Neuroimaging reveals a potential brain-based pre-existing mechanism that confers vulnerability to development of chronic painful chemotherapy-induced peripheral neuropathy (CIPN)

Marta Seretny; Liana Romaniuk; Heather Whalley; Kim Sladdin; Stephen M Lawrie; Catherine Elizabeth Warnaby; Neil Roberts; Lesley Colvin; Irene Tracey; Marie T Fallon

doi:10.1016/j.bja.2022.09.026

Neuroimaging reveals a potential brain-based pre-existing mechanism that confers vulnerability to development of chronic painful chemotherapy-induced peripheral neuropathy (CIPN)

Marta Seretny^*, Liana Romaniuk, Heather Whalley, Kim Sladdin, Stephen M Lawrie, Catherine Elizabeth Warnaby, Neil Roberts, Lesley Colvin, Irene Tracey, Marie T Fallon

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

Abstract / Description of output

Background
Chemotherapy-induced peripheral neuropathy (CIPN) is a debilitating condition impacting 30% of cancer survivors. This study is the first to explore whether a brain-based vulnerability to chronic sensory CIPN exists.
Methods
This prospective, multicentre cohort study recruited from three sites across Scotland. Brain functional MRI (fMRI) scans (3 Tesla) were carried out on chemotherapy naïve patients at a single fMRI centre in Edinburgh, Scotland. Nociceptive stimuli (with a 256 mN monofilament) were administered during the fMRI. Development of chronic sensory/painful CIPN (CIPN+) was determined based upon European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Chemotherapy-Induced Peripheral Neuropathy 20 changes conducted 9 months after chemotherapy, and imaging data analysed using standard software.
Results
Of 30 patients recruited (two lung, nine gynaecological, and 19 colorectal malignancies), data from 20 patients at 9 months after chemotherapy was available for analysis. Twelve were classified as CIPN+ (mean age, 63.2[9.6] yr, 9.6; six female), eight as CIPN– (mean age 62.9 [SD 5.5] yr, four female). In response to punctate stimulation, group contrast analysis showed that CIPN+ compared with CIPN– had robust activity in sensory, motor, attentional, and affective brain regions. An a priori chosen region-of-interest analysis focusing on the periaqueductal grey, an area hypothesised as relevant for developing CIPN+, showed significantly increased responses in CIPN– compared with CIPN+ patients. No difference in subcortical volumes between CIPN+ and CIPN– patients was detected.
Conclusions
Before administration of any chemotherapy or appearance of CIPN symptoms, we observed altered patterns of brain activity in response to nociceptive stimulation in patients who later developed chronic sensory CIPN. This suggests the possibility of a pre-existing vulnerability to developing CIPN centred on brainstem regions of the descending pain modulatory system.

Original language	English
Pages (from-to)	83-93
Journal	British Journal of Anaesthesia
Volume	130
Issue number	1
Early online date	14 Nov 2022
DOIs	https://doi.org/10.1016/j.bja.2022.09.026
Publication status	Published - 11 Jan 2023

Access to Document

10.1016/j.bja.2022.09.026

2022_Seretny_CIPN_BJA_draftAccepted author manuscript, 1.38 MBLicence: Creative Commons: Attribution (CC-BY)

Cite this

Seretny, M., Romaniuk, L., Whalley, H., Sladdin, K., Lawrie, S. M., Warnaby, C. E., Roberts, N., Colvin, L., Tracey, I., & Fallon, M. T. (2023). Neuroimaging reveals a potential brain-based pre-existing mechanism that confers vulnerability to development of chronic painful chemotherapy-induced peripheral neuropathy (CIPN). British Journal of Anaesthesia, 130(1), 83-93. https://doi.org/10.1016/j.bja.2022.09.026

@article{88b1401ccad347cba235dd9cea6c076c,

title = "Neuroimaging reveals a potential brain-based pre-existing mechanism that confers vulnerability to development of chronic painful chemotherapy-induced peripheral neuropathy (CIPN)",

abstract = "BackgroundChemotherapy-induced peripheral neuropathy (CIPN) is a debilitating condition impacting 30% of cancer survivors. This study is the first to explore whether a brain-based vulnerability to chronic sensory CIPN exists.MethodsThis prospective, multicentre cohort study recruited from three sites across Scotland. Brain functional MRI (fMRI) scans (3 Tesla) were carried out on chemotherapy na{\"i}ve patients at a single fMRI centre in Edinburgh, Scotland. Nociceptive stimuli (with a 256 mN monofilament) were administered during the fMRI. Development of chronic sensory/painful CIPN (CIPN+) was determined based upon European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Chemotherapy-Induced Peripheral Neuropathy 20 changes conducted 9 months after chemotherapy, and imaging data analysed using standard software.ResultsOf 30 patients recruited (two lung, nine gynaecological, and 19 colorectal malignancies), data from 20 patients at 9 months after chemotherapy was available for analysis. Twelve were classified as CIPN+ (mean age, 63.2[9.6] yr, 9.6; six female), eight as CIPN– (mean age 62.9 [SD 5.5] yr, four female). In response to punctate stimulation, group contrast analysis showed that CIPN+ compared with CIPN– had robust activity in sensory, motor, attentional, and affective brain regions. An a priori chosen region-of-interest analysis focusing on the periaqueductal grey, an area hypothesised as relevant for developing CIPN+, showed significantly increased responses in CIPN– compared with CIPN+ patients. No difference in subcortical volumes between CIPN+ and CIPN– patients was detected.ConclusionsBefore administration of any chemotherapy or appearance of CIPN symptoms, we observed altered patterns of brain activity in response to nociceptive stimulation in patients who later developed chronic sensory CIPN. This suggests the possibility of a pre-existing vulnerability to developing CIPN centred on brainstem regions of the descending pain modulatory system.",

author = "Marta Seretny and Liana Romaniuk and Heather Whalley and Kim Sladdin and Lawrie, {Stephen M} and Warnaby, {Catherine Elizabeth} and Neil Roberts and Lesley Colvin and Irene Tracey and Fallon, {Marie T}",

note = "Funding Information: Our heartfelt thanks to all the patients who gave their time for this study. We acknowledge and thank the Edinburgh Cancer Centre Palliative and Supportive Care Team for their help with data collection and running of the study. Thanks to Andrew Macintosh from the University of Edinburgh Department of Psychiatry for his support and input. Thank you also to Scott Semple senior physicist at the University of Edinburgh Imaging Centre, and Jonathan Brooks from the University of Bristol for their help with study set up. We acknowledge and thank the MRI Radiographers who conducted the study, and Jonathan Murnane, who helped with data collection. Finally, we acknowledge and thank Olivia Faull; Katy Vincent, Mark Jenkinson, and the FSL team from the University of Oxford for their input regarding data analysis for this study. Funding Information: MS and this study were funded by the Welcome Trust through the Scottish Translational Medicine and Therapeutics Initiative (STMTI). Publisher Copyright: {\textcopyright} 2022 British Journal of Anaesthesia",

year = "2023",

month = jan,

day = "11",

doi = "10.1016/j.bja.2022.09.026",

language = "English",

volume = "130",

pages = "83--93",

journal = "British Journal of Anaesthesia",

issn = "0007-0912",

publisher = "PROF SCI PUBL",

number = "1",

}

Seretny, M, Romaniuk, L , Whalley, H, Sladdin, K, Lawrie, SM, Warnaby, CE, Roberts, N, Colvin, L, Tracey, I & Fallon, MT 2023, 'Neuroimaging reveals a potential brain-based pre-existing mechanism that confers vulnerability to development of chronic painful chemotherapy-induced peripheral neuropathy (CIPN)', British Journal of Anaesthesia, vol. 130, no. 1, pp. 83-93. https://doi.org/10.1016/j.bja.2022.09.026

Neuroimaging reveals a potential brain-based pre-existing mechanism that confers vulnerability to development of chronic painful chemotherapy-induced peripheral neuropathy (CIPN). / Seretny, Marta; Romaniuk, Liana ; Whalley, Heather et al.
In: British Journal of Anaesthesia, Vol. 130, No. 1, 11.01.2023, p. 83-93.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

T1 - Neuroimaging reveals a potential brain-based pre-existing mechanism that confers vulnerability to development of chronic painful chemotherapy-induced peripheral neuropathy (CIPN)

AU - Seretny, Marta

AU - Romaniuk, Liana

AU - Whalley, Heather

AU - Sladdin, Kim

AU - Lawrie, Stephen M

AU - Warnaby, Catherine Elizabeth

AU - Roberts, Neil

AU - Colvin, Lesley

AU - Tracey, Irene

AU - Fallon, Marie T

N1 - Funding Information: Our heartfelt thanks to all the patients who gave their time for this study. We acknowledge and thank the Edinburgh Cancer Centre Palliative and Supportive Care Team for their help with data collection and running of the study. Thanks to Andrew Macintosh from the University of Edinburgh Department of Psychiatry for his support and input. Thank you also to Scott Semple senior physicist at the University of Edinburgh Imaging Centre, and Jonathan Brooks from the University of Bristol for their help with study set up. We acknowledge and thank the MRI Radiographers who conducted the study, and Jonathan Murnane, who helped with data collection. Finally, we acknowledge and thank Olivia Faull; Katy Vincent, Mark Jenkinson, and the FSL team from the University of Oxford for their input regarding data analysis for this study. Funding Information: MS and this study were funded by the Welcome Trust through the Scottish Translational Medicine and Therapeutics Initiative (STMTI). Publisher Copyright: © 2022 British Journal of Anaesthesia

PY - 2023/1/11

Y1 - 2023/1/11

N2 - BackgroundChemotherapy-induced peripheral neuropathy (CIPN) is a debilitating condition impacting 30% of cancer survivors. This study is the first to explore whether a brain-based vulnerability to chronic sensory CIPN exists.MethodsThis prospective, multicentre cohort study recruited from three sites across Scotland. Brain functional MRI (fMRI) scans (3 Tesla) were carried out on chemotherapy naïve patients at a single fMRI centre in Edinburgh, Scotland. Nociceptive stimuli (with a 256 mN monofilament) were administered during the fMRI. Development of chronic sensory/painful CIPN (CIPN+) was determined based upon European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Chemotherapy-Induced Peripheral Neuropathy 20 changes conducted 9 months after chemotherapy, and imaging data analysed using standard software.ResultsOf 30 patients recruited (two lung, nine gynaecological, and 19 colorectal malignancies), data from 20 patients at 9 months after chemotherapy was available for analysis. Twelve were classified as CIPN+ (mean age, 63.2[9.6] yr, 9.6; six female), eight as CIPN– (mean age 62.9 [SD 5.5] yr, four female). In response to punctate stimulation, group contrast analysis showed that CIPN+ compared with CIPN– had robust activity in sensory, motor, attentional, and affective brain regions. An a priori chosen region-of-interest analysis focusing on the periaqueductal grey, an area hypothesised as relevant for developing CIPN+, showed significantly increased responses in CIPN– compared with CIPN+ patients. No difference in subcortical volumes between CIPN+ and CIPN– patients was detected.ConclusionsBefore administration of any chemotherapy or appearance of CIPN symptoms, we observed altered patterns of brain activity in response to nociceptive stimulation in patients who later developed chronic sensory CIPN. This suggests the possibility of a pre-existing vulnerability to developing CIPN centred on brainstem regions of the descending pain modulatory system.

AB - BackgroundChemotherapy-induced peripheral neuropathy (CIPN) is a debilitating condition impacting 30% of cancer survivors. This study is the first to explore whether a brain-based vulnerability to chronic sensory CIPN exists.MethodsThis prospective, multicentre cohort study recruited from three sites across Scotland. Brain functional MRI (fMRI) scans (3 Tesla) were carried out on chemotherapy naïve patients at a single fMRI centre in Edinburgh, Scotland. Nociceptive stimuli (with a 256 mN monofilament) were administered during the fMRI. Development of chronic sensory/painful CIPN (CIPN+) was determined based upon European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Chemotherapy-Induced Peripheral Neuropathy 20 changes conducted 9 months after chemotherapy, and imaging data analysed using standard software.ResultsOf 30 patients recruited (two lung, nine gynaecological, and 19 colorectal malignancies), data from 20 patients at 9 months after chemotherapy was available for analysis. Twelve were classified as CIPN+ (mean age, 63.2[9.6] yr, 9.6; six female), eight as CIPN– (mean age 62.9 [SD 5.5] yr, four female). In response to punctate stimulation, group contrast analysis showed that CIPN+ compared with CIPN– had robust activity in sensory, motor, attentional, and affective brain regions. An a priori chosen region-of-interest analysis focusing on the periaqueductal grey, an area hypothesised as relevant for developing CIPN+, showed significantly increased responses in CIPN– compared with CIPN+ patients. No difference in subcortical volumes between CIPN+ and CIPN– patients was detected.ConclusionsBefore administration of any chemotherapy or appearance of CIPN symptoms, we observed altered patterns of brain activity in response to nociceptive stimulation in patients who later developed chronic sensory CIPN. This suggests the possibility of a pre-existing vulnerability to developing CIPN centred on brainstem regions of the descending pain modulatory system.

U2 - 10.1016/j.bja.2022.09.026

DO - 10.1016/j.bja.2022.09.026

M3 - Article

SN - 0007-0912

VL - 130

SP - 83

EP - 93

JO - British Journal of Anaesthesia

JF - British Journal of Anaesthesia

IS - 1

ER -

Neuroimaging reveals a potential brain-based pre-existing mechanism that confers vulnerability to development of chronic painful chemotherapy-induced peripheral neuropathy (CIPN)

Abstract / Description of output

Access to Document

Fingerprint

Cite this