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Biomedical subjects

H O Handwerker

Publications and source records attributed to H O Handwerker.

At least 91 records · Page 5Linked to original sources
PubMed1990

Carrageenan inflammation increases bradykinin sensitivity of rat cutaneous nociceptors.

The present study examined the hypothesis that the sensitivity of polymodal nociceptors to bradykinin (BK) might be increased in inflamed tissue. Inflammation was induced in the rat dorsal hindpaw skin by subcutaneous injection of blue stained carrageenan. Three hours later skin and saphenous nerve were excised and the chemical sensitivity of mechano-heat-sensitive C- and A delta fibres was examined in vitro using repeated superfusion of the receptive fields with 10(-5) M BK. Only units within and at the border of the inflamed area showed signs of sensitization, in the form of ongoing activity and lower thresholds to heat stimuli. No sensitization to mechanical (von Frey) stimulation occurred. The incidence of BK responsiveness was significantly higher and the tachyphylaxis to repeated BK application was smaller inside the inflamed skin than outside or in unconditioned skin. Thus, more nociceptive afferents would be driven more effectively than in normal skin, supporting the particular role of BK in inflammatory pain.

Action Potentials↗
PubMed1990

Automatic classification and analysis of microneurographic spike data using a PC/AT.

Using a standard PC-AT with a commercial analog data interface a system was designed which supports microneurographic experiments and which may also be used for other types of extracellular spike recordings. The signal is sampled on-line at 25 kHz and a spike is detected if the signal passes a certain threshold. The spikes are displayed on the screen and stored on disk. A second on-line mode records the responses of the examined unit to electrical stimulations, which are used to identify the type of fibre and to test the subsequent spike classification. The spikes are classified off-line using a template matching algorithm, which has unsupervised learning and discrimination phases. The results are displayed in a time-frequency plot and may be checked with the responses to electrical stimulations. Artifacts from EMG and other electrical fields are reliably sorted out. In recordings, which include more than one unit, their spikes are discriminated with a low error rate.

Action Potentials↗
PubMed1990

Properties of transdermal histamine iontophoresis: differential effects of season, gender, and body region.

Histamine iontophoresis is demonstrated to be a reliable model for the study of inflammatory skin responses. It has the advantage of a non-invasive and uniform mode of application and is free of unwanted side effects. The wheal and flare responses to histamine are linearly related to dose over a wide range of stimulus strengths (r = 0.88). In summer, wheal responses were smaller, probably due to increased thickness of the epidermis. Female subjects generally expressed larger wheal responses than males, presumably due to differences in epidermal thickness and structure. There were significant regional differences in wheal, flare, and laser Doppler recorded flux responses. Ratings of itch sensations also showed clear, but less pronounced, differences of body regions. Significant regional differences of wheal and flare responses existed. Sensory discrimination of different stimulus levels was demonstrated with visual analogue scale ratings.

Administration, Cutaneous↗
PubMed1990

Chemosensitivity of fine afferents from rat skin in vitro.

1. Properties of sensory receptors with slowly conducting nerve fibers (less than 10 m/s) were studied using a rat skin-saphenous nerve in vitro preparation where receptive fields of identified single units can be isolated and superfused at the corium side with defined chemical solutions. 2. With mechanical search stimuli, 150 slowly adapting units were identified, 88% C-fibers, and the remainder, A delta-fibers. The majority of these units (65%) were categorized as mechano-heat sensitive ("polymodal") with controlled radiant heat stimulation. The remaining units were classified as low- or high-threshold mechanoreceptors according to their von Frey thresholds. 3. Bradykinin (BK), in concentrations of 10(-8) to 10(-4) M, was repeatedly applied for 1 min at 10-min intervals. Fifty-six percent of the polymodal C-fibers responded to BK (up to 10(-5) M), in contrast to 17% of the heat-insensitive units (P less than 0.01). No correlation between BK sensitivity and conduction velocity or von Frey threshold was found. 4. The BK "threshold concentrations" to excite C- and A delta-fibers were about equally distributed over a range from 10(-8) to 10(-5) M. 5. There was a large interindividual variability in pattern and magnitude of the response to BK. Intraindividually, a marked tachyphylaxis upon repeated BK stimulation was observed. 6. In fibers with a slow development of tachyphylaxis, the effects of conditioning application of different chemicals on BK responsiveness were studied. Norepinephrine in 10(-7) M concentration did not produce a significant effect, whereas 10(-5) M and 10(-4) M seemed to increase the BK responses. 7. Prostaglandin E2 (10(-6) M) caused a weak sensitization to BK on average (n.s.), but serotonin (10(-6) M) was clearly effective (P less than 0.05). 8. The strongest sensitization to BK (P = 0.01) resulted from conditioning heat stimulation, which also uncovered a responsiveness in some units initially insensitive to BK. 9. In some experiments the calcium concentration in the superfusate of receptive fields was lowered to 0.3 mM, which induced ongoing activity in C-fibers and markedly increased the BK responses in two polymodal units tested. Increasing the calcium concentration to 3.0 mM reversed these effects. 10. After completing the BK test protocol, polymodal C-fibers were exposed to other chemicals.(ABSTRACT TRUNCATED AT 400 WORDS)

Afferent Pathways↗
PubMed1989

Skin reactions and itch sensation induced by epicutaneous histamine application in atopic dermatitis and controls.

Itch sensations and skin reactions induced by histamine iontophoresis at six different current intensities were studied in 27 atopic dermatitis (AD) patients and 20 healthy controls. Subjective itch ratings were assessed on a visual analogue scale (VAS) for 8-min periods after 10-sec histamine application, while changes of skin blood flow were simultaneously measured using two Laser Doppler flowmeters. Ten minutes after each histamine application, the areas of wheal and flare reactions were planimetrically evaluated. When no or weak current was applied, AD patients revealed stronger wheal and flare reactions than controls, possibly due to disturbed skin barrier function. Higher histamine doses, however, produced weaker subjective and vascular reactions in AD patients. In contrast to the controls, AD patients were unable to distinguish between weak and strong histamine stimulation, as shown by their VAS ratings. These results imply that AD patients have an altered histamine response. In particular, their afferent cutaneous nerve fibers show a decreased ability to signal itching to the central nervous system and to release vasoactive neuropeptides upon histamine stimulation.

Administration, Cutaneous↗
PubMed1989

[Pathophysiology of orofacial pain].

The pathophysiology of different kinds of orofacial pains is discussed. (a) Stimulus-induced pain may be elicited e.g. by surgical interventions at the teeth. Nociceptors stimulated by noxious stimulation induce not only pain sensations but contribute also to regulating the blood flow, directly by releasing vasoactive peptides, and indirectly by inducing sympathetic reflexes, (b) Inflammatory pain has its origin in an sensitization of nociceptor units by several kinds of endogenous neuro-vasoactive substances. (c) Chronic pains are either the consequence of motor or vegetative dysregulations or of neuropathic origin. The implications for different kinds of pain pathophysiology for therapeutic strategies are discussed.

Facial Pain↗
PubMed1988

Selective excitation by capsaicin of mechano-heat sensitive nociceptors in rat skin.

The effect of close-by arterial injections of capsaicin on single afferent fibers of the saphenous nerve was studied on 82 units from control rats and on 44 units from rats pretreated with capsaicin (total dose 200 mg/kg applied subcutaneously under anesthesia 3 days before the experiment). In control rats low doses of capsaicin selectively excited mechano-heat sensitive cutaneous nociceptors (polymodal C fiber nociceptors and MH-A delta nociceptors). The median threshold dose for polymodal nociceptors was 0.1 micrograms. Repeated injections of capsaicin in near-threshold doses evoked reproducible effects without obvious signs of desensitization. In contrast A delta high-threshold mechanoreceptors, hair follicle receptors, cold receptors and C fiber mechanoreceptors were not excited by capsaicin even at doses of 5 micrograms. These high doses activated, however, some SA-II mechanoreceptors after a time lag, probably due to increased tissue turgor induced by plasma extravasation. Systemic capsaicin pretreatment of adult rats resulted in a selective decrease in the proportion of polymodal nociceptors among the afferent C-units, and an increment in the threshold dose of capsaicin of the responding polymodal nociceptors. It is concluded that in the adult rat capsaicin exerts a selective stimulatory and blocking effect on cutaneous mechano-heat sensitive nociceptors conducting both in the C fiber and A delta fiber range.

Animals↗
PubMed1988

Measurement of the analgesic effects of aspirin with a new experimental algesimetric procedure.

Using controlled long lasting noxious squeeze stimuli applied to the interdigital webs we have tried to develop experimental methods allowing us to measure the effects of peripherally acting analgesics. In the present double-blind cross-over study with 12 subjects we tested the effects of aspirin (1000 and 1500 mg) vs. placebo on subjective pain induced by alternately applied 12 N (Newton) and 8 N stimuli. During the sessions blood samples were taken in regular intervals to measure acetylsalicylate (ASA)- and salicylate (SA)-plasma levels. Analyses of variance were computed with several psychophysical parameters. Both the '12 N' and the '8 N' ratings discriminated between placebo and aspirin, however, only the ratings obtained from the stronger stimuli discriminated between two doses of aspirin. Subsequently we computed analyses of covariance with the ASA- and SA-plasma levels as covariates. Significant (negative) correlations of pain ratings and SA-plasma levels were found for the high dose of aspirin, but there were no significant correlations of ASA levels and ratings.

Analgesia↗
PubMed1988

Prolonged noxious mechanical stimulation of the rat's tail: responses and encoding properties of dorsal horn neurones.

1. Single-unit electrical activity has been recorded from dorsal horn neurones in the sacral (S1-S2) segments of the spinal cord of barbiturate-anaesthetized rats. Fifty-two neurones responding to a manually applied pinch of their receptive fields in the tail were selected. They were subsequently tested for their responses to four successive 2 min pinches at noxious intensities delivered by a feed-back-controlled mechanical device. 2. Neurones were tested with both innocuous (i.e. brushing and stroking) and noxious (i.e. pinching, pin-prick, and in some cases heating about 45 degrees C) stimulation of their cutaneous receptive fields. Three of the tested cells were driven exclusively by innocuous skin stimulation (mechanoreceptive or class 1), thirty-six were driven by both innocuous and noxious skin stimulation (multireceptive or class 2) and thirteen were driven exclusively by noxious skin stimulation (nocireceptive or class 3). 3. All of the multireceptive and nocireceptive neurones responded to the 2 min noxious pinch with an initial phasic discharge followed by sustained firing that showed little evidence of adaptation throughout the stimulus period. The three mechanoreceptive neurones responded to the 2 min noxious pinch with a short discharge at the stimulus onset, but were silent for the remainder of the stimulus period. 4. Thirty-one cells were tested with successive 2 min pinches of 4, 6 and 8 N (and in some cases, a further 4 N pinch) applied at 10 min intervals. Different encoding properties were observed during the sustained part of the neuronal response according to: (i) the afferent fibre input characteristics of the cell; (ii) whether or not the tail had received a test series of pinches earlier in the same experiment. 5. None of the multireceptive cells with only an A-fibre afferent input encoded the stimulus strength. However, the multireceptive cells with both an A- and a C-fibre afferent input and all nocireceptive cells did encode the stimulus strength, providing that no previous noxious test stimuli had been applied to the tail. The encoding nocireceptive neurones had in general a steeper stimulus-response curve than the encoding multireceptive neurones, though the two groups overlapped to some extent. 6. Three encoding cells (two multireceptive and one nocireceptive) were tested with a second series of pinches (4, 6, 8 and 4 N), 40 min subsequent to the initial test series. These cells did not encode this second test series, but were more excitable, producing a greater response to a given test force.(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials↗
PubMed1987

Laser Doppler measurements of skin vasodilation elicited by percutaneous electrical stimulation of nociceptors in humans.

This study was designed to assess the quantitative features of the skin protecting mechanism of axon reflexes by monitoring stimulus related changes in skin blood flow using laser Doppler flowmetry. Skin vasodilatation induced by trains of brief transcutaneous electrical pulses (0.5 ms, 150 V) was strictly related in magnitude to the number of pulses (trains of 1-32). This vascular response was reduced by 95% when the skin had been pretreated by painting it for two days with a 1% alcoholic solution of capsaicin. The sensitivity of vascular responses to activation of afferent C-fibers indicates a role of this mechanism in the protection of the skin against noxious events.

Adult↗
PubMed1987

Discharge patterns of afferent cutaneous nerve fibers from the rat's tail during prolonged noxious mechanical stimulation.

Feedback controlled constant force stimuli of 4, 6 and 8 N intensities and of 120 s duration were applied to the receptive fields of cutaneous afferent fibers in the rat's tail. Two types of nociceptive units showed sustained discharges during these stimuli: "polymodal" unmyelinated C-units (MH-C units, N = 18, c.v. 0.5-0.9 m/s) and high-threshold mechanoreceptive A-delta-units (HTM-units, N = 10, c.v. 1.9-11.2 m/s). In addition two classes of sensitive low threshold mechanoreceptors, SA I (N = 6) and SA II (N = 5) units, responded to the prolonged mechanical stimuli. At the onset of a noxious pressure, 11 of the 18 polymodal nociceptors exhibited dynamic responses (lasting about 10 s) which were followed by slowly adapting tonic discharges that lasted for the duration of the stimuli. The remaining polymodal C-fiber units (8/18) did not show dynamic discharges at 4 and 6 N. Phasic and tonic discharges were positively correlated with stimulus strength. The HTM-units encoded stimulation intensity mainly by their dynamic discharges. The tonic discharges of these units displayed faster adaptation rates with stronger mechanical stimuli, i.e. encoding of stimulation intensity became progressively weaker during the tonic phase. The discharges of sensitive SA I and SA II units with A beta axons were not positively correlated with the strength of noxious pressure stimuli. Tonic discharge rates of SA I units were negatively correlated to stimulus strength, whereas SA II units usually stopped firing in the course of a stimulus and became reversibly irresponsive to mechanical stimulation. Possible afferent mechanisms underlying the induction of pain by sustained noxious mechanical stimulation are discussed.

Afferent Pathways↗
PubMed1987

Sensitization of nociceptive cutaneous nerve fibers from the rat's tail by noxious mechanical stimulation.

This single fiber study on rat tail nerve afferents attempts to establish a peripheral neural correlate for the hyperalgesia to mechanical stimulation which follows injury to the skin. Mechano-heat sensitive C fibers (MH-C or "polymodal" nociceptors) and high-threshold mechanoreceptive A delta fibers (HTM-A delta) were examined with a series of constant noxious pressure stimulations (4-6-8-4 N on 25 mm2, 120 s each, 5 min intervals). These injurious stimuli were either directed to the most sensitive spot of the receptive fields (central stimulation) or closely outside their borders (1-5 mm). With this protocol no clear sensitization was seen in MH-C fibers apart from a stronger dynamic response to central stimulation in some of them. In contrast, most HTM-A delta units, irrespective of the site of noxious stimulation, developed spontaneous activity, lowering of their von Frey thresholds and expansion of their receptive fields. All HTM-A delta units responded to outside stimulation: upon the first stimulus (4 N) there was a delayed discharge of continuously increasing frequency ("recruited response"), but the onset of the last stimulation (4 N repeated) evoked vigorous dynamic responses in many fibers. The recruitment of HTM-A delta nociceptor activity may contribute to post-injury hyperalgesia to mechanical stimulation and it may counteract adaptation of the single afferent fiber during prolonged noxious influence.

Animals↗
PubMed1987

Nociceptor functions in intact skin and in neurogenic or non-neurogenic inflammation.

Acute neurogenic or non-neurogenic inflammation was elicited in skin patches innervated by the saphenous nerve of anaesthetized Sprague Dawley rats. Lambda carrageenan was used to induce non-neurogenic inflammation, mustard oil (allyl-iso-thio-cyanate) or antidromic nerve stimulation to induce neurogenic inflammation. Antidromic nerve stimulation yielded plasma extravasation but no significant sensitization of unmyelinated nociceptor units. In contrast, mustard oil and carrageenan yielded plasma extravasation and sensitization of nociceptors, though carrageenan sensitized only part of them. Sensitization resulted in ongoing spike discharges and in a shift of response curves to lower temperatures when controlled radiant heat stimuli were applied to the receptive fields. Responses to mechanical stimuli with v. FREY hairs were not significantly altered. Effects of neurogenic and non-neurogenic inflammation on unmyelinated nociceptor units are compared.

Animals↗
PubMed1987

Electrically evoked skin vasodilatation: a quantitative test of nociceptor function in man.

Direct stimulation of intact forearm skin affects adjacent microvascular blood flux. Pulses of current, known to activate C-fibres effectively, were applied over a period of 1-16 seconds at 2 Hz using transcutaneous stimulation. An increase of up to 50% was observed in skin microvascular blood flux. Increased blood flux correlated well with increasingly painful sensations. Some subjects responded to one or two pulses at 2 Hz, 0.5 ms in duration and 150 volts. A response onset latency of 4-15 s, lasting up to 5 minutes, was recorded. At higher frequencies (4-8 Hz) and more pulses (16-32) vasoconstriction was frequently observed before the usual flux increase. After administration of local anaesthesia (2% ligocaine) the resting skin blood flux increased, but electrical stimulation still produced vasodilatation. The local cutaneous flare response to electrical stimulation was abolished or greatly reduced by capsaicin pretreatment. Excitation of small intracutanous forearm nerve C-fibres produces increased microvascular blood flux which is dependent on local release of vasodilator substances. Thus the neurogenic flare (axon reflex) may have a physiological role in regulating skin blood flow, and nociceptor function may be measured by applying the aforementioned transcutaneous electrical stimulation.

Axons↗
PubMed1986

Algesimetry--a necessity in research on analgesic drugs.

In addition to the methods of clinical algesimetry, the investigation of the actions of analgesic drugs requires reliable and sensitive methods of experimental algesimetry. In contrast to the clinical investigation of analgesic actions, the methodology of the experimental testing of analgesics in humans is still rudimentary. The difficulties encountered in experimental algesimetry are discussed in this contribution, and an algesimetric study is presented illustrating experimental methods with which the pharmacodynamics of peripherally acting analgesics may be investigated.

Analgesics↗
PubMed1984

Suppression of C-fibre discharges upon repeated heat stimulation may explain characteristics of concomitant pain sensations.

Nociceptors with unmyelinated axons were recorded from the superficial radial nerves of 7 volunteers. A sequence of uniform radiant heat stimuli of 18 s duration, starting from an individually adjusted adapting temperature were used to raise the skin surface temperature by 6 degrees C to a painful level (41-43 degrees C). These stimuli followed each other at 3 different interstimulus intervals of 35 s, 70 s and 105 s, occurring in a random order. The subjects were asked to track the time course of the stimulus-evoked sensation by manipulating the length of a light bar. Adaptation and stimulus temperatures were chosen to induce sensations of heat and/or pain. All nociceptors studied responded to these stimuli with a phasic response of 3-5 s duration, often followed by a low frequency tonic discharge, lasting as long as the stimulus. No discharges were seen in interstimulus periods. Discharge rates during the phasic responses were linearly related to interval duration, whereas tonic discharges were not influenced by the preceding interval. In parallel readings of pain responses were lower up to the 10th second of the stimulus after short rather than after long intervals. These results indicate that the suppression of C-fibre nociceptor discharges during repetitive stimulation may explain concomitant reductions in the magnitude of human pain sensations.

Adult↗
PubMed1984

Afferent C-fibres in rats after neonatal capsaicin treatment.

Excitability of afferent C-fibres in a skin nerve was studied in 28 rats treated with capsaicin on day two of their lives (80 mg/kg, s.c.). At the age of 4-5 months they were subjected to experiments in which recordings were made from single C-fibre units of saphenous nerve. The effectivity of neonatal capsaicin treatment in blocking reactions to the irritating action of the toxin was evaluated with the wiping test. Five untreated rats served as controls. In capsaicin treated animals afferent cutaneous C-fibres were diminished by more than 50%. No significant change was found, however, in the spectrum of kinds of cutaneous receptors. In particular, the ratio between nociceptors responding to heat and mechanical stimuli (polymodal nociceptors, MH-units) and other C-fibre receptors, such as sensitive cold units was not changed significantly. Furthermore, in the animals neonatally treated with capsaicin conduction velocities of afferent C-fibres and thresholds to mechanical and thermal stimuli were not significantly altered. In both capsaicin treated and control samples, the spike conduction in most of the mechano- and heat sensitive C-nociceptors was blocked by acute topical application of this toxin to the nerve stem. It is concluded that part of the afferent C-fibres survived neonatal capsaicin treatment, even in those rats that showed complete intensitivity to the toxin in behavioural tests.

Administration, Topical↗