A comparison of analgesia and suppression of oxytocin release by opiates

Abstract

The potency of opiates for suppressing oxytocin release relative to their potency as analgesics was tested in lactating rats. Oxytocin release was evoked by the sucking of the young in urethane-anaesthetized and unanaesthetized rats, and was detected by the characteristic behaviour of the young and milk yield respectively. The tail-flick test, using noxious radiant heat, was used to assess analgesia. Intraperitoneal injection of morphine (1 mg kg-1 and 5 mg kg-1) significantly reduced milk yield in unanaesthetized rats. Urethane-anaesthetized rats displayed a pattern of reflex milk-ejection responses similar to that found in conscious rats. This reflex was significantly inhibited in a dose-related, naloxone-reversible manner by buprenorphine (ED50 0.18 mg kg-1), meptazinol (ED50: 14.0 mg kg-1), morphine (ED50: 0.67 mg kg-1), pentazocine (ED50: 15.0 mg kg-1) and pethidine (ED50: 7.9 mg kg-1). Although intraperitoneal injection of morphine (5 mg kg-1) abolished the increase in intramammary pressure occurring at reflex milk-ejection, that evoked by intravenous oxytocin (0.5-1 mu) was unaffected. Each opiate also caused significant, dose-related, naloxone-reversible increases in tail-flick latency. The ED50 doses were buprenorphine (ED50: 0.14 mg kg-1), meptazinol (ED50: 12.5 mg kg-1), morphine (ED50: 5.0 mg kg-1), pentazocine (ED50: 12.5 mg kg-1) and pethidine (ED50: 6.1 mg kg-1). The order of potency for analgesia and for suppression of oxytocin release were identical, namely: buprenorphine greater than morphine greater than pethidine greater than meptazinol greater than pentazocine. The results obtained with lactating rats suggest that secretion of the hormone oxytocin is substantially reduced during opiate-induced analgesia.