; Chi Young Chang; Hwon Heo; Yunhee Kim Kwon
Study Objectives: Children with the obstructive sleep apnea syndrome (OSAS) have impaired responses to hypercapnia, subatmospheric pressure, and inspiratory resistive loading during sleep. This may be due, in part, to an impairment in the afferent limb of the upper airway sensory pathway. Therefore, we hypothesized that children with OSAS had diminished upper airway sensation compared to controls. Design: Case-control Setting: Academic hospital Participants: Subjects with OSAS aged 6–16 years, and age- and BMI-matched controls. Interventions: Two-point discrimination (TPD) was measured during wakefulness with modified calipers in the anterior tongue, right interior cheek, and hard palate. Results: Thirteen children with OSAS and 9 controls were tested. The age (mean ± SD) for OSAS and controls was 11 ± 4 vs. 13 ± 2 years (NS); OSAS BMI Z score 2.4 ± 0.5, controls 2.2 ± 0.5 (NS); OSAS apnea hypopnea index 31 ± 48, controls 0.4 ± 0.5 events/hour (P < 0.001). Children with OSAS had impaired TPD in the anterior tongue (median [range]) = 9 [3–14] mm, controls 3 [1–7], P = 0.002) and hard palate (OSAS 6 [3–9] mm, controls 3 [1–4], P < 0.001). TPD in the cheek was similar between the groups (P = 0.12). Conclusion: TPD in the anterior tongue and hard palate was impaired in children with OSAS during wakefulness. We speculate that this impairment might be due to a primary sensory function abnormality or secondary to nerve damage and/or hypoxemia caused by OSAS. Further studies after treatment of OSAS are needed. Citation: Tapia IE; Bandla P; Traylor J; Karamessinis L; Huang J; Marcus CL. Upper airway sensory function in children with obstructive sleep apnea syndrome. SLEEP 2010;33(7):968–972.
Tapia, Ignacio E.; Bandla, Preetam; Traylor, Joel; Karamessinis, Laurie; Huang, Jingtao; Marcus, Carole L.
Current therapies for treating skeletal pain have significant limitations as available drugs (nonsteroidal anti-inflammatory drugs and opiates) have significant unwanted side effects. Targeting nerve growth factor or it's cognate receptor Tropomysin receptor kinase A (TrkA) has recently become an attractive target for inhibition of adult skeletal pain. Here we explore whether sustained administration of a selective small molecule Trk inhibitor that blocks TrkA, TrkB and TrkC kinase activity with nanomolar affinity reduces skeletal pain while allowing the maintenance of sensory and sympathetic neurons in the adult mouse. Twice-daily administration of a Trk inhibitor was begun 1 day post fracture and within 8 hours of acute administration fracture pain related behaviors were reduced by 50% without significant sedation, weight gain or inhibition of fracture healing. Following administration of the Trk inhibitor for 7 weeks, there was no significant decline in the density of unmyelinated, myelinated sensory or sympathetic nerve fibers, measures of acute thermal pain, acute mechanical pain, or general neuromuscular function. The present results suggest that sustained administration of a peripherally selective TrkA, B & C inhibitor significantly reduces skeletal pain without having any obvious detrimental effects on adult sensory and sympathetic nerve fibers or early fracture healing. As with any potential therapeutic advance, understanding whether the benefits of NGF blockade by ARRY-470 are associated with any risks or unexpected effects will be required to fully appreciate the patient populations that may benefit from this therapy.
Ghilardi, Joseph R.; Freeman, Katie T.; Jimenez-Andrade, Juan M.; Mantyh, William G.; Bloom, Aaron P.; Bouhana, Karyn S.; Trollinger, David; Winkler, James; Lee, Patrice; Andrews, Steven W.; Kuskowski, Michael A.; Mantyh, Patrick W.
The present investigation in concerned with the topography and ultrastructure of sensory nerve endings in the joint capsules of the Kowari (Dasyuroides byrnei), an Australian marsupial. Material for light and electron microscopy was obtained from shoulder, elbow and knee joint capsules. On the basis of differences in the organization of the connective tissue belonging to the fibrous layer, 3 variants of capsule structure have been distinguished: a rigid, a flaccid and an intermediate type. Whilst the rigid type is characterized by dense connective tissue in the clearly demarcated fibrous layer, the flaccid type shows loose, irregularly arranged connective tissue in the fibrous layer which merges into the synovial layer of the joint capsule. The morphology of the intermediate type corresponds to an intermediate stage between the former two types. In the fibrous layer of the joint capsules three different types of sensory nerve endings were observed: free nerve endings, Ruffini corpuscles and lamellated corpuscles. The free nerve endings are supplied by myelinated afferent axons (1-2 microns in diameter); the terminal thickenings of which are incompletely surrounded by a terminal Schwann cell. Ruffini corpuscles are present in three different varieties: small corpuscles without a perineural capsule predominantly within the flaccid part of the capsule; slightly larger corpuscles with an incomplete perineural capsule and large corpuscles resembling Golgi tendon organs which predominantly occur in the rigid parts of the capsule. The afferent myelinated axons measure 2-4 microns in diameter. The lamellated corpuscles show two variants: small corpuscles with a 2 to 4-layered perineural capsule in the rigid parts of the joint capsules and large corpuscles with two longitudinal clefts of the inner core in the flaccid parts. Both types are supplied by myelinated axons of 3-5 microns in diameter. Thus, in the fibrous layer of the rigid type of joint capsules large Ruffini and small lamellated corpuscles predominate, whereas the fibrous layer of the flaccid type coincides with small Ruffini and large lamellated corpuscles. The present data, therefore, corroborate the concept that the morphology of mechanoreceptors depends upon the texture of the surrounding connective tissue. PMID:3605642
Strasmann, T; Halata, Z; Loo, S K
BACKGROUND: Several groups have shown that the performance of motor neuroprostheses can be significantly improved by detecting specific sensory events related to the ongoing motor task (e.g., the slippage of an object during grasping). Algorithms have been developed to achieve this goal by processing electroneurographic (ENG) afferent signals recorded by using single-channel cuff electrodes. However, no efforts have been made
Stanisa Raspopovic; Jacopo Carpaneto; Esther Udina; Xavier Navarro; Silvestro Micera
Rats were fed for 6 weeks with a 40% galactose diet to chronically stimulate the polyol pathway. Sciatic motor and saphenous sensory nerve conduction velocity deficits of 22% and 14% respectively developed. Treatment with evening primrose oil or doxazosin from galactosaemia induction partially (approximately 60%) prevented the development of reduced motor and sensory conduction, the former treatment being more successful
Kevin C. Dines; Mary A. Cotter; Norman E. Cameron
The effect of sympathectomy and sensory denervation on vascular smooth muscle cell (SMC) differentiation was investigated in hypercholesterolemic rats. Newborn rats received injections of guanethidine, capsaicin or both for denervations. Shams received injections of vehicles. The four groups were fed 1% cholesterol diet for 3 months. Intact normocholesterolemic rats were also exploited. Serum total cholesterol and systolic blood pressure (SBP) were measured. Lipid presence in the arterial wall was shown by Red-Oil-O staining. Catecholamine- and CGRP-containing fibres, vimentin and the adult SMC markers alpha-SMC-actin, desmin and h-caldesmon were analysed in abdominal aorta by western blot and confocal microscope. The sympathetic (catecholamine) fibres and SBP increased after sensory denervation while the sensory (CGRP) fibres increased and SBP decreased after sympathectomy. SBP was not changed after double denervation. Total cholesterol increased in sham and rose further after sympathectomy. Vimentin and the three adult SMC markers were not influenced by hypercholesterolemia. However, in the sympathectomized aorta, vimentin increased, desmin did not change, whereas alpha-SMC-actin and h-caldesmon decreased. In the sensory-denervated aorta, vimentin decreased, desmin increased, alpha-SMC-actin did not change and h-caldesmon decreased but less than in sympathectomized aorta. In the doubly denervated aorta, vimentin did not change and the three adult SMC markers decreased, although less than in sympathectomized aorta for alpha-SMC-actin and h-caldesmon. Thickened intima was identified by Red-Oil-O staining in the sympathectomized and (less remarkably) doubly denervated aortas containing SMCs not fully dedifferentiated. Our findings suggest that sympathectomy induces intimal thickening and favours SMC dedifferentiation, whereas sensory denervation favours SMC differentiation. PMID:20181536
Hachani, Rafik; Dab, Houcine; Sakly, Mohsen; Vicaut, Eric; Callebert, Jacques; Sercombe, Richard; Kacem, Kamel
Myelin-associated glycoprotein (MAG) binds to the nerve cell surface and inhibits nerve regeneration. The nerve cell surface ligand(s) for MAG are not established, although sialic acid-bearing glycans have been implicated. We identify the nerve cell surface gangliosides GD1a and GT1b as specific functional ligands for MAG-mediated inhibition of neurite outgrowth from primary rat cerebellar granule neurons. MAG-mediated neurite outgrowth inhibition
Alka A. Vyas; Himatkumar V. Patel; Susan E. Fromholt; Marija Heffer-Lauc; Kavita A. Vyas; Jiyoung Dang; Melitta Schachner; Ronald L. Schnaar
Background Although many nerve prostheses have been proposed in recent years, in the case of consistent loss of nervous tissue peripheral nerve injury is still a traumatic pathology that may impair patient's movements by interrupting his motor-sensory pathways. In the last few decades tissue engineering has opened the door to new approaches;: however most of them make use of rigid channel guides that may cause cell loss due to the lack of physiological local stresses exerted over the nervous tissue during patient's movement. Electrospinning technique makes it possible to spin microfiber and nanofiber flexible tubular scaffolds composed of a number of natural and synthetic components, showing high porosity and remarkable surface/volume ratio. Results In this study we used electrospun tubes made of biodegradable polymers (a blend of PLGA/PCL) to regenerate a 10-mm nerve gap in a rat sciatic nerve in vivo. Experimental groups comprise lesioned animals (control group) and lesioned animals subjected to guide conduits implantated at the severed nerve stumps, where the tubular scaffolds are filled with saline solution. Four months after surgery, sciatic nerves failed to reconnect the two stumps of transected nerves in the control animal group. In most of the treated animals the electrospun tubes induced nervous regeneration and functional reconnection of the two severed sciatic nerve tracts. Myelination and collagen IV deposition have been detected in concurrence with regenerated fibers. No significant inflammatory response has been found. Neural tracers revealed the re-establishment of functional neuronal connections and evoked potential results showed the reinnervation of the target muscles in the majority of the treated animals. Conclusion Corroborating previous works, this study indicates that electrospun tubes, with no additional biological coating or drug loading treatment, are promising scaffolds for functional nervous regeneration. They can be knitted in meshes and various frames depending on the cytoarchitecture of the tissue to be regenerated. The versatility of this technique gives room for further scaffold improvements, like tuning the mechanical properties of the tubular structure or providing biomimetic functionalization. Moreover, these guidance conduits can be loaded with various fillers like collagen, fibrin, or self-assembling peptide gels or loaded with neurotrophic factors and seeded with cells. Electrospun scaffolds can also be synthesized in different micro-architectures to regenerate lesions in other tissues like skin and bone.
Panseri, Silvia; Cunha, Carla; Lowery, Joseph; Del Carro, Ubaldo; Taraballi, Francesca; Amadio, Stefano; Vescovi, Angelo; Gelain, Fabrizio
Pieces of hairy skin tissue of fetal rat were transplanted into the anterior eye chamber of adult rats. The ability of autonomic and sensory nerve fibers from the host iris to innervate the grafted skin tissue was immunohistochemically and enzyme-histochemically examined using antisera against tyrosine hydroxylase (TH), substance P (SP), calcitonin gene-related peptide (CGRP) and vasoactive intestinal peptide (VIP), and
Norito Katoh; Shuichi Ueda; Yasuhiro Matsumoto; Saburo Kishimoto; Hirokazu Yasuno; Mitsuhiro Kawata
We have previously demonstrated that profound and persistent neuropathic pain as displayed by mechanical and cold allodynia and thermal hyperalgesia can be produced by a lumbar 5 ventral root transection (L5 VRT) model in adult rats in which only the motor nerve fibers were injured without axotomy of sensory neurons. However, the underlying mechanisms remain to be determined. In this
Li Li; Cory J Xian; Jin-Hua Zhong; Xin-Fu Zhou
An in vitro preparation of rabbit cornea was used to compare anatomical specialization and electrophysiological responses of A delta and C fiber sensory afferents which terminate as free nerve endings. Living nerve endings were visualized using epifluorescence microscopy and the vital dye 4-di2-ASP, and response properties were determined using microstimulation and recording of fiber discharge activity. Fiber type was determined based on conduction velocity measurement and preferred stimulus energy (modality) of each fiber. Four modality-specific fiber populations were identified: (1) slowly adapting C fiber cold receptors (conduction velocity of 0.25-1.6 m/sec), (2) C fiber chemosensitive units with mixed phasic and tonic activity (1.1-1.8 m/sec), (3) rapidly adapting mechanosensitive A delta fibers (1.5-2.8 m/sec), and (4) high-threshold mechano/heat (> 350 dyne or > 40 degrees C) phasic A delta afferents (3.5-4.4 m/sec). In addition to these physiological differences, anatomical specialization was also noted. A delta fiber nerve endings were distinguished from those of C fibers by thin, elongated sensory endings that ran parallel to the corneal surface; C fiber endings formed short, branching clusters that ran mostly perpendicular to the surface. The elongated structure of A delta nerve endings was associated with directional selectivity for mechanical stimuli. These results substantiate previous suggestions that free nerve endings can exhibit both structural and functional specialization. PMID:8410200
MacIver, M B; Tanelian, D L
This study examined the relationship between repetitive behaviors and sensory processing issues in school-aged children with high functioning autism (HFA). Children with HFA (N = 61) were compared to healthy, typical controls (N = 64) to determine the relationship between these behavioral classes and to examine whether executive dysfunction explained any relationship between the variables. Particular types of repetitive behavior (i.e., stereotypy and compulsions) were related to sensory features in autism; however, executive deficits were only correlated with repetitive behavior. This finding suggests that executive dysfunction is not the shared neurocognitive mechanism that accounts for the relationship between restricted, repetitive behaviors and aberrant sensory features in HFA. Group status, younger chronological age, presence of sensory processing issues, and difficulties with behavior regulation predicted the presence of repetitive behaviors in the HFA group. PMID:21475640
Boyd, Brian A; McBee, Matthew; Holtzclaw, Tia; Baranek, Grace T; Bodfish, James W
This study examined the relationship between repetitive behaviors and sensory processing issues in school-aged children with high functioning autism (HFA). Children with HFA (N = 61) were compared to healthy, typical controls (N = 64) to determine the relationship between these behavioral classes and to examine whether executive dysfunction explained any relationship between the variables. Particular types of repetitive behavior (i.e., stereotypy and compulsions) were related to sensory features in autism; however, executive deficits were only correlated with repetitive behavior. This finding suggests that executive dysfunction is not the shared neurocognitive mechanism that accounts for the relationship between restricted, repetitive behaviors and aberrant sensory features in HFA. Group status, younger chronological age, presence of sensory processing issues, and difficulties with behavior regulation predicted the presence of repetitive behaviors in the HFA group.
Boyd, Brian A.; McBee, Matthew; Holtzclaw, Tia; Baranek, Grace T.; Bodfish, James W.
BACKGROUND: Although many nerve prostheses have been proposed in recent years, in the case of consistent loss of nervous tissue peripheral nerve injury is still a traumatic pathology that may impair patient's movements by interrupting his motor-sensory pathways. In the last few decades tissue engineering has opened the door to new approaches;: however most of them make use of rigid
Silvia Panseri; Carla Cunha; Joseph Lowery; Ubaldo Del Carro; Francesca Taraballi; Stefano Amadio; Angelo Vescovi; Fabrizio Gelain
An experimental autoimmune model of nerve growth factor (NGF) deprivation has been used to assess the role of NGF in the development of various cell types in the nervous system. Adult rats immunized with 2.5S mouse NGF in complete Freund's adjuvant produced antibodies that crossreacted with their own NGF and that were transferred in utero to the fetus and in
Pamela Dolkart Gorin; Eugene M. Johnson
There have been several reports on the use of extracorporeal shock waves in the treatment of pseudarthrosis, calcifying tendinitis, and tendinopathies of the elbow. However, the pathomechanism of pain relief has not been clarified. To investigate the analgesic properties of shock wave application, we analyzed whether it produces morphologic changes in cutaneous nerve fibres. In normal rat skin, the epidermis
Seiji Ohtori; Gen Inoue; Chikato Mannoji; Takashi Saisu; Kenji Takahashi; Shigeru Mitsuhashi; Yuichi Wada; Kazuhisa Takahashi; Masatsune Yamagata; Hideshige Moriya
Paclitaxel chemotherapy frequently induces neuropathic pain during and often persisting after therapy. The mechanisms responsible for this pain are unknown. Using a rat model of paclitaxel-induced painful peripheral neuropathy, we have performed studies to search for peripheral nerve pathology. Paclitaxel-induced mechano-allodynia and mechano-hyperalgesia were evident after a short delay, peaked at day 27 and finally resolved on day 155. Paclitaxel-
Sarah J. L. Flatters; Gary J. Bennett
A terminal transferase-mediated dUTP nick end labeling (TUNEL) method was utilized for detection of neuronal death in the subcortical relay nuclei of the trigeminosensory system following the infraorbital nerve transection in newborn rats. At 18–24 h after injury, numerous TUNEL-positive profiles were found within the ventroposteromedial thalamic nucleus (VPM) contralateral to the injury, whereas the VPM on the ipsilateral side
Tomosada Sugimoto; Chun Xiao; Akihiro Takeyama; Yi-Fen He; Teruko Takano-Yamamoto; Hiroyuki Ichikawa
Introduction In the auditory system, a specialised subset of sensory neurons are responsible for correctly relaying precise pitch and temporal cues to the brain. In individuals with severe-to-profound sensorineural hearing impairment these sensory auditory neurons can be directly stimulated by a cochlear implant, which restores sound input to the brainstem after the loss of hair cells. This neural prosthesis therefore depends on a residual population of functional neurons in order to function effectively. Areas covered In severe cases of sensorineural hearing loss where the numbers of auditory neurons are significantly depleted, the benefits derived from a cochlear implant may be minimal. One way in which to restore function to the auditory nerve is to replace these lost neurons using differentiated stem cells, thus re-establishing the neural circuit required for cochlear implant function. Such a therapy relies on producing an appropriate population of electrophysiologically functional neurons from stem cells, and on these cells integrating and reconnecting in an appropriate manner in the deaf cochlea. Expert opinion Here we review progress in the field to date, including some of the key functional features that stem cell-derived neurons would need to possess and how these might be enhanced using electrical stimulation from a cochlear implant.
Needham, K; Minter, R.L.; Shepherd, R.K.; Nayagam, B.A.
Studies of the effects of lead absorption on sensory evoked and slow brain potentials in children are reviewed. Studies of slow-wave voltage in children during sensory conditioning indicated a linear relationship to blood lead level in two studies; an effect that could not be replicated in an independent sample of children. Results of a fourth study indicated that slow-voltage measures were more sensitive to lead during active rather than passive conditioning. Conflicting evidence of lead effects on pattern-reversal visual evoked potentials in children was found in three studies. Evidence of increased latencies of brainstorm auditory evoked potentials at blood lead levels above 25/dl were reported in two studies. Sensory evoked potentials hold considerable promise as noninvasive, clinically valid, culture-free measures of the effects of lead exposure on sensory-nerve conduction, but further study is needed in humans and animals to clarify inconsistencies in the existing literature.
Nerve growth factor (NGF), which has a tertiary structure based on a cluster of 3 cystine disulfides and 2 very extended, but distorted beta-hairpins, is the prototype of a larger family of neurotrophins. Prior to the availability of cloning techniques, the mouse submandibular gland was the richest source of NGF and provided sufficient material to enable its biochemical characterization. It binds as a dimer to at least 2 cell-surface receptor types expressed in a variety of neuronal and non-neuronal cells. Residues involved in these interactions and in the maintenance of tertiary and quaternary structure have been identified by chemical modification and site-directed mutagenesis, and this information can be related to their location in the 3-dimensional structure. For example, interactions between aromatic residues contribute to the stability of the NGF dimer, and specific surface lysine residues participate in receptor contacts. The conclusion from these studies is that receptor interactions involve broad surface regions, which may be composed of residues from both promoters in the dimer.
Bradshaw, R. A.; Murray-Rust, J.; Ibanez, C. F.; McDonald, N. Q.; Lapatto, R.; Blundell, T. L.
Nerve conduction studies (NCS) and electromyography (EMG), often shortened to 'EMGs', are a useful adjunct to clinical examination of the peripheral nervous system and striated skeletal muscle. NCS provide an efficient and rapid method of quantifying nerve conduction velocity (CV) and the amplitude of both sensory nerve action potentials (SNAPs) and compound motor action potentials (cMAPs). The CV reflects speed of propagation of action potentials, by saltatory conduction, along large myelinated axons in a peripheral nerve. The amplitude of SNAPs is in part determined by the number of axons in a sensory nerve, whilst amplitude of cMAPs reflects integrated function of the motor axons, neuromuscular junction and striated muscle. Repetitive nerve stimulation (RNS) can identify defects of neuromuscular junction (NMJ) transmission, pre- or post-synaptic. Needle EMG examination can detect myopathic changes in muscle and signs of denervation. Combinations of these procedures can establish if motor and/or sensory nerve cell bodies or peripheral nerves are damaged (e.g. motor neuronopathy, sensory ganglionopathy or neuropathy), and also indicate if the primary target is the axon or the myelin sheath (i.e. axonal or demyelinating neuropathies). The distribution of nerve damage can be determined as either generalised, multifocal (mononeuropathy multiplex) or focal. The latter often due to compression at the common entrapment sites (such as the carpal tunnel, Guyon's canal, cubital tunnel, radial groove, fibular head and tarsal tunnel, to name but a few of the reported hundred or so 'entrapment neuropathies'). PMID:22614870
Kane, N M; Oware, A
We have recently shown that manual stimulation of target muscles promotes functional recovery after transection and surgical repair to pure motor nerves (facial: whisking and blink reflex; hypoglossal: tongue position). However, following facial nerve repair, manual stimulation is detrimental if sensory afferent input is eliminated by, e.g., infraorbital nerve extirpation. To further understand the interplay between sensory input and motor recovery, we performed simultaneous cut-and-suture lesions on both the facial and the infraorbital nerves and examined whether stimulation of the sensory afferents from the vibrissae by a forced use would improve motor recovery. The efficacy of 3 treatment paradigms was assessed: removal of the contralateral vibrissae to ensure a maximal use of the ipsilateral ones (vibrissal stimulation; Group 2), manual stimulation of the ipsilateral vibrissal muscles (Group 3), and vibrissal stimulation followed by manual stimulation (Group 4). Data were compared to controls which underwent surgery but did not receive any treatment (Group 1). Four months after surgery, all three treatments significantly improved the amplitude of vibrissal whisking to 30° versus 11° in the controls of Group 1. The three treatments also reduced the degree of polyneuronal innervation of target muscle fibers to 37% versus 58% in Group 1. These findings indicate that forced vibrissal use and manual stimulation, either alone or sequentially, reduce target muscle polyinnervation and improve recovery of whisking function when both the sensory and the motor components of the trigemino-facial system regenerate. PMID:21526334
Bendella, H; Pavlov, S P; Grosheva, M; Irintchev, A; Angelova, S K; Merkel, D; Sinis, N; Kaidoglou, K; Skouras, E; Dunlop, S A; Angelov, Doychin N
The objective of this work was to determine the technological feasibility of using horsemeat as a human food. Beef and horsemeat Longissimus dorsi was stored at 4°C for a total study time of 15 days. Collagen content was lower for horsemeat than for beef, although sensory analysis showed no significant difference in tenderness. Instrumental and sensory color analysis showed significant
CARACTERIZAÇĂO FISICOQUÍMICA; MICROBIOLOGICA DE CARNE DE CAVALO
Background Our goal is to develop a peripheral nerve electrode with long-term stability and fidelity for use in nerve-machine interfaces. Microelectromechanical systems (MEMS) use silicon probes that contain multi-channel actuators, sensors, and electronics. We tested the null hypothesis that implantation of MEMS probes do not have a detrimental effect on peripheral nerve function or regeneration. Methods A rat hindlimb, peroneal nerve model was utilized in all experimental groups: a) intact nerve (Control, n= 10); b) nerve division and repair (Repair, n= 9); and c) Nerve division, insertion of MEMS probe, and repair (Repair + Probe, n=9). Nerve morphology, nerve to muscle compound action potential (CMAP) studies, walking tracks, and extensor digitorum longus (EDL) muscle function tests were evaluated following an 80 day recovery. Results Repair and Repair + Probe showed no differences in axon count, axon size, percent non-neural area, CMAP amplitude, latency, muscle mass, muscle force, or walking track scores. Though there was some local fibrosis around each MEMS probe, this did not lead to measurable detrimental effects in any anatomic or functional outcome measurements. Conclusions The lack of a significant difference between Repair and Repair + Probe groups in histology, CMAP, walking tracks, and muscle force suggests that MEMS electrodes are compatible with regenerating axons and show promise for establishing chemical and electrical interfaces with peripheral nerves.
Urbanchek, Melanie G; Wei, Benjamin; Egeland, Brent M; Abidian, Mohammad R; Kipke, Daryl R; Cederna, Paul S
Adrenal steroids modulate the function of nerve cells. Some, but not all actions of these steroids take place after binding to intracellular receptor systems and translocation of the steroid-receptor complex into the cell nucleus. Studies on the rat brain revealed heterogeneity of receptors. One population of receptor sites is present in abundance in extrahypothalamic limbic brain regions, e.g. neurons of
E. R. de Kloet
A simple device is described, consisting of 12 weighted 23 gauge disposable needles (0.2 to 5.2 g), for testing sensation in busy diabetic clinics. The pinprick sensory threshold (PPT) is the lightest weighted needle which consistently elicits a sharp sensation. The subjects were 48 healthy controls (hospital staff), 44 diabetic patients without neuropathic symptoms, and 35 diabetic patients with chronic
A W Chan; I A MacFarlane; D Bowsher; J A Campbell
|This study examined the relationship between repetitive behaviors and sensory processing issues in school-aged children with high functioning autism (HFA). Children with HFA (N = 61) were compared to healthy, typical controls (N = 64) to determine the relationship between these behavioral classes and to examine whether executive dysfunction…
Boyd, Brian A.; McBee, Matthew; Holtzclaw, Tia; Baranek, Grace T.; Bodfish, James W.
Several surgical techniques have been proposed for the reconstruction of the smile in facial paralysis. The 2-stage approach utilising a cross-facial nerve graft (CFNG) and subsequent free functional muscle transfer represents the "gold standard". A single-stage alternative is the use of the masseteric nerve as donor nerve. Here we have retrospectively analysed the outcome of 8 patients who were treated with either of these procedures (4 per treatment group). We compared the oral commisure excursion between the 2 groups. Use of the masseteric nerve led to reinnervation of the muscle graft within 3 months. The 2-stage procedure required more than 12 months from the first procedure until first muscle contractions could be observed. A spontaneous smile could not be achieved in all patients when the masseteric nerve was used. The oral commisure excursion was symmetrical when compared to the healthy side in both groups, however the excursion was significantly higher in the masseteric nerve group compared to the CFNG group of patients. Most patients with the masseteric nerve as a donor nerve underwent a secondary procedure, which involved thinning of the muscle flap. In conclusion, the use of the masseteric nerve as a donor nerve for facial reanimation surgery is a single-stage alternative to the use of a CFNG as donor nerve. It delivers reliable results with strong muscle contractions with limitations in regard to achieving a spontaneous smile. PMID:23970401
Eisenhardt, S U; Thiele, J R; Stark, G B; Bannasch, H
In this study we investigated the effect of recent and chronic lead exposure, and its interaction with ergonomic stressors, on peripheral nerve function. In a cross-sectional design, we used retrospective exposure data on 74 primary lead smelter workers. We measured blood and bone lead levels and, from historical records, calculated lead dose metrics reflecting cumulative lead exposure: working-lifetime integrated blood lead (IBL) and working-lifetime weighted-average blood lead (TWA). We additionally created five metrics related to IBL that cumulated exposure only above increasing blood lead levels ranging from 20 to 60 microg/dL (IBL20-IBL60). Current perception threshold (CPT) assessed large myelinated (CPT2000), small myelinated (CPT250), and unmyelinated (CPT5) sensory nerve fibers. Using multiple linear regression, we modeled CPT on the different measures of lead dose after adjusting for relevant covariates. CPT had a curvilinear relationship with TWA, with a minimum at a TWA of 28 microg/dL. Both TWA and IBL accounted for a significant percentage of the variance of CPT2000 (DeltaR2 = 8.7% and 3.9%, respectively). As the criterion blood lead level increased from IBL20 through IBL60, so did the percentage of CPT2000 variance explained, with DeltaR2 ranging from 5.8% (p < 0.03) for IBL20 to 23.3% (p < 0.00) for IBL60. IBL60 also significantly contributed to the explanation of variance of CPT250 and significantly interacted with ergonomic stressors. Measures of chronic blood lead exposure are associated with impairment of large and small myelinated sensory nerve fibers. This effect is enhanced at the highest doses by ergonomic stressors. PMID:16330355
Bleecker, Margit L; Ford, D Patrick; Vaughan, Christopher G; Lindgren, Karen N; Tiburzi, Michael J; Walsh, Karin Scheetz
The clinical features of idiopathic polyneuritis in 22 patients admitted to the University of Kentucky Medical Center between July 1965 and June 1970 are described. Serial studies of peripheral nerve function in 12 patients followed to clinical recovery showed changes in nerve conduction velocity, distal motor latency, and/or muscle action potential amplitude. Six children and one adult, showing a change in all three parameters, exhibited a strong correlation between the degree of slowing and the shortness of their illness. Assessment of immune status, by quantitative measurement of cerebrospinal fluid immunoglobulin G(11 patients) and by the degree of lymphocyte transformation on exposure to specific brain protein and/or a homogenate of sciatic nerve (10 patients), bore no consistent relation to the severity or course of the illness. A double-blind trial of short-term, high dose adrenocorticotrophic hormone has yielded no valid evidence to date for or against the effectiveness of such therapy in this illness.
McQuillen, Michael P.
Dr. Joe Zwislocki served as my dissertation advisor during those tumultuous years in cochlear physiology when our understanding of outer hair cell (OHC) function was evolving from that of a sensory cell to that of a mechanical amplifier. Spoendlin had recently demonstrated that 90%-95% of auditory-nerve afferents originated from inner hair cells (IHCs), but the characteristics of IHC receptor potentials remained an enigma. Otoacoustic emissions and OHC electromotility were terms yet to be defined. Theories relating auditory-nerve activity to basilar-membrane mechanics included concepts of second filters, basilar-membrane nonlinearities, and phase opposition. It was a fertile time for theories and experiments attempting to describe a black-box system that did not yield its mysteries easily. Around 1977, IHC receptor potentials were found to be as sharply tuned as auditory-nerve responses, and the era of cochlear micromechanics began. Joe Zwislocki, as usual, has played a primary role in defining this new era, utilizing the relationships between the OHC stereocilia and the tectorial membrane as his modeling clay.
Schmiedt, Richard A.
This study examines the relationship between sensory responsiveness and social severity in children with high functioning\\u000a autism spectrum disorders (HFASD; N = 36) and age-matched controls (N = 26) between 6 and 10 years old. Significant relationships were found between social responsiveness scale scores and each\\u000a of the six sensory profile sensory system scores for children with HFASD and controls. Multivariate regression analyses revealed\\u000a atypical
Claudia L. HiltonJacquelyn; Jacquelyn D. Harper; Rachel Holmes Kueker; Andrea Runzi Lang; Anna M. Abbacchi; Alexandre Todorov; Patricia D. LaVesser
The objective of this study was to assess the anatomical variation of the marginal mandibular nerve, and evaluate the risk of nerve malfunction after neck dissection. The method involved clinical assessment of the anatomy and function of the marginal mandibular nerve in 133 neck dissections. When the neck was extended the nerve was displaced in an anterior and downward direction
R. W. Nason; A. Binahmed; M. G. Torchia; J. Thliversis
An analysis of a population response recorded from the primary afferents was undertaken to study the neural signs of intensity coding in the peripheral somatosensory system. Short air-puff stimuli were applied to the volar aspect of the tip of the index finger to obtain both neural and psychophysical responses. The detection threshold (So) was first determined and 6 levels of stimulus intensity above threshold (So + 0.25 kg/cm2, So + 1.25 kg/cm2, So + 2.50 kg/cm2, So + 3.75 kg/cm2, So + 5.00 kg/cm2, and So + 6.25 kg/cm2) were adopted for magnitude estimation using the stimulus level of So + 2.50 kg/cm2 as the standard stimulus. The subject was asked to give a numerical estimate of the intensity of a series of stimuli randomly presented. Compound sensory nerve action potentials (SNAPs) were also recorded from surface electrodes over the median nerve at the wrist for the 6 stimulus intensities. Eight SNAP components (4 positive and 4 negative) were recorded within 10 msec following stimulation. A simple power function with an exponent of 0.85 provided an adequate description of the magnitude estimation function, as was verified by the high correlation coefficient (r = 0.89, P less than 0.001). Similarly, stimulus-amplitude functions of individual SNAP components were well represented by straight lines in double logarithmic plots. The function of the late N2-P3 component had the highest power exponent (0.80) and also the highest correlation coefficient (r = 0.59, P less than 0.001). The functions of other SNAP components had considerably lower power exponents with lower correlation coefficients. Thus, a mismatch between neural and psychophysical functions was obvious when individual neural functions were compared with the psychophysical function. Conversely, it was found likely that the total number or time-integral of peaks in the population response was a more pertinent parameter of neural activity and, thus, had a closer correlation with the psychophysical response. PMID:1710966
Hashimoto, I; Gatayama, T; Yoshikawa, K; Sasaki, M; Nomura, M
. ?Action potentials and electrotonic responses to 300-ms depolarizing and hyperpolarizing currents for human motor and sensory\\u000a myelinated nerve fibres have been simulated on the basis of double cable models. The effects of blocked nodal or internodal\\u000a potassium (fast or slow) channels on the fibre action potentials, early and late adaptations to 30-ms suprathreshold slowly\\u000a increasing depolarizing stimuli have been examined.
D. I. Stephanova; K. Mileva
This study examines the relationship between sensory responsiveness and social severity in children with high functioning autism spectrum disorders (HFASD; N = 36) and age-matched controls (N = 26) between 6 and 10 years old. Significant relationships were found between social responsiveness scale scores and each of the six sensory profile sensory system scores for children with HFASD and controls. Multivariate regression analyses revealed atypical scores from multisensory responsiveness, and responsiveness of the proximal senses of oral sensory/olfactory and touch as the strongest predictors of greater social impairment in the participants. Findings suggest that the relationship between sensory responsiveness and other autistic traits is more important than previously recognized and addressing sensory modulation issues in children with HFASD may be more critical than previously understood. PMID:20108030
Hilton, Claudia L; Harper, Jacquelyn D; Kueker, Rachel Holmes; Lang, Andrea Runzi; Abbacchi, Anna M; Todorov, Alexandre; LaVesser, Patricia D
Novel approaches are required in peripheral nerve injury management because current surgical techniques, which do not address axotomy-induced neuronal death, lead to deficient sensory recovery. Sensory neuronal death has functional preference with cutaneous neurons dying in great numbers whilst muscle afferents survive axotomy. This offers the potential of comparing similar cell types that suffer distinct fates upon nerve injury.Here, a
Adam J. Reid; Susan G. Shawcross; Alex E. Hamilton; Mikael Wiberg; Giorgio Terenghi
While substantial alterations in myelination and axonal growth have been described during maturation, their interactions with the configuration and activity of axonal membrane ion channels to achieve impulse conduction have not been fully elucidated. The present study utilized axonal excitability techniques to compare the changes in nerve function across healthy infants, children, adolescents and adults. Multiple excitability indices (stimulus-response curve, strength-duration time constant, threshold electrotonus, current-threshold relationship and recovery cycle) combined with conventional neurophysiological measures were investigated in 57 subjects (22 males, 35 females; age range 0.46-24 years), stimulating the median motor nerve at the wrist. Maturational changes in conduction velocity were paralleled by significant alterations in multiple excitability parameters, similarly reaching steady values in adolescence. Maturation was accompanied by reductions in threshold (P < 0.005) and rheobase (P = 0.001); depolarizing and hyperpolarizing electrotonus progressively reduced (P < 0.001), or 'fanned-in'; resting current-threshold slope increased (P < 0.0001); accommodation to depolarizing currents prolonged (P < 0.0001); while greater threshold changes in refractoriness (P = 0.001) and subexcitability (P < 0.01) emerged. Taken together, the present findings suggest that passive membrane conductances and the activity of K(+) conductances decrease with formation of the axo-glial junction and myelination. In turn, these functional alterations serve to enhance the efficiency and speed of impulse conduction concurrent with the acquisition of motor skills during childhood, and provide unique insight into the evolution of postnatal human peripheral nerve function. Significantly, these findings bring the dynamics of axonal development to the clinical domain and serve to further illuminate pathophysiological mechanisms that occur during development. PMID:23006483
Farrar, Michelle A; Park, Susanna B; Lin, Cindy S-Y; Kiernan, Matthew C
While nuptial food gifts come in various forms in arthropods, their evolutionary origins are unclear. A previous study on insects has shown that such gifts may arise as a sensory trap that exploits a female's underlying motivation to feed. Here I present independent evidence of a sensory trap in spiders. In certain visually oriented spiders, I suggest that males initially exploit the maternal care instinct by producing a nuptial gift that closely resembles the female egg sac. Males of the spider Pisaura mirabilis cover their prey gift with a silk layer, transforming it into a white round object. In a laboratory experiment I tested whether the colour of the gift affected the rate that females accepted males displaying their gifts. I found that the brighter and the more alike the nuptial gift to a female's egg sac, the faster the female responded by grabbing the gift. My results support the hypothesis that the nuptial gift in P. mirabilis works as a sensory trap.
Simultaneous recording of activity in the vagal and sympathetic supplies to the heart has revealed that in reflexly and centrally evoked activity these two "antagonists" do not necessarily change action reciprocally. Coactivation occurs in chemoreceptor reflexes and related reactions, upon stretching of the sinoatrial nodal region of the right atrium and when certain hypothalamic regions are stimulated. The objective of the present work was to assay the physiological importance of coactivation of the two potentially antagonistic cardiac nerves in anesthetized dogs. Output from the heart was monitored by recording volume flow in the thoracic aorta just below the aortic arch; cardiac contractility was measured as left ventricular dp/dt. Tape recordings of vagus and sympathetic nerve activity during chemoreceptor and baroreceptor reflexes, during reciprocal and nonreciprocal changes produced by hypothalamic stimulation, and during hypoxia and hypercapnia were used to trigger stimulators feeding a stimulus per action potential to cardiac vagus and sympathetic nerves after central connections were cut. The vagus stimulation alone produced a decrease in aortic blood flow; stimulation of the sympathetic nerve alone resulted in increased aortic blood flow. Simultaneous stimulation of vagus and sympathetic, however, produced an even greater cardiac output (measured by aortic blood flow). Intermediate degrees of heart rate and strength of myocardial contraction were maintained in coactivation. Obviously, an association of increased vagus and sympathetic actions, which can be effected reflexly or by action of higher centers, is of physiological benefit. In control reactions that relate cardiac function to body need, both reciprocal and synergistic actions (coactivation) of cardiac nerves are used. Images
Koizumi, K; Terui, N; Kollai, M; Brooks, C M
Although autogenous nerve grafting remains the gold standard for repair of peripheral nerve defects, the use of various conduits can be a substitute provided these conduits meet the above-mentioned prerequisites. For the moment, autogenous vein grafts or denatured muscle grafts can be used to bridge short defects, especially in distal sensory nerves. Incorporation of muscle into a vein graft expands
Huan Wang; William C. Lineaweaver
When functional neuromuscular stimulation (FNS) is used to restore the use of paralyzed limbs after a spinal cord injury or stroke, it may be possible to control the stimulation using feedback information relayed by natural sensors in the skin. In this study the authors tested the hypothesis that the force applied on glabrous skin can be extracted from the electroneurographic
Morten K. Haugland; J. Andy Hoffer; Thomas Sinkjaer
Pain normally subserves a vital role in the survival of the organism, prompting the avoidance of situations associated with tissue damage. However, the sensation of pain can become dissociated from its normal physiological role. In conditions of neuropathic pain, spontaneous or hypersensitive pain behavior occurs in the absence of the appropriate stimuli. Our incomplete understanding of the mechanisms underlying chronic pain hypersensitivity accounts for the general ineffectiveness of currently available options for the treatment of chronic pain syndromes. Despite its complex pathophysiological nature, it is clear that neuropathic pain is associated with short- and long-term changes in the excitability of sensory neurons in the dorsal root ganglia (DRG) as well as their central connections. Recent evidence suggests that the upregulated expression of inflammatory cytokines in association with tissue damage or infection triggers the observed hyperexcitability of pain sensory neurons. The actions of inflammatory cytokines synthesized by DRG neurons and associated glial cells, as well as by astrocytes and microglia in the spinal cord, can produce changes in the excitability of nociceptive sensory neurons. These changes include rapid alterations in the properties of ion channels expressed by these neurons, as well as longer-term changes resulting from new gene transcription. In this chapter we review the diverse changes produced by inflammatory cytokines in the behavior of sensory neurons in the context of chronic pain syndromes.
Miller, Richard J.; Jung, Hosung; Bhangoo, Sonia K.; White, Fletcher A.
Rats that had been injected with monosodium glutamate (MSG) neonatally were studied for up to 70 weeks and compared with age-matched control rats to study changes in glucose tolerance and in sympathetic and sensory nerves. At 61 and 65 weeks of age, there were significant differences in glucose tolerance between the MSG and control groups, and the MSG group had raised fasting blood glucose. These changes were not associated with changes in the number of beta-cells in the islets of Langerhans. In addition, the diabetic MSG-treated rats had central obesity and cataracts. Hypoalgesia to thermal stimuli was present in MSG-treated rats as early as 6 weeks and persisted at 70 weeks. However, no differences were observed in the distribution of substance P, the neurokinin-1 receptor or calcitonin gene-related peptide in the dorsal horn of L3-L5 at this age (70 weeks). Diabetic MSG-treated animals at 65 and 70 weeks of age had significantly reduced noradrenaline concentrations in the heart, tail artery and ileum, while concentrations in the adrenal gland and corpus cavernosum were significantly increased. There was also a significant increase in adrenal adrenaline, dopamine and serotonin, largely attributable to changes in weight of the adrenal gland in the MSG-treated animals. The results indicate that MSG-treated animals develop a form of type II diabetes by about 60 weeks of age, and that there are significant changes in amine levels in various tissues associated with these developments. PMID:17911358
Morrison, John F B; Shehab, Safa; Sheen, Rajan; Dhanasekaran, Subramanian; Shaffiullah, Mohammed; Mensah-Brown, Eric
Neurological disorders and conditions affecting the maxillofacial region result in disabilities that affect an individual's functioning. Sensory or motor disturbances of the nerves may be caused by trauma, infections, pressure effect or infiltration by tumours or other health conditions. Two rare cases of nerve afflictions are described here with their typical clinical features. The first case had an involvement of maxillary, mandibular and ophthalmic divisions of the trigeminal nerve (sensory) due to herpes zoster infection in a very young patient and the second case had a unilateral isolated hypoglossal nerve palsy (motor) secondary to infiltration of the nerve by carcinoma of pyriform fossa. PMID:24145506
Thada, Smitha Rani; Gadda, Rohit; Pai, Keerthilatha
Dorsal root ganglionopathies present with sensory ataxia, areflexia and asymmetrical positive and negative sensory phenomenon of both limb often with trigeminal involvement. There may be associated Adie's pupil(1) Despite their classical features and relatively discrete list of causes they can be difficult to definitively diagnose. We present such a case in whom biopsy of the thoracic dorsal root ganglion resulted in identifying of continued inflammation despite normal haematological makers thereby altering subsequent management. A 54 year old telecommunications officer with a background of anterior uveitis presented with a 3 year history of progressive altered sensation of his right hand and a 2 month history of altered sensation of the right side of his face including oral mucosa. There was unilateral facial sensory loss to pin prick, right upper limb pseudoathetosis, hyperaesthesia of C5 to C8 and impaired proprioception to wrist. He was hyporeflexic throughout. He was on no regular medication, was a lifelong smoker, drank minimal alcohol and denied any family history. His immunology demonstrated a positive cANCA at 7 (0-5) and positive ENA (anti-La ). He had normal inflammatory markers, vitamins B6 and B12, homocysteine, methylmalonic acid, folate, serial antineuronal antibodies, HIV, angiotensin converting enzyme, phytanic acid, protein electrophoresis, chest X-ray, contrast MRI imaging of brain, cervical spine and brachial plexus. He had 3 large volume CSF analyses with normal cell count, protein, glucose ratio, and negative oligoclonal banding and cytology. His neurophysiology was positive for a possible right sided ganglionopathy. There was an associated parathyroid adenoma which was removed. Repeat CT of chest abdomen and pelvis demonstrated a pulmonary nodule with no change noted on serial images and follow up FDG-PET at 2 years was normal. He was initially treated with IV methylprednisolone and oral taper. He also received immunoglobulin. There was further clinical deterioration so was initiated. Despite these immunosuppressive therapies he continued to clinically deteriorate with distal mild weakness, areflexia and worsening proprioceptive deficits to his left wrist and MTP joints bilaterally. Inflammatory markers were persistently normal throughout. A radial nerve biopsy demonstrated axonal loss with no evidence of active inflammation. It was therefore unclear whether his ongoing deterioration was related to neurodegeneration or ongoing inflammation. A thoracic DRG biopsy was therefore undertaken. This demonstrated florid macrophage-mediated neuropathy with frequent myelin digestion. Due to evidence of an active inflammatory process he was treated with pulsed IV cyclophosphamide to a total of 10g with stabilisation of his limb signs. He is now maintained on Azathioprine. Our case demonstrates the important information that can be gained from DRG biopsy in those with clinical deterioration despite immunosuppressive treatment. DRG is invasive, however reports demonstrate high diagnostic yield and low post-operative complication rates when thoracic ganglions are biopsied.(2.) PMID:24108992
Waddell, Briony; Farmer, Simon; Lunn, Mike; O'Riordan, Jonathon I
A controlled trial of retraining of the sensory function of the hand was undertaken in hemiplegic patients after the period of spontaneous recovery. Twenty hemiplegic patients with sensory deficit in the hand, two or more years after stroke, received systematic retraining three times a week for six weeks. Sensation in the plegic hand was tested before and after this period in these patients and in 19 untreated control patients. The treated group showed large and significant gains on all sensory tests (P < 0.001), while no change occurred in the control group. It is concluded that somatosensory deficit can be alleviated even years after stroke and that rehabilitation for stroke patients should include sensory retraining for those with sensory deficit.
Yekutiel, M; Guttman, E
ObjectiveTo quantitatively identify and grade trigeminal sensory functions after 3 major surgical procedures of trigeminal neuralgia using a newly developed quantitative sensory testing technique, current perception threshold measurement (CPTM).
Chen Ruoping; Ouyang Huoniu; Wang Bingyu; Ding Meixiu; Charles J. Hodge Jr.
Since its inception in the 1970s, peripheral neuromodulation has become an increasingly common procedure to treat chronic neuropathic disorders. Historically, peripheral nerve stimulation (PNS) originated with the placement of large surface cuff electrodes, which was refined by the introduction of functional nerve mapping with circumferential electrical stimulation. This substantially improved the targeting of sensory fascicles. Surgical placement of spinal cord stimulation (SCS) 'button type' paddle electrodes was replaced when the introduction of percutaneous cylindrical SCS electrodes expanded the spectrum of PNS applications and improved the ability to target afferent sensory fibers as well as reducing the complication rate. To further refine functional mapping for the placement of these percutaneous electrodes, radiofrequency needle probes have more recently been employed to elicit paresthesias in awake patients to map the pain generators and guide treatment. In this chapter, we provide a description of the development and basic mechanisms of peripheral nerve stimulation, as well as a more detailed description of the two most commonly employed forms of peripheral nerve stimulation: occipital nerve stimulation for occipital neuralgia, and subcutaneous peripheral nerve field stimulation to stimulate free nerve endings within the subcutaneous tissue when the pain is limited to a small, well-localized area. The closely related ideas of internal and external targeted subcutaneous stimulation are also discussed. PMID:21422775
Aló, Kenneth M; Abramova, Marina V; Richter, Erich O
Background: Low vitamin B12 and high homocysteine (Hcy) levels are common in older adults and may be associated with worse neurological function. The aim of this study is to determine whether changes in B12 or Hcy levels are associated with longitudinal changes in peripheral nerve function and clinical neurological signs and symptoms. Methods: Participants aged 60 years and older at baseline (n = 678; 72.2 ± 6.2 years; 43.5% male) were from the InCHIANTI Study. Low B12 (<260 pmol/L) and high Hcy (?13 ?mol/L) were measured at baseline and 3-year follow-up. Neurological function was assessed by peroneal nerve conduction amplitude (compound motor action potential) and velocity, neurological examination, and peripheral neuropathy symptoms at baseline, 3-year, and 6-year follow-up. Results: At baseline, 43.8% had low B12 levels and 58.6% had high Hcy levels. Over 6 years, 12.4% declined to poor compound motor action potential (<1 mV) and 42.1% declined to poor nerve conduction velocity (<40 m/s). In mixed models analyses, sustained high Hcy was associated with worse compound motor action potential compared with sustained normal Hcy (p = .04), adjusting for demographics, diabetes, and folate level. Participants whose Hcy level became high at follow-up were more likely to become unable to detect monofilament at 6-year follow-up compared with those with sustained normal Hcy (odds ratio: 5.4; 95% CI: 1.5–19.0), adjusting for demographics, diabetes, body mass index, and peripheral arterial disease. There was no association with vitamin B12 level or with symptoms. Conclusions: High Hcy may be associated with worse sensory and motor peripheral nerve function. Because poor nerve function has been associated with lower strength and physical performance, these results have important implications for disability in older adults.
Leishear, Kira; Ferrucci, Luigi; Lauretani, Fulvio; Boudreau, Robert M.; Studenski, Stephanie A.; Rosano, Caterina; Abbate, Rosanna; Gori, Anna M.; Corsi, Anna M.; Di Iorio, Angelo; Guralnik, Jack M.; Bandinelli, Stefania; Newman, Anne B.
Mercury (Hg) is a potent neurotoxicant. We hypothesized that single nucleotide polymorphisms (SNPs) in genes coding glutathione-related proteins, selenoproteins and metallothioneins may modify the relationship of mercury biomarkers with changes in peripheral nerve function. Dental professionals (n=515) were recruited in 2009 and 2010. Sensory nerve function (onset latency, peak latency and amplitude) of the median, ulnar and sural nerves was recorded. Samples of urine, hair and DNA were collected. Covariates related to demographics, nerve function and elemental and methyl-mercury exposure were also collected. Subjects included 244 dentists (47.4%) and 269 non-dentists (52.2%; mostly dental hygienists and dental assistants). The mean mercury levels in urine (1.06 ?g/L) and hair (0.51 ?g/g) were not significantly different from the US general population (0.95 ?g/L and 0.47 ?g/g, respectively). In multivariate linear models predicting nerve function adjusting for covariates, only 3 out of a total of 504 models showed stable and statistically significant interaction of SNPs with mercury biomarkers. Overall, given the possibility of false positives, the results suggested little evidence of effect modification of the SNPs on the relationship between mercury biomarkers with peripheral nerve function at exposure levels that are relevant to the general US population. PMID:22236634
Wang, Yi; Goodrich, Jaclyn M; Werner, Robert; Gillespie, Brenda; Basu, Niladri; Franzblau, Alfred
Objective To evaluate artificial reflex arcs for micturition using urodynamics and electrophysiological recordings. Design Sixteen beagles were equally and randomly divided into two groups. Methods In group A, anastomosis of the proximal end of the left L7 ventral root (VR) and distal end of the left S2 VR was performed, as well as anastomosis of the L7 dorsal root (DR) and S2 DR to reconstruct the sensory and the motor function of the bladder. In group B the proximal end of the left L7 VR and the distal end of the left S2 VR were anastomosed, while the left L7 DR was kept intact to reconstruct the motor function of the bladder. Outcome measures included electrophysiological testing and the urodynamic measures. In addition, we also monitored urinary infection rates. Results Stimulation to the left S2 DR in groups A and B both elevated the bladder pressure before and after the spinal lower motor neuron lesion. Single stimulation of the two groups both elicited evoked action potentials. Urinary infections occurred in group A (three occurrences) and in group B (eight occurrences) during the 3 months after the spinal lower motor neuron lesion. Conclusion Data showed that both reconstructive methods could induce bladder micturition and evoked action potentials. However, in group A the micturition response was better and the urinary infection rates were lower after the spinal lower motor neuron lesion. Thus, the artificial physiological reflex arc reconstruction method used in group A, with sensory input above the lesion, might provide a better alternative in clinical practice.
Ma, Jun; Sui, Tao; Zhu, YuCheng; Zhu, AiXiang; Wei, ZhongQing; Cao, Xiao Jian
Cancer chemotherapeutics like paclitaxel and oxaliplatin produce a dose-limiting chronic sensory peripheral neuropathy that is often accompanied by neuropathic pain. The cause of the neuropathy and pain is unknown. In animal models, paclitaxel-evoked and oxaliplatin-evoked painful peripheral neuropathies are accompanied by an increase in the incidence of swollen and vacuolated mitochondria in peripheral nerve axons. It has been proposed that mitochondrial swelling and vacuolation are indicative of a functional impairment and that this results in a chronic axonal energy deficiency that is the cause of the neuropathy's symptoms. However, the significance of mitochondrial swelling and vacuolation is ambiguous and a test of the hypothesis requires a direct assessment of the effects of chemotherapy on mitochondrial function. The results of such an assessment are reported here. Mitochondrial respiration and ATP production were measured in rat sciatic nerve samples taken 1-2 days after and 3-4 weeks after induction of painful peripheral neuropathy with paclitaxel and oxaliplatin. Significant deficits in Complex I-mediated and Complex II-mediated respiration and significant deficits in ATP production were found for both drugs at both time points. In addition, prophylactic treatment with acetyl-l-carnitine, which inhibited the development of paclitaxel-evoked and oxaliplatin-evoked neuropathy, prevented the deficits in mitochondrial function. These results implicate mitotoxicity as a possible cause of chemotherapy-evoked chronic sensory peripheral neuropathy. PMID:21907196
Zheng, Huaien; Xiao, Wen Hua; Bennett, Gary J
Residual function in peripheral nerve stumps of amputees: implications for neural control of artificial limbs 1 1 No benefits in any form have been received or will be received from a commercial party related directly or indirectly to the subject of this article
PurposeIt is not known whether motor and sensory pathways associated with a missing or denervated limb remain functionally intact over periods of many months or years after amputation or chronic peripheral nerve transection injury. We examined the extent to which activity on chronically severed motor nerve fibers could be controlled by human amputees and whether distally referred tactile and proprioceptive
Gurpreet S Dhillon; Stephen M Lawrence; Douglas T Hutchinson; Kenneth W Horch
Tyrosine hydroxylase (TH) is transiently detectable in cells distributed throughout cranial sensory ganglia during early stages of gangliogenesis (embryonic day (E) 10.5-15.51. Although TH cells appear in embryonic ganglia of both neural crest and placode origin, mature cranial sensory neurons that express catecholaminergic properties are restricted to placode derivatives. The mechanism(s) underlying the loss of TH expression in crest-derived sensory
David M. Katz
A chemical receptor specific to traces of organophosphorus nerve agents (OPs) has been synthesized and grafted to carbon nanotubes and silicon nanowires in order to make electrical sensors. Our results show that it is possible to detect efficiently sub-ppm traces of OPs with excellent selectivity notably with the use of silicon nanowires by monitoring the Drain-Source current of the SiNW-FET at an optimum back Gate voltage as a function of time. First developments of a prototype have also been realized.
Simonato, Jean-Pierre; Clavaguera, Simon; Carella, Alexandre; Delalande, Michael; Raoul, Nicolas; Lenfant, Stephane; Vuillaume, Dominique; Dubois, Emmanuel
TRPA1 is a receptor expressed by sensory neurons, that is activated by low temperature (<17°C) and plant derivatives such as cinnamaldehyde and isoeugenol, to elicit sensations including pain. Using immunohistochemistry, we have, for the first time, localised TRPA1 in human DRG neurons, spinal cord motoneurones and nerve roots, peripheral nerves, intestinal myenteric plexus neurones, and skin basal keratinocytes. TRPA1 co-localised
U. Anand; W. R. Otto; P. Facer; N. Zebda; I. Selmer; M. J. Gunthorpe; I. P. Chessell; M. Sinisi; R. Birch; P. Anand
Following peripheral nerve injury repair, improved behavioural outcome may be the most important evidence of functionality of axon regeneration after any repair strategy. A range of behavioural testing paradigms have been developed for peripheral nerve injury research. Complete injury of the adult rat sciatic nerve is frequently used in combination with walking track analysis. Despite its wide-spread use, these walking
A. Bozkurt; R. Deumens; J. Scheffel; D. M. O’Dey; J. Weis; E. A. Joosten; T. Führmann; G. A. Brook; N. Pallua
We have examined changes that develop in the synaptic interactions of sensory and motor nerve cells following surgical lesions to the central nervous system of the leech. In one type of operation an individual ganglion was isolated from the rest of the nervous system by severing all the incoming and outgoing fibres. During the next few weeks, marked changes appeared in synaptic interactions. 1. In chronically isolated ganglia inhibitory potentials were recorded in the motoneurone which raises the skin into ridges (the AE cell) following impulses in sensory neurones that respond to pressure (P) or noxious (N) stimuli. In contrast the same AE cell in ganglia taken from normal animals shows excitatory synaptic potentials when the P or N sensory cells are stimulated. 2. Another altered synaptic interaction in ganglia isolated by lesions was that between sensory cells responding to touch and a motoneurone that supplies longitudinal muscles (L cell). Instead of the pure, electrical coupling potential seen normally, a large, additional chemically mediated excitatory potential was also apparent. 3. Some of the changes in synaptic interactions were not restricted to synapses within the isolated ganglion, but appeared gradually over the following year in successive ganglia along the length of the ventral nerve cord. 4. Indirect evidence suggests that the altered synaptic potentials that became conspicuous after operations are also present but smaller and obscured in normal animals. 5. It is concluded that some synapses in the leech nervous system are more readily changed than others by cutting the connectives. Furthermore, these changes influence in a predictable manner the way in which the animal behaves in response to mechanical stimuli.
Jansen, J. K. S.; Muller, K. J.; Nicholls, J. G.
We present a new approach to studying functional connectivity in the human brain. This approach is based on the observation that when we engage in motor activity, a discharge corollary to the motor command is sent from motor to sensory structures. Thus, as long as movement-related sensory input is either prevented or masked, modulation of neuronal activity in sensory structures
Tomáš Paus; Sean Marrett; Keith Worsley; Alan Evans
Neurotrophins and semaphorin 3A are present along pathways and in targets of developing axons of dorsal root ganglion (DRG) sensory neurons. Growth cones of sensory axons are probably regulated by interaction of cytoplasmic signaling trig- gered coincidentally by both types of guidance molecules. We investigated the in vitro interactions of neurotrophins and semaphorin 3A (Sema3A) in modulating growth cone behaviors
Vassil D. Dontchev; Paul C. Letourneau
Although a variety of industrial chemicals, as well as several chemotherapeutic agents used to treat cancer or HIV, preferentially induce a peripheral sensory neuropathy what remains unclear is why these agents induce a sensory vs. a motor or mixed neuropathy. Previous studies have shown that the endothelial cells that vascularize the dorsal root ganglion (DRG), which houses the primary afferent
Juan M Jimenez-Andrade; Monica B Herrera; Joseph R Ghilardi; Marina Vardanyan; Ohannes K Melemedjian; Patrick W Mantyh
An experimental model for local administration of neurotrophic growth factor (NGF) in peripheral nerve lesions is tested. The model consists of a subcutaneous reservoir connected to the sciatic nerve neurorrhaphy. The right sciatic nerves were exposed, severed, and repaired at a level 1.5 cm proximal to their trifurcation. Then, a dome-shaped silicone reservoir connected to the proximal end of a silicone tube was placed subcutaneously in the dorsum of the experimental animal. The distal end of the connecting tube was located in the nerve neurorrhaphy. Two experimental groups were made: Group A (n = 90) received daily doses of a solution containing NGF-7S during the first 4 weeks after surgery and a single weekly dose thereafter. Within this group, three subgroups of 30 rats each were made: A-4 sacrificed 4 weeks after surgery, A-8 sacrificed after 8 weeks, and A-12 after 12 weeks. Group B (n = 90) received the same vehicle solution without NGF under the same schedule and volume as in Group A. Three subgroups were also made as in Group A depending on the survival period. In order to locate the neurons in the dorsal root ganglia, the retrograde tracer horseradish peroxidase was administered at the proximal stump of the sciatic nerve (tibialis branch), which was severed 1 cm distal to the sciatic trifurcation. In respect of the nonoperated side, the percentage between the number of dorsal root ganglia neurons in the NGF-treated group was significantly higher than in the control group (P < 0.001). These results demonstrate that percutaneous administration of multiple doses of NGF in this model enhances sensory nerve regeneration after sciatic lesions evaluated by horseradish peroxidase labeling of dorsal root ganglia neurons. PMID:10469442
Santos, X; Rodrigo, J; Hontanilla, B; Bilbao, G
To study the mechanism of osteophyte formation in the ankle joints of adjuvant arthritic (AA) rats, the localization of peripheral nerves and immune cells in the synovia were investigated in both axotomized AA rats, whose sciatic nerves were resected before adjuvant injection, and sham-operated ones, using immunohistochemistry for low-affinity nerve growth factor receptor (p75NGFR), growth-associated protein (GAP)-43, calcitonin gene-related peptide
Zhou Wu; Kengo Nagata; Tadahiko Iijima
Activation of renal mechanosensory nerves is enhanced by a high-sodium diet and suppressed by a low-sodium diet. Angiotensin (Ang) II and endothelin (ET)-1 each contributes to the impaired responsiveness of renal mechanosen- sory nerves in a low-sodium diet. We examined whether stimulation of ETA receptors (Rs) contributes to Ang II-induced suppression of the responsiveness of renal mechanosensory nerves. In anesthetized
Ulla C. Kopp; Michael Z. Cicha; Lori A. Smith
The course of spinal accessory nerve in the posterior triangle, the innervation of the sternocleidomastoid and trapezius muscles and the contributions from the cervical plexus were studied in 20 cadaveric dissections. The nerve was most vulnerable to iatrogenic injuries after leaving the sternocleidomastoid. Direct innervation of trapezius by cervical plexus branches was noted in five dissections, whereas connections between the
Z. H. DAILIANA; H. MEHDIAN; A. GILBERT
We studied the roles of glycogen in axonal pathways of the central nervous system (CNS) and peripheral nervous system (PNS). By using electrophysiological recordings, in combination with biochemical glycogen assay, it was possible to determine whether glycogen was crucial to axon function under different conditions. Glycogen was present both in mouse optic nerve (MON) and in mouse sciatic nerve (MSN). Aglycemia caused loss of the compound action potential (CAP) in both pathways after a latency of 15 min (MON) and 120 min for myelinated axons (A fibers) in the MSN. With the exception of unmyelinated axons (C fibers) in the MSN, CAP decline began when usable glycogen was exhausted. Glycogen was located in astrocytes in the MON and in myelinating Schwann cells in the MSN; it was absent from the Schwann cells surrounding unmyelinated C fibers. In MON, astrocytic glycogen is metabolized to lactate and "shuttled" to axons to support metabolism. The ability of lactate to support A fiber conduction in the absence of glucose suggests a common pathway in both the CNS and the PNS. Lactate is released from MON and MSN in substantial quantities. That lactate levels fall in MSN in the presence of diaminobenzidine, which inhibits glycogen phosphorylase, strongly suggests that glycogen metabolism contributes to lactate release under resting conditions. Glycogen is a "backup" energy substrate in both the CNS and the PNS and, beyond sustaining excitability during glucose deprivation, has the capacity to subsidize the axonal energy demands during times of intense activity in the presence of glucose. PMID:23633387
Evans, Richard D; Brown, Angus M; Ransom, Bruce R
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.
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.
BACKGROUND: Functional abdominal pain syndrome (FAPS) has chronic unexplained abdominal pain and is similar to the psychiatric diagnosis of somatoform pain disorder. A patient with irritable bowel syndrome (IBS) also has chronic unexplained abdominal pain, and rectal hypersensitivity is observed in a majority of the patients. However, no reports have evaluated the visceral sensory function of FAPS precisely. We aimed
Tsukasa Nozu; Miwako Kudaira
This study evaluated the role of poly(ADP-ribose) polymerase in systemic oxidative stress and 4-hydoxynonenal adduct accumulation in diabetic peripheral neuropathy. Control and streptozotocin-diabetic rats were maintained with or without treatment with the PARP inhibitor, 1,5-isoquinolinediol, 3 mg kg?1d?1, for 10 weeks after initial 2 weeks. Treatment efficacy was evaluated by poly(ADP-ribosyl)ated protein content in peripheral nerve and spinal cord (Western blot analysis) and dorsal root ganglion neurons and non-neuronal cells (fluorescent immunohistochemistry), as well as by indices of peripheral nerve function. Diabetic rats displayed increased urinary isoprostane and 8-hydroxy-2'-deoxyguanosine excretion (ELISA), 4-hydroxynonenal adduct accumulation in endothelial and Schwann cells of the peripheral nerve, neurons, astrocytes, and oligodendrocytes of the spinal cord, and neurons and glial cells of the dorsal root ganglia (double-label fluorescent immunohistochemistry) as well as motor and sensory nerve conduction velocity deficits, thermal hypoalgesia, and tactile allodynia. PARP inhibition counteracted diabetes-induced systemic oxidative stress and 4-hydroxynonenal adduct accumulation in peripheral nerve and spinal cord (Western blot analysis) and dorsal root ganglion neurons (perikarya, fluorescent immunohistochemistry) which correlated with improvement of large and small nerve fiber function. The findings reveal the important role of PARP activation in systemic oxidative stress and 4-hydroxynonenal adduct accumulation in diabetic peripheral neuropathy.
Lupachyk, Sergey; Shevalye, Hanna; Maksimchyk, Yury; Drel, Viktor R.; Obrosova, Irina G.
Pesticide spraying operation is associated with the increased risk of adverse health effects among sprayers who do not follow safe farm work practices. A study was conducted among pesticide sprayers in North India to evaluate the clinical and subclinical variations in their vital health parameters before and after the pesticide spraying season. Blood cholinesterase levels, pulmonary function test, nerve conduction velocity and self-reported symptoms were studied among 18 eligible and consenting male sprayers. Mean acetylcholinesterase activity was reduced by 55 % in the post-exposure assessment (P?0.001) as compared to pre-exposure levels. Mean forced expiratory volume in 1 s was 20 % lower in the post-exposure assessment as compared to the pre-exposure level (P?0.05). No significant change was observed in the motor and sensory nerve conduction velocity in the median nerve of sprayers before and after the spraying activity. Also, no significant variation was observed with respect to self-reported symptoms except weakness in arms and legs (P?0.05). The significant decline in lung function and acetylcholinesterase level after pesticide exposure reflects the strongly negative effect of exposure to pesticides during spraying activity. More longitudinal studies among pesticide sprayers must be undertaken to further substantiate the cause-effect relationship between pesticide exposure and its subclinical effects. There is a strong necessity to minimise the exposure through the use of personal protective equipment in pesticide sprayers. PMID:23636596
Pathak, Manoj Kumar; Fareed, Mohammad; Srivastava, Anup Kumar; Pangtey, Balram Singh; Bihari, Vipin; Kuddus, Mohammed; Kesavachandran, C
The diversity of sensory cilia on Caenorhabditis elegans neurons allows the animal to detect a variety of sensory stimuli. Sensory cilia are assembled by intraflagellar transport (IFT) kinesins, which transport ciliary precursors, bound to IFT particles, along the ciliary axoneme for incorporation into ciliary structures. Using fluorescence microscopy of living animals and serial section electron microscopy of high pressure-frozen, freeze-substituted IFT motor mutants, we found that two IFT kinesins, homodimeric OSM-3 kinesin and heterotrimeric kinesin II, function in a partially redundant manner to build full-length amphid channel cilia but are completely redundant for building full-length amphid wing (AWC) cilia. This difference reflects cilia-specific differences in OSM-3 activity, which serves to extend distal singlets in channel cilia but not in AWC cilia, which lack such singlets. Moreover, AWC-specific chemotaxis assays reveal novel sensory functions for kinesin II in these wing cilia. We propose that kinesin II is a "canonical" IFT motor, whereas OSM-3 is an "accessory" IFT motor, and that subtle changes in the deployment or actions of these IFT kinesins can contribute to differences in cilia morphology, cilia function, and sensory perception. PMID:16492809
Evans, James E; Snow, Joshua J; Gunnarson, Amy L; Ou, Guangshuo; Stahlberg, Henning; McDonald, Kent L; Scholey, Jonathan M
Objectives The National Social Life, Health, and Aging Project assessed functioning of all 5 senses using both self-report and objective measures. We evaluate the performance of the objective measures and model differences in sensory function by gender and age. In the process, we demonstrate how to use and interpret these measures. Methods Distance vision was assessed using a standard Sloan eye chart, and touch was measured using a stationary 2-point discrimination test applied to the index fingertip of the dominant hand. Olfactory function (both intensity detection and odor identification) was assessed using odorants administered via felt-tip pens. Gustatory function was measured via identification of four taste strips. Results The performance of the objective measures was similar to that reported for previous studies, as was the relationship between sensory function and both gender and age. Discussion Sensory function is important in studies of aging and health both because it is an important health outcome and also because a decline in functioning can be symptomatic of or predict other health conditions. Although the objective measures provide considerably more precision than the self-report items, the latter can be valuable for imputation of missing data and for understanding differences in how older adults perceive their own sensory ability.
McClintock, Martha; Williams, Sharon; Leitsch, Sara; Lundstrom, Johan; Hummel, Thomas; Lindau, Stacy Tessler
A series of 18 patients undergoing surgery for cerebellopontine angle tumors is reported. Patients were grouped according to size of tumor (0 to 2.5 cm, 11 cases; more than 2.5 cm, 7 cases). In all, the facial nerve was identified and conductance assessed by monitoring the facial electromyographic response to facial nerve stimulation. Postoperative facial nerve function was graded clinically after 3 months according to the House scale. Tumor removal was complete in all cases. In patients with tumors up to 2.5 cm the facial nerve was intact to visual inspection at the end of the procedure in all but one, where partial division was evident. In this group intraoperative facial nerve stimulation indicated electrical integrity in 8 of the 11 cases, all of which regained good facial nerve function postoperatively (House grades I and II). Nerve conduction was lost during the operation in the remaining three patients with small tumors; two subsequently developed a moderately severe (grade IV) dysfunction and the third, a total paralysis (grade VI). In the large (more than 2.5 cm) tumor group the facial nerve was anatomically intact in five of the seven cases, partially divided in one, and completely sectioned in the remaining case. Facial nerve stimulation indicated functional integrity in three patients, two of whom developed moderate (grade III) and the third a severe (grade V) dysfunction. In the other four cases nerve function could not be detected at operation; three of these developed a moderate facial nerve dysfunction (grade III/IV) and the final case a complete paralysis (grade VI). Intraoperative facial nerve monitoring appeared to predict eventual facial function accurately in the small tumor group, but did not predict facial nerve recovery reliably following surgery for larger tumors.
Kirkpatrick, P. J.; Watters, G.; Strong, A. J.; Walliker, J. R.; Gleeson, M. J.
Gangliosides, sialylated glycosphingolipids which are the predominant glycans on vertebrate nerve cell surfaces, are emerging as components of membrane rafts, where they can mediate important physiological functions. Myelin associated glycoprotein (MAG), a minor constituent of myelin, is a sialic acid binding lectin with two established physiological functions: it is involved in myelin-axon stability and cytoarchitecture, and controls nerve regeneration. MAG
Alka A. Vyas; Ronald L. Schnaar
PURPOSE: The aim of this study was to compare functional data of different nerve-gap bridging materials evaluated in rat experiments by means of a systematic review. MATERIALS AND METHODS: A systematic review was conducted, searching MEDLINE, HTS and CENTRAL to identify all trials evaluating functional recovery of artificial nerve conduits in the rat model. RESULTS: There was a trend towards
Nektarios Sinis; Armin Kraus; Nikolaos Tselis; Max Haerle; Frank Werdin; Hans-Eberhard Schaller
Glaucoma leads to morphologic changes of the optic nerve head and to functional defects. Morphologic changes in the three-dimensional surface structure of the optic nerve head at its entrance site into the globe can be examined by laser scanning tomography. The standard technique for evaluating functional defects in glaucoma is static computerized perimetry. We compared these two techniques to determine
Karl U Bartz-Schmidt; Gabriele Thumann; Christian P Jonescu-Cuypers; Gunther K Krieglstein
The goal of the current study was to determine if T and B lymphocytes play a role in functional recovery after peripheral nerve injury. The time course of behavioral recovery following facial nerve crush injury at the stylomastoid foramen was established in scid mice which lack functional T and B cells and reconstituted scid mice as compared to wild-type mice.
Craig J. Serpe; Julie E. Tetzlaff; Susanna Coers; Virginia M. Sanders; Kathryn J. Jones
PurposeTo preserve sexual function following radical prostatectomy, one must avoid injury to the neurovascular bundles (NVBs). In the conventional open surgical technique, the use of energy sources for hemostasis is avoided to prevent damage to the cavernous nerves. In contrast, during laparoscopic radical prostatectomy, electrosurgical and ultrasonic energy sources are frequently used for hemostasis during dissection of the prostate. In
ALBERT M. ONG; LI-MING SU; IOANNIS VARKARAKIS; TAKESHI INAGAKI; RICHARD E. LINK; SAM B. BHAYANI; ALEX PATRICIU; BARBARA CRAIN; PATRICK C. WALSH
Insects are the most successful group of living things in terms of the number of species, the biomass and their distribution. Entomological research has revealed that the insect sensory systems are crucial for their success. Compared to human brains, the insect central nerve systems are extremely primitive and simple, both structurally and functionally, and are of minimal learning ability. Faced
Axel W. Krings
2,4-Dithiobiuret exposure causes a delayed onset muscle weakness in rats that has been attributed to depressed neuromuscular transmission. he present study compares the effects of DTB on sensory and motor function in rats. dult male Long-Evans hooded rats were exposed to saline, ...
The balance between excitation and inhibition (E\\/I balance) is tightly regulated in adult cortices to maintain proper nervous system function. Disturbed E\\/I balance is associated with numerous neuropsychological disorders, such as autism, epilepsy and schizophrenia. The present review will discuss aspects of Hebbian and homeostatic mechanisms regulating excitatory and inhibitory balance related to sensory processing in somatosensory cortex of rodents.
Zhi Zhang; Qian-Quan Sun
2,4-Dithiobiuret (DTB) exposure causes a delayed onset muscle weakness in rats that has been attributed to depressed neuromuscular transmission. The present study compares the effects of DTB on both sensory and motor function in rats. Adult male Long-Evan...
K. M. Crofton K. F. Dean R. C. Hamrick W. K. Boyes
Functional MR imaging (fMRI) of the cervical spinal cord was carried out in 13 healthy volunteers. A cold stimulus was applied, at different times, to three different sensory dermatome regions overlying the right hand and forearm: the thumb side of the palm, the little finger side of the palm, and the forearm below the elbow. Stimulation of these areas is
P. W. Stroman; V. Krause; K. L. Malisza; U. N. Frankenstein; B. Tomanek
Summary The results of recent investigations designed to elucidate the neuroeffector functions of sensory fibres, the cause of migraine headache and the mechanism of action of antimigraine drugs are reviewed and discussed. Neurogenic inflammation (vasodilatation and neurogenic plasma extravasation) is one explanation for the development of headaches and the blood flow changes which occur during migraine headache. Numerous studies have
M. A. Moskowitz; M. G. Buzzi
There is no study in the literature dealing with re-innervation of the cardiopulmonary vagus nerve after its transection followed by re-anastomosis. In the present study, we explored the bronchomotor, heart rate and respiratory responses in rats at 2, 3 and 6 months after re-anastomosis of one cervical vagus trunk. The conduction velocity of A, B and C waves was calculated in the compound vagal action potential. We searched for afferent vagal activities in phase with pulmonary inflation to assess the persistence of pulmonary stretch receptor (PSR) discharge in re-innervated lungs. In each animal, data from the stimulation or recording of one re-anastomosed vagus nerve were compared with those obtained in the contra-lateral intact one. Two and three months after surgery, the conduction velocities of A and B waves decreased, but recovery of conduction velocity was complete at 6 months. By contrast, the conduction velocity of the C wave did not change until 6 months, when it was doubled. The PSR activity was present in 50% of re-anastomosed vagus nerves at 2 and 3 months and in 75% at 6 months. Respiratory inhibition evoked by vagal stimulation was significantly weaker from the re-anastomosed than intact nerve at 2 but not 3 months. Vagal stimulation did not elicit cardiac slowing or bronchoconstriction 6 months after re-anastomosis. Our study demonstrates the capacity of pulmonary vagal sensory neurones to regenerate after axotomy followed by re-anastomosis, and the failure of the vagal efferents to re-innervate both the lungs and heart.
Bregeon, Fabienne; Alliez, Jean Roch; Hery, Geraldine; Marqueste, Tanguy; Ravailhe, Sylvie; Jammes, Yves
Deficits in sensorimotor control are experienced immediately after nerve injury due to changes in the periphery and central nervous system. Muscle denervation and sensory loss often disrupt prehensile coordination requiring the use of alternative strategies. To effectively foster coordination postinjury clinicians should address not only impairments and function but motor control issues through the prescription of specific sensory and motor
Susan V. Duff
The pathophysiology of postural instability in Parkinson's disease remains poorly understood. Normal postural function depends in part on the ability of the postural control system to integrate visual, proprioceptive, and vestibular sensory information. Degeneration of cholinergic neurons in the brainstem pedunculopontine nucleus complex and their thalamic efferent terminals has been implicated in postural control deficits in Parkinson's disease. Our aim was to investigate the relationship of cholinergic terminal loss in thalamus and cortex, and nigrostriatal dopaminergic denervation, on postural sensory integration function in Parkinson's disease. We studied 124 subjects with Parkinson's disease (32 female/92 male; 65.5 ± 7.4 years old; 6.0 ± 4.2 years motor disease duration; modified Hoehn and Yahr mean stage 2.4 ± 0.5) and 25 control subjects (10 female/15 male, 66.8 ± 10.1 years old). All subjects underwent (11)C-dihydrotetrabenazine vesicular monoaminergic transporter type 2 and (11)C-methylpiperidin-4-yl propionate acetylcholinesterase positron emission tomography and the sensory organization test balance platform protocol. Measures of dopaminergic and cholinergic terminal integrity were obtained, i.e. striatal vesicular monoaminergic transporter type 2 binding (distribution volume ratio) and thalamic and cortical acetylcholinesterase hydrolysis rate per minute (k3), respectively. Total centre of pressure excursion (speed), a measure of total sway, and sway variability were determined for individual sensory organization test conditions. Based on normative data, principal component analysis was performed to reduce postural sensory organization functions to robust factors for regression analysis with the dopaminergic and cholinergic terminal data. Factor analysis demonstrated two factors with eigenvalues >2 that explained 52.2% of the variance, mainly reflecting postural sway during sensory organization test Conditions 1-3 and 5, respectively. Regression analysis of the Conditions 1-3 postural sway-related factor [R(2)adj = 0.123, F(5,109) = 4.2, P = 0.002] showed that decreased thalamic cholinergic innervation was associated with increased centre of pressure sway speed (? = -0.389, t = -3.4, P = 0.001) while controlling for covariate effects of cognitive capacity and parkinsonian motor impairments. There was no significant effect of cortical cholinergic terminal deficits or striatal dopaminergic terminal deficits. This effect could only be found for the subjects with Parkinson's disease. We conclude that postural sensory integration function of subjects with Parkinson's disease is modulated by pedunculopontine nucleus-thalamic but not cortical cholinergic innervation. Impaired integrity of pedunculopontine nucleus cholinergic neurons and their thalamic efferents play a role in postural control in patients with Parkinson's disease, possibly by participating in integration of multimodal sensory input information. PMID:24056537
Müller, Martijn L T M; Albin, Roger L; Kotagal, Vikas; Koeppe, Robert A; Scott, Peter J H; Frey, Kirk A; Bohnen, Nicolaas I
Objective: Improved selection criteria have lead to an increasing number of nerve-sparing radical retropubic prostatectomies (RRP) in patients with clinically localised prostate cancer (PCA). Patient questionnaire based outcome analysis on post-operative erectile function after uni- or bilateral nerve-sparing RRP is described.Methods: Between January 1992 and March 1999, 366 patients (mean age 62.5 years) underwent uni- or bilateral nerve-sparing RRP at
Joachim Noldus; Uwe Michl; Markus Graefen; Alexander Haese; Peter Hammerer; Hartwig Huland
The first detection of the magnetic field of a stimulated peripheral nerve in man is presented. The measurement was performed noninvasively and in vivo on a healthy subject. The spatio-temporal field distribution is utilized to calculate the location of bioelectric activity on the basis of the equivalent current dipole model. The localization of the active nerve tissue is confirmed by a computer tomography image of the upper arm cross-section. Furthermore, a calculation of the total current distribution in the nerve explains the observed morphology of the signal. Images FIGURE 5
Trahms, L; Erne, S N; Trontelj, Z; Curio, G; Aust, P
Tight ligation and transection of the L5 spinal nerve (SNL) gives rise to pain which is dependent upon activity in the sympathetic nervous system. It also results in novel adrenergic sympathetic innervation of the dorsal root ganglion (DRG) with the formation of pericellular axonal basket structures around some DRG neurons. Since the sympathetic sprouting and basket formation may represent an
Matt S. Ramer; Patricia G. Murphy; Peter M. Richardson; Mark A. Bisby
One of the challenges facing prosthetic designers and engineers is to restore the missing sensory function inherit to hand amputation. Several different techniques can be employed to provide amputees with sensory feedback: sensory substitution methods where the recorded stimulus is not only transferred to the amputee, but also translated to a different modality (modality-matched feedback), which transfers the stimulus without translation and direct neural stimulation, which interacts directly with peripheral afferent nerves. This paper presents an overview of the principal works and devices employed to provide upper limb amputees with sensory feedback. The focus is on sensory substitution and modality matched feedback; the principal features, advantages and disadvantages of the different methods are presented. PMID:23278223
Antfolk, Christian; D'Alonzo, Marco; Rosén, Birgitta; Lundborg, Göran; Sebelius, Fredrik; Cipriani, Christian
The aim of this study was to investigate the use of ultrasound (US) guidance to perform sciatic and saphenous nerve blocks in dogs. Five dogs were sedated with medetomidine and butorphanol. A high-resolution US transducer was used to locate the nerves, guide placement of the needle and visualise the perineural injection of lidocaine 2%. Electrostimulation was used to confirm correct placement prior to the sciatic block. Nerve functions were evaluated over a 3 h period following administration of atipamezole. Successful identification of the nerves and the quality of the blocks were recorded. Location of the nerves, complete sensory block of the saphenous nerve, and partial to complete sensory and motor blocks of the sciatic nerve were achieved in all dogs. The resultant US guidance is potentially valuable for blocking the sciatic and saphenous nerves in dogs, although further work will be required to ensure a complete block of the sciatic nerve. PMID:19919902
Costa-Farré, Cristina; Blanch, Xavier Sala; Cruz, J Ignacio; Franch, Jordi
The possibility of olfactory function being affected at a very early stage of Alzheimer's disease (AD) was investigated by comparing patients with questionable AD with normal controls on odor and taste detection and short-term odor-and visual-recognition memory, including familiarity ratings. Taste and vision were studied for comparison. The questionable AD patients compared with the controls had higher thresholds for odor
Steven Nordin; Claire Murphy
Pharmacological evidence suggests a functional role for spinal nitric oxide (NO) in the modulation of thermal and\\/or inflamma- tory hyperalgesia. To assess the role of NO in nerve injury- induced tactile allodynia, we examined neuronal NO synthase (nNOS) expression in the spinal cord and dorsal root ganglia (DRG) of rats with tactile allodynia because of either tight ligation of the
Z. David Luo; S. R. Chaplan; B. P. Scott; D. Cizkova; N. A. Calcutt; T. L. Yaksh
Transient receptor potential (TRP) A1 and TRPM8 are ion channels that have been localized to afferent nociceptive nerves. These TRP channels may be of particular relevance to respiratory nociceptors in that they can be activated by various inhaled irritants and/or cold air. We addressed the hypothesis that mouse vagal sensory nerves projecting to the airways express TRPA1 and TRPM8 and that they can be activated via these receptors. Single cell RT-PCR analysis revealed that TRPA1 mRNA, but not TRPM8, is uniformly expressed in lung-labelled TRPV1-expressing vagal sensory neurons. Neither TRPA1 nor TRPM8 mRNA was expressed in TRPV1-negative neurons. Capsaicin-sensitive, but not capsaicin-insensitive, lung-specific neurons responded to cinnamaldehyde, a TRPA1 agonist, with increases in intracellular calcium. Menthol, a TRPM8 agonist, was ineffective at increasing cellular calcium in lung-specific vagal sensory neurons. Cinnamaldehyde also induced TRPA1-like inward currents (as measured by means of whole cell patch clamp recordings) in capsaicin-sensitive neurons. In an ex vivo vagal innervated mouse lung preparation, cinnamaldehyde evoked action potential discharge in mouse vagal C-fibres with a peak frequency similar to that observed with capsaicin. Cinnamaldehyde inhalation in vivo mimicked capsaicin in eliciting strong central-reflex changes in breathing pattern. Taken together, our results support the hypothesis that TRPA1, but not TRPM8, is expressed in vagal sensory nerves innervating the airways. TRPA1 activation provides a mechanism by which certain environmental stimuli may elicit action potential discharge in airway afferent C-fibres and the consequent nocifensor reflexes.
Nassenstein, Christina; Kwong, Kevin; Taylor-Clark, Thomas; Kollarik, Marian; MacGlashan, Donald M; Braun, Armin; Undem, Bradley J
Activation of renal mechanosensory nerves is enhanced by a high-sodium diet and suppressed by a low-sodium diet. Angiotensin (Ang) II and endothelin (ET)-1 each contributes to the impaired responsiveness of renal mechanosensory nerves in a low-sodium diet. We examined whether stimulation of ETA receptors (Rs) contributes to Ang II-induced suppression of the responsiveness of renal mechanosensory nerves. In anesthetized rats fed a low-sodium diet, renal pelvic administration of the Ang type I receptor (AT1-R) antagonist losartan enhanced the afferent renal nerve activity (ARNA) response to increasing renal pelvic pressure 7.5 mm Hg from 7+/-2% to 15+/-2% and the prostaglandin (PG) E(2)-mediated substance P release from 0+/-1 to 8+/-1 pg/min. Adding the ETA-R antagonist BQ123 to the renal pelvic perfusate containing losartan did not produce any further enhancement of the ARNA response or PGE(2)-mediated release of substance P (17+/-3% and 8+/-1 pg/min). Likewise, renal pelvic administration of BQ123 and BQ123+losartan resulted in similar enhancements of the ARNA responses to increased renal pelvic pressure and PGE(2)-mediated substance P release. In high-sodium-diet rats, pelvic administration of Ang II reduced the ARNA response to increased renal pelvic pressure from 27+/-4% to 8+/-3% and the PGE(2)-mediated substance P release from 9+/-0 to 1+/-1 pg/min. Adding BQ123 to the renal pelvic perfusate containing Ang II restored the increases in ARNA and the PGE(2)-mediated substance P release toward control (27+/-6% and 7+/-1 pg/min). In conclusion, stimulation of ETA-R plays an important contributory role to the Ang II-mediated suppression of the activation of renal mechanosensory nerves in conditions of low-sodium diet. PMID:17060503
Kopp, Ulla C; Cicha, Michael Z; Smith, Lori A
Lipofibromatous hamartoma of the nerve is a very uncommon, congenital, benign, peripheral nerve tumor. It is mostly encountered in the extremities of young adults, involving the median nerve in the majority of cases. The nerve tissue is infiltrated by diffuse fibroadipose tissue which dissociates the fasciculi without invasion. Patients with lipofibromatous hamartoma of the median nerve usually present with symptoms of carpal tunnel syndrome, usually accompanied by marked macrodactyly. Lipofibromatous hamartoma of the median nerve was encountered in an 18-year-old female patient, involving the wrist, causing macrodactyly of the index finger, and resulting in symptoms of carpal tunnel syndrome. Median nerve release and partial excision of the adipose tissue along the mass were performed. Fourteen months postoperatively, the patient had no complaints and the mass decreased in size without any motor or sensory functional losses. PMID:12510101
Bagatur, A Erdem
Sensory relearning (SR) first described in the 1970s by Wynn-Parry and Dellon has evolved over the last 20 years as a result of new insights into cortical plasticity. It has eluded precise definition, and a detailed description of its “key ingredients” is rarely documented in published studies investigating effectiveness.The purpose of this two-part study was to define SR and describe the
The caspases comprise a family of cysteine proteases that function in various cellular processes, including apoptosis. However, how the balance is struck between the caspases’ role in cell death and their nonapoptotic functions is unclear. To address this issue, we monitored the protein turnover of an endogenous caspase inhibitor, Drosophila IAP1 (DIAP1). DIAP1 is an E3 ubiquitin ligase that promotes the ubiquitination of caspases and thereby prevents caspase activation. For this study, we developed a fluorescent probe to monitor DIAP1 turnover in the external sensory organ precursor (SOP) lineage of living Drosophila. The SOP divides asymmetrically to make the shaft, socket, and sheath cells, and the neuron that comprise each sensory organ. We found that the quantity of DIAP1 changed dramatically depending on the cell type and maturity, and that the temporal regulation of DIAP1 turnover determines whether caspases function nonapoptotically in cellular morphogenesis or cause cell death.
Koto, Akiko; Kuranaga, Erina
Biological systems display impressive capabilities in effectively responding to environmental signals in real time. There is increasing evidence that organisms may indeed be employing near optimal Bayesian calculations in their decision-making. An intriguing question relates to the properties of optimal encoding methods, namely determining the properties of neural populations in sensory layers that optimize performance, subject to physiological constraints. Within an ecological theory of neural encoding/decoding, we show that optimal Bayesian performance requires neural adaptation which reflects environmental changes. Specifically, we predict that neuronal tuning functions possess an optimal width, which increases with prior uncertainty and environmental noise, and decreases with the decoding time window. Furthermore, even for static stimuli, we demonstrate that dynamic sensory tuning functions, acting at relatively short time scales, lead to improved performance. Interestingly, the narrowing of tuning functions as a function of time was recently observed in several biological systems. Such results set the stage for a functional theory which may explain the high reliability of sensory systems, and the utility of neuronal adaptation occurring at multiple time scales.
Yaeli, Steve; Meir, Ron
The trigeminal nerve is the largest of the cranial nerves. It provides sensory input from the face and motor innervation to the muscles of mastication. The facial nerve is the cranial nerve with the longest extracranial course, and its main functions include motor innervation to the muscles of facial expression, sensory control of lacrimation and salivation, control of the stapedial reflex and to carry taste sensation from the anterior two-thirds of the tongue. In order to be able adequately to image and follow the course of these cranial nerves and their main branches, a detailed knowledge of neuroanatomy is required. As we are dealing with very small anatomic structures, high resolution dedicated imaging studies are required to pick up normal and pathologic nerves. Whereas CT is best suited to demonstrate bony neurovascular foramina and canals, MRI is preferred to directly visualize the nerve. It is also the single technique able to detect pathologic processes afflicting the nerve without causing considerable expansion such as is usually the case in certain inflammatory/infectious conditions, perineural spread of malignancies and in very small intrinsic tumours. Because a long course from the brainstem nuclei to the peripheral branches is seen, it is useful to subdivide the nerve in several segments and then tailor the imaging modality and the imaging study to that specific segment. This is particularly true in cases where topographic diagnosis can be used to locate a lesion in the course of these nerves. PMID:15690205
Tumor necrosis factor- (TNF) is implicated in the initiation of neuropathic pain. In vitro, TNF activates p38 mitogen-activated kinase. Accord- ingly, we investigated whether TNF activates the p38 cascade in vivo to trigger pain behavior after spinal nerve ligation (SNL). Treatment starting 2 d before SNL with the TNF antagonist etanercept (1 mg, i.p., every third day) attenuated mechanical allodynia.
Maria Schafers; Camilla I. Svensson; Claudia Sommer; Linda S. Sorkin
The objective of this study was to determine whether the Hodgkin–Huxley model for unmyelinated nerve fibres could be modified\\u000a to predict excitability behaviour at Ranvier nodes. Only the model parameters were modified to those of human, with the equations\\u000a left unaltered. A model of a single Ranvier node has been developed as part of a larger model to describe excitation
Jacoba E. Smit; Tania Hanekom; Johan J. Hanekom
In this study, we extended application of face transplantation model in rat by incorporation of vascularized premaxilla, and nose with infraorbital and facial nerves for evaluation of allotransplanted sensory and motor nerve functional recovery. In group I (n = 3) the dissection technique is studied. In group II (n = 5) isotransplantations were performed. In group III (n = 5) allotransplantations were performed under Cyclosporin A monotherapy. Grafts; composed of nose, lower lip, and premaxilla; were dissected. Infraorbital nerve and facial nerve were included into the transplant. A heterotopic transplantation was performed to inguinal region of recipient. Nerve coaptations were performed between infraorbital-sapheneous nerve and facial-femoral nerve. CT scan, somatosensory-evoked potential testing (SSEP), motor-evoked potential testing (MEP), and microangiography were used for evaluation. All transplants survived indefinitely over 100 days. Microangiography showed preserved vascularization of the graft. Computed tomography revealed vital premaxillary bone segments. SSEP and MEP confirmed recovery of motor and sensory functions and latencies reached 67% of normal infraorbital nerve value and 70% of normal facial nerve value at 100 days post-transplant. We have introduced new midface transplant model of composite midface allograft with sensory and motor units. In this model, motor and sensory functional recovery was confirmed at 100 days post-transplant. PMID:20028492
Zor, Fatih; Bozkurt, Mehmet; Nair, Dileep; Siemionow, Maria
Cultured spinal cord explants in which little spontaneous bioelectric activity was present showed, when monitored using sensory ganglion-evoked monosynaptic action potentials, diffuse innervation by ingrowing afferent fibers at 3–4 weeks in vitro. In contrast, highly active cultures of the same age showed a strong tendency for functional sensory connections to be made within the dorsal half of the cord. Regional
M. A. Corner; R. E. Baker; A. M. M. C. Habets
There has been much debate recently over the functional role played by the planum temporale (PT) within the context of the dorsal auditory processing stream. Some studies indicate that regions in the PT support spatial hearing and other auditory functions, whereas others demonstrate sensory-motor response properties. This multifunctionality has led to the claim that the PT is performing a common computational pattern matching operation, then routing the signals (spatial, object, sensory-motor) into an appropriate processing stream. An alternative possibility is that the PT is functionally subdivided with separate regions supporting various functions. We assess this possibility using a within subject fMRI block design. DTI data were also collected to examine connectivity. There were four auditory conditions: stationary noise, moving noise, listening to pseudowords, and shadowing pseudowords (covert repetition). Contrasting the shadow and listen conditions should activate regions specific to sensory-motor processes, while contrasting the stationary and moving noise conditions should activate regions involved in spatial hearing. Subjects (N = 16) showed greater activation for shadowing in left posterior PT, area Spt, when the shadow and listen conditions were contrasted. The motion vs. stationary noise contrast revealed greater activation in a more medial and anterior portion of left PT. Seeds from these two contrasts were then used to guide the DTI analysis in an examination of connectivity via streamline tractography, which revealed different patterns of connectivity. Findings support a heterogeneous model of the PT, with functionally distinct regions for sensory-motor integration and processes involved in auditory spatial perception. PMID:21932266
Isenberg, A Lisette; Vaden, Kenneth I; Saberi, Kourosh; Muftuler, L Tugan; Hickok, Gregory
Somatosensory deficit syndromes represent a common impairment following stroke and have a prevalence rate of around 80% in stroke survivors. These deficits restrict the ability of survivors to explore and manipulate their environment and are generally associated with a negative impact on quality of life and personal safety. Sensory impairments affect different sensory modalities in diverse locations at varying degrees, ranging from complete hemianesthesia of multiple modalities to dissociated impairment of somatosensory submodalities within a particular region of the body. Sensory impairments induce typical syndromal patterns which can be differentiated by means of a careful neurological examination, allowing the investigator to deduce location and size of the underlying stroke. In particular, a stroke located in the brainstem, thalamus, and the corticoparietal cortex result in well-differentiable sensory syndromes. Sensory function following stroke can be regained during rehabilitation even without specific sensory training. However, there is emerging evidence that specialized sensory interventions can result in improvement of somatosensory and motor function. Herein, we summarize the clinical presentations, examination, differential diagnoses, and therapy of sensory syndromes in stroke. PMID:22377851
Klingner, Carsten M; Witte, Otto W; Günther, Albrecht
Distal sensory polyneuropathy (DSP) with associated neuropathic pain is the most common neurological disorder affecting patients with human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS). Viral protein R (Vpr) is a neurotoxic protein encoded by HIV-1 and secreted by infected macrophages. Vpr reduces neuronal viability, increases cytosolic calcium and membrane excitability of cultured dorsal root ganglion (DRG) sensory neurons, and is associated with mechanical allodynia in vivo. A clinical trial with HIV/AIDS patients demonstrated that nerve growth factor (NGF) reduced the severity of DSP-associated neuropathic pain, a problem linked to damage to small diameter, potentially NGF-responsive fibers. Herein, the actions of NGF were investigated in our Vpr model of DSP and we demonstrated that NGF significantly protected sensory neurons from the effects of Vpr. Footpads of immunodeficient Vpr transgenic (vpr/RAG1(-/-)) mice displayed allodynia (p<0.05), diminished epidermalinnervation (p<0.01) and reduced NGF mRNA expression (p<0.001) compared to immunodeficient (wildtype/RAG1(-/-)) littermate control mice. Compartmented cultures confirmed recombinant Vpr exposure to the DRG neuronal perikarya decreased distal neurite extension (p<0.01), whereas NGF exposure at these distal axons protected the DRG neurons from the Vpr-induced effect on their cell bodies. NGF prevented Vpr-induced attenuation of the phosphorylated glycogen synthase-3 axon extension pathway and tropomyosin-related kinase A (TrkA) receptor expression in DRG neurons (p<0.05) and it directly counteracted the cytosolic calcium burst caused by Vpr exposure to DRG neurons (p<0.01). TrkA receptor agonist indicated that NGFacted through the TrkA receptor to block the Vpr-mediated decrease in axon outgrowth in neonatal and adult rat and fetal human DRG neurons (p<0.05). Similarly, inhibiting the lower affinity NGF receptor, p75, blocked Vpr's effect on DRG neurons. Overall, NGF/TrkA signaling or p75 receptor inhibition protects somatic sensory neurons exposed to Vpr, thus laying the groundwork for potential therapeutic options for HIV/AIDS patients suffering from DSP. PMID:23912036
Webber, C A; Salame, J; Luu, G-L S; Acharjee, S; Ruangkittisakul, A; Martinez, J A; Jalali, H; Watts, R; Ballanyi, K; Guo, G F; Zochodne, D W; Power, C
We sought to evaluate the motor-sensory specificity of the motor and primary sensory neurons after the end-to-side neurorrhaphy. We divided 90 rats into three groups: (1) end-to-side neurorrhaphy using the ulnar nerve as donor nerve and the musculocutaneous nerve as recipient nerve; (2) normal control; and (3) transected nerve with the stumps buried. At 5 months, we monitored the grooming test, the electromyographic recordings, the histologic changes in the nerve, and quantitatively evaluated motoneurons and dorsal root ganglion (DRG) neurons following their retrograde labeling by Fluoro-Gold (Sigma, St. Louis, MO) applied to the musculocutaneous nerve and its biceps brachii branch. Grooming and electrophysiological investigations recovered successfully in the end-to-side group. The implanted musculocutaneous nerve contained varying but satisfactory numbers of axons. In the end-to-side group, the proportion of motoneurons for the biceps brachii branch of musculocutaneous nerve was very similar to the musculocutaneous nerve sections proximal to this branch (17.3% ± 2.7% and 21.7% ± 3.7%, respectively), but it did not correspond with the proportion of the biceps brachii branch of musculocutaneous nerve in the normal group (28.3% ± 3.5%). The present study confirms that limited but functional reinnervation can occur after the end-to-side neurorrhaphy, and the motor-sensory specificity is not important. PMID:23757157
Yu, Qing; Chen, Chengwang; Zhang, Xiaolei; Lv, Lei; Lin, Kang; Chi, Yonglong; Gao, Weiyang
The cochlear nerve is most commonly located on the caudoventral portion of the capsule of vestibular schwannomas and rarely on the dorsal portion. In such a condition, total removal of the tumor without cochlear nerve dysfunction is extremely difficult. The purpose of our study was to identify the frequency of this anatomical condition and the status of postoperative cochlear nerve function; we also discuss the preoperative radiological findings. The study involved 114 patients with unilateral vestibular schwannomas operated on via a retrosigmoid (lateral suboccipital) approach. Locations of the cochlear nerve on the tumor capsule were ventral, dorsal, caudal, and rostral. Ventral and dorsal locations were further subdivided into rostral, middle, and caudal third of the tumor capsule. The postoperative cochlear nerve function and preoperative magnetic resonance (MR) findings were reviewed retrospectively. In 56 patients that had useful preoperative hearing, useful hearing was retained in 50.0% (28 of 56) of patients after surgery. The cochlear nerve was located on the dorsal portion of the tumor capsule in four patients (3.5%), and useful hearing was preserved in only one of these patients (25%) in whom the tumor had been partially resected. This tumor-nerve anatomical relationship was identified in all tumors of <2 cm at preoperative MR cisternography. MR cisternography has the potential to identify the tumor-nerve anatomical relationship, especially in small-sized tumors that usually require therapeutic intervention that ensures hearing preservation. Hence, careful evaluation of the preoperative MR cisternography is important in deciding the therapeutic indications. PMID:22696159
Nakamizo, Akira; Amano, Toshiyuki; Mizoguchi, Masahiro; Yoshimoto, Koji; Sasaki, Tomio
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.
Sanders, Richard D.
Fetal sheep are increasingly used as animal models for fetal surgical interventions such as repair of myelomeningocele. Since\\u000a behavioral observations cannot provide objective information about preservation of sensory function, we have developed a technique\\u000a for reliably recording somatosensory evoked potentials in neonatal sheep. We determined anatomic criteria for placement of\\u000a recording electrodes over the somatosensory cortex using external landmarks, and
Charles D. Yingling; Claudia Meuli-Simmen; Martin Meuli; Gregory B. Timmel; N. Scott Adzick; Michael Harrison
This study determined the reliability of muscle function and sensory perception measures of the wrist extensors. The test-retest reliability of the measurements was determined by an intraclass correlation coefficient (ICC), coefficient of variation (CV), standard error of measurements (SEMs), and one-way repeated measures ANOVA using the values collected from 25 young (20.6?±?1.3 years) healthy male volunteers on two occasions separated
Peanchai Khamwong; Kazunori Nosaka; Ubon Pirunsan; Aatit Paungmali
Here, we investigated an Immunoglobulin (Ig) superfamily protein IgSF8 which is abundantly expressed in olfactory sensory neuron (OSN) axons and their developing synapses. We demonstrate that expression of IgSF8 within synaptic neuropil is transitory, limited to the period of glomerular formation. Glomerular expression decreases after synaptic maturation and compartmental glomerular organization is achieved, although expression is maintained at high levels within the olfactory nerve layer (ONL). Immunoprecipitations indicate that IgSF8 interacts with tetraspanin CD9 in the olfactory bulb (OB). CD9 is a component of tetraspanin-enriched microdomains (TEMs), specialized microdomains of the plasma membrane known to regulate cell morphology, motility, invasion, fusion and signaling, in both the nervous and immune systems, as well as in tumors. In vitro, both IgSF8 and CD9 localize to puncta within axons and growth cones of OSNs, consistent with TEM localization. When the olfactory epithelium (OE) was lesioned, forcing OSN regeneration en masse, IgSF8 was once again able to be detected in OSN axons terminals as synapses were reestablished. Finally, we halted synaptic maturation within glomeruli by unilaterally blocking functional activity and found that IgSF8 did not undergo exclusion from this subcellular compartment and instead continued to be detected in adult glomeruli. These data support the hypothesis that IgSF8 facilitates OSN synapse formation.
Ray, Arundhati; Treloar, Helen B.
Ethosuximide is a medication used to treat seizure disorders in humans, and we previously demonstrated that ethosuximide can delay age-related changes and extend the lifespan of the nematode Caenorhabditis elegans. The mechanism of action of ethosuximide in lifespan extension is unknown, and elucidating how ethosuximide functions is important for defining endogenous processes that influence lifespan and for exploring the potential of ethosuximide as a therapeutic for age-related diseases. To identify genes that mediate the activity of ethosuximide, we conducted a genetic screen and identified mutations in two genes, che-3 and osm-3, that cause resistance to ethosuximide-mediated toxicity. Mutations in che-3 and osm-3 cause defects in overlapping sets of chemosensory neurons, resulting in defective chemosensation and an extended lifespan. These findings suggest that ethosuximide extends lifespan by inhibiting the function of specific chemosensory neurons. This model is supported by the observation that ethosuximide-treated animals displayed numerous phenotypic similarities with mutants that have chemosensory defects, indicating that ethosuximide inhibits chemosensory function. Furthermore, ethosuximide extends lifespan by inhibiting chemosensation, since the long-lived osm-3 mutants were resistant to the lifespan extension caused by ethosuximide. These studies demonstrate a novel mechanism of action for a lifespan-extending drug and indicate that sensory perception has a critical role in controlling lifespan. Sensory perception also influences the lifespan of Drosophila, suggesting that sensory perception has an evolutionarily conserved role in lifespan control. These studies highlight the potential of ethosuximide and related drugs that modulate sensory perception to extend lifespan in diverse animals.
Collins, James J.; Evason, Kimberley; Pickett, Christopher L.; Schneider, Daniel L.; Kornfeld, Kerry
Compression neuropathy of a single digital nerve is a rare entity. We report the case of a patient with numbness in the distribution of the radial digital nerve of the thumb caused by the use of a walking stick. The nerve was compressed between the handle of the stick, the loop and the radial sesamoid bone of the first metacarpophalangeal joint. The site of the lesion was confirmed by electrophysiologic examination. Orthodromic recording of the sensory response from the radial palmar digital nerve of the thumb documented a complete absence of nerve action potential whereas the ulnar digital thumb nerve showed a normal response. Sensory function was restored when a padded ski glove was used to protect the area of the metacarpophalangeal joint whilst using the stick. PMID:15071968
Hug, U; Burg, D; Baldi, S V; Meyer, V E
The present study explored parallel changes in the physiology and structure of myelinated (A?) and unmyelinated (C) small diameter axons in the cavernous nerve of rats associated with streptozotocin-induced hyperglycemia. Damage to these axons is thought to play a key role in diabetic autonomic neuropathy and erectile dysfunction, but their pathophysiology has been poorly studied. Velocities in slow conducting fibers were measured by applying multiple unit procedures; histopathology was evaluated with both light and electron microscopy. To our knowledge, these are the initial studies of slow nerve conduction velocities in the distal segments of the cavernous nerve. We report that hyperglycemia is associated with a substantial reduction in the amplitude of the slow conducting response, as well as a slowing of velocities within this very slow range (<2.5 m/sec). Even with prolonged hyperglycemia (> 4 months), histopathological abnormalities were mild and limited to the distal segments of the cavernous nerve. Structural findings included dystrophic changes in nerve terminals, abnormal accumulations of glycogen granules in unmyelinated and preterminal axons, and necrosis of scattered smooth muscle fibers. The onset of slowing of velocity in the distal cavernous nerve occurred subsequent to slowing in somatic nerves in the same rats. The functional changes in the cavernous nerve anticipated and exceeded the axonal degeneration detected by morphology. The physiologic techniques outlined in these studies are feasible in most electrophysiologic laboratories and could substantially enhance our sensitivity to the onset and progression of small fiber diabetic neuropathy.
Zotova, Elena G.; Schaumburg, Herbert H.; Raine, Cedric S.; Cannella, Barbara; Tar, Moses; Melman, Arnold; Arezzo, Joseph C.
The ulnar nerve has to bear a large amount of compression, especially in the cubital tunnel, which can be deducted from the topographic relation of this nerve to the elbow. Apart from tightness of the tunnel, intraarticular changes can also cause compression of the nerve. A further narrow tunnel in the course of the ulnar nerve is the "loge de GUYON", situated in the hypothenar region. A careful neurological examination of sensory and motor signs as well as an accurate electromyographical examination differentiate compression syndromes from other neuropathies. Two unusual cases of a functional cubital tunnel syndrome are demonstrated: their cause was primarily a chondromatosis of the elbow joint in one case a functional vasal compression in the other case. PMID:7250791
Thümler, P; Goymann, V
Junctional adhesion molecule-C (JAM-C) is an adhesion molecule expressed at junctions between adjacent endothelial and epithelial cells and implicated in multiple inflammatory and vascular responses. In addition, we recently reported on the expression of JAM-C in Schwann cells (SCs) and its importance for the integrity and function of peripheral nerves. To investigate the role of JAM-C in neuronal functions further, mice with a specific deletion of JAM-C in SCs (JAM-C SC KO) were generated. Compared to wild-type (WT) controls, JAM-C SC KO mice showed electrophysiological defects, muscular weakness, and hypersensitivity to mechanical stimuli. In addressing the underlying cause of these defects, nerves from JAM-C SC KO mice were found to have morphological defects in the paranodal region, exhibiting increased nodal length as compared to WTs. The study also reports on previously undetected expressions of JAM-C, namely on perineural cells, and in line with nociception defects of the JAM-C SC KO animals, on finely myelinated sensory nerve fibers. Collectively, the generation and characterization of JAM-C SC KO mice has provided unequivocal evidence for the involvement of SC JAM-C in the fine organization of peripheral nerves and in modulating multiple neuronal responses. PMID:22090315
Colom, Bartomeu; Poitelon, Yannick; Huang, Wenlong; Woodfin, Abigail; Averill, Sharon; Del Carro, Ubaldo; Zambroni, Desirée; Brain, Susan D; Perretti, Mauro; Ahluwalia, Amrita; Priestley, John V; Chavakis, Triantafyllos; Imhof, Beat A; Feltri, M Laura; Nourshargh, Sussan
The changes that occur in the distribution and density of the encapsulated endings and Merkel cell-neurite complexes of the lingual gingival and alveolar mucosa of the mandible of kittens from birth to 28 d of age were observed through the use of methylene blue vital staining. The distribution of encapsulated endings showed a tendency to increase over the total area of the mucosae, but Merkel cell-neurite complexes tended to group into bands across the gingivae. While the density of the nerve endings of the former showed a continuous increase over the time period from the day of birth, when they totalled 13/cm2, to the 28th d by which that figure had increased to 144/cm2, the latter showed no such marked increase, totalling only 35/cm2 and 50/cm2, respectively. Further observations were made of the ultrastructures of organized endings in adult cat. PMID:3400879
Tazaki, M; Sakada, S
Background—The pathogenesis of anorectal dysfunction, which occurs frequently in patients with diabetes mellitus, is poorly defined. Recent studies indicate that changes in the blood glucose concentration have a major reversible effect on gastrointestinal motor function. ?Aims—To determine the effects of physiological changes in blood glucose and hyperglycaemia on anorectal motor and sensory function in normal subjects. ?Subjects—In eight normal subjects measurements of anorectal motility and sensation were performed on separate days while blood glucose concentrations were stabilised at 4, 8, and 12 mmol/l. ?Methods—Anorectal motor and sensory function was measured using a sleeve/sidehole catheter incorporating a balloon, and electromyography. ?Results—The number of spontaneous anal relaxations was greater at 12 mmol/l than at 8 and 4 mmol/l glucose (p<0.05 for both). Anal squeeze pressures were less at a blood glucose of 12 mmol/l when compared with 8 and 4 mmol/l (p<0.05 for both). During rectal distension, residual anal pressures were not significantly different between the three blood glucose concentrations. Rectal compliance was greater (p<0.05) at a blood glucose of 12 mmol/l when compared with 4 mmol/l. The threshold volume for initial perception of rectal distension was less at 12 mmol/l when compared with 4 mmol/l (40 (20-100) ml versus 10 (10-150) ml, p<0.05). ?Conclusions—An acute elevation of blood glucose to 12 mmol/l inhibits internal and external anal sphincter function and increases rectal sensitivity in normal subjects. In contrast, physiological changes in blood glucose do not have a significant effect on anorectal motor and sensory function. ?? Keywords: hyperglycaemia; anorectum; motility; sensation; diabetes mellitus
Russo, A; Sun, W; Sattawatthamrong, Y; Fraser, R; Horowitz, M; Andrews, J; Read, N
A study was made with intra-operative flash--visual evoked potentials (VEP) monitored using a fibre-optic/contact lens photo stimulator in 57 patients undergoing intra-orbital surgical procedures with potential risk to the optic nerve. The VEPs recorded under enflurane and nitrous oxide anaesthesia did not differ significantly in latency or amplitude from the pre-operative recordings. Transient abolition of the VEP was seen under many circumstances and did not correlate with the outcome of surgery, but absence of a previously normal VEP for more than four minutes during surgical manipulation within the orbit did show a correlation with post operative impairment of vision. The technique provides early warning to the surgeon of threats to the integrity of the optic nerve.
Harding, G F; Bland, J D; Smith, V H
Sensory impulses derived from the bladder and urinary sphincter system play an important role in the control of detrusor-sphincter function. Conscious sensation is essential to ensure the storage phase and to allow micturition at a functionally and socially acceptable time. Adequate sensation of the lower urinary tract requires an intact urothelium--peripheral nervous system--spinal cord--brain stem--midbrain--sensory cortex axis. This article reviews the current anatomical, physiological and pathophysiological knowledge concerning the afferent (sensory) nerve pathways of the bladder and urethra, with particular emphasis on their physiological and therapeutic implications. PMID:17373230
Comperat, Eva; Reitz, André; Mozer, Pierre; Robain, Gilberte; Denys, Pierre; Chartier-Kastler, Emmanuel
Abstract Introduction. Morphological evidence for reinnervation of pancreatic islet grafts is plentiful. However, to what extent intra-graft nerves influence the endocrine functions of the islet transplant is largely unknown. We therefore aimed to directly stimulate nerves leading to islet grafts with electrodes and measure insulin secretion in response to this. Methods. We implanted syngeneic islets under the renal capsule of rats, and examined them 1 or 7-9 months later. In anesthetized rats blood samples were collected from the renal vein and femoral artery, respectively, during electrode stimulation of the nerves leading to the islet grafts. Results. As expected, nerve stimulation decreased renal blood flow. However, serum insulin concentrations in samples derived from the renal vein or femoral artery changed in concert with one another, both during normoglycemia and acute hyperglycemia. Conclusion. Reinnervation which occurs after islet transplantation under the renal capsule has minor effects on graft endocrine function. PMID:23977866
Jansson, Leif; Kampf, Caroline; Källskog, Orjan
This paper describes the ultrastructural modifications that cockroach campaniform sensilla undergo at three major stages in the molting cycle and finds that the sensilla are physiological functional at all developmental stages leading to ecdysis. Late stage animals on the verge of ecdysis have two completely separate cuticles. The campaniform sensillum sends a 220-mum extension of the sensory process through a hole in its cap in the new (inner) cuticle across a fluid-filled molting space to its functional insertion in the cap in the old (outer) cuticle. Mechanical stimulation of the old cap excites the sensillum. The ultrastructural geometry of late stage sensilla, coupled with the observation they are physiolgically functional, supports the hypotheses (a) that sensory transduction occurs at the tip of the sensory process, and (b) that cap identation causes the cap cuticle to pinch the tip of the sensory process, thereby stimulating the sensillum.
Auditory perception is mediated through a finite number of mechanosensory hair cells located in a specialized sensory epithelium within the inner ear. The formation of the appropriate number of hair cells and the location of those cells is crucial for normal auditory function. However, the factors that regulate the formation of this epithelium remain poorly understood. Truncating mutations in the transcription factor GLI3, a downstream effector of the Hedgehog (HH) pathway, lead to a partial loss of HH signaling and cause Pallister-Hall syndrome (PHS). Here we report that cochleae from a mouse model of PHS (Gli3?699), which produces only the truncated, repressor form of Gli3, have a variably penetrant phenotype that includes an increase in the size of the sensory epithelium and the development of large ectopic sensory patches in Kölliker’s Organ (KO). Consistent with the mouse model, some PHS individuals exhibit hearing loss across a broad range of frequencies. Moreover, inhibition of HH signaling in vitro results in an increase in the size of the prosensory domain, a precursor population that gives rise to the sensory epithelium, while treatment with Sonic Hedgehog (Shh) inhibits prosensory formation. Finally, we demonstrate that HH signaling within the cochlea regulates expression of prosensory markers and that the effects of HH in KO are dependent on activation of Notch, an inducer of prosensory fate. These results suggest that HH signaling plays a key role in the specification, size, and location of the prosensory domain, and therefore of hair cells, within the cochlea.
Driver, Elizabeth Carroll; Pryor, Shannon P.; Hill, Patrick; Turner, Joyce; Ruther, Ulrich; Biesecker, Leslie G.; Griffith, Andrew J.; Kelley, Matthew W.
Single-unit recordings obtained from the auditory nerve of the Mongolian gerbil, Meriones unguiculatus, revealed functional differences in the response properties of neurons tuned to low and high frequencies. The distribution of neural thresholds displayed a distinct rise for auditory nerve fibers with characteristic frequencies] (CFs) between 3–5 kHz. This frequency band also marked abrupt changes in both the distribution of
K. K. Ohlemiller; S. M. Echteler
Human peripheral nerves are composed of thousands of individual nerve fibers whose signal conduction velocities vary from 0.2 to 100 m\\/s. Though good correlation exist between fiber velocity and the physiological function subserved by these fibers, considerable variation is found for specific end organs (20 to 40 m\\/s for a single muscle). Though clinical neurophysiologists have routinely measured the maximum
L. J. Leifer; M. A. Meyer; M. Morf; B. Petrig
Background Motor nerve function decreases with age and can cause abnormalities in motor function. Using newly designed methods, we used evoked electromyograms to evaluate change in motor nerve function. Material/Methods Motor function was assessed by grip strength, timed up-and-go test, 5-m normal walk, and 5-m fastest walk. In addition, motor nerve conduction velocity was calculated by measuring latency differences (NCV) in elderly and young subjects. We also investigated motor nerve conduction velocity by correlation coefficient (NCVCC) and the difference between NCV and NCVCC (DNCV). Results Significant differences were observed in the motor function of elderly and young persons in grip strength, the timed up-and-go test, and the 5-m fastest walk; however, no difference was observed in the 5-m normal walk test. NCVCC was lower than NCV in both elderly and young. The correlation coefficient peak of the NCVCC calculation was lower in elderly than in young. A negative correlation was observed between correlation coefficient peak and DNCV in elderly subjects. Conclusions NCVCC compares the overall shape of compound muscle action potential and reflects not only the fastest motor unit, but also the motor nerve conduction velocity of other motor unit components. A significant negative correlation between DNCV and the correlation coefficient peak was observed only in elderly subjects, suggesting that older individuals, including those that maintain a high level of physical strength, experience a loss of motor nerve function. Thus, changes in motor nerve function among elderly persons can potentially be further examined for clinical use.
Nishihara, Ken; Kawai, Hisashi; Kanemura, Naohiko; Hara, Motohiko; Naruse, Hideo; Gomi, Toshiaki
The objective was to assess the effect of topically administered diclofenac on peripheral nerve regeneration and functional recovery. Eighty male healthy white Wistar rats were divided into four experimental groups (n = 20), randomly: In transected group (TC), left sciatic nerve was transected and stumps were fixed in the adjacent muscle. In treatment group defect was bridged using an artery graft (AG/DICLO) filled with 10 ?L diclofenac (0.1 mg/kg). In artery graft group (AG), the graft was filled with phosphate-buffered saline alone. In sham-operated group (SHAM), sciatic nerve was exposed and manipulated. Each group was subdivided into four subgroups of five animals each and regenerated nerve fibers were studied 4, 8, 12 and 16 weeks after surgery. Behavioral testing, sciatic nerve functional study, gastrocnemius muscle mass and morphometric indices confirmed faster recovery of regenerated axons in AG/DICLO than AG group (p < 0.05). In immunohistochemistry, location of reactions to S-100 in AG/DICLO was clearly more positive than that in AG group. When loaded in an artery graft, diclofenac improved functional recovery and morphometric indices of sciatic nerve. Topical application of this readily available agent offers the benefit of cost savings as well as avoiding the complications associated with systemic administration. PMID:23354315
Mohammadi, Rahim; Hirsaee, Mohammad-Adel; Amini, Keyvan
The aim of this study was to evaluate the functional outcome of facial nerve repair with fibrin glue in end-to-end anastomosis and intermediate nerve graft. Thirty-six patients undergoing facial nerve repair by end–to-end anastomosis or facial nerve grafting using exclusively fibrin glue between 1986 and 1999 were included in this retrospective study. The population comprised ten vestibular schwannomas (28%), nine
Alexis Bozorg Grayeli; Isabelle Mosnier; Nicolas Julien; Hani El Garem; Didier Bouccara; Olivier Sterkers
Thinly myelinated A?-fiber and unmyelinated C-fiber cardiac sympathetic (spinal) sensory nerve fibers are activated during myocardial ischemia to transmit the sensation of angina pectoris. Although recent observations showed that myocardial ischemia increases the concentrations of opioid peptides and that the stimulation of peripheral opioid receptors inhibits chemically induced visceral and somatic nociception, the role of opioids in cardiac spinal afferent signaling during myocardial ischemia has not been studied. The present study tested the hypothesis that peripheral opioid receptors modulate cardiac spinal afferent nerve activity during myocardial ischemia by suppressing the responses of cardiac afferent nerve to ischemic mediators like bradykinin and extracellular ATP. The nerve activity of single unit cardiac afferents was recorded from the left sympathetic chain (T?-T?) in anesthetized cats. Forty-three ischemically sensitive afferent nerves (conduction velocity: 0.32-3.90 m/s) with receptive fields in the left and right ventricles were identified. The responses of these afferent nerves to repeat ischemia or ischemic mediators were further studied in the following protocols. First, epicardial administration of naloxone (8 ?mol), a nonselective opioid receptor antagonist, enhanced the responses of eight cardiac afferent nerves to recurrent myocardial ischemia by 62%, whereas epicardial application of vehicle (PBS) did not alter the responses of seven other cardiac afferent nerves to ischemia. Second, naloxone applied to the epicardial surface facilitated the responses of seven cardiac afferent nerves to epicardial ATP by 76%. Third, administration of naloxone enhanced the responses of seven other afferent nerves to bradykinin by 85%. In contrast, in the absence of naloxone, cardiac afferent nerves consistently responded to repeated application of ATP (n = 7) or bradykinin (n = 7). These data suggest that peripheral opioid peptides suppress the responses of cardiac sympathetic afferent nerves to myocardial ischemia and ischemic mediators like ATP and bradykinin. PMID:23645463
Fu, Liang-Wu; Longhurst, John C
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 (Tc) and IBAT (TIBAT) temperature responses. CGRP content was significantly decreased in capsaicin-treated IBAT demonstrating successful sensory nerve destruction. TIBAT and Tc 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.
Vaughan, Cheryl H.
Conventional total superficial parotidectomy (TP) has commonly been used, but partial superficial parotidectomy (PP) offers the possibility of better preserving glandular function and avoiding palsy of the facial nerves. In this study, the extent to which saliva secretion and facial nerve function were conserved in patients who received TP vs. PP was compared. Data were collected from patients who received a PP (n=163) or a TP (n=105) for benign primary tumours in the superficial lobe of the parotid glands between 1995 and 2009 at a single hospital. The incidence of transient facial paralysis was significantly lower in patients who received PP than in those who received TP. Secretory function was preserved for patients with a conserved Stensen's duct, whereas patients in whom the duct had been ligated lost secretory function. Partial superficial parotidectomy reduces the incidence of postoperative facial nerve dysfunction and is conducive to preserving Stensen's duct and saliva secretion. PMID:23623783
Zhang, S S; Ma, D Q; Guo, C B; Huang, M X; Peng, X; Yu, G Y
Junctional adhesion molecule-C (JAM-C) is an adhesion molecule expressed at junctions between adjacent endothelial and epithelial cells and implicated in multiple inflammatory and vascular responses. In addition, we recently reported on the expression of JAM-C in Schwann cells (SCs) and its importance for the integrity and function of peripheral nerves. To investigate the role of JAM-C in neuronal functions further, mice with a specific deletion of JAM-C in SCs (JAM-C SC KO) were generated. Compared to wild-type (WT) controls, JAM-C SC KO mice showed electrophysiological defects, muscular weakness, and hypersensitivity to mechanical stimuli. In addressing the underlying cause of these defects, nerves from JAM-C SC KO mice were found to have morphological defects in the paranodal region, exhibiting increased nodal length as compared to WTs. The study also reports on previously undetected expressions of JAM-C, namely on perineural cells, and in line with nociception defects of the JAM-C SC KO animals, on finely myelinated sensory nerve fibers. Collectively, the generation and characterization of JAM-C SC KO mice has provided unequivocal evidence for the involvement of SC JAM-C in the fine organization of peripheral nerves and in modulating multiple neuronal responses.—Colom, B., Poitelon, Y., Huang, W., Woodfin, A., Averill, S., Del Carro, U., Zambroni, D., Brain, S. D., Perretti, M., Ahluwalia, A., Priestley, J. V., Chavakis, T., Imhof, B. A., Feltri, M. L., Nourshargh, S. Schwann cell-specific JAM-C-deficient mice reveal novel expression and functions for JAM-C in peripheral nerves.
Colom, Bartomeu; Poitelon, Yannick; Huang, Wenlong; Woodfin, Abigail; Averill, Sharon; Del Carro, Ubaldo; Zambroni, Desiree; Brain, Susan D.; Perretti, Mauro; Ahluwalia, Amrita; Priestley, John V.; Chavakis, Triantafyllos; Imhof, Beat A.; Feltri, M. Laura; Nourshargh, Sussan
An implantable wireless system was developed for recording muscle afferent activity and stimulating peripheral nerves with cuff electrodes. The proposed system was fabricated into the nerve cuff electrode, neural amplifier, neural stimulator, and wireless communication system with battery power. The nerve cuff electrode and neural amplifier were designed to improve the signal-to-interference ratio and signal-to-noise ratio. The wireless communication system was designed based on the medical implant communication service regulations to be suitable for implantation. The main function of this system was to extract muscle afferent activity from peripheral nerve during functional electrical stimulation. The cuff electrodes were chronically implanted on the sciatic nerve for recording and on the tibial and peroneal nerves for stimulation. When the extension and flexion movements of ankle joint were elicited from alternative electrical stimuli, the corresponding neural signals and ankle angles were recorded simultaneously. The muscle afferent activity was then extracted from the recorded neural signal through a simple blanking process. The experimental results showed that the ankle movements could be detected from the extracted muscle afferent activity. PMID:24110511
Song, Kang-Il; Shon, Ahnsei; Chu, Jun-Uk; Choi, Kuiwon; Hwang, Dosik; Youn, Inchan
Objective(s): Crocin is a constituent of saffron and has many biological functions. The present study aimed to investigate the effects of intraperitoneal (IP) injection of crocin on sciatic nerve regeneration in male Wistar rats. Materials and Methods: Fifty-four rats were divided into 9 groups: groups 1-4 (intact + normal saline and intact + crocin at doses of 5, 20 and 80 mg/kg, respectively); group 5 (sham surgery + normal saline); groups 6-9 (crush + normal saline and crush + crocin at doses of 5, 20 and 80 mg/kg, respectively). Normal saline and crocin were IP injected for 10 consecutive days after induction of a standard crush injury in left sciatic nerve. Footprints were obtained 1 day before and weekly after induction of nerve injury for evaluation of sciatic functional index (SFI). Blood samples were taken for evaluation of malondialdehyde (MDA) levels. Histopathological changes of sciatic nerve were investigated by light microscopy. Results: Sciatic nerve crush-injured rats showed SFI values reduction, increased plasma MDA levels and produced Wallerian degeneration in sciatic nerve. Crocin at a dose of 5 mg/kg had no significant effects. At doses of 20 and 80 mg/kg, crocin accelerated the SFI recovery, decreased MDA levels and reduced Wallerian degeneration severity. Conclusion: The present study suggests that the neuroprotective effects afforded by crocin may be due in part to reduction of free radicals-induced toxic effects. PMID:23638296
Tamaddonfard, Esmaeal; Farshid, Amir Abbas; Ahmadian, Elham; Hamidhoseyni, Abbas
... that primarily affects the sensory nerve cells (sensory neurons), which transmit information about sensations such as pain, ... the sensations of pain, temperature, and touch (sensory neurons). The mutations involved in HSAN2A result in an ...
The ability of adult peripheral sensory neurons to undergo functional and anatomical recovery following nerve injury is due in part to successful activation of transcriptional regulatory pathways. Previous in vitro evidence had suggested that the transcription factor Sox11, a HMG-domain containing protein that is highly expressed in developing sensory neurons, is an important component of this regenerative transcriptional control program.
Michael P. Jankowski; Sabrina L. McIlwrath; Xiaotang Jing; Pamela K. Cornuet; Kathleen M. Salerno; H. Richard Koerber; Kathryn M. Albers
Current theories suggest that disrupting cortical information integration may account for the mechanism of general anesthesia in suppressing consciousness. Human cognitive operations take place in hierarchically structured neural organizations in the brain. The process of low-order neural representation of sensory stimuli becoming integrated in high-order cortices is also known as cognitive binding. Combining neuroimaging, cognitive neuroscience, and anesthetic manipulation, we examined how cognitive networks involved in auditory verbal memory are maintained in wakefulness, disrupted in propofol-induced deep sedation, and re-established in recovery. Inspired by the notion of cognitive binding, an functional magnetic resonance imaging-guided connectivity analysis was utilized to assess the integrity of functional interactions within and between different levels of the task-defined brain regions. Task-related responses persisted in the primary auditory cortex (PAC), but vanished in the inferior frontal gyrus (IFG) and premotor areas in deep sedation. For connectivity analysis, seed regions representing sensory and high-order processing of the memory task were identified in the PAC and IFG. Propofol disrupted connections from the PAC seed to the frontal regions and thalamus, but not the connections from the IFG seed to a set of widely distributed brain regions in the temporal, frontal, and parietal lobes (with exception of the PAC). These later regions have been implicated in mediating verbal comprehension and memory. These results suggest that propofol disrupts cognition by blocking the projection of sensory information to high-order processing networks and thus preventing information integration. Such findings contribute to our understanding of anesthetic mechanisms as related to information and integration in the brain. PMID:21932265
Liu, Xiaolin; Lauer, Kathryn K; Ward, Barney D; Rao, Stephen M; Li, Shi-Jiang; Hudetz, Anthony G
Quantitative sensory testing (QST) consists of several non-invasive, standardised tests aimed at examining different aspects of the entire somatosensory nervous system. Important advantages of QST over existing supplementary tests such as electromyography are the ability to test the function of thin and unmyelinated nerve fibres as well as the subjective sensation of a somatosensory stimulus. QST is validated in diagnosing small fibre neuropathy, diabetic neuropathy chemotherapy-induced peripheral neuropathy and neuropathic pain. In scientific research, QST is useful in the study into pathophysiological mechanisms of diseases and syndromes with sensory symptoms and in the evaluation of the effect of analgesic treatment on the function of the somatosensory nervous system. In the future, QST could be a useful diagnostic and prognostic test in more forms of neuropathy and in other clinical conditions such as chronic unexplained pain syndromes (e.g. fibromyalgia and whiplash-associated disorder. PMID:23369816
Verberne, Wouter R; Snijders, Tom J; Liem, K Seng; Baakman, Anne Catrien; Veldhuijzen, Dieuwke S
In order to investigate the usefulness of immunohistochemical detection of regenerating axons as a correlate of functional recovery, reinnervation of mouse foot pads, hairy skin, and muscle were studied at several intervals along 3 months after sciatic nerve crush using immunohistochemical markers PGP 9.5 and CGRP. These histological results were compared with functional recovery of sweat glands (SGs), plantar muscles,
Enrique Verdú; Xavier Navarro
Energy drinks have increased in popularity in recent years due to the claimed energy boost provided by functional ingredients. A multitude of functional ingredients have been utilized; however, there is limited research on their sensory effects in energy drink formulations. A 13-member descriptive analysis panel was conducted to investigate the effects on the sensory and rheological properties of 3 common functional ingredients-caffeine, ginseng, and taurine-in a noncarbonated model energy drink solution. Combinations of these functional ingredients at 3 levels (low, medium, high) were added to create a total of 27 different solutions (3 x 3 x 3 factorial design). Analysis of variance was performed to evaluate the sensory effects of the varying concentrations of functional ingredients in solution. Principal component analysis (PCA) was performed to summarize the relationship among the attributes and solutions. In general, high levels of caffeine in solution resulted in low ratings of fruity attributes and high ratings of bitter tea and fruit bitter attributes. The high level of ginseng in solution was characterized by high ratings of bitter attributes. A horns effect was observed as the sweet, artificial lemon-lime, pear, mango, and pineapple attributes were rated lower in intensity with increased ginseng levels. Taurine levels of up to 416 mg/100 mL had no significant effect on the sensory attribute ratings of the model energy drink solutions. These findings can be utilized to predict the changes in sensory characteristics when formulating energy drinks containing these popular functional ingredients. PMID:20722948
Tamamoto, Lauren C; Schmidt, Shelly J; Lee, Soo-Yeun
The serotonin transporter MRNA has been found throughout the trigeminal sensory system late in gestation and during early postnatal development, a period known to be critical for maturation of the sensory circuitry. The purpose of the present study was to determine whether sensory denervation in newborn rat pups would alter either the density or pattern of expression of the 5-HT
Stefan R Hansson; Theresa M Cabrera-Vera; Beth J Hoffman
Exposure to many neurotoxic compounds has been shown to produce a sensory system dysfunction. Neurophysiological assessment of sensory function in humans and animal models often uses techniques known as sensory evoked potentials. Because both humans and animals show analogous res...
\\u000a Together, the relationship between the mechanical response of neural tissues and the related mechanisms of injury provide\\u000a a foundation for defining relevant thresholds for injury. The nerves and nerve roots are biologic structures with specific\\u000a and important functions, and whose response to mechanical loading can have immediate, long-lasting and widespread consequences.\\u000a In particular, when nerves or nerve roots are mechanically
Kristen J. Nicholson; Beth A. Winkelstein
A growing body of evidence is available about the functioning of fetal sensory systems during gestation. This article aims at reviewing data concerning (i) the presence of potential sensory stimulation in the fetal milieu, (ii) the sequential functional development of the sensory systems and (iii) physiological and behavioral responses of fetuses to various types of stimulation. Human data are compared
Jean-Pierre Lecanuet; Benoist Schaal
Bioenergetic deficits in peripheral nerve sensory axons during chemotherapy-induced neuropathic pain resulting from peroxynitrite-mediated post-translational nitration of mitochondrial superoxide dismutase.
Many of the widely used anticancer drugs induce dose-limiting peripheral neuropathies that undermine their therapeutic efficacy. Animal models of chemotherapy-induced painful peripheral neuropathy (CIPN) evoked by a variety of drug classes, including taxanes, vinca alkaloids, platinum-complexes, and proteasome-inhibitors, suggest that the common underlying mechanism in the development of these neuropathies is mitotoxicity in primary nerve sensory axons (PNSAs) arising from reduced mitochondrial bioenergetics [eg adenosine triphosphate (ATP) production deficits due to compromised respiratory complex I and II activity]. The causative mechanisms of this mitotoxicity remain poorly defined. However, peroxynitrite, an important pro-nociceptive agent, has been linked to mitotoxicity in several disease states and may also drive the mitotoxicity associated with CIPN. Our findings reveal that the development of mechano-hypersensitivity induced by paclitaxel, oxaliplatin, and bortezomib was prevented by administration of the peroxynitrite decomposition catalyst Mn(III) 5,10,15,20-tetrakis(N-n-hexylpyridinium-2-yl)porphyrin (MnTE-2-PyP(5+)) without interfering with their anti-tumor effects. Peak CIPN was associated with the nitration and inactivation of superoxide dismutase in the mitochondria, but not in the cytosol, as well as a significant decrease in ATP production within the PNSAs; all of these events were attenuated by MnTE-2-PyP(5+). Our results provide continued support for the role of mitotoxicity in the development of CIPN across chemotherapeutic drug classes, and identify peroxynitrite as a key mediator in these processes, thereby providing the rationale towards development of "peroxynitrite-targeted" therapeutics for CIPN. PMID:23891899
Janes, Kali; Doyle, Timothy; Bryant, Leesa; Esposito, Emanuela; Cuzzocrea, Salvatore; Ryerse, Jan; Bennett, Gary J; Salvemini, Daniela
Objective. Electrical stimulation of the pudendal nerve (PN) is being developed as a means to restore bladder function in persons with spinal cord injury. A single nerve cuff electrode placed on the proximal PN trunk may enable selective stimulation of distinct fascicles to maintain continence or evoke micturition. The objective of this study was to design a nerve cuff that enabled selective stimulation of the PN. Approach. We evaluated the performance of both flat interface nerve electrode (FINE) cuff and round cuff designs, with a range of FINE cuff heights and number of contacts, as well as multiple contact orientations. This analysis was performed using a computational model, in which the nerve and fascicle cross-sectional positions from five human PN trunks were systematically reshaped within the nerve cuff. These cross-sections were used to create finite element models, with electric potentials calculated and applied to a cable model of a myelinated axon to evaluate stimulation selectivity for different PN targets. Subsequently, the model was coupled to a genetic algorithm (GA) to identify solutions that used multiple contact activation to maximize selectivity and minimize total stimulation voltage. Main results. Simulations did not identify any significant differences in selectivity between FINE and round cuffs, although the latter required smaller stimulation voltages for target activation due to preserved localization of targeted fascicle groups. Further, it was found that a ten contact nerve cuff generated sufficient selectivity for all PN targets, with the degree of selectivity dependent on the relative position of the target within the nerve. The GA identified solutions that increased fitness by 0.7-45.5% over single contact activation by decreasing stimulation of non-targeted fascicles. Significance. This study suggests that using an optimal nerve cuff design and multiple contact activation could enable selective stimulation of the human PN trunk for restoration of bladder function.
Kent, Alexander R.; Grill, Warren M.
The release of transmitter at neuromuscular junctions (NMJ) of the opener muscle in crayfish is quantal in nature. This NMJ offers the advantage of being able to record quantal events at specific visually identified release sites, thus allowing measurement of the physiological parameters of vesicle release and its response to be directly correlated with synaptic structure. These experiments take advantage of areas between the varicosities on the nerve terminal that we define as "stems." Stems were chosen as the region to study because of their low synaptic output due to fewer synaptic sites. Through 3D reconstruction from hundreds of serial sections, obtained by transmission electron microscopy (TEM), at a site in which focal macropatch recordings were obtained, the number of synapses and AZs are revealed. Thus, physiological profiles with various stimulation conditions can be assessed in regards to direct synaptic structure. Here, we used the properties of the quantal shape to determine if distinct subsets of quantal signatures existed and if differences in the distributions are present depending on the frequency of stimulation. Such a quantal signature could come about by parameters of area, rise time, peak amplitude, latency, and tau decay. In this study, it is shown that even at defined sites on the stem, with few active zones, synaptic transmission is still complex and the quantal responses appear to be variable even for a given synapse over time. In this study, we could not identify a quantal signature for the conditions utilized. PMID:20730805
Johnstone, A F M; Viele, K; Cooper, R L
The objective of the study was to evaluate unilateral nerve sparing prostate surgery. Patient files of men who underwent unilateral nerve sparing radical prostatectomy were analyzed retrospectively after a minimum follow-up period of 18 months. Of 46 patients who received unilateral nerve sparing surgery, 14 (30.4%) regained full potency after surgery. In 92.9% of these patients, recovery occurred within a
F Van der Aa; S Joniau; D De Ridder; H Van Poppel
Optic nerve hypoplasia (ONH), which is defined as a congenital deficiency of retinal ganglion cells, may also involve more distal layers of the retina. We investigated electrophysiological function of the retina in ONH using electroretinograms (ERGs). ERGs were recorded from 48 subjects (3.5–35 months) with unilateral or bilateral ONH. Pattern reversal (4° checks) was presented under chloral hydrate sedation, using
Daphne L. McCulloch; P. Garcia-Fillion; G. B. van Boeme; M. S. Borchert
Functional MR imaging (fMRI) of the cervical spinal cord was carried out in 13 healthy volunteers. A cold stimulus was applied, at different times, to three different sensory dermatome regions overlying the right hand and forearm: the thumb side of the palm, the little finger side of the palm, and the forearm below the elbow. Stimulation of these areas is expected to involve the 6(th), 8(th), and 5(th) cervical spinal cord segments respectively. Whereas true activations are expected to correspond to the region being stimulated, false activations such as arising from noise and motion, are not. The results demonstrate that clustering of active pixels into groups based on their intensity time courses discriminates false activations from true activations. Following clustering, the distribution of activity observed with fMRI matched the expected regions of neuronal activation with the different areas of stimulation on the hand and forearm. PMID:11973024
Stroman, P W; Krause, V; Malisza, K L; Frankenstein, U N; Tomanek, B
Summary Spinal muscular atrophy (SMA) is a lethal human disease characterized by motor neuron dysfunction and muscle deterioration due to depletion of the ubiquitous Survival Motor Neuron (SMN) protein. Drosophila SMN mutants have reduced muscle size and defective locomotion, motor rhythm and motor neuron neurotransmission. Unexpectedly, restoration of SMN in either muscles or motor neurons did not alter these phenotypes. Instead, SMN must be expressed in proprioceptive neurons and interneurons in the motor circuit to non-autonomously correct defects in motor neurons and muscles. SMN depletion disrupts the motor system subsequent to circuit development and can be mimicked by the inhibition of motor network function. Furthermore, increasing motor circuit excitability by genetic or pharmacological inhibition of K+ channels can correct SMN-dependent phenotypes. These results establish sensory-motor circuit dysfunction as the origin of motor system deficits in this SMA model and suggest that enhancement of motor neural network activity could ameliorate the disease.
Imlach, Wendy L.; Beck, Erin S.; Choi, Ben Jiwon; Lotti, Francesco; Pellizzoni, Livio; McCabe, Brian D.
Introduction Below ground orientation in insects relies mainly on olfaction and taste. The economic impact of plant root feeding scarab beetle larvae gave rise to numerous phylogenetic and ecological studies. Detailed knowledge of the sensory capacities of these larvae is nevertheless lacking. Here, we present an atlas of the sensory organs on larval head appendages of Melolontha melolontha. Our ultrastructural and electrophysiological investigations allow annotation of functions to various sensory structures. Results Three out of 17 ascertained sensillum types have olfactory, and 7 gustatory function. These sensillum types are unevenly distributed between antennae and palps. The most prominent chemosensory organs are antennal pore plates that in total are innervated by approximately one thousand olfactory sensory neurons grouped into functional units of three-to-four. In contrast, only two olfactory sensory neurons innervate one sensillum basiconicum on each of the palps. Gustatory sensilla chaetica dominate the apices of all head appendages, while only the palps bear thermo-/hygroreceptors. Electrophysiological responses to CO2, an attractant for many root feeders, are exclusively observed in the antennae. Out of 54 relevant volatile compounds, various alcohols, acids, amines, esters, aldehydes, ketones and monoterpenes elicit responses in antennae and palps. All head appendages are characterized by distinct olfactory response profiles that are even enantiomer specific for some compounds. Conclusions Chemosensory capacities in M. melolontha larvae are as highly developed as in many adult insects. We interpret the functional sensory units underneath the antennal pore plates as cryptic sensilla placodea and suggest that these perceive a broad range of secondary plant metabolites together with CO2. Responses to olfactory stimulation of the labial and maxillary palps indicate that typical contact chemo-sensilla have a dual gustatory and olfactory function.
Hansson, Bill S.; Hilker, Monika; Reinecke, Andreas
Long-term whisker removal alters the balance of excitation and inhibition in rodent barrel cortex, yet little is known about the contributions of individual cells and synapses in this process. We studied synaptic inhibition in four major types of neurons in live tangential slices that isolate layer 4 in the posteromedial barrel subfield. Voltage-clamp recordings of layer 4 neurons reveal that fast decay of synaptic inhibition requires alpha1-containing GABA(A) receptors. After 7 weeks of deprivation, we found that GABA(A)-receptor-mediated inhibitory postsynaptic currents (IPSCs) in the inhibitory low-threshold-spiking (LTS) cell recorded in deprived barrels exhibited faster decay kinetics and larger amplitudes in whisker-deprived barrels than those in nondeprived barrels in age-matched controls. This was not observed in other cell types. Additionally, IPSCs recorded in LTS cells from deprived barrels show a marked increase in zolpidem sensitivity. To determine if the faster IPSC decay in LTS cells from deprived barrels indicates an increase in alpha1 subunit functionality, we deprived alpha1(H101R) mutant mice with zolpidem-insensitive alpha1-containing GABA(A) receptors. In these mice and matched wild-type controls, IPSC decay kinetics in LTS cells were faster after whisker removal; however, the deprivation-induced sensitivity to zolpidem was reduced in alpha1(H101R) mice. These data illustrate a change of synaptic inhibition in LTS cells via an increase in alpha1-subunit-mediated function. Because alpha1 subunits are commonly associated with circuit-specific plasticity in sensory cortex, this switch in LTS cell synaptic inhibition may signal necessary circuit changes required for plastic adjustments in sensory-deprived cortex. PMID:19584253
Li, Peijun; Rudolph, Uwe; Huntsman, Molly M
Research on the senses spans the enormous range from analysis of individual molecules involved in sensory transduction to the attempted elucidation of conscious sensation. Because the variety of conceptual and experimental approaches varies so broadly across the field, it is impossible to delineate a single direction for future research. Two trends are nonetheless apparent. At the reductionistic end of the spectrum, in the analysis of sensory transduction, studies on all the senses will increasingly be driven by the techniques of molecular biology. The advent of techniques for producing cDNA libraries from small ensembles of receptor cells, or even from individual cells, will permit the recognition of new constituents of receptor cells and of factors involved in their specification, differentiation, and maintenance. In the integrative realm of sensory neurobiology, future studies will increasingly rely on optical techniques for the study of activity patterns on the surfaces of sensory areas of the cerebral cortex and on noninvasive functional imaging for the investigation of neural responses in human subjects. These techniques will continue to strengthen our understanding of the relation between neuronal activity and conscious sensory experience. PMID:9751666
Hudspeth, A J; Tanaka, K
Recovery of mimic function after facial nerve transection is poor: the successful regrowth of axotomized motoneurons to their targets is compromised by (1) poor axonal navigation and excessive collateral branching, (2) abnormal exchange of nerve impulses between adjacent regrowing axons, and (3) insufficient synaptic input to facial motoneurons. As a result, axotomized motoneurons get hyperexcitable and unable to discharge. Since improvement of growth cone navigation and reduction of the ephaptic cross talk between axons turn out be very difficult, we concentrated our efforts on the third detrimental component and proposed that an intensification of the trigeminal input to axotomized electrophysiologically silent facial motoneurons might improve specificity of reinnervation. To test our hypothesis we compared behavioral, electrophysiological, and morphological parameters after single reconstructive surgery on the facial nerve (or its buccal branch) with those obtained after identical facial nerve surgery but combined with direct or indirect stimulation of the ipsilateral infraorbital (ION) nerve. We found that in all cases, trigeminal stimulation was beneficial for the outcome by improving the quality of target reinnervation and recovery of vibrissa! motor performance. PMID:23322155
Skouras, Emmanouil; Pavlov, Stoyan; Bendella, Habib; Angelov, Doychin N
Children, in contrast to adults, show an excellent clinical recovery after a peripheral nerve injury, which may be explained by better peripheral nerve regeneration and a superior plasticity in the young brain. Our aim was to study the long-term electrophysiological outcome after nerve repair in children and young adults and to compare it with the clinical outcome. Forty-four patients, injured at an age younger than 21 years, were assessed by electrophysiology (amplitude, conduction velocity and distal motor latency) at a median of 31 years after a complete median or ulnar nerve injury at the level of the forearm. Electrophysiological evaluation showed pathology in all parameters and in all patients, irrespective of age at injury. No significant differences were observed in the electrophysiological results between those injured in childhood, that is, before the age of 12 years, and those injured in adolescence, that is, between 12 and 20 years of age. In contrast, the clinical nerve function was significantly better for those injured in childhood (87% of complete recovery, P=0.002) compared with those injured in adolescence. We conclude that the mechanism behind the superior clinical outcome in children is not located at the periphery, but is explained by cerebral plasticity. PMID:23142851
Chemnitz, Anette; Andersson, Gert; Rosén, Birgitta; Dahlin, Lars B; Björkman, Anders
Cutaneous afferent activities recorded by a nerve cuff electrode have been used to detect the stance phase in a functional electrical stimulation system for foot drop correction. However, the implantation procedure was difficult, as the cuff electrode had to be located on the distal branches of a multi-fascicular nerve to exclude muscle afferent and efferent activities. This paper proposes a new gait phase detection scheme that can be applied to a proximal nerve root that includes cutaneous afferent fibers as well as muscle afferent and efferent fibers. To test the feasibility of this scheme, electroneurogram (ENG) signals were measured from the rat sciatic nerve during treadmill walking at several speeds, and the signal properties of the sciatic nerve were analyzed for a comparison with kinematic data from the ankle joint. On the basis of these experiments, a wavelet packet transform was tested to define a feature vector from the sciatic ENG signals according to the gait phases. We also propose a Gaussian mixture model (GMM) classifier and investigate whether it could be used successfully to discriminate feature vectors into the stance and swing phases. In spite of no significant differences in the rectified bin-integrated values between the stance and swing phases, the sciatic ENG signals could be reliably classified using the proposed wavelet packet transform and GMM classification methods. PMID:23604025
Chu, Jun-Uk; Song, Kang-Il; Han, Sungmin; Lee, Soo Hyun; Kang, Ji Yoon; Hwang, Dosik; Suh, Jun-Kyo Francis; Choi, Kuiwon; Youn, Inchan
In this study we examined the effect of leukemia inhibitory factor (LIF) on delayed repair of injured nerves. In a standard entubulation gap repair model of sciatic nerve in the rat, repair was performed immediately and after delays of 1 day, 1 week, and 4 weeks. Repaired nerves were treated with either LIF (10 ng) or saline, and assessment was by muscle mass and force contraction at 12 weeks after repair. After immediate nerve repair LIF administration resulted in 2.5- to 3-fold improvements compared with saline. In the 1-day delayed group, both saline and LIF treatment groups were comparable with that achieved with immediate repair combined with LIF. This result is consistent with the concept of preconditioning. In the 1-week delayed repair groups with LIF, muscle mass recovery and maximum force contraction were improved by 32% and 55%, respectively, compared with saline, whereas repairs delayed for 4 weeks showed increases of 50% and 36%. All delayed repairs treated with LIF were more effective than immediate repair with saline, but not as effective as primary repair with LIF. Our findings support the view that factors such as LIF may be efficacious for improving recovery of function in cases of delayed peripheral nerve repair. PMID:12457356
Brown, David L; Bennett, Timothy M; Dowsing, Bruce J; Hayes, Alan; Abate, Massimo; Morrison, Wayne A
Background Functional ability following nerve transfer for upper brachial plexus injuries relies on both the function and magnitude of force recovery of targeted muscles. Following nerve transfers targeting either the axillary nerve, suprascapular nerve, or both, it is unclear whether functional ability is restored in face of limited muscle force recovery. Methods We used a computer model to simulate flexing the elbow while maintaining a functional shoulder posture for 3 nerve transfer scenarios. The minimum restored force capacity necessary to perform the task, associated compensations by neighboring muscles, and the effect of altered muscle coordination on movement effort, were assessed. Results The minimum force restored by the axillary, suprascapular, and combined nerve transfers that was required for the model to simulate the desired movement was 25%, 40%, and 15% of the unimpaired muscle force capacity, respectively. When the deltoid was paralyzed, the infraspinatus and subscapularis muscles generated higher shoulder abduction moments to compensate for deltoid weakness. For all scenarios, movement effort increased as restored force capacity decreased. Conclusions Combined axillary and suprascapular nerve transfer required the least restored force capacity to perform the desired elbow flexion task, while single suprascapular nerve transfer required the most restored force capacity to perform the same task. Though compensation mechanisms allowed all scenarios to perform the desired movement despite weakened shoulder muscles, compensation increased movement effort. Dynamic simulations allowed independent evaluation of the effect of restored force capacity on functional outcome in a way that is not possible experimentally. Clinical Relevance Simultaneous nerve transfer to suprascapular and axillary nerves yields the best simulated biomechanical outcome for lower magnitudes of muscle force recovery in this computer model. Axillary nerve transfer performs nearly as well as the combined transfer, while suprascapular nerve transfer is more sensitive to the magnitude of reinnervation and therefore avoided.
Crouch, Dustin L.; Li, Zhongyu; Barnwell, Jonathan C.; Plate, Johannes F.; Daly, Melissa; Saul, Katherine R.
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:23102114
Chuang, Ting-Hsien; Wilson, Robin E; Love, James M; Fisher, John P; Shah, Sameer B
Background Sciatic nerve injuries often cause partial or total loss of motor, sensory and autonomic functions due to the axon discontinuity, degeneration, and eventual death which finally result in substantial functional loss and decreased quality of life. Nerve growth factor (NGF) plays a critical role in peripheral nerve regeneration. However, the lack of efficient NGF delivery approach limits its clinical applications. We reported here by fusing with the N-terminal domain of agrin (NtA), NGF-? could target to nerve cells and improve nerve regeneration. Methods Laminin-binding assay and sustained release assay of NGF-? fused with NtA (LBD-NGF) from laminin in vitro were carried out. The bioactivity of LBD-NGF on laminin in vitro was also measured. Using the rat sciatic nerve crush injury model, the nerve repair and functional restoration by utilizing LBD-NGF were tested. Findings LBD-NGF could specifically bind to laminin and maintain NGF activity both in vitro and in vivo. In the rat sciatic nerve crush injury model, we found that LBD-NGF could be retained and concentrated at the nerve injury sites to promote nerve repair and enhance functional restoration following nerve damages. Conclusion Fused with NtA, NGF-? could bind to laminin specifically. Since laminin is the major component of nerve extracellular matrix, laminin binding NGF could target to nerve cells and improve the repair of peripheral nerve injuries.
Sun, Wenjie; Sun, Changkai; Zhao, Hui; Lin, Hang; Han, Qianqian; Wang, Jingyu; Ma, Hui; Chen, Bing; Xiao, Zhifeng; Dai, Jianwu
Extensive research has focused on transplantation of pluripo- tent stem cells for the treatment of central nervous system disorders, the therapeutic potential of stem cell therapy for injured peripheral nerves is largely unknown. We used a rat sciatic nerve transection model to test the ability of implanted embryonic stem (ES) cell-derived neural progenitor cells (ES- NPCs) in promoting repair of
Lin Cui; Jun Jiang; Ling Wei; Xin Zhou; Jamie L. Fraser; B. Joy Snider; Shan Ping Yu
The objective of the study was to evaluate unilateral nerve sparing prostate surgery. Patient files of men who underwent unilateral nerve sparing radical prostatectomy were analyzed retrospectively after a minimum follow-up period of 18 months. Of 46 patients who received unilateral nerve sparing surgery, 14 (30.4%) regained full potency after surgery. In 92.9% of these patients, recovery occurred within a period of 18 months. Age is the single most important factor in the recuperation of potency after unilateral nerve sparing surgery. Most of the patients (84.8%) reported the ability to achieve orgasm. Of eight patients with positive section margins, two had positive section margins at the spared side only. Unilateral nerve sparing surgery remains a feasible treatment option for prostate cancer. PMID:12664068
Van der Aa, F; Joniau, S; De Ridder, D; Van Poppel, H
Summary Image-analysis was used to measure nerves immunoreactive to the general neuronal marker protein gene product 9.5 (PGP 9.5-IR) and the neuropeptides calcitonin gene-related peptide and vasoactive intestinal polypeptide in standardised leg skin biopsies of three age-matched groups of young subjects: non-diabetic (n=14), diabetic patients with normal small fibre function (non-neuropathic, (n=11) and diabetic patients with abnormal small fibre function (neuropathic,
D. M. Levy; G. Terenghi; X.-H. Gu; R. R. Abraham; D. R. Springall; J. M. Polak
Background The definitive diagnosis of glaucoma is currently based on congruent damage to both optic nerve structure and function. Given\\u000a widespread quantitative assessment of both structure (imaging) and function (automated perimetry) in glaucoma, it should be\\u000a possible to combine these quantitative data to diagnose disease. We have therefore defined and tested a new approach to glaucoma\\u000a diagnosis by combining imaging and
Michael V Boland; Harry A Quigley
Background The molecular mechanisms responsible for the survival and preservation of function for adult parasympathetic ganglion neurons following injury remain incompletely understood. However, advances in the neurobiology of growth factors, neural development, and prevention of cell death have led to a surge of clinical interest for protective and regenerative neuromodulatory strategies, as surgical therapies for prostate, bladder, and colorectal cancers often result in neuronal axotomy and debilitating loss of sexual function or continence. In vitro studies have identified neurturin, a glial cell line-derived neurotrophic factor, as a neuromodulator for pelvic cholinergic neurons. We present the first in vivo report of the effects of neurturin upon the recovery of erectile function following bilateral cavernous nerve crush injury in the rat. Methods In these experiments, groups (n = 8 each) consisted of uninjured controls and animals treated with injection of albumin (blinded crush control group), extended release neurotrophin-4 or neurturin to the site of cavernous nerve crush injury (100 ?g per animal). After 5 weeks, recovery of erectile function (treatment effect) was assessed by cavernous nerve electrostimulation and peak aortic pressures were measured. Investigators were unblinded to specific treatments after statistical analyses were completed. Results Erectile dysfunction was not observed in the sham group (mean maximal intracavernous pressure [ICP] increase of 117.5 ± 7.3 cmH2O), whereas nerve injury and albumin treatment (control) produced a significant reduction in ICP elevation of 40.0 ± 6.3 cmH2O. Neurturin facilitated the preservation of erectile function, with an ICP increase of 55% at 62.0 ± 9.2 cmH2O (p < 0.05 vs control). Extended release neurotrophin-4 did not significantly enhance recovery of erectile function with an ICP change of 46.9 ± 9.6. Peak aortic blood pressures did not differ between groups. No significant pre- and post-treatment weight differences were observed between control, neurotrophin-4 and neurturin cohorts. All animals tolerated the five-week treatment course. Conclusion Treatment with neurturin at the site of cavernous nerve crush injury facilitates recovery of erectile function. Results support further investigation of neurturin as a neuroprotective and/or neuroregenerative agent facilitating functional recovery after cavernous or other pelvic autonomic nerve injuries.
Bella, Anthony J; Fandel, Thomas M; Tantiwongse, Kavirach; Brant, William O; Klein, Robert D; Garcia, Carlos A; Lue, Tom F
Gestational exposure to environmental contaminants such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) poses a significant threat to normal growth and differentiation of the developing brain. To characterize the impact of gestational TCDD exposure on subsequent cortical function, pregnant Long Evans rats were exposed to a single acute dose (100 or 700ng/kg b.w. via gavage) on gestational day 15. This dosing regimen had no significant effect on birth index. After the TCDD-exposed animals were born and reached maturity, neural activity was recorded under urethane anesthesia from neurons in primary somatic sensory cortex. Spontaneous activity was reduced by approximately 50% in barrel cortex compared to corn oil vehicle controls. The magnitude of neuronal response to sensory (whisker) stimuli also was significantly reduced, and responses did not achieve control levels at any stimulus intensity. The greatest deficit was in the short latency component of the cortical responses. These decrements in cortical responsiveness were present in young F1 generation TCDD-exposed animals and persisted for up to 180 days. Because glutamate receptors are crucial to the evoked responses and show developmental regulation, selected iontotropic glutamate receptor subunits (NMDA NR2A+NR2B and GluR1) were profiled for RNA levels in the cortex of F1 generation rats. The expression of NR2B (NMDA receptor) and GluR1 (AMPA receptor) subunits was significantly reduced in the TCDD-exposed F1 generation animals compared to vehicle controls. The results indicate that gestational TCDD exposure results in cortical deficits that are paralled by diminished expression of certain NMDA and AMPA receptor subunits at a time when synapses are being formed for the first time in cortex. PMID:16839606
Hood, Darryl B; Woods, Letha; Brown, La'nissa; Johnson, Salynn; Ebner, Ford F
A major limitation in the utilization of a functional electrical stimulation (FES) orthosis for routine, daily standing and walking of the spinal-cord-injured person is that visual monitoring is required to maintain balance and the walking pace. For standing and walking to be continuous and automatic with such an orthosis, a closed-loop sensory feedback system is proposed and evaluated; it provides vibrotactile feedback as a substitute to one's own visual sensation. Eight blindfolded experimental subjects were utilized as 'imitators' to interpret the footfalls of a second person (the pace setter). The experimental objective was to test the hypothesis that sufficient information could be transferred by way of the sensory (tactile) feedback system to the 'imitator' and to determine effectively foot position and anticipate the next step of the pacesetter. Quantitative analysis evaluated the effect of three different levels of training, under two different levels of cognitive load. The results disclosed a significant improvement in subject performance at the higher training levels compared with the 'no training' level (P = 0.01). Neither the cognitive load nor the interaction of training and cognitive load altered significantly the effect of training on subject performance. The experimental hypothesis is therefore satisfied that sufficient information was indeed transferred using the apparatus described. Such information (when utilized in conjunction with a thorough training programme) could be used in a practical sense by a paraplegic individual to interpret his own foot steps. Through continued use and training, it is likely that this information could become subconscious and automatic.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:2033956
Phillips, C A; Koubek, R J; Hendershot, D M
Purpose To test the hypothesis that alterations of RNFL birefringence precede changes in RNFL thickness (RNFLT) in an experimental model of RGC injury. Secondarily, to determine the time course of RGC functional abnormalities relative to RNFL birefringence and RNFL thickness changes. Methods RNFL birefringence was measured by scanning laser polarimetery (GDx VCC, Carl Zeiss Meditec, Inc). RNFL thickness was measured by spectral domain optical coherence tomography (sd-OCT, Spectralis™ HRA+OCT, Heidelberg Engineering, GmbH). Retinal function was assessed by three forms of electroretinography (ERG): slow-sequence multifocal ERG (mfERG, VERIS, EDI); pattern-reversal ERG (PERG, Utas-E3000, LKC Technologies, Inc); and photopic full-field flash ERG (ff-ERG, Utas-E3000). All measurements were obtained in both eyes of four adult rhesus macaque monkeys (Macaca mulatta) during two baseline sessions, and again 1-week and 2-weeks after unilateral optic nerve transection (ONT). Results ONT was successfully completed in 3 subjects. RNFL birefringence declined by 15% one week after ONT (p = 0.043), while there was no significant change in RNFL thickness (+1%, p = 0.42). Two weeks after ONT, RNFL retardance had declined by 39% (p = 0.018) while RNFL thickness had declined by only 15% (p = 0.025). RGC functional abnormalities were present 1-week after ONT, including decreased amplitudes relative to baseline of the mfERG high frequency components (?65%, p = 0.018); the PERG N95 component (?70%, p = 0.007) and the photopic negative response of the ff-ERG (?44%, p = 0.005). Conclusions RNFL birefringence declined prior to, and faster than RNFL thickness after ONT. RGC functional abnormalities were present 1-week after ONT, when RNFL thickness had not yet begun to change. RNFL birefringence changes after acute RGC injury are associated with RGC dysfunction. Together, they reflect RGC abnormalities that precede axonal caliber changes and loss.
Fortune, Brad; Cull, Grant A.; Burgoyne, Claude F.
The human body has five basic sensory functions: touch, vision, hearing, taste, and smell. The effectiveness of one or more of these human sensory functions can be impaired as a result of trauma, congenital defects, or the normal ageing process. Converting one type of function into another, or translating a function to a different part of the body, could result in a better quality of life for a person with diminished sensorial capabilities.
The topography of primary sensory cortical hand area following a monohemispheric lesion (sudden=stroke; progressive=neoplasm) was investigated in relationship with clinical recovery of sensorimotor deficits. Twenty seven patients with monohemispheric lesions were studied in a clinically stabilized condition. Functional informations from magnetoencephalography (MEG) were integrated with anatomical data from magnetic resonance imaging (MRI). MEG localizations of the neurons firing at early
P. M Rossini; F Tecchio; V Pizzella; D Lupoi; E Cassetta; P Pasqualetti; G. L Romani; A Orlacchio
Background: Schizophrenic disorders are thought to involve widespread abnormalities in information pro- cessing. The present study used functional magnetic reso- nance imaging and a simple and robust paradigm that involved auditory and visual activation to examine ba- sic sensory input circuits. Our aim was to determine which stages of the input processing network are disturbed in first-episode schizophrenic patients. Methods:
Dieter F. Braus; Wolfgang Weber-Fahr; Heike Tost; Matthias Ruf; Fritz A. Henn
Extracellular purines play multiple roles in a variety of sensory systems acting as neural signalling and humoral factors via purinoceptors. For example, ATP and adenosine have a neurosignalling role in autonomic sensory–motor reflexes, mechanoreception and chemoreception mediated via vagus nerve afferents, and in nociception. Purinergic neuromodulation of vision via adenosine in the retina is well established and there is mounting
Peter R. Thorne; Gary D. Housley
Polymersomes are nanosized vesicles formed from amphiphilic block copolymers, and have been identified as potential drug delivery vehicles to the inner ear. The aim of this study was to provide targeting to specific cells within the inner ear by functionalizing the polymersome surface with Tet1 peptide sequence. Tet1 peptide specifically binds to the trisialoganglioside clostridial toxin receptor on neurons and was expected to target the polymersomes toward the cochlear nerve. The Tet1 functionalized PEG-b-PCL polymersomes were administered using routine drug delivery routes: transtympanic injection and cochleostomy. Delivery via cochleostomy of Tet1 functionalized polymersomes resulted in cochlear nerve targeting; in contrast this was not seen after transtympanic injection. PMID:22403485
Zhang, Ya; Zhang, Weikai; Johnston, Alexander H; Newman, Tracey A; Pyykkö, Ilmari; Zou, Jing
In animal models of peripheral nerve injury, leukemia inhibitory factor (LIF) is normally expressed at very low levels. Following nerve injury, its expression is rapidly increased in the nerve at the injury site and promotes both sensory and motor neuron survival. Once normal nerve function is restored, LIF expression returns to negligible levels. For this reason, LIF is considered to be a peripheral nerve trauma factor. We wished to determine whether LIF is also upregulated in human nerves following trauma and whether it is expressed in neuromas of varying age. Immunohistochemical staining for the presence of LIF was performed on injured and control human nerves from a number of subjects. Results demonstrate that LIF expression is increased in nerves within hours of injury and, in the case of neuroma formation, can persist for several years. LIF immunoreactivity was consistently found in Schwann cells, in peripheral nerve axons, and, at stages when an inflammatory response was present, also in neutrophils, mast cells, macrophages, and blood vessel walls. The level of staining within the connective tissue of injured nerves was elevated compared to control nerves, which may be due to the presence of LIF bound to the soluble secreted form of the LIF receptor. Whether the continued expression of LIF is unhealed injured nerves promotes the development of neuromas remains to be resolved. PMID:11721746
Dowsing, B J; Romeo, R; Morrison, W A
A significant fraction of military soldiers sustain nerve injury and use tobacco or nicotine containing products. Healing of nerve injuries is influenced by many factors, such as degree of original injury, healing potential of the nerve, and general health of patient. However, recently, it has been demonstrated that the presence of retained insoluble metal fragments decreases healing. The effects of systemic nicotine administration, with or without metal fragments at the site of nerve injury, were evaluated. Both the nicotine-administered groups (nicotine, nicotine + shrapnel) showed significant increase in the peroneal function compared with untreated controls, as assessed by paw area (p < 0.05). Furthermore, to test possible role of altered sensory function, we used the hot plate assay. Latency to withdraw paw from a hot plate was significantly shorter in nicotine groups (p < 0.05). These data indicate that nicotine improves sensory and motor aspects of nerve function, in the presence or absence of shrapnel. PMID:22165666
Rittenhouse, Bradley; Hill-Pryor, Crystal D; McConathy, Adam; Parker, Peter; Franco, Nelson; Toussaint, Esra; Barker, Darrell; Prasad, Balakrishna; Pizarro, Jose M
Studies of the effects of lead absorption on sensory evoked and slow brain potentials in children are reviewed. Studies of slow wave voltage in children during sensory conditioning indicated a linear relationship to blood lead level in two studies; an effect that could not be rep...
Distinct classes of primary sensory neurons in dorsal root ganglia subserve different sensory modalities, terminate in different dorsoventral locations in the spinal cord, and display different neurotrophin response profiles. Large diameter muscle afferents that terminate in the ventral spinal cord are NT-3 responsive, whereas small diameter afferents subserving pain and temperature are NGF responsive and terminate in the dorsal spinal
Elizabeth K Messersmith; E. David Leonardo; Carla J Shatz; Marc Tessier-Lavigne; Corey S Goodman; Alex L Kolodkin
ome nerve injuries require repair in order to regain sen- sory or motor function. Although this article focuses pri- marily on trigeminal nerve (TN) injuries and repairs, the facts presented may apply to any peripheral nerve repair. The primary indications for nerve repair or grafting are 1) an injury or continuity defect in a nerve, as a result of trauma,
LARRY M. WOLFORD; EBER L. L. STEVAO
ABSTRACT Purpose: To evaluate the effectiveness of muscle rehabilitation modalities, it is first necessary to develop a model to test measures that would assess physiological, sensory, and functional muscle recovery. This study attempted to develop such a model for wrist injury. Subjects: Healthy male and female adults (n = 25). Methods: Subjects performed wrist muscle damage assessment, soreness, discomfort, difficulty, and functional motor task tests before and 1, 2, and 7 days after eccentric wrist muscle contractions. Wrist-related motor task tests, including the perception of discomfort and difficulty during performance, were also conducted. Results: At 24 hours post–eccentric exercises, wrist extension and flexion force declined (p < 0.05) and soreness (p < 0.05) and circumference (p < 0.05) increased; all returned to normal by 7 days post-exercise. At 24 and 48 hours post-exercise, perception of discomfort and difficulty was elevated during performance of motor tasks (p < 0.05). The completion speed of motor tasks was unaffected at any time post–eccentric exercise (p > 0.05). Conclusions: Loss of wrist muscle force, increased soreness, task discomfort, and difficulty were noted following eccentric exercise. However, subjects appeared able to compensate, such that the speed of completion of motor tasks was not slowed. Longer or more specific motor tasks may be necessary to mimic real work performance decrement and recovery.
Brown, Lindsay; Brant, Aron; Enns, Deborah; Bryden, Pamela J.
Pain is one of the most severe and debilitating symptoms associated with several forms of cancer. Various types of carcinomas and sarcomas metastasize to skeletal bones and cause spontaneous bone pain and hyperalgesia, which is accompanied by bone degradation and remodeling of peripheral nerves. Despite recent advances, the molecular mechanisms underlying the development and maintenance of cancer-evoked pain are not well understood. Several types of non-hematopoietic tumors secrete hematopoietic colony-stimulating factors that act on myeloid cells and tumor cells. Here we report that receptors and signaling mediators of granulocyte- and granulocyte-macrophage colony-stimulating factors (G-CSF and GM-CSF) are also functionally expressed on sensory nerves. GM-CSF sensitized nerves to mechanical stimuli in vitro and in vivo, potentiated CGRP release and caused sprouting of sensory nerve endings in the skin. Interruption of G-CSF and GM-CSF signaling in vivo led to reduced tumor growth and nerve remodeling, and abrogated bone cancer pain. The key significance of GM-CSF signaling in sensory neurons was revealed by an attenuation of tumor-evoked pain following a sensory nerve-specific knockdown of GM-CSF receptors. These results show that G-CSF and GM-CSF are important in tumor-nerve interactions and suggest that their receptors on primary afferent nerve fibers constitute potential therapeutic targets in cancer pain. PMID:19525966
Schweizerhof, Matthias; Stösser, Sebastian; Kurejova, Martina; Njoo, Christian; Gangadharan, Vijayan; Agarwal, Nitin; Schmelz, Martin; Bali, Kiran Kumar; Michalski, Christoph W; Brugger, Stefan; Dickenson, Anthony; Simone, Donald A; Kuner, Rohini
Coronary vasospasm and diminished coronary blood flow reserve have often been reported in patients with hypertrophic cardiomyopathy (HCM). However, the mechanism of coronary spasm in HCM is unknown. Thus, coronary endothelial function and sympathetic nerve function in 11 patients with HCM and 11 control patients matched for age and sex were examined. The diameter of the left anterior descending coronary artery was assessed by quantitative coronary angiography, and the change in coronary blood flow was estimated using an intracoronary Doppler flow wire. To assess myocardial sympathetic nerve function, metaiodobenzylguanidine images – 15 min and 180 min after the injection of 123I-metaiodoben-zylguanidine at a dosage of 111 MBq – were obtained, and the heart to mediastinum (H/M) count ratio and the washout rate (WR) were calculated. The H/M ratio was significantly lower in patients with HCM (2.1±0.3) than in control patients (2.6±0.4) (P<0.01). In addition, the WR was higher in patients with HCM (35±6%) than in control patients (28±3%) (P<0.01). The HCM subjects with coronary spasm had lower H/M ratios and higher WRs than HCM subjects without coronary spasm (P<0.05, respectively). In conclusion, impaired sympathetic nerve function may be associated with coronary vasospasm and diminished coronary blood flow reserve in HCM.
Matsuo, Shinro; Matsumoto, Tetsuya; Nakae, Ichiro; Horie, Minoru
Neurites of nerve growth factor-enhanced fetal mouse dorsal root ganglion cells can not only establish characteristic sensory synaptic network functions in dorsal regions of attached spinal cord explants, but some of the neurites may grow through the cord tissue in these cultures and make similar functional synaptic connections with specific types of \\
Stanley M. Crain; Edith R. Peterson
We report use of thin films of the nematic liquid crystal E7 supported on chemically functionalized surfaces to indicate the presence of vapors of the organophosphorous nerve agents sarin (GB), soman (GD), tabun (GA) and VX. The surfaces were prepared by the deposition of metal perchlorate salts onto carboxylic acid-terminated self-assembled monolayers. When using surfaces prepared from aluminum perchlorate salts,
Katie D. Cadwell; Nathan A. Lockwood; Barbara A. Nellis; Mahriah E. Alf; Colin R. Willis; Nicholas L. Abbott
A 58-year-old woman with chronic renal failure had been undergoing maintenance hemodialysis. Ampulla cardiomyopathy recurred in association with prolonged sympathetic nerve function disorder. Periodical evaluation of the patient's condition using 123I-metaiodobenzylguanidine (MIBG) myocardial scintigraphy was continued since the first attack at age 55 years. The initial washout rate was high at 58.3%, and was still high at 33.0% when she was discharged following improvement in wall motion, and remained high at 45.4% 1 year after discharge. Recurrence occurred at age 58 years, when a high washout rate of 48.6% was observed. High washout rate values of 49.5% and 40.1% were also observed 2 and 9 months after discharge, respectively, following improvement in wall motion abnormalities. 123I-MIBG can be used to assess the course of recurrent ampulla cardiomyopathy, and can objectively evaluate sympathetic nerve function disorders. This interesting case suggests that sympathetic nerve function disorder is closely related to the pathophysiology of this disorder. PMID:17552294
Kawase, Tomoharu; Yamashina, Shohei; Nanjo, Shuji; Kiuchi, Shunsuke; Inoue, Aritomo; Nakano, Hajime; Yamazaki, Junichi
Traumatic brain injury (TBI) induces transient or persistent dysfunction of gait and balance. Enhancement of cholinergic transmission has been reported to accelerate recovery of cognitive function after TBI, but the effects of this intervention on locomotor activity remain largely unexplored. The hypothesis that enhancement of cholinergic function by inhibition of acetylcholinesterase (AChE) improves locomotion following TBI was tested in Sprague-Dawley male rats after a unilateral controlled cortical impact (CCI) injury of the motor-sensory cortex. Locomotion was tested by time to fall on the constant speed and accelerating Rotarod, placement errors and time to cross while walking through a horizontal ladder, activity monitoring in the home cages, and rearing behavior. Assessments were performed the 1st and 2nd day and the 1st, 2nd, and 3rd week after TBI. The AChE inhibitor physostigmine hemisulfate (PHY) was administered continuously via osmotic minipumps implanted subcutaneously at the rates of 1.6-12.8??mol/kg/day. All measures of locomotion were impaired by TBI and recovered to initial levels between 1 and 3 weeks post-TBI, with the exception of the maximum speed achievable on the accelerating Rotarod, as well as rearing in the open field. PHY improved performance in the accelerating Rotarod at 1.6 and 3.2??mol/kg/day (AChE activity 95 and 78% of control, respectively), however, higher doses induced progressive deterioration. No effect or worsening of outcomes was observed at all PHY doses for home cage activity, rearing, and horizontal ladder walking. Potential benefits of cholinesterase inhibition on locomotor function have to be weighed against the evidence of the narrow range of useful doses. PMID:21787180
Holschneider, Daniel P; Guo, Yumei; Roch, Margareth; Norman, Keith M; Scremin, Oscar U
Muscle degeneration and impairment following nerve injury could lead to apoptosis as a result of increased levels of reactive oxygen species. This activates the apoptotic cascade through mitochondrial dysfunction and damage to lipids, proteins, and DNA. In considering of the multifactorial protective properties of green tea polyphenols (-)-epigallocatechin-3-gallate (EGCG), this study investigates whether EGCG treatment does improve skeletal muscle function impairments, induced by crushing of the sciatic nerve. Compared to the saline-treated injured group of animals, EGCG treatment of axonotomized animals showed significant motor enhancement in the toe spread and foot positioning analysis and gain in the percentage motor deficit. The proprioceptive function expressed by the hopping response showed significant progression in the EGCG-treated group. Recovery of sensory innervation was followed by a slowly retreating neuropathic pain-like syndrome in the EGCG-treated animals. Muscle tissues from injured limb showed severe histopathological alterations that were significantly attenuated by EGCG treatment at the end of week 3 post-surgery. Semi-quantitative desmin immunohistochemistry revealed intense staining in the saline-treated injured animals, whereas EGCG treatment decreased the desmin immunoreactivity back to sham control levels. Using RT-PCR, EGCG treatment induced a significant anti-apoptotic effect in injured muscle tissues by normalizing the Bax/Bcl-2 ratio back to baseline levels and inhibiting overexpression of the p53 apoptotic gene at days 3 and 7 post-surgery. In conclusion, our results demonstrate that EGCG enhances functional recovery, protects muscle fibers from cellular death by activating anti-apoptotic signaling pathway, and improves morphological recovery in skeletal muscle after nerve injuries. PMID:22573016
Renno, Waleed M; Al-Maghrebi, May; Al-Banaw, Anwar
Rodents vary the frequency of whisking movements during exploratory and discriminatory behaviours. The effect of whisking frequency on whisker cortical maps was investigated by simulating whisking at physiological frequencies and imaging the whisker representations with blood-oxygen-level-dependent (BOLD) functional magnetic resonance imaging (fMRI). Repetitive deflection of many right-sided whiskers at 10 Hz evoked a positive BOLD response that extended across contralateral primary somatosensory cortex (SI) and secondary somatosensory cortex (SII). In contrast, synchronous deflection of two adjacent whiskers (right C1 and C2) at 10 Hz evoked separate positive BOLD responses in contralateral SI and SII that were predominantly located in upper cortical layers. The positive BOLD responses were separated and partially surrounded by a negative BOLD response that was mainly in lower cortical layers. Two-whisker representations varied with the frequency of simulated whisking. Positive BOLD responses were largest with 7 Hz deflection. Negative BOLD responses were robust at 10 Hz, but were weaker or absent with 7 Hz or 3 Hz deflection. Our findings suggest that sensory inputs attributable to the frequency of whisking movements modify whisker cortical representations.
de Celis Alonso, Benito; Lowe, Andrew S.; Dear, John P.; Lee, Kalok C.; Williams, Steven C. R.; Finnerty, Gerald T.
PurposeBotulinum neurotoxin type A (BoNT\\/A) is effective in the treatment of intractable detrusor overactivity (DO). In addition to its known inhibitory effect on presynaptic release of acetylcholine by motor terminals, there is increasing evidence that BoNT\\/A may affect sensory fibers. We investigated a possible effect of BoNT\\/A on human bladder afferent mechanisms by studying the sensory receptors P2X3 and TRPV1
A. APOSTOLIDIS; R. POPAT; Y. YIANGOU; D. COCKAYNE; A. P. D. W. FORD; J. B. DAVIS; P. DASGUPTA; C. J. FOWLER; P. ANAND
Introduction: Many studies have demonstrated the existence of an anti-inflammatory, parasympathetic pathway, termed as the inflammatory reflex. Burn-induced heart failure has been investigated in many previous studies. Proinflammatory cytokines, such as TNF-alpha, IL-1beta, and IL-6, have been shown to play a key pathogenetic role and vagus nerve stimulation attenuates proinflammatory cytokine production. This study was designed to evaluate postburn alterations of cardiac functional parameters after vagal electrostimulation. Material and Methods: A 30% total body surface area standardized, full-thickness rat burn model was used. Electric stimulation of the vagus nerve was performed. The following functional cardiac parameters were measured by ventricular microcatheterization: Maximal and minimal left ventricular pressure, mean left ventricular pressure, end-diastolic pressure (EDP), positive and negative pressure rise and fall (+/-dP/dt), cardiac contractility index, and assessment of the heart rate. Results: Vagus nerve stimulation improved maximal and minimal left ventricular pressure values compared with burn-only animals. End-diastolic pressure was elevated significantly in stimulated animals; however, EDP values were comparable with those in sham-injured animals. Analyzing positive and negative pressure development, +/-dP/dt was restored to levels measured in sham-injured animals but not to control animal levels. No variations in heart rate were found. Conclusion: We as well as others have shown that inflammation after burn injury is a key pathogenetic element, and this study provides new evidence that cardiac function is also improved by vagus nerve stimulation. These results lead us to consider novel therapeutic options for the treatment of postburn cardiac dysfunction. PMID:20596235
Niederbichler, Andreas D; Papst, Stephan; Claassen, Leif; Jokuszies, Andreas; Ipaktchi, Kyros; Reimers, Kerstin; Hirsch, Tobias; Steinstraesser, Lars; Kraft, Theresia; Vogt, Peter M
Several different integrins participate in the complex interactions that promote repair of the peripheral nervous system. The role of the integrin alpha6beta4 in peripheral nerve regeneration was investigated in mice by cre-mediated deletion of the Itgb4 (beta4) gene in Schwann cells. After a crush lesion of the sciatic nerve, the recovery of motor, but not that of sensory, nerve function
C. E. E. M. van der Zee; M. Kreft; G. Beckers; A. Kuipers; A. Sonnenberg
Pathological diagnosis of neuropathy has traditionally depended on ultrastructural examinations of nerve biopsy specimens, particularly for sensory neuropathies affecting unmyelinated and small-myelinated nociceptive nerves. These sensory nerves terminate in the epidermis of the skin, and the pathology of neuropathy usually begins from nerve terminals. We investigated the feasibility of diagnosing small-fiber sensory neuropathy by evaluating cutaneous innervation. Skin biopsy specimens
Hsiung-Fei Chien; To-Jung Tseng; Whei-Min Lin; Chih-Chao Yang; Yang-Chyuan Chang; Rong-Chi Chen; Sung-Tsang Hsieh
Background Functional abdominal pain syndrome (FAPS) has chronic unexplained abdominal pain and is similar to the psychiatric diagnosis of somatoform pain disorder. A patient with irritable bowel syndrome (IBS) also has chronic unexplained abdominal pain, and rectal hypersensitivity is observed in a majority of the patients. However, no reports have evaluated the visceral sensory function of FAPS precisely. We aimed to test the hypothesis that FAPS would show altered visceral sensation compared to healthy controls or IBS. The present study determined the rectal perceptual threshold, intensity of sensation using visual analogue scale (VAS), and rectal compliance in response to rectal balloon distention by a barostat in FAPS, IBS, and healthy controls. Methods First, the ramp distention of 40 ml/min was induced and the thresholds of discomfort, pain, and maximum tolerance (mmHg) were measured. Next, three phasic distentions (60-sec duration separated by 30-sec intervals) of 10, 15 and 20 mmHg were randomly loaded. The subjects were asked to mark the VAS in reference to subjective intensity of sensation immediately after each distention. A pressure-volume relationship was determined by plotting corresponding pressures and volumes during ramp distention, and the compliance was calculated over the linear part of the curve by calculating from the slope of the curve using simple regression. Results Rectal thresholds were significantly reduced in IBS but not in FAPS. The VAS ratings of intensity induced by phasic distention (around the discomfort threshold of the controls) were increased in IBS but significantly decreased in FAPS. Rectal compliance was reduced in IBS but not in FAPS. Conclusion An inconsistency of visceral sensitivity between lower and higher pressure distention might be a key feature for understanding the pathogenesis of FAPS.
Children with autism may have atypical sensory processing abilities, which are known to impact child's performance and participation. However, lack of information exists regarding the expression of these abilities in specific groups on the spectrum, as children with high-functioning autism spectrum disorder (HFASD). This study aimed to characterize the sensory processing abilities of children with HFASD and examine their relationship
Michal Hochhauser; Batya Engel-Yeger
The aim of the present study was to examine the physiological consequences of a unilateral infraorbital nerve lesion and\\u000a its regeneration at different levels of the somatosensory neuraxis. In animals whose right infraorbital nerve had been crushed,\\u000a a large unresponsive area was found in the main brainstem trigeminal nucleus (Pr5). Responses evoked by ipsilateral vibrissal\\u000a deflection in the middle of
Zsolt Kis; Tamás Farkas; Katalin Rábl; Edina Kis; Katalin Kóródi; László Simon; Ildikó Marusin; Imre Rojik; József Toldi
Direct interfacing of transected peripheral nerves with advanced robotic prosthetic devices has been proposed as a strategy for achieving natural motor control and sensory perception of such bionic substitutes, thus fully functionally replacing missing limbs in amputees. Multi-electrode arrays placed in the brain and peripheral nerves have been used successfully to convey neural control of prosthetic devices to the user. However, reactive gliosis, micro hemorrhages, axonopathy and excessive inflammation currently limit their long-term use. Here we demonstrate that enticement of peripheral nerve regeneration through a non-obstructive multi-electrode array, after either acute or chronic nerve amputation, offers a viable alternative to obtain early neural recordings and to enhance long-term interfacing of nerve activity. Non-restrictive electrode arrays placed in the path of regenerating nerve fibers allowed the recording of action potentials as early as 8 days post-implantation with high signal-to-noise ratio, as long as 3 months in some animals, and with minimal inflammation at the nerve tissue-metal electrode interface. Our findings suggest that regenerative multi-electrode arrays of open design allow early and stable interfacing of neural activity from amputated peripheral nerves and might contribute towards conveying full neural control and sensory feedback to users of robotic prosthetic devices. PMID:19506704
Garde, Kshitija; Keefer, Edward; Botterman, Barry; Galvan, Pedro; Romero, Mario I
The present study investigated morpho-functional relations of the aortic depressor nerve (ADN) 5, 15 and 120 days after the onset of streptozotocin-induced diabetes in rats. Time control animals received vehicle. Under pentobarbital anesthesia, ADN activity was recorded simultaneously with arterial pressure. After the recordings, nerves were prepared for light microscopy study and morphometry. ADN function was accessed by means of pressure-nerve activity curve (fitted by sigmoidal regression) and cross-spectral analysis between mean arterial pressure (MAP) and ADN activity. The relation between morphological (myelinated fibers number and density, total myelin area, total fiber area and percentage of occupancy) and functional (gain, signal/noise relation, frequency) parameters were accessed by linear regression analysis and correlation coefficient calculations. Functional parameters obtained by means of the sigmoidal regression curve as well as by cross-spectral analysis were similar in diabetic and control rats. Morphometric parameters of the ADN were similar between groups 5 days after the onset of diabetes. Average myelin area and myelinated fiber area were significantly smaller on diabetic rats 15 and 120 days after the onset of diabetes, being the myelinated fiber and respective axons area and diameter also smaller on 120 days group. Nevertheless, G ratio (ratio between axon and fiber diameter) was nearly 0.6 and not different between groups or experimental times. No significant relationship between morphological and functional parameters was detected in all experimental groups. The present study suggests that ADN diabetic neuropathy was time-dependent, with damage to myelinated fibers to be the primary event, not evidenced by physiological methods. PMID:21108968
do Carmo, Jussara Márcia; Júnior, Rubens Fazan; Salgado, Helio Cesar; Fazan, Valéria Paula Sassoli
Functional properties (anthocyanins, antioxidant, ascorbic acid and tannin) and sensory score were determined in pomegranate\\u000a fruits at two storage temperatures (3 and 5 °C) after treatment with 2 mM putrescine and 1 : 10 carnauba wax (carnauba wax\\u000a : water). The treatments (putrescine and carnauba wax) were given by immersion method followed by storage up to 60 days. Both\\u000a treatments retained significantly higher
Kalyan Barman; Ram Asrey; R. K. Pal; Charanjit Kaur; S. K. Jha
Bacteriorhodopsin (BR) from Halobacterium salinarum as well as halorhodopsin (pHR) and sensory rhodopsin II (pSRII) from Natronobacterium pharaonis were functionally expressed in E. coli using the method of Shimono et al. [FEBS Lett. (1997) 420, 54–56]. The histidine tagged proteins were purified with yields up to 1.0 mg\\/l cell culture and characterized by ESI mass spectrometry and their photocycle. The
Ilja P Hohenfeld; Ansgar A Wegener; Martin Engelhard
Osteocalcin, the most abundant member of the family of extracellular mineral binding gamma-carboxyglutamic acid proteins is synthesized primarily by osteoblasts. Its affinity for calcium ions is believed to limit bone mineralization. Several of the numerous hormones that regulate synthesis of osteocalcin, including glucocorticoids and parathyroid hormone, are also affected by stressful stimuli that require energy for an appropriate response. Based on our observations of OC responding to stressful sensory stimuli, the expression of OC in mouse and rat sensory ganglia was confirmed. It was thus hypothesized that the behavioral responses of the OC knockout mouse to stressful sensory stimuli would be abnormal. To test this hypothesis, behaviors related to sensory aspects of the stress response were quantified in nine groups of mice, aged 4-14 months, comparing knockout with their wild-type counterparts in six distinctly different behavioral tests. Resulting data indicated the following statistically significant differences: open field grooming frequency following saline injection, wild-type > knockout; paw stimulation with Von Frey fibers, knockout < wild-type; balance beam, knockout mobility < WT; thermal sensitivity to heat (tail flick), knockout < wild-type; and cold, knockout < wild-type. Insignificant differences in hanging wire test indicate that these responses are unrelated to reduced muscle strength. Each of these disparate environmental stimuli provided data indicating alterations of responses in knockout mice that suggest participation of osteocalcin in transmission of information about those sensory stimuli. PMID:22350212
Patterson-Buckendahl, Patricia; Sowinska, Agnieszka; Yee, Stephanie; Patel, Dhara; Pagkalinawan, Stephen; Shahid, Muhammad; Shah, Ankit; Franz, Christopher; Benjamin, Daniel E; Pohorecky, Larissa A
Regeneration and Functional Recovery of Intrapelvic Nerves Removed During Extensive Surgery by a New Artificial Nerve Conduit: A Breakthrough to Radical Operation for Locally Advanced and Recurrent Rectal Cancers
Purpose In the current strategy against locally advanced and recurrent rectal cancers possibly involving intrapelvic nerves, there\\u000a has been a serious dilemma between extensive surgery and limited surgery. The former can attain high tumor curability by sacrificing\\u000a the nerve functions while the latter prioritizes the patient quality of life by preserving the nerve functions but with a\\u000a compromised curability. Here we
Hiroyuki Tsujimoto; Tatsuo Nakamura; Tsuneharu Miki; Toshikazu Kubo; Eigo Otsuji; Hisakazu Yamagishi; Akeo Hagiwara
Male-male courtship behavior was recently reported to be induced in large populations of Drosophila (e.g., 600-1500 flies) by ectopic expression of the white (w) gene. Little is known about the basis of this behavior; in male-female courtship, sensory cues are believed to play an important role. Previous data are consistent with the possibility that misexpression of w causes abnormal reception or processing of sensory information. We show here that w-induced male-male courtship occurs in isolated pairs of flies. Thus the behavior does not depend on sensory cues found only among large populations of flies, or on cues produced only by a small subset of such populations. This finding enabled quantitative analysis of mechanisms that underlie the behavior. Specifically, male-male courtship does not depend on the reception of olfactory information, nor on the reception or generation of auditory cues, as determined by surgical ablation of antennae, maxillary palps, or wings. Although the rapid onset of the behavior following w induction suggested that its basis could lie in a modulation of sensory physiology, we found visual, olfactory, and gustatory function to be normal in physiological or behavioral tests. The only sensory deprivation to produce an effect on male-male courtship was testing under dim red light; the percentage of flies courting another male was reduced to one-fourth of control values. A striking age dependence of the behavior is also documented: courtship between paired male mini-w+ flies was not observed in tests of very young (1-day-old) flies, but occurs at high levels between the ages of 1 and 4 weeks. PMID:8844509
Hing, A L; Carlson, J R
Novel silk fibroin conduits were designed with appropriate porosity for peripheral nerve repair. The aim of this work was to utilize these conduits to examine cell inflammatory responses and functional recovery in a sciatic nerve defect model. 45 randomized Lewis rats were utilized to create an 8-mm defect bridged by a silk guide, commercial collagen guide, or an autograft. After 1, 4 and 8 weeks, macrophage recruitment, percentage of newly formed collagen, number of myelinated axons, and gastrocnemius muscle mass were evaluated. Following 8 weeks, ED1+ cells in autograft and silk conduits decreased to < 1% and 17% of week 1 values, respectively. Collagen formation revealed no difference all measured time points, suggesting a similar foreign body response. Myelinated axon counts within the silk guide revealed a greater number of proximal spouts and distal connections than collagen guides. Gastrocnemius weights demonstrated a 27% decrease between silk and autografts after 8 weeks. This study demonstrates that, in addition to tailorable degradation rates, our silk conduits possess a favorable immunogenicity and re-myelination capacity for nerve repair.
Ghaznavi, Amir Mahan; Kokai, Lauren E.; Lovett, Michael L.; Kaplan, David L.; Marra, Kacey G.
1 The ability of intravenous L-DOPA to block sympathetic and parsympathetic nerves has been studied in cats and dogs pretreated with a monoamine oxidase inhibitor. 2 L-DOPA inhibited positive chronotropic and pressor responses to dimethylphenylpiperazinium (DMPP) and McN-A-343 in dogs, and contractions of the nictitating membrane produced by these ganglion stimulants in cats. 3 Responses of the cat nictitating membrane to preganglionic stimulation were inhibited by L-DOPA to a greater extent than those to postganglionic stimulation of the cervical sympathetic chain. 4 In dogs, L-DOPA had no vagolytic action, but depressed vasoconstrictor responses elicited in the perfused hind-limb by electrical stimulation of the lumbar sympathetic chain. 5 The degree of lumbar sympathetic chain inhibition correlated with the pressor response following L-DOPA, and both effects were prevented by prior decarboxylase inhibition. 6 These results suggest that the decarboxylation products of L-DOPA do not impair parasympathetic nerve activity but depress sympathetic nerve function predominantly by inhibiting both muscarinic and nicotinic sites of sympathetic ganglia.
Antonaccio, M.J.; Robson, R.D.
Stimulation of the nervous system by substance P, a G protein-coupled receptor, and subsequent receptor internalization causes dendrites to change their shape from homogeneous cylinders to a heterogeneous string of swollen varicosities (beads) connected by thin segments. In this paper we have analyzed this phenomenon and propose quantitative mechanisms to explain this type of physical shape transformation. We developed a mathematical solution to describe the relationship between the initial radius of a cylindrical nerve fiber and the average radii of the subsequently created varicosities and connecting segments, as well as the periodicity of the varicosities along the nerve fiber. Theoretical predictions are in good agreement with our own and published experimental data from dorsal root ganglion neurons, spinal cord, and brain. Modeling the electrical properties of these beaded fibers has led to an understanding of the functional biophysical consequences of nerve fiber transformation. Several hypotheses for how this shape transformation can be used to process information within the nervous system have been put forth. Images FIGURE 1 FIGURE 6
Tanelian, D L; Markin, V S
Olfactory sensory neurons connect to the antennal lobe of the fly to create the primary units for processing odor cues, the glomeruli. Unique amongst antennal-lobe neurons is an identified wide-field serotonergic neuron, the contralaterally-projecting, serotonin-immunoreactive deutocerebral neuron (CSDn). The CSDn spreads its termini all over the contralateral antennal lobe, suggesting a diffuse neuromodulatory role. A closer examination, however, reveals a restricted pattern of the CSDn arborization in some glomeruli. We show that sensory neuron-derived Eph interacts with Ephrin in the CSDn, to regulate these arborizations. Behavioural analysis of animals with altered Eph-ephrin signaling and with consequent arborization defects suggests that neuromodulation requires local glomerular-specific patterning of the CSDn termini. Our results show the importance of developmental regulation of terminal arborization of even the diffuse modulatory neurons to allow them to route sensory-inputs according to the behavioural contexts. PMID:23637622
Singh, Ajeet Pratap; Das, Rudra Nayan; Rao, Gururaj; Aggarwal, Aman; Diegelmann, Soeren; Evers, Jan Felix; Karandikar, Hrishikesh; Landgraf, Matthias; Rodrigues, Veronica; Vijayraghavan, K
Changes in renal sympathetic nerve activity (SNA) are postulated to influence renal function in selective ways, such that different levels of activation produce particular renal responses, initially in renin release, then sodium excretion, with changes in renal hemodynamics occurring only with much greater stimulus intensities. The aim of this study was to determine the renal hemodynamic and excretory responses to graded physiological increases in renal SNA induced by breathing different hypoxic gas mixtures. Experiments were performed in seven conscious rabbits subjected to four gas mixtures (14% O2, 10% O2, 10% O2 + 3% CO2, and 10% O2 + 5% CO2) and instrumented for recording of renal nerve activity. After a 30-min control period, rabbits were subjected to one of the four gas mixtures for 30 min, and then room air was resumed for a further 30 min. The four gas mixtures increased renal SNA by 14, 38, 49, and 165% respectively, but arterial pressure (thus renal perfusion pressure) was not altered by any of the gas mixtures. The greatest level of sympathetic activation produced significant falls in glomerular filtration rate (GFR), renal blood flow, sodium and fluid excretion, and significant increases in plasma renin activity. These returned to levels not significantly different from control conditions in the 30-min period after the gas mixture. When the changes to the various gas mixtures were analyzed within each rabbit, a significant linear relationship was found with all variables to the increase in SNA. Renal denervation in a separate group of seven rabbits completely abolished all of the above responses to the different gas mixtures. Thus graded activation of renal nerves induced by changes in inspired gas mixtures resulted in graded decreases in renal blood flow, GFR, and sodium excretion and graded increases in renin activity, with the changes occurring across a similar range of nerve activities; there was no evidence for a selective change in any renal variable. PMID:8997344
Malpas, S C; Shweta, A; Anderson, W P; Head, G A
Excitatory postsynaptic potentials and action potentials of neurons of the principal sensory trigeminal nucleus evoked by stimulation of sensory branches of the trigeminal nerves were recorded in cats with intracellular microelectrodes. Neurons of the pri...
Y. P. Limanskii
Excitatory postsynaptic potentials and action potentials of the neurones of main sensory triple nucleus in response to stimulation of sensory branches of the triple nerves of cat have been recorded intracellularly by means of microelectrodes. The neurones...
Y. P. Limanskii
Objective: In the interventional treatment of movement disorders, the thalamic ventral intermediate nucleus (VIM) and the subthalamic nucleus (STN) are the most relevant electrode targets for deep brain stimulation (DBS). This study tested the value of somatosensory evoked potentials (SEP) for the functional identification of VIM and STN. Methods: Median nerve SEP were recorded from the final stimulation electrodes targeted at STN and VIM. Throughout the stereotactic procedure SEP were recorded during short electrode stops above STN/VIM and within the presumed target areas. After digital filtering, high and low frequency SEP components were analysed separately to parameterise both the 1000 Hz SEP burst and low frequency (<100 Hz) components. Results: SEP recorded in the VIM target region could unequivocally be distinguished from SEP recorded in STN. The 1000 Hz burst signal was significantly larger in VIM than in STN without any overlap of amplitude values. In the low frequency band, a primary high amplitude negativity was obtained in VIM, contrasting with a low amplitude positivity in STN. SEP waveshapes in recordings above target positions resembled SEP obtained in STN. When entering VIM, a sharp amplitude increase was observed over a few millimetres only. Conclusions: Based on SEP criteria, the VIM target but not the STN region can be identified by typical SEP configuration changes, when penetrating the target zone. The approach is independent of the patient's cooperation and vigilance and therefore feasible in general anaesthesia. It provides an easy, reliable, and robust tool for the final assessment of electrode positions at the last instance during electrode implantation when eventual electrode revisions can easily be performed.
Klostermann, F; Vesper, J; Curio, G
This study investigated changes in gene expression in lumbar dorsal root ganglia (DRG), contralateral and ipsilateral to a sciatic nerve crush in control and streptozotocin (STZ)-induced diabetic rats. After 10 weeks of diabetes, the left sciatic nerves of all rats were crushed at mid-thigh level, and the rats were maintained for a further 2 weeks. Northern blots, with internal standards, were made from L4 and L5 (pooled) DRG on each side to compare RNA hybrids from ganglia attached to crushed nerves with those attached to intact nerves. The expression of growth-associated proteins, GAP-43 and Talpha1 alpha-tubulin mRNA in DRG, was stimulated (all P < 0.05) by crush injury in control and diabetic rats. Steady-state expression of transcripts for neurofilament (NF) proteins (NF-L, NF-H) and the high-affinity NGF receptor, trkA was decreased by diabetes in the contralateral ganglia to the crush (all P < 0.05). Crush injury further decreased expression of these transcripts in both control and diabetic rats (all P < 0.05). This reduced expression of mRNA coding for both growth-associated proteins, and neurofilament proteins in ganglia of diabetic rats could participate in the reduced competence of the regenerative response to nerve crush. PMID:9392496
Mohiuddin, L; Tomlinson, D R
To further explore the effect of antioxidants in preventing diabetes-induced vascular and neural dysfunction we treated streptozotocin-induced diabetic rats daily with subcutaneous injections of 10?mg?kg?1 of M40403 (n=11) and compared the results obtained from 17 control rats and 14 untreated diabetic rats. M40403 is a manganese(II) complex with a bis(cyclo-hexylpyridine)-substituted macrocyclic ligand that was designed to be a selective functional mimetic of superoxide dismutase. Thus, M40403 provides a useful tool to evaluate the roles of superoxide in disease states. Treatment with M40403 significantly improved diabetes-induced decrease in endoneurial blood flow, acetylcholine-mediated vascular relaxation in arterioles that provide circulation to the region of the sciatic nerve, and motor nerve conduction velocity (P<0.05). M40403 treatment also reduced the appearance of superoxide in the aorta and epineurial vessels and peroxynitrite in epineurial vessels. Treating diabetic rats with M40403 reduced the diabetes-induced increase in thiobarbituric acid reactive substances in serum but did not prevent the decrease in lens glutathione level. Treating diabetic rats with M40403 did not improve sciatic nerve Na+/K+ ATPase activity or the sorbitol, fructose or myo-inositol content of the sciatic nerve. These studies provide additional evidence that diabetes-induced oxidative stress and the generation of superoxide and perhaps peroxynitrite may be partially responsible for the development of diabetic vascular and neural complications.
Coppey, Lawrence J; Gellett, Jill S; Davidson, Eric P; Dunlap, Joyce A; Lund, Donald D; Salvemini, Daniela; Yorek, Mark A
Summary A previously unrecognized neuropathy was identified in Bulgarian gypsies, and was designated hereditary motor and sensory neuropathy-Lom (HMSNL) after the town where the initial cases were found. It was subsequently identified in other gypsy communities. The disorder, which is of autosomal recessive inheritance, was mapped to chromosome 8q24. It begins consistently in the first decade of life with gait
Luba Kalaydjieva; Amelia Nikolova; Ivo Turnev; Julia Petrova; Anna Hristova; Boryana Ishpekova; Iva Petkova; Alexander Shmarov; Stella Stancheva; L. Middleton; Luciano Merlini; A. Trogu; J. R. Muddle; R. H. M. King; P. K. Thomas
Methods to measure damage to sensory systems following toxicant exposure vary from rapid and subjective tests (e.g., pinna reflex) to time-consuming and objective tests (e.g., psychophysical tests). eflex modification of the startle response represents an alternative technique in...
Background Facial motor evoked potential (FMEP) amplitude ratio reduction at the end of the surgery has been identified as a good predictor\\u000a for postoperative facial nerve outcome. We sought to investigate variations in FMEP amplitude and waveform morphology during\\u000a vestibular schwannoma (VS) resection and to correlate these measures with postoperative facial function immediately after\\u000a surgery and at the last follow-up.\\u000a \\u000a \\u000a \\u000a \\u000a Methods Intraoperative
Marcus André Acioly; Alireza Gharabaghi; Marina Liebsch; Carlos Henrique Carvalho; Paulo Henrique Aguiar; Marcos Tatagiba
WARP is a recently identified extracellular matrix molecule with restricted expression in permanent cartilages and a distinct subset of basement membranes in peripheral nerves, muscle, and the central nervous system vasculature. WARP interacts with perlecan, and we also demonstrate here that WARP binds type VI collagen, suggesting a function in bridging connective tissue structures. To understand the in vivo function of WARP, we generated a WARP-deficient mouse strain. WARP-null mice were healthy, viable, and fertile with no overt abnormalities. Motor function and behavioral testing demonstrated that WARP-null mice exhibited a significantly delayed response to acute painful stimulus and impaired fine motor coordination, although general motor function was not affected, suggesting compromised peripheral nerve function. Immunostaining of WARP-interacting ligands demonstrated that the collagen VI microfibrillar matrix was severely reduced and mislocalized in peripheral nerves of WARP-null mice. Further ultrastructural analysis revealed reduced fibrillar collagen deposition within the peripheral nerve extracellular matrix and abnormal partial fusing of adjacent Schwann cell basement membranes, suggesting an important function for WARP in stabilizing the association of the collagenous interstitial matrix with the Schwann cell basement membrane. In contrast, other WARP-deficient tissues such as articular cartilage, intervertebral discs, and skeletal muscle showed no detectable abnormalities, and basement membranes formed normally. Our data demonstrate that although WARP is not essential for basement membrane formation or musculoskeletal development, it has critical roles in the structure and function of peripheral nerves.
Allen, Justin M.; Zamurs, Laura; Brachvogel, Bent; Schlotzer-Schrehardt, Ursula; Hansen, Uwe; Lamande, Shireen R.; Rowley, Lynn; Fitzgerald, Jamie; Bateman, John F.
Matrix metalloproteinases (MMPs) and their related gene products regulate essential cellular functions. An imbalance in MMPs has been implicated in various neurological disorders, including traumatic injuries. Here, we report a role for MMPs and their related gene products in the modulation of cochlear responses to acoustic trauma in rats. The normal cochlea was shown to be enriched in MMP enzymatic activity, and this activity was reduced in a time-dependent fashion after traumatic noise injury. The analysis of gene expression by RNA-seq and qRT-PCR revealed the differential expression of MMPs and their related genes between functionally specialized regions of the sensory epithelium. The expression of these genes was dynamically regulated between the acute and chronic phases of noise-induced hearing loss. Moreover, noise-induced expression changes in two endogenous MMP inhibitors, Timp1 and Timp2, in sensory cells were dependent upon the stage of nuclear condensation, suggesting a specific role for MMP activity in sensory cell apoptosis. A short-term application of doxycycline, a broad-spectrum inhibitor of MMPs, prior to noise exposure reduced noise-induced hearing loss and sensory cell death. By contrast, a 7-day treatment compromised hearing sensitivity and potentiated noise-induced hearing loss. This detrimental effect of the long-term inhibition of MMPs on noise-induced hearing loss was further confirmed using targeted Mmp7 knockout mice. Together, these observations suggest that MMPs and their related genes participate in the regulation of cochlear responses to acoustic overstimulation and that the modulation of MMP activity can serve as a novel therapeutic target for the reduction of noise-induced cochlear damage.
Hu, Bo Hua; Cai, Qunfeng; Hu, Zihua; Patel, Minal; Bard, Jonathan; Jamison, Jennifer; Coling, Donald
Neuronal circuits are formed according to a genetically predetermined program and then reconstructed in an experience-dependent manner. While the existence of experience-dependent plasticity has been demonstrated for the visual and other sensory systems, it remains unknown whether this is also the case for motor systems. Here we examined the effects of eliminating sensory inputs on the development of peristaltic movements in Drosophila embryos and larvae. The peristalsis is initially slow and uncoordinated, but gradually develops into a mature pattern during late embryonic stages. We tested whether inhibiting the transmission of specific sensory neurons during this period would have lasting effects on the properties of the sensorimotor circuits. We applied Shibire-mediated inhibition for six hours during embryonic development (15–21 h after egg laying [AEL]) and studied its effects on peristalsis in the mature second- and third-instar larvae. We found that inhibition of chordotonal organs, but not multidendritic neurons, led to a lasting decrease in the speed of larval locomotion. To narrow down the sensitive period, we applied shorter inhibition at various embryonic and larval stages and found that two-hour inhibition during 16–20 h AEL, but not at earlier or later stages, was sufficient to cause the effect. These results suggest that neural activity mediated by specific sensory neurons is involved in the maturation of sensorimotor circuits in Drosophila and that there is a critical period for this plastic change. Consistent with a role of chordotonal neurons in sensory feedback, these neurons were activated during larval peristalsis and acute inhibition of their activity decreased the speed of larval locomotion.
Fushiki, Akira; Kohsaka, Hiroshi; Nose, Akinao
Although peripheral nerves can regenerate after injury, proximal nerve injury in humans results in minimal restoration of motor function. One possible explanation for this is that injury-induced axonal growth is too slow. Heat shock protein 27 (Hsp27) is a regeneration-associated protein that accelerates axonal growth in vitro. Here, we have shown that it can also do this in mice after peripheral nerve injury. While rapid motor and sensory recovery occurred in mice after a sciatic nerve crush injury, there was little return of motor function after sciatic nerve transection, because of the delay in motor axons reaching their target. This was not due to a failure of axonal growth, because injured motor axons eventually fully re-extended into muscles and sensory function returned; rather, it resulted from a lack of motor end plate reinnervation. Tg mice expressing high levels of Hsp27 demonstrated enhanced restoration of motor function after nerve transection/resuture by enabling motor synapse reinnervation, but only within 5 weeks of injury. In humans with peripheral nerve injuries, shorter wait times to decompression surgery led to improved functional recovery, and, while a return of sensation occurred in all patients, motor recovery was limited. Thus, absence of motor recovery after nerve damage may result from a failure of synapse reformation after prolonged denervation rather than a failure of axonal growth. PMID:21965333
Ma, Chi Him Eddie; Omura, Takao; Cobos, Enrique J; Latrémoličre, Alban; Ghasemlou, Nader; Brenner, Gary J; van Veen, Ed; Barrett, Lee; Sawada, Tomokazu; Gao, Fuying; Coppola, Giovanni; Gertler, Frank; Costigan, Michael; Geschwind, Dan; Woolf, Clifford J
Calcitonin gene-related peptide (CGRP) is a major neurotransmitter and CGRP-containing primary sensory neurons play an important role in nociception and potent vasodilation. CGRP-containing nerves in mesenteric arteries are decreased in pathological animal models (hypertension, diabetes, and atherosclerosis). In apolipoprotein E–knockout mice, which have atherosclerosis and peripheral sensory nerve defects, nerve growth factor (NGF)-mediated CGRP nerve facilitation was down-regulated, which may have been caused by the impairment of the Akt–NO–cGMP pathway. In addition, NGF-