Intraepidermal nerve fiber expression of calcitonin gene-related peptide, vasoactive intestinal peptide and substance P in psoriasis

In order to evaluate more fully the role of neuropeptides in the pathogenesis of psoriasis, skin biopsies were obtained from 36 patients with psoriasis to identify substance P (SP), vasoactive intestinal peptide (VIP) and calcitonin gene-related peptide (CGRP). Lesional and nonlesional skin was examined from these biopsies and the results compared with those from biopsies taken from patients with a variety of other inflammatory dermatoses, including lichen planus, lichen simplex chronicus, spongiotic dermatitis, and seborrheic dermatitis. Also studied was a series of nine biopsies taken from patients with no known skin disorders. We found an increase in the number of SP-positive nerve fibers within the epidermis in biopsies from lesional skin of psoriasis patients (8.4 nerves per 3-mm biopsy) compared with nonlesional psoriatic skin (2.6 nerves per 3-mm biopsy) and normal skin (2.0 nerves per 3 mm biopsy). Other inflammatory disorders also demonstrated fewer SP-positive nerves than lesional psoriatic skin; lichen planus (0 nerves per 3 mm biopsy) and lichen simplex chronicus (1.3 nerves per 3 mm biopsy). The difference in SP-positive nerve expression between lesional psoriatic skin and the group comprising nonlesional skin, normal skin, lichen planus, and lichen simplex chronicus attained statistical significance ( P < 0.013). SP-positive intraepidermal nerve fibers in lesional psoriatic specimens were fewer than in spongiotic dermatitis (17.4 nerves per 3 mm biopsy). There was no significant difference in numbers of VIP- or CGRP-immunopositive intraepidermal nerve fibers between psoriatic skin and the group comprising all other material tested. However, in five patients with psoriasis, there was a marked increase in the expression of intraepidermal CGRP (up to 10.7 nerves per 3-mm biopsy) and VIP (up to 8.3 nerves per 3-mm biopsy) which was not observed in control groups. These findings suggest that neuropeptides SP, CGRP, and VIP play a role in the pathogenesis of psoriasis. Received: 3 March 1997     

Immunohistochemical study of epidermal nerve fibres in involved and uninvolved psoriatic skin using confocal laser scanning microscopy

Abstract Psoriasis is a typical hyperproliferative epidermal disease whose aetiopathogenesis is still to be defined. One of the most likely hypotheses is that it has a neurogenic origin correlated with an altered release of some neuropeptides by sensitive cutaneous nerves via antidromic pathways. As there are conflicting reports about the existence of cutaneous nerve alterations in psoriasis, we carried out an immunolocalization study using the protein gene product 9.5 as a marker for neuronal structures observed by confocal laser scanning microscopy in order to determine the pattern of sensory nerves in psoriatic skin. The investigation was carried out on cutaneous biopsies taken from involved (mature and long-established lesions) and uninvolved skin of ten patients with extensive chronic plaque psoriasis. In uninvolved psoriatic skin a significant decrease in epidermal nerve fibres was found, a further decrease was observed in mature lesions and almost a complete lack of epidermal nerve fibres in long-established psoriatic lesions. The reduction in epidermal nerve fibres and the consequent loss of relationship between these nerve structures and the skin immunocompetent cells (antigen-presenting cells, Langerhans cells, keratinocytes) might be a factor of fundamental importance in the self-maintenance of the disease. Received: 26 May 1997     

Immunohistochemical analysis of sensory nerves and neuropeptides,and their contacts with mast cells in developing and mature psoriatic lesions

The distribution of the neuropeptides substance P (SP), vasoactive intestinal polypeptide (VIP) and calcitonin gene related peptide (CGRP) was studied immunohistochemically in psoriatic skin during the Koebner response (6 h, 2 days, 7 days, 14 days, 21 days), and in mature psoriatic plaques, of 37 psoriatic patients. The morphological association of sensory nerves, SP and VIP with papillary mast cells was also monitored. The nerves containing SP, VIP or CGRP were very scanty in control skin, and in non-lesional and Koebner-negative psoriatic skin. The first psoriatic lesions were seen 7 days after tape stripping the symptomless psoriatic skin. SP- and VIP-containing nerves were slightly increased in Koebner-positive specimens, but the increase was very prominent in dermal papillae of mature psoriatic plaques. In the plaques, nerve-mast cell contacts were significantly increased (p<0.001) compared with non-lesional psoriatic skin. Only SP-positive fibres were detected in the epidermis and in contact with papillary mast cells. VIP was mainly located around capillaries where SP was also found. No change was noted in CGRP-positive fibres between lesional and non-lesional specimens. The appearance of SP and VIP in the capillary walls is morphological evidence for their function as vasodilators in psoriatic lesion. A slight increase in SP- and VIP-positive fibres in Koebner-positive specimens suggests that these neuropeptides may participate in the inflammatory reaction at an early stage. Their prominence in mature psoriatic plaques in turn indicates a role for them in the maintenance of psoriatic lesions. Morphological contacts between mast cells and SP-containing nerves give further evidence to the view that SP is capable of amplifying the inflammatory reaction also through the axon-reflex mechanism.Part of this work was presented at the meeting of the European Society for Dermatological Research, London, UK, 4–7 April 1992     

Study of substance P and its receptor neurokinin-1 in psoriasis and their relation to chronic stress and pruritus

Substance P and its receptor(R) neurokinin (NK)-1 may have a role in the pathogenesis of psoriasis. Stress has been reported to play a role in the onset and exacerbation of psoriasis, which might include the substance P-NK-1 receptor(R) pathway. A feature of psoriasis, that has been correlated to the severity of stress and secretion of substance P, is pruritus. The objective of this study was to investigate the expression of substance P and the NK-1R in involved and noninvolved psoriatic skin, using a biotinylated streptavidin technique. Moreover, a possible correlation between the patient′s level of chronic stress, measured by salivary cortisol samples, degree of lesional pruritus, measured by means of a visual analogue scale, and the expression of substance P- and the NK-1R, was investigated. There was a low number of substance P positive nerve fibres in noninvolved and involved skin, the major immunoreactivity for substance P being found in inflammatory cells. The number of substance P- and NK-1R positive inflammatory cells was increased in involved compared to noninvolved psoriatic skin. The substance P positive cells were mostly lymphocytes, while most of the NK-1R positive cells were mast cells. NK-1R immunoreactivity was also seen as a reticular pattern in the upper part of the epidermis of involved skin in the majority of the patients. Low cortisol ratios in the patients, being an indicator of chronic stress, were correlated to an increased number of substance P- and NK-1R positive inflammatory cells in noninvolved psoriatic skin, and higher cortisol ratios to the presence of keratinocyte NK-1R immunoreactivity in involved skin. The degree of pruritus could not be correlated to the number of substance P positive fibers nor cells. Nonneuronal substance P and its receptor NK-1 might have a role in psoriasis, also during chronic stress.     

Double-labeled immunofluorescence study of cutaneous nerves in psoriasis

Background and objective In recent years, many reports have suggested an active role of neuropeptides in the pathogenesis of psoriasis. Increased numbers of neuropeptide-containing nerves positive for substance P (SP), vasoactive intestinal polypeptide (VIP), and calcium gene-related peptide (CGRP) have been reported in psoriatic tissue. As psoriatic epidermis has a larger mass/volume, however, it is expected to have more nerves and a higher number of neuropeptergic fibers. Therefore, instead of demonstrating a larger number of neuropeptergic fibers, a more significant study is to investigate whether the neuropeptergic fibers are denser in psoriatic tissue. In this study, we applied a double labeled immunofluorescence technique. This method allows the identification of the total number of nerve fibers and the number of nerves positive for specific neuropeptides. Materials and methods We obtained biopsies from nine lesional and seven non-lesional psoriatic skins and six normal controls. Biopsies were snap frozen and then cut into 14 μm cryosections. The tissues were first treated with anti-microtubule associated protein (MAP)2 antibody to stain the nerves. This was followed by a second set of stainings for SP, VIP, and CGRP. Primary antibodies were used in dilutions of 1 : 200 for anti-MAP2, 1 : 200 for anti-SP, 1 : 800 for anti-VIP, and 1 : 400 for anti-CGRP. Results We found that the percentage of SP-positive fibers was twofold greater and the percentage of CGRP-positive fibers was 2.5 times greater in the psoriatic epidermis than in the epidermis of normal skin. Psoriatic epidermis had 30.1 ± 3.9% SP-positive nerve fibers compared with 15.7 ± 3.7% in the normal control. The corresponding values for CGRP-positive nerve fibers were 30.1 ± 3.9% and 12.0 ± 4.2%. Conclusions The results of our study suggest that SP- and CGRP-containing neuropeptide nerve fibers are more dense in the psoriatic epidermis. Both SP and CGRP are chemotactic to neutrophils and mitogenic to keratinocytes and endothelial cells. In addition, SP activates T lymphocytes and induces adhesion molecules on the endothelial cells. Our observations suggest that neuropeptides may play a significant role in the inflammatory and proliferative process of psoriasis.     

寻常性银屑病皮损处神经纤维的数量及其与朗格汉斯细胞关系的观察

目的 观察寻常性银屑病患者皮损处神经纤维的数量变化及其与朗格汉斯细胞的关系.方法采用免疫组化过氧化物酶法观察28例寻常性银屑病患者皮损处神经纤维的数量变化;采用免疫荧光双标记及共聚焦激光扫描显微镜技术观察寻常性银屑病患者皮损处神经纤维与朗格汉斯细胞的关系.结果寻常性银屑病患者皮损处神经纤维长度显著增加,与正常人对照比较有统计学差异(t=4.09,P＜0.001).皮损表皮内神经纤维与朗格汉斯细胞的接触明显增多,与正常人对照比较有统计学差异(t=3.55,P＜0.01).结论寻常性银屑病皮损处神经纤维长度显著增加,表明此部位神经纤维增生明显,并且表皮内神经纤维与朗格汉斯细胞的直接接触明显增加,提示银屑病患者神经系统的免疫调控作用可能是通过改变朗格汉斯细胞的功能实现的。     

Quantitative analysis of contact sites between mast cells and sensory nerves in cutaneous psoriasis and lichen planus based on a histochemical double staining technique

Summary The aim of the present study was to test further our previous hypothesis that the inflammatory reaction in psoriasis is neurogenic. For this purpose, contact sites between mast cells and sensory nerves were morphometrically analysed in the basement membrane zone, papillary dermis and three dermal zones of lesional/non-lesional psoriatic and lichen planus skin as well as in healthy control skin. The analyses were made on sections stained with a histochemical double stain developed for this study. With the double stain, active mast cell tryptase was stained blue enzyme histochemically, and the sensory nerves black using specific monoclonal anti-neurofilament antibodies with immunogold. In psoriatic lesions, both mast cells and mast cell — nerve contacts were markedly more frequent in the basement membrane zone and in the papillary dermis when compared with the corresponding areas in the other groups. Mast cell numbers were increased in both lesional and symptom-free skin in lichen planus, but no increase was found in the mast cell — nerve contacts. Increased contacts between mast cells and sensory nerves indicate that the elements exist for neurogenic inflammation in psoriatic lesions. These increased contacts are not due to the extensive inflammatory reaction only, because they were not observed in lichen planus lesions.     

Neuropeptides in psoriasis: an immunocytochemical and radioimmunoassay study

The present study examines the presence of neuropeptides in the skin and plasma of patients with psoriasis using the techniques of immunocytochemistry and radioimmunoassay. Immunocytochemistry failed to demonstrate differences in the pattern of neuropeptide innervation in psoriatic lesional skin when compared to normal skin. However, radioimmunoassay of skin biopsy extracts, both substance P and vasoactive intestinal polypeptide, were significantly elevated in psoriatic lesional skin when compared with both psoriatic non-lesional and normal control skin (p less than 0.001). There was no significant difference between the plasma levels of neuropeptides in psoriatic patients compared to those of control subjects, and no significant correlation among the plasma levels of neuropeptides with the surface area of involvement with psoriasis. The finding of elevated levels of substance P and vasoactive intestinal polypeptide in lesional psoriatic skin suggests that these peptides may be involved in the pathogenesis or maintenance of the psoriatic skin lesion and the development of safe and stable antagonists of these neuropeptides may have applications in the treatment of psoriasis.     

Altered cutaneous innervation in psoriatic skin as revealed by PGP 9.5 immunohistochemistry

Summary There is conflicting evidence in the literature as to whether cutaneous nerves are altered in psoriasis or not. In this study, antibodies to protein gene product (PGP) 9.5 were used to visualize cutaneous nerves in biopsies from involved and uninvolved skin of nine patients with psoriasis and from normal skin of eight healthy controls. A profound reduction in the epidermal nerve fibre density was observed in the involved psoriatic skin. These intraepidermal nerve fibres were also mostly short and found in the basal layer. Only a few nerve fibres were found in the suprabasal layer and they were non-varicose, long fibres going straight up without branching. In the uninvolved skin of psoriatic patients, the distribution and number of the intraepidermal nerve fibres was similar to that observed in normal skin. In the dermis, the distribution and the number of the nerve fibres showed no differences between involved psoriatic skin, uninvolved psoriatic skin, and normal skin. The results support previous studies in which alterations of cutaneous nerves in psoriasis have been described.     

Evaluation of epidermal nerve density and opioid receptor levels in psoriatic itch

Background Psoriasis is a complex, multifactorial inflammatory skin disease with genetic and environmental interactions. Patients with psoriasis exhibit erythematous plaques with itch, but the mechanisms of psoriatic itch are poorly understood. Objectives This study was performed to investigate epidermal nerve density and opioid receptor levels in psoriatic skin with or without itch. Methods Twenty‐four patients with psoriasis aged between 39 and 82 years were included in this study. The number of epidermal nerve fibres, the levels of semaphorin 3A (Sema3A) and the expression patterns of μ‐ and κ‐opioid systems were examined immunohistologically in skin biopsies from psoriatic patients with or without itch and healthy volunteers as controls. Results The number of epidermal nerve fibres tended to increase in approximately 40% of psoriatic patients with itch compared with healthy controls, while such intraepidermal nerves were not observed in other itchy patients. In comparison with healthy controls, Sema3A levels also tended to decrease in the epidermis of psoriatic patients with itch. However, no relationship was found between nerve density and Sema3A levels in the epidermis of psoriatic patients with itch. The levels of μ‐opioid receptor and β‐endorphin in the epidermis were the same in healthy controls and psoriatic patients with or without itch. The levels of κ‐opioid receptor and dynorphin A were significantly decreased in the epidermis of psoriatic patients with itch compared with healthy controls. Conclusions Based on Sema3A levels in the epidermis, epidermal opioid systems, rather than hyperinnervation, may be involved in the pathogenesis of psoriatic itch.     

Substance P induction of murine keratinocyte PAM 212 interleukin 1 production is mediated by the neurokinin 2 receptor (NK-2R)

The neurological system plays an important role in modulating some inflammatory skin diseases. Neuro-cutaneous interactions may be mediated by the release of neuropeptides such as substance P (SP) which activate immunocompetent cells in the skin by binding to high affinity neurokinin receptors (NKR). Since epidermal keratinocytes produce a variety of cytokines and are intimately associated with cutaneous sensory fibers, we tested the ability of these cells to participate in the cutaneous neuroimmune system by the secretion of potent cytokines such as interleukin 1 (IL-1) in response to released SP. RT-PCR studies demonstrated that cultured PAM 212 murine keratinocytes expressed mRNA for NK-2R but not NK-1R. Correspondingly, the addition of SP to these cells resulted in a rapid increase in intracellular Ca2+ levels that could be specifically blocked by an NK-2R antagonist. NK-2R was also shown in normal mouse epidermis by immunohistochemistry. SP augmented the expression of PAM 212 keratinocyte IL-1alpha mRNA in a dose and time dependent manner and this induction was inhibited by an NK-2R antagonist. Secretion of bioactive IL-1alpha by the PAM 212 keratinocytes was likewise stimulated by SP in a dose dependent manner. These data support the hypothesis that SP released from cutaneous sensory nerves contributes to neuroimmune inflammatory responses in the skin by modulating the expression and release of cytokines from epidermal keratinocytes.     

Expression of growth-associated protein 43 and nerve growth factor receptor in human skin: a comparative immunohistochemical investigation.

The growth-associated protein 43 (GAP43) is a neuronal membrane protein involved in axonal growth and regeneration as well as in the modulation of synaptic plasticity. It is present in sensory and sympathetic neurons, where it is consistently associated with the expression of nerve growth factor receptor (NGFr). We investigated, by means of immunohistochemistry, the presence and distribution of the GAP43-immunoreactivity (IR) and of the NGFr-IR in the adult normal human skin from various body regions. In adjacent sections, a comparison with the distribution of the neuronal markers protein gene product 9.5 (PGP 9.5), substance P (SP), and calcitonin gene-related peptide (CGRP) was performed. Our results indicate that in adult human skin 1) a GAP43-IR is morphologically present in epidermal and dermal nerve fibers; 2) a NGFr-IR is associated with neuronal as well as non-neuronal elements of cutaneous nerves; 3) the basal epidermal cell layer expresses a NGFr-IR, which is unevenly distributed according to the different body areas; and 4) there is suggestive evidence for a simultaneous expression of GAP43-, NGFr-, PGP 9.5-, SP-, and CGRP-IR in at least part of the cutaneous nerve fibers. The presence of GAP43-immunoreactive nerve fibers might be a marker of a continuous synaptic remodeling in adult skin, whereas the distribution of the NGFr-IR could be relevant for our understanding of the maintenance of the neuronal-target relationship(s).     

Changes in cutaneous sensory nerve fibers induced by skin-scratching in mice

BACKGROUND: Skin-scratching behavior, a common response observed in patients with pruritus, is supposed to promote the sprouting of cutaneous sensory nerve fibers. Thus, it sometimes exacerbates the original lesions. However, the precise changes that develop in cutaneous sensory nerve fibers after skin-scratching have not yet been elucidated. OBJECTIVE: To investigate how and what kinds of cutaneous sensory nerve fibers increase and how nerve growth factor (NGF) and its receptors change after skin-scratching. METHODS: After scratching the dorsal skin of anesthetized ICR mice, change in cutaneous nerve fibers was detected by immunofluorescence for protein gene product 9.5 (PGP9.5), substance P (SP) and/or calcitonin gene-related peptide (CGRP). To investigate the involvement of NGF signaling, the production of NGF and the expression of its receptors were examined using ELISA and/or immunofluorescence, respectively. RESULTS: Skin-scratching dramatically induced the sprouting of cutaneous nerve fibers. Both dermal and epidermal nerve fibers began to increase and reached a peak at days 3-7. At the same time, nerve fibers containing SP or CGRP increased significantly. NGF in the scratched skin increased immediately and reached a peak at days 1-3. The expression of NGF receptors, such as phosphorylated trk A and p75, on nerve fibers was remarkably upregulated within 2 days. CONCLUSIONS: Skin-scratching induced the sprouting of cutaneous sensory nerve fibers in the skin within several days, thus possibly leading to enhanced neurogenic inflammation. Analyses of the expression of NGF and its receptors suggest that NGF signaling may be, at least in part, involved in these changes.     

Erratum to "changes in cutaneous sensory nerve fibers induced by skin-scratching in mice"

BACKGROUND: Skin-scratching behavior, a common response observed in patients with pruritus, is supposed to promote the sprouting of cutaneous sensory nerve fibers. Thus, it sometimes exacerbates the original lesions. However, the precise changes that develop in cutaneous sensory nerve fibers after skin-scratching have not yet been elucidated. OBJECTIVE: To investigate how and what kinds of cutaneous sensory nerve fibers increase and how nerve growth factor (NGF) and its receptors change after skin-scratching. METHODS: After scratching the dorsal skin of anesthetized ICR mice, change in cutaneous nerve fibers was detected by immunofluorescence for protein gene product 9.5 (PGP9.5), substance P (SP) and/or calcitonin gene-related peptide (CGRP). To investigate the involvement of NGF signaling, the production of NGF and the expression of its receptors were examined using ELISA and/or immunofluorescence, respectively. RESULTS: Skin-scratching dramatically induced the sprouting of cutaneous nerve fibers. Both dermal and epidermal nerve fibers began to increase and reached a peak at days 3-7. At the same time, nerve fibers containing SP or CGRP increased significantly. NGF in the scratched skin increased immediately and reached a peak at days 1-3. The expression of NGF receptors, such as phosphorylated trk A and p75, on nerve fibers was remarkably upregulated within 2 days. CONCLUSIONS: Skin-scratching induced the sprouting of cutaneous sensory nerve fibers in the skin within several days, thus possibly leading to enhanced neurogenic inflammation. Analysis of the expression of NGF and its receptors suggest that NGF signaling may be, at least in part, involved in these changes.     

Characterization and activity of phospholipase A2 in normal human epidermis and in lesion-free epidermis of patients with psoriasis or eczema

The kinetic properties of phospholipase A2 isolated from single large specimens of normal human epidermis and 'uninvolved' (lesion-free) psoriatic epidermis were determined. The enzymes from the two sources behaved identically with respect to changes in protein concentration, Ca2+ concentration and pH, but the enzymes responded differently to changes in substrate concentration. Furthermore, the specific activity of the enzyme derived from lesion-free psoriatic epidermis was higher than that from normal epidermis under all conditions used. Increased specific activity of the enzyme in the lesion-free epidermis was also found when biopsy specimens taken from thirty-five patients with psoriasis vulgaris at varying severity were compared with biopsies of normal epidermis from thirty-one control volunteers (P less than 0.001). Mixing experiments, in which homogenates of lesion-free psoriatic epidermis and control epidermis were combined, suggested that the relatively low activity of the enzyme in normal epidermis was due to the presence of an inhibitor. As the activity of the enzyme was not elevated in the lesion-free epidermis from twelve cases of eczema, which is also an inflammatory condition of the epidermis and superficial dermis, it is suggested that the raised phospholipase A2 activity demonstrated in the lesion-free epidermis of psoriasis may play an important role in the pathogenesis of the disease.     

Neuropeptides and general neuronal marker in psoriasis an immunohistochemical study

Nerve fibres immunoreactive to antibodies to vasoactive intestinal polypeptide (VIP) and substance P (SP) were increased in lesional psoriatic skin when assessed semi-quantitatively. Biopsies from psoriatic plaques on the arm were studied in 13 patients and compared with biopsies from non-lesional areas (in three of the same psoriatic subjects) and from normal skin in seven non-psomtic controls. Immunohistochemical methods were used on cryocut skin sections to demonstrate the neuropeptides SP, VIP, calcitonin gene-related peptide and neuropeptide Y, and the general neuronal marker protein gene product (PGP) 9.5. The immunofluorescence was examined by semiquantitative and, for PGP 9.5, by quantitative methods. VIP reactive nerve fibres were increased at areas of eccrine sweat glands throughout the dermis, at the dermo-epidermal junction, and in the epidermis, in psoriasis lesional skin. SP reactive nerve fibres were increased at the dermo-epidermal junction, where the nerves ran parallel with and perpendicularly through the junction. PGP 9.5 reactive nerve fibres showed an increase at the dermo-epidermal junction, in the papillary dermis, and at the eccrine sweat glands in lesional psoriatic skin but not in non-lesional, or in control skin. These findings support the hypothesis that neuropeptides may be involved in the pathogenesis of psoriasis.     

NEUROPEPTIDES IN PSORIASIS: POSSIBLE ROLE OF BETA-ENDORPHIN IN THE PATHOMECHANISM OF THE DISEASE

Background. An increased concentration of neuropeptides in psoriatic lesional skin may be responsible for alterations in the neurogenic erythematous response and transmission of stimuli through sensory nerve fibers (sensation of pruritus). Methods. Increasing doses of capsaicin from 0.125 to 4 μg/ cm² were applied to nonlesional psoriatic skin to establish the minimal dose that induced the substance P-mediated neurogenic response in 30 patients with psoriasis. Plasma beta-endorphin was quantitated in 71 psoriatics by radioimmunoassay using NEN 1251-RIA kit. Results. The mean beta-endorphin concentration was increased about 2-fold compared to normals, whereas doses of capsaicin needed to induce erythema were higher (1–4 μg/ cm2) in psoriatics (mainly in patients with type II psoriasis) than in healthy subjects (0.125–0.25 ug/cm2). Conclusions. The data indicate that increased beta-endorphin in psoriatic skin might affect both substance P-mediated neurogenic inflammation and transmission of sensory stimuli due to local antinociceptive effects of this opioid. The differences in the neurogenic response in type I and II psoriasis may be related to the degradation of substance P and beta-endorphin by neutral proteinases in the lesional skin.     

Neuronal changes in psoriasis exacerbation

Background The nervous system contributes to inflammatory skin diseases.
Objective The aim of this investigation was to study the neuronal contribution to psoriasis at the remission and exacerbation phases.
Methods We examined the expression of the neuronal markers protein gene product 9.5 (PGP 9.5), growth-associated protein-43 (GAP-43) and substance P, in addition to its receptor (R), neurokinin-1R (NK-1R) in psoriatic skin from seven female patients at remission and exacerbation, using immunohistochemistry.
Results The number of epidermal PGP 9.5 immunoreactive nerve fibres in the involved skin during exacerbation was decreased ( P  < 0.01) compared to involved skin at remission and non-involved skin at the exacerbation phase. GAP-43-positive nerve fibres were decreased ( P  < 0.05) in the involved skin in contrast to non-involved skin, during exacerbation. Substance P expression was seen on both immunoreactive nerve fibres and cells with a down-regulation ( P  < 0.01) in the number of positive nerve fibres in the involved skin compared to non-involved skin, at the exacerbation phase. The number of substance P-positive cells was slightly lower in the involved skin at exacerbation than at remission. The number of NK-1R immunoreactive cells was increased ( P  < 0.01) in the involved skin in contrast to non-involved skin, at the exacerbation phase.
Conclusion Our findings suggest a crosstalk between the nervous system and inflammation during psoriasis exacerbation in the form of an altered expression of nerve fibres, substance P and its NK-1R.