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Serotonergic modulation in neuropathy induced by oxaliplatin: effect on the 5HT2C receptor

Daniela Baptista-de-Souza1, Lorenzo Di Cesare Mannelli2, Matteo Zanardelli2

  • 1Psychobiology Group/Department of Psychology/CECH-UFSCar, São Carlos, SP 13565-905, Brazil; Joint Graduate Program in Physiological Sciences UFSCar/UNESP., São Carlos, SP 13565-905, Brazil; Department of Neuroscience, Psychology, Drug Research and Child Health - Neurofarba - Pharmacology and Toxicology Section, University of Florence, Viale Pieraccini 6, 50139 Florence, Italy.

European Journal of Pharmacology
|May 3, 2014
PubMed

Insights

Fluoxetine treatment alleviates oxaliplatin-induced neuropathic pain by altering 5-HT2C receptor expression in key pain pathways. This study highlights fluoxetine

Area of Science:

  • Neuroscience
  • Pharmacology
  • Pain Research

Background:

  • Neuropathic pain is a debilitating condition often associated with chemotherapy drugs like oxaliplatin.
  • Fluoxetine, an SSRI, shows potential in managing neuropathic pain, partly through its interaction with the 5-HT2C receptor.
  • The 5-HT2C receptor is implicated in pain modulation, making it a target for therapeutic interventions.

Purpose of the Study:

  • To investigate the efficacy of repeated fluoxetine treatments in mitigating oxaliplatin-induced neuropathic pain in rats.
  • To examine the impact of both oxaliplatin and fluoxetine on 5-HT2C receptor mRNA and protein expression in specific brain regions.
  • To correlate changes in 5-HT2C receptor levels with the observed pain responses.

Main Methods:

  • Neuropathic pain was induced using oxaliplatin in a rat model.
  • Nociceptive responses were assessed using paw-pressure, cold plate, and Von Frey tests.
  • Quantitative analysis of 5-HT2C receptor mRNA and protein levels was performed in the spinal cord (SC), rostral ventral medulla (RVM), periaqueductal gray (PAG), and amygdala (Amy) using ex vivo methods.

Main Results:

  • Fluoxetine effectively prevented mechanical hypersensitivity and altered pain thresholds caused by oxaliplatin, without affecting weight gain.
  • Oxaliplatin increased 5-HT2C receptor mRNA and protein in the SC and PAG, while decreasing it in the amygdala.
  • Fluoxetine modulated these oxaliplatin-induced changes in 5-HT2C receptor expression in the SC and amygdala, and increased protein levels in the amygdala and mRNA/protein in the PAG.

Conclusions:

  • Fluoxetine demonstrates significant efficacy in reversing oxaliplatin-induced neuropathic pain behaviors.
  • The therapeutic effects of fluoxetine are associated with significant alterations in 5-HT2C receptor expression within the central nervous system.
  • Targeting 5-HT2C receptors may represent a viable strategy for managing chemotherapy-induced neuropathic pain.
Keywords:
5-HT(2C) receptorsAmygdalaFluoxetineOxaliplatinPeriaqueductal gray matter (PAG)Spinal cord

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