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‐HT₁ and 5‐HT₂ 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.