Chronic Itch Research Articles

Mindfulness as Predictor of Itch Catastrophizing in Patients With Atopic Dermatitis: Results of a Cross-Sectional Questionnaire Study.

Itch and worry about itch are predominant symptoms in atopic dermatitis (AD). Mindfulness refers to paying attention in a certain way, non-judgementally and on purpose. In patients with chronic pain, which shares several similarities with chronic itch, a significant relationship between pain intensity, mindfulness and pain catastrophizing has been found. The aim of this study was to investigate whether itch intensity and mindfulness are related to itch catastrophizing in AD patients. Participants receiving treatment for AD (n = 155; 58 male; mean age: 46.5 ± 12 years) completed measures of itch-related catastrophizing (Itch Cognitions Questionnaire; ICQ) and mindfulness (Comprehensive Inventory of Mindfulness; CHIME) during their stay at a rehabilitation center in Borkum, Germany. In addition to other variables, their average itch intensity during the last 2 weeks was assessed by means of a visual analog scale. A positive relationship between itch intensity and itch catastrophizing was found (r = 0.409; p < 0.01). Moreover, the mindfulness scales “acting with awareness,” “accepting and non-judgemental orientation,” and “non-reactive orientation” were negatively related to itch catastrophizing. A linear regression analysis revealed that itch intensity in combination with “acting with awareness” was able to explain more than 27 % (corrected R2 = 0.274; p < 0.001) of the variance of itch catastrophizing. Thus, itch intensity and certain facets of mindfulness were associated with itch catastrophizing in AD patients. Psychological interventions aiming to increase acting with awareness might have a buffering effect on itch catastrophizing, which in turn could lead to lower itch intensity in patients with AD. Future RCTs should test this hypothesis.

Pruritus as a Distinctive Feature of Type 2 Inflammation.

Pruritus is a common symptom of several skin diseases, both inflammatory and neoplastic. Pruritus might have a tremendous impact on patients’ quality of life and strongly interfere with sleep, social, and work activities. We review the role of type-2 inflammation and immunity in the pathogenesis of chronic pruritic conditions of the skin. Type 2 cytokines, including IL-4, IL-13, thymic stromal lymphopoietin, periostin, IL-31, IL-25, and IL-33 are released by mast cells, innate lymphoid cells 2, keratinocytes, and type 2 T lymphocytes, and are master regulators of chronic itch. These cytokines might act as direct pruritogen on primary sensory neurons (pruriceptors) or alter the sensitivity to other itch mediators Type 2 inflammation- and immunity-dominated skin diseases, including atopic dermatitis, prurigo nodularis, bullous pemphigoid, scabies, parasitic diseases, urticaria, and Sézary syndrome are indeed conditions associated with most severe pruritus. In contrast, in other skin diseases, such as scleroderma, lupus erythematosus, hidradenitis suppurativa, and acne, type 2 inflammation is less represented, and pruritus is milder or variable. Th2 inflammation and immunity evolved to protect against parasites, and thus, the scratching response evoked by pruritus might have developed to alert about the presence and to remove parasites from the skin surface.

The CysLT2R receptor mediates leukotriene C4-driven acute and chronic itch

Acute and chronic itch are burdensome manifestations of skin pathologies including allergic skin diseases and atopic dermatitis, but the underlying molecular mechanisms are not well understood. Cysteinyl leukotrienes (CysLTs), comprising LTC4, LTD4, and LTE4, are produced by immune cells during type 2 inflammation. Here, we uncover a role for LTC4 and its signaling through the CysLT receptor 2 (CysLT2R) in itch. Cysltr2 transcript is highly expressed in dorsal root ganglia (DRG) neurons linked to itch in mice. We also detected CYSLTR2 in a broad population of human DRG neurons. Injection of leukotriene C4 (LTC4) or its nonhydrolyzable form NMLTC4, but neither LTD4 nor LTE4, induced dose-dependent itch but not pain behaviors in mice. LTC4-mediated itch differed in bout duration and kinetics from pruritogens histamine, compound 48/80, and chloroquine. NMLTC4-induced itch was abrogated in mice deficient for Cysltr2 or when deficiency was restricted to radioresistant cells. Itch was unaffected in mice deficient for Cysltr1, Trpv1, or mast cells (WSh mice). CysLT2R played a role in itch in the MC903 mouse model of chronic itch and dermatitis, but not in models of dry skin or compound 48/80- or Alternaria-induced itch. In MC903-treated mice, CysLT levels increased in skin over time, and Cysltr2-/- mice showed decreased itch in the chronic phase of inflammation. Collectively, our study reveals that LTC4 acts through CysLT2R as its physiological receptor to induce itch, and CysLT2R contributes to itch in a model of dermatitis. Therefore, targeting CysLT signaling may be a promising approach to treat inflammatory itch.

How Do Neurons Signal Itch?

Mechanistic theories of itch are based on neuronal specificity, stimulus intensity, and temporal or spatial discharge patterns. Traditionally, these theories are conceptualized as mutually exclusive, assuming that finding evidence for one theory would exclude the others and could sufficiently explain itch. Current experimental data primarily support the specificity or pattern theory of itch. However, in contrast to an assumed inherent exclusivity, recent results have shown that even within itch-specific pathways in the spinal cord, temporal discharge patterns are important as sustained pruriceptor is required to allow successful transsynaptic signal progression. Also, optogenetic activation of pruriceptors suggest that the combination of neuronal specificity and temporal pattern determines the sensory effect: tonic activation of pruriceptors is required to induce scratching behavior whereas short-lasting stimulation rather causes withdrawal. In addition to the mere duration of discharge, also the temporal pattern or spatial aspects could critically contribute to elicit pruritus instead of pain. Basic neurophysiological studies trying to validate neuronal theories for pruritus in their pure form provide unitary concepts leading from neuronal discharge to the itch sensation. However, the crucial clinical questions have the opposite perspective: which mechanisms explain the chronic itch in a given patient or a given disease? In trying to solve these clinical problems we should not feel bound to the mutual exclusive nature of itch theories, but rather appreciate blending several theories and also accept combinations of itch and pain. Thus, blended versions of itch theories might better suffice for an explanation of chronic itch in patients and will improve the basis for mechanistic treatment options.

A plant-derived TRPV3 inhibitor suppresses pain and itch.

Itching is the most frequent pathology in dermatology that has significant impacts on people's mental health and social life. Transient receptor potential vanilloid 3 (TRPV3) channel is a promising target for treating pruritus. However, few selecetive and potent antagonists have been reported. This study was designed to identify selective TRPV3 antagonist and elucidate its anti-pruritus pharmacology. FlexStation and calcium fluorescence imaging were conducted to track the functional compounds. Whole-cell patch clamp was used to record itch-related ion channel currents. Homologous recombination and site-directed mutagenesis were employed to construct TRPV3 channel chimeras and point mutations for exploring pharmacological mechanism. Mouse models were used for in vivo anti-pruritus assay. An acridone alkaloid (citrusinine-II) was purified and characterized from Atalantia monophylla. It directly interacts with Y564 within S4 helix of TRPV3 to selectively inhibit the channel with a half maximal inhibitory concentration (IC50 ) of 12.43 μM. Citrusinine-II showed potential efficacy to attenuate both chronic and acute itch. Intradermal administration of citrusinine-II (143 ng/skin site) nearly completely inhibited itch behaviours. It also shows significant analgesic effects. Little side effects of the compound are observed. By acting as a selective and potent inhibitor of TRPV3 channel, citrusinine-II shows valuable therapeutic effects in pruritus animal models and is a promising candidate drug and/or lead molecule for the development of anti-pruritus drugs.

Neuropathic Itch: Routes to Clinical Diagnosis.

Neuropathic itch occurs due to damage of neurons of the peripheral or central nervous system. Several entities, including metabolic, neurodegenerative, orthopedic, infectious, autoimmune, malignant, and iatrogenic conditions, may affect the somatosensory system and induce neuropathic itch. Due to the complex nature of neuropathic itch, particularly concerning its clinical presentation and possible etiological factors, diagnostic work-up of this condition is challenging. A detailed medical history, especially in regard to the itch, and a comprehensive physical examination are relevant to detect characteristic signs and symptoms of neuropathic itch and to rule out other possible causes for chronic itch. Complementary diagnostic exams, especially laboratory tests, determination of the intraepidermal nerve fiber density via a skin biopsy and radiological examinations may be indicated to confirm the diagnosis of neuropathic itch and to identify underlying etiological factors. Functional assessments such as quantitative sensory testing, nerve conduction studies, evoked potentials, or microneurography may be considered in particular cases. This review article provides a comprehensive overview of the diagnostic work-up recommended for patients with neuropathic itch.

Scabies-induced lichen simplex chronicus misdiagnosed as psychogenic pruritus: a case report

IntroductionLichen simplex chronicus has been defined as a localized skin condition characterized by thickening, hyperpigmentation and accentuated skin markings from chronic itching and from repeated scratching. The affected skin area is usually described as demarcated, and often circumscribed. It has even been defined as a “psychogenic pruritic disorder”. The idea of a neurological component has also been suggested, hence the term 'neurodermatitis circumscripta'. However, the pathophysiology of this condition remains unclear. Several associations and etiologies have been reported in literature, including strong links with mental disorders—anxiety and obsessive compulsive disorder to be specific. We report this case, most importantly, to highlight the value of an open-minded approach to patients and the 'old-fashioned' physician character of empathy, the skill of detailed history taking and physical examination, and lastly to suggest that lichen simplex chronicus may not always present as a localized, 'circumscripta' or demarcated area of skin.Case descriptionWhen a sixty-five year-old Caucasian female presented to our clinic agitated, intensely scratching her entire body and complaining of severe pruritus, an open-minded detailed approach during history taking and physical examination led to the working diagnosis of diffuse lichenification from chronic scratching secondary to a “possible” cutaneous disorder. Her medical history was unremarkable, but her psychiatric history was significant for Anxiety disorder. She remained on her anxiolytic medication. Her presenting symptom was reported to have persisted for more than 9 months. Review of previous unremarkable lab results and a remarkable findings on detailed skin inspection led to an empiric, trial regimen consisting of three topical preparations: an anti-pruritic—to break the itch-scratch cycle, anti-inflammatory—to curb any inflammatory/immune response and a 'last-ditch' scabicidal application. Follow-up was scheduled, but the patient called the office requesting an earlier follow up appointment. The lesions had significantly improved and the hyper-pigmented, indurated and escoriated skin appearance had resolved; and most importantly, the pruritus.ConclusionThus we conclude that lichen simplex chronicus may not always present as circumscribed or localized area of skin as currently noted in literature. Also, in patients with psychiatric conditions including anxiety and obsessive-compulsive disorder in particular, effort should be made to avoid stereotyping their presentation as part of their mental disorder spectrum. The value of detailed history and physical examination, mixed with empathy is highlighted. We make our recommendation considering the profound turnaround in the patient's condition and quality of life after several months of emotional and psychological suffering.

100 Hz Electroacupuncture Alleviated Chronic Itch and GRPR Expression Through Activation of Kappa Opioid Receptors in Spinal Dorsal Horn.

BackgroundClinical studies have shown that electroacupuncture (EA) alleviates chronic itch. Gastrin-releasing peptide receptor (GRPR) and dynorphin (DYN) in the spinal dorsal horn positively or negatively regulate itch, respectively. However, which frequency of EA is effective on relieving chronic itch and reducing the expression of GRPR, whether DYN-A in the spinal cord is involved in the underlying mechanism of the antipruritus effect of EA remains unknown.MethodsThe mixture of acetone and diethyl ether (1:1) [designated as AEW (acetone/diethyl ether and water) treatment] was used to induce the dry skin model of chronic itch. EA was applied to Quchi (LI11) and Hegu (LI4). Western blot was used to detect the expression of GRPR and DYN-A. Immunofluorescence was used to detect the expression of DYN-A.ResultsThe AEW administration induced remarkable spontaneous scratching, enhanced the expression of GRPR, and reduced the expression of DYN-A. Compared with the sham EA, 2 Hz EA, or 15 Hz EA group, 100 Hz EA was the most effective frequency for relieving chronic itch, reducing the expression of GRPR, and increasing the expression of DYN-A in the cervical dorsal horn. Furthermore, intraperitoneal injection of kappa opioid receptors (KORs) antagonist nor-Binaltorphimine dihydrochloride (nor-BNI) significantly reversed the effect of 100 Hz EA on the inhibition of both itching behavior and GRPR expression.ConclusionEA at 100 Hz is the most effective frequency that inhibits chronic itch and GRPR expression through activation of KORs in the spinal dorsal horn, which can effectively guide the clinical treatment and improve the antipruritic effect of acupuncture.

Formalin Itch Test: Low-Dose Formalin Induces Histamine-Independent, TRPA1-Mediated Itch in Mice.

Chronic itch is a common distressing symptom of many diseases, which reduced patient's quality of life. The mechanistic study on itch and screening for new anti-itch drugs require the development of new pre-clinical itch animal models. Herein, we established an acute itch model by intradermal (i.d.) injection of low-dose formalin into the neck or cheek in mice. In mice, i.d. injection of formalin (0.1–5%) in the nape of the neck evoked robust scratching behavior in a dose-dependent manner and the dose–response curves showed an inverted “U” shape. I.d. injection of formalin (0.3–0.6%) into the cheek evoked scratching in mice but wiping in rats, while formalin (1.25–5%) induced mixed wiping and scratching behavior in both mice and rats. Further, we found that 0.3% formalin-induced scratching was histamine-independent and significantly attenuated by transient receptor potential ion channel A1 (TRPA1) inhibitor (HC030031) or in TRPA1 knockout (KO) mice, but not affected by transient receptor potential ion channel V1 (TRPV1) inhibitor (capsazepine) or in TRPV1 KO mice. Additionally, 0.3% formalin-induced up-regulation of phosphorylation of extracellular regulated protein kinases (p-ERK) in the dorsal root ganglion (DRG) and scratching were suppressed by intrathecal injection of MEK inhibitor U0126 in mice. Incubation of 0.03% formalin induced the accumulation of intracellular reactive oxygen species (ROS) in the cultured DRG-derived cell line ND7-23, and formalin-induced itch was suppressed by antioxidants in mice. Finally, perfusion of 0.03% formalin induced elevation of intracellular calcium in a subset of primary cultured DRG neurons of mice. Thus, these results indicate that low-dose formalin induced non-histaminergic itch by activation of TRPA1 in mice, which may be employed as a useful acute itch model for screening potential anti-itch drugs.

Chronic Itch of Unknown Origin Is Associated With an Enhanced Th2 Skin Immune Profile.

Chronic pruritus of unknown origin (CPUO) is described as chronic itch lasting longer than 6 weeks in the absence of a defined skin rash and any known causative disease process. A retrospective study was performed on biopsy samples from patients with CPUO and normal controls to compare the immune profiles of these patients with healthy individuals. We used dual CD3/T-bet and CD3/GATA3 immunohistochemical staining to assess for T-cells expressing Th1 versus Th2 transcription factors, respectively. Our data showed that CD3+ cells of patients with CPUO co-express significantly more GATA3 compared with normal controls. Meanwhile, the normal control skin showed a much more balanced T-bet/GATA3 ratio of co-expression. Our data suggest an enrichment of Th2 cells in CPUO skin by T cell/GATA3 co-staining, supporting that CPUO is increasingly considered a type 2/Th2 cell-associated disease. We thus speculate that type 2 cytokine blockade-based therapies may represent effective treatments for CPUO.

The Role of Gut Microbiota in Chronic Itch-Evoked Novel Object Recognition-Related Cognitive Dysfunction in Mice.

The high incidence of patients with chronic itch highlights the importance of fundamental research. Recent advances in the interface of gut microbiota have shed new light into exploring this phenomenon. However, it is unknown whether gut microbiota plays a role in chronic itch in rodents with or without cognitive dysfunction. In this study, the role of gut microbiota in diphenylcyclopropenone (DCP)-evoked chronic itch was investigated in mice and hierarchical cluster analysis of novel object recognition test (ORT) results were used to classify DCP-evoked itch model in mice with or without cognitive dysfunction (CD)-like phenotype and 16S ribosomal RNA (rRNA) gene sequencing was used to compare gut bacterial composition between CD (Susceptible) and Non-CD phenotypes (Unsusceptible) in chronic itch mice. Results showed that the microbiota composition was significantly altered by DCP-evoked chronic itch and chronic itch induced novel object recognition-related CD. However, abnormal gut microbiota composition induced by chronic itch may not be correlated with novel object recognition-related CD.

Increased grey matter volume and associated resting-state functional connectivity in chronic spontaneous urticaria: A structural and functional MRI study

Background and purposeChronic itch is one of the most common irritating sensations, yet its mechanisms have not been fully elucidated. Although some studies have revealed relationships between itching and brain function, the structural changes in the brain induced by chronic itching, such as those accompanying chronic spontaneous urticaria (CSU), remain unclear. In this study, we aimed to explore the potential changes in brain structure and the associated functional circuitry in CSU patients to generate insights to aid chronic itch management. MethodsForty CSU patients and forty healthy controls (HCs) were recruited. Seven-day urticaria activity score (UAS7) values were collected to evaluate clinical symptoms. Voxel-based morphometry (VBM) and seed-based resting-state functional connectivity (rs-FC) analysis were used to assess structural changes in the brain and associated changes in functional circuitry. ResultsCompared with HCs, CSU patients had significantly increased grey matter (GM) volume in the right premotor cortex, left fusiform cortex, and cerebellum. UAS7 values were positively associated with GM volume in the left fusiform cortex. In CSU patients relative to HCs, the left fusiform cortex as extracted by VBM analysis demonstrated decreased functional connectivity with the right orbitofrontal cortex, medial prefrontal cortex (mPFC), premotor cortex, primary motor cortex (MI), and cerebellum and increased functional connectivity with the right posterior insular cortex, primary somatosensory cortex (SI), and secondary somatosensory cortex (SII). The left cerebellum as extracted from VBM analysis demonstrated decreased functional connectivity with the right supplementary motor area (SMA) and MI in CSU patients relative to HCs. ConclusionsOur findings indicate that patients suffering from chronic itching conditions, such as CSU, are likely to demonstrate altered GM volume in some brain regions. These changes may affect not only the sensorimotor area but also brain regions associated with cognitive function.

Acupuncture ameliorates not only atopic dermatitis-like skin inflammation but also acute and chronic serotonergic itch possibly through blockade of 5-HT2 and 5-HT7 receptors in mice

Acupuncture has been known to be effective for atopic dermatitis, especially ameliorating itch; however, its mechanisms are still unclear. The aim of this study was to test the anti-itch effects of acupuncture and to investigate its possible mechanisms. Acupuncture was performed at Gok-Ji (LI11) acupoints just before the injection of pruritogens in the mouse cheek model of acute itch and of MC903-induced atopic dermatitis displaying serotonergic chronic itch. Acupuncture significantly reduced acute itch triggered by compound 48/80, chloroquine, or especially serotonin. It also markedly reduced scratching behaviors evoked by the serotonin 5-HT2 receptor agonist α-methylserotonin and selective 5-HT7 receptor agonist LP 44. In addition, acupuncture treatment at LI11 had the preventive and therapeutic effects on persistent itch as well as the robust skin inflammation with epidermal thickening in mice with MC903-induced atopic dermatitis. It also considerably reduced the increased expression of 5-HT2A, 5-HT2B and 5-HT7 receptors in atopic dermatitis-like skin lesions in mice treated with MC903. Taken together, these findings highlight that acupuncture significantly ameliorates not only skin inflammation, but also acute and chronic serotonergic itch, possibly through blockade of serotonin 5-HT2 and 5-HT7 receptors.

Pruriplastic Itch-A Novel Pathogenic Concept in Chronic Pruritus.

The International Association for the Study of Pain (IASP) defined three descriptors for pain: nociceptive pain is “pain that arises from actual or threatened damage to non neural tissue and is due to the activation of nociceptors”; neuropathic pain is “pain caused by a lesion or disease of the somatosensory nervous system”; and nociplastic pain is “pain that arises from altered nociception despite no clear evidence of actual or threatened tissue damage causing the activation of peripheral nociceptors or evidence for disease or lesion of the somatosensory system causing the pain.” Based on clinical and pathophysiological arguments, a similar definition of “pruriplastic pruritus” should be made. Pruriplastic pruritus would include psychogenic pruritus, as well as some cases of pruritus ani, vulvar pruritus, sensitive skin or other poorly understood cases of pruritus. This new descriptor of itch could serve as systematic screening for altered pruriceptive function in patients who suffer from chronic itch and it may also help in defining better tailored treatment by identifying patients who are likely to respond better to centrally rather than to peripherally targeted therapies.

Clinical Characteristics of Itch in Renal Transplant Recipients.

Background: Chronic itch is the most common symptom in dermatology. End-stage renal disease-associated chronic itch (ESRDCI) is a common burden affecting up to 35% of patients treated with hemodialysis. Kidney transplant (KTx) is believed to be the best renal replacement therapy leading to the elimination of ESRDCI. The study was undertaken to characterize and assess the prevalence of itch among patients after renal transplantation.Methods: Between October 2019 and January 2020, we analyzed the data of 197 patients comprising 121 males (61.4%) and 76 females (38.6%) and aged 54.5 ± 13.6 years. The data collection was performed with a specially designed questionnaire. Level of itch after renal transplantation was assessed with the use of a Numeral Rating Scale, a Visual Rating Scale, and 4-Item Itch Questionnaire. Moreover, the previous 3 days of itching were evaluated.Results: The patients suffered from chronic renal disease for 20.2 ± 12.3 years, with a mean time of pre-transplant dialysis of 2.6 ± 2.4 years and a mean time after the KTx of 8.0 ± 6.5 years. The itch was present in 38.6% of the patients during the hemodialysis, and in 73.7% of cases, the itch ceased completely after the successful transplantation. Moreover, only 2.63% of the cases had no improvement. Nevertheless, the itch was reported in 42 (21.3%) renal transplant recipients (RTR), and in 22 (52.4%) cases, the itch appeared after transplantation. The majority of patients suffering from itch were women (54.8%). Itch in the last 3 days was reported in 21 patients. The itch's severity was assessed with a numerical rating scale (NRS), with the worst severity measured at 6 ± 2.2 points indicating moderate itch. In most cases (57.1%), itch affected multiple body areas. Extremities (50%) and the back (50%) were among the most frequently affected areas. The sensation had a mostly short duration and was most frequently reported in the evening. Only eight patients suffered for the whole day. Hot water was the most frequently reported (16.7%) alleviating factor, whilst sweat was responsible for itch aggravation in 35.9% of cases.Conclusion: Our analysis on representative patients' population indicates that itch after KTx is an important problem. Moreover, it is worth noting that more than half of the RTR did not suffer from itch during dialysis.

Electrically Evoked Itch in Human Subjects.

Administration of chemicals (pruritogens) into the skin evokes itch based on signal transduction mechanisms that generate action potentials mainly in mechanically sensitive and insensitive primary afferent C-fibers (pruriceptors). These signals from peripheral neurons are processed in spinal and supra-spinal centers of the central nervous system and finally generate the sensation of itch. Compared to chemical stimulation, electrical activation of pruriceptors would allow for better temporal control and thereby a more direct functional assessment of their activation. Here, we review the electrical stimulation paradigms which were used to evoke itch in humans in the past. We further evaluate recent attempts to explore electrically induced itch in atopic dermatitis patients. Possible mechanisms underlying successful pruritus generation in chronic itch patients by transdermal slowly depolarizing electrical stimulation are discussed.

Notaljia Parestetikalı Hastalardaki Omurga Patolojileri ve Güçlendirme Egzersizlerinin Kaşıntıyı Gidermede Olumlu Etkisi: Olgu Serisi

Objectives: Notalgia paresthetica is a subgroup of localized neuropathic chronic itch and is due to a nerve entrapment limited to the corresponding dermatome. Neuropathic itching often includes signs of sensitive skin syndrome (numbness, burning, stinging, tingling, etc.). It does not respond to antipruritic treatments used in other itchy dermatoses. The relationship between neuropathic itching and spinal pathology has been reported in many studies. Degenerative disc hernias may play a role in chronic itching localized to the back, hand, and brachioradial areas. We aimed to remind these patients we encountered in our clinical practice. Material and Methods: The files of 12 patients with notalgia paresthetica who applied to our dermatology outpatient clinic between 2016-2018 were reviewed. Diagnostic criteria are: No primary skin lesions in the affected skin area, the absence of any other itchy skin disease, detection of spinal pathology compatible with the itching area in magnetic resonance imaging, no other history of systemic disease or medication to explain itching. Results: Spinal canal stenosis, herniated nucleus pulposus, dural sac compression, and non-compressive bulging and protrusions were seen as spinal pathology. Itching completely disappeared in one of the four patients who conformed to the program, and the itch severity decreased in the other three patients. Conclusion: It should be kept in mind that itching may be of neuropathic origin in patients with localized chronic itching. Spine strengthening and stretching exercises may be a good option as primary or adjuvant therapy in neuropathic itching due to spinal pathology. Advanced clinical studies are needed.

A new synthetic protectin D1 analog 3-oxa-PD1n-3 DPA reduces neuropathic pain and chronic itch in mice.

The resolution of inflammation is a biosynthetically active process controlled by the interplay between oxygenated polyunsaturated mediators and G-protein coupled receptor-signaling pathways. These enzymatically oxygenated polyunsaturated fatty acids belong to distinct families of specialized pro-resolving autacoids. The protectin family of mediators has attracted an interest because of their potent pro-resolving and anti-inflammatory actions verified in several in vivo disease models. Herein, we present the stereoselective synthesis and biological evaluations of 3-oxa-PD1n-3 DPA, a protectin D1 analog. Results from mouse models indicate that the mediators protectin D1, PD1n-3 DPA and the new analog 3-oxa-PD1n-3 DPA all relieved streptozotocin-induced diabetic neuropathic pain at doses of 90 and 300 pmol, equivalent to 30 and 100 ng, respectively, following intrathecal (I.T.) injection. Of interest, at a low dose of only 30 pmol (10 ng; I.T.) only 3-oxa PD1n-3 DPA was able to alleviate neuropathic pain, directly compared to vehicle controls. Moreover, using a chronic itch model of cutaneous T-cell lymphoma (CTCL), all three compounds at 300 pmol (100 ng) showed a significant reduction in itching for several hours. The biomolecular information on the structure-functions of the protectins and the new synthetic analog 3-oxa-PD1n-3 DPA is of interest towards developing new immunoresolvents.

Perceived stress and coping methods with stress in patients with chronic itching

Perceived stress and coping methods with stress in patients with chronic itching

A Case of Bilateral Peripheral Ulcerative Keratitis

Peripheral ulcerative keratitis (PUK) is an aggressive, potentially sight-threatening cause for peripheral corneal thinning. It may precede the diagnosis of the systemic condition and therefore these cases require urgent investigation. A 43-year-old woman presented with bilateral tearing and ocular pain persisting for 7 months. Visual acuity was 6/6 in both eyes. On biomicroscopic examination, presence of crescent shaped corneal ulcer with perilesional haziness. A tear film study demonstrated decreased Schirmer test results (5mm in both eyes) and tear film break-up time (5 sec in both eyes). The interrogation and the patient revealed he had recurrent skin lesions in both legs with chronic itching, and recurrent oral and genital ulcers healing spontaneously. The diagnosis of Behcet disease was proposed. Pathergy test was negative, HLA B51 was positif. Systemic therapy was started with colchicine at a dose of 2mg/day. Eye drops and systemic prednisolone at 1mg/kg/day was continued with progressive decrease. The follow up at 3 months and 6 months showed no signs of recurrence of ulceration in both eyes. Corneal manifestation has rarely been reported in Behcet’s disease. Combined intraocular anterior and posterior segment inflammation are most common features of ocular Behcet disease. Collaborative management of ophthalmic patients having systemic illness along with internists improves overall outcomes and prevents morbidity in such patients.