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Query: UMLS:C0033774 (pruritus)
 14,546 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Classical description of syndromes produced by cutaneous leishmaniasis (CL) does not include sensory manifestations such as pain and/or itching, despite the evident upregulation of proinflammatory cytokines. Using a murine model of CL we report on evident hyperalgesia, as assessed by acute pain tests, and sustained upregulation of interleukin (IL-1beta) and nerve growth factor (NGF). This upregulation, especially that of NGF, may explain the observed hyperalgesia, in the light of recent evidence on the role of cytokines in the sensitization of nerve afferents and the subsequent hyperalgesia.
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PMID:Hyperalgesia and upregulation of cytokines and nerve growth factor by cutaneous leishmaniasis in mice. 1078 22

Symptoms of allergic rhinitis are produced by inflammatory mediators that are released upon activation of mast cells by antigen-IgE interaction. These mediators target the end organs directly or indirectly. Stimulation of sensory nerves by histamine, for example, leads to sneezing, pruritus, rhinorrhea, and nasal congestion. The clinical presentation of allergic rhinitis is also characterized by the phenomenon of hyperresponsiveness to nonallergic stimuli, such as cold air and various irritants. This phenomenon is believed to result from the effect of allergic inflammation on the sensory nerves that supply the upper airway mucosa. Various nonallergic triggers have been shown to act on the nasal mucosa through sensorineural stimulation. In allergic rhinitis, responsiveness to these stimuli is increased compared with the healthy state. A similar phenomenon is observed against such products of the allergic reaction as his-tamine and bradykinin. Also, in allergic rhinitis, stimulation of sensory nerves per se can produce inflammatory changes, a phenomenon known as neurogenic inflammation. The mechanism behind the development of sensorineural hyperresponsiveness and of increased propensity for neurogenic inflammation is unknown. However, evidence exists that the neurotrophin nerve growth factor, which can induce all these changes on sensory nerves, is produced in the human nasal mucosa and found in higher quantities in nasal secretions of patients with perennial allergic rhinitis as compared with healthy control subjects. Also, nerve growth factor is acutely released into nasal fluids after allergen provocation of patients with allergic disease. In patients with asthma of atopic origin, allergic rhinitis is almost ubiquitous. Because the nose is the air conditioner of the respiratory system, its dysfunction may negatively affect the lower airways. In addition to the conditioning of inhaled air, the association between allergic rhinitis and asthma may involve various mechanisms. For example, allergen provocation in the nose of a patient with asthma can lead to reductions in pulmonary function and to increased lower airway responsiveness after several hours. Also, nasal inflammation may propagate through a systemic route to affect the lower airways.
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PMID:Unique mechanistic features of allergic rhinitis. 1085 64

Neurotrophins and their receptors play an important role in cutaneous nerve development and reconstruction after injury. Recent developments indicate that this group of molecules not only exert a neurotrophic action, but are also involved in immune responses and inflammation. Prurigo nodularis is a skin disease characterized by neurohyperplasia and intense itch. In the present study, the localization and distribution of nerve growth factor (NGF) and its receptors were explored by immunohistochemical methods, with the aim of detecting the cause of the neurohyperplasia in the disease. In normal healthy volunteers and in uninvolved skin, NGF immunoreactivity was seldom seen in the basal layer of the epidermis or in the dermis. In prurigo nodularis skin, there was also very little NGF immunoreactivity in the epidermis. However, in the dermis, a huge number of cells showed an NGF-like immunoreactivity. In normal skin of healthy volunteers, only a weak staining for tyrosine kinase A (trkA) was seen in the epidermis, whereas in the dermis, there was no trkA staining seen at all. However, in the prurigo nodularis tissue, the hyperplastic nerves clearly showed trkA immunoreactivity, and it seemed that the staining was only present in the axons. By NGF and p75 NGF receptor double-labelling, both immunoreactivities showed weak staining in the epidermis and dermis of normal skin. However, in the dermis of prurigo nodularis, strong staining for both NGF and NGF receptor antibodies was seen. NGF receptor-immunoreactive nerves were more dense in areas where there were more NGF-immunoreactive cells. The results indicate that in prurigo nodularis skin, NGF is overexpressed, locally infiltrated inflammatory cells may be the source of this NGF, and NGF and its receptors may contribute to the neurohyperplasia of the disease.
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PMID:Increased nerve growth factor- and tyrosine kinase A-like immunoreactivities in prurigo nodularis skin -- an exploration of the cause of neurohyperplasia. 1187 44

The cutaneous neurosensory system is suggested to be involved in the pathophysiology of pruritus and skin diseases such as psoriasis. We investigated if repeated subinflammatory doses of ultraviolet B (UVB) irradiation similar to those used to treat pruritus or psoriasis would affect the cutaneous neurosensory system. Sprague-Dawley rats were irradiated thrice weekly for 2-4 weeks with subinflammatory doses of UVB. Three days after the last UVB exposure: (i), the skin contents of substance P (SP), calcitonin gene-related peptide (CGRP), and nerve growth factor (NGF) were quantified; (ii), the skin nerve fiber density was observed; and (iii), the effect of UVB on mustard oil-induced neurogenic inflammation was determined. UV exposure significantly increased SP and CGRP content and mustard oil-induced neurogenic inflammation in UV-irradiated but not non-irradiated skin; however, it did not affect cutaneous NGF content or overall nerve fiber density. These data suggest that repeated subinflammatory UVB irradiation locally increases the content of cutaneous SP and CGRP by an increase of neuropeptide content of nerve fibers rather than by an increase of overall nerve fiber density.
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PMID:Repeated subinflammatory ultraviolet B irradiation increases substance P and calcitonin gene-related peptide content and augments mustard oil-induced neurogenic inflammation in the skin of rats. 1218 38

Although the possible involvement of neurotrophic factors in itchy skins of atopic dermatitis has been predicted, the exact mechanism by which itch is induced remains unclear. Since nerve growth factor (NGF) has crucial effects on development and functions of sensory nerves, we determined production of NGF and extension of nerve fibers in skins of NC/NgaTnd mice with or without atopic dermatitis. NC/NgaTnd mice spontaneously develop atopic dermatitis-like skin lesions when they are raised in air-unregulated conventional circumstances. We quantified scratching behavior of NC/NgaTnd mice during the development of dermatitis using a novel analytical system and compared to clinical skin severity scores. A significant correlation between the severity of dermatitis and the increase in the number of scratches was identified, indicating that scratching behavior may associate with clinical skin conditions. NGF contents in the skin lesions of conventional NC/NgaTnd mice were significantly higher than those in SPF mice. Positive reactions for NGF were observed in keratinocytes and fibroblasts in affected skins of conventional NC/NgaTnd mice. Immunohistochemical analysis showed the extension of protein gene product 9.5-positive nerve fibers from the dermis toward the epidermis at the skin lesions. These results suggest that sensory nerves induced by NGF may contribute to development of itch, and that NGF produced at the affected site may provide abnormal skin sensitivity in atopic dermatitis.
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PMID:Expression of nerve growth factor in itchy skins of atopic NC/NgaTnd mice. 1621 Aug 4

It is suggested that atopic dermatitis is a skin disease associated with itching as subjective symptoms, and histamine H(1) receptor antagonists are used in order to prevent the itching, and the deterioration for scratch by itching. Histamine H(1) receptor selective anti-histamine olopatadine hydrochloride (olopatadine; Allelock shows consistent efficacy and safety in the treatment of allergic disorders. We investigated the possible efficacy of olopatadine on the number of scratching induced by repeated application of oxazolone in BALB/c mice. The repeated treatment of olopatadine significantly inhibited the ear swelling and the increased number of scratching. It significantly inhibited the increased production of interleukin (IL)-4, IL-1beta and granulocyte-macrophage colony-stimulating factor (GM-CSF) in the lesioned ear. Moreover, it significantly inhibited the increased production of nerve growth factor (NGF) and substance P. On the other hand, loratadine, bepotastine and chlorpheniramine did not inhibit the ear swelling and the increased number of scratching. These results indicate that olopatadine inhibited not only the increased production of cytokines but also NGF and substance P unlike other histamine H(1) receptor antagonists. It was suggested that olopatadine suppressed the increased number of scratching by the anti-inflammatory effects. Therefore, olopatadine appears to exert additional biological effects besides its blockade of a histamine H(1) receptor.
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PMID:The effects of olopatadine hydrochloride on the number of scratching induced by repeated application of oxazolone in mice. 1625 75

Itching is one of the major clinical symptoms in atopic dermatitis (AD) and complicates the management of this pathological condition. An animal model of AD-like pruritus would contribute to a better understanding of AD and could lead to the development of safe and effective antipruritic agents. DS non-hair (DS-Nh) mice raised under conventional conditions spontaneously develop pruritus, which is associated with a dermatitis similar to human AD. There is a significant positive correlation between disease severity and the period of scratching behaviour in DS-Nh mice. In the present study, we found that levels of histamine and nerve growth factor (NGF) in serum and/or skin tissue were higher in DS-Nh mice with AD-like dermatitis than in age-matched mice without dermatitis. The histopathological data indicated that nerve fibres extend into and mast cells infiltrate the surrounding area of the skin lesion. NGF production by XB-2 cells, which was derived from mouse keratinocytes, was enhanced by histamine via the H1 receptor. We also found that prolonged treatment with an H1-antagonist was effective against pruritus through depression of the production of NGF, which is thought to be generated by keratinocytes. We conclude that DS-Nh mice can serve as a suitable model for gaining a better understanding of pruritus in AD, and that prolonged treatment with an H1-antagonist may be beneficial in patients with AD-associated pruritus.
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PMID:Spontaneous scratching behaviour in DS-Nh mice as a possible model for pruritus in atopic dermatitis. 1682 90

The nose provides defensive and homeostatic functions requiring rapid responses to physical and chemical stimuli. As a result, it is armed with a complex nervous system that includes sensory, parasympathetic, and sympathetic nerves. Sensory nerves transmit signals from the mucosa, generating sensations, such as pruritus; motor reflexes, such as sneezing; and parasympathetic and sympathetic reflexes that affect the glandular and vascular nasal apparatuses. Reflexes directed to the nose are also generated by inputs from other body regions. Hence all symptoms that constitute the nosologic entity of rhinitis can be triggered through neural pathways. In addition, neural signals generated in the nose can influence distal physiology, such as that of the bronchial tree and the cardiovascular system. Neural function can be chronically upregulated in the presence of mucosal inflammation, acutely with an allergic reaction, or even in the absence of inflammation, as in cases of nonallergic rhinitis. Upregulation of the nasal nervous system can occur at various levels of the reflex pathways, resulting in exaggerated responses (neural hyperresponsiveness), as well as in increased capacity for generation of neurogenic inflammation, a phenomenon that depends on the release of neuropeptides on antidromic stimulation of nociceptive sensory nerves. The molecular mechanisms of hyperresponsiveness are not understood, but several inflammatory products appear to be playing a role. Neurotrophins, such as the nerve growth factor, are prime candidates as mediators of neural hyperresponsiveness. The many interactions between the nervous and immune systems contribute to nasal physiology but also to nasal disease.
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PMID:The role of the nervous system in rhinitis. 1708 22

Perceived stress has long been allied with disturbances of the dynamic equilibrium established between the nervous, endocrine and immune systems, thus triggering or aggravating disease manifestation. Several common skin diseases are now acknowledged to be worsened by psychological stress, particularly immunodermatoses such as atopic dermatitis, psoriasis, seborrheic eczema, prurigo nodularis, lichen planus, chronic urticaria, alopecia areata and pruritus sine materia. Itch (pruritus) is perhaps the most common symptom associated with a majority of these inflammatory skin diseases, and acute as well as chronic stress perceptions are recognized to trigger or enhance pruritus. A wealth of mediators released systemically or locally in the skin in response to stress increase sensory innervation, upregulate the production of other pruritogenic agents, perpetuate (neurogenic) inflammation and lower the itch threshold. In the present review, we explore recent frontiers in both stress and pruritus research and portray the perpetuation of chronic skin inflammation and itch as a neuroendocrine-immune 'misalliance'. We argue that key candidate molecules of the stress response with strong pruritogenic potential, such as nerve growth factor, corticotropin-releasing hormone and substance P, and mast cells, which may be considered as 'central cellular switchboards of pruritogenic inflammation', need to be further explored systematically in order to develop more effective therapeutic combination strategies for itch management in chronic, stress-vulnerable inflammatory skin diseases.
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PMID:From the brain-skin connection: the neuroendocrine-immune misalliance of stress and itch. 1770 57

Role of neurotrophic factors including nerve growth factor (NGF) in the mechanism of overgrowth and hypersensitivity of sensory nerve in atopic dermatitis (AD) has been proposed. Glial cell line-derived neurotrophic factor (GDNF) is a member of neurotrophic factors of the nervous systems; however, the role of GDNF in dermatitis is unknown. IL-18 promotes Th2 type allergic condition in skin and various organs in the absence of IL-12. In this report, we evaluated the expression of GDNF in AD and its association with NGF and IL-18. Mice expressing skin-specific IL-18 (KIL18Tg) or caspase-1, an IL-18 converting enzyme, (KCASP1Tg) were used as AD models; GDNF expression was examined by RT-PCR, enzyme immunoassay, and immunohistochemistry. The mRNA expressions of GDNF and NGF were detected in the epidermis and they were increased in the skin of KIL18Tg and KCASP1Tg mice. GDNF protein production in the skin was also elevated in both transgenic mice and mostly expressed at the basal layer of the epidermis as assessed by immunohistochemistry. Furthermore, the number of nerve fibers was increased in KCASP1Tg, suggesting increased cutaneous innervation. The present results suggest that in addition to NGF, elevated production and secretion of GDNF in the skin associated with overproduction of IL-18 may also be a potent causative factor of itching in AD.
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PMID:Enhanced production and secretion of glial cell line-derived neurotrophic factor and nerve growth factor from the skin in atopic dermatitis mouse model. 1844 10


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