Reduced ΔFosB expression in the rat nucleus accumbens has causal role in the neuropathic pain phenotype

Neurosci Lett. 2019 May 29:702:77-83. doi: 10.1016/j.neulet.2018.11.036. Epub 2018 Nov 29.

Abstract

The neuropathic pain phenotype is the consequence of functional and morphological reorganization of the PNS and CNS. This reorganization includes DRGs and the spinal cord, and extends to multiple supraspinal areas including the limbic and reward systems. Several recent papers show that acute manipulation of cortical and subcortical brain areas causally correlates with the cognitive, emotional and sensory components of neuropathic pain, yet mechanisms responsible for pain chronification remain largely unknown. Here we show that nucleus accumbens expression of ΔFos-B, a transcription factor that plays a critical role in addiction and in the brain response to stress, is reduced long term following peripheral neuropathic injury. Conversely, boosting ΔFos-B expression in the nucleus accumbens by viral transfection causes a significant and long-lasting improvement of the neuropathic allodynia. We suggest that ΔFos-B in the nucleus accumbens is a key modulator of long term gene expression leading to pain chronification.

Keywords: Chronic pain; Gene expression; Immediate early genes; Limbic system.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Chronic Pain / metabolism*
  • Chronic Pain / physiopathology
  • Chronic Pain / psychology
  • Cold Temperature
  • Dependovirus / genetics
  • Hyperalgesia / metabolism
  • Hyperalgesia / physiopathology
  • Hyperalgesia / psychology
  • Male
  • Neuralgia / metabolism*
  • Neuralgia / physiopathology
  • Neuralgia / psychology
  • Nucleus Accumbens / metabolism*
  • Phenotype
  • Physical Stimulation
  • Proto-Oncogene Proteins c-fos / genetics
  • Proto-Oncogene Proteins c-fos / metabolism*
  • Rats, Sprague-Dawley
  • Touch

Substances

  • Fosb protein, rat
  • Proto-Oncogene Proteins c-fos