COMMENTARY
Motor training-induced cortical plastic changes and its disruption by chronic pain: A puzzle with more pieces than expected Accepted for publication 6 April 2014 doi:10.1002/ejp.531
In this issue, you will find a paper by Rittig-Rasmussen et al. titled ‘Effect of training on corticomotor excitability in clinical neck pain’ (Rittig-Rasmussen et al., 2014). In this study, the authors compared the effects of motor neck training on corticomotor excitability in patients with neck pain, patients with knee pain and healthy volunteers. Neck disorders leading to neck pain are prevalent, cause absenteeism, have a negative impact on quality of life and represent a major health problem. Exercise and training have relatively low effect sizes and variable efficacy but remain mainstay treatment options for this disorder. Several studies have attempted to dissect the cortical modifications set forth by motor training as a way to improve its effectiveness. One way to noninvasively gain access to the central processes occurring after motor training is by the use of cortical excitability measurements. These are a group of neurophysiological tests obtained by the application of transcranial magnetic stimulation (TMS) to the scalp and by subsequent recording of evoked responses in the targeted muscles. One frequent approach is to stimulate the primary motor cortex and to measure motor-evoked potentials (MEPs). MEPs are thought to reflect the ‘strength’ of the corticospinal projections related to a certain body area and can be influenced by pharmacological and physiological factors. Changes in MEPs are thought to be markers of cortical plasticity changes. Plasticity can be defined as the capability for change of a system, and plastic changes are defined as alterations of the excitability (or function) of a network. Thus, MEPs are a simple, quick and noninvasive way to measure the cortical effects of a therapeutic intervention. It has been shown that motor skill training is linked to enhanced cortical excitability of the motor cortex, as measured by MEP amplitudes. In a previous study, Rittig-Rasmussen et al. (2013) reported that specific (load-dependent) neck training significantly increased © 2014 European Pain Federation - EFIC®
the amplitude of MEPs in the trapezius muscle (67% from baseline) starting at 30 min and lasting up to 7 days after a single session of training in healthy volunteers. No effects were noticed in a distant control muscle. In the present study (Rittig-Rasmussen et al., 2014), the authors found that patients with neck pain who underwent a 20-min weight lifting training session actually presented a decrease in MEP amplitudes compared with baseline values, which could be detected 30 min after training. However, knee pain patients who also underwent the same training programme presented an increase in MEP amplitudes up to an hour after training. No changes were detected in the pain-free control group. These results may seem to conflict with data from healthy subjects undergoing neck training. However, such discrepancies could be related to the presence of pain and its interference in normal motor plasticity in neck pain patients. In fact, M1 plasticity is modified by noxious inputs, which can also interfere with the learning of new tasks. In an elegant study, Boudreau et al. (2007) showed that a tongue-protrusion exercise was associated with increases in tongue MEPs, which were blocked by experimental pain induced by the oral application of capsaicin. It is known that the human M1 is essential for early motor consolidation. This area is engaged during the acquisition phase of new motor skills, and these changes can be monitored noninvasively by TMS. Animal studies have indicated that increased task learning is associated with increased synaptic efficiency in the M1. These findings surely offer interesting perspectives with the potential for both practical and theoretical implications, which need to be critically interpreted. One point is whether MEP changes can be considered as unequivocal surrogate markers of trainingrelated neuroplasticity. Different from expected, a significant correlation between MEP changes after Eur J Pain 18 (2014) 1081–1082
1081
Commentary
training and motor learning has not been consistently found across studies. This is the case of the present paper and the reports from healthy subjects.. This absence of correlation could be explained by the degree of learning. It has been shown that higher changes in MEPs after training correlate with more efficacious learning, suggesting that low learning rates after an exercise could be insufficient to trigger changes in MEPs. Other cortical excitability parameters could also be employed to assess the effects of motor learning on pain. Measurements derived from MEPs such as intracortical inhibition and facilitation provide further insights into the excitability of the motor cortex and local GABAergic and glutamatergic networks, respectively. For instance, it has been reported that these parameters are altered in different chronic pain syndromes, such as neuropathic pain, complex regional pain syndrome and fibromyalgia. Interestingly, it has been demonstrated that these alterations correlate with the severity of pain and its associated symptoms, such as fatigue and catastrophizing, and could be restored towards normal ranges after successful pain relief by neuromodulation. It would be useful to assess how motor training would affect these parameters and pain. Another important point is that changes in MEPs after practicing a new motor task are dynamic, leading to an initial increase in its amplitudes with subsequent decreases to normal levels when the new skill has been acquired or overlearned (Muellbacher et al., 2001). This is in line with the data from neck (Rittig-Rasmussen et al., 2013) and tongue (Boudreau et al., 2007) training in healthy subjects and neck pain patients, in whom changes in MEPs could be detected immediately or a few minutes after training a new task. Because changes in MEPs after training are expected to decrease once the motor skill is learned, it could be useful to perform MEP monitoring between training sessions as a way to monitor learning of the task. For instance, decreases in MEP amplitudes during sessions could indicate that the new task has been fully acquired by the patient, and new degrees of complexity could be added to the rehabilitation programme, which could increase training efficacy.
1082 Eur J Pain 18 (2014) 1081–1082
In conclusion, MEPs are one of the cortical excitability parameters that can be noninvasively measured by TMS as a way to assess motor cortex plasticity. MEPs change after motor training, at least until the new motor task is fully learned. These changes are dynamic, occur immediately after the exercise and can last for several days. The presence of pain interferes with this process, but the correlation between MEP changes and learning are not obvious. These findings could be used to monitor rehabilitation programmes as a way to improve their efficacy. Daniel Ciampi de Andrade Pain Center, Department of Neurology, University of São Paulo, Brazil Pain Center, Instituto do Câncer do Estado de São Paulo, Brazil Transcranial Magnetic Stimulation Laboratory, Psychiatry Institute, University of São Paulo, Brazil Divisão de Clínica Neurológica, Instituto Central, Hospital das Clínicas FMUSP Av. Dr Eneas de Carvalho Aguiar 255, 5.o andar, sala 5084 05403-900 São Paulo, Brazil Correspondence Daniel Ciampi de Andrade E-mail: [email protected] Conflicts of interest None.
References Boudreau, S., Romaniello, A., Wang, K., Svensson, P., Sessle, B.J., Arendt-Nielsen, L. (2007). The effects of intra-oral pain on motor cortex neuroplasticity associated with short-term novel tongue-protrusion training in humans. Pain 132, 169–178. Muellbacher, W., Ziemann, U., Boroojerdi, B., Cohen, L., Hallett, M. (2001). Role of the human motor cortex in rapid motor learning. Exp Brain Res 136, 431–438. Rittig-Rasmussen, B., Kasch, H., Fuglsang-Frederiksen, A., Jensen, T.S., Svensson, P. (2013). Specific neck training induces sustained corticomotor hyperexcitability as assessed by motor evoked potentials. Spine 38, E979–E984. Rittig-Rasmussen, B., Kasch, H., Fuglsang-Frederiksen, A., Svensson, P., Jensen, T.S. (2014). Effect of training on corticomotor excitability in clinical neck pain. Eur J Pain 18, 1207–1216.
© 2014 European Pain Federation - EFIC®
Motor training-induced cortical plastic changes and its disruption by chronic pain: A puzzle with more pieces than expected Accepted for publication 6 April 2014 doi:10.1002/ejp.531
In this issue, you will find a paper by Rittig-Rasmussen et al. titled ‘Effect of training on corticomotor excitability in clinical neck pain’ (Rittig-Rasmussen et al., 2014). In this study, the authors compared the effects of motor neck training on corticomotor excitability in patients with neck pain, patients with knee pain and healthy volunteers. Neck disorders leading to neck pain are prevalent, cause absenteeism, have a negative impact on quality of life and represent a major health problem. Exercise and training have relatively low effect sizes and variable efficacy but remain mainstay treatment options for this disorder. Several studies have attempted to dissect the cortical modifications set forth by motor training as a way to improve its effectiveness. One way to noninvasively gain access to the central processes occurring after motor training is by the use of cortical excitability measurements. These are a group of neurophysiological tests obtained by the application of transcranial magnetic stimulation (TMS) to the scalp and by subsequent recording of evoked responses in the targeted muscles. One frequent approach is to stimulate the primary motor cortex and to measure motor-evoked potentials (MEPs). MEPs are thought to reflect the ‘strength’ of the corticospinal projections related to a certain body area and can be influenced by pharmacological and physiological factors. Changes in MEPs are thought to be markers of cortical plasticity changes. Plasticity can be defined as the capability for change of a system, and plastic changes are defined as alterations of the excitability (or function) of a network. Thus, MEPs are a simple, quick and noninvasive way to measure the cortical effects of a therapeutic intervention. It has been shown that motor skill training is linked to enhanced cortical excitability of the motor cortex, as measured by MEP amplitudes. In a previous study, Rittig-Rasmussen et al. (2013) reported that specific (load-dependent) neck training significantly increased © 2014 European Pain Federation - EFIC®
the amplitude of MEPs in the trapezius muscle (67% from baseline) starting at 30 min and lasting up to 7 days after a single session of training in healthy volunteers. No effects were noticed in a distant control muscle. In the present study (Rittig-Rasmussen et al., 2014), the authors found that patients with neck pain who underwent a 20-min weight lifting training session actually presented a decrease in MEP amplitudes compared with baseline values, which could be detected 30 min after training. However, knee pain patients who also underwent the same training programme presented an increase in MEP amplitudes up to an hour after training. No changes were detected in the pain-free control group. These results may seem to conflict with data from healthy subjects undergoing neck training. However, such discrepancies could be related to the presence of pain and its interference in normal motor plasticity in neck pain patients. In fact, M1 plasticity is modified by noxious inputs, which can also interfere with the learning of new tasks. In an elegant study, Boudreau et al. (2007) showed that a tongue-protrusion exercise was associated with increases in tongue MEPs, which were blocked by experimental pain induced by the oral application of capsaicin. It is known that the human M1 is essential for early motor consolidation. This area is engaged during the acquisition phase of new motor skills, and these changes can be monitored noninvasively by TMS. Animal studies have indicated that increased task learning is associated with increased synaptic efficiency in the M1. These findings surely offer interesting perspectives with the potential for both practical and theoretical implications, which need to be critically interpreted. One point is whether MEP changes can be considered as unequivocal surrogate markers of trainingrelated neuroplasticity. Different from expected, a significant correlation between MEP changes after Eur J Pain 18 (2014) 1081–1082
1081
Commentary
training and motor learning has not been consistently found across studies. This is the case of the present paper and the reports from healthy subjects.. This absence of correlation could be explained by the degree of learning. It has been shown that higher changes in MEPs after training correlate with more efficacious learning, suggesting that low learning rates after an exercise could be insufficient to trigger changes in MEPs. Other cortical excitability parameters could also be employed to assess the effects of motor learning on pain. Measurements derived from MEPs such as intracortical inhibition and facilitation provide further insights into the excitability of the motor cortex and local GABAergic and glutamatergic networks, respectively. For instance, it has been reported that these parameters are altered in different chronic pain syndromes, such as neuropathic pain, complex regional pain syndrome and fibromyalgia. Interestingly, it has been demonstrated that these alterations correlate with the severity of pain and its associated symptoms, such as fatigue and catastrophizing, and could be restored towards normal ranges after successful pain relief by neuromodulation. It would be useful to assess how motor training would affect these parameters and pain. Another important point is that changes in MEPs after practicing a new motor task are dynamic, leading to an initial increase in its amplitudes with subsequent decreases to normal levels when the new skill has been acquired or overlearned (Muellbacher et al., 2001). This is in line with the data from neck (Rittig-Rasmussen et al., 2013) and tongue (Boudreau et al., 2007) training in healthy subjects and neck pain patients, in whom changes in MEPs could be detected immediately or a few minutes after training a new task. Because changes in MEPs after training are expected to decrease once the motor skill is learned, it could be useful to perform MEP monitoring between training sessions as a way to monitor learning of the task. For instance, decreases in MEP amplitudes during sessions could indicate that the new task has been fully acquired by the patient, and new degrees of complexity could be added to the rehabilitation programme, which could increase training efficacy.
1082 Eur J Pain 18 (2014) 1081–1082
In conclusion, MEPs are one of the cortical excitability parameters that can be noninvasively measured by TMS as a way to assess motor cortex plasticity. MEPs change after motor training, at least until the new motor task is fully learned. These changes are dynamic, occur immediately after the exercise and can last for several days. The presence of pain interferes with this process, but the correlation between MEP changes and learning are not obvious. These findings could be used to monitor rehabilitation programmes as a way to improve their efficacy. Daniel Ciampi de Andrade Pain Center, Department of Neurology, University of São Paulo, Brazil Pain Center, Instituto do Câncer do Estado de São Paulo, Brazil Transcranial Magnetic Stimulation Laboratory, Psychiatry Institute, University of São Paulo, Brazil Divisão de Clínica Neurológica, Instituto Central, Hospital das Clínicas FMUSP Av. Dr Eneas de Carvalho Aguiar 255, 5.o andar, sala 5084 05403-900 São Paulo, Brazil Correspondence Daniel Ciampi de Andrade E-mail: [email protected] Conflicts of interest None.
References Boudreau, S., Romaniello, A., Wang, K., Svensson, P., Sessle, B.J., Arendt-Nielsen, L. (2007). The effects of intra-oral pain on motor cortex neuroplasticity associated with short-term novel tongue-protrusion training in humans. Pain 132, 169–178. Muellbacher, W., Ziemann, U., Boroojerdi, B., Cohen, L., Hallett, M. (2001). Role of the human motor cortex in rapid motor learning. Exp Brain Res 136, 431–438. Rittig-Rasmussen, B., Kasch, H., Fuglsang-Frederiksen, A., Jensen, T.S., Svensson, P. (2013). Specific neck training induces sustained corticomotor hyperexcitability as assessed by motor evoked potentials. Spine 38, E979–E984. Rittig-Rasmussen, B., Kasch, H., Fuglsang-Frederiksen, A., Svensson, P., Jensen, T.S. (2014). Effect of training on corticomotor excitability in clinical neck pain. Eur J Pain 18, 1207–1216.
© 2014 European Pain Federation - EFIC®
