Abstract # 1720 T lymphocytes are required for resolution of inflammatory pain and depression-like behavior

Abstract

Transient pain and depressed mood commonly develop in response to inflammation. While normally reversible once the peripheral inflammation has resolved, depression and pain persist in some individuals. On the basis of previous studies showing that T lymphocytes contribute to homeostasis and repair in the nervous system, we hypothesized that T lymphocytes promote endogenous resolution of comorbid depression-like behavior and pain. Transient pain and depression-like behavior were induced by systemic administration of lipopolysaccharide (LPS) or by intraplantar injection of complete Freund’s adjuvant (CFA). In both models, depression-like behavior, mechanical allodynia and ongoing pain (measured by analgesic-induced conditioned place preference) were substantially prolonged in mice lacking mature lymphocytes (Rag1 and Rag2 KO mice). Reconstitution of Rag KO mice with T cells normalized resolution of depression-like behavior, mechanical allodynia and ongoing pain. Increased expression of the tryptophan-metabolizing enzyme indoleamine 2,3-dioxygenase (IDO1) in the brain which mediates depression-like behavior in response to peripheral inflammation was also prolonged in absence of T cells. The anti-inflammatory cytokine IL-10 and the ATP-degrading enzyme CD73 were upregulated in the prefrontal cortex (PFC) of WT mice after they had recovered, but not in Rag KO mice at the same time point. These findings demonstrate an important role for T lymphocytes in the endogenous resolution of inflammatory pain and depression.