Early life inflammation is associated with spinal cord excitability and nociceptive sensitivity in human infants

Maria M. Cobo; Gabrielle Green; Foteini Andritsou; Luke Baxter; Ria Evans Fry; Annika Grabbe; Deniz Gursul; Amy Hoskin; Gabriela Schmidt Mellado; Marianne van der Vaart; Eleri Adams; Aomesh Bhatt; Franziska Denk; Caroline Hartley; Rebeccah Slater

doi:10.1038/s41467-022-31505-y

Early life inflammation is associated with spinal cord excitability and nociceptive sensitivity in human infants

Maria M. Cobo, Gabrielle Green, Foteini Andritsou, Luke Baxter, Ria Evans Fry, Annika Grabbe, Deniz Gursul, Amy Hoskin, Gabriela Schmidt Mellado, Marianne van der Vaart, Eleri Adams, Aomesh Bhatt, Franziska Denk, Caroline Hartley, Rebeccah Slater^*

^*Corresponding author for this work

Wolfson Centre for Age Related Diseases

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

1 Citation (Scopus)

Abstract

Immune function and sensitivity to pain are closely related, but the association between early life inflammation and sensory nervous system development is poorly understood—especially in humans. Here, in term-born infants, we measure brain activity and reflex withdrawal activity (using EEG and EMG) and behavioural and physiological activity (using the PIPP-R score) to assess the impact of suspected early-onset neonatal infection on tactile- and noxious-evoked responses. We present evidence that neonatal inflammation (assessed by measuring C-reactive protein levels) is associated with increased spinal cord excitability and evoked brain activity following both tactile and noxious stimulation. There are early indications that this hyperalgesia could be maintained post-inflammation, supporting pre-clinical reports of early-life immune dysfunction influencing pain sensitivity in adults.

Original language	English
Article number	3943
Journal	Nature Communications
Volume	13
Issue number	1
DOIs	https://doi.org/10.1038/s41467-022-31505-y
Publication status	Published - Dec 2022

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Cobo, M. M., Green, G., Andritsou, F., Baxter, L., Evans Fry, R., Grabbe, A., Gursul, D., Hoskin, A., Mellado, G. S., van der Vaart, M., Adams, E., Bhatt, A., Denk, F., Hartley, C., & Slater, R. (2022). Early life inflammation is associated with spinal cord excitability and nociceptive sensitivity in human infants. Nature Communications, 13(1), [3943]. https://doi.org/10.1038/s41467-022-31505-y

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title = "Early life inflammation is associated with spinal cord excitability and nociceptive sensitivity in human infants",

abstract = "Immune function and sensitivity to pain are closely related, but the association between early life inflammation and sensory nervous system development is poorly understood—especially in humans. Here, in term-born infants, we measure brain activity and reflex withdrawal activity (using EEG and EMG) and behavioural and physiological activity (using the PIPP-R score) to assess the impact of suspected early-onset neonatal infection on tactile- and noxious-evoked responses. We present evidence that neonatal inflammation (assessed by measuring C-reactive protein levels) is associated with increased spinal cord excitability and evoked brain activity following both tactile and noxious stimulation. There are early indications that this hyperalgesia could be maintained post-inflammation, supporting pre-clinical reports of early-life immune dysfunction influencing pain sensitivity in adults.",

author = "Cobo, {Maria M.} and Gabrielle Green and Foteini Andritsou and Luke Baxter and {Evans Fry}, Ria and Annika Grabbe and Deniz Gursul and Amy Hoskin and Mellado, {Gabriela Schmidt} and {van der Vaart}, Marianne and Eleri Adams and Aomesh Bhatt and Franziska Denk and Caroline Hartley and Rebeccah Slater",

note = "Funding Information: The study was funded by the Wellcome Trust via a Senior Wellcome Fellowship awarded to Rebeccah Slater (Grant number 207457/Z/17/Z) and a Bliss research grant. Caroline Hartley is a Wellcome Trust/Royal Society Sir Henry Dale Fellow (213486/Z/18/Z). We would like to thank the newborn participants and their parents for taking part in this study. Funding Information: The study was funded by the Wellcome Trust via a Senior Wellcome Fellowship awarded to Rebeccah Slater (Grant number 207457/Z/17/Z) and a Bliss research grant. Caroline Hartley is a Wellcome Trust/Royal Society Sir Henry Dale Fellow (213486/Z/18/Z). We would like to thank the newborn participants and their parents for taking part in this study. Publisher Copyright: {\textcopyright} 2022, The Author(s).",

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Cobo, MM, Green, G, Andritsou, F, Baxter, L, Evans Fry, R, Grabbe, A, Gursul, D, Hoskin, A, Mellado, GS, van der Vaart, M, Adams, E, Bhatt, A, Denk, F, Hartley, C & Slater, R 2022, 'Early life inflammation is associated with spinal cord excitability and nociceptive sensitivity in human infants', Nature Communications, vol. 13, no. 1, 3943. https://doi.org/10.1038/s41467-022-31505-y

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AU - Cobo, Maria M.

AU - Green, Gabrielle

AU - Andritsou, Foteini

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AU - Evans Fry, Ria

AU - Grabbe, Annika

AU - Gursul, Deniz

AU - Hoskin, Amy

AU - Mellado, Gabriela Schmidt

AU - van der Vaart, Marianne

AU - Adams, Eleri

AU - Bhatt, Aomesh

AU - Denk, Franziska

AU - Hartley, Caroline

AU - Slater, Rebeccah

N1 - Funding Information: The study was funded by the Wellcome Trust via a Senior Wellcome Fellowship awarded to Rebeccah Slater (Grant number 207457/Z/17/Z) and a Bliss research grant. Caroline Hartley is a Wellcome Trust/Royal Society Sir Henry Dale Fellow (213486/Z/18/Z). We would like to thank the newborn participants and their parents for taking part in this study. Funding Information: The study was funded by the Wellcome Trust via a Senior Wellcome Fellowship awarded to Rebeccah Slater (Grant number 207457/Z/17/Z) and a Bliss research grant. Caroline Hartley is a Wellcome Trust/Royal Society Sir Henry Dale Fellow (213486/Z/18/Z). We would like to thank the newborn participants and their parents for taking part in this study. Publisher Copyright: © 2022, The Author(s).

PY - 2022/12

Y1 - 2022/12

N2 - Immune function and sensitivity to pain are closely related, but the association between early life inflammation and sensory nervous system development is poorly understood—especially in humans. Here, in term-born infants, we measure brain activity and reflex withdrawal activity (using EEG and EMG) and behavioural and physiological activity (using the PIPP-R score) to assess the impact of suspected early-onset neonatal infection on tactile- and noxious-evoked responses. We present evidence that neonatal inflammation (assessed by measuring C-reactive protein levels) is associated with increased spinal cord excitability and evoked brain activity following both tactile and noxious stimulation. There are early indications that this hyperalgesia could be maintained post-inflammation, supporting pre-clinical reports of early-life immune dysfunction influencing pain sensitivity in adults.

AB - Immune function and sensitivity to pain are closely related, but the association between early life inflammation and sensory nervous system development is poorly understood—especially in humans. Here, in term-born infants, we measure brain activity and reflex withdrawal activity (using EEG and EMG) and behavioural and physiological activity (using the PIPP-R score) to assess the impact of suspected early-onset neonatal infection on tactile- and noxious-evoked responses. We present evidence that neonatal inflammation (assessed by measuring C-reactive protein levels) is associated with increased spinal cord excitability and evoked brain activity following both tactile and noxious stimulation. There are early indications that this hyperalgesia could be maintained post-inflammation, supporting pre-clinical reports of early-life immune dysfunction influencing pain sensitivity in adults.

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VL - 13

JO - Nature Communications

JF - Nature Communications

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ER -

Early life inflammation is associated with spinal cord excitability and nociceptive sensitivity in human infants

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