A multi-target ligand (JM-20) prevents morphine-induced hyperalgesia in naïve and neuropathic rats.

Autor: Garrido-Suárez BB; Centro de Investigación y Desarrollo de Medicamentos, Ave 26, No. 1605 Boyeros y Puentes Grandes, CP 10600, La Habana, Cuba; Instituto de Ciencias del Mar, Loma y 37, Nuevo Vedado, Havana, CP 10300, Cuba. Electronic address: barbara.suarez79@gmail.com., Garrido G; Departamento de Ciencias Farmacéuticas, Facultad de Ciencias, Edificio Ñ3, Universidad Católica del Norte, Angamos, 0610, Antofagasta, CP 124000, Chile. Electronic address: gabino.garrido@gmail.com., Bellma-Menéndez A; Centro de Investigación y Desarrollo de Medicamentos, Ave 26, No. 1605 Boyeros y Puentes Grandes, CP 10600, La Habana, Cuba., Aparicio-López G; Centro de Investigación y Desarrollo de Medicamentos, Ave 26, No. 1605 Boyeros y Puentes Grandes, CP 10600, La Habana, Cuba., Valdés-Martínez O; Centro de Investigación y Desarrollo de Medicamentos, Ave 26, No. 1605 Boyeros y Puentes Grandes, CP 10600, La Habana, Cuba., Morales-Aguiar RA; Instituto de Ciencias del Mar, Loma y 37, Nuevo Vedado, Havana, CP 10300, Cuba., Fernández-Pérez MD; Instituto de Ciencias del Mar, Loma y 37, Nuevo Vedado, Havana, CP 10300, Cuba., Ochoa-Rodríguez E; Laboratorio de Síntesis Orgánica de La Facultad de Química de La Universidad de La Habana, Zapata s/n entre G y Carlitos Aguirre, Vedado Plaza de la Revolución, CP 10400, La Habana, Cuba., Verdecia-Reyes Y; Laboratorio de Síntesis Orgánica de La Facultad de Química de La Universidad de La Habana, Zapata s/n entre G y Carlitos Aguirre, Vedado Plaza de la Revolución, CP 10400, La Habana, Cuba., Delgado-Hernández R; Clinical Pharmacy and Pharmaceutical Care Unit, Department of Pharmacy and Pharmaceutical Technology, and Physical Chemistry, Faculty of Pharmacy and Food Sciences, Universitat de Barcelona, Av. Joan XXIII, 27-31, 08028, Barcelona, Spain.
Jazyk: angličtina
Zdroj: European journal of pharmacology [Eur J Pharmacol] 2024 Nov 15; Vol. 983, pp. 176992. Date of Electronic Publication: 2024 Sep 10.
DOI: 10.1016/j.ejphar.2024.176992
Abstrakt: The present study examines the possible inhibitory effect of JM-20, a multi-target neuroprotective compound, on the development of morphine-induced hyperalgesia in Male Sprague-Dawley naïve rats. Additionally, the impact of JM-20 on chronic constriction injury (CCI) rats under chronic morphine exposure was investigated, and its efficacy in reducing mechanical hypersensitivity and histopathological changes in the sciatic nerve was assessed. JM-20 (20 mg/kg, per os [p.o.]), administered 60 min before morphine (10 mg/kg, s.c. twice daily at 12 h intervals) for ten days, significantly inhibited the development of morphine-induced hyperalgesia assessed using an electronic pressure-meter paw test, hot-plate, and formalin test, as well as the appearance of spontaneous withdrawal somatic symptoms in rats. Furthermore, JM-20 decreases spinal pro-inflammatory interleukin-1β and restores glutathione to close physiological concentrations, biomarkers directly related to the intensity of mechanical hypernociception. After CCI and sham surgery, co-treatment with JM-20 (10 mg/kg, p.o.) for five days decreased morphine increased-mechanical hypersensitivity, even 12 days after its discontinuation. Continued morphine treatment imposed a neuroinflammatory challenge in CCI animals, further increasing cellularity (>75% immune cell infiltration) with lymphocytes and macrophages. However, JM-20 co-treatment still reduced the presence of cellular infiltrates (51-75%) with a predominance of lymphocytes. Even in the absence of nerve injury, JM-20 attenuated the peripheral neuroinflammatory response observed in morphine-treated sham-operated animals (0% vs. 1-25%). These findings suggest that JM-20 could prevent morphine-induced hyperalgesia by anti-inflammatory and antioxidant mechanisms.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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