Figure 1 Surrogate mechanisms of DEX involved in relieving visceral pain(A) DEX attenuates visceral pain via locus coeruleus. DEX activates alpha-2 adrenoreceptors in the locus coeruleus, then decreases the release of CGRP, glutamate, and substance P in the dorsal horn of spinal cord, which alleviate visceral pain from surgical insults. (B) Immunomodulatory effects of DEX contribute to reduce visceral pain. DEX suppresses the expression of CD40 and CD86 expression on the surface of macrophages, promotes polarization of macrophages from M1 to M2, and decreases secretion of inflammatory cytokines, including TNF-α, IL-1β, IL-6, IL-8 and CD8+ T cells. (C) DEX preserves the gut barrier integrity. The expression of claudin and occludin are upregulated after the administration of DEX, and these decrease intestinal barrier injury after surgical insult. Concurrently, it attenuates the magnitude of systemic inflammatory response. (D) DEX improves sleep quality through sympatholytic effects and altered sleep architectures, which is conducive to relieve visceral pain. DEX – dexmedetomidine; CGRP – calcitonin gene-related peptide; CD40 – cluster of differentiation 40; CD86 – cluster of differentiation 86; Arg1 – arginase1; LC – locus coeruleus; TNF-α – tumor necrosis factor-α; IL – interleukin; iNOS – inducible nitric oxide synthase; TGF-β1 – transforming growth factor-β1; B cell – B lymphocytes; NK cell – natural killer cell; Thl/Th2 – T helper 1/T helper 2 cells. Solid lines indicate directed actions; dashed line indicates potential interplay. The figure was created using BioRender.com.