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Anti–nerve growth factor therapy increases spontaneous day/night activity in mice with orthopedic surgery–induced pain

Majuta, Lisa A.; Guedon, Jean-Marc G.; Mitchell, Stefanie A.T.; Ossipov, Michael H.; Mantyh, Patrick W.

doi: 10.1097/j.pain.0000000000000799
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Total knee arthroplasty (TKA) and total hip arthroplasty (THA) are 2 of the most common and successful surgical interventions to relieve osteoarthritis pain. Control of postoperative pain is critical for patients to fully participate in the required physical therapy which is the most influential factor in effective postoperative knee rehabilitation. Currently, opiates are a mainstay for managing postoperative orthopedic surgery pain including TKA or THA pain. Recently, issues including efficacy, dependence, overdose, and death from opiates have made clinicians and researchers more critical of use of opioids for treating nonmalignant skeletal pain. In the present report, a nonopiate therapy using a monoclonal antibody raised against nerve growth factor (anti-NGF) was assessed for its ability to increase the spontaneous activity of the operated knee joint in a mouse model of orthopedic surgery pain–induced by drilling and coring the trochlear groove of the mouse femur. Horizontal activity and velocity and vertical rearing were continually assessed over a 20 hours day/night period using automated activity boxes in an effort to reduce observer bias and capture night activity when the mice are most active. At days 1 and 3, after orthopedic surgery, there was a marked reduction in spontaneous activity and vertical rearing; anti-NGF significantly attenuated this decline. The present data suggest that anti-NGF improves limb use in a rodent model of joint/orthopedic surgery and as such anti-NGF may be useful in controlling pain after orthopedic surgeries such as TKA or THA.

Supplemental Digital Content is Available in the Text.Using an automated system that continually monitored rodent activity, sequestration of nerve growth factor increased spontaneous day/night activity and rearing in mice with acute post–orthopedic surgery pain.

aDepartment of Pharmacology, University of Arizona, Tucson, AZ, USA

bCancer Center, University of Arizona, Tucson, AZ, USA

Corresponding author. Address: Department of Pharmacology, University of Arizona, 1501 N. Campbell Ave, PO Box 245050, Tucson, AZ 85724, USA. Tel.: (520) 626-0742; fax: (520) 626-8869. E-mail address: pmantyh@email.arizona.edu (P.W. Mantyh).

Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article.

Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Web site (www.painjournalonline.com).

Received August 08, 2016

Received in revised form October 31, 2016

Accepted November 14, 2016

© 2017 International Association for the Study of Pain
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