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Sensori-motor function in older persons with diabetes.

Twenty-five persons with diabetes (aged 55-83 years) who were living independently in the community, and 40 age- and sex-matched non-diabetic controls were assessed for tactile sensitivity, vibration sense, proprioception, quadriceps strength and body sway. In both men and women, those with diabetes performed significantly worse in tests of body sway on firm and compliant surfaces compared with the control subjects after controlling for weight and body mass index. The female diabetic subjects also performed significantly worse in tests of peripheral sensation and strength compared with controls. Age-related declines in sensori-motor function were greater in the diabetic group (r = 0.55-0.75) than in the controls (r < 0.44), while within the diabetic group, duration of diabetes and vibration sense were significantly correlated with sway on a compliant (foam rubber) surface with the eyes open (partial r = 0.52, p < 0.01 and r = 0.55, p < 0.01, respectively). The study findings provide evidence that older people with diabetes have problems with stability and related sensori-motor factors which may place them at increased risk of falls.

Adult↗

Prevention of deterioration of renal and sensory-nerve function by more intensive management of insulin-dependent diabetic patients. A two-year randomised prospective study.

74 insulin-dependent diabetic patients with background retinopathy were randomised to continue with usual diabetic care (group U) or to a more intensive programme (group A) using ultralente insulin as basal cover and soluble insulin at mealtimes. Group A attended the clinic more frequently, received closer dietary supervision, and were taught home blood glucose monitoring. Group A had a significantly lower mean glycosylated haemoglobin level during the study, although the mean level also fell in group U towards the end of year 2. Renal and sensory-nerve function were significantly better preserved in group A than in group U. Significant improvements were also seen in low-density-lipoprotein-cholesterol and whole-blood low-shear viscosity. The rate of progression of retinopathy was similar in both groups. It appears that a modest improvement in diabetic control, obtainable in most clinics, has been associated with a reduction in the progression of diabetic tissue damage.

Blood Glucose↗

The urothelium in overactive bladder: passive bystander or active participant?

The urothelium was once purported to be a passive membrane. However, a growing body of evidence indicates that the urothelium actively participates in sensory functions, expressing various receptors and ion channels, as well as releasing neurotransmitters in response to stimuli. Vanilloid receptors, P2X3 purinergic receptors, adenosine triphosphate, nitric oxide, and acetylcholine have been implicated in urothelial-neuronal interactions. Substances released from urothelial cells can alter the excitability of bladder afferent nerves acutely and chronically; these observations appear to be of particular importance in chronic bladder conditions and in the aging bladder. Evidence suggests that the involvement of the muscarinic receptor in bladder function extends beyond detrusor contractility and into afferent sensory functioning. These observations have significant implications for a more complete understanding of the effects of currently used drugs on these sensory mechanisms and for identifying potential targets for pharmacologic intervention in bladder disorders.

Adenosine Triphosphate↗

Capsaicin evoked pain and allodynia in post-herpetic neuralgia.

The hypothesis that the pain and allodynia associated with post-herpetic neuralgia (PHN) is maintained by a combination of input from preserved primary afferent nociceptors and sensitization of central pain transmitting neurons was examined in 17 subjects with PHN. Pain, allodynia, thermal sensory function, cutaneous innervation, and response to controlled application of 0.075% capsaicin were measured. Compared to mirror-image skin, applying capsaicin on a 9 cm(2) area of PHN skin significantly increased overall PHN pain and allodynia in 11 of 17 subjects. These 'capsaicin responders' were characterized by higher average daily pain, higher allodynia ratings, and relatively preserved sensory function at baseline compared to the non-responders. In three of the 'capsaicin responders' the area of allodynia expanded into previously non-allodynic and non-painful skin that had normal sensory function and cutaneous innervation. These observations support the hypothesis that allodynia in some PHN patients is a form of chronic secondary hyperalgesia maintained by input from intact and possibly 'irritable' primary afferent nociceptors to a sensitized CNS.

Administration, Topical↗

Sensory re-education after median nerve lesions.

Technique for re-educating sensory function after median nerve lesions at the wrist is described. Results of re-education of Twenty-three patients are presented. The functional results are good and belie the traditional view of sensory function after nerve suture. Recent advances in sensory neuro-physiology are discussed which may explain the successes of this technique.

Evaluation Studies as Topic↗

Specific N- or C-terminus modified dynorphin and beta-endorphin peptides can selectively block excitatory opioid receptor functions in sensory neurons and unmask potent inhibitory effects of opioid agonists.

We recently showed that the opioid alkaloids, etorphine, dihydroetorphine and diprenorphine, have remarkably potent antagonist actions on excitatory opioid receptor functions in mouse sensory dorsal root ganglion (DRG) neurons. Pretreatment of naive nociceptive types of neurons with pM concentrations of these antagonists blocks excitatory prolongation of the calcium-dependent component of the action potential duration (APD) elicited by pM-nM morphine or other bimodally acting mu, delta and kappa opioid agonists and unmasks inhibitory APD shortening which usually requires much higher (ca. microM) concentrations. The present study demonstrates that pM concentrations of [des-Tyr1] fragments of dynorphin and beta-endorphin, as well as beta-endorphin-(1-27), can also selectively block excitatory opioid receptor functions in DRG neurons and unmask potent inhibitory effects of low concentrations of bimodally acting mu, delta and kappa opioid peptides and alkaloid agonists. These N- or C-terminus modified dynorphin or beta-endorphin peptides can be readily formed in neurons by specific peptidase activities. Since sustained activation of excitatory opioid receptor functions is essential for the development of tolerance/dependence in chronic morphine-treated DRG neurons in culture, the present in vitro study may help to account for the unexplained efficacy of [des-Tyr1] dynorphin fragments, as well as the endogenous opioids dynorphin A and beta-endorphin, in suppressing development and expression of naloxone-precipitated withdrawal and morphine tolerance in vivo.

Action Potentials↗

Adenosine reduces secondary hyperalgesia in two human models of cutaneous inflammatory pain.

UNLABELLED: Secondary hyperalgesia is characterized by increased sensitivity to noxious mechanical stimuli in the area surrounding injured skin. The pathophysiological mechanisms involve increased excitability of second-order neurons located in the spinal cord, i.e., central sensitization. The mechanisms behind this phenomenon may be of importance in clinical pain, including neuropathic pain. To study the effects of systemic infusion of the endogenous compound adenosine (ADO) on sensory function, a superficial cutaneous burn injury was induced by the 4-min topical application of mustard oil or by heat (47 degrees C for 7 min) during i.v. ADO infusion (60 microg x kg(-1) x min(-1)). Healthy human subjects (n = 10 for each model) were tested, using a blinded, placebo-controlled procedure. The area of secondary hyperalgesia, as well as tactile and thermal sensory function, was tested using psychophysical methods during and after treatments. ADO significantly reduced the area of secondary hyperalgesia in both models. The maximal reduction compared with placebo was 58% +/- 20% (heat burn) and 39% +/- 13% (mustard oil burn). No other differences in sensory function were observed. The results are interpreted as an ADO-induced modulatory effect on the mechanisms of central sensitization. IMPLICATIONS: We tested the effects of adenosine on the development of increased sensitivity in the skin surrounding a superficial skin injury in humans. A superficial skin bum was induced with a chemical irritant or heat. The results show that adenosine reduces the skin area with increased sensitivity surrounding the injury.

Adenosine↗

The long-term outcome of arm function after stroke: results of a follow-up study.

PURPOSE: To assess the long-term motor and functional recovery of arm function after stroke. DESIGN: Cohort study. SUBJECTS: Fifty-four patients with a first stroke, who underwent inpatient rehabilitation, were measured early after stroke, after 16 weeks and after 4 years. MEASURES: Fugl-Meyer Motor Assessment (FM, upper extremity), Action Research Arm Test (ARA), Barthel Index, Arm Function Questionnaire, shoulder pain and range of motion, sensory function, Ashworth Scale and a perceived problem score. RESULTS: Although most of the improvement occurred during the first 16 weeks after stroke, improvement in the FM score continued after 16 weeks in 10 patients. In 13 patients the recovery of arm function only started after 16 weeks. After 4 years a fair to good recovery of arm motor function (FM score > 20) was found in 31 patients. Twenty-seven patients had fair to good functional abilities of the hemiplegic arm (ARA > 25). Submaximal ARA scores for the unaffected arm were found in 11 patients. Barthel scores > 60 were found in 52 patients. Serious shoulder pain persisted in 11 patients. Intact sensory function was found in only 14 patients. It was associated with good motor recovery (FM score > 35 in 11 patients). Loss of arm function was perceived as a major problem by 36 patients. CONCLUSION: This is the first study to investigate the recovery of arm function after stroke over a period of 4 years. It is encouraging to note that even after 16 weeks improvement still occurred in some patients. However, considerable long-term loss of arm function, associated disability and perceived problems were found. There is an obvious need to develop effective treatment methods for hemiplegic arm function.

Adolescent↗

Vestibular function and sensory interaction in altered gravity.

The effects of weightlessness on vestibular function have been studied since the beginning of manned spaceflight. The results of these studies have been highly variable and to some extent even contradictory, which makes it difficult to draw unambiguous conclusions. This variability is probably due to at least three factors: (1) individual differences in the adaptive process, (2) non-standardized experimental methods and conditions, (3) a lack of integrated experiments. For this reason, we have used a single integrated approach with a specially developed battery of tests. The results thus obtained for 21 cosmonauts on short- and long-term flights are reviewed here, and discussed in the light of the results obtained by others. Changes in the operation of the vestibular system and in all functions based on vestibular afferent input are commonly observed in spaceflight. These changes are characteristic for the process of adaptation and re-adaptation to altered gravity. They occur in a high proportion of persons exposed to such conditions, although there are individual differences with regard to severity, nature, time and duration of occurrence, and the dynamics of the process. Analysis of the observations in a large number of cosmonauts has permitted to distinguish three types of adaptation of the system to altered gravity. The first type of adaptation is characterized by a strong response to any stimulus during the initial adaptation period. The second type of adaptation is characterized by responses that are drastically decreased or even absent. The third type of adaptation is distinguished by the selective response of the sensory system to certain types of stimulation only. After long-term missions the process of re-adaptation usually takes a more severe course than the earlier process of adaptation to microgravity. Both adaptation and re-adaptation follow an undulating course, in which adaptation and re-adaptation are alternating. This is most conspicuous during long-term flights, and it suggests that in the initial stage of adaptation to weightlessness the vestibular input plays a dominant role, while at the end of the adaptation process the visual input prevails.

Eye Movements↗

Sensory-motor function of human periodontal mechanoreceptors.

Natural teeth are equipped with periodontal mechanoreceptors that signal information about tooth loads. In the present review, the basic force-encoding properties of human periodontal receptors will be presented along with a discussion about their likely functional role in the control of human mastication. Microneurographic recordings from single nerve fibres reveal that human periodontal receptors adapt slowly to maintained tooth loads. Most receptors are broadly tuned to the direction of force application, and about half respond to forces applied to more than one tooth. Populations of periodontal receptors, nevertheless, reliably encode information about both the teeth stimulated, and the direction of forces applied to the individual teeth. Information about the magnitude of tooth loads is made available in the mean firing rate response of periodontal receptors. Most receptors exhibit a markedly curved relationship between discharge rate and force amplitude, featuring the highest sensitivity to changes in tooth load at very low force levels (below 1 N for anterior teeth and 4 N for posterior teeth). Thus, periodontal receptors efficiently encode tooth load when subjects contact and gently manipulate food using the teeth. It is demonstrated that signals from periodontal receptors are used in the fine motor control of the jaw and it is clear from studies of various patient groups (e.g. patients with dental implants) that important sensory-motor functions are lost or impaired when these receptors are removed during the extraction of teeth.

Adaptation, Physiological↗

The Caenorhabditis elegans aristaless orthologue, alr-1, is required for maintaining the functional and structural integrity of the amphid sensory organs.

The homeobox-containing aristaless-related protein ARX has been directly linked to the development of a number of human disorders involving mental retardation and epilepsy and clearly plays a critical role in development of the vertebrate central nervous system. In this work, we investigate the role of ALR-1, the Caenorhabditis elegans aristaless orthologue, in amphid sensory function. Our studies indicate that ALR-1 is required for maintenance of the amphid organ structure throughout larval development. Mutant analysis indicates a progressive loss in the amphid neurons' ability to fill with lipophilic dyes as well as a declining chemotactic response. The degeneration in amphid function corresponds with a failure of the glial-like amphid socket cell to maintain its specific cell shape and cell-cell contacts. Consistent with ALR-1 expression within the amphid socket cell, our results indicate a cell autonomous role for ALR-1 in maintaining cell shape. Furthermore, we demonstrate a role for ALR-1 in the proper morphogenesis of the anterior hypodermis. Genetic interaction tests also suggest that ALR-1 may function cooperatively with the cell adhesion processes in maintaining the amphid sensory organs.

Animals↗

Venoarterial bypass: a technique for spinal cord protection.

In the present study, we examined the effects of various levels of oxygen tension on spinal cord blood flow while using somatosensory evoked potentials to monitor spinal cord sensory function during hypoxia. In this experiment, six adult, mongrel dogs were heparinized and placed on right atrial-femoral artery bypass with an oxygenator in the bypass circuit. The aorta was cross-clamped proximal to the left subclavian artery, and bypass flow and fluid balance were adjusted so as to maintain a distal aortic perfusion pressure of greater than 80 mm Hg. Oxygen flow to the oxygenator was lowered by graded decrements to provide decreasing levels of oxygen tension, which ultimately approached pure venoarterial bypass. Each successive oxygen level was maintained for 30 minutes. Spinal cord blood flow was measured with radioactive microspheres, and latency and amplitude of somatosomatic evolved potentials were continuously monitored. The somatosensory evolved potential signal was invariably present as long as the distal aortic pressure was greater than 80 mm Hg; there were several transient hypotensive episodes (less than 5 minutes), which were accompanied by reversible loss of somatosensory evolved potentials. The spinal cord blood flow increased from 13.6 to 119.7 ml/100 gm/min as the distal oxygen tension fell to a mean value of 30 mm Hg, while latency of somatosensory evolved potentials increased 19.3% and amplitude decreased 43.3%. These results suggest the following conclusions: (1) In response to hypoxia, spinal cord blood flow dramatically increases and somatosensory evolved potentials deteriorate (increase in latency and decrease in amplitude). (2) However, during prolonged hypoxia, spinal cord sensory function can be maintained by sufficiently high flow rates and perfusion pressures. (3) Somatosensory evolved potentials can be used to monitor continuously spinal cord sensory function under these conditions.

Animals↗

The analgesic effect of intravenous ketamine and lidocaine on pain after spinal cord injury.

BACKGROUND: Pain following spinal cord injury (SCI) is a therapeutic challenge. Only a few treatments have been assessed in randomized, controlled trials. The primary objective of the present study was to examine the analgesic effect of ketamine and lidocaine in a group of patients with neuropathic pain below the level of spinal cord injury. We also wanted to assess sensory abnormalities to see if this could help us to identify responders and if treatments resulted in changes of sensibility. METHODS: Ten patients with spinal cord injury and neuropathic pain below the level of injury were included. The analgesic effect of ketamine 0.4 mg kg(-1) and lidocaine 2.5 mg kg(-1) was investigated. Saline was used as placebo. The drugs were infused over 40 min. A randomized, double-blind, three-period, three-treatment, cross-over design was used. Systemic plasma concentrations of ketamine and lidocaine were assessed. Pain rating was performed using a visual analogue scale (VAS). Sensory function was assessed with a combination of traditional sensory tests and quantitative measurement of temperature thresholds. RESULTS: Response to treatment, defined as 50% reduction in VAS-score during infusion, was recorded in 5/10 in the ketamine, 1/10 in the lidocaine and 0/10 in the placebo groups. Neither ketamine nor lidocaine changed temperature thresholds or assessments of mechanical; dynamic and static sensibility. Nor could these sensory assessments predict response to treatment in this setting. Lidocaine and particularly ketamine were associated with frequent side-effects. CONCLUSION: Ketamine but not lidocaine showed a significant analgesic effect in patients with neuropathic pain after spinal cord injury. The pain relief was not associated with altered temperature thresholds or other changes of sensory function.

Adult↗

[Clinico-physiological characteristics of the effectiveness of conservative therapy in traumatic neuropathies].

The effect of electroneuromyostimulation (ENMS) combined with Nootropil administration for trauma neuropathies was assessed using clinical and physiological tests in 58 patients. The combined intervention considerably accelerated the restoration of motor and sensory functions after the reconstructive neurosurgery on the extremities. Sensory functions substantially improved in 78% of the patients receiving ENMS and Nootropil and in 23% of those receiving the conventional treatment. The ENMS plus Nootropil treatment has been found to have advantages as compared with the conventional one.

Adolescent↗

[Nerve transfer (neurotization) for functional reconstruction of arm functions in cervical root avulsions].

Neurotization procedures represent an important therapeutic option in patients with complete root avulsion due to traumatic brachial plexus injuries. A variety of normal donor nerves can be used, including intercostal nerves, accessory nerve, parts of the cervical plexus, phrenic nerve, and/or the contralateral C7 nerve root. The reconstructive neurotization procedure should be performed within 3-6 months following the trauma and, when successful, can lead to substantial improvement in motor function for the shoulder and upper arm and in sensory function for the forearm, hand and finger region. Neurotization can also be combined with neurolysis and/or transplantation to restore upper limb motor and sensory function in order to achieve greater therapeutic benefit for patients with posttraumatic brachial plexus lesions.

Arm↗

Distribution of A-delta and C-fiber receptors in the cervical facet joint capsule and their response to stretch.

BACKGROUND: It has been proposed that cervical facet joint capsules are a major source of whiplash pain. However, there is a paucity of neurophysiologic data to support this hypothesis. The purposes of this study were to determine the distribution of A-delta and C-fiber sensory receptors in the facet joint capsule and to test their patterns of response to stretch and related sensory function. METHODS: Laminectomy from C4 to C7 was performed in seventeen goats, while they were under general anesthesia, to expose the C6 nerve roots. Customized dual bipolar electrodes were used to record neural activity from one of the C6 branches. An 8 or 15-V electrical stimulus was used to provoke receptor activity in nine designated areas on the dorsal part of the C5-C6 facet joint capsule. Receptors were classified on the basis of conduction velocities. The waveform of an identified receptor was set up as a template to determine its neural activity in response to capsular stretch. The characteristics of each single receptor's response to capsular stretch were analyzed to determine its sensory function as a mechanoreceptor or nociceptor. RESULTS: Two hundred and forty-eight receptors on the dorsal part of the C5-C6 facet joint capsule were evoked by electrical stimulation in the seventeen goats. More C-fiber receptors were found on the dorsolateral aspect of the facet joint capsule, where tendons and muscles were attached. The response to stretch of 120 receptors, from twelve goats, were analyzed to classify them into one of four categories (high-threshold mechanoreceptors, non-saturated low-threshold mechanoreceptors, saturated low-threshold mechanoreceptors, and silent receptors) or as unclassified receptors. CONCLUSIONS: The existence of receptors in the facet joint capsule indicates that the capsule has pain and proprioceptive sensory functions.

Animals↗

Evaluation of clinical, electrophysiologic, and computed tomographic parameters in replanted hands.

OBJECTIVE: To compare clinical, electrophysiologic, and computed tomography (CT) imaging correlates of reinnervation in replanted limbs. DESIGN: Patients were assessed between 8 and 194 months after replantation of completely severed hands. SETTING: University hospital, departments for neurology and for plastic and reconstructive surgery. PARTICIPANTS: Thirteen patients, 10 with total and 3 with subtotal type V amputation, whose hands had been reattached. INTERVENTIONS: Clinical assessment of function of hand and finger muscles; electromyographic tests of sensory nerve action potentials (SNAPs) of median, ulnar, and radial nerves; and compound motor action potentials (CMAPs) of abductor pollicis brevis, first dorsal interosseus, and abductor digiti minimi muscles. CT assessment of motor unit action potentials. Measurements of both replanted and normal hands. MAIN OUTCOME MEASURES: Medical Research Council scale of force; sensory functions of anatomic areas of nerves; SNAP and CMAP amplitudes; CT area, mean absorption, standard deviation (SD) from mean absorption, and root mean square SD of absorption. RESULTS: Correlates of reinnervation were evidenced by all methods, except by surface recordings of SNAPs, which could not be elicited even in hands with good sensory function. CMAP amplitudes were the electrophysiologic parameter that correlated best with the clinical restoration. Of the CT measures, the cross-sectional area was the most useful parameter for the detection of denervation, but no CT parameter was sufficiently sensitive to detect reinnervation. In cases with good functional recovery, CMAP amplitudes were superior to clinical rating in showing incomplete reinnervation. CONCLUSION: The combination of clinical and electrophysiologic methods supplied sufficient data for a reliable evaluation of reinnervation. Usually, CT parameters did not add useful information.

Action Potentials↗

Impaired thermal perception in cluster headache.

Cluster headache is characterized by attacks of severe periorbital pain. Repetitive burst activity in afferent fibers may induce plastic alterations in somatosensory synaptic processing as a prerequisite for recurring and chronic pain. This psychophysical study addressed hypothesized dysfunctions in craniofacial somatosensory processing in cluster headache disease. Thermal and mechanical sensory functions in the periorbital region were assessed by quantitative sensory testing (QST) in 25 cluster headache patients and 60 healthy volunteers. Perception of warmth (p<0.01), cold (p<0.000001), and pressure pain (p<0.05) was reduced on the cluster side as compared with the contralateral asymptomatic side. In contrast to healthy volunteers, warm detection threshold (WDT) and thermal sensory limen (TSL) on one side did not positively correlate with the other side. WDT and TSL negatively correlated with the elapsed time since last attack. All patients showed QST abnormalities on the headache side in comparison to healthy controls. Loss of sensory functions strongly preponderated gain. Several lines of evidence indicate a pivotal role of the hypothalamus in cluster headache pathophysiology. The impairment of warm and cold perception in patients may be based upon a dysfunction of the hypothalamus which is strongly involved in thermosensory control.

Adult↗