Deficits in spontaneous burrowing behavior in the rat bilateral monosodium iodoacetate model of osteoarthritis: an objective measure of pain-related behavior and analgesic efficacy.

OBJECTIVE

To characterize deficits in burrowing behavior - an ethologically-relevant rodent behavior - in the monosodium iodoacetate (MIA) rat model of osteoarthritis (OA), and the sensitivity of these deficits to reversal by analgesic drugs of both prototypical and novel mechanisms of action. A second objective was to compare the burrowing assay to a spontaneous locomotor activity (sLA) assay.

METHOD

Male Wistar Han rats (200-220 g) received intrarticular (i.a.) injections of MIA or saline for sham animals. A deficit in the amount of sand burrowed from steel tubes filled with 2.5 kg of sand was used as a measure of pain-related behavior, and sensitivity to reversal of these deficits by analgesic drugs was assessed in bilaterally MIA-injected rats.

RESULTS

Bilateral MIA injections induced a significant impairment of burrowing behavior, which was concentration-dependent. The temporal pattern of the deficits was biphasic: a large deficit at 3 days post-injection, resolving by day 14 and returning at the 21 and 28 day time points. At the 3 day time point ibuprofen, celecoxib and an anti-nerve growth factor (NGF) monoclonal antibody (mAb) were able to significantly reinstate burrowing behavior, whereas the fatty acid amide hydrolase (FAAH) inhibitor PF-04457845 and morphine displayed no reversal effect. Morphine impaired burrowing behavior at 3 mg/kg in sham animals. Deficits in rearing frequency in the locomotor activity assay proved irreversible by analgesics.

CONCLUSION

Burrowing behavior provides an objective, non-reflexive read-out for pain-related behavior in the MIA model that has predictive validity in detecting analgesic efficacy of nonsteroidal anti-inflammatory drugs (NSAIDs) and an anti-NGF mAb.