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NEUROPHARMACOLOGY

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

Department of Pharmacology, College of Medicine, National Taiwan University, Taipei, Taiwan (J.-K.C., R.C.-C.C., L.-C.C.) and Department of Physiology, Taipei Medical University, Taipei, Taiwan (L.-L.H.)

Orexin A and B (hypocretin 1 and 2) are the endogenous ligands of orexin receptors, a G-protein-coupled orphan receptor family containing orexin 1 (OX₁) and orexin 2 (OX₂) types. Orexin A induces analgesia in acute and inflammatory pain models. We further elucidated the possible antiallodynic effect of intrathecal orexins in a rat model of postoperative pain. Mechanical allodynia was induced by incising the rat hind paw and evaluated with the withdrawal threshold to von Frey filament stimulation. Intrathecal orexin A (0.03-1 nmol) and orexin B (0.1–3 nmol) dose dependently attenuated the incision-induced allodynia. Orexin A (ED₅₀ = 0.06 nmol) is more potent than orexin B. The effects of orexin A and B were abolished by their respective antibodies, but not by naloxone, and were attenuated by suramin and strychnine, the P_2X purinergic and glycine receptor antagonists, respectively. SB-334867, an OX₁ receptor antagonist, at 30 nmol completely blocked the effect of orexin A but, even at 100 nmol, only partially antagonized the effect of orexin B. Orexin A antibody, SB-334867, suramin, strychnine, or naloxone enhanced the incision-induced allodynic response. It is concluded that intrathecal orexins reduce incision-induced allodynia through OX₁ receptors. Glycine and P_2X purinergic receptors, but not opioid receptors, might be involved in the antiallodynic effects of orexins. Endogenous orexin might be released after incision injury to activate the spinal OX₁ receptors as an endogenous analgesic protector.

Address correspondence to: Dr. Lih-Chu Chiou, Department of Pharmacology, College of Medicine, National Taiwan University, 1, Jen-Ai Rd., Section 1, Taipei 100, Taiwan. E-mail: lcchiou{at}ha.mc.ntu.edu.tw

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