Association of neuropathic limb pain in multiple sclerosis with cognition , behaviour, and measures of brain structure: a case-control MRI neuroimaging study

Peter Foley (Lead / Corresponding author), Cyril Pernet, Maria Valdes Hernandez, Ramune Margeviciute, Neil Roberts, Yazhou Kong, Robert Sellar, Lesley Colvin, Christopher Weir, Thomas Bak, Siddharthan Chandran, Irene Tracey, Marie Fallon

Research output: Contribution to journalMeeting abstract

Abstract

Background: Neuropathic limb pain commonly affects people with multiple sclerosis but is incompletely understood. Emotional, psychological, and executive functions, acting via brainstem pathways, have been linked to pain modulation. We aimed to compare these functions, as well as MRI measures of brain structure, in adults with multiple sclerosis with and without pain. We hypothesised that, in those with pain, the ability to suppress or reappraise stimuli would be reduced, with altered lesion distribution or grey matter volume loss.

Methods: Adults with relapsing remitting multiple sclerosis with and without neuropathic limb pain were recruited from clinic; they were matched for sex, age, disability, duration of multiple sclerosis, and education. None used strong opioids. Participants underwent targeted psychological and neuropsychological assessment, with 1 mm3 MPRAGE (magnetisation-prepared rapid gradient-echo), T2, and FLAIR (fluid attenuation inversion recovery) brain MRI at 3 Tesla. Distribution of multiple sclerosis lesions was analysed by semi-automated segmentation, probability mapping, and permutation analysis. Grey matter volume was analysed by voxel based morphometry (VBM). Significance thresholds adjusted for multiple comparisons.

Findings: We recruited 31 adults with pain and 16 matched controls. Participants with pain more often used adjuvant analgesics than did controls (22/31 [71·0%] vs 3/16 [18·8%], p=0·002). They described more depressive symptoms (Hospital Depression Scale median 5·0 [IQR 2·0–8·5] vs 1·5 [0·0–6·0], p=0·005), fatigue (Fatigue Severity Scale 51·0 [43·5–56·5] vs 33·0 [26·8–43·8], p=0·003), and catastrophising (Pain Catastrophizing Scale 16·0 [12·5–25·0] vs 8·5 [0·8–15·0], p=0·004). Patients with pain displayed impaired reappraisal (Delis Kaplan card test set 1 recognition scores 12·0 [8·0–20·0] vs 24·0 [21·0–24·0], p<0·0001). Multiple sclerosis lesion volume overall did not significantly differ between groups. Brainstem lesion volume was significantly higher in those with pain (p=0·0049). VBM did not reveal altered cortical volumes between groups.

Interpretation: This cross-sectional study suggests that neuropathic limb pain in relapsing remitting multiple sclerosis is associated with specific emotional, psychological, and executive dysfunction, and brainstem location of lesions. Adjuvant analgesics can affect neuropsychological performance, but are less likely to affect imaging measures. Longitudinal or interventional studies could clarify any mechanistic or therapeutic implications of our findings.
Original languageEnglish
Pages (from-to)S45
Number of pages1
JournalThe Lancet
Volume387
Issue numberSupplement 1
DOIs
Publication statusPublished - 25 Feb 2016

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Neuralgia
Neuroimaging
Cognition
Multiple Sclerosis
Extremities
Pain
Brain
Brain Stem
Relapsing-Remitting Multiple Sclerosis
Psychology
Fatigue
Analgesics
Catastrophization
Depression
Aptitude
Executive Function
Opioid Analgesics
Cross-Sectional Studies
Education

Cite this

Foley, Peter ; Pernet, Cyril ; Valdes Hernandez, Maria ; Margeviciute, Ramune ; Roberts, Neil ; Kong, Yazhou ; Sellar, Robert ; Colvin, Lesley ; Weir, Christopher ; Bak, Thomas ; Chandran, Siddharthan ; Tracey, Irene ; Fallon, Marie. / Association of neuropathic limb pain in multiple sclerosis with cognition , behaviour, and measures of brain structure : a case-control MRI neuroimaging study. In: The Lancet. 2016 ; Vol. 387, No. Supplement 1. pp. S45.
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title = "Association of neuropathic limb pain in multiple sclerosis with cognition , behaviour, and measures of brain structure: a case-control MRI neuroimaging study",
abstract = "Background: Neuropathic limb pain commonly affects people with multiple sclerosis but is incompletely understood. Emotional, psychological, and executive functions, acting via brainstem pathways, have been linked to pain modulation. We aimed to compare these functions, as well as MRI measures of brain structure, in adults with multiple sclerosis with and without pain. We hypothesised that, in those with pain, the ability to suppress or reappraise stimuli would be reduced, with altered lesion distribution or grey matter volume loss.Methods: Adults with relapsing remitting multiple sclerosis with and without neuropathic limb pain were recruited from clinic; they were matched for sex, age, disability, duration of multiple sclerosis, and education. None used strong opioids. Participants underwent targeted psychological and neuropsychological assessment, with 1 mm3 MPRAGE (magnetisation-prepared rapid gradient-echo), T2, and FLAIR (fluid attenuation inversion recovery) brain MRI at 3 Tesla. Distribution of multiple sclerosis lesions was analysed by semi-automated segmentation, probability mapping, and permutation analysis. Grey matter volume was analysed by voxel based morphometry (VBM). Significance thresholds adjusted for multiple comparisons.Findings: We recruited 31 adults with pain and 16 matched controls. Participants with pain more often used adjuvant analgesics than did controls (22/31 [71·0{\%}] vs 3/16 [18·8{\%}], p=0·002). They described more depressive symptoms (Hospital Depression Scale median 5·0 [IQR 2·0–8·5] vs 1·5 [0·0–6·0], p=0·005), fatigue (Fatigue Severity Scale 51·0 [43·5–56·5] vs 33·0 [26·8–43·8], p=0·003), and catastrophising (Pain Catastrophizing Scale 16·0 [12·5–25·0] vs 8·5 [0·8–15·0], p=0·004). Patients with pain displayed impaired reappraisal (Delis Kaplan card test set 1 recognition scores 12·0 [8·0–20·0] vs 24·0 [21·0–24·0], p<0·0001). Multiple sclerosis lesion volume overall did not significantly differ between groups. Brainstem lesion volume was significantly higher in those with pain (p=0·0049). VBM did not reveal altered cortical volumes between groups.Interpretation: This cross-sectional study suggests that neuropathic limb pain in relapsing remitting multiple sclerosis is associated with specific emotional, psychological, and executive dysfunction, and brainstem location of lesions. Adjuvant analgesics can affect neuropsychological performance, but are less likely to affect imaging measures. Longitudinal or interventional studies could clarify any mechanistic or therapeutic implications of our findings.",
author = "Peter Foley and Cyril Pernet and {Valdes Hernandez}, Maria and Ramune Margeviciute and Neil Roberts and Yazhou Kong and Robert Sellar and Lesley Colvin and Christopher Weir and Thomas Bak and Siddharthan Chandran and Irene Tracey and Marie Fallon",
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Foley, P, Pernet, C, Valdes Hernandez, M, Margeviciute, R, Roberts, N, Kong, Y, Sellar, R, Colvin, L, Weir, C, Bak, T, Chandran, S, Tracey, I & Fallon, M 2016, 'Association of neuropathic limb pain in multiple sclerosis with cognition , behaviour, and measures of brain structure: a case-control MRI neuroimaging study', The Lancet, vol. 387, no. Supplement 1, pp. S45. https://doi.org/10.1016/S0140-6736(16)00432-3

Association of neuropathic limb pain in multiple sclerosis with cognition , behaviour, and measures of brain structure : a case-control MRI neuroimaging study. / Foley, Peter (Lead / Corresponding author); Pernet, Cyril; Valdes Hernandez, Maria; Margeviciute, Ramune; Roberts, Neil; Kong, Yazhou; Sellar, Robert; Colvin, Lesley; Weir, Christopher; Bak, Thomas; Chandran, Siddharthan; Tracey, Irene; Fallon, Marie.

In: The Lancet, Vol. 387, No. Supplement 1, 25.02.2016, p. S45.

Research output: Contribution to journalMeeting abstract

TY - JOUR

T1 - Association of neuropathic limb pain in multiple sclerosis with cognition , behaviour, and measures of brain structure

T2 - a case-control MRI neuroimaging study

AU - Foley, Peter

AU - Pernet, Cyril

AU - Valdes Hernandez, Maria

AU - Margeviciute, Ramune

AU - Roberts, Neil

AU - Kong, Yazhou

AU - Sellar, Robert

AU - Colvin, Lesley

AU - Weir, Christopher

AU - Bak, Thomas

AU - Chandran, Siddharthan

AU - Tracey, Irene

AU - Fallon, Marie

PY - 2016/2/25

Y1 - 2016/2/25

N2 - Background: Neuropathic limb pain commonly affects people with multiple sclerosis but is incompletely understood. Emotional, psychological, and executive functions, acting via brainstem pathways, have been linked to pain modulation. We aimed to compare these functions, as well as MRI measures of brain structure, in adults with multiple sclerosis with and without pain. We hypothesised that, in those with pain, the ability to suppress or reappraise stimuli would be reduced, with altered lesion distribution or grey matter volume loss.Methods: Adults with relapsing remitting multiple sclerosis with and without neuropathic limb pain were recruited from clinic; they were matched for sex, age, disability, duration of multiple sclerosis, and education. None used strong opioids. Participants underwent targeted psychological and neuropsychological assessment, with 1 mm3 MPRAGE (magnetisation-prepared rapid gradient-echo), T2, and FLAIR (fluid attenuation inversion recovery) brain MRI at 3 Tesla. Distribution of multiple sclerosis lesions was analysed by semi-automated segmentation, probability mapping, and permutation analysis. Grey matter volume was analysed by voxel based morphometry (VBM). Significance thresholds adjusted for multiple comparisons.Findings: We recruited 31 adults with pain and 16 matched controls. Participants with pain more often used adjuvant analgesics than did controls (22/31 [71·0%] vs 3/16 [18·8%], p=0·002). They described more depressive symptoms (Hospital Depression Scale median 5·0 [IQR 2·0–8·5] vs 1·5 [0·0–6·0], p=0·005), fatigue (Fatigue Severity Scale 51·0 [43·5–56·5] vs 33·0 [26·8–43·8], p=0·003), and catastrophising (Pain Catastrophizing Scale 16·0 [12·5–25·0] vs 8·5 [0·8–15·0], p=0·004). Patients with pain displayed impaired reappraisal (Delis Kaplan card test set 1 recognition scores 12·0 [8·0–20·0] vs 24·0 [21·0–24·0], p<0·0001). Multiple sclerosis lesion volume overall did not significantly differ between groups. Brainstem lesion volume was significantly higher in those with pain (p=0·0049). VBM did not reveal altered cortical volumes between groups.Interpretation: This cross-sectional study suggests that neuropathic limb pain in relapsing remitting multiple sclerosis is associated with specific emotional, psychological, and executive dysfunction, and brainstem location of lesions. Adjuvant analgesics can affect neuropsychological performance, but are less likely to affect imaging measures. Longitudinal or interventional studies could clarify any mechanistic or therapeutic implications of our findings.

AB - Background: Neuropathic limb pain commonly affects people with multiple sclerosis but is incompletely understood. Emotional, psychological, and executive functions, acting via brainstem pathways, have been linked to pain modulation. We aimed to compare these functions, as well as MRI measures of brain structure, in adults with multiple sclerosis with and without pain. We hypothesised that, in those with pain, the ability to suppress or reappraise stimuli would be reduced, with altered lesion distribution or grey matter volume loss.Methods: Adults with relapsing remitting multiple sclerosis with and without neuropathic limb pain were recruited from clinic; they were matched for sex, age, disability, duration of multiple sclerosis, and education. None used strong opioids. Participants underwent targeted psychological and neuropsychological assessment, with 1 mm3 MPRAGE (magnetisation-prepared rapid gradient-echo), T2, and FLAIR (fluid attenuation inversion recovery) brain MRI at 3 Tesla. Distribution of multiple sclerosis lesions was analysed by semi-automated segmentation, probability mapping, and permutation analysis. Grey matter volume was analysed by voxel based morphometry (VBM). Significance thresholds adjusted for multiple comparisons.Findings: We recruited 31 adults with pain and 16 matched controls. Participants with pain more often used adjuvant analgesics than did controls (22/31 [71·0%] vs 3/16 [18·8%], p=0·002). They described more depressive symptoms (Hospital Depression Scale median 5·0 [IQR 2·0–8·5] vs 1·5 [0·0–6·0], p=0·005), fatigue (Fatigue Severity Scale 51·0 [43·5–56·5] vs 33·0 [26·8–43·8], p=0·003), and catastrophising (Pain Catastrophizing Scale 16·0 [12·5–25·0] vs 8·5 [0·8–15·0], p=0·004). Patients with pain displayed impaired reappraisal (Delis Kaplan card test set 1 recognition scores 12·0 [8·0–20·0] vs 24·0 [21·0–24·0], p<0·0001). Multiple sclerosis lesion volume overall did not significantly differ between groups. Brainstem lesion volume was significantly higher in those with pain (p=0·0049). VBM did not reveal altered cortical volumes between groups.Interpretation: This cross-sectional study suggests that neuropathic limb pain in relapsing remitting multiple sclerosis is associated with specific emotional, psychological, and executive dysfunction, and brainstem location of lesions. Adjuvant analgesics can affect neuropsychological performance, but are less likely to affect imaging measures. Longitudinal or interventional studies could clarify any mechanistic or therapeutic implications of our findings.

U2 - 10.1016/S0140-6736(16)00432-3

DO - 10.1016/S0140-6736(16)00432-3

M3 - Meeting abstract

VL - 387

SP - S45

JO - Lancet

JF - Lancet

SN - 0140-6736

IS - Supplement 1

ER -