TRIM14-NF-κB pathway in the anterior cingulate cortex modulates comorbid depressive symptoms in chronic pain.

Abstract

Depression is commonly observed in individuals suffering from chronic pain, but the exact molecular mechanisms behind these symptoms are still not fully understood. This study highlights the important role of the TRIM14-NF-κB pathway in the anterior cingulate cortex (ACC) in regulating comorbid depressive symptoms associated with chronic pain. Our results show that the CFA model induces both chronic pain and depression-like behaviors in mice, with significant activation of the ACC brain regions. Specifically, the protein expression of TRIM14 was notably elevated in the ACC of CFA mice. Furthermore, reducing TRIM14 expression alleviated both chronic pain and depression-like behaviors in these mice. In addition, we also discovered that NF-κB may act as a downstream target of TRIM14, as silencing TRIM14 expression led to a reduction in the levels of phosphorylated NF-κB. Notably, inhibiting NF-κB produced similar improvements in chronic pain and depression-like behaviors, mirroring the effects observed with TRIM14 knockdown. In summary, our findings emphasize the critical role of the TRIM14-NF-κB pathway in regulating chronic pain and depression-like behaviors in the CFA mouse model. These insights provide a foundation for further exploration of the molecular mechanisms underlying chronic pain and depression, and may guide the development of targeted therapeutic strategies.