Patterns of cortical reorganization parallel impaired tactile discrimination and pain intensity in complex regional pain syndrome
Introduction
The complex regional pain syndrome (CRPS) can occur after a trauma to a limb. Pain as the leading symptom is often disproportional to the initial trauma and therefore subject of interdisciplinary treatment (Baron and Wasner, 2001). According to the classification of the International Association for the Study of Pain (IASP), CRPS is subdivided into two types: type I corresponds to the former reflex sympathetic dystrophy and occurs without an obvious peripheral nerve lesion, whereas type II, formerly called causalgia, refers to cases where a defined peripheral nerve lesion is present (Stanton-Hicks et al., 1995, Bruehl et al., 1999). In both subtypes, the injured extremity is affected without any restriction to single nerve territories and with a predominantly distal manifestation. Autonomic dysfunction (Wasner et al., 1999, Drummond, 2001, Baron et al., 2002), sensory changes (Rommel et al., 2001) and motor impairment (Schwartzman, 1993, Veldman et al., 1993) are known as typical clinical signs, changing with increasing duration and differing individually (Bruehl et al., 2002). Pain that sometimes spreads into distant body regions may be due to an aberrant central pain regulation (Maleki et al., 2000). The neglect-like syndrome (Galer et al., 1995), multifocal dystonia (van Hilten et al., 2001), and hemisensory impairment (Rommel et al., 2001) are discussed as possible indicators of an altered central nervous processing.
Recent experiments using somatosensory-evoked potential (SSEP) mapping or magnetic source imaging during non-painful stimulation of the skin revealed a smaller representation of the CRPS-affected hand on the primary somatosensory cortex (SI) contralateral to the affected side (Juottonen et al., 2002, Maihöfner et al., 2003, Pleger et al., 2004). The amount of this cortical reorganization appeared to be linked to complaints of CRPS pain: low pain was linked to small hemispherical side-to-side differences, while subjects with a distinctive asymmetry reported the highest pain levels (Maihöfner et al., 2003, Pleger et al., 2004).
In the present study, we investigated whether pain-related changes, which only have been reported for SI, can also be found in the secondary somatosensory cortex (SII). Moreover, we questioned whether signal changes in SI or SII might be accompanied by perceptual changes within associated skin territories. To test this hypothesis, we combined functional magnetic resonance imaging (fMRI) during electrical stimulation of the index finger (IF) with assessments of 2-point discrimination thresholds as a marker for tactile perception.
Section snippets
Methods
The study was approved by the Ethics Committee of the Ruhr-University Bochum and was performed in accordance with the 1964 Declaration of Helsinki. Subjects gave their written informed consent. We recruited 17 right-handed patients (10 female, age: 40.1 ± 9.5 years (mean value ± standard deviation), ranging from 22 to 54 years) with spontaneous pain due to CRPS type I of one upper limb without any definable nerve lesion (Stanton-Hicks et al., 1995). All of them fulfilled the revised criteria of
Two-point discrimination thresholds
Two-point discrimination thresholds of the CRPS-affected IF (3.23 ± 0.71 mm (mean ± SD)) were significantly higher than of the contralateral non-affected IF (2.2 ± 0.46 mm, P < 0.001) and the corresponding IF of healthy controls (right IF: 1.97 ± 0.39 mm, P < 0.001; left IF: 1.98 mm ± 0.35 mm, P < 0.001, Fig. 1). We found no differences between the non-affected IF and the corresponding IF of healthy controls (right IF: P = 0.13; left IF: P = 0.12, Fig. 1).
Linear correlation analysis (Pearson)
Two-point discrimination thresholds
Discussion
In the present study, we investigated cortical responses elicited by non-painful stimulations of the skin in CRPS. We found that hemodynamic responses from the cortical representation of the CRPS-affected hand were significantly reduced. In line with recent studies, this may suggest a shrinkage of the extension of the cortical representation for the CRPS-affected side (Juottonen et al., 2002, Maihöfner et al., 2003, Pleger et al., 2004). This was true not only for SI but also for SII. The
Acknowledgments
This work was supported by grants from the Richard Sackler Foundation (C.M. and A.-F.F.) and by the BMBF (NR. 01EM0102). We thank Sonja Sellenmerten for data collection and Steve Langan for his skilful editing of the manuscript.
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