Effect of pretreatment with intrathecal excitatory amino acid receptor antagonists on the development of pain behavior caused by plantar incision.
BACKGROUND
Drugs that block spinal excitatory amino acid receptor activation may prevent pain after surgery. The authors previously studied the effect of excitatory amino acid receptor antagonists after incision. In the present study, we examined the role of N-methyl-d-aspartate (NMDA), non-NMDA, and metabotropic glutamate receptors (mGluRs) on the development of pain behavior after plantar incision.


METHODS
Rats with lumbar intrathecal catheters were anesthetized with halothane. Fifteen minutes before an incision was made, drug [40 nmol MK-801; 20 nmol NBQX; or 200 nmol (+)-MCPG] or vehicle was injected intrathecally followed by an infusion of the same drug for 75 min. Withdrawal thresholds to calibrated von Frey filaments applied adjacent to the wound and response frequencies to a blunt mechanical stimulus applied directly to the wound were measured before incision and 1, 2, 4, and 6 h after incision and then once daily for 6 days.


RESULTS
Preincision treatments with antagonists against the NMDA (MK-801) and group I and II metabotropic receptors [(+)-MCPG] did not inhibit the development of mechanical hyperalgesia caused by incision. Preincision treatment with the non-NMDA receptor antagonist NBQX increased withdrawal thresholds at 1 and 2 h and on postoperative day 1 compared with the vehicle group; response frequencies were reduced 1 and 2 h after incision and on postoperative day 2 (P < 0.05). In an additional group, postincision treatment with NBQX was similar to preincision treatment.


CONCLUSIONS
Spinal NMDA and mGluR antagonists may not be useful for preventing postsurgical pain. Spinal non-NMDA receptor antagonists reduced pain behaviors, but a preventive effect using preincision treatment was not apparent.
Department of Anesthesia, University of Iowa, Iowa City 52242-1079, USA.
E M
EM
Pogatzki
P K
PK
Zahn
T J
TJ
Brennan
D000698:Analgesia; D000769:Anesthesia, Inhalation; D018685:Anesthetics, Inhalation; D000818:Animals; D016291:Dizocilpine Maleate / Q000008:administration & dosage / Q000627:therapeutic use*; D018691:Excitatory Amino Acid Antagonists / Q000008:administration & dosage / Q000627:therapeutic use*; D005528:Foot / Q000601:surgery; D006221:Halothane; D007278:Injections, Spinal; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D010149:Postoperative Pain / Q000209:etiology / Q000517:prevention & control*; D011810:Quinoxalines / Q000008:administration & dosage / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley
D018685:Anesthetics, Inhalation; D018691:Excitatory Amino Acid Antagonists; D011810:Quinoxalines; C062865:2,3-dioxo-6-nitro-7-sulfamoylbenzo(f)quinoxaline; D016291:Dizocilpine Maleate; D006221:Halothane