Acute pain is a protection for organisms caused by the activation of primary nociceptors, while chronic pain is a condition that often emerges as a clinical symptom of inflammatory diseases and tends to develop into central or peripheral sensitization. It has been widely accepted that the immune system critically contributes to the occurrence and maintenance of hyperalgesia. Cross‑talk between macrophages and nociceptor sensory neurons is vital for the pathogenesis of pain, characterized by the proliferation of tissue‑resident macrophages, infiltration of peripheral macrophages, and secretion of inflammatory mediators in the peripheral and central nervous systems. The article examines the molecules involved in the interaction between macrophages in dorsal root ganglia (DRG) and primary nociceptors, as well as recently emerging targets, including substance P (SP), type 2 angiotensin Ⅱ receptor (AT2R), microRNA (miRNA), and exosomes, in order to provide novel ideas for the treatment of hyperalgesia.