Musculoskeletal injuries and degenerative conditions of the knee joint are common causes of missed competitive time in sports and disability, respectively. Despite best efforts, full recovery of muscle function is often not achieved, and the deficits can persist for a prolonged period of time. The origin of this persistent weakness is likely neurological in nature, with the inability to fully contract the muscle (known as arthrogenic muscle inhibition, AMI) demonstrated in traumatic injury (anterior cruciate ligament reconstruction, ACLR) and degenerative conditions (e.g. osteoarthritis, OA) of the knee joint. Importantly, it has been postulated that AMI is a critical barrier to the effectiveness of rehabilitation programmes [1].

Despite the phenomenon of AMI being well-documented, the mechanisms and mediators remain poorly understood. In the acute stages following ACLR, and, to some extent, in degenerative conditions of the knee such as OA, reduced spinal reflex excitability has been proposed as a possible mechanism, mediated by joint effusion, pain, inflammation, and damaged joint receptors. These mediators have the capacity to alter the intrinsic excitability of motoneurons which attach to groups of muscle fibres to form a motor unit (MU) that transforms the activation signal into contractile activity. The intrinsic excitability of spinal motoneurons is regulated by dendritic persistent inward currents (PIC), which generate strong depolarising inward currents in response to monoaminergic inputs (serotonin, noradrenaline) released from the brainstem [2]. Additionally, PICs can be downregulated by local inhibitory inputs [3]. Our studies in ACLR and knee OA individuals demonstrate that PICs are likely implicated in reduced motor unit discharge rate, and thus AMI. However, the mechanisms of dampened PICs appear to differ between ALCR and knee OA individuals, with the latter exhibiting features in MU discharge patterns consistent with both altered local inhibitory inputs as well as monoaminergic inputs, likely due to chronic pain and/or inflammation. Subsequently, by altering the proposed mediators of AMI with joint aspiration, local anaesthetic and corticosteroids, we demonstrate the relative contribution of mediators to the mechanisms of dampened MU discharge rate, ultimately leading to AMI and reduced muscle function. Taken together, our findings indicate the importance of joint effusion and inflammation in motoneuronal function, which likely contributes to persistent weakness in musculoskeletal conditions of the knee joint.