Role of M1/M2 macrophages in pain modulation.

Pain is a signal of inflammation that can have both protective and pathogenic effects. Macrophages, significant components of the immune system, play crucial roles in the occurrence and development of pain, particularly in neuroimmune communication. Macrophages exhibit plasticity and heterogeneity, adopting either pro-inflammatory M1 or anti-inflammatory M2 phenotypes depending on their functional orientation. Recent research highlights the contribution of macrophages to pain dynamics by undergoing changes in their functional polarity, leading to macrophage activation, tissue infiltration, and cytokine secretion. M1 macrophages release pro-inflammatory mediators that are not only essential in defending against infections, but also contributing to tissue damage and the elicitation of pain. However, this process can be counteracted by M2 macrophages, facilitating pain relief through producing anti-inflammatory cytokines and opioid peptides or enhancing efferocytosis. M1 and M2 macrophages play important roles in both the initiation and mitigation of pain.