Morphine exposure during early life alters thermal and mechanical thresholds in rats
Autor: | Iraci Lucena da Silva Torres, Wolnei Caumo, Jonnsin Kuo, Isabel Cristina de Macedo, Liciane Fernandes Medeiros, Éllen Almeida Nunes, Joice Soares de Freitas, Andressa de Souza, Joanna Rippol Rozisky |
---|---|
Rok vydání: | 2016 |
Předmět: |
0301 basic medicine
Male Nociception medicine.medical_specialty Aging 03 medical and health sciences 0302 clinical medicine Neurochemical Developmental Neuroscience Internal medicine medicine Animals Nerve Growth Factors Hot plate test Rats Wistar biology Dose-Response Relationship Drug Morphine business.industry Temperature Brain Rats Analgesics Opioid 030104 developmental biology medicine.anatomical_structure Endocrinology Nerve growth factor Allodynia Cerebral cortex Hyperalgesia Touch Anesthesia Sensory Thresholds biology.protein medicine.symptom business 030217 neurology & neurosurgery Developmental Biology Neurotrophin medicine.drug |
Zdroj: | International journal of developmental neuroscience : the official journal of the International Society for Developmental Neuroscience. 60 |
ISSN: | 1873-474X |
Popis: | Background Morphine is an opioid analgesic used to relieve moderate-to-severe pain, including pain in neonates at the intensive care unit. In our previous study, we showed that repeated morphine exposure during early life could trigger long-lasting implications on the developing nervous system, such as long-term neurochemical and behavioral alterations in adult rats. Aims The aim of our study was to determine the short-, intermediate-, and long-term effects of repeated morphine administration during early life on the thermal and mechanical thresholds and on the central levels (cerebral cortex and brainstem) of neurotrophins (brain-derived neurotrophic factor [BDNF] and nerve growth factor [NGF]) and cytokines (interleukin-6 [IL-6] and IL-10). Methods Male Wistar rats were administered morphine (5 μg/day, s.c.) or saline for 7 days from postnatal day 8 (P8) until P14. The nociceptive effect was assessed by evaluating the thermal response using the hot plate test (HPT) and the mechanical response by Von Frey (VFT) and Randall-Selitto (RST) tests at P16, P30, and P60. BDNF, NGF, IL-6, and IL-10 levels were measured in the cerebral cortex and brainstem. Results In HPT, no difference in latency was observed at P16; however, at P30 and P60, the morphine-treated group exhibited a less increase in the nociceptive threshold compared to the saline group. VFT and RST demonstrated an interaction between group and age, where the morphine group showed a less pronounced increase in latency with age, which is indicative of allodynia. In the cerebral cortex, an association between BDNF and NGF levels and age was observed, where neurotrophin level increased with age in the saline group, and decreased with age in the morphine group. In addition, IL-10 levels decreased with age in both groups; however, there was no significant difference in IL-6 levels. In the brainstem, BDNF, NGF, IL-6, and IL-10 levels increased with age. Discussion Repeated morphine exposure during neonatal life triggered alterations in the nociceptive behavior, including thermal hyperalgesia and mechanical allodynia, as well as decreased levels of BDNF and NGF in the cerebral cortex. Our study highlights the importance of extensive comprehension of the pharmacological interventions during CNS maturation. |
Databáze: | OpenAIRE |
Externí odkaz: |