An investigation into enlarging and reducing the size of mirror reflections of the hand on experimentally induced cold-pressor pain in healthy volunteers

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].