Psychophysical stress can cause neural changes that increase nociception in the orofacial region, particularly the masseter muscle (MM). The nucleus raphe magnus (NRM), which is located in the brain stem, serves the crucial role of regulating nociception through descending modulatory pain control. However, it remains unclear if neural activities in the NRM are affected under psychophysical stress conditions. This study conducted experiments to assess (1) whether neural activity, indicated by Fos expression in an NRM that has experienced MM injury, is affected by the stress of repeated forced swim tests (FST); and (2) whether the selective serotonin reuptake inhibitor fluoxetine administered daily after an FST could affect the number of Fos-positive neurons in the NRM. Results revealed that the stress from repeated FSTs significantly increased the number of Fos-positive neurons in an NRM that had been affected by MM injury. Fluoxetine inhibited increases in the number of Fos-positive neurons in the NRM that occurred as a result of FSTs, but this was not observed in sham rats. These findings indicate that the stress from FSTs could increase nociceptive neural activity in an NRM that has experienced MM injury. This could be due, in part, to changes in serotonergic mechanisms.