title: Evidence for the involvement of descending pain-inhibitory mechanisms in the attenuation of cancer pain by carvacrol aided through a docking study.
abstract: OBJECTIVE
  The present study evaluated the carvacrol (CARV) effect on hyperalgesia and nociception induced by sarcoma 180 (S180) in mice.
  
  
  METHODS
  Carvacrol treatment (12.5-50mg/kgs.c.) once daily for 15days was started 24h after injection of the sarcoma cells in the hind paw (s.c.). Mice were evaluated for mechanical sensitivity (von Frey), spontaneous and palpation-induced nociception, limb use and tumor growth on alternate days. CARV effects on the central nervous system were evaluated through immunofluorescence for Fos protein. Molecular docking studies also were performed to evaluate intermolecular interactions of the carvacrol and muscimol, as ligands of interleukin-10 and GABAA receptors.
  
  
  RESULTS
  CARV was able to significantly reduce mechanical hyperalgesia and spontaneous and palpation-induced nociception, improve use paw, decrease the number of positively marked neurons in lumbar spinal cord and activate periaqueductal gray, nucleus raphe magnus and locus coeruleus. CARV also caused significant decreased tumor growth. Docking studies showed favorable interaction overlay of the CARV with IL-10 and GABAA.
  
  
  CONCLUSIONS
  Together, these results demonstrated that CARV may be an interesting option for the development of new analgesic drugs for the management of cancer pain.
authors.affiliation: Department of Health Education, Federal University of Sergipe, Lagarto, SE, Brazil.
authors.forename: Adriana G
authors.initials: AG
authors.lastname: Guimarães
authors.affiliation: Federal University of Paraíba, João Pessoa, PB, Brazil.
authors.forename: Luciana
authors.initials: L
authors.lastname: Scotti
authors.affiliation: Federal University of Paraíba, João Pessoa, PB, Brazil.
authors.forename: Marcus Tullius
authors.initials: MT
authors.lastname: Scotti
authors.affiliation: State University of Paraiba, Biological Science Department, Laboratory of Synthesis and Drug Delivery, 58070-450 João Pessoa, PB, Brazil.
authors.forename: Francisco J B
authors.initials: FJ
authors.lastname: Mendonça Júnior
authors.affiliation: Department of Physiology, Federal University of Sergipe, SãoCristóvão, SE, Brazil.
authors.forename: Nayara S R
authors.initials: NS
authors.lastname: Melo
authors.affiliation: Department of Physiology, Federal University of Sergipe, SãoCristóvão, SE, Brazil.
authors.forename: Rafael S
authors.initials: RS
authors.lastname: Alves
authors.affiliation: Department of Morphology, Federal University of Sergipe, SãoCristóvão, SE, Brazil.
authors.forename: Waldecy
authors.initials: W
authors.lastname: De Lucca Júnior
authors.affiliation: Oswaldo Cruz Foundation, Laboratory of Tissue Engineering and Immunopharmacology, Salvador, BA, Brazil.
authors.forename: Daniel P
authors.initials: DP
authors.lastname: Bezerra
authors.affiliation: Department of Biochemistry, Federal University of Rio Grande do Sul, Porto Alegre, RS, Brazil.
authors.forename: Daniel P
authors.initials: DP
authors.lastname: Gelain
authors.affiliation: Department of Physiology, Federal University of Sergipe, SãoCristóvão, SE, Brazil. Electronic address: lapec.ufs@gmail.com.
authors.forename: Lucindo J
authors.initials: LJ
authors.lastname: Quintans Júnior
mesh_terms: D000700:Analgesics / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D000081007:Cymenes; D004305:Dose-Response Relationship, Drug; D006930:Hyperalgesia / Q000188:drug therapy* / Q000209:etiology; D016753:Interleukin-10 / Q000378:metabolism; D008297:Male; D051379:Mice; D062105:Molecular Docking Simulation; D039821:Monoterpenes / Q000008:administration & dosage / Q000494:pharmacology*; D009118:Muscimol / Q000494:pharmacology; D059225:Nociception / Q000187:drug effects; D010146:Pain / Q000188:drug therapy* / Q000209:etiology; D010487:Periaqueductal Gray / Q000187:drug effects / Q000378:metabolism; D011963:Receptors, GABA-A / Q000378:metabolism; D012510:Sarcoma 180 / Q000150:complications* / Q000473:pathology; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism
chemical_list: D000700:Analgesics; D000081007:Cymenes; D039821:Monoterpenes; D011963:Receptors, GABA-A; D016753:Interleukin-10; D009118:Muscimol; C073316:carvacrol
keywords: Cancer pain; Carvacrol; Carvacrol (PubChem CID: 10364); Hyperalgesia; Monoterpene; Morphine (PubChem CID: 5288826); Nociception