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.