Mechanical Joint Loading as an Alternative Model for OA-Associated Pain

Noninvasive mechanical joint loading (MJL) has been used as an alternative model for the pain associated with osteoarthritis (OA), inducing both OA lesions and a reproducible pain phenotype that can be reversed with the use of known analgesics for OA pain, according to data  published in Arthritis & Rheumatology.

The investigators sought to characterize and pharmacologically test the pain phenotype of a noninvasive MJL model of OA, thus offering an alternative murine model for OA pain. They loaded the right knees of male mice at 9N or 11N (40 cycles administered 3×/week for 2 weeks). Behavioral measurements of limb disuse, mechanical hypersensitivity, and thermal sensitivity were obtained before MJL and were monitored for 6 weeks post-MJL. The Osteoarthritis Research Society International loading system was used to establish the severity of the articular cartilage lesions. Additionally, 9N-loaded mice were treated for 4 weeks with diclofenac 10 mg/kg, gabapentin 100 mg/kg, or anti-nerve growth factor (NGF) 3 mg/kg.

Results of the study showed that mechanical hypersensitivity worsened significantly (P <.001) among 9N-loaded and 11N-loaded mice 2 weeks postloading compared with baseline measurements and nonloaded control mice. Weight-bearing among 9N-loaded mice and 11N-loaded mice differed significantly compared with values among nonloaded controls (P =.0024 and P =.0343, respectively). Furthermore, maximum OA scores of ipsilateral knees confirmed the presence of increased cartilage lesions among 9N-loaded (2.8±0.2) and 11N-loaded (5.3±0.3 mice) vs nonloaded control mice (1.0±0.0). 

The use of gabapentin and diclofenac restored pain behavior to baseline values after 2 weeks of daily treatment, with gabapentin shown to be more effective than diclofenac. Moreover, a single injection of anti-NGF alleviated nociception 2 days after treatment, remaining effective for 2 weeks. A second dose of anti-NGF induced stronger, more prolonged analgesia.

The investigators concluded that MJL generates OA lesions and a robust pain phenotype that can be reversed with the use of analgesics known to relieve pain among patients with OA, thus establishing the use of MJL as an alternative model for OA pain.

Reference                                                                                                                      

Ter Heegde F, Luiz AP, Santana-Varela S, et al. Non-invasive mechanical joint loading as an alternative model for osteoarthritic pain [published online January 14, 2019]. Arthritis Rheumatol. doi:10.1002/art.40835