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Ultra-Low Doses of Naltrexone Enhance the Antiallodynic Effect of Pregabalin or Gabapentin in Neuropathic Rats.
Drug Dev Res. 2017 12; 78(8):371-380.DD

Abstract

Preclinical Research Treatment of neuropathic pain is an area of largely unmet medical need. Pregabalin and gabapentin are anticonvulsants widely used for the treatment of neuropathic pain. Unfortunately, these drugs are only effective in 50-60% of the treated patients. In addition, both drugs have substantial side effects. Several studies have reported that ultralow doses of opioid receptor antagonists can induce analgesia and enhance the analgesic effect of opioids in rodents and humans. The objective of the present study was to assess the antiallodynic synergistic interaction between gabapentinoids and naltrexone in rats. Oral administration of pregabalin (ED50 = 2.79 ± 0.16 mg/kg) or gabapentin (ED50 = 21.04 ± 2.87 mg/kg) as well as intrathecal naltrexone (ED50 = 0.11 ± 0.02 ng) reduced in a dose-dependent manner tactile allodynia in rats. Maximal antiallodynic effects (∼100%) were reached with 30 mg/kg of pregabalin, 300 mg/kg of gabapentin or 0.5 ng of naltrexone. Co-administration of pregabalin or gabapentin and naltrexone in a fixed-dose ratio (1:1) remarkably reduced spinal nerve ligation-induced tactile allodynia showing a synergistic interaction. The data indicate that combinations of pregabalin or gabapentin and ultra-low doses of naltrexone are able to reduce tactile allodynia in neuropathic rats with lower doses that those used when drugs are given individually and with an improved side effects profile. Drug Dev Res 78 : 371-380, 2017. © 2017 Wiley Periodicals, Inc.

Authors+Show Affiliations

Neurobiology of Pain Laboratory, Departamento de Farmacobiología, Centro de Investigación y de Estudios Avanzados, Unidad Coapa Calzada de los Tenorios 235, Col. Granjas Coapa, Tlalpan, 14330, Ciudad de México, Mexico.Catedra Conacyt, Estudios Moleculares Avanzados, Instituto de Ecología AC (INECOL). Carretera antigua a Coatepec 351, El Haya, Xalapa, Veracruz, Mexico.Neurobiology of Pain Laboratory, Departamento de Farmacobiología, Centro de Investigación y de Estudios Avanzados, Unidad Coapa Calzada de los Tenorios 235, Col. Granjas Coapa, Tlalpan, 14330, Ciudad de México, Mexico.Laboratorio Médico Químico Biológico S.A. de C.V. (Bioquimed), Ciudad de México, Mexico.Neurobiology of Pain Laboratory, Departamento de Farmacobiología, Centro de Investigación y de Estudios Avanzados, Unidad Coapa Calzada de los Tenorios 235, Col. Granjas Coapa, Tlalpan, 14330, Ciudad de México, Mexico.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

28868795

Citation

Pineda-Farias, Jorge B., et al. "Ultra-Low Doses of Naltrexone Enhance the Antiallodynic Effect of Pregabalin or Gabapentin in Neuropathic Rats." Drug Development Research, vol. 78, no. 8, 2017, pp. 371-380.
Pineda-Farias JB, Caram-Salas NL, Salinas-Abarca AB, et al. Ultra-Low Doses of Naltrexone Enhance the Antiallodynic Effect of Pregabalin or Gabapentin in Neuropathic Rats. Drug Dev Res. 2017;78(8):371-380.
Pineda-Farias, J. B., Caram-Salas, N. L., Salinas-Abarca, A. B., Ocampo, J., & Granados-Soto, V. (2017). Ultra-Low Doses of Naltrexone Enhance the Antiallodynic Effect of Pregabalin or Gabapentin in Neuropathic Rats. Drug Development Research, 78(8), 371-380. https://doi.org/10.1002/ddr.21409
Pineda-Farias JB, et al. Ultra-Low Doses of Naltrexone Enhance the Antiallodynic Effect of Pregabalin or Gabapentin in Neuropathic Rats. Drug Dev Res. 2017;78(8):371-380. PubMed PMID: 28868795.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Ultra-Low Doses of Naltrexone Enhance the Antiallodynic Effect of Pregabalin or Gabapentin in Neuropathic Rats. AU - Pineda-Farias,Jorge B, AU - Caram-Salas,Nadia L, AU - Salinas-Abarca,Ana B, AU - Ocampo,Jorge, AU - Granados-Soto,Vinicio, Y1 - 2017/09/03/ PY - 2017/07/14/received PY - 2017/08/14/accepted PY - 2017/9/5/pubmed PY - 2018/7/14/medline PY - 2017/9/5/entrez KW - combination KW - gabapentin KW - naltrexone KW - pregabalin KW - tactile allodynia SP - 371 EP - 380 JF - Drug development research JO - Drug Dev Res VL - 78 IS - 8 N2 - Preclinical Research Treatment of neuropathic pain is an area of largely unmet medical need. Pregabalin and gabapentin are anticonvulsants widely used for the treatment of neuropathic pain. Unfortunately, these drugs are only effective in 50-60% of the treated patients. In addition, both drugs have substantial side effects. Several studies have reported that ultralow doses of opioid receptor antagonists can induce analgesia and enhance the analgesic effect of opioids in rodents and humans. The objective of the present study was to assess the antiallodynic synergistic interaction between gabapentinoids and naltrexone in rats. Oral administration of pregabalin (ED50 = 2.79 ± 0.16 mg/kg) or gabapentin (ED50 = 21.04 ± 2.87 mg/kg) as well as intrathecal naltrexone (ED50 = 0.11 ± 0.02 ng) reduced in a dose-dependent manner tactile allodynia in rats. Maximal antiallodynic effects (∼100%) were reached with 30 mg/kg of pregabalin, 300 mg/kg of gabapentin or 0.5 ng of naltrexone. Co-administration of pregabalin or gabapentin and naltrexone in a fixed-dose ratio (1:1) remarkably reduced spinal nerve ligation-induced tactile allodynia showing a synergistic interaction. The data indicate that combinations of pregabalin or gabapentin and ultra-low doses of naltrexone are able to reduce tactile allodynia in neuropathic rats with lower doses that those used when drugs are given individually and with an improved side effects profile. Drug Dev Res 78 : 371-380, 2017. © 2017 Wiley Periodicals, Inc. SN - 1098-2299 UR - https://www.unboundmedicine.com/medline/citation/28868795/Ultra_Low_Doses_of_Naltrexone_Enhance_the_Antiallodynic_Effect_of_Pregabalin_or_Gabapentin_in_Neuropathic_Rats_ L2 - https://doi.org/10.1002/ddr.21409 DB - PRIME DP - Unbound Medicine ER -