Elsevier

NeuroImage

Volume 32, Issue 1, 1 August 2006, Pages 256-265
NeuroImage

An fMRI study of cerebral processing of brush-evoked allodynia in neuropathic pain patients

https://doi.org/10.1016/j.neuroimage.2006.03.024Get rights and content

Abstract

Previous human imaging studies have revealed a network of brain regions involved in the processing of allodynic pain; this includes prefrontal areas, insula, cingulate cortex, primary and secondary somatosensory cortices and parietal association areas. In this study, the neural correlates of the perceived intensity of allodynic pain in neuropathic pain patients were investigated. In eight patients, dynamic mechanical allodynia was provoked and brain responses recorded using functional magnetic resonance imaging (fMRI). Voxels in which the magnitude of fMRI signal correlated linearly with the ratings of allodynic pain across the group were determined in a whole brain analysis using a general linear model. To ensure that activation reflected only allodynic pain ratings, a nuisance variable containing ratings of ongoing pain was included in the analysis. We found that the magnitude of activation in the caudal anterior insula (cAI) correlates with the perceived intensity of allodynic pain across subjects, independent of the level of ongoing pain.

However, the peak of activation in the allodynic condition was located in the rostral portion (rAI). This matches the representation of other clinical pain syndromes, confirmed by a literature review. In contrast, experimental pain in healthy volunteers resides predominantly in the cAI, as shown by the same literature review. Taken together, our data and the literature review suggest a functional segregation of anterior insular cortex.

Introduction

Pain in response to a normally innocuous stimulus, i.e. allodynia, is an important characteristic of neuropathic pain and is one of its diagnostic criteria (Dworkin et al., 2003). Cerebral responses to provoked neuropathic pain have been investigated in several patient studies using different imaging modalities such as functional magnetic resonance imaging (fMRI) (Peyron et al., 2000a, Peyron et al., 2004), positron emission tomography (PET) (Peyron et al., 1998, Peyron et al., 2000a, Petrovic et al., 1999) and magnetoencephalography (MEG) (Lorenz et al., 1998, Maihofner et al., 2003). These studies revealed that a variety of brain regions are involved in the processing of allodynic pain, such as insular cortex, anterior cingulate cortex, primary and secondary somatosensory cortices, thalamus, cerebellum, prefrontal cortex and parietal association areas. Instead of being uniquely associated with allodynic pain, these regions are commonly involved in the processing of experimental pain in healthy volunteers as shown in a large body of imaging studies (see reviews by Apkarian et al., 2005, Peyron et al., 2000b).

The perceived intensity of experimental pain is strongly associated with the magnitude of PET and fMRI signals across several brain regions (Bornhovd et al., 2002, Coghill et al., 1999, Craig et al., 2000, Derbyshire et al., 1997, Porro, 2003, Tolle et al., 1999). Among the brain areas where the perceived intensity of experimental pain is encoded are sensorimotor cortices, cingulate cortex and insula. A recent meta-analysis suggests that clinical pain processing differs from experimental pain processing (Apkarian et al., 2005), and the question arises if the perceived intensity of clinical and experimental pain is differently encoded. Data on the encoding of perceived intensity of clinical pain have been published (Petrovic et al., 1999, Willoch et al., 2003); however, these studies either investigate ongoing pain (Willoch et al., 2003) or “total pain intensity”, consisting of provoked and ongoing pain (Petrovic et al., 1999), contrasting the phasic nature of stimuli used in most studies of experimental pain.

Here, we examine specifically if the magnitude of the fMRI signal reflects the perceived intensity of provoked allodynic pain, independent of the ongoing pain component; in addition, we expand the existing literature of central processing of brush-evoked allodynia in neuropathic pain patients.

Section snippets

Patients

FMRI data were obtained from 8 neuropathic pain patients whose clinical details are outlined in Table 1. Patients were recruited from the Oxford Pain Relief Unit and selected according to the following criteria: (1) presence of neuropathic pain of peripheral origin or caused by plexus avulsion, (2) presence of pronounced dynamic mechanical allodynia, (3) constant ongoing pain or no ongoing pain and (4) absence of any major psychiatric disorder or systemic disease. To ensure a constant

Clinical and psychophysical data

According to BDI scores, 2 patients displayed mild symptoms of depression, and in one patient, there was an indication of moderate depressive symptoms (BDI score: 20), for the remaining, BDI scores were in the range of non-depressed values. All State-Trait Anxiety Inventory scores, both for trait and for state scales, lay in the range of adult normative data.

Pain ratings of the allodynic stimulation in the imaging session ranged from 3.5 to 9 (mean: 5.8, SD: 1.9, median: 6) (Table 1). None of

Discussion

With this study, we expand results of previous imaging studies of clinical allodynia (Petrovic et al., 1999, Peyron et al., 1998, Peyron et al., 2004) by demonstrating that the perceived intensity of brush-evoked allodynia pain is reflected by the magnitude of fMRI signal in the caudal anterior insula (cAI) in neuropathic pain patients. This matches the portion of the insula where encoding of perceived intensity of experimental pain in healthy volunteers is consistently found (Coghill et al.,

Acknowledgments

We are very grateful to all patients who were willing to participate in this study. We thank Dr. Giandomenico Iannetti for valuable comments on an earlier version of the manuscript. We gratefully acknowledge financial assistance by GlaxoSmithKline (PS), HEFCE (IT), The Dr. Hawden Trust for Humane Research (JB) and MRC (FMRIB Centre).

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