Objective Neuropathic pain, often caused by nerve injury, is commonly observed among patients with different diseases.Because its basic mechanisms are poorly understood, effective medications are limited.Previous investigations of basic pain mechanisms and drug discovery efforts have focused mainly on early sensory neurons such as dorsal root ganglion and spinal dorsal horn neurons, and few synaptic-level studies or new drugs are designed to target the injury-related cortical plasticity that accompanies neuropathic pain.Our previous work has demonstrated that calcium-stimulated adenylyl cyclase 1 (AC1) is critical for nerve injury-induced synaptic changes in the anterior cingulate cortex.Methods Rational drug design and chemical screening, a variety of behavioral tests, electrophysiological methods and toxicity studies were performed in the present study.Results It was identified that a lead candidate AC 1 inhibitor, NB001, was relatively selective for AC 1 over other adenylate cyclase isoforms.NB001 has an analgesic effect in animal models of neuropathic pain, without any apparent side effects when administered intraperitoneally or orally.Conclusion AC1 could be a productive therapeutic target for neuropathic pain and describes a new agent for the possible treatment ofneuropathic pain.