Projection field of primary afferent fibers innervating the ventral portion of the lumbar intervertebral disc in the spinal cord dorsal horn.

In the present study, we investigated the central projection of afferent fibers innervating the lumbar intervertebral disc using the fluorescent neurotracer 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate (Dil). The tracer Dil was applied to the ventrolateral portion of the L5-L6 intervertebral disc in 11 adult rats. Fluorescent sites were observed microscopically on spinal cord transverse sections. Fluorescent spots in laminae I-III were plotted on the central projection map of cutaneous afferents. In six of 11 rats, Dil was restricted to the application site. Of these six rats, three showed no evident fluorescent sites. In the remaining three rats, small fluorescent spots were scattered in the dorsal horn. Fluorescent spots in dorsal horn lamina I were located in the central projection fields of the low back and groin skin. Fluorescent spots were observed, also sporadically, in Clarke's column in T12-L1 segments. The central projection of afferent fibers innervating the rat lumbar intervertebral disc was indistinct with Dil labeling. We presumed this was due to the scarcity of central terminal arbors of disc afferent fibers. Spotty projections in laminae I-IllIIere present near the central projection fields of the loin and groin, indicating that pain would be perceived in the groin.

Expression and co-expression of VR1, CGRP, and IB4-binding glycoprotein in dorsal root ganglion neurons in rats: differences between the disc afferents and the cutaneous afferents.

STUDY DESIGN: The expression of vanilloid receptor 1 (VR1), calcitonin gene-related peptide (CGRP), and isolectin B4 (IB4)-binding glycoprotein in dorsal root ganglion (DRG) neurons innervating the lumbar disc and the plantar skin was investigated. OBJECTIVE: To characterize the DRG neurons innervating lumbar discs and those innervating cutaneous tissue in rats. SUMMARY AND BACKGROUND DATA: Small nociceptive DRG neurons are divided into nerve growth factor (NGF) sensitive and glial cell line-derived neurotrophic factor (GDNF)-sensitive neurons. CGRP and IB4-binding glycoprotein are recognized as specific markers for NGF and GDNF-sensitive neurons, respectively. VR1 is localized in small DRG neurons. METHODS: Using histochemical staining and retrograde tracing methods, the expression of VR1, CGRP, and IB4-binding glycoprotein in DRG neurons innervating the L5-L6 disc and the plantar skin was examined in rats. RESULTS: DRG neurons innervating the disc showed positive staining as: 23.4% VR1, 54.4% CGRP, and 1.0% IB4-binding glycoprotein. The following distribution was found for DRG neurons innervating the skin: 35.1% VR1, 41.1% CGRP, and 19.5% IB4-binding glycoprotein. Percentages of neurons positive for VR1 and IB4-binding glycoprotein were significantly lower in DRG neurons innervating the disc than in DRG neurons innervating the skin (P < 0.05), while no significant difference was observed in the percentage of neurons positive for CGRP. CONCLUSIONS: VR1 is less abundant in lumbar disc than in cutaneous tissue. Our data suggest that nociceptive information from the disc is transmitted mostly by NGF-sensitive neurons, while that from the cutaneous tissue is transmitted by both NGF-sensitive and GDNF-sensitive neurons.

Disc inflammation potentially promotes axonal regeneration of dorsal root ganglion neurons innervating lumbar intervertebral disc in rats.

STUDY DESIGN: The expression of growth-associated protein 43 (GAP-43), a marker of axonal growth, in the dorsal root ganglion (DRG) neurons innervating the lumbar intervertebral disc was assessed using the retrograde tracing method and immunohistochemistry. OBJECTIVES: To study whether disc inflammation affects GAP-43 expression in DRG neurons innervating the disc in rats. SUMMARY AND BACKGROUND DATA: Persistent inflammation and nerve ingrowth into the inner layer of degenerated discs can be a cause of discogenic pain. Although the presence of GAP-43-expressing nerve fibers in painful discs has been reported, the expression of GAP-43 in DRG neurons innervating the disc has not been studied. METHODS: Seven days after the application of Fluoro-Gold to the L5-L6 disc, 50 microL of saline (n = 10, control group) or complete Freund's adjuvant (n = 10, inflammatory group) was applied to the disc in rats. Ten days after the Fluoro-Gold application, T13-L5 DRGs were double-stained with GAP-43 and either calcitonin gene-related peptide or isolectin B4 (IB4). RESULTS: The percentage of Fluoro-Gold-labeled neurons that were positive for GAP-43 was significantly higher in the inflammatory group (44%) than in the control group (24%, P < 0.001). In both groups, the majority of GAP-43-positive neurons were small and positive for calcitonin gene-related peptide but not IB4. CONCLUSIONS: The present results suggest that disc inflammation potentially promotes axonal growth of DRG neurons innervating the disc. In light of the strong correlation between the expression of calcitonin gene-related peptide and nerve growth factor receptor, it is most likely that nerve growth factor-sensitive DRG neurons extend their axons following disc inflammation.

P2X3-immunoreactive primary sensory neurons innervating lumbar intervertebral disc in rats.

The P2X(3) receptor is normally localized in a sub-population of small-diameter dorsal root ganglion (DRG) neurons, and is thought to be related to pain perception. The aim of this study in rats was to examine P2X(3)-immunoreactivity in DRG neurons innervating the lumbar disc and in DRG neurons innervating cutaneous tissues. Fluoro-Gold was applied to the L5-L6 disc, the plantar skin of the hind paw (L4-L5 dermatomes), and the back skin (L1-L2 dermatomes). It has been reported that the L5-L6 disc is innervated by T13-L5 DRG neurons. We performed immunostaining using antibodies against the P2X(3) receptor of T13-L5 DRGs to examine the L5-L6 disc, L4 and L5 DRGs to examine plantar skin and L1 and L2 DRGs to examine back skin. The P2X(3)-immunoreactivity was detected in 22.0 and 22.8% of neurons, labeled by Fluoro-Gold applied to plantar and back skin, respectively. However, P2X(3)-immunoreactivity was detected in only 4.0% of the neurons projecting to the L5-L6 disc. The proportion of P2X(3)-immunoreactive neurons was significantly larger in the DRG neurons innervating the plantar or the back skin, than in the DRG neurons innervating the lumbar disc. These results suggest that the P2X(3) receptors are abundant in DRG neurons innervating cutaneous tissues, but not in neurons innervating the lumbar disc. It is likely therefore that the P2X(3) receptor is less related to the mechanism of discogenic pain, than to cutaneous tissue pain.

Malignant fibrous histiocytoma associated with diaphyseal medullary stenosis.

An unusual presentation of secondary malignant fibrous histiocytoma of the femur in a patient with diaphyseal medullary stenosis is described. The patient, a 42-year-old man, presented with a painful lump in the right knee. A radiograph of the right femur showed lytic destruction. Characteristic features of longitudinal linear striations in the metaphysis and medullary stenosis in the diaphysis were observed in radiographs of the long tubular bones. A radiograph of the pelvis showed bilateral acetabular bone scleroses. After chemotherapy, surgical resection was done. On light microscopic examination, the tumor had features characteristic of malignant fibrous histiocytoma. Specimens from the diaphyseal medullary stenosis from the femur and tibia showed typical features of bone infarction. Radiographs of other members of the patient's family showed similar features of linear striation, cortical bone thickening, and acetabular sclerosis, including wavy, open growth plate of the iliac crest. The patient's aunt had died of a bone sarcoma in the shoulder region. It is important to recognize this extremely rare clinicopathologic type of diaphyseal medullary stenosis that frequently is associated with secondary high-grade sarcomas.