Refractory chronic cough may be mainly caused by central hypersensitivity, leading to a new concept of diagnosis of cough hypersensitivity syndrome.The neurotransmitters including γ-aminobutyric acid receptor and N-methyl-D-aspartic acid receptor are involved in the pathogenesis of cough hypersensitivity, which is highly similar to the central sensitization of neuropathic pain.Therefore, the neuromodulator has also been used for the treatment of refractory chronic cough.Currently, the commonly used neuromodulators such as gabapentin, pregabalin, baclofen and amitriptyline have been confirmed to be effective in the treatment of refractory chronic cough.However, a considerable part of the patients with refractory chronic cough do not respond to the therapy with the neuromodulators.The adverse effects on central nervous system also limit their clinical application.Thus, to screen the patients with refractory chronic cough suitable for the treatment with neuromodulators is necessary to improve their therapeutic success rate and minimize the adverse effects, which needs further research in the future.