Formalin injected subcutaneously into the hindpaw of the rat produces an animal model of inflammation that exhibits a phasic component and a tonic component of paint We evaluated the effects of a nitric bride synthase inhibitor, Nω-nitro-L-arginine methyl ester (L-NAME), on a formalin-induced behavior, hindpaw licking, and on Fos-labeling of nuclei in the fifth lumbar spinal segment. Our results demonstrated that pretreatment with intrathecal doses of 0.3 and 1.0 mg of L-NAME significantly reduced licking behavior associated with injection of formalin into the left hindpaw of the rat. In addition, these same doses of L-NAME reduced formalin-induced Fos-labeling in the ipsilateral dorsal gray matter (as compared to the contralateral gray matter). Qualitative assessment suggested that the reduction in labeling occurred primarily in the superficial dorsal horn. The stereoisomer, D-NAME, administered at the same doses had little to no effect on either formalin-induced licking or Fos-labeling. Finally, our results revealed that total licking time was related to Fos-labeling. Rats that spent less time licking the hindpaw exhibited a smaller increase in Fos-labeling. Our results suggest that the production of nitric oxide is associated with licking behavior resulting from formalin injection into the hindpaw of rats. Our results also suggest that the production of nitric oxide and Fos are associated. Indeed, these substances may be involved in spinal pathways associated with nociception.
Bibliographical noteFunding Information:
We thank Darryl Hamamoto and Mark Kleive for their careful reading and comments on an earlier version of this report. We also thank Alvin J. Beitz for use of the image-analysis equipment, and Kelly Kitto for help with the intrathecal injections. This research was supported by grants from the National Institutes for Neurological Diseases and Stroke (NS29567 to KCK) and from the National Institute for Drug Abuse (RO1-DA-04274 and KO2-DA-00145 to GLW).
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