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Biomedical subjects

H O Handwerker

Publications and source records attributed to H O Handwerker.

At least 109 records · Page 6Linked to original sources
PubMed1984

Vascular reactions correlated with pain due to cold.

Psychophysical experiments with healthy volunteers were conducted to study the relationships between cold pain and blood perfusion of the skin. By means of a thermode the left middle finger was cooled to a constant temperature near 0 degrees C for 45 min. During this stimulation period, the subject regularly rated the pain on an electronically controlled visual analogue scale. Two variables of vascular reactions were measured: the finger photoplethysmogram of the cooled finger and the thermal flux at the skin surface of this finger. Cross correlograms computed between these noninvasive physiologic parameters of blood flow and the pain ratings revealed that pain intensity and degree of vasoconstriction were strongly correlated. The implications of these findings for the peripheral nociceptor mechanism of cold pain are discussed. We conclude that the nociceptors for this type of pain are most probably situated in deeper skin structures and that they are excited by temperatures ranging approximately from 3 to 20 degrees C.

Adult↗
PubMed1984

Nociceptor discharges and sensations due to prolonged noxious mechanical stimulation--a paradox.

Forceps were used to induce controlled squeeze stimuli to small skin folds of the dorsal surface of the hand of human volunteers. Psychophysical and microneurographic experiments were performed to characterize sensations and afferent input induced by stimuli exerting a constant force during a period of 120 s. The psychophysical data showed that forces greater than 4 N exerted on forceps faces of 30 mm2 elicited pain, which had two main characteristics: (a) stronger stimuli evoked a stronger pain response, (b) pain had a tendency to increase throughout the 120-s stimulus duration. In contrast, discharges of polymodal C-fibre nociceptors showed an initial high frequency dynamic discharge followed by adaptation. It was found that the ratio of C-fibre activity to activity in myelinated SA-fibres provided a better correlate of the time course of the stimulus-induced pain sensations than C-fibre activity alone. Possible reasons for the mismatch between nociceptor input and pain sensations are discussed.

Afferent Pathways↗
PubMed1984

Some aspects of pain measurement in man.

Methods of clinical and experimental algesimetry are described that have been used to evaluate effects of peripherally and centrally acting analgesics. Since pain is a complex psychophysical phenomenon, algesimetry has a lot of inherent problems which are discussed.

Aspirin↗
PubMed1983

Assessment of experimentally induced pain. Old and new methods.

The term "algesimetry" refers to the experimental triggering and the quantitative recording of pain sensations in man. Since clinical pain and experimentally induced pain differ in important ways, the value of this type of research has often been questioned. A clear definition of target areas to be investigated is a prerequisite for successful future efforts in this area. Algesimetric methods, which may aid neurologic diagnosis, are not necessarily suited for testing analgesics. Tests or test batteries that lend themselves to the study of aspirin-type analgesics are not necessarily the most appropriate for the evaluation of narcotic analgesics. If algesimetry is to become an important instrument in clinical pharmacology, it is necessary to design tests that are sensitive to the effects of known analgesics (standards), with the consideration of different dosages and kinetics. Old and new methods for inducing pain are discussed, such as heat, cold, electrical and mechanical stimulation. With regard to the measurement of pain reactions, objective processes--in particular the method of recording evoked potentials--are compared with subjective processes. Special attention is paid to processes that involve several dimensions of pain. The selection of subjects is discussed, as are the possible clinical applications of algesimetric methods.

Analgesics↗
PubMed1983

Altered excitability of afferent C-fibres of the rat distal to a nerve site exposed to capsaicin.

Excitability of afferent C-fibres in saphenous and coccygeal nerves of rats was studied distal to a nerve site treated with 1% capsaicin for half an hour one day before. This treatment induced the following changes. (a) Fewer C-fibres than in control nerves were excited by natural skin stimulation among those driven by electrical nerve stimulation. Comparison of compound action potentials derived from capsaicin-treated and from untreated contralateral coccygeal nerves indicated that the total number of excitable C-fibres was also diminished. (b) Whereas in a normal rat nerve virtually all unmyelinated nociceptors responding to heat stimulation are also driven by strong mechanical stimuli (MH-nociceptors, polymodal nociceptors), most of them were found to respond only to heat stimulation after local capsaicon treatment of the nerve.

Action Potentials↗
PubMed1983

Unmyelinated nociceptive units in two skin areas of the rat.

Responses of unmyelinated afferent fibres were investigated in two skin nerves of Sprague-Dawley rats. The units were tested as to whether they responded to mechanical probing of the skin, to controlled radiant heat stimulation, and/or to cooling of the skin (to less than or equal to 5 degrees C). Ninety-six units in a n. saphenaus and 129 units in a n. coccygealis were studied, which were identified as afferents by means of the above-mentioned stimuli. In both nerves mechano- and heat-sensitive units (CMHs) were most frequent (56% in n. saphenaus and 74% in n. coccygealis). There were, however, significantly more purely mechanoceptive units (CMs) in n. saphenaus than in n. coccygealis (30% vs 5%). In contrast cold-sensitive units (CCs) were more frequent in n. coccygealis. They constituted 25% of the afferent C-fibres in this nerve. When testing heat sensitivity of CMHs with ramp stimuli raising the temperature to 55 degrees C at a rate of 0.8 degree C/s, heat thresholds had a wide range of between 30 and 55 degrees C. Since CMHs with low heat thresholds had the highest discharge rates and the greatest dynamic sensitivity in the range of noxious temperatures, they most probably also had nociceptive functions. It was shown that the low heat thresholds of some CMHs were not due to sensitization by preceding heat stimuli. It is argued that low-frequency discharges (less than or equal to 2 Hz) observed in some nociceptive CMHs of the rat at non-noxious temperatures are insignificant for nociception. When comparing discharges during a first ramp heat stimulus to 50 degrees C (rise time 1 degree C/s) with those during a second stimulus of identical time course delivered 5-10 min later, 44% of the CMHs were sensitized, 24% were desensitized and the remainder were not clearly influenced. We did not find a significant correlation between initial heat thresholds and tendency to sensitization or desensitization.

Afferent Pathways↗
PubMed1983

The effect of capsaicin application to a peripheral nerve on impulse conduction in functionally identified afferent nerve fibres.

Capsaicin applied locally to a coccygeal or saphenous nerve of rats was shown to block impulse conduction in unmyelinated afferent nerve fibres. Shortly after application of capsaicin (1% dissolved in 10% Tween 80 in paraffin oil) conduction of C-fibre--but not A-fibre--compound action potentials across the application site was markedly diminished. No recovery occurred during the period of observation, i.e. up to 2 h afterwards. C-Fibre compound action potentials stimulated and recorded proximal to the application site seemed to be unaffected. Solvent application had no effect. Recording from single units revealed that nociceptive C-fibres responding to strong mechanical and heat stimulation (MH units, polymodal nociceptors) were blocked. In contrast, unmyelinated cold fibres were not affected. The selective block of MH units indicates different membrane properties of unmyelinated MH and cold units not only at the receptive nerve endings, but also at the axons, to which capsaicin was applied.

Action Potentials↗
PubMed1982

Single unit activity in the rat's midbrain during nocifensive tail flick reaction.

Single units have been recorded extracellularly from the periaqueductal central grey and from adjacent structures in behaving rats during tail flick reflexes elicited by controlled radiant heat. Together with the spike recordings, the heart rate of the animal and a thoracic myogram as an indicator of overall motor activity, have been recorded. Twenty-seven medial midbrain units have been studied, which were all characterized by being spontaneously active and by receiving input from myelinated afferent fibres from the tail, as shown by weak transcutaneous electrical stimulation. These units showed a variety of changes in discharge pattern. The most frequently observed change in activity was an increase of firing in the pre-flick period (10 of 27 units) and a decrease of firing below the prestimulus level in the post-flick period (12 of 27 units). It is suggested that changes in the discharge patterns were more closely related to behavioral output than to the input side of nociceptive behaviour.

Animals↗
PubMed1982

Detection of temperature increases in the operating range of warm receptors and of nociceptors.

In healthy subjects the ability to detect small temperature increases in a 'two-alternative forced choice' experiment was tested from different basic temperatures ranging between 36 and 46 degrees C. Detection improved up to an adapting temperature (AT) of 40 degrees C, a further increase of AT into the operating range of nociceptors did not change detection rate. In several experiments the subjects have been asked to rate their confidence after each forced choice on a 6-point scale. From these confidence ratings two measures developed in the context of 'Sensory Decision Theory' have been calculated, one of 'discrimination' and one of 'bias.' A bias towards higher confidence in having detected temperature increases was found to be the clearest sign of transition into the operating range of nociceptors.

Hot Temperature↗
PubMed1980

Latencies of chemically evoked discharges in human cutaneous nociceptors and of the concurrent subjective sensations.

Percutaneous recordings from single nociceptive A delta- and C-fibers have been performed from the superficial radial nerves of conscious human subjects. Nociceptors were tested with a chemical irritant substance, which induced a burning sensation when applied to the intact skin. A comparison of the onset of spike discharges in nociceptors and the onset of the subjective burning sensation indicated that under the conditions of our experiments summation of input from nociceptors is needed in order to induce pain sensations. In particular, our results indicate spatial summation.

Adult↗
PubMed1980

Differential effects of noxious and non-noxious input on neurones according to location in ventral periaqueductal grey or dorsal raphe nucleus.

Nociceptive and non-nociceptive input to the dorsal raphe nucleus (DR) and to the surrounding periaqueductal grey (PAG) was studied in chloralose-anaesthetized rats. Single units in the midbrain responding to electrical stimulation of a coccygeal nerve were recorded with glass micropipettes. A fluorescence histochemical technique was applied to identify recording sites in the DR and PAG. 109 DR-units, 141 PAG-units and 95 units from surrounding structures were tested for responsiveness to electrical nerve stimulation. In 53% of the DR-units, but in only 20% of the PAG- and SN-units, ongoing activity was inhibited by electrical stimulation (I-units) while 42% of the PAG- and SN-units but only 24% of the DR-units were electrically excited (E-units). 40 E-units and 24 I-units were tested with repeated noxious radiant heat stimuli applied to the tail or hindpaws. 70% of the E-units were excited by heating, and in 54% of the I-units ongoing activity was inhibited by heating. The majority of the former units were located in the PAG, and most of the latter were proven to be DR-neurones. In 75% of the E-units and in 12.5% of the I-units the heat effect was in the opposite direction. The findings are discussed in terms of the now well-established role of the PAG-region in the descending control of pain. The properties of the PAG-E-units suggest that this system is involved in a negative feedback circuit by which pain transmission to the CNS limits itself. DR-I-units may be involved via an additional small loop with the PAG to disinhibit the activation of the PAG pain control system.

Animals↗
PubMed1979

A comparison between the discharges of human nociceptive nerve fibres and the subject's ratings of his sensations.

1. Impulses in cutaneous nerve fibres were recorded percutaneously with tungsten micro-electrodes from the superficial radial nerve of adult human subjects. 2. Eight units studied had conduction velocities below 1.5 m/sec, and thus belong to the class of C fibres. On the basis of their responsiveness to mechanical and to thermal stimuli the units were classified as 'polymodal nociceptors'. 3. Units were tested with 12 sec heat pulses starting from a base line temperature of 43.0-43.5 degrees C. Heat stimuli reaching three different maximal levels were applied in randomized order, the subjects being blind with respect to stimulus size. Each of the eight units studied was tested with more tha 20 stimuli and with four of them were 80-125 stimulus repetitions. 4. After each stimulus the subjects had to rate his sensations on a six-point rating scale extending from 'just noticeable' to 'very hot, painful'. 5. Discrimination between the three stimulus levels by the integtated spike discharges and by the ratings of the subject was compared using the P(A) measure of the Signal Detection Theory. It was found that both the neurophysiological and the psychophysical measurements provided about equal discrimination. 6. In addition it has been found that spike discharges and ratings share a common variance beyond their common dependence on the stimulus level. Among the factors contributing to this interdependence a 'temporal position effect' was the most significant. 7. In spite of this interdependence between discharge rates and subjective ratings, the latter gave a better estimation of the stimulus size than of the discharge rates of the individual C fibre under study. 8. It was concluded that the polymodal C-nociceptors might be instrumental for the quantitative aspects of heat pain sensation. The hypothesis was derived from the present results that, under the conditions of cour experiments, the loss of information in the course of central processing might be about equal to the gain by the parallel processing in a population of nociceptors excited by a stimulus.

Action Potentials↗
PubMed1976

Characteristics of C-fibre receptors in the cat's foot responding to stepwise increase of skin temperature ot noxious levels.

1. Response characteristics of unmyelinated cutaneous fibres with receptors sensitive to heating of the skin were determined by controlled radiant heat stimulation applied to the foot sole of anaesthetized cats. To evaluate response characteristics without repetivie stimulation the skin surface temperature was raised stepwise ("staircase") up to noxious levels in each trial. 2. A monotonically increasing discharge rate on increasing temperature (up to the highest temperatures tested, 52-55 degrees C) was shown by 29 out of 47 heat sensitive C-fibres, i.e. by about 60% of the receptors, whereas 13 fibres, about 30%, had discharges which were found to be presumably unsuitable for discriminating temperature levels above 50 degrees C. The threshold temperatures of both fibre groups were found to be usually near 40 degrees C. Thus our results indicate different temperature ranges among heat receptors with potential nociceptive functions. 3. Five fibres of our sample, i.e. about 10%, could be identified as "warm fibres". They had tresholds near 30 degrees C and had their discharge maxima at 44 degrees C. In contrast to the "heat-fibres" mentioned above they were inactivated during tonic noxious heat stimulation and in the time following. Though warm fibres respond with a burst of high frequency when the skin temperature is raised suddenly from normal to noxious levels and though they start to discharge again irregularly at noxious temperatures (e.g. 50 degrees C) after a silent period, when stimulated tonically, warm fibres seem to transmit little quantitative information about noxious temperature levels. Therefore they can presumably be discarded as "nociceptors".

Animals↗