Institute of Bone and Joint Surgery

The etiology of osteoarthritis is multifactorial, with inflammatory, metabolic, and mechanical causes. Pain in osteoarthritis is initiated by mild intra-articular inflammation and degeneration of articular cartilage and subchondral bone. The principle of treatment with acetaminophen or non-steroidal anti-inflammatory drugs is to reduce pain and improve joint function. Recently animal models for osteoarthritic pain behavior have been established. The most frequently used rat model for analyzing properties of drugs on the pathology of osteoarthritis is the injection of the metabolic inhibitor, monosodium iodoacetate, into the joint which inhibits the activity of glyceraldehyde-3-phosphate dehydrogenase in chondrocytes. Here, we characterize the effect on pain behavior of lacosamide, a member of a family of functionalized amino acids, more specifically analogues of the endogenous amino acid and D-serine, in the monosodium iodoacetate rat model for osteoarthritis in comparison to diclofenac and morphine. Lacosamide (3, 10, and 30 mg/kg) was able to reduce mechanical allodynia and hyperalgesia comparable to morphine (3 mg/kg). In contrast, diclofenac (30 mg/kg) was only effective in reducing mechanical hyperalgesia. During the first week pain is induced mainly by inflammation in the iodoacetate model afterwards inflammation only plays a minor role. Lacosamide was able to inhibit pain at day 3, 7 and 14 after induction of arthritis. This shows that lacosamide is able to reduce pain behavior induced by multiple mechanisms in animals.