The precise definition of the International Association for the Study of Pain (IASP) revised in 2008 states that neuropathic pain is a type of pain arising as a direct consequence of a lesion or disease affecting the somatosensory system. This kind of pain is due to long-term dysfunction of the nervous system and is clinically characterized by spontaneous and evoked types of chronic pain, which are involved by various distinct pathophysiological mechanisms in the peripheral and central nervous systems. It is relatively common, with an incidence estimated at 0.6% to 1.5% in the US population. Unfortunately, there was no effective therapy until recently. Our research team found an effective strategy in treating neuropathic pain that resulted from interactions between leukocyte-derived opioid peptides and their receptors on peripheral sensory neurons. Here, we briefly review granulocyte colony stimulating factor (G-CSF) therapy in an animal model of neuropathic pain. Our studies also proved that G-CSF can increase the number of opioid-contained polymorphonuclear cells and significantly relieve neuropathic pain. These studies have led to an increased understanding of the opioids and cytokines -modulating peripheral analgesia effect on neuropathic pain, which opens a new avenue in its treatment.