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)

Allergic contact dermatitis is a common skin disease associated with inflammation and persistent pruritus. Transient receptor potential (TRP) ion channels in skin-innervating sensory neurons mediate acute inflammatory and pruritic responses following exogenous stimulation and may contribute to allergic responses. Genetic ablation or pharmacological inhibition of TRPA1, but not TRPV1, inhibited skin edema, keratinocyte hyperplasia, nerve growth, leukocyte infiltration, and antihistamine-resistant scratching behavior in mice exposed to the haptens, oxazolone and urushiol, the contact allergen of poison ivy. Hapten-challenged skin of TRPA1-deficient mice contained diminished levels of inflammatory cytokines, nerve growth factor, and endogenous pruritogens, such as substance P (SP) and serotonin. TRPA1-deficient sensory neurons were defective in SP signaling, and SP-induced scratching behavior was abolished in Trpa1(-/-) mice. SP receptor antagonists, such as aprepitant inhibited both hapten-induced cutaneous inflammation and scratching behavior. These findings support a central role for TRPA1 and SP in the integration of immune and neuronal mechanisms leading to chronic inflammatory responses and pruritus associated with contact dermatitis.
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PMID:TRPA1 controls inflammation and pruritogen responses in allergic contact dermatitis. 2372 16

Allergic contact dermatitis (ACD) is a common skin condition caused by a type-IV hypersensitivity reaction. Even though ACD is considered as a T-cell mediated disease, indications exists that peptidergic nerve fibers at the site of allergen exposure and associated with the draining lymph node play a prominent role in both induction and elicitation of ACD. This neuro-immune cross talk seems rely on neuropeptides such as Substance P secreted by nerve fiber terminals. It is hypothesized that local complete or partial cutaneous denervation/defunctionalization of peptidergic fibers in humans could be a feasible approach towards treating allergic contact dermatitis. Recently, human experimental protocols for prominent, temporary defunctionalization of peptidergic fibers have been published relying on prolonged application of 8% topical capsaicin patches. Combined with human experimental ACD models the importance of peptidergic nerve fibers in the induction and elicitation phases of ACD could be accurately established. Understanding the role of cutaneous peptidergic fibers in the pathogenesis and potentially of ACD and how contact sensitization can be modulated by topical defunctionalization of these fibers could lead to new approaches to treatment for ACD. In patients with localized ACD occurring to an allergen that is difficult or unfeasible to evade this would have particular relevance.
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PMID:High-concentration topical capsaicin may abolish the clinical manifestations of allergic contact dermatitis by effects on induction and elicitation. 2811 Jun 99