Herniated lumbar disc material as a source of free glutamate available to affect pain signals through the dorsal root ganglion.
METHODS
Combined prospective human cohort and prospective controlled animal model.


OBJECTIVE
To determine whether free glutamate is available in herniated disc material in concentrations sufficient to diffuse to glutamate receptors and affect the activity of neurons in the dorsal root ganglion that may transmit pain information.


BACKGROUND
The severity of lumbar radicular pain cannot be fully explained by physical pressure on nerve roots or ganglions. In experimental models, inflammatory processes are relatively modest under conditions of disc herniation. The hypothesis for the current study was that the proteoglycan link and core proteins, which contain high fractions of acidic amino acids, may be a source of glutamate when enzymatically degraded in an environment 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 nonherniated portions in patients undergoing elective lumbar disc surgery and subjected to immunohistochemistry and high-performance liquid chromatography for assessment of the presence of extracellular disc matrix glutamate. Miniosmotic pumps with differing concentrations of radiolabeled glutamate based on human data were implanted in the rat epidural space for 72 hours and dorsal root ganglion (DRG) in the region were harvested.


RESULTS
Densitometry of disc matrix demonstrated immunohistochemical evidence for significant extracellular glutamate (P < 0.002). High performance liquid chromatography showed significant concentrations of glutamate in disc material and significantly more in herniated than in nonherniated disc material (P < 0.05). Significant radiolabeling of the dorsal root ganglion after epidural glutamate infusion was found at concentrations two orders of magnitude below measured disc glutamate levels. Autoradiography demonstrated radiolabeling of adjacent DRG.


CONCLUSIONS
Glutamate originating from degenerated disc proteoglycan may diffuse to the dorsal root ganglion and effect glutamate receptors. Consideration may be given to treating disc radiculopathy with epidural glutamate receptor antagonists.
Harrington
J F
JF
Brown University School of Medicine and the Rhode Island Hospital, Providence, Rhode Island, USA. JHarringtonJr@brown.edu
Messier
A A
AA
Bereiter
D
D
Barnes
B
B
Epstein
M H
MH
D000328:Adult; D000818:Animals; D001345:Autoradiography; D002851:Chromatography, High Pressure Liquid; D004343:Drug Implants; D018691:Excitatory Amino Acid Antagonists / Q000008:administration & dosage / Q000627:therapeutic use; D005727:Ganglia, Spinal / Q000187:drug effects / Q000503:physiopathology*; D018698:Glutamic Acid / Q000008:administration & dosage / Q000302:isolation & purification / Q000378:metabolism*; D006801:Humans; D007268:Injections, Epidural; D007403:Intervertebral Disc / Q000737:chemistry* / Q000378:metabolism; D007405:Intervertebral Disc Displacement / Q000150:complications / Q000378:metabolism / Q000601:surgery; D017116:Low Back Pain / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism*; D008159:Lumbar Vertebrae; D008297:Male; D008875:Middle Aged; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D011446:Prospective Studies; D011843:Radiculopathy / Q000150:complications / Q000188:drug therapy / Q000378:metabolism; D051381:Rats; D017470:Receptors, Glutamate / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects* / Q000502:physiology
D004343:Drug Implants; D018691:Excitatory Amino Acid Antagonists; D017470:Receptors, Glutamate; D018698:Glutamic Acid