Histamine- and pruritogen-induced itch is inhibited by a TRPM8 agonist: a randomized vehicle-controlled human trial.

BACKGROUND: Allergies often present challenges in managing itch and the effects of histamine. Cooling agents that act via transient receptor potential melastatin 8 (TRPM8) agonism have shown potential in itch management. However, animal studies on itch have limitations, as animals cannot communicate subjective events and their fur-coated skin differs from that of humans. Human studies offer more direct and reliable information. OBJECTIVES: To investigate the effects of a specific TRPM8 agonist gel (cryosim-1) on itch induced by various pruritogens in human skin. METHODS: Calcium imaging experiments determined the binding of cryosim-1 and histamine to their respective receptors. Thirty healthy volunteers underwent skin prick tests with pruritogens and a control vehicle. Itch and pain intensity were measured using a numerical rating scale (NRS) across 10 min. Participants were randomly assigned to pretreatments with vehicle or TRPM8 agonist gel. Tests were repeated at a later date, and skin moisture, transepidermal water loss and mechanical sensitivity were measured. RESULTS: The in vitro study confirmed that histamine is not a TRPM8 agonist and cryosim-1 does not act as an agonist or antagonist on the human histamine 1 receptor. The TRPM8 agonist gel significantly reduced the itch intensity for all pruritogens compared with the vehicle-only gel. It also reduced itch NRS and the integrated itch score. Mechanical sensitivity was also reduced. CONCLUSIONS: The specific TRPM8 agonist gel effectively suppressed human skin itch induced by various pruritogens. These versatile actions suggest that cooling agents may be promising treatments for multiple forms of itch stimuli.

Managing itching and the effects of histamine can be difficult for people with allergies. Cooling the skin or applying menthol provides some relief from itch, but the way they work is not fully understood. Cooling agents interact with a protein called TRPM8 (also known as the 'cold and menthol receptor') and have shown potential for the management of itch. However, much of the research has been done on animals and has limitations when compared with human studies. Antihistamine medications can help with histamine-induced itching, but they may not work for other causes of itch. This study investigated the effects of a specific TRPM8 agonist (a chemical that activates a receptor to produce a biologic response) gel called cryosim-1 on itch in human skin. To do this, we conducted tests on 30 healthy people using five different substances that cause itching. Participants rated the itch intensity and pain using a scale and we measured various aspects of their skin. The results showed that all substances caused significant itching compared to a control substance, but itchiness gradually decreased over time. Histamine and compound 48/80 also caused pain. However, when participants applied the TRPM8 activator gel before exposure, they experienced less itching and lower itch intensity versus the gel without the activator. There were no significant differences in pain between the TRPM8 activator and the gel without it. In summary, our findings showed that activating TRPM8 receptors with a specific substance effectively relieved itching caused by various irritants on human skin. This suggests its potential as a treatment for itch-related conditions. Further research is needed to understand its mechanisms better and evaluate its effectiveness in real-life situations.

Treatment of Brachioradial Pruritus: A Tertiary Center Retrospective Analysis.

This retrospective study investigates the efficacy of 2 treatment regimens, pregabalin alone versus pregabalin combined with ketamine, amitriptyline, and lidocaine cream, in reducing itch in patients with brachioradial pruritus at a tertiary care center. Electronic medical records of 64 brachioradial pruritus patients seen at the University of Miami Itch Center were analyzed. A significant reduction in itch scores was seen with both treatments, with no significant difference between the groups. A small number of patients experienced adverse effects, including drowsiness and weight gain with pregabalin and skin irritation with ketamine, amitriptyline, and lidocaine cream. Ultimately, our findings underscore the potential of utilizing combined therapy for difficult-to-treat brachioradial pruritus cases and implementing individualized approaches for managing neuropathic pruritus. Further controlled clinical trials are needed to establish optimal treatment protocols.

The efficacy and safety of difelikefalin for pruritus in hemodialysis patients: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Chronic kidney disease-associated pruritus (CKD-ap) is a common complication that negatively affects the quality of life. Difelikefalin has emerged as a novel FDA-approved drug to manage CKD-ap. This systematic review and meta-analysis will assess the efficacy and safety of Difelikefalin versus placebo to manage CKD-ap. METHODS: PubMed, Scopus, WOS, Central, and Embase were systematically searched until November 2023. RevMan was used to perform meta-analysis. Quality assessment was conducted using the Cochrane RoB 2.0 tool. Results were reported as risk ratio (RR) and mean difference (MD) with a 95% confidence interval (CI). PROSPERO ID: (CRD42023485979). RESULTS: Five RCTs with a total of 896 participants were included. Difelikefalin significantly decreased the weekly mean WI-NRS score (MD: -0.99 [-1.22, -0.75], p ˂ .00001), 5-D itch scale total score (MD: -1.51 [-2.26, -0.76], p > .0001), and Skindex-10 total score (MD: -7.39 [-12.51, -2.28], p = .005), but showed significantly higher adverse events (RR: 1.26 [1.03, 1.55], p = .03), versus placebo. However, there was no significant difference between both groups in serious adverse events (RR: 1.42 [0.78, 2.57], p = .25) or death (RR: 0.81 [0.19, 3.34], p = .77). CONCLUSION: Difelikefalin appears to be a promising agent for the management of CKD-induced pruritus in patients with end-stage renal disease. However, evidence is still underpowered due to the paucity of the current data; therefore, more robust RCTs are required to confirm the benefit of Difelikefalin.

Prolonged Antipruritic Effect of Botulinum Toxin Type A on Cowhage-induced Itch: A Randomized, Single-blind, Placebo-controlled Trial.

Botulinum toxin type A (Botox) is thought to have antipruritic effects through inhibition of pruritic factors, including acetylcholine, substance P, and glutamate. The aim of this randomized, single-blind, placebo-controlled trial was to test the effect of botulinum toxin type A on cowhage, a non-histaminergic model for chronic itch. Botulinum toxin type A was injected into the arm of 35 healthy subjects, with a saline control injected into the contralateral arm. Thermal sensory parameters (warmth and heat thresholds and heat pain intensity) and itch intensity after cowhage application were examined on test areas. Botulinum toxin type A reduced itch intensity, overall perceived itch (area under the curve (AUC); percentage change from baseline), and peak itch intensity compared with the control at 1 week, 1 month, and 3 months. Botulinum toxin type A had no effect on thermal thresholds or heat pain intensity. In conclusion, botulinum toxin type A reduced cowhage itch for at least 3 months, which suggests that botulinum toxin type A is a potential long-lasting treatment for localized, non-histaminergic itch.

The Effects of Cannabinoid Agonist, Heat Shock Protein 90 and Nitric Oxide Synthase Inhibitors on Increasing IL-13 and IL-31 Levels in Chronic Pruritus.

BACKGROUND: Heat shock protein 90 (Hsp90) inhibitor and cannabinoid agonists ameliorate dry skin-induced chronic itch. We have recently reported that cannabinoids, hsp90 and nitric oxide (NO) are involved in dry skin-induced itch. Here, we investigated the contribution of the Th2 cell signaling pathway to the antipruritic effect of the hsp90 inhibitor 17-Alilamino-17-demethoxygeldanamycin (17-AAG), nitric oxide synthase (NOS) inhibitor Nω-Nitro-L-arginine methyl ester hydrochloride (L-NAME) and cannabinoid agonist WIN 55,212-2 on a dry skin-induced scratch. METHODS: Dry skin-induced chronic itching was created by topical application of AEW (acetone/diethyl ether/water). WIN 55,212-2 (1 mg/kg, i.p.), L-NAME (1 mg/kg, i.p.) and increasing doses of 17-AAG (1, 3 and 5 mg/kg,i.p.) were administered to Balb/c mice (for each group, n = 6). After these applications, skin tissues were taken from the nape region of all of the mice. Gene and protein expressions of IL-13 and IL-31 were evaluated in skin tissues by RT-PCR and immunohistochemistry, respectively. RESULTS: IL-13 and IL-31 mRNA expressions and immune positive cell counts were increased in the AEW applied groups. WIN 55,212-2 reduced both of the increased cytokines levels, while L-NAME decreased only the IL-13. 17-AAG dose-dependently reduced the increased cytokine levels. IL-13 and IL-31 levels significantly decreased following the co-administration of these agents. CONCLUSION: These results show that increased levels of IL-13 and IL-31 are associated with pruritus. Hsp90 inhibition and cannabinoid system activation may induce antipruritic effects through down-regulation of these cytokines.

Antipruritic Effect of Topical Acetaminophen Gel in Histaminergic and Non-histaminergic Itch Provocation: A Double-blind, Vehicle-controlled Pilot Study.

There is a need for new topical antipruritics that are effective on many types of itch. This study examined the antipruritic efficacy of a new formulation of topical acetaminophen. In vitro skin permeability studies showed that 2.5% and 5% formulations are able to rapidly deliver an adequate amount of the drug into the skin. In a double-blind, vehicle-controlled, randomized study in 17 healthy volunteers, 1%, 2.5% and 5% acetaminophen gels and a vehicle gel were applied to the skin prior to histaminergic and non-histaminergic itch induction and assessment of thermal pain thresholds. The 2.5% and 5% gel formulations significantly reduced the itch intensity time course and the area under the curve for both histamine and cowhage itch. No effect was noted on heat pain thresholds and no adverse effects were observed. These results suggest that topical acetaminophen would be a safe and effective over-the-counter medication for itch.

"Because There's Just Something About That Menthol": Exploring African American Smokers' Perspectives on Menthol Smoking and Local Menthol Sales Restrictions.

INTRODUCTION: Local governments are pursuing policies to limit the availability of menthol cigarettes at the point-of-sale. Although African Americans are disproportionately impacted by menthol cigarettes, little is known about African American smokers' perspectives on emerging menthol policy. The purpose of this study was to fill a gap in the literature by exploring African American adult (25+) smoker perspectives on menthol and a local menthol sales restriction. METHODS: In-depth semi-structured interviews were conducted with African American smokers (n = 27) in the Minneapolis-St. Paul area June-September 2017. Interviews explored smoking behaviors, harm perceptions, perspectives of menthol in the community and reactions to local menthol sales restrictions. The framework method guided identification of key themes and synthesis of findings. RESULTS: Almost all (96%) participants smoked Newport cigarettes. The majority of participants indicated that menthol cigarettes were more harmful than non-menthol cigarettes, citing strength and additives and because they were targeted to African Americans. Some participants were receptive to policy change while others viewed the policy as inconvenient and unfair. Overall, there was a lack of understanding of the policy's intended public health impact. Some participants indicated that the policy would have no impact on their purchasing or smoking behaviors while others who were contemplating quitting noted that a menthol restriction was encouragement to prompt a quit attempt. CONCLUSIONS: Sales restrictions can provide a unique opportunity to persuade menthol smokers to quit. Efforts are needed to increase awareness and support of these policies as well as to support African American menthol smokers achieve cessation. IMPLICATIONS: There is growing momentum to restrict local menthol tobacco sales; however, little is known about perceptions among populations most impacted. In Minneapolis-St. Paul, where menthol restrictions were passed in 2017, African American smokers expressed limited awareness and uneven policy support. While some participants were unconvinced the restriction would impact smoking, others indicated it would encourage decreased consumption and prompt quit attempts. There is a need for public education to increase awareness of menthol's harms, to help menthol smokers quit, and to increase support for menthol policies.

Use of Butorphanol as Treatment for Cholestatic Itch.

BACKGROUND: Pruritus is a debilitating symptom of cholestatic diseases such as primary biliary cholangitis and primary sclerosing cholangitis and often results in major reduction in quality of life for afflicted patients. Classic treatment options for the treatment of cholestatic pruritus include antihistamines, bile acid resins, serotonin reuptake inhibitors, and mu-opioid antagonists. Unfortunately, these drugs are not always successful in treating pruritus of cholestasis and may be associated with adverse effects. Recent advances in our understanding of itch pathophysiology have led to the use of butorphanol, a kappa-opioid agonist and mu-opioid antagonist, for the treatment of various forms of pruritus. Reports of butorphanol to treat cholestatic itch specifically are rare. AIMS: To better understand the role of butorphanol in the treatment of cholestatic pruritus, including characterization of its side effect profile. METHODS: We present a case series of eight adult patients with cholestatic disease who were treated with butorphanol in hopes of alleviating intractable pruritus. Patients were identified through a clinical data request form serviced by University of Miami Information Technology. RESULTS: Five out of eight patients (62.5%) reported successful reductions in itch severity after treatment with butorphanol, two patients reported no (or transient) change in itch severity, and one patient reported a paradoxical increase in itching. Side effects included somnolence, sedation, nausea, vomiting, and dizziness. CONCLUSIONS: Butorphanol was safe and leads to clinically significant symptomatic improvement. Clinicians should be aware of butorphanol as an off-label treatment option for pruritus of cholestasis. Further studies are needed to better characterize the effect of butorphanol on cholestatic itch.

The Biological Impact of Menthol on Tobacco Dependence.

In the 1920s, tobacco companies created a marketing campaign for what would one day be their most profitable series of products: mentholated tobacco cigarettes. Menthol provides the smoker with a pleasant mint flavor in addition to a cooling sensation of the mouth, throat, and lungs, giving relief from the painful irritation caused by tobacco smoke. Promising a healthier cigarette using pictures of doctors in white coats and even cartoon penguins, tobacco companies promoted these cigarettes to young, beginner smokers and those with respiratory health concerns. Today, smoking tobacco cigarettes causes one in five US Americans to die prematurely, crowning it as the leading cause of preventable death. In contrast to the dubious health claims by tobacco companies, mentholated cigarettes are in fact more addictive. Smokers of mentholated cigarettes have lower successful quit rates and in some cases are resistant to both behavioral and pharmacological treatment strategies. There is now considerable evidence, especially in the last 5 years, that suggest menthol might influence the addictive potential of nicotine-containing tobacco products via biological mechanisms. First, menthol alters the expression, stoichiometry, and function of nicotinic receptors. Second, menthol's chemosensory properties operate to mask aversive properties of using tobacco products. Third, menthol's chemosensory properties aid in serving as a conditioned cue that can both enhance nicotine intake and drive relapse. Fourth, menthol alters nicotine metabolism, increasing its bioavailability. This review discusses emerging evidence for these mechanisms, with an emphasis on preclinical findings that may shed light on why menthol smokers exhibit greater dependence. IMPLICATIONS: Mentholated cigarettes have been shown to have greater addictive potential than their nonmentholated counterparts. Evidence is pointing toward multiple mechanisms of action by which menthol may alter tobacco dependence. Understanding menthol's biological functions as it pertains to nicotine dependence will be helpful in crafting novel pharmacotherapies that might better serve menthol smokers. In addition, a better understanding of menthol's pharmacology as it relates to tobacco dependence will be valuable for informing policy decisions on the regulation of mentholated cigarettes.

Evaluating a Real World Ban on Menthol Cigarettes: An Interrupted Time-Series Analysis of Sales.

BACKGROUND: Menthol in cigarettes has been shown to increase regular cigarette smoking and nicotine dependence, and decrease success in smoking cessation. Owing to these reasons, in May 2015, the province of Ontario introduced a menthol ban on tobacco products that came into effect in January 2017 prior to a Federal Canadian Ban in October 2017. The objective of this article was to assess the effect of a provincial menthol ban on cigarette wholesale sales in Ontario. METHODS: Wholesale data submitted by tobacco manufacturers to Health Canada pursuant to the federal Tobacco Reporting Regulations from October 2012 to September 2017 were analyzed using interrupted time-series analysis. Changes in sales of cigarettes with and without menthol were estimated, using the province of British Columbia as a comparison. Analyses were seasonally adjusted. RESULTS: Sales of menthol and nonmenthol cigarettes increased from 2013 until the implementation of the 2017 provincial ban. Subsequently, a sharp decline of 55 million menthol cigarettes and 128 million total cigarettes was observed in Ontario. As a comparison, no significant changes were observed in British Columbia. CONCLUSION: This study supports the conclusion that implementation of a menthol ban in Ontario was associated with significant reduction of menthol cigarette sales and total cigarettes sales, compared to British Columbia where there was no provincial menthol ban. This suggests that menthol regulations in jurisdictions with a larger percentage of menthol smokers are likely to be highly effective. IMPLICATIONS: The 2017 menthol ban was associated with significant reduction of menthol cigarette sales and total cigarette sales suggesting that menthol regulations will have important effects on cigarette consumption.

Challenges in Clinical Research and Care in Pruritus.

Chronic pruritus is a frequent global condition. The pathophysiology, underlying aetiology, clinical manifestation, associated burden and response to therapy of chronic pruritus varies from patient to patient, making clinical research and management of this condition challenging. There are still several unmet needs, such as the need to standardize translational research protocols, diagnostic and therapeutic procedures and to enhance the knowledge of the humanistic and economic burden associated with chronic pruritus. Basic and clinical research is of the utmost importance to target these matters. Clinical research has the potential to identify new relevant mechanisms in affected patients, which may lead to identification of novel therapy targets. This article discusses in depth current shortcomings in the daily care of patients with chronic pruritus and the challenges clinical researchers and physicians treating chronic pruritus face in addressing these matters.

A New Generation of Treatments for Itch.

For decades, antihistamines have been the mainstay of treatment for chronic pruritus, yet they often only work by making patients drowsy and forgetful of their itch. A new era of antipruritic drugs is quickly approaching, presenting more effective treatments for patients suffering from chronic itch. Several treatments have been developed targeting specific receptors in the nervous system, such as the transient receptor potential channels, sodium channels, neurokinin-1 receptors, opioid receptors, and many more. Additionally, antipruritic therapies developed to work on the immune system have become more targeted, leading to greater safety and efficacy measures. These include crisaborole, several interleukin antagonists, and janus kinase inhibitors. The promising results presented with these new antipruritic therapies allow physicians to be better equipped to treat their itchy patients.

Mechanisms and Management of Itch in Dry Skin.

Chronic itch is a burdensome clinical problem that often accompanies pathological dry skin-based conditions, such as atopic dermatitis, and systemic disorders, such as kidney diseases, with an unclear pathomechanism and treatments. One of the basic mouse models to investigate mechanisms of itch associated with dry skin is a mixture of acetone and ether followed by water. Animal studies using the acetone and ether followed by water model have revealed that many mediators and receptors, e.g. mas-related G protein-coupled receptor family, transient receptor potential, and chemokines, are responsible for itch and its hypersensitivity, supporting the hypothesis that dry skin-induced itch is a histamine-independent pathway. New insights have been acquired into the interplay between neurones and non-neuronal cells in the initiation, modulation, and sensitization of itch. Several thera-peutic options for itching have thus been developed. This review summarizes the updated pathogenesis and therapeutic strategies for itch in dry skin conditions.

Use of Systemic Treatment in Patients with Chronic Pruritus: A Survey of Dermatologists in the Netherlands.

Treatment of chronic pruritus can be a challenge for clinicians. Several systemic treatments have been suggested to reduce itch, such as gabapentinoids and antidepressants. The aim of this study was to assess the current practice of dermatologists regarding systemic treatment in patients with chronic pruritus, and to identify possible barriers in the prescription of these treatments. An online survey was sent to all dermatologists and dermatology residents in the Netherlands between July 2017 and April 2018. A total of 193 physicians completed the questionnaire (response rate 27.0%). Overall, 61.7% prescribed gabapentinoids or antidepressants in patients with chronic pruritus. Amitriptyline was prescribed most frequently, followed by gabapentin, doxepin and mirtazapine. Reasons not to prescribe systemic treatment included lack of knowledge or experience, risk of side-effects, and lack of available evidence. As only a minority of respondents felt comfortable prescribing these drugs, more education on effective and safe dosing is needed.

Aprepitant in Anti-histamine-refractory Chronic Nodular Prurigo: A Multicentre, Randomized, Double-blind, Placebo-controlled, Cross-over, Phase-II trial (APREPRU).

The aim of this multicentre, randomized, double-blind, placebo-controlled, cross-over, phase-II study was to determine the antipruritic effect of aprepitant vs. placebo in 58 patients with anti-histamine-refractory chronic pruritus in chronic nodular prurigo. Patients were randomized to receive either first oral aprepitant 80 mg/day or placebo for 4 weeks. Following a 2-week wash-out phase, the patients were crossed-over to receive the other treatment for 4 weeks. Primary efficacy criterion was the intra-individual difference between mean itch intensity (visual analogue scale) at baseline compared with the end of treatment period. Prurigo lesions, pruritus course, quality of life, patient benefits, and safety were secondary parameters. No significant differences were found between aprepitant treatment and placebo for any of the parameters investigated. Under the experimental conditions of the study, aprepitant, 80 mg daily for 4 weeks, did not have an antipruritic effect in patients with chronic prurigo. (DRKS00005594; EudraCT Number: 2013-001601-85).

Responses of thalamic neurons to itch- and pain-producing stimuli in rats.

Understanding of processing and transmission of information related to itch and pain in the thalamus is incomplete. In fact, no single unit studies of pruriceptive transmission in the thalamus have yet appeared. In urethane-anesthetized rats, we examined responses of 66 thalamic neurons to itch- and pain- inducing stimuli including chloroquine, serotonin, ß-alanine, histamine, and capsaicin. Eighty percent of all cells were activated by intradermal injections of one or more pruritogens. Forty percent of tested neurons responded to injection of three, four, or even five agents. Almost half of the examined neurons had mechanically defined receptive fields that extended onto distant areas of the body. Pruriceptive neurons were located within what appeared to be a continuous cell column extending from the posterior triangular nucleus (PoT) caudally to the ventral posterior medial nucleus (VPM) rostrally. All neurons tested within PoT were found to be pruriceptive. In addition, neurons in this nucleus responded at higher frequencies than did those in VPM, an indication that PoT might prove to be a particularly interesting region for additional studies of itch transmission. NEW & NOTEWORTHY Processing of information related to itch within in the thalamus is not well understood, We show in this, the first single-unit electrophysiological study of responses of thalamic neurons to pruritogens, that itch-responsive neurons are concentrated in two nuclei within the rat thalamus, the posterior triangular, and the ventral posterior medial nuclei.

Stand-alone Emollient Treatment Reduces Flares After Discontinuation of Topical Steroid Treatment in Atopic Dermatitis: A Double-blind, Randomized, Vehicle-controlled, Left-right Comparison Study.

Prevention of the flares is a main goal in the long-term treatment of atopic dermatitis (AD). Therefore we investigated the efficacy of a water-in-oil emollient, containing licochalcone A, omega-6-fatty acids, ceramide 3 and glycerol, for prevention of the flares in adults with mild to moderately severe AD, treated with topical steroids, that led to clearing of the inflammatory lesions and had been discontinued prior to inclusion. The study was a 12-week, double-blind, randomized, vehicle-controlled, left-right comparison test with the number of relapses, defined as re-occurrence of erythema for at least 3 consecutive days, considered the primary outcome. Compared with the vehicle, the active formulation significantly reduced the number of relapses and maintained the barrier homeostasis of the respective arm. To the best of knowledge, this is the first study to show prevention of the AD flares by the use of stand-alone emollient treatment, based on comparison with the corresponding vehicle while excluding concomitant/rescue medications.

Early Relief of Pruritus in Atopic Dermatitis with Crisaborole Ointment, A Non-steroidal, Phosphodiesterase 4 Inhibitor.

Pruritus occurs in all patients with atopic dermatitis and requires quick relief to reduce disease exacerbation and improve quality of life. Crisaborole ointment is a non-steroidal phosphodiesterase 4 inhibitor for the treatment of mild-to-moderate atopic dermatitis. This post hoc analysis explores crisaborole ointment for early relief of pruritus in patients with mild to moderate atopic dermatitis from 2 phase III studies. Patients received crisaborole or vehicle twice daily for 28 days. Pruritus was graded on a 4-point scale of none (0) to severe (3). Early improvement in pruritus required a score of none (0) or mild (1), with a ≥ 1-grade improvement from baseline on day 6. Significantly more patients experienced early improvement in pruritus with crisaborole than with vehicle (56.6% vs 39.5%; p< 0.001), including at earliest assessment (day 2, 34.3% vs 27.3%; p = 0.013). Crisaborole is a topical treatment option that can rapidly relieve atopic dermatitis-associated pruritus.

Substance P Antagonist Aprepitant Shows no Additive Effect Compared with Standardized Topical Treatment Alone in Patients with Atopic Dermatitis.

Atopic dermatitis (AD) is a chronic, itchy, inflammatory skin disorder that may worsen due to stress and anxiety. Tachykinins have been suggested to be involved in the inflammation in AD, as well as pruritus. Aprepitant is a NK-1 receptor antagonist. This open randomized trial evaluated the effect of aprepitant added to topical treatment in adult patients with moderate-severe AD. The treatment group (n = 19) received 80 mg/day aprepitant for 7 days as a supplement to standardized topical treatment with a moderately strong steroid and a moisturizer. The control group (n = 20) received topical treatment alone. Patients were monitored for the extent of the disease (using SCORing of Atopic Dermatitis; SCORAD), pruritus, and scratching movements. In both the aprepitant-treated and the control groups there was a decrease in SCORAD, pruritus and scratching movements. However, there was no significant additional improvement in any of these parameters in the aprepitant-treated group compared with the control group.

[Menthol in the control of bladder activity: A review]. / Le menthol dans le contrôle de l'activité de la vessie : revue de littérature.

INTRODUCTION: Menthol is a natural compound, of which the known effects on human physiology are manifold (a feeling of freshness, decongestant, bowel antispasmodic). Its implication in vesico-sphincteral physiopathology has been studied since the nineties. METHOD: Literature review of the previous studies having implied menthol in pelvi-perineal physiology through the articles indexed on the Pubmed database, with keywords menthol, menthol and bladder, menthol and toxicity, and TRPM8. Only articles in English were selected. RESULTS: Of the 30 articles that were included, most demonstrated the existence of a micturition reflex to menthol and cold, mediated by the C-type nerve to the spine through activation of TRPM8 urothelial receptors. More recent experiments paradoxically showed an inhibitory effect of menthol on detrusor contractility, independently of TRPM8, when muscle tissue is directly exposed to the compound. However, similar effects of targeted cutaneous exposure or urothelial exposure on detrusorian function have also been demonstrated through TRPM8. This receptor also appears to be involved in interstitial cystitis and idiopathic detrusor overactivity. Lastly, the potential toxicity of menthol appears negligible. Most of the referenced studies are related to animal experiments. Of the three studies that implied humans, only one elucidates some therapeutic applications. CONCLUSION: It seems that menthol and its receptors are involved in vesico-sphincteral physiopathology and could provide therapeutic potential in detrusorian overactivity and interstitial cystitis with reduced toxicity.