Impairment of Nociceptive Responses After Neonatal Anoxia Correlates With Somatosensory Thalamic Damage: A Study in Rats

Chronic neuropathic pain resulting from damage to the central or peripheral nervous system is a prevalent and debilitating condition affecting 7-18% of the population. Symptoms include spontaneous pain, dysesthesia, paresthesia, allodynia and hyperalgesia. The reported sensory symptoms are comorbid with behavioral disabilities such as insomnia and depression. Neonatal anoxia, a worldwide clinical problem in both neonatal and pediatric care, causes long-term deficits similar to those mentioned. The effect of neonatal anoxia on the maturation of nociceptive pathways has been sparsely explored. To address this question and to determine whether the effects differ depending on sex, a neonatal anoxia model was used in which Wistar rat pups approximately 30 h old and of both sexes were placed in a chamber with 100% nitrogen flow at 3.5 L/min for 25 min at 36 °C ± 1 °C. After recovery, the animals (n = 16 in each group (anoxia and control; males and females)) were returned to their mothers. The control animals were subjected to the same conditions, but no gas exchange was performed. At postnatal day (PND) 18 and PND43, the animals were subjected to pain testing by stimulation of the hind paws with von Frey monofilaments. The results revealed a significant reduction (approximately 50%) in the pain threshold in the animals exposed to anoxia in comparison with their respective controls. The pain threshold increased between PND18 and PND43. A sex-based difference was observed in the male control group at PND18. Histological analysis revealed decreased cell numbers in the ventral posterolateral thalamic nucleus (VPL), with sex differences. These results demonstrate the long-lasting negative impact of neonatal anoxia and indicate the relevance of performing suitable approaches taking in consideration the possible sex differences.

Keywords: Mechanical allodynia; Neonatal anoxia; NeuN; Sex difference; Thalamus (VPL); Von frey monofilaments.