Impairment in locomotor activity as an objective measure of pain and analgesia in a rat model of osteoarthritis

Abstract

A major problem with current animal models of pain is their lack of face validity and their vulnerability for false positive results. The present study evaluated the efficacy of the open field locomotor system, as an objective measure of pain-related behavior and analgesic efficacy in rodents. Adult, male, Sprague-Dawley rats (180-250 g) received intra-articular injections of monoiodoacetate (MIA; 1 mg) in the left knee joint. Mechanical allodynia using von Frey filaments, the weight bearing difference test and the open field locomotor activity test were performed every other day for 21 days, following the MIA injection. The antinociceptive effects of ibuprofen (50 and 100 mg/kg) on the MIA-induced nociception were also evaluated. MIA induced a significant reduction in the paw withdrawal threshold (PWT) and a significant alteration in the weight bearing difference compared with control rats. Similarly, MIA induced a significant reduction in locomotor activity, with respect to X total counts, that represent the overall locomotor activity in the horizontal plane, and X ambulatory counts, which in turn represent small scale movements, such as scratching and grooming, and lastly, Z total counts, that represent rearing or standing. Both doses of ibuprofen resulted in a significant reversal of the MIA-induced alterations in PWT and weight bearing difference. Furthermore, the two doses of ibuprofen resulted in a significant reversal of the MIA-induced reduction in locomotor activity, with respect to X ambulatory counts, but not Z total counts. Only the higher dose of ibuprofen reversed the X total counts. The open field locomotor system may successfully be used to predict the analgesic efficacy of compounds in models of joint inflammation and osteoarthritis.

Osteoarthritis Pain in Old Mice Aggravates Neuroinflammation and Frailty: The Positive Effect of Morphine Treatment

“…It is increasingly recognized that in OA patients it is of great importance to enhance physical activity with appropriate therapy besides relieving pain. Our data confirm the importance to evaluate complementary outcomes in animal models, in order to increase clinical relevance [ 44 , 45 , 46 , 47 , 48 ]. Although we are aware that it is difficult to reproduce frailty conditions in mice and elaborate appropriate scales to measure them, the non-invasive–31-item frailty index [ 23 , 36 ] may be a good surrogate [ 23 ].…”

Effects of Palm Tocotrienol-Rich Fraction Alone or in Combination with Glucosamine Sulphate on Grip Strength, Cartilage Structure and Joint Remodelling Markers in a Rat Model of Osteoarthritis

“…Besides, MIA induction also caused an initial reduction in body weight of rats in this study, which rebounded after 2-3 weeks. Previous studies have reported that osteoarthritis induced by MIA is associated with the altered locomotion of rats, particularly the rearing and standing activities necessary when the rats reach for food [43,44]; this is probably due to joint pain. Thus, the reduction in body weight observed in this study might be associated with reduced food intake, although it was not recorded by the researchers.…”

Hypertension contributes to exacerbated osteoarthritis pathophysiology in rats in a sex-dependent manner

“…In knee OA studies, open-field activity has been more commonly used as a non-evoked pain assay to assess exploratory activity [ 46 ]. Here, reductions in distance traveled is as a surrogate measure of movement-evoked pain (or avoidance of movement-evoked pain).…”