Cortical pain responses in human infants - towards a rational analgesic strategy

Lead Research Organisation: University College London
Department Name: Cell and Developmental Biology

Abstract

Babies in hospital, especially those that are born very premature, are regularly exposed to painful procedures as part of their routine medical treatment. However, infants are unable to say whether or not it hurts and other methods are needed to assess the amount of pain they feel. This study offers an insight into how best to manage pain relief in very young infants. We aim to assess the way in which babies respond to painful stimulation and other sensations while they are having their routine blood tests. Non painful sensations, such as light touch with nylon hairs and vibration will also be used. Brain activity will be monitored with electrodes gently placed on the infant’s scalp to see whether any waves arise in specific parts of the brain following a painful and non-painful stimulus. We will test how these responses change with age, whether they are affected by the number of painful procedures a baby has experienced, and most importantly whether they are reduced by current pain relieving medicines.

Technical Summary

Infants in intensive care necessarily undergo repeated invasive procedures and yet treatment for their pain remains sporadic and suboptimal. Clinical trials of analgesics in preterm infants are urgently needed but cannot be undertaken without direct, objective and quantitative measures of pain responses in this population. In this study we will record cortical somatosensory potentials in preterm infants evoked by noxious (heel lance) and non-noxious (touch, electrical and vibration) stimulation. We will test whether (i) noxious stimulation evokes neural activity in the human infant somatosensory cortex that can be measured using neurophysiological methods (ii) infant cortical responses to noxious stimulation increase with postmenstrual age (iii) repeated invasive intensive care procedures influence the cortical response to noxious stimulation (iv) cortical and brainstem/spinal reflex responses to noxious stimulation are differentially regulated and not predictive of one another (v) existing analgesic regimes using i.v. morphine and oral sucrose reduce cortical responses to noxious stimulation. The data will provide the first objective measure of infant cortical pain processing and test the effectiveness of putative analgesic agents in preterm infants. The study can be used as a basis for larger studies and trials to test new analgesic strategies.

Publications

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Fitzgerald M (2009) Infant pain management: a developmental neurobiological approach. in Nature clinical practice. Neurology

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Fitzgerald M (2009) When is an analgesic not an analgesic? in Pain

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Slater R (2006) Cortical pain responses in human infants. in The Journal of neuroscience : the official journal of the Society for Neuroscience

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Slater R (2010) Evoked potentials generated by noxious stimulation in the human infant brain. in European journal of pain (London, England)

 
Description Fetal Awareness of Pain - evidence to Goverment select committee
Geographic Reach National 
Policy Influence Type Gave evidence to a government review
Impact Evidence for review of UK abortion law based on scientific evidence
URL http://www.publications.parliament.uk/pa/cm200607/cmselect/cmsctech/1045/104505.htm
 
Description British Pain Society Equipment Grant
Amount £25,000 (GBP)
Organisation British Pain Society 
Sector Charity/Non Profit
Country United Kingdom
Start 01/2006 
End 01/2007
 
Description Grunenthal Prize Grant for pain research/Grunenthal
Amount £14,000 (GBP)
Organisation Grunenthal Ltd. 
Sector Private
Country Germany
Start 01/2009 
End 01/2010
 
Description IASP Early Career Grant for a postdoc/International Association for the Study of Pain
Amount £12,000 (GBP)
Organisation International Association for the Study of Pain (IASP) 
Sector Learned Society
Country United States
Start 01/2010 
End 01/2011
 
Description MRC DTA studentship
Amount £45,000 (GBP)
Organisation Medical Research Council (MRC) 
Sector Academic/University
Country United Kingdom
Start 10/2009 
End 10/2012
 
Description MRC PhD Studentship
Amount £45,000 (GBP)
Organisation Medical Research Council (MRC) 
Sector Academic/University
Country United Kingdom
Start 10/2006 
End 10/2009
 
Description MRC Project grant
Amount £1,105,707 (GBP)
Funding ID MR/M006468/1 
Organisation Medical Research Council (MRC) 
Sector Academic/University
Country United Kingdom
Start 09/2014 
End 08/2018
 
Description UCLH trustees project grant
Amount £40,579 (GBP)
Organisation University College London Hospital 
Department Special Trustees of University College London Hospital (UCLH)
Sector Charity/Non Profit
Country United Kingdom
Start 01/2006 
End 01/2007
 
Description Welcome Trust project grant
Amount £685,065 (GBP)
Organisation Wellcome Trust 
Sector Charity/Non Profit
Country United Kingdom
Start 03/2009 
End 08/2012
 
Title PCA analysis of evoked nociceptive potentials 
Description A mathod of accessing EEG traces and performing principal component analsysis on it 
Type Of Material Improvements to research infrastructure 
Provided To Others? No  
Impact Greatly increased the information that can be obtained from our EEG recordings 
 
Title neonatal pain assessment 
Description A new method of measuring cortical pain processing in infants 
Type Of Material Physiological assessment or outcome measure 
Provided To Others? No  
Impact We hope that this will lead to a method of measuring analgesia in clinical trials 
 
Description Dept Statistics, UCL 
Organisation University College London
Department Department of Statistical Science
Country United Kingdom 
Sector Academic/University 
PI Contribution Collabration with academic statistician at UCL who has provided new statistical analysis of our complex EEG data
Collaborator Contribution Whole new way of analysing the results. LF, a postdoc on this grant has learned a lot of sophisticated analytic and statistical techniques as a result of this work
Impact New methods of analysis that were included in: 20438855 and 20817247
Start Year 2008
 
Description FIMRIB, Oxford 
Organisation University of Oxford
Department Oxford Centre for Functional MRI of the Brain (FMRIB)
Country United Kingdom 
Sector Academic/University 
PI Contribution Knowledge of neonatal pain in infants
Collaborator Contribution Training in fMRI for a PhD and a postdoc
Impact PhD student training. New techniques to address the question
Start Year 2009
 
Description Neonatology, Institute Womens Health, UCLH 
Organisation University College London Hospitals NHS Foundation Trust
Country United Kingdom 
Sector Public 
PI Contribution Expertise in infant pain processing. Collaboration for MRC grant.
Collaborator Contribution Expertise in brain structure and MRI of premature infants. Access to neonated in NICU
Impact MRC DTA studentship, MRC grants
Start Year 2009
 
Description Lab experience for disadvantaged science school students 
Form Of Engagement Activity Participation in an open day or visit at my research institution
Part Of Official Scheme? Yes
Geographic Reach Regional
Primary Audience Schools
Results and Impact Six students from one of Londons most disadvantaged areas spent 2 weeks in the lab in their summer holiday

More confidence in applying for top universities to read biological subjects
Year(s) Of Engagement Activity 2010,2011,2012,2013,2014
URL http://www.ucl.ac.uk/news/news-articles/0913/11092013-in2scienceUK-out-of-the-classroom-and-into-the...
 
Description Nurse study days 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? Yes
Geographic Reach National
Primary Audience Health professionals
Results and Impact Pain Study Days at GOSH for nurses and junior doctors, 2007, 2009, 2011, 2013

Educational - very well received
Year(s) Of Engagement Activity 2007,2009,2011,2013
 
Description The press 
Form Of Engagement Activity A magazine, newsletter or online publication
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact Substantial media engagement over our research on infant pain; appearance on Sky News, interviews and articles in all major newspapers, 2006 and 2008. Interview on Wellcome Trust site, 2013.

experience in dealing with the media
Year(s) Of Engagement Activity 2006,2008,2009
URL https://thinkneuroscience.wordpress.com/2013/02/06/paediatric-pain/