Reciprocal circuits involved in nitroglycerin-induced neuronal activation of autonomic regions and pain pathways: a double immunolabeling and tract-tracing study.

This study uses tract-tracing protocols to determine the circuitry of specific nuclei involved in nitroglycerin-induced activation. Combined retrograde and anterograde tracers were injected into nuclei which consistently demonstrate robust Fos expression following our systemic nitroglycerin injection paradigm. The nuclei, which conform to these criteria, that we have evaluated in this study are the locus coeruleus, parabrachial nucleus and paraventricular nucleus of the hypothalamus. Dual Fos/tracer immunocytochemistry in treated animals documented the existence of a subset of autonomic nuclei which are activated by nitroglycerin injection and have reciprocal connections. From the nature of this rich interconnection we suggest that nitroglycerin activates autonomic responses involved in cardiovascular pressor mechanisms. Nuclei which show strong Fos labeling following nitroglycerin administration, but not traced in this study, include the nucleus trigeminalis caudalis and the ventrolateral column of the periaqueductal gray, both of which mediate nociceptive modalities. These data confirm and expand on our previous findings and demonstrate that nitroglycerin activates a complex set of structures that are functionally and structurally interconnected to articulate an integrated response.