Abstract
ABSTRACTClinical and experimental data suggests that noxious stimulation at critical stages of development results in long‐term changes on nociceptive processing in later life. Here, we use an established, well‐documented rat model of repetitive noxious procedures closely mimicking the clinical situation in the NICU. In order to understand molecular changes underlying the long‐term consequences of repetitive stimulation of the developing nociceptive system the present study aims to analyze the presence of the µ‐opioid‐receptor‐1 (OPRM1). Neonatal rats received either four needle pricks per day in the left hind‐paw from postnatal day 0–7 as a model of procedural pain in infancy. Control pups were handled in the same way but were instead tactile stimulated, or were left undisturbed. At the age of 8 weeks, all animals received an ipsilateral hind‐paw incision as a model for post‐operative pain, and mechanical sensitivity was tested at multiple time‐points. Before, and 1 or 5 days post‐incision, spinal cord tissue was collected for immunostaining of opioid receptor OPRM1. Semi‐quantitative immunocytochemical analysis of superficial laminae in lumbar spinal dorsal horn revealed that: (1) early life repetitive tactile or noxious procedures do not alter baseline levels of OPRM1 staining intensity and (2) early life repetitive tactile or noxious procedures lead to a decrease in OPRM1 staining intensity 5 days after incision in adulthood compared to undisturbed controls. We conclude that early life repetitive tactile or noxious procedures affect the intensity of OPRM1‐immunoreactivity in the lumbar superficial spinal cord dorsal horn after adulthood injury, without affecting baseline intensity. © 2018 The Authors. Developmental Neurobiology Published by Wiley Periodicals, Inc. Develop Neurobiol 78: 417–426, 2018
Highlights
Exposure to painful procedures during the early postnatal period leads to altered pain perception in adulthood (Schwaller and Fitzgerald, 2014; Ren et al, 2004; Laprairie and Murphy, 2009)
The intensity of OPRM1 staining of the superficial spinal cord dorsal horn (SCDH) was measured as mean gray value, and values of L4 and L5 ipsi- and contralateral dorsal horns were pooled as expression did not significantly differ within each group
The semi-quantitative immune-cytochemical analysis as in the present study shows that early life repetitive noxious or tactile procedures do not alter baseline levels of OPRM1 staining in the adult lumbar spinal cord dorsal horn
Summary
Exposure to painful procedures during the early postnatal period leads to altered pain perception in adulthood (Schwaller and Fitzgerald, 2014; Ren et al, 2004; Laprairie and Murphy, 2009). Changes in descending inhibitory control of the local spinal nociceptive network have been identified (Schwaller and Fitzgerald, 2014; Laprairie and Murphy, 2009; Walker et al, 2015) These changes may underlie the observed differences in sensitivity and pain perception in adulthood, as it leads to increased hypersensitivity with reinjury of the same dermatome. In this respect, further research on the consequences of early life pain on the (descending) inhibitory opioid system is of particular interest, as the opioid system is important in control of the local spinal nociceptive network and because opioids are the drug of choice when treating acute postoperative pain later in life (Argoff, 2014). M-opioid receptors are present in the rat CNS at birth and increase in density to adult
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