Peripheral neuropathic pain induced by the chemotherapeutic cisplatin can persist for months to years after treatment. Histone deacetylase 6 (HDAC6) inhibitors have therapeutic potential for cisplatin-induced neuropathic pain since they persistently reverse mechanical hypersensitivity and spontaneous pain in rodent models. In this presentation, Dr. Grace will present new data demonstrating that this apparent reversal is dependent on tonic enkephalin-delta opioid receptor (DOR) signaling in peripheral sensory neurons. HDAC6 inhibitors restore DOR expression in sensory neurons after cisplatin treatment, and induce tonic secretion of enkephalin from T cells. Blocking the delta opioid receptor or its ligand enkephalin unmasks CIPN in mice treated with an HDAC6 inhibitor (latent sensitization). This work provides insight into the mechanisms by which treatment with an HDAC6 inhibitor apparently reverses CIPN