In this first exploratory study on principles of brain plasticity in improving sensorimotor function of the knee, we found no effect of temporary anesthesia of the skin area above and below the knee on sensorimotor function of the ipsilateral knee and leg in uninjured subjects.
Although self-reported and objective function is improved by neuromuscular and/or strength training, it is unclear whether sensorimotor function can be fully restored after knee injury and knee OA. In a recent study, we found that at least one-third of patients with anterior cruciate ligament (ACL) injury or reconstruction had not recovered normal muscle function 2 to 5 years after injury [42
]. Possible reasons for this may be that the injury causes a disturbance in the sensory system [43
] with possible effects on the central mechanisms and motor response [1
], and/or that neuromuscular and strength training programs are not sufficiently effective in improving or restoring sensorimotor function. Moreover, it has been questioned whether training after knee injury can lead to improvement in sensory function although improvement in motor function can be obtained [44
Good sensorimotor function is of importance for the overall outcome after injury [6
] and in preventing OA [2
]. Although improvements are achieved by neuromuscular and/or strength training, impairment in sensorimotor function often persists [1
]. Thus, it can be argued that training programs need to be more effective in order to improve or restore sensorimotor function after knee injury and knee OA. Hypothetically, the principle of temporary cutaneous anesthesia of adjacent body parts in combination with training, that has been shown to be more effective in improving sensorimotor function of the hand than training only [28
], could also be used to improve sensorimotor function of the knee. An advantage is that the selective anesthesia does not affect motor function of the leg. Thus, the individual can use the leg during training while parts of the leg are anesthetized.
The only difference that we found was a lower value for TDPM, indicating better knee kinesthesia, after compared with before treatment in the placebo group. However, the 95% CI was close to zero (Table ), indicating a small change. Moreover, in a previous study on test-retest reliability, we found that there may be a learning effect in TDPM, shown as a significantly lower value in TDPM on the second test session than on the first test session. In that study, the 95% CI was also quite close to zero and, therefore, we questioned the clinical relevance of this learning effect [38
]. Since the 95% CI in the current study was close to zero and our previous study show that there may be a learning effect in TDPM, the clinical relevance of the improvement of 0.40 degrees (95% CI -0.05, -0.73), can be questioned.
There may be several reasons for the lack of effect from temporary cutaneous anesthesia of the skin area above and below the knee on sensorimotor function of the ipsilateral knee and leg in the uninjured subjects in our study. Sensorimotor function may not be impaired in uninjured subjects. Thus, the chance of achieving an improvement in sensorimotor function in these subjects by the short-term intervention that we used is most likely limited. For example, a ceiling effect was noted in some of the measures. The subjects in our study had low values (good sensory function) for both knee kinesthesia and skin sensitivity before EMLA/placebo, limiting the chance of improving these measures by treatment. In addition, the effect sizes were generally small, indicating that the magnitude of change by treatment was small. In previous studies on knee kinesthesia, patients with knee injury have higher values (poorer kinesthesia) than uninjured subjects [44
]. Thus, the possibility of improving kinesthesia by temporary cutaneous anesthesia may be greater in subjects with knee injury than in uninjured subjects. We tested one site for perception of touch, while several sites were tested in the corresponding study of the foot [29
]. In an effort to reduce the ceiling effect, several sites around the knee could be tested in further studies. However, the perception of touch of the knee is not as delicate and discriminative as in the hand or the foot sole. Thus, large effects from temporary cutaneous anesthesia may be needed to detect a change in perception of touch of the knee. Due to the exploratory character of our study, the a priori sample size calculation was based on predictions. A post-hoc sample size calculation estimated that about 30 subjects in each group would be needed to detect improvement in the EMLA group compared with the placebo group for the measures of sensory function and between 5 and 9 subjects in each group for the measures of motor function, with 80% power at the 5% significance level. Thus, the risk of a type II error in the present study cannot be ruled out, implying a need for a larger group of subjects in further studies.
It is well known from animal and human experiments that temporary cutaneous anesthesia of one body part leads to cortical re-organization resulting in a corresponding silent area in the sensory cortex. This allows adjacent nearby body parts to rapidly expand at the expense of the silent cortical area [21
]. Previous studies on the upper and lower extremity [27
] as well as the present study have been done on subjects without pain. A peripheral nociceptive stimulus, e.g., a painful knee, is known to induce plasticity changes in the spinal cord and at subcortical and cortical levels. Thus, treating patients with a painful joint using cutaneous deafferentation may give a different result compared to that for individuals without pain. This needs to be addressed in future studies. Neurophysiologic mechanisms in the lower extremity may also differ from those in the upper extremity. Large overlaps in the sensorimotor activation have been shown following movement of the knee, ankle and toes as opposed to the fingers [46
]. However, the same plasticity mechanisms likely occur in both the upper and lower extremity, thus making it possible to manipulate plasticity mechanisms also in the lower extremity in order to improve sensorimotor function.
In previous studies on the upper extremity [27
], the anesthetic cream was applied to the volar aspect of the forearm and in the previous study on the lower extremity the anesthetic cream was applied circumferentially on the lower leg [29
]. Based on these previous studies, it would be logical to deafferentate the foot and lower leg in the current study. However, it is very difficult to anesthetize the entire foot using EMLA due to problems with absorption of the EMLA in the sole of the foot and applying an occlusive bandage. Therefore, we decided to anesthetize the skin area adjacent to the knee knowing that following deafferentation, the adjacent cortical areas rapidly occupy the anesthetized area. We also decided to deafferentate circumferentially on the lower extremity because the cortical area devoted to the lower extremity is small compared to the hand and we, therefore, expected that a larger deafferentated skin area was needed (compared to the upper extremity) in order to allow the knee to expand in the primary somatosensory and motor cortex.
We believe that the amount of EMLA that we used (50 grams) and placing of the anesthetic cream (above and below the knee) is adequate in order to expect an increased cortical knee representation. However, the cortical area of the knee is smaller than the cortical area of the hand [17
]. Thus, larger effects of treatment are needed in order to detect an increase in the cortical area of the knee than in that of the hand. In line with this reasoning, we found no effect of temporary cutaneous anesthesia of adjacent body parts in the measures of sensory or motor functions of the knee in healthy subjects, whereas previous studies reported improvement in sensory function of the hand and foot in healthy subjects after such treatment [27
]. This could be due to lack of cortical re-organization following the cutaneous anesthesia or that the re-organization was too small to result in a detectable improvement. However, we did not investigate whether the lack of improvement in these measures corresponds to a lack of cortical re-organization. In further studies, neuroimaging methods, such as functional magnetic resonance imaging, can be used to address this question.
Due to the loss of mechanoreceptors after knee injury, the sensory system is disturbed [43
], possibly causing effects on sensory and motor functions. Thus, treatment leading to improved sensorimotor function would be of value for patients with knee injury. In line with observations in individuals with hand nerve injury, the sensory deficiency after knee injury can, at least hypothetically, be associated with functional re-organization of the somatosensory cortex of the brain. Thereby, it can be argued that the principle of temporary cutaneous anesthesia in improving sensorimotor function can be used also on the knee. In current neuromuscular training programs for patients with knee injury, principles of brain plasticity such as training of the contralateral extremity are included [1
]. The aim of these neuromuscular training programs is to enhance unconscious motor responses by stimulating both afferent signals and central mechanisms responsible for dynamic joint control [47
]. From the present study, we cannot exclude that there is no effect of temporary cutaneous anesthesia of the skin area above and below the knee on sensorimotor function of the ipsilateral knee and leg in uninjured subjects. However, based on the reasoning above, studies on the effect of temporary cutaneous anesthesia for improving sensorimotor function in patients with knee injury and functional limitations are warranted.