Analgesia and autonomic function following intrathecal administration of morphine and norepinephrine to the rat.

The acute intrathecal (i.t.) administration of 10, 25, 50, and 100 microgram morphine and 7.5, 10, 15, and 30 microgram (-)norepinephrine (NE) to the rat produced dose-dependent, long-lasting analgesia as assessed by the tail-flick and hot-plate tests. For i.t. morphine, maximum analgesia was observed 30-60 min after drug administration. The duration of analgesia in the tail-flick test ranged from 30 to 150 min; the duration of analgesia in the hot-plate test ranged from 60 to 120 min. For i.t. NE, maximum analgesia was observed 15-60 min after drug infusion. The duration of NE-induced analgesia in the hot-plate test ranged from 45 to 120 min and was 120 min in the tail-flick test. The effects of acute i.t. and intravenous (i.v.) infusions of morphine (10 microgram) and NE (15 microgram) on heart rate, blood pressure, arterial pH, partial pressure of oxygen (Po2), partial pressure of carbon dioxide (Pco2), and standard bicarbonate were determined over 45 min in rats anesthetized with alpha-chloralose (70 mg/kg). Morphine significantly decreased Po2 throughout the experiment but did not affect blood pressure, heart rate, pH, Pco2 and standard bicarbonate. A significant increase in blood pressure (137% of control) was observed 2.5 min after i.t. administration of NE. Intravenous NE produced a marked increase in blood pressure (246% of control) followed by a compensatory decrease in heart rate. There were no significant changes in blood gases with i.t. and i.v. NE. The data suggest that i.t. morphine and NE can produce effective analgesia with minimal effects on cardiovascular and respiratory function.