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

Pain. 2008 Nov 30;140(2):305-322. doi: 10.1016/j.pain.2008.09.006. Epub 2008 Oct 18.


We recently showed that peripheral and spinal 5-HT2A receptors (5-HT2AR) are involved in a rodent model of neuropathy induced by a 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 (0.1mg/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 root ganglion cells expressing the 5-HT2AR was increased by 38%, and 5-HT2AR immunolabelling was 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 a 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) of the spinal cord, but also in intermediate layers, suggesting that Abeta 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 in the sensitization of peripheral nociceptors and spinal nociceptive processing.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Hot Temperature
  • Hyperesthesia / chemically induced*
  • Hyperesthesia / metabolism*
  • Male
  • Neuralgia / chemically induced*
  • Neuralgia / metabolism*
  • Oncogene Proteins v-fos / metabolism*
  • Rats
  • Rats, Wistar
  • Receptor, Serotonin, 5-HT2A / metabolism*
  • Spine / physiopathology*
  • Touch
  • Vincristine*


  • Oncogene Proteins v-fos
  • Receptor, Serotonin, 5-HT2A
  • Vincristine