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. 2014 May 12;9(5):e96474.
doi: 10.1371/journal.pone.0096474. eCollection 2014.

Central pain processing in chronic chemotherapy-induced peripheral neuropathy: a functional magnetic resonance imaging study

Affiliations

Central pain processing in chronic chemotherapy-induced peripheral neuropathy: a functional magnetic resonance imaging study

Elaine G Boland et al. PLoS One. .

Abstract

Life expectancy in multiple myeloma has significantly increased. However, a high incidence of chemotherapy induced peripheral neuropathy (CIPN) can negatively influence quality of life during this period. This study applied functional magnetic resonance imaging (fMRI) to compare areas associated with central pain processing in patients with multiple myeloma who had chemotherapy induced peripheral neuropathy (MM-CIPN) with those from healthy volunteers (HV). Twenty-four participants (n = 12 MM-CIPN, n = 12 HV) underwent Blood Oxygen Level-Dependent (BOLD) fMRI at 3T whilst noxious heat-pain stimuli were applied to the foot and then thigh. Patients with MM-CIPN demonstrated greater activation during painful stimulation in the precuneus compared to HV (p = 0.014, FWE-corrected). Patients with MM-CIPN exhibited hypo-activation of the right superior frontal gyrus compared to HV (p = 0.031, FWE-corrected). Significant positive correlation existed between the total neuropathy score (reduced version) and activation in the frontal operculum (close to insular cortex) during foot stimulation in patients with MM-CIPN (p = 0.03, FWE-corrected; adjusted R2 = 0.87). Painful stimuli delivered to MM-CIPN patients evoke differential activation of distinct cortical regions, reflecting a unique pattern of central pain processing compared with healthy volunteers. This characteristic activation pattern associated with pain furthers the understanding of the pathophysiology of painful chemotherapy induced peripheral neuropathy. Functional MRI provides a tool for monitoring cerebral changes during anti-cancer and analgesic treatment.

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Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Figure 1
Figure 1. CIPN-myeloma patients demonstrated a) hypo-activation of superior frontal gyrus during heat-pain stimulation, compared with healthy volunteers.
Functional imaging data are shown overlaid on both axial (z = 48 mm) and sagittal (x = 6 mm) slices through a canonical single-subject T1-weighted image. For display purposes, the statistical threshold is pb) Contrast estimates and 90% CI at co-ordinate 6, 39, 48 for both healthy volunteer and CIPN-myeloma patient groups.
Figure 2
Figure 2. CIPN-myeloma patients demonstrated a0 hyper-activation of precuneus during heat-pain stimulation, compared with healthy volunteers.
Functional imaging data are shown overlaid on both axial (z = 27 mm) and sagittal (x = −18 mm) slices through a canonical single-subject T1-weighted image. For display purposes, the statistical threshold is pb) Contrast estimates and 90% CI at co-ordinate −18, −61, 27 for both healthy volunteer and CIPN-myeloma patient groups.
Figure 3
Figure 3. a: CIPN-myeloma patients demonstrated activation in the operculo-insular cortex.
This activation was during painful heat stimulation, the degree of which correlated with TNS-reduced version. For display purposes, the statistical threshold is pb: Linear correlation between the TNS-reduced version and BOLD response within the operculo-insular cortex.

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