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Int J Pharm ; 662: 124538, 2024 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-39079594

RESUMO

Neuropathic pain is a high-intensity pain that can be caused by compression, transection, injury, nerve infiltration and drug treatment of cancer. Furthermore, drug therapy has low clinical efficacy, many adverse effects and remission of painful symptoms. In this way, natural products derived from plants constitute a promising therapeutic alternative. Therefore, the aim of this study was to evaluate the antihyperalgesic effect of γ-terpinene (γ-TPN) e γ-terpinene in ß-cyclodextrin inclusion complexes (TPN/CD) on neuropathic pain induced by tumor cells. Complexation extended the effect time for another 5 h and daily treatment for six days with γ-TPN (50 mg/kg, p.o.) and γ-TPN/ß-CD (50 mg/kg, p.o.) significantly reduced (p < 0.001) the mechanical hyperalgesia induced by the administration of 2x106 sarcoma cells 180 in the around the sciatic nerve. In addition, the Grip and Rota-rod techniques demonstrated that there was no interference on the muscle strength and motor coordination of the animals, suggesting that the compound under study does not have central nervous system depressant effects at the doses used. Molecular docking studies demonstrate favorable binding energies between γ-TPN and ß-CD, and alpha-2 adrenergic, glutamatergic, opioid and cholinergic receptors. Thus, this study demonstrates the potential of terpinene complexation in controlling neuropathic pain induced by tumor cells.


Assuntos
Monoterpenos Cicloexânicos , Hiperalgesia , Monoterpenos , Neuralgia , beta-Ciclodextrinas , Animais , beta-Ciclodextrinas/química , beta-Ciclodextrinas/administração & dosagem , Neuralgia/tratamento farmacológico , Hiperalgesia/tratamento farmacológico , Masculino , Monoterpenos/farmacologia , Monoterpenos/química , Monoterpenos/administração & dosagem , Camundongos , Analgésicos/farmacologia , Analgésicos/química , Analgésicos/administração & dosagem , Modelos Animais de Doenças , Nervo Isquiático/efeitos dos fármacos , Nervo Isquiático/lesões , Linhagem Celular Tumoral , Simulação de Acoplamento Molecular , Sarcoma 180/tratamento farmacológico , Sarcoma 180/patologia
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