J Korean Pain Soc.  2004 Dec;17(2):105-112. 10.3344/jkps.2004.17.2.105.

Antihyperalgesic Effects of Intrathecal Gabapentin and CNQX, Non-NMDA Receptor Antagonist, in a Rat Model for Postoperative Pain

• Park HJ
• Song JH
• Song JM
• Lee HS
• Lee CS
• Chung CK
• Cha YD
• Kim BS
• Ryu JH

• KMID: 2104838
• DOI: http://doi.org/10.3344/jkps.2004.17.2.105

Abstract

BACKGROUND
Although the descriptions of the pharmacological action mechanisms of gabapentin remain incomplete, gabapentin has been proven to provide analgesic effects in inflammatory, burn injury and neuropathic pain models. However, the analgesic effect of gabapentin in postoperative pain has not been demonstrated. Of the antagonists of the excitatory neurotransmitter receptor in the spinal dorsal horn, only the antagonists of the non-NMDA receptor have proven effective in a postoperative acute pain model. In the current study, the antihyperalgesic effects of intrathecal gabapentin and CNQX (6-cyano-7-nitroquinoxaline-2, 3-dione) were determined in a rat model of postoperative pain. Furthermore, the drug interaction when both drugs were co-administrated was also tested. METHODS: A lumbar intrathecal catheter was implanted into Sprague-Dawley rats (weight 300-350 g) and the rats then assigned to receive one of several doses of gabapentin (10, 30, 100, 300microgram), CNQX (1, 5, 10, 25microgram) and gabapentin + CNQX (1/2 ED50 for each drug, 1/4 ED50, 1/8 ED50), and the level of withdrawal threshold to the von Frey Filament near the incision site determined. The dose response curves were obtained, and the ED50 of each drug calculated. Isobolographic and fractional analyses were performed to study the drug interaction. RESULTS: Both gabapentin and CNQX displayed dose dependent antihyperalgesic effects. The ED50 for gabapentin and CNQX were 56.2microgram (95% confidence interval [CI], 45.3-69.7microgram) and 4.6microgram (CI, 3.2-6.5microgram), respectively. When both drugs were co-administrated, the ED50 for gabapentin and CNQX were 23.4microgram (CI, 20.2-27.1microgram) and 1.6microgram (CI, 1.3-1.8microgram), respectively. In the fractional analysis, the fraction obtained using this numeric value was 0.77. In the isobologram analysis, the obtained ED50 value of the gabapentin-CNQX mixture was below the theoretical additive value on the diagonal line, but this was not statistically significant. CONCLUSIONS: The intrathecal co-administration of gabapentin and CNQX showed an additive antihyperalgesic effect in our rat model of postoperative pain.

Keyword

acute pain rat model; CNQX; gabapentin

MeSH Terms

6-Cyano-7-nitroquinoxaline-2,3-dione*
Acute Pain
Animals
Burns
Catheters
Drug Interactions
Horns
Models, Animal*
Neuralgia
Pain, Postoperative*
Rats*
Rats, Sprague-Dawley
Receptors, Neurotransmitter
6-Cyano-7-nitroquinoxaline-2,3-dione
Receptors, Neurotransmitter