LETTER TO THE EDITOR
Authors’ reply to the comment by Harvie and Moseley doi:10.1002/j.1532-2149.2014.00480.x
Harvie and Moseley (2014) have provided an insightful comment on our study (Foell et al., 2014), which examined the behavioural and neuronal consequences of mirror therapy in persons with chronic phantom limb pain. We appreciate their thoughts on the methodology, findings and consequences of our study and would like to comment on some of their insights. We agree that it is remarkable that even after more than a decade of phantom limb pain, a brief mirror treatment intervention can have a large impact on pain levels. Further, we agree that the finding warrants further research to its specificity and that we need placebo-controlled studies. With respect to the finding that telescoping impeded recovery from phantom pain, we also agree with the authors that it is unlikely that having a normal phantom would eliminate phantom limb pain, although pain and telescoping are highly positively correlated (Grüsser et al., 2001). However, we must note that we did not have an a priori expectation that telescoping would impede recovery from phantom limb pain via mirror treatment. On the contrary, we expected that successful mirror treatment would lead to a normalization of the telescoped limb (by ‘pulling’ the phantom into a normal position), and that this mechanism would relieve phantom pain by providing feedback of a normal limb perception. It is thus unlikely that a specific expectation of the therapists may have yielded this result. It was truly a serendipitous finding and since this was a post hoc analysis we also agree with the authors that this must be tested in an a priori design with the proper control implemented. The relationship between our study and the one by Makin et al. (2013) is indeed interesting and deserves further discussion. As Harvie and Moseley (2014) have noted, one difference relates to the measurement of activation magnitude as opposed to location. Furthermore, the reported persistence of primary somatosensory cortex refers to the hand representation, whereas the shift reported in our study relates to the representation of the lip and was in line with expectations based on dysfunctional reorganization (Flor et al., 2006). It is noteworthy that only two patients of the Makin et al. (2013) sample were pain free, which © 2014 European Pain Federation - EFIC®
did not make it possible to directly compare painful and non-painful phantoms in the traumatic amputee group (Flor et al., 2013). Makin et al. also used a region of interest that was combined for the patients and controls and may have contained activations from areas other than the hand representation zone. Using an amputee-specific region of interest revealed no significant correlation between phantom limb-related activation and phantom pain (Andoh et al., unpublished data); however, virtual mirror box rather than phantom limb movement was employed in this study. Previous studies suggest that the somatosensory cortex consists of several representational maps (Haggard and Wolpert, 2005) and can switch between them rapidly depending on the current task (Braun et al., 2001). The ostensible contradiction between a persistent limb representation in primary somatosensory cortex and a clear reorganizational shift in the same region might thus arise from a difference in task (stimulation vs. movement) and thus task-specific maps, body location (hand vs. lip movement), region of interest (averaged vs. patient specific), type of reorganization measure (intensity vs. location of brain activation) or a combination of these. We wholeheartedly agree that these questions necessitate further studies and believe that longitudinal studies are needed to make progress in this field. Jens Foell1, Robin Bekrater-Bodmann2, Martin Diers2, Herta Flor2 1 Department of Psychology, Florida State University, Tallahassee, USA 2 Department of Cognitive and Clinical Neuroscience, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany Conflicts of interest None declared. References Braun, C., Heinz, U., Schweizer, R., Wiech, K., Birbaumer, N., Topka, H. (2001). Dynamic organization of the somatosensory cortex induced by motor activity. Brain 124, 2259–2267.
Eur J Pain 18 (2014) 603–604
603
Letter to the Editor
Flor, H., Diers, M., Andoh, J. (2013). The neural basis of phantom limb pain. Trends Cogn Sci 17, 307–308. Flor, H., Nikolajsen, L., Staehelin Jensen, T. (2006). Phantom limb pain: A case of maladaptive CNS plasticity? Nat Rev Neurosci 7, 873–881. Foell, J., Bekrater-Bodmann, R., Diers, M., Flor, H. (2014). Mirror therapy for phantom limb pain: Brain changes and the role of body representation. Eur J Pain 18, 729–739. Grüsser, S.M., Winter, C., Mühlnickel, W., Denke, C., Karl, A., Villringer, K., Flor, H. (2001). The relationship of perceptual phenomena and cortical reorganization in upper extremity amputees. Neuroscience 102, 263–272.
604 Eur J Pain 18 (2014) 603–604
Haggard, P., Wolpert, D.M. (2005). Disorders of body scheme. In Higherorder Motor Disorders: From Neuroanatomy and Neurobiology to Clinical Neurology, H.-J. Freund, M. Jeannerod, M. Hallett, R. Leiquarda, eds. (New York, NY, USA: Oxford University Press). Harvie, D., Moseley, G.L. (2014). Exploring changes in the brain associated with recovery from phantom limb pain – The potential importance of telescoping. Eur J Pain 18, 601–602. Makin, T.R., Scholz, J., Filippini, N., Henderson Slater, D., Tracey, I., Johansen-Berg, H. (2013). Phantom pain is associated with preserved structure and function in the former hand area. Nat Commun 4, 1570.
© 2014 European Pain Federation - EFIC®
Authors’ reply to the comment by Harvie and Moseley doi:10.1002/j.1532-2149.2014.00480.x
Harvie and Moseley (2014) have provided an insightful comment on our study (Foell et al., 2014), which examined the behavioural and neuronal consequences of mirror therapy in persons with chronic phantom limb pain. We appreciate their thoughts on the methodology, findings and consequences of our study and would like to comment on some of their insights. We agree that it is remarkable that even after more than a decade of phantom limb pain, a brief mirror treatment intervention can have a large impact on pain levels. Further, we agree that the finding warrants further research to its specificity and that we need placebo-controlled studies. With respect to the finding that telescoping impeded recovery from phantom pain, we also agree with the authors that it is unlikely that having a normal phantom would eliminate phantom limb pain, although pain and telescoping are highly positively correlated (Grüsser et al., 2001). However, we must note that we did not have an a priori expectation that telescoping would impede recovery from phantom limb pain via mirror treatment. On the contrary, we expected that successful mirror treatment would lead to a normalization of the telescoped limb (by ‘pulling’ the phantom into a normal position), and that this mechanism would relieve phantom pain by providing feedback of a normal limb perception. It is thus unlikely that a specific expectation of the therapists may have yielded this result. It was truly a serendipitous finding and since this was a post hoc analysis we also agree with the authors that this must be tested in an a priori design with the proper control implemented. The relationship between our study and the one by Makin et al. (2013) is indeed interesting and deserves further discussion. As Harvie and Moseley (2014) have noted, one difference relates to the measurement of activation magnitude as opposed to location. Furthermore, the reported persistence of primary somatosensory cortex refers to the hand representation, whereas the shift reported in our study relates to the representation of the lip and was in line with expectations based on dysfunctional reorganization (Flor et al., 2006). It is noteworthy that only two patients of the Makin et al. (2013) sample were pain free, which © 2014 European Pain Federation - EFIC®
did not make it possible to directly compare painful and non-painful phantoms in the traumatic amputee group (Flor et al., 2013). Makin et al. also used a region of interest that was combined for the patients and controls and may have contained activations from areas other than the hand representation zone. Using an amputee-specific region of interest revealed no significant correlation between phantom limb-related activation and phantom pain (Andoh et al., unpublished data); however, virtual mirror box rather than phantom limb movement was employed in this study. Previous studies suggest that the somatosensory cortex consists of several representational maps (Haggard and Wolpert, 2005) and can switch between them rapidly depending on the current task (Braun et al., 2001). The ostensible contradiction between a persistent limb representation in primary somatosensory cortex and a clear reorganizational shift in the same region might thus arise from a difference in task (stimulation vs. movement) and thus task-specific maps, body location (hand vs. lip movement), region of interest (averaged vs. patient specific), type of reorganization measure (intensity vs. location of brain activation) or a combination of these. We wholeheartedly agree that these questions necessitate further studies and believe that longitudinal studies are needed to make progress in this field. Jens Foell1, Robin Bekrater-Bodmann2, Martin Diers2, Herta Flor2 1 Department of Psychology, Florida State University, Tallahassee, USA 2 Department of Cognitive and Clinical Neuroscience, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany Conflicts of interest None declared. References Braun, C., Heinz, U., Schweizer, R., Wiech, K., Birbaumer, N., Topka, H. (2001). Dynamic organization of the somatosensory cortex induced by motor activity. Brain 124, 2259–2267.
Eur J Pain 18 (2014) 603–604
603
Letter to the Editor
Flor, H., Diers, M., Andoh, J. (2013). The neural basis of phantom limb pain. Trends Cogn Sci 17, 307–308. Flor, H., Nikolajsen, L., Staehelin Jensen, T. (2006). Phantom limb pain: A case of maladaptive CNS plasticity? Nat Rev Neurosci 7, 873–881. Foell, J., Bekrater-Bodmann, R., Diers, M., Flor, H. (2014). Mirror therapy for phantom limb pain: Brain changes and the role of body representation. Eur J Pain 18, 729–739. Grüsser, S.M., Winter, C., Mühlnickel, W., Denke, C., Karl, A., Villringer, K., Flor, H. (2001). The relationship of perceptual phenomena and cortical reorganization in upper extremity amputees. Neuroscience 102, 263–272.
604 Eur J Pain 18 (2014) 603–604
Haggard, P., Wolpert, D.M. (2005). Disorders of body scheme. In Higherorder Motor Disorders: From Neuroanatomy and Neurobiology to Clinical Neurology, H.-J. Freund, M. Jeannerod, M. Hallett, R. Leiquarda, eds. (New York, NY, USA: Oxford University Press). Harvie, D., Moseley, G.L. (2014). Exploring changes in the brain associated with recovery from phantom limb pain – The potential importance of telescoping. Eur J Pain 18, 601–602. Makin, T.R., Scholz, J., Filippini, N., Henderson Slater, D., Tracey, I., Johansen-Berg, H. (2013). Phantom pain is associated with preserved structure and function in the former hand area. Nat Commun 4, 1570.
© 2014 European Pain Federation - EFIC®
