Antinociception with intrathecal alpha-methyl-5-hydroxytryptamine, a 5-hydroxytryptamine 2A/2C receptor agonist, in two rat models of sustained pain

Anesth Analg. 2003 Apr;96(4):1072-1078. doi: 10.1213/01.ANE.0000050560.15341.A8.


Type 2 serotonin (5-hydroxytryptamine [5-HT](2)) receptors in the spinal cord have been reported to mediate antinociception using pain threshold tests, but little is known about the actions of spinal 5-HT(2) receptors in sustained pain. In rats, we examined antinociceptive effects of the intrathecal administration of a 5-HT(2A/2C) receptor agonist, alpha-methyl-5-HT maleate (alpha-m-5-HT), using the formalin test and the chronic constriction injury (CCI) model. An intrathecal catheter was implanted for injection of drugs. In the formalin test, flinches were counted from Minute 1 to 2 and Minute 5 to 6 (Phase 1) and then for 1-min periods at 5-min intervals from 10 to 60 min (Phase 2). In rats with CCI, hind paw withdrawal latency after thermal stimulation was measured. In the formalin test, intrathecal administration of alpha-m-5-HT (1 to 100 microg) dose-dependently suppressed the number of flinches in both Phases 1 and 2. In the CCI model, intrathecally administered alpha-m-5-HT (10 to 100 microg) attenuated thermal hyperalgesia in a dose-dependent manner. These effects were reversed by intrathecal pretreatment with a 5-HT(2A/2C) antagonist, ketanserin (30 microg), or a muscarinic receptor antagonist, atropine (30 microg). These findings suggest that spinal 5-HT(2A/2C) receptors mediate antinociception in inflammatory pain and neuropathic pain, and the muscarinic receptors contribute to this action.

Implications: Activation of spinal 5-hydroxytryptamine(2A/2C) receptors mediate antinociception in rat-sustained pain models such as inflammatory pain and neuropathic pain, and spinal muscarinic receptors are involved in this action.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Behavior, Animal / drug effects
  • Chronic Disease
  • Dose-Response Relationship, Drug
  • Formaldehyde
  • GABA-A Receptor Antagonists
  • GABA-B Receptor Antagonists
  • Hyperalgesia / drug therapy
  • Hyperalgesia / psychology
  • Injections, Spinal
  • Male
  • Muscarinic Antagonists / pharmacology
  • Pain / drug therapy*
  • Pain Measurement / drug effects
  • Rats
  • Rats, Wistar
  • Reaction Time / drug effects
  • Receptor, Serotonin, 5-HT2A
  • Receptor, Serotonin, 5-HT2C
  • Receptors, Serotonin / drug effects*
  • Serotonin / administration & dosage
  • Serotonin / analogs & derivatives*
  • Serotonin / pharmacology*
  • Serotonin Antagonists / pharmacology
  • Serotonin Receptor Agonists / administration & dosage
  • Serotonin Receptor Agonists / pharmacology*


  • GABA-A Receptor Antagonists
  • GABA-B Receptor Antagonists
  • Muscarinic Antagonists
  • Receptor, Serotonin, 5-HT2A
  • Receptor, Serotonin, 5-HT2C
  • Receptors, Serotonin
  • Serotonin Antagonists
  • Serotonin Receptor Agonists
  • Formaldehyde
  • alpha-methylserotonin
  • Serotonin