Spinal
neostigmine produces
analgesia in chronically prepared rats, but not in sheep. However, since
pain itself activates bulbospinal inhibitory pathways,
neostigmine may be more effective in the postoperative period. We examined in sheep the antinociceptive effect of intrathecal
neostigmine in the acute postoperative period and determined the
muscarinic receptor subtype activated by
neostigmine. A cervical intrathecal
catheter was inserted via a
laminotomy in 14 sheep that then received, in random order 1 mg of spinal
neostigmine or saline on postoperative Day 1 and the other injection on postoperative Day 2. Three additional sheep received, on separate days, intrathecal
neostigmine alone or with the
muscarinic receptor subtype-specific antagonists
pirenzepine (M1) 2 mg or AFDX-116 (M2) 2 mg. Antinociception was tested using a mechanical stimulus after each injection. Baseline withdrawal threshold did not change postoperatively. Intrathecal
neostigmine, but not saline caused antinociception on both of the first two postoperative days. In contrast, intrathecal
neostigmine caused no antinociception in another similar study performed at least 5 days after surgery.
Pirenzepine, but not AFDX-116, abolished antinociception from
neostigmine, suggesting an action on M1 subtype
muscarinic receptors. Intrathecal
neostigmine is antinociceptive in sheep during the acute postoperative period, and these data suggest that spinal
cholinergic tone, and hence intrathecal
neostigmine's
analgesic effect, may be enhanced during the acute postoperative period.