Physiological and behavioral evidence for focal nociception induced by epidural glutamate infusion in rats.
METHODS
Blinded animal study.


OBJECTIVE
To determine if an increased concentration of epidural glutamate can cause a focal nociceptive response in the lower extremities that is consistent with sciatica.


BACKGROUND
It is believed that the origin of sciatic pain is related to more than physical pressure on the nerve roots. Recently, it was determined that disc material may be a significant source of free glutamate, resulting from the enzymatic degradation of matrix aggrecan proteins. We believe that this free glutamate acts as a neurotransmitter at glutamate receptors on the dorsal root ganglion (DRG) cell bodies, thereby initiating a nociceptive response.


METHODS
Rats were subject to a 72-hour epidural glutamate infusion via a mini osmotic pump. Von Frey behavioral testing was performed 24 hours before, and 24 and 72 hours after the onset of the infusion. DRG and dorsal horn tissues were analyzed for changes in receptor expression, which have been previously shown to correlate with a nociceptive state.


RESULTS
Von Frey behavioral tests showed focal hyperalgesia that was maximal at the 0.02 mmol/L glutamate concentration. Significant changes in DRG glutamate receptor expression were seen for alpha-amino-3-hydroxy-5-methyl-4-isoxazoleproprionic acid, kainite, and N-methyl-D aspartate receptors. Analysis of dorsal horn glutamate receptors also showed patterns in alpha-amino-3-hydroxy-5-methyl-4-isoxazoleproprionic acid and kainate receptor expression that were consistent with a nociceptive state.


CONCLUSIONS
Epidural glutamate elicits a focal nociceptive response. Free glutamate that has been liberated from the disc material may be an important factor in the development of sciatic pain.
Harrington
J Frederick
JF
Department of Neurosurgery, Brown University School of Medicine, and Rhode Island Hospital, Providence, RI, USA. JFHarrington@lifespan.org
Messier
Arthur A
AA
Hoffman
Laurie
L
Yu
Elizabeth
E
Dykhuizen
Matthew
M
Barker
Kelly
K
D000818:Animals; D015415:Biomarkers; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005260:Female; D005727:Ganglia, Spinal / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D018698:Glutamic Acid / Q000494:pharmacology*; D006930:Hyperalgesia / Q000139:chemically induced* / Q000473:pathology / Q000503:physiopathology; D015918:Infusion Pumps, Implantable; D007268:Injections, Epidural; D008159:Lumbar Vertebrae / Q000294:innervation; D009619:Nociceptors / Q000187:drug effects* / Q000503:physiopathology; D010146:Pain / Q000139:chemically induced* / Q000503:physiopathology; D017288:Pain Threshold / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D017470:Receptors, Glutamate / Q000187:drug effects / Q000378:metabolism; D016037:Single-Blind Method; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology
D015415:Biomarkers; D017470:Receptors, Glutamate; D018698:Glutamic Acid