The role of macrophages in chronic pain

Chronic pain typically lasts or recurs for more than three months and is an unpleasant sensory and emotional experience, including neuropathic pain, long-term tissue damage, tumors, and viral or bacterial infections.The unpleasantness associated with pain affects the basic life of patients and has become a truly global problem. Macrophages, a powerful immune effector cell whose functional plasticity leads to polarization into different subtypes and opposite effects in different environments, are also indispensable in the development of pain.In recent years, there has been an increasing number of studies on the effects of macrophages on pain, and there are multiple pathways that regulate macrophage polarization, including lipopolysaccharide induction and IL-4/IL-13 stimulation.In addition, pathways involving macrophages and macrophage polarization have been found to have an exacerbating or mitigating role in the progression of chronic pain, with M1 macrophages generally exacerbating pain progression and M2 macrophages mitigating pain progression.Therefore, modulating macrophage polarization holds great promise as an intervention in chronic pain. In this paper, we synthesize multiple macrophage pathways as well as mechanisms affecting their pain processes in the context of different types of chronic pain, providing new avenues for chronic pain relief.