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

American Journal of Physiology - Regulatory Integrative and Comparative Physiology - Tập 291 Số 2 - Trang R327-R334 - 2006
Naomi L. Chillingworth1, Scott G. Morham, Lucy F. Donaldson2
1Department of Physiology, University of Bristol, School of Medical Sciences, Faculty of Medical and Veterinary Sciences, University Walk, Bristol BS8 1TD, UK.
2Bristol Neuroscience

Tóm tắt

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.

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Tài liệu tham khảo

10.1007/BF01972383

10.1002/art.1780221208

10.1016/S0304-3959(99)00167-0

10.1016/j.pain.2005.10.030

10.1196/annals.1286.022

10.1016/0304-3959(93)90156-J

Arthritis Research Campaign. Arthritis: The Big Picture, 2002. [The data are available at http://www.arc.org.uk/about_arth/bigpic.htm]

10.1073/pnas.180319297

10.1016/0014-5793(96)00604-7

10.1017/S0140525X97221485

10.1006/phrs.2001.0872

10.1007/BF01964912

10.1016/S0304-3959(99)00253-5

10.1002/cne.903550208

10.1002/cne.903220309

10.1016/0304-3959(92)90133-V

10.1016/S0304-3959(99)00075-5

10.1016/S0165-0270(03)00147-X

10.1046/j.1460-9568.2000.00979.x

10.4049/jimmunol.170.9.4738

10.1016/S1297-319X(01)00334-7

10.1172/JCI117060

10.1046/j.0953-816x.2001.01614.x

Dirig DM, Isakson PC, and Yaksh TL. Effect of COX-1 and COX-2 inhibition on induction and maintenance of carrageenan-evoked thermal hyperalgesia in rats. J Pharmacol Exp Ther 285: 1031–1038. 1998.

10.1016/S0014-2999(97)01053-4

10.1007/978-1-4615-4793-8_58

10.1345/aph.1C418

Donaldson LF. The primary Afferent Nociceptor and Neuropeptide Gene Expression: Importance in Experimental Arthritis. (PhD thesis). Edinburgh, UK: University of Edinburgh, 1994.

Donaldson LF. Unilateral arthritis: contralateral effects. Trends Neurosci 22: 495–496, 1999.

10.1016/0165-0270(93)90103-X

10.1016/j.prostaglandins.2004.06.001

10.1113/jphysiol.2001.013473

10.1126/science.1103333

10.1016/S0304-3940(98)00325-5

10.1038/sj.bjp.0704937

10.1007/s10227-001-0137-3

10.1016/S0304-3959(99)00119-0

10.1016/S0024-3205(00)01018-3

10.1023/A:1022350111213

10.1007/s000110050285

10.1016/S0014-2999(98)00508-1

10.1096/fj.02-0239fje

10.1177/0091270003256061

10.1016/0304-3959(88)90026-7

10.1016/S0149-2918(03)90017-8

10.1016/S0306-4522(96)00598-2

10.1007/s00228-003-0635-x

10.1111/j.1365-3083.1995.tb03632.x

10.1016/S0006-2952(01)00861-9

10.1093/rheumatology/37.7.773

10.1016/S0306-4522(03)00203-3

10.1002/1097-4598(200101)24:1<37::AID-MUS4>3.0.CO;2-8

10.1093/rheumatology/35.8.711

10.1016/S0166-2236(98)01302-2

10.1016/0092-8674(95)90126-4

10.3346/jkms.2000.15.1.88

10.1211/0022357021778475

10.1016/S0028-3908(01)00020-X

Meli R, Antonelli E, and Cirino G. Analgesia and cyclo-oxygenase inhibitors. Dig Liver Dis 33: S8–S11, 2001.

10.1902/jop.1993.64.11.1075

10.1016/0092-8674(95)90125-6

10.1002/1529-0131(200012)43:12<2687::AID-ANR8>3.0.CO;2-9

10.1016/S1472-6483(10)61849-4

10.1016/S0090-6980(01)00171-X

10.1161/hs0202.102732

10.1007/PL00012435

10.1172/JCI23618

10.1016/j.bbrc.2005.08.031

10.1038/35068566

10.1053/gast.2002.33647

10.1016/S1043-6618(03)00188-9

10.1073/pnas.95.22.13313

10.1007/s000110050755

10.1016/S0304-3959(01)00487-0

10.1016/S0301-0082(00)00063-0

Walker JS and Carmody JJ. Experimental pain in healthy human subjects: gender differences in nociception and in response to ibuprofen. Anesth Analg 86: 1257–1262, 1998.

10.1016/S0016-5085(98)70370-1

10.1053/gast.2000.16510

Wilder RL. Rheumatoid arthritis: epidemiology, patholgy, and pathogenesis In: Primer on the Rhuematic Diseases (10th ed.), edited by Schumacher R, Klippel J, and Koopman W. Atlanta, GA: The Arthritis Foundation, 1993, p. 86–89.

10.1002/art.1780250906

10.1038/sj.bjp.0701548

10.1006/bbrc.2000.2303

10.1016/S0306-4522(00)00052-X

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American Journal of Physiology - Regulatory Integrative and Comparative Physiology

Tập 291 Số 2

R327-R334

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