Psychophysical Stress Enhances Orofacial Nociception in the Rostral Ventromedial Medulla

Objectives: Emotional stress has facilitatory roles on orofacial pain through neural changes in the rostral ventromedial medulla (RVM) which projects serotonin fibers to trigeminal caudalis (Vc) to regulate orofacial nociception. Previously we showed that repeated psychophysical stress enhanced masseter muscle (MM) nociception via functional changes in Vc region. The aim of this study was to test if chronic stress had modulatory effects on MM nociception in the RVM.
Methods: Male rats were subjected to repeated forced swim stress (FS) or sham (no FS but being placed in empty cylinder) conditionings for 3 days (10 min/d). On Day 4 neural activities indicated by Fos-immunoreactive cells in RVM were determined using immunohistochemical methods 2 hours after MM injury with saline or 5% formalin injection. We also assessed Serotonin-positive cells in the RVM. The number of Fos- and Serotonin-positive cells/section was quantified at several regions within the RVM including the nucleus raphe magnus (NRM) and reticularis gigantocellularis pars alpha (GiA) and compared between FS and sham rats. Five to seven rats were analyzed in each group.
Results: MM injection of formalin significantly increased Fos expression in NRM and GiA regions compared to that of saline injection in sham and FS rats. In FS rats Fos expression evoked by formalin was significantly increased in NRM (~56 cells) and GiA (~18) compared to sham (NRM: ~34 cells, GiA:~13 cells) rats, indicating that neural activity in the NRM was enhanced under psychophysical stress condition. FS alone showed a small but not significant increase in Fos expression in NRM (~11 cells) and GiA (~2 cells) compared to sham rats (~5 and ~1.1 cells in NRM and GiA). The number of 5HT positive neurons was not affected by FS conditionings in the NRM and GiA.
Conclusions: Enhanced MM nociception under psychophysical stress conditions could be attributed to functional changes in descending pain control systems.