Repetitive pain exposure of neonates in the neonatal intensive care unit (NICU) might affect proper fine-tuning of the nociceptive network, a process which continues in the postnatal period. In ex-NICU children altered basal nociception in the absence of an injury has been shown. However, the impact on nociception after an injury, e.g. surgery, is unknown. In this study we aimed to determine the effect of neonatal repetitive small painful skin-breaking procedures in both sexes on nociception in the absence and in the presence of an ongoing injury in later life. To this end the repetitive needle prick animal model was used in which neonatal Sprague-Dawley male and female rat pups received four needle pricks per day into one hind paw during the first week of life and control animals received non-painful tactile stimuli. Nociceptive thresholds to mechanical stimuli in the absence of injury, i.e. basal nociception, were not affected by neonatal repetitive needle pricking. Only male animals which received neonatal needle pricks showed increased hypersensitivity to mechanical stimuli at 24. h after ipsilateral CFA-injection. Our study shows that repetitive small needle pricks during the first week of life result in increased hypersensitivity to mechanical stimuli at 24. h after ipsilateral CFA-injection in later life in male animals and not in females.

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Keywords Inflammation, Neonatal pain, Rat, Sex differences
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Journal Neuroscience Letters
Knaepen, L, Patijn, J, Tibboel, D, & Joosten, E.A. (2012). Sex differences in inflammatory mechanical hypersensitivity in later life of rats exposed to repetitive needle pricking as neonates. Neuroscience Letters, 516(2), 285–289. doi:10.1016/j.neulet.2012.04.012