Original contributionN-methyl-d-aspartate-induced excitation and sensitization of normal and inflamed nociceptors
Section snippets
Experimental procedures
All experiments were approved by the University Animal Care and Use Committee and followed the guidelines for the ethical care and use of laboratory animals (Zimmermann, 1983). Steps were taken to minimize both the number of animals used and their discomfort.
Results
Intraplantar injection of 100 μl CFA resulted in a considerable increase in hind-paw swelling (thickness), redness (rubor) and temperature (calor) by 2 days post-injection compared with baseline (P<0.05, Friedman’s test, Fig. 1A–C). The increased hind-paw thickness and redness persisted at 7 days and the inflamed paw was still significantly different from baseline and from the contralateral non-inflamed paw (P<0.05, t-test). Although the temperature of the inflamed hind paw at 7 days was no
Discussion
The presence of NMDA receptors on peripheral nociceptors in normal skin is confirmed (Carlton et al., 1995) as is the increase in the proportion of NMDAR1-labeled axons that occurs 2 days post-CFA injection (Carlton and Coggeshall, 1999). New findings are that the proportion of NMDA-expressing axons is still significantly increased at 7 days post-CFA injection but returns to normal after 14 days, in concert with the overall progression of the persistent inflammation. In behavioral studies, we
Conclusion
In summary, peripheral NMDA receptor activation contributes to acute nociception and to the pain of persistent inflammation. The increase in number of NMDAR1-expressing peripheral axons and the enhanced responses of nociceptors following NMDA receptor activation in inflamed animals indicates that these receptors are important in the maintenance of inflammatory pain and thus may be peripheral targets for analgesics. Targeting peripheral NMDA receptors will avoid the serious side effects that
Acknowledgements
The authors thank Zhixia Ding for assistance in the immunohistochemistry and electron microscopy and Vicki Wilson for her excellent secretarial assistance. This work was supported by NS27910 and NS40700 to S.M.C., NS10161 to R.E.C. and NS11255 to S.M.C. and R.E.C.
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