The antinociceptive and sedative effects of carbachol and oxycodone administered into brainstem pontine reticular formation and spinal subarachnoid space in rats.

To clarify the supraspinal and spinal actions of a cholinergic agonist, carbachol, and an opioid, oxycodone, we studied their antinociceptive and behavioral effects when administered into brainstem medial pontine reticular formation (mPRF) or spinal subarachnoid space with or without pretreatment of muscarinic receptor subtype antagonist. Sprague-Dawley rats were implanted with a 24gauge stainless steel guide cannula into the mPRF and chronically implanted with a lumbar intrathecal catheter. Antinociception was tested using tail flick latency, motor coordination was evaluated by the rotarod test, and overt sedation was assessed using a behavioral checklist. Carbachol (0.5‐ 4.0 mg) administered into the mPRF produced significant dose- and time-dependent antinociception, sedation, and motor dysfunction. These were completely blocked by pretreatment with atropine and the M2 muscarinic antagonist, methoctramine, and partially blocked by pretreatment with M1 pirenzepine but not with M3 p-fHHSiD. Oxycodone administered into the mPRF did not produce such effects. Spinal carbachol and oxycodone produced antinociception without any behavioral effects; their antinociceptive effects were completely blocked by pretreatment with atropine and M2 antagonist. These results suggest that the antinociceptive action of carbachol is mediated by muscarinic cholinergic receptor activation, especially by M2 receptor subtype in mPRF and spinal cord, and that although oxycodone seems unlikely to affect the cholinergic transmission of mPRF, spinal oxycodone-induced analgesia is at least partly mediated via the activation of M2 receptor subtype at the spinal cord. (Anesth Analg 2001;92:1307‐15)