There are sustained interests in understanding the interactions between stress response and nociception. Here we examined some combination of chronic pain models with social defeat stress model to address whether social stress modulates nociceptive behavior of mice subjected to chronic pain models.
C57BL/6Jcl male mice were subjected to peripheral nerve injury (PNI) induced neuropathic pain model. After spontaneous remission was observed at day 35 post-PNI, social defeats was loaded by aggressor mice, and 50% paw withdrawal threshold was measured with von Frey filament. In this procedure, we found that loading single social defeat stress induced a decrease of paw withdrawal threshold again. This effect similarly occurred in other chronic pain models that were induced in complete Freund‘s adjuvant induced inflammatory pain model and reserpine induced pain model, but was not seen in naïve mice. Intraperitoneal LPS and intravenous IL6 administration induced similar relapse. Immunohistochemical analysis of iba-1 represented a sustained microglial activation in the spinal dorsal horn of stress loaded neuropathic pain model mice.
Our results demonstrated that social defeat stress itself could induce recurrence of experienced chronic pain state in which reactivation of spinal microglia may correlated with the phenomenon.