Papers of the Week

Neuropathic pain is a debilitating health concern and there is an urgent need for non-opioid analgesic targets. Our group has identified GPR183 as a novel potential therapeutic target for neuropathic pain. GPR183 is a G-protein coupled receptor that promotes the migration of immune cells in response to its ligand, 7α,25-dihydroxycholesterol (7α,25-OHC). We have shown that GPR183 is upregulated in the dorsal horn spinal cord during neuropathic pain states in rodents and intrathecal injections of 7α,25-OHC is able to induce allodynia in mice in a GPR183-dependent manner. However, the mechanism by which GPR183 activation leads to pain is unknown. These studies aim to elucidate the molecular signaling pathways that contribute to 7α,25-OHC-induced hypersensitivity. Based on previous literature, we hypothesized that GPR183 activation in the spinal cord would activate mitogen-activated protein kinases (MAPKs), extracellular signal-regulated kinase (ERK) and p38, leading to the production of neuroexcitatory cytokines contributing to hypersensitivity.