Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0033774 (pruritus)
 14,546 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
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PMID:Expression of vanilloid receptor subtype 1 in cutaneous sensory nerve fibers, mast cells, and epithelial cells of appendage structures. 1498 52

Histamine is known to excite a subset of C-fibers and cause itch sensation. Despite its well-defined excitatory action on sensory neurons, intracellular signaling mechanisms are not understood. Previously, we demonstrated that bradykinin excited sensory neurons by activating TRPV1 via the phospholipase A(2) (PLA(2)) and lipoxygenase (LO) pathway. We, thus, hypothesized that histamine excited sensory neurons via the PLA(2)/LO/TRPV1 pathway. Application of histamine elicited a rapid increase in intracellular Ca(2+) ([Ca(2+)](i)) that desensitized slowly in cultured dorsal root ganglion neurons. Histamine-induced [Ca(2+)](i) was dependent on extracellular Ca(2+) and inhibited by capsazepine and by SC0030, competitive antagonists of TRPV1. Quinacrine and nordihydroguaiaretic acid, a PLA(2) and an LO inhibitor, respectively, blocked the histamine-induced Ca(2+) influx in sensory neurons, while indomethacin (a cyclooxygenase inhibitor) did not. We thus conclude that histamine activates TRPV1 after stimulating the PLA(2)/LO pathway, leading to the excitation of sensory neurons. These results further provide an idea for potential use of TRPV1 antagonists as anti-itch drugs.
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PMID:Histamine-induced Ca(2+) influx via the PLA(2)/lipoxygenase/TRPV1 pathway in rat sensory neurons. 1513 18

Endocannabinoids have analgesic/anti-inflammatory properties. The biology of endocannabinoids, their receptors, signalling mechanisms and role in the regulation of physiological processes have been extensively reviewed. This review focuses on the role of palmitoylethanolamide (PEA), an endogenous fatty acid amide analogue of the endocannabinoid anandamide, in tissue protective mechanisms. PEA was first identified almost five decades ago in lipid extracts of various natural products, and its anti-inflammatory and antinociceptive effects were established later. Evidence exists that PEA is synthesised during inflammation and tissue damage and a number of beneficial effects, including the relief of inflammation and pruritus, have been shown to be useful in the control of neurogenic and neuropathic pain. The postulated hypotheses as to the mode of action of PEA include a possible local autacoid-like mediator activity regulating mast-cell activity and putative activation of cannabinoids and vanilloid TRPV1 receptors via "entourage" effects. The large number of scientific investigations into the effects of PEA and PEA-related compounds has given rise to new therapeutic opportunities. In spite of the multitude of therapies currently employed to control inflammation, pain, pruritus and tissue damage, the possibility of using a natural compound, such as PEA to manipulate endogenous protective mechanisms may be considered a beneficial novel therapeutic strategy in veterinary medicine.
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PMID:Palmitoylethanolamide, endocannabinoids and related cannabimimetic compounds in protection against tissue inflammation and pain: potential use in companion animals. 1655 78

Transient receptor potential (TRP) ion channels mediate key aspects of taste, smell, pain, temperature sensation, and pheromone detection. To deepen our understanding of TRP channel physiology, we require more diverse pharmacological tools. Citral, a bioactive component of lemongrass, is commonly used as a taste enhancer, as an odorant in perfumes, and as an insect repellent. Here we report that citral activates TRP channels found in sensory neurons (TRPV1 and TRPV3, TRPM8, and TRPA1), and produces long-lasting inhibition of TRPV1-3 and TRPM8, while transiently blocking TRPV4 and TRPA1. Sustained citral inhibition is independent of internal calcium concentration, but is state-dependent, developing only after TRP channel opening. Citral's actions as a partial agonist are not due to cysteine modification of the channels nor are they a consequence of citral's stereoisoforms. The isolated aldehyde and alcohol cis and trans enantiomers (neral, nerol, geranial, and geraniol) each reproduce citral's actions. In juvenile rat dorsal root ganglion neurons, prolonged citral inhibition of native TRPV1 channels enabled the separation of TRPV2 and TRPV3 currents. We find that TRPV2 and TRPV3 channels are present in a high proportion of these neurons (94% respond to 2-aminoethyldiphenyl borate), consistent with our immunolabeling experiments and previous in situ hybridization studies. The TRPV1 activation requires residues in transmembrane segments two through four of the voltage-sensor domain, a region previously implicated in capsaicin activation of TRPV1 and analogous menthol activation of TRPM8. Citral's broad spectrum and prolonged sensory inhibition may prove more useful than capsaicin for allodynia, itch, or other types of pain involving superficial sensory nerves and skin.
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PMID:Citral sensing by Transient [corrected] receptor potential channels in dorsal root ganglion neurons. 1846 Nov 59

Itch is one of the major complications of skin diseases. Although there are various substances that induce itch or pruritus, it is evident that histamine is the best known endogenous agent that evokes itch. Even though histamine-induced itch has been studied for some time, the underlying mechanism of itch is just beginning to emerge. Although various downstream signaling pathways of histamine receptors have been revealed, more studies are required to determine the cause of histamine-induced itch. It appears that itch and pain involve different neuronal pathways. Pain generally inhibits itch, which indicates an inter-communication between the two. Complex interactions between itch and pain may be expected based on reports on disease states and opioids. In this review, we discuss the molecular mechanism and the pharmacological aspects of histamine-induced itch. Especially, the underlying mechanism of TRPV1 (an anti-pruritus target) has been determined to some extent.
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PMID:Histamine-induced itch and its relationship with pain. 1866 87

Although mosquito allergy induces the release of histamine, the itch-related response, scratching, is not effectively suppressed by blockade of H1 histamine receptors. To address this question, we examined the effects of neonatal capsaicin treatment on allergic reactions and H1 histamine receptor-expressing sensory neurones in mice. Neonatal capsaicin treatment almost completely abolished allergy-associated scratching, without effects on plasma extravasation or increase in serum concentrations of immunoglobulins E and G1. An injection of edema contents from an animal exhibiting allergic reaction elicited scratching in naive animals, suggesting the production of pruritogen(s) by allergic reaction; this production was not suppressed by neonatal capsaicin treatment. This treatment markedly decreased the number of sensory neurones immunoreactive for TRPV1 capsaicin receptor, with little effect on sensory neurones immunoreactive for neurofilament 200, a marker of myelinated A-fibre neurones. In addition, there was a trend towards a reduction in numbers of sensory neurones immunoreactive for H1 histamine receptor. The results suggest that capsaicin-sensitive sensory neurones that lack H1 histamine receptors play a key role in signalling of allergic itch.
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PMID:Different roles of capsaicin-sensitive and H1 histamine receptor-expressing sensory neurones in itch of mosquito allergy in mice. 1877 80

Transient receptor potential receptors (TRP) on primary afferent neurons respond to noxious and/or thermal stimuli. TRPV1 receptors can be activated by noxious heat, acid, capsaicin and resiniferatoxin, leading to burning pain or itch mediated by discharges in C polymodal and Adelta mechano-heat nociceptors and in central neurons, including spinothalamic tract (STT) cells. Central nociceptive transmission involves both non-NMDA and NMDA receptors, and inhibitory interneurons as well as projection neurons contribute to the neural interactions. Behavioral consequences of intradermal injection of capsaicin include pain, as well as primary and secondary hyperalgesia and allodynia. Primary hyperalgesia depends on sensitization of peripheral nociceptors, whereas, secondary hyperalgesia and allodynia result from sensitization of central nociceptive neurons, such as STT cells. Central sensitization is associated with enhanced responses to excitatory amino acids and decreased responses to inhibitory amino acids. The mechanism of the increase in responses to excitatory amino acids includes phosphorylation of NR1 subunits of NMDA receptors and GluR1 subunits of AMPA receptors. Central sensitization depends on activation of several protein kinases and other enzymes, such as nitric oxide synthase. This process is regulated by protein phosphatases. Central sensitization can be regarded as a spinal cord form of long-term potentiation.
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PMID:The role of TRPV1 receptors in pain evoked by noxious thermal and chemical stimuli. 1929 70

According to epidemiological studies, up to 50% of adults report facial sensitivity with various distinctive symptoms, such as prickling, burning, tingling, pain or itching. This is termed sensitive skinand represents a syndrome of physiological reactions rather than a disease entity. In this review, we discuss the currently available literature on this syndrome and describe the possible underlying neuronal pathomechanisms. The sensory receptors expressed on unmyelinated nerve fibres and keratinocytes involved in nociception, such as TRPV1 and endothelin receptors, are hypothesized to play a role in the induction of sensitive skin. Furthermore, we discuss the role of neurotrophins and the influence of stress on sensitive skin.
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PMID:Putative neuronal mechanisms of sensitive skin. 1938 11

The mechanisms that generate itch are poorly understood at both the molecular and cellular levels despite its clinical importance. To explore the peripheral neuronal mechanisms underlying itch, we assessed the behavioral responses (scratching) produced by s.c. injection of various pruritogens in PLCbeta3- or TRPV1-deficient mice. We provide evidence that at least 3 different molecular pathways contribute to the transduction of itch responses to different pruritogens: 1) histamine requires the function of both PLCbeta3 and the TRPV1 channel; 2) serotonin, or a selective agonist, alpha-methyl-serotonin (alpha-Me-5-HT), requires the presence of PLCbeta3 but not TRPV1, and 3) endothelin-1 (ET-1) does not require either PLCbeta3 or TRPV1. To determine whether the activity of these molecules is represented in a particular subpopulation of sensory neurons, we examined the behavioral consequences of selectively eliminating 2 nonoverlapping subsets of nociceptors. The genetic ablation of MrgprD(+) neurons that represent approximately 90% of cutaneous nonpeptidergic neurons did not affect the scratching responses to a number of pruritogens. In contrast, chemical ablation of the central branch of TRPV1(+) nociceptors led to a significant behavioral deficit for pruritogens, including alpha-Me-5-HT and ET-1, that is, the TRPV1-expressing nociceptor was required, whether or not TRPV1 itself was essential. Thus, TRPV1 neurons are equipped with multiple signaling mechanisms that respond to different pruritogens. Some of these require TRPV1 function; others use alternate signal transduction pathways.
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PMID:TRPV1-expressing primary afferents generate behavioral responses to pruritogens via multiple mechanisms. 1956 17

The temperature-sensitive transient receptor potential (TRP) channels, is also called thermo TRP, including TRPV1, TRPV2, TRPV3, TRPV4, TRPM8 and TRPA1, which are expressed in sensory neurons and non-neuronal cells (e.g.keratinocyte, mast cell) of the skin. Thermo TRP channels are activated/sensitized by physical and chemical mediators, which participate in thermosensation and thermoregulation, so that they are key players in pruritus or pain pathogenesis. Thermo TRP channels are also involved in cutaneous neurogenic inflammation, thus they are regarded as molecular targets for future therapy in skin inflammation, pruritus and pain. In addition, following a basic syntax and molecular substrate of nociception and pruriception established by TRP channels-centered concept, the sensory categories can be distinguished and re-defined. Thermo TRP channels should be taken into account when analyzing the pathogenesis and management of itch or pruritic dermatosis.
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PMID:[Role of thermo TRP channels in cutaneous neurogenic inflammation and itch]. 1969 81


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