The Thalamic Projection of Pain Sensations to the Posterior Dorsal Fundus in the Insula: Comment on Mandonnet Et Al.

Letter to the Editor: We concur with Luis Garcia-Larrea9 that the article by Mandonnet et al.12 represents a valuable contribution to our understanding of the role of the insula for our pain perception, most critically because it conclusively shows in humans that the nociceptive input to the dorsal posterior insular cortex is not relayed there through other cortical regions, as was long suggested,13,16 but arrive through ascending fibers from the thalamus. However, this important contribution is, quite unnecessarily, tainted by the authors' failure to name the thalamic nucleus that projects to the posterior insula, writing instead that “it has been suggested that a subpart of the Po-SG specifically projects to an area in the posterior dorsal fundus in the insula,” despite the fact that this “subpart” was identified as a distinct nucleus several decades ago and was designated the VMpo (the posterior part of the ventromedial nucleus).6 It was given this name, which adheres to the commonly used nomenclature for the mammalian thalamus,10 because it lies adjacent (and posterior) to the VMb (the basal part of the ventromedial nucleus), together with which it provides a homeostatic afferent input to the insular cortex, that from VMpo arising from neurons in the spinal and trigeminal superficial dorsal horn and that from VMb from the nucleus of the solitary tract.3 Tract-tracing and electrophysiological recordings in macaque monkeys clearly identified VMpo, and neither the suprageniculate (SG) nor the posterior nucleus (Po), as the target of spinal lamina I projection neurons encoding pain and temperature modalities2,7 and as the source of thalamocortical projections to the dorsal posterior fundus of the insula.4 VMpo is readily identifiable in brain sections both from monkey and human thalamus1,2 (Fig. 1).Figure 1.: Adjacent frontal sections through the mesodiencephalic border zone of the human brain, stained with thionin (A) and for calbindin immunoreactivity (B). Dorsal is upward and lateral is to the left. Arrowheads in (A) indicate the borders of the VMpo nucleus. Note the medial lemniscus (ml) ventral to VMpo and heading toward the ventroposterior nuclei. Panel (B) shows how calbindin-positive fibres, identifying the lamina I spinothalamic tract,7 from the spinal lemniscus (arrowheads in B) enter the VMpo nucleus and form dense terminal-like patches. The same capillaries are indicated by “x” in each pair of images for orientation. Li, nucleus limitans; MG, medial geniculate nucleus; Pla, anterior pulvinar; Sg, suprageniculate nucleus; VMpo, posterior part of the ventromedial nucleus; VPL, ventroposterolateral nucleus. Reprinted from Ref. 1; with permission.We are certainly aware that some 20 years ago, when the available data were still incomplete, influential investigators put a curse on the VMpo by questioning its existence (and consequently also the critical role of its insular projection for the perception of pain)11,16 (but see Ref. 5). However, as pointed out by Vierck et al.15 already in 2013, the arguments that were put forward against VMpo were since long dated, being superseded by subsequent evidence, and became even more so in following years. Today, the role of VMpo as a dedicated thalamoinsular relay for pain and temperature, and other information on the condition of the body, from lamina I of the spinal and trigeminal dorsal horn is thoroughly established.3,4,8,14,15 We therefore believe that it is long past time to cite the seminal studies demonstrating for the first time the existence of the primate spino-thalamo-insular pathway that has become so crucial to the field of pain9,12 and to recognize the VMpo in this context. Conflict of interest statement The authors declare no conflicts of interest.