Neonatal repetitive needle pricking: Plasticity of the spinal nociceptive circuit and extended postoperative pain in later life

Abstract

Repetitive exposure of neonates to noxious events is inherent to their health status monitoring in neonatal intensive care units (NICU). Altered basal nociception in the absence of an injury in later life has been demonstrated in ex-NICU children, but the impact on pain hypersensitivity following an injury in later life is unknown. Also, underlying mechanisms for such long-term changes are relatively unknown. The objective of this study is to investigate acute and long-term effects of neonatal repetitive painful skin-breaking procedures on nociception and to investigate plasticity of the nociceptive circuit. The repetitive needle prick animal model was used in which neonatal rats received four needle pricks into the left hind paw per day during the first postnatal week and control animals received nonpainful tactile stimuli. Repetitive needle pricking during the first week of life induced acute hypersensitivity to mechanical stimuli. At the age of 8 weeks, increased duration of postoperative hypersensitivity to mechanical stimuli after ipsilateral hind paw incision was shown in needle prick animals. Basal nociception from 3 to 8 weeks of age was unaffected by neonatal repetitive needle pricking. Increased calcitonin gene-related peptide expression was observed in the ipsilateral and contralateral lumbar spinal cord but not in the hind paw of needle prick animals at the age of 8 weeks. Innervation of tactile Aβ-fibers in the spinal cord was not affected. Our results indicate both acute and long-term effects of repetitive neonatal skin breaking procedures on nociception and long-term plasticity of spinal but not peripheral innervation of nociceptive afferents.

Neonatal Invasive Procedures Predict Pain Intensity at School Age in Children Born Very Preterm

“…Rodent studies of long-term effects of early pain on pain thresholds have shown hyper- and hypo- sensitivity, depending on the nature of the pain stimulus [7,8]. Consistent with these animal findings, human studies comparing preterm and full-term children show that the direction of pain responses depends on duration and type of stimulus.…”

Repeated exposure to sucrose for procedural pain in mouse pups leads to long-term widespread brain alterations

“…Methodological differences may account for these findings, inflammatory pain or pain from injections may not have the same consequences as needle-pricks. We question the invasiveness of our needle-prick pain stimulus, given that we used very thin needles (30G) and did not penetrate deeper layers, such as tendon or bone, in contrast to the apparently more invasive procedures used in needle-prick pain in previous rat studies [1,27,41]. It should be noted that we undertook interventions 10 times daily for six days, based on the median exposure to painful procedures during NICU care [54].…”

Developmental Fluoxetine Exposure Normalizes the Long-Term Effects of Maternal Stress on Post-Operative Pain in Sprague-Dawley Rat Offspring

“…Plantar hind paw incision was performed at the age of 8 weeks, a young-adult age at which alterations in the nociceptive network organization and in hind paw incision pain have been evidenced following neonatal pain exposure [41]. After baseline nociceptive and locomotor activity testing, all male offspring received an injury to the left hind paw, i.e.…”