The hypothesis of this exploratory RCT on principles of brain plasticity in improving sensorimotor function of the knee in subjects with severe traumatic knee ligament injury was not confirmed. No effect was found of temporary cutaneous anesthesia of the skin area above and below the knee on sensorimotor function of the ipsilateral knee and leg in these subjects.
The forearm is located next to the hand in the somatotopic map [13
] and by anaesthetizing the forearm, the cortical hand area can expand over the forearm area [46
]. Thus, more nerve cells can be available for the hand, resulting in improved hand function. This principle has been successfully used in subjects with or without hand nerve injury [24
], and was recently also efficiently applied to the foot in subjects with or without diabetes [33
Diminished activation in several sensorimotor cortical areas has been observed in subjects with ACL injury compared with controls, indicating that the injury causes re-organization of the central nervous system [28
]. Conversely, it may be assumed that cortical re-organization can be achieved by an efficient intervention. By assessing sensory function in the knee, we indirectly assessed a possible cortical re-organization. An improved sensory function, as found in the hands following forearm anesthesia [46
], would indicate a cortical re-organization with an expanded cortical knee area in subjects with anesthetized leg areas. Although no such changes were seen, this does not completely rule out cortical changes following treatment. However, if cortical changes did occur they were likely very subtle. This, in combination with the fact that the knee normally has a very small representation in the somatosensory cortex, makes is difficult or perhaps even impossible in this case to detect changes in the cortical knee area using neuroimaging methods such as fMRI. With this in mind, and because no effects were found in the sensorimotor function tests in the present study or in a previous study in healthy subjects [34
], we decided not to perform fMRI because the likelihood of finding an cortical expansion-difference would be small.
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 [27
]. 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, such as that reported for the foot [33
Because this was an RCT with a blinded design, that is, both the assessor and the subject were blinded to group allocation, numbness in the area where the EMLA®/placebo was applied (see Figure ) was not verified. However, the amount of EMLA® used (50
g) is a dosage of active substance per cm2
well within the recommendations to achieve cutaneous anesthesia.
The placing of the cream (above and below the knee) is most likely adequate in order to expect an increased cortical knee representation. Because the cortical area devoted to the lower extremity is small compared to the hand, we expected that a larger deafferented skin area was needed (compared to the upper extremity) in order to allow the knee to expand in the primary somatosensory and motor cortex. Therefore, the EMLA® or placebo was applied circumferentially on the skin both above and below the knee.
The effect sizes were generally small for all outcome measures, indicating that the magnitude of change by treatment was small. In previous studies on the hand and foot, focus was on assessing improvements of temporary anesthesia in sensory function (perception of touch, vibration sense) [24
], as these measures are relevant to the patient’s daily activities [24
]. Because we applied this concept to the knee, these sensory measures were included also in the present study. The perception of touch of the knee is not as delicate, discriminative or vital as in the hand or the foot sole. Therefore, the relevance of this measure for patients with knee injury, as used in the present study, may be questioned. The first study evaluating vibration sense in patients with ACL injury was recently reported [38
]. Vibration perception threshold was not impaired in these patients compared with matched controls [38
]. Perhaps a ceiling effect was present, limiting the chance of improving perception of touch and/or vibration sense in these patients by intervention using temporary anesthesia.
Several studies have shown a deficiency in proprioceptive acuity (kinesthesia, joint position sense) in patients with ACL injury; recently reported in a review [49
]. While measures of motor function (muscle strength, functional performance) appear relevant for patients with knee injury [7
], the association between sensory function (proprioceptive acuity) and patient-reported and motor functions is generally low [49
]. For this reason, the development of more accurate and precise methods for assessing sensory function was proposed [49
]. Possibly, measures of motor function may be more essential for activities of daily life and more demanding activities than measures of sensory function for subjects with knee injury. However, the possibilities of affecting motor outcomes by temporary anesthesia may be more difficult to achieve than for sensory outcomes [24
The major strength of the current and previous [34
] studies is the design; the subjects were randomized to anesthetic or placebo cream, the test leader was blinded to group allocation, and group allocation was concealed to the person analyzing the data until the results were completed. However, from the results of the present and previous [34
] studies, temporary cutaneous anesthesia was not a successful intervention to improve sensorimotor function for patients with severe traumatic knee ligament injury. The need for development and evaluation of methods to improve the effects of treatment on sensorimotor function after knee injury and knee OA remains.