LAUSR

Psychophysical stresses frequently increase sensitivity and response to pain, which is termed stress-induced hyperalgesia (SIH). However, the mechanism remains unknown. The rostral ventromedial medulla (RVM) and locus coeruleus (LC) are core elements of the descending pain modulatory system, which modulate nociceptive transmission in the spinal dorsal horn. In the present study we examined the acetylation of histone H3 in the RVM and LC after repeated restraint stress for 3 weeks to clarify changes in the descending pain modulatory system in the rat with SIH. The repeated restraint stress induced mechanical hypersensitivity in the hindpaw and an increase in acetylation of histone H3 in the RVM but not the LC. The number of acetylated histone H3-IR cells in the RVM was significantly higher in the repeated restraint group (282.9 ± 43.1) than that in the control group (134.7 ± 15.6, p <  0.05). Furthermore, the repeated restraint stress increased acetylation of histone H3 in the RVM GABAergic neurons but not the RVM serotonergic neurons. The GAD67 protein level in the RVM was significantly higher in repeated restraint group (144.9 ± 17.0%) than that in the control group (100.0 ± 8.9%, p < 0.05). These findings suggest the possibility that the stress-induced neuroplasticity in the RVM GABAergic neurons is involved in the mechanical hypersensitivity due to the dysfunction of the descending pain modulatory system.