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J Neurophysiol 93: 3594-3604, 2005. First published January 19, 2005; doi:10.1152/jn.01075.2004
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Effect of Chronic Inflammation on Dorsal Horn Nociceptive Neurons in Aged Rats

Junichi Kitagawa1,5, Kenro Kanda2, Miho Sugiura3, Yoshiyuki Tsuboi1,5, Akiko Ogawa4, Kohei Shimizu1, Natsu Koyama6, Hiroshi Kamo1, Tatsuhisa Watanabe1, Ke Ren8 and Koichi Iwata1,5,7

1Department of Physiology, School of Dentistry, Nihon University, 2Motor and Autonomic Nervous System Integration Research Group, Tokyo Metropolitan Institute of Gerontology, and 3Graduate School of Humanities and Sciences, Ochanomizu University, Tokyo Japan; 4Department of Dental Anesthesiology, Osaka University, Graduate School, Faculty of Dentistry, Osaka, 5Division of Functional Morphology, Dental Research Center, Nihon University School of Dentistry, Tokyo, 6Department of Physiology, Shiga University of Medical Science, Otsu, and 7Division of Applied System Neuroscience Advanced Medical Research Center, Nihon University Graduate School of Medical Science, Tokyo, Japan; and 8Department of Biomedical Sciences, University of Maryland Dental School, Baltimore, Maryland

Submitted 13 October 2004; accepted in final form 9 January 2005

To elucidate the effect of chronic inflammation on spinal nociceptive neurons in the elderly, we compared nocifensive behavior, peripheral inflammatory responses, and spinal dorsal horn neuronal activities between the aged (29–34 mo) and adult (7–12 mo) male rats after injection of complete Freund's adjuvant (CFA) into the hind paw. Aged rats exhibited a significantly lower mechanical paw withdrawal threshold before inflammation. However, after CFA injection mechanical allodynia developed in both adult and aged rats after CFA injection. The changes of foot temperature and thickness after CFA injection were greater and lasted longer in aged than in adult rats. Sets of 124 wide dynamic range (WDR) neurons (aged: 59, adult: 65) and 26 nociceptive specific (NS) neurons (aged: 13, adult: 13) were recorded from the lumber spinal dorsal horn. NS neurons from the inflamed adult rats showed significantly higher responses to noxious mechanical stimulation than those in aged rats, whereas WDR neurons from inflamed adult and aged rats were similar. Background activity of WDR neurons from the adult rats increased after CFA, whereas WDR neurons of aged rats and NS neurons from either group were not. The afterdischarge followed by noxious mechanical stimulation was significantly greater for WDR neurons in both adult and aged rats, whereas no significant differences were observed in NS neurons. Two days after CFA injection, Fos expression increased similarly in aged and adult rats. Thus the aged rats showed enhanced peripheral inflammatory responses to CFA injection with only a slight change in dorsal horn neuronal activity. Together with our previous finding that nociceptive neurons in aged rats exhibit hyperexcitability, these results suggest that the dorsal horn nociceptive system becomes sensitized with advancing age and its excitability cannot be further increased by inflammation.


Address for reprint requests and other correspondence: K. Iwata, Department of Physiology, School of Dentistry, Nihon University, 1-8-13 Kandasurugadai, Chiyoda-ku Tokyo, 101-8310, Japan (E-mail: iwata-k{at}dent.nihon-u.ac.jp)







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