The cortical areas processing periodontal ligament nociception in mice

Objectives: Toothaches are often poorly localized. Although periodontal pain is better localized, it can spread to other areas. Ultimately, the cerebral cortex processes nociception, with somatotopic organization possibly playing a role in localizing the origin. However, the exact cortical area in the periodontal ligament (PDL) remains unclear. Methods: This study examined cortical responses to electrical stimulation of the molar PDL in anesthetized male mice using in vivo optical imaging with a voltage-sensitive dye, autofluorescent flavin fluorescence, and immunohistochemistry for c-Fos protein expression. Results: On optical imaging, cortical responses to the stimulation of the ipsilateral and contralateral PDL of the upper and lower teeth were observed in the primary somatosensory cortex (S1) and area from the insular cortex (IC) to the ventral edge of the secondary somatosensory cortex (S2), defined as the area caudal to the middle cerebral artery (C-area). Responses in S1 were faint and unstable, but were consistent in the C-area. The initial response locations were similar regardless of which PDL was stimulated, and the activated areas in the C-area almost overlapped. Three-dimensional construction of c-Fos-immunopositive cells responding to upper or lower PDL stimulation revealed bilateral distribution in the cingulate gyrus, secondary auditory cortex, temporal association cortex, ectorhinal cortex, and IC, but not in the S1 and S2. Conclusion: These results suggest that the somatotopic organization of the S1, S2, and IC cannot explain the localization of PDL nociception. The predominance of responses in the contralateral IC may provide clues for identifying the laterality.