title: Role of 5-HT(1)  receptor subtypes in the modulation of pain and synaptic transmission in rat spinal superficial dorsal horn.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  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
  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.affiliation: Pain Management Research Institute, Kolling Institute of Medical Research, Northern Clinical School, University of Sydney at Royal North Shore Hospital, NSW, Australia.
authors.forename: Hyo-Jin
authors.initials: HJ
authors.lastname: Jeong
authors.affiliation: Pain Management Research Institute, Kolling Institute of Medical Research, Northern Clinical School, University of Sydney at Royal North Shore Hospital, NSW, Australia.
authors.forename: Vanessa A
authors.initials: VA
authors.lastname: Mitchell
authors.affiliation: Pain Management Research Institute, Kolling Institute of Medical Research, Northern Clinical School, University of Sydney at Royal North Shore Hospital, NSW, Australia.
authors.forename: Christopher W
authors.initials: CW
authors.lastname: Vaughan
mesh_terms: D059787:Acute Pain / Q000188:drug therapy / Q000503:physiopathology*; D000700:Analgesics / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D020671:Posterior Horn Cells / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D044263:Receptors, Serotonin, 5-HT1 / Q000502:physiology*; D017366:Serotonin Receptor Agonists / Q000494:pharmacology / Q000627:therapeutic use; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*
chemical_list: D000700:Analgesics; D044263:Receptors, Serotonin, 5-HT1; D017366:Serotonin Receptor Agonists