Role of 5-HT1 receptor subtypes in the modulation of pain and synaptic transmission in rat spinal superficial dorsal horn

BACKGROUND AND PURPOSE 5-HT receptor agonists have variable nociceptive effects within the spinal cord. While there is some evidence for 5-HT1A spinally-mediated analgesia, the role of other 5-HT1 receptor subtypes remains unclear. In the present study, we examined the spinal actions of a range of 5-HT1 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-HT1A agonist R +/- 8-OH-DPAT (30-300 nmol) produced a dose-dependent thermal, but not mechanical, analgesia. Sumatriptan and the 5-HT1B, 5-HT1D, 5-HT1F agonists CP93129, PNU109291 and LY344864 (100 nmol) had no effect on either acute pain assay. R +/- 8-OH-DPAT (1 mu M) and sumatriptan (3 mM) both reduced the amplitude of the evoked EPSC. In contrast, CP93129, PNU109291 and LY344864 (0.3-3 mu M) had no effect on the evoked EPSC. The actions of both R +/- 8-OH-DPAT and sumatriptan were abolished by th e 5-HT1A antagonist WAY100635 (3 mu M). CONCLUSIONS AND IMPLICATIONS These findings indicate that the 5-HT1A receptor subtype predominantly mediates the acute antinociceptive and cellular actions of 5-HT1 ligands within the rat superficial dorsal horn.