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Biomedical subjects

H O Handwerker

Publications and source records attributed to H O Handwerker.

At least 55 records · Page 3Linked to original sources
PubMed1997

Cutaneous norepinephrine application in complex regional pain syndrome.

Patients with complex regional pain syndrome (CRPS) (n=20) were examined in order to evaluate cutaneous reactions to norepinephrine (NE) on both the affected and the unaffected limb in comparison to healthy controls. Sixteen female and four male patients suffering from very acute and therefore untreated CRPS with a mean duration of 5.5 weeks were included in this study. Two groups of healthy volunteers served as control groups: the first group (n=18) according to the same study protocol as CRPS patients, and the second group (n=10) after warming up one limb. Norepinephrine was iontophoresized (0.2 mA, 120 s) and vasoconstriction was recorded by laser-doppler flowmetry. Pain sensations were simultaneously rated on a visual analogue scale (VAS). Five patients underwent a second trial with higher intracutaneous NE concentrations in order to study possible dose-dependent effects of NE on pain sensation. After acclimatization, skin temperature was recorded by infra-red thermography. The NE-induced reduction of skin blood flow was significantly higher in the affected limb in the patient group (33.0 vs 11.2%, p<0.005). None of the patients reported pain or hyperalgesia. The skin temperature of CRPS patients was significantly higher in the affected limb (34.7 vs 32.5 degrees C, p<0.001). The first control group did not show any difference between left and right sides concerning NE-induced vasoconstriction or skin temperature. The second control group had an increased unilateral skin temperature after warming up (35.0 vs 34.3 degrees C, p<0.006) and demonstrated a significantly increased vasoconstriction on the warmer side (52.0 vs 20.2%, p<0.03) corresponding to findings in patients with acute CRPS. The present study proves that there are signs of decreased sympathetic activity in the affected limb in very acute CRPS. However, no indication was found for increased sensitivity of vascular alpha-receptors in the very acute stages of CRPS, and there was also no indication for a significant direct contribution of the sympathetic nervous system to pain in very acute CRPS.

Journal Article↗
PubMed1997

Recordings from brain stem neurons responding to chemical stimulation of the subarachnoid space.

The subarachnoid space at the base of the skull was perfused continuously with artificial cerebrospinal fluid in anesthetized rats. A combination of inflammatory mediators consisting of histamine, bradykinin, serotonin, and prostaglandin E2 (10(-5) M) at pH of 6.1 was introduced into the flow for defined periods to stimulate meningeal primary afferents. Secondary neurons in the caudal nucleus of the trigeminal brain stem were searched by electrical stimulation of the cornea. Of the units receiving oligosynaptic input from the cornea, 44% were excited by stimulation of the meninges with inflammatory mediators. Most of these units had small receptive fields including cornea and the periorbital region, and their responsiveness was restricted to stimuli of noxious intensity. Three types of responses to stimulation of the meninges with algogenic agents were encountered: responses that did not outlast the stimulus period, responses outlasting the stimulus period for several minutes, and oscillating response patterns containing periods of enhanced and suppressed activity. The response pattern of a unit was reproducible, however, upon repetitive stimulation at 20-min intervals; the response magnitude showed tachyphylaxis upon stimulus repetition. The preparation presented mimics pathophysiolocial states normally accompanied by headache, e.g., subarachnoidal bleeding. Responsiveness of neurons in the caudal nucleus of the trigeminal brain stem to inflammatory mediators may play a role in the generation and maintenance of headache, e.g., migraine.

Afferent Pathways↗
PubMed1997

Innervation territories of mechanically activated C nociceptor units in human skin.

Innervation territories of mechanically activated C nociceptor units in human skin. J. Neurophysiol. 78: 2641-2648, 1997. Innervation territories of single mechanically activated C nociceptors in the skin of the leg and foot were explored in normal human subjects. Microneurographic recordings were obtained in the peroneal nerve from 70 mechano-heat responsive (CMH) and 7 mechano-(but not heat) responsive (CM) units. Units were identified by their constant long-latency response to intracutaneous electrical stimulation of their terminals. Responsiveness to mechanical, heat, or transcutaneous electrical stimuli was verified by transient slowing of conduction velocity after activation by such stimuli. We determined their thresholds to mechanical stimuli (mean 33.7 mN, median 30 mN, range 3-750 mN) and heat (mean 42.5 degrees C, median 42.5 degrees C, range 37-49 degrees C). Most mechano-receptive fields (mRFs) were found on the foot dorsum (60 units) and some on the lower leg (14 units) and toes (3 units). Most units had one continuous mRF, but 10 units had more complex fields. Areas of mRFs mapped with a von Frey filament (750 mN) ranged from 10 to 363 mm2 (mean, 106 mm2). The mRFs were oval or irregularly shaped with greatest diameters ranging from 3 to 45 mm. Mean areas of mRFs were largest on the lower leg (198 mm2), smaller on the foot dorsum (88 mm2), and smallest on the toes (35 mm2). Forty-nine of the 77 units had identical mRFs and electro-receptive fields (eRFs). Twenty-six units had larger eRFs than mRFs, whereas the opposite was found for two units only. Areas of eRFs ranged from 16 to 511 mm2 (mean 121 mm2). An estimate of the innervation density based on the present data and the presumed number of C fibers in cutaneous fascicles of the peroneal nerve suggests a considerable overlap of nociceptive endings in the skin. Such overlapping nociceptor innervation in the skin allows for substantial spatial summation in response to punctate noxious stimuli, which may be a prerequisite for high accuracy in localizing painful events from a C-fiber input. The reduction in size of innervation territories distally allows for finer discrimination of spatial dimensions of noxious stimuli distally as compared with proximal regions of the extremities. Mean maximal diameters of the mechano-receptive fields of CMH and CM units on the lower leg (22.3 mm) and foot (15.3 mm) are of similar size as the radius of axon reflex flares evoked by noxious mechanical stimuli in these regions.

Adult↗
PubMed1996

Asymmetry and time-course of cutaneous sympathetic reflex responses following sustained excitation of chemosensitive nociceptors in humans.

Sympathetic reflex responses were elicited in human volunteers by sustained selective excitation of nociceptors by noxious chemicals, namely topical application of mustard oil which elicited burning pain, or histamine which induced itching in a skin area of 5 cm2 on the volar aspect of one forearm. Stimulus-related sympathetic reflex responses were studied by means of computer-assisted infrared thermography of the palmar aspects of both hands. Nociceptive stimulation induced a decrease of skin surface temperature in both hands interpreted as vasoconstriction. The magnitude of the reflex cooling was correlated with the magnitude of the sensation (r = 0.49), but independent of the quality of sensation (itch or pain). The temperature reduction was maintained for more than 30 min and its time-course matched the time-courses of pain or itch sensations. It is concluded that the sustained and selective excitation of nociceptors elicits a sustained sympathetic reflex response, which adapts very slowly. The time-course of the reflexes suggests that these are not arousal responses, but may be indicators of nociceptive processing in conscious humans. Contralateral temperature decreases were consistently smaller than ipsilateral ones. Thus, sustained nociceptive-specific vasoconstrictor reflexes may be somatotopically organised with an emphasis on areas close to the painful stimulus (homotopic), which has so far only been shown in animals. The study thus demonstrates for the first time in humans the presence of a sympathetic reflex asymmetry, which is specific for nociceptive afferent input.

Adult↗
PubMed1996

Limitation of sensitization to injured parts of receptive fields in human skin C-nociceptors.

Unmyelinated cutaneous mechano-heat fibers (CMH) in the peroneal nerve of healthy human volunteers were studied by means of a "marking" technique which allows stable recordings from identified single units over extended periods. Mechanoreceptive field sizes were 105 +/- 13 mm2 in 25 units. These large receptive fields indicate extensive terminal branching of C fibers in the skin of foot and lower leg. Sensitization of CMHs was tested by assessment of thresholds for mechanical (von Frey hair) and heat stimuli before and after topical application of mustard oil (allyl isothiocyanate) and capsaicin (8-methyl-N-vanillyl-6-noneamide). While in a group of 14 CMHs the entire receptive field was treated with these irritant substances, in another group of 11 CMH units only parts of the receptive field were treated to check for signs of spreading sensitization through axon collaterals. Mustard oil application did not change mechanical thresholds, regardless of whether parts of or complete receptive fields were treated. However, mean heat thresholds dropped by 5.6 degrees C to 36.5 +/- 1.5 degrees C in completely treated receptive fields and by 5.7 degrees C to 37.3 +/- 3.4 degrees C in treated parts of receptive fields ("primary sensitization"). In contrast, heat thresholds in the nontreated parts did not change significantly (42.1 +/- 3.4 degrees C vs 41.2 +/- 3.9 degrees C), i.e. "secondary sensitization" to heat was lacking. The absence of primary sensitization to probing with von Frey hairs indicates that sensitization of insensitive C fibers and recruitment of insensitive axon collaterals may be more important for mechanical hyperalgesia than sensitization of conventional CMH units-apart from the contribution of central mechanisms. The lack of spread of sensitization to untreated parts of the receptive fields o CMHs ("secondary sensitization") indicates that this fiber group is probably not involved in any form of secondary hyperalgesia to heating.

Adult↗
PubMed1996

[Antipruritic effect of antihistaminic and local anesthetic topical agents after iontophoretic histamine stimulation].

No adequate topical therapy is available for pruritus. As little is known about the local influence of antihistamines and topical anaesthetics on the pruritic effect of histamine, we studied these agents in 12 volunteers. The antipruritic effect of 15-min topical application of dimethindene maleate (Fenistil gel) and different agents (Optiderm, EMLA, Xylocaine-Salbe 5%) on subsequent focal histamine stimulus (20 mC) given by iontophoresis was evaluated. The results were compared with those of pretreatment with the corresponding placebo creams and observations on skin. Wheal and flare areas were evaluated planimetrically. Itch or pain ratings were entered on a scale every minute over a 24-min period. The examination also comprised alloknesis, i.e. elicitation of perifocal itch sensation by usually non-itch-inducing (e.g. mechanical) stimuli. Remarkably, all topically applied substances, regardless of antihistaminic or anaesthetic potential, reduced the area of alloknesis significantly. This is likely to be a result of diminished excitability of the cutaneous mechanoreceptors. Itching was significantly reduced by all active substances, including the placebo cream corresponding to Optiderm, which might be due to the presence of urea.

Adult↗
PubMed1996

Hemodynamic and sympathetic nerve responses to painful stimuli in normotensive and borderline hypertensive subjects.

Observations in animals and humans show that pain sensitivity might be lower (and pain tolerance higher) in hypertensive as compared to normotensive subjects. One hypothesis, derived from experimental studies, assumes that enhanced activation of baroreceptors leads to an enhanced central inhibition. A central hypothesis assumes changes in the central (endogenous) control of the nociceptive system. To investigate these two hypotheses we quantitatively assessed the minute-by-minute changes in mean arterial pressure (MAP), central venous pressure (CVP) heart rate (HR), muscle sympathetic nerve activity (MSNA), and individual pain ratings during noxious mechanostimulation in 10 normotensive (NT) and 13 borderline hypertensive (BH) subjects. Linear regression analysis indicated a close negative correlation for the overall data between resting levels of MAP and pain ratings (r = -0.57, P < 0.0001). The BH group exhibited a lower pain sensitivity compared to the NT group (P < 0.001). The extent of baroreceptor activation during the application of pain was not different between the two groups (P = NS) as assessed by almost identical increases in MAP (+8 +/- 1 vs. +9 +/- 1 mmHg NT vs. BH group), CVP (+0.7 +/- 0.1 vs. +0.5 +/- 0.1 mmHg), HR (+2 +/- 1 vs. +2 +/- 1 beats/min), and MSNA (+5 +/- 1 +4 +/- 1 bursts/min). The NT subjects exhibited significant correlations between the pain ratings and the increases in MAP (r = +0.52; P < 0.05) and MSNA (r = +0.49; P < 0.05) whereas the BH subjects did not show such a relationship. Thus, the increased pain tolerance in human hypertension cannot be explained by hemodynamically mediated differences in the activation of baroreceptors or by an altered baroreflex sensitivity during the application of pain. We conclude, that the reduced pain sensitivity in hypertensive humans is more likely related to central changes.

Adult↗
PubMed1996

Atopic eczema and histamine-induced sensations.

BACKGROUND: In previous studies we observed diminished pruritogenic effects and reduced flare reactions after iontophoretic application of histamine in patients with acute atopic eczema (AE). OBJECTIVE: To determine a possible mechanism acting on peripheral and central nervous components of the histamine-mediated itch reaction. METHODS: Forty-eight individuals with different predispositions to AE were included. According to an 'atopic score', 16 individuals had no history of atopic symptoms, another group of 16 individuals showed a disposition to AE and a further group of 16 individuals had a clear history of AE. However, all individuals were devoid of acute atopic symptoms and their IgE levels were below 150 U/ml. Histamine was iontophoretically applied to the skin of the forearm, and stimulus-induced itching and burning sensations were rated on visual analogue scales. RESULTS: Individuals with previous episodes of AE reported weaker itch sensations after histamine. In addition, the sensations were often described as burning by this group. CONCLUSION: The results suggest an altered central nervous responsiveness already in symptom-free individuals, since peripheral vascular reactions to histamine were not significantly reduced.

Adult↗
PubMed1995

Neurogenic flare responses are heterogeneous in superficial and deep layers of human skin.

Infrared thermography and video image analysis were used to compare the development of the neurogenic flare response in deep and superficial skin layers. Neurogenic vasodilatation was induced by injection or iontophoretic application of histamine. Thermograms were recorded every 10 s to evaluate the local warming reaction. Color-video image analysis was used for computerized delineation of the visible flare. Images derived from video analysis were superimposed to the thermograms after linear transformation. The thermal reaction started within 10 s simultaneously at 2-5 distinct spots after histamine application at distances of 4-25 mm from the application site while the flare reaction seemed to spread from the application site when it became visible after a delay often exceeding 20 s. The visible flare but not the warming reaction was suppressed by topically applied local anesthetic (EMLA). Warming at focal spots was also observed during post-occlusive hyperemia. About 70% of these spots were identical to those activated by histamine. The results indicate that the vascular axon reflex is differently organized in different layers of the skin.

Adult↗
PubMed1995

Function of thick and thin nerve fibers in carpal tunnel syndrome before and after surgical treatment.

Present studies evaluated the functions of thick and thin nerve fibers in carpal tunnel syndrome (CTS) to determine whether data of thin nerve fibers can add further information to the diagnosis of CTS. Measurements were performed in 22 patients and 16 age-matched control subjects. Motor and sensory nerve conduction, vibratory testing, thresholds of warmth and cold sensations, suprathreshold magnitude of pain and flare response, as well as sympathetic reflexes induced by noxious mechanostimulation were examined before and 1, 3, 6, 12, and 18 months after decompression of the median nerve. Nerve dysfunction in CTS was mainly indicated by the electrophysiological parameters of thick myelinated nerve fibers. Impairment of thin nerve functions in CTS and postoperative recovery was demonstrated by quantitative somatosensory thermotesting. In contrast, assessment of flare response and sympathetic reflexes using infrared thermography and photoplethysmography did not add further information for the diagnosis of CTS.

Adult↗
PubMed1995

Delayed responses to electrical stimuli reflect C-fiber responsiveness in human microneurography.

The slowing of impulse conduction during the relative refractory period has often been used to assess activation of C-fibers, in particular, in human microneurography. This study aimed to evaluate the sensitivity of this method and the factors affecting it. Thirty cutaneous C-fibers were recorded from the peroneal nerves of healthy human subjects. Intracutaneous electrical stimulation in the receptive field at 4 s intervals, after some minutes of adaptation, induced spike discharges at constant latency. One or more conditioning stimulus pulses were interpolated at different intervals and the increase in latency after the subsequent regular pulse was assessed. The latency shift was found to depend on the number of interposed pulses, on the time interval between conditioning and conditioned stimulus, and on the conduction velocity of the C-unit. The increase in latency was larger with greater distance between stimulating and recording electrodes, indicating a contribution of the conductile membrane over its whole length. On the other hand, slowing was more pronounced, on average, in slower conducting C-units and conduction velocities were slower when recordings were performed more distally. These findings indicate that the slower terminal nerve branches contribute most to the latency increases. Even a single additional spike in between two regular pulses caused a reliable latency shift of 1.2 +/- 0.2 ms (mean +/- SEM) and additional pulses lead to an approximately linear latency increase (2 pulses: 2.3 +/- 0.3 ms; 4 pulses: 5.9 +/- 0.7 ms). In contrast to the number of interposed stimuli, different intervals between interposed and regular stimuli had only a minor impact on the latency shifts.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Parameters of thick and thin nerve-fiber functions as predictors of pain in carpal tunnel syndrome.

Pain intensity in carpal tunnel syndrome (CTS) was correlated with neuro- and psychophysiological parameters related to the function of different nerve fiber classes within the median nerve in 23 patients. Control data were obtained from 16 normal subjects. Mean intensity of all pain attacks which occurred 14 days before surgical treatment was assessed on visual analogue scales (average CTS pain). Functions of thick myelinated nerve fibers were determined by motor and sensory nerve conduction studies. Functions of thin myelinated and unmyelinated nerve fibers were evaluated by measuring thresholds of warmth, cold and heat pain on the index and little finger. Pain intensity and neurogenic vasodilatation following noxious mechano-stimulation on the interdigital web between index and middle finger provided additional information on the functioning of nociceptive nerve fibers. Sympathetic reflexes induced by these painful stimuli were assessed by means of infrared thermography and photoplethysmography. Mean intensity of pain attacks (40 +/- 19% VAS) correlated significantly with latency (r = 0.58, P < 0.01) and amplitude (r = -0.50, P < 0.01) of the compound action potential from abductor pollicis brevis muscle following distal median nerve stimulation. Thresholds of warmth, cold and heat pain on index finger were significantly increased during CTS when compared to the control subjects. The magnitude of neurogenic vasodilatation and sympathetic vasoconstrictor reflexes were not significantly different. Average CTS pain correlated inversely to the threshold of heat pain on index (r = -0.46, P < 0.05), but also on the little finger (r = -0.41, P < 0.05), which is not innervated by the median nerve.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Inflammatory models of cutaneous hyperalgesia are sensitive to effects of ibuprofen in man.

A new experimental procedure was developed to quantify the analgesic actions of non-steroidal anti-inflammatory drugs (NSAIDs) in healthy human subjects. In order to mimic the clinical situation, the drug was 'therapeutically' administered 1 day after induction of inflammation by freezing a small skin area. The procedure was easily tolerated and led to a marked hyperalgesia without ongoing pain which was tested using mechanical impact stimulation and magnitude estimation. For comparison, we used a previously established model of repeated noxious pinching of an interdigital skin web which induces a hyperalgesia to pressure (rated via visual analogue scale), and topical application of capsaicin which leads to quantifiable flare and allodynia responses. The effects of a cumulative drug regime of ibuprofen in 2 different doses (3 x 400 mg and 3 x 800 mg at 2-h intervals) were tested versus placebo using a double-blind cross-over design with 24 volunteers of either gender. Ibuprofen caused a significant suppression of the hyperalgesia to repeated pinching and of the hyperalgesia to impact stimulation following freeze trauma. In contrast, there was no effect on the areas of flare and allodynia induced by capsaicin application and on the impact evoked sensations from untreated skin. The two dosages of ibuprofen, however, appeared to be equally effective in a way that suggests a plateauing of the antihyperalgesic effect. The two models in which hyperalgesia is affected by ibuprofen, i.e., repeated pinching and impact stimulation after freeze trauma, seem to provide comparable sensitivity. The freeze model may in the future have the advantage to allow for a better temporal resolution of the drug's action profile.

Adult↗
PubMed1995

Stimulation of sudomotor axon reflex mechanism by carbachol in healthy subjects and patients suffering from diabetic polyneuropathy.

Sudomotor axon reflex (SAR) mechanism was stimulated by percutaneous iontophoresis of carbachol in healthy subjects and patients suffering from diabetic polyneuropathy (PNP) of differing severity (stage I-III). SAR response was assessed by hygrometry and compared with histamine induced neurogenic vasodilation (laser-Doppler flowmetry) and itching sensation (visual analogue scale), which may provide information on neuro-secretion and afferent function of nociceptive unmyelinated nerve fibers. Carbachol induced long lasting SAR response with maximal sweating rates 20-30 minutes after stimulus onset. In diabetic patients the carbachol induced SAR response and the histamine induced itching sensation were significantly reduced in stage III of PNP. In contrast, histamine induced vasodilatation was significantly impaired in all stages of PNP. It is concluded that prolonged SAR response following iontophoresis of carbachol can simplify evaluation of sudomotor function when compared to established tests using intradermal application of acetylcholine. Furthermore, to demonstrate impairment of unmyelinated nerve fibers in PNP, histamine induced vasodilatation was found to be more sensitive than SAR response.

Adult↗
PubMed1995

Histamine-induced itch and alloknesis (itchy skin) in atopic eczema patients and controls.

Alloknesis ("itchy skin") after histamine iontophoresis was studied together with itch sensations and skin reactions in 19 atopic eczema patients and 20 controls at the forearm and at the scapular area. Compared to controls, atopic eczema patients showed significantly reduced alloknesis or total lack of it in the area around a skin site to which histamine had been iontophoretically applied, although histamine elicited itching in most patients. As previously demonstrated, patients with atopic eczema also developed significantly smaller flares. However, covariance analysis revealed that the smaller alloknesis areas in atopic patients were not statistically related to the smaller flares. Our results suggest that in atopic eczema a diminished responsiveness of primary afferent nerves to histamine is not compensated by a higher central nervous sensitivity reflected in more vivid alloknesis responses to histamine. Therefore, we conclude that histamine is probably not the key factor of the spontaneous itch experienced by patients with atopic eczema.

Administration, Cutaneous↗
PubMed1995

Comparison of different algorithms for evaluation of respiratory sinus arrhytmia: cross-correlation function histogram analysis and regression analysis.

Three algorithms for assessment of respiratory sinus arrhythmia (RSA) have been evaluated: cross-correlation function, histogram analysis and regression plot. The algorithms were tested experimentally in a group of 11 subjects. A cross-correlation function with a high time resolution (1 ms) was used for investigation of the time lag between instantaneous heart rate and respiration (CTL). This time lag was not affected by the breathing rate in a range of 8 to 29 breaths per minute. A mathematical model of CTL compared with experimental results indicates that respiratory sinus arrhythmia is probably modulated directly by the respiratory network in the brainstem rather than by a baroreflex in the range of breathing rate investigated. Histogram analysis reflects the impact of inspiration and expiration on respiratory sinus arrhythmia. For this purpose heart rate changes were separated into two distributions (inspiration-expiration). The result value (U-VAL) of the Mann-Whitney U-test reflects the impact of respiration on heart rate variability. Regression analysis of heart rate versus respiration shows that the heart rate increase is more closely coupled to inspiration than the heart rate decrease to expiration. Both, CTL and U-VAL are thought to be useful parameters for clinical investigation of RSA.

Adult↗
PubMed1994

Sensitization of insensitive branches of C nociceptors in human skin.

1. Eighteen cutaneous mechanosensitive C nociceptors were recorded from the peroneal nerves of healthy human subjects. Their identity was continuously monitored by intracutaneous electrical stimulation, and their activation by mechanical or transcutaneous electrical stimulation was detected by slowing of conduction velocity during the relative refractory period. 2. Mechanoreceptive fields (mRFs) mapped with suprathreshold von Frey hair stimuli covered an area of 99 +/- 21 mm2 (mean +/- S.E.M.). Two of the units had separate mRFs, with borders about 0.5-1.5 cm apart from each other and the largest of these units had a maximal diameter of 4.5 cm. 3. Successive topical application of mustard oil and capsaicin induced expansions of mRFs by 57 +/- 14 mm2 in eight of fifteen units. 4. In twelve units transcutaneous electrical stimulation delivered through a pointed electrode was used for mapping the electroreceptive fields (eRFs). The borders of the eRFs and the mRFs were identical for two of twelve units only. In the other ten units additional mechano-insensitive areas (55 +/- 22 mm2) were detected from which transcutaneous electrical stimuli could activate the respective unit. 5. Application of mustard oil and capsaicin to these mechano-insensitive areas sensitized five of eight units to mechanical stimuli. In these cases the mRF after sensitization exactly corresponded to the eRF. 6. It is concluded that there are insensitive branches in human mechanosensitive cutaneous C nociceptors that can be detected by transcutaneous electrical stimulation and sensitized by topical application of chemical irritants. Activation of those branches in the course of inflammatory processes may contribute to spatial summation at central synapses and hence to hyperalgesia.

Adult↗