Abstract
In the present study, we investigated the effects of intrathecal gabapentin on nociceptive behaviors and the numbers of spinal Fos-like immunoreactive (Fos-LI) neurons evoked by injection of 0.25 to 2.5% formalin in the hindpaw of the rat. Pretreatment with gabapentin dose dependently decreased flinches and weighted pain scores in phase 2, but not phase 1, at each concentration of formalin. The highest dose of gabapentin (100 μg) shifted the EC50 values of formalin for both flinches and weighted pain scores to the right by 2.5-fold, suggesting that formalin was perceived to be significantly less noxious. Gabapentin also decreased phase 2 behaviors when administered after formalin but was only one third as potent. Unlike its inhibition of formalin-evoked nociceptive behaviors, the effect of gabapentin on the expression of Fos-like immunoreactivity in the spinal cord was highly dependent on the concentration of formalin. Intrathecal pretreatment with 100 μg of gabapentin did not decrease the numbers of Fos-LI neurons evoked by 0.5% formalin, yet this dose decreased the numbers of Fos-LI neurons in laminae I–II and VII–X of rats that received 1.25% formalin and uniformly decreased by 50% the numbers of Fos-LI neurons in all laminae of rats that received 2.5% formalin. These latter findings suggest that gabapentin neither nonselectively decreases the excitability of spinal cord neurons nor uniformly inhibits the release of all neurotransmitters from primary afferent terminals. Rather, its effects may be preferential for those neurotransmitters released by higher, more noxious concentrations of formalin and for conditions in which there is a greater induction of central sensitization.
Footnotes
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Send reprint requests to: Donna L. Hammond, Ph.D., Department of Anesthesia and Critical Care, University of Chicago, 5841 S. Maryland Ave., MC 4028, Chicago, IL 60637. E-mail:dh15{at}midway.uchicago.edu
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↵1 This work was supported by an unrestricted grant from Parke-Davis/Warner Lambert.
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↵2 These authors contributed equally to this work.
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↵3 Current address: Neuroscience Program, University of Arizona, 611 Gould-Simpson Bldg., P.O. Box 210077, Tucson, AZ 85721.
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↵4 Department of Toxicology, Pfizer, Z1 Poce-sur-Cisse BP159, Amboise 37401, France.
- Abbreviations:
- i.t.
- intrathecal
- Fos-LI
- Fos-like immunoreactive(ity)
- NMDA
- N-methyl-d-aspartate
- Received August 4, 1999.
- Accepted November 8, 1999.
- The American Society for Pharmacology and Experimental Therapeutics
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