Administration of acetylcholine and vasoactive intestinal polypeptide to atopic eczema patients

Responses to acetylcholine (ACh) and vasoactive intestinal polypeptide (VIP) were investigated in atopic eczema (AE) patients. To elucidate the involvement of histamine to ACh-provoked vasoreactions and sensations, we applied a selective H1-antagonist (cetirizine) 3 h prior to the ACh-administration. Solutions of acetylcholine (ACh, 0.55 M) and vasoactive intestinal polypeptide (VIP, 1.5x 10(-5) M) were injected (10 microl) intracutaneously into the volar forearm of 14 healthy subjects and 14 atopic eczema (AE) patients. The substances were applied as single stimulus as well as in combination. Sensations evoked by the stimulation were recorded using 2 visual analog scales (VAS). Vasoreactions were analyzed with the new technique of computer assisted video image analysis. With this method we measured the dynamics of the flare development and the extension of the final flare size independent of the observer's assessment. In control subjects the development and extension of the final flare size was almost similar, regardless whether ACh and VIP were applied in combination or separately. Compared to healthy controls, after injection of ACh, VIP and the combination of VIP and ACh smaller flare sizes were recorded in AE patients. After VIP was given, the control subjects reported pruritus, which was significantly augmented compared to AE patients. In contrast, controls reported a burning pain after the injection of ACh, whereas AE patients felt predominantly pruritus. Itch sensation after the combined application of VIP and ACh was significantly elevated in AE patients. Consequently, we assume that mediators of sudomotor neurons, i.e., VIP and ACh meet in AE patients apparently sensitized nociceptive primary afferents and induce exaggerated itch, pain and flare responses. When pretreated with the selective H1-antagonist cetirizine before ACh was injected, pain and erythema due to ACh was diminished in healthy controls. In contrast, cetirizine did not influence the size of erythema and the magnitude of sensation in AE patients. We conclude, that the release of histamine is not involved in ACh-induced erythema and pruritus in AE. These data provide evidence that pruritus can be elicited in atopic eczema by a cholinergic, histamine independent mechanism.     

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

Abstract 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. Received: 24 July 1997     

Efficacy of naltrexone on acetylcholine-induced alloknesis in atopic eczema

Atopic eczema (AE) is a chronically pruritic inflammatory skin disease. Although the mediators and exact mechanisms eliciting and sustaining pruritus are not completely known, AE patients in clinical trials have been shown to benefit under treatment with morphine antagonists. Naltrexone (NAL) is a relatively pure morphine antagonist that blocks the effects of opioids twice as much as naloxone. NAL exhibits minimal pharmacological activity and displaces endorphines at mu- and kappa-receptors without its own intrinsic activity. NAL's excellent oral bioavailability and linear increases in the area under plasma concentration-time curve make it ideal for use in experimental studies. We designed our present experiments similar to former experiments evaluating both peripheral cutaneous sensations and central itch procession in order to gain more information about the possible distribution of opioid receptors and their involvement in the pathophysiology of pruritus. Eleven AE patients participated in our double-blind study. Either 25 mg of NAL (Nemexin) or a placebo (PLA) was given to the participants 60 min prior to the acetylcholine (ACH) injection [intracutaneous (i.c.) injection of 0.02 ml of 0.55 M]. A PLA stimulus with buffered saline served as control on the opposite forearm. We used laser Doppler flowmetry to measure the vasomotoric changes after ACH injection and recorded the duration and intensity of itch with a visual analogue scale (VAS). Following the evaluation of wheal and flare sensation, we obtained the area of itchy skin around the injection site (alloknesis) by gently stroking the surrounding skin with a brush in the centripetal direction towards the injection site. The results were planimetrically evaluated. Oral NAL reduced the perifocal itch significantly (P < 0.009). In four of our observations the area of alloknesis completely disappeared. Itch duration was reduced by 20 s and the intensity of itch was diminished, yet not significantly. NAL had no significant effects on cholinergic vasoreactions measured by the laser Doppler (P > 0.50) and especially failed to decrease the initial flux response, which is a typical sign of an altered vascular reaction (P > 0.25). The decrease of wheal (P = 0.008) and flare (P = 0.01) extension indicates an appropriate dosage of our treatment for this experiment. The most significant effects of NAL were observed in parameters of itch processing such as alloknesis (P = 0.009) and flare extension (P = 0.01). Therefore we favour the concept that NAL might have a stronger impact on central nervous mechanisms than on peripheral nociceptive structures.     

Lack of efficacy of topical capsaicin in serotonin-induced itch

Capsaicin (CAP) has been demonstrated to be an effective topical inhibitor of cutaneous vasodilatation, pain and pruritus induced by a variety of chemical and physical stimuli. In a previous study, we showed a significantly inhibitory effect of topical CAP treatment on histamine-induced itch and cutaneous vascular reactions in healthy subjects compared to atopic eczema patients. As serotonin is proposed to play a pathophysiological role in some types of pruritus (e.g. uremic and hepatic pruritus) and CAP has been described to be successful in hemodialysis-related pruritus, we investigated the antipruritic effect of topical CAP on serotonin-induced reactions in 10 healthy volunteers in comparison to untreated skin (UPS) and placebo substance (vehicle)-treated skin (VS). On the first day, serotonin iontophoresis was performed in untreated skin. One week later, the treatments started, using either CAP 0.05% liniment or a placebo liniment (vehicle) 3 times daily over a 5-day period. On day 6, serotonin was applied by iontophoresis within the pretreated skin. After another 1-week break, the treatments were performed vice versa on the corresponding infrascapular region. Weal and flare areas were planimetrically evaluated. Itch sensations were documentated by the volunteer on a scale over a 24-min follow-up period. The examination also comprised alloknesis, which stands for induction of perifocal sensations by usually non-itching stimuli. In CAP-treated skin, serotonin-induced wheals were significantly larger post-application compared to non-pretreated skin. Wheals were significantly larger in VS than in UPS. Comparison of serotonin-induced flares in the different study arms did not reveal any significant differences. Itch sensations were not significantly reduced by topical CAP application. The areas of alloknesis were smaller in capsaicin-treated skin compared to VS and UPS, but did not reach significant value. In conclusion, topical CAP application is not effective in serotonin-induced itching in healthy volunteers. Serotonin is most unlikely to play a role in the mechanism of action of CAP.     

Clinical potential of Melanotan® (NDP-α-MSH) in skin protection – current status and future perspective

Non-histaminergic pruritus of any origin is difficult to treat and requires evaluation of new therapeutic strategies which were offered by recent neurophysiologic findings. For example, the discovery of opioid receptors on mast cells and nerve fibers enables the effective administration of opioid receptor antagonists. Up to now, 130 patients with pruritus of different origin were successfully treated with the oral opioidantagonist naltrexone. A significant therapeutic response was achieved under 50–150 mg daily in 66% of patients. In prurigo nodularis, naltrexone also contributed to healing of the skin lesions. Tachyphylaxis was infrequent, and adverse drug effects, in particular nausea, were of short duration. Only recently, the vanilloid receptor 1 (VR1) was demonstrated on nerve fibers and mast cells what explains the antipruritic efficacy of the topical application of capsaicin. Upon continual therapy with this VR1-ligand, neuropeptides are depleted and the nerve fiber is desensitized. A total of 53 patients with pruritus of different origin (prurigo nodularis, psoriasis, eczema, aquagenic pruritus, PUVA itch, hydroxyethyl starch-induced itch, and lymphoma) were selected to receive capsaicin four to six times daily in gradually increasing concentrations (0.025–0.1%). After cessation of the symptoms of neurogenic inflammation, all of the patients experienced a complete elimination of pruritus within 12 days. In addition, capsaicin largely contributed to healing of the skin lesions in prurigo nodularis.     

The antipruritic effect of a 5-HT3 receptor antagonist (tropisetron) is dependent on mast cell depletion – an experimental study

The background of this study is that 5-HT3 receptor antagonists are reported to have an antipruritic effect in uremic and cholestatic pruritus. Recently, we could not confirm such an effect in healthy subjects under experimental conditions. Therefore, it was the aim of the present study to further evaluate a possible antipruritic effect of a 5-HT3 receptor antagonist (tropisetron) on serotonin- and histamine-induced itch before and after skin mast cell depletion in 10 healthy subjects. The results were compared to serotonin and histamine iontophoresis in non-pretreated and pretreated skin with an orally applied antihistamine (cetirizine). Skin mast cell depletion was performed by iontophoretical application of compound 48/80. Wheals and flares were planimetrically evaluated. Itching and burning sensations were rated on an analog scale over a 24-min period. The test protocol also comprised alloknesis, defined as induction of perifocal itch sensations by a mechanical stimulus. When serotonin was iontophoretically applied after mast cells had been depleted before, oral tropisetron resulted not only in significantly lower whealing, itching and alloknesis but also reduced flares. In contrast, after oral pretreatment with tropisetron histamine-induced reactions before and after mast cell depletion did not significantly change. Our study demonstrates that in this model, tropisetron as a 5-HT3 receptor antagonist does not effect histamine-induced itch but has a measurable effect in serotonin-induced reactions when mast cells were depleted before. From these data evidence now exists why tropisetron is to some extent effective in certain types of pruritus such as uremic pruritus, known for increased histamine liberation and increased serotonin levels as well as degranulated and diffusely spread mast cells in the skin.     

Mouse model of touch-evoked itch (alloknesis)

Lightly touching normal skin near a site of itch can elicit itch sensation, a phenomenon known as alloknesis. To investigate the neural mechanisms of alloknesis, we have developed an animal model. Low-threshold mechanical stimulation of the skin normally does not elicit any response in naive C57/BL6 mice. Following acute intradermal (i.d.) injection of histamine in the rostral back, mechanical stimulation 7 mm from the injection site elicited discrete hindlimb scratch bouts directed toward the stimulus. This began at 10 minutes and peaked 20-40 minutes post histamine injection, declining over the next hour. Histamine itself elicited bouts of scratching not associated with the mechanical stimulus, which ceased after 30 minutes. Histamine- and touch-evoked scratching was inhibited by the μ-opiate antagonist naltrexone. Touch-evoked scratching was observed following i.d. 5-HT (5-hydroxytryptamine), a protease-activated receptor (PAR)-4 agonist, and an MrgprC11 agonist BAM8-22, but not chloroquine or a PAR-2 agonist. The histamine H1 receptor antagonist terfenadine prevented scratching and alloknesis evoked by histamine, but not 5-HT, a PAR-4 agonist or an MrgprC11 agonist. In mice with experimental dry skin, there was a time-dependent increase in spontaneous and touch-evoked scratching. This animal model appears to be useful to investigate neural mechanisms of itch and alloknesis.     

Atopic eczema or atopiform dermatitis

Please cite this paper as: Atopic eczema or atopiform dermatitis. Experimental Dermatology 2010. Abstract: Age period prevalence of atopic eczema (AE), a very common skin disease, has increased during the past decennia. This expansion seems to be ending in wealthy countries, while an increase is observed in developing nations, for which there is no firm explanation. Recent steps in understanding AE are the detection of skin barrier related filaggrin null mutations in approximately 25% of patients and the recognition of IL‐31 as a molecule possibly involved in the itch (pruritus). Also interesting are the recognition of thymus and activation‐regulated chemokine (TARC) and proliferating‐inducing ligand (APRIL), as being associated with AE severity and activity. Immunocentric and corneocentric views on pathogenesis (the inside‐outside paradigm) and the diagnostic entity atopiform dermatitis (AFD) are discussed here. We emphasize that diagnosing AE is not simple but challenging. We accentuate that a diagnosis of AE is only possible when there is allergen‐specific IgE. Advice as to the need for elimination of allergens and adjustment of lifestyle are only proficient in patients having atopy and true AE, not in those having AFD.     

Itching in the psychiatric ward

Chronic itch is known to have psychogenic elements; however, there is no data on itch prevalence and characteristics among hospitalized psychiatric patients. We investigated the prevalence and types of itching among hospitalized psychiatric patients who met DSM-IV criteria for schizophrenia, affective or other psychiatric disorders. A validated itch questionnaire based on the McGill Pain Questionnaire, which examines the incidence and characteristics of itching, was administered to 111 patients, hospitalized in an Israeli university hospital. Patients with atopic eczema, psoriasis, or systemic diseases that cause pruritus were excluded. Thirty-six patients (32% of those screened) reported itching. Few sought help or used anti-pruritic therapy. Itching should be addressed during psychiatric assessments, in order to provide appropriate treatment.     

Pruritus und Psoriasis

Pruritus is a frequent but often unrecognized and underestimated symptom in patients with psoriasis. The underreporting may be due to lower frequency and reduced intensity of pruritus compared to other pruritic diseases such as atopic eczema or uremic pruritus, as well as impairment of psychosocial well-being caused by e.g. depression, social withdraw and secretiveness. Recent studies show pruritus being more prevalent in psoriasis, especially plaque-type psoriasis, than previously believed and severely affecting patients' quality of life. The assessment of pruritus and its associated effects is a significant component of clinical management of psoriasis. The presented suggest we should not underestimate pruritus in psoriasis and must consider this symptom in planning therapy.     

Antipruritic effects of pimecrolimus and tacrolimus

The development of topical calcineurin inhibitors resulted in a significant improvement in the treatment of inflammatory skin diseases such as atopic dermatitis. In addition, an excellent amelioration of pruritus could be observed. Other itchy dermatoses such as chronic irritative hand dermatitis, rosacea, graft-versus-host-disease, renal pruritus, lichen sclerosus, prurigo simplex, prurigo nodularis, scrotal eczema, and inverse psoriasis also have been treated successfully with pimecrolimus and tacrolimus. The antipruritic effect currently is believed to be related to the inhibition of inflammatory cytokines. Furthermore, recent investigations indicate a release of neuropeptides from sensory nerve fibers and degranulation of mast cells mediated by pimecrolimus and tacrolimus. Similar effects have been observed during capsaicin treatment. These findings may provide a possible explanation for initially observed calcineurin inhibitors related side-effects such as burning and pruritus. Moreover, the antipruritic potency may be related to a direct effect on nerve fibers leading to suppression of itch mediated by unknown mechanisms.     

What’s new in atopic eczema? An analysis of systematic reviews published in 2018. Part 1: prevention and topical therapies

This review is part of a series of annual updates that summarize the evidence base for atopic eczema (AE). The aim is to provide a succinct guide for clinicians on the key findings from 14 systematic reviews on the prevention and topical treatment of AE published or indexed in 2018. Various supplements, including long-chain polyunsaturated fatty acids, vitamin D and the probiotic Lactobacillus rhamnosus GG, given prenatally and postnatally, have not been shown to prevent AE in infants, although mixed strains of probiotics may decrease the risk of AE if given to the mother during pregnancy and to the infant for the first 6 months of life. In the postnatal period, there is no evidence that hydrolysed formula, compared with cow’s milk formula (CMF), reduces the risk of AE in partially breastfed infants. However, weak evidence suggests that a specific partially hydrolysed whey formula decreases the risk of AE compared with CMF. No specific skin practices can be recommended to reduce the eczema risk in healthy term babies. There is weak evidence of a low risk of reversible hypothalamic–pituitary–adrenal axis suppression following 2–4 weeks of treatment with low-potency topical steroids, and conflicting evidence as to whether bleach bathing affects skin flora or AE severity. A single study demonstrated that the topical Janus kinase inhibitor tofacitinib at 2% significantly reduces the Eczema Area and Severity Index compared with vehicle. Topical naltrexone cream 1% improves pruritus (measured using a visual analogue scale) by 30% more than placebo. There is weak evidence that topical alternative therapies, including antioxidants, micronutrients and some herbal medicines, may improve AE.     

Acetylcholine Is an Inducer of Itching in Patients with Atopic Eczema

As previous experimental studies disproved histamine as the main mediator of eliciting pruritus in atopic eczema (AE), we examined the neurocutaneous sensations in 15 patients with AE and in 15 age- and sex-matched non-atopic controls after i.c. injection of acetylcholine (Ach, 0.5 M, 20 μl) or buffered saline. The sensory perceptions were rated by the participants of the study with regard to their quality and intensity using a visual analogue scale. Simultaneously, the vascular reactions to Ach were recorded by the examinators via laser Doppler fluxmetry as well as flare and wheal planimetry. In contrast to the approximately equal flare and wheal extensions in either group, the cutaneous sensations differed significantly. The patients complained of ‘pure’ itching that developed shortly after Ach injection, whereas the control subjects reported only burning pain. Moreover, the patients perceived their sensations significantly earlier and significantly longer than did the controls. The study provides evidence that Ach plays an important role in the pathogeny of pruritus in patients with AE. Further investigations of the neuronal mechanisms involved in this atopy-related effect of Ach have to be performed.     

Do Training‐Dependent Differences in Perspiration Exist between Healthy and Atopic Subjects?

Sweating (perspiratio sensibilis) serves predominantly for thermoregulation and is triggered, among other stimuli, by physical stress. Although consensus on sex-dependent differences in sweating has not been reached so far and recent studies revealing abnormal diminution of the sweating capacity in atopic subjects are mainly based on heat exposure experiments, the influence of endurance training on perspiration in atopics has not yet been evaluated. Using a special sweat collector device reliable even during intensive body movement, we compared the sweat production of age-matched male and female healthy controls (14 m, 10 f) to that of in-patients with atopic eczema (AE: 14 m, 10 f) during and 5 min after physical exercise (30 min) with a bicycle ergometer under standardized experimental conditions. The individual stress limit was determined by a previous endurance test including repeated lactate blood level measurements and continuous heart rate control. Informed consent was obtained from every participant in the study. One half of both the patients and the controls underwent three week endurance training, and the preceding sweat measurements were repeated in all patients and controls after the training period under identical conditions. On average, the healthy males perspired nearly twice as much as the corresponding females (p < 0.0016). Highly significant mean differences of maximum sweat secretion rates were also found between the atopics and the controls. Healthy individuals of both sexes perspired nearly three times as much as did the patients with AE (males: p < 0.0004; females: p < 0.00009). Among the atopics there were remarkable, yet statistically insignificant, sexual differences in sweat production. After three weeks, sweating rates were similar to the initial ones in the training group as well as in the non-trained control group. Gender differences in perspiration do not only exist between healthy males and females but also in patients with atopic skin disorder, yet the latter ones at significantly lower levels as compared to healthy control subjects. No influence of a three-week-exercise phase on sweat secretion in atopics and controls could be proven. For designing further studies on intra- or intersexual differences of drug-independent perspiration, standardized physical stress can be recommended as an experimental prerequisite for sweat measurements.     

Naltrexone: A case report of pruritus from an antipruritic

Intense, generalized pruritus associated with mycosis fungoides was relieved using subcutaneous naloxone but intensified when changed to the new oral opioid antagonist, naltrexone. Rechallenge again led to worsening in pruritus. This unexpected adverse effect is surprising as naltrexone and naloxone are currently thought to work via similar opioid receptor binding. The worsening of the itch may have been due to adaptation in opioid receptor expression induced by prolonged naloxone therapy, possibly highlighting differential opioid receptor affinity between naltrexone and naloxone, or may have represented an idiosyncratic adverse reaction. Naltrexone and naloxone have been reported to reduce pruritus due to cholestasis, uraemia, morphine epidurals, and possibly atopic dermatitis and urticaria. Naltrexone has the convenience of oral administration and a longer half-life. The role of the opioid system and naltrexone in pruritus is reviewed.     

SERUM IGE LEVEL AND WHITE DERMOGRAPHISM IN ATOPIC DERMATITIS,ATOPIC SKIN,AND INFANTILE ECZEMA

Serum IgE levels and white dermographism were evaluated in atopic dermatitis, atopic skin, and infantile eczema. Elevated serum IgE levels were found in some atopics. In atopic dermatitis there was an increase in serum IgE levels and a more constant presence of white dermagraphism in association with increased severity of dermatitis. Likewise, in atopic skin there was an association of increased serum IgE levels with white dermographism. In infantile eczema, IgE was not increased above normal adult levels nor was there white dermographism.     

Pathophysiology of pruritus in atopic dermatitis: an overview

Pruritus is an essential feature of atopic dermatitis (AD) and the diagnosis of active AD cannot be made without the history of itching. Because of the high impact on life quality, most of the patients measure the severity of eczema by the intensity of pruritus rather than appearance of skin lesions. However, although pruritus is a cardinal symptom of AD, its mechanism and association with the cutaneous nervous system is not completely understood. Recently, a considerable progress has been achieved in clarifying the complex pathophysiology of pruritus in AD. As a cutaneous sensory perception, itch requires excitation of neuropeptide-containing free nerve endings of unmyelinated nociceptor fibers. It is well known that histamine and acetylcholine provoke itch by direct binding to 'itch receptors' and several mediators such as neuropeptides, proteases or cytokines indirectly via histamine release. Interestingly, some variations of these complex mechanisms could be demonstrated in patients with AD. This review highlights the recent knowledge of different mechanisms which may be involved in regulating pruritus in patients with AD potentially leading to new therapeutic applications for the treatment of itch in AD.     

Impact of acute stress on itch sensation and scratching behaviour in patients with atopic dermatitis and healthy controls

Patients with atopic dermatitis (eczema) often report that stress is a major factor to worsen their itchy skin. This study investigated the effects of acute stress on itch, urge to scratch, and scratching behavior in subjects with atopic dermatitis compared to healthy controls. Stress was created in a standardized way using the Trier Social Stress Test (TSST), where subjects were asked to perform a public speaking task and mental arithmetic. In a second control visit, instead of being stressed, subjects watched a non-stressful video of landscape scenes. Both subjects with atopic dermatitis and healthy subjects reported feeling stressed after the TSST. Interestingly, atopic dermatitis subjects who were more sensitive to stress also had higher eczema severity. Before and after the TSST or landscape video, cowhage (a plant that causes itch) was applied to the arm of each subject. Patients with atopic dermatitis reported less itch from cowhage and less urge to scratch after they had been stressed by the TSST. However, despite reporting less itch, they actually scratched their limbs significantly more when they were stressed. Healthy individuals did not have any difference in itch, urge to scratch, or scratching behavior in the stressful condition compared to the control landscape video condition. This study shows that acute stress can affect itch and scratching differently in chronic itch patients compared to healthy individuals. Stress led to more scratching in those with atopic dermatitis. Over time, this response to stress could lead to increased skin damage from scratching and therefore worse eczema and itch.     

The cellular inflammatory response in nicotinate skin reactions

Sequential skin biopsies of nicotinate-treated skin from nine normal subjects, three aspirin-pretreated normal subjects and six atopic eczema patients were examined. An erythematous skin reaction was seen in the nine normal subjects and to a lesser degree in one atopic eczema patient, but not in the aspirin-pretreated subjects nor in five remaining atopics. Accumulation of a mononuclear cell perivascular infiltrate was seen from 15 min onwards in the normal subjects. Neutrophils became the predominant cell invading thickened vessel walls and in the perivascular space beginning at 2 h and persisting up to 48 h. Leucocytoclasis was observed at 24 h. Immunofluorescence studies showed only non-specific fibrinogen deposits in papillary capillaries in the three groups of subjects. The chloroacetate esterase reaction and immunohistochemical labelling with OKM I confirmed a marked neutrophilia at 2 h and 24 h. Neutrophils were seen in one atopic eczema patient, but were not observed in the remainder, nor in the skin of the aspirin-pretreated normal subjects. Topical application of nicotinate causes non-allergenic, leucocytoclastic vascular damage in normal skin which can be inhibited by aspirin and which is reduced or absent in atopic eczema.     

Electrode design for skin electroporation with minimal nerve stimulation

Itch is one of the major symptoms of various skin diseases. Although specific neuronal pathways for itch were identified both peripherally and centrally, they still fail to explain itchy skin observed in patients with chronic pruritus. In this study, sensitivity to itchy and painful stimuli in patients with atopic dermatitis was investigated. Histamine-prick evoked enormous itch in their lesional skin, while less itch in their non-lesional skin than healthy subjects. Flare reaction was not significantly different between their non-lesional and lesional skin, rather smaller than healthy subjects. Mechanical (pin-pricks), electrical, heat and chemical (injection of pH3 solution) stimuli evoked intense itch in their lesional skin and partly also in their non-lesional skin, while only pain in healthy subjects. Itch was also, but not intensely, evoked in healthy subjects by injection of pH3 solution after sufficient histamine stimuli. These results confirm the presence of itchy skin with hyperkinesis (excessive itch by itchy stimuli) and allokinesis (itch by non-itchy stimuli) in patients with atopic dermatitis, which is so intense that painful stimuli cannot suppress but evoke itch, and suggest that neuronal sensitization is involved in their itch not only peripherally but also centrally.