Abstract: The agrin protein was shown to be important in preventing the development of neuropathic pain, as well as in treating neuropathic pain. Both agrin protein and gene expression were shown to be down-regulated in mammals with neuropathic pain. Increasing either agrin gene expression or protein resulted in a decrease in the development of neuropathic pain. Agrin protein or the C-terminal agrin fragments can be administered in a number of ways, preferably by intrathecal injection. In addition, agrin can be increased by administering a compound shown to affect agrin gene expression or agrin protein concentration, e.g., SCP-I and SCP-M1 (also known as JMM). Agrin protein decrease was shown to be prevented by administering an NMDA receptor antagonist, e.g., MK801. Agrin and a C-terminal agrin fragment also induced phosphorylation of the NMDA receptor subunit NR1 at the serine residue site which led to suppression of neuropathic pain.