The contribution of TNF-α in the amygdala to anxiety in mice with persistent inflammatory pain

Abstract

Tumor necrosis factor alpha (TNF-α) is known for its role in inflammation and pain, which are strongly associated with mood disorders such as anxiety and depression. The amygdala is a forebrain structure that modulates anxiety. However, little is known about the role of TNF-α in the development of anxiety in animals with chronic pain. In the present study, we examined TNF-α expression in the basolateral amygdala (BLA) following injection of complete Freund's adjuvant (CFA) into the hind paw of mice to induce inflammation. We also determined the effects of TNF-α expression on the development of anxiety in these mice. TNF-α expression was increased in the BLA during the chronic phase of CFA-induced peripheral inflammation. The local infusion of TNF-α-neutralizing antibody infliximab in the BLA reversed anxiety-like behaviors in mice with persistent inflammatory pain. In vitro slice recordings revealed that TNF-α significantly enhanced AMPA-receptor-mediated glutamatergic excitatory synaptic transmission and inhibited GABAA-receptor-mediated inhibitory synaptic transmission in the BLA. Our findings, therefore, provide strong evidence that TNF-α contributes to the development of anxiety in mice with persistent inflammatory pain.