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Open Access Highly Accessed Research article

Antinociceptive efficacy of lacosamide in the monosodium iodoacetate rat model for osteoarthritis pain

Bettina Beyreuther1*, Noëlle Callizot2 and Thomas Stöhr1

Author Affiliations

1 Schwarz BioSciences GmbH, Department of Pharmacology/Toxicology, Alfred-Nobel-Str., 40789 Monheim, Germany

2 Neurofit, Parc d'Innovation, Rue J Sapidus, 67400 Illkirch, France

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Arthritis Research & Therapy 2007, 9:R14  doi:10.1186/ar2121

Published: 6 February 2007

Abstract

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 that are analogues of endogenous amino acids 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 secondary mechanical allodynia and hyperalgesia similarly to morphine (3 mg/kg). In contrast, diclofenac (30 mg/kg) was only effective in reducing secondary mechanical hyperalgesia. During the first week, pain is induced mainly by inflammation in the iodoacetate model, but afterwards inflammation plays only a minor role in pain. Lacosamide was able to inhibit pain at days 3, 7 and 14 after induction of arthritis. This shows that lacosamide is able to reduce pain behavior induced by multiple mechanisms in animals.