Antinociceptive interaction of gabapentin with minocycline in murine diabetic neuropathy
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Diabetic neuropathy (DN) is the most common complication of diabetes and pain is one of the main symptoms of diabetic neuropathy, however, currently available drugs are often ineffective and complicated by adverse events. The purpose of this research was to evaluate the antinociceptive interaction between gabapentin and minocycline in a mice experimental model of DN by streptozocin (STZ).
The interaction of gabapentin with minocycline was evaluated by the writhing and hot plate tests at 3 and 7 days after STZ injection or vehicle in male CF1 mice.
STZ (150 mg/kg, i.p.) produced a marked increase in plasma glucose levels on day 7 (397.46 ± 29.65 mg/dL) than on day 3 (341.12 ± 35.50 mg/dL) and also developed neuropathic pain measured by algesiometric assays. Gabapentin produced similar antinociceptive activity in both writhing and hot plate tests in mice pretreated with STZ. However, minocycline was more potent in the writhing than in the hot plate test in the same type of mice. The combination of gabapentin with minocycline produced synergistic interaction in both test.
The combination of gabapentin with minocycline in a 1:1 proportion fulfills all the criteria of multimodal analgesia and this finding suggests that the combination provide a therapeutic alternative that could be used for human neuropathic pain management.
KeywordsNeuropathy Diabetes Streptozocin Minocycline Gabapentin Synergism
This work was partially supported by project from Andres Bello University.
Compliance with ethical standards
Conflict of interest
The authors declare no conflicts of interest in this manuscript.
- Cho IH, Lee MJ, Jang M, Gwak NG, Lee KY, Jung HS (2012) Minocycline markedly reduces acute visceral nociception via inhibiting neuronal ERK phosphorylation. Mol Pain 24:8–13Google Scholar
- Goldstein A, Aronov L, Kalman SM (1974) Principles of drug action, 2nd edn. Wiley, New York, pp 89–96Google Scholar
- IASP (2015) Pain clinical update. Halting the march of painful diabetic neuropathy. Pain 4:1–8Google Scholar
- Ik-Hyun C, Lee CNM, Gwak G, Lee Y (2012) Minocycline markedly reduces acute visceral nociception via inhibiting neuronal ERK phosphorylation. Mol Pain 8:13–26Google Scholar
- King J (2012) The use of animal models in diabetes research. J Pharmacol 166:877–894Google Scholar
- Li D, Liang X, Sun B, Ding X, Han H, Rong W, Zhang G (2015) Impairments of the primary afferent nerves in a rat model of diabetic visceral hyposensitivity. Mol Pain 11:74–81Google Scholar
- Tallarida RJ (2001) Drug synergism: its detection and applications. Pharmacol Exp Ther 298:865–872Google Scholar
- Vanelderen P, Rouwette T, Kozicz T, Heylen R, Van Zundert J, Roubos EW, Vissers K (2013) Effects of chronic administration of amitriptyline, gabapentin and minocycline on spinal brain-derived neurotrophic factor expression and neuropathic pain behavior in a rat chronic constriction injury model. Reg Anesth Pain Med 38:124–130CrossRefPubMedGoogle Scholar
- Wu J, Yang LJ (2015) Streptozocin-induced type 1 diabetes in rodents as a model for studying mitochondrial mechanisms of diabetic β cell glucotoxicity. Diabetes Metab Syndr Obes Targets Ther 8:181–188Google Scholar