Background　The underlying mechanism of hyperalgia is still remained unclear． Many previous researches focused on the up-regulation of excitable neurotransmitters. Recently it has been noticed that the expression of potassium-chloride co-transporter2（KCC2）， a functional protein of γ-aminobutyric acid A（GABAA） receptors， was altered during the development of hyperalgesia， which caused the neurons from inhibition to excitation．The KCC2 establishes the low intraneuronal Cl- levels required for the hyperpolarizing inhibitory postsynaptic potentials mediated by ionotropic GABAA receptors and glycine（Gly） receptors.　Objective　The role of KCC2 in pain sensitization and it's pathways is reviewed.　Content　Various extracellular signals may activate microglia and upregulate P2X4Rs. P2X4R activation triggers the release of brain-derived neurotrophic factor（BDNF） from microglia. BDNF-tyrosine kinase B receptor（TrkB） signaling alters KCC2 function leading to a reduced Cl- extrusion capacity which dampens GABAA receptor/Gly receptor mediated inhibition.　Trend　Understanding the molecular mechanism of KCC2 in hyperalgesia can provide novel targets for therapeutic approaches.