Table 3.

The 5-phases of Oral Mucositis Adapted from Sonis [27]

Phase I—Initiation	Chemotherapy or radiation-induced reactive oxygen species (ROS) and lipid peroxidation results in DNA damage, release of pathogen-associated molecular pattern (PAMP) and damage-associated molecular pattern molecules (DAMPs) and cellular apoptosis
Phase II—Signaling	ROS stimulate the NF-kB pathway, which induces production of proinflammatory cytokines (TNF-α, IL-1β, IL-6)
Phase III – Amplification	Proinflammatory cytokines trigger tissue injury, apoptosis, vascular permeability, and activation of cyclooxygenase-2
Phase IV—Ulceration	Ulceration occurs, which serves as a portal of entry for microorganisms. The presence of bacteria activate macrophages and neutrophils to further produce proinflammatory cytokines
Phase V—Healing	Signaling from the submucosa promotes epithelial migration, proliferation and differentiation