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 add receptor activatio n may prevent pain after surgery. The authors previously studied the effect of excitatory amino acid receptor antagonists after incision. In the prese nt study, we examined the role of N-methyl-D-aspartate (NMDA), non-NMDA, an d metabotropic glutamate receptors (mGluRs) on the development of pain beha vior after plantar incision. Methods: Rats with lumbar intrathecal catheters were anesthetized with halo thane. Fifteen minutes before an Incision was made, drug [40 nmol MK-801; 2 0 nmol NBQX; or 200 nmol (+)-MCPG] or vehicle was injected intrathecally fo llowed by an infusion of the same drug for 75 min. Withdrawal thresholds to calibrated von Frey filaments applied adjacent to the wound and response f requencies to a blunt mechanical stimulus applied directly to the wound wer e measured before incision and 1, 2, 4, and 6 h after incision and then onc e daily for 6 days. Results: Preincision treatments with antagonists against the NMDA (Mg-801) and group I and II metabotropic receptors [(+)-MCPG] did not inhibit the de velopment of mechanical hyperalgesia caused by incision. Preincision treatm ent with the non-NMDA receptor antagonist NBQX increased withdrawal thresho lds 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 postope rative day 2 (P < 0.05). In an additional group, postincision treatment wit h NBQX was similar to preincision treatment. Conclusion: Spinal NMDA and mGluR antagonists may not be useful for prevent ing postsurgical pain. Spinal non-NMDA receptor antagonists reduced pain be haviors, but a preventive effect using preincision treatment was not appare nt.