title: 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.
abstract: 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.
authors: Drug Discovery Research, Astellas Pharma Inc., 21 Miyukigaoka, Tsukuba, Ibaraki 305-8585, Japan. Electronic address: go.ishikawa@astellas.com.
authors: G
authors: G
authors: Ishikawa
authors: Drug Discovery Research, Astellas Pharma Inc., 21 Miyukigaoka, Tsukuba, Ibaraki 305-8585, Japan. Electronic address: yukari.koya@astellas.com.
authors: Y
authors: Y
authors: Koya
authors: Drug Discovery Research, Astellas Pharma Inc., 21 Miyukigaoka, Tsukuba, Ibaraki 305-8585, Japan. Electronic address: hirotsugu.tanaka@astellas.com.
authors: H
authors: H
authors: Tanaka
authors: Drug Discovery Research, Astellas Pharma Inc., 21 Miyukigaoka, Tsukuba, Ibaraki 305-8585, Japan. Electronic address: yukinori.nagakura@astellas.com.
authors: Y
authors: Y
authors: Nagakura
mesh_terms: D018712:Analgesics, Non-Narcotic / Q000008:administration & dosage / Q000627:therapeutic use*; D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000627:therapeutic use; D001169:Arthritis, Experimental / Q000150:complications / Q000188:drug therapy*; D004334:Drug Administration Schedule; D004353:Drug Evaluation, Preclinical / Q000379:methods; D004487:Edema / Q000188:drug therapy; D007592:Joint Diseases / Q000188:drug therapy; D008297:Male; D009038:Motion; D020932:Nerve Growth Factor / Q000037:antagonists & inhibitors* / Q000276:immunology; D010003:Osteoarthritis / Q000150:complications / Q000188:drug therapy*; D010146:Pain / Q000188:drug therapy* / Q000209:etiology; D010147:Pain Measurement / Q000379:methods; D017207:Rats, Sprague-Dawley; D016896:Treatment Outcome
chemical_list: D018712:Analgesics, Non-Narcotic; D000911:Antibodies, Monoclonal; C502240:NGF protein, human; D020932:Nerve Growth Factor
keywords: Antibody of nerve growth factor; Joint edema and lesion; Osteoarthritis; Pain during motion; Sodium monoiodoacetate