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

• Published in: Pain (Amsterdam) Vol. 158; no. 4; pp. 605 - 617
• Main Authors: Majuta, Lisa A., Guedon, Jean-Marc G., Mitchell, Stefanie A.T., Ossipov, Michael H., Mantyh, Patrick W.
• Format: Journal Article
• Language: English
• Published: United States Wolters Kluwer 01-04-2017
• Subjects: Analysis of Variance; Animals; Antibodies, Monoclonal - pharmacology; Antibodies, Monoclonal - therapeutic use; Circadian Rhythm - drug effects; Disease Models, Animal; Immunologic Factors - pharmacology; Immunologic Factors - therapeutic use; Locomotion - drug effects; Male; Mice; Nerve Growth Factor - immunology; Orthopedic Procedures - adverse effects; Pain - drug therapy; Pain - etiology; Treatment Outcome
• ISSN: 0304-3959; 1872-6623
• DOI: 10.1097/j.pain.0000000000000799

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.