Brain projections from the medullary dorsal reticular nucleus: An anterograde and retrograde tracing study in the rat

Abstract

In the last 15 years a role has been ascribed for the medullary dorsal reticular nucleus as a supraspinal pain modulating area. The medullary dorsal reticular nucleus is reciprocally connected with the spinal dorsal horn, is populated mainly by nociceptive neurons and regulates spinal nociceptive processing. Here we analyze the distribution of brain projections from the medullary dorsal reticular nucleus using the iontophoretic administration of the anterograde tracer biotinylated-dextran amine and the retrograde tracer cholera toxin subunit B. Fibers and terminal boutons labeled from the medullary dorsal reticular nucleus were located predominately in the brainstem, although extending also to the forebrain. In the medulla oblongata, anterograde labeling was observed in the orofacial motor nuclei, inferior olive, caudal ventrolateral medulla, rostral ventromedial medulla, nucleus tractus solitarius and most of the reticular formation. Labeling at the pons-cerebellum level was present in the locus coeruleus, A5 and A7 noradrenergic cell groups, parabrachial and deep cerebellar nuclei, whereas in the mesencephalon it was located in the periaqueductal gray matter, deep mesencephalic, oculomotor and anterior pretectal nuclei, and substantia nigra. In the diencephalon, fibers and terminal boutons were found mainly in the parafascicular, ventromedial, and posterior thalamic nuclei and in the arcuate, lateral, posterior, peri- and paraventricular hypothalamic areas. Telencephalic labeling was consistent but less intense and concentrated in the septal nuclei, globus pallidus and amygdala. The well-known role of the medullary dorsal reticular nucleus in nociception and its pattern of brain projections in rats suggests that the nucleus is possibly implicated in the modulation of: (i) the ascending nociceptive transmission involved in the motivational-affective dimension of pain; (ii) the endogenous supraspinal pain control system centered in the periaqueductal gray matter-rostral ventromedial medulla-spinal cord circuitry; (iii) the motor reactions associated with pain.

Projections from the brain to the spinal cord in the mouse

“…In the dorsal portion of MdD, IRt, and MdV, labeled cells are more numerous in the more caudal regions. These findings are consistent with similar studies in other mammals (Peterson et al 1975;Hayes and Rustioni 1981;Leong et al 1984;Carlton et al 1985;Leite-Almeida et al 2006).…”

Central modulation of pain

“…However, other studies established that lesions of the RVM or the PAG did not block DNIC (130) and that DNIC was integrated at the level of the dorsal reticular nucleus (130). The dorsal reticular nucleus (DRt) receives nociceptive inputs from spinal projections and communicates with the PAG and RVM as well as the thalamus and amygdala and sends pain modulatory projections to the spinal cord (131)(132)(133). Moreover, the DRt sends and receives projections from cortical sites as well, and a single DRt neuron can project to different CNS sites, thus potentially modulating pain through several mechanisms (134).…”

The Striatum and Pain Modulation

“…Although, the lesion of the RVM suppressed the inhibitory action of the striatum, it is not clear what projections from the basal ganglia arrived to the RVM. However, afferents from the GP and the SNr to medullary dorsal reticular nucleus in the rat has been reported, which in turn is connected with the RVM (Leite- Almeida et al 2006).…”