Distinct signaling pathways mediate touch and osmosensory responses in a polymodal sensory neuron. (1/1361)

The Caenorhabditis elegans ASH sensory neurons mediate responses to nose touch, hyperosmolarity, and volatile repellent chemicals. We show here that distinct signaling pathways mediate the responses to touch and hyperosmolarity. ASH neurons distinguish between these stimuli because habituation to nose touch has no effect on the response to high osmolarity or volatile chemicals (1-octanol). Mutations in osm-10 eliminate the response to hyperosmolarity but have no effect on responses to nose touch or to volatile repellents. OSM-10 is a novel cytosolic protein expressed in ASH and three other classes of sensory neurons. Mutations in two other osmosensory-defective genes, eos-1 and eos-2, interact genetically with osm-10. Our analysis suggests that nose touch sensitivity and osmosensation occur via distinct signaling pathways in ASH and that OSM-10 is required for osmosensory signaling.  (+info)

The distribution of zinc selenite and expression of metallothionein-III mRNA in the spinal cord and dorsal root ganglia of the rat suggest a role for zinc in sensory transmission. (2/1361)

Zinc appears to play a role in synaptic transmission in the hippocampus. We tested the hypothesis that zinc is similarly involved in sensory transmission by determining whether vesicular zinc and metallothionein-III (MT-III), a zinc-binding protein, are localized in rat primary afferent neurons. MT-III mRNA, measured using RT-PCR, and MT-III immunoreactivity, were both present in the spinal cord as well as the thoracic and lumbar dorsal root ganglia (DRG). At a time (24 hr) that allows retrograde transport of zinc selenite to cell bodies, only small-diameter neurons and neurons scattered throughout lamina V of the spinal cord were stained by sodium selenite injected intrathecally. This stain disappeared if a ligature was placed on the dorsal root to block axonal transport, demonstrating that these cells are, in fact, zinc-containing primary afferent neurons. When assessed 1 hr after sodium selenite, stain was distributed throughout the neuropil of the spinal cord, especially in lamina III and the area surrounding the central canal. Even in rhizotomized animals, large- and small-diameter DRG neuronal cell bodies were also stained with either selenite (1 hr) or 6-methoxy 8-para-toluene sulfonamide quinoline (TSQ). Paradoxically, this unique pool of zinc was eliminated in large-diameter DRG neurons after neonatal capsaicin treatment, which had no effect on selenite stain or MT-III mRNA content in small-diameter DRG neurons. In summary, we demonstrate that there is a population of capsaicin-insensitive small-diameter primary afferent neurons that are zinc-containing. In addition, there is a unique pool of capsaicin-sensitive zinc that is associated with large-diameter cell bodies.  (+info)

Effects of duodenal distension on antropyloroduodenal pressures and perception are modified by hyperglycemia. (3/1361)

Marked hyperglycemia (blood glucose approximately 15 mmol/l) affects gastrointestinal motor function and modulates the perception of gastrointestinal sensations. The aims of this study were to evaluate the effects of mild hyperglycemia on the perception of, and motor responses to, duodenal distension. Paired studies were done in nine healthy volunteers, during euglycemia ( approximately 4 mmol/l) and mild hyperglycemia ( approximately 10 mmol/l), in randomized order, using a crossover design. Antropyloroduodenal pressures were recorded with a manometric, sleeve-side hole assembly, and proximal duodenal distensions were performed with a flaccid bag. Intrabag volumes were increased at 4-ml increments from 12 to 48 ml, each distension lasting for 2.5 min and separated by 10 min. Perception of the distensions and sensations of fullness, nausea, and hunger were evaluated. Perceptions of distension (P < 0.001) and fullness (P < 0.05) were greater and hunger less (P < 0.001) during hyperglycemia compared with euglycemia. Proximal duodenal distension stimulated pyloric tone (P < 0.01), isolated pyloric pressure waves (P < 0.01), and duodenal pressure waves (P < 0.01). Compared with euglycemia, hyperglycemia was associated with increases in pyloric tone (P < 0.001), the frequency (P < 0.05) and amplitude (P < 0.01) of isolated pyloric pressure waves, and the frequency of duodenal pressure waves (P < 0.001) in response to duodenal distension. Duodenal compliance was less (P < 0.05) during hyperglycemia compared with euglycemia, but this did not account for the effects of hyperglycemia on perception. We conclude that both the perception of, and stimulation of pyloric and duodenal pressures by, duodenal distension are increased by mild hyperglycemia. These observations are consistent with the concept that the blood glucose concentration plays a role in the regulation of gastrointestinal motility and sensation.  (+info)

Physiological changes in blood glucose do not affect gastric compliance and perception in normal subjects. (4/1361)

Marked hyperglycemia (blood glucose approximately 14 mmol/l) slows gastric emptying and affects the perception of sensations arising from the gut. Elevation of blood glucose within the physiological range also slows gastric emptying. This study aimed to determine whether physiological changes in blood glucose affect proximal gastric compliance and/or the perception of gastric distension in the fasting state. Paired studies were conducted in 10 fasting healthy volunteers. On a single day, isovolumetric and isobaric distensions of the proximal stomach were performed using an electronic barostat while the blood glucose concentration was maintained at 4 and 9 mmol/l in random order. Sensations were quantified using visual analog scales. The blood glucose concentration had no effect on the pressure-volume relationship during either isovolumetric or isobaric distensions or the perception of gastric distension. At both blood glucose concentrations, the perceptions of fullness, nausea, bloating, and abdominal discomfort, but not hunger or desire to eat, were related to intrabag volume (P +info)

Interstitial Ca2+ undergoes dynamic changes sufficient to stimulate nerve-dependent Ca2+-induced relaxation. (5/1361)

We recently described a perivascular sensory nerve-linked dilator system that can be activated by interstitial Ca2+ (Ca2+isf). The present study tested the hypothesis that Ca2+isf in the rat duodenal submucosa varies through a range that is sufficient to activate this pathway. An in situ microdialysis method was used to estimate Ca2+isf. When the duodenal lumen was perfused with Ca2+-free buffer, Ca2+isf was 1.0 +/- 0.13 mmol/l. Ca2+isf increased to 1.52 +/- 0.04, 1.78 +/- 0.10, and 1.89 +/- 0.1 when the lumen was perfused with buffer containing 3, 6, and 10 mmol/l Ca2+, respectively (P < 0.05). Ca2+isf was 1.1 +/- 0.06 mmol/l in fasted animals and increased to 1. 4 +/- 0.06 mmol/l in free-feeding rats (P < 0.05). Wire myography was used to study isometric tension responses of isolated mesenteric resistance arteries. Cumulative addition of extracellular Ca2+-relaxed serotonin- and methoxamine-precontracted arteries with half-maximal effective doses of 1.54 +/- 0.05 and 1.67 +/- 0.08 mmol/l, respectively (n = 5). These data show that duodenal Ca2+isf undergoes dynamic changes over a range that activates the sensory nerve-linked dilator system and indicate that this system can link changes in local Ca2+ transport with alterations in regional resistance and organ blood flow.  (+info)

The neural consequences of conflict between intention and the senses. (6/1361)

Normal sensorimotor states involve integration of intention, action and sensory feedback. An example is the congruence between motor intention and sensory experience (both proprioceptive and visual) when we move a limb through space. Such goal-directed action necessitates a mechanism that monitors sensorimotor inputs to ensure that motor outputs are congruent with current intentions. Monitoring in this sense is usually implicit and automatic but becomes conscious whenever there is a mismatch between expected and realized sensorimotor states. To investigate how the latter type of monitoring is achieved we conducted three fully factorial functional neuroimaging experiments using PET measures of relative regional cerebral blood flow with healthy volunteers. In the first experiment subjects were asked to perform Luria's bimanual co-ordination task which involves either in-phase (conditions 1 and 3) or out-of-phase (conditions 2 and 4) bimanual movements (factor one), while looking towards their left hand. In half of the conditions (conditions 3 and 4) a mirror was used that altered visual feedback (factor two) by replacing their left hand with the mirror image of their right hand. Hence (in the critical condition 4) subjects saw in-phase movements despite performing out-of-phase movements. This mismatch between intention, proprioception and visual feedback engendered cognitive conflict. The main effect of out-of-phase movements was associated with increased neural activity in posterior parietal cortex (PPC) bilaterally [Brodmann area (BA) 40, extending into BA 7] and dorsolateral prefrontal cortex (DLPFC) bilaterally (BA 9/46). The main effect of the mirror showed increased neural activity in right DLPFC (BA 9/ 46) and right superior PPC (BA 7) only. Analysis of the critical interaction revealed that the mismatch condition led to a specific activation in the right DLPFC alone (BA 9/46). Study 2, using an identical experimental set-up but manipulating visual feedback from the right hand (instead of the left), subsequently demonstrated that this right DLPFC activation was independent of the hand attended. Finally, study 3 removed the motor intentional component by moving the subjects' hand passively, thus engendering a mismatch between proprioception and vision only. Activation in the right lateral prefrontal cortex was now more ventral than in studies 1 or 2 (BA 44/45). A direct comparison of studies 1 and 3 (which both manipulated visual feedback from the left hand) confirmed that a ventral right lateral prefrontal region is primarily activated by discrepancies between signals from sensory systems, while a more dorsal area in right lateral prefrontal cortex is activated when actions must be maintained in the face of a conflict between intention and sensory outcome.  (+info)

Quantitative and selective assessment of sensory block during lumbar epidural anaesthesia with 1% or 2% lidocaine. (7/1361)

We have examined sensory block during lumbar epidural anaesthesia using a cutaneous current perception threshold (CPT) sensory testing device in 20 patients who received 10 ml of either 1% or 2% lidocaine (lignocaine). CPT at 2000, 250 and 5 Hz stimulation at the trigeminal (V), ninth thoracic (T9) and second lumbar (L2) dermatomes, and dermatomal levels of block to light touch, temperature and pinprick discrimination were measured before and every 5 min until 60 min after epidural lidocaine. There were significant differences between 1% and 2% epidural lidocaine in all CPT at T9 and L2, in addition to maximal cephalad spread of the three sensory modalities. After 2% lidocaine, all CPT increased significantly at T9 and L2. In contrast, only at 250 and 5 Hz for L2 did epidural block with 1% lidocaine produce significant increases in CPT. Maximal level of loss of touch sensation after 1% lidocaine was significantly lower than that of cold and pinprick sensations. We conclude that the dose of lidocaine affected intensity of sensory block during lumbar epidural anaesthesia. In addition, differential neural block resulting from epidural anaesthesia appeared to be associated with a differential effect on nerve fibres of different sizes.  (+info)

External thoracic restriction, respiratory sensation, and ventilation during exercise in men. (8/1361)

Multiple factors may contribute to the dyspnea associated with restrictive ventilatory disease (RVD). Simple models that examine specific features of this problem are likely to provide insight into the mechanisms. Previous models of RVD utilizing elastic loads may not represent completely the impact on pulmonary and chest wall receptors derived from breathing at low thoracic volumes. The purpose of this study was to investigate the sensory consequences of breathing at low lung volumes induced by external thoracic restriction in an attempt to further elucidate the etiology of dyspnea in this setting. Ten men were studied, with and without an inelastic corset applied at residual volume (restriction resulted in mean reductions in vital capacity, functional residual capacity, residual volume, and forced expired volume in 1 s of 44, 31, 12.5, and 42%, respectively). During 10-min steady-state exercise tests (at a workload set to achieve approximately 65% maximum heart rate), restriction resulted in significant increases, compared with control, in minute ventilation (61 vs. 49 l/min), respiratory frequency (43 vs. 23 breaths/min), and visual analog scale measurements of respiratory discomfort (65 vs. 20 mm). Alveolar hyperventilation (end-tidal PCO2 = 39 vs. 44 Torr for control) and mild O2 desaturation (arterial blood O2 saturation = 93 vs. 95% for control) occurred. Hypoxemia, atelectasis, increased work and effort of breathing, or a decrease in the volume-related feedback from chest wall and/or lungs could be responsible for the increased dyspnea reported. External thoracic restriction provides a useful model to study mechanisms of dyspnea in RVD.  (+info)