title: Antinociceptive efficacy of lacosamide in the monosodium iodoacetate rat model for osteoarthritis pain.
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.
authors.affiliation: Schwarz BioSciences GmbH, Department of Pharmacology/Toxicology, Alfred-Nobel-Str, 40789 Monheim, Germany. bettina.beyreuther@schwarzpharma.com
authors.forename: Bettina
authors.initials: B
authors.lastname: Beyreuther
authors.forename: Noëlle
authors.initials: N
authors.lastname: Callizot
authors.forename: Thomas
authors.initials: T
authors.lastname: Stöhr
mesh_terms: D000081:Acetamides / Q000494:pharmacology / Q000627:therapeutic use*; D000700:Analgesics / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D004195:Disease Models, Animal; D007461:Iodoacetates / Q000633:toxicity*; D000078334:Lacosamide; D008297:Male; D010003:Osteoarthritis / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D010146:Pain / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D010147:Pain Measurement / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar
chemical_list: D000081:Acetamides; D000700:Analgesics; D007461:Iodoacetates; D000078334:Lacosamide