Serotonin 5-HT2A receptor involvement and Fos expression at the spinal level in vincristine-induced neuropathy in the rat

We recently showed that peripheral and spinal 5-HT2A receptors (5-HT2AR) are involved in it rodent model of neuropathy induced by it nucleoside analogue reverse transcriptase inhibitor. In this paper, we show that 5-HT2AR are also involved in neuropathy induced by an anti-neoplasic drug, vincristine. Vincristine-treated rats (0.1 mg/kg, daily i.p. administration for two 5-day cycles) developed thermal allodynia and mechanical hypersensitivity, which decreased in a dose-related manner after epidural injection a 5-HT2A receptor antagonist. Moreover, 5-HT2A-/- mice did not develop vincristine-induced neuropathy contrarily to their 5-HT2A+/+ littermates. In vincristine-treated rats, the number of nociceptive dorsal Toot ganglion cells expressing the 5-HT2AR was increased by 38%, and 5-HT2AR immunolabelling wits enhanced in layers I-IV of the dorsal horn. At the EM level, a 76.3%) increase in the density of 5-HT2AR immunopositive axon terminals within Superficial layers of the dorsal horn was noted after vincristine treatment. Immunocytochemical study of Fos expression in vincristine-treated rats revealed it significant increase in the number of Fos-positive neurons not only in regions where nociceptive fibres terminate Superficial (I-II) and deep layers (V-VI) or the spinal cord, but also ill intermediate layers, Suggesting that A beta fibres Could be involved in the spinal sensitization observed in this model. Double labelling experiments showed that fos-positive neurons were endowed with 5-HT2AR immunolabelling in the dorsal horn of vincristine-treated rats. These data provide Support to the idea that, in vincristine-induced neuropathy, 5-HT2AR are involved ill the sensitization or peripheral nociceptors and spinal nociceptive processing. (c) 2008 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.