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Serotonin transporter deficiency protects mice from mechanical allodynia and heat hyperalgesia in vincristine neuropathy.

Abstract：

:Painful vincristine (VCR) neuropathy is a frequent and dose-limiting problem in cancer treatment. Here, we investigated how pain behavior is modulated in mice lacking the serotonin transporter (5-HTT-/- mice) after inducing neuropathy by intraperitoneal injections of VCR. We used standard tests for evoked pain, high performance liquid chromatography to measure serotonin (5-HT), and immunohistochemistry of L4/5 dorsal root ganglia (DRG) to assess neuronal injury and inflammation. After injections of VCR, 5-HTT-/- mice did not develop hypersensitivity to heat, in contrast to their wildtype (wt) littermates (p<0.05). Also, 5-HTT-/- mice recovered faster from mechanical hypersensitivity than wt mice (p<0.05). 5-HT levels were lower in the peripheral and central nervous tissue of vehicle or VCR-treated 5-HTT-/- mice compared to wt mice. VCR-treated mice had higher numbers of injured neurons as identified by immunostaining for activating transcription factor 3, and more immunoreactive macrophages in the L4/5 DRG than vehicle-treated mice. There was no difference between genotypes. Thus the 5-HTT-/- genotype did not protect mice from VCR-induced neuronal injury and macrophage infiltration in the DRG. Our results suggest that the reduced peripheral 5-HT levels of 5-HTT-/- mice in VCR neuropathy underlie the lack of heat hyperalgesia. Conversely, attenuation of mechanical allodynia in 5-HTT-/- mice may indicate reduced 5-HT-mediated facilitation in the central nervous system.

journal_name

Neurosci Lett

journal_title

Neuroscience letters

authors

Hansen N,Uçeyler N,Palm F,Zelenka M,Biko L,Lesch KP,Gerlach M,Sommer C

doi

10.1016/j.neulet.2011.03.035

subject

Has Abstract

pub_date

2011-05-16 00:00:00

pages

93-7

issue

2

eissn

0304-3940

issn

1872-7972

pii

S0304-3940(11)00327-2

journal_volume

495

pub_type

杂志文章

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