Herniated lumbar disc material as a source of free glutamate available to affect pain signals through the dorsal root ganglion

Study Design. Combined prospective human cohort and prospective controlled animal model. Objectives. To determine whether free glutamate is available in herniated d isc material in concentrations sufficient to diffuse to glutamate receptors and affect the :activity of neurons in the dorsal root ganglion that may t ransmit pain information. Summary of Background Data. The severity of lumbar radicular pain cannot be fully explained by physical pressure on nerve roots or ganglions. In exper imental models, inflammaton/processes are relatively modest under condition s of disc herniation. The hypothesis for the current was that the proteogly can link and core proteins, which contain high fractions of acidic amino ac ids, may be a source of glutamate when enzymatically degraded in an environ ment without glutamate reuptake systems. Glutamate would be free to diffuse to the dorsal root ganglion to affect glutamate receptors. Methods. Disc material was harvested during surgery from herniated and nonh erniated portions in patients undergoing elective lumbar disc surgery and s ubjected to immunohistochemistry and high-performance liquid chromatography for assessment of the presence of extracellular disc matrix glutamate. Min iosmotic pumps with differing concentrations of radiolabeled glutamate base d on human data were implanted in the rat epidural space for 72 hours and d orsal root ganglion (DRG) in the region were harvested. Results. Densitometry of disc matrix demonstrated immunohistochemical evide nce for significant extracellular glutamate (P < 0.002). High performance l iquid chromatography showed significant concentrations of glutamate in disc material and significantly more in herniated than in nonherniated disc mat erial (P < 0.05). Significant radiolabeling of the dorsal root ganglion aft er epidural glutamate infusion was found at concentrations two orders of ma gnitude below measured disc glutamate levels. Autoradiography;Ct demonstrat ed radiolabeling of adjacent DRG. Conclusions. Glutamate originating from degenerated disc proteoglycan may d iffuse to the dorsal root ganglion and effect glutamate receptors. Consider ation may be given to treating disc radiculopathy with epidural glutamate r eceptor antagonists.