Pain vulnerability and DNA methyltransferase 3a involved in the affective dimension of chronic pain

Wei Wang, Caiyue Li, Youqing Cai, Zhizhong Z. Pan

Research output: Contribution to journalArticlepeer-review

14 Scopus citations

Abstract

Chronic pain with comorbid emotional disorders is a prevalent neurological disease in patients under various pathological conditions, yet patients show considerable difference in their vulnerability to developing chronic pain. Understanding the neurobiological basis underlying this pain vulnerability is essential to develop targeted therapies of higher efficiency in pain treatment of precision medicine. However, this pain vulnerability has not been addressed in preclinical pain research in animals to date. In this study, we investigated individual variance in both sensory and affective/emotional dimensions of pain behaviors in response to chronic neuropathic pain condition in a mouse model of chronic pain. We found that mice displayed considerably diverse sensitivities in the chronic pain-induced anxiety- and depression-like behaviors of affective pain. Importantly, the mouse group that was more vulnerable to developing anxiety was also more vulnerable to developing depressive behavior under the chronic pain condition. In contrast, there was relatively much less variance in individual responses in the sensory dimension of pain sensitization. Molecular analysis revealed that those mice vulnerable to developing the emotional disorders showed a significant reduction in the protein level of DNA methyltransferase 3a in the emotion-processing central nucleus of the amygdala. In addition, social stress also revealed significant individual variance in anxiety behavior in mice. These findings suggest that individual pain vulnerability may be inherent mostly in the emotional/affective component of chronic pain and remain consistent in different aspects of negative emotion, in which adaptive changes in the function of DNA methyltransferase 3a for DNA methylation in central amygdala may play an important role. This may open a new avenue of basic research into the neurobiological mechanisms underlying pain vulnerability.

Original languageEnglish (US)
JournalMolecular pain
Volume13
DOIs
StatePublished - Aug 1 2017

Keywords

  • DNA methyltransferase 3a
  • Pain vulnerability
  • affective pain
  • central amygdala
  • chronic pain
  • negative emotion

ASJC Scopus subject areas

  • Molecular Medicine
  • Cellular and Molecular Neuroscience
  • Anesthesiology and Pain Medicine

Fingerprint

Dive into the research topics of 'Pain vulnerability and DNA methyltransferase 3a involved in the affective dimension of chronic pain'. Together they form a unique fingerprint.

Cite this