There is great interest in developing and utilizing non-pharmacological/non-invasive forms of therapy for osteoarthritis (OA) pain including exercise and other physical fitness regimens. Aims The present experiments determined the effects of prior wheel running on OA-induced weight asymmetry and trabecular bone microarchitecture. Main methods Wheel running included 7 or 21 days of prior voluntary access to wheels followed by OA induction, followed by 21 days post-OA access to wheels. OA was induced with monosodium iodoacetate (MIA), and weight asymmetry was measured using a hind limb weight bearing apparatus. Bone microarchitecture was characterized using ex vivo μCT. Key findings Relative to saline controls, MIA (3.2 mg/25 μl) produced significant weight asymmetry measured on post-days (PDs) 3, 7, 14, 21 in sedentary rats. Seven days of prior running failed to alter MIA-induced weight asymmetry. In contrast, 21 days of prior running resulted in complete reversal of MIA-induced weight asymmetry on all days tested. As a comparator, the opioid agonist morphine (3.2– 10 mg/kg) dose-dependently reversed weight asymmetry on PDs 3, 7, 14, but was ineffective in later-stage (PD 21) OA. In runners, Cohen’s d (effect sizes) for OA vs. controls indicated large increases in bone volume fraction, trabecular number, trabecular thickness, and connective density in lateral compartment, and large decreases in the same parameters in medial compartment. In contrast, effect sizes were small to moderate for sedentary OA vs. controls. Significance Results indicate that voluntary exercise may protect against OA pain, the effect varies as a function of prior exercise duration, and is associated with distinct trabecular bone modifications.

The therapeutic index (TI) inversely varied as a function of amount of SNC80 in the mixture, such that lower amounts of SNC80 produced a higher TI, and larger amounts produced a lower TI. Compared to literature using standard pain-elicited assays, the orderly relationship between SNC80 and TI reported here may be a unique function of assessing pain-depressed behavior.

There has been recent interest in characterizing the effects of pain-like states on motivated behaviors in order to quantify how pain modulates goal-directed behavior and the persistence of that behavior. The current set of experiments assessed the effects of an incisional post-operative pain manipulation on food-maintained responding under a progressive-ratio (PR) operant schedule. Independent variables included injury state (plantar incision or anesthesia control) and reinforcer type (grain pellet or sugar pellet); dependent variables were tactile sensory thresholds and response breakpoint. Once responding stabilized on the PR schedule, separate groups of rats received a single ventral hind paw incision or anesthesia (control condition). Incision significantly reduced breakpoints in rats responding for grain, but not sugar. In rats responding for sugar, tactile hypersensitivity recovered within 24 hrs, indicating a faster recovery of incision-induced tactile hypersensitivity compared to rats responding for grain, which demonstrated recovery at PD2. The NSAID analgesic, diclofenac (5.6 mg/kg) completely restored incision-depressed PR operant responding and tactile sensitivity at 3 hr following incision. The PR schedule differentiated between sucrose and grain, suggesting that relative reinforcing efficacy may be an important determinant in detecting pain-induced changes in motivated behavior.

The current set of experiments characterized the effects of incisional pain on food‐maintained responding under progressive ratio operant schedules. Rats were trained to press a lever for food on a FR 1 schedule of reinforcement. The ratio requirement was gradually increased to 5, and following stable responding rats were assigned to one of four progressive ratio schedules: PR2, PR5, Log1 (j=0.17), Log2 (j=0.20). The effects of reinforcer type (grain vs. sugar pellets) limited hold duration (min), and ratio progression (logarithmic vs. arithmetic) were manipulated to develop a schedule with (1) low intra‐animal variability in breakpoint, (2) high rates of responding, and (3) session lengths shorter than 60 min to facilitate future drug testing. The Log2‐LH15 min schedule was chosen as terminal schedule. Rats received either incision + anesthesia or anesthesia only. Parallel studies assessed mechanical allodynia. For rats responding for grain, the incisional pain manipulation produced significant reductions in breakpoints and mechanical thresholds across three days. In contrast, for rats responding for sugar, incisional pain produced no change in breakpoints and decreased mechanical threshold only at post‐6hr. Given that PR schedules are interpreted to reflect workload and/or motivation, these schedules may have utility as a preclinical model for assessing pain / motivation / cognition interactions in rodents.Funding: NIAMS/NIH 2R15AR054975‐02A1 to GWS