Role of 5-HT(1) receptor subtypes in the modulation of pain and synaptic transmission in rat spinal superficial dorsal horn.

Abstract

BACKGROUND AND PURPOSE:

5-HT receptor agonists have variable nociceptive effects within the spinal cord. While there is some evidence for 5-HT(1A) spinally-mediated analgesia, the role of other 5-HT(1) receptor subtypes remains unclear. In the present study, we examined the spinal actions of a range of 5-HT(1) agonists, including sumatriptan, on acute pain, plus their effect on afferent-evoked synaptic transmission onto superficial dorsal horn neurons.

EXPERIMENTAL APPROACH:

For in vivo experiments, 5-HT agonists were injected via chronically implanted spinal catheters to examine their effects in acute mechanical and thermal pain assays using a paw pressure analgesymeter and a Hargreave's device. For in vitro experiments, whole-cell patch-clamp recordings of primary afferent-evoked glutamatergic EPSC were made from lamina II neurons in rat lumbar spinal slices.

KEY RESULTS:

Intrathecal (i.t.) delivery of the 5-HT(1A) agonist R ± 8-OH-DPAT (30-300 nmol) produced a dose-dependent thermal, but not mechanical, analgesia. Sumatriptan and the 5-HT(1B), 5-HT(1D), 5-HT(1F) agonists CP93129, PNU109291 and LY344864 (100 nmol) had no effect on either acute pain assay. R ± 8-OH-DPAT (1 µM) and sumatriptan (3 µM) both reduced the amplitude of the evoked EPSC. In contrast, CP93129, PNU109291 and LY344864 (0.3-3 µM) had no effect on the evoked EPSC. The actions of both R ± 8-OH-DPAT and sumatriptan were abolished by the 5-HT(1A) antagonist WAY100635 (3 µM).

CONCLUSIONS AND IMPLICATIONS:

These findings indicate that the 5-HT(1A) receptor subtype predominantly mediates the acute antinociceptive and cellular actions of 5-HT(1) ligands within the rat superficial dorsal horn.

• Authors: Hyo-Jin Jeong, Vanessa A Mitchell, Christopher W Vaughan
• Journal: British journal of pharmacology (Br J Pharmacol) Vol. 165 Issue 6 Pg. 1956-1965 (Mar 2012) ISSN: 1476-5381 [Electronic] England
• PMID: 21950560 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2011 The Authors. British Journal of Pharmacology © 2011 The British Pharmacological Society.

Chemical References

• Analgesics
• Receptors, Serotonin, 5-HT1
• Serotonin Receptor Agonists

Topics

• Acute Pain (drug therapy, physiopathology)
• Analgesics (pharmacology, therapeutic use)
• Animals
• Posterior Horn Cells (drug effects, physiology)
• Rats
• Rats, Sprague-Dawley
• Receptors, Serotonin, 5-HT1 (physiology)
• Serotonin Receptor Agonists (pharmacology, therapeutic use)
• Synaptic Transmission (drug effects, physiology)