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Biomedical subjects

F McGlone

Publications and source records attributed to F McGlone.

At least 19 recordsLinked to original sources

Controlled dermal cell damage as human in vivo model for localised pain and inflammation.

OBJECTIVE AND DESIGN: An unspecific human in vivo model of dermal pain and inflammation was developed by means of limited, localised and controlled cell damage. SUBJECTS: Twelve participants were recruited. TREATMENT: Dermal microdialysis was used to deliver randomised and single blinded aqueous sodium dodecyl sulphate (SDS) at concentrations of 0.01%, 0.1% and 0.5% w/v to the volar forearm. METHODS: Nociceptive responses were recorded on a numerical scale, vasodilatation was assessed by laser Doppler scanning and sampled tissue fluid was analysed for PGE2 by ELISA. RESULTS: Saline control and 0.01% SDS did not differ in their ability to cause vasodilatation, flare reaction or pain. In contrast, SDS (0.1 and 0.5%) evoked a significant increase of blood flow (p<0.005), a widespread reddening (p<0.01), and stinging-burning pain (p<0.005). PGE2 concentration in the dialysate did not change during 0.01% SDS perfusion (p>0.9), but increased significantly following the stimulation with 0.1% and 0.5% SDS (20 to 30-fold). No significant differences of released PGE2 levels were determined between 0.1% and 0.5% SDS stimulation (p>0.05). CONCLUSIONS: We demonstrated that localised intradermal administration of SDS induces a limited pain and inflammatory response in humans. Excitation of nociceptors was accompanied by a massive PGE2 release. Employing this experimental model, the relative contribution of endogenous mediators to induce, maintain or facilitate pain and vasodilatation can be investigated.

Adult↗

Histamine induced responses are attenuated by a cannabinoid receptor agonist in human skin.

OBJECTIVE AND DESIGN: In the present study we examined the effects of the cannabinoid receptor agonist HU210 on histamine-evoked somatosensory and vascular responses in humans. SUBJECTS: Two sets of experiments were performed, in which twelve (Study 1, iontophoresis) and six participants (Study 2, microdialysis) were recruited. TREATMENT: HU210 was administered peripherally by skin patch (50 mM) or dermal microdialysis (5 mM), whereas histamine was applied by iontophoresis (50 microAmps) or dermal microdialysis (5 microM). METHODS: Skin blood flow was monitored by laser Doppler, widespread flare reaction was evaluated planimetrically, extravasation of plasma proteins was measured in the dialysate and perceived itch was recorded using a visual analogue scale. Data were evaluated by analysis of variance. RESULTS: Experimentally induced itch was significantly reduced by peripheral administration of HU210 (p < 0.05). Additionally, skin blood flow and neurogenic mediated flare responses were attenuated (p < 0.003 and p < 0.03, respectively), whereas protein extravasation due to histamine was enhanced by co-administration of HU210, as investigated by dermal microdialysis. CONCLUSIONS: In humans peripheral administration of a cannabinoid receptor agonist attenuates histamine-induced itch. The observation that protein extravasation was not decreased demonstrates that the alleviation of itch is not due to an anti-histaminergic property of HU210. The reduced neurogenic flare reaction indicates an attenuated antidromic nerve fibre activation and neuropeptide release.

Administration, Topical↗

Representations of pleasant and painful touch in the human orbitofrontal and cingulate cortices.

The cortical areas that represent affectively positive and negative aspects of touch were investigated using functional magnetic resonance imaging (fMRI) by comparing activations produced by pleasant touch, painful touch produced by a stylus, and neutral touch, to the left hand. It was found that regions of the orbitofrontal cortex were activated more by pleasant touch and by painful stimuli than by neutral touch and that different areas of the orbitofrontal cortex were activated by the pleasant and painful touches. The orbitofrontal cortex activation was related to the affective aspects of the touch, in that the somatosensory cortex (SI) was less activated by the pleasant and painful stimuli than by the neutral stimuli. This dissociation was highly significant for both the pleasant touch (P < 0.006) and for the painful stimulus (P < 0.02). Further, it was found that a rostral part of the anterior cingulate cortex was activated by the pleasant stimulus and that a more posterior and dorsal part was activated by the painful stimulus. Regions of the somatosensory cortex, including SI and part of SII in the mid-insula, were activated more by the neutral touch than by the pleasant and painful stimuli. Part of the posterior insula was activated only in the pain condition and different parts of the brainstem, including the central grey, were activated in the pain, pleasant and neutral touch conditions. The results provide evidence that different areas of the human orbitofrontal cortex are involved in representing both pleasant touch and pain, and that dissociable parts of the cingulate cortex are involved in representing pleasant touch and pain.

Adult↗

Counter-stimulatory effects on pain perception and processing are significantly altered by attention: an fMRI study.

Counter-stimulation reduces pain perception; however, the role of attention during this process is rarely discussed despite attention itself being a well known modulator of pain perception. This study investigated the effect of attentional modulation on pain perception during counter-stimulation using fMRI. Subjects received a noxious thermal stimulus together with an innocuous vibratory counter-stimulus. Subjects directed their attention towards either pain, vibration, or a neutral visual stimulus. During painful and counter-stimulation all subjects reported a reduction in pain perception when attending to counter-stimulation compared with attending to pain. Imaging data supported this behavioural finding showing reduced activity in pain processing areas (anterior cingulate, insula, thalamus). These results suggest attention plays an important part in the pain relief experienced from counter-stimulation.

Adult↗

Cortical responses to single mechanoreceptive afferent microstimulation revealed with fMRI.

The technique of intraneural microneurography/microstimulation has been used extensively to study contributions of single, physiologically characterized mechanoreceptive afferents (MRAs) to properties of somatosensory experience in awake human subjects. Its power as a tool for sensory neurophysiology can be greatly enhanced, however, by combining it with functional neuroimaging techniques that permit simultaneous measurement of the associated CNS responses. Here we report its successful adaptation to the environment of a high-field MR scanner. Eight median-nerve MRAs were isolated and characterized in three subjects and microstimulated in conjunction with fMRI at 3.0 T. Hemodynamic responses were observed in every case, and these responses were robust, focal, and physiologically orderly. The combination of fMRI with microstimulation will enable more detailed studies of the representation of the body surface in human somatosensory cortex and further studies of the relationship of that organization to short-term plasticity in the human SI cortical response to natural tactile stimuli. It can also be used to study many additional topics in sensory neurophysiology, such as CNS responses to additional classes of afferents and the effects of stimulus patterning and unimodal/crossmodal attentional manipulations. Finally, it presents unique opportunities to investigate the basic physiology of the BOLD effect and to compare the operating characteristics of fMRI and EEG as human functional neuroimaging modalities in an unusually specific and well-characterized neurophysiological setting.

Brain Mapping↗

Vision influences tactile perception at body sites that cannot be viewed directly.

Previous research has demonstrated that vision of a body site, without proprioceptive orienting of eye and head to that site, could affect tactile perception. The body site viewed was the hand, which can be seen directly under normal viewing conditions. The current research asked three further questions: First, can vision similarly affect tactile perception at a body site that cannot normally be viewed directly such as the face or neck? Second, does prior experience of seeing a body site, such as occurs when viewing the face in mirrors, produce larger effects of viewing than body sites rarely seen such as the back of the neck? And third, how quickly can visual information affect tactile target detection? We observe that: detection of tactile targets at these body sites was influenced by whether or not they were viewed, this effect was greater when viewing the more familiar site of the face than that of the neck, and significant effects were observed when the stimulus onset asynchrony between visual display and tactile target was as little as 200 ms.

Adult↗

Representation of pleasant and aversive taste in the human brain.

In this study, the representation of taste in the orbitofrontal cortex was investigated to determine whether or not a pleasant and an aversive taste have distinct or overlapping representations in this region. The pleasant stimulus used was sweet taste (1 M glucose), and the unpleasant stimulus was salt taste (0.1 M NaCl). We used an ON/OFF block design in a 3T fMRI scanner with a tasteless solution delivered in the OFF period to control for somatosensory or swallowing-related effects. It was found that parts of the orbitofrontal cortex were activated (P < 0.005 corrected) by glucose (in 6/7 subjects) and by salt (in 6/7 subjects). In the group analysis, separate areas of the orbitofrontal cortex were found to be activated by pleasant and aversive tastes. The involvement of the amygdala in the representation of pleasant as well as aversive tastes was also investigated. The amygdala was activated (region of interest analysis, P < 0.025 corrected) by the pleasant taste of glucose (5/7 subjects) as well as by the aversive taste of salt (4/7 subjects). Activation by both stimuli was also found in the frontal opercular/insular (primary) taste cortex. We conclude that the orbitofrontal cortex is involved in processing tastes that have both positive and negative affective valence and that different areas of the orbitofrontal cortex may be activated by pleasant and unpleasant tastes. We also conclude that the amygdala is activated not only by an affectively unpleasant taste, but also by a taste that is affectively pleasant, thus providing evidence that the amygdala is involved in effects produced by positively affective as well as by negatively affective stimuli.

Amygdala↗

Sensory-specific satiety-related olfactory activation of the human orbitofrontal cortex.

When a food is eaten to satiety, its reward value decreases. This decrease is usually greater for the food eaten to satiety than for other foods, an effect termed sensory-specific satiety. In an fMRI investigation it was shown that for a region of the orbitofrontal cortex the activation produced by the odour of the food eaten to satiety decreased, whereas there was no similar decrease for the odour of a food not eaten in the meal. This effect was shown both by a voxel-wise SPM contrast (p <0.05 corrected) and an ANOVA performed on the mean percentage change in BOLD signal in the identified clusters of voxels (p <0.006). These results show that activation of a region of the human orbitofrontal cortex is related to olfactory sensory-specific satiety.

Eating↗

Sensory-specific satiety-related olfactory activation of the human orbitofrontal cortex.

When a food is eaten to satiety, its reward value decreases. This decrease is usually greater for the food eaten to satiety than for other foods, an effect termed sensory-specific satiety. In an fMRI investigation it was shown that for a region of the orbitofrontal cortex the activation produced by the odour of the food eaten to satiety decreased, whereas there was no similar decrease for the odour of a food not eaten in the meal. This effect was shown both by a voxel-wise SPM contrast (p<0.05 corrected) and an ANOVA performed on the mean percentage change in BOLD signal in the identified clusters of voxels (p<0.006). These results show that activation of a region of the human orbitofrontal cortex is related to olfactory sensory-specific satiety.

Brain Mapping↗

fMRI of the responses to vibratory stimulation of digit tips.

Three studies were carried out to assess the applicability of fMRI at 3.0 T to analysis of vibrotaction in humans. A novel piezoelectric device provided clean sinusoidal stimulation at 80 Hz, which was initially applied in separate runs within a scanning session to digits 2 and 5 of the left hand in eight subjects, using a birdcage RF (volume) coil. Significant clusters of activation were found in the primary somatosensory cortex (SI), the secondary somatosensory cortex (SII), subcentral gyrus, the precentral gyrus, posterior insula, posterior parietal regions (area 5), and the posterior cingulate. Digit separation in SI was possible in all subjects and the activation sites reflected the known lateral position of the representation of digit 2 relative to that of digit 5. A second study carried out in six additional subjects using a surface coil, replicated the main contralateral activation patterns detected in study one and further improved the discrimination of the digits in SI. Significant digit separation was also found in SII and in the posterior insula. A third study to investigate the frequency dependence of the response focused on the effect of an increase in vibrotactile frequency from 30 to 80 Hz, with both frequencies applied to digit 2 during the same scanning session in four new subjects. A significant increase in the number of pixels activated within both SII and the posterior insula was found, while the number of pixels activated in SI declined. No significant change in signal intensity with frequencies was found in any of the activated areas.

Adult↗

Inhibition of return is supramodal: a demonstration between all possible pairings of vision, touch, and audition.

Inhibition of return' (IOR) refers to the delayed detection often found for targets at the same location as a preceding event. We examined whether IOR reflects a truly supramodal phenomenon, in an experiment designed to avoid criticisms of previous crossmodal research. We presented a random sequence of visual, tactile, and auditory targets to either the left or right of central fixation, and tested for IOR between targets in all three modalities when presented successively to the same versus different side. Speeded detection for targets in all three modalities was indeed slower if the preceding target had been presented from the same position, regardless of the modality, of this preceding target. These results demonstrate for the first time that IOR is truly supramodal.

Acoustic Stimulation↗

Mast cell mediators other than histamine induce pruritus in atopic dermatitis patients: a dermal microdialysis study.

While histamine is the crucial mediator of pruritus in type 1 allergic reactions, its role in atopic dermatitis (AD) is unclear. In this study, the role of mast cell mediators in protein extravasation and pruritus was evaluated using intradermal microdialysis. The microdialysis capillaries were used to apply the mast cell degranulating substance compound 48/80 (C48/80; 0.05%) or histamine (0.01%) and also to deliver H1-blockers (cetirizine, 200 microg mL-1) in nine AD patients and nine controls. Large pore size membranes (3000 kDa) enabled simultaneous analysis of protein extravasation. Itch sensation was measured psychophysically and weal and flare reaction were evaluated planimetrically. Protein extravasation induced by histamine and C48/80 was significantly reduced in AD patients. Blockade of H1-receptors by cetirizine significantly reduced C48/80-induced protein extravasation in AD patients and controls to an identical level. C48/80-induced pruritus was abolished by cetirizine in controls, whereas pruritus in AD patients was unchanged after H1 blockade. We conclude that mast cell mediators others than histamine are involved in C48/80-induced pruritus in AD patients. Whether the reduced capacity of AD patients to induce protein extravasation is of pathophysiological relevance for pruritus remains to be established.

Adult↗

The representation of pleasant touch in the brain and its relationship with taste and olfactory areas.

Although there has been much investigation of brain pathways involved in pain, little is known about the brain mechanisms involved in processing somatosensory stimuli which feel pleasant. Employing fMRI it was shown that pleasant touch to the hand with velvet produced stronger activation of the orbitofrontal cortex than affectively neutral touch of the hand with wood. In contrast, the affectively neutral but more intense touch produced more activation of the primary somatosensory cortex than the pleasant stimulus. This indicates that part of the orbitofrontal cortex is concerned with representing the positively affective aspects of somatosensory stimuli, and in further experiments it was shown that this orbitofrontal area is different from that activated by taste and smell. The finding that three different primary or unlearned types of reinforcer (touch, taste, and smell) are represented in the orbitofrontal cortex helps to provide a firm foundation for understanding the neural basis of emotions, which can be understood in terms of states elicited by stimuli which are rewarding or punishing.

Brain↗

Passive, active and intra-active (self) touch.

A series of experiments are described in which magnitude estimates of the perceived size of steel balls were made when the balls were actively rolled between the fingertip and several other body sites (thumb, thenar eminence, forearm). This movement, called scripting, involves actively-moving an object by a touching surface over another surface of the body which is passively being touched. We define this active/passive activity as "intra-active touch" and the results show that the perceptual size of the balls is dependent upon the body part passively being activated. An additional series of experiments decoupled the actively generated and passively received tactile information by having subjects either perform the scripting on another individual's body site or by having the other individual roll the balls on the subject's various sites. The latter experiments showed that the passive body can contribute to the overall impression of the size of the balls, but only when the intra-active touching involved the glabrous skin of the hands. Intra-active touch between the active finger and the passively touched hairy skin of the forearm showed no effect of the touched surface on the perceived size of the balls. The results suggest that the mechanisms of intra-active touch are different when glabrous skin activates glabrous skin than when glabrous skin activates hairy skin.

Adult↗

Mechanisms of attention in touch.

A series of experiments demonstrated the role of higher level cognitive processes, such as attention, in tactile perception. The first series of experiments demonstrated that automatic orienting to a tactile stimulus resulted in inhibition of subsequent stimuli at that body site--inhibition of return (IOR). A possible explanation suggests that inhibition of saccades to a body site can cause the inhibition of subsequent stimuli presented to that same site. In contrast, when the subjects strategically oriented attention to the stimulus, the processing of subsequent stimuli at that body site was facilitated. In both of these experiments the skin received exactly the same test stimuli, (100 Hz sine wave presented for 50 ms), but very different effects were observed depending upon attentional strategy. Experimental manipulations showed that this cannot be due to a peripheral masking of the receptors after cue presentation to the target. Rather the results may be explained centrally by cognitive, particularly attentional mechanisms. Cross-modal interactions suggest that tactile processes are facilitated when vision is oriented to the body site receiving stimulation. Possible explanations come from recent findings of spatiotopic maps of different sensory modalities in the superior colliculus of the midbrain and in the parietal lobe. These are integrated with motor systems that control saccades and head orientation towards sensory inputs. Excitatory links among these maps could be the source of the observed facilitation effects.

Adolescent↗

Vision influences tactile perception without proprioceptive orienting.

The perception of tactile stimuli is facilitated when subjects look towards the stimulated body site: this facilitation even takes place when visual information is unavailable, as when orienting in the dark. It is not known whether the facilitation is due entirely to such proprioceptive orienting of eye and head, or whether visual information of the body site can also facilitate touch. An experiment is reported which dissociates vision and proprioception, and demonstrates for the first time that vision of a body part, independent of proprioceptive orienting, can indeed effect somatosensation.

Adult↗

Peroperative monitoring during percutaneous thermocoagulation of the Gasserian ganglion for the treatment of trigeminal neuralgia.

A bipolar electrode has been designed to assess the possibility of locating accurately the electrode tip position within a nerve pathway prior to its thermal coagulation without having recourse to a wake-up procedure. By electrically stimulating each of the peripheral divisions of the trigeminal nerve and recording the evoked activity pre-ganglionically from the electrode, using an averaging computer, a clear triphasic response is recorded. The amplitude of this wave is largest when the electrode is within the stimulated division, thereby confirming electrically the anatomical location. By incorporating a thermocouple in the tip of the electrode a precisely controlled thermocoagulation can then be achieved using a radiofrequency generator. A preliminary series of 12 patients with trigeminal neuralgia requiring operative treatment were assessed in this study. In eight cases a clear response was obtained, in two the signal-to-noise ratio was too small, in one stimulus artefact obscured the response and in one a blood vessel was hit.

Electrocoagulation↗

Effects of corticosteroid hormones on the electrophysiology of rat distal colon: implications for Na+ and K+ transport.

1. Conventional microelectrodes, the Na+ channel blocker amiloride (0.1 mM), and the K+ channel blocker tetraethylammonium chloride (TEA, 30 mM) were used to examine the effects of corticosteroid hormones administered in vivo on the Na+ and K+ transport properties of isolated rat distal colon. The cell membrane changes induced by aldosterone (a specific mineralocorticoid), RU 28362 (a synthetic glucocorticoid with negligible affinity for mineralocorticoid receptors), and dexamethasone (an activator of both mineralocorticoid and glucocorticoid receptors) were compared. 2. In control animals, there was no amiloride-sensitive apical Na+ conductance, and only a relatively small TEA-sensitive apical K+ conductance. 3. Hyperaldosteronism secondary to dietary Na+ depletion for 10-14 days, dexamethasone (600 micrograms 100 g-1 day-1 for 3 days), and RU 28362 (600 micrograms 100 g-1 day-1 for 3 days) induced amiloride-sensitive electrogenic Na+ transport, with the potency of aldosterone greater than dexamethasone greater than RU 28362. 4. With each corticosteroid, increased electrogenic Na+ transport reflected enhanced apical Na+ conductance, and in the case of aldosterone and dexamethasone, 3.3-fold and 2-fold increases respectively in the maximum activity of the basolateral Na+-K+ pump. In contrast, RU 28362 suppressed the maximum activity of the basolateral Na+-K+ pump by 45%. 5. All three corticosteroids enhanced the K+ conductance of the apical membrane, with the potency of aldosterone greater than dexamethasone greater than RU 28362. 6. Co-administration of spironolactone (5 mg 100 g-1 day-1) inhibited the effects of aldosterone on Na+ and K+ transport, but in dexamethasone-treated animals spironolactone resulted in a pattern of response similar to that found in RU 28362-treated animals. 7. The results support the view that mineralocorticoid receptors mediate changes in colonic Na+ and K+ transport which differ quantitatively and qualitatively from those mediated by glucocorticoid receptors. Dexamethasone and similar 'glucocorticoids' activate both types of receptor, with an overall epithelial response which mimics that induced by aldosterone.

Aldosterone↗