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

Boros, Krisztina

Jancsó, Gábor

Dux, Mária

Bencsik, PĂ©ter

Oszlács, Orsolya

Katona, Márta

Ferdinandy, PĂ©ter

Sántha, Péter

Elsevier

2015

R1 Medicine (General) / orvostudomány általában

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
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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.

magyar

Article

NonPeerReviewed

info:eu-repo/semantics/article

text

http://real.mtak.hu/28905/1/NSAP-S-15-00239%283%29.pdf

Boros, Krisztina and Jancsó, Gábor and Dux, Mária and Bencsik, Péter and Oszlács, Orsolya and Katona, Márta and Ferdinandy, Péter and Sántha, Péter (2015) Multiple impairments of cutaneous nociceptor function induced by cardiotoxic doses of adriamycin in the rat. Naunyn-Schmiedeberg's Archive of Pharmacology. (Submitted)

http://real.mtak.hu/28905/

NSAP-S-15-00239