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Sex differences in complex regional pain syndrome type I (CRPS-I) in mice

Authors Tang C, Li J, Tai WL, Yao WF, Zhao B, Hong J, Shi S, Wang S, Xia Z

Received 11 April 2017

Accepted for publication 10 July 2017

Published 31 July 2017 Volume 2017:10 Pages 1811—1819

DOI https://doi.org/10.2147/JPR.S139365

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Amy Norman

Peer reviewer comments 3

Editor who approved publication: Dr Katherine Hanlon

Chaoliang Tang,1 Juan Li,2 Wai Lydia Tai,3 Weifeng Yao,4 Bo Zhao,1 Junmou Hong,5 Si Shi,1 Song Wang,2 Zhongyuan Xia1

1Department of Anesthesiology, Renmin Hospital of Wuhan University, Wuhan, Hubei Province, 2Department of Anesthesiology, Anhui Provincial Hospital of Anhui Medical University, Hefei, Anhui Provence, 3Department of Anaesthesiology, The University of Hong Kong, Hong Kong SAR, 4Department of Anesthesiology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong Province, 5Department of Cardiovascular Surgery, Renmin Hospital of Wuhan University, Wuhan, Hubei Province, China

Background: Sex differences have been increasingly highlighted in complex regional pain syndrome (CRPS) in clinical practice. In CRPS type I (CRPS-I), although inflammation and oxidative stress have been implicated in its pathogenesis, whether pain behavior and the underlying mechanism are sex-specific is unclear. In the present study, we sought to explore whether sex differences have an impact on inflammation, oxidative stress, and pain sensitivity in CRPS-I.
Methods: Chronic post-ischemia pain (CPIP) was established in both male and female mice as an animal model of CRPS-I. Edema and mechanical allodynia of bilateral hind paws were assessed after reperfusion. Blood samples were analyzed for serum levels of oxidative stress markers and inflammatory cytokines.
Results: Both male and female mice developed edema. Male mice developed CPIP at day 3 after reperfusion; female mice developed CPIP at day 2 after reperfusion. Female mice displayed significantly earlier and higher mechanical allodynia in the ischemic hind paw, which was associated with higher serum levels of IL-2, TNF-α, isoprostanes, 8 OhdG, and malondialdehyde at day 2 after reperfusion. Moreover, female mice showed significantly lower SOD and IL-4 compared to male mice at day 2 after reperfusion.
Conclusion: Our results indicate that sex differences in inflammatory and oxidative stress states may play a central role in the sex-specific nociceptive hypersensitivity in CRPS-I, and offer a new insight into pharmacology treatments to improve pain management with CRPS.

Keywords: sex differences, complex regional pain syndrome, chronic post-ischemia pain, inflammatory response, oxidative stress

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