title: Chlorogenic acid administered intrathecally alleviates mechanical and cold hyperalgesia in a rat neuropathic pain model.
abstract: Chlorogenic acid (CGA), one of the most abundant dietary polyphenols, is known to have various physiological properties. Although CGA is reported to have an antinociceptive effect on acute and inflammatory pain, little is known about its effect on neuropathic pain or its action site. The aim of the present study was to determine whether intrathecally administered CGA can ameliorate hyperalgesia in a neuropathic pain model. Chronic constriction injury to the sciatic nerve was induced in male Sprague-Dawley rats. CGA (0.5, 1, or 2mg) was administered intrathecally to examine the 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. To identify the neurotransmitter pathway involved in the spinal action of CGA, the present study examined the effect of intrathecal pretreatment with several antagonists of spinal pain processing receptors on the action of CGA in the electronic von Frey test and cold plate test. Spinally applied CGA dose-dependently alleviated mechanical and cold hyperalgesia. Conversely, CGA had no effect on thermal hyperalgesia. At the highest dose, CGA affected motor performance. The antihyperalgesic action of CGA was partially reversed by bicuculline, an γ-aminobutyric acidA (GABAA) receptor antagonist, at a dose that did not affect baseline behavioral responses. These findings suggest that CGA ameliorates mechanical and cold hyperalgesia partly by activating GABAergic transmission in the spinal cord, and that CGA may be useful for novel treatments for neuropathic pain.
authors.affiliation: Department of Anesthesiology, University of Occupational and Environmental Health, School of Medicine, 1-1, Iseigaoka, Yahatanishiku, Kitakyushu 807-8555, 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, 1-1, Iseigaoka, Yahatanishiku, Kitakyushu 807-8555, Japan.
authors.forename: Yasunori
authors.initials: Y
authors.lastname: Haranishi
authors.affiliation: Department of Anesthesiology, University of Occupational and Environmental Health, School of Medicine, 1-1, Iseigaoka, Yahatanishiku, Kitakyushu 807-8555, Japan.
authors.forename: Kazunori
authors.initials: K
authors.lastname: Kataoka
authors.affiliation: Department of Anesthesiology, University of Occupational and Environmental Health, School of Medicine, 1-1, Iseigaoka, Yahatanishiku, Kitakyushu 807-8555, Japan.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Takahashi
authors.affiliation: Department of Anesthesiology, University of Occupational and Environmental Health, School of Medicine, 1-1, Iseigaoka, Yahatanishiku, Kitakyushu 807-8555, Japan.
authors.forename: Tadanori
authors.initials: T
authors.lastname: Terada
authors.affiliation: Department of Anesthesiology, University of Occupational and Environmental Health, School of Medicine, 1-1, Iseigaoka, Yahatanishiku, Kitakyushu 807-8555, Japan.
authors.forename: Motohiro
authors.initials: M
authors.lastname: Nakamura
authors.affiliation: Department of Anesthesiology, University of Occupational and Environmental Health, School of Medicine, 1-1, Iseigaoka, Yahatanishiku, Kitakyushu 807-8555, Japan.
authors.forename: Takeyoshi
authors.initials: T
authors.lastname: Sata
mesh_terms: D000700:Analgesics / Q000008:administration & dosage / Q000627:therapeutic use*; D000818:Animals; D002726:Chlorogenic Acid / Q000008:administration & dosage / Q000627:therapeutic use*; D003080:Cold Temperature; D004195:Disease Models, Animal; D006358:Hot Temperature; D006930:Hyperalgesia / Q000188:drug therapy*; D007278:Injections, Spinal; D008297:Male; D009437:Neuralgia / Q000188:drug therapy*; D051381:Rats; D017207:Rats, Sprague-Dawley; D045442:Rotarod Performance Test
chemical_list: D000700:Analgesics; D002726:Chlorogenic Acid
keywords: CCI model; GABAergic transmission; Motor performance; Polyphenol; Spinal cord