J Knee Surg 2017; 30(04): 364-371
DOI: 10.1055/s-0036-1592145
Original Article
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Does Anterior Cruciate Ligament Innervation Matter for Joint Function and Development of Osteoarthritis?

Christopher V. Nagelli
1   Orthopedic Biomechanics Laboratory, Orthopedic Surgery, and Sports Medicine Center, Mayo Clinic, Rochester, Minnesota
2   Department of Biomedical Engineering and Physiology, Mayo Clinic, Rochester, Minnesota
3   Department of Biomedical Engineering, The Ohio State University, Columbus, Ohio
James L. Cook
4   Thompson Laboratory for Regenerative Orthopaedics, University of Missouri, Columbia, Missouri
5   Department of Orthopaedic Surgery, University of Missouri, Columbia, Missouri
Kei Kuroki
4   Thompson Laboratory for Regenerative Orthopaedics, University of Missouri, Columbia, Missouri
Chantelle Bozynski
4   Thompson Laboratory for Regenerative Orthopaedics, University of Missouri, Columbia, Missouri
5   Department of Orthopaedic Surgery, University of Missouri, Columbia, Missouri
Richard Ma
4   Thompson Laboratory for Regenerative Orthopaedics, University of Missouri, Columbia, Missouri
5   Department of Orthopaedic Surgery, University of Missouri, Columbia, Missouri
Timothy E. Hewett
1   Orthopedic Biomechanics Laboratory, Orthopedic Surgery, and Sports Medicine Center, Mayo Clinic, Rochester, Minnesota
2   Department of Biomedical Engineering and Physiology, Mayo Clinic, Rochester, Minnesota
3   Department of Biomedical Engineering, The Ohio State University, Columbus, Ohio
6   Physical Medicine and Rehabilitation, Mayo Clinic, Rochester, Minnesota
› Author Affiliations
Further Information

Publication History

30 June 2016

25 July 2016

Publication Date:
20 September 2016 (online)


Complications following anterior cruciate ligament (ACL) injury and reconstruction that include chronic dysfunction, second ACL injury, and posttraumatic osteoarthritis (OA) may be interrelated and stem from the inability to fully restore native ACL integrity and function. The loss of ACL sensory input following injury may significantly contribute to joint dysfunction. We developed a novel preclinical animal model to assess the contributions of ACL sensory afferents to knee joint function and health. We hypothesized that ACL sensory denervation would manifest in knee joint dysfunction and development of early OA. Purpose-bred, adult research dogs (n = 9 dogs, 18 knees) underwent arthroscopic surgery to create three treatment groups: (1) partial ACL tear, (2) ACL denervated, and (3) whole-joint denervated. A neurotoxin injected directly into the ACL or into the joint space was used to induce sensory denervation, and sham procedures were done on contralateral knees. After intervention, dogs participated in a regimented exercise program. Gait analysis and clinically relevant functional assessments were performed. At week 12, the animals were humanely euthanatized for arthroscopic, gross, and histologic assessments. ACL partial tear group demonstrated the greatest overall knee dysfunction. Clinical measures of function revealed a significant difference between the ACL partial tear and ACL denervated group (p < 0.05), but these differences were not observed between the ACL and whole-joint denervated groups (p > 0.05). A significant reduction in limb loading was experienced by the ACL partial tear group compared with controls (p < 0.05) but not between other groups. Arthroscopic evaluation found no evidence for overt articular cartilage damage, meniscal pathology, or osteophyte formation was noted in any group. No significant differences (p > 0.05) were observed in ACL pathology and OA severity scores between the ACL partial tear and the ACL denervated groups. The results of our study indicate that ACL sensory loss may contribute to joint dysfunction and subsequent OA changes. Further investigation and development of this model are important to improve clinical therapies and optimize patient outcomes following ACL injury.

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