Acute Molecular Response Post ACL Injury: Connection to Ami and Motor Control

Anterior cruciate ligament (ACL) injuries are common, particularly among athletes, leading to significant functional impairment, prolonged rehabilitation, and an elevated risk of secondary complications. The ACL plays a critical role in knee stabilization, and its rupture initiates a cascade of molecular and neuromuscular changes that disrupt joint stability and motor control. One of the primary consequences of an ACL injury is the onset of Arthrogenic Muscle Inhibition (AMI), a neurological phenomenon characterized by reduced voluntary muscle activation, particularly in the quadriceps, resulting from altered afferent feedback, nociceptive inputs, and local inflammatory responses. The acute phase is dominated by pro-inflammatory cytokines such as IL-1β, IL-6, and TNF-α, which propagate local inflammation, sensitize nociceptors, and disrupt both spinal and supraspinal motor pathways. This leads to central and peripheral sensitization, exacerbating AMI and impairing rehabilitation. As the injury progresses, an anti-inflammatory shift marked by IL-10 and IL-4 promotes tissue repair and resolution of inflammation. However, dysregulation in this transition can result in chronic inflammation and fibrosis, further complicating recovery. Understanding the temporal dynamics of these molecular mediators is essential for developing targeted interventions. This review explores the complex interplay between cytokine profiles and neuromuscular adaptations post-ACL injury, highlighting potential therapeutic targets and personalized rehabilitation strategies that could optimize functional recovery and mitigate long-term complications.