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)

Symptoms of allergic rhinitis are produced by inflammatory mediators that are released upon activation of mast cells by antigen-IgE interaction. These mediators target the end organs directly or indirectly. Stimulation of sensory nerves by histamine, for example, leads to sneezing, pruritus, rhinorrhea, and nasal congestion. The clinical presentation of allergic rhinitis is also characterized by the phenomenon of hyperresponsiveness to nonallergic stimuli, such as cold air and various irritants. This phenomenon is believed to result from the effect of allergic inflammation on the sensory nerves that supply the upper airway mucosa. Various nonallergic triggers have been shown to act on the nasal mucosa through sensorineural stimulation. In allergic rhinitis, responsiveness to these stimuli is increased compared with the healthy state. A similar phenomenon is observed against such products of the allergic reaction as his-tamine and bradykinin. Also, in allergic rhinitis, stimulation of sensory nerves per se can produce inflammatory changes, a phenomenon known as neurogenic inflammation. The mechanism behind the development of sensorineural hyperresponsiveness and of increased propensity for neurogenic inflammation is unknown. However, evidence exists that the neurotrophin nerve growth factor, which can induce all these changes on sensory nerves, is produced in the human nasal mucosa and found in higher quantities in nasal secretions of patients with perennial allergic rhinitis as compared with healthy control subjects. Also, nerve growth factor is acutely released into nasal fluids after allergen provocation of patients with allergic disease. In patients with asthma of atopic origin, allergic rhinitis is almost ubiquitous. Because the nose is the air conditioner of the respiratory system, its dysfunction may negatively affect the lower airways. In addition to the conditioning of inhaled air, the association between allergic rhinitis and asthma may involve various mechanisms. For example, allergen provocation in the nose of a patient with asthma can lead to reductions in pulmonary function and to increased lower airway responsiveness after several hours. Also, nasal inflammation may propagate through a systemic route to affect the lower airways.
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PMID:Unique mechanistic features of allergic rhinitis. 1085 64

Protein extravasation (PE) is known to play an important role in inflammatory conditions. In this study we used dermal microdialysis to apply inflammatory mediators (histamine, bradykinin, serotonin) to human skin. Locally induced PE was compared to pain ratings and axon reflex erythema measured simultaneously. Linear microdialysis capillaries (outer diameter 0.4 mm; cut-off 3000 kDa) were inserted intracutaneously at a length of 1.5 cm in the volar forearm of healthy volunteers. The capillaries were perfused with Ringer's solution at a constant flow rate of 4 microl/min. The perfusate was sampled at 15-min intervals and was analysed for total protein concentration. After a baseline of 60 min, the perfusion was switched to inflammatory mediators for 30 min and then back to vehicle again. Sensations evoked by the stimulation were assessed on a visual analogue scale and visible axon reflex erythema was measured planimetrically.Dose-dependent increases in PE could be assessed for all inflammatory mediators tested. Bradykinin (10(-7)M) induced a significant PE, whereas serotonin was effective only at a concentration of 10(-3)M. While serotonin in lower concentrations induced moderate burning pain and an axon reflex flare but no PE, bradykinin provoked PE without pain or axon reflex flare at a concentration of 10(-7)M. Application of histamine similarly evoked PE at lower concentrations as compared to the induction of itch sensation and axon reflex flare. It is concluded that there is no link between nociceptor activation and protein extravasation induced by inflammatory mediators in healthy human skin.
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PMID:Nociceptor activation and protein extravasation induced by inflammatory mediators in human skin. 1139 22

Patients suffering from pruritus due to atopic dermatitis show, in asymptomatic skin, reduced itch and flare responses to histamine, the major pruritogenic mediator. We hypothesized that this apparent loss in histamine sensitivity may be overcompensated in inflamed skin and investigated the interactions between histamine and bradykinin, the major inflammatory mediator. The studies were performed using the isolated rat skin-nerve preparation. Forty-two fibres were tested following four different experimental protocols. After characterization of the sensory properties, six fibres were treated repetitively with histamine (HIS1, HIS2) to exclude the possibility that the responses (spikes/min) increase simply by repetition. In 12 other units, histamine (HIS1) was followed by a wash-out period prior to bradykinin (BK) stimulation; in another 12 units, BK followed immediately after HIS1. A further 12 fibres were examined without preceding heat stimulation in order to avoid possible sensitization. If BK was administered after a wash-out period following HIS1, the BK responses were significantly higher than the HIS1 response. The BK response showed a peak discharge which was absent if BK followed directly upon HIS1. If HIS2 was applied directly following BK, the induced discharge was significantly larger than the first histamine response and not different from the BK response, whereas a washout period before HIS2 abolished the sensitizing effect of previous BK.A unidirectional sensitization by previous bradykinin or heat stimulation on the histamine responsiveness of polymodal nociceptors has been demonstrated. If 'itch fibres' in humans were subject to similar interactions of histamine with inflammatory mediators, this may compensate for a down-regulation of histamine receptors in eczematic skin and possibly account for the pruritus.
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PMID:Interactions of histamine and bradykinin on polymodal C-fibres in isolated rat skin. 1139 27

Since adverse effects due to angiotensin-converting enzyme (ACE) inhibitors frequently occur in cutaneous locations, this review summarizes the spectrum of expected and unexpected adverse effects of these drugs, possible associated mechanisms, and their basic functions for dermatologists. ACE inhibitors block the activity of the metalloproteinase ACE by binding to its active site, thus displacing angiotensin I and preventing its conversion to vasopressive angiotensin II. Furthermore, ACE degrades bradykinin, substance P, enkephalins and some of the reproductive peptide hormones. The overall incidence of adverse effects to ACE inhibitors is estimated at 28%, approximately half of which occurs in the skin. General reactions are first-dose hypotension, hyperkalaemia and renal failure. Cutaneous reactions comprise life-threatening angioedema, pruritus, bullous eruptions, urticaria, other generalized rashes, photosensitivity and hair loss. ACE inhibitors thus mimic a broad variety of skin diseases, why these drugs should be thought of when sudden, unexplainable skin eruptions are observed.
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PMID:Angiotensin-converting enzyme inhibitors as inducers of adverse cutaneous reactions. 1180 Jan 36

Vasoneuroactive substances were applied through intradermal microdialysis membranes and characterized as itch- or pain-inducing in psychophysical experiments. Histamine always provoked itching and rarely pain, capsaicin always pain but never itching. Prostaglandin E(2) (PGE(2)) led preferentially to moderate itching. Serotonin, acetylcholine, and bradykinin induced pain more often than itching. Subsequently the same substances were used in microneurography experiments to characterize the sensitivity profile of human cutaneous C-nociceptors. The responses of 89 mechanoresponsive (CMH, polymodal nociceptors), 52 mechanoinsensitive, histamine-negative (CMi(His-)), and 24 mechanoinsensitive, histamine-positive (CMi(His+)) units were compared. CMi(His+) units were most responsive to histamine and to PGE(2) and less to serotonin, ACh, bradykinin, and capsaicin. CMH units (polymodal nociceptors) and CMi(His-) units showed significantly weaker responses to histamine, PGE(2), and acetylcholine. Capsaicin and bradykinin responses were not significantly different in the two classes of mechano-insensitive units. We conclude that CMi(His+) units are "selective," but not "specific" for pruritogenic substances and that the pruritic potency of a mediator increases with its ability to activate CMi(His+) units but decreases with activation of CMH and CMi(His-) units.
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PMID:Chemical response pattern of different classes of C-nociceptors to pruritogens and algogens. 1261 75

Itching is defined as an unpleasant cutaneous sensation leading to the desire to scratch. It serves as a physiological self-protective mechanism as do other cutaneous sensations like pain, touch, vibration, cold, and heat to help defend the skin against harmful external agents. Pruritus can be evoked in the skin directly by mechanical and thermal stimuli or indirectly through chemical mediators. It may also be generated in the central nervous system independently of peripheral stimulation. Single-nerve-fiber recordings have shown that histamine-evoked itch is transmitted by selective slow-conducting subpopulations of unmyelinated C-polymodal neurons. Recent experimental studies using improved methods have demonstrated which of the suspected chemical itch mediators such as histamine, neuropeptides, prostaglandins, serotonin, acetylcholine, or bradykinin act pruritogenically on C-fibers. Moreover, investigations have revealed new receptor systems such as vanilloid, opioid, and cannabinoid receptors on cutaneous sensory nerve fibers that may modulate itch and thereby represent targets for antipruritic therapy. This review focuses on the peripheral generation of itch, including neurotransmitters, neuropeptides, and inflammatory mediators.
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PMID:Neurophysiology of pruritus: cutaneous elicitation of itch. 1462 6

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

Both, pruritus and pain are aversive, but clearly distinct sensations originating in the peripheral and central nervous system. During the last years, many interactions between itch and pain in acute transmission and sensitization processes have been identified. It is common experience that the itch sensation can be reduced by the painful sensations caused by scratching. Vice versa analgesia may reduce this inhibition and thus enhance itch. This phenomenon is particularly relevant to spinally administered mu-opioid receptor agonists, which induce segmental analgesia often combined with segmental pruritus. The peripheral and central sensitization to pain and to itch exhibits striking similarities. Classical inflammatory mediators such as bradykinin have been shown to sensitize nociceptors for both itch and pain. Also regulation of gene expression induced by trophic factors, such as NGF, plays a major role in persistently increased neuronal sensitivity for itch and pain. Finally, itch and pain exhibit corresponding patterns of central sensitization. The knowledge of antagonistic interaction, but also of similar sensitization processes has major implication for antipruritic therapeutic approaches.
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PMID:Chronic itch and pain--similarities and differences. 1667 56

Histamine, substance P, serotonin and bradykinin were applied by iontophoresis to lesional and visually non-lesional skin of 14 patients with atopic dermatitis, and normal skin of 15 healthy volunteers. Itch could be evoked by light stroking of skin with a cotton swab (alloknesis) in all lesional skin sites, but not in non-lesional or normal skin. Substances were applied in the same skin area before and 3 h after administration of placebo or antihistamine (olopatadine hydrochloride: H1-receptor-blocker). Intensities of itch and pain sensation and areas of flare and wheal were measured. All the substances induced significantly more intense itch in lesional skin than in non-lesional skin of patients. Even bradykinin, which evoked only weak itch and pain of similar intensities in non-lesional skin of patients and in healthy volunteers, induced intense itch in lesional skin, while the simultaneously increased pain did not suppress the itch sensation, indicating central sensitization. Histamine- and substance P-induced itch was almost completely suppressed by antihistamines, whereas bradykinin- and serotonin-induced itch was not. This suggests that substance P is a histamine-dependent pruritogen also in lesional skin under sensitized conditions but that bradykinin and serotonin are histamine-independent pruritogens in lesional skin. It is concluded that serotonin and bradykinin, classic endogenous algogens, can turn into potent histamine-independent pruritogens in lesional skin of atopic dermatitis.
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PMID:Bradykinin is a potent pruritogen in atopic dermatitis: a switch from pain to itch. 1684 20

A man with no atopic antecedent, but who was being treated with a Angiotensin-converting enzyme inhibitor (ACE), was admitted to hospital for an edema affecting the face and tongue. The symptoms included dyspnea and dysphagia but not pruritus or dermal erythema. The patient was resistant to corticoid treatment, antihistaminic drugs and epinephrine. Treatment with C1 inhibitor concentrate (1000u) made the clinical symptoms disappear within 20 minutes. The resulting angioedema induced seems to be linked to the bradykinin metabolism, which would not be any better served by the angiotensin-converting enzyme, which normally inactivates about 75% of it.
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PMID:[Angiotensin-converting enzyme inhibitor-related angioedema: emergency treatment with complement C1 inhibitor concentrate]. 1809 74


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