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Am J Physiol Regul Integr Comp Physiol 291: R327-R334, 2006. First published March 23, 2006; doi:10.1152/ajpregu.00901.2005
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Sex and Gender in Pain and Inflammation

Sex differences in inflammation and inflammatory pain in cyclooxygenase-deficient mice

Naomi L. Chillingworth,1 Scott G. Morham,2 and Lucy F. Donaldson1

1Department of Physiology, University of Bristol School of Medical Sciences, University Walk, Bristol, United Kingdom; and 2Myriad Genetics, Salt Lake City, Utah

Submitted 21 December 2005 ; accepted in final form 14 March 2006

There are two cyclooxygenase (COX) genes encoding characterized enzymes, COX-1 and COX-2. Nonsteroidal anti-inflammatory drugs are commonly used as analgesics in inflammatory arthritis, and these often inhibit both cyclooxygenases. Recently, inhibitors of COX-2 have been used in the treatment of inflammatory arthritis, as this isoform is thought to be critical in inflammation and pain. The objective of this study was to determine the effect of COX-1 or COX-2 gene disruption on the development of chronic Freund’s adjuvant-induced arthritis and inflammatory pain in male and female mice. The effect of COX-1 or COX-2 gene disruption on inflammatory hyperalgesia, allodynia, inflammatory edema, and arthritic joint destruction was studied. COX-2 knockout mice (COX-2 –/–) showed reduced edema and joint destruction in female, but not male, animals. In addition, neither male nor female COX-2 –/– mice developed thermal hyperalgesia or mechanical allodynia, either ipsilateral or contralateral to the inflammation. COX-1 gene disruption also reduced inflammatory edema and joint destruction in female, but not male mice, although females of both COX –/– lines did show some bony destruction. There was no difference in ipsilateral allodynia between COX-1 knockout and wild-type animals, but female COX-1 –/– mice showed reduced contralateral allodynia compared with male COX-1 –/– or wild-type mice. These data show that the gene products of both COX genes contribute to pain and local inflammation in inflammatory arthritis. There are sex differences in some of these effects, and this suggests that the effects of COX inhibitors may be sex dependent.

allodynia; arthritis; hyperalgesia



Address for reprint requests and other correspondence: L. F. Donaldson, Dept. of Physiology, Univ. of Bristol, School of Medical Sciences, Faculty of Medical and Veterinary Sciences, University Walk, Bristol BS8 1TD, UK (E-mail: Lucy.Donaldson{at}bris.ac.uk)




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