Analgesic responses to morphine and placebo in individuals with postoperative pain

The effects of placebo and varying doses of intravenous morphine were studied in 74 patients. All patients underwent extraction of impacted mandibular third molars. Two hours after onset of anesthesia all patients received a placebo (intravenous saline). One hour after the placebo administration each patient received either a second placebo or, 4, 6, 8 or 12 mg of morphine, double blind, via a hidden intravenous line. Pain level was evaluated 50 min after morphine administration using a visual analog scale. Pooled data from all patients produced a dose-response curve asymptotic by 8 mg. The mean pain relief following the second placebo was found to be between that obtained following hidden administration of 4 and 6 mg of morphine.

When pain level reports for individuals were plotted two unexpected features appeared. First, no patient reported complete relief, even at the highest dose of morphine (12 mg). Second, pain level reports 50 min following each dose of morphine tended to be in two clusters. Within each cluster the average pain was independent of the dose of morphine administered. However, in groups receiving progressively higher doses of morphine, the percentage of patients within the low pain level cluster increased. These latter observations are most consistent with the concept that there is a step component for narcotic analgesia.     

Paratyphoid orchitis

A case of pyogenic orchitis due to infection with Salmonella enteriditis ser. Paratyphi B is discussed. Unlike previously reported cases of Salmonella orchitis, this patient developed infection by bacteremic spread and not direct extension from the epididymis. Therapy with chloramphenicol resulted in an excellent clinical response.     

Potentiation of morphine antinociception by monoamine reuptake inhibitors in the rat spinal cord

Potentiation of the antinociceptive effects of morphine by the tricyclic antidepressants was assayed in awake restrained rats using the tail-flick test. Intrathecally administered amitriptyline, desipramine or sertraline at doses that had no effect themselves (25-30 micrograms) potentiated a subthreshold parenteral dose of morphine (0.5 mg/kg). The morphine potentiating effect of amitriptyline was prevented by prior administration of parachlorophenylalanine (PCPA). This effect of PCPA was not restored by 5-hydroxytryptophan (5-HTP) but was restored when the animals were left for 14 days to replete. The morphine potentiating effects of amitriptyline, desipramine and sertraline were blocked by intrathecal administration of low doses of the serotonin antagonist methysergide and the alpha-adrenergic antagonists yohimbine and phentolamine but not by the beta-adrenergic antagonist propranolol. The results are consistent with the hypothesis that the potentiation of morphine's antinociceptive effect by tricyclic antidepressants depends on activation of both spinopetal serotonin and adrenergic neurons.