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Abstrato

Effects of Intra-articular Injection of Anti-nerve Growth Factor Neutralizing Antibody on Pain in Osteoarthritis Rat

Koji Aso, Izumi M, Okanoue Y and Ikeuchi M

Background: Nerve Growth Factor (NGF) has been recognized as an important mediator of chronic knee pain
caused by Osteoarthritis (OA). We investigated the effect of intraarticular injection of anti-NGF neutralizing antibody on
pain-related behavior and histological changes in Mono-iodoacetate (MIA)-induced OA rats.
Methods: All rats had OA induced by intra-articular injection of 1 mg MIA. Anti-NGF neutralizing antibody (0.1
and 0.5 mg/kg) was intra-articularly or intraperitoneally administered at 14, 21, 28, 35 days after MIA injection.
In the control group, saline was intraperitoneally administered in a same timing. Pain-related behavior was
assessed by paw withdrawal threshold to punctate stimulation of the hind-paw. OA progression was assessed
using Osteoarthritis Research Society International histological grading. The effect of combination of anti-NGF
therapy and forced treadmill running (30 cm/s for 60 min: an intense amount for rats) on OA progression was also
evaluated.
Results: Intra-articular injection of anti-NGF neutralizing antibody (0.1 and 0.5 mg/kg) and intraperitoneal injection
(0.5 mg/kg) significantly reversed the OA-induced pain behavior. Analgesic effects of intra-articular injection on
OA-induced pain behavior were significantly greater than intraperitoneal injection at a same dose. There were no
significant differences in OA progression between control (MIA) and MIA plus anti-NGF antibody (intra-articular and
intraperitoneal injection). Forced treadmill running did not affect the OA progression.
Conclusion: Analgesic effects of intra-articular injection of anti-NGF neutralizing antibody were greater than
intraperitoneal injection, which means that intra-articular injection is an effective route for anti-NGF antibodies. The
MIA-induced OA model failed to clarify histological differences caused by anti-NGF therapy or combination of the
therapy with forced treadmill running. Future research should seek to confirm the influence of anti-NGF antibody on
OA progression.
Keywords: Knee joint; Osteoarthritis