Collateral projections of neurons in laminae I, III, and IV of rat spinal cord to thalamus, periaqueductal gray matter, and lateral parabrachial area

Abstract

Projection neurons in lamina I, together with those in laminae III–IV that express the neurokinin 1 receptor (NK1r), form a major route through which nociceptive information reaches the brain. Axons of these cells innervate various targets, including thalamus, periaqueductal gray matter (PAG), and lateral parabrachial area (LPb), and many cells project to more than one target. The aims of this study were to quantify projections from cervical enlargement to PAG and LPb, to determine the proportion of spinothalamic neurons at lumbar and cervical levels that were labelled from PAG and LPb, and to investigate morphological differences between projection populations. The C7 segment contained fewer lamina I spinoparabrachial cells than L4, but a similar number of spino-PAG cells. Virtually all spinothalamic lamina I neurons at both levels were labelled from LPb and between one-third and one-half from PAG. This suggests that significant numbers project to all three targets. Spinothalamic lamina I neurons differed from those labelled only from LPb in that they were generally larger, were more often multipolar, and (in cervical enlargement) had stronger NK1r immunoreactivity. Most lamina III/IV NK1r cells at both levels projected to LPb, but few were labelled from PAG. The great majority of these cells in C7 and over one-fourth of those in L4 were spinothalamic, and at each level some projected to both thalamus and LPb. These results confirm that neurons in these laminae have extensive collateral projections and suggest that different neuronal subpopulations in lamina I have characteristic patterns of supraspinal projection. J. Comp. Neurol. 515:629–646, 2009.

Neurons in the lateral part of the lumbar spinal cord show distinct novel axon trajectories and are excited by short propriospinal ascending inputs

“…The main axon in these cells bifurcated within the dorsal grey matter and while one branch followed the regular path of PNs, the other one entered the dorsal funiculus and ascended there in the ipsilateral side. Lamina I PNs with collaterals crossing the midline at the supraspinal level and thus achieving bilateral projections have been reported before (Al-Khater and Todd, 2009). In case of the four bilateral projection neurons in our sample the splitting of the main axon occurs earlier and the two equally strong branches seemingly ascend in different tracts from the beginning.…”

A central role for spinal dorsal horn neurons that express neurokinin-1 receptors in chronic itch

“…We observed retrogradely labeled neurons to be located predominantly in the superficial dorsal horn at upper cervical (C1-2) and caudal medullary levels following Fluorogold injections in the lateral parabrachial nucleus or ventral posteromedial thalamus, confirming recent studies in mice [15], and rats [9; 10]. Using a double-label strategy, we observed that 89% of spinoparabrachial and 94% of spinothalamic projections neurons co-expressed NK1R.…”

Transmitting Pain and Itch Messages: A Contemporary View of the Spinal Cord Circuits that Generate Gate Control

“…The PB, in turn, provides rapid access to forebrain limbic structures, including the amygdala and hypothalamus, which are presumed to contribute to the emotional quality of the pain experience. Other spinal cord projection neurons target the midbrain periaqueductal gray (PAG), reticular formation, hypothalamus and thalamus (Bernard et al, 1995; Burstein et al, 1990; Todd et al, 2000) and many spinal cord projection neurons collateralize to multiple supraspinal sites (Al-Khater and Todd, 2009; Spike et al, 2003). As to neurochemistry, most PB-projecting neurons (~80%) express the neurokinin 1 receptor (NK1), which is targeted by substance P-expressing primary afferent nociceptors (SP; (Ding et al, 1995; Todd et al, 1998) as well as SP-expressing local interneurons.…”