Intrathecal excitatory amino acid (EAA) agonists increase tail flick latencies (TFLs) of spinal rats.
The facilitation of spinal nociceptive reflexes that occurs after spinal transection reveals the existence of descending, supraspinally mediated inhibition. Substantial evidence indicates that the excitatory amino acids (EAAs) are involved in these spinal circuits. Therefore, it was hypothesized that reflex facilitation in the spinal animal might be due to the removal of inhibitory input normally exerted on the spinal action of EAAs. If so, the facilitatory decrease in reflex latency, observed in the spinal preparation, might be potentiated by intrathecal (IT) administration of EAA agonists. This was tested by comparing the effect of IT injections of N-methyl-D-aspartate (NMDA) and alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) on the thermally elicited tail flick (TF) response of Intact and acute spinal rats. In intact rats, a low (0.25 nM) dose of NMDA produced a hyperalgesic decrease in latency, relative to saline, whereas higher doses produced an overall increase in latency. A large dose (0.5 microM) produced overt signs of toxicity (crippling, self-mutilation, and loss of the reflex). Only the highest (1.0 nM) dose of AMPA affected the response, resulting in a significant increase. After spinal transection, the hyperalgesic reaction to 0.25 nM of NMDA was absent, and latencies were significantly increased by 1.0 nM. The toxic reaction to 0.5 microM appeared to be potentiated. Tail flick responses to AMPA were also significantly increased in spinal rats. Contrary to the prediction, reflex latencies were significantly increased by these drugs after spinal transection. It was suggested that, although the spinal action of EAAs appears to be supraspinally modulated, this influence may be facilitatory rather than inhibitory.
Advokat
C
C
Department of Psychology, Louisiana State University, Baton Rouge 70803.
Ghorpade
A
A
Wolf
E
E
D000818:Animals; D002818:Cordotomy; D018846:Excitatory Amino Acids / Q000819:agonists*; D007278:Injections, Spinal; D008297:Male; D016202:N-Methylaspartate / Q000494:pharmacology; D010147:Pain Measurement / Q000187:drug effects*; D004856:Postural Balance / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time / Q000187:drug effects; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000494:pharmacology
D018846:Excitatory Amino Acids; D016202:N-Methylaspartate; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid