Analgesic effect of intrathecally administered orexin-A in the rat formalin test and in the rat hot plate test.
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 affinity for orexin-2 receptors. 2. Orexins are also known to be concentrated in superficial 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 effect of intrathecal injection of either orexin-A or orexin-B in the rat formalin test (a model of inflammatory pain) and in the rat hot plate test. The paw formalin injection induces biphasic flinching (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 flinches in phases 1 and 2 in the formalin test and increased the hot plate latency. These effects 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 effect 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 effects in the rat formalin test and in the rat hot plate test.
Department of Anesthesiology, Chiba University Hospital, 1-8-1 Inohana, Chuo-ku, Chiba-shi, Chiba 260-8677, Japan. yamatat@med.m.chiba-u.ac.jp
Tatsuo
T
Yamamoto
Natsuko
N
Nozaki-Taguchi
Tanemichi
T
Chiba
D018712:Analgesics, Non-Narcotic / Q000494:pharmacology*; D000818:Animals; D001583:Benzoxazoles / Q000494:pharmacology; D002352:Carrier Proteins / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D007150:Immunohistochemistry; D007278:Injections, Spinal; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D009270:Naloxone / Q000494:pharmacology; D009287:Naphthyridines; D009479:Neuropeptides / Q000008:administration & dosage / Q000494:pharmacology*; D000068797:Orexins; D010147:Pain Measurement; D051381:Rats; D017207:Rats, Sprague-Dawley; D014508:Urea / Q000031:analogs & derivatives* / Q000494:pharmacology
C420062:1-(2-methylbenzoxazol-6-yl)-3-(1,5)naphthyridin-4-yl urea; D018712:Analgesics, Non-Narcotic; D001583:Benzoxazoles; D002352:Carrier Proteins; D047908:Intracellular Signaling Peptides and Proteins; D009287:Naphthyridines; D009479:Neuropeptides; D000068797:Orexins; D009270:Naloxone; D014508:Urea