Investigation into the antinociceptive potential of remoxipride administered intrathecally in sheep

Systemic administration of remoxipride, a dopamine (D2) antagonist, to sheep has previously been shown to generate an antinociceptive action without producing a significant motor impairment. The present study examined whether a spinal locus of action was responsible for this action of remoxipride. Remoxipride (17.7 mg) administered intrathecally via chronically indwelling catheters produced a greatly variable but significant (p<0.05) increase in nociceptive thresholds as judged by a focused mechanical stimulus (blunt pin) applied to the forelimb of four sheep. However, this dose of remoxipride induced a marked forelimb motor impairment as judged by a subjective visual analogue scoring system. Conversely, intrathecal xylazine (100 and 200 microg), an alpha-adrenergic agonist with antinociceptive properties, did not produce forelimb weakness although the higher dose (200 microg) produced significant sedation. In vitro autoradiography was performed on cervical spinal cord sections taken from sheep. Remoxipride displaced [3H] YM-09151-2, a selective D2 antagonist, from densely-labelled areas in the superficial layer of the dorsal horn, lamina X and ventral horn. Even though there are possible anatomical substrates within the spinal cord for both an antinociceptive and motor disturbance action of remoxipride, the behavioural data suggest that the spinal cord is unlikely to be the primary site of antinociceptive action for systemically-administered doses of remoxipride.