Multiple impairments of cutaneous nociceptor function induced by cardiotoxic doses of Adriamycin in the rat

Boros, Krisztina and Jancsó, Gábor and Dux, Mária and Fekécs, Zoltán and Bencsik, Péter and Oszlács, Orsolya and Katona, Márta and Ferdinandy, Péter and Nógrádi, Antal and Sántha, Péter (2016) Multiple impairments of cutaneous nociceptor function induced by cardiotoxic doses of Adriamycin in the rat. Naunyn-Schmiedeberg's Archives in Pharmacology, 389 (9). pp. 1009-1020. ISSN 0028-1298 (Print) 1432-1912 (Online)

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Besides their deleterious action on cardiac muscle, anthracycline-type cytostatic agents exert significant neurotoxic effects on primary sensory neurons. Since cardiac sensory nerves confer protective effects on heart muscle and share common traits with cutaneous chemosensitive nerves, this study examined the effects of cardiotoxic doses of adriamycin on the function and morphology of epidermal nerves. Sensory neurogenic vasodilatation, plasma extravasation and the neural CGRP release evoked by TRPV1 and TRPA1 agonists in vitro were examined by using laser Doppler flowmetry, the Evans blue technique and ELISA, respectively. Carrageenan-induced hyperalgesia was assessed with the Hargreaves method. Immunohistochemistry was utilized to study cutaneous innervation. Adriamycin treatment resulted in profound reductions in the cutaneous neurogenic sensory vasodilatation and plasma extravasation evoked by the TRPV1 and TRPA1 agonists capsaicin and mustard oil, respectively. The in vitro capsaicin-, but not high potassium-evoked neural release of the major sensory neuropeptide, CGRP, was markedly attenuated after adriamycin treatment. Carrageenan-induced inflammatory hyperalgesia was largely abolished following the administration of adriamycin. Immunohistochemistry revealed a substantial loss of epidermal TRPV1-expressing Powered by Editorial Manager® and ProduXion Manager® from Aries Systems Corporation nociceptive nerves and a marked thinning of the epidermis. These findings indicate impairments in the functions of TRPV1 and TRPA1 receptors expressed on cutaneous chemosensitive nociceptive nerves and the loss of epidermal axons following the administration of cardiotoxic doses of adriamycin. Monitoring of the cutaneous nociceptor function in the course of adriamycin therapy may well be of predictive value for early detection of the deterioration of cardiac nerves which confer protection against the deleterious effects of the drug.

Item Type: Article
Subjects: R Medicine / orvostudomány > R1 Medicine (General) / orvostudomány általában > R850-854 Experimental medicine / kisérleti orvostudomány
Depositing User: Dr. Péter Bencsik
Date Deposited: 27 Sep 2016 12:39
Last Modified: 27 Sep 2016 12:39

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