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Seventeen patients with intractable pain due to progressive malignancies were treated by electrical stimulation of the brain after more conventional pain therapies applied in the University of California, Los Angeles Cancer Pain Clinic had failed. Electrodes were stereotactically implanted under local anesthesia in the periaqueductal grey (PAG) or periventricular grey (PVG) in 11 patients. In six patients electrodes were placed in both PAG-PVG targets and in the sensory thalamic nuclei. Thirteen of the 17 patients achieved virtually total pain relief and 2 others achieved partial pain relief. At the hospital discharge only 4 of 17 patients required narcotic analgesics for pain relief. Follow-up periods ranged from 1 to 21 months and 6 patients remain alive. Fourteen patients eventually required narcotics for pain relief, usually in the terminal few weeks of their lives. Pain relief was achieved in spite of the fact that all patients were tolerant to large doses of systematically or intraspinally administered narcotics at the time of electrode placement. No complications related to brain stimulation were identified. Brain stimulation is a safe and effective method for treatment of intractable pain due to malignancy in certain patients.

Survival under hypoxia (5% O2; 95% N2) was tested in mice 1 day to 50-weeks-old. Survival Rate (ratio of number of animals that survived 30 min under 5% O2 to total number of animals exposed) and the time from onset of exposure until the last gasp (Survival Time) were maximum in newborn animals and decreased as a function of age. Survival Rate and Survival Time were strongly influenced by drugs affecting cholinergic transmission. Atropine decreased the high survival under hypoxia of 1-week-old mice in a dose-related manner. Physostigmine increased survival under hypoxia in mice 3 to 50-weeks-old. This effect was not related to a peripheral action of the drug since it was not mimicked by neostigmine, a cholinesterase inhibitor without central actions. Moreover, peripheral cholinergic blockade with glycopyrrolate, a quaternary cholinergic blocker, did not prevent the protective effect of physostigmine. Since atropine impairs the ability of very young mice to survive hypoxia and physostigmine improves survival at later ages, it is concluded that a central cholinergic mechanism, possibly related to blood flow regulation, plays a significant role in the acute adaptation to hypoxia.

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