Intrathecal St-587: effects on nociceptive reflexes and blood pressure in the rat

The purpose of this study was to determine the effect of i.t. St 587 (lumbar injection) on tail-flick (TF) latency and paw pressure (PP) withdrawal threshold in conscious rats, and the effect of i.t. (midthoracic injection) and i.v. St 587 on blood pressure in urethane-anesthetized rats. Unlike i.t. methoxamine (alpha 1 agonist), which produced antinociception, i.t. St 587 (0.5-30 micrograms) decreased TF latency and PP threshold below base line. Hyperalgesia was also produced by i.t. Wy 27127 (alpha 2-selective antagonist). At i.t. doses of St 587 > 3 micrograms, there was an apparent but incomplete return of TF latency and PP threshold toward base line. Pretreatment with i.t. prazosin (2.5 micrograms) enhanced the hyperalgesic effect of 30 micrograms, but not 1 microgram of St 587. Intrathecal St 587 and Wy 27127 each antagonized the antinociceptive effect of i.t. guanfacine (alpha 2 agonist) in the TF and PP tests. Intravenous St 587 produced a dose-dependent pressor effect that was antagonized by pretreatment with i.v. prazosin (0.14 mg/kg; 52-fold increase in the ED50), but weakly antagonized by Wy 27127 (0.5 mg/kg; 1.5-fold increase in the ED50). ST-587 also produced a dose-dependent pressor response after i.t. injection which was antagonized by i.t. prazosin (10 micrograms) or i.v. hexamethonium (10 mg/kg).(ABSTRACT TRUNCATED AT 250 WORDS)