Antinociceptive interaction of gabapentin with minocycline in murine diabetic neuropathy.
OBJECTIVE
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).


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Faculty of Medicine, School of Pharmacy, Andres Bello University, República 590, Santiago, Chile. hmiranda@med.uchile.cl.|Pharmacology Program, ICBM, Faculty of Medicine, University of Chile, Independencia 1027, Santiago, Chile. hmiranda@med.uchile.cl.
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Miranda
Pharmacology Program, ICBM, Faculty of Medicine, University of Chile, Independencia 1027, Santiago, Chile.|Faculty of Odontology, Finis Terrae University, Pedro de Valdivia 1509, Providencia, Chile.
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Sierralta
Faculty of Medicine, School of Pharmacy, Andres Bello University, República 590, Santiago, Chile.
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Jorquera
Faculty of Medicine, School of Pharmacy, Andres Bello University, República 590, Santiago, Chile.
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Poblete
Faculty of Medicine, School of Pharmacy, Andres Bello University, República 590, Santiago, Chile.|Cardiovascular Department, Clinic Hospital, University of Chile, Santos Dumont 999, Santiago, Chile.
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Prieto
Faculty of Medicine, School of Pharmacy, Andres Bello University, República 590, Santiago, Chile.|Cardiovascular Department, Clinic Hospital, University of Chile, Santos Dumont 999, Santiago, Chile.
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Noriega
D000588:Amines / Q000008:administration & dosage* / Q000378:metabolism; D000700:Analgesics / Q000008:administration & dosage* / Q000378:metabolism; D000818:Animals; D003509:Cyclohexanecarboxylic Acids / Q000008:administration & dosage* / Q000378:metabolism; D003929:Diabetic Neuropathies / Q000188:drug therapy* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions / Q000502:physiology; D004359:Drug Therapy, Combination; D000077206:Gabapentin; D008297:Male; D051379:Mice; D008911:Minocycline / Q000008:administration & dosage* / Q000378:metabolism; D010147:Pain Measurement / Q000187:drug effects* / Q000379:methods; D005680:gamma-Aminobutyric Acid / Q000008:administration & dosage* / Q000378:metabolism
D000588:Amines; D000700:Analgesics; D003509:Cyclohexanecarboxylic Acids; D005680:gamma-Aminobutyric Acid; D000077206:Gabapentin; D008911:Minocycline
Diabetes; Gabapentin; Minocycline; Neuropathy; Streptozocin; Synergism