Orthodontic pain: c-Fos expression in rat brain nuclei after rapid maxillary expansion

Published:November 04, 2022DOI:


      • The rapid maxillary expansion is followed by pain during and after the opening of the midpalatal suture.
      • The cause of the pain resulting from orthodontic treatment is not entirely clear.
      • The sites of processing for the nociceptive information originating in the midpalatal suture after rapid maxillary expansion have not been investigated to date in the trigeminal subnucleus complex and parabrachial area.



      The aim of this in vivo study was to quantitatively evaluate pain after rapid maxillary expansion (RME) in young rats by analyzing the activation of nociception-related structures, that is, the caudalis, interpolaris, and oralis subnuclei, according to the Fos expression.


      A total of 65 Wistar rats were assigned to three groups: control group (n = 15) with no treatment, positive control group (n = 25), and experimental group (n = 25) with RME. The experimental animals were euthanized at 6, 12, 24, 48, and 72 hours after RME, and the brain was later carefully collected. Coronal sections through the spinal trigeminal caudalis, spinal trigeminal interpolaris, and spinal trigeminal oralis were cut (thickness of 40 µm) on a cryostat and processed for Fos immunohistochemistry. Images from the sections were captured under light microscopy, and ImageJ software was used to count Fos-like immunoreactive neurons. The Analysis of variance (ANOVA) and Tukey test were used for statistical analysis, and the significance level was set at 5%.


      RME induced incisor distalization and opening of the midpalatal suture, as well as neuronal activation of the spinal trigeminal nucleus. The experimental group demonstrated significantly more Fos-positive neurons in subnuclei caudalis and subnuclei interpolaris 6 hours after the maxillary expansion. The Fos immunoreactivity significantly decreased at 12 hours and increased again at 24 and 48 hours (P < 0.001).


      The RME increases the neural activation of brain regions involved in the nociception region, as determined by the Fos expression. The most intense Fos-like immunoreactive expression was detected in the brain 6 hours after the start of the palatal expansion.
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