title: In vitro and in vivo characterization of the new analgesic combination Beta-caryophyllene and docosahexaenoic Acid.
abstract: Beta-caryophyllene (BCP) and docosahexaenoic acid (DHA) are components of several plants with documented anti-inflammatory and analgesic effects in animal pain models. In the present study, in vitro and in vivo tests were carried out to evaluate their effects, alone or in combination, during long-lasting administration in a model of persistent pain. IR spectra of the two compounds were obtained to determine their chemical stability and then in vitro toxicity was evaluated in fibroblasts and astrocytes. In the in vivo tests, the analgesic effects of BCP and BCP+DHA were determined in male rats subjected to a model of persistent recurrent pain (three repetitions of the formalin test once a week) to mimic recurrent pain. Both substances were administered per os in almond oil for 2 weeks. Gonadal hormones were determined at the end of the tests to evaluate treatment-induced effects on their levels. BCP changed fibroblast and astrocyte survival in a dose-dependent manner and the effect was counteracted by DHA coadministration. In the in vivo tests, pain responses were significantly decreased in the BCP and BCP+DHA groups with respect to OIL after 1 and 2 weeks of treatment. Estradiol and testosterone levels were increased only in the BCP group. In conclusion, BCP alone or at lower concentration in combination with DHA was efficacious in modulating pain, showing a clear analgesic activity.
authors.affiliation: Department of Medicine, Surgery and Neuroscience, University of Siena, Via Aldo Moro, 53100 Siena, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Fiorenzani
authors.affiliation: Department of Biotechnology, Chemistry and Pharmacy, University of Siena, Via Aldo Moro, 53100 Siena, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Lamponi
authors.affiliation: Department of Biotechnology, Chemistry and Pharmacy, University of Siena, Via Aldo Moro, 53100 Siena, Italy.
authors.forename: Agnese
authors.initials: A
authors.lastname: Magnani
authors.affiliation: Department of Medicine, Surgery and Neuroscience, University of Siena, Via Aldo Moro, 53100 Siena, Italy.
authors.forename: Ilaria
authors.initials: I
authors.lastname: Ceccarelli
authors.affiliation: Department of Medicine, Surgery and Neuroscience, University of Siena, Via Aldo Moro, 53100 Siena, Italy.
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Aloisi
references.citation: Curr Opin Investig Drugs. 2008 Jan;9(1):65-75
references.pmid: 18183533
references.citation: Mol Cell Biochem. 2003 Apr;246(1-2):83-90
references.pmid: 12841347
references.citation: Pharmacol Ther. 1997;74(2):129-80
references.pmid: 9336020
references.citation: Neurosci Res. 2013 Apr;75(4):316-23
references.pmid: 23419864
references.citation: Mol Pain. 2007 Nov 01;3:33
references.pmid: 17974036
references.citation: Mol Pain. 2010 Oct 26;6:69
references.pmid: 20977699
references.citation: Handb Exp Pharmacol. 2005;(168):385-423
references.pmid: 16596782
references.citation: Br J Anaesth. 2008 Jul;101(1):59-68
references.pmid: 18515270
references.citation: Curr Pharm Des. 2006;12(18):2319-25
references.pmid: 16787257
references.citation: Proc Natl Acad Sci U S A. 2008 Jul 1;105(26):9099-104
references.pmid: 18574142
references.citation: Mult Scler. 2004 Apr;10(2):158-64
references.pmid: 15124761
references.citation: Pain. 2006 May;122(1-2):36-42
references.pmid: 16563625
references.citation: Am J Physiol Gastrointest Liver Physiol. 2006 Aug;291(2):G364-71
references.pmid: 16574988
references.citation: Pain. 2003 Jul;104(1-2):35-47
references.pmid: 12855312
references.citation: J Pharmacol Exp Ther. 2010 Sep 1;334(3):887-96
references.pmid: 20498253
references.citation: Br J Pharmacol. 2004 Mar;141(5):775-85
references.pmid: 14757702
references.citation: Chem Biol Interact. 2012 Apr 15;197(1):58-67
references.pmid: 22465178
references.citation: J Leukoc Biol. 2007 Sep;82(3):532-41
references.pmid: 17537989
references.citation: J Cereb Blood Flow Metab. 2007 Jul;27(7):1387-96
references.pmid: 17245417
references.citation: Proc Natl Acad Sci U S A. 2006 Jan 17;103(3):696-701
references.pmid: 16407142
references.citation: Annu Rev Nutr. 2012 Aug 21;32:203-27
references.pmid: 22404117
references.citation: J Neurotrauma. 2010 Sep;27(9):1617-24
references.pmid: 20597639
references.citation: Proc Natl Acad Sci U S A. 1999 Dec 7;96(25):14228-33
references.pmid: 10588688
references.citation: Pain. 1983 Jun;16(2):109-110
references.pmid: 6877845
references.citation: Pain Pract. 2010 Sep-Oct;10(5):428-50
references.pmid: 20492579
references.citation: Ther Clin Risk Manag. 2008 Feb;4(1):245-59
references.pmid: 18728714
references.citation: Brain Res. 2005 Aug 2;1052(1):105-11
references.pmid: 16005855
references.citation: Eur Neuropsychopharmacol. 2014 Apr;24(4):608-20
references.pmid: 24210682
references.citation: Pain Physician. 2012 Jul;15(3 Suppl):ES111-8
references.pmid: 22786450
references.citation: Eur J Pharmacol. 1998 Oct 16;359(1):1-18
references.pmid: 9831287
references.citation: Reprod Biol Endocrinol. 2011 Feb 18;9:26
references.pmid: 21332999
references.citation: Pain. 2001 Sep;93(3):239-245
references.pmid: 11514083
references.citation: J Nutr. 2010 Apr;140(4):869-74
references.pmid: 20181786