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PubMed1996

Update on the concepts and probable role of peptidergic nerves in dentine sensitivity and pain mechanisms.

Both, myelinated (A-) and unmyelinated (C-) and efferent sympathetic nerves are found in the dental pulp. The myelinated nerves are sensory and respond to stimulation of dentine with external stimuli. The A-fibres may be responsible for the sharp piercing pain sensations induced by stimulation of dentine in human subjects. C-fibres respond only when the stimuli reach the pulp proper. Activation of C-fibres may be responsible for the dull, delayed pain which radiates to the rest of the face. Immunohistochemical studies have demonstrated the existence of intradental peptidergic nerves. These are the substance P (SP), calcitonin gene-related peptide (CGRP) and vasoactive intestinal polypeptide (VIP) nerves. It is suggested that peptidergic intradental nerves may play a role in increased dentine sensitivity during inflammation and dentine hypersensitivity.

Calcitonin Gene-Related Peptide↗

PubMed1990

Carbon dioxide-responsive laryngeal receptors in the dog.

The purpose of this study was to relate the carbon dioxide (CO2) response of laryngeal receptors to their behavior during the breathing cycle (i.e. their response to transmural pressure changes, laryngeal movement or decreases in temperature) or during exposure to irritant stimuli (water or cigarette smoke). In 9 anesthetized mongrel dogs breathing spontaneously through a tracheostomy, unit activity from the superior laryngeal nerve was recorded while warmed and humidified gas mixtures (air or 10% CO2 in O2) were passed, for 1 min, through the functionally isolated upper airway in the expiratory direction. None of the 10 cold receptors studied were affected by CO2. Eleven of 20 laryngeal non-modulated mechano-receptors were stimulated (from 0.3 to 1.6 imp/sec) by exposure to CO2. These CO2-responsive receptors were also stimulated by known irritant stimuli (cigarette smoke, water), although not all receptors which responded to these irritants were stimulated by CO2. Twelve of 33 respiratory-modulated receptors were affected by CO2; 4 were stimulated and 8 inhibited. Receptors inhibited by CO2 were also inhibited by negative pressure while receptors stimulated by CO2 were also stimulated by negative pressure. These results show that CO2-responsive laryngeal receptors are not specialized endings. Although it is not clear to what extent each separate group of laryngeal receptors is involved, each may contribute to the reflex bradypnea which has been observed during exposure of the upper airway to elevated levels of CO2. However, the importance of CO2-responsive laryngeal receptors in physiological conditions remains unclear.

Animals↗

PubMed1995

Increases in hippocampal and frontal cortical acetylcholine release associated with presentation of sensory stimuli.

In vivo microdialysis was employed to monitor acetylcholine release in the hippocampus and frontal cortex of freely behaving rats. Four stimuli were presented on separate occasions in the course of a dialysis session to rats with microdialysis probes implanted in the hippocampus or frontal cortex. Visual, auditory, olfactory and tactile stimuli elicited a number of different responses such as exploratory and consummatory behaviours. Presentation of two of the stimuli (auditory and tactile) also produced periods of alert immobility (freezing). All of the stimuli increased acetylcholine release in both the hippocampus and cortex: in the hippocampus, this increase was statistically significant with all except the olfactory stimulus, whereas in the cortex all but the visual stimulus resulted in significant increases. In the hippocampus, there were no significant differences between the increases in acetylcholine release produced by the four stimuli. In contrast, in the cortex, there was significant variation between the magnitude of acetylcholine release produced by the different stimuli: acetylcholine release elicited by tactile stimulation was greater than that produced by the other stimuli. There was no significant variation in the duration of increases in acetylcholine release produced by the stimuli in either the hippocampus or cortex. These results provide evidence that acetylcholine release is associated with a variety of behavioural responses to stimuli designed to produce arousal, and point to a role for cortical and hippocampal cholinergic mechanisms in arousal or attention. Further, the results suggest that under some circumstances cortical and hippocampal acetylcholine release may be regulated differentially.

Acetylcholine↗

PubMed2006

Reduction of intractable deafferentation pain by navigation-guided repetitive transcranial magnetic stimulation of the primary motor cortex.

The precentral gyrus (M1) is a representative target for electrical stimulation therapy of pain. To date, few researchers have investigated whether pain relief is possible by stimulation of cortical areas other than M1. According to recent reports, repetitive transcranial magnetic stimulation (rTMS) can provide an effect similar to that of electrical stimulation. With this in mind, we therefore examined several cortical areas as stimulation targets using a navigation-guided rTMS and compared the effects of the different targets on pain. Twenty patients with intractable deafferentation pain received rTMS of M1, the postcentral gyrus (S1), premotor area (preM), and supplementary motor area (SMA). Each target was stimulated with ten trains of 10-s 5-Hz TMS pulses, with 50-s intervals in between trains. Intensities were adjusted to 90% of resting motor thresholds. Thus, a total of 500 stimuli were applied. Sham stimulations were undertaken at random. The effect of rTMS on pain was rated by patients using a visual analogue scale (VAS) and the short form of the McGill Pain Questionnaire (SF-MPQ). Ten of the 20 patients (50%) indicated that stimulation of M1, but not other areas, provided significant and beneficial pain relief (p<0.01). Results indicated a statistically significant effect lasting for 3 hours after the stimulation of M1 (p<0.05). Stimulation of other targets was not effective. The M1 was the sole target for treating intractable pain with rTMS, in spite of the fact that M1, S1, preM, and SMA are located adjacently.

Adult↗

PubMed1986

Artistic creation as stimulated by superimposed versus combined-composite visual images.

The creative role of homospatial thinking in visual art was assessed in an experiment with 39 highly talented young artists. In order to compare the creative effects of visual elements occupying the same space with identical elements arrayed in a combined foreground and background organization, superimposed slide images were presented to a randomly selected portion of the subject group, and the other portion of the subject group viewed the same slide images constructed into a figure-ground composite. Both groups produced three drawings stimulated by the slide stimuli, and these drawings were independently judged by three art experts. Results were that drawings produced by the group exposed to the superimposed images were rated higher in creative potential than those stimulated by the figure-ground controls. These results extend previous experimental findings of a tendency toward homospatial thinking in creative individuals in literature and visual art.

Art↗

PubMed2001

The temporal profile of interactions between sensory information from both hands in the secondary somatosensory cortex.

OBJECTIVE: To elucidate the temporal profile of interactions between sensory information from both hands in the somatosensory cortex. METHODS: Somatosensory evoked fields (SEFs), generated by stimulation applied to the right index finger after a preceding stimulation to the left index finger, were recorded using a whole head-type magnetoencephalography (MEG). The paired electrical stimuli were applied with a stimulation onset asynchrony (SOA) of 50, 100, 200, 300, or 400 ms. RESULTS: The mean SEF intensities in the primary somatosensory area (SI) of five subjects, which were evoked approximately 40 ms after the latter of the paired stimuli, were not significantly smaller than that evoked in the control condition when only the right finger was stimulated. In contrast, SEFs in the secondary somatosensory area (SII), generated approximately 100 ms after the stimuli, were suppressed when the paired stimuli were applied at an SOA of 100 ms (P<0.05, t test). In addition, SEFs at approximately 150 ms after the stimuli were significantly suppressed at SOAs of 50, 100 (P<0.05), 200, and 300 ms (P<0.1). CONCLUSION: Within a time window of approximately 300 ms, sensory information from the left finger significantly affected the SEFs generated by sensory inputs from the right finger. This time window may be required for the integration of sensory input.

Adult↗

PubMed2006

A novel modelling and experimental technique to predict and measure tissue temperature during CO2 laser stimuli for human pain studies.

Laser nerve stimulation is now accepted as one of the preferred methods for applying painful stimuli to human skin during pain studies. One of the main concerns, however, is thermal damage to the skin. We present recent work based on using a CO2 laser with a remote infrared (IR) temperature sensor as a feedback system. A model for predicting the subcutaneous skin temperature derived from the signal from the IR detector allows us to accurately predict the laser parameters, thus maintaining an optimum pain stimulus whilst avoiding dangerous temperature levels, which could result in thermal damage. Another aim is to relate the modelling of the CO2 fibre laser interaction to the pain response and compare these results with practical measurements of the pain threshold for various stimulus parameters. The system will also allow us to maintain a constant skin temperature during the stimulus. Another aim of the experiments underway is to review the psychophysics for pain in human subjects, permitting an investigation of the relationship between temperature and perceived pain.

Adolescent↗

PubMed1999

Selective activation and functional significance of p38alpha mitogen-activated protein kinase in lipopolysaccharide-stimulated neutrophils.

Activation of leukocytes by proinflammatory stimuli selectively initiates intracellular signal transduction via sequential phosphorylation of kinases. Lipopolysaccharide (LPS) stimulation of human neutrophils is known to result in activation of p38 mitogen-activated protein kinase (MAPk); however, the upstream activator(s) of p38 MAPk is unknown, and consequences of p38 MAPk activation remain largely undefined. We investigated the MAPk kinase (MKK) that activates p38 MAPk in response to LPS, the p38 MAPk isoforms that are activated as part of this pathway, and the functional responses affected by p38 MAPk activation. Although MKK3, MKK4, and MKK6 all activated p38 MAPk in experimental models, only MKK3 was found to activate recombinant p38 MAPk in LPS-treated neutrophils. Of p38 MAPk isoforms studied, only p38alpha and p38delta were detected in neutrophils. LPS stimulation selectively activated p38alpha. Specific inhibitors of p38alpha MAPk blocked LPS-induced adhesion, nuclear factor-kappa B (NF-kappaB) activation, and synthesis of tumor necrosis factor-alpha (TNF-alpha). Inhibition of p38alpha MAPk resulted in a transient decrease in TNF-alpha mRNA accumulation but persistent loss of TNF-alpha synthesis. These findings support a pathway by which LPS stimulation of neutrophils results in activation of MKK3, which in turn activates p38alpha MAPk, ultimately regulating adhesion, NF-kappaB activation, enhanced gene expression of TNF-alpha, and regulation of TNF-alpha synthesis.

Calcium-Calmodulin-Dependent Protein Kinases↗

PubMed1980

Anatomical and physiological evidence for a relationship between the 'cingular' vocalization area and the auditory cortex in the squirrel monkey.

With the aid of the autoradiographic tracing technique the projections from cortical limbic vocalization areas to the auditory cortex in the superior temporal gyrus were studied in the squirrel monkey. The vocalization areas were identified by exploring the anterior limbic cortex with moving electrodes until a site was found where electrical stimulation yielded vocalization. Projections from the region around the cingulate sulcus and supracallosal anterior cingulate gyrus have their terminal fields in the lower part of the superior temporal gyrus (STG) and upper bank of the superior temporal sulcus. Injections just in front of the genu of the corpus callosum and in the subcallosal gyrus and gyrus rectus lead to terminal fields in the middle part of STG. No projections were found in the upper part of STG, i.e. the primary auditory cortex. To test the functional properties of this pathway, action potentials of single neurons in the auditory cortex were recorded during electrical stimulation of the cingular vocalization area. From a total of 135 STG neurons, an effect on spontaneous activity was seen in 27 cells. All except one of these neurons also reacted to acoustic stimuli. In most cases, stimulation of the cingular area caused a decrease in the discharge rate of the STG neurons. In 4 neurons, stimulation of the vocalization area had an influence on the acoustic reactivity of the STG neurons. The results provide evidence that during phonation the 'cingular' vocalization area exerts a predominantly inhibitory influence on auditory cortex neurons. This effect probably is mediated via the extreme capsule. Its possible function is discussed.

Animals↗

PubMed1989

Evidence for inhibition of opossum LES through intrinsic gastric nerves.

We have studied the mechanical responses of the isolated opossum gastroesophageal junction to a variety of stimuli. Lower esophageal sphincter (LES) relaxations were readily produced by gastric stretch and by electrical stimulation of the intramural gastric nerves. Gastric stimulation also led in 60% of stimuli to a contraction of circular muscle (the off response) in the distal esophagus, but in less than 15% of stimuli to a contraction of longitudinal esophageal muscle (the duration response). Mechanical or electrical stimulation of the esophagus led to a mechanical response of the stomach (relaxation, contraction, or both) in 76% of stimuli. The LES relaxation produced by esophageal stimulation was not as long as that produced by gastric stimulation. Direct electrical stimulation of the esophageal or gastric muscle produced a ring contraction that spread readily across the gastroesophageal junction but did not produce a relaxation of the LES or a contraction of the longitudinal esophageal muscle. Thus intramural nervous pathways can coordinate the mechanical activity of the esophagus, LES, and stomach. LES relaxations may occur as part of intrinsic reflexes that mediate gastric accommodation to volume.

Animals↗

PubMed1981

Response properties and behavioral modulation of "mouth" neurons of the postarcuate cortex (area 6) in macaque monkeys.

Single neurons were recorded from the "mouth area" of the postarcuate cortex in macaque monkeys. According to their responses to somatosensory stimuli and their activity during the animal's movements, the neurons were subdivided into three classes: (1) neurons activated only by external stimuli; (2) neurons showing an enhancement of their response when a specific motor act followed the external stimulation; (3) neurons responding reliably to external stimuli only if the stimulation triggered a specific, related motor act. Of the recorded neurons, 50% also responded to visual stimuli.

Animals↗

PubMed1985

Stimulus-dependent inhibition of superoxide generation by prostaglandins.

Infiltrating phagocytes generate superoxide anion (O2-) and prostaglandin (PG) at sites of inflammation. Thus PG-O2- interactions may be important to the initiation and control of inflammation. PGE1, PGE2, and PGD2 inhibit O2- generation (as measured by superoxide dismutase-inhibitable reduction of ferricytochrome c) in a dose-dependent manner (10(-6)-10(-9) M) when human peripheral blood polymorphonuclear leucocytes (PMN) are stimulated with 10(-7) M of the chemotactic peptide, N-formyl-methionyl-leucyl-phenylalanine (FMLP). These PG did not alter O2- generation when PMN were stimulated with 0.1 microgram/ml phorbol myristate acetate (PMA) or 1 mg/ml serum-treated zymosan (STZ). Increments of cyclic AMP (cAMP) (peak: fourfold) in PGE1, PGE2, and PGD2 treated PMN stimulated with PMA or STZ (in which O2- was not reduced) were similar to those in PG-treated PMN stimulated with FMLP (in which O2- was reduced markedly). High concentrations of theophylline and dibutyryl cAMP reduced FMLP and STZ stimulated O2- generation but had no effect on PMA stimulation, suggesting that the stimuli induce different sensitivities to the effects of cellular cAMP. PGF2 alpha had little effect on O2- generation or cAMP levels regardless of the stimulus. PGE1 did not inhibit binding of FML(3H)P to PMN and did not scavenge O2- anions. Therefore the effect of PG on O2- production is dependent on the specific stimulator and an increased concentration of cAMP in activated PMN is by itself not sufficient to limit O2- generation induced by all stimuli.

Alprostadil↗

PubMed1977

Topographic organization and convergence in corticotectal projections from areas 17, 18, and 19 in the cat.

1. Electrical stimulation in areas 17, 18 and 19 of the cat's visual cortex activated neurons in the superficial gray layer of the superior colliculus. The threshold for such excitation was lowest when the receptive fields of cells at the stimulus site lay inside the receptive field of the collicular cell under observation. 2. A substantial percentage of the recorded collicular cells received convergent excitatory input from more than one of the stimulated cortical areas. When stimuli could be applied in parts of areas 17, 18, and 19 related retinotopically to a collicular cell, over half of the units were activated from all three cortical areas by low-intensity stimulation. 3. Cells located near one another in the colliculus received excitatory cortical input from regions of areas 17, 18, and 19 which were not identical in size. This may be attributable to the disparate dimensions of collicular dendritic fields, which permit neighboring cells to sample dissimilar regions of the topographically organized cortical input. It is argued that this projection system preserves the functional unity of cortical and tectal cell groups processing information from a given retinal point.

Animals↗

PubMedDate not supplied

[Effect of rhythmic and tonic stimulation on the neuronal activity of the olfactory bulb in the newt Triturus cristatus].

Studies have been made of the dependence of neuronal reactions in the olfactory bulb of the newt on the pattern of presentation of a test solution (glutamine 10(-5) M) into the nasal cavity. Responses to stimulation at a frequency 6/min (which corresponds to the minimal rhythm of normal buccal movements) varied in the intensity and sign. The peak of excitation was usually observed after the 2nd or the 3rd stimuli. The increase of stimulation frequency up to 12-24/min increased the number of the inhibitory reactions and the intensity of inhibition. Replacement of rhythmic flow by a constant one results in inhibition of 34% of neurones which reacted by activation to the rhythmic series of 6/min. The data obtained are discussed in relation to the pattern of olfactory perception in newts under natural conditions.

Animals↗

PubMed1998

Covariation between human intrinsic hand muscles of the silent periods and compound muscle action potentials evoked by magnetic brain stimulation: evidence for common inhibitory connections.

Transcranial magnetic stimuli at different stimulus intensities were applied in six healthy subjects to test the hypothesis that, in different intrinsic hand muscles, the duration of the resultant cortically evoked silent periods (C-SPs) from each stimulus would be positively correlated between muscles, indicating a common inhibitory mechanism. A figure-of-eight coil discharging through a Magstim 200 stimulator delivered 25 stimuli at each stimulus intensity at a minimum of five intensities ranging from 55% to 160% of the individual resting motor threshold. In each subject, simultaneous surface recordings from pairs of muscles were made from the first dorsal interosseous (FDI), opponents pollicis (OP), abductor pollicis brevis (APB) and abductor digiti minimi (ADM). The C-SP durations within all three muscle pairs tested were highly correlated (P<0.001). The amplitude of the preceding compound-muscle action potentials (CMAPs) was positively correlated between FDI and OP, but not between APB and ADM or FDI and ADM. C-SP duration was linearly related to stimulus intensity, but did not correlate with the latency or amplitude of the preceding CMAP. SPs elicited by peripheral nerve stimuli in pairs of hand muscles did not co-vary significantly. The results provide evidence that inhibitory influences of cortical origin are distributed widely to intrinsic hand muscles. In contrast, covariation of excitatory effects only appears between muscles synergistically involved in a motor task.

Action Potentials↗

PubMed1977

Alpha blocking: absence in visuobehavioral deprivation.

Subjects with congenital deficits that allowed only diffuse light perception through one eye were examined for blocking of the alpha rhythm. With only the deprived eye open the electroencephalogram is dominated by alpha rhythm that is not blocked by photic stimulation, even though the stimuli evoke a response from occipital cortex.

Adult↗

PubMed1980

Study of sensation and muscle twitch responses to spinal cord stimulation.

Electrically induced sensation and muscle twitches were studied in a group of 43 patients in whom epidural electrodes were percutaneously placed for the evaluation of the effect of spinal cord stimulation on modification of their impaired motor control. Mean stimulus strength for sensory threshold was 5.25 +/- 2.75 mA and the tolerance level was at the stimulus strength of 10.8 +/- 4.4 mA. Muscle twitches with short latencies were recorded in limb and trunk muscles within the segments at the stimulating cathode. Exceptionally, higher stimuli elicited muscle twitches of distant segments.

Adolescent↗

PubMed1990

Aversive taste stimuli increase CGRP levels in the gustatory insular cortex of the rat.

Calcitonin gene-related peptide-like immunoreactivity (CGRP-IR) was surveyed immunohistochemically in the insular cortex of the rat, and the levels of insular cortical CGRP-IR were measured with the radioimmunoassay method following intraoral stimulation with various taste stimuli. CGRP-IR was localized in nerve fibers within the agranular and dysgranular insular cortices. The CGRP-IR levels in the rostral (gustatory) part of the insular cortex were increased significantly by strongly aversive taste stimuli such as quinine hydrochloride and conditioned taste stimuli (NaCl and sucrose) which animals had been taught to avoid. The results suggest that CGRP in the gustatory insular cortex is concerned with rejection or avoidance behaviors to aversive taste stimuli.

Animals↗