Flare Area Research Articles

The effects of the TRPV1 antagonist SB-705498 on TRPV1 receptor-mediated activity and inflammatory hyperalgesia in humans

TRPV1 is a cation channel activated by a range of noxious stimuli and highly expressed in nociceptive fibres. TRPV1 receptors are involved in pain and sensitisation associated with tissue injury and inflammation; hence, TRPV1 antagonists are potentially useful for the treatment of such pain states. SB-705498 is a potent, selective and orally bioavailable TRPV1 antagonist with demonstrated efficacy in a number of preclinical pain models. In this first-time-into-human study, we have investigated the pharmacodynamic and antihyperalgesic activity of SB-705498. The compound was safe and well tolerated at single oral doses up to 400 mg. In a cohort of 19 healthy volunteers, we used a randomised placebo-controlled single-blind cross-over design to assess the effects of SB-705498 (400 mg) on heat-evoked pain and skin sensitisation induced by capsaicin or UVB irradiation. Compared with placebo, SB-705498 reduced the area of capsaicin-evoked flare ( P = 0.0047). The heat pain threshold on non-sensitised skin was elevated following SB-705498 (estimated difference from placebo [95% confidence intervals]: 1.3 °C [0.07, 2.53], P = 0.019). Following capsaicin sensitisation, the heat pain threshold and tolerance were similar between SB-705498 and placebo. However, SB-705498 increased heat pain tolerance at the site of UVB-evoked inflammation (estimated difference from placebo: 0.93 °C [0.25, 1.6], P = 0.0054). The magnitude of the pharmacodynamic effects of SB-705498 appeared to be related to plasma concentration. These results indicate that SB-705498, at a clinically safe and well-tolerated dose, has target-specific pharmacodynamic activity in humans. These data provide the first clinical evidence that a TRPV1 antagonist may alleviate pain and hyperalgesia associated with inflammation and tissue injury.

Nociceptor sensitization to mechanical and thermal stimuli in pig skin in vivo

Primary hyperalgesia to mechanical and thermal stimuli are major clinical symptoms of inflammatory pain and can be induced experimentally by ultraviolet-B (UV-B) irradiation in humans. We set-up a pig model in order to have more options for pharmacological intervention on primary hyperalgesia. Pig skin was irradiated with a dose one- to threefold higher than the minimum erythema dose (MED) and investigated for mechanical and heat responsiveness 24 and 48 h post UV-B treatment. C-fiber activation upon mechanical and thermal stimulation was assessed indirectly by extent of the axon reflex erythema (flare) measured by laser Doppler imaging. Mechanical stimulation with von Frey filaments (100 mN) induced flare responses in UV-B treated skin at 24 and 48 h, but no effect was measured in normal untreated skin. Increased mechanical stimulation (600 mN) elicited a small flare response in normal skin in an area of 1.8 cm 2 on average that was extending about 2.5 cm 2 in the UV-B irradiated sites. Thermal stimuli provoked in normal pig skin flare areas of approximately 2 cm 2 (45 °C, 10 s) and 4.5 cm 2 (47 °C, 10 s) which increased to about 3.5 cm 2 (45 °C) and 5.5 cm 2 (47 °C) following UV-B irradiation at 24 and 48 h. No significant differences of mechanically or thermally induced hypersensitivity were seen between 24 and 48 h after irradiation. We conclude that UV-B induced mechanical and heat sensitization of primary afferent nociceptors can be assessed in pig skin, providing a new human-like model of primary hyperalgesia. Sensitization of primarily mechano-insensitive (silent) nociceptors, which are underlying the flare response in humans, most probably contributes to the observation presented here.

Spatial Size and Plasma Variables of RHESSI Flares

We have analysed 64 flares observed with GOES and RHESSI in the 3.1 – 24.8 keV band (0.5 – 4 A). Flares were randomly chosen to represent different GOES classes, between B1 and M6. RHESSI was used to image the flaring region on the surface of the Sun. We derived the spatial area of the flare on the surface of the Sun from the imaging observations, scaled it dimensionally to volume, and used the spectroscopically derived emission measure to obtain several flare parameters. We experimented with several imaging methods and selected the use of 50% maximum image photon flux contours to define the flare area (F50%). Most of the flares showed a single spherical loop-top source. The volume measurement for V, temperature T, and electron density N produced power indices that showed no correlation within the boundaries of error. Larger flares by loop-top source volume are thus neither hotter nor denser. The background-subtracted GOES flux – RHESSI Total Emission Measure (TEMRHESSI) and TEMGOES – TEMRHESSI dependencies were in agreement with the instrument characteristics and earlier studies. Nonthermal flux was noticed to increase with thermal energy and TEM, which can be said to agree with the “Big Flare Syndrome,” with nonthermal photon flux being considered as one flare manifestation.

Botulinum Toxin type A reduces capsaicin-evoked pain and neurogenic vasodilatation in human skin

The effect of Botulinum Toxin type A (BoNT/A) on pain and neurogenic vasodilatation induced by application to the human skin of thermal stimuli and capsaicin was evaluated in a double blind study. A capsaicin cream (0.5 ml of a 0.075%) was applied to the skin of both forearms of eighteen subjects randomly pretreated with either BoNT/A (Botox ®) or 0.9% saline (NS). Capsaicin was applied to a skin area either inside (protocol A) or adjacent to the BoNT/A treated area (protocol B). Pre-treatment with BoNT/A did not affect thermal-specific and thermal-pain thresholds (by quantitative sensory testing). However, capsaicin-induced pain sensation (by a visual analogue scale), flare area (by acetate sheet) and changes in cutaneous blood flow (CBF, by laser Doppler flowmetry) were reduced when capsaicin was administered inside (protocol A) the BoNT/A treated area. In Protocol B, capsaicin-induced pain was unchanged, and capsaicin-induced flare/increase in CBF were reduced only in the area treated with BoNT/A, but not in the BoNT/A untreated area. Results indicate that (i) BoNT/A reduces capsaicin-induced pain and neurogenic vasodilatation without affecting the transmission of thermal and thermal-pain modalities; (ii) reduction in capsaicin-induced pain occurs only if capsaicin is administered into the BoNT/A pretreated area; (iii) reduction in neurogenic vasodilatation by BoNT/A does not contribute to its analgesic action. BoNT/A could be tested for the treatment of conditions characterised by neurogenic inflammation and inflammatory pain.

Histamine Is Released following Aminolevulinic Acid-Photodynamic Therapy of Human Skin and Mediates an Aminolevulinic Acid Dose-Related Immediate Inflammatory Response

Acute skin inflammation occurs following topical aminolevulinic acid-photodynamic therapy (ALA-PDT), but its nature and mediation are ill defined. As we observed an urticarial response, a potential role for histamine was explored. In 13 healthy volunteers, we assessed the time course and dose-response of the acute cutaneous response(s) to ALA-PDT, the impact of H(1) antihistamine blockade, and measured dermal histamine release. An ALA dose series was iontophoresed into ventral forearm skin and exposed to red light. All participants exhibited an immediate urticarial response, both wheal and flare correlating with log ALA dose. Subsequently, a dose-related erythema developed at treatment sites by 3 hours and persisted at 24 hours. H(1) blockade with oral cetirizine doubled the median minimal urticating dose of ALA and reduced the slope of dose-response for wheal and flare, whereas at the highest ALA dose, mean wheal and flare areas reduced by 68 and 60%, respectively. In contrast, cetirizine did not influence the 24 hour minimal phototoxic dose or erythema dose-response. Histamine release after ALA-PDT mirrored the urticarial response, levels peaking within 30 minutes and returning to baseline by 24 hours. Thus, two discrete acute inflammatory responses to topical ALA-PDT occur in human skin; histamine mediates the immediate response, but does not appear involved in the delayed phototoxicity.

Bradykinin is a potent pruritogen in atopic dermatitis: A switch from pain to itch

Histamine, substance P, serotonin and bradykinin were applied by iontophoresis to lesional and visually non-lesional skin of 14 patients with atopic dermatitis, and normal skin of 15 healthy volunteers. Itch could be evoked by light stroking of skin with a cotton swab (alloknesis) in all lesional skin sites, but not in non-lesional or normal skin. Substances were applied in the same skin area before and 3 h after administration of placebo or antihistamine (olopatadine hydrochloride: H1-receptor-blocker). Intensities of itch and pain sensation and areas of flare and wheal were measured. All the substances induced significantly more intense itch in lesional skin than in non-lesional skin of patients. Even bradykinin, which evoked only weak itch and pain of similar intensities in non-lesional skin of patients and in healthy volunteers, induced intense itch in lesional skin, while the simultaneously increased pain did not suppress the itch sensation, indicating central sensitization. Histamine- and substance P-induced itch was almost completely suppressed by antihistamines, whereas bradykinin- and serotonin-induced itch was not. This suggests that substance P is a histamine-dependent pruritogen also in lesional skin under sensitized conditions but that bradykinin and serotonin are histamine-independent pruritogens in lesional skin. It is concluded that serotonin and bradykinin, classic endogenous algogens, can turn into potent histamine-independent pruritogens in lesional skin of atopic dermatitis.

Intradermal Capsaicin Causes Dose-Dependent Pain, Allodynia, and Hyperalgesia in Humans

BackgroundIntradermal capsaicin is a human pain model that produces reliable pain and sensitization. This model facilitates controlled testing of analgesic efficacy via a crossover design while minimizing confounding variables in...

Conduit-vent structures and related proximal deposits in the Las Cañadas caldera, Tenerife, Canary Islands

The Las Canadas caldera wall and the outer slopes of the caldera provide three-dimensional exposures of numerous proximal-welded fallout deposits and have been mapped in detail. As a result, some parts of the Ucanca and Guajara Formations of the stratigraphy of Marti et al. (1994) have been divided into members that correspond to individual eruptions. Mapping has also revealed the occurrence of conduit-vent structures associated with proximal-welded fallout deposits. Conduit-vent structures consist of an upper flaring area and a lower narrow conduit. Conduit-vent geometry and dimensions include cylindrical plugs and eruptive fissures steeply dipping towards the caldera depression and elongated vents. The flaring area can be rather asymmetric and is usually filled by down-vent rheomorphic flow of the proximal fallout deposit. The lower conduits are filled by lava plug, agglutination of juveniles onto conduit walls and dyke intrusion with eventual dome extrusion. The eruption dynamics of welded fallout deposits and magma fragmentation within the conduit are consistent with an evolution from explosive to effusive. In this context conduit flow regimes evolve from turbulent to annular flow in which the conduit is progressively choked, and laminar flow leading to the final conduit closure.

Extremely energetic 4B/X17.2 flare and associated phenomena

We observed 4B/X17.2 flare in Hα from super-active region NOAA 10486 at ARIES, Nainital. This is one of the largest flares of current solar cycle 23, which occurred near the Sun’s center and produced extremely energetic emission almost at all wavelengths from γ-ray to radio-waves. The flare is associated with a bright/fast full-halo earth directed CME, strong type II, type III and type IV radio bursts, an intense proton event and GLE. This flare is well observed by SOHO, RHESSI and TRACE. Our Hα observations show the stretching/de-twisting and eruption of helically twisted S shaped (sigmoid) filament in the south-west direction of the active region with bright shock front followed by rapid increase in intensity and area of the gigantic flare. The flare shows almost similar evolution in Hα, EUV and UV. We measure the speed of Hα ribbon separation and the mean value is ∼ 70 km s-1. This is used together with photospheric magnetic field to infer a magnetic reconnection rate at three HXR sources at the flare maximum. In this paper, we also discuss the energetics of active region filament, flare and associated CME.

Allergy skin test responses during experimental infection with respiratory syncytial virus

Allergy skin testing is one of the most frequently performed physician office procedures. Many factors can affect the results of those tests, including the well-defined suppressive effect of systemic antihistamines. False-positive allergen skin test results are known to occur; however, contributing factors are not well understood. To determine whether a viral upper respiratory tract infection affects allergy skin test responsiveness. We performed skin tests with histamine and a panel of geographically relevant inhalant allergens on 16 adults before and 3, 6, and 21 days after experimental exposure to respiratory syncytial virus (RSV), a virus that causes signs and symptoms of a cold. The RSV exposure, with and without documented infection, caused increased wheal and flare areas to histamine and allergen and de novo positive allergen test responses in individuals with no measurable responses at baseline. These were noted as late as 21 days after RSV exposure and may be consistent with mediation by up-regulated neurogenic inflammation during RSV infection. These results may have implications for explaining the cause of such well-known complications of RSV infection as otitis media, bronchiolitis, and asthmatic exacerbation.

The effects of Botulinum Toxin type A on capsaicin-evoked pain, flare, and secondary hyperalgesia in an experimental human model of trigeminal sensitization

The trigeminovascular system is involved in migraine. Efficacy of Botulinum Toxin type A (BoNT-A) in migraine has been investigated in clinical studies but the mechanism of action remains unexplored. It is hypothesized that BoNT-A inhibits peripheral sensitization of nociceptive fibers and indirectly reduces central sensitization. We examined the effect of intramuscular injection of BoNT-A on an experimental human model of trigeminal sensitization induced by intradermal capsaicin injection to the forehead. BoNT-A (BOTOX ®) or saline was injected intramuscularly in precranial, neck and shoulder muscles to 32 healthy male volunteers in a double blind-randomized manner. Intradermally capsaicin-induced pain, flare and secondary hyperalgesia were obtained before and 1, 4 and 8 weeks after the above treatments. A significant suppressive effect of BoNT-A on pain, flare and hyperalgesia area was observed. The pain intensity area was significantly smaller in BoNT-A group (9.16 ± 0.83 cm × s) compared to saline group (15.41 ± 0.83 cm × s) ( P = 0.011). The flare area was also reduced significantly in BoNT-A group (29.81 ± 0.69 cm 2) compared to saline group (39.71 ± 0.69 cm 2) ( P < 0.001). Similarly, the mean area of secondary hyperalgesia was significantly smaller in BoNT-A group (4.25 ± 0.91 cm 2) compared to saline group (7.03 ± 0.91 cm 2) ( P = 0.040). Post hoc analysis showed significant differences across the trials with a remarkable suppression effect of BoNT-A on capsaicin-induced sensory and vasomotor reactions as early as week1 ( P < 0.001). BoNT-A presented suppressive effects on the trigeminal/cervical nociceptive system activated by intradermal injection of capsaicin to the forehead. The effects are suggested to be caused by a local peripheral effect of BoNT-A on cutaneous nociceptors.

A human experimental capsaicin model for trigeminal sensitization. Gender-specific differences

Migraine is much more common in women (18%) than in men (6%). Menstrual migraine in female migraineurs also varies from 7 to 19%. The main goals of the present study were (1) to investigate gender specific differences in an experimental capsaicin model of trigeminal sensitization (a proposed mechanism of migraine) and (2) to explore the influence of menstrual cycle phases. Twenty-eight healthy female and male volunteers were studied. Capsaicin (100 μg/0.1 ml) was injected intradermally to the forehead. Pain intensity and distribution together with the visual flare and allodynic area (central sensitization) were assessed for females (during their menstrual and luteal phases) and for males. Pain area significantly changed across the menstrual cycle with 19.2±2.0 cm×min at menstrual and 16.4±0.9 cm×min at luteal phase ( P<0.001). The area was significantly larger in both phases for females compared to males (14.2±1.3 cm×min, P<0.0001). Flare area at menstrual phase (69.2±4.2 cm 2) was significantly ( P<0.0001) larger than luteal phase (58.6±2.1 cm 2). Females, in both phases, showed larger flare area compared to males (44.9±3.6 cm 2, P<0.0001). Area of brush-evoked allodynia was also larger at the menstrual phase compared to the luteal phase ( P<0.0001) and males ( P<0.0001). A significant difference was found in the capsaicin-evoked pain distribution with a greater response in menstrual phase compared to the luteal phase ( P<0.01) and men ( P<0.0001). Capsaicin induced trigeminal sensitization and evoked gender specific sensory and vaso-motor responses, with menstruating females generally showing the strongest manifestations. The model may be further applied to explore mechanisms of human trigeminal sensitization.

Effect of topical vapocoolant spray on skin test wheal, flare, and pain responses

Skin puncture and intradermal tests are commonly used to evaluate allergic rhinitis. Ethyl chloride, a topical vapocoolant spray, provides skin analgesia before venipuncture, but it has not been studied with allergy skin testing. To determine the effects of ethyl chloride vs placebo on skin puncture testing (SPT) and intradermal allergy testing. We enrolled 20 healthy adults with a history of positive aeroallergen skin test results in a randomized, double-masked, placebo-controlled study. Ethyl chloride and placebo sprays were randomly placed on the upper back. Paired SPT was performed with saline, histamine, and standardized aeroallergens, including Bermuda grass, Kentucky blue grass, timothy grass, cat, Dermatophagoides pteronyssinus, and Dermatophagoides farinae. Serial dilutional end-point intradermal tests were then performed using 1 standardized aeroallergen. Wheal and flare areas were outlined, scanned, and digitally measured. Participants used a 10-cm visual analog scale to record pain during skin testing. Eighteen individuals completed the study. Compared with placebo, ethyl chloride had no significant effect on histamine wheal (P = .53), histamine flare (P = .39), aeroallergen wheal (P = .10), or aeroallergen flare (P = .71) area for SPT. Serial dilutional end-point intradermal testing was similar after ethyl chloride and placebo application (P = .75). Mean pain scores for SPT were improved with ethyl chloride compared with paired placebo skin tests, although pain scores did not reach significance for SPT (P = .21) or intradermal testing (P = .87). Ethyl chloride does not significantly reduce histamine and aeroallergen wheal and flare areas during SPT and intradermal allergy skin testing. Ethyl chloride, vs placebo, reduced pain in some individuals during skin testing, although this did not attain statistical significance.

Comparison of on-site and photographic evaluations of the suppressive effects of cetirizine, loratadine, and fexofenadine on skin response to histamine lontophoresis: A double-blind, crossover study in healthy volunteers

Background: The standard method used to determine the potency of antihistaminesis to assess the degree of suppression of skin response to histamine challenge. Objectives: The aims of this study were to compare the efficacy of 3 antihistaminesusing a histamine challenge test and the usefulness of on-site evaluation with that of photographic evaluation of skin-test reactions. Methods: In this prospective, double-blind, crossover study, healthy volunteerswere given cetirizine 5 mg (CTZ-5) and 10 mg (CTZ-10), loratadine 10 mg (LOR), fexofenadine 60 mg BID (FEX), and placebo (PLC), in a randomly assigned order, with an interval of at least 1 week between treatments. Before and 0.5 to 24 hours after administration, the areas of flare and wheal induced by histamine iontophoresis were measured directly (on site) by 1 evaluator and by another evaluator using photographic images on a computer monitor. Results: Ten healthy volunteers (6 men, 4 women; mean age, 28.2 years[range, 20–39 years]; mean weight, 60.7 kg [range, 41–81 kg]) were enrolled. The data from 9 subjects were analyzed; the data from 1 subject were omitted because the subject used an over-the-counter cold medication containing diphenhydramine several times during the study. By both methods, all antihistamines were shown to suppress flare significantly from 4 to 24 hours after administration. CTZ was most potent in suppressing both flare and wheal. For flare, the areas as measured using on-site evaluation were larger overall than those measured using photographic evaluation, but the shapes of the time-course graphs were similar for both. Overall, the flare area measurements started to decrease significantly from baseline values 4 hours after drug administration, reached a nadir at 10.5 hours, and remained significantly lower compared with baseline values at 24 hours. Comparisons between antihistamines showed significant differences in mean flare areas between the 2 doses of CTZ and LOR from 8 to 12 hours after administration in both evaluation methods. The wheal areas were significantly reduced from baseline values by most of the antihistamines 4 to 12 hours after drug administration, reached their lowest values at 10.5 hours, and returned to near-baseline values at 24 hours. Comparisons with PLC values at each time point, however, showed significant differences only for CTZ-5 and CTZ-10 from 4 to 12 hours after administration. Comparison between antihistamines showed significant differences in mean flare areas between the 2 doses of CTZ and LOR from 8 to 12 hours after administration in both evaluation methods. Although the flare areas measured by both methods correlated linearly ( r = 0.90; P < 0.001), the correlation for wheal areas was weaker ( r = 0.76; P < 0.001). Conclusions: In this study in healthy volunteers, single doses of CTZ 5 mg and CTZ 10 mg were more potent compared with single-dose LOR 10 mg and FEX 60 mg BID in suppressing skin response. Although linear correlations were found between skin-response areas, as measured by on-site and photographic evaluation, it was difficult to differentiate between wheal and flare by photographic evaluation, especially when a typical wheal was suppressed to slightly edematous erythema by antihistamines.

Reduction of nickel-induced contact hypersensitivity reactions by topical tea tree oil in humans

Whilst the anti-microbial properties of tea tree oil (TTO) are established, the anti-inflammatory effects of TTO in human skin remain largely anecdotal and require evaluation. This study examined the effect of topically applied TTO on nickel-induced contact hypersensitivity reactions in human dorsal skin. TTO (100%), a 5% TTO lotion, a placebo lotion (no TTO), or 100% macadamia oil were applied at days 3 and 5 after nickel exposure. The flare area and erythema index were measured on days 3, 5 and 7. The regulatory effects of TTO were also investigated on the proliferative response to nickel or polyclonal mitogens by peripheral blood mononuclear cells from nickel-sensitive and control subjects. TTO (100%) significantly reduced the flare area and erythema index when compared to the nickel-only sites. With respect to the erythema index, the anti-inflammatory effects were predominantly, but not exclusively, seen in a subgroup of nickel-sensitive subjects with a prolonged development phase of nickel-induced contact hypersensitivity response. The 5% TTO lotion, the placebo lotion and the 100% macadamia oil were all without significant effect. TTO significantly inhibited proliferation to nickel but not to non-specific polyclonal mitogens by peripheral blood mononuclear cells from nickel-sensitive subjects. Topical application of 100% TTO may have therapeutic benefit in nickel-induced contact hypersensitivity in human skin. The mode of action of TTO requires further investigation, but may be an effect on the antigen presenting cells or the antigen presenting process in nickel-induced contact hypersensitivity, as well as vascular changes associated with this response.

Zolmitriptan Reduces the Size of the Neurogenic Flare Reaction and the Primary Hyperalgesia after Electrical Stimulation

The triptan's mode of action (migraine medication) is not fully understood. Experimental data suggest a peripheral and a central pathomechanism. The aim of this study was the evaluation of zolmitriptan's (Z) impact on the peripheral neuropeptide release (neurogenic flare) and the primary and secondary hyperalgesia after electrical stimulation. Moreover, systematic differences between migraine patients and controls were examined. The study was performed in a double-blind, placebo-controlled and cross-over design. Ten migraine patients (8 female, 2 male; age 26.4±1.4 years) and 10 healthy controls (5 female, 5 male; 24.8±0.8 years) were included. Each participant underwent 2 sessions: one 90 minutes after oral administration of Z and the other 90 minutes after placebo exposure. Four microdialysis fibers equipped with stainless steel for electrical stimulation were inserted into the right ventral thighs and perfused with NaCl. Electrical current was delivered via a constant-current generator (Digitimer) and stepwise increased to 20mA. Electrically-induced pain was rated on a visual analogue scale (VAS) every minute. The electrically-induced axon-reflex flare was measured by a laser Doppler imager. The analysis of the heat pain threshold (TSA 2001) and the mechanical hyperalgesia for pinprick stimuli (Pinprick, intensity 8–512 mN) and dynamic mechanical allodynia (Q-tip, cotton wisp, brush) were assessed directly before and after electrical exposure. For statistical analysis an ANCOVA was calculated. Neurogenic flare: Z downsized the area of the neurogenic flare significantly (p<0.002). No influence on the intensity of the flare (laser Doppler flux) could be observed (ns). The pain rating on the VAS was significantly reduced after Z administration (p<0.04). QST: After electrical stimulation a significant heat- and pinprick hyperalgesia was found in the area of primary hyperalgesia (p<0.05). The hyperalgesia to pinprick but not to heat was significantly decreased by Z (p<0.05). QST parameters in the area of secondary hyperalgesia were unaffected by Z (ns). Our results indicate that Z 1) reduces the excitability of primary afferents resulting in a downsizing of the neurogenic flare and 2) induces a reduction of primary hyperalgesia in our pain-model. The secondary hyperalgesia which is normally interpreted as a sensitization of central neuroceptive neurons was unaffected. These data suggest that Z inhibits the release of neuropeptides and the sensitization of primary afferents.

Chemically and electrically induced sweating and flare reaction

Both thin afferent (nociceptors) and efferent (sympathetic sudomotor) nerve fibers can be activated electrically and chemically, resulting in neurogenic erythema and sweating. These reactions have been used before to assess the impairment of sympathetic and nociceptor fibers in humans. In this study, electrically induced sweating and erythema were assessed simultaneously in the foot dorsum and thigh, and were compared to chemically induced activation. Reproducible intensity–response relations (stimulation intensities 0–30 mA, 1 Hz) were obtained from 32 subjects. The steepest increase of the sweat response was induced at lower intensities as compared to that of the erythema (18.3 mA vs. 25.7 mA, p<0.01) and reached a plateau for intensities above 25 mA, suggesting lower electrical thresholds for sudomotor fibers. Maximum flare areas induced electrically with 30 mA were smaller than those evoked chemically (flare size: 4.5 cm 2 vs. 10.6 cm 2). In contrast, the electrically evoked sweating rate was higher than that evoked chemically (acetylcholine, or ACh; sweating rate 0.31 vs. 0.21 μl/cm 2/min, p<0.01), which might be attributed to an increased effectiveness of synchronized discharge in sympathetic fibers upon electrical stimulation.

Comparative activity of cetirizine and desloratadine on histamine-induced wheal-and-flare responses during 24 hours

Cetirizine and desloratadine are antihistamines active in the treatment of symptoms associated with seasonal allergic rhinitis and chronic urticaria. To compare the antihistamine activity of desloratadine, the active metabolite of loratadine, with that of cetirizine in the skin wheal-and-flare responses during 24 hours. This was a double-blind, randomized, placebo-controlled, single oral dose, crossover study. Skin reaction to histamine (100 mg/mL), administered by prick tests, was measured by the wheal and flare surface areas for 24 hours (before treatment and at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, and 24 hours). Eighteen healthy volunteers (mean age, 33.9 years; 13 women) participated in this study. The areas under the curves of the wheal-and-flare responses as a function of time (primary efficacy variables) were compared using analysis of variance. A highly significant overall treatment effect (P < .001) was detected for wheal and flare inhibition, with the activity of cetirizine and desloratadine significantly superior to that of placebo (P < .001). In addition, the activity of cetirizine was significantly superior to that of desloratadine (P < .001). With desloratadine, only 3 of the 18 subjects achieved a wheal inhibition of at least 70%, occurring between 2 and 4 hours, whereas all subjects using cetirizine reached a wheal inhibition of at least 70% between 0.5 and 3 hours (median time, 1.7 hours). The difference between the 2 active drugs was highly significant (P < .001). The median duration of wheal inhibition of at least 70% was zero with placebo and desloratadine and was 21.9 hours with cetirizine (P < .001). No serious adverse events were reported, and no subject withdrew from the study due to an adverse event. Cetirizine was associated with significantly greater suppression of skin reactivity to histamine compared with desloratadine during 24 hours after a single dose, with a consistent duration of action for cetirizine, as previously reported.

Soft X-ray heating of the solar chromosphere during the gradual phase of two solar flares

In this paper we perform an analysis of the energetics of the solar flaring chromosphere irradiated by soft X-rays (SXR) emitted from overlying hot flare loops. To study an expected SXR heating we used the observations of two solar flares obtained with the Multichannel Subtractive Double Pass (MSDP) spectrograph attached to the Large Coronagraph of the Wrocław University. SXR observations of these flares come from the Yohkoh SXR telescope (SXT). From MSDP spectral images we derived mean Hα line profiles which were then used to construct semi-empirical non-LTE models of the chromosphere in the analyzed areas of flares. On the basis of SXR observations we calculated the mean emission measure EM and the temperature in flaring coronal structures located above the Hα kernels under study and these two quantities were used to compute the SXR irradiation of the chromosphere between 1–300 Å. For each flare model we then evaluated the energy deposit due to such irradiation and compared it with the net radiative cooling rates at all depths in the chromosphere. By means of such modelling we were able to demonstrate that the enhanced emission of selected Hα kernels observed during the gradual phase of these two solar flares cannot be explained in terms of the SXR heating of the chromosphere. We found that radiative losses in all layers of the chromosphere exceeded the amount of the energy deposited by the SXR radiation. However, for stronger flares with much enhanced EM a certain contribution of SXR to the heating cannot be ruled out.

The distribution of hyperaemia induced by skin burn injury is not correlated with the development of secondary punctate hyperalgesia

This study in 20 volunteers examines whether changes in cutaneous blood flow distribution (laser Doppler flow scanning, LDS) and visible flare correlate in time and in distribution with the development of secondary hyperalgesia (SH, punctate stimulation of a 45-g von Frey filament) induced by a superficial skin burn injury. Areas of LDS and flare were at their largest at 5 minutes after the burn injury (58 ± 30 and 20 ± 11 cm 2, respectively), whereas the largest area of SH was seen after 60 minutes (50 ± 45 cm 2). Although the maximum areas of LDS and SH were of the same magnitude, the blood flow response was essentially abolished when the maximal SH area was noticed at 60 minutes. Furthermore, on an individual basis, there was no correlation between the size of maximal LDS area (at 5 minutes) and maximal SH area (at 60 minutes) ( r = 0.27; P = .26). Therefore, peripheral mechanisms associated with the neurogenic inflammation reaction surrounding a skin burn injury are not directly associated with the induction of SH. Perspective Tissue trauma and inflammation-induced sensory abnormalities are important because they are involved in acute nociceptive pain, as well as in chronic pain conditions. This study notes the significance of central sensitization for the development of secondary hyperalgesia, an important phenomenon underlying many clinical pain conditions.