single subject experimental design

Reduction of pain-related fear in complex regional pain syndrome
As promised, at last a post on graded exposure for pain-related anxiety and avoidance, as applied to complex regional pain syndrome, or CRPS. This paper was published in 2005, and as far as I know, there have not been any replications carried out, so it must be seen as an initial experimental approach that needs a good deal of refinement before being applicable to people with CRPS in general, but I think the model itself has received considerable support, and therefore it merits further examination.

So, what did they do? Well the basic premise of the pain-related anxiety and avoidance model is that people can rapidly develop a ‘phobia’ for movements that are associated with increased pain and/or fear of further harm. As a result of this fear, individuals avoid movements that are the same or similar to those that they associate with increased pain or harm. And the resultant avoidance interferes significantly with participating in normal life tasks.

So far, this model has been strongly supported in people with a wide range of types of pain, and treatments based on this model have similarly given some very useful results, although not always as positive as those in the initial few papers.

In CRPS, many people describe their painful limb in terms bordering on disgust, loathing and resentment. Some ignore the limb, while others ask for it to be amputated. It’s not clear to me whether this resentment or desire for it to be removed is an artifact of having pain in a distal part of the body (where amputation is possible – unlike back pain), or whether it represents some degree of neglect as in stroke. Nevertheless, people with CRPS often report being unwilling and/or unable to use their limb in normal functional activities. As a result, their pain interferes with normal life to a considerable extent.

High distress, high reported pain intensity, and avoidance of many activities can result – and some continue to fear that their limb has not ‘healed’ and that they are continuing to ‘damage’ or ‘harm’ their painful extremity.

In this paper, de Jong and colleagues in Maastricht, The Netherlands, set out to test whether the graded exposure approach that had been used for low back pain could also be applied to CRPS. The aim of the study was: ‘Using a replicated single case experimental design, we decided to experimentally examine whether the validity of graded exposure in vivo extends to patients with CRPS-I. The main research question of this study was whether the reduction of pain-related fear through graded exposure in vivo also resulted in a decrease of disability in a subgroup of patients with CRPS-I who report substantial pain-related fear.’

This paper also again illustrates the utility of the replicated single case experimental design for testing the effect of an intervention – for me, clinically, this model of research has a good deal of merit, because it can be applied routinely as part of normal treatment, and doesn’t require elaborate randomisation or the use of control groups, as the subjects act as their own controls, and the interventions are experimentally and systematically manipulated and the results measured.

The study took 8 female patients with CRPS-1, aged 40 years (+/-10 years), and a mean duration of pain of 3 years. In two patients CRPS-I was located in the right lower extremity, one patient in the left lower extremity, four patients in the right upper extremity, and one patient in the left upper extremity. In six patients, CRPS-I occurred on the dominant side. The IASP criteria was used to determine CRPS diagnosis, and it was evaluated both by physician and based on Bruehl et al. (1999), and Veldman et al. (1993) signs: altered skin color, altered skin temperature, edema (swelling), reduced range of motion, trophic (hair, nail skin). Additionally, other inclusion criteria were that the patients reported substantial fear of movement/(re)injury (Tampa Scale for Kinesiophobia (TSK: Miller et al., 1991) score >39), pain for at least 6 months and age between 18 and 65. The TSK score was the median of the TSK distribution from a previous study of low back pain patients.

The paper clearly describes the study design – an ABCD -design with random determination of the start of the intervention. At point A – baseline measures were undertaken. All patients received education, then measures were taken (B), Graded exposure was then undertaken (C), and finally there was a 6 month follow up (D). Commencement of the various treatment phases was started at random time periods. A number of outcome measures were also taken including functional disability – measured in the upper limb by the Radboud Skills Questionnaire (RASQ: Oerlemans et al., 1999, 2000); and in the lower limb the Walking Stairs Questionnaire (WSQ: Roorda et al., 1996a; 2004) and Questionnaire Rising and Sitting Down (QRS: Roorda et al.,1996b) were used.

Fear of movement was assessed using the Tampa Scale for Kinesiophobia, and the PHODA, or Photographs of Daily Living. The final set of measures were self reports of signs and symptoms, using a daily diary method.

I’ll describe the exposure treatment more fully. Each person developed an individualised fear hierarchy by means of the Photograph series of Daily activities for the upper extremities (PHODA-UE: Dubbers and Vikstro¨m, 2003) or the lower extremities (PHODA-LE: Jelinek et al., 2003).

The most essential step consisted of graded exposure to the situations the patients had identified as ‘dangerous’ or ‘threatening’. Based on the graded hierarchy of fear-eliciting situations (PHODA), individually tailored practice tasks were developed. Further, the general principles for exposure were followed. The patient agreed to perform certain activities or movements or stay in situations that he or she had been avoiding. Patients were also encouraged to engage in these fearful activities, movements or situations as much as possible until anxiety levels had decreased. The therapist first modeled each activity or movement. Finally, the graded exposure was presented as a start only, and the patient was encouraged to continue exposing him or herself to more activities in everyday life after termination of the treatment sessions. To facilitate independence and to promote generalization, the presence of the therapist was gradually withdrawn, and contexts were created that mimicked those of the home situation.

Well, what did the study show? The first surprising result was that ‘in every case, at the end of the GEXP all the patients report a positive change for the better in CRPS-related signs and symptoms.’

For all patients a significant reduction in TSK scores is observed at the end of graded exposure and during followup as compared to baseline and education alone. TSK scores decrease from a mean score of 55.0 (>80th percentile) to a mean score of 19.75 (<10th percentile). Similar results were found for the PHODA.

And functionally? All patients reported reduction in pain-related disability as measured both by standardised measures, and on the individualised tasks the patients had identified as things they would like to work on.

To summarise, all the patients reported, after the graded exposure treatment, decreasing levels of pain-related fear, pain disability, and pain intensity. As the authors say ‘This last result is remarkable because pain intensity is not the target of the graded exposure treatment.’

For theorists, it would be great to try to work out how this approach works – graded exposure in vivo is a strategy that aims to activate cortical networks. Graded exposure may disrupt internal body schema by focusing on how the body prepares for movement (eg motor intent), perhaps by practicing a movement the mismatch between motor intent and sensory feedback is ‘rewired’. Alternatively it could have been the process of visual and mental attention on the limb which reintegrates the neural networks, reorganising the cortical representation of the painful limb.

For me, graded exposure directly addresses the meaning people attach to their pain (in particular the belief that ‘I can’t cope with variations in pain’, or ‘this pain means harm’), as well as the behavioural avoidance that interferes so much with daily function – and serves to reinforce the belief that ‘I can’t cope with this pain’. We know that pain intensity is influenced by the meaning people associate with the sensation – and the judgements about what the pain means about them and their lives. If we can help people gradually return to enjoyable activities, we will be doing them a real favour.

I encourage you to review single subject experimental design – and I’ll post more on it!
I also encourage you to consider developing your skills in graded exposure and perhaps reduce the focus in CRPS on avoiding activities that ‘flare pain up’ and instead, consider gradually working up to normal and enjoyable activities on the basis of addressing and experimenting with fears and avoidance.

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DEJONG, J., VLAEYEN, J., ONGHENA, P., CUYPERS, C., HOLLANDER, M., RUIJGROK, J. (2005). Reduction of pain-related fear in complex regional pain syndrome type I: The application of graded exposure in vivo. Pain, 116(3), 264-275. DOI: 10.1016/j.pain.2005.04.019

Bruehl S, Harden RN, Galer BS, Saltz S, Bertram M, Backonja M,
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Rehabilitation Research (iRv); 2003.

Jelinek S, Germes D, Leyckes N. The Photograph Series of Daily Activities
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Research (iRv); 2003.

Miller RP, Kori, SH, Todd, DD. The Tampa Scale for Kinisophobia.
Unpublished Report, Tampa, FL; 1991.

Oerlemans HM, Oostendorp RA, de Boo T, Goris RJ. Pain and reduced
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Oerlemans HM, Oostendorp RA, de Boo T, van der Laan L, Severens JL,
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Roorda LD, Roebroeck ME, Lankhorst GJ, van Tilburg TG. The walking
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Veldman PH, Reynen HM, Arntz IE, Goris RJ. Signs and symptoms of
reflex sympathetic dystrophy: prospective study of 829 patients. Lancet