Figure 4.

Scheme of central and peripheral actions of dexmedetomidine.

Surgery-induced inflammatory pain activates the corticotropic axis via the stimulation of afferent nociceptive pathways and promotes local production of protumor cytokines such as IL-1β, IL-6 and TNF-α. The hypothalamus produces corticotropin-releasing hormone (CRH), which stimulates the synthesis of adrenocorticotropic hormone (ACTH) by the pituitary gland. In response to ACTH, adrenal glands release cortisol and catecholamines (epinephrine and norepinephrine) into the systemic circulation. Catecholamines, potentiated by tumorigenic cytokines, act on α- and β-adrenoceptors (α-AR, β-AR) located on the surface of tumor cells to enhance their proliferation, survival and migration. These protumor molecules inhibit the chemotaxis and cytotoxicity of the immune effectors (T, B, NK cells) in the tumor bed and its microenvironment (TME). Dexmedetomidine (DEX) could alleviate both corticotropic axis activity and the release of protumor cytokines by optimally controlling inflammatory pain. Through its agonist effect on α-adrenoceptor, DEX might also impair the malignant properties of tumor cells directly. Created with https://www.BioRender.com