Specific neurons in the brainstem and spinal cord have been described that control pain responses in animals and pain perception in humans. However, the interactions among these neurons and the function of the neural circuits, of which these neurons are a part, is poorly understand. The major goal of the research in my laboratory is to provide a detailed analysis of these pain control circuits. Current research projects are designed to determine the anatomical and functional connections among specific neurochemically-identified neurons in the brainstem and spinal cord that are involved in controlling pain responses in rats. Anatomical experiments using both light and electron microscopy are used to determine the neurotransmitters contained in these neurons and the anatomical connections among these immunochemically-identified neurons. These experiments determine axonal trajectories, the location of neurotransmitter receptors, and the location and immunochemical content of synapses formed by these neurons. The function of anatomically identified neurons is determined by selectively activating specific neurons using electrical or chemical stimulation and determining the resulting effects on both nociception and electrophysiological recordings of postsynaptic neurons. In addition, pharmacological analysis of the effects of selective neurotransmitter agonists and antagonists is used to provide evidence for the function of specific neurochemically-identified neurons in pain modulation. These anatomical, electrophysiological, and pharmacological experiments are designed to provide detailed converging evidence that is used to define specific neuronal circuits in the brainstem and spinal cord that modulate nociception. The ultimate goal of this research is to provide a detailed circuit model that can be used to more clearly understand the function of pain control systems and to provide a rational basis for the development of more effective pain control methods.