Work by the PI and colleagues established that extensive dog hindlimb deafferentation by L4-S1 ganglionectomy plus ad-lib ambulation caused no biochemical or morphological changes in femoral condylar cartilage within 16 months, as would have been expected were protective muscular reflexes compromised. Subsequent work revealed that if knee joint instability (by anterior cruciate ligament (ACL) transection) is superimposed upon a deafferented limb. Local pathology of femoral condylar cartilage may occur within 3 weeks. Although neurogenically intact dogs with knee joint instability may develop similar lesions (osteoarthritis), this pathology is usually not morphologically evident at 3 weeks. On the basis of these results, we concluded that the reflexes that protect a stable joint form exceeding its normal range of excursions and becoming pathologic may not be initiated by nerve endings located within peri- and intraarticular tissues. However, we also hypothesize that local nerve endings may initiate muscular reflexes which protect an unstable joint from breaking down. We propose to test this latter hypothesis by transecting the primary articular nerves of the canine knee and subsequently creating joint instability by ACL transection, and sacrificing 7 animals at 4, ,8 and 16 weeks after surgery. The pathology which develops in these animals will be compared to that which develops in dogs with intact sensory nerves but unstable joints, and dogs with cut nerves and stable joints.