Neonatal anoxia increases nociceptive response in rats: Sex differences and lumbar spinal cord and insula alterations

• Published in: International journal of developmental neuroscience Vol. 81; no. 8; pp. 686 - 697
• Main Authors: Helou, Ammir Yacoub, Martins, Daniel Oliveira, Arruda, Bruna Petrucelli, Souza, Matheus Cerussi, Cruz‐Ochoa, Natalia Andrea, Nogueira, Maria Inês, Chacur, Marucia
• Format: Journal Article
• Language: English
• Published: United States 01-12-2021
• Subjects: Animals; Female; GFAP; Hypoxia - physiopathology; insular cortex; Insular Cortex - physiopathology; Male; neonatal anoxia; Neurons - physiology; nociception; Nociception - physiology; Rats; Rats, Wistar; Sex Factors; spinal cord; Spinal Cord - physiopathology; nociception; neonatal anoxia; insular cortex; spinal cord; GFAP
• ISSN: 0736-5748; 1873-474X
• DOI: 10.1002/jdn.10145

Neonatal anoxia is a well‐known world health problem that results in neurodevelopmental deficits, such as sensory alterations that are observed in patients with cerebral palsy and autism disorder, for which oxygen deprivation is a risk factor. Nociceptive response, as part of the sensory system, has been reported as altered in these patients. To determine whether neonatal oxygen deprivation alters nociceptive sensitivity and promotes medium‐ and long‐term inflammatory feedback in the central nervous system, Wistar rats of around 30 h old were submitted to anoxia (100% nitrogen flux for 25 min) and evaluated on PND23 (postpartum day) and PND90. The nociceptive response was assessed by mechanical, thermal, and tactile tests in the early postnatal and adulthood periods. The lumbar spinal cord (SC, L4–L6) motor neurons (MNs) and the posterior insular cortex neurons were counted and compared with their respective controls after anoxia. In addition, we evaluated the possible effect of anoxia on the expression of astrocytes in the SC at adulthood. The results showed increased nociceptive responses in both males and females submitted to anoxia, although these responses were different according to the nociceptive stimulus. A decrease in MNs in adult anoxiated females and an upregulation of GFAP expression in the SC were observed. In the insular cortex, a decrease in the number of cells of anoxiated males was observed in the neonatal period. Our findings suggest that oxygen‐deprived nervous systems in rats may affect their response at the sensorimotor pathways and respective controlling centers with sex differences, which were related to the used stimulus.
Neonatal anoxia increased hyperalgesia and allodynia with long‐lasting outcomes. Adult anoxia females presented more allodynia and hypersensitivity than anoxia males. There were sex and age differences to tactile allodynia, thermal hypensensitivity, and mechanical hyperalgesia. Adult anoxia females had more cell loss at spinal cord than anoxia males. Adolescent anoxia males had more cell loss at posterior insula than anoxia females. Adult female rats had increased GFAP in the lumbar spinal cord than anoxia males.