Ross Hauser, MD, Danielle Matias, PA-C, Demi Foster, APRN
Patellofemoral pain is an overuse injury frequently seen in runners, with a higher prevalence in females than in males. When the problem becomes chornic, it can be diagnosed as Patellofemoral pain syndrome. This condition is often seen as being a mystery. A patient can have more pain that their testing or imaging reveals. More recently doctors have speculated that Patellofemoral pain syndrome maybe problems of peripheral and central sensitization of the nervous system, in other words the brain and spinal cord have become hypersensitized to pain and sharing amplified pain signals, again for no apparent reason.
A serious problem for female runners
In April 2017, Brazilian and English researchers combined to publish research in the Journal of Science and Medicine in Sport suggesting a serious problem for female runners.
- Women who had a lower pain threshold in their knees found themselves with heightened pain throughout their bodies.
- Additionally, this heightened pain, which is related to self-reported knee function, appears to be increased by greater running volumes. (1)
We touched on this briefly above, overtraining, physical therapy, the continuance of running may make for more pain than the damage should be creating.
A combined research team from the University of Kentucky and the University of Iowa wrote in the Clinical Journal of Pain:
- Little is understood of how pain processing is changed with Patellofemoral Pain Syndrome and how a patient can suffer from hyperalgesia or hypoesthesia (a reduced sense of pain) and what type of alterations to natural knee movement can cause these changes.
In their study, the researchers looked at twenty females diagnosed with Patellofemoral Pain and 20 age-matched pain-free females participated in this study. What they found was the frontal plane knee angle (an unnatural knee alignment) existed in the Patellofemoral Pain group which was not present in the control group.
- This suggested that Patellofemoral Pain Syndrome is characterized by an increase in both localized and centralized pain sensitivity that is related to movement mechanics. Knee pain and knee instability caused greater and heightened pain. (2)
Fear of movement
In March 2022 doctors writing in the Journal of sport rehabilitation (3) evaluated brain activity during experimental knee pain and its relationship to kinesiophobia in patients with patellofemoral pain. They were looking specifically at young females. What they found was greater kinesiophobia was positively associated with greater brain activity and associated with alterations in central nociceptive processing.
A December 2025 study in the Journal of bodywork and movement therapies (4) explored if fear of movement is linked to the strength of hip and knee muscles, trunk and lower limb movements, plantar pressure, and balance measures in women both with and without patellofemoral pain. Thirty-six women divided into two groups of 18, those with patellofemoral pain and those without took strength tests for knee extensors, hip abductors, and hip extensors, and did a single-leg squat test to assess trunk, pelvis, and knee angles. The researchers found greater fear of movement is associated with lower strength in knee extensors and hip abductors, greater trunk inclination on the same side, and instability in posture among women with patellofemoral pain.
Muscle Weakness
In February 2023, doctors writing in the International journal of sports physical therapy (5) measured and compared pain sensitivity using QST methods (A standardized psychophysical test that evaluates nerve function by finding out how well a person can detect sensations such as vibration, cold, warmth, and pain) in active female runners, both those with and without patellofemoral pain.
The study included twenty healthy female runners and 17 female runners suffering from chronic patellofemoral pain symptoms. The researchers found that female runners suffering from chronic patellofemoral pain symptoms show signs of both peripheral sensitization, indicated by a lower pressure pain threshold at the knee area, and central sensitization, which is identified through a decreased pressure pain threshold at distant sites in the lower legs. Interventions to address the nervous system sensitization may be needed in some patients in order to achieve optimal outcomes.
Hip and knee strengthening (physical therapy and exercise) may not be adequate to heal the problem. Are they actually making it worse? Especially in women?
A November 2025 study in the Journal of athletic training (6) looked an inhibition (a protective function that prevents the muscle from fully activating) of the gluteus medius. They note women experiencing patellofemoral pain often show weakness in their hip muscles compared to those who do not have patellofemoral pain. In this study, women who had patellofemoral pain had lower gluteus medius central activation ratio (the muscle was not responding as well) as top those women measured who did not have patellofemoral pain. The researchers suggested assessment of gluteal voluntary activation (target exercise) could assist with a treatment programs for patellofemoral pain.
Doctors in the Netherlands writing in the medical journal Pain Medicine, (7) reviewed the theory that repeated stress and overloading on a knee with patellofemoral pain may sensitize nociceptors (nerve cell endings) to be even more sensitive to painful stimuli (hyperalgesia).
- Let’s sidetrack for a moment. The person with patellofemoral pain may have gotten that way because of repeated overload, as in running. He/she may have embarked on an aggressive physical therapy campaign to get themselves back to running. Their symptoms got worse. See below for how this impacts women runners.
Here is the conclusion from this research: “Local and generalized pressure hyperalgesia, suggesting alterations in both peripheral and central pain processing (you feel pain more), were present in patients with patellofemoral pain, though females with patellofemoral pain were most likely to suffer from generalized hyperalgesia.”
- In women, the pain became more generalized and pain spread beyond the knee.
In January 2026, a paper in the German journal Ortyhopedics (8) suggested “Idiopathic anterior knee pain is a common and often serious clinical condition. The challenge of this condition lies in its complexity. Therapeutic outcomes are frequently disappointing and show a high tendency for recurrence. . . Malalignment and maltracking are predisposing factors that exert their effects within the context of dysfunctional musculature, central and peripheral sensitization, as well as emotional disturbances. Treatment should not only address the local problem but also consider systemic factors such as core musculature, trigger points, and psychovegetative state.”
Solving Patellofemoral Pain Syndrome is recognizing the problem of knee instability
Patellofemoral Pain Syndrome is a problem of knee instability. A problem that can be treated with regenerative medicine injections beyond botulinum toxin injection.
In the articles below we discuss treatment options.
References
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