A capsaicin-receptor antagonist, capsazepine, reduces inflammation-induced hyperalgesic responses in the rat: evidence for an endogenous capsaicin-like substance
Section snippets
Experimental procedures
Inflammation was induced in male Sprague–Dawley rats weighing 250–350 g by intradermal injection of 6 mg carrageenan (λ-carrageenan, Sigma, St Louis, MO, U.S.A.) dissolved in 150 μl, 0.9% NaCl in the foot pads of the hind-paws. In another group of animals, varying doses of capsazepine (0.05, 0.3, 0.6, or 1.5 mg in 150 μl of vehicle; Research Biochemicals International, Natick, MA, U.S.A.) were injected in the left foot, and vehicle (saline containing 50% dimethylsulphoxide) for capsazepine was
Effect of capsazepine on carrageenan-induced Fos-like immunoreactivity
As shown in Fig. 1, intradermal injection of carrageenan (6 mg in 150 μl saline) resulted in an increased expression of Fos-LI in neurons in the ipsilateral dorsal horn of the spinal cord. There were many cells exhibiting Fos-LI clustering in the superficial layer (lamina I and II) of the dorsal horn after carrageenan injection (Fig. 1A, B). Many cells exhibiting Fos-LI were also found in the deep laminae of the dorsal horn, primarily in lamina V, VI, and X and occasionally in lamina III and IV.
Discussion
Because pain and pain-associated reflexes are evoked by capsaicin, it is widely accepted that capsaicin receptors have a role in nociceptive neural transmission, however such a role has not been tested previously and the presence of an endogenous ligand at these receptors has not been previously demonstrated. In the present study, we showed that carrageenan inflammation-induced hyperalgesic responses were reduced by the capsaicin receptor antagonist, capsazepine. This result clearly indicates
Conclusions
In summary, we have observed that capsazepine reduced the hyperalgesic responses evoked during carrageenan-induced inflammation, without affecting the inflammation itself. Thus, the present study presents clear evidence for the presence of an endogenous capsaicin-like substance that mediates the pain associated with inflammation. Identification and characterization of this substance and the associated receptor/channels may aid in the development of more specific analgesics.
Acknowledgements
This work was supported by the Ministry of Health and Welfare of Korea and by a grant from the Korea Science and Engineering Foundation through the Research Center for New Drug Development.
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