Resolvin D2 attenuates chronic pain–induced depression‐like behavior in mice

Abstract

Aim We previously demonstrated that intracerebroventricular injection of resolvin D2 (RvD2), a bioactive lipid mediator derived from docosahexaenoic acid, ameliorated depression‐like behavior in lipopolysaccharide‐induced and chronic mild stress–induced mouse models of depression. In the present study, we examined the antidepressant effect of RvD2 on chronic pain–induced depression‐like behavior. Methods To prepare the neuropathic pain model, mice were subjected to surgery for unilateral spared nerve injury. Two weeks after surgery, the antidepressant effect of RvD2 was examined using the tail suspension test. Results Chronic pain significantly increased immobility time, and this depression‐like behavior was attenuated by intracerebroventricular injection of RvD2 (10 ng). No effect of RvD2 on the locomotor activity was observed. Conclusion RvD2 produces an antidepressant effect in a murine model of chronic pain–induced depression and may be a promising lead for the development of novel antidepressants.

Uncovering the Power of GPR18 Signalling: How RvD2 and Other Ligands Could Have the Potential to Modulate and Resolve Inflammation in Various Health Disorders

“…A long immobility time indicates a high level of depression. The immobility time was reduced after intracerebroventricular (ICV) injection of RvD2 (10 ng) and this antidepressive role of RvD2 was transduced through activation of mTORC1 signalling [ 48 ]. Of interest, the same research group also demonstrated the antidepressant properties of RvD2 (at the same concentration of 10 ng) in two other mouse models of depression induced using endotoxin from Gram-negative bacteria lipopolysaccharide (LPS) or chronic unpredictable stress [ 49 , 50 ].…”

Roles of Resolvins in Chronic Inflammatory Response

“…In terms of anti-depression, RvD1 plays an anti-depression role through the transmission of glutamic acid or PI3K/AKT signaling, while RvD2 can also act on MEK/ERK [ 127 ]. The activation of mTORC1 signaling is the key anti-depressive role of RvD1, RvD2, RvE1, RvE2, and RvE3 [ 25 , 128 , 129 , 130 , 131 , 132 ]. In addition, RvD2 promotes the healing of periapical bone lesions and the regeneration of pulp-like tissue by enhancing the expression of dentin matrix acidic phosphoprotein 1 (DMP1) and the phosphorylation of STAT3 [ 133 ].…”