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Biomedical subjects

B Bromm

Publications and source records attributed to B Bromm.

At least 73 records · Page 4Linked to original sources

Imipramine reduces experimental pain.

In a homogeneous sample of 20 healthy male students, the analgesic effects of the tricyclic antidepressant imipramine (100 mg) were compared to those of the narcotic meperidine (150 mg) and a further tricyclic compound with assumed analgesic properties (fluradoline, 450 mg). Drugs were orally administered, using a placebo controlled, double-blind repeated measures Latin Square design. Phasic pain was induced by intracutaneous electrical shocks with random intensities and interstimulus intervals. Each stimulus block consisted of 80 stimuli and lasted for 20 min. Pain estimates, somatosensory evoked cerebral potentials (SSEPs) and power spectral density of the electroencephalogram (EEG) were measured under each drug condition. Under placebo, pain ratings and SSEP amplitudes were constant within the entire session lasting for approximately 4 h. Meperidine analgesia was evident within 30 min of drug application, reaching a maximum after about 90 min. Imipramine produced a comparable degree of pain reduction, however, with a delay of 2 h. Under both drugs, the decrease in pain ratings was accompanied by decreased amplitudes of the late components of the SSEP, as well as by a reduction in alpha activity and an enhancement of slow EEG waves. Effects of fluradoline on experimental pain could not be affirmed. These findings are discussed in terms of pain relief and decrease in vigilance.

Adult↗

Pentazocine and flupirtine effects on spontaneous and evoked EEG activity.

Somatosensory (SEP), auditory evoked potentials (AEP) and power spectral density of ongoing EEG (PSD) were investigated under different drug conditions: the opioid pentazocine (30 mg), the centrally acting non-narcotic analgesic flupirtine (80 mg) and placebo were administered i.v. in a double-blind cross-over study (intersession interval 7 days) with 20 healthy male subjects. Intracutaneous electrical stimuli were applied to the finger tip with randomized intensities of two- and threefold individual pain threshold. One stimulus block consisted of 80 trials. Mean values of two stimulus blocks per session were analyzed: one block before and one block 30 min after treatment. Pentazocine significantly reduced the peak-to peak amplitude of the late SEP components (N150-P240) from pretreatment to posttreatment blocks, and flupirtine diminished this amplitude to nearly the same degree. With placebo no substantial reduction was found. In contrast to these drug-induced changes in SEP, the AEP components showed no significant alterations after any treatment. The PSD under pentazocine showed a reduction of total power. This effect was mainly due to a reduced power in the alpha band. The PSD under flupirtine showed slight increases in power of theta, alpha and beta activity. Again, under placebo no changes from pretreatment to posttreatment conditions occurred. The difference in EEG change might suggest different sites of action of the two analgesics.

Aminopyridines↗

Tonic pain inhibits phasic pain: evoked cerebral potential correlates in man.

In a sample of 10 healthy volunteers phasic pain ratings and evoked cerebral potentials (EPs) elicited by brief electrical skin stimuli were investigated in periods before, during, and after contralateral tonic ischemia pain. In all subjects the phasic pain ratings and the late EP components P80-N150 and N150-P260 were depressed under concurrent tonic pain. The magnitude of the mean reduction (31%, 40%, and 26%) is comparable to morphine analgesia. The early EP components with latencies below 80 ms, which are considered to be correlates of mechanosensitivity, were not influenced. The findings of tonic pain inhibiting phasic pain are discussed on the basis of changes in attention as well as of pain-specific physiological mechanisms like diffuse noxious inhibitory control.

Adult↗

Modern techniques to measure pain in healthy man.

This paper describes a series of experimental prerequisites in assessments to measure the efficacy of analgesic drugs in healthy man. Of course, there is no doubt that an analgesic has to prove its validity exactly where it ought to help; i.e. in the patient suffering from pain. But to objectify the mode of action, or to measure dose-response functions, to evaluate the optimal therapeutic dosage, or to compare the relative efficacy of the drug tested with known substances--all these investigations can best be performed in a sample of healthy, informed, intelligent and cooperative volunteers, as homogenous as possible. Various kinds of stimuli used in the experimental pain laboratory will be compared with respect to their usefulness in algesimetry; for example the CO2 laser stimulus and the intracutaneous electrical shock. New examples in the analysis of cerebral potentials evoked by painful stimuli will be presented, such as the principal component analysis, the maximum entropy method, and procedures of cerebral potential mappings. It will be shown that frequency transformation of stimulus-induced changes in the electroencephalogram can result in a powerful tool to verify effects even of the so-called weak analgesics, such as acetyl salicylic acid (Aspirin).

Adult↗

Responses of human cutaneous afferents to CO2 laser stimuli causing pain.

Microelectroneurographic studies in man allow the comparison of stimulus induced activity in the single peripheral nerve unit with the subject's ratings of sensation. Relationships between stimulus intensity, single unit discharges, and pain ratings were investigated using a CO2 laser stimulator which delivers radiant heat pulses of 50 ms duration. Recordings were performed percutaneously from the radial nerve at the wrist. Receptor types were identified by their response to different stimulus modalities and by their reaction delay to electrical test stimuli within the receptive field. Receptive fields of identified units were stimulated with randomised series of different radiant heat intensities between half and double the individual pain threshold (5 to 20 W; stimulation area 64 mm2). The largest receptor class observed to be activated by CO2 laser stimuli were polymodal C-nociceptors. None of them was spontaneously active. High discharge rates up to 75/s were not necessarily associated with pain but, if pain was felt, the impulse trains usually lasted for more than 60 ms. Inter-spike intervals were distributed over a wide range between 8 and 145 ms with a peak at about 25 ms. This peak was only slightly shifted by increasing the stimulus intensity. Higher correlations were found between the number of spikes and stimulus intensity. Measures of Signal Detection Theory indicated that the single unit discharges discriminated stimulus intensities better than the subjects' ratings. These findings underline the importance of temporal summation in the processing of C-fibre input with a considerable loss of information in the nociceptive system.

Humans↗

Nerve fibre discharges, cerebral potentials and sensations induced by CO2 laser stimulation.

Short radiant heat pulses, emitted by a high power CO2 laser, were used to investigate single nociceptor activity, cerebral potentials and concomitant sensations. Stimuli of 20 and 50 ms duration with different intensities were randomly applied to the hairy skin of the hand. Microelectroneurography was performed from the radial nerve at the wrist; 26 stable recordings were evaluated. Pre- and post-stimulus EEG segments were recorded from vertex versus linked ear lobes. Sensation was assessed on an eight-step category scale, an adjective scale, and by reaction times. In some experiments an A-fibre block was applied in order to isolate C-fibre responses. The main results were: Short heat stimuli activate C-units. In addition one of two identified A delta-units responded. None of the 15 A beta-units investigated was activated by the heat pulses. Short heat stimuli evoked cerebral potentials having a main vertex positive component at about 400 ms. These potentials were ascribed to A delta-fibre input. Laser induced pain consisted of an immediate stinging component, followed by a burning pain which often lasted several seconds. Reaction time to first pain ranged from 400-500 ms. Weak laser stimuli induced non-painful sensations mostly of tactile character. High correlations were found between the number of spikes elicited by a given stimulus and the intensity of the evoked sensation. Intensity discrimination, as evaluated by measures of Signal Detection Theory, was better in the peripheral C-units than in the subjective ratings. If conduction of A-fibres was blocked by pressure, A delta-related cerebral potential components vanished.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

The intracutaneous stimulus: a new pain model for algesimetric studies.

An intracutaneous pain stimulus is described for psychophysiological studies in man, which can easily be applied and which elicits highly reliable pain reactions in sessions repeated on different days, as well as in long-lasting sessions within a single day. The common electrical skin stimulation technique was modified by producing a circumscribed reduction in skin resistance under the stimulating electrode. A standardized procedure is described to reproducibly reduce this resistance by a factor of about 0.1 in a defined skin area of 1 sqmm. After this procedure, a definite and clear pain sensation could be elicited by current pulses which did not cause any sensation when conventionally applied. The reproducibility of pain reactions (pain ratings and late cerebral potentials) was tested in single sessions lasting up to 8 hours, as well as in weekly repeated experiments. First examples for applying these stimuli in algesimetric studies are given by double blind experiments with meperidine.

Adult↗

Evoked cerebral potential correlates of C-fibre activity in man.

CO2 laser emitted radiant heat pulses of 20 ms duration were used to activate predominantly slowly conducting nociceptive cutaneous afferents in man. Stimuli of two-fold individual pain threshold caused stinging and burning pain and elicited cerebral potentials with latencies consistent with A delta-fibre activity. After preferential block of the myelinated nerve fibres by pressure only the burning pain remained with significantly increased reaction time (about 1433 ms). The A delta-fibre-induced evoked potential components disappeared, and a marked ultralate positive component became visible with mean peak latency of 1260 ms, consistent with C-fibre activity.

Afferent Pathways↗

Oscillating repolarization in action potentials of frog sensory myelinated nerve fibres.

Current and voltage clamp experiments were performed in single myelinated sensory nerve fibres of Rana esculenta. The K current was blocked by external tetraethylammonium-chloride and internal CsCl. Negative prepotentials led to the formation of a plateau in the repolarization phase of the action potential, and further regenerative depolarizations emerged from this plateau. A three-state model for Na inactivation based on voltage clamp data was sufficient to simulate these observations.

Action Potentials↗

Antagonism between tilidine and naloxone on cerebral potentials and pain ratings in man.

The effects of the opioid tilidine and the opiate antagonist naloxone on somatosensory evoked potentials (SSEP) and pain ratings (E), elicited by electrical skin stimuli with randomized intensities, were investigated for different, orally administered tilidine and naloxone combinations in a double-blind Latin square design in 15 healthy humans. A high correlation between SSEP amplitudes and E was found for all treatments investigated. Tilidine (100 mg) decreased both SSEP amplitudes and E by about 25% compared to the placebo. No significant differences were found between the analgesic effects of tilidine and TN8 (tilidine 100 mg; naloxone 8 mg). The effects of both treatments were significantly different from those of the naloxone, placebo and TN32 treatments (tilidine 100 mg; naloxone 32 mg), indicating a marked naloxone-induced reversal of tilidine analgesia. Naloxone (32 mg) increased the SSEP amplitudes. No naloxone-induced hyperalgesia was seen in the pain ratings.

Adult↗

Development of Na inactivation in motor and sensory myelinated nerve fibres of Rana esculenta.

Development of Na permeability inactivation was investigated in myelinated motor (N = 12) and sensory (N = 12) nerve fibres of Rana esculenta at 20 degrees C. The K currents were blocked by 10 mM tetraethylammonium chloride, added to the superfusing solution. Additionally, in 4 fibres of each group internal CsCl was applied by diffusion from the cut internodes. Development of Na inactivation was approximated by the sum of two exponentials. The time constants of the fast and slow inactivation phase (tau h1 and tau h2) were dependent on membrane potential (E) with similar values in both fibre types for a given E. In contrast, significant differences were found in the contribution of both phases. In motor nerve fibres the amplitude of the fast phase was g = 0.70 (mean value of 12 fibres) throughout the potential range investigated (-30 mV less than or equal to E less than or equal to 40 mV). In sensory fibres g was potential dependent, increasing from 0.76 (mean value of 12 fibres) at E = -30 mV to unity at E greater than 30 mV. This difference in Na permeability inactivation is a further distinguishing property between motor and sensory nerve fibres.

Action Potentials↗

CO2 laser radiant heat pulses activate C nociceptors in man.

Cerebral potentials evoked by noxious CO2 laser stimuli in man have been referred to nociceptive A delta units. This paper shows 1) that ultra short (5 - 50 ms) high power (less than or equal to 50 W) CO2 laser skin stimuli are able to activate nociceptive C units in man, and 2) that these C nociceptors have to be assumed to terminate in the very superficial skin layer (less than or equal to 300 microns depth).

Carbon Dioxide↗

A sensitive method to evaluate effects of analgesics in man.

In recent papers (8, 12, 13) it has been shown that the analysis of event related brain potentials has become a powerful tool in attempts to quantify pain experience in man. However, the following conditions have to be fulfilled when cerebral potentials are used to measure experimentally induced pain, as well as pain relief under pharmacological treatments: 1) randomization of stimulus intensities to minimize effects of habituation within and between sessions (3), 2) randomization of interstimulus intervals with a minimum distance of about 15 seconds to avoid overlapping effects, and 3) control of the power spectral density of brain activity immediately before the stimulus is applied. In searching for pain related cerebral potentials a principal component analysis was utilized. The grand mean of all evoked potentials (analysis period 500 ms) was built, and the brain potentials were decomposed into basic waveforms for the different experimental conditions (painful-nonpainful; different kinds of skin stimuli). Two components were found as correlates of the painfulness in a sample of 8 healthy untreated subjects (4). In order to demonstrate the usefulness and sensitivity of the here described methods to quantify analgesic effects in man, the opioide tilidine and the opiate antagonist naloxone were orally administered in different combinations. In detail, the 5 treatments: tilidine (100 mg), naloxone (32 mg), tilidine (100 mg) + naloxone (8 mg), tilidine (100 mg) + naloxone (32 mg), and placebo, were given double blind (3 replications of 5 X 5 Latin squares) in 15 healthy subjects, each participating in 5 sessions with exactly 3 days intervals.(ABSTRACT TRUNCATED AT 250 WORDS)

Analgesics↗

Principal component analysis of pain-related cerebral potentials to mechanical and electrical stimulation in man.

Single trial event-related cerebral potentials (ERPs) in response to skin stimuli of various intensities and qualities in man were investigated in respect to their nociceptive information content. Electrical constant current stimuli (20 msec, 2 - 8 mA) and mechanical force controlled stimuli (20 msec, 0.8 - 3.2 N) were applied to the tip of the left middle finger. Four intensities of each stimulus quality were given, each intensity appearing 40 times in standardized randomized order. EEG segments (between 5 sec before and 500 msec after stimulus onset) were subjected to computer analysis. ERP wave form was shown to depend upon the amount of alpha waves in the prestimulus EEG. For analysis, only subjects with low power in the alpha band were selected. Principal component analysis was applied to all single trial ERPs measured using the variance-covariance matrix of association. Six principal components (PCs) were extracted accounting for about 90% of total variance. Five of the extracted PCs had well located loading maxima: PC1 (50 - 80 msec), PC4 (140 - 160 msec), PC3 (200 - 250 msec), PC4 (280 - 360 msec), PC5 (400 - 500 msec); PC6 appeared polyphasic. Analysis of variance of the mean PC scores revealed that one PC (PC1) discriminated between quality, and 4 PCs (PC1 - PC4) between quantity of stimulation. Eliminating effects of stimulus intensity resulted in two PCs (PC2, PC4) which distinguished exclusively between non-pain and pain. PCA applied to disjunctive subsets of ERPs, corresponding to the different experimental conditions, yielded practically identical sets of PCs, such that no specific ERP component emerged when pain was reported.

Adult↗

Response plasticity of pain evoked reactions in man.

Pain estimation (E), evoked cerebral potential (EP), electrooculogram (EOG), electromyogram of withdrawal reflex activity (EMG) and skin conductance reaction (SCR) were measured in response to electrical skin stimuli in 11 male volunteers (age 21-31 years). Constant current stimuli (20 msec; 2, 3, 6, 10 mA) were applied to a finger tip (averaged pain threshold at 5.1 mA). Interstimulus intervals (20-40 sec) and stimulus intensities were delivered in quasi-randomized order, each intensity appearing 40 times per session. Four sessions were repeated with intervals of two days between sessions. With randomized stimulus intensities, power spectral density functions of the prestimulus EEG indicated a stable non-specific arousal level between and within sessions. Under these conditions no significant response plasticity was found for E and EP, not in the prepain or the pain range, and also not between or within sessions. In contrast, the amplitudes of EOG, EMG and SCR decreased drastically with time, especially between the first and second session, and between the first 10 and second 10 stimuli of equal intensity in each session. EP and E remained highly correlated in repeated sessions. A EOG-EP contamination could be ruled out because of their different time course to repeated stimuli.

Adult↗

The influence of tilidine and prazepam on withdrawal reflex, skin resistance reaction and pain rating in man.

Pain rating, withdrawal reflex and skin resistance reaction upon electrical skin stimuli were studied on 15 male volunteers under placebo, tilidine and prazepam. Tilidine (Valoron) is an orally applicable narcotic analgesic, with a mode of pain relief presumably similar to morphine; the tranquilizer prazepam (Demetrin) belongs to the benzodiazepine group. Significant reduction in all measured reaction amplitudes was found under tilidine, whereas prazepam reduced significantly only the skin resistance reaction. The relative drug-induced changes in reaction amplitudes, related to the corresponding placebo value, were independent of stimulus intensity for all investigated reactions. Therefore, fitted power functions re = a . Sn between reaction amplitudes re and stimulus intensity S showed a decrease in parameter a under the investigated drugs, whereas the exponent n remained constant. High correlations between parameters a and corresponding reciprocal threshold currents could be shown for all reactions measured. Furthermore the drug-induced changes of withdrawal reflex amplitude and of subjective estimation were found to be correlated over subjects. In contrast, no correlations were found between variations in skin resistance reaction and magnitude estimation due to the selected drugs, i.e., the influence of the drugs on the sensory component of pain sensation and on the skin resistance reaction were independent effects.

Analgesia↗

A three-state model for inactivation of sodium permeability.

The inactivation of Na+ permeability in single myelinated motor nerve fibres of Rana esculenta was investigated under voltage and current clamp conditions at 20 degrees C in Ringer's solution and under blocked K+ currents. Development of inactivation and its recovery was described by two potential-dependent time constants: The smaller time constant followed the usual bell-shaped function of membrane potential, whereas the larger one was monotone-increasing with more negative potentials. Several three-state models for inactivation were investigated. The experiments could best be approximated by a model with two open and one closed state for inactivation following: open in equilibrium closed in equilibrium open. Rate constants were determined for all transitions shown from the voltage clamp experiments. The action potentials computed by means of the proposed model were in good agreement with those measured, both in Ringer's solution and under blocked K+ current conditions.

Animals↗