Adult spinal opioid receptor μ1 expression after incision is altered by early life repetitive tactile and noxious procedures in rats

Dev Neurobiol. 2018 Apr;78(4):417-426. doi: 10.1002/dneu.22583. Epub 2018 Feb 28.

Abstract

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 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.

Keywords: neonate; opioid receptor; post-operative pain; procedural pain; spinal cord.

MeSH terms

  • Animals
  • Animals, Newborn
  • Disease Models, Animal
  • Female
  • Intensive Care, Neonatal
  • Male
  • Pain Threshold
  • Pain, Postoperative / metabolism*
  • Pain, Postoperative / pathology
  • Physical Stimulation
  • Rats, Sprague-Dawley
  • Receptors, Opioid, mu / metabolism*
  • Spinal Cord / growth & development*
  • Spinal Cord / metabolism*
  • Spinal Cord / pathology
  • Touch / physiology*
  • Wounds and Injuries / metabolism*

Substances

  • Oprm1 protein, rat
  • Receptors, Opioid, mu