Intervertebral disc injury or degeneration is a common cause of low back pain, and yet the specific source of pain remains ambiguous in many cases. Previous research indicates that the central vertebral endplate is highly innervated and can elicit pain responses to pressure. In effort to trace the origin of nerves located at the endplate, we used protein gene product 9.5 (PGP 9.5) to stain neurofibers and then quantified the spatial pattern of nerve distribution within a human L4 lumbar vertebra. The majority of nerves were adjacent to blood vessel walls, and consequently the nerve distribution closely resembled previously established vascularity patterns. We observed that the majority of nerves enter the vertebral body posteriorly, via the basivertebral foramen, and cluster in the vertebral center. These nerves follow the course of the nutrient artery, which enters the vertebral body through the basivertebral foramen, then branches toward the superior and inferior endplates. Our observations support the notion that nerves found at the central endplate could originate from sinuvertebral nerves accompanying the nutrient artery into the vertebral body. We also stained neighboring histological sections with calcitonin gene-related protein and noted significant co-localization with PGP 9.5, substantiating a nociceptive role for the nerves constituting our distribution pattern.

The congenital heart disease 5 (CHD5)/tryptophan rich basic protein (WRB) is a protein containing a tryptophanrich carboxy-terminal region, which was discovered in the human fetal heart. In humans, this CHD5/WRB is located between the markers ACTL5-D21S268 within the Down syndrome (DS) Region-2 at chromosome 21. Congenital heart disease is commonly linked to DS patients. The functions of this gene product are unknown. To identify the functions of CHD5/WRB in heart formation during embryogenesis, the medaka CHD5 cDNA (mCHD5) was isolated and its gene expression pattern and the localization of its gene product were investigated. The obtained mCHD5 belongs to the CHD5 superfamily, whose members include coiled-coil proteins. The mCHD5 gene was found to be expressed in the developing heart after stage 28 at which the chamber (ventricle and atrium) differentiation in the heart tube is initiated in the embryo. Its gene product was also detected in the developing heart at embryonic stage 28 and 35. Knocking-down of mCHD5 function caused severe cardiac disorder, including abnormal chamber differentiation, abnormal looping and ocular abnormality such as Cyclops. Our results provide the mCHD5 gene expression pattern as well as its physiological role during heart formation in a vertebrate model system.

Purpose Characterize the distribution of nerves within a single S1 vertebral body, with particular emphasis on the superior endplate that interfaces with the L5/S1 disc. Methods Musculature and connective tissue surrounding the sacrum was carefully dissected away for close visual inspection of penetrating nerve fibers. The S1 vertebral body was then isolated for histology and serial coronal sections were cut and stained with a ubiquitous neural antibody marker (PGP 9.5). Slides were analyzed and nerves were manually marked on high resolution, composite captured images, rendering 3D depictions of internal nerve distribution. Results The vast majority of nerves were closely associated with blood vessels within the marrow space with a uniform distribution in both the superior and inferior endplates of the S1 vertebral body. The highest nerve density was seen at the centrum (anatomic center) of the S1 vertebral body with smaller peaks seen at the lateral borders. Nerve fibers were observed branching from anterior sacral nerves and penetrating the lateral border of the S1 (during dissection), corresponding with peaks on nerve density maps. Conclusions Our results demonstrate that the S1 body and endplate are densely innervated and the peak in nerve density at the vertebral center coincides with vasculature patterns previously described in lumbar vertebral bodies. In the sacrum, however, there is no posterior nutrient foramen that facilitates nerve penetration through the vertebral cortex. Rather, our data indicate that nerves penetrate the S1 via the lateral aspects, consistent with being branches of the anterior sacral nerve. Since PGP 9.5 is a ubiquitous neural marker these identified nerves are likely composed of a mixed population of nociceptive and autonomic fibers.