title: Nauclea latifolia Smith (Rubiaceae) exerts antinociceptive effects in neuropathic pain induced by chronic constriction injury of the sciatic nerve.
abstract: BACKGROUND
  The roots of Nauclea latifolia Smith (Rubiaceae) popularly known as "koumkouma" is used in traditional Cameroonian medicine as neuropathic pain remedy and for the treatment of headache, inflammatory pain and convulsion. This study was conducted to evaluate the antinociceptive effects of the alkaloid fraction isolated from Nauclea latifolia in neuropathic pain induced by chronic constriction injury (CCI) of the sciatic nerve in rat.
  
  
  METHODS
  Bioactive-guided fractionation of the root extracts of Nauclea latifolia using the Von Frey in a rat model of neuropathic pain (Benett model), afforded a potent anti-hyperalgesic fraction IV. Further fractionation of this fraction was performed by high-performance liquid chromatography (HPLC), yielded eight sub-fractions (F1-F8) which were tested for antinociceptive effects. The alkaloid fraction (F3) collected by HPLC, exhibited potent antinociceptive effects, and the anti-allodynic and anti-hyperalgesic effects of this fraction (8, 16, 40 and 80 mg/kg) were determined using the von Frey and acetone tests respectively in a rat model of neuropathic pain. Rota-rod performance and catalepsy tests were used for the assessment of motor coordination.
  
  
  RESULTS
  The alkaloid fraction (80 mg/kg) administered intraperitoneally induced a completely decreased hyperalgesia 90 min post-dosing. In the acetone test, the Nauclea latifolia fraction at 80mg/kg showed its maximal anti-allodynic effects 120 min post-injection. The areas under the curve (AUC) of the anti-allodynic or anti-hyperalgesic effects produced by the alkaloid fraction at 80 mg/kg were significantly (p<0.001) greater than the AUC of effects produced by vehicle in CCI rats. The alkaloid fraction did not exhibit any significant effects on the spontaneous locomotor activity of the mice in rota-rod performance and no sign of catalepsy was observed.
  
  
  CONCLUSIONS
  The analysis of the effects, expressed as the time course of AUC, supports the traditional use of Nauclea latifolia in neuropathic pain therapy. The pharmacological and chemical studies are continuing in order to characterize the mechanism(s) responsible for this anti-hyperalgesic and anti-allodynic action and also to identify the active substances present in the roots extracts of Nauclea latifolia.
authors.affiliation: Department of Zoology and Animal Physiology, Faculty of Science, University of Buea, P.O. Box 63, Buea, Cameroon; Unité Inserm U836, Grenoble Institute of Neuroscience, Chemin Fortuné Ferrini, Site santé de la Tronche, P.O. Box 170, 38042 Cedex 9 Grenoble, France; Université Joseph Fourier, Grenoble, France. Electronic address: taiwe_sotoing@yahoo.fr.
authors.forename: Germain Sotoing
authors.initials: GS
authors.lastname: Taïwe
authors.affiliation: Department of Biological Sciences, Faculty of Science, University of Ngaoundéré, P.O. Box 454 Ngaoundéré, Cameroon.
authors.forename: Elisabeth Ngo
authors.initials: EN
authors.lastname: Bum
authors.affiliation: Department of Chemistry, Faculty of Science, University of Ngaoundéré, P.O. Box 454, Ngaoundéré, Cameroon.
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Talla
authors.affiliation: Department of Animal Biology and Physiology, Faculty of Science, University of Yaoundé I, P.O. Box 812 Yaoundé, Cameroon.
authors.forename: Théophile
authors.initials: T
authors.lastname: Dimo
authors.affiliation: Department of Chemistry, Higher Teachers' Training College, University of Maroua, P.O. Box 55, Maroua, Cameroon.
authors.forename: Amadou
authors.initials: A
authors.lastname: Dawe
authors.affiliation: Unité Inserm U836, Grenoble Institute of Neuroscience, Chemin Fortuné Ferrini, Site santé de la Tronche, P.O. Box 170, 38042 Cedex 9 Grenoble, France; Université Joseph Fourier, Grenoble, France.
authors.forename: Valérie
authors.initials: V
authors.lastname: Sinniger
authors.affiliation: Unité Inserm U836, Grenoble Institute of Neuroscience, Chemin Fortuné Ferrini, Site santé de la Tronche, P.O. Box 170, 38042 Cedex 9 Grenoble, France; Université Joseph Fourier, Grenoble, France.
authors.forename: Bruno
authors.initials: B
authors.lastname: Bonaz
authors.affiliation: Université Joseph Fourier, Grenoble, France; Unité CNRS 5063, Department of Medicinal Chemistry, P.O. Box 53, 38041 Grenoble Cedex 9, France; Smartox Biotechnologies, Floralis, Biopolis, 5 Avenue du Grand Sablon, 38700 La Tronche, France.
authors.forename: Ahcène
authors.initials: A
authors.lastname: Boumendjel
authors.affiliation: Unité Inserm U836, Grenoble Institute of Neuroscience, Chemin Fortuné Ferrini, Site santé de la Tronche, P.O. Box 170, 38042 Cedex 9 Grenoble, France; Université Joseph Fourier, Grenoble, France; Smartox Biotechnologies, Floralis, Biopolis, 5 Avenue du Grand Sablon, 38700 La Tronche, France.
authors.forename: Michel
authors.initials: M
authors.lastname: De Waard
mesh_terms: D000470:Alkaloids / Q000737:chemistry / Q000627:therapeutic use; D000700:Analgesics / Q000737:chemistry / Q000627:therapeutic use*; D000818:Animals; D002470:Cell Survival; D002908:Chronic Disease; D004305:Dose-Response Relationship, Drug; D005260:Female; D008297:Male; D051379:Mice; D009020:Morphine / Q000627:therapeutic use; D009437:Neuralgia / Q000188:drug therapy*; D018517:Plant Roots / Q000737:chemistry; D051381:Rats; D017208:Rats, Wistar; D019666:Rubiaceae / Q000737:chemistry*; D012584:Sciatic Nerve / Q000293:injuries*
chemical_list: D000470:Alkaloids; D000700:Analgesics; D009020:Morphine
keywords: 3-(4,5 dimethylthiazol-2-yl)-2, 5-diphenyl-tetrazolium bromide; ANOVA; ATCC; AUC; American type culture collection; Anti-allodynic; Anti-hyperalgesic; CCI; CHO; Chinese hamster ovary; EC(50); F(1); HPLC; LD(50); MTT; N(ω)-l-nitro-arginine methyl ester; NIH; National Institutes of Health; Nauclea latifolia; Neuropthic pain; Traditional medicine.; analysis of variance; areas under the curve; chronic constriction injury; fractions; high-performance liquid chromatography; l-NAME; median lethal dose; the 50% effective concentration