RGD Reference Report - Serotonin 5-HT2A receptor involvement and Fos expression at the spinal level in vincristine-induced neuropathy in the rat. - Rat Genome Database

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

Authors: Thibault, Karine  Van Steenwinckel, Juliette  Brisorgueil, Marie-Jeanne  Fischer, Jacqueline  Hamon, Michel  Calvino, Bernard  Conrath, Marie 
Citation: Thibault K, etal., Pain. 2008 Nov 30;140(2):305-322. doi: 10.1016/j.pain.2008.09.006. Epub 2008 Oct 18.
RGD ID: 401938600
Pubmed: PMID:18930597   (View Abstract at PubMed)
DOI: DOI:10.1016/j.pain.2008.09.006   (Journal Full-text)

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.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
HTR2AHumaninflammatory and toxic neuropathy treatmentISORGD:61800 RGD 
Htr2aRatinflammatory and toxic neuropathy treatmentIMP  RGD 
Htr2aMouseinflammatory and toxic neuropathy treatmentISORGD:61800 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Htr2a  (5-hydroxytryptamine receptor 2A)

Genes (Mus musculus)
Htr2a  (5-hydroxytryptamine (serotonin) receptor 2A)

Genes (Homo sapiens)
HTR2A  (5-hydroxytryptamine receptor 2A)


Additional Information