Postnatal Temporal, Spatial and Modality Tuning of Nociceptive Cutaneous Flexion Reflexes in Human Infants

Laura Cornelissen,Alan Worley,Deborah Patten,Lorenzo Fabrizi,Judith Meek,Rebeccah Slater,Stewart Boyd,Maria Fitzgerald,Michael Costigan

doi:10.1371/journal.pone.0076470

Laura Cornelissen, Alan Worley + Show 7 more

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https://doi.org/10.1371/journal.pone.0076470

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Abstract

Cutaneous flexion reflexes are amongst the first behavioural responses to develop and are essential for the protection and survival of the newborn organism. Despite this, there has been no detailed, quantitative study of their maturation in human neonates. Here we use surface electromyographic (EMG) recording of biceps femoris activity in preterm (<37 weeks gestation, GA) and term (≥37 weeks GA) human infants, less than 14 days old, in response to tactile, punctate and clinically required skin-breaking lance stimulation of the heel. We show that all infants display a robust and long duration flexion reflex (>4 seconds) to a single noxious skin lance which decreases significantly with gestational age. This reflex is not restricted to the stimulated limb: heel lance evokes equal ipsilateral and contralateral reflexes in preterm and term infants. We further show that infant flexion withdrawal reflexes are not always nociceptive specific: in 29% of preterm infants, tactile stimulation evokes EMG activity that is indistinguishable from noxious stimulation. In 40% of term infants, tactile responses are also present but significantly smaller than nociceptive reflexes. Infant flexion reflexes are also evoked by application of calibrated punctate von Frey hairs (vFh), 0.8–17.2 g, to the heel. Von Frey hair thresholds increase significantly with gestational age and the magnitude of vFh evoked reflexes are significantly greater in preterm than term infants. Furthermore flexion reflexes in both groups are sensitized by repeated vFh stimulation. Thus human infant flexion reflexes differ in temporal, modality and spatial characteristics from those in adults. Reflex magnitude and tactile sensitivity decreases and nociceptive specificity and spatial organisation increases with gestational age. Strong, relatively non-specific, reflex sensitivity in early life may be important for driving postnatal activity dependent maturation of targeted spinal cord sensory circuits.

Highlights

The flexion withdrawal reflex is a fundamental sensory behaviour that protects the body from harm
Numerous anatomical and electrophysiological studies in rat pups have shown that the properties of nociceptive reflexes and their underlying dorsal horn nociceptive circuits differ in early postnatal life from those in adults [12,16,17,18]
Nociceptive flexion reflexes are greater in magnitude and duration in younger infants To test whether infant nociceptive flexion reflex responses change with gestational age, we compared the biceps femoris EMG activity evoked by a clinically required time-locked heel lance in preterm (,37 weeks gestation at time of study, n = 19) and term infants ($ 37 weeks gestation at time of study, n = 20)

Summary

Introduction

The flexion withdrawal reflex is a fundamental sensory behaviour that protects the body from harm. Numerous anatomical and electrophysiological studies in rat pups have shown that the properties of nociceptive reflexes and their underlying dorsal horn nociceptive circuits differ in early postnatal life from those in adults [12,16,17,18]. Withdrawal reflexes in rat pups have lower thresholds, in the innocuous range, and are greater in amplitude and duration than adult rats and the underlying dorsal horn neurons and reflex motoneurones have larger, disorganised cutaneous receptive fields [16,19,20,21,22]. Newborn rat dorsal horn neurons receive stronger synaptic input from low threshold mechanoreceptor afferents than adults [21,23] due to exuberant A fibre terminals[17,24] (Beggs et al, 2002; Granmo et al, 2008) and immature glycinergic signalling [18,25]

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