Dr. Heinricher's laboratory investigates brainstem mechanisms involved in pain modulation. Their focus is on opioid-sensitive circuits within the rostral ventral medulla (RVM), which is a crucial element in a pain-modulating network with links in the midbrain, medulla and spinal cord. This network contributes to the variability in pain sensitivity seen in different situations (for example under conditions of fear or extreme stress), and it is an important substrate for opioids and other analgesic drugs such as cannabinoids. The laboratory uses single cell recording in combination with pharmacological tools to analyze how this system is activated, and they have identified two distinct classes of pain modulating neurons.
- ON cells are directly sensitive to opioids, and they recently showed that these neurons facilitate nociceptive transmission.
- OFF-cells exert a net inhibitory effect on nociception, and they were able to demonstrate that disinhibition of these neurons is central to the antinociceptive actions of opioids within the medulla.
Currently, they are interested in identifying neurotransmitters that activate these two cell classes differentially to promote or suppress pain. They are also interested in how this modulatory system is activated under physiological conditions, and are looking at the inputs from limbic forebrain structures such as the hypothalamus to the rostral ventral medulla in an attempt to investigate this issue.
The central neural control of autonomic outflow to all tissues of the body is an integral component of the physiological mechanisms contributing to homeostasis. Dysregulation of autonomic function contributes to the etiology, morbidity, and mortality associated with many of the disease states and pathological conditions prevalent in modern society, such as obesity, diabetes, hypertension, sudden cardiac death, stroke, infection and sepsis.
Dr. Madden's research is directed toward understanding the detailed functional organization of the central neural circuits regulating metabolism, glucose homeostasis, cardiovascular function, and thermogenesis and how alterations in this regulation contribute to the pathology of disease. They currently use in vivo electrophysiological techniques, including direct simultaneous recordings of peripheral nerve activities and central nervous system single cell discharge, as well as, pharmacological, functional neuroanatomical, molecular biological, and optogenetic techniques to investigate the central neural circuits that regulate cardiovascular function, blood glucose homeostasis, body temperature, and energy metabolism.