Long-term analgesic effect of a single dose of anti-NGF antibody on pain during motion without notable suppression of joint edema and lesion in a rat model of osteoarthritis

• Published in: Osteoarthritis and cartilage 2015-06, Vol.23 (6), p.925-932
• Main Authors: Ishikawa, G, Koya, Y, Tanaka, H, Nagakura, Y
• Format: Article
• Language: English
• Subjects: Analgesics, Non-Narcotic - administration & dosage; Analgesics, Non-Narcotic - therapeutic use; Animals; Antibodies, Monoclonal - administration & dosage; Antibodies, Monoclonal - therapeutic use; Antibody of nerve growth factor; Arthritis, Experimental - complications; Arthritis, Experimental - drug therapy; Drug Administration Schedule; Drug Evaluation, Preclinical - methods; Edema - drug therapy; Joint Diseases - drug therapy; Joint edema and lesion; Male; Motion; Nerve Growth Factor - antagonists & inhibitors; Nerve Growth Factor - immunology; Osteoarthritis; Osteoarthritis - complications; Osteoarthritis - drug therapy; Pain - drug therapy; Pain - etiology; Pain during motion; Pain Measurement - methods; Rats, Sprague-Dawley; Rheumatology; Sodium monoiodoacetate; Treatment Outcome
• ISSN: 1063-4584; 1522-9653
• DOI: 10.1016/j.joca.2015.02.002

Summary Objective Osteoarthritis (OA) patients experience exaggerated pain during movements such as walking. Anti-nerve growth factor (NGF) antibodies have recently shown analgesic effects in OA patients. We examined the effect of a single dose of anti-NGF antibody on pain during motion, joint edema and lesion in a rat model of OA to determine whether the analgesic effect demonstrated in clinical studies can be translated to a preclinical model. Methods Sodium monoiodoacetate (MIA)-induced arthritic rats that develop a right-left gait imbalance when walking as an index of pain during motion. This imbalance was assessed using a gait analysis system called “CatWalk”. Edema size and lesion score in the relevant knee joint were also measured. The effect of a single intravenous injection of an anti-NGF monoclonal antibody AS2886401-00 on these parameters was assessed. Results AS2886401-00 administered at 0.3 or 1 mg/kg on Day 3 post-MIA injection resulted in a statistically significant improvement in gait imbalance even on Day 35. When gait measurement was set on Week 3 post-MIA administration, administration of the antibody at a timing close to the gait measurement, i.e., 1 or 24 h prior to the measurement, was less effective. AS2886401-00 did not suppress either edema or lesion. Conclusions A single dose of anti-NGF antibody exerts a long-lasting analgesic effect on pain during motion in a rat model of OA. This finding could be associated with the analgesic efficacies that anti-NGF antibodies have exhibited in clinical studies. It appears unlikely that analgesia is secondary to inhibition of joint edema and lesion.