Antihyperalgesic Effect of Hesperidin Improves with Diosmin in Experimental Neuropathic Pain.
Neuropathic pain is caused by a primary lesion, dysfunction, or transitory perturbation in the peripheral or central nervous system. In this study, we investigated the hesperidin antihyperalgesic effects alone or combined with diosmin in a model of neuropathic pain to corroborate a possible synergistic antinociceptive activity. Mechanical and thermal hyperalgesia were assessed in the aesthesiometer and plantar tests, respectively, after chronic constriction injury (CCI) model in rats receiving hesperidin (HS, 5 doses from 10 to 1000 mg/kg) alone or combined with diosmin (DS, 10 and 100 mg/kg) in comparison to gabapentin (31.6 mg/kg). UHPLC-MS analysis of cerebral samples was used to recognize the central concentrations of these flavonoids. Participation of different receptors was also investigated in the presence of haloperidol, bicuculline, and naloxone antagonists. Acute hesperidin administration significantly decreased mechanical and thermal hyperalgesia in CCI rats. Antihyperalgesic response of hesperidin, improved by a combination with diosmin (DS10/HS100) in both stimuli, was blockaded by haloperidol, bicuculline, and naloxone, but not WAY100635, antagonists. Both flavonoids were detected in brain samples. In conclusion, hesperidin alone and combined with diosmin produces antihyperalgesic response in the CCI model in rats. Antihyperalgesic effect of DS10/HS100 combination involves central activity partially modulated by D2, GABAA, and opioids, but not by 5-HT1A, receptors.
Laboratorio No. 7 "Dolor y Analgesia" del Departamento de Farmacobiología, Cinvestav-Sede Sur, Calz. de los Tenorios No. 235, Col. Granjas Coapa, CP 14330, México, DF, Mexico; Laboratorio de Neurofarmacología de Productos Naturales de la Dirección de Investigaciones en Neurociencias, Instituto Nacional de Psiquiatría "Ramón de la Fuente Muñiz", Av. México-Xochimilco No. 101, Col. San Lorenzo Huipulco 14370, México, DF, Mexico.
Azucena I
0000-0001-7104-8501
AI
Carballo-Villalobos
Laboratorio de Neurofarmacología de Productos Naturales de la Dirección de Investigaciones en Neurociencias, Instituto Nacional de Psiquiatría "Ramón de la Fuente Muñiz", Av. México-Xochimilco No. 101, Col. San Lorenzo Huipulco 14370, México, DF, Mexico.
María-Eva
0000-0002-4399-1508
ME
González-Trujano
Laboratorio de Neurofarmacología de Productos Naturales de la Dirección de Investigaciones en Neurociencias, Instituto Nacional de Psiquiatría "Ramón de la Fuente Muñiz", Av. México-Xochimilco No. 101, Col. San Lorenzo Huipulco 14370, México, DF, Mexico.
Francisco
F
Pellicer
Laboratorio No. 7 "Dolor y Analgesia" del Departamento de Farmacobiología, Cinvestav-Sede Sur, Calz. de los Tenorios No. 235, Col. Granjas Coapa, CP 14330, México, DF, Mexico.
Francisco J
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