Involvement of the PKA pathway and inhibition of voltage gated Ca2+ channels in antihyperalgesic activity of Lippia grata/β-cyclodextrin.

Autor: Siqueira-Lima PS; Multiuser Health Center Facility (CMulti-Saúde), Brazil; Department of Physiology (DFS). Federal University of Sergipe (UFS), São Cristóvão, SE, 49100-000 Brazil., Quintans JSS; Multiuser Health Center Facility (CMulti-Saúde), Brazil; Department of Physiology (DFS). Federal University of Sergipe (UFS), São Cristóvão, SE, 49100-000 Brazil. Electronic address: jullyana@pq.cnpq.br., Heimfarth L; Multiuser Health Center Facility (CMulti-Saúde), Brazil; Department of Physiology (DFS). Federal University of Sergipe (UFS), São Cristóvão, SE, 49100-000 Brazil., Passos FRS; Multiuser Health Center Facility (CMulti-Saúde), Brazil; Department of Physiology (DFS). Federal University of Sergipe (UFS), São Cristóvão, SE, 49100-000 Brazil., Pereira EWM; Multiuser Health Center Facility (CMulti-Saúde), Brazil; Department of Physiology (DFS). Federal University of Sergipe (UFS), São Cristóvão, SE, 49100-000 Brazil., Rezende MM; Multiuser Health Center Facility (CMulti-Saúde), Brazil; Department of Physiology (DFS). Federal University of Sergipe (UFS), São Cristóvão, SE, 49100-000 Brazil., Menezes-Filho JER; Multiuser Health Center Facility (CMulti-Saúde), Brazil; Department of Physiology (DFS). Federal University of Sergipe (UFS), São Cristóvão, SE, 49100-000 Brazil., Barreto RSS; Multiuser Health Center Facility (CMulti-Saúde), Brazil; Department of Physiology (DFS). Federal University of Sergipe (UFS), São Cristóvão, SE, 49100-000 Brazil., Coutinho HDM; Regional University of Cariri. Universidade Regional do Cariri (URCA), Crato/CE, 63105-000, Brazil., Araújo AAS; Department of Pharmacy, Federal University of Sergipe (UFS), São Cristóvão, SE, 49100-000, Brazil., Medrado AS; Federal University of Minas Gerais. Belo Horizonte, MG, CEP 31270-901, Brazil., Naves LA; Federal University of Minas Gerais. Belo Horizonte, MG, CEP 31270-901, Brazil., Bomfim HF; Post-Graduate Program in Biotechnology, State University of Feira de Santana, Feira de Santana, BA, 44036-900, Brazil., Lucchese AM; Post-Graduate Program in Biotechnology, State University of Feira de Santana, Feira de Santana, BA, 44036-900, Brazil., Gandhi SR; Multiuser Health Center Facility (CMulti-Saúde), Brazil., Quintans-Júnior LJ; Multiuser Health Center Facility (CMulti-Saúde), Brazil; Department of Physiology (DFS). Federal University of Sergipe (UFS), São Cristóvão, SE, 49100-000 Brazil. Electronic address: lucindojr@gmail.com.
Jazyk: angličtina
Zdroj: Life sciences [Life Sci] 2019 Dec 15; Vol. 239, pp. 116961. Date of Electronic Publication: 2019 Oct 22.
DOI: 10.1016/j.lfs.2019.116961
Abstrakt: Neuropathic pain (NP) is a difficult condition to treat because of the modest efficacy of available drugs. New treatments are required. In the study we aimed to investigate the effects of the essential oil from Lippia grata alone or complexed in β-cyclodextrin (LG or LG-βCD) on persistent inflammatory and neuropathic pain in a mouse model. We also investigated Ca 2+ currents in rat dorsal root ganglion (DRG) neurons. Male Swiss mice were treated with LG or LG/β-CD (24 mg/kg, i.g.) and their effect was evaluated using an acute inflammatory pleurisy model and nociception triggered by intraplantar injection of an agonist of the TRPs channels. We also tested their effect in chronic pain models: injection of Freund's Complete Adjuvant and partial sciatic nerve ligation (PSNL). In the pleurisy model, LG reduced the number of leukocytes and the levels of TNF-α and IL-1β. It also inhibited cinnamaldehyde and menthol-induced nociceptive behavior. The pain threshold in mechanical and thermal hyperalgesia was increased and paw edema was decreased in models of inflammatory and neuropathic pain. PSNL increased inflammatory protein contents and LG and LG-βCD restored the protein contents of TNF-α, NF-κB, and PKA, but not IL-1β and IL-10. LG inhibited voltage gated Ca 2+ channels from DRG neurons. Our results suggested that LG or LG-βCD produce anti-hyperalgesic effect in chronic pain models through reductions in TNF-α levels and PKA, and inhibited voltage-gated calcium channels and may be innovative therapeutic agents for the management of NP.
(Copyright © 2019. Published by Elsevier Inc.)
Databáze: MEDLINE
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