Multimodal pain assessment improves discrimination between noxious and non‐noxious stimuli in infants

Abstract

Infants in neonatal intensive care units frequently experience clinically necessary painful procedures, which elicit a range of behavioral, physiological, and neurophysiological responses. However, the measurement of pain in this population is a challenge and no gold standard exists. The aim of this study was to investigate how noxious‐evoked changes in facial expression, reflex withdrawal, brain activity, heart rate, and oxygen saturation are related and to examine their accuracy in discriminating between noxious and non‐noxious stimuli. In 109 infants who received a clinically required heel lance and a control non‐noxious stimulus, we investigated whether combining responses across each modality, or including multiple measures from within each modality improves our ability to discriminate the noxious and non‐noxious stimuli. A random forest algorithm was used to build data‐driven models to discriminate between the noxious and non‐noxious stimuli in a training set which were then validated in a test set of independent infants. Measures within each modality were highly correlated, while different modalities showed less association. The model combining information across all modalities had good discriminative ability (accuracy of 0.81 in identifying noxious and non‐noxious stimuli), which was higher than the discriminative power of the models built from individual modalities. This demonstrates the importance of including multiple modalities in the assessment of infant pain.

Quantifying noxious-evoked baseline sensitivity in neonates to optimise analgesic trials

“…The noxious-evoked brain activity measure used here quantifies the evoked potential produced at the central vertex electrode site (Cz), which has been shown to have the greatest and most reproducible response size amplitude compared to other electrodes sites across the brain (Hartley et al, 2017;Verriotis et al, 2015). This measure does not represent all nociceptive activity across the brain and cannot be used to investigate the various aspects of pain perception ; a multi-modal approach to pain assessment is therefore important in follow-on studies (Vaart et al, 2019). However, in the absence of verbalisation, neuroimaging methods provide an objective proxy approach which has been used to infer pain perception following noxious events (Baxter et al, 2020;Duff et al, 2020;Gursul et al, 2019;Hartley et al, 2017).…”

Inferring pain experience in infants using quantitative whole-brain functional MRI signatures: a cross-sectional, observational study

“…Therefore, we advocate a multimodal measurement approach to provide the best proxy of infant pain. 37 Infant behavioural pain scores have been extensively studied, and brain-derived EEG signatures have been associated with infant nociception. 22 , 23 EEG-based measures have been validated for use as the primary outcome measure in clinical trials aiming to assess the efficacy of analgesic interventions, 17 , 38 and validation was achieved by considering the specificity of the EEG response to nociceptive input and characterising responses to established pain modulators.…”

Inferring the infant pain experience: a translational fMRI-based signature study

“…Despite its advantages, it is important to appreciate that a single modality, such as fMRI, cannot capture the full complexity of the processes that underlie a conscious experience. Therefore, we strongly advocate a multimodal measurement approach to provide the best proxy of infant pain 56,57 . Infant behavioural pain scores have been extensively studied, and brain-derived EEG signatures have been linked to infant nociception 34,58–63 .…”