Anesthesiology
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Cholinesterase inhibitors which reach the central nervous system produce pain relief but are poorly tolerated because of gastrointestinal side effects. Here, the authors tested whether donepezil, a central nervous system penetrant cholinesterase inhibitor with a low incidence of gastrointestinal side effects, would relieve hypersensitivity in an animal model of neuropathic pain. ⋯ Donepezil, a well-tolerated cholinesterase inhibitor used in the treatment of Alzheimer dementia, reduces hypersensitivity in this rat model of neuropathic pain by actions on muscarinic receptors in the spinal cord. Lack of tolerance to this effect, in contrast to rapid tolerance to direct receptor agonists, suggests that cholinesterase inhibition may be useful in the treatment of neuropathic pain.
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The authors determined whether desflurane altered myocardial excitation-contraction coupling and electrophysiologic behavior in the same manner as isoflurane and sevoflurane. ⋯ Myocardial depression by desflurane is due to decreased Ca(2+) influx, whereas depolarization-activated sarcoplasmic reticulum Ca(2+) release is modestly depressed, similar to the actions of isoflurane and sevoflurane. Desflurane depressed the delayed outward K(+) current associated with significant lengthening of cardiac action potentials.