title: Antinociceptive effects of intrathecal 5-HT agonists in sheep.
abstract: OBJECTIVE
  To examine the role of spinal 5-hydroxytryptamine (5-HT) binding sites in nociceptive processing in conscious sheep and to study the role of 5-HT agonists in mediating analgesia.
  
  
  METHODS
  Prospective controlled study.
  
  
  METHODS
  Nine adult healthy female sheep (Swaledale, Swaledale-cross or Clun Forest) weighing 45-65 kg.
  
  
  METHODS
  Intrathecal (IT) catheters were implanted at the cervical (n = 5) or lumbar (n = 4) level of the spinal cord under general anaesthesia. At least 1 week later, and at 1 week intervals thereafter, the effects of intrathecal Ringer's solution (control), xylazine (100 μg), 5-HT creatinine sulphate (200, 400 and 800 μg), RU24969 (200 μg), α-Methyl-5-HT and 1-(3-Chlorophenyl)-biguanide (CPBG) on the mechanical nociceptive threshold (MT) were studied. Results were plotted as mean variable versus time curves. Areas under portions of the curves (0-30 and 0-60 minutes) were measured and expressed as mean ± standard error. Differences between values for control and drug trials were examined using the two-tailed Student's t-test.
  
  
  RESULTS
  Baseline values of MT were lower on the hind limbs than on the forelimbs. Intrathecal Ringer's solution did not alter MT in the cervical or lumbar region. Xylazine (100 μg) produced a characteristic elevation in MT between 5 and 60 + minutes. Lumbar IT injection of 5-HT (800 μg) raised the MT more than cervical injection, while cervical injection of RU24969 (200 μg) raised the MT more than lumbar administration. Cervical IT injection of α-Me-5-HT (500 μg) produced a marked and significant increase in MT while lumbar application had no effect. CPBG (500 μg) injection caused no significant effect on MT with either cervical or lumbar applications.
  
  
  CONCLUSIONS
  The activation of 5-HT1and 5-HT2receptors particularly at the cervical level appears to be involved in spinal nociceptive processing in the sheep.
  
  
  CONCLUSIONS
  These effects, which lasted about 60 minutes, may have an implication in the development of new analgesic strategies for animals.
authors.affiliation: Zeneca Pharmaceuticals, Alderly Edge, Macclesfield, Cheshire SK10 4TG, UK.
authors.forename: B R
authors.initials: BR
authors.lastname: Roberts
authors.affiliation: Western College of Veterinary Medicine, University of Saskatchewan, 52 Campus Drive, Saskatoon S7N 5B4, Canada.
authors.forename: A
authors.initials: A
authors.lastname: Livingston
authors.affiliation: Department of Clinical Veterinary Science, School of Veterinary Science, Langford House, Langford, Bristol BS40 5TD, UK.
authors.forename: A E
authors.initials: AE
authors.lastname: Waterman-Pearson
keywords: 5-HT receptors; intrathecal; nociception