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Gamma-aminobutyric acid (GABA), a non-protein-producing amino acid synthesized from the excitatory amino acid glutamate via the enzyme glutamic acid decarboxylase, is extensively found in microorganisms, plants and vertebrates, and is abundantly expressed in the spinal cord and brain. It is the major inhibitory neurotransmitter in the mammalian nervous system. GABA plays crucial roles in the regulation of synaptic transmission, the promotion of neuronal development and relaxation, and the prevention of insomnia and depression. As the major inhibitory neurotransmitter, GABA plays pivotal roles in the regulation of pain sensation, which is initiated by the activation of peripheral nociceptors and transmitted to the spinal cord and brain along nerves. GABA exerts these roles by directly acting on three types of receptors: ionotropic GABA A and GABA C receptors and G protein-coupled GABA B receptor. The chloride-permeable ion channel receptors GABA A and GABA C mediate fast neurotransmission, while the metabotropic GABA B receptor mediates slow effect. Different GABA receptors regulate pain sensation via different signaling pathways. Here we highlight recent updates on the involvement of specific GABA receptors and their subtypes in the process of pain sensation. Further understanding of different GABA receptors and signaling pathways in pain sensation will benefit the development of novel analgesics for pain management by targeting specific GABA receptor subtypes and signaling pathways. [Display omitted] • GABA regulates synaptic transmission contributing to pain sensation. • GABA A receptor regulates membrane potential depending on transmembrane chloride gradient. • GABA A receptor-mediated analgesic effects rely on subunits compositions. • GABA B receptor modulates pain transmission. [ABSTRACT FROM AUTHOR]