title: Nanoemulsion Thermoreversible Pluronic F127-Based Hydrogel Containing Hyptis pectinata (Lamiaceae) Leaf Essential Oil Produced a Lasting Anti-hyperalgesic Effect in Chronic Noninflammatory Widespread Pain in Mice.
abstract: We evaluated if a nanostructured thermoreversible Pluronic F127-based hydrogel incorporated with Hyptis pectinata leaf essential oil (NE-EOH) produces a long-lasting anti-hyperalgesic effect on chronic muscle pain in an animal model. We induced chronic muscle pain by injecting the gastrocnemius with saline injections. Paw and muscle withdrawal thresholds and motor performance were evaluated after treatment and compared with morphine, diazepam, or vehicle. Naloxone and methysergide administration tested the involvement of opioid and serotonin receptors, respectively. Sites of action in the central nervous system for the NE-EOH were examined by measuring substance P (SP) levels in the spinal cord and Fos protein in the brainstem. NE-EOH increased paw and muscle withdrawal thresholds when compared with vehicle but had no effect on motor function. This analgesic effect was reversed by both naloxone and methysergide. NE-EOH decreased elevated substance P levels and reduced Fos-labeled neurons in the spinal cord and increased the number of Fos-labeled neurons in the periaqueductal gray (PAG), nucleus raphe magnus (NRM), and locus coeruleus (LC). NE-EOH was shown to produce a lasting anti-hyperalgesic effect. It uses opioid and serotonin receptors, activates brainstem inhibitory pathways, and reduces the release of excitatory neurotransmitters in the spinal cord and is a substance with potential to be used in the treatment of noninflammatory pain conditions. Graphical Abstract.
authors.affiliation: Department of Physiology (DFS), Laboratory of Neuroscience and Pharmacological Assays (LANEF), Federal University of Sergipe (UFS), Av. Marechal Rondom, s/n, São Cristóvão, SE, Brazil. lucindojr@gmail.com.|Department of Physical Therapy and Rehabilitation Science, Carver College of Medicine, University of Iowa (UI), Iowa City, IA, USA. lucindojr@gmail.com.
authors.forename: Lucindo J
authors.initials: LJ
authors.lastname: Quintans-Júnior
authors.affiliation: Department of Physiology (DFS), Laboratory of Neuroscience and Pharmacological Assays (LANEF), Federal University of Sergipe (UFS), Av. Marechal Rondom, s/n, São Cristóvão, SE, Brazil.|Department of Physical Therapy and Rehabilitation Science, Carver College of Medicine, University of Iowa (UI), Iowa City, IA, USA.
authors.forename: Renan G
authors.initials: RG
authors.lastname: Brito
authors.affiliation: Department of Physiology (DFS), Laboratory of Neuroscience and Pharmacological Assays (LANEF), Federal University of Sergipe (UFS), Av. Marechal Rondom, s/n, São Cristóvão, SE, Brazil.
authors.forename: Jullyana S S
authors.initials: JSS
authors.lastname: Quintans
authors.affiliation: Department of Physiology (DFS), Laboratory of Neuroscience and Pharmacological Assays (LANEF), Federal University of Sergipe (UFS), Av. Marechal Rondom, s/n, São Cristóvão, SE, Brazil.
authors.forename: Priscila L
authors.initials: PL
authors.lastname: Santos
authors.affiliation: Department of Chemistry, Federal University of Sergipe (UFS), São Cristóvão, SE, Brazil.
authors.forename: Zaine T
authors.initials: ZT
authors.lastname: Camargo
authors.affiliation: Department of Chemistry, Federal University of Sergipe (UFS), São Cristóvão, SE, Brazil.
authors.forename: Péricles A
authors.initials: PA
authors.lastname: Barreto
authors.affiliation: Department of Agronomy, Federal University of Sergipe (UFS), São Cristóvão, SE, Brazil.
authors.forename: Maria F
authors.initials: MF
authors.lastname: Arrigoni-Blank
authors.affiliation: Department of Morphology, Federal University of Sergipe (UFS), São Cristóvão, SE, Brazil.
authors.forename: Waldecy
authors.initials: W
authors.lastname: Lucca-Júnior
authors.affiliation: Department of Chemistry, Federal University of Paraíba (UFPB), João Pessoa, PB, Brazil.
authors.forename: Luciana
authors.initials: L
authors.lastname: Scotti
authors.affiliation: Department of Chemistry, Federal University of Paraíba (UFPB), João Pessoa, PB, Brazil.
authors.forename: Marcus T
authors.initials: MT
authors.lastname: Scotti
authors.affiliation: Department of Physical Therapy and Rehabilitation Science, Carver College of Medicine, University of Iowa (UI), Iowa City, IA, USA.
authors.forename: Sandra J
authors.initials: SJ
authors.lastname: Kolker
authors.affiliation: Department of Physical Therapy and Rehabilitation Science, Carver College of Medicine, University of Iowa (UI), Iowa City, IA, USA.
authors.forename: Kathleen A
authors.initials: KA
authors.lastname: Sluka
mesh_terms: D000700:Analgesics / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D059350:Chronic Pain / Q000188:drug therapy* / Q000378:metabolism; D004195:Disease Models, Animal; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D019686:Lamiaceae; D008297:Male; D051379:Mice; D009822:Oils, Volatile / Q000494:pharmacology / Q000627:therapeutic use*; D010147:Pain Measurement; D010487:Periaqueductal Gray / Q000187:drug effects / Q000378:metabolism; D010936:Plant Extracts / Q000494:pharmacology / Q000627:therapeutic use*; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism; D013373:Substance P / Q000378:metabolism
chemical_list: D000700:Analgesics; D009822:Oils, Volatile; D010936:Plant Extracts; D016760:Proto-Oncogene Proteins c-fos; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D013373:Substance P
keywords: Hyperalgesia; Hyptis pectinata; Muscle; Opioid; Pain; Pluronic; Serotonin; Substance P