A developmental shift in habituation to pain in human neonates

Mohammed Rupawala; Oana Bucsea; Maria Pureza Laudiano-Dray; Kimberley Whitehead; Judith Meek; Maria Fitzgerald; Sofia Olhede; Laura Jones; Lorenzo Fabrizi

doi:10.1016/j.cub.2023.02.071

A developmental shift in habituation to pain in human neonates

Mohammed Rupawala, Oana Bucsea, Maria Pureza Laudiano-Dray, Kimberley Whitehead, Judith Meek, Maria Fitzgerald, Sofia Olhede, Laura Jones, Lorenzo Fabrizi

Digital Health & Applied Tech Assessment

Univ London, Birkbeck University London, University College London, University of London Royal Veterinary College, University of London, St Georges University London, Imperial College London, Kings College London, Royal Holloway University London, Queen Mary University London, Div Populat Hlth Sci & Educ
New York University
UCL Hospitals NHS Foundation Trust

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

9 Citations (Scopus)

Abstract

Habituation to recurrent non-threatening or unavoidable noxious stimuli is an important aspect of adaptation to pain. Neonates, especially if preterm, are exposed to repeated noxious procedures during their clinical care. They can mount strong behavioral, autonomic, spinal, and cortical responses to a single noxious stimulus; however, it is not known whether the developing nervous system can adapt to the recurrence of these inputs. Here, we used electroencephalography to investigate changes in cortical microstates (representing the complex sequential processing of noxious inputs) following two consecutive clinically required heel lances in term and preterm infants. We show that stimulus repetition dampens the engagement of initial microstates and associated behavioral and autonomic responses in term infants, while preterm infants do not show signs of habituation. Nevertheless, both groups engage different longer-latency cortical microstates to each lance, which is likely to reflect changes in higher-level stimulus processing with repeated stimulation. These data suggest that while both age groups are capable of encoding contextual differences in pain, the preterm brain does not regulate the initial cortical, behavioral, and autonomic responses to repeated noxious stimuli. Habituation mechanisms to pain are already in place at term age but mature over the equivalent of the last trimester of gestation and are not fully functional in preterm neonates.

Original language	English
Pages (from-to)	1397-1406.e5
Journal	Current biology : CB
Volume	33
Issue number	8
DOIs	https://doi.org/10.1016/j.cub.2023.02.071
Publication status	Published - 24 Apr 2023

Keywords

Infant
Humans
Infant, Newborn
Infant, Premature/physiology
Habituation, Psychophysiologic
Physical Stimulation
Pain
Electroencephalography

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10.1016/j.cub.2023.02.071

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title = "A developmental shift in habituation to pain in human neonates",

abstract = "Habituation to recurrent non-threatening or unavoidable noxious stimuli is an important aspect of adaptation to pain. Neonates, especially if preterm, are exposed to repeated noxious procedures during their clinical care. They can mount strong behavioral, autonomic, spinal, and cortical responses to a single noxious stimulus; however, it is not known whether the developing nervous system can adapt to the recurrence of these inputs. Here, we used electroencephalography to investigate changes in cortical microstates (representing the complex sequential processing of noxious inputs) following two consecutive clinically required heel lances in term and preterm infants. We show that stimulus repetition dampens the engagement of initial microstates and associated behavioral and autonomic responses in term infants, while preterm infants do not show signs of habituation. Nevertheless, both groups engage different longer-latency cortical microstates to each lance, which is likely to reflect changes in higher-level stimulus processing with repeated stimulation. These data suggest that while both age groups are capable of encoding contextual differences in pain, the preterm brain does not regulate the initial cortical, behavioral, and autonomic responses to repeated noxious stimuli. Habituation mechanisms to pain are already in place at term age but mature over the equivalent of the last trimester of gestation and are not fully functional in preterm neonates.",

keywords = "Infant, Humans, Infant, Newborn, Infant, Premature/physiology, Habituation, Psychophysiologic, Physical Stimulation, Pain, Electroencephalography",

author = "Mohammed Rupawala and Oana Bucsea and Laudiano-Dray, {Maria Pureza} and Kimberley Whitehead and Judith Meek and Maria Fitzgerald and Sofia Olhede and Laura Jones and Lorenzo Fabrizi",

note = "Funding Information: This work was funded by the Medical Research Council UK ( MR/S003207/1 ) and the European Research Council ( CoG 2015-682172NETS ) within the Seventh European Union Framework Program. O.B. was supported by the Canadian Institutes of Health Research ( FBD–170829 ). The research was performed at the University College London Hospitals (UCLH) Maternity and Neonatal Units. The authors thank the families of the infants that participated in this research. The authors also thank Stephanie Koch for discussions of the results. For the purpose of open access, the author has applied a Creative Commons Attribution (CC BY) license to any Author Accepted Manuscript version arising. Funding Information: This work was funded by the Medical Research Council UK (MR/S003207/1) and the European Research Council (CoG 2015-682172NETS) within the Seventh European Union Framework Program. O.B. was supported by the Canadian Institutes of Health Research (FBD–170829). The research was performed at the University College London Hospitals (UCLH) Maternity and Neonatal Units. The authors thank the families of the infants that participated in this research. The authors also thank Stephanie Koch for discussions of the results. For the purpose of open access, the author has applied a Creative Commons Attribution (CC BY) license to any Author Accepted Manuscript version arising. Conceptualization of study, L.J. L.F. and M.F.; data collection and preparation, L.J. M.P.L.-D. and K.W.; clinical supervision, J.M.; data analysis, M.R. L.J. O.B. and S.O.; data interpretation, M.R. L.J. and L.F.; manuscript preparation, M.R. L.J. and L.F. All authors discussed the results and commented on the manuscript. The authors declare no competing interests. Publisher Copyright: {\textcopyright} 2023 The Authors",

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doi = "10.1016/j.cub.2023.02.071",

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AU - Rupawala, Mohammed

AU - Bucsea, Oana

AU - Laudiano-Dray, Maria Pureza

AU - Whitehead, Kimberley

AU - Meek, Judith

AU - Fitzgerald, Maria

AU - Olhede, Sofia

AU - Jones, Laura

AU - Fabrizi, Lorenzo

N1 - Funding Information: This work was funded by the Medical Research Council UK ( MR/S003207/1 ) and the European Research Council ( CoG 2015-682172NETS ) within the Seventh European Union Framework Program. O.B. was supported by the Canadian Institutes of Health Research ( FBD–170829 ). The research was performed at the University College London Hospitals (UCLH) Maternity and Neonatal Units. The authors thank the families of the infants that participated in this research. The authors also thank Stephanie Koch for discussions of the results. For the purpose of open access, the author has applied a Creative Commons Attribution (CC BY) license to any Author Accepted Manuscript version arising. Funding Information: This work was funded by the Medical Research Council UK (MR/S003207/1) and the European Research Council (CoG 2015-682172NETS) within the Seventh European Union Framework Program. O.B. was supported by the Canadian Institutes of Health Research (FBD–170829). The research was performed at the University College London Hospitals (UCLH) Maternity and Neonatal Units. The authors thank the families of the infants that participated in this research. The authors also thank Stephanie Koch for discussions of the results. For the purpose of open access, the author has applied a Creative Commons Attribution (CC BY) license to any Author Accepted Manuscript version arising. Conceptualization of study, L.J. L.F. and M.F.; data collection and preparation, L.J. M.P.L.-D. and K.W.; clinical supervision, J.M.; data analysis, M.R. L.J. O.B. and S.O.; data interpretation, M.R. L.J. and L.F.; manuscript preparation, M.R. L.J. and L.F. All authors discussed the results and commented on the manuscript. The authors declare no competing interests. Publisher Copyright: © 2023 The Authors

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N2 - Habituation to recurrent non-threatening or unavoidable noxious stimuli is an important aspect of adaptation to pain. Neonates, especially if preterm, are exposed to repeated noxious procedures during their clinical care. They can mount strong behavioral, autonomic, spinal, and cortical responses to a single noxious stimulus; however, it is not known whether the developing nervous system can adapt to the recurrence of these inputs. Here, we used electroencephalography to investigate changes in cortical microstates (representing the complex sequential processing of noxious inputs) following two consecutive clinically required heel lances in term and preterm infants. We show that stimulus repetition dampens the engagement of initial microstates and associated behavioral and autonomic responses in term infants, while preterm infants do not show signs of habituation. Nevertheless, both groups engage different longer-latency cortical microstates to each lance, which is likely to reflect changes in higher-level stimulus processing with repeated stimulation. These data suggest that while both age groups are capable of encoding contextual differences in pain, the preterm brain does not regulate the initial cortical, behavioral, and autonomic responses to repeated noxious stimuli. Habituation mechanisms to pain are already in place at term age but mature over the equivalent of the last trimester of gestation and are not fully functional in preterm neonates.

AB - Habituation to recurrent non-threatening or unavoidable noxious stimuli is an important aspect of adaptation to pain. Neonates, especially if preterm, are exposed to repeated noxious procedures during their clinical care. They can mount strong behavioral, autonomic, spinal, and cortical responses to a single noxious stimulus; however, it is not known whether the developing nervous system can adapt to the recurrence of these inputs. Here, we used electroencephalography to investigate changes in cortical microstates (representing the complex sequential processing of noxious inputs) following two consecutive clinically required heel lances in term and preterm infants. We show that stimulus repetition dampens the engagement of initial microstates and associated behavioral and autonomic responses in term infants, while preterm infants do not show signs of habituation. Nevertheless, both groups engage different longer-latency cortical microstates to each lance, which is likely to reflect changes in higher-level stimulus processing with repeated stimulation. These data suggest that while both age groups are capable of encoding contextual differences in pain, the preterm brain does not regulate the initial cortical, behavioral, and autonomic responses to repeated noxious stimuli. Habituation mechanisms to pain are already in place at term age but mature over the equivalent of the last trimester of gestation and are not fully functional in preterm neonates.

KW - Infant

KW - Humans

KW - Infant, Newborn

KW - Infant, Premature/physiology

KW - Habituation, Psychophysiologic

KW - Physical Stimulation

KW - Pain

KW - Electroencephalography

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VL - 33

SP - 1397-1406.e5

JO - Current biology : CB

JF - Current biology : CB

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ER -

A developmental shift in habituation to pain in human neonates

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Keywords

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