Grading of monosodium iodoacetate-induced osteoarthritis reveals a concentration-dependent sensitization of nociceptors in the knee joint of the rat.
Osteoarthritis (OA) is a degenerative joint disease characterized by joint pain for which there is currently no effective treatment. Previous studies have found that intra-articular injection of monosodium iodoacetate (MIA) caused a dose-dependent destruction of rat knees with concomitant increased pain. In this study, varying degrees of OA were induced by intra-articular injection of 0.1 mg, 0.3 mg and 3 mg MIA. Electrophysiological recordings were made from knee joint primary afferents in response to rotation of the joint and firing frequencies were determined and compared to saline-injected control joints. The analgesic effect of local application of the classic non-steroidal anti-inflammatory drug (NSAID) diclofenac (0.1 mg/0.1 ml bolus) was also determined in each group. Joint afferent firing frequency was significantly enhanced in OA knees compared to saline injected control joints and the magnitude of this sensitization showed a direct relationship with increasing dose of MIA. Diclofenac reduced nociception significantly in the 3 mg MIA treated joint, but had no effect on nerve mechanosensitivity in rats with milder OA. This study shows for the first time that MIA produces a graded sensitization of joint nociceptors making this a useful model for the study of pain mechanisms in joints with progressive OA severity. The anti-nociceptive effect of diclofenac further indicates that the MIA model offers an attractive means of objectively testing potential therapeutic agents.
Schuelert
Niklas
N
Department of Physiology & Pharmacology, University of Calgary, 3330, Hospital Drive NW, Calgary, AB, T2N 4N1 Canada.
McDougall
Jason J
JJ
D000200:Action Potentials / Q000187:drug effects; D000477:Alkylating Agents / Q000008:administration & dosage / Q000009:adverse effects*; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D004008:Diclofenac / Q000494:pharmacology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D007461:Iodoacetates / Q000008:administration & dosage / Q000009:adverse effects*; D007719:Knee Joint / Q000187:drug effects / Q000294:innervation / Q000503:physiopathology*; D008297:Male; D009068:Movement / Q000187:drug effects / Q000502:physiology; D009475:Neurons, Afferent / Q000187:drug effects / Q000502:physiology; D009619:Nociceptors / Q000187:drug effects / Q000502:physiology*; D020370:Osteoarthritis, Knee / Q000139:chemically induced* / Q000188:drug therapy / Q000503:physiopathology*; D010146:Pain / Q000139:chemically induced / Q000188:drug therapy / Q000503:physiopathology; D010812:Physical Stimulation; D051381:Rats; D017208:Rats, Wistar; D012399:Rotation
D000477:Alkylating Agents; D000894:Anti-Inflammatory Agents, Non-Steroidal; D007461:Iodoacetates; D004008:Diclofenac