Orphanin FQ (OFQ) and endomorphins (EM) are newly characterized members of opioid peptide family. OFQ has been shown to antagonize morphine analgesia at supraspinal level, whereas endomorphins are highly selective endogenous ligands for mu receptor, showing analgesic effect at both spinal and supraspinal level. OFQ and EM-2 (EM2) immunoreactivity (ir) was measured by radioimmunoassay in nociception-related brain areas of rats subjected to L5/L6 spinal nerve ligation, using shamoperated rats as control. Itwasfound that: (1) the content of EM2-ir of spinal nerve ligated rats showed a significant increase (778%) in periaqueductal gray (PAG), and a significant decrease (43%) in striatum, compared with the control group. (2) a significant increase of the content of OFQ-ir was found in amygdala (1841%) and PAG (1459%), respectively in spinal nerve ligated rats. High pressure liquid chromatography showed that the EM2-ir and OFQ-ir were both heterogeneous with the major part eluting at the position of EM2 and OFQ standard, respectively. These results suggest that spinal nerve ligation induces significant changes in the content of EM2-ir and OFQ-ir in some discrete brain areas, which may play a role in nociceptive modulation.