Effect of daily treadmill running exercise on masseter muscle nociception associated with social defeat stress in mice

Abstract

We investigated the effects of social defeat stress (SDS) and treadmill running on masseter muscle nociception, which was quantified by the orofacial formalin test and c-Fos and FosB immunoreactivities in the upper cervical spinal cord (C1/C2) region in male mice. After daily SDS or non-SDS conditioning for 10 days, SDS-conditioned mice were categorized into SDS-susceptible versus resilient mice. Several mice, including non-SDS-conditioned, SDS-susceptible, and resilient mice, were selected to assess masseter muscle nociception on Day 11. SDS conditioning for 10 days increased masseter muscle-evoked nocifensive behaviors and c-Fos and FosB expression in SDS-susceptible compared to non-SDS and resilient mice. The remaining SDS-susceptible and non-SDS mice were subjected to an additional 10 days of SDS plus treadmill running or sedentary sessions before assessing masseter muscle nociception on Day 21. Daily treadmill running sessions reduced enhanced masseter muscle nociception in SDS-susceptible mice but not in non-SDS mice. The preventive effects of daily treadmill running immediately after each SDS conditioning for 10 days on orofacial nocifensive behaviors were assessed on Day 11. Treadmill running conducted immediately after daily SDS inhibited enhanced orofacial nocifensive behaviors. These findings indicate that repeated SDS increases masseter muscle nociception, which could be prevented by daily treadmill running exercise.

Effects of stress contagion on anxiogenic‐ and orofacial inflammatory pain‐like behaviors with brain activation in mice

“…Psychological stress increases neural activities in the C1/C2 region, which is critical in facilitating deep craniofacial nociception [6, 41]. Consistent with our previous reports [8–10], stress contagion mice also increased both c‐Fos and FosB expressions in the C1/C2 region in the absence or presence of masseter muscle stimulation. These findings indicate that increases in neural activities in the C1/C2 region could result in the facilitation of orofacial inflammatory pain‐like behaviors under stress contagion.…”

“…The orofacial formalin test was conducted to quantify orofacial inflammatory pain‐like behaviors [10]. Briefly, 2.5% formalin (2 μL in 0.9% saline) was administered to the mid‐region of the left masseter muscle using a Hamilton syringe.…”

“…Our previous report described the social defeat stress conditioning procedure in detail [10]. In brief, the ICR mice (aggressors) were screened for aggressive behavioral activi- ties by placing C57BL/6J mice in their home cages.…”

“…The first aim of this study was to determine if stress contagion changed masseter muscle nociception. Previously, we reported that increases in formalin‐evoked orofacial inflammatory pain‐like behaviors in mice subjected to repeated social defeat stress conditionings could be relying on increased neural activities in the upper cervical spinal cord (C1/C2) region [6, 10]. Given that stress contagion has increased anxiogenic‐like responses [3, 11], it is reasonable to hypothesize that stress contagion could increase masseter muscle nociception, as seen in social defeat stressed mice [10].…”

“…Previously, we reported that increases in formalin-evoked orofacial inflammatory pain-like behaviors in mice subjected to repeated social defeat stress conditionings could be relying on increased neural activities in the upper cervical spinal cord (C1/C2) region [6,10]. Given that stress contagion has increased anxiogenic-like responses [3,11], it is reasonable to hypothesize that stress contagion could increase masseter muscle nociception, as seen in social defeat stressed mice [10]. However, it is unknown if stress contagion could affect neural activities in the brain associated with masseter muscle nociception.…”