Cytoarchitectonic and immunohistochemical characterization of a specific pain and temperature relay, the posterior portion of the ventral medial nucleus, in the human thalamus

Abstract

Previous studies in the macaque monkey have identified a thalamic nucleus, the posterior portion of the ventral medial nucleus (VMpo), as a dedicated lamina I spinothalamocortical relay for pain and temperature sensation. The dense plexus of calbindin-immunoreactive fibres that characterizes VMpo in primates enables its homologue to be identified in the human thalamus by immunohistochemical labelling for calbindin. We have now analysed in detail the cytoarchitectonic characteristics of VMpo and its relationship with immunoreactivity for calbindin, substance P and calcitonin gene-related peptide (CGRP) in the human thalamus. The area in the posterolateral thalamus in which dense calbindin-immunoreactive fibre terminations are present coincides nearly completely with a distinct region that contains small to medium-sized cells with round or oval shapes that are aggregated in clusters separated by cell sparse areas. This region, which we identify as VMpo, is located posteromedial to the ventral posterior lateral (VPL) and ventral posterior medial (VPM) nuclei, ventral to the anterior pulvinar and centre médian nuclei, lateral to the limitans and parafascicular nuclei and dorsal to the medial geniculate nucleus. Calbindin-immunoreactive fibres enter VMpo from the spinal lemniscus and form large patches of dense terminal-like staining over clusters of VMpo neurons. A few of these clusters also display terminal-like substance P labelling. Small bursts of CGRP staining are intercalated between the calbindin-labelled clusters, but there is little or no overlap between these two markers. CGRP immunoreactivity is also present over small, non-clustered neurons in the calbindin-negative area that separates VMpo from the VPL and VPM nuclei, which we denote as the posterior nucleus (Po). These observations provide a concise description of VMpo in the human thalamus. Further, they suggest that the lamina I spinothalamic tract fibres (represented by calbindin and probably also substance P immunoreactivity) and vagal-solitary-parabrachial afferents (represented by CGRP immunoreactivity) form closely related, but separate, termination fields that can be considered to represent different aspects of enteroceptive information regarding the physiological status of the tissues and organs of the body. The location of VMpo and the adjacent Po fits with clinical descriptions of the thalamic area from which pain, temperature and visceral sensations can be evoked by microstimulation, and where nociceptive and thermoreceptive neurons have been recorded in humans. It also corresponds to the area in which infarcts cause analgesia and thermoanaesthesia and can lead to the paradoxical development of central pain.

Lesions Limited to the Human Thalamic Principal Somatosensory Nucleus (Ventral Caudal) Are Associated with Loss of Cold Sensations and Central Pain

“…None of these lesions involved VMpo, which was located posterior to Vc-only lesions and ventral to Vc-plus lesions ( Fig. 1) (Blomqvist et al, 2000). We conclude that lesions of Vc are sufficient to impair cold and tactile sensations and that thalamic lesions leading to CPSP do not necessarily include VMpo.…”

“…This was also performed by local linear registration based on the borders of the third ventricle, ambient cistern, habenular commissure, posterior commissure, superior colliculus, pulvinar, the posterior border of Vc, and the posteromedial aspect of the internal capsule. VMpo was not seen, and thus is not shown, on some of the Schaltenbrand atlas maps in this figure (Schaltenbrand and Bailey, 1959;Blomqvist et al, 2000).…”

“…To locate VMpo on these atlas maps, axial sections showing the proposed location of this nucleus were registered with the sections of the Schaltenbrand atlas (Blomqvist et al, 2000). This was also performed by local linear registration based on the borders of the third ventricle, ambient cistern, habenular commissure, posterior commissure, superior colliculus, pulvinar, the posterior border of Vc, and the posteromedial aspect of the internal capsule.…”

“…This technique of determining VMpo was used because the only sections showing human VMpo do not identify standard surgical landmarks used to align the magnetic resonance image, such as the commissures (Blomqvist et al, 2000). In addition, there is uncertainty in the existence and location of VMpo, as determined by STT terminations and staining for calcium-binding proteins (Willis et al, 2001;Craig, 2004;Graziano and Jones, 2004).…”

“…The estimated position of VMpo is indicated in the appropriate sections of Figure 1 (see Materials and Methods) (Blomqvist et al, 2000;Montes et al, 2005). None of these lesions had involvement of VMpo because they were located anterior to VMpo (Vc-only lesions), or lateral and dorsal (Vc-plus lesions).…”