Skip to content

Novel Model for Evaluation of Pain Treatments for Long-Bone Fracture

Key findings

  • This study investigated whether functional outcome measures (gait analysis and weight-bearing) correlated with longitudinal recovery in a rat model of tibia fracture
  • Hindlimb duty factor imbalance, hindlimb temporal symmetry and phase dispersion were strongly associated with bone healing over eight weeks
  • The research team plans to use this model in assessing the efficacy of local non-opioid analgesics in relieving postsurgical pain and enhancing functional recovery after long-bone fracture

Tibia fractures can be associated with severe pain that increases the risk of complications, prolonged hospital stay, delayed recovery, and readmission. Preclinical pain management studies in this setting have focused extensively on bone healing. Still, there is a need to explore the efficacy of pain treatment regimens on functional recovery as well.

Researchers at Massachusetts General Hospital have developed the first animal model in which gait is used as a marker of longitudinal functional recovery after fracture. Yingfang Fan, MD, PhD, instructor, and Ebru Oral, PhD, associate director of Biomaterials in the Harris Orthopaedics Laboratory in the Department of Orthopaedic Surgery, and colleagues report its utility in BMC Musculoskeletal Disorders.


Under anesthesia, 17 rats underwent osteotomy of the tibia of the right hindlimb, which was immediately repaired by abutting the bone surfaces with a thick Y-plate. Postoperatively the animals received buprenorphine at 12-hour intervals for 72 hours.

Evaluations of recovery and healing were performed using micro-CT and X-ray analysis, as well as histological examination after euthanasia. Concurrently, video recordings were used to evaluate weight-bearing asymmetry and gait patterns.

Four gait metrics were compared with a database of healthy animals:

  • Duty factor (the ratio of the ground contact time to the stride time)
  • Temporal symmetry
  • Spatial symmetry
  • Phase dispersion (the temporal relationship between placement of two paws within a step cycle)

Toe spread in the right (surgical) hindlimb was also measured regularly and compared with the left hindlimb.


Imaging and histology showed a decline in fracture volume over time, with formation of new trabecular bone, and histology also demonstrated progressive resolution of inflammation. Bone union was achieved at six weeks in all animals but healing continued until the end of the study at eight weeks.

Longitudinal improvements in three gait metrics were correlated with bone healing: hindlimb duty factor imbalance, hindlimb temporal symmetry and right hindlimb to left forelimb phase dispersion. Increasing toe spread in the right hindlimb was also a good indicator of recovery.

Laying the Groundwork

These findings emphasize the direct link between bone healing and functional outcomes. The research team's long-term goal is to use this model to compare the locally administered non-opioid analgesics to current pain management methods for enhancing pain control and functional recovery after long-bone fractures.

Learn more about the Harris Orthopaedics Lab

Refer a patient to the Hip & Knee Replacement Service at Mass General

Related topics


The Harris Orthopaedic Laboratory at Massachusetts General Hospital is driving research and innovation to eliminate infection and improve pain management related to total joint arthroplasty.


In this video, Orhun Muratoglu, PhD, director of Harris Orthopaedics Laboratory at Massachusetts General Hospital, and Ebru Oral, PhD, associate director of biomaterials at Harris Orthopaedics Laboratory, discuss their work in improving outcomes in total joint patients.