Chronic Stress Is Associated with Pain Precipitation and Elevation in DeltaFosb Expression

Abstract

A number of acute or repeated stimuli can induce expression of DeltaFosB (ΔFosB), a transcription factor derived from the fosB gene (an osteosarcoma viral oncogene) via alternative splicing. ΔFosB protein is currently viewed as a ‘molecular switch’ to repeated stimuli that gradually converts acute responses into relatively stable adaptations underlying long-term neural and behavioral plasticity. ΔFosB has received extensive attention in drug addition, depression, and stress adaptation, but changes in ΔFosB protein expression during pain is not fully understood. In this study we explored ΔFosB expression in the medial prefrontal cortex (mPFC) of rats experiencing chronic or acute stress-induced pain. Our data reveal that chronic pain induced by neonatal colorectal distension, chronic constriction injury (CCI) of the sciatic nerve, or maternal separation was associated with an increase in ΔfosB protein expression in mPFC, but acute application of acetic acid or zymosan did not alter the ΔFosB protein expression. ΔFosB expression in the rat visual cortex, a non pain-related brain region, did not change in response to (CCI) of the sciatic nerve and acetic acid treatment. In conclusion, our results indicate that ΔFosB protein expression is significantly elevated in rats that have experienced chronic pain and stress, but not acute pain. The ΔFosB protein may serve as an important transcription factor for chronic stress-induced pain. Further research is needed to improve the understanding of both the upstream signaling leading to ΔFosB protein expression as well as the regulation of ΔFosB gene expression in cortical neurons.

Toll-Like Receptor 4 in Paraventricular Nucleus Mediates Visceral Hypersensitivity Induced by Maternal Separation

“…The MS protocol was conducted as previously described in detail ( Leon Rodriguez and Duenas, 2013 ; Wang et al, 2016 ). Briefly, male and female mice in both the Tlr4 +/+ and Tlr4 -/- strains were mated for litters.…”

The Medial Prefrontal Cortex as a Central Hub for Mental Comorbidities Associated with Chronic Pain

“…Only recently, the specificity of mPFC subregions is receiving more attention [170,[205][206][207][208][209]. In particular, electrophysiological recordings of L5 pyramidal cells reveal relevant functional differences between PrL and IL: the GABA A antagonist bicuculline modulates neuron activity in PrL, whereas cannabinoid receptor CB1 and mGLuR5 are relevant components in IL [22,27,210].…”

Small-Conductance Ca2+-Activated K+ Channel 2 in the Dorsal Horn of Spinal Cord Participates in Visceral Hypersensitivity in Rats

“…The mechanism of visceral hypersensitivity and pain is still poorly understood due to the diverse nature of visceral hypersensitivity compounded by multiple factors such as sexual dimorphism, psychological and physical stresses, genetic and epigenetic traits, and the nature of predisposed disease ( Chen et al, 2015 ; Elsenbruch and Enck, 2016 ). We recently demonstrated that early life stresses, for example, neonatal colorectal distension (CRD), maternal separation, could induce visceral hypersensitivity in rats ( Wang et al, 2016 ; Zhang et al, 2016a , b ). Visceral information is collected by thoracolumbar and sacral spinal visceral afferents, and coded by viscerosomatic neurons in spinal cord, thalamus, limbic system, and cortex ( Larauche et al, 2012 ; Moloney et al, 2015 ).…”