Pain is a complicated physiological and psychological activity, which is always accompanied by various diseases. It has become an urgent problem to be solved because of its flexible etiology and complex mechanisms. This article mainly elaborates the progress of research on synaptic plasticity remodeling in pain, introduces the transduction and synaptic plasticity of pain signals, the role of synaptic structure and functional plasticity in pain, and review the treatment of pain based on synaptic plasticity. The aim of this review is to better understand the mechanism of pain, provides a novel idea for its subsequent treatment, and gives more reliable evidence for clinical pain treatment.