Targeting pain-suppressed behaviors in preclinical assays of chronic pain: Effects of varying acquisition duration on osteoarthritis-induced suppression of wheel running in rats

Pain increases the frequency and intensity of some behaviors (e.g. withdrawal responses) and suppresses other behaviors (e.g. locomotion, feeding, grooming). Our laboratories are developing assays for testing analgesic drug candidates using measurements of pain-suppressed behaviors. Such assays may model important aspects of clinical pain and complement traditional assays that measure pain-increased behaviors. We have previously shown that open-field locomotor activity and running wheel activity can be reliably suppressed by a sub-acute noxious stimulus (i.p. injection of acetic acid) and a chronic pain manipulation (MIA-induced osteoarthritis) in mice and rats, respectively. The present study extended these findings by assessing the effects of varying the duration of running wheel acquisition on MIA-suppressed wheel running in rats. Rats had 24hr voluntary access to running wheels. The duration of running wheel acquisition was manipulated in rats that received the highest dose (3.2mg) of MIA. Rats had either (1) no running wheel acquisition, (2) three weeks of running wheel acquisition, or (3) six weeks of running wheel acquisition prior to 3.2 mg MIA injection. Wheel activity was monitored for 28 consecutive days following MIA administration. The degree of MIA-induced suppression of wheel running varied directly with the duration of acquisition. Results are discussed in the context of traditional learning theory. Parallel experiments were conducted to measure MIA pain-increased behaviors (with von Frey monofilaments) and MIA-induced changes in posture (weight-bearing). Concurrent studies are exploring the effects of MIA on knee joint bone morphology using fMRI technology.

Funded by NIAMS/NIH grant R15 AR054975-01 (GWS)