Intrathecal administration of excitatory amino acid receptor antagonists or nitric oxide synthase inhibitor reduced autotomy behavior in rats.
Peripheral nerve injury may produce neuropathic pain. At the spinal cord level, excitatory amino acid receptors play a role in nociceptive signal modulation. N-methyl-D-aspartate (NMDA) receptor activation initiates the NO-cGMP pathway and further modulates nociceptive signal. Using the autotomy model, we examined the effect of an NMDA and a non-NMDA receptor antagonist, and nitric oxide synthase inhibitor in the treatment of autotomy behavior in rats. A right-side brachial plexus (C5-T1) transection was performed in all rats. In the treatment groups, MK-801, 1-(4-chlorobenzoyl)-piperazine-2,3-dicarboxylic acid (a non-NMDA antagonist), and L-NG-nitro arginine methyl ester (L-NAME) were infused intrathecally via an osmotic pump for 7 days at doses of 10, 4, and 400 microg/h, respectively. Saline was infused to control animals. Autotomy behavior was observed daily for 8 wk. The incidence of autotomy was 85% in the control group. MK-801, the non-NMDA antagonist, and L-NAME reduced the autotomy incidence to 10%, 20%, and 10% (P < 0.0001), respectively. All treatments delayed the onset of the autotomy behavior from 15+/-4.5 days in the control group to 52+/-3.8, 43+/-5.6, and 54+/-2.9 (P < 0.001) days in the treatment groups, respectively. The average autotomy scores were also attenuated significantly by these treatments. We conclude that the excitatory amino acid receptors and their intracellular signal messenger NO play a role in deafferentation behavior development. Inhibition of this signaling pathway may be of use for neuropathic pain relief.


CONCLUSIONS
The excitatory amino acid receptors and their intracellular signal messenger NO play a role in deafferentation behavior development. Inhibition of this signaling pathway may be of use for neuropathic pain relief.
Wong
C S
CS
Department of Anesthesiology, Tri-Service General Hospital and National Defense Medical Center, Taipei, Taiwan, Republic of China. w82556@ndmc1.ndmctsgh.edu.tw
Cherng
C H
CH
Tung
C S
CS
D000818:Animals; D003080:Cold Temperature; D016291:Dizocilpine Maleate / Q000008:administration & dosage / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D018691:Excitatory Amino Acid Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D007278:Injections, Spinal; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000008:administration & dosage / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D010147:Pain Measurement / Q000187:drug effects; D010523:Peripheral Nervous System Diseases / Q000188:drug therapy* / Q000523:psychology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017470:Receptors, Glutamate / Q000187:drug effects*; D012652:Self Mutilation / Q000188:drug therapy / Q000523:psychology; D013997:Time Factors
D004791:Enzyme Inhibitors; D018691:Excitatory Amino Acid Antagonists; D017470:Receptors, Glutamate; D016291:Dizocilpine Maleate; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester