Targeting endoplasmic reticulum stress: a novel therapeutic strategy for neuropathic pain

Neuropathic pain (NP) is a chronic and debilitating condition arising from lesions or diseases of the somatosensory system. Increasing evidence identifies endoplasmic reticulum (ER) stress as a central mechanism contributing to NP pathogenesis. Activation of the unfolded protein response disrupts cellular homeostasis and promotes many pathological processes, including neuroinflammation, oxidative stress, apoptosis, and ferroptosis. Notably, ER stress signaling exhibits strong cell-type specificity, affecting neurons, glial cells, and immune cells across both peripheral and central nervous systems. Targeting ER stress has therefore emerged as a promising therapeutic strategy. However, ER stress signaling remains complex, and clinical translation is still limited. This review summarizes current mechanisms and highlights emerging ER stress-targeted therapies for NP.