Docosahexaenoic Acid Attenuates Visceral Pain by Suppressing Spinal CXCL10/CXCR3/ERK Signaling.

Background

Visceral pain is the primary symptom of functional gastrointestinal disorders, yet its spinal molecular mechanisms remain poorly defined.

Methods

Using a 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced chronic inflammatory visceral pain model, the role of the spinal CXCL10/CXCR3/ERK signaling axis and the analgesic effect of docosahexaenoic acid (DHA) were investigated.

Results

TNBS significantly upregulated CXCL10 and CXCR3 in spinal dorsal horn neurons and increased ERK phosphorylation. Intrathecal CXCL10-neutralizing antibody or CXCR3 antagonist NBI-74330 reduced visceral hypersensitivity and suppressed spinal ERK activation in TNBS mice. Exogenous CXCL10 induced CXCR3-dependent hyperalgesia and ERK phosphorylation in the spinal cord. Intrathecal DHA attenuated TNBS-induced visceral pain, downregulated spinal CXCL10/CXCR3 expression, and inhibited ERK signaling. In Neuro-2a cells, DHA also blocked LPS-induced activation of the same pathway.

Conclusions

This study suggests that the analgesic effect of DHA may involve the inhibition of the spinal CXCL10/CXCR3/ERK signaling pathway.