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

Jen Kun Cheng, Robert Chang Chih Chou, Ling Ling Hwang, Lih Chu Chiou

Research output: Contribution to journalArticle

66 Citations (Scopus)

Abstract

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 (ED 50 = 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 P2X 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 P2X 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.

Original languageEnglish
Pages (from-to)1065-1071
Number of pages7
JournalJournal of Pharmacology and Experimental Therapeutics
Volume307
Issue number3
DOIs
Publication statusPublished - Dec 2003

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Postoperative Pain
Orexin Receptors
Hyperalgesia
Suramin
Strychnine
Orexins
Naloxone
Purinergic P2X Receptor Antagonists
Purinergic P2X Receptors
Glycine Receptors
Antibodies
Acute Pain
Opioid Receptors
G-Protein-Coupled Receptors
Analgesia
Glycine
Analgesics

ASJC Scopus subject areas

  • Pharmacology

Cite this

Antiallodynic Effects of Intrathecal Orexins in a Rat Model of Postoperative Pain. / Cheng, Jen Kun; Chou, Robert Chang Chih; Hwang, Ling Ling; Chiou, Lih Chu.

In: Journal of Pharmacology and Experimental Therapeutics, Vol. 307, No. 3, 12.2003, p. 1065-1071.

Research output: Contribution to journalArticle

Cheng, Jen Kun ; Chou, Robert Chang Chih ; Hwang, Ling Ling ; Chiou, Lih Chu. / Antiallodynic Effects of Intrathecal Orexins in a Rat Model of Postoperative Pain. In: Journal of Pharmacology and Experimental Therapeutics. 2003 ; Vol. 307, No. 3. pp. 1065-1071.
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