Spinal 5-HT3 receptor mediates nociceptive effect on central neuropathic pain; possible therapeutic role for tropisetron

J Spinal Cord Med. 2016;39(2):212-9. doi: 10.1179/2045772315Y.0000000047. Epub 2015 Sep 4.

Abstract

Objectives: To test the analgesic effect of 5-HT-3 receptor antagonist, tropisetron, in a clip compression injury model of spinal cord pain in rats.

Methods: Four weeks post compression of the spinal cord at lumbar level, tropisetron was administered intrathecally at 100 μg and 150 μg dosages. Behavioral tests were assessed before administration. Fifteen minutes after injection, behavioral tests were repeated. Randall-Sellitto and plantar test was used for mechanical and thermal hyperalgesia, respectively. Mechanical and cold allodynia were evaluated by Von Frey filament and acetone droplets, respectively. The analgesic effect of tropisetron was compared with intrathecal administration of salicylate. Locomotor score was evaluated by Basso, Beattie and Bresnahan (BBB) test every week after spinal cord injury.

Results: Intrathecal administration of tropisetron, decreased hyperalgesia and mechanical allodynia, but not cold allodynia were observed after compression of the spinal cord.

Conclusion: Blockade of 5-HT-3 receptors by tropisetron at the spinal level induces an antinociceptive effect on chronic central neuropathic pain and suggests that this compound may have potential clinical utility for the management of central neuropathic pain, particularly in patients with hyperalgesia and tactile allodynia.

Keywords: 5-hydroxytryptamine-3; Central neuropathic pain; Clips compression injury; Spinal cord.

MeSH terms

  • Analgesics / administration & dosage
  • Analgesics / pharmacology*
  • Analgesics / therapeutic use
  • Animals
  • Indoles / administration & dosage
  • Indoles / pharmacology*
  • Indoles / therapeutic use
  • Injections, Spinal
  • Male
  • Neuralgia / drug therapy*
  • Neuralgia / etiology
  • Nociception / drug effects
  • Rats
  • Rats, Wistar
  • Receptors, Serotonin, 5-HT3 / metabolism
  • Serotonin 5-HT3 Receptor Antagonists / administration & dosage
  • Serotonin 5-HT3 Receptor Antagonists / pharmacology*
  • Serotonin 5-HT3 Receptor Antagonists / therapeutic use
  • Spinal Cord / drug effects
  • Spinal Cord / metabolism
  • Spinal Cord Injuries / complications
  • Spinal Cord Injuries / drug therapy*
  • Tropisetron

Substances

  • Analgesics
  • Indoles
  • Receptors, Serotonin, 5-HT3
  • Serotonin 5-HT3 Receptor Antagonists
  • Tropisetron