Emotion, Pain and Pain Control Circuits

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DESCRIPTION (provided by applicant): The periaqueductal gray (FAG) and the adjoining dorsal raphe nucleus (DRN) are mesencephalic cell groups that can act to control pain perception. A consensus has arisen that the PAG functions in initiating and implementing behavioral coping strategies to situations involving stress, fear or pain. The DRN is a major source of forebrain serotonin, which modulates many behaviors and has been implicated in the pathophysiology of depression. Control of pain by these two nuclei is likely a single element of a multimodal response pattern to stressful situations. Substance P (SP) is a neuropeptide well known for playing a role in pain transmission. When released, SP binds the neurokinin 1 (NK1) receptor and precipitates receptor activation and internalization. The NK1 receptor is enriched within the dorsal and ventrolateral FAG as well as the DRN. In this region, focal application of SF is antinociceptive, eliciting the local release of endogenous opioids. In addition, SP neurotransmission is associated with anxiety, cardiovascular adjustments and grooming behavior. Therefore the PAG and DRN represent potential sites where SP may influence several individual components of behavioral coping strategies. The proposed experiments will examine internalization of the NK1 receptor produced by exogenous and endogenous SP using immunohistochemical methods to gain insight into the role of SP neurotransmission in the FAG and DRN. The topography of NK1 internalization by these stimuli will reveal the potential overlap of neural circuits used in coping with these stimuli. In addition, the proposed AIMS will broadly establish the neural circuitry that SP engages to modulate these areas. That is, the hypothesis that enkephalin- or serotonin-containing neurons have the NK1 receptor will be tested using light and electron microscopic analysis. The results of these studies will-yield insight into how distinct modes of stressful stimuli impact SP neurotransmission within neural circuits that coordinate defensive coping strategies.