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B Bromm

Publications and source records attributed to B Bromm.

At least 19 recordsLinked to original sources

How best to fight that nasty itch - from new insights into the neuroimmunological, neuroendocrine, and neurophysiological bases of pruritus to novel therapeutic approaches.

While the enormous clinical and psychosocial importance of pruritus in many areas of medicine and the detrimental effects of chronic 'itch' on the quality of life of an affected individual are widely appreciated, the complexity of this sensation is still often grossly underestimated. The current Controversies feature highlights this complexity by portraying pruritus as a truly interdisciplinary problem at the crossroads of neurophysiology, neuroimmunology, neuropharmacology, protease research, internal medicine, and dermatology, which is combated most successfully if one keeps the multilayered nature of 'itch' in mind and adopts a holistic treatment approach - beyond the customary, frequently frustrane monotherapy with histamine receptor antagonists. In view of the often unsatisfactory, unidimensional, and altogether rather crude standard instruments for pruritus management that we still tend to use in clinical practice today, an interdisciplinary team of pruritus experts here critically examines recent progress in pruritus research that future itch management must take into consideration. Focusing on new insights into the neuroimmunological, neuroendocrine, and neurophysiological bases of pruritus, and discussing available neuropharmacological tools, specific research avenues are highlighted, whose pursuit promises to lead to novel, and hopefully more effective, forms of pruritus management.

Dermatology↗

[Laser-evoked potentials: diagnostic approach to the dorsal root].

Functional diagnostics of the dorsal root are especially effective via nociceptive fibers on account of less intersegmental overlap compared to large-diameter fibers of the mechanoreceptive afferents. Laser-evoked potentials (LEP) are induced by short, painful heat stimuli. The aim of this work was to describe changes of the LEP in cases of dorsal root damage. The recorded LEP changes will be discussed with regard to their prognostic value as well as pathophysiologic aspects of dorsal root damage. Dorsal root function was tested in 21 patients suffering from clinically proven radiculopathy in one of the segments L4 to S1. Mechanosensibility and thermosensibility were clinically investigated. LEP were induced by slightly painful stimuli (80 on the affected and 80 on the contralateral unaffected dermatome). The LEP were evaluated by amplitude of the averaged electroencephalogram (EEG). In addition, a subjective pain rating was recorded after each stimulus. Investigation of dorsal root function by LEP in patients with radiculopathy yields two typical changes of the amplitude. On the one hand, there were significant reductions of amplitude, and on the other hand, a complete loss of LEP was found. LEP changes allow a graduation of patients who show no obvious differences in their clinical appearance. Which mechanisms are responsible as concerns deafferentiation and neuropathy of the dorsal root fibers are discussed. With regard to the LEP changes, a prognostic relevance in patients with dorsal root affections is likely. This question will be addressed in a prospective study soon.

Adult↗

Single trial fMRI reveals significant contralateral bias in responses to laser pain within thalamus and somatosensory cortices.

Pain is processed in multiple brain areas, indicating the complexity of pain perception. The ability to locate pain plays a pivotal role in immediate defense and withdrawal behavior. However, how the brain localizes nociceptive information without additional information from somatotopically organized mechano-receptive pathways is not well understood. We used single-trial functional magnetic resonance imaging (fMRI) to assess hemodynamic responses to right and left painful stimulation. Thulium-YAG-(yttrium-aluminium-granate)-laser-evoked pain stimuli, without concomitant tactile component, were applied to either hand in a randomized order. A contralateral bias of the BOLD response was investigated to determine areas involved in the coding of the side of stimulation, which we observed in primary (SI) and secondary (SII) somatosensory cortex, insula, and the thalamus. This suggests that these structures provide spatial information of selective nociceptive stimuli. More importantly, this contralateral bias of activation allowed functionally segregated activations within the SII complex, the insula, and the thalamus. Only distinct subregions of the SII complex, the posterior insula and the lateral thalamus, but not the remaining SII complex, the anterior insula and the medial thalamus, showed a contralaterally biased representation of painful stimuli. This result supports the hypothesis that sensory-discriminative attributes of painful stimuli, such as those related to body side, are topospecifically represented within the forebrain projections of the nociceptive system and highlights the concept of functional segregation and specialization within these structures.

Adult↗

Subcortical structures involved in pain processing: evidence from single-trial fMRI.

Pain is processed in multiple cortical and subcortical brain areas. Subcortical structures are substantially involved in different processes that are closely linked to pain processing, e.g. motor preparation, autonomic responses, affective components and learning. However, it is unclear to which extent nociceptive information is relayed to and processed in subcortical structures. We used single-trial functional magnetic resonance imaging (fMRI) to identify subcortical regions displaying hemodynamic responses to painful stimulation. Thulium-YAG (yttrium-aluminum-granate) laser evoked pain stimuli, which have no concomitant tactile component, were applied to either hand of healthy volunteers in a randomized order. This procedure allowed identification of areas displaying differential fMRI responses to right- and left-sided stimuli. Hippocampal complex, amygdala, red nucleus, brainstem and cerebellum were activated in response to painful stimuli. Structures related to the affective processing of pain showed bilateral activation, whereas structures involved in the generation of withdrawal behavior, namely red nucleus, putamen and cerebellum displayed differential (i.e. asymmetric) responses according to the side of stimulation. This suggests that spatial information about the nociceptive stimulus is made available in these structures for the guidance of defensive and withdrawal behavior.

Adult↗

Differential effects of isoflurane on excitatory and inhibitory synaptic inputs to thalamic neurones in vivo.

BACKGROUND: Mechanosensory thalamocortical relay neurones (TCNs) receive glutamatergic excitatory input and are subjected to gamma-aminobutyric acid (GABA)Aergic inhibitory input. This study assessed the effects of an increase in concentration of isoflurane on thalamic excitatory and inhibitory mechanisms. METHODS: TCNs (n = 15) of the thalamic ventral posteromedial nucleus responding to mechanical stimulation of whiskers were investigated in rats anaesthetized with end-tidal concentrations of isoflurane of approximately 0.9% (ISOlow, baseline) and approximately 1.9% (ISOhigh). Response activity induced by controlled vibratory movement of single whiskers was recorded before, during and after iontophoretic administration of the GABAA receptor antagonist bicuculline to the vicinity of the recorded neurone. RESULTS: The increase in concentration of isoflurane induced a suppression of vibratory responses to 14 (4)% [mean (SEM)] of baseline activity. Blockade of GABAA receptors by bicuculline during ISOlow and ISOhigh caused increases in response activity to 259 (32)% and 116 (25)% of baseline activity, respectively. The increase in isoflurane concentration enhanced overall inhibitory inputs by 102 (38)%, whilst overall excitatory inputs were reduced by 54 (7)%. CONCLUSIONS: These data suggest that doubling the concentration of isoflurane doubles the strength of GABAAergic inhibition and decreases the excitatory drive of TCNs by approximately 50%. The isoflurane-induced enhancement of GABAAergic inhibition led to a blockade of thalamocortical information transfer which was not accomplished by the effects of isoflurane on glutamatergic synaptic transmission alone. Thus, it appears that, with respect to transmission of information in the thalamus, the most prominent action of isoflurane is an enhancement of GABAAergic synpatic inhibition, and that effects on glutamatergic neurotransmission may contribute to a lesser extent.

Anesthetics, Inhalation↗

Painful stimuli evoke different stimulus-response functions in the amygdala, prefrontal, insula and somatosensory cortex: a single-trial fMRI study.

Only recently have neuroimaging studies moved away from describing regions activated by noxious stimuli and started to disentangle subprocesses within the nociceptive system. One approach to characterizing the role of individual regions is to record brain responses evoked by different stimulus intensities. We used such a parametric single-trial functional MRI design in combination with a thulium:yttrium-aluminium-granate infrared laser and investigated pain, stimulus intensity and stimulus awareness (i.e. pain-unrelated) responses in nine healthy volunteers. Four stimulus intensities, ranging from warm to painful (300-600 mJ), were applied in a randomized order and rated by the subjects on a five-point scale (P0-4). Regions in the dorsolateral prefrontal cortex and the intraparietal sulcus differentiated between P0 (not perceived) and P1 but exhibited no further signal increase with P2, and were related to stimulus perception and subsequent cognitive processing. Signal changes in the primary somatosensory cortex discriminated between non-painful trials (P0 and P1), linking this region to basic sensory processing. Pain-related regions in the secondary somatosensory cortex and insular cortex showed a response that did not distinguish between innocuous trials (P0 and P1) but showed a positive linear relationship with signal changes for painful trials (P2-4). This was also true for the amygdala, with the exception that, in P0 trials in which the stimulus was not perceived (i.e. 'uncertain' trials), the evoked signal changes were as great as in P3 trials, indicating that the amygdala is involved in coding 'uncertainty', as has been suggested previously in relation to classical conditioning.

Adult↗

Local GABA(A) receptor blockade reverses isoflurane's suppressive effects on thalamic neurons in vivo.

Many in vitro effects of volatile anesthetics are known, but the mechanisms of action are still under debate. Because suppression of sensory perception is one of the major goals of general anesthesia, we studied the effects of isoflurane on the processing of somatosensory information in anesthetized rats. Local iontophoretic administration of the gamma-aminobutyric acid-A (GABA(A)) receptor antagonist bicuculline in the thalamic ventral posteromedial nucleus reversed suppressive effects of isoflurane on thalamocortical relay neurons (TCNs). The action potential discharges of TCNs (n = 23) in response to defined mechanical stimulation of receptive fields seen with small concentrations of isoflurane (0.79% +/- 0.01%, mean +/- SEM) were suppressed under large concentrations (1.44% +/- 0.04%). In addition, the tonic response pattern was lost, which initially encoded the information about the stimulus features. In 70% of TCNs, bicuculline administration reestablished the initially present tonic response pattern under large isoflurane concentrations. These results indicate that isoflurane suppresses somatosensory information transfer at the thalamic level in vivo, apparently by enhancing thalamic GABA(A) receptor-mediated inhibition.

Anesthetics, Inhalation↗

Brain images of pain.

Combined magneto- and encephalography proves the sequential involvement of multiple cortical structures in pain processing. Bilateral activity in secondary somatosensory cortices reflects the sensory-discriminative component and is reduced in states of unconsciousness. Later activity in the posterior cingulum reflects the emotional-aversive component, which is blocked by narcoanalgesics.

Brain↗

The pain inhibiting pain effect: an electrophysiological study in humans.

This study examines the counterirritation phenomenon of experimental pain in human subjects. Phasic pain induced by intracutaneous electrical stimuli was simultaneously applied with tonic pain induced by ischemic muscle work. Pain ratings, spontaneous EEG and evoked potentials were measured. We found a significant reduction of phasic pain ratings during and 10 min after tonic pain. The late somatosensory evoked potentials as neurophysiological correlates of phasic pain sensation were attenuated until 20 min after tonic pain offset. The extent of phasic pain relief due to concomitant tonic pain was small but significant, comparable to the effect of a regular systemic dose of a narco-analgesic drug in this experimental pain model. On the other hand, no modulations in the late components of the auditory evoked potential and the power spectrum of the spontaneous EEG were observed. These variables reflect the attention and vigilance of the subject and are well-known to be affected by opioids. The only exception was an increase of beta power, which might reflect hyperarousal during tonic pain. These results support the suggestion, that the analgesic effect of heterotopic noxious stimulation in humans is based on the activation of a specific inhibitory pain control system. Systemic release of endogenous opioids is unlikely to be involved, because the typical effects of opioids on the EEG were not observed.

Adult↗

Topography of clonidine-induced electroencephalographic changes evaluated by principal component analysis.

BACKGROUND: Principal component analysis is a multivariate statistical technique to facilitate the evaluation of complex data dimensions. In this study, principle component analysis was used to reduce the large number of variables from multichannel electroencephalographic recordings to a few components describing changes of spatial brain electric activity after intravenous clonidine. METHODS: Seven healthy volunteers (age, 26 +/- 3 [SD] yr) were included in a double-blind crossover study with intravenous clonidine (1.5 and 3.0 microg/kg). A spontaneous electroencephalogram was recorded by 26 leads and quantified by standard fast Fourier transformation in the delta, theta, alpha, and beta bands. Principle component analysis derived from a correlation matrix calculated between all electroencephalographic leads (26 x 26 leads) separately within each classic frequency band. The basic application level of principle component analysis resulted in components representing clusters of electrodes positions that were differently affected by clonidine. Subjective criteria of drowsiness and anxiety were rated by visual analog scales. RESULTS: Topography of clonidine-induced electroencephalographic changes could be attributed to two independent spatial components in each classic frequency band, explaining at least 85% of total variance. The most prominent effects of clonidine were increases in the delta band over centroparietooiccipital areas and decreases in the alpha band over parietooccipital regions. Clonidine administration resulted in subjective drowsiness. CONCLUSIONS: Data from the current study supported the fact that spatial principle component analysis is a useful multivariate statistical procedure to evaluate significant signal changes from multichannel electroencephalographic recordings and to describe the topography of the effects. The clonidine-related changes seen here were most probably results of its sedative effects.

Adult↗

Isoflurane induces dose-dependent changes of thalamic somatosensory information transfer.

In spite of several reports about suppressive effects of volatile anesthetics on somatosensation, their neuronal mechanisms are largely unknown. The present study investigates somatosensory impulse transmission at the thalamic level in rats under varied concentrations of isoflurane by recordings of neuronal responses to mechanical stimulation of the body surface. Single-unit recordings of thalamo-cortical relay neurons (TCNs, third order neurons; n=28) and presumed trigemino-thalamic fibers (TTFs, second order neurons; n=7) were performed in the ventral posteromedial nucleus. Functional response characteristics were quantified following defined tactile stimulation (trapezoidal or vibratory deflection of sinus hairs or fur) applied to the neuronal receptive fields. End-tidal isoflurane concentration was increased in steps of 0.2% between 0.6% (baseline) and 2.0%. The response activity in all TCNs studied was suppressed in a dose-dependent manner (2.0% isoflurane decreased responses to 3. 5+/-1.1% of baseline; mean+/-S.E.M.); the response activity in TTFs was much less affected (decrease to 55.0+/-8.2%). Suppression of ongoing activity, however, was similar for both, TCNs and TTFs. Furthermore, in TCNs, the response characteristics changed with increasing isoflurane between 1.0% and 1.8%: tonic and sustained responses were converted to phasic on-responses. In contrast, the tonic and sustained response characteristics of TTFs were preserved even at higher isoflurane concentrations. The results indicate that isoflurane attenuates the output of somatosensory signals in the specific nucleus of the rat's thalamus, while its input is only marginally affected. The observed changes of thalamic neuronal response characteristics, at least in part, may cause the loss in sensory discrimination observed during general anesthesia.

Anesthetics, Inhalation↗

Abeta-fiber mediated activation of cingulate cortex as correlate of central post-stroke pain.

A patient is presented who suffered a lateral brainstem infarction which selectively abolished pain and temperature sensitivity in the lower right limb. One year later central post-stroke pain had developed in the affected limb with touch and cold allodynia. P40m dipoles calculated from magnetoencephalographic fields after electrical stimulation of both tibial nerves were localized in SI as is seen in normal subjects. However, stimulation of the affected side caused deep pain sensations and elicited a large N80m component, best explained by an additionally active dipole in cingulate cortex. This early co-activation in a limbic structure suggests peripheral Abeta-fiber mediation and lemniscal projection. Abnormal link to the pain system may be due to sensitization and reorganization above the level of nociceptive deafferentation.

Brain Stem↗

Differentiation of conversive sensory loss and malingering by P300 in a modified oddball task.

We applied the methodology of evoked potentials (EP) to reveal the functional level of abnormality in a patient with circumscribed complete anaesthesia due to conversion disorder. EP components related to sensory and perceptual processing of both innocuous electrical and noxious laser stimuli were normal. However, a P300 component indicating cognitive processing failed to appear when using a modified oddball task with rare stimuli applied to the anaesthetic right hand. P300 was present with this paradigm stimulating the healthy left hand, as well as in a 'malingerer' - a healthy subject who was instructed to feign the same deficit. These results suggest cognitive deficits underlying sensory loss as conversion symptom which can be differentiated from malingering by use of P300.

Adult↗

Neurophysiological evaluation of pain.

Neurophysiological techniques for the evaluation of pain in humans have made important advances in the last decade. A number of features of neuroanatomy and physiology of nociception qualifies pain as a multidimensional phenomenon which is rather unique among the sensory systems and which poses a number of technical and procedural requirements for its appropriate diagnostic assessment. Various stimulation techniques to induce defined pain in humans and used in combination with the methodology of evoked electrical brain potentials and magnetic fields are presented. Most recent knowledge gathered from scalp topography and dipole source analysis of pain-relevant evoked potentials and fields is discussed. Particular emphasis is put upon laser-evoked potentials and their application for diagnosis, pathophysiological description and monitoring of patients with neurological disorders and abnormal pain states. Future perspectives in this growing field of research are discussed briefly.

Electroencephalography↗

Pain-evoked blink reflex.

The electrically evoked blink reflex (BR) consists of an ipsilateral R1 component (R1) at 11 ms and two bilateral components R2 at 33 ms and R3 at 83 ms. It is still unclear whether the R2 is mediated by activation of tactile or nociceptive afferents. For testing the nociceptive hypothesis, nociceptors of the supraorbital nerve were selectively activated by infrared laser stimuli in 10 subjects. Only painful laser stimuli evoked a bilateral early polyphasic BR response (LR2) at 71 ms. Stimulation of infraorbital and mental nerve dermatomes was equally effective. A late bilateral reflex response at 130 ms was occasionally observed. Regarding the nociceptor activation time of about 40 ms, onset latencies were within the range of the electrically evoked R2 and R3, respectively. The good accordance of R2 and LR2 may be due to activation of identical nociceptive fibers or to convergence of electrically evoked tactile and laser-elicited nociceptive input onto common multireceptive neurons.

Adult↗

[The Eppendorf Pruritus Questionnaire].

In dermatological practice, itch is the leading symptom of many skin diseases with a variety of psychophysiological aspects. However, a complete inventory for the qualitative evaluation of these central nervous factors is missing, whereas in pain research, the McGill Pain Questionnaire is well established for this purpose. Thus, therapeutic effects of antipruritic agents are only incompletely described by visual analog scales or parameters of skin physiology. Here, a questionnaire modified in analogy to the McGill pain questionnaire is presented, developed in cooperation between dermatologists and neurophysiologists.

Diagnosis, Differential↗

Differential changes of laser evoked potentials, late auditory evoked potentials and P300 under morphine in chronic pain patients.

The present study investigates the differential behavior of laser evoked brain potentials (LEPs), late auditory evoked potentials (AEP) and the endogenous P300 in response to morphine treatment, examined in 6 chronic pain patients. The main result was that in parallel with marked clinical pain relief, amplitudes of the long latency LEP positivity (P400) were significantly reduced under morphine. One patient suffering from extremely painful osteoporosis for 20 years exhibited a large middle latency component (N170) which was prominently attenuated by morphine. In contrast to LEP amplitude reductions, auditory N1 and P2 potentials appeared either unchanged or even enlarged during morphine treatment. Also P300 amplitude was slightly increased under morphine. Reaction time and mood scales also failed to indicate any sedation. Obviously, LEPs reflected specifically the analgesic morphine effect in this study, while stability or enhancement of AEPs and P300 during morphine treatment indicated lack of sedation or even improved perception and concentration due to the removal of persistent pain as a disruptive perceptual-cognitive stressor.

Adult↗