The ventrolateral periaqueductal gray projects to caudal brainstem depressor regions: a functional-anatomical and physiological study.

The reaction of shock, a precipitous, life-threatening fall in arterial pressure and heart rate, is evoked often by the combination of deep pain and blood loss following traumatic injury. A similar "shock-like" pattern of response can be evoked by excitation of the ventrolateral midbrain periaqueductal gray. Further, ventrolateral periaqueductal gray neurons are selectively activated by deep somatic or visceral pain and haemorrhage. The pathways mediating ventrolateral periaqueductal gray evoked hypotension and bradycardia are not known. In this study, the projections from the ventrolateral periaqueductal gray to "cardiovascular" regions in the caudal medulla of the rat were examined. Injections of the anterograde tracer, biotinylated dextran amine at physiologically-defined, ventrolateral periaqueductal gray depressor sites, revealed strong projections to the caudal midline medulla and to the depressor region of the caudal ventrolateral medulla. Injections of excitatory amino acids established that substantial falls in arterial pressure could be evoked from the ventrolateral periaqueductal gray-recipient parts of the caudal midline medulla. Injections of the retrograde tracer, cholera toxin subunit B at physiologically-defined, depressor sites in the caudal midline medulla and the caudal ventrolateral medulla confirmed the existence of substantial projections from the ventrolateral periaqueductal gray. Although previous studies have emphasized the importance of projections from the ventrolateral periaqueductal gray to the pressor region of the rostral ventrolateral medulla, this study has revealed the existence of strong ventrolateral periaqueductal gray projections to depressor regions within the caudal medulla (caudal midline medulla and caudal ventrolateral medulla) which likely contribute to ventrolateral periaqueductal gray-mediated hypotension and bradycardia.