Neurogenic Inflammation (neurogenic + inflammation)

Distribution by Scientific Domains
Distribution within Medical Sciences


Selected Abstracts


Effects Of Topically Applied Capsaicin Cream On Neurogenic Inflammation And Thermal Sensitivity In Rats

JOURNAL OF THE PERIPHERAL NERVOUS SYSTEM, Issue 2 2000
M. Yoshimura
The effects of capsaicin cream on neurogenic inflammation and thermal nociceptive threshold were investigated in rats. Firstly, for topical application of capsaicin cream to hind paw, we shaped boots from dental cement to prevent the animals from licking off the drug. Capsaicin cream (1%) led to significant increases in the amounts of Evans blue and substance P (SP) released into the perfusate, and the former response was significantly suppressed by pretreatment with RP67580, an NK1-receptor antagonist, but not by treatment with an NK2-receptor antagonist. Subsequent electrical stimulation of the sciatic nerve resulted in a significant reduction in Evans blue and SP extravasation 24 h after topical application of capsaicin cream. On the other hand, when capsaicin cream was repeatedly applied to both hind paws once a day, withdrawal latency for noxious heat stimulation decreased after 24 h, and this thermal hyperalgesia was reversed 3 days later. These results suggest that capsaicin cream initially affects neurogenic inflammation mechanisms and then blocks the pain transmission mechanism. [source]


Neurogenic mechanisms in bronchial inflammatory diseases

ALLERGY, Issue 11 2004
D. A. Groneberg
Neurogenic inflammation encompasses the release of neuropeptides from airway nerves leading to inflammatory effects. This neurogenic inflammatory response of the airways can be initiated by exogenous irritants such as cigarette smoke or gases and is characterized by a bi-directional linkage between airway nerves and airway inflammation. The event of neurogenic inflammation may participate in the development and progression of chronic inflammatory airway diseases such as allergic asthma or chronic obstructive pulmonary disease (COPD). The molecular mechanisms underlying neurogenic inflammation are orchestrated by a large number of neuropeptides including tachykinins such as substance P and neurokinin A, or calcitonin gene-related peptide. Also, other biologically active peptides such as neuropeptide tyrosine, vasoactive intestinal polypeptide or endogenous opioids may modulate the inflammatory response and recently, novel tachykinins such as virokinin and hemokinins were identified. Whereas the different aspects of neurogenic inflammation have been studied in detail in laboratory animal models, only little is known about the role of airway neurogenic inflammation in human diseases. However, different functional properties of airway nerves may be used as targets for future therapeutic strategies and recent clinical data indicates that novel dual receptor antagonists may be relevant new drugs for bronchial asthma or COPD. [source]


Does the Addition of Dexamethasone to Standard Therapy for Acute Migraine Headache Decrease the Incidence of Recurrent Headache for Patients Treated in the Emergency Department?

ACADEMIC EMERGENCY MEDICINE, Issue 12 2008
A Meta-analysis, Systematic Review of the Literature
Abstract Objectives:, Neurogenic inflammation is thought to play a role in the development and perpetuation of migraine headache. The emergency department (ED) administration of dexamethasone in addition to standard antimigraine therapy has been used to decrease the incidence of recurrent headaches at 24 to 72 hours following evaluation. This systematic review details the completed trials that have evaluated the use of dexamethasone in this role. Methods:, The authors searched MEDLINE, EMBASE, CINAHL, LILACS, recent emergency medicine scientific abstracts, and several prepublication trial registries for potential investigations related to the research question. The authors included studies that incorporated randomized, double-blind, placebo-controlled methodology and that were performed in the ED. A fixed-effects and random-effects model was used to obtain summary risk ratios (RRs) and 95% confidence intervals (CIs) for the self-reported outcome of moderate or severe headache on follow-up evaluation. Results:, A pooled analysis of seven trials involving 742 patients suggests a modest but significant benefit when dexamethasone is added to standard antimigraine therapy to reduce the rate of patients with moderate or severe headache on 24- to 72-hour follow-up evaluation (RR = 0.87, 95% CI = 0.80 to 0.95; absolute risk reduction = 9.7%). The treatment of 1,000 patients with acute migraine headache using dexamethasone in addition to standard antimigraine therapy would be expected to prevent 97 patients from experiencing the outcome of moderate or severe headache at 24 to 72 hours after ED evaluation. The sensitivity analysis yielded similar results with sequential trial elimination, indicating that no single trial was responsible for the overall result. Adverse effects related to the administration of a single dose of dexamethasone were infrequent, mild, and transient. Conclusions:, These results suggest that dexamethasone is efficacious in preventing headache recurrence and safe when added to standard treatment for the management of acute migraine headache in the ED. [source]


Peripheral sensitization in migraine,role for P2X purinergic receptors in the dura,vascular sensory pathway

DRUG DEVELOPMENT RESEARCH, Issue 6 2007
Ernest A. Jennings
Abstract Peripheral sensitization is still considered a prime contributor underlying the mechanisms of migraine. Trigeminal primary afferent neurons are the first neurons in the dural nociceptive pathway, and activation results in conscious perception of pain. Peripheral sensitization can lower the activation threshold of primary afferent neurons, rendering them more excitable, allowing for increases in release of neurotransmitter from both central and peripheral terminals. Increase in neurotransmitter release from central terminals contributes to excitation of second-order neurons, while the release of peptides from peripheral terminals has been implicated in neurogenic inflammation. Adenosine 5,-triphosphate (ATP) causes pain in human studies, and depolarize sensory neurons. There is evidence of the action of ATP at many levels in the dura,vascular sensory pathway. Animal studies have shown that some P2X receptors are located in neurons innervating the dura, including the P2X3 receptor, which is most often shown to be involved in nociceptive pathways. In this article, we briefly review peripheral sensitization in relation to migraine and provide emphasis for P2X receptor involvement where it is available. Drug Dev Res 68:321,328, 2007. © 2007 Wiley-Liss, Inc. [source]


Neurophysiological and neurochemical basis of modern pruritus treatment

EXPERIMENTAL DERMATOLOGY, Issue 3 2008
Sonja Ständer
Abstract:, Chronic pruritus of any origin is a frequent discomfort in daily medical practice, and its therapy is challenging. Frequently, the underlying origin may not be identified and symptomatic therapy is necessary. Conventional treatment modalities such as antihistamines often lack efficacy, and hence new therapeutic strategies are necessary. The neuronal mechanisms underlying chronic pruritus have been partly identified during the past years and offer new therapeutic strategies. For example, mast cell degranulation, activation of neuroreceptors on sensory nerve fibres and neurogenic inflammation have been identified to be involved in induction and chronification of the symptom. Accordingly, controlling neuroreceptors such as cannabinoid receptors by agonists or antagonists showed high antipruritic efficacy. Pruritus is transmitted to the central nervous system by specialized nerve fibres and sensory receptors. It has been demonstrated that pruritus and pain have their own neuronal pathways with broad interactions. Accordingly, classical analgesics for neuropathic pain (gabapentin, antidepressants) also exhibit antipruritic efficacy upon clinical use. In summary, these recent developments show that highlighting the basis of pruritus offers modern neurophysiological and neurochemical therapeutic models and the possibility to treat patients with refractory itching of different origin. [source]


Hair growth inhibition by psychoemotional stress: a mouse model for neural mechanisms in hair growth control

EXPERIMENTAL DERMATOLOGY, Issue 1 2006
Eva M. J. Peters
Abstract:, Stress has long been discussed controversially as a cause of hair loss. However, solid proof of stress-induced hair growth inhibition had long been missing. If psychoemotional stress can affect hair growth, this must be mediated via definable neurorendocrine and/or neuroimmunological signaling pathways. Revisiting and up-dating relevant background data on neural mechanisms of hair growth control, we sketch essentials of hair follicle (HF) neurobiology and discuss the modulation of murine hair growth by neuropeptides, neurotransmitters, neurotrophins, and mast cells. Exploiting an established mouse model for stress, we summarize recent evidence that sonic stress triggers a cascade of molecular events including plasticity of the peptidergic peri- and interfollicular innervation and neuroimmune crosstalk. Substance P (SP) and NGF (nerve growth factor) are recruited as key mediators of stress-induced hair growth-inhibitory effects. These effects include perifollicular neurogenic inflammation, HF keratinocyte apoptosis, inhibition of proliferation within the HF epithelium, and premature HF regression (catagen induction). Intriguingly, most of these effects can be abrogated by treatment of stressed mice with SP-receptor neurokinin-1 receptor (NK-1) antagonists or NGF-neutralizing antibodies , as well as, surprisingly, by topical minoxidil. Thus there is now solid in vivo -evidence for the existence of a defined brain- HF axis. This axis can be utilized by psychoemotional and other stressors to prematurely terminate hair growth. Stress-induced hair growth inhibition can therefore serve as a highly instructive model for exploring the brain-skin connection and provides a unique experimental model for dissecting general principles of skin neuroendocrinology and neuroimmunology well beyond the HF. [source]


Pimecrolimus , an anti-inflammatory drug targeting the skin

EXPERIMENTAL DERMATOLOGY, Issue 12 2004
M. Grassberger
Abstract:, Pimecrolimus is the most recent member of calcineurin inhibitors available for the therapy for inflammatory skin diseases. It targets T-cells and mast cells and inhibits the production and release of cytokines and other inflammatory mediators, as well as the expression of signals essential for the activation of inflammatory T-lymphocytes. Pimecrolimus has a cell-selective mode of action. In contrast to corticosteroids, it does not affect, e.g., Langerhans'cells/dendritic cells (LC/DC), as demonstrated in vitro with human monocyte-derived DC and in vivo with epidermal LC in mice, nor human primary fibroblasts. As shown in vitro with human skin and by comparison of clinical pharmacokinetic data from patients with atopic dermatitis, pimecrolimus permeates less through skin than tacrolimus and much less than corticosteroids. It, thus, has a lower potential for transcutaneous resorption after topical administration, resulting in a lower risk of systemic effects. Pimecrolimus has high anti-inflammatory activity in animal models of skin inflammation, including a model reflecting neurogenic inflammation, but a more favourable balance of anti-inflammatory vs. immunosuppressive activity than tacrolimus. Pimecrolimus does not affect sensitization in a murine model of allergic contact dermatitis and has a lower potency in various models of immunosuppression after systemic administration, compared to tacrolimus. In conclusion, the results of preclinical studies show that pimecrolimus has a selective pharmacological profile, suited for effective and safe treatment for inflammatory skin diseases. [source]


Role of protease-activated receptor-2 during cutaneous inflam-mation and the immune response

EXPERIMENTAL DERMATOLOGY, Issue 9 2004
M. Steinhoff
Protease-activated receptors (PARs) constitute a new subfamily of G-protein-coupled receptors with seven transmembrane domains which are activated by various serine proteases such as thrombin, cathepsin G, trypsin or tryptase, and bacterial proteases or mite antigens, for example. PAR2 is a receptor for mast cell tryptase or house dust mite allergens, which is released during inflammation and allergic reactions. In the skin, PAR2 is diversely expressed by keratinocytes, endothelial cells, and occasionally sensory nerves of human skin in various disease states. Moreover, immunocompetent cells such as T cells and neutrophils express functional PAR2, thereby contributing to inflammation and host defense. Own data revealed that PAR2 contributes to neurogenic inflammation by releasing neuropeptides from sensory nerves resulting in oedema, plasma extravasation and infiltration of neutrophils. Thus, mast cells may communicate with sensory nerves in inflammatory tissues by activating PAR2 via tryptase. Moreover, PAR2 agonists upregulate the expression of certain cell-adhesion molecules and cytokines such as interleukin-6 and interleukin-8 on dermal microvascular endothelial cells or regulate neutrophil migration, indicating that PAR2 plays an important role in leucocyte/endothelial interactions. These effects may be partly mediated by NF-,B, an important transcription factor during inflammation and immune response. PAR2 stimulation results in the activation of NF-,B on microvascular endothelial cells and keratinocytes, thereby regulating ICAM-1 expression. We also demonstrate evidence for a diverse expression of PAR2 in various skin diseases and highlight the recent knowledge about the important role of PAR2 during inflammation and the immune response. Together, PAR2 -modulating agents may be new tools for the treatment of inflammatory and allergic diseases in the skin. [source]


In vitro interactions between sensory nerves, epidermis, hair follicles and capillaries in a tissue-engineered reconstructed skin

EXPERIMENTAL DERMATOLOGY, Issue 9 2004
V. Gagnon
Recent findings have established that cutaneous nerves modulate both skin homeostasis and various skin diseases, by influencing cell growth and differentiation, inflammation and wound healing. In order to study the influence of epidermis, hair follicles and capillaries on sensory neurons, and vice-versa, we developed a tissue-engineered model of innervated endothelialized reconstructed skin (MIERS). Mouse dorsal root ganglia neurons were seeded on a collagen sponge populated with human fibroblasts and human endothelial cells. Keratinocytes or mice newborn immature hair follicle buds were then seeded on the opposite side of the MIERS to study their influence on sensory nerves growth, and vice versa. A vigorous neurite elongation was detected inside the reconstructed dermis after 14 and 31 days of neurons culture. The presence of endothelial cells induced a significant increase of the neurite elongation after 14 days of culture. The addition of human keratinocytes totally avoided the twofold decrease in the amount of neurites observed between 14 and 31 days in controls. We have successfully developed the MIERS that allowed us to study the effects of epidermis and capillaries on nerve growth. This model will be a useful tool to study the modulation of sensory nerves on wound healing, angiogenesis, hair growth and neurogenic inflammation in the skin. [source]


Induction of neuropeptides in skin innervating sensory neurons by stress and nerve growth factor as a possible reason for hair growth alteration

EXPERIMENTAL DERMATOLOGY, Issue 9 2004
A. Kuhlmei
Recently, we introduced a mouse model launching experimental evidence for stress-induced hair growth inhibition (HGI), pointing to the existence of a brain-hair follicle axis (BFA). We suggested that nerve growth factor (NGF), besides neuropeptide substance P (SP), is a candidate mediator along the BFA. Published data further indicate that stress-related neuropeptides, e.g. calcitonin gene-related peptide (CGRP) and SP may be involved in HGI. SP and CGRP are synthesized in dorsal root ganglia (DRG) and released after axonal transport in the skin. Thus, aim of the present study was to investigate the effect of stress or subcutaneous injection of NGF, which mimics stress and regulates neuropeptide genes in sensory neurons, on the expression of SP and CGRP in DRG. Anagen was induced in C57BL/6 mice by depilation and retrograde tracing was employed on day 9 post-depilation (PD). On day 14 PD, mice were either exposed to sound stress (n = 4) injected subcutaneously with NGF (n = 4) or served as control (n = 4). On day 16 PD, DRG (mean of 30/mouse) were harvested and SP and CGRP in skin-specific sensory neurons, as identified by the tracer dye, were labelled by immunohistochemistry and counted. Stress exposure as well as NGF injection leads to a significant induction of SP and CGRP in retrograde-labelled neurons. This allows us to conclude that sensitive dermal nerve fibres are likely to originate from the presently identified neuropeptide-positive neurons. Peripheral activation of SP-expressing afferent nerve fibres via NGF-dependent pathways may cause neurogenic inflammation, eventually resulting in HGI. [source]


Expression of vanilloid receptor subtype 1 in cutaneous sensory nerve fibers, mast cells, and epithelial cells of appendage structures

EXPERIMENTAL DERMATOLOGY, Issue 3 2004
Sonja Ständer
Abstract:, The vanilloid receptor subtype 1 (VR1)/(TRPV1), binding capsaicin, is a non-selective cation channel that recently has been shown in human keratinocytes in vitro and in vivo. However, a description of VR1 localization in other cutaneous compartments in particular cutaneous nerve fibers is still lacking. We therefore investigated VR1 immunoreactivity as well as mRNA and protein expression in a series (n = 26) of normal (n = 7), diseased (n = 13) [prurigo nodularis (PN) (n = 10), generalized pruritus (n = 1), and mastocytosis (n = 2)], and capsaicin-treated human skin (n = 6). VR1 immunoreactivity could be observed in cutaneous sensory nerve fibers, mast cells, epidermal keratinocytes, dermal blood vessels, the inner root sheet and the infundibulum of hair follicles, differentiated sebocytes, sweat gland ducts, and the secretory portion of eccrine sweat glands. Upon reverse transcriptase-polymerase chain reaction and Western blot analysis, VR1 was detected in mast cells and keratinocytes from human skin. In pruritic skin of PN, VR1 expression was highly increased in epidermal keratinocytes and nerve fibers, which was normalized after capsaicin application. During capsaicin therapy, a reduction of neuropeptides (substance P, calcitonin gene-related peptide) was observed. After cessation of capsaicin therapy, neuropeptides re-accumulated in skin nerves. In conclusion, VR1 is widely distributed in the skin, suggesting a major role for this receptor, e.g. in nociception and neurogenic inflammation. [source]


Low Leptin Levels in Migraine: A Case Control Study

HEADACHE, Issue 7 2008
Baburhan Guldiken MD
Background., Obesity has been shown to be a risk factor for transformation of episodic migraine to chronic form, and adipocytokines have been implicated to modulate some of the cytokins such as interleukin-6 and tumor necrosis factor, which also act in the neurogenic inflammation in migraine. The aim of the study was to assess leptin levels, one of the adipocytokines, in headache-free period of migraine patients and investigate its relation to vascular risk factors. Material and Methods., Sixty-one patients with episodic migraine headaches and 64 control subjects were enrolled in the study. Demographic data and anthropometric measurements were obtained from all participants; body mass index and fat mass values were calculated. Glucose and lipid parameters were measured by oxidase technique and cholesterol esterase enzymatic assays, and leptin levels were measured by ELISA in serum samples obtained after an overnight fasting. Results., Leptin levels were found significantly lower in migraineurs than controls (40.1 ± 21.2 ng/mL, 48.5 ± 24.5 ng/mL; P < .05). Although body mass index did not differ between 2 groups, fat mass, and fat percentages were significantly lower in migraine patients (19.4 ± 8.8 kg, 26.0 ± 8.7 kg; P < .001 and 28 ± 9%, 34 ± 5%; P < .001, respectively). Conclusion., Migraine patients have low leptin levels and fat mass which may be related to the pathogenesis of migraine. The importance and impact of our findings on the prevalence, characteristics, and treatment of migraine needs to be investigated in further detailed studies. [source]


The contribution of neurogenic inflammation to sensitive skin: concepts, mechanisms and cosmeceutical intervention

INTERNATIONAL JOURNAL OF COSMETIC SCIENCE, Issue 6 2009
A. Ferrer-Montiel
IFSCC Magazine, 11 (2008) (4) 311,315 This paper was presented as a keynote lecture at the IFSCC Congress 2008, Barcelona, Spain. Cutaneous neurogenic inflammation is emerging as an underlying mechanism for several skin conditions. The intimate cross-talk between the cutaneous immune system and the peripheral nervous system is fundamental for skin biology. However, an imbalance or dysfunction results in the onset of an inflammatory state that is reinforced by the synergic and complementary action of both systems. Cumulative evidence indicates that the thermoreceptor TRPV1 is a key player of neurogenic inflammation. This receptor is activated by both physical and chemical stimuli, and its activity is potentiated by pro-inflammatory mediators. An increase in TRPV1 activity results in an increment of neuronal excitability that leads to the release of proalgesic agents that stimulate the immune system. Therefore, the TRPV1 receptor is being considered as a cosmeceutical target, and agents that reduce its activity will be useful cosmeceuticals. Keywords:, Algogens, epidermis, immune system, nociceptor, sensitization [source]


Effects Of Topically Applied Capsaicin Cream On Neurogenic Inflammation And Thermal Sensitivity In Rats

JOURNAL OF THE PERIPHERAL NERVOUS SYSTEM, Issue 2 2000
M. Yoshimura
The effects of capsaicin cream on neurogenic inflammation and thermal nociceptive threshold were investigated in rats. Firstly, for topical application of capsaicin cream to hind paw, we shaped boots from dental cement to prevent the animals from licking off the drug. Capsaicin cream (1%) led to significant increases in the amounts of Evans blue and substance P (SP) released into the perfusate, and the former response was significantly suppressed by pretreatment with RP67580, an NK1-receptor antagonist, but not by treatment with an NK2-receptor antagonist. Subsequent electrical stimulation of the sciatic nerve resulted in a significant reduction in Evans blue and SP extravasation 24 h after topical application of capsaicin cream. On the other hand, when capsaicin cream was repeatedly applied to both hind paws once a day, withdrawal latency for noxious heat stimulation decreased after 24 h, and this thermal hyperalgesia was reversed 3 days later. These results suggest that capsaicin cream initially affects neurogenic inflammation mechanisms and then blocks the pain transmission mechanism. [source]


Neurogenic mechanisms in bronchial inflammatory diseases

ALLERGY, Issue 11 2004
D. A. Groneberg
Neurogenic inflammation encompasses the release of neuropeptides from airway nerves leading to inflammatory effects. This neurogenic inflammatory response of the airways can be initiated by exogenous irritants such as cigarette smoke or gases and is characterized by a bi-directional linkage between airway nerves and airway inflammation. The event of neurogenic inflammation may participate in the development and progression of chronic inflammatory airway diseases such as allergic asthma or chronic obstructive pulmonary disease (COPD). The molecular mechanisms underlying neurogenic inflammation are orchestrated by a large number of neuropeptides including tachykinins such as substance P and neurokinin A, or calcitonin gene-related peptide. Also, other biologically active peptides such as neuropeptide tyrosine, vasoactive intestinal polypeptide or endogenous opioids may modulate the inflammatory response and recently, novel tachykinins such as virokinin and hemokinins were identified. Whereas the different aspects of neurogenic inflammation have been studied in detail in laboratory animal models, only little is known about the role of airway neurogenic inflammation in human diseases. However, different functional properties of airway nerves may be used as targets for future therapeutic strategies and recent clinical data indicates that novel dual receptor antagonists may be relevant new drugs for bronchial asthma or COPD. [source]


Capsaicin delays regeneration of the neuromuscular junction of rat extensor digitorum longus muscle after ischemia

MUSCLE AND NERVE, Issue 4 2006
Béla Turchányi MD
Abstract Trauma or the tourniquet used in orthopedic surgery is often associated with ischemia,reperfusion (I/R) injury with a consequent decrease of muscle power. To explore whether components of the neuromuscular junction (NMJ) are involved in this muscle dysfunction, NMJs were ultrastructurally characterized in the extensor digitorum longus muscle of rats at reperfusion times of 1, 24, 72, and 168 h after a 120-min arterial occlusion. Disorganization of the presynaptic membrane and mitochondrial injury was noted at 1 h, followed by fragmentation and partial engulfment of nerve terminals by Schwann cells at 24 and 72 h. The magnitude of degenerative changes declined at 168 h, suggesting the commencement of regeneration. The postsynaptic membrane remained intact throughout the whole period. In our previous study, deafferentation with pretreatment of the sciatic nerve with capsaicin, which reduces neurogenic inflammation and has a selective effect on nociceptive fibers, improved functional recovery of the muscle after I/R. The present results document a significantly delayed structural regeneration of the motor nerve terminals after combined capsaicin and I/R treatment. Since capsaicin treatment alone had no discernible effect on the structure of NMJs, the findings point to a possibly indirect effect of capsaicin on the motor nerves, which may predispose them to increased susceptibility unmasked only by a subsequent injury. The mismatch between the enhanced functional improvement of the muscle and delayed regeneration of the nerve after capsaicin pretreatment questions the efficient use of such deafferentation to protect the integrity of neuromuscular junctions in I/R injury. Muscle Nerve, 2006 [source]


Current Understandings on Complex Regional Pain Syndrome

PAIN PRACTICE, Issue 2 2009
Marissa De Mos MD
Abstract The mechanisms underlying complex regional pain syndrome (CRPS) have been increasingly studied over the past decade. Classically, this painful and disabling disorder was considered to emerge from pathology of the central nervous system. However, the involvement of additional peripheral disease mechanisms is likely, and recently these mechanisms have also attracted scientific attention. The present article provides an overview of the current understandings regarding pathology of the autonomic and somatic nervous system in CRPS, as well as the roles of neurogenic inflammation, hypoxia, and the contribution of psychological factors. Potential connections between the separate disease mechanisms will be discussed. Additionally, currently known risk factors for CRPS will be addressed. Insight into risk factors is of relevance as it facilitates early diagnosis and tailored treatment. Moreover, it may provide clues for further unraveling of the pathogenesis and etiology of CRPS. [source]


Prurigo nodularis: A review

AUSTRALASIAN JOURNAL OF DERMATOLOGY, Issue 4 2005
Michael R Lee
SUMMARY Prurigo nodularis is a chronic condition characterized by a papulonodular pruriginous eruption of unknown aetiology. This condition is a difficult disease to treat and causes frustration to both the patient and the treating doctor. A variety of systemic conditions have been reported to be associated with prurigo nodularis. The mechanism by which these disorders may trigger prurigo nodularis is unknown. Nerve growth factor has been implicated in the pathogenesis of prurigo nodularis. Calcitonin gene-related peptide and substance P immunoreactive nerves are markedly increased in prurigo nodularis when compared with normal skin. These neuropeptides may mediate the cutaneous neurogenic inflammation and pruritus in prurigo nodularis. Topical or intralesional glucocorticoids are the treatment of choice. Other topical treatments such as topical vitamin D3, and topical capsaicin have also been reported to be effective. Oral treatments such as cyclosporin and thalidomide have been shown to improve both appearance of the skin and pruritus. We review the clinical features, associations, pathology, pathogenesis and treatment of prurigo nodularis. [source]


CGRP blockers in migraine therapy: where do they act?

BRITISH JOURNAL OF PHARMACOLOGY, Issue 7 2008
L Edvinsson
Calcitonin gene-related peptide (CGRP) is expressed throughout the CNS and peripheral nervous system, consistent with control of vasodilatation, nociception, motor function, secretion and olfaction. ,CGRP is prominently localized in primary afferent C and A, fibres of spinal and trigeminal ganglia. Activation of the trigeminal nerve results in antidromic release of CGRP, acting through a CGRP1 receptor. Antagonists of CGRP1 receptors reduce signalling in the trigeminovascular pathway at multiple sites, putatively inside the blood,brain barrier. Other ways of interacting with CGRP mechanisms have appeared limiting the availability of CGRP in the circulation with a specific CGRP antibody or with a CGRP-binding RNA-Spiegelmer. Either way reduces neurogenic inflammation and attenuates signalling within the trigeminovascular pathway. Specific CGRP receptor blockade has been shown to reduce the effect of released CGRP and to abort acute migraine attacks. The novel approach of reducing available CGRP is limited by the blood,brain barrier; its usefulness may be more as prophylaxis rather than as acute treatment of migraine. British Journal of Pharmacology (2008) 155, 967,969; doi:fn1; published online 8 September 2008 [source]


The NK-2 receptor antagonist SR 48968C does not improve adenosine hyperresponsiveness and airway obstruction in allergic asthma

CLINICAL & EXPERIMENTAL ALLERGY, Issue 2 2001
J. Kraan
When stimulated, excitatory nonadrenergic noncholinergic (e-NANC) nerves locally release tachykinins like Neurokinin (NK) A and Substance P, causing neurogenic inflammation and airway obstruction via activation of specific NK-1 and NK-2 receptors. The recently developed nonpeptide NK-2 receptor antagonist SR 48968C has a high affinity for the NK-2 receptor, and is a strong and selective antagonist of NK-2 receptor mediated airway obstruction. In a placebo-controlled cross-over study, we investigated the effect of SR 48968C, administrated orally once-daily in a dosage of 100 mg during 9 days, on airway responsiveness to adenosine 5,-monophosphate (AMP) in 12 allergic asthmatic patients. Furthermore, we assessed its effect on airway obstruction, by measuring FEV1 on the first and last day of each treatment period and by peak flow registration at home throughout the study period. SR 48968C had no significant effect on PC20AMP or on FEV1 measured on day 1 and 9, and morning and evening peakflow measured at home on day 2,8. Thus, although SR 48968C was administrated in a dosage that might cause a demonstrable blocking effect on airway NK-2 receptors in asthma, it did not have a significant bronchodilatory or bronchoprotective effect against adenosine hyperresponsiveness in this study. Further studies are needed to assess the value of SR 48968C and other NK receptor antagonists in the treatment of asthma [source]