Noxious stimuli in the neonatal period in rats can cause important peripheral nervous system alterations that persist on adults in a sex-dependent manner

Advances in medicine have increased the survival of preterm neonates, that are constantly submitted to invasive procedures, such as heelsticks, insertion of indwelling venous and arterial catheters, causing repetitive painful experiences in the neonate period. However, the consequence of early painful experiences in the peripheral nervous system remains unexplored. We aimed to evaluate the possible alterations in the sural nerves of male and female adult Wistar rats, after painful stimulation in the neonatal period. Wistar rats were followed birth to 180 days of life, separated in 4 groups: 1) Control-male group; 2) Control-female group; 3) Pain-male group; 4) Pain-female group. Pain groups received repetitive needle insertion in plantar and lateral area of the right paw, twice a day for 15 days starting at birth. Control groups were stimulated with a cotton swab, twice per day for 15 days starting at birth. When animals completed 180 days of life, they were killed, and the sural nerves were dissected, and prepared for light microscopy. Visual morphometry was performed with the aid of computer software to measure the fascicular and myelinated fiber parameters (fascicular area, number and density of myelinated fibers and Schwann cell nuclei, area and diameter of myelinated fibers and respective axons and g ratio). Female rats from the pain group show smaller sural nerve, myelinated fibers, and myelinated axon areas compared to female controls. Furthermore, the myelinated fibers diameter distribution shows that the female pain group present larger number of smaller fiber. Males showed no significant difference between groups. These results suggest that male and females can respond on different ways to neonatal injury with females showing changes in peripheral sensory nerve morphometry. In conclusion, noxious stimuli in the neonatal period in rats can cause important peripheral nervous system alterations that persist on adults in a sex-dependent manner.