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Biomedical subjects

W Magerl

Publications and source records attributed to W Magerl.

At least 19 recordsLinked to original sources
PubMed2006

Quantitative sensory testing in the German Research Network on Neuropathic Pain (DFNS): standardized protocol and reference values.

The nationwide multicenter trials of the German Research Network on Neuropathic Pain (DFNS) aim to characterize the somatosensory phenotype of patients with neuropathic pain. For this purpose, we have implemented a standardized quantitative sensory testing (QST) protocol giving a complete profile for one region within 30 min. To judge plus or minus signs in patients we have now established age- and gender-matched absolute and relative QST reference values from 180 healthy subjects, assessed bilaterally over face, hand and foot. We determined thermal detection and pain thresholds including a test for paradoxical heat sensations, mechanical detection thresholds to von Frey filaments and a 64 Hz tuning fork, mechanical pain thresholds to pinprick stimuli and blunt pressure, stimulus/response-functions for pinprick and dynamic mechanical allodynia, and pain summation (wind-up ratio). QST parameters were region specific and age dependent. Pain thresholds were significantly lower in women than men. Detection thresholds were generally independent of gender. Reference data were normalized to the specific group means and variances (region, age, gender) by calculating z-scores. Due to confidence limits close to the respective limits of the possible data range, heat hypoalgesia, cold hypoalgesia, and mechanical hyperesthesia can hardly be diagnosed. Nevertheless, these parameters can be used for group comparisons. Sensitivity is enhanced by side-to-side comparisons by a factor ranging from 1.1 to 2.5. Relative comparisons across body regions do not offer advantages over absolute reference values. Application of this standardized QST protocol in patients and human surrogate models will allow to infer underlying mechanisms from somatosensory phenotypes.

Adolescent↗
PubMed2006

Quantitative sensory testing: a comprehensive protocol for clinical trials.

We have compiled a comprehensive QST protocol as part of the German Research Network on Neuropathic Pain (DFNS) using well established tests for nearly all aspects of somatosensation. This protocol encompasses thermal as well as mechanical testing procedures. Our rationale was to test for patterns of sensory loss (small and large nerve fiber functions) or gain (hyperalgesia, allodynia, hyperpathia), and to assess both cutaneous and deep pain sensitivity. The practicality of the QST protocol was tested in 18 healthy subjects, 21-58 years, half of them female. All subjects were tested bilaterally over face, hand and foot. We determined thermal detection and pain thresholds including a test for the presence of paradoxical heat sensations, mechanical detection thresholds to von Frey filaments and a 64-Hz tuning fork, mechanical pain thresholds to pinprick stimuli and blunt pressure, stimulus-response-functions for pinprick and dynamic mechanical allodynia (pain to light touch), and pain summation (wind-up ratio) using repetitive pinprick stimulation. The full protocol took 27+/-2.3 min per test area. The majority of QST parameters were normally distributed only after logarithmic transformation (secondary normalization) except for the frequency of paradoxical heat sensations, cold and heat pain thresholds, and for vibration detection thresholds. Thresholds were usually lowest over face, followed by hand, and then foot. Only thermal pain thresholds, wind-up ratio and vibration detection thresholds were not significantly dependent on the body region. There was no significant right-to-left difference for any of the QST parameters; left-to-right correlation coefficients ranged between 0.78 and 0.97, thus explaining between 61% and 94% of the variance. This study has shown that a complete somatosensory profile of one affected area and one unaffected control area, which will be necessary to characterize patients with a variety of diseases, can be obtained within 1 h. Case examples of selected patients illustrate the value of z-transformed QST data for an easy survey of individual symptom profiles.

Adult↗
PubMed2006

Generalized hyperalgesia in patients with chronic tension-type headache.

Increased pain sensitivity in the central nervous system may play an important role in the pathophysiology of chronic tension-type headache (CTTH). Previous studies using pain thresholds as a measure of central pain sensitivity have yielded inconsistent results and only a few studies have examined perception of muscle pain without involvement of adjacent tissues. It has been suggested that suprathreshold testing might be more sensitive than threshold measurements in evaluation of central hyperexcitability in CTTH. The aim of the study was to compare pain ratings to suprathreshold single and repetitive (2 Hz) electrical stimulation of muscle and skin in cephalic (temporal and trapezius) and extracephalic (anterior tibial) regions between patients with CTTH and healthy subjects. In addition, we aimed to examine gender differences in pain ratings to suprathreshold stimulation and degree of temporal summation of pain between patients and controls. Pain ratings to both single and repetitive suprathreshold stimulation were higher in patients than in controls in both skin and muscle in all examined cephalic and extracephalic regions (P < 0.04). Pain ratings to both single and repetitive suprathreshold electrical stimulation were significantly higher in female compared with male patients (P < 0.001) and in female compared with male controls (P < or = 0.001). The degree of temporal summation of muscular and cutaneous pain tended to be higher in patients than in controls but the differences were not statistically different. This study provides evidence for generalized increased pain sensitivity in CTTH and strongly suggests that pain processing in the central nervous system is abnormal in this disorder. Furthermore, it indicates that suprathreshold stimulation is more sensitive than recording of pain thresholds for evaluation of generalized pain perception.

Adult↗
PubMed2005

Deep pain thresholds in the distal limbs of healthy human subjects.

Pressure pain thresholds (PPTs) in distal limbs have been under-investigated despite their potential clinical importance. Therefore, we compared PPTs over nail bed, bony prominences, and muscle in distal parts of upper and lower limbs. We investigated 12 healthy subjects using three handheld devices: a spring-loaded, analogue pressure threshold meter (PTM) with two operating ranges, and an electronic Algometer. PPTs were determined with three series of ascending stimulus intensities with a ramp of about 50 kPa/s. PPTs were normally distributed in logarithmic space. PPTs over different tissues varied significantly (ANOVA, p<0.001): mean thresholds and 95% confidence intervals were 615 kPa (266-1424 kPa) over the nail bed, 581 kPa (271-1245 kPa) over bony prominences, and 520 kPa (246-1100 kPa) over muscles. PPTs on the foot were higher than on the hand (ANOVA, p<0.01), except over muscles. PPTs were significantly lower with the Algometer than with PTMs (ANOVA, p<0.01); again these differences were least when testing over muscle. There was no significant right-left difference (ANOVA, p=0.33). In spite of considerable variability across subjects, reproducibility within subjects was high (correlation coefficients>0.90). For within-subject comparisons, threshold elevations beyond 33-43% would be abnormal (95% confidence intervals), whereas only deviations from the group mean by at least a factor of two would be abnormal with respect to absolute normative values. PPTs over distal muscles were comparable to published values on proximal limb and trunk muscles. These findings suggest that pressure pain testing over distal muscles may be a sensitive test for deep pain sensitivity and that the simple and less expensive devices are sufficient for testing this tissue type. Intra-individual site-to-site comparisons will be more sensitive than absolute normative values.

Adult↗
PubMed2005

Increased muscular and cutaneous pain sensitivity in cephalic region in patients with chronic tension-type headache.

Increased excitability of the central nervous system generated by repetitive and sustained pericranial myofascial nociception may be responsible for transformation of episodic tension-type headache into chronic form. We aimed to compare mechanical and electrical (intramuscular and cutaneous) pain thresholds in trapezius and anterior tibial regions between 20 patients with chronic tension type headache and 20 healthy controls. Pain thresholds to three types of electrical stimulation (single pulse, 2 and 100 Hz) were significantly lower in patients than in controls in trapezius muscle (P < 0.02) and in skin overlying the trapezius muscle (P < 0.05), whilst electrical pain thresholds did not differ between groups in anterior tibial muscle and skin. Quantitative sensory testing revealed increased pain sensitivity in patients as assessed by pressure-controlled manual palpation (local tenderness score, LTS; P < 0.01) and by pressure algometry (mechanical pain thresholds; P < 0.05) in test areas over the trapezius muscle, but not the anterior tibial muscle. In summary, this study demonstrates lower pain thresholds in muscle and skin of the cephalic region but not in lower limb muscle and skin in patients with chronic tension-type headache than in healthy controls. Increased sensitivity in nociceptive pathways from cephalic region may be of importance in the pathophysiology of chronic tension type headache.

Adult↗
PubMed2004

Static mechanical hyperalgesia without dynamic tactile allodynia in patients with restless legs syndrome.

Pain sensitivity was assessed in 11 patients (age 60 +/- 10 years) with 'primary' restless leg syndrome (RLS) (disease duration 18 +/- 15 years) and 11 age- and gender-matched healthy control subjects. Stimulus-response functions for pricking pain were obtained with seven calibrated punctate mechanical stimulators activating Adelta-high threshold mechano-nociceptors. Stimuli at the foot were significantly more painful than at the hand in both patients and healthy control subjects both in the morning and evening. Generally, pin-prick pain ratings in RLS patients were significantly elevated, by a factor of 5.3 in the upper limb and by a factor of 6.4 in the lower limb indicating a significant generalized static hyperalgesia more pronounced in the lower limb. In contrast, pain to light touch (allodynia = dynamic mechanical hyperalgesia) as tested by a battery of three gentle tactile stimuli was never reported. Acute single-dose dopaminergic treatment with 100 mg levodopa + 25 mg benserazide, 90 min prior to the evening measurements, largely resolved patients' RLS symptoms, but had no effect on pin-prick pain. Static hyperalgesia to pin-prick, however, was significantly reversed (median reduction -74%) by long-term individually tailored dopaminergic treatment. Our study shows that patients with RLS exhibit a profound static mechanical hyperalgesia to pin-prick stimuli, but no dynamic mechanical hyperalgesia (allodynia). This type of hyperalgesia is probably mediated by central sensitization to Adelta-fibre high-threshold mechanoreceptor input, a hallmark sign of the hyperalgesia type of neuropathic pain. The reduction of hyperalgesia in RLS patients by long-term dopaminergic treatment suggests that the pathophysiology of RLS includes disturbed supraspinal pain modulation involving the basal ganglia and/or descending dopaminergic pathways.

Adult↗
PubMed2004

Contribution of Ca2+-activated K+ channels to hyperpolarizing after-potentials and discharge pattern in rat supraoptic neurones.

The contribution of Ca(2+)-activated K(+) channels to hyperpolarizing after-potentials (HAP) of action potentials, to spike-frequency adaptation and thus to the shaping of discharge pattern, was examined in rat supraoptic magnocellular neurosecretory cells. In addition, the expression of BK channels and SK3 subunits of SK channels was studied using double immunofluorescence detection. The presence of BK channels and SK3 subunits was detected in many supraoptic neurones containing either vasopressin or oxytocin. Current-clamp recordings of current-induced spike trains revealed that HAPs comprise a fast and a slow HAP (fHAP and sHAP). Correlation analyses revealed that the increase of the fHAP in amplitude and spike broadening were correlated to a moderate gradual increase of the interspike interval and thus to weak spike-frequency adaptation. By contrast, marked prolongation of the interspike interval and strong spike-frequency adaptation depended on the appearance and on the amplitude of the sHAP. The sHAP and spike-frequency adaptation were blocked by cadmium, as well as by the SK channel antagonist apamin. The fHAP was attenuated by the BK channel antagonist iberiotoxin (IbTX), by the BK/IK channel antagonist charybdotoxin (ChTX) and by apamin. ChTX attenuated fHAPs throughout the entire spike train. By contrast, the IbTX-induced attenuation of the fHAP was restricted to the initial part of the spike train, while the apamin-induced attenuation slowly increased with the progression of the spike train. These results suggest that strong spike-frequency adaptation in supraoptic neurones essentially depends on the generation of the sHAP by activation of SK channels. Comparison of effects of IbTX, ChTX and apamin suggests a complementary contribution of SK-, BK- and IK-channels to fHAPs.

Action Potentials↗
PubMed2001

Spatial discrimination thresholds for pain and touch in human hairy skin.

The traditional concept that pain is poorly localized has been challenged by recent studies, where subjects were able to point to the stimulated spot on the skin with an accuracy of 10-20 mm. Pointing movements themselves, however, have errors of about 15 mm. To determine the limits of sensory performance of the nociceptive system independent of motor performance, point localization of heat pain (540 mJ punctate laser stimuli, 5 mm diameter), mechanical pain (256 mN punctate probe, 200 microm diameter), and touch (16 mN von Frey probe, 1.1 mm diameter) were tested in a two-alternative forced-choice paradigm in 12 healthy subjects. Stimuli were applied in randomized order to two parallel lines on the back of the hand (4-32 mm distance). The cumulative distribution functions for correct localization were of similar sigmoid shape for all test stimuli, indicating logarithmic normal distributions. The 75% correct localization threshold for painful heat was 8.6 mm (3.1 +/- 0.1 log2 units) and did not differ significantly from that of non-painful touch (9.0 mm, 3.2+/-0.2 log2 units). Localization of mechanically-induced pain (5.1 mm, 2.4 +/- 0.2 log2 units) was significantly more accurate than both heat pain and touch, possibly due to a synergism of two different sensory channels, the tactile channel and the nociceptive channel, which were activated simultaneously. For all three stimuli, discrimination was significantly better in radial-ulnar compared to proximal-distal direction, which might be related to oval receptive field shapes. Sequential spatial discrimination for touch was significantly better than simultaneous spatial discrimination tested with a grating orientation task (18.9 mm), but both were one order of magnitude worse than at the finger tip (1.3 mm, 0.4 +/- 0.1 log2 units). In conclusion, pain evoked by radiant heat pulses and touch evoked by von Frey probes were localized with similar precision on the back of the hand. These findings indicate that outside the tactile fovea at finger tips or lips the spatial discrimination capacities of the nociceptive and tactile systems are about equal.

Adult↗
PubMed2001

Roles of capsaicin-insensitive nociceptors in cutaneous pain and secondary hyperalgesia.

Polymodal nociceptors respond to mechanical, thermal and chemical stimuli. Whereas sensitivities to heat and to the irritant substance capsaicin have recently been linked via the properties of the vanilloid receptor type 1 receptor ion channel, sensitivity to noxious mechanical stimuli such as the pinpricks used in clinical neurology seems to be unrelated. We investigated the peripheral neural basis of pinprick pain using quantitative psychophysical techniques combined with selective conduction block by nerve compression and selective desensitization by topical capsaicin treatment. Complete A-fibre block by compression of the superficial radial nerve (criterion: loss of first pain sensation) lowered the stimulus-response function for pinprick pain (-82 +/- 6% versus baseline). Topical pretreatment of the skin with a 10% capsaicin cream also lowered the pinprick stimulus-response function (-32 +/- 10%), whereas laser-evoked heat pain was eliminated completely (-96 +/- 2%). Under combined capsaicin desensitization and A-fibre blockade, pinprick pain was eliminated completely (-98 +/- 1%). Intradermal injection of 40 microg capsaicin into normal skin between two skin areas that had been pretreated with either capsaicin cream or vehicle produced secondary hyperalgesia with a 260% enhancement of the stimulus-response function for pinprick pain in both areas. In contrast, axon reflexive flare spread only into the vehicle-treated area. These results suggest that capsaicin-sensitive afferents, including polymodal A-fibre and C-fibre nociceptors, make a small contribution to pinprick pain and that capsaicin-insensitive C-fibres do not contribute significantly to either mechanical or heat pain. Pinprick pain is mediated primarily by capsaicin-insensitive A-fibre nociceptors, which include high-threshold mechanoreceptors and type I mechano-heat nociceptors. In addition, central sensitization to input from these A-fibre nociceptors is the primary mechanism that accounts for the enhanced pain in response to punctate mechanical stimuli in the zone of secondary hyperalgesia. These capsaicin-insensitive A-fibre nociceptors may also mediate hyperalgesia in neuropathic pain.

Adult↗
PubMed2001

Mechanisms and predictors of chronic facial pain in lateral medullary infarction.

The purpose of this study was to identify clinical predictors and anatomical structures involved in patients with pain after dorsolateral medullary infarction. Eight out of 12 patients (67%) developed poststroke pain within 12 days to 24 months after infarction. The pain occurred in the ipsilateral face (6 patients) and/or the contralateral limbs and trunk (5 patients, 3 of whom also had facial pain). Ipsilateral facial pain was significantly correlated with lower medullary lesions, including those of the spinal trigeminal tract and/or nucleus, as documented by magnetic resonance imaging. The R2 blink reflex component was abnormal only in patients with facial pain. Likewise, pain and temperature sensation in the ipsilateral face was decreased in all patients with facial pain but not in patients without pain. Ipsilateral touch sensation in the face was also decreased in all patients with facial pain, but the lesions revealed on magnetic resonance imaging did not involve the principal sensory nucleus of the fifth cranial nerve, and the R1 blink reflex latencies were normal. Although facial pain was correlated with lesions of the spinal trigeminal tract and/or nucleus, none of the lesions involved the subnucleus caudalis, which contains most nociceptive neurons. These findings suggest that facial pain after medullary infarction is due to lesions of the lower spinal trigeminal tract (axons of primary afferent neurons), leading to deafferentation of spinal trigeminal nucleus neurons.

Aged↗
PubMed1999

Secondary hyperalgesia to punctate mechanical stimuli. Central sensitization to A-fibre nociceptor input.

Tissue injury induces enhanced pain sensation to light touch and punctate stimuli in adjacent, uninjured skin (secondary hyperalgesia). Whereas hyperalgesia to light touch (allodynia) is mediated by A-fibre low-threshold mechanoreceptors, hyperalgesia to punctate stimuli may be mediated by A- or C-fibre nociceptors. To disclose the relative contributions of A- and C-fibres to the hyperalgesia to punctate stimuli, the superficial radial nerve was blocked by pressure at the wrist in nine healthy subjects. Secondary hyperalgesia was induced by intradermal injection of 40 microg capsaicin, and pain sensitivity in adjacent skin was tested with 200 micron diameter probes (35-407 mN). The progress of conduction blockade was monitored by touch, cold, warm and first pain detection and by compound sensory nerve action potential. When A-fibre conduction was blocked completely but C-fibre conduction was fully intact, pricking pain to punctate stimuli was reduced by 75%, but burning pain to capsaicin injection remained unchanged. In normal skin without A-fibre blockade, pain ratings to the punctate probes increased significantly by a factor of two after adjacent capsaicin injection. In contrast, pain ratings to the punctate probes were not increased after capsaicin injection when A-fibre conduction was selectively blocked. However, hyperalgesia to punctate stimuli was detectable immediately after block release, when A-fibre conduction returned to normal. In conclusion, the pricking pain to punctate stimuli is predominantly mediated by A-fibre nociceptors. In secondary hyperalgesia, this pathway is heterosynaptically facilitated by conditioning C-fibre input. Thus, secondary hyperalgesia to punctate stimuli is induced by nociceptive C-fibre discharge but mediated by nociceptive A-fibres.

Adult↗
PubMed1998

Secondary hyperalgesia and perceptual wind-up following intradermal injection of capsaicin in humans.

Wind-up and secondary hyperalgesia both are related to central sensitization, but whereas the former is explained by homosynaptic facilitation, the latter is due to heterosynaptic facilitation. To investigate possible interactions between both types of facilitation, we tested for alterations of perceptual wind-up in the secondary hyperalgesic skin zone adjacent to a capsaicin injection with light touch (by a cotton wisp) and punctate stimuli (calibrated von Frey hairs and pin pricks). Temporal summation of pain sensation (perceptual wind-up) was only observed with a clearly noxious stimulus (pin prick) presented at a repetition frequency of 0.6 s(-1), but not 0.2 s(-1). Pain ratings to trains of pin pricks reached a plateau after 3-4 repetitions, which was 1.65 times the initial rating ('wind-up ratio'). Injection of capsaicin induced a tenderness to mechanical stimuli in adjacent uninjured skin (secondary hyperalgesia), including hyperalgesia to light touch (allodynia) and hyperalgesia to punctate stimuli. Hyperalgesia to punctate stimuli was characterized by a leftward shift of the stimulus response function, corresponding to a decrease in pain threshold and an increase of painfulness of suprathreshold stimuli by a factor of 3-4. After capsaicin, the difference between the ratings of the first and last stimuli of trains of pin pricks was increased, but the ratio was unchanged. This behavior is equivalent to an increase in effective stimulus intensity, and could be mimicked by increasing the pin prick force from 20 mN to 40 and 80 mN in normal skin. Thus, the leftward shift of the stimulus response function fully accounts for all alterations of pain sensitivity to punctate stimuli in the zone of secondary hyperalgesia. We conclude that when the gain of spinal transmission was changed in secondary hyperalgesia, the gain of wind-up remained unchanged. These findings indicate that secondary hyperalgesia (heterotopic facilitation) and wind-up of pain sensation (homotopic facilitation) are independent phenomena.

Adolescent↗
PubMed1996

Heat-evoked vasodilatation in human hairy skin: axon reflexes due to low-level activity of nociceptive afferents.

1. Spreading vasodilatation of the axon reflex type was evoked by contact heat stimulation of the hairy skin in the human forearm (13.3 cm2 stimulus area) and was detected by laser Doppler flowmetry at 8, 19 and 30 mm distance. 2. From a base temperature of 35 degrees C, rapidly rising short heat stimuli (4 degrees C s-1, 2 s plateau) elicited vasodilatation at an average threshold of 39.4 degrees C. For slowly rising sustained heat stimuli (64 s duration) the average threshold was 39.6 degrees C (n.s.) Laser Doppler flowmetry revealed a rapid onset within about 4 s, a long duration of several minutes beyond the end of the stimulus, and a rapid spread of vasodilatation to remote skin areas. These characteristics are typical for vasodilatation by an axon reflex of nociceptive afferents. 3. Axon reflex thresholds matched the lower range of C fibre nociceptor heat thresholds. Thermal stimuli that were adjusted to elicit about half-maximal phasic responses in warm fibres (steps from 30 to 35 degrees C), but were below the range of C fibre nociceptor thresholds, did not cause any vasodilatation. 4. Pain thresholds were higher than axon reflex thresholds for both rapidly and slowly rising heat stimuli and strongly depended on the stimulus pattern (40.1 degrees C for rapidly rising stimuli and > 43 degrees C for slowly rising stimuli). This observation is consistent with recent reports that the phasic response of nociceptive afferents is essential to overcome the summation requirements at central synapses. 5. In conclusion, axon reflex vasodilatation in response to heat stimuli in the hairy skin of humans is elicited by activation of heat-sensitive nociceptors, even in the absence of a conscious perception of heat pain. The dissociation of pain and vasodilatation thresholds supports the concept of two operating ranges of primary nociceptive afferents. Warm fibres do not contribute to axon reflex vasodilatation in the hairy skin of the human forearm. Release of vasoactive peptides by nociceptive primary afferents may also contribute to local heat-evoked vasodilatation at temperatures above 40 degrees C.

Adolescent↗
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↗
PubMed1992

Differential effects of dipyrone, ibuprofen, and paracetamol on experimentally induced pain in man.

In a double-blind cross-over study on 22 healthy subjects the analgesic efficacies of the antipyretic analgesic drugs ibuprofen, dipyrone and paracetamol were tested against placebo using a model of experimentally induced pain. To this purpose interdigital webs were pinched repeatedly for 2 min periods. The painfulness of these stimuli was assessed by the subjects on an electronically controlled visual analogue scale at 10 sec intervals. In addition to the subjective pain ratings the stimulus induced reflex diminution of the blood flow in the stimulated hand was measured with photoplethysmography and laser Doppler flow analysis. The flare response around the stimulated area was assessed with infrared thermography. In this assay system ibuprofen and dipyrone, but not paracetamol, showed statistically significant analgesic effects by preventing hyperalgesia which is normally induced by the repeated stimulation of a skin site. This hypoalgesic effect was not related to the subjective impression of the subjects of the analgesic potency of the respective drug. Sympathetic reflex vasoconstriction was not quantitatively related to the drug induced hypoalgesia. Ibuprofen and, to a minor extent, the other antipyretic analgesic drugs also diminished the stimulus induced flare reaction around the stimulated skin sites.

Acetaminophen↗
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↗