Abstract
In this study, we investigated the effectiveness of gabapentin (Neurontin), administered spinally with a microdialysis fiber, in reducing nociceptive behavioral responses induced by a knee joint inflammation model. This model is produced by injection of the knee joint with kaolin and carrageenan in rats. The resultant knee joint inflammation produces a secondary hyperalgesia to radiant heat applied to the hindpaw. Both pretreatment and post-treatment protocols were examined. Spinal administration of gabapentin (10 mg/ml) infused 1.5 h before induction of knee joint inflammation, although having no effect on the baseline, prevented the development of heat hyperalgesia. Gabapentin also prevented the development of other pain-related behaviors scored subjectively. Gabapentin had no effect, however, on the joint circumference increase typical in this model. In animals with fully developed knee joint inflammation, gabapentin produced a reversal of heat hyperalgesia. The paw withdrawal latency responses and subjective pain scores were no longer significantly different from baseline, but joint circumference increases remained. These data suggest that gabapentin is an effective antinociceptive agent when administered either before or after induction of knee joint inflammation acting through a central neurogenic mechanism.
Footnotes
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Send reprint requests to: Karin N. Westlund High, Ph.D., Department of Anatomy and Neurosciences, Cell Biology Program, University of Texas Medical Branch, 301 University Blvd., Galveston, TX 77555-1069. E-mail: kwhigh{at}utmb.edu
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↵1 This work was supported by National Institutes of Health Grant NS32778.
- Abbreviations:
- PWL
- paw withdrawal latency
- aCSF
- artificial cerebrospinal fluid
- NK
- neurokinin
- NMDA
- N-methyl-d-aspartate
- GABA
- γ-aminobutyric acid
- Received December 1, 1998.
- Accepted March 2, 1999.
- The American Society for Pharmacology and Experimental Therapeutics
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