Brainstem processing of peripheral punctate stimuli in patients with and without chemotherapy-induced peripheral neuropathy: a prospective cohort functional MRI study

Marta Seretny, Liana Romaniuk, Heather Sibley, Catherine Warnaby, Jonathan Murnane, Neil Roberts, Stephen M. Lawrie, Lesley Colvin, Irene Tracey, Marie Fallon

Research output: Contribution to journalMeeting abstract

Abstract

Background: Chemotherapy-induced peripheral neuropathy affects 30% of cancer survivors. Findings from animal studies suggest that brainstem descending inhibitory pathways are important in chronic neuropathic pain. An aberrant descending pain modulation system has been implicated in human neuropathic pain. Whether aberrant descending pain modulation before chemotherapy is associated with development of chemotherapy-induced peripheral neuropathy is unclear. We aimed to assess descending pain modulation systems using functional MRI (fMRI) in chemotherapy-naive patients with cancer to determine whether differences are associated with subsequent development of the neuropathy.

Methods: In this multicentre prospective cohort study, adult patients with cancer and no chronic pain, neuropathy, or risk factors for neuropathy were recruited from the oncology clinic before onset of chemotherapy. After patients had given written informed consent, descending inhibitory pathways were challenged (jittered punctate stimuli 256 mN Somedic von Frey filament) during a 3T fMRI scan, and images analysed with FSL software. Sample size was based on published fMRI estimates. Chemotherapy-induced peripheral neuropathy was diagnosed with the CIPN20 questionnaire.

Findings: 30 patients were recruited (mean age 60·4 years [SD 7·9]). We report a preliminary analysis of the first 12 patients (60·6 [8·3], six women); six had colorectal cancer, four gynaecological cancer, and two lung cancer. Seven patients (three men, four women) developed chemotherapy-induced peripheral neuropathy. After data brain extraction, registration, B0 unwarping, and motion correction, FEAT was used for first and second level analysis. Mean group level comparisons between patients with and without the neuropathy were conducted with mixed-effects analysis (z threshold 2·3, regions considered significant at p<0·05, cluster uncorrected for preliminary analysis) and adjusted for sex, age, and cancer type. Patients with chemotherapy-induced peripheral neuropathy had increased activation in the nucleus cuneiformis and primary somatosensory cortex compared with patients who did not develop the disorder.

Interpretation: These preliminary results suggest that baseline differences exist, before peripheral nerve injury, in the descending pain modulation system of patients who go on to develop chemotherapy-induced peripheral neuropathy. These differences might aid development of biomarkers to guide chemotherapy choices. Limitations of the study include the small sample size for the present analysis, the observational nature of the study, and the possibility of unknown confounders. Strengths include the prospective design in a unique patient cohort and the high sensitivity of fMRI.
Original languageEnglish
Pages (from-to)S15
Number of pages1
JournalThe Lancet
Volume387
Issue numberSupplement 1
Early online date25 Feb 2016
DOIs
Publication statusPublished - 25 Feb 2016

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Peripheral Nervous System Diseases
Brain Stem
Magnetic Resonance Imaging
Drug Therapy
Pain
Neuralgia
Chronic Pain
Sample Size
Lung Neoplasms
Neoplasms
Peripheral Nerve Injuries
Somatosensory Cortex
Informed Consent
Observational Studies
Survivors
Colorectal Neoplasms
Cohort Studies
Software
Biomarkers
Prospective Studies

Cite this

Seretny, Marta ; Romaniuk, Liana ; Sibley, Heather ; Warnaby, Catherine ; Murnane, Jonathan ; Roberts, Neil ; Lawrie, Stephen M. ; Colvin, Lesley ; Tracey, Irene ; Fallon, Marie. / Brainstem processing of peripheral punctate stimuli in patients with and without chemotherapy-induced peripheral neuropathy : a prospective cohort functional MRI study. In: The Lancet. 2016 ; Vol. 387, No. Supplement 1. pp. S15.
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title = "Brainstem processing of peripheral punctate stimuli in patients with and without chemotherapy-induced peripheral neuropathy: a prospective cohort functional MRI study",
abstract = "Background: Chemotherapy-induced peripheral neuropathy affects 30{\%} of cancer survivors. Findings from animal studies suggest that brainstem descending inhibitory pathways are important in chronic neuropathic pain. An aberrant descending pain modulation system has been implicated in human neuropathic pain. Whether aberrant descending pain modulation before chemotherapy is associated with development of chemotherapy-induced peripheral neuropathy is unclear. We aimed to assess descending pain modulation systems using functional MRI (fMRI) in chemotherapy-naive patients with cancer to determine whether differences are associated with subsequent development of the neuropathy.Methods: In this multicentre prospective cohort study, adult patients with cancer and no chronic pain, neuropathy, or risk factors for neuropathy were recruited from the oncology clinic before onset of chemotherapy. After patients had given written informed consent, descending inhibitory pathways were challenged (jittered punctate stimuli 256 mN Somedic von Frey filament) during a 3T fMRI scan, and images analysed with FSL software. Sample size was based on published fMRI estimates. Chemotherapy-induced peripheral neuropathy was diagnosed with the CIPN20 questionnaire.Findings: 30 patients were recruited (mean age 60·4 years [SD 7·9]). We report a preliminary analysis of the first 12 patients (60·6 [8·3], six women); six had colorectal cancer, four gynaecological cancer, and two lung cancer. Seven patients (three men, four women) developed chemotherapy-induced peripheral neuropathy. After data brain extraction, registration, B0 unwarping, and motion correction, FEAT was used for first and second level analysis. Mean group level comparisons between patients with and without the neuropathy were conducted with mixed-effects analysis (z threshold 2·3, regions considered significant at p<0·05, cluster uncorrected for preliminary analysis) and adjusted for sex, age, and cancer type. Patients with chemotherapy-induced peripheral neuropathy had increased activation in the nucleus cuneiformis and primary somatosensory cortex compared with patients who did not develop the disorder.Interpretation: These preliminary results suggest that baseline differences exist, before peripheral nerve injury, in the descending pain modulation system of patients who go on to develop chemotherapy-induced peripheral neuropathy. These differences might aid development of biomarkers to guide chemotherapy choices. Limitations of the study include the small sample size for the present analysis, the observational nature of the study, and the possibility of unknown confounders. Strengths include the prospective design in a unique patient cohort and the high sensitivity of fMRI.",
author = "Marta Seretny and Liana Romaniuk and Heather Sibley and Catherine Warnaby and Jonathan Murnane and Neil Roberts and Lawrie, {Stephen M.} and Lesley Colvin and Irene Tracey and Marie Fallon",
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Seretny, M, Romaniuk, L, Sibley, H, Warnaby, C, Murnane, J, Roberts, N, Lawrie, SM, Colvin, L, Tracey, I & Fallon, M 2016, 'Brainstem processing of peripheral punctate stimuli in patients with and without chemotherapy-induced peripheral neuropathy: a prospective cohort functional MRI study', The Lancet, vol. 387, no. Supplement 1, pp. S15. https://doi.org/10.1016/S0140-6736(16)00402-5

Brainstem processing of peripheral punctate stimuli in patients with and without chemotherapy-induced peripheral neuropathy : a prospective cohort functional MRI study. / Seretny, Marta; Romaniuk, Liana; Sibley, Heather; Warnaby, Catherine; Murnane, Jonathan; Roberts, Neil; Lawrie, Stephen M.; Colvin, Lesley; Tracey, Irene; Fallon, Marie.

In: The Lancet, Vol. 387, No. Supplement 1, 25.02.2016, p. S15.

Research output: Contribution to journalMeeting abstract

TY - JOUR

T1 - Brainstem processing of peripheral punctate stimuli in patients with and without chemotherapy-induced peripheral neuropathy

T2 - a prospective cohort functional MRI study

AU - Seretny, Marta

AU - Romaniuk, Liana

AU - Sibley, Heather

AU - Warnaby, Catherine

AU - Murnane, Jonathan

AU - Roberts, Neil

AU - Lawrie, Stephen M.

AU - Colvin, Lesley

AU - Tracey, Irene

AU - Fallon, Marie

N1 - Funding: Wellcome Trust via Scottish Translational Medicine and Therapeutics Initiative (STMTI).

PY - 2016/2/25

Y1 - 2016/2/25

N2 - Background: Chemotherapy-induced peripheral neuropathy affects 30% of cancer survivors. Findings from animal studies suggest that brainstem descending inhibitory pathways are important in chronic neuropathic pain. An aberrant descending pain modulation system has been implicated in human neuropathic pain. Whether aberrant descending pain modulation before chemotherapy is associated with development of chemotherapy-induced peripheral neuropathy is unclear. We aimed to assess descending pain modulation systems using functional MRI (fMRI) in chemotherapy-naive patients with cancer to determine whether differences are associated with subsequent development of the neuropathy.Methods: In this multicentre prospective cohort study, adult patients with cancer and no chronic pain, neuropathy, or risk factors for neuropathy were recruited from the oncology clinic before onset of chemotherapy. After patients had given written informed consent, descending inhibitory pathways were challenged (jittered punctate stimuli 256 mN Somedic von Frey filament) during a 3T fMRI scan, and images analysed with FSL software. Sample size was based on published fMRI estimates. Chemotherapy-induced peripheral neuropathy was diagnosed with the CIPN20 questionnaire.Findings: 30 patients were recruited (mean age 60·4 years [SD 7·9]). We report a preliminary analysis of the first 12 patients (60·6 [8·3], six women); six had colorectal cancer, four gynaecological cancer, and two lung cancer. Seven patients (three men, four women) developed chemotherapy-induced peripheral neuropathy. After data brain extraction, registration, B0 unwarping, and motion correction, FEAT was used for first and second level analysis. Mean group level comparisons between patients with and without the neuropathy were conducted with mixed-effects analysis (z threshold 2·3, regions considered significant at p<0·05, cluster uncorrected for preliminary analysis) and adjusted for sex, age, and cancer type. Patients with chemotherapy-induced peripheral neuropathy had increased activation in the nucleus cuneiformis and primary somatosensory cortex compared with patients who did not develop the disorder.Interpretation: These preliminary results suggest that baseline differences exist, before peripheral nerve injury, in the descending pain modulation system of patients who go on to develop chemotherapy-induced peripheral neuropathy. These differences might aid development of biomarkers to guide chemotherapy choices. Limitations of the study include the small sample size for the present analysis, the observational nature of the study, and the possibility of unknown confounders. Strengths include the prospective design in a unique patient cohort and the high sensitivity of fMRI.

AB - Background: Chemotherapy-induced peripheral neuropathy affects 30% of cancer survivors. Findings from animal studies suggest that brainstem descending inhibitory pathways are important in chronic neuropathic pain. An aberrant descending pain modulation system has been implicated in human neuropathic pain. Whether aberrant descending pain modulation before chemotherapy is associated with development of chemotherapy-induced peripheral neuropathy is unclear. We aimed to assess descending pain modulation systems using functional MRI (fMRI) in chemotherapy-naive patients with cancer to determine whether differences are associated with subsequent development of the neuropathy.Methods: In this multicentre prospective cohort study, adult patients with cancer and no chronic pain, neuropathy, or risk factors for neuropathy were recruited from the oncology clinic before onset of chemotherapy. After patients had given written informed consent, descending inhibitory pathways were challenged (jittered punctate stimuli 256 mN Somedic von Frey filament) during a 3T fMRI scan, and images analysed with FSL software. Sample size was based on published fMRI estimates. Chemotherapy-induced peripheral neuropathy was diagnosed with the CIPN20 questionnaire.Findings: 30 patients were recruited (mean age 60·4 years [SD 7·9]). We report a preliminary analysis of the first 12 patients (60·6 [8·3], six women); six had colorectal cancer, four gynaecological cancer, and two lung cancer. Seven patients (three men, four women) developed chemotherapy-induced peripheral neuropathy. After data brain extraction, registration, B0 unwarping, and motion correction, FEAT was used for first and second level analysis. Mean group level comparisons between patients with and without the neuropathy were conducted with mixed-effects analysis (z threshold 2·3, regions considered significant at p<0·05, cluster uncorrected for preliminary analysis) and adjusted for sex, age, and cancer type. Patients with chemotherapy-induced peripheral neuropathy had increased activation in the nucleus cuneiformis and primary somatosensory cortex compared with patients who did not develop the disorder.Interpretation: These preliminary results suggest that baseline differences exist, before peripheral nerve injury, in the descending pain modulation system of patients who go on to develop chemotherapy-induced peripheral neuropathy. These differences might aid development of biomarkers to guide chemotherapy choices. Limitations of the study include the small sample size for the present analysis, the observational nature of the study, and the possibility of unknown confounders. Strengths include the prospective design in a unique patient cohort and the high sensitivity of fMRI.

U2 - 10.1016/S0140-6736(16)00402-5

DO - 10.1016/S0140-6736(16)00402-5

M3 - Meeting abstract

VL - 387

SP - S15

JO - Lancet

JF - Lancet

SN - 0140-6736

IS - Supplement 1

ER -