Abstract
Despite increasing interest, there remain limited treatments for chronic pain, with opioids continuing to be one of the top prescribed medications. Marine natural products present a wealth of untapped potential for new treatments for chronic pain. In this study, we investigated the analgesic effects of the sea sponge ligand barettin in a mouse model of chemotherapy-induced peripheral neuropathy (CIPN). Barettin exhibited efficacious antihyperalgesic activity in male mice with no efficacy shown in females. Through the use of a PRESTO-Tango assay, we found that barettin acts as an inverse agonist at the 5HT2A receptor while also presenting no activity at the μ-opioid receptor. Head twitch experiments confirmed no hallucinogenic activity, suggesting that barettin may be a promising nonopioid, nonhallucinogenic, marine-derived therapeutic agent for the treatment of chronic pain.