Expression of sodium channel NaV 1.8 in dorsal root ganglia after Paclitaxel treatment

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LEVIN Shahaf DUBOVÝ Petr JOUKAL Marek

Rok publikování 2019
Druh Další prezentace na konferencích
Fakulta / Pracoviště MU

Lékařská fakulta

Citace
Popis Introduction: The chemotherapeutic agent Paclitaxel causes the adverse reaction of peripheral neuropathy. The Nav sodium channel family has an important role in pain sensation. The subtype Nav 1.8 is the more abundantly expressed Tetrodotoxin resistant (TTX-R) sodium channel expressed in nociceptive Dorsal Root Ganglia (DRG) neurons. The aim of our study was to assess possible changes in Nav 1.8 channel expression in the DRG after intraperitoneal Paclitaxel application. Material and methods: Wistar rats (n=27, males) were used in our experiments. Intraperitoneal injections of Paclitaxel in 4 doses with a cumulative dose of 8 mg/kg were performed on experimental rats, while control animals received only the excipient (alcohol and cremophor EL; 1:1). The animals were left to survive for 1, 7, 14 and 21 days from the last application. Experimental and control rats were sacrificed together with naive rats and perfused transcardially by Zambonis fixative. Longitudinal cryostat sections through the lumbar DRGs were cut and immunostained for Nav 1.8. The intensity of Nav 1.8 immunofluorescence in the DRGs was measured and statistically analyzed. Results: The presence of Nav 1.8 immunofluorescence was found in lumbar DRG neurons in naive, control and Paclitaxel treated animals. Statistically significant increase in Nav 1.8 immunofluorescence was found in the DRGs of Paclitaxel treated animals in comparison to both control and naive animals. Interestingly, positivity was also detected in vessels walls within the DRG. Conclusions: Our results indicate that DRG neurons react to Paclitaxel application by increasing Nav 1.8 channel expression. These changes might be associated with the symptoms of chemotherapy induced peripheral neuropathy.
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