Pharmacologic Evidence That Spinal Muscarinic Analgesia is Mediated by an L-Arginine/Nitric Oxide/Cyclic GMP Cascade in Rats1

This study was designed to determine if the antinociception produced by intrathecally (i.t.) administered muscarinic ago-nists in male Sprague-Dawley rats is mediated by an L-arginine/ nitric oxide/cyclic GMP cascade. Seven days after implantation of intrathecal catheters, antinociception was produced with graded doses of (+)-cis-methyldioxolane (CD). The ED50 values for CD in the hot-plate and tail-flick tests were 2.6 and 2.0 nmol, respectively. The corneal and righting reflexes, as well as step-ping and negative geotaxic responses, were not affected by CD. Six-minute pretreatment with 50 nmol of the nitric oxide synthase inhibitor L-N#{176}-nitroarginine (NNR) significantly inhib-ited CD-produced hot-plate and tail-flick antinociception as evidenced by 6-fold shifts to the right of the CD dose-response curves. Coadministration of 150 nmol of L-arginine with NN