title: β-caryophyllene, a dietary cannabinoid, complexed with β-cyclodextrin produced anti-hyperalgesic effect involving the inhibition of Fos expression in superficial dorsal horn.
abstract: OBJECTIVE
  Evaluate the anti-hyperalgesic effect of the complex containing β-caryophyllene (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.
  
  
  METHODS
  The βCP-βCD complex were prepared and characterized through the DSC, TG/DTG, FTIR, XRD and SEM. The model of chronic muscle pain was induced by two injections of pH4.0 saline (20μL) into left gastrocnemius 5days apart. After confirming hyperalgesia, male mice were treated with βCP-βCD (10 or 20mg/kg; p.o.) or vehicle (saline 0.9%, p.o.) daily for 9days. 1h 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 with βCP-βCD (20mg/kg; p.o.) or vehicle (saline 0.9%, p.o.) and 90min. after, were perfused, the lumbar spinal cord collected, crioprotected, cut and submitted in an immunofluorescence protocol for Fos protein.
  
  
  RESULTS
  The characterization tests indicated that βCP were efficiently incorporated into βCD. The oral treatment with βCP-βCD, at all doses tested, produced a significant (p<0.05) reduction on mechanical hyperalgesia and a significant (p<0.05) increase in muscle withdrawal thresholds, without produce any alteration in force. In addition, βCP-βCD was able to significantly (p<0.05) decrease Fos expression in the superficial dorsal horn.
  
  
  CONCLUSIONS
  Thus, βCP-βCD attenuates the non-inflammatory chronic muscle pain in mice and inhibits the Fos expression in the lumbar spinal cord.
authors.affiliation: Department of Physiology, Federal University of Sergipe, São Cristóvão, Sergipe, Brazil; Department of Food Engineering, Federal University of Sergipe, São Cristóvão, Sergipe, Brazil. Electronic address: lucindojr@gmail.com.
authors.forename: Lucindo J
authors.initials: LJ
authors.lastname: Quintans-Júnior
authors.affiliation: Department of Pharmacy, Federal University of Sergipe, São Cristóvão, Sergipe, Brazil.
authors.forename: Adriano A S
authors.initials: AA
authors.lastname: Araújo
authors.affiliation: Department of Physiology, Federal University of Sergipe, São Cristóvão, Sergipe, Brazil; Department of Food Engineering, Federal University of Sergipe, São Cristóvão, Sergipe, Brazil.
authors.forename: Renan G
authors.initials: RG
authors.lastname: Brito
authors.affiliation: Department of Physiology, Federal University of Sergipe, São Cristóvão, Sergipe, Brazil.
authors.forename: Priscila L
authors.initials: PL
authors.lastname: Santos
authors.affiliation: Department of Physiology, Federal University of Sergipe, São Cristóvão, Sergipe, Brazil.
authors.forename: Jullyana S S
authors.initials: JS
authors.lastname: Quintans
authors.affiliation: Department of Pharmacy, Federal University of Sergipe, São Cristóvão, Sergipe, Brazil.
authors.forename: Paula P
authors.initials: PP
authors.lastname: Menezes
authors.affiliation: Department of Pharmacy, Federal University of Sergipe, São Cristóvão, Sergipe, Brazil.
authors.forename: Mairim R
authors.initials: MR
authors.lastname: Serafini
authors.affiliation: Department of Food Engineering, Federal University of Sergipe, São Cristóvão, Sergipe, Brazil.
authors.forename: Gabriel F
authors.initials: GF
authors.lastname: Silva
authors.affiliation: Department of Mineralogy and Petrology, University of São Paulo, São Paulo, Brazil.
authors.forename: Flavio M S
authors.initials: FM
authors.lastname: Carvalho
authors.affiliation: Department of Pharmaceutical Sciences and Experimental Therapeutics, College of Pharmacy, University of Iowa, Iowa City, IA, USA.
authors.forename: Nicole K
authors.initials: NK
authors.lastname: Brogden
authors.affiliation: Physical Therapy and Rehabilitation Science, Carver College of Medicine, University of Iowa, Iowa City, IA, USA.
authors.forename: Kathleen A
authors.initials: KA
authors.lastname: Sluka
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal; D002186:Cannabinoids / Q000008:administration & dosage*; D004359:Drug Therapy, Combination; D005786:Gene Expression Regulation; D006930:Hyperalgesia / Q000188:drug therapy / Q000378:metabolism*; D008297:Male; D051379:Mice; D000081223:Polycyclic Sesquiterpenes; D016760:Proto-Oncogene Proteins c-fos / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D012717:Sesquiterpenes / Q000008:administration & dosage*; D066148:Spinal Cord Dorsal Horn / Q000187:drug effects / Q000378:metabolism*; D016896:Treatment Outcome; D047392:beta-Cyclodextrins / Q000008:administration & dosage*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D002186:Cannabinoids; D000081223:Polycyclic Sesquiterpenes; D016760:Proto-Oncogene Proteins c-fos; D012717:Sesquiterpenes; D047392:beta-Cyclodextrins; C024714:caryophyllene
keywords: Chronic pain; Fos; Hyperalgesia; Pain; β-Caryophyllene; β-Cyclodextrin