title: α-Terpineol, a monoterpene alcohol, complexed with β-cyclodextrin exerts antihyperalgesic effect in animal model for fibromyalgia aided with docking study.
abstract: The anti-hyperalgesic effect of the complex containing α-terpineol (αTPN) and β-cyclodextrin (βCD) was analyzed in a non-inflammatory chronic muscle pain model, as well as its mechanism of action through docking study for a possible interaction with receptors. The αTPN-βCD complex was prepared and characterized through the thermogravimetry/derivate thermogravimetry (TG/DTG), Fourier transform infrared spectroscopy (FTIR) and scanning electron microscope (SEM). The model of chronic muscle pain was induced by two injections of pH 4.0 saline (20 μl) into the left gastrocnemius 5 days apart. After confirming hyperalgesia, male mice were treated with αTPN-βCD (25, 50 or 100 mg/kg; p.o.) or vehicle (saline 0.9%, p.o.) daily for 10 days. 1 h after the mechanical hyperalgesia, motor performance was evaluated. In addition, the systemic administration of naloxone and ondansetron tested the analgesic effect on the active opioid and serotonin receptors, respectively. The characterization tests indicated that αTPN was efficiently incorporated into βCD. The oral treatment with αTPN-βCD, at all doses tested, produced a significant (p < 0.001) decrease in the mechanical hyperalgesia, without causing any alteration in the force and in motor performance. This analgesic effect was reversed by the systemic administration of naloxone or ondansetron. These findings are corroborated by the docking study described in the present study, which verified a possible interaction of αTPN-βCD with opioid (MU, Kappa, Delta) and 5-HT receptors. Thus, it can be concluded that αTPN-βCD reduced the hyperalgesia followed by the chronic muscle pain model, probably evoked by the descending inhibitory pain system, specifically by opioid and serotoninergic receptors.
authors.affiliation: Department of Physiology, Federal University of Sergipe, Av. Tancredo Neves, S/N, Rosa Elza, São Cristóvão, Sergipe, CEP 49.000-100, Brazil. Electronic address: makson_gbo@hotmail.com.
authors.forename: Makson G B
authors.initials: MG
authors.lastname: Oliveira
authors.affiliation: Department of Physiology, Federal University of Sergipe, Av. Tancredo Neves, S/N, Rosa Elza, São Cristóvão, Sergipe, CEP 49.000-100, Brazil. Electronic address: guedes_renan@hotmail.com.
authors.forename: Renan G
authors.initials: RG
authors.lastname: Brito
authors.affiliation: Department of Physiology, Federal University of Sergipe, Av. Tancredo Neves, S/N, Rosa Elza, São Cristóvão, Sergipe, CEP 49.000-100, Brazil. Electronic address: priscila.laise@gmail.com.
authors.forename: Priscila L
authors.initials: PL
authors.lastname: Santos
authors.affiliation: Department of Physiology, Federal University of Sergipe, Av. Tancredo Neves, S/N, Rosa Elza, São Cristóvão, Sergipe, CEP 49.000-100, Brazil. Electronic address: heitorgaf@gmail.com.
authors.forename: Heitor G
authors.initials: HG
authors.lastname: Araújo-Filho
authors.affiliation: Department of Physiology, Federal University of Sergipe, Av. Tancredo Neves, S/N, Rosa Elza, São Cristóvão, Sergipe, CEP 49.000-100, Brazil. Electronic address: jullyanaquintans@gmail.com.
authors.forename: Jullyana S S
authors.initials: JS
authors.lastname: Quintans
authors.affiliation: Department of Pharmacy, Federal University of Sergipe, Av. Tancredo Neves, S/N, Rosa Elza, São Cristóvão, Sergipe, CEP 49.100-000, Brazil. Electronic address: paula.dp.menezes@gmail.com.
authors.forename: Paula P
authors.initials: PP
authors.lastname: Menezes
authors.affiliation: Department of Pharmacy, Federal University of Sergipe, Av. Tancredo Neves, S/N, Rosa Elza, São Cristóvão, Sergipe, CEP 49.100-000, Brazil. Electronic address: maiserafini@hotmail.com.
authors.forename: Mairim R
authors.initials: MR
authors.lastname: Serafini
authors.affiliation: Department of Pharmacy, Federal University of Sergipe, Av. Tancredo Neves, S/N, Rosa Elza, São Cristóvão, Sergipe, CEP 49.100-000, Brazil. Electronic address: yasmimgomess@gmail.com.
authors.forename: Yasmim M B G
authors.initials: YM
authors.lastname: Carvalho
authors.affiliation: Department of Pharmacy, Federal University of San Francisco Valley, Petrolina, Pernambuco, CEP 56.304-917, Brazil. Electronic address: larbacjuliane@hotmail.com.
authors.forename: Juliane C
authors.initials: JC
authors.lastname: Silva
authors.affiliation: Department of Pharmacy, Federal University of San Francisco Valley, Petrolina, Pernambuco, CEP 56.304-917, Brazil. Electronic address: guedesjackson@yahoo.com.br.
authors.forename: Jackson R G S
authors.initials: JR
authors.lastname: Almeida
authors.affiliation: Department of Chemistry, Federal University of Paraíba, João Pessoa, Paraíba, CEP 58051900, Brazil. Electronic address: luciana.scotti@gmail.com.
authors.forename: Luciana
authors.initials: L
authors.lastname: Scotti
authors.affiliation: Department of Chemistry, Federal University of Paraíba, João Pessoa, Paraíba, CEP 58051900, Brazil. Electronic address: mtscotti@gmail.com.
authors.forename: Marcus T
authors.initials: MT
authors.lastname: Scotti
authors.affiliation: Department of Pharmacy, Federal University of Sergipe, Av. Tancredo Neves, S/N, Rosa Elza, São Cristóvão, Sergipe, CEP 49.100-000, Brazil. Electronic address: saranflora04@gmail.com.
authors.forename: Saravanan
authors.initials: S
authors.lastname: Shanmugam
authors.affiliation: Bioprospecting Laboratory, Department of Botany, Bharathiar University, Coimbatore, 641 046, Tamil Nadu, India. Electronic address: drparimel@gmail.com.
authors.forename: Parimelazhagan
authors.initials: P
authors.lastname: Thangaraj
authors.affiliation: Department of Pharmacy, Federal University of Sergipe, Av. Tancredo Neves, S/N, Rosa Elza, São Cristóvão, Sergipe, CEP 49.100-000, Brazil. Electronic address: adriasa2001@yahoo.com.br.
authors.forename: Adriano A S
authors.initials: AA
authors.lastname: Araújo
authors.affiliation: Department of Physiology, Federal University of Sergipe, Av. Tancredo Neves, S/N, Rosa Elza, São Cristóvão, Sergipe, CEP 49.000-100, Brazil. Electronic address: lucindojr@gmail.com.
authors.forename: Lucindo J
authors.initials: LJ
authors.lastname: Quintans-Júnior
mesh_terms: D000700:Analgesics / Q000494:pharmacology; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001665:Binding Sites; D000081005:Cyclohexane Monoterpenes; D053138:Cyclohexenes / Q000737:chemistry* / Q000494:pharmacology* / Q000627:therapeutic use; D004195:Disease Models, Animal; D005356:Fibromyalgia / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D006930:Hyperalgesia / Q000139:chemically induced / Q000188:drug therapy / Q000473:pathology; D008297:Male; D051379:Mice; D062105:Molecular Docking Simulation; D039821:Monoterpenes / Q000737:chemistry* / Q000494:pharmacology* / Q000627:therapeutic use; D009270:Naloxone / Q000494:pharmacology; D017294:Ondansetron / Q000494:pharmacology; D017434:Protein Structure, Tertiary; D017465:Receptors, Opioid, delta / Q000737:chemistry* / Q000378:metabolism; D017473:Receptors, Opioid, kappa / Q000737:chemistry* / Q000378:metabolism; D017450:Receptors, Opioid, mu / Q000737:chemistry* / Q000378:metabolism; D047392:beta-Cyclodextrins / Q000737:chemistry*
chemical_list: D000700:Analgesics; D000081005:Cyclohexane Monoterpenes; D053138:Cyclohexenes; D039821:Monoterpenes; D017465:Receptors, Opioid, delta; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; D047392:beta-Cyclodextrins; C016775:alpha-terpineol; D009270:Naloxone; D017294:Ondansetron; C031215:betadex
keywords: Chronic pain; Fibromyalgia; Opioid; Pain; α-Terpineol; β-Cyclodextrin