Does Compression Sensory Axonopathy in the Proximal Tibia Contribute to Noncontact Anterior Cruciate Ligament Injury in a Causative Way?-A New Theory for the Injury Mechanism

Anterior cruciate ligament injury occurs when the ligament fibers are stretched, partially torn, or completely torn. The authors propose a new injury mechanism for non-contact anterior cruciate ligament injury of the knee. Accordingly, non-contact anterior cruciate ligament injury could not happen without the acute compression microinjury of the entrapped peripheral proprioceptive sensory axons of the proximal tibia. This would occur under an acute stress response when concomitant microcracks-fractures in the proximal tibia evolve due to the same excessive and repetitive compression forces. The primary damage may occur during eccentric contractions of the acceleration and deceleration moments of strenuous or unaccustomed fatiguing exercise bouts. This primary damage is suggested to be an acute compression/crush axonopathy of the proprioceptive sensory neurons in the proximal tibia. As a result, impaired proprioception could lead to injury of the anterior cruciate ligament as a secondary damage, which is suggested to occur during the deceleration phase. Elevated prostaglandin E2, nitric oxide and glutamate may have a critical neuro-modulatory role in the damage signaling in this dichotomous neuronal injury hypothesis that could lead to mechano-energetic failure, lesion and a cascade of inflammatory events. The presynaptic modulation of the primary sensory axons by the fatigued and microdamaged proprioceptive sensory fibers in the proximal tibia induces the activation of N-methyl-D-aspartate receptors in the dorsal horn of the spinal cord, through a process that could have long term relevance due to its contribution to synaptic plasticity. Luteinizing hormone, through interleukin-1 beta, stimulates the nerve growth factor-tropomyosin receptor kinase A axis in the ovarian cells and promotes tropomyosin receptor kinase A and nerve growth factor gene expression and prostaglandin E2 release. This luteinizing hormone induced mechanism could further elevate prostaglandin E2 in excess of the levels generated by osteocytes, due to mechanical stress during strenuous athletic moments in the pre-ovulatory phase. This may explain why non-contact anterior cruciate ligament injury is at least three-times more prevalent among female athletes.

Automated summary

The authors propose a new mechanism for non-contact anterior cruciate ligament injury, suggesting that it is caused by acute compression microinjury of entrapped peripheral proprioceptive sensory axons in the proximal tibia. They highlight the importance of primary damage during strenuous exercises and secondary damage during deceleration. Elevated prostaglandin E2, nitric oxide, and glutamate may play critical roles in the neuro-modulation, leading to mechano-energetic failure and inflammatory events.