There was no statistically significant increase of the sensory threshold or pain tolerance, as detected by pressure algometer, throughout the study. There was a reduction of VAS, which correlated with increase of kinesiophobia. However, the latter notion should be interpreted with caution, as such correlations on small datasets are highly susceptible to outliers—as demonstrated through removing the one most extreme outlier, resulting in a non-significant correlation. As there is a consensus of using exercise therapy in the treatment of OA patients, this study adds support to a pain modulation mechanism in medical exercise therapy, though it is not correlated to tolerance for mechanical pressure at the knee nor at the ankle.
Increased pain sensitivity outside the areas of clinical pain has been reported for other regional pain syndromes, such as tension-type headache , temporomandibular disorder , and localized trapezius myalgia . Hyperalgesia represents an appropriate increase in vigilance to prevent potential harm, and could be explained by the activation of cutaneous polymodal nociceptors in the skin sensitive to heat, pressure and sympathetic stimulation . In therapy, it is generally of great importance to investigate both local and central factors that might explain the overall symptoms of the patients. The more widespread and generalized the pain, the less important local findings, for example in the knee, which in turn might have implications for the treatment package and priorities.
The mechanisms of knee OA-related pain are complex , particularly in chronic pain conditions where pain experience is believed to be more a result of changes in the nervous system than in tissue structures , which somehow reflects a paradigm shift in the understanding of the pathology of pain related to knee OA. Because of the plasticity of the nervous system, pain lowers the threshold level of the nociceptive receptor system , making it more sensitive to stimuli during normal movements like walking, which is loading allodynia. These changes occur in the peripheral receptor system located in the knee and in the receptor system in the spinal cord resulting in changes in the nervous system, i.e., peripheral and central sensitization . As the pain perception may be more related to the nervous system than the knee, it is easier to understand why there are low correlations between structural degenerative changes of the knee, pain, and functioning . However, this study suggests pain modulation, though not explained by changes in the central perception of pressure sensitivity.
Physical exercise is an important component in the treatment and rehabilitation of many patients with long-term pain, as well as vital to the overall health and well-being of any individual . The predicted effects of exercise in achieving pain modulation, alone, are an indication for clinical use; although the underlying mechanisms are poorly documented, good pain modulating effects are observed in clinic . According to Bergmann et al. , a central pain sensitization may cause changes in the diffuse noxious inhibitory control system. This afferent/efferent system operates via the sensory nociceptive nerve system, and a defect in the diffuse noxious inhibitory control system seems to lead to a state of more diffuse hyperalgesia, as seen in many chronic pain conditions such as chronic osteoarthritis .
Pain sensitivity has been found to be changed following exercise. A number of investigators have found diminished sensitivity to pain (hypoalgesia) during and following exercise [i.e. 4]. Importantly, laboratory studies have found that acute exercise reduces sensitivity to painful stimuli in healthy individuals, indicating a hypoalgesic response. This phenomenon has been termed exercise-induced analgesia or exercise-induced hypoalgesia . Hypoalgesia is a decreased sensitivity to painful impact , and hypoalgesia can probably be activated at both central and spinal levels during physical exercise. One anticipated mechanism explaining hypoalgesia during exercise is blocking nociceptors from liberated opioids . Another potential mechanism is an interaction between central pain modulation and the cardiovascular system . For example, control of pain and blood pressure involve the same neurons in the brainstem and the same neurotransmitters (e.g., monoamines). A third possible mechanism for exercise-induced hypoalgesia is activation of ascending (e.g., activation of muscle afferent A- and C-fibers) and descending (e.g., activity-induced distraction and changed attention) pathways in the spinal cord . The present study, however, was not able to detect any long-term effect of exercise therapy on pain, as measured by pressure algometer.
It is currently unclear what type of exercise, as well as the duration and intensity of the exercise, that is necessary and sufficient to influence tolerance to nociceptive stimuli , particularly over long periods (months). There are studies on people without pain showing that endurance training provides greater tolerance for sustained nociception, and that higher intensity provides greater pain tolerance than low intensity endurance training . In patients, it might be of great importance to assess more knowledge in this field, especially since a majority might not be able to perform high-intensity strength and/or endurance training. As medical exercise therapy consists of many repetitions of the exercises—though relative low intensity—one might expect a significant influence over long time, as tested in the present study.
An understanding of how exercise may influence pain perception is necessary to optimize the clinical utility of exercise therapy as a method of pain management. Several experimental studies have investigated the possible effects of acute exercise as a response to induced noxious stimulation. A variety of exercise modalities, as well as a variety of pain induction techniques and measurement procedures, have been included in these trials. Exercise modalities have included aerobic and isometric exercise, as well as dynamic resistance exercises . Isometric exercises involve a static contraction without any change in the joint angle. Dynamic resistance exercises involve muscle contractions that produce joint movement. These different exercise modes have variations across dimensions such as the type, intensity, and duration of the exercise. Also, techniques of how pain has been induced have included thermal, pressure, electrical and other forms of noxious stimulation . There is, however, still a lack of knowledge as to whether the same phenomenon is present in pain patients, though the present study suggests that there is, but not expressed by changes in pressure sensitivity.
Context may be an important factor in clinical pain measurement . There is hardly a measure of the tissue trauma that causes pain, i.e., the local tissue damage does not explain the whole pain response. The patient nevertheless rarely receives training in how to scale pain. Thus, it may be a measure of pain intensity, colored by the emotional experience of pain. Pressure algometry is a golden standard in research of pain, but a major limitation will always be the fact that the measure is based on a subjective sensation of pain.
Several research groups have reported a reduction in temporal summation of pain following physical activity, in line with the development of hypoalgesia [i.e. 32]. Temporal summation of pain is commonly used to reflect the amount of the central nervous system-involved nociception. Central nervous system-involved nociception is often hypothesized as being sensitive to increases in both acute and chronic pain, suggesting that exercise may provide benefits in both the central and peripheral nervous system pathways important for pain .
A Cochrane review  concludes that there is high-quality evidence for the use of exercise as a longtime pain modulator for knee OA. Furthermore, they found moderate-quality evidence for the use of exercise to improve function. The Osteoarthritis Research Society International (OARSI), as a non-pharmacologic modality , also recommends exercise.
A lack of healthy controls’ response to the same tests is a limitation in this study. Another possible limitation is the reduced standardization in the point of pressure of the pressure algometer, both in the knee and the ankle. A lack of significant pain history is also a limitation.