Additional Information
Dr. Lewis's past and current NIH- and GSK-funded projects have fostered a multidisciplinary research program with expertise in peripheral/central ventilatory processing, autonomic neurophysiology/neuropharmacology and techniques ranging including in vivo recording/stimulation of autonomic and sensory nerves; recording and manipulation of cardiorespiratory systems; in situ brainstem electrophysiology preparation with multi-array recording of intrinsic neuron activity and recording of phrenic, vagal and sympathetic nerve activities; single cell patch-clamp electrophysiology of carotid body glomus cells, multi-array recordings in autonomic ganglia; tract-tracing in brain/peripheral tissues; and molecular approaches. Of specific relevance to current proposal is that we have used this array of techniques to address mechanisms by which opioid receptor agonists such as morphine and fentanyl elicit their central and peripherally-mediated effects on breathing, arterial blood gas (ABG) chemistry, hemodynamic status and analgesia (e.g., references a-d of 200 peer-reviewed publications). Our current projects are address our novel findings that systemic injection of D-cysteine ethyl ester (D-CYSee) and related compounds elicit a rapid and sustained reversal of the negative effects of morphine and fentanyl on breathing, ABG chemistry and gas exchange within the lungs in adult rats, without compromising opioid-induced analgesia. This multidisciplinary and multi-institutional project will address (1) the sites within the periphery and brain by which fentanyl and morphine exert their effects on breathing, hemodynamics, ABG chemistry, Alveolar-arterial (A-a) gradient (index of gas exchange in the lungs), and analgesia, and (2) the sites of action and molecular mechanisms by which D-CYSee elicits its positive actions against the opioids.