Analgesic effect of intrathecally administered orexin‐A in the rat formalin test and in the rat hot plate test

Abstract

1 Orexin-A and orexin-B (also known as hypocretin-1 and hypocretin-2) are hypothalamic peptides and regulate feeding behaviour, energy metabolism and the sleep-wake cycle. Orexin-A binds equally to both orexin-1 and orexin-2 receptors, while orexin-B has a preferential a nity for orexin-2 receptors. 2 Orexins are also known to be concentrated in super®cial laminae of the spinal dorsal horn, and orexin-A and orexin-1 receptors are found in the dorsal root ganglion cells. 3 In the present study, the authors examined the e ect of intrathecal injection of either orexin-A or orexin-B in the rat formalin test (a model of in¯ammatory pain) and in the rat hot plate test. The paw formalin injection induces biphasic¯inching (phase 1: 0 ± 6 min; phase 2: 10 ± 60 min) of the injected paw. 4 Intrathecal injection of orexin-A, but not orexin-B, decreased the sum of¯inches in phases 1 and 2 in the formalin test and increased the hot plate latency. These e ects of orexin-A were completely antagonized by pre-treatment with SB-334867, a selective orexin-1 receptor antagonist. Intrathecal injection of SB-334867 alone had no e ect in the formalin test or in the hot plate test. 5 Intrathecal injection of orexin-A suppressed the expression of Fos-like immunoreactivity (Fos-LI), induced by paw formalin injection, in laminae I-II of L4 ± 5 of the spinal cord. 6 These data suggest that the spinal orexin-1 receptor is involved in the nociceptive transmission and that the activation of the spinal orexin-1 receptor produces analgesic e ects in the rat formalin test and in the rat hot plate test.

Antiallodynic Effects of Intrathecal Orexins in a Rat Model of Postoperative Pain

“…However, the effect of orexin B, different from that of orexin A, is partly mediated by OX 1 receptors. This finding is different from the report of Yamamoto et al (2002) that no analgesic effect of intrathecal orexin B at doses up to 3 nmol was observed by hot-plate and formalin tests in rats. The reason for this discrepancy is not clear.…”

“…Bingham et al (2001) found that orexin A injected intravenously or intracerebroventricularly displayed an analgesic effect mediated through OX 1 receptors in the hot-plate test and carrageenan-induced thermal hyperalgesia. Yamamoto et al (2002; also reported that intrathecal injection of orexin A produced antinociceptive effects in formalin-induced inflammatory pain, hot-plate test, and sciatic nerve partial ligation-induced neuropathic pain models. We further demonstrated that, in the rat model of postoperative pain, intrathecal injection of orexin A exerted antiallodynic effect through OX 1 receptors.…”

Changes in Biochemical Markers of Pain Perception and Stress Response After Spinal Manipulation

“…21,33,67 Emerging evidence shows that the central nervous system administration (intracranial ventricle or intrathecal injection) of orexin A can suppress mechanical allodynia and thermal hypersensitivity in multiple pain models, suggesting the regulation of nociceptive processing via spinal and supraspinal mechanisms. 8,70 In addition, orexins showed antinociceptive effects on models of pain, such as neuropathic pain, carrageenan test, and postoperative pain. 47,48 There is a lack of literature that analyzes the effect of physical therapy techniques on orexin A expression.…”

Intracerebroventricular Application of Dexmedetomidine Produces Antinociception and Does not Cause Neurotoxicity in Rats

“…Motor function: Stepping and righting reflexes were evaluated using the Yamamoto scoring system (14). The responses obtained during these tests ranged between 0 and 2 (0=no motor response; 1=slower than normal motor response; 2=normal motor response).…”