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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

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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.

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Authors and Affiliations

  1. 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

    Lucindo J. Quintans-Júnior, Renan G. Brito, Jullyana S. S. Quintans & Priscila L. Santos

  2. Department of Physical Therapy and Rehabilitation Science, Carver College of Medicine, University of Iowa (UI), Iowa City, IA, USA

    Lucindo J. Quintans-Júnior, Renan G. Brito, Sandra J. Kolker & Kathleen A. Sluka

  3. Department of Chemistry, Federal University of Sergipe (UFS), São Cristóvão, SE, Brazil

    Zaine T. Camargo & Péricles A. Barreto

  4. Department of Agronomy, Federal University of Sergipe (UFS), São Cristóvão, SE, Brazil

    Maria F. Arrigoni-Blank

  5. Department of Morphology, Federal University of Sergipe (UFS), São Cristóvão, SE, Brazil

    Waldecy Lucca-Júnior

  6. Department of Chemistry, Federal University of Paraíba (UFPB), João Pessoa, PB, Brazil

    Luciana Scotti & Marcus T. Scotti

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  1. Lucindo J. Quintans-Júnior
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Correspondence to Lucindo J. Quintans-Júnior.

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Research Funding

This study was supported by CNPq, Brazil [Grant nos. 441969/2014-3, 200636/2012-0, 470774/2011-8]; FAPITEC, SE, Brazil; CAPES, Brazil; and FINEP, Brazil. This study was also supported by National Institutes of Health grants AR061371 and AR052316 to KAS.

Conflict of Interest

The authors report no conflict of interest. KAS serves as a consultant for Bayer, Inc. and receives research support from Medtronic.

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Quintans-Júnior, L.J., Brito, R.G., Quintans, J.S.S. et al. 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. Mol Neurobiol 55, 1665–1675 (2018). https://doi.org/10.1007/s12035-017-0438-1

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