Table 1.

Cells and molecules involved in the pathophysiology for post-burn pruritus.

Cells and Molecules		Mechanism
Acute phase	Keratinocyte	Keratinocyte secretes a variety of inflammatory substances which induce pruritus; histamine, calcitonin gene related peptides (CGRP), Substance P, etc. [20]
	Mast cell	Mast cell releases histamine into post-burn lesion [38]
	Histamine	Histamine appears to be a key initiator of impulses predominantly in the initial stages of healing after burn, but the role of histamine in post-burn itch is minimal [46] It helps keratinocyte produce inflammatory agents [34,37]
	Substance P Calcitonin gene related peptides (CGRP)	Substance P and CGRP are the main transduction medias involved in C fiber. Substance P and CGRP increase IL-1α, IL-8, and TNF-α mRNA expression [22,35]
	Transient receptor Potential vanilloid (TRPV) 1,3	TRPV 1 and 3 increase intracellular calcium, triggering activation of calcineurin and NFAT, resulting in a release of TSLP extracellularly [40,41]
	Thymic stromal lymphopoietin (TSLP)	TSLP activate sensory neurons directly to cause an itch. TSLP induce inflammatory immune response to mast cells and T helper 2 cells [39,42]
	Interleukin-31 (IL-31)	IL-31 stimulates the afferent neurons which have TRPV1/TRPA1. IL-31 amplify the inflammation of the skin through chemokine induction, causing T-cell recruitment [36]
Chronic phase	Nerve growth factor Substance P Histamine Neurokinin A Eicosanoids Bradykinin	These inflammatory substances cause CNS sensitization in chronic burns by upregulating C-fiber activation [25]
	Gamma-aminobutyric acid (GABA)	Degeneration of GABA interneurons decrease inhibition to nociceptive pathway and contribute to hypersensitivity [25]
	TRPA1 TRPV4 TRPV3 IL-31	Their receptors elevated more in the burn scar resulting in an increase of TSLP [8,44]
	Norepinephrine 5-Hydroxytryptamine(5-HT) Serotonin Dopamine	These molecules exist in the descending pathway with anti-nociceptive activity. Disinhibition in this pathway results in excitability in the CNS [25]