ABSTRACT
Quadriceps muscles play a pivotal role in knee osteoarthritis (OA) progression and symptom manifestation, particularly pain. This research investigates the therapeutic effectiveness of muscle enhancement and support therapy (MEST), a recently developed device intended for intramuscular insertion of cog polydioxanone filaments, in quadriceps restoration to alleviate OA pain. Knee OA was induced in Sprague Dawley rats via monoiodoacetate injections. MEST or sham treatment was performed in OA or Naive rat quadriceps. Pain was assessed using paw withdrawal threshold and weight bearing. Quadriceps injury and recovery via MEST were evaluated using biomarkers, tissue morphology, muscle mass, contractile force and hindlimb torque. Satellite cell and macrophage activation, along with their activators, were also assessed. Data were compared at 1- and 3-weeks post-MEST treatment (M-W1 and M-W3). MEST treatment in OA rats caused muscle injury, indicated by elevated serum aspartate transferase and creatinine kinase levels, and local ß-actin changes at M-W1. This injury triggered pro-inflammatory macrophage and satellite cell activation, accompanied by heightened interleukin-6 and insulin-like growth factor-1 levels. However, by M-W3, these processes gradually shifted toward inflammation resolution and muscle restoration. This was seen in anti-inflammatory macrophage phenotypes, sustained satellite cell activation and injury markers regressing to baseline. Quadriceps recovery in mass and strength from atrophy correlated with substantial OA pain reduction at M-W3. This study suggests that MEST-induced minor muscle injury triggers macrophage and satellite cell activation, leading to recovery of atrophied quadriceps and pain relief in OA rats.
ABSTRACT
A recently established therapeutic strategy, involving the insertion of biodegradable cog polydioxanone filaments into the quadriceps muscles using the Muscle Enhancement and Support Therapy (MEST) device, has demonstrated significant efficacy in alleviating knee osteoarthritis (OA) pain. This study investigated changes in peripheral sensitization as the potential mechanism underlying MEST-induced pain relief in monoiodoacetate (MIA) induced OA rats. The results revealed that MEST treatment potently reduces MIA-induced sensitization of L3/L4 dorsal root ganglion (DRG) neurons, the primary nociceptor pathway for the knee joint. This reduction in DRG sensitization, as elucidated by voltage-sensitive dye imaging, is accompanied by a diminished overexpression of TRPA1 and NaV1.7, key nociceptor receptors involved in mechanical pain perception. Importantly, these observed alterations strongly correlate with a decrease in mechanically-evoked pain behaviors, providing compelling neurophysiological evidence that MEST treatment alleviates OA pain by suppressing peripheral sensitization.
