Antidepressants Fine-Tune Brain Reward Pathway to Lessen Neuropathic Pain

According to a study recently published in journal Proceedings of the National Academy of Sciences, commonly used antidepressant drugs change levels of a key signaling protein in the brain region that processes both pain and mood. The newly understood mechanism could yield insights into more precise future treatments for nerve pain and depression. Past studies have shown that chronic neuropathic pain often leads to depression, but the brain mechanisms underlying this connection were previously unknown, as were the mechanisms by which common antidepressant drugs counter both pain and depression-related symptoms. The current study found that the molecular adaptations required for recovery from pain and depression are controlled by a gene (RGS9) and the protein it codes for, named RGS9-2. Mice that lacked the gene responsible for encoding RGS9-2 responded much earlier to very low doses of antidepressants, showed significant improvement of sensory deficits and had no signs of depression-related behaviors. “Our data reveals that antidepressants that target specific neurotransmitters in the brain, particularly [tricyclic antidepressants] and [Serotonin-Norepinephrine inhibitors], regulate chronic pain and depression-related symptoms through actions in the nucleus accumbens,” said an associate professor in the department of neuroscience at the Friedman Brain Institute of the Icahn School of Medicine. Researchers don’t yet know if the typical pain-processing pathways in the spinal cord and the pathways the identified in the brain’s reward center are directly linked. However, they now know more about the cellular pathways that need to be activated in order to achieve pain relief, and that effective treatments need to target both pathways. To read more about this study, click here.