Adult spinal opioid receptor 1 expression after incision is altered by early life repetitive tactile and noxious procedures in rats

Nynke J. van den Hoogen*, Roel R. I. van Reij, Jacob Patijn, Dick Tibboel, Elbert A. J. Joosten

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review


Clinical 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 mu-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. (c) 2018 The Authors. Developmental Neurobiology Published by Wiley Periodicals, Inc. Develop Neurobiol 78: 417-426, 2018
Original languageEnglish
Pages (from-to)417-426
Number of pages10
JournalDevelopmental neurobiology
Issue number4
Publication statusPublished - 1 Apr 2018


  • neonate
  • spinal cord
  • procedural pain
  • post-operative pain
  • opioid receptor
  • CORD

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