Synergic Antinociceptive Interaction between Tramadol and Gabapentin after Local, Spinal and Systemic Administration

Vol. 74, No. 4, 2005

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Original Paper

Synergic Antinociceptive Interaction between Tramadol and Gabapentin after Local, Spinal and Systemic Administration
Vinicio Granados-Soto^a, Carlos F. Argüelles^b

^aDepartamento de Farmacobiología, Centro de Investigación y de Estudios Avanzados, Coapa, y
^bLaboratorio de Farmacología, Centro Nacional de Rehabilitación, Secretaría de Salud, México, D.F., México

Address of Corresponding Author

Pharmacology 2005;74:200-208 (DOI: 10.1159/000085700)

Key Words

Gabapentin
Tramadol
Synergism
Pain

Abstract

The possible interaction between tramadol and gabapentin on formalin-induced nociception in the rat was assessed. Tramadol, gabapentin or a fixed-dose ratio combination of gabapentin and tramadol were administered peripherally, spinally and orally to rats, and the antinociceptive effect was determined in the 1% formalin test. Isobolographic analyses were used to define the nature of the interactions between drugs. Tramadol, gabapentin and tramadol-gabapentin combinations produced a dose-dependent antinociceptive effect when administered locally, spinally or orally. ED₃₀ values were estimated for the individual drugs and isobolograms were constructed. Theoretical ED₃₀ values for the combination estimated from the isobolograms were 126.8 ± 11.1 µg/paw, 23.1 ± 2.6 µg/rat, and 2.23 ± 0.32 mg/kg for the local, intrathecal and oral routes, respectively. These values were significantly higher than the actually observed ED₃₀ values which were 13.3 ± 2.1 µg/paw, 8.1 ± 0.6 µg/rat and 0.71 ± 0.10 mg/kg, indicating a synergistic interaction. Although efficacy was not improved, local peripheral administration resulted in the highest increase in potency, being about tenfold. Spinal and systemic administration increased potency threefold. Data indicate that low doses of the tramadol-gabapentin combination can interact synergistically to reverse formalin-induced nociception and may represent a therapeutic advantage for clinical treatment of inflammatory pain.

Author Contacts

Vinicio Granados-Soto, PhD
Departamento de Farmacobiología, Centro de Investigación y de
Estudios Avanzados del Instituto Politécnico Nacional, Calzada Tenorios 235
Col. Granjas Coapa, 14330 México, D.F. (Mexico)
Tel. +52 55 5061 2868, Fax +52 55 5061 2863, E-Mail vgranados@prodigy.net.mx

Article Information

Received: December 14, 2004
Accepted after revision: March 10, 2005
Published online: May 10, 2005
Number of Print Pages : 9
Number of Figures : 5, Number of Tables : 2, Number of References : 55

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