THE ROLE OF TRANSIENT RECEPTOR POTENTIAL (TRPA1) CHANNEL IN PRURITUS.

Abstract

Pruritus or itch is defined as the sensation that causes the desire to scratch, and it can be induced by mechanical, thermal and chemical stimuli. Persistent itch accompanying diseases of the skin and other organs can significantly impair the quality of life. There is a growing body of evidence implicating abnormal transient receptor potential (TRP) channel function, as a product of excessive or deficient channel activity, in pathological skin conditions such as pruritus and dermatitis. These data supports the notion that non-histaminergic itch mediators require the activation of TRPA1 channel that has previously been implicated in pain and thermal sensation. In the present paper, we investigated whether chemical inducers of itch, including non-histaminergic mediators, elicit signs of thermal and mechanical hyperalgesia (increased pain to a noxious stimulus). We measured nociceptive thermal paw withdrawal latencies and mechanical thresholds bilaterally in mice at various time points following intraplantar injection of non-histaminergic mediators like as chloroquine and the bovine adrenal medulla peptide 8-22 (BAM8-22) producing hyperalgesia. We showed that chloroquine and BAM8-22 induced statistically significant dose-dependence hyperalgesia compare to vehicle control in both test. When pretreated with the TRPA1 antagonist (HC-030031) we found a significant attenuation of thermal and mechanical hyperalgesia. We showed, thus, for the first time that non-histaminergic pruritogens elicit thermal and mechanical hyperalgesia through the activation of TRPA1 channel.

• Authors: I Nozadze, N Tsiklauri, G Gurtskaia, M Tsagareli
• Journal: Georgian medical news (Georgian Med News) 2018 Jul-Aug Issue 280-281 Pg. 134-137 ISSN: 1512-0112 [Print] Georgia (Republic)
• PMID: 30204112 (Publication Type: Journal Article)

Chemical References

• 2-(1,3-dimethyl-2,6-dioxo-1,2,3,6-tetrahydro-7H-purin-7-yl)-N-(4-isopropylphenyl)acetamide
• Acetanilides
• Peptide Fragments
• Purines
• TRPA1 Cation Channel
• Trpa1 protein, rat
• bovine adrenal medulla 8-22
• Chloroquine

Topics

• Acetanilides (pharmacology)
• Animals
• Cattle
• Chloroquine (pharmacology)
• Hyperalgesia (metabolism, physiopathology)
• Male
• Peptide Fragments (pharmacology)
• Pruritus (metabolism, physiopathology)
• Purines (pharmacology)
• Rats
• TRPA1 Cation Channel (antagonists & inhibitors, metabolism)