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Biomedical subjects

H O Handwerker

Publications and source records attributed to H O Handwerker.

At least 19 recordsLinked to original sources
PubMed1998

Spatial extension of sudomotor axon reflex sweating in human skin.

Acetylcholine (ACh) applied to human skin is known to elicit a sweat response, which consists of a direct muscarinergic (M3) activation of sweat glands and a nicotinic axon reflex response from sudomotor terminals. To visualize the extent of axon reflex sweating after ACh-iontophoresis, iodine starch staining was used. Iontophoresis was performed under occlusion at the peroneal aspects of the lower leg and the center of the foot dorsum of healthy volunteers (n = 10). Ten minutes after stimulation, the area of dark blue staining was recorded by a video camera. Control experiments were performed with saline, histamine, pilocarpine and nicotine iontophoresis. The stained area was measured and the maximum and minimum distance of its boundary from the edge of the iontophoresis probe was determined (maximum/minimum radius). Sizes of stained areas and maximum radii were significantly greater on the lower leg compared to the foot (P < 0.01). The median sizes of the stained areas on the leg were 14.6 cm2 and on the foot dorsum 8.0 cm2. The respective median maximum radii were 3.1 cm on the leg and 2.3 cm on the foot dorsum (median minimum, leg 1.1 cm, foot 0.8 cm). These results match microneurographic findings of innervation territories of sympathetic efferent units. Area sizes of stained skin showed a close correlation between both stimulation sites (R = 0.96, P < 0.01), i.e. the sizes of sweat responses on leg and foot show a constant relation (foot/leg = 0.57) in spite of their great interindividual variability. This novel technique of establishing sweat responses provides information on the size of sudomotor innervation territories and may be useful for clinical studies in patients with suspected impairment of sympathetic functions.

Acetylcholine↗
PubMed1998

Effects of naloxone on hemodynamic and sympathetic nerve responses to pain in normotensive vs. borderline hypertensive men.

Pain sensitivity decreases with increasing resting blood pressure. This blood pressure-pain interaction may be mediated by endogenous opioids which have been shown to affect both blood pressure and nociception. To test this hypothesis, we measured mean arterial blood pressure (MAP), central venous pressure (CVP), heart rate (HR), muscle sympathetic nerve activity (MSNA), serum catecholamines, and individual pain rating scales during 2 min periods of noxious mechanostimulation (skin fold pinching) in nine young (26 +/- 2 year), male normotensive (NT) subjects and in 12 age and weight matched males with borderline hypertension (BHT). Measurements were performed before and after the i.v. administration of naloxone (0.15 mg/kg) and placebo in a randomized double-blind cross-over trial. In the pre-naloxone trials, pain led to similar changes in MAP, CVP, MSNA and plasma catecholamines in the two groups except for a higher increase in HR in the BHT group as compared to the NT group (3 +/- 1 vs. 1 +/- 1 bpm; P < 0.005). Opioid blockade with naloxone increased MSNA responses to pain in the NT group (from 5 +/- 1 to 9 +/- 1 bursts/min, and, from 100 +/- 23 to 204 +/- 36 units/min, respectively; P < 0.05) but did not significantly affect the MSNA response to pain in the BHT group. Pain induced responses of MAP, CVP, and catecholamines were not altered by naloxone in either group. Overall, there was a highly significant inverse correlation between pain perception and resting blood pressure which was not significantly affected by naloxone. The BHT subjects exhibited a lower pain perception compared to the NT subjects (P < 0.005). Naloxone increased pain rating in the NT group (from 194 +/- 9 to 218 +/- 13; P < 0.005) but not in the borderline hypertensive group (160 +/- 8 vs. 168 +/- 10; P = 0.36). Except for a decreased HR response in the BHT group, placebo had no effect on the responses to pain. Our data do not indicate a major role of the endogenous opioid system for the blood pressure-pain interaction in man. Endogenous opioids affect pain perception and sympathetic nerve activity responses to pain in normotensive men but their activity seems to be attenuated in borderline hypertensive subjects. Therefore, the lower pain sensitivity in human essential hypertension is probably mediated by non-opioid mechanisms.

Adult↗
PubMed1998

Effect of topical capsaicin on the cutaneous reactions and itching to histamine in atopic eczema compared to healthy skin.

Capsaicin (trans-8-methyl-N-vanillyl-6-nonenamide) is thought to produce analgesic and possibly also antipruritic effects when applied topically. Capsaicin 0.05% was applied three times daily over a 5-day period to the same infrascapular region. The effects of the pretreatment upon the pruritogenic and wheal and flare reactions to subsequent histamine iontophoresis (20 mC) were evaluated on the following day. The antipruritic effects of the pretreatment were compared with the effects of placebo pretreatment and no pretreatment. Wheal and flare areas were evaluated planimetrically. Itch or pain were rated every minute over a 24-min period. The areas of alloknesis, i.e. the induction of perifocal itch sensation by usually nonitching (e.g. mechanical) stimuli, were also evaluated. In control subjects, but not in atopic eczema (AE) patients, capsaicin pretreatment significantly reduced the flare area. Compared with control subjects, AE patients showed a lack of alloknesis or significantly smaller areas of alloknesis in pretreated and nonpretreated skin. In control subjects, capsaicin pretreatment significantly reduced itch sensations compared with nonpretreated skin, whereas in AE patients no differences were seen. Itch sensations in capsaicin-pretreated skin were significantly lower in control subjects than in AE patients. We conclude that capsaicin does effectively suppress histamine-induced itching in healthy skin but has less effect in AE. The diminished itch sensations and the absence of alloknesis in atopic individuals indicate that histamine is not the key factor in itching in AE.

Administration, Topical↗
PubMed1998

Histamine and cutaneous nociception: histamine-induced responses in patients with atopic eczema, psoriasis and urticaria.

Having observed altered itch and flare reactions after histamine application in patients with atopic eczema, we tried to determine these reactions in patients with urticaria and psoriasis. We investigated 16 healthy non-atopic subjects, 16 atopics in an eczema-free interval, 16 with acute atopic eczema, 16 with urticaria and 16 with psoriasis. Histamine was iontophoretically applied. The resulting sensations were rated on a visual analogue scale. Flare areas were measured 6 min after stimulation. Itch ratings of urticaria and psoriasis patients did not differ significantly from controls, whereas both atopic groups, regardless of acute or symptom-free state, reported significantly reduced intensity of itching. Flares were significantly diminished in all subjects with acute skin disease (psoriasis, urticaria and atopic eczema), regardless of diagnosis. However, flares were "normal" in symptom-free atopics and were not significantly different from controls. In conclusion, all "acute" patients showed a diminished axon-reflex function, possibly due to a downregulation of C-fiber responsiveness to histamine or an increased turnover rate of inflammatory mediators. Both atopic groups reported weaker itching, suggesting altered central nervous processing of itch.

Acute Disease↗
PubMed1998

Innervation territories of single sympathetic C fibers in human skin.

Microneurography techniques were used to record action potentials from unmyelinated nerve fibers (C fibers) in the cutaneous fascicles of the peroneal nerve in healthy volunteers. C units were identified by their long latency responses to electrical stimulation of their terminals in the skin. Their responsiveness to mechanical or heat stimuli applied to the skin or to sympathetic reflex provocation tests was determined by transient slowing of conduction velocity following activation (marking technique). In a sample of 381 C units, 59 were unresponsive to mechanical and thermal stimulation of their endings, but responded to sympathetic reflex provocation tests, e.g., arousal or deep inspiration. They were classified as sympathetic efferent units. On average, conduction velocities of sympathetic units were lower (0.78 +/- 0.12 m/s, mean +/- SD) than those of mechano-heat (CMH) or mechanoresponsive (CM) afferent C units (0.91 +/- 0.14 m/s). Endings of most of the sympathetic units were located in the skin of toes or in the foot dorsum. Innervation territories of 16 sympathetic units were mapped by means of conditioning transcutaneous electrical stimuli. Twelve units had one continuous skin territory, whereas two units had two and two other units had three and five separate territories, respectively. The mean innervated area was 128 mm2 (range: 24-350 mm2). Innervation territories of sympathetic units were of approximately the same size in different skin regions on the lower leg, foot, or toes. Based on responses to whole body cooling and warming, two units were tentatively classified as vasoconstrictor and sudomotor units, respectively. Eleven units were tested for responsiveness to iontophoresis of acetylcholine in their innervation territories. In five of them, activity was induced that was not due to central reflex activity but instead due to antidromic activation from the peripheral terminals. Iontophoresis of saline or histamine was ineffective. These findings confirm the existence of excitatory cholinergic receptors in the terminal membrane of some sympathetic units, possibly sudomotors.

Acetylcholine↗
PubMed1998

Activation of neurons in rat trigeminal subnucleus caudalis by different irritant chemicals applied to oral or ocular mucosa.

To investigate the role of trigeminal subnucleus caudalis in neural mechanisms of irritation, we recorded single-unit responses to application of a variety of irritant chemicals to the tongue or ocular mucosa in thiopental-anesthetized rats. Recordings were made from wide dynamic range (WDR) and nociceptive-specific units in superficial layers of the dorsomedial caudalis (0-3 mm caudal to obex) responsive to mechanical stimulation and noxious heating of the ipsilateral tongue ("tongue" units) and from WDR units in ventrolateral caudalis (0-2 caudal to obex) responsive to mechanical and noxious thermal stimulation of cornea-conjunctiva and frequently also surrounding skin ("cornea-conjunctival" units). The following chemicals were delivered topically (0.1 ml) onto the dorsal anterior tongue or instilled into the ipsilateral eye: capsaicin (0.001-1% = 3.3 x 10(-2) to 3.3 x 10(-5) M), ethanol (15-80%), histamine (0.01-10% = 9 x 10(-1) to 9 x 10(-4) M), mustard oil (allyl-isothiocyanate, 4-100% = 4 x 10(-1) to 10 M), NaCl (0.5-5 M), nicotine (0.01-10% = 6 x 10(-1) to 6 x 10(-4) M), acidified phosphate buffer (pH 1-6), piperine (0.01-1% = 3.5 x 10(-2) to 3.5 x 10(-4) M), serotonin (5-HT; 0.3-3% = 1.4 x 10(-1) to 1.4 x 10(-2) M), and carbonated water. The dose-response relationship and possible tachyphylaxis were tested for each chemical. Of 32 tongue units, 31 responded to one or more, and frequently all, chemicals tested. The population responded to 75.3% of the various chemicals tested (</=10 per unit). The incidence of responses was independent of the order of chemicals tested, except for capsaicin, which reduced subsequent responses. Responses to histamine, nicotine, 5-HT, and ethanol had a more rapid onset and shorter duration compared with capsaicin, acid, and mustard oil. Responses to all chemicals increased in a dose-related manner. Successive responses to repeated application decreased significantly for nicotine, 5-HT, capsaicin, and piperine. Spontaneous firing increased significantly 5-10 min after initial application of capsaicin. Of 31 corneal-conjunctival units, 29 responded to one or more chemicals, and the population responded to 65% of all chemicals tested. Responses increased in a dose-related manner for all chemicals, and successive responses decreased significantly for histamine, nicotine, ethanol, acid, and capsaicin. Responses of tongue units to histamine and nicotine were reduced significantly by ceterizine (H1 antagonist) and mecamylamine, respectively. Mecamylamine also significantly reduced responses of corneal-conjunctival units to nicotine. Different classes of irritant chemicals contacting the oral or ocular mucosa can activate individual sensory neurons in caudalis, presumably via independent peripheral transduction mechanisms. Multireceptive units with input from the tongue or cornea-conjunctiva exhibited a similar spectrum of excitability to different irritant chemicals. Such neurons would not be capable of discriminating among different chemically evoked irritant sensations but could contribute to a common chemical sense.

Alkaloids↗
PubMed1997

Specific C-receptors for itch in human skin.

In microneurography experiments 56 unmyelinated nerve fibers were studied in the cutaneous branch of the peroneal nerve of healthy volunteers. Units were identified with the "marking" technique as mechanically and heat-responsive (CMH; n = 30), heat-responsive (CH; n = 13), or unresponsive to mechanical and heat stimulation (CMiHi; n = 13). None of the units showed spontaneous activity. These units were tested for responsiveness to iontophoresis of histamine (1 mA, 20 sec) from a small probe (diameter, 6 mm), which induced itch sensations lasting several minutes. Twenty-three units were unresponsive to histamine, and 25 units responded weakly with a few spike discharges after iontophoresis. Eight units, however, responded with sustained discharges to histamine, and their discharge patterns were matching the time course of the itch sensations. All C-units in this group were mechanically insensitive, and five of them were heat-responsive. They had very low conduction velocities of only 0.5 m/sec, on average, which is significantly lower than conduction velocities of the "polymodal" CMH units. This slow conduction velocities attributable to small axon diameters may be one reason why these units have not been encountered in previous studies. Histamine-sensitive C-units had very large innervation territories extending up to a diameter of 85 mm on the lower leg. We conclude that these C-fibers represent a new class of afferent nerve fibers with particularly thin axons but excessive terminal branching. This type of C-fiber probably represents the afferent units long searched for mediating itch sensations.

Adult↗
PubMed1997

Intracutaneous injections of platelets cause acute pain and protracted hyperalgesia.

Suspensions of autologous, washed platelets were intracutaneously injected at the volar forearms of healthy volunteers. Injections of serum and vehicle served as control. Subjects and experimenter were blind with respect to the sequence of injections. In contrast to serum and solvent solution, platelets induced graded burning pain lasting several minutes. Platelet but not serum or vehicle injections dose-dependently caused large axon-reflex flares. At the site of platelet injections an induration developed and in parallel delayed mechanical and heat hyperalgesia was observed. Hyperalgesia to pressure and impact stimulation reached a maximum after 6 h and subsided during the following 48 h. Also, the threshold to heat stimuli decreased moderately by about 1 degree C, on average, after 24 h. Neither indurations nor hyperalgesia could be detected at the injection sites of serum or vehicle. The pathophysiological significance of this new inflammatory model for the research of posttraumatic hyperalgesia is discussed.

Acute Disease↗
PubMed1997

Effects of cutaneous histamine application in patients with sympathetic reflex dystrophy.

Thirty-six patients suffering from acute reflex sympathetic dystrophy (RSD) were examined in order to evaluate nociceptive C-fibers. Axon reflex vasodilatation was induced by iontophoresis of histamine and recorded (laser Doppler flux). The strength of concomitant sensation was rated on a visual analogue scale, and the quality was characterized as itching or burning pain. Skin temperature was recorded by infrared thermography. The results were compared with investigations of unaffected limbs of patients and volunteers. The histamine-induced sensation on the symptomatic side was more often burning pain than itching (P < 0.001), and skin temperature was increased on the affected limb (P < 0.001). Axon reflex vasodilatation and the strength of sensations were unaltered. In conclusion, this study rules out a significant deterioration of afferent C-fibers in RSD, but gives evidence of sensitization of nociceptive function. This nociceptive sensitization has to be taken into consideration for effective treatment of RSD.

Adult↗
PubMed1997

Flare responses of atopic eczema patients analysed with true colour images.

OBJECTIVE AND DESIGN: Attenuated flare responses of atopic eczema (AE) patients to histamine are well documented, but their origin is still unknown. SUBJECTS AND METHODS: Here we studied the development of erythema after histamine iontophoresis in 12 AE patients and 12 healthy volunteers by means of a RGB-camera for recording true colour images. TREATMENT: 10 mg cetirizine or placebo was administered orally 3 h before the experiment in a crossover design. RESULTS: The flare reaction was found to develop after termination of histamine iontophoresis in two phases: a first phase lasting 1-2 min in which the flare increased by about 10 mm2/s and a second phase lasting another 10-15 min characterized by a slower growth in the range of 1 mm2/s. CONCLUSIONS: Flare size was diminished in AE patients, mainly due to a slower or absent growth in the second phase. Oral application of the H1-antagonist cetirizine (Zyrtec) reduced the flare reaction in both groups of volunteers significantly, indicating that the reaction is dependent on the activation of chemosensitive nerve fibres via H1-receptors.

Adult↗
PubMed1997

Sudomotor function in sympathetic reflex dystrophy.

Sudomotor functions were studied in 27 patients suffering from reflex sympathetic dystrophy (RSD) according to the criteria established by Bonica (18 women, 9 men; mean age 50 +/- 12.3 years; median duration of disease 8 weeks, range 2-468 weeks). To measure local sweating rates, two small chambers (5 cm2) were affixed to corresponding areas of hairy skin on the affected and unaffected limbs. Dry nitrogen gas was passed through the chambers (270 ml/min) and evaporation was recorded at both devices with hygrometers. Thermoregulatory sweating (TST) was induced by raising body temperature (intake of 0.5 1 hot tea and infra-red irradiation). Local sweating was also induced through an axon reflex (QSART) by transcutaneous iontophoretic application of carbachol (5 min, 1 mA). In addition, skin temperature was measured on the affected and unaffected side by infra-red thermography. Mean skin temperature was significantly higher on the affected side (P < 0.003). In spite of the temperature differences, there was no difference in basal sweating on the affected and unaffected side. However, both methods of sudomotor stimulation lead to significantly greater sweating responses on the affected compared to the unaffected side (TST: P < 0.05, QSART: P < 0.004). Latency to onset of sweating was significantly shorter on the affected side under both test conditions (P < 0.04 and P < 0.003, respectively). Sweat responses were not correlated to absolute skin temperature but were probably related to the increased blood flow on the affected side. Our findings imply a differential disturbance of vasomotor and sudomotor mechanisms in affected skin. Whereas vasoconstrictor activity is apparently lowered, sudomotor output is either unaltered or may even be enhanced.

Axons↗
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↗