Ongoing pain in the MIA model of osteoarthritis

Abstract

Osteoarthritis (OA) is a chronic pain condition characterized by pain during joint use as well as pain at rest (i.e., ongoing pain). Although injection of monosodium iodoacetate (MIA) into the intra-articular space of the rodent knee is a well established model of OA pain that is characterized by changes in weight bearing and hypersensitivity to tactile and thermal stimuli, it is not known if this procedure elicits ongoing pain. Further, the time-course and possible underlying mechanisms of these components of pain remain poorly understood. In these studies, we demonstrated the presence of ongoing pain in addition to changes in weight bearing and evoked hypersensitivity. Twenty-eight days following MIA injection, spinal clonidine blocked changes in weight bearing and thermal hypersensitivity and produced place preference indicating that MIA induces ongoing and evoked pain. These findings demonstrate the presence of ongoing pain in this model that is present at a late-time point after MIA allowing for mechanistic investigation.

Figure 1

A) MIA induced a shift in weight bearing from the ipsilateralhindlimb was observed 28 days following MIA injection (Post-MIA). The MIA-induced shift was reversed by spinal administration of clonidine (10 μg). *indicates p<0.05 compared to post-MIA, n=8. B) MIA-induced reduction in paw withdrawal thresholds to calibrated von Frey filaments was observed 28 days post MIA injection indicating referred tactile allodynia (Post-MIA). Spinal clonidine (10 μg) reversed the MIA induced tactile allodynia. *indicates p<0.05 compared to post-MIA, n=8. C) MIA-induced reduction in paw withdrawal latency to noxious thermal stimulation was observed 28 days post MIA (Post-MIA). The MIA-induced referred thermal hyperalgesia was reversed by spinal administration of clonidine. Of note, spinal clonidine at this dose also induced thermal antinociception in the saline control animals. *indicates p<0.05 compared to Post-MIA, n=8.

Figure 2

A) Spinal clonidine administered 28 days post MIA induced conditioned place preference in MIA treated rats. Spinal clonidine did not induce chamber preference in saline controls. *indicates p<0.05 compared to pre-conditioning time, n=7. B) Difference scores (test time-preconditioning time) confirm that MIA, but not saline control rats increased time spent in the clonidine paired chamber. *indicates p<0.05 compared to saline.