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.

Background and Purpose: Depression is a neuropsychiatric disorder accompanied by a decrease in the brain‐derived neurotrophic factor (BDNF) signalling cascade in the hippocampus. Fenofibrate is a selective agonist of PPAR‐α. In this study, we investigated the antidepressant‐like effects of fenofibrate in C57BL/6J mice.Experimental Approach: The antidepressant‐like effects of fenofibrate were first identified in the forced swim test (FST) and tail suspension test (TST), and then assessed in the chronic social defeat stress (CSDS) model. The changes in the hippocampal BDNF signalling pathway and adult hippocampal neurogenesis after CSDS and fenofibrate treatment were further investigated. A PPAR‐α inhibitor, cannabinoid system inhibitors and BDNF signalling inhibitors were also used to determine the antidepressant mechanisms of fenofibrate.Key Results: Fenofibrate administration exhibited antidepressant‐like effects in the FST and TST without affecting the locomotor activity of mice. Chronic fenofibrate treatment also prevented the depressive‐like symptoms induced by CSDS. Moreover, fenofibrate restored the CSDS‐induced decrease in the hippocampal BDNF signalling cascade and adult hippocampal neurogenesis. The antidepressant‐like effects of fenofibrate could be blocked by a PPAR‐α inhibitor and BDNF signalling inhibitors.Conclusions and Implications: Taken together, these results suggest that fenofibrate has antidepressant‐like effects mediated through the promotion of the hippocampal BDNF signalling cascade.

S-propargyl-cysteine (SPRC), an H₂S donor, is a structural analogue of S-allycysteine (SAC). It was investigated for its potential anti-cancer effect on SGC-7901 gastric cancer cells and the possible mechanisms that may be involved. SPRC treatment significantly decreased cell viability, suppressed the proliferation and migration of SPRC-7901 gastric cancer cells, was pro-apoptotic as well as caused cell cycle arrest at the G₁/S phase. In an in vivo study, intra-peritoneal injection of 50 mg/kg and 100 mg/kg of SPRC significantly reduced tumor weights and tumor volumes of gastric cancer implants in nude mice, with a tumor growth inhibition rate of 40–75%. SPRC also induced a pro-apoptotic effect in cancer tissues and elevated the expressions of p53 and Bax in tumors and cells. SPRC treatment also increased protein expression of cystathione-γ-lyase (CSE) in cells and tumors, and elevated H₂S levels in cell culture media, plasma and tumoral CSE activity of gastric cancer-induced nude mice by 2, 2.3 and 1.4 fold, respectively. Most of the anti-cancer functions of SPRC on cells and tumors were significantly suppressed by PAG, an inhibitor of CSE activity. Taken together, the results of our study provide insights into a novel anti-cancer effect of H₂S as well as of SPRC on gastric cancer through inducing the activity of a new target, CSE.