The role of trigeminal interpolaris-caudalis transition zone in persistent orofacial pain

Abstract

Previous studies have established the role of the medullary dorsal horn or the subnucleus caudalis of the spinal trigeminal complex, a homolog of the dorsal horn of the spinal cord, in trigeminal pain processing. In addition to the medullary dorsal horn, recent studies have pointed out increased excitability and sensitization of trigeminal interpolaris and caudalis transition zone (Vi/Vc) following deep orofacial injury, involving neuron-glia-cytokine interactions. The Vi/Vc transition zone accesses rostral brain regions that are important for descending pain modulation, and somatovisceral and somatoautonomic processing and plays a unique role in coordinating trigeminal nocifensive responses.

Fig. 1

Digital photomicrograph illustrating the trigeminal Vi/Vc transition zone and laminated subnucleus caudalis (Vc). The sections in A and B were immunostained against anti-CGRP antibodies to illustrate the appearance of the Vi/Vc transition zone (A, about 0.4 mm rostral to the obex) and laminated Vc, or Medullary Dorsal Horn (MDH) (B, about 1.0 mm caudal to the obex). Note the the delineation of the Vi in the ventral Vi/Vc transition zone by calcitonin gene-related peptide staining (A). Scale bar = 0.2 mm. 12, hypoglossal nucleus; cc, central canal; Gr, gracile nucleus; NTS, Nucleus Tractus Solitarius; Py, pyramidal tract; Sp5, spinal trigeminal tract; Vi, subnucleus interpolaris of the spinal trigeminal complex. (Adapted from Wang et al., 2006, with permission from John Willey and Sons, License number: 2514340553127).

Fig. 2

Rostrocaudal distribution of Fos-immunoreactive neurons in the spinal trigeminal complex after orofacial stimulation. Cartoons on the right show site of stimulation. The number of Fos-positive cells is plotted against the distance from the subnucleus interpolaris. 0 ≈ obex level, positive = rostral, negative = caudal. Note bi-modal distribution of Fos-positive cells along the Vi/Vc and Vc/C1,2 ipsilateral to stimulation and one peak of Fos-positive cells at the Vi/Vc level contralateral to stimulation. (Adapted from Strassman and Vos, 1993, with permission from John Willey and Sons, License number: 2514340716050).

Fig. 3

Summary of the role of the trigeminal Vi/Vc transition zone in persistent orofacial pain. Orofacial injury-related inputs not only activate caudal Vc neurons, but also reach the Vi/Vc transition zone. The Vi/Vc output accesses hypothalamus (Hypoth), rostral ventromedial medulla (RVM), parabrachial nucleus (PB), and nucleus submedius of the thalamus (Submed) to play a role in autonomic responses to injury, descending pain modulation and pain-related emotionality. The Vi/Vc transition zone also receives input from RVM and Vi/Vc neuronal activation is regulated by caudal Vc through internuclear connections, the adrenal cortex (Ad) through circulating glucocorticoids and vagal afferents. Also shown is the Vc output that is relayed through the thalamic medial ventrolateral nucleus (VPM) and posterior thalamic nucleus (PO) for discriminative pain. The Vi/Vc transition zone may play a minor role in discriminative pain (dashed arrows).