Efficacy of drugs with different mechanisms of action in relieving spontaneous pain at rest and during movement in a rat model of osteoarthritis

Synovial fluid pro-inflammatory profile differs according to the characteristics of knee pain

“…In a study in rats, analgesic drugs with different mechanisms of action were shown to have different effects in rectifying the imbalance in gait (indicator of movement related pain) or weight bearing (indicator of rest pain) (26). In humans, pain at rest and during movement were also shown to respond differently to different analgesics (27,28).…”

Antinociceptive effect of clinical analgesics in a nonhuman primate model of knee osteoarthritis

“…As mentioned earlier, morphine (1-6 mg/kg) shows efficacy in a number of behavioral endpoints, including weight bearing, in rodent osteoarthritis models. Attenuation of pain-related behavior with morphine in rodents is within the 40-70% range, 100% being fully efficacious (Chandran et al, 2009;Fernihough et al, 2004;Ishikawa et al, 2014). By contrast, in the current nonhuman primate model, maximal efficacy of 6 mg/kg morphine in the weight bearing test and knee pressure test was 14% and 24%, respectively.…”

“…1 (weight bearing) and Fig. 2 rodent osteoarthritis models, utilizing various behavioral endpoints, are sensitive to the antinociceptive of effect morphine (Chandran et al, 2009;Fernihough et al, 2004;Ishikawa et al, 2014;Knights et al, 2012). The preclinical findings are supported by clinical findings, in that opioids significantly reduce osteoarthritic pain (Zhang et al, 2010).…”

“…An acute dose of duloxetine (30-45 mg/kg) improves gait disturbance and weight bearing in monosodium iodoacetate-treated rats (Chandran et al, 2009;Ishikawa et al, 2014). Duloxetine's effects on other pain-related behaviors, such as mechanical hyperalgesia, in rodent osteoarthritis models have yet to be determined.…”

Complete Freund's adjuvant‐induced reduction of exploratory activity in a novel environment as an objective nociceptive endpoint for sub‐acute inflammatory pain model in rats

“…In the current study, CFAinduced reduction of exploratory activity in a novel environment (CRANE) was characterized as an experimenter-independent, spontaneous endpoint for sub-acute inflammatory pain. However, it is possible that behaviours not captured with the current activity monitors could be significantly decreased/ increased in the current pain state and that drugs could increase/lower these behaviours (Brodkin et al, 2014;Ishikawa et al, 2014). Consequently, pain sensation is aggravated due to the movement and reduced by avoiding exploratory behaviours.…”