title: Effects of intrathecal and intracerebroventricular administration of luteolin in a rat neuropathic pain model.
abstract: Luteolin, a major component of flavones, is known to have various physiological properties. Although luteolin reportedly has an antinociceptive effect on acute and inflammatory pain, little is known about its effect on neuropathic pain. The aim of the present study was to determine whether luteolin could ameliorate hyperalgesia in the central nervous system using a neuropathic pain model. Chronic constriction injury to the sciatic nerve was induced in male Sprague-Dawley rats. Luteolin (0.1-1.5 mg) was administered intrathecally or intracerebroventricularly to examine the central effects on mechanical, thermal, and cold hyperalgesia using the electronic von Frey test, plantar test, and cold plate test, respectively. A rotarod test was also performed to assess motor function in normal rats. Spinally applied luteolin dose-dependently attenuated mechanical and cold hyperalgesia, but it had no effect on thermal hyperalgesia. At the highest dose, luteolin affected motor performance. The spinal action of luteolin on mechanical hyperalgesia was inhibited by intrathecal pretreatment with the γ-aminobutyric acidA (GABAA) receptor antagonist bicuculline and μ-opioid receptor antagonist naloxone, but not by intrathecal pretreatment with either the benzodiazepine receptor antagonist flumazenil or glycine receptor antagonist strychnine. Supraspinal application of luteolin had no antihyperalgesic effects in any test. These findings suggest that luteolin ameliorates mechanical and cold hyperalgesia at least in part by activating GABAA receptors in a flumazenil-insensitive manner and μ-opioid receptors in the spinal cord, but that the supraspinal regions are unlikely to contribute to the antihyperalgesic action of luteolin. Luteolin could be a candidate therapeutic agent for neuropathic pain.
authors.affiliation: Department of Anesthesiology, University of Occupational and Environmental Health, School of Medicine, Japan. Electronic address: kojihara@med.uoeh-u.ac.jp.
authors.forename: Koji
authors.initials: K
authors.lastname: Hara
authors.affiliation: Department of Anesthesiology, University of Occupational and Environmental Health, School of Medicine, Japan.
authors.forename: Yasunori
authors.initials: Y
authors.lastname: Haranishi
authors.affiliation: Department of Anesthesiology, University of Occupational and Environmental Health, School of Medicine, Japan.
authors.forename: Tadanori
authors.initials: T
authors.lastname: Terada
authors.affiliation: Department of Anesthesiology, University of Occupational and Environmental Health, School of Medicine, Japan.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Takahashi
authors.affiliation: Department of Anesthesiology, University of Occupational and Environmental Health, School of Medicine, Japan.
authors.forename: Motohiro
authors.initials: M
authors.lastname: Nakamura
authors.affiliation: Department of Anesthesiology, University of Occupational and Environmental Health, School of Medicine, Japan.
authors.forename: Takeyoshi
authors.initials: T
authors.lastname: Sata
mesh_terms: D000700:Analgesics / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D004195:Disease Models, Animal; D006930:Hyperalgesia / Q000188:drug therapy; D057967:Infusions, Intraventricular; D007278:Injections, Spinal; D047311:Luteolin / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D009437:Neuralgia / Q000188:drug therapy*; D010147:Pain Measurement; D017207:Rats, Sprague-Dawley; D013997:Time Factors
chemical_list: D000700:Analgesics; D047311:Luteolin
keywords: Central nervous system; Flavonoid; GABAergic transmission; Opioid system; Polyphenol