Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P20366 (substance P)
 21,176 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Neurokinins are a family of peptides which are released from sensory nerves. This family involves substance P, neurokinin A and B which stimulate neurokinin-NK1, -NK2 and -NK3 receptors respectively. The neurokinins as well as C.G.R.P. (calcitonin gene related peptide) and V.I.P. (vasoactive intestinal peptide) are the mediators of the non adrenergic non cholinergic (N.A.N.C.) nervous system. All these peptides can be released by nerve fibres innervating the skin. They are mainly inflammatory mediators. At skin level, the neurokinin induce itch, wheal and flare. Itch and flare are partly due to histamine release from mast cells in response to substance P.
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PMID:[Neurokinins and the skin]. 769 70

Systemic sclerosis is characterized by vascular dysfunction. Itch is sometimes present in early stages of the disease. This prompted us to study the innervation of the skin by immunocytochemistry. Antibodies to neuropeptide Y and vasoactive intestinal peptide were used for autonomic nerves. Sensory innervation was studied using antibodies to substance P and calcitonin gene-related peptide. Protein gene product 9.5 was used as a general neuronal marker. Skin biopsies from affected (lower arm) and non-affected (upper back) sites on 10 patients with systemic sclerosis and from corresponding sites on 10 sex- and age-matched healthy controls were studied. Regional variations were found in the occurrence of peptidergic nerve fibers. In the patients the density of nerve fibers (measured semiquantitatively) stained by the panneuronal marker was lower in affected than in unaffected skin (p < 0.05). There were no significant differences in peptidergic innervation between patients and controls. However, there was a tendency to higher density of neuropeptide Y-positive nerve fibers in the forearm skin in 6 to 10 patients, as compared to only 1 of 10 healthy controls.
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PMID:Occurrence and distribution of peptidergic nerve fibers in skin biopsies from patients with systemic sclerosis. 874 Feb 66

Itch is thought to be signaled by a sub-population of pruritogen-selective C-fiber primary afferents. To assess a possible role of the neuropeptide, substance P (SP), in the central neurotransmission of itch, we investigated itch-related scratching behavior elicited by intradermal injection of serotonin (5-HT; 0.03-0.3%) in normal mice (wildtype, WT) and knockout mice (KO) with deletion of the preprotachykinin A gene. Both KO and WT groups showed dose-related increases in the number of 5-HT-evoked scratching bouts over the 44 min observation period. There were no significant differences in the numbers or durations of scratching bouts between WT and KO groups, although KO mice exhibited numerically more spontaneous and 5-HT-evoked scratching. It is concluded that either SP is not involved in the central neurotransmission of itch-related scratching behavior in this strain of mouse, or that compensatory developmental changes in the KO mice allow itch-related signaling.
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PMID:Deletion of the preprotachykinin A gene in mice does not reduce scratching behavior elicited by intradermal serotonin. 1261 3

Itch, also known as pruritus, is the major symptom in skin diseases with a variety of etiologies and pathophysiologies. Significant progress has been achieved in understanding the pathophysiology of itch in the last 5 years. Neurophysiological experiments in humans and animals have revealed that itch is carried by specific C nerve fibers. Recent studies have demonstrated that peripheral mediators other than histamine are involved in induction of itch. Mast cell tryptase seems to be an important mediator in itch by its activation of proteinase activated receptor 2 in the sensory nerves. Opioids have central and peripheral itch producing activity. Neuropeptides, such as substance P, induce itch by their effect on mast cells. Based upon our improved understanding of the neurophysiology of itch a clinical classification of itch has been proposed. The classification highlights differences between peripheral pruritoceptive itch, neuropathic itch (itch related to damage to afferent nerve fibers) and neurogenic itch (itch originating in the central nervous system without any evidence of nerve damage). Emerging therapies based on these findings include topical vanilloid receptor antagonists, topical antihistamines, and topical arachidonic acid inhibitors, as well as inhibitors of non-histamine inflammatory mediators, immunomodulators and strontium salts. Systemic therapies include thalidomide, opioid antagonists, phototherapy with narrow band UVB and experimental treatments with cutaneous field stimulation and vagal nerve stimulation. With the new information it seems we will be able to better help our dermatologic patients who have itch, however we are not closer to identifying a single agent specifically targetable to this symptom.
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PMID:Itch associated with skin disease: advances in pathophysiology and emerging therapies. 1292 80

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

Perceived stress has long been allied with disturbances of the dynamic equilibrium established between the nervous, endocrine and immune systems, thus triggering or aggravating disease manifestation. Several common skin diseases are now acknowledged to be worsened by psychological stress, particularly immunodermatoses such as atopic dermatitis, psoriasis, seborrheic eczema, prurigo nodularis, lichen planus, chronic urticaria, alopecia areata and pruritus sine materia. Itch (pruritus) is perhaps the most common symptom associated with a majority of these inflammatory skin diseases, and acute as well as chronic stress perceptions are recognized to trigger or enhance pruritus. A wealth of mediators released systemically or locally in the skin in response to stress increase sensory innervation, upregulate the production of other pruritogenic agents, perpetuate (neurogenic) inflammation and lower the itch threshold. In the present review, we explore recent frontiers in both stress and pruritus research and portray the perpetuation of chronic skin inflammation and itch as a neuroendocrine-immune 'misalliance'. We argue that key candidate molecules of the stress response with strong pruritogenic potential, such as nerve growth factor, corticotropin-releasing hormone and substance P, and mast cells, which may be considered as 'central cellular switchboards of pruritogenic inflammation', need to be further explored systematically in order to develop more effective therapeutic combination strategies for itch management in chronic, stress-vulnerable inflammatory skin diseases.
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PMID:From the brain-skin connection: the neuroendocrine-immune misalliance of stress and itch. 1770 57

Pruritus is not the equivalent of the cough of the skin, but itch and scratch can certainly be defined as such. In physiological conditions, they share the same function: to exclude a foreign body. Itch/scratching and cough could be selective responses for the same diseases, mainly atopic diseases, and their pathophysiology is similar (role of C fibers and mast cells; role of histamine, substance P and tachykinins). This is an intriguing analogy rather than a pathophysiological identity. It may be inappropriate for many disease settings. Itch and cough can be triggered or enhanced by stress. This similarity is very interesting because it could give rise to many new research ideas.
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PMID:Are pruritus and scratching the cough of the skin? 1803 92

Uremic pruritus is a common and sometimes severe complication of chronic renal failure. Itch affects 50-90% of patients undergoing peritoneal dialysis or hemodialysis and 25% of patients with preterminal chronic renal failure. The mechanism underlying uremic pruritus is poorly understood; possibilities include histamin, proteases, interleukin-2 and TNF- produced by skin mast-cells, substance P, neuropathy and neurological changes, high level of Ca, P, PTH, Al, Mg, divalent ion abnormalities, hypervitaminosis A, inflammation, or some combination of these. Therapeutic measures include regular efficient dialysis, transplantation, topical measures as an emollients, topical steroids, systemic measures as diet, opioids and physical treatment with phototherapy, acupuncture etc. Treatment results are highly variable and more research is needed to understand the patophysiology of this condition and to establish more reliable treatments. Most effective treatments in this moment are efficient dialysis, dietary restrictions, phosphate-binding therapy and phototherapy.
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PMID:[Uremic pruritus]. 1857 30

Itch is thought to be signaled by pruritogen-responsive neurons in the superficial spinal dorsal horn. Many neurons here express the substance P NK-1 receptor. We investigated whether neurotoxic destruction of spinal NK-1-expressing neurons affected itch-related scratching behavior. Rats received intracisternal substance P conjugated to saporin (SP-SAP), or saporin (SAP) only (controls), and were subsequently tested for scratching behavior elicited by intradermal 5-hydroxytryptamine. SAP controls exhibited dose-related hindlimb scratching, which was significantly attenuated in SP-SAP-treated rats. There was a virtual absence of NK-1 immunoreactive neurons in superficial laminae of the upper cervical and medullary dorsal horn in SP-SAP-treated rats. These results indicate that superficial dorsal horn neurons expressing NK-1 receptors play a key role in spinal itch transmission.
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PMID:Dorsal horn neurons expressing NK-1 receptors mediate scratching in rats. 2012 52

Itch is a complication of liver disease. It is hypothesized that this type of itch is mediated, at least in part, by increased central opioidergic tone; a peripheral component may coexist. The role of serotonin, bile acids, substance P, and lipophosphatidic acid and the activity of the enzyme that generates it, autotoxin, has been proposed in the pathogenesis of itch. Scratching activity was significantly suppressed in association with the placebo tablet in a controlled, double-blind study; this finding supports the exploration of the placebo effect on the itch sensation and the inclusion of behavioral methodology in clinical trials in patients with this complication of liver disease.
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PMID:The itch of liver disease. 2176 69


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