Pharmacological modulation of movement-evoked pain in a rat model of osteoarthritis.
This study was conducted to characterize movement-induced pain in a rat model of knee joint osteoarthritis and validate this behavioral assessment by evaluating the effects of clinically used analgesic compounds. Unilateral intra-articular administration of a chondrocyte glycolytic inhibitor monoiodoacetate, was used to induce knee joint osteoarthritis in Sprague-Dawley rats. In this osteoarthritis model, histologically erosive disintegration of the articular surfaces of the ipsilateral joint are observed which closely mimic the clinical picture of osteoarthritis. Movement-induced pain behavior was measured using hind limb compressive grip force evaluation. The animals exhibited pain behaviors epitomized by a long-lasting decrement in bilateral compressive hind limb grip force following unilateral knee injury. The effects of clinically used reference analgesics were evaluated 20 days following i.a. injection of monoiodoacetate. Full analgesic activity was observed for tramadol, celecoxib and diclofenac; moderate effects for indomethacin, duloxetine and gabapentin but weak or no effects for acetaminophen, ibuprofen and lamotrigine. As morphine reduced grip force in naïve rats, its analgesic effects could not be accurately evaluated in this model. Finally, the effects of celecoxib were maintained following chronic dosing. The results indicate that this in vivo model utilizing a movement-induced pain behavior spawned by knee joint osteoarthritis may provide a valuable tool in examining the role of potential analgesic targets in osteoarthritic pain. As the model is clinically relevant, it will further enhance the mechanistic understanding of chronic arthritic joint pain and help in developing newer and better therapeutic strategies to manage osteoarthritis pain.
Neuroscience Research, Global Pharmaceutical Research and Development, Abbott Laboratories, Abbott Park, IL 60064-6115, USA. Prasant.Chandran@abbott.com
Prasant
P
Chandran
Madhavi
M
Pai
Eric A
EA
Blomme
Gin C
GC
Hsieh
Michael W
MW
Decker
Prisca
P
Honore
D000082:Acetaminophen / Q000494:pharmacology / Q000627:therapeutic use; D000700:Analgesics / Q000494:pharmacology* / Q000627:therapeutic use; D000701:Analgesics, Opioid / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology / Q000627:therapeutic use; D004195:Disease Models, Animal; D008297:Male; D009068:Movement; D010003:Osteoarthritis / Q000150:complications / Q000188:drug therapy*; D010146:Pain / Q000150:complications / Q000188:drug therapy* / Q000209:etiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results; D013997:Time Factors
D000700:Analgesics; D000701:Analgesics, Opioid; D000894:Anti-Inflammatory Agents, Non-Steroidal; D000082:Acetaminophen