This review explores current evidence to demonstrate that botulinum neurotoxins (BoNTs) exert antipruritic effects. Both experimental and clinical conditions in which botulinum neurotoxins have been applied for pruritus relief will be presented and significant findings will be highlighted. Potent....... Potential mechanisms underlying antipruritic effects will also be discussed and ongoing challenges and unmet needs will be addressed.......This review explores current evidence to demonstrate that botulinum neurotoxins (BoNTs) exert antipruritic effects. Both experimental and clinical conditions in which botulinum neurotoxins have been applied for pruritus relief will be presented and significant findings will be highlighted...
George, Mathew; Joseph, Lincy; Ramaswamy
This study investigated antipruritic and anti-inflammatory effect of Centella asiatica extract in rats and anti-allergic in vitro using sheep (Capra hircus) serum method and compound 48/80 induced mast cell degranulation method, compared with standard drug ketotifen fumarate. In rats, extract of Centella asiatica administered orally was examined for anti-pruritic study and chlorpheniramine maleate was used as standard drug while carageenan paw induced inflammatory method was used for the antiinfammatory study. The results show that the extracts of Centella asiatica exhibited antiallergic, anti-pruritic and anti-inflammatory activities.
This study investigated antipruritic and anti-inflammatory effect of Centella asiatica extract in rats and anti-allergic in vitro using sheep (Capra hircus) serum method and compound 48/80 induced mast cell degranulation method, compared with standard drug ketotifen fumarate. In rats, extract of Centella asiatica administered ...
Cevikbas, Ferda; Braz, Joao M; Wang, Xidao; Solorzano, Carlos; Sulk, Mathias; Buhl, Timo; Steinhoff, Martin; Basbaum, Allan I
Despite recent insights into the pathophysiology of acute and chronic itch, chronic itch remains an often intractable condition. Among major contributors to chronic itch is dysfunction of spinal cord gamma aminobutyric acidergic (GABAergic) inhibitory controls. We sought to test the hypothesis that selective GABA agonists as well as cell transplant-derived GABA are antipruritic against acute itch and in a transgenic mouse model of atopic dermatitis produced by overexpression of the T H 2 cell-associated cytokine, IL-31 (IL-31Tg mice). We injected wild-type and IL-31Tg mice with combinations of GABA-A (muscimol) or GABA-B (baclofen) receptor agonists 15 to 20 minutes prior to injection of various pruritogens (histamine, chloroquine, or endothelin-1) and recorded spontaneous scratching before and after drug administration. We also tested the antipruritic properties of intraspinal transplantation of precursors of GABAergic interneurons in the IL-31Tg mice. Systemic muscimol or baclofen are antipruritic against both histamine-dependent and -independent pruritogens, but the therapeutic window using either ligand alone was very small. In contrast, combined subthreshold doses of baclofen and muscimol produced a significant synergistic antipruritic effect, with no sedation. Finally, transplant-mediated long-term enhancement of GABAergic signaling not only reduced spontaneous scratching in the IL-31Tg mice but also dramatically resolved the associated skin lesions. Although additional research is clearly needed, existing approved GABA agonists should be considered in the management of chronic itch, notably atopic dermatitis. Copyright © 2017 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.
Gonzales, Andrea J; Fleck, Timothy J; Humphrey, William R; Galvan, Betsy A; Aleo, Michelle M; Mahabir, Sean P; Tena, Jezaniah-Kira; Greenwood, Karen G; McCall, Robert B
Pruritus is a characteristic clinical sign of allergic skin conditions including atopic dermatitis (AD) in the dog. IL-31 is a cytokine found in the serum of some dogs with AD and can induce pruritic behaviours in laboratory beagle dogs. The objectives were to characterize an IL-31-induced pruritus model by evaluating the efficacy of prednisolone, dexamethasone and oclacitinib, and to compare the speed of anti-pruritic effects of oclacitinib against those of prednisolone and dexamethasone. Purpose-bred beagle dogs were used in all studies. Randomized, blinded, placebo-controlled studies were designed to evaluate and compare the anti-pruritic properties of prednisolone, dexamethasone and oclacitinib following a single intravenous injection of recombinant canine IL-31. Video surveillance was used to monitor and score pruritic behaviours in study animals. Prednisolone [0.5 mg/kg, per os (p.o.)] reduced IL-31-induced pruritus when given 10 h prior to observation. When the time interval between drug treatment and observation was shortened to 1 h, dexamethasone (0.2 mg/kg, intramuscular) but not prednisolone (0.25 or 0.5 mg/kg, p.o.) reduced IL-31-induced pruritus. Oclacitinib (0.4 mg/kg, p.o.) reduced pruritus when given 1, 6, 11 and 16 h prior to the observation period, and the anti-pruritic activity of oclacitinib was greater when compared to prednisolone and dexamethasone at all time points assessed. The efficacy of prednisolone, dexamethasone and oclacitinib in the IL-31-induced pruritus model gives confidence that this may be a relevant model for acute pruritus associated with allergic dermatitis including AD and can be used to evaluate novel compounds or formulations. © 2015 Zoetis Inc. Veterinary Dermatology published by John Wiley & Sons Ltd on behalf of ESVD and ACVD.
Andersen, Hjalte H.; Melholt, Camilla; Hilborg, Sigurd D.
A frequent empirical observation is that cold-induced counter-irritation may attenuate itch. The aim of this randomized, single-blinded, exploratory study was to evaluate the counter-irritation effects of cold-stimulation and topical application of transient receptor potential TRPA1/M8-agonists...... and trans-cinnamaldehyde had antipruritic efficacy similar to doxepin (p Cold-induced counter-irritation had an inhibitory effect on histaminergic itch, suggesting that agonists of cold transduction receptors could be of potential antipruritic value....... (measured by laser-speckle perfusion-imaging). Homotopic thermal counter-irritation was performed with 6 temperatures, ranging from 4°C to 37°C, using a 3 × 3-cm thermal stimulator. Chemical “cold-like” counter-irritation was conducted with 40% L-menthol and 10% trans-cinnamaldehyde, while 5% doxepin...
Andersen, Hjalte H; Melholt, Camilla; Hilborg, Sigurd D; Jerwiarz, Anne; Randers, Amalie; Simoni, Amalie; Elberling, Jesper; Arendt-Nielsen, Lars
A frequent empirical observation is that cold-induced counter-irritation may attenuate itch. The aim of this randomized, single-blinded, exploratory study was to evaluate the counter-irritation effects of cold-stimulation and topical application of transient receptor potential TRPA1/M8-agonists (trans-cinnamaldehyde/L-menthol, respectively), on histamine-induced itch, wheals and neurogenic inflammation in 13 healthy volunteers. Histamine 1% was applied to the volar forearms using skin prick-test lancets. Recorded outcome-parameters were itch intensity, wheal reactions, and neurogenic inflammation (measured by laser-speckle perfusion-imaging). Homotopic thermal counter-irritation was performed with 6 temperatures, ranging from 4°C to 37°C, using a 3 × 3-cm thermal stimulator. Chemical "cold-like" counter-irritation was conducted with 40% L-menthol and 10% trans-cinnamaldehyde, while 5% doxepin was used as a positive antipruritic control/comparator. Cold counter-irritation stimuli from 4°C to 22°C inhibited itch in a stimulus-intensity-dependent manner (p cold-like" counter-irritation with both L-menthol and trans-cinnamaldehyde had antipruritic efficacy similar to doxepin (p Cold-induced counter-irritation had an inhibitory effect on histaminergic itch, suggesting that agonists of cold transduction receptors could be of potential antipruritic value.
used for experiments 1 and 2 was the Mantadil base (polawax, mineral oil, white petrolatum, methyl paraben and purified water USP) and was prepared...experiments 1 and 2 was the antadil base (polawax, mineral oil, white petrolatum, methyl paraben and purified water USP) and was prepared by the Burroughs
Beningo, K E; Scott, D W; Miller, W H; Rothstein, E
Tetracycline and niacinamide were administered in combination to 19 atopic dogs to determine their effectiveness in controlling pruritus. The pruritus was controlled successfully in only one dog. One dog experienced diarrhea that was severe enough to warrant stopping the medication. PMID:10200886
Beningo, K E; Scott, D W; Miller, W H; Rothstein, E
Tetracycline and niacinamide were administered in combination to 19 atopic dogs to determine their effectiveness in controlling pruritus. The pruritus was controlled successfully in only one dog. One dog experienced diarrhea that was severe enough to warrant stopping the medication.
Andersen, H. H.; Marker, J. B.; Hoeck, E. A.
%, administered prick test lancets) and cowhage (40–45 spicules) were applied to the pretreated areas. Evoked itch and pain intensities were recorded for 10 min using a visual analogue scale (0–10 cm), while sensitivity to touch-evoked itch was evaluated using von Frey filaments before and after itch provocations...
Odan, Masahide; Ishizuka, Natsuki; Hiramatsu, Yoshiharu; Inagaki, Masanao; Hashizume, Hiroshi; Fujii, Yasuhiko; Mitsumori, Susumu; Morioka, Yasuhide; Soga, Masahiko; Deguchi, Masashi; Yasui, Kiyoshi; Arimura, Akinori
Our lead compound 1 showed high affinity for both CB1 and CB2 receptors, suggesting the possibility of inducing psychoactive side effects through the CB1 receptor in the brain. To solve this issue, polar functional groups were introduced at the 3-position of the pyridone core of compound 1 to find CB1/2 dual agonists such as 17 and 20 which did not show any CNS side effects. Copyright © 2012 Elsevier Ltd. All rights reserved.
Lee, Hyun Joo; Cho, Sang Hyun
Korean red ginseng (KRG) and ginsenosides exhibit diverse biological effects, including anti-inflammatory and anti-allergic. We aimed to investigate the therapeutic effect of KRG in a murine model of atopic dermatitis (AD) is mediated whether by diminishing the pruritus or by suppressing the inflammation. Thirty NC/Nga mice were randomly divided to 5 groups. AD-like skin lesions were induced by percutaneous challenge with 2,4,6-trinitro-1-chrolobenzene (TNCB) on the ears and backs of NC/Nga mice. KRG extract, evening primrose oil, cyclosporine, and phosphate-buffered saline were administered orally by a gastric tube. Each study group was also divided into scratching-permitted and scratching-restricted subgroups to evaluate the impact of scratching behavior on AD. The effects of KRG and the other agents were assessed by measuring the clinical severity score, ear thickness, extent of transepidermal water loss (TEWL), number of scratching movements, total systemic immunoglobulin E (IgE) and interleukin (IL)-31 levels, histologic changes of cutaneous lesions, and mRNA expression levels of tumor necrosis factor (TNF)-α, interferon (IFN)-γ, thymic stromal lymphopoietin (TSLP), and IL-31. KRG exerts therapeutic effects against AD by inhibiting the T helper 2 (Th2) mediated inflammation as well as by diminishing the itching sensation. Moreover, restricting scratching behavior suppresses the vicious cycle of itching and scratching, thus reducing clinical and systemic inflammation in our murine model of AD. © 2017 The Korean Academy of Medical Sciences.
A comparison of dexamethasone, ondansetron, and dexamethasone plus ondansetron as prophylactic antiemetic and antipruritic therapy in patients receiving intrathecal morphine for major orthopedic surgery.
In a prospective, double-blinded, randomized trial, we evaluated the efficacy of IV (a) dexamethasone 8 mg, (b) ondansetron 8 mg, and (c) dexamethasone 8 mg plus ondansetron 4 mg for the prevention of postoperative nausea, vomiting (PONV), and pruritus in 130 (ASA physical status I to III) patients undergoing elective major orthopedic surgery after spinal anesthesia with hyperbaric 0.5% bupivacaine and intrathecal morphine. After spinal anesthesia, patients were randomized to one of three groups. Failure of PONV prophylaxis in the 24-h postoperative period occurred more frequently in patients who received dexamethasone alone (29 of 40; 73%) compared with those who received either ondansetron alone (23 of 47; 49%) (P = 0.02) or dexamethasone plus ondansetron together (19 of 43; 44%)(P = 0.01). There was no difference in the incidence of failure of prophylaxis of pruritus (70%, 72%, and 70% in dexamethasone 8 mg, ondansetron 8 mg, and dexamethasone 8 mg plus ondansetron 4 mg, respectively) (P > 0.1) in the 24-h postoperative period. We conclude that the administration of dexamethasone 8 mg with ondansetron 4 mg has no added benefit compared with ondansetron 8 mg alone in the prophylaxis of PONV and pruritus. IMPLICATIONS: Postoperative nausea and vomiting (PONV) and pruritus are common side effects after spinal opioid administration. In this study, dexamethasone 8 mg plus ondansetron 4 mg was as effective as ondansetron 8 mg. The administration of dexamethasone alone was associated with a frequent incidence of PONV, demonstrating a lack of efficacy. This has important cost implications.
... use. (i) Topically: Use either ointment in dogs and cats for anti-inflammatory, antipruritic... ointment in dogs and cats for the treatment of acute and chronic otitis and interdigital cysts, and in dogs.... Not intended for treatment of deep abscesses or deep-seated infections. Not for ophthalmic use...
Conclusion: The current study found for the first time that RGE effectively blocks histamine-induced itch in peripheral sensory neurons. We believe that the current results will provide an insight on itch transmission and will be helpful in understanding how RGE exerts its antipruritic effects.
African J. TradCAM
It is also used for dry coughs and gastric ulcers (Winston, 2004). Recent research indicates Shatavari enhances immune function, increases corticosteroid production, and promotes cell regeneration (Rege et al., 1999). In Thailand the root is claimed as a galactagogue, antidysenteric, antipeptic, antipruritic, antirheumatic,.
BACKGROUND: The incidence of pruritus after elective caesarean section under spinal anaesthesia with subarachnoid morphine may be 60-100%, and is a common cause of maternal dissatisfaction. Ondansetron has been shown to reduce pruritus but the effect is short-lived. The objective of this randomized double-blind trial was to evaluate the anti-pruritic efficacy of granisetron compared with ondansetron. METHODS: Eighty ASA I or II women undergoing elective caesarean section received spinal anaesthesia with 0.5% hyperbaric bupivacaine 10 mg, fentanyl 25 microg and preservative-free morphine 150 microg. After delivery of the baby and clamping of the umbilical cord, they were randomised to receive granisetron 3mg i.v. (group G) or ondansetron 8 mg i.v. (group O). RESULTS: The two groups were similar for age, gestational age, height and weight. According to visual analogue pruritus scores, patients in group G experienced less pruritus at 8h (P=0.003) and 24h (P=0.01). Fewer patients in group G (n=8) than group O (n=18) required rescue anti-pruritic medication (P=0.03). Satisfaction scores were also higher in group G than in group O (P=0.03). There was no difference in overall incidence of pruritus, nausea and vomiting, and visual analogue pain scores between the two groups. CONCLUSIONS: Administration of granisetron 3mg i.v. reduces the severity of pruritus and the use of rescue anti-pruritic medication, and improves satisfaction but does not reduce the overall incidence of pruritus in women who have received subarachnoid morphine 150 microg compared to ondansetron 8 mg i.v.
Kido-Nakahara, Makiko; Furue, Masutaka; Ulzii, Dugarmaa; Nakahara, Takeshi
Chronic itch in inflammatory skin diseases, such as atopic dermatitis, markedly diminishes the quality of life of affected individuals. Comprehensive progress has been made in understanding itch signaling and associated mediators in the skin, dorsal root ganglia, spinal cord, and central nervous system, which may amplify or suppress atopic itch. Conventional therapies for atopic dermatitis are capable of reducing atopic itch; however, most patients are not satisfied with the antipruritic capacity of conventional treatments. Exploring itch pathways and mechanisms may lead to novel therapeutic approaches for atopic itch. Copyright Â© 2016 Elsevier Inc. All rights reserved.
Salaga, M; Polepally, P R; Zielinska, M; Marynowski, M; Fabisiak, A; Murawska, N; Sobczak, K; Sacharczuk, M; Do Rego, J C; Roth, B L; Zjawiony, J K; Fichna, J
The opioid system plays a crucial role in several physiological processes in the CNS and in the periphery. It has also been shown that selective opioid receptor agonists exert potent inhibitory action on pruritus and pain. In this study we examined whether two analogues of Salvinorin A, PR-37 and PR-38, exhibit antipruritic properties in mice. To examine the antiscratch effect of PR-37 and PR-38 we used a mouse model of compound 48/80-induced pruritus. In order to elucidate the mechanism of action of tested compounds, specific antagonists of opioid and cannabinoid receptors were used. The effect of PR-37 on the CNS was assessed by measuring motor parameters and exploratory behaviours in mice. PR-37 and PR-38, jnjected s.c., significantly reduced the number of compound 48/80-induced scratching behaviours in mice in a dose- and time-dependent manner. PR-38 was also active when orally administered. The antiscratch activity of PR-37 was blocked by the selective κ opioid receptor antagonist, nor-binaltorphimine, and that of PR-38 by the selective μ opioid receptor antagonist, β-funaltrexamine. In conclusion, a novel framework for the development of new antipruritic drugs derived from salvinorin A has been validated. © 2015 The British Pharmacological Society.
Stull, Carolyn; Lavery, Michael J; Yosipovitch, Gil
Chronic pruritus is a common symptom that arises from both dermatologic and non-dermatologic conditions including chronic kidney disease, cholestasis, lymphoma and neuropathy. Over the past decade, research has elucidated many of the receptors, neuropeptides and cytokines involved in itch sensation and transmission. In addition, the first biomarker for cholestatic itch has been discovered. These findings have led to the development of a host of novel antipruritic medications, both on the market and in the pipeline. A summary of new and emerging treatments for pruritus, as well as possible targets for future therapeutic development is provided. At present, there is no universally effective treatment available for all types of chronic pruritus. A combination of topical and systemic therapies addressing peripheral mediators, and a top-down approach targeting the brain and spinal cord, seems preferable to a single agent approach. Neural hypersensitization plays a significant role in many forms of chronic pruritus and may be downregulated by new treatments. In addition, specific neuropeptides are now targeted by novel antipruritic therapies. Furthermore, targeted biologic agents are anticipated to play a significant role in treating pruritus of inflammatory origin.
Wohlrab, Johannes; Kreft, Daniela
Niacinamide, an amide of vitamin B3 (niacin), is a hydrophilic endogenous substance. Its effects after epicutaneous application have long been described in the literature. Given a sufficient bioavailability, niacinamide has antipruritic, antimicrobial, vasoactive, photo-protective, sebostatic and lightening effects depending on its concentration. Within a complex metabolic system niacinamide controls the NFκB-mediated transcription of signalling molecules by inhibiting the nuclear poly (ADP-ribose) polymerase-1 (PARP-1). Niacinamide is a well-tolerated and safe substance often used in cosmetics. Clinical data for its therapeutic use in various dermatoses can increasingly be found in the literature. Although the existing data are not sufficient for a scientifically founded evaluation, it can be stated that the use of niacinamide in galenic preparations for epicutaneous application offers most interesting prospects. © 2014 S. Karger AG, Basel.
Roelofzen, J.H.J.; Aben, K.K.H.; Van Der Valk, P.G.M.; Van Houtum, J.L.M.; Van De Kerkhof, P.C.M.; Kiemeney, L.A.L.M. [Radboud University Nijmegen Medical Center, Nijmegen (Netherlands). Dept. of Dermatology
Coal tar is one of the oldest treatments for psoriasis and eczema. It has anti-inflammatory, antibacterial, antipruritic and antimitotic effects. The short-term side effects are folliculitis, irritation and contact allergy. Coal tar contains carcinogens. The carcinogenicity of coal tar has been shown in animal studies and studies in occupational settings. There is no clear evidence of an increased risk of skin tumors or internal tumors. Until now, most studies have been fairly small and they did not investigate the risk of coal tar alone, but the risk of coal tar combined with other therapies. New, well-designed, epidemiological studies are necessary to assess the risk of skin tumors and other malignancies after dermatological use of coal tar.
Haemorrhoids or piles are varicosities in the anal canal caused by local pressure. Sometimes they prolapse. Symptoms may include itching, discomfort, pain and bleeding. Haemorrhoids are common in pregnancy. Constipation aggravates piles, so a healthy diet with plenty of water and fibre is advisable. Some sufferers need an appropriate laxative as well. Cleanliness of the anal area is important. Proprietary moist toilet tissues are sold for this purpose and can be soothing and helpful. Relief of symptoms is by haemorrhoid creams, ointments and suppositories. Active ingredients typically include antiseptics, anti-inflammatories, anti-pruritics and local anaesthetics. Many are available from pharmacies without a prescription. If in doubt, always refer the patient to a doctor. For example, rectal bleeding may be due to some more serious condition, or pruritus to anal thrush. In the case of children the advice of a doctor should be sought.
Lee, Heeseung; Ko, Mei-Chuan
How neuropeptides in the primate spinal cord regulate itch and pain is largely unknown. Here we elucidate the sensory functions of spinal opioid-related peptides and gastrin-releasing peptide (GRP) in awake, behaving monkeys. Following intrathecal administration, β-endorphin (10-100 nmol) and GRP (1-10 nmol) dose-dependently elicit the same degree of robust itch scratching, which can be inhibited by mu-opioid peptide (MOP) receptor and GRP receptor (BB2) antagonists, respectively. Unlike β-endorphin, which produces itch and attenuates inflammatory pain, GRP only elicits itch without affecting pain. In contrast, enkephalins (100-1000 nmol) and nociceptin-orphanin FQ (3-30 nmol) only inhibit pain without eliciting itch. More intriguingly, dynorphin A(1-17) (10-100 nmol) dose-dependently attenuates both β-endorphin- and GRP-elicited robust scratching without affecting pain processing. The anti-itch effects of dynorphin A can be reversed by a kappa-opioid peptide (KOP) receptor antagonist nor-binaltorphimine. These nonhuman primate behavioral models with spinal delivery of ligands advance our understanding of distinct functions of neuropeptides for modulating itch and pain. In particular, we demonstrate causal links for itch-eliciting effects by β-endorphin-MOP receptor and GRP-BB2 receptor systems and itch-inhibiting effects by the dynorphin A-KOP receptor system. These studies will facilitate transforming discoveries of novel ligand-receptor systems into future therapies as antipruritics and/or analgesics in humans.
Thomas, Jackson; Carson, Christine F; Peterson, Greg M; Walton, Shelley F; Hammer, Kate A; Naunton, Mark; Davey, Rachel C; Spelman, Tim; Dettwiller, Pascale; Kyle, Greg; Cooper, Gabrielle M; Baby, Kavya E
Globally, scabies affects more than 130 million people at any time. In the developed world, outbreaks in health institutions and vulnerable communities result in a significant economic burden. A review of the literature demonstrates the emergence of resistance toward classical scabicidal treatments and the lack of effectiveness of currently available scabicides in reducing the inflammatory skin reactions and pyodermal progression that occurs in predisposed patient cohorts. Tea tree oil (TTO) has demonstrated promising acaricidal effects against scabies mites in vitro and has also been successfully used as an adjuvant topical medication for the treatment of crusted scabies, including cases that did not respond to standard treatments. Emerging acaricide resistance threatens the future usefulness of currently used gold standard treatments (oral ivermectin and topical permethrin) for scabies. The imminent development of new chemical entities is doubtful. The cumulative acaricidal, antibacterial, antipruritic, anti-inflammatory, and wound healing effects of TTO may have the potential to successfully reduce the burden of scabies infection and the associated bacterial complications. This review summarizes current knowledge on the use of TTO for the treatment of scabies. On the strength of existing data for TTO, larger scale, randomized controlled clinical trials are warranted. © The American Society of Tropical Medicine and Hygiene.
Full Text Available Menthol is a naturally occurring monoterpene alcohol possessing remarkable biological properties including antipruritic, analgesic, antiseptic, anti-inflammatory and cooling effects. Here, we examined the menthol-evoked Ca2+ signals in breast and prostate cancer cell lines. The effect of menthol (50â500Â ÂµM was predicted to be mediated by the transient receptor potential ion channel melastatin subtype 8 (TRPM8. However, the intensity of menthol-evoked Ca2+ signals did not correlate with the expression levels of TRPM8 in breast and prostate cancer cells indicating a TRPM8-independent signaling pathway. Menthol-evoked Ca2+ signals were analyzed in detail in Du 145 prostate cancer cells, as well as in CRISPR/Cas9 TRPM8-knockout Du 145 cells. Menthol (500Â ÂµM induced Ca2+ oscillations in both cell lines, thus independent of TRPM8, which were however dependent on the production of inositol trisphosphate. Results based on pharmacological tools point to an involvement of the purinergic pathway in menthol-evoked Ca2+ responses. Finally, menthol (50â500Â ÂµM decreased cell viability and induced oxidative stress independently of the presence of TRPM8 channels, despite that temperature-evoked TRPM8-mediated inward currents were significantly decreased in TRPM8-knockout Du 145 cells compared to wild type Du 145 cells. Keywords: Ca2+ oscillations, TRPM8, Menthol, Oxidative stress, Purinergic signaling
Thomas, Jackson; Carson, Christine F.; Peterson, Greg M.; Walton, Shelley F.; Hammer, Kate A.; Naunton, Mark; Davey, Rachel C.; Spelman, Tim; Dettwiller, Pascale; Kyle, Greg; Cooper, Gabrielle M.; Baby, Kavya E.
Globally, scabies affects more than 130 million people at any time. In the developed world, outbreaks in health institutions and vulnerable communities result in a significant economic burden. A review of the literature demonstrates the emergence of resistance toward classical scabicidal treatments and the lack of effectiveness of currently available scabicides in reducing the inflammatory skin reactions and pyodermal progression that occurs in predisposed patient cohorts. Tea tree oil (TTO) has demonstrated promising acaricidal effects against scabies mites in vitro and has also been successfully used as an adjuvant topical medication for the treatment of crusted scabies, including cases that did not respond to standard treatments. Emerging acaricide resistance threatens the future usefulness of currently used gold standard treatments (oral ivermectin and topical permethrin) for scabies. The imminent development of new chemical entities is doubtful. The cumulative acaricidal, antibacterial, antipruritic, anti-inflammatory, and wound healing effects of TTO may have the potential to successfully reduce the burden of scabies infection and the associated bacterial complications. This review summarizes current knowledge on the use of TTO for the treatment of scabies. On the strength of existing data for TTO, larger scale, randomized controlled clinical trials are warranted. PMID:26787146
Veraldi, Stefano; De Micheli, Paolo; Schianchi, Rossana; Lunardon, Luisa
Atopiclair (Zarzenda) is a topical non-steroidal anti-inflammatory agent for the treatment of allergic diseases of the skin. Three main ingredients are contained in this product: glycyrrhetinic acid, telmesteine and Vitis vinifera extracts. Other ingredients include: allantoin, alpha-bisabolol, capryloyl glycine, hyaluronic acid, shea butter and tocopheryl acetate. Two previous randomized, double-blind, vehicle-controlled clinical studies provided evidence that Atopiclair is effective in the treatment of atopic dermatitis. This article presents an open, multicenter, sponsor-free, study on the anti-pruritic activity of this product in adult patients with mild-to-moderate atopic dermatitis. The Median Visual Analogue Scale (VAS) values were: at the start of the study (TO), median VAS was 48.5 mm; three weeks later (T1), median VAS was 34.1 mm (-14.4 mm from baseline); six weeks later (T2), median VAS was 24.6 mm (-23.9 mm from baseline). Statistical analysis revealed that differences between TO versus T1, TO versus T2 and T1 versus T2 were highly significant (p<0.001). Side effects (local burning) were relatively common, although mild in severity. On the basis of the results of this study, Atopiclair showed efficacy in relief of pruritus in adult patients with mild-to-moderate atopic dermatitis.
Cho, Byoung Ok; Che, Denis Nchang; Yin, Hong Hua; Shin, Jae Young; Jang, Seon Il
Atopic dermatitis, a chronic relapsing and pruritic inflammation of the skin also thought to be involved in, or caused by immune system destruction is an upsetting health problem due to its continuously increasing incidence especially in developed countries. Mast cell infiltration in atopic dermatitis skin lesions and its IgE-mediated activation releases various cytokines and chemokines that have been implicated in the pathogenesis of atopic dermatitis. This study was aimed at investigating synergistic anti-inflammatory, anti-pruritic and anti-atopic dermatitis effects of Diospyros lotus leaf extract (DLE) and Muscat bailey A grapefruit stem extract (GFSE) in atopic dermatitis-like induced skin lesions in mice. Combinations of DLE and GFSE inhibited TNF-α and IL-6 production more than DLE or GFSE in PMA plus calcium ionophore A23187-activated HMC-1 cells. DLE and GFSE synergistically inhibited compound 48/80-induced dermal infiltration of mast cells and reduced scratching behavior than DLE or GFSE. Furthermore, DLE and GFSE synergistically showed a stronger ameliorative effect in skin lesions by reducing clinical scores; dermal infiltration of mast cells; ear and dorsal skin thickness; serum IgE and IL-4 production in atopic dermatitis-like mice. Collectively, these results suggest that DLE and GFSE synergistically exhibit anti-atopic dermatitis effects in atopic dermatitis-like skin lesions in mice. Copyright © 2017. Published by Elsevier Masson SAS.
Kim, Jong Rhan; Choi, Jinhwan; Kim, Jiyoung; Kim, Heejeung; Kang, Heerim; Kim, Eun Hye; Chang, Jeong-Hwa; Kim, Yeong-Eun; Choi, Young Jin; Lee, Ki Won; Lee, Hyong Joo
Ginseng and ginsenosides are frequently used in the treatment of chronic inflammatory diseases. Recently, 20-O-β-d-glucopyranosyl-20(S)-protopanaxadiol (GPD), the main metabolite of ginsenosides, was reported to have both anti-allergic and anti-pruritic effects. The immunomodulatory effects of GPD-fortified ginseng extract (GFGE) on atopic dermatitis (AD)-like symptoms in mice were investigated. This study was designed to investigate the preventive effect of GFGE on AD-like symptoms. The effects of orally administered GFGE on Dermatophagoides farinae body extract (DFE)-induced AD-like symptoms in NC/Nga mice were assessed by analyzing dermatitis score, ear thickness, scratching time, skin histological changes, and serum level of macrophage-derived chemokine (MDC). In addition, splenocytes were isolated from the mice and stimulated with anti-CD3 and anti-CD28 monoclonal antibodies to produce cytokines. Oral administration of GFGE significantly attenuated DFE-induced increases in dermatitis score, ear thickness, scratching time, and severity of skin lesions in NC/Nga mice. GFGE treatment also reduced level of MDC in serum, infiltration of eosinophils and mast cells in skin, and production of cytokines in splenocytes. These results suggest that GFGE might ameliorate DFE-induced AD-like symptoms and be an alternative therapeutic agent for the prevention of AD. © 2013 Published by Elsevier Ireland Ltd.
Full Text Available Nalfurafine hydrochloride [(E-N-[17-(cyclopropylmethyl-4,5α-epoxy-3,14-dihydroxymorphinan-6β-yl]-3-(furan-3-yl-N-methylprop-2-enamide monohydrochloride; nalfurafine] is used in Japan as an antipruritic for the treatment of intractable pruritus in patients undergoing hemodialysis or with chronic liver disease. It is a potent and selective agonist at the κ opioid receptor, but also has weak and partial agonist activity at μ opioid receptors. Opioids, especially those acting at μ receptors, carry a risk of abuse. This is an important factor in the consideration of therapeutic risk vs. benefit in clinical use and the potential for misuse as a public health problem. It is therefore necessary to carefully evaluate the reinforcing effects of nalfurafine. To this end, we investigated intravenous self-administration of nalfurafine in rhesus monkeys. The number of self-administration of nalfurafine at doses of 0.0625, 0.125 and 0.25 μg/kg/infusion was not higher than that of saline in rhesus monkeys that frequently self-administered pentazocine (0.25 mg/kg/infusion. These results indicate that nalfurafine has no reinforcing effect in rhesus monkeys in the intravenous self-administration paradigm.
Brasileiro, Lízie Emanuelle Eulalio; Barreto, Dayanna Patrícia de Carvalho; Nunes, Emerson Arcoverde
Among the wide range of symptoms neglected or resistant to conventional treatments in clinical practice, itch is emerging gradually as a theme to be studied. Itch complaints and the negative effects in the quality of life are observed in several medical fields. Although the partially obscure pathophysiology, some researchers decided to check and test the use of psychotropic drugs in resistant itch to conventional topical treatments and antihistamines. The objective of this study was to evaluate scientific evidence in psychotropic use in the treatment of itch of various causes. This is a systematic review of scientific literature. The following databases were used: PubMed, Web of Science, Scopus and Scielo. Randomized controlled trials that should focus on treatment with psychotropic drugs of pruritus of various causes were the inclusion criteria. All articles were analyzed by the authors, and the consensus was reached in cases of disagreement. Fifteen articles were included after analysis and selection in databases, with the majority of clinical trials focusing on psychopharmacological treatment of itch on account of chronic kidney disease. Clinical trials with psychotropic drugs mostly indicated significant improvement in the itching. In most trials of chronic kidney disease as basal disease for itch, greater effectiveness was observed with the use of psychotropic drugs compared with placebo or other antipruritic. However, the small amount of controlled trials conducted precludes the generalization that psychiatric drugs are effective for itch of various causes. PMID:28099602
Szepietowski, J C; Reich, A
Psoriasis is one of the most common chronic inflammatory skin diseases, found in about 1-3% of the general population. Pruritus affects about 60-90% of patients with psoriasis. The aim of this review was to summarize current knowledge about the pathogenesis and treatment of this symptom in psoriasis patients. Majority of psoriatic patients consider pruritus as the most bothersome symptom. The pathogenesis of pruritus is still unknown but the major concept of its origin is focused on neurogenic inflammation. Possible itch mediators include neuropeptides released from dermal nerve endings upon various stimuli, which were found to be abnormally expressed in itchy psoriatic plaques. Another important phenomenon supporting the idea of neurogenic inflammation as a key player in pruritus accompanying psoriasis is abnormal innervations of psoriatic skin. Possibly increased innervation density in psoriasis may decrease the threshold for pruritic stimuli. It is also suggested that pruritus in psoriasis might be related to abnormal functioning of the peripheral opioid system. Despite the high frequency of pruritus in psoriasis, to date there is no single antipruritic therapy dedicated specifically to treat itch in this disease. Neurogenic inflammation seems to be important for itchiness in psoriasis. Treatment of pruritus in patients with psoriasis should be directed towards the resolution of skin lesions, as disease remission usually is linked with pruritus relief. © 2015 European Pain Federation - EFIC®
Full Text Available Reverse osmosis (RO concentrate from wastewater reuse facilities contains concentrated emerging pollutants, such as pharmaceuticals. In this research, a paper-like composite sheet consisting of titanium dioxide (TiO2 and zeolite was synthesized, and removal of the antipruritic agent crotamiton from RO concentrate was studied using the TiO2/zeolite composite sheet. The RO concentrate was obtained from a pilot-scale municipal secondary effluent reclamation plant. Effective immobilization of the two powders in the sheet made it easy to handle and to separate the photocatalyst and adsorbent from purified water. The TiO2/zeolite composite sheet showed excellent performance for crotamiton adsorption without obvious inhibition by other components in the RO concentrate. With ultraviolet irradiation, crotamiton was simultaneously removed through adsorption and photocatalysis. The photocatalytic decomposition of crotamiton in the RO concentrate was significantly inhibited by the water matrix at high initial crotamiton concentrations, whereas rapid decomposition was achieved at low initial crotamiton concentrations. The major degradation intermediates were also adsorbed by the composite sheet. This result provides a promising method of mitigating secondary pollution caused by the harmful intermediates produced during advanced oxidation processes. The cyclic use of the HSZ-385/P25 composite sheet indicated the feasibility of continuously removing crotamiton from RO concentrate.
Full Text Available Chronic pruritus is a difficult condition to treat and is associated with several comorbidities, including insomnia, depression, and decreased quality of life. Treatment for chronic itch includes corticosteroids, antihistamines, and systemic therapies such as naltrexone, gabapentin, UV light therapy, and immunomodulatory treatments, including azathioprine, methotrexate, and cellcept. However, some patients still remain refractory to conventional therapy. Aprepitant is a neurokinin-1 receptor antagonist approved for the prevention of chemotherapy-induced and postoperative nausea and vomiting (CINV, PONV. Recently, aprepitant has demonstrated effectiveness in several case series and open label trials in relieving pruritus for patients refractory to other treatments. Patients with pruritus associated with Sézary syndrome, mycosis fungoides, lung adenocarcinoma, breast carcinoma, sarcomas, metastatic solid tumors, chronic kidney disease, hyperuricemia, iron deficiency, brachioradial pruritus, and Hodgkin’s lymphoma have experienced considerable symptom relief with short-term use of aprepitant (up to two weeks. Due to differences in reporting and evaluation of drug effects, the mechanism of aprepitant’s role is difficult to understand based on the current literature. Herein, we evaluate aprepitant’s antipruritic effects and discuss its mechanism of action and adverse effects. We propose that aprepitant is an alternative for patients suffering from pruritus who do not obtain enough symptom relief from conventional therapy.
Thomas, Jackson; Peterson, Greg M; Walton, Shelley F; Carson, Christine F; Naunton, Mark; Baby, Kavya E
Scabies is an ancient disease (documented as far back as 2500 years ago). It affects about 300 million people annually worldwide, and the prevalence is as high as about 60% in Indigenous and Torres Strait Islander children in Australia. This is more than six times the rate seen in the rest of the developed world. Scabies is frequently complicated by bacterial infection leading to the development of skin sores and other more serious consequences such as septicaemia and chronic heart and kidney diseases. This causes a substantial social and economic burden especially in resource poor communities around the world. Very few treatment options are currently available for the management of scabies infection. In this manuscript we briefly discuss the clinical consequences of scabies and the problems found (studies conducted in Australia) with the currently used topical and oral treatments. Current scabies treatment options are fairly ineffective in preventing treatment relapse, inflammatory skin reactions and associated bacterial skin infections. None have ovicidal, antibacterial, anti-inflammatory and/or anti-pruritic properties. Treatments which are currently available for scabies can be problematic with adverse effects and perhaps of greater concern the risk of treatment failure. The development of new chemical entities is doubtful in the near future. Though there may be potential for immunological control, the development of a vaccine or other immunotherapy modalities may be decades away. The emergence of resistance among scabies mites to classical scabicides and ineffectiveness of current treatments (in reducing inflammatory skin reactions and secondary bacterial infections associated with scabies), raise serious concerns regarding current therapy. Treatment adherence difficulties, and safety and efficacy uncertainties in the young and elderly, all signal the need to identify new treatments for scabies.
Thurmond, Robin L; Venable, Jennifer; Savall, Brad; La, David; Snook, Sandra; Dunford, Paul J; Edwards, James P
The discovery of the histamine H 4 receptor (H 4 R) provided a new avenue for the exploration of the physiological role of histamine, as well as providing a new drug target for the development of novel antihistamines. The first step in this process was the identification of selective antagonists to help unravel the pharmacology of the H 4 R relative to other histamine receptors. The discovery of the selective H 4 R antagonist JNJ 7777120 was vital for showing a role for the H 4 R in inflammation and pruritus. While this compound has been very successful as a tool for understanding the function of the receptor, it has drawbacks, including a short in vivo half-life and hypoadrenocorticism toxicity in rats and dogs, that prevented advancing it into clinical studies. Further research let to the discovery of JNJ 39758979, which, similar to JNJ 7777120, was a potent and selective H 4 R antagonist and showed anti-inflammatory and anti-pruritic activity preclinically. JNJ 39758979 advanced into human clinical studies and showed efficacy in reducing experimental pruritus and in patients with atopic dermatitis. However, development of this compound was terminated due to the occurrence of drug-induced agranulocytosis. This was overcome by developing another H 4 R antagonist with a different chemical structure, toreforant, that does not appear to have this side effect. Toreforant has been tested in clinical studies in patients with rheumatoid arthritis, asthma, or psoriasis. In conclusions there have been many H 4 R antagonists reported in the literature, but only a few have been studied in humans underscoring the difficulty in finding ligands with all of the properties necessary for testing in the clinic. Nevertheless, the clinical data to date suggests that H 4 R antagonists can be beneficial in treating atopic dermatitis and pruritus.
Grahofer, Alexander; Bannoehr, Jeanette; Nathues, Heiko; Roosje, Petra
Scabies is a contagious skin disease rarely described in miniature pigs. To the best of the authors' knowledge, a zoonotic transfer from infected pet pigs to humans has not been reported previously. This case report describes the infestation with Sarcoptes scabiei mites in two miniature pigs presenting with unusual clinical signs, and disease transmission to a child. Two 7-month-old male castrated miniature pig siblings were examined. Both had developed skin lesions, one animal was presented for neurological signs and emaciation. They were housed together in an indoor- and outdoor enclosure. Dermatological examination revealed a dull, greasy coat with generalized hypotrichosis and multifocal erythema. Microscopic examination of skin scrapings, impression smears of affected skin and ear swabs revealed high numbers of Sarcoptes mites in both animals as well as bacterial overgrowth. A subcutaneous injection of ivermectin 0.3 mg/kg was administered to both animals and repeated after 2 weeks. Both miniature pigs received subcutaneous injections with butafosfan and cyanocobalamin, were washed with a 3% chlorhexidine shampoo and were fed on a well-balanced diet. Pig enclosures were cleaned. The infested child was examined by a physician and an antipruritic cream was prescribed. Both miniature pigs and the child went into clinical remission after treatment. Sarcoptic mange is rare or even eradicated in commercial pig farming in many countries but miniature pigs may represent a niche for Sarcoptes scabiei infections. This case report indicates that miniature pigs kept as pets can efficiently transmit zoonotic disease to humans. In addition, these animals may represent a niche for Sarcoptes scabiei infestation in countries where sarcoptic mange in commercial pig farms has been eradicated and could therefore pose, a hazard for specific pathogen free farms.
Alexandru D P Papoiu
Full Text Available Histamine is the prototypical pruritogen used in experimental itch induction. However, in most chronic pruritic diseases, itch is not predominantly mediated by histamine. Cowhage-induced itch, on the other hand, seems more characteristic of itch occurring in chronic pruritic diseases.We tested the validity of cowhage as an itch-inducing agent by contrasting it with the classical itch inducer, histamine, in healthy subjects and atopic dermatitis (AD patients. We also investigated whether there was a cumulative effect when both agents were combined.Fifteen healthy individuals and fifteen AD patients were recruited. Experimental itch induction was performed in eczema-free areas on the volar aspects of the forearm, using different itch inducers: histamine, cowhage and their combination thereof. Itch intensity was assessed continuously for 5.5 minutes after stimulus application using a computer-assisted visual analogue scale (COVAS.In both healthy and AD subjects, the mean and peak intensity of itch were higher after the application of cowhage compared to histamine, and were higher after the combined application of cowhage and histamine, compared to histamine alone (p<0.0001 in all cases. Itch intensity ratings were not significantly different between healthy and AD subjects for the same itch inducer used; however AD subjects exhibited a prolonged itch response in comparison to healthy subjects (p<0.001.Cowhage induced a more intense itch sensation compared to histamine. Cowhage was the dominant factor in itch perception when both pathways were stimulated in the same time. Cowhage-induced itch is a suitable model for the study of itch in AD and other chronic pruritic diseases, and it can serve as a new model for testing antipruritic drugs in humans.
Kamatou, Guy P P; Vermaak, Ilze; Viljoen, Alvaro M; Lawrence, Brian M
Menthol is a cyclic monoterpene alcohol which possesses well-known cooling characteristics and a residual minty smell of the oil remnants from which it was obtained. Because of these attributes it is one of the most important flavouring additives besides vanilla and citrus. Due to this reason it is used in a variety of consumer products ranging from confections such as chocolate and chewing gum to oral-care products such as toothpaste as well as in over-the-counter medicinal products for its cooling and biological effects. Its cooling effects are not exclusive to medicinal use. Approximately one quarter of the cigarettes on the market contain menthol and small amounts of menthol are even included in non-mentholated cigarettes. Natural menthol is isolated exclusively from Mentha canadensis, but can also be synthesised on industrial scale through various processes. Although menthol exists in eight stereoisomeric forms, (-)-menthol from the natural source and synthesised menthol with the same structure is the most preferred isomer. The demand for menthol is high and it was previously estimated that the worldwide use of menthol was 30-32,000 metric tonnes per annum. Menthol is not a predominant compound of the essential oils as it can only be found as a constituent of a limited number of aromatic plants. These plants are known to exhibit biological activity in vitro and in vivo such as antibacterial, antifungal, antipruritic, anticancer and analgesic effects, and are also an effective fumigant. In addition, menthol is one of the most effective terpenes used to enhance the dermal penetration of pharmaceuticals. This review summarises the chemical and biological properties of menthol and highlights its cooling effects and toxicity. Copyright © 2013 Elsevier Ltd. All rights reserved.
Lopes, Cristina; Silva, Diana; Delgado, Luís; Correia, Osvaldo; Moreira, André
Atopic dermatitis (AD) is a relapsing inflammatory skin disease with a considerable social and economic burden. Functional textiles may have antimicrobial and antipruritic properties and have been used as complementary treatment in AD. We aimed to assess their effectiveness and safety in this setting. We carried out a systematic review of three large biomedical databases. GRADE approach was used to rate the levels of evidence and grade of recommendation. Meta-analyses of comparable studies were carried out. Thirteen studies (eight randomized controlled trials and five observational studies) met the eligibility criteria. Interventions were limited to silk (six studies), silver-coated cotton (five studies), borage oil, and ethylene vinyl alcohol (EVOH) fiber (one study each). Silver textiles were associated with improvement in SCORAD (2 of 4), fewer symptoms, a lower need for rescue medication (1 of 2), no difference in quality of life, decreased Staphyloccosus aureus colonization (2 of 3), and improvement of trans-epidermal water loss (1 of 2), with no safety concerns. Silk textile use was associated with improvement in SCORAD and symptoms (2 of 4), with no differences in quality of life or need for rescue medication. With borage oil use only skin erythema showed improvement, and with EVOH fiber, an improvement in eczema severity was reported. Recommendation for the use of functional textiles in AD treatment is weak, supported by low quality of evidence regarding effectiveness in AD symptoms and severity, with no evidence of hazardous consequences with their use. More studies with better methodology and longer follow-up are needed. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
Rachel A Gibson
Full Text Available Transient receptor potential vanilloid type 1 (TRPV1 is a non-selective cation channel widely expressed in skin tissues, and peripheral sensory nerve fibres. Activation of TRPV1 releases neuropeptides; the resulting neurogenic inflammation is believed to contribute to the development of pruritus. A TRPV1 antagonist has the potential to perform as an anti-pruritic agent. SB705498 is a TRPV1 antagonist that has demonstrated in vitro activity against cloned TRPV1 human receptors and when orally administered has demonstrated pharmacodynamic activity in animal models and clinical studies.To select a topical dose of SB705498 using the TRPV1 agonist capsaicin; to confirm engagement of the TRPV1 antagonistic action of SB705498 and assess whether the dose selected has an effect on itch induced by two challenge agents.A clinical study was conducted in 16 healthy volunteers to assess the effects of 3 doses of SB705498 on skin flare induced by capsaicin. Subjects with a robust capsaicin response were chosen to determine if the selected topical formulation of SB705498 had an effect on challenge agent induced itch.Following capsaicin challenge the greatest average reduction in area of flare was seen for the 3% formulation. This dose was selected for further investigation. Itch intensity induced by two challenge agents (cowhage and histamine was assessed on the Computerised Visual Analogue Scale. The difference in average itch intensity (Weighted Mean Over 15 Mins between the 3% dose of SB705498 and placebo for the cowhage challenge was -0.64, whilst the histamine challenge showed on average a -4.65 point change.The 3% topical formulation of SB705498 cream was clinically well tolerated and had target specific pharmacodynamic activity. However there were no clinically significant differences on pruritus induced by either challenge agent in comparison to placebo. SB705498 is unlikely to be of symptomatic benefit for histaminergic or non-histaminergic induced
Lin, Tzu-Kai; Man, Mao-Qiang; Santiago, Juan-Luis; Park, Kyungho; Roelandt, Truus; Oda, Yuko; Hupe, Melanie; Crumrine, Debra; Lee, Hae-Jin; Gschwandtner, Maria; Thyssen, Jacob P; Trullas, Carles; Tschachler, Erwin; Feingold, Kenneth R; Elias, Peter M
Systemic antagonists of the histamine type 1 and 2 receptors (H1/2r) are widely used as anti-pruritics and central sedatives, but demonstrate only modest anti-inflammatory activity. Because many inflammatory dermatoses result from defects in cutaneous barrier function, and because keratinocytes express both Hr1 and Hr2, we hypothesized that H1/2r antagonists might be more effective if they were used topically to treat inflammatory dermatoses. Topical H1/2r antagonists additively enhanced permeability barrier homeostasis in normal mouse skin by the following mechanisms: (i) stimulation of epidermal differentiation, leading to thickened cornified envelopes; and (ii) enhanced epidermal lipid synthesis and secretion. As barrier homeostasis was enhanced to a comparable extent in mast cell-deficient mice, with no further improvement following application of topical H1/2r antagonists, H1/2r antagonists likely oppose mast cell-derived histamines. In four immunologically diverse, murine disease models, characterized by either inflammation alone (acute irritant contact dermatitis, acute allergic contact dermatitis) or by prominent barrier abnormalities (subacute allergic contact dermatitis, atopic dermatitis), topical H1/2r agonists aggravated, whereas H1/2r antagonists improved, inflammation and/or barrier function. The apparent ability of topical H1r/2r antagonists to target epidermal H1/2r could translate into increased efficacy in the treatment of inflammatory dermatoses, likely due to decreased inflammation and enhanced barrier function. These results could shift current paradigms of antihistamine utilization from a predominantly systemic to a topical approach.
Buddenkotte, Jörg; Maurer, Marcus; Steinhoff, Martin
Itching (pruritus) is perhaps the most common symptom associated with inflammatory skin diseases and can be a lead symptom ofextracutaneous disease (e.g., malignancy, infection, metabolic disorders). In atopic dermatitis itching sensations constitute one of the most prominent and distressing features. The most characteristic response to itching is the scratch reflex: a more or less voluntary, often sub-conscious motor activity, to counteract the itch by slightly painful stimuli. The benefit of a short-termed relieve from itching through this scratch reflex though is counteracted by a simultaneous damage of the epidermal layer of the skin which leads to increased transepidermal water loss and drying, which in turn results in a cycle of more itching and more scratching. A wide range of peripheral itch-inducing stimuli generated within or administered to the skin are able to trigger pruritus, one of them being histamine. Based on early experiments, histamine has been suggested to may play a key role in the pathogenesis ofAD. This is reflected by a history for antihistamines in the therapeutic medication of AD patients. Antihistamines are believed to share a common antipruritic effect and therefore are prescribed to the vast majority of AD patient suffering from itch to act alleviating. The level of evidence in support of the benefits of antihistamine treatment, however, is low. To assess the benefit of antihistamines in the treatment of AD in a better way, their mechanisms and specific effects need to be understood more precisely. In particular their precise indication is crucial for successful use. This book chapter will therefore summarize and assess the role of histamine in AD and the efficacy of antihistamines in its treatment based on results of basic research and clinical studies.
Sanfilippo, Angela M; Barrio, Victoria; Kulp-Shorten, Carol; Callen, Jeffrey P
Skin lesions are encountered in all areas of medicine, and it is therefore important for physicians to understand the fundamentals of explaining and diagnosing common skin conditions. This article begins with a discussion of description and documentation of skin lesions based on color, size, morphology, and distribution. Pigmentation disorders such as vitiligo are depicted. Cutaneous growths that are found in the pediatric and adolescent population include acrochordons, dermatofibromas, keloids, milia, neurofibromas, and pyogenic granulomas. Treatment of these growths usually involves observation or curettage with electrodessication.Psoriasis, atopic dermatitis, poison ivy, and eczema are comprised of scaling patches and plaques; poison ivy and atopic dermatitis may also present with bullous and vesicular changes. Therapy typically consists of topical emollients and corticosteroids; phototherapy is reserved for refractory cases. Acne vulgaris is the most common skin disease of the pediatric and adolescent population. This condition can be psychologically debilitating and, therefore, proper treatment is of paramount importance. Therapeutic options include topical as well as oral antibiotics and retinoids. Extreme caution must be used when prescribing retinoids to post-pubescent females, as these agents are teratogenic. Vascular anomalies are most commonly exemplified as port wine stains and hemangiomas. Port wine stains may be treated with pulsed dye laser or may be observed if they are not of concern to the patient or physician. Hemangiomas typically spontaneously regress by age ten; however, there has been recent concern that certain cases may need to be treated. Dermal rashes may be localized or generalized. Treatment of generalized drug eruptions involves elimination of the inciting agent, topical antipruritics, and systemic corticosteroids for severe reactions. Infectious etiologic agents of skin disease include bacteria, fungi, and viruses. Many sexually
Kamata, Yayoi; Kimura, Utako; Matsuda, Hironori; Tengara, Suhandy; Kamo, Atsuko; Umehara, Yoshie; Iizumi, Kyoichi; Kawasaki, Hiroaki; Suga, Yasushi; Ogawa, Hideoki; Tominaga, Mitsutoshi; Takamori, Kenji
Atopic dermatitis (AD) is a multifactorial inflammatory skin disease characterized by skin barrier dysfunction, allergic inflammation and intractable pruritus resistant to conventional antipruritic treatments, including H 1 -antihistamines. Granzymes (Gzms) are a family of serine proteases expressed by cytotoxic T lymphocytes and natural killer cells that have been shown to modulate inflammation. However, the relationship between Gzms and pathology in AD remains unclear. This study assessed the correlation between plasma GzmB levels and severity of pruritus and dermatitis, in AD patients. Plasma was collected from 46 patients with AD, 24 patients with psoriasis, and 30 healthy controls. AD severity was assessed with the scoring atopic dermatitis (SCORAD) index, psoriasis severity with the psoriasis area and severity index (PASI), and degree of pruritus by visual analogue scale (VAS) score. GzmA, GzmB and gastrin releasing peptide (GRP) levels were measured by enzyme-linked immunosorbent assays. Plasma GzmB concentrations were significantly higher in patients with AD and psoriasis than in healthy controls. Correlation analyses showed that plasma GzmB concentrations positively correlated with SCORAD and serum levels of severity markers such as thymus and activation-regulated chemokine, and lactate dehydrogenase in AD patients. Moreover, plasma levels of GRP, an itch-related peptide, were higher in patients with AD, positively correlating with VAS score and plasma GzmB level. In addition, plasma GzmB concentration was significantly lower in the treatment group than the untreated group with AD. Meanwhile, there were no correlations among GzmB levels, VAS score and PASI score in patients with psoriasis. In contrast to the results of plasma GzmB, plasma GzmA levels were unchanged among AD, psoriasis and healthy groups, and showed no correlations with VAS score and SCORAD index in patients with AD. Plasma GzmB levels may reflect the degree of pruritus and dermatitis in
Robin L. Thurmond
Full Text Available The histamine H4 receptor (H4R was first noted as a sequence in genomic databases that had features of a G-protein coupled receptor. This putative receptor was found to bind histamine consistent with its homology to other histamine receptors and thus became the fourth member of the histamine receptor family. Due to the previous success of drugs that target the H1 and H2 receptors, an effort was made to understand the function of this receptor and determine if it represented a drug target. Taking advantage of the vast literature on histamine, a search for histamine activity that did not appear to be mediated by the other three histamine receptors was undertaken. From this asthma and pruritus emerged as areas of particular interest. Histamine has long been suspected to play a role in the pathogenesis of asthma, but antihistamines that target the H1 and H2 receptors have not been shown to be effective for this condition. The use of selective ligands in animal models of asthma has now potentially filled this gap by showing a role for the H4R in mediating lung function and inflammation. A similar story exists for chronic pruritus associated with conditions such as atopic dermatitis. Antihistamines that target the H1 receptor are effective in reducing acute pruritus, but are ineffective in pruritus experienced by patients with atopic dermatitis. As for asthma, animal models have now suggested a role for the H4R in mediating pruritic responses, with antagonists to the H4R reducing pruritus in a number of different conditions. The anti-pruritic effect of H4R antagonists has recently been shown in human clinical studies, validating the preclinical findings in the animal models. A selective H4R antagonist inhibited histamine-induced pruritus in health volunteers and reduced pruritus in patients with atopic dermatitis. The history to date of the H4R provides an excellent example of the deorphanization of a novel receptor and the translation of this into
Ahuja, Rajeev B; Gupta, Gaurav K
Post-burn itch is a distressing symptom in burns rehabilitation and its treatment often proves frustrating for the patient and the multidisciplinary burns team. Traditionally, the mainstay of antipruritic therapy for decades has been antihistamines and massage with emollients. With a better understanding of the neurophysiology of itch emerged a new dimension in the treatment of post-burn pruritus. Gabapentin, a centrally modulating anti-epileptic agent and α2δ ligand, proved in clinical trials to be immensely better in the treatment of post-burn pruritus. Pregabalin is a newer structural analog of gabapentin. It has a much better anxiolytic effect and pharmacokinetic profile as compared to gabapentin. The current study was initiated to specifically study the role of pregabalin in relieving post-burn itch as this has never been investigated before. This double blind, randomized and placebo controlled study had four arms and was carried out on 80 adult patients (20 each). The four arms were: pregabalin, cetirizine with pheniramine maleate, combination of pregabalin, cetirizine and pheniramine maleate, and placebo (vit. B comp.). Massage with coconut oil was integral to all groups. Drug dosage was determined by initial VAS (visual analog scale) scores. All groups matched in demographic data and initial VAS scores. VAS scores were evaluated over next 28 days (days 3, 7, 14, 21 and 28). In patients with mild itch (VAS scores 2-5) or moderate itch (VAS scores 6-8) near complete remission of itch was seen in combination group and pregabalin group where the response was comparable and close to 95%. This was significantly better response than antihistaminic combination or massage alone. However, massage alone was sufficient in decreasing mean scores in mild itch, in a large percentage of patients. Amongst the patients with severe itch (VAS scores 9-10), 3/6 and 6/7 patients dropped out of trial in the antihistaminic and placebo groups, respectively. Combination therapy
Ya. O. Butko
Full Text Available Introduction. Local therapy is an important method for treatment of dermatitis used to suppress the skin inflammation and the main related symptoms: hyperemia, edema, pruritus, lichenification etc. However today it is important to pay more attention to elimination of the skin dryness, restoration of the damaged epithelium and improvement of the skin barrier functions in dermatitis therapy. Considering all the requirements mentioned above, cream and ointment that correspond to the modern requirements of the local therapy were developed. They promote the decrease of inflammatory processes in skin (Mometasone furoate and Methylprednisolone atseponat are strong GCS with antipruritic, anti-inflammatory, vasoconstrictive, antiproliferative action and with minimum side effects, eliminate excessive skin dryness, restore the damaged epithelium, improve the skin condition and normalize the barrier functions of the skin (ceramides are the natural ceramides of the human’s skin. The purpose of this work was morphological study of the rats’ skin during treatment with cream “Mometasone with ceramides” and ointment “Methylprednisolone with ceramides” in the conditions of contact dermatitis inducted by turpentine. Materials and methods. Skin of animals was an object of the research after its treatment with cream “Mometasone with ceramides” and ointment “Methylprednisolone with ceramides”. The comparator preparations were cream “Elocom” and ointment “Advantan”. In the experiment 36 rats divided into groups were used. All the preparations were applied on the skin in a thin layer once a day. After the 5th day of the treatment animals were taken out of the experiment and all the tissue materials were fixed in 10% solution of formalin for morphological studies carrying out. Sections were stained with hematoxylin and eosine. An examination was carried out under the microscope Micros 400. Results of the research. The results showed that
Full Text Available Marie-Françoise Aries,1 Hélène Hernandez-Pigeon,1 Clémence Vaissière,1 Hélène Delga,1 Antony Caruana,1 Marguerite Lévêque,1 Muriel Bourrain,1,2 Katia Ravard Helffer,1 Bertrand Chol,3 Thien Nguyen,1 Sandrine Bessou-Touya,1 Nathalie Castex-Rizzi1 1Pierre Fabre Dermo-Cosmétique, Centre de Recherche & Développement Pierre Fabre, Toulouse, 2Sorbonne Universités, UPMC Univ Paris 06, CNRS, Laboratoire de Biodiversité et Biotechnologies Microbiennes (LBBM, Observatoire Océanologique, Banyuls/Mer, France; 3Centre d’Immunologie Pierre Fabre, Saint-Julien-en-Genevois, France Background: Atopic dermatitis (AD is a common skin disease characterized by recurrent pruritic inflammatory skin lesions resulting from structural and immune defects of the skin barrier. Previous studies have shown the clinical efficacy of Avène thermal spring water in AD, and a new microorganism, Aquaphilus dolomiae was suspected to contribute to these unique properties. The present study evaluated the anti-inflammatory, antipruritic, and immunomodulatory properties of ES0, an original biological extract of A. dolomiae, in immune and inflammatory cell models in order to assess its potential use in the treatment of AD.Materials and methods: An ES0 extract containing periplasmic and membrane proteins, peptides, lipopolysaccharides, and exopolysaccharides was obtained from A. dolomiae. The effects of the extract on pruritus and inflammatory mediators and immune mechanisms were evaluated by using various AD cell models and assays.Results: In a keratinocyte model, ES0 inhibited the expression of the inflammatory mediators, thymic stromal lymphopoietin, interleukin (IL-18, IL-4R, IL-8, monocyte chemoattractant protein-3, macrophage inflammatory protein-3α, and macrophage-derived chemokine and induced the expression of involucrin, which is involved in skin barrier keratinocyte terminal differentiation. In addition, ES0 inhibited protease-activated receptor-2 activation in
Ana Cristina Gomes Barros Salgado
Full Text Available Dermatological inflammatory diseases such as atopic dermatitis, psoriasis and seborrhoeic dermatitis often affect the scalp and the eyebrows. Although there are many dosage forms available, these are particularly critical anatomic regions for application of topical formulations because of the presence of hair. Lotions are therefore the recommended type of drug delivery system for these areas. The presence of hair may limit the application and thus the acceptability of the formulation and its compliance. Because of its low apparent viscosity, lotion application is unpleasant. Gels, given their consistency and adhesiveness, are a suitable alternative to lotions in this situation. The aim of this study was to formulate a stable gel containing mometasone furoate, which is an anti-inflammatory and anti-pruritic corticosteroid, in order to improve topical treatment of scalp dermatitis. In this study, pharmaceutical development, physical-chemical characterization, stability and in vitro permeation studies were performed. In terms of the pH, viscosity, assay and macroscopic and microbiological properties, the gel was stable over the period of study. The in vitro permeation studies allowed the characterization of the mometasone furoate permeation profile for the gel through different membranes. Mometasone furoate presented a slow permeation through the skin. This gel appears safe for topical application.Afecções dermatológicas do tipo inflamatório como a dermatite atópica, psoríase e dermatite seborreica, afetam freqüentemente o couro cabeludo e sobrancelhas. Apesar de existirem várias formas farmacêuticas para o seu tratamento, apenas as loções são indicadas para estas zonas, mas devido à baixa viscosidade, a aplicação de loções torna-se desagradável. Os geles, pela maior consistência e capacidade de adesão, apresentam-se como alternativa nesta situação. Neste trabalho procedeu-se ao desenvolvimento galênico de um gel com furoato
Fisara, Petr; Sargent, Roger M; Shipstone, Michael; von Berky, Andrew; von Berky, Janet
Background Canine flea-allergy dermatitis (FAD), a hypersensitivity response to antigenic material in the saliva of feeding fleas, occurs worldwide and remains a common presentation in companion animal veterinary practice despite widespread availability of effective systemic and topical flea-control products. Hypothesis/Objectives To evaluate the clinical response in dogs with FAD treated topically with indoxacarb, a novel oxadiazine insecticide. Animals Twenty-five client-owned dogs in Queensland, Australia diagnosed with pre-existing FAD on the basis of clinical signs, flea-antigen intradermal and serological tests. Methods An open-label, noncontrolled study, in which all dogs were treated with topical indoxacarb at 4 week intervals, three times over 12 weeks. Results Twenty-four dogs completed the study. Complete resolution of clinical signs of FAD was observed in 21 cases (87.5%), with nearly complete resolution or marked improvement in the remaining three cases. Mean clinical scores (Canine Atopic Dermatitis Extent and Severity Index-03) were reduced by 93.3% at week 12. Mean owner-assessed pruritus scores were reduced by 88% by week 12. Mean flea counts reduced by 98.7 and 100% in weeks 8 and 12, respectively. Conclusions and clinical importance Topical indoxacarb treatment applied every 4 weeks for 12 weeks, without concomitant antipruritic or ectoparasiticide therapy, completely alleviated flea infestations in all dogs and associated clinical signs of FAD in a high proportion of this population of dogs in a challenging flea-infestation environment. Résumé Contexte La dermatite par allergie aux piqures de puces (FAD), une hypersensibilité aux antigènes salivaires des puces, est décrite dans le monde entier et reste une présentation fréquente en médicine vétérinaire des animaux de compagnie malgré une large gamme d'antiparasitaires topiques et systémiques efficaces disponibles. Hypothèses/Objectifs Estimer la réponse clinique des chiens