The orexins are important for the regulation of several behavioral patterns, including feeding, arousal state, drug seeking, voluntary locomotion and nociception. Two orexins (A and B), and two different orexin receptors are known, which have differential distribution. This suggests that orexins and distinct orexin receptors may regulate specific behaviors such as immobility associated analgesia. The periaqueductal gray (PAG) is considered to be the main center for the analgesia and immobility responses in the central nervous system (CNS). Here we compared the effect of orexin A (OX-A) and orexin B (OX-B) after intracerebroventricular (ICV) or the ventrolateral periaqueductal gray (vl-PAG) injection. Two forms of immobility responses were studied: cataleptic (CAT) and tonic (TI) responses. The latter was associated with analgesia as part of a defensive response in several species. We observed that OX-A was more effective than OX-B to reduce CAT; OX-B was slightly more potent than OX-A to decrease TI and neither orexins were able to induce analgesia when orexins were injected ICV. After microinjection into vl-PAG CAT was unaffected by orexins and both orexins significantly decrease TI. Microinjected OX-A did not show analgesic activity but OX-B produced significant analgesic effect assessed by tail-flick test.