Antinociceptive effects of intrathecal 5-HT agonists in sheep.

Objectives: 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.

Study Design: Prospective controlled study.

Animals: 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-HT and 5-HT receptors particularly at the cervical level appears to be involved in spinal nociceptive processing in the sheep.

Clinical Relevance: These effects, which lasted about 60 minutes, may have an implication in the development of new analgesic strategies for animals.