Antipruritic effects of two different 5-HT3 receptor antagonists and an antihistamine in haemodialysis patients

Pruritus is the most distressing symptom in haemodialysis (HD) patients. Its aetiology has not yet been delineated, and thus there are no good therapeutical options. Case reports and series attribute antipruritic potency to the serotonin receptor antagonists of the 5-HT3 type in renal pruritus. It was the aim of this study to investigate the antipruritic effect of two different 5-HT3 receptor antagonists and an antihistamine in 11 patients undergoing HD. Pruritus was induced by iontophoresis with serotonin and histamine and recorded before and after HD. These data were compared to those obtained after oral pretreatment with the 5-HT3 receptor antagonists tropisetron 5 mg and ondansetron 8 mg and the antihistamine cetirizine 10 mg. Ten healthy volunteers served as a control group. Vasocutaneous parameters (wheal and flare), skin temperature and alloknesis were also determined. Itching in HD patients and controls was not significantly diminished by oral pretreatment with the serotonin receptor antagonists. In controls, but not in HD patients, cetirizine significantly reduced itching, skin temperature and vasocutaneous parameters. Our data additionally demonstrate that there are no significant differences in vasocutaneous parameters, itching and alloknesis in HD patients before and after dialysis. We conclude that 5-HT3 receptor blockers such as tropisetron and ondansetron and the antihistamine cetirizine do not sufficiently reduce serotonin- and histamine-induced itching in haemodialyis patients.     

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.     

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     

Recent studies of cutaneous nociception in atopic and non-atopic subjects

Itching reflects a distinct quality of cutaneous nociception elicited by chemical or other stimuli to neuronal receptors at the superficial layers of the skin and muco-cutaneous orifices. Although recent experimental studies of the conduction and perception of itch have yielded deeper insight into the physiology of this sensory quality, little is known about the neuromechanisms involved in pruritus accompanying many inflammatory skin diseases, in particular, in atopic eczema. Previous case-control studies of our research group with patients suffering from atopic eczema (AE) revealed significantly diminished itch perception after iontophoretic application of different doses of histamine as well as substance P (i.c. injected). Further experiments using acetylcholine (ACh, i.c.) clearly demonstrated that ACh elicits pruritus instead of pain in patients with AE. The first part of the present review deals with the results of our most recent case-control studies on histamine-induced itch perception in atopics devoid of eczema as well as in patients with urticaria or psoriasis compared to atopics with or without manifest eczema. We demonstrated that both focal itch and perifocal alloknesis (i.e., itch elicited by a slight mechanical, otherwise non-itching stimulus) were significantly reduced in eczema-free atopics yet were normal in non-atopics suffering from urticaria or psoriasis. In further studies using ACh i.c. injected into the uninvolved skin of patients with AE, lichen ruber, psoriasis, type IV contact eczema, or non-specific nummular eczema (n = 10/each group), all the atopics and 6/10 psoriatics felt itch instead of burning pain, but none of the others did. Different doses of vasoactive intestinal peptide (VIP) i.c. applied to the controls and the atopics with or without eczema did not markedly increase the intensity of nociceptive sensations. However, ACh induced pain in the controls, pure pruritus in the atopics with acute eczema, and a 'mixture' of pain and itch in the atopics just free from eczema. Obviously, the quality of sensations evoked by ACh and VIP depends on the inflammatory or non-inflammatory state of the atopic skin. In a placebo-controlled, double blind study on histamine-induced focal itch and alloknesis with healthy subjects (n = 15) using naltrexone (opioid receptor antagonist) and cetirizine (H1-blocking agent), naltrexone was found to significantly reduce both itching and alloknesis. Cetirizine reduced focal itch but failed to influence the alloknesis phenomenon. The wheal and flare reaction was suppressed only by cetirizine. These different effects point to a mainly CNS-based activity of naltrexone but a peripheral level effect of cetirizine. Due to long-lasting experience with group sport as a supporting adjuvant for inpatients with AE, we evaluated, by clinical, psychometric, and physiological studies, the therapeutic efficacy of controlled physical exercise in addition to otherwise equal anti-eczematous therapy for both voluntary participants and non-participants in sports by performing several case-control studies, one followed-up to 6 months after the patients' discharge from the hospital. Regular moderate exercises neither deteriorated nor impeded the recovery from AE, ameliorated the participants' scratch controlling ability and significantly their depressed emotional mood. The non-participants failed to achieve these aims. Sweating-induced itch was inhibited in almost all participants if simple skin care (clearing by warm shower, ointment) and short-term rest were used by informed patients. In conclusion, there are several indications that itching is elicited in individuals inclined to cutaneous atopy, regardless of their eczematous or just eczema-free state, by a different physiological pathway from that in non-atopic individuals. Therefore, antipruritic agents influencing the centrally altered nociception of atopics are needed and may be expected in near future. (ABSTRACT TRUNCATED)     

Anti pruritic effects of topical crotamiton, capsaicin, and a corticosteroid on pruritogen-induced scratching behavior

Itch accompanies various skin diseases. As a number of mediators other than histamine can be involved in the itch sensation, H1 receptor antagonists are not necessarily effective in treating itch. External application of antipruritic drugs is occasionally used as an alternative therapy for pruritic skin conditions, such as pruritus on primary non-diseased, non-inflamed skin. Even so, the actual effects of these drugs on the itch sensation have yet to be studied in detail. To verify the antipruritic effects of crotamiton, capsaicin, and a corticosteroid on the itch sensation, we examined the inhibitory effects of these drugs on various pruritogen-induced scratching behaviors in mice. Topical application of 10% crotamiton moderately inhibited histamine-, serotonin-, and PAR-2 agonist-induced scratching behaviors. Topical capsaicin (0.025%) also exerted a moderate suppressive effect on histamine-, substance P-, and PAR-2 agonist-induced itch responses. Notably, topical corticosteroid (0.05% clobetasol propionate) remarkably inhibited the scratching behaviors induced by all of the pruritogenic agents tested. Therapeutic effects of capsaicin on substance P-induced pruritus did not seem to be mediated by desensitization of the TRPV1 (+) C fibers and/or by altered responsiveness of the mast cells. In addition, the antipruritic effects of crotamiton and corticosteroid appear to be, at least partly, associated with a TRPV1-independent pathway. This study examined the itch responses to pruritogens and demonstrated the mode of action of the externally applied antipruritic drugs.     

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.     

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.     

Polidocanol inhibits cowhage ‐ but not histamine‐induced itch in humans

Polidocanol is a local anaesthetic and antipruritic compound that is used in the treatment of itching skin conditions such as eczema. Its mechanisms of action are largely ill defined. This study has compared the antipruritic efficacy of topical polidocanol in histamine‐induced itch and a histamine‐independent, cowhage‐induced model of pruritus. Polidocanol (3%) or vehicle was applied topically under occlusion for 1 h to the forearms of 45 healthy volunteers before itch was provoked by rubbing in 40–45 spicules of cowhage or skin prick testing with 10 mg/ml histamine. Itch was recorded at 1‐min intervals for 30 min on a 100‐mm visual analogue scale. Polidocanol significantly reduced the area under the curve for cowhage‐induced itch by 58% (P < 0.05), but had no significant effect on histamine‐induced itch. This result underlines the importance of histamine‐independent itch models in the development of topical antipruritic agents.     

The effect of topically applied salicylic compounds on serotonin-induced scratching behaviour in hairless rats

There is a strong need for antipruritic substances for treating itch in clinical dermatology. In one recent human study, topically applied acetylsalicylic acid has been described to rapidly decrease histamine-induced itch. We have established a model for periferally elicited pruritus by injecting serotonin into the rostral back area (neck) in rats. Using this model, we aimed to investigate the antipruritic potential of four different salicylic compounds, which all possess different skin penetration characteristics. Eighteen rats were studied for 6 weeks. Prior to serotonin injections (2 mg/ml, 50 micro l), 10 micro l of test substances was applied to a circular area 18 mm in diameter. The four substances were salicylic acid, butyl salicylate, diethylamine salicylate and salicylamide, all solubilized in dimethyl isosorbide to a concentration of 5% w/w. Diethylamine salicylate and salicylamide were previously shown to be slowly absorbed through rat skin in contrast to salicylic acid and butyl salicylate. After serotonin injections, scratching was monitored by video recording for 1.5 h. Compared with the vehicle, a lower number of scratch sequences were seen when diethylamine salicylate (P < 0.001) and salicylamide (P = 0.005) had been applied. The numbers of scratch sequences were lower with diethylamine salicylate and salicylamide than with the vehicle throughout the 1.5-h study period. We conclude that topical application of diethylamine salicylate and salicylamide could suppress serotonin-induced scratching in rats. The antipruritic effect seems to be related to the slow drug release of the two substances. The results may be clinically relevant as serotonin induces itch in humans.     

Neurophysiology of pruritus: cutaneous elicitation of itch

Itching is defined as an unpleasant cutaneous sensation leading to the desire to scratch. It serves as a physiological self-protective mechanism as do other cutaneous sensations like pain, touch, vibration, cold, and heat to help defend the skin against harmful external agents. Pruritus can be evoked in the skin directly by mechanical and thermal stimuli or indirectly through chemical mediators. It may also be generated in the central nervous system independently of peripheral stimulation. Single-nerve-fiber recordings have shown that histamine-evoked itch is transmitted by selective slow-conducting subpopulations of unmyelinated C-polymodal neurons. Recent experimental studies using improved methods have demonstrated which of the suspected chemical itch mediators such as histamine, neuropeptides, prostaglandins, serotonin, acetylcholine, or bradykinin act pruritogenically on C-fibers. Moreover, investigations have revealed new receptor systems such as vanilloid, opioid, and cannabinoid receptors on cutaneous sensory nerve fibers that may modulate itch and thereby represent targets for antipruritic therapy. This review focuses on the peripheral generation of itch, including neurotransmitters, neuropeptides, and inflammatory mediators.     

The sensitivity of uremic and normal human skin to histamine

Cutaneous reactions induced by intradermal histamine injection were studied in uremic patients with and without pruritus who were undergoing maintenance hemodialysis and also in healthy subjects. Flare reactions were significantly smaller in both groups of patients than in controls. However, the itch responses following histamine injection were greater in patients with pruritus than in non-pruritic patients and healthy subjects, indicating an augmented sensitivity to pruritogens in these patients. The development of histamine tachyphylaxis was demonstrated in healthy human skin. After repeated histamine injections at intervals of 90 min, both itch and flare responses decreased rapidly. A similar decline in histamine reactivity occurred when the interval between injections was extended to 24 h. The phenomenon of histamine tolerance was confirmed in 2 uremic patients.     

Topically applied aspirin decreases histamine-induced wheal and flare reactions in normal and SLS-inflamed skin,but does not decrease itch. A randomized,double-blind and placebo-controlled human study

Topically applied aspirin has recently been reported to decrease histamine-induced itch in human volunteers. Our aim is to confirm this and to study the antipruritic ability of topical aspirin in inflamed skin. In 24 non-atopic volunteers, an inflammatory skin reaction was induced in forearm skin at 5 different sites by sodium lauryl sulphate contained in Finn Chambers. Aspirin 10%, aspirin 1%, mepyramine 5% and vehicle were applied to the inflamed and corresponding non-inflamed areas 20 min before itch induction with intradermal histamine injection. Itch and pain were scored on a visual analogue scale at regular intervals. Wheal and flare areas were measured. No difference in itch intensities was found after application of aspirin, mepyramine and vehicle, but more itch was induced in aspirin and mepyramine pretreated sites in inflamed skin compared to normal skin (p<0.05). In normal skin, flare areas were smaller after pretreatment with aspirin 10% (p<0.05) and mepyramine (p<0.001), as were wheal areas after mepyramine (p<0.01), compared to vehicle pretreatments. In inflamed skin, flare areas were smaller after pretreatment with aspirin 10% (p<0.01) and mepyramine (p<0.001), as were wheal areas after aspirin 10% (p<0.01), aspirin 1% (p<0.05) and mepyramine (p<0.001). We conclude that despite a significant skin penetration as measured by the influence on wheal and flare reactions, topically applied aspirin did not decrease histamine-induced itch in the model used.     

Antipruritic and thermal sensation effects of hydrocortisone creams in human skin

Few studies evaluate the effect of topical corticosteroids on thermal sensation and in alleviation of itch produced by intradermal injection of histamine. We evaluated the antipruritic effect of hydrocortisone (1% and 2.5%) on histamine-induced itch and sensory effects by measuring itch magnitude, itch duration and thermal thresholds using a computerized thermal sensory analyzer (TSA). This was a double-blind, random, comparative, controlled, single-dose and single-center study. Itch was experimentally induced in both forearms by intracutaneous injection of histamine in 18 subjects. Hydrocortisone 1%, 2.5% and placebo were applied to test sites on both forearms. The thermal threshold for warmth sensation, cold sensation, cold and heat pain was measured with the TSA. Itch magnitude was measured each minute after histamine injection for 10 min with a visual analogue scale (VAS). Itch duration was also recorded. In comparison to placebo, 2.5% hydrocortisone significantly (p = 0.03) reduced itch duration from 12.6 +/- 11.0 min (mean +/- SD) to 8.6 +/- 8.2 min (the reducing rate was 32%) as well as itch magnitude (at minutes 3, 6, 7 and overall). Placebo, 1% and 2.5% hydrocortisone significantly altered (p <0.05) the cold sensation threshold. No treatment altered cold or heat pain thresholds. These data suggest that topical application of 2.5% hydrocortisone may be significantly beneficial for the treatment of histamine-induced itch. The correlation between thermal measurements and antipruritic effects warrants further study.     

Some historical and epistemological remarks on itch and pruritus

Although very common, itch is very hard to describe. It can be considered as one of the most distressing physical sensations we experience. Going back historically, old Latin and Greek writers cited it in ancient papers. So, etymology is of central importance to investigation in the field of itch, regarding the formation of a word with antique origins and different meanings. Scientists, poets, and painters for centuries tried to describe and represent itch. The study of their work reveals the development of the itch's significance. Today, a clinically relevant distinction defines pruritus and itch as two different sensations. Moreover, some terms like hyperknesis, alloknesis, atmoknesis, protopathic itch, and epicritic itch are described to approaching the complexity of this sensation and are utilized in clinical practice.     

Suppression of histamine-induced pruritus by hydroxyzine and various neuroleptics.

This study evaluates the ability of hydroxyzine and various neuroleptics to suppress histamine-induced pruritus in ten volunteer subjects with the use of a double-blind crossover protocol. The itch threshold was determined in each volunteer by intradermal injection of gradually increasing concentrations of histamine. Volunteers were then given the study drugs and placebo at the same interval of time, under near identical conditions, and the itch threshold was determined. Thiothixene, hydroxyzine hydrochloride, chlorpromazine, thioridazine, and a lactose placebo were evaluated. Compared to other drugs, hydroxyzine alone was more effective in the suppression of histamine-induced itch. Consequently, hydrozyzine may be more effective in histamine-induced pruritus. The neuroleptic drugs used in this study do not significantly suppress histamine-induced pruritus, but they may be beneficial in nonhistamine-induced pruritus or psychogenic pruritus.     

Noxious heat and scratching decrease histamine-induced itch and skin blood flow

The aim of this study was to assess the effect of thermal stimuli or distal scratching on skin blood flow and histamine-induced itch in healthy volunteers. Twenty-one healthy volunteers participated in the study. Baseline measurements of skin blood flow were obtained on the flexor aspect of the forearm. These measurements were compared with skin blood flow after various stimuli: heating the skin, cooling the skin, noxious cold 2 degrees C, noxious heat 49 degrees C, and scratching via a brush with controlled pressure. Afterwards histamine iontophoresis was performed and skin blood flow and itch intensity were measured immediately after the above-mentioned stimuli. Scratching reduced mean histamine-induced skin blood flow and itch intensity. Noxious heat pain increased basal skin blood flow but reduced histamine-induced maximal skin blood flow and itch intensity. Cold pain and cooling reduced itch intensity, but neither affected histamine-induced skin blood flow. Sub-noxious warming the skin did not affect the skin blood flow or itch intensity. These findings suggest that heat pain and scratching may inhibit itch through a neurogenic mechanism that also affects skin blood flow.     

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.     

Influence of grenz rays and psychological factors on experimental pruritus induced by histamine and compound 48/80

Summary The interaction between grenz rays and experimentally induced pruritus was evaluated in 14 healthy subjects. Grenz rays were administered once weekly for 4 weeks on restricted areas of the upper arms. Pruritus was evoked by intradermal injection of histamine and the histamine liberator compound 48/80. The results were compared with unconditioned values and with those obtained following a placebo treatment procedure. The influence of psychosocial and psychosomatic factors was also evaluated. Grenz-ray therapy reduced itch but not flare responses. The influence of grenz rays was, however, not statistically different from that observed after placebo treatment. Psychosocial and psychosomatic factors were good predictors of individual skin responsiveness. The results indicate that grenz rays do not interfere with experimental histamine-induced pruritus more than placebo and emphasize the importance of knowing individual characteristics and coping strategies.     

Electrical ear acupuncture reduces histamine-induced itch (alloknesis)

In order to assess an objective measure for the outcome of ear acupuncture, we evaluated the effect of electrical ear acupuncture on areas of histamine-induced alloknesis in 32 healthy volunteers. In a first assessment 5 min after histamine application on both volar forearms, 16 subjects received right ear and 16 left ear acupuncture. Immediately before and 5 min after acupuncture, alloknesis areas on both forearms were planimetrically evaluated. A second assessment was carried out 4 weeks later with the same patients. They underwent histamine application once more, but received no acupuncture. Alloknesis areas were then compared with reference to time, assessment and therapy side. Forearms relating to ipsilateral acupuncture showed significantly reduced or even no alloknesis areas after therapy. On the contralateral sides and during the "non-acupuncture" assessment 4 weeks later, alloknesis areas were significantly enlarged compared with sides ipsilateral to right and left ear acupuncture. Hence, results verify the effects of electrical ear acupuncture by objective measures.     

Repetitive scratching and noxious heat do not inhibit histamine-induced itch in atopic dermatitis

BACKGROUND: Repetitive scratching is the most common behavioural response to itch in atopic dermatitis (AD). Patients with chronic itch often report that very hot showers inhibit itch. We recently reported that scratching and noxious heat stimuli inhibit histamine-induced itch in healthy subjects. However, no psychophysical studies have been performed in AD to assess the effects of repetitive heat pain stimuli and scratching on histamine-induced itch. OBJECTIVES: To examine the effects of repetitive noxious heat and scratching on itch intensity in patients with AD using quantitative sensory testing devices. METHODS: Itch was induced with histamine iontophoresis in 16 patients with AD in both lesional and nonlesional skin as well as in 10 healthy subjects. Repetitive noxious heat and scratching were applied 3 cm distal to the area of histamine iontophoresis. Subjects rated their perceived intensity of histamine-induced itch with a computerized visual analogue scale. RESULTS: Our results demonstrate that repetitive noxious heat and scratching do not inhibit itch intensity in lesional and nonlesional AD skin but do so in healthy skin. Of note, both these stimuli increase itch intensity in lesional AD skin. CONCLUSIONS: Our results strongly suggest that scratching and noxious thermal stimuli have a different effect upon histamine-induced itch perception in patients with AD when compared with healthy controls. This difference may be associated with both peripheral and central sensitization of nerve fibres in AD.