Pilot comparison of outcome measures across chemical and surgical experimental models of chronic osteoarthritis in the rat (Rattus norvegicus).

Relatively little work has evaluated both the disease of osteoarthritis (OA) and clinically-relevant pain outcome measures across different OA models in rats. The objective of this study was to compare sensitivity, pain, and histological disease severity across chemical and surgical models of OA in the rat. Stifle OA was induced in Sprague-Dawley rats via intraarticular injection of monoiodoacetate (MIA) or surgical transection of anterior cruciate ligament and/or destabilization of medial meniscus (ACL+DMM or DMM alone). Reflexive (e.g., mechanical and thermal stimuli) measures of sensitivity and non-reflexive assays (e.g., lameness, static hindlimb weight-bearing asymmetry, dynamic gait analysis) of pain were measured over time. Joint degeneration was assessed histologically. Six-weeks post OA-induction, the ACL+DMM animals had significantly greater visually observed lameness than MIA animals; however, both ACL+DMM and MIA animals showed equal pain as measured by limb use during ambulation and standing. The MIA animals showed increased thermal, but not mechanical, sensitivity compared to ACL+DMM animals. Joint degeneration was significantly more severe in the MIA model at 6 weeks. Our pilot data suggest both the ACL+DMM and MIA models are equal in terms of clinically relevant pain behaviors, but the MIA model is associated with more severe histological changes over time potentially making it more suitable for screening disease modifying agents. Future work should further characterize each model in terms of complex pain behaviors and biochemical, molecular, and imaging analysis of the sensory system and joint tissues, which will allow for more informed decisions associated with model selection and investigative outcomes.

A novel device to measure static hindlimb weight-bearing forces in pronograde rodents.

BACKGROUND: Joint pain is composed of both spontaneous and movement-induced pain. In animal models, static bodyweight distribution is a surrogate for spontaneous joint pain. However, there are no commercially-available instruments that measure static bodyweight distribution in normal, pronograde rodents. NEW METHOD: We designed a Static Horizontal Incapacitance Meter (SHIM) to measure bodyweight distribution in pronograde standing rodents. We assessed the device for feasibility, repeatability, and sensitivity to quantify hindlimb bodyweight distribution. Mice and rats with unilateral inflammatory pain induced by subcutaneous injections of capsaicin or Complete Freund's Adjuvant (CFA) into the plantar surface of the left hind paw were used to measure static weight-bearing. The ability to attenuate inflammatory pain-associated weight-bearing asymmetry was tested by administering a non-steroidal anti-inflammatory drug, meloxicam. RESULTS: The SHIM's ability to detect significant reductions in limb loading on the injected hindlimb in mice and rats was validated using both acute and sub-chronic pain models. Treatment with meloxicam partially reversed CFA-induced effects. COMPARISON WITH EXISTING METHODS: In contrast with assays that measure kinetic or static weight-bearing forces (e.g., walking, or standing at a 45 ° incline), the SHIM allows evaluation of weight-bearing in rodents that are standing at rest in their normal pronograde position. CONCLUSIONS: The SHIM successfully detected: (a) asymmetric weight-bearing in acute and sub-chronic pain models; and (b) the analgesic effects of meloxicam. This study provides a novel tool to objectively evaluate limb use dysfunction in rodents.