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)

We studied the effect of tranilast on the growth of carrageenin-induced granulation and the increase in capillary permeability induced by inflammatory agents in rats. In the carrageenin-induced granulation model, tranilast (50 or 100-200 mg/kg, p.o.) decreased significantly and dose-dependently the weight and the hydroxyproline content of the granulation tissue. Tranilast, however, showed no effect on the healing day of locally wounded dorsal skin of rats. Triamcinolone (10 mg/kg, p.o.) also showed an inhibitory effect on the carrageenin-induced granulation model. Tranilast (50-400 mg/kg, p.o.) dose-dependently inhibited the enhancement of capillary permeability induced by the Ca ionophore A23187, bradykinin and xanthine oxidase. Moreover, tranilast (30 and 300 microM) suppressed superoxide production induced by FMLP in human neutrophils, but did not act as a superoxide scavenger. Considering that hypertrophic scar and keloid are conditions characterized by abnormal cell proliferation and excessive collagen accumulation accompanied with itch and pain, these results suggest that tranilast is useful as a therapeutic drug for hypertrophic scars and keloids.
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PMID:[Effect of tranilast, an anti-allergic drug, on carrageenin-induced granulation and capillary permeability in rats]. 137 12

A problem in the study of nociceptors is that intense stimuli are used to locate the receptive field (RF), and thus the receptor may be damaged before the first responses are recorded. In addition, some nociceptors do not respond to the mechanical stimuli often used to search for the RF. To overcome these problems, an electrical search technique was developed to locate the RF of cutaneous nociceptors. In the hairy skin of anesthetized monkey, we used this technique to locate the RF of 63 A delta-fibers and 22 C-fibers that had extremely high thresholds or were unresponsive to mechanical stimuli. We refer to these afferents as mechanically insensitive afferents (MIAs). Ten A delta-fiber MIAs had a short latency response to stepped heat stimuli and could be responsible for first pain sensation. Five A delta-fiber MIAs and one C-fiber MIA did not respond to mechanical or heat stimuli but did respond to injection into the electrical RF of an artificial inflammatory soup containing histamine, bradykinin, prostaglandin E1, and serotonin. These chemoreceptors might be responsible for the pain and itch sensations that result from chemical stimuli. Some MIAs became more responsive to mechanical stimuli after injection into the RF of the inflammatory soup and, thus, may contribute to the hyperalgesia to mechanical stimuli associated with cutaneous injury. A large proportion of the A delta-fiber (48%) and C-fiber (30%) afferents in this study were insensitive to mechanical stimuli. The role of these MIAs in sensation needs to be studied further. The electrical search technique enables a systematic study of these afferents to be performed. This technique may also be of use to identify and characterize dorsal horn neurons that have inputs from MIAs.
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PMID:Mechanically insensitive afferents (MIAs) in cutaneous nerves of monkey. 180 41

1. The structure-activity relationship of kinins within the nose has been investigated in atopic rhinitic (n = 7) and non-rhinitic (n = 7) subjects. On 4 separate days, each separated by a week, subjects randomly underwent nasal challenge with incremental doses of either the B1 agonist [Des-Arg9]-bradykinin, the B2 agonists kallidin or bradykinin, or vehicle placebo in a double-blind comparative study. The nasal response was monitored objectively by measurement of nasal airways resistance (NAR) by active posterior rhinomanometry and subjectively by symptom reporting of nasal blockage, rhinorrhoea, nasal itch and nasal pain. 2. The B2 agonists kallidin and bradykinin both induced a dose-dependent increase in NAR (P less than 0.001) and were associated with symptomatic reporting of nasal blockage (P less than 0.05), rhinorrhoea (P less than 0.01) and nasal discomfort (P less than 0.05) compared to placebo. In contrast the effects of the B1 agonist [Des-Arg9]-bradykinin on NAR and symptom reporting were indistinguishable from placebo. No difference could be identified in the nasal response to kallidin and bradykinin between rhinitic and non-rhinitic subjects and there was no evidence of B1 receptor upregulation in the disease state. For the whole group the provocative dose of agonist inducing a 50% increase in NAR (PD50) was 1.77 x 10(-4) mol for bradykinin and 2.86 x 10(-4) mol for kallidin (P greater than 0.05). 3. These findings identify that the nasal effects of kinins are mediated through B2 receptors and the advent of B2 receptor antagonists will permit a further evaluation of the role of kinins in rhinitis.
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PMID:Comparative nasal effects of bradykinin, kallidin and [Des-Arg9]-bradykinin in atopic rhinitic and normal volunteers. 189 Jun 50

In the present experiments the role of unmyelinated sensory fibres in the mechanism of cutaneous inflammatory reactions under normal and pathological conditions has been studied in man and animals. Dye leakage responses to histamine, serotonin, compound 48/80, bradykinin and substance P were significantly reduced, while neurogenic inflammation was completely abolished in rats treated neonatally with capsaicin, as studied quantitatively by the Evans blue technique. Neurogenic inflammation could also be elicited by mustard oil in normally innervated human skin, but not in skin areas affected by herpes zoster or in a patient suffering from congenital analgesia. Repeated topical treatment of the skin with capsaicin (local desensitization) abolished the neurogenic inflammatory response for several days. Chemical pain sensitivity was strongly reduced, and thresholds for warmth and heat pain sensations were significantly elevated. Local capsaicin desensitization of the skin prevented whealing, flare and itch in patients with acquired cold and heat urticaria. The findings indicate that peptide-containing sensory nerves are involved in the mediation of chemogenic and heat pain, and possibly itch, and are responsible for initiation of the neurogenic inflammatory response. The results also provide direct evidence of the involvement of these particular sensory nerves in the modulation of the permeability-increasing effects of putative mediators of acute inflammatory reactions. It is concluded that, through modulation of cutaneous vascular reactions, peptidergic sensory nerves may play a hitherto unrecognized role in the pathomechanism of certain diseases of human skin.
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PMID:The modulation of cutaneous inflammatory reactions by peptide-containing sensory nerves. 241 73

The causes of pruritus in patients undergoing hemodialysis and the mechanism of the antipruritic effect of Neurotropin, an extract isolated from the inflamed dermis of rabbits inoculated with vaccinia virus and clinically used in Japan as an analgesic and antiallergic drug, were investigated by measuring the levels of C3a, C5a, bradykinin and lipid peroxides in venous blood collected before dialysis, and at 15 min and 4 hr after starting hemodialysis. C3a increased considerably in pruritic patients compared to non-pruritic patients at 15 min after starting hemodialysis. Neurotropin significantly suppressed the C3a level and improved the condition of pruritic patients. There was no significant difference in the level of bradykinin between pruritic patients and non-pruritic patients. Therefore, bradykinin was not thought to be related to the incidence of pruritus in such patients. A tendency towards lowering of the levels of lipid peroxides in the patients' plasma by Neurotropin was also observed. It seems possible that elevation of C3a may be one of the underlying causes for the appearance of pruritus, and that Neurotropin may exert its antipruritic effect through suppression of the activation of C3 in patients undergoing hemodialysis.
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PMID:Study on pruritus in hemodialysis patients and the antipruritic effect of neurotropin: plasma levels of C3a, C5a, bradykinin and lipid peroxides. 261 18

The effect of a conditioning bradykinin application on histamine induced excitation of cutaneous nociceptors and on histamine induced sensations of volunteers was studied. Using an in vitro skin nerve preparation, unmyelinated polymodal nociceptor units of rats (n = 11) were tested by bathing their receptive fields from the corium side with 10(-5) M solutions of bradykinin and histamine. Following bradykinin superfusion the histamine induced discharges were enhanced, and previously unresponsive units were excited by histamine. Corresponding psychophysical experiments were carried out in 13 healthy volunteers. Histamine iontophoresis (30 mC) induced predominantly itching sensations after an intracutaneous control injection of physiological saline. However, following bradykinin injections (100 microliters of a 10(-7) M solution) histamine induced little itch but rather a burning sensation lasting 1-2 min. Itching remained suppressed even after the burning sensations had subsided. These data support a hypothesis according to which itching is mediated by a sub-population of polymodal nociceptor units, and pain is induced whenever a larger nociceptor population is recruited. In the CNS itch processing is either occluded (masked) by pain processing, or suppressed by inhibitory processes.
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PMID:Conditioning of histamine by bradykinin alters responses of rat nociceptor and human itch sensation. 851 62

Previous studies show that oral antihistamines affect the weal and flare response to intradermal injections of the inflammatory mediators platelet-activating factor (PAF) and bradykinin (BK). The aim of this study was to compare the effects of terfenadine (an H1-antagonist) and cimetidine (an H2-antagonist) on weal and flare responses to PAF and BK in healthy non-atopic human volunteers. The effects of doxepin on PAF responses were investigated, as there is evidence that doxepin may have direct anti-PAF effects in addition to its known antihistaminic actions. Terfenadine significantly reduced weal and flare responses to PAF (mean reduction 53 and 73%, respectively) and flare responses to BK (mean reduction 78%) but had no effect on weal responses to BK. Doxepin significantly reduced both weal and flare responses to PAF (mean reduction 43 and 68%, respectively, at higher doses of PAF). Cimetidine had no effect on weal or flare responses to PAF or BK. These findings suggest that the flare response to intradermal BK is mediated via histamine release while the weal response is not. The effects of the various antagonists of PAF-induced responses suggest that its effects too may be mediated via histamine, the similarity of the effects of terfenadine and doxepin on these responses indicating that the effects of doxepin may be due to its known antihistamine activity rather than to any specific PAF-antagonistic properties. Platelet-activating factor (PAF) is a phospholipid which is released from a wide range of cell types and also from vascular endothelium. PAF is formed by the conversion of ether-linked phospholipids initially to the biologically inactive lyso-PAF and then by acetylation to PAF. Intradermal injection of PAF in human skin causes vasodilatation and increased vascular permeability, producing a weal and flare response with accompanying pruritus. Bradykinin (BK) is a vasoactive polypeptide formed by the action of enzymes known as kallikreins on inactive precursors called kininogens. Its effects include an increase in blood flow and vascular permeability and stimulation of the release of prostaglandins and histamine. On intradermal injection in human skin it causes a weal and flare response with associated pain rather than pruritus. Previous studies have suggested that the weal and flare response to PAF may be mediated in part by histamine release. Given that BK is known to cause histamine release it appears possible that the responses to both compounds may be modified by conventional antihistamines. Experiments based on this premise have found that antihistamines have a pronounced effect on the flare response to PAF but a less marked effect on weal responses. The weal response to BK was unaffected by systemic antihistamines but studies have produced conflicting results with regard to effects on the flare response. The aim of this study was to compare the effects of terfenadine (an H1-antagonist) and cimetidine (an H2-antagonist) on PAF- and BK-induced weal and flare responses in healthy, non-atopic human volunteers. Based on the treatment of cold urticaria it has been suggested that doxepin, which has known H1- and H2-antagonistic effects, may in addition show specific anti-PAF activity. We compared the effects of doxepin on PAF-induced intradermal responses with those of terfenadine and cimetidine in this study.
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PMID:Effects of H1- and H2-antihistamines on platelet-activating factor and bradykinin-induced inflammatory responses in human skin. 868 66

We have recently reported that IL-2 activates a third of cutaneous C-fibre polymodal nociceptors. Responses were dose-dependent and concentration threshold was below 1.2 U/3 microliters. Potent tachyphylaxis characterized the response to subsequent injections of the same dose. These nociceptors were also activated by histamine and bradykinin. However, the cross-reactivity between inflammatory mediators was not assessed due to experimental limitations. Nevertheless, we found in preliminary studies that BK enhanced the responsiveness of polymodal nociceptors to IL-2 by reversing IL-2-induced tachyphylaxis and increasing response magnitude. The fact that BK potentiated the responsiveness of nociceptors to a chemical stimulus was unexpected and needed further investigation. In the present study, 40 cutaneous C-fibre polymodal nociceptors were isolated in 26 rat saphenous nerve preparations. Nociceptors were identified by their conduction velocity and response thresholds to electrical, mechanical and thermal stimuli. Two series of experiments were conducted: in the first series of experiments, IL-2 (1.2 U/3 microliters) was injected twice prior to BK (150 ng/3 microliters) and injected again twice after BK. In the second series of experiments, BK preceded the two injections of IL-2. In the first series of experiments, responses to IL-2 were increased by 55% after BK and this difference was statistically significant in a paired-sample t-test (P < 0.02). In the second series of experiments, units responded to IL-2 with a vigorous and irregular (bursting) sustained discharge (255 +/- 35 action potentials/300 s) and no tachyphylaxis appeared to the second IL-2 injection. In addition, potent thermal sensitization occurred after BK. Possible cellular and sub-cellular mechanisms of BK-induced potentiation to IL-2 are discussed. We conclude that BK enhances the responsiveness of cutaneous C-fibre polymodal nociceptors to IL-2, which may explain the occurrence of pruritus in the healing process of inflamed skin.
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PMID:Bradykinin potentiates the chemoresponsiveness of rat cutaneous C-fibre polymodal nociceptors to interleukin-2. 881 9

We have investigated the effects of interleukin-2 on identified cutaneous C- and A delta- fibre nociceptors in an in vivo rat saphenous nerve preparation. A fraction of C-polymodal (33%), A delta- (22%) and C- (7.5%) mechanical nociceptors were activated by intradermal injection of interleukin-2. For C-fibre polymodal nociceptors, concentration thresholds were < or = 0.12 unit/3 microliters and the percentage of interleukin-2-activated nociceptors did not increase with concentrations above 0.06 unit/3 microliters. Responses were dose-dependent and characterized by potent tachyphylaxis for subsequent injections of the same dose. C-fibre polymodal nociceptors activated by interleukin-2 were also activated by subsequent chemical stimuli as follows: 81% were activated by histamine (300 ng/3 microliters), 87% by bradykinin (75 ng/3 microliters), 100% by topical acetic acid and 87% by capsaicin (3 micrograms/3 microliters). In contrast, C-fibre polymodal nociceptors that could not be activated by interleukin-2 responded less frequently to histamine (17%) and bradykinin (24%) but were generally activated by noxious chemicals, including acetic acid (82%) and capsaicin (70%). In conclusion, this study demonstrates that interleukin-2 is a potent activator of a discrete population of cutaneous C-polymodal nociceptors, which are chemosensitive to endogenous inflammatory mediators. The fact that these nociceptors respond to a variety of endogenous mediators is consistent with the concept of multiple humoral mechanisms of itch and, consequently, the difficulties in reducing itch associated with inflammation.
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PMID:Interleukin-2 activates a sub-population of cutaneous C-fibre polymodal nociceptors in the rat hairy skin. 933 85

Congenital C1-inhibitor deficiency, or hereditary angioneurotic edema (HAE), is a rare autosomal dominant disease due to alterations in the C1 inhibitor gene that results in a deficiency of antigenic and/or functional C1-INH. Affected patients are heterozygous, and their deficiency is incomplete, many of them having up to 20% of the normal amount of the inhibitor. The disease is characterised by recurrent, circumscribed, non-pitting, and non-pruritic subepithelial swellings of sudden onset, which fade during the course of 48-72 hours, but can persist up to 1 week. Lesions can be solitary or multiple and primarily involve the extremities, larynx, face, and bowel wall. Bradykinin is believed to be the main, but certainly not the sole, mediator responsible for the bouts of edema in HAE. The diagnosis is suggested by family history, the lack of accompanying pruritus or urticaria, the presence of recurrent gastrointestinal attacks of colics, and episodes of laryngeal edema. Diminished C4 concentrations during symptomatic periods are highly suggestive for the diagnosis. Further laboratory diagnosis depends on demonstrating a deficiency of C1-INH antigen (type I) in most kindreds, but some kindreds have an antigenically intact but dysfunctional protein (type II) and require a functional assay to establish the diagnosis. Prophylactic administration of either attenuated androgens or protease inhibitors has proved useful in reducing frequency or severity of attacks. Infusions of a vapour-heated C1-INH concentrate are safe and effective means of both preventing and treating attacks. Nevertheless, this treatment is expensive and this extract is not readily available. It is emphasised that administration of angiotensin converting enzyme inhibitors is contraindicated in patients suffering from protease inhibitor deficiency states.
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PMID:Hereditary angioneurotic edema: review of the literature. 1078 4


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