Clinical and Biochemical Pharmacology Laboratory
Investigator Profiles
Click on an investigator's name to access the personal profile including the specific research focus, publications, and contact information.-
Jeevendra Martyn, M.D.
basic, translational, clinical, anesthesia, critical care, neuroscience, pain, opioid, muscle wasting,innate immune responses
acute pain; anti-inflammatory agents; apoptosis; burns; chronic pain; critical illness; innate immunity; insulin signaling; macrophages; microglia; mitochondria; motor neuron disease; motor neurons; muscle protein breakdown; muscle skeletal; muscle weakness; myopathies; neuromuscular junction; neuromuscular nondepolarizing agents; pain medicine; receptors cholinergic; receptors opioid; sepsis
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Mohammed A.S Khan, Ph.D.
basic, translational, clinical, anesthesia, critical care, neuroscience, pain, opioid
amitriptyline; anesthetics, local; area under curve; bupivacaine; epinephrine
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Shingo Yasuhara, M.D., Ph.D.
basic, translational, clinical, anesthesia, critical care, neuroscience, pain, opioid
burns; carbolines; metabolic anomalies; microcirculation; microscopic imaging; muscle skeletal; muscular dystrophies; myopathies; phosphodiesterase 5 inhibitors
Overview
Mitigation of Critical Illness-induced Muscle Wasting and Exaggerated Pain
Our current research thrust is in two main areas – muscle wasting of critical illness and major injury-related exaggerated pain and associated opioid tolerance.
Neurobiology of critical illness-induced muscle wasting
Critical illness (e.g., major burn injury) with and without sepsis, which is invariably associated with immobilization, leads to loss of skeletal muscle mass loss and muscle weakness. The skeletal muscle weakness results in hypoventilation, difficulties in weaning off respirators, contractures and decreased mobilization. Despite increased survival rates following burn injury and critical illness, the survivors have prolonged muscle weakness which requires rehabilitation extending from months to years.
A recognized pathway for accelerated muscle proteolysis is the ubiquitin-proteasome pathway. Our group has identified apoptosis together with mitochondrial dysfunction as an additional mechanisms for loss of muscle mass. Our studies are, therefore, focused on decreasing the protein catabolic signals and enhancing the anabolic signals in muscle by genetic and pharmacotherapeutic manipulations. A recent paradigm shift is the study of the role of the gut dysbiosis-related systemic- and neuro-inflammation in the muscle changes. We posit that modulation of the gut microbiome and innate immune responses will decrease the muscle changes.
Neuroscience of injury-related exaggerated Pain
Any form of injury causes acute exaggerated pain and decreased response to opioids. Our second area of interest is the study of the etiology of the markedly exaggerated pain of injury and the persistent memory of the injury-induced pain long after healing of injury/wound. This immune memory of the injury results in augmented pain responses when the same patient comes back for reconstructive or other forms of surgery. We posit that both injury and the use of opioids induce epigenetic changes that result in more vigorous response to the “second-hit” (e.g., exposure to surgery or opioids). Our studies focus on modulating the epigenetic changes with the goal of suppressing the memory of injury- and opioid-induced pain and exploits the anti-inflammatory properties of receptors expressed in immune cells to mitigate the exaggerated acute and chronic pain.