Clinicn Investigator, Full Prf Anesthesia, Critical Care and Pain Medicine, Mass General Research Institute

Professor of Anaesthesia Harvard Medical School

Anesthetist Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital

F.R.C.A. Anesthesiology Diplomate, American Board of Anesthesiology 1976

MD University of Ceylon, Sri Lanka 1969

S.C.C.M. Critical Care Science Critical Care Boards (Anesthesiology) 1986

F.R.C.A. Anesthesiology Fellow, Royal College of Anaesthetists, U.K. 1975

MA (Hons) Science Harvard University 1993

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

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.