April 2019

Is There a Sprain–Brain Connection That Leads to Chronic Injury?

Research shows that ankle health plays a role in the recruitment of the muscles around it

By Nicole Wetsman

Millions of people sprain their ankles each year, from athletes to weekend warriors to vacationers stepping off the curb wrong. The injury is common, and for most people, treatable with ice, painkillers, and rest. Recovery from a mild sprain usually only takes a few days and patients are quickly back on their feet.

However, research demonstrates that the consequences of an ankle sprain can linger after pain subsides. Indeed, injuries can have long-term effects on neuromuscular control which are apparent in both physical tests and, according to recent research, in the brain. That work is leading orthopaedic researchers to recommend more active, thoughtful treatment following sprains.

“As technology has been improving, it’s allowed us to dive deeper and take a better look at the widespread effects of an ankle injury,” said Lindsey Lepley, PhD, assistant professor of orthopaedic surgery and kinesiology at the University of Connecticut. “Innovative work is showing that there are actually brain-related changes—it’s not just an ankle sprain.”

Mechanisms of Injury

Estimates suggest that anywhere from 30% to 80% of people who experience an ankle sprain will develop chronic ankle instability, characterized by laxity at the joint, reduced strength, mechanical problems, and a high probability of recurrent sprain—which can increase risk for osteoarthritis.1

The mechanisms of how and why instability develops remain unclear, though the neuromuscular changes observed at and around the ankle joint provide an initial picture of the condition. Ankle sprains are injuries to the ligament, which are usually thought of as having only a static role holding the bones together, said Jay Hertel, DO, professor of sports medicine at the University of Virginia. “That’s only part of the function of ligaments,” he said. “They have sensory receptors, and those are responsible for sensing changes in the joint position. When you have ligament damage, you lose that sensory component.”

“The assumption is that ligament insult and the associated afferent sensory changes must be having an influence on efferent outputs.”

Initial models of chronic ankle instability focused on the way the sprain disrupts the afferent signals traveling from the ankle to the brain and prevents the nervous system from accurately understanding the position of the joint.2 Because of that disconnect, the central nervous system was unable to recognize and successfully recruit the required muscles to keep the joint stable during activity and motion. Subsequent research has identified changes in postural control, motor control, and reflex response, highlighting the additional role of altered efferent signaling in chronic instability.

Due to the nature of the injury, much of the research on ankle instability and muscular activity is retrospective. Some work in animal models has looked to bridge that gap, such as a 2016 study in the Journal of Athletic Training conducted by Lepley and colleagues.3 “One of the things we’ve done with animal models is make them clinically translatable,” she said. Rather than surgically open the joint capsule to simulate a sprain, the researchers manually induced a sprain in the lateral ankle ligaments of 5 adult male rats.

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The rats had electromyography measurements taken at their biceps femoris, medial gastrocnemius, vastus lateralis, and tibialis anterior muscles both at baseline, and daily for one week following the induction of the sprain. They had detectable changes in the vastus lateralis and tibialis anterior muscles after sprain. “There were prolonged, persistent alterations,” Lepley said.

There has been a significant body of research documenting the strength and reflexive changes at the joint, and other work has identified lower neural excitability of associated muscles. Now, new research is working to piece together that information, and identify the parts of the brain that might be involved at the intersection. “The assumption is that ligament insult and the associated afferent sensory changes must be having an influence on efferent outputs,” said Phillip Gribble, PhD, ATC, FNATA, director in the division of athletic training at the University of Kentucky. “So, is there something in these higher brain centers that’s not intact?”

Gribble turned to existing research that examined the structural integrity of white matter tracts in elderly people who had balance deficiencies as a model for that inquiry. “We figured, why not look at another population with a balance deficiency to see if a similar relationship is there? It’s one way of documenting what potential changes we could see,” he said.

In November, Gribble published a study4 in the journal Medicine and Science in Sports and Exercise that used diffusion tensor imaging to examine the white matter microstructure of 10 patients with a history of ankle sprain and 10 people without. They found that there were significant differences in the white matter tracts of participants who had previous ankle sprains, and that those changes were in areas associated with postural control.

The findings showed that the initial assumption, that sprain would change the way sensory information was gathered and distributed, appeared sound, Gribble said. “I hope this is making a little connection between what might be happening in the higher brain centers and can start to synthesize afferent information and efferent output,” he said.

In many ways, the work on ankle sprains, stability, and the brain parallels the work done on anterior cruciate ligament (ACL) tears, which also affect neuromuscular control, Leply said. “Any time we knock out a ligament, a whole host of events cause acute and chronic changes. ACL is in a sense easier to study because we know the one, traumatic event,” she said. “The ankle literature is using a lot of the same techniques as the ACL literature. At end of the day, they’re both traumatic joint injuries. Mechanistically, it makes a lot of sense.”

“…patients who get through their first 12 months after a sprain without a recurrent sprain see their risk of sprain return back to baseline.”

Changing Treatment Standards

Although clinical research clearly illustrates the risk of long-term consequences after ankle sprain and highlights the way the injury affects the sensorimotor and central nervous system, for the most part, there are not standard rehabilitation and treatment protocols following injury. Researchers working in this space stress that those practices need to change.

“The research is driving new ways to look at rehab,” Gribble said. “Both acutely, when they have the sprain, and for people who are living with chronic instability. There’s a spectrum that needs to be addressed.”

People with more severe ankle sprains might be more likely to experience long-term problems, but researchers are still not entirely sure how to identify patients at risk for chronic instability. “We still see patients with relatively minor injuries that can still develop these deficiencies,” he said. “They’re not free from long-term problems. They can sustain a mild injury, which is no big deal, but it’s not managed well and just left to a bit of rest.”

Under current protocols, Hertel said, patients with more severe injuries might actually be better positioned to have successful recoveries. “More severe ankle sprains tend to do pretty well, probably because they’re more protected. Sometimes with less severe injuries, people return to play quickly, and problems can linger. They don’t allow healing,” he said.

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Ideally, the researchers agreed, all patients should be offered some type of rehabilitation after a sprain.

“There’s good evidence to show that individuals who performed a supervised rehabilitation program for at least 4 weeks were at a substantially decreased risk of recurrent ankle sprain,” Hertel said.

However, the vast majority of patients do not receive any physical therapy. In a study5 of more than 800,000 ankle sprain patients published in 2017, Hertel and colleagues found that only 6.8% received physical therapy within 30 days of their injury.

Part of the problem, Gribble said, is that there aren’t solid, established practices for treatment after an ankle sprain. He hopes that such practices might be solidified through research in the next few years, and then trickle down to doctors and athletic trainers.

Research to identify the best way to rehabilitate ankle sprain is ongoing, Hertel said—comparing things like supervised rehabilitation and exercise programs and looking at the effect of gait retraining. One of the most important findings so far, he said, is that patients who get through their first 12 months after a sprain without a recurrent sprain see their risk of sprain return back to baseline. “We’re really trying to emphasize prevention initiatives in that first year,” he said. Hertel put that into practice in his own family: when his son sprained his ankle playing soccer, they were sure to brace and tape the joint for an entire year.

There’s good evidence to show that individuals who performed a supervised rehabilitation program for at least 4 weeks were at a substantially decreased risk of recurrent ankle sprain.

However, widespread adoption of aggressive management and active rehabilitation could be a challenge, Gribble noted, because people with an ankle sprain typically feel better fairly quickly, even without it.

“What’s going to be really important is showing what’s happening on the back end, decades later—those simple injuries mean that in your midlife years you might not have as much physical activity. You might have lower quality of life and more pain,” Gribble said. “We’re trying to connect the dots, to go back to when you sustain a simple injury, and where we might be able to interrupt this long-term issue by doing some complete rehab.”

Nicole Wetsman is a freelance science and medical writer in New York City.

  1. Hiller CE, Kilbreath SL, Refshauge KM. Chronic ankle instability: evolution of the model. J Athl Train. 2011;462:133–141
  2. Hertel J. Sensorimotor deficits with ankle sprains and chronic ankle instability. Clin Sports Med. 2008;27:353–370
  3. Lepley LK, McKeon PO, Fitzpatrick SG, Beckemeyer CL, Uhl TL, Butterfield TA. Neuromuscular alterations after ankle sprains: an animal model to establish causal links after injury. J Athl Train. 2016;51(10): 797–805.
  4. Terada M, Johnson N, Kosik K, Gribble P. Quantifying Brain White Matter Microstructure of People with Lateral Ankle Sprain. Med Sci Sports Exerc. 2018; doi: 10.1249/MSS.0000000000001848. Epub Ahead of Print.
  5. Feger MA, Glaviano NR, Donovan L, Hart JM, Saliba SA, Park JS, Hertel J. Clin J Sport Med. 2017;27:145-152

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