An investigation into enlarging and reducing the size of mirror reflections of the hand on experimentally induced cold-pressor pain in healthy volunteers
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Stephen Butler
In this issue, Johnson and Gohil raise some interesting points in their article on a technique, mirror therapy, which can modify brain function to assist in rehabilitation in a number of diverse clinical situations [1]. Although they did not show any effect in their experimental paradigm, the literature does indicate effects in patients with chronic pain (phantom limb pain, complex regional pain syndrome (CRPS)) and in healthy volunteers exposed to experimental pain. In the studies in healthy volunteers where the mirror image is changed from normal, the effects are ambiguous, often opposite to the effects seen in patients as the authors point out [1].
1 Mirror therapy has effects on abnormal cortical representation (in fMRI) of a longstanding painful limb
What is most striking in the pain patients is the fMRI evidence that cortical changes induced by the clinical problems can be partially reversed with this therapy [2]. This is a somewhat unique proof of the central mechanisms involved in both the pain and pain reduction, and in the case of CRPS, improved function as well [2]. As the authors correctly state there is a significant difference between the clinical situation and their volunteer subjects [1]. In patients with an absent limb (phantom limb pain) and in the painful limb in CRPS, there is evidence for reorganization of the cortical representation of the absent limb (phantom limb pain) and of the painful limb (in CRPS) [2].
This is obviously not present in normal volunteers and therefore the effects of mirror therapy on pain perception may not involve the same mechanism (s) in healthy volunteers as in various patient groups. This raises the question of the appropriateness of both preclinical and clinical models used in studies of pain.
2 Animal models of pain and human experimental pain differ from the chronic pain experience in patients
There is a marked difference among animal models of pain, human experimental pain models and clinical chronic pain states. We have ample evidence that robust preclinical effects in animal pain models may be difficult to reproduce in patients. Witness the phenomenon of NK-receptor antagonist MK-801 where there was a stark contrast between pre-clinical pain studies exhibiting marked effects in all animal models but minimal effects in clinical trials.
3 The context-sensitive therapeutic effects in clinical care
The present study showing no effect on experimental cold-pain of either enlarging or decreasing the image of the hand in ice slurry is important in that that context is different from the clinical paradigm used to study treatments for chronic pain, in which there often is a positive context effect on patients [3,4]. The authors point out possible problems with their paradigm which is critical. They indicate a possible negative bias also, but we must also consider possible positive bias in the other models with different and positive results [3]; the context sensitive analgesic effect in patients can be significant and long-lasting [4].
4 The Scandinavian Journal of Pain encourages publication of “negative” studies if the methodology is sound [5]
This brings up the importance of reporting negative studies, a point the authors used in justifying their submission of this article [1]. Rowbotham, in an editorial in Pain, makes a case for publishing negative results in clinical trials and examines publication bias effects when only positive studies are published [6]. A balance with both positive and negative trials allows us to analyze the influence of study design, statistics, subject- and patient-selection, and more. This enables us to gain a clearer picture of effects. This is particularly important in the case of medications for pain and other symptoms where there is a strong reporting bias towards positive results, especially in industry sponsored studies. Although, the study of Johnson and Gohil is not industry sponsored and is not related to patient care directly, it is important to highlight that experimental design can be very important with regard to experimental outcome.
5 The therapeutic context of mirror-therapy influences outcome
It appears that mirror therapy cannot be considered out of the context in which it is used i.e. pain patients are very different from healthy volunteers exposed to short-lasting experimental pain with regard to brain function. It is also possible that cold pain and heat pain, which may involve different pain processing mechanisms, are not equally sensitive to mirror therapy and this information may have clinical relevance related to patient selection for treatment with this therapy. The authors comment that they will repeat this study with a refined design [1]. Should the results be similar, then this is an important finding concerning the mechanism (s) of mirror therapy that can influence the selection of clinical phenotypes that might respond better to this treatment [3,7].
DOI of refers to article: http://dx.doi.org/10.1016/j.sjpain.2015.07.003.
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Conflict of interest: The author declares no conflict of interest.
References
[1] Johnson, MI, Gohil, M. An investigation into enlarging and reducing the size of mirror reflections of the hand on experimentally-induced cold-pressor pain in healthy human participants. Scand J Pain 2016;10:19–25.Search in Google Scholar
[2] Foell J, Bekrater-Bodmann R, Diers M, Flor M. Mirror therapy for phantom limb pain: brain changes and the role of body representation. Eur J Pain 2014;18:729–39.Search in Google Scholar
[3] Al Sayegh SA, Filén T, Johansson M, Sandström S, Stiewe G, Butler S. Topical review: mirror therapy for complex regional pain syndrome (CRPS) - a literature review and an illustrative case report. Scand J Pain 2013;4:200–7.Search in Google Scholar
[4] Finniss DG, Kaptchuk TJ, Miller F, Benedetti F. Biological, clinical, and ethical advances of placebo effects. Lancet 2010;375:686–95.Search in Google Scholar
[5] Kontinen V, Kalso E. Why we are proud to publish well-performed negative clinical studies? Scand J Pain 2013;4:15–6, http://dx.doi.org/10.1016/j.sjpain.2012.11.008.Search in Google Scholar
[6] Rowbotham MC. The case for publishing “negative” clinical trials. Pain 2009;146:225–6.Search in Google Scholar
[7] Breivik H, Allen SM, Stubhaug A. Mirror-therapy: an important tool in the management of complex regional pain syndrome (CRPS). Scand J Pain 2013;4:198–9.Search in Google Scholar
© 2015 Scandinavian Association for the Study of Pain
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- Editorial comment
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- An investigation into enlarging and reducing the size of mirror reflections of the hand on experimentally induced cold-pressor pain in healthy volunteers
- Original experimental
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- Targeting glial dysfunction to treat post-surgical neuropathic pain
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- Glial dysfunction and persistent neuropathic postsurgical pain
- Editorial comment
- Mechanisms of cognitive impairment in chronic pain patients can now be studied preclinically by inducing cognitive deficits with an experimental animal model of chronic neuropathic pain
- Original experimental
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