neuropeptide-y and Pruritus

Topics: Animals; Chronic Pain; Interneurons; Neuropeptide Y; Pruritus; Receptors, Neuropeptide Y; Spinal Cord

Itch is a somatosensory sensation that informs the organism about the presence of potentially harmful substances or parasites, and initiates scratching to remove the threat. Itch-inducing (pruritogenic) substances activate primary afferent neurons in the skin through interactions with specific receptors that converts the stimulus into an electrical signal. These signals are conveyed to the dorsal horn of the spinal cord through the release of neurotransmitters such as natriuretic polypeptide b and somatostatin, leading to an integrated response within a complex spinal interneuronal network. A large sub-population of somatostatin-expressing spinal interneurons also carry the Neuropeptide Y (NPY) Y1 receptor, indicating that NPY and somatostatin partly regulate the same neuronal pathway. This review focuses on recent findings regarding the role of the NPY/Y1 and somatostatin/SST

Topics: Animals; Humans; Neural Pathways; Neurons; Neuropeptide Y; Pruritus; Receptors, Neuropeptide Y; Receptors, Somatostatin; Somatostatin; Spinal Cord

The aims of this study were to validate the efficacy of progressive muscle relaxation (PMR) in patients with atopic dermatitis and to evaluate the serological parameters that may serve as objective measures of the efficacy of PMR. A total of 25 patients with atopic dermatitis were randomly assigned to either a PMR group (n = 15) or a control group (n = 10). Serum levels of nerve growth, neuropeptide Y, and Th2 cytokines (IL-4, IL-5, and IL-13) were measured at baseline and after one month. At baseline, only anxiety was positively correlated with pruritus score (state anxiety: R = 0.496, p = 0.014; trait anxiety: R = 0.423, p = 0.04). Serum levels of neuropeptide Y were inversely related to the State-Trait Anxiety Inventory (STAI) (state anxiety: R = -0.475, p = 0.019; trait anxiety: R = -0.418, p = 0.042) and pruritus scores (R = -0.451, p = 0.035). After one month of PMR therapy, the degree of pruritus and loss of sleep was significantly decreased in the PMR group (p < 0.001), but not among controls. State anxiety scores showed significant improvement after treatment only in the PMR group (p = 0.005). There were no significant changes in the serological parameters in either group. Reductions in Eczema Area and Severity Index (EASI) scores were significant, but similar, in both groups. PMR may be a useful adjunctive modality for the management of atopic dermatitis through the reduction of anxiety. No change was found in biological parameters, but it was observed that neuropeptide Y may be related to high levels of anxiety in atopic dermatitis at baseline.

Topics: Adolescent; Adult; Anxiety; Child; Dermatitis, Atopic; Female; Humans; Interleukin-13; Interleukin-4; Interleukin-5; Male; Muscle Relaxation; Nerve Growth Factor; Neuropeptide Y; Pruritus; Relaxation Therapy; Severity of Illness Index; Sleep Wake Disorders; Statistics, Nonparametric; Surveys and Questionnaires; Treatment Outcome; Young Adult

Somatosensory information is processed by a complex network of interneurons in the spinal dorsal horn. It has been reported that inhibitory interneurons that express neuropeptide Y (NPY), either permanently or during development, suppress mechanical itch, with no effect on pain. Here, we investigate the role of interneurons that continue to express NPY (NPY-INs) in the adult mouse spinal cord. We find that chemogenetic activation of NPY-INs reduces behaviours associated with acute pain and pruritogen-evoked itch, whereas silencing them causes exaggerated itch responses that depend on cells expressing the gastrin-releasing peptide receptor. As predicted by our previous studies, silencing of another population of inhibitory interneurons (those expressing dynorphin) also increases itch, but to a lesser extent. Importantly, NPY-IN activation also reduces behavioural signs of inflammatory and neuropathic pain. These results demonstrate that NPY-INs gate pain and itch transmission at the spinal level, and therefore represent a potential treatment target for pathological pain and itch.

Topics: Animals; Interneurons; Mice; Neuralgia; Neuropeptide Y; Pruritus; Spinal Cord; Spinal Cord Dorsal Horn

Lightly stroking the lips or gently poking some skin regions can evoke mechanical itch in healthy human subjects. Sensitization of mechanical itch and persistent spontaneous itch are intractable symptoms in chronic itch patients. However, the underlying neural circuits are not well defined. We identified a subpopulation of excitatory interneurons expressing Urocortin 3::Cre (Ucn3

Topics: Animals; Central Nervous System Sensitization; Glutamic Acid; Interneurons; Mechanoreceptors; Mice; Neural Inhibition; Neural Pathways; Neuropeptide Y; Physical Stimulation; Pruritus; Skin; Spinal Cord; Toll-Like Receptor 5; Urocortins

Light mechanical stimulation of hairy skin can induce a form of itch known as mechanical itch. This itch sensation is normally suppressed by inputs from mechanoreceptors; however, in many forms of chronic itch, including alloknesis, this gating mechanism is lost. Here we demonstrate that a population of spinal inhibitory interneurons that are defined by the expression of neuropeptide Y::Cre (NPY::Cre) act to gate mechanical itch. Mice in which dorsal NPY::Cre-derived neurons are selectively ablated or silenced develop mechanical itch without an increase in sensitivity to chemical itch or pain. This chronic itch state is histamine-independent and is transmitted independently of neurons that express the gastrin-releasing peptide receptor. Thus, our studies reveal a dedicated spinal cord inhibitory pathway that gates the transmission of mechanical itch.

Topics: Action Potentials; Animals; Hair; Interneurons; Mechanoreceptors; Mechanotransduction, Cellular; Mice; Mice, Transgenic; Neural Inhibition; Neuropeptide Y; Pruritus; Skin; Spinal Cord; Synaptic Transmission

Psychological stress and atopic dermatitis (AD) symptoms appear to form a vicious cycle. This study compared the degree of stress and impairment of dermatology life quality between patients with AD and healthy controls, and examined for neuropeptides and neurotrophins associated with stress in AD. Questionnaires, comprising five tests evaluating depression, anxiety, interaction anxiousness, private body consciousness, and dermatology life quality, were examined in age- and sex-matched patients with AD (n = 28) and healthy controls (n = 28). Immunohistochemical staining of nerve growth factor, substance P, corticotrophin-releasing factor receptor and neuropeptide Y was performed in the AD-involved and normal skin. Patients with AD showed high scores on all of the questionnaires, including Beck Depression Inventory, state anxiety, trait anxiety, Interaction Anxiousness Scale, Private Body Consciousness subscale, and Dermatology Life Quality Index. All of the parameters, except for Beck Depression Inventory, showed higher values in AD than healthy controls (p < 0.001). Statistically significant correlations were observed between each psychological parameter and Dermatology Life Quality Index. Among the clinical parameters, only pruritus was positively correlated with state anxiety (R = 0.573, p < 0.05) and trait anxiety (R = 0.525, p < 0.05). The Eczema Area and Severity Index score did not show any significant correlations with psychological parameters. Nerve growth factor-reactive cells were observed more abundantly and intensely in both epidermis and dermis of AD involved skin (n = 4) than in healthy controls (n = 3) (p = 0.022 and 0.029, respectively). Also, the number and intensity of neuropeptide Y-positive cells was significantly greater in the entire epidermis of patients with AD than in healthy controls (n = 3) (p = 0.029 and 0.026, respectively). We conclude that anxiety may be associated with the induction of pruritus through neuro-peptide Y and nerve growth factor.

Topics: Adolescent; Adult; Anxiety; Biopsy; Case-Control Studies; Child; Depression; Dermatitis, Atopic; Female; Humans; Immunohistochemistry; Male; Middle Aged; Nerve Growth Factor; Neuropeptide Y; Prognosis; Pruritus; Quality of Life; Receptors, Corticotropin-Releasing Hormone; Republic of Korea; Severity of Illness Index; Skin; Stress, Psychological; Substance P; Surveys and Questionnaires; Young Adult

Atopic dermatitis (AD) is an inflammatory skin disease of a chronic course. The role of neuropeptides in pathogenesis of this disorder is probably not crucial; however, there is evidence that these substances influence the development and course of AD.. The aim of this study was to evaluate the plasma level of substance P, neuropeptide Y (NPY) and calcitonin gene related peptide (CGRP) in AD patients during exacerbation and remission of the disease.. Forty-nine patients with AD, aged 17 to 56 years, participated in the study. Among this group, there were 25 males (51%) and 24 females (49%). The disease lasted from 1 to 55 years. The severity of the disease was assessed with SCORAD index. The severity of pruritus was evaluated with Visual Analog Scale and a specially designed questionnaire. Neuropeptides plasma level was detected with radioimmunoassay.. Substance P plasma level in AD patients during exacerbation and remission was significantly higher than in the control group. There was a negative correlation between substance P plasma level and total IgE level. CGRP plasma level during exacerbation of AD was significantly lower than in healthy controls and increased in the remission. Significantly higher CGRP concentration was observed in patients suffering from severe pruritus; however, both in patients with more and less severe pruritus, CGRP plasma level was lower than in controls. Higher CGRP plasma level was also observed in patients with more severe disease. NPY plasma level in patients with AD was significantly increased both during exacerbation and remission. During remission of AD, NPY concentration was higher than during exacerbation.

Topics: Adolescent; Adult; Calcitonin Gene-Related Peptide; Case-Control Studies; Dermatitis, Atopic; Female; Humans; Immunoglobulin E; Inflammation; Male; Middle Aged; Neuropeptide Y; Pain Measurement; Pruritus; Severity of Illness Index; Skin; Substance P