All animals, including humans, react with distinct emotional coping strategies when confronted with stressors. The immediate reactions to stressors are innate behavior patterns with a phylogenetic history of enabling individuals to cope with threats. The prototypical threat to an individual is exposure to a painful stimulus, and recent findings indicate that painful stimuli engage neural circuits that control the execution of defensive behaviors. Within this context, the emotional dimension of pain belongs to a class of sensory experience that represents threat to the individual and governs the production of defensive reactions that enable the individual cope with the threat. Because the neural circuits that control the execution of defensive behaviors are known to a considerable degree, these circuits can be used to evaluate the mechanisms that underlie the innate emotional reaction to painful stimuli. An understanding of how these neural circuits are engaged by a painful stimulus also provides a foundation to study how the immediate emotional reactions to pain produce enduring effects on the individual. Alterations in the circuitry that controls defensive responding are implicated in conditions such as fear, anxiety, depression, frustration, and anger. These secondary emotional reactions are components of the human pain experience, and contribute to the suffering and disability associated with pain. Rats produce a particular type of vocalization (vocalization after discharge, VAD) when exposed to a painful stimulus or confronted with a predator. These vocalizations reflect the rat's immediate emotional reaction to threatening stimuli. These vocalizations are used as a model behavioral system to investigate how painful stimuli engage mesolimbic circuits that control execution of defensive reactions to threats. Two interconnected core structures (ventromedial hypothalamus and periaqueductal gray) control execution of defensive behaviors, and the proposal initiates a systematic evaluation of how painful stimulation activates this neural circuit. The amygdala is the best-characterized modulator of these core structures, and the proposal also evaluates how amygdaloid subnuclei (medial, basolateral, central) enhance or suppress pain transmission through these sites. ? ?
