A segmental chronic pain syndrome in rats associated with intrathecal infusion of NMDA: evidence for selective action in the dorsal horn.
We explored the effects of chronic lumbar intrathecal NMDA infusion (mini-osmotic pumps) in Sprague-Dawley rats on motor and sensory axon integrity. Several different infusion protocols, each given over a 4 week period were examined: 0.15 M NMDA in phosphate buffered saline; phosphate buffered saline without NMDA; and 0.20 M magnesium sulfate plus 0.15 M NMDA; 0.35 M NMDA. In two additional protocols, 0.15 M NMDA or phosphate buffered saline were infused for a total of 8 weeks. Within 1-2 weeks of the onset of NMDA, but not phosphate buffered saline infusions, the rats exhibited irritability, circling, biting and excessive grooming resulting in loss of hair, and skin ulcerations from autotomy localized to lumbar and sacral innervated dermatomes. Co-infusion of NMDA with magnesium sulfate almost completely prevented these findings. The behavioural changes were not associated with abnormalities of sensory or motor conduction. Intrathecal infusion of NMDA induces a chronic "central" experimental pain disorder in rats, localized to the cord segment with the greatest exposure to the infusion, without involvement of peripheral sensory axons and sparing the axonal integrity of anterior horn cells.
Zochodne
D W
DW
Department of Clinical Neurosciences, University of Calgary, Alberta, Canada.
Murray
M
M
Nag
S
S
Riopelle
R J
RJ
D000818:Animals; D000870:Anterior Horn Cells / Q000187:drug effects / Q000502:physiology; D001369:Axons / Q000187:drug effects / Q000502:physiology; D001522:Behavior, Animal / Q000187:drug effects; D002908:Chronic Disease; D004594:Electrophysiology; D007278:Injections, Spinal; D008278:Magnesium Sulfate / Q000494:pharmacology; D008297:Male; D009046:Motor Neurons / Q000187:drug effects / Q000502:physiology; D016202:N-Methylaspartate / Q000008:administration & dosage; D009412:Nerve Fibers / Q000187:drug effects / Q000502:physiology; D009413:Nerve Fibers, Myelinated / Q000187:drug effects / Q000502:physiology; D009431:Neural Conduction / Q000187:drug effects / Q000502:physiology; D009434:Neural Pathways / Q000187:drug effects / Q000502:physiology; D009475:Neurons, Afferent / Q000187:drug effects / Q000502:physiology; D009619:Nociceptors / Q000187:drug effects; D010146:Pain / Q000139:chemically induced / Q000503:physiopathology* / Q000523:psychology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000187:drug effects / Q000502:physiology*
D016202:N-Methylaspartate; D008278:Magnesium Sulfate