β-caryophyllene, a dietary cannabinoid, complexed with β-cyclodextrin produced anti-hyperalgesic effect involving the inhibition of Fos expression in superficial dorsal horn Lucindo J. Quintans-J´unior, Adriano A.S. Ara´ujo, Renan G. Brito, Priscila L. Santos, Jullyana S.S. Quintans, Paula P. Menezes, Mairim R. Serafini, Gabriel F. Silva, Flavio M.S. Carvalho, Nicole K. Brogden, Kathleen A. Sluka PII: DOI: Reference:
S0024-3205(16)30099-6 doi: 10.1016/j.lfs.2016.02.049 LFS 14734
To appear in:
Life Sciences
Received date: Revised date: Accepted date:
25 October 2015 11 February 2016 11 February 2016
Please cite this article as: Quintans-J´ unior Lucindo J., Ara´ ujo Adriano A.S., Brito Renan G., Santos Priscila L., Quintans Jullyana S.S., Menezes Paula P., Serafini Mairim R., Silva Gabriel F., Carvalho Flavio M.S., Brogden Nicole K., Sluka Kathleen A., β-caryophyllene, a dietary cannabinoid, complexed with β-cyclodextrin produced anti-hyperalgesic effect involving the inhibition of Fos expression in superficial dorsal horn, Life Sciences (2016), doi: 10.1016/j.lfs.2016.02.049
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ACCEPTED MANUSCRIPT β-caryophyllene, a dietary cannabinoid, complexed with β-cyclodextrin produced anti-hyperalgesic effect involving the inhibition of Fos expression in superficial
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dorsal horn
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Lucindo J. Quintans-Júnior1,3,#*, Adriano A.S. Araújo2,#, Renan G. Brito1,3, Priscila L.
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Santos1, Jullyana S.S. Quintans1, Paula P. Menezes2, Mairim R. Serafini2, Gabriel F.
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Department of Physiology,
Department of Pharmacy.
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Department of Food
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Silva3, Flavio M.S. Carvalho4, Nicole K. Brogden5, Kathleen A. Sluka6
Engineering. Federal University of Sergipe, São Cristóvão, Sergipe, Brazil. Department of Mineralogy and Petrology, University of São Paulo, São Paulo, Brazil.
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Department of Pharmaceutical Sciences and Experimental Therapeutics, College of
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Pharmacy, University of Iowa, Iowa City, Iowa, USA. Physical Therapy and Rehabilitation Science, Carver College of Medicine, University
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of Iowa, Iowa City, Iowa, USA.
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These authors contributed equally for the development of the paper.
*Author for correspondence: Lucindo J. Quintans-Júnior, Department of Physiology, Laboratory of Neuroscience and Pharmacological Assay. Federal University of Sergipe, Av. Marechal Rondon, s/n, São Cristóvão, Sergipe, Brazil (fax +55-79-2105-6640, Email:
[email protected];
[email protected]).
Conflict of interest: The authors report no conflict of interest.
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ACCEPTED MANUSCRIPT Abstract Aims: Evaluate the anti-hyperalgesic effect of the complex containing β-caryophyllene
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(βCP) and β-cyclodextrin (βCD) in a non-inflammatory chronic muscle pain mice model and investigated its action on superficial dorsal horn of the lumbar spinal cord.
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Main Methods: The βCP-βCD complex were prepared and characterized through the
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DSC, TG/DTG, FTIR, XRD and SEM. The model of chronic muscle pain was induced by two injections of pH 4.0 saline (20 µl) into left gastrocnemius 5 days apart. After
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confirming hyperalgesia, male mice were treated with βCP-βCD (10 or 20 mg/kg; p.o.)
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or vehicle (saline 0,9%, p.o.) daily for 9 days. 1 h after, the mechanical hyperalgesia, muscle withdrawal thresholds and motor performance were evaluated. To evaluate the βCP-βCD action on spinal cord, animals induced with chronic muscle pain were treated
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with βCP-βCD (20 mg/kg; p.o.) or vehicle (saline 0,9%, p.o.) and 90 min. after, were perfused, the lumbar spinal cord collected, crioprotected, cut and submitted in an
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imunofluorescence protocol for Fos protein. Key findings: The characterization tests indicated that βCP were efficiently incorporated into βCD. The oral treatment with βCPβCD, at all doses tested, produced a significant (p