Elsevier

NeuroImage

Volume 32, Issue 2, 15 August 2006, Pages 503-510
NeuroImage

Patterns of cortical reorganization parallel impaired tactile discrimination and pain intensity in complex regional pain syndrome

https://doi.org/10.1016/j.neuroimage.2006.03.045Get rights and content

Abstract

In the complex regional pain syndrome (CRPS), several theories proposed the existence of pathophysiological mechanisms of central origin. Recent studies highlighted a smaller representation of the CRPS-affected hand on the primary somatosensory cortex (SI) during non-painful stimulation of the affected side. We addressed the question whether reorganizational changes can also be found in the secondary somatosensory cortex (SII). Moreover, we investigated whether cortical changes might be accompanied by perceptual changes within associated skin territories. Seventeen patients with CRPS of one upper limb without the presence of peripheral nerve injuries (type I) were subjected to functional magnetic resonance imaging (fMRI) during electrical stimulation of both index fingers (IFs) in order to assess hemodynamic signals of the IF representation in SI and SII. As a marker of tactile perception, we tested 2-point discrimination thresholds on the tip of both IFs. Cortical signals within SI and SII were significantly reduced contralateral to the CRPS-affected IF as compared to the ipsilateral side and to the representation of age- and sex-matched healthy controls. In parallel, discrimination thresholds of the CRPS-affected IF were significantly higher, giving rise to an impairment of tactile perception within the corresponding skin territory. Mean sustained, but not current pain levels were correlated with the amount of sensory impairment and the reduction in signal strength. We conclude that patterns of cortical reorganization in SI and SII seem to parallel impaired tactile discrimination. Furthermore, the amount of reorganization and tactile impairment appeared to be linked to characteristics of CRPS pain.

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.

References (59)

  • B.S. Galer et al.

    Case reports and hypothesis: a neglect-like syndrome may be responsible for the motor disturbance in reflex sympathetic dystrophy (Complex Regional Pain Syndrome-1)

    J. Pain Symptom. Manage

    (1995)
  • S. Geyer et al.

    Areas 3a, 3b, and 1 of human primary somatosensory cortex. Part 2. Spatial normalization to standard anatomical space

    NeuroImage

    (2000)
  • E.G. Jones et al.

    Adaptive responses of monkey somatosensory cortex to peripheral and central deafferentation

    Neuroscience

    (2002)
  • K. Juottonen et al.

    Altered central sensorimotor processing in patients with complex regional pain syndrome

    Pain

    (2002)
  • C. Maihöfner et al.

    Brain processing during mechanical hyperalgesia in complex regional pain syndrome: a functional MRI study

    Pain

    (2005)
  • J. Maleki et al.

    Patterns of spread in complex regional pain syndrome, type I (reflex sympathetic dystrophy)

    Pain

    (2000)
  • K. Moriwaki et al.

    Topographical features of cutaneous tactile hypoesthetic and hyperesthetic abnormalities in chronic pain

    Pain

    (1999)
  • R. Morris et al.

    Spinal dorsal horn neurone targets for nociceptive primary afferents: do single neurone morphological characteristics suggest how nociceptive information is processed at the spinal level

    Brain Res. Brain Res. Rev.

    (2004)
  • R. Peyron et al.

    Functional imaging of brain responses to pain. A review and meta-analysis

    Neurophysiol. Clin.

    (2000)
  • B. Pleger et al.

    Functional imaging of perceptual learning in human primary and secondary somatosensory cortex

    Neuron

    (2003)
  • O. Rommel et al.

    Hemisensory impairment in patients with complex regional pain syndrome

    Pain

    (1999)
  • O. Rommel et al.

    Quantitative sensory testing, neurophysiological and psychological examination in patients with complex regional pain syndrome and hemisensory deficits

    Pain

    (2001)
  • P. Schwenkreis et al.

    Assessment of reorganization in the sensorimotor cortex after upper limb amputation

    Clin. Neurophysiol.

    (2001)
  • M. Stanton-Hicks et al.

    Reflex sympathetic dystrophy: changing concepts and taxonomy

    Pain

    (1995)
  • P.H. Veldman et al.

    Signs and symptoms of reflex sympathetic dystrophy: prospective study of 829 patients

    Lancet

    (1993)
  • R. Baron et al.

    Complex regional pain syndromes

    Curr. Pain Headache Rep.

    (2001)
  • N. Birbaumer et al.

    Effects of regional anesthesia on phantom limb pain are mirrored in changes in cortical reorganization

    J. Neurosci.

    (1997)
  • M.C. Bushnell et al.

    Pain perception: is there a role for primary somatosensory cortex?

    Proc. Natl. Acad. Sci. U. S. A.

    (1999)
  • M.R. Clark et al.

    Neurobiology of pain

    Adv. Psychosom. Med.

    (2004)
  • Cited by (249)

    • The sensorimotor theory of pathological pain revisited

      2022, Neuroscience and Biobehavioral Reviews
    View all citing articles on Scopus
    View full text