The antiallodynic effect of intrathecal tianeptine is exerted by increased serotonin and norepinephrine in the spinal dorsal horn

Neurosci Lett. 2014 Nov 7:583:103-7. doi: 10.1016/j.neulet.2014.09.022. Epub 2014 Sep 16.

Abstract

The purpose of this study was to validate the effects of tianeptine on serotonergic and noradrenergic neurotransmission in a rat model of neuropathic pain. Neuropathic pain was induced by ligating the L5 and L6 spinal nerves in male Sprague-Dawley rats, and mechanical allodynia was assessed using von Frey filaments. The effects of intrathecally administered tianeptine on mechanical allodynia were assessed. Dihydroergocristine or yohimbine, a serotonergic or α-2 adrenergic receptor antagonists, respectively, were intrathecally administered 10min before tianeptine to investigate its mechanism of action. Additionally microdialysis studies were performed to measure the extracellular levels of serotonin (5-HT) and norepinephrine (NE) in the spinal dorsal horn following tianeptine administration. Intrathecal tianeptine significantly increased the paw withdrawal thresholds in a dose-dependent manner and the antiallodynic effect was antagonized by dihydroergocristine and yohimbine. Microdialysis studies revealed that tianeptine increased the levels of 5-HT and NE in the spinal dorsal horn. These findings suggest that tianeptine may be effective for the management of neuropathic pain and that its analgesic mechanism is exerted by increased levels of 5-HT and NE in the synaptic cleft at the spinal level.

Keywords: Antinociception; Intrathecal; Microdialysis; Norepinephrine; Serotonin; Tianeptine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenergic Antagonists / pharmacology
  • Analgesics / pharmacology*
  • Analgesics / therapeutic use
  • Animals
  • Antidepressive Agents / pharmacology*
  • Antidepressive Agents / therapeutic use
  • Hyperalgesia / drug therapy*
  • Hyperalgesia / physiopathology
  • Injections, Spinal
  • Male
  • Microdialysis
  • Norepinephrine / metabolism*
  • Physical Stimulation
  • Rats, Sprague-Dawley
  • Serotonin / metabolism*
  • Serotonin Antagonists / pharmacology
  • Spinal Cord Dorsal Horn / drug effects*
  • Spinal Cord Dorsal Horn / metabolism
  • Spinal Nerves / injuries
  • Synaptic Transmission
  • Thiazepines / pharmacology*
  • Thiazepines / therapeutic use
  • Touch

Substances

  • Adrenergic Antagonists
  • Analgesics
  • Antidepressive Agents
  • Serotonin Antagonists
  • Thiazepines
  • tianeptine
  • Serotonin
  • Norepinephrine