No abstract

The organization of efferent projections from the spinal cervical enlargement to the parabrachial (PB) area and the periaqueductal gray (PAG) was studied in the rat by using microinjections of Phaseolus vulgaris-leucoagglutinin (PHA-L) into different laminae around the C7 level. The results demonstrated two areas of cervical enlargement which project in different ways to the PB area and PAG. First, the superficial laminae (I, II) showed a very dense projection, with a clear contralateral dominance at the coronal level where the inferior colliculus merges with the pons, to a restricted "superficial" portion of the PB area, namely the lateral crescent area, the dorsal lateral, the superior lateral (PBsl), and the outer portion of the external lateral PB subnuclei. Less dense projections were observed in the Kölliker-Fuse nucleus (KF) and in the ventrolateral/lateral quadrant of the caudal and mid PAG. By contrast, the labeling was weak or absent in the other PB subnuclei and the outer adjacent regions; in particular, no, or very little, labeling was found in the cuneiform nucleus. The PB area appeared to be the supraspinal target that received the densest projection from laminae I and II. Projections were less dense in the PAG and the thalamus and markedly less in other sites such as the ventrolateral medulla, the subnucleus reticularis dorsalis, and the nucleus of the solitary tract. Second, the reticular portion of lamina V, the medial portion of laminae IV-VI up to X and lamina VIII, showed bilateral projections with a weak ipsilateral dominance and a high to medium density on a very restricted portion of the PB area, namely the internal lateral PB subnucleus. A lesser projection was also observed in the adjacent portion of the PBsl, the KF, and the lateral quadrant of the PAG. These results suggest that signals carried by neurons from lamina I-II converge on a restricted superficial portion of the PB area and the ventral part of the lateral quadrant of the PAG. These results are discussed in the context of the role of the spino-PB and spino-PAG pathways in nociception.

No abstract

While functional imaging and deep brain stimulation studies point to a pivotal role of the hypothalamus in the pathophysiology of migraine and trigeminal autonomic cephalalgias, the circuitry and the mechanisms underlying the modulation of medullary trigeminovascular (Sp5C) neurons have not been fully identified. We investigated the existence of a direct anatomo-functional relationship between hypothalamic excitability disturbances and modifications of the activities of Sp5C neurons in the rat. Anterograde and retrograde neuronal anatomical tracing, intrahypothalamic microinjections, extracellular single-unit recordings of Sp5C neurons, and behavioral trials were used in this study. We found that neurons of the paraventricular nucleus of the hypothalamus (PVN) send descending projections to the superior salivatory nucleus, a region that gives rise to parasympathetic outflow to cephalic and ocular/nasal structures. PVN cells project also to laminae I and outer II of the Sp5C. Microinjections of the GABA A agonist muscimol into PVN inhibit both basal and meningeal-evoked activities of Sp5C neurons. Such inhibitions were reduced in acutely restrained stressed rats. GABA A antagonist gabazine infusions into the PVN facilitate meningeal-evoked responses of Sp5C neurons. PVN injections of the neuropeptide pituitary adenylate cyclase activating peptide (PACAP38) enhance Sp5C basal activities, whereas the antagonist PACAP6-38 depresses all types of Sp5C activities. 5-HT1 B/D receptor agonist naratriptan infusion confined to the PVN depresses both basal and meningeal-evoked Sp5C activities. Our findings suggest that paraventricular hypothalamic neurons directly control both spontaneous and evoked activities of Sp5C neurons and could act either as modulators or triggers of migraine and/or trigeminal autonomic cephalalgias by integrating nociceptive, autonomic, and stress processing mechanisms.