J Korean Med Sci.  2004 Aug;19(4):581-585. 10.3346/jkms.2004.19.4.581.

Interaction between Intrathecal Gabapentin and Adenosine in the Formalin Test of Rats

Affiliations
  • 1Department of Anesthesiology and Pain Medicine, Chonnam National University, Medical School, Gwangju, Korea. mhyoon@chonnam.ac.kr

Abstract

Spinal gabapentin and adenosine have been known to display an antinociceptive effect. We evaluated the nature of the interaction between gabapentin and adenosine in formalin-induced nociception at the spinal level. Male Sprague-Dawley rats were prepared for intrathecal catheterization. Pain was evoked by injection of formalin solution (5%, 50 microliter) into the hindpaw. After examination of the effects of gabapentin and adenosine, the resulting interaction was investigated with isobolographic and fractional analyses. Neither gabapentin nor adenosine affected motor function. Gabapentin or adenosine decreased the sum of the number of flinches during phase 2, but not during phase 1 in the formalin test. Isobolographic analysis, in phase 2, revealed an additive interaction between gabapentin and adenosine. Taken together, intrathecal gabapentin and adenosine attenuated the facilitated state and interacted additively with each other.

Keyword

Pain Measurement; Antinociception; Adenosine; Gabapentin; Drug Interactions; Injections, Spinal

MeSH Terms

*Adenosine/administration & dosage/metabolism/therapeutic use
*Amines/administration & dosage/metabolism/therapeutic use
*Analgesics/administration & dosage/metabolism/therapeutic use
Animals
*Cyclohexanecarboxylic Acids/administration & Dose-Response Relationship, Drug
Formaldehyde/*toxicity
Injections, Spinal
Male
Motor Activity/physiology
Pain Measurement
Rats
Rats, Sprague-Dawley
Research Support, Non-U.S. Gov't
*gamma-Aminobutyric Acid/administration & dosage/metabolism/therapeutic

Figure

  • Fig. 1 Time-effect curve of intrathecal gabapentin (A) and adenosine (B) for flinching in the formalin test. Drugs were administered 10 min before formalin injection. Formalin (F) was injected at time 0. Data are presented as the number of flinches. Each line represents mean±SEM of 5-9 rats.

  • Fig. 2 Dose-response curve of intrathecal gabapentin (A) and adenosine (B) for flinching during phase 1 and phase 2 in the formalin test. Data are presented as the sum of the number of flinches. Gabapentin and adenosine dose-dependently decreased flinches during phase 2, but not phase 1. Each line represents mean±SEM of 5-9 rats. Compared with vehicle, *p<0.01, †p<0.001.

  • Fig. 3 Isobologram for the interaction between intrathecal gabapentin and adenosine during phase 2 in the formalin test. The ED50 values for each agent are plotted on the x- and y-axes, respectively, with the thick lines representing the SEM of the ED50. The straight line connecting each ED50 value is the theoretical additive line, where the point on this line is the theoretical additive ED50 (A). The experimental ED50 point (B) was not significantly different from the theoretical ED50 point (A), indicating an additive interaction.


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