Skip to main content
SpringerLink
Log in

Antinociceptive interaction of gabapentin with minocycline in murine diabetic neuropathy

  • Original Article
  • Published:
Inflammopharmacology Aims and scope Submit manuscript

An Erratum to this article was published on 12 June 2017

Abstract

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.

Conclusion

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  • Bijnsdorp IV, Giovannetti E, Peters G (2011) Analysis of drug interactions. Methods Mol Biol 731:421–434

    Article  CAS  PubMed  Google Scholar 

  • Chaudhry ZZ, Morris DL, Moss DR, Sims EK, Chiong Y, Kono T, Evans-Molina C (2013) Streptozocin is equally diabetogenic whether administered to fed or fasted mice. Lab Anim 47:257–265

    Article  PubMed  PubMed Central  Google Scholar 

  • Cheng JK, Chiou LC (2006) Mechanisms of the antinoceptive action of gabapentin. J Pharmacol Sci 100:471–486

    Article  CAS  PubMed  Google Scholar 

  • 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 24:8–13

    Google Scholar 

  • Colleoni M, Sacerdote P (2010) Murine models of human neuropathic pain. Biochim Biophys Acta 1802:924–933

    Article  CAS  PubMed  Google Scholar 

  • Feng Y, Cui M, Willis WD (2003) Gabapentin markedly reduces acetic acid-induced visceral nociception. Anesthesiology 98:729–733

    Article  CAS  PubMed  Google Scholar 

  • Gao F, Zheng ZM (2014) Animal models of diabetic. Exp Clin Endocrinol Diabetes 122:100–106

    Article  CAS  PubMed  Google Scholar 

  • Goldstein A, Aronov L, Kalman SM (1974) Principles of drug action, 2nd edn. Wiley, New York, pp 89–96

    Google Scholar 

  • IASP (2015) Pain clinical update. Halting the march of painful diabetic neuropathy. Pain 4:1–8

    Google Scholar 

  • Ik-Hyun C, Lee CNM, Gwak G, Lee Y (2012) Minocycline markedly reduces acute visceral nociception via inhibiting neuronal ERK phosphorylation. Mol Pain 8:13–26

    Google Scholar 

  • Jensen TS, Baron R, Haanpää M, Kalso E, Loeser JD, Rice ASC, Treede RD (2011) A new definition of neuropathic pain. Pain 152:2204–2205

    Article  PubMed  Google Scholar 

  • Kilic FS, Sirmagul B, Yildirim E, Oner S, Erol K (2012) Antinociceptive effects of gabapentin & its mechanism of action in experimental animal studies. Indian J Med Res 135:630–635

    CAS  PubMed  PubMed Central  Google Scholar 

  • Kim TH, Kim HI, Kim J, Park M, Song JH (2011) Effects of minocycline on Na+ currents in rat dorsal root ganglion neurons. Brain Res 1370:34–42

    Article  CAS  PubMed  Google Scholar 

  • King J (2012) The use of animal models in diabetes research. J Pharmacol 166:877–894

    CAS  Google 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 11:74–81

    Google Scholar 

  • Miranda HF, Noriega V, Olavarría L, Zepeda RJ, Sierralta F, Prieto JC (2001) Antinocicepcion and anti-inflammation induced by simvastatin in algesiometric assay in mice. Basic Clin Pharmacol Toxicol 109:438–442

    Article  Google Scholar 

  • Miranda HF, Sierralta F, Pinardi G (2002) Neostigmine interactions with non steroidal anti-inflammatory drugs. Br J Pharmacol 135:1591–1597

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Miranda HF, Puig MM, Prieto JC, Pinardi G (2006) Synergism between paracetamol and nonsteroidal anti-inflammatory drugs in experimental acute pain. Pain 121:22–28

    Article  CAS  PubMed  Google Scholar 

  • Obrosova IG (2009) Diabetic painful and insensate neuropathy: pathogenesis and potential treatments. Neurotherapeutics 6:638–647

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Pabreja K, Dua K, Sharma S, Padi SS, Kulkarni SK (2011) Minocycline attenuates the development of diabetic neuropathic pain: possible anti-inflammatory and anti-oxidant mechanisms. Eur J Pharmacol 661:15–21

    Article  CAS  PubMed  Google Scholar 

  • Padi SS, Kulkarni SK (2008) Minocycline prevents the development of neuropathic pain, but not acute pain: possible anti-inflammatory and antioxidant mechanisms. Eur J Pharmacol 601:79–87

    Article  CAS  PubMed  Google Scholar 

  • Schreiber AK, Nones CFM, Reis RC, Chichorro JG, Cunha JM (2015) Diabetic neuropathic pain: physiopathology and treatment. World J Diabetes 6:432–444

    Article  PubMed  PubMed Central  Google Scholar 

  • Stepanovic-Petrovic RM, Tomic MA, Vuckovic SM, Paranos S, Ugresic ND, Prostran MS, Milovanovic S, Boskovic B (2008) The antinociceptive effects of anticonvulsants in a mouse visceral pain model. Anesth Analg 106:1897–1903

    Article  CAS  PubMed  Google Scholar 

  • Syngle A, Verma I, Krishan P, Garg N, Syngle V (2014) Minocycline improves peripheral and autonomic neuropathy in type 2 diabetes: MIND study. Neurol Sci 35:1067–1073

    Article  PubMed  Google Scholar 

  • Tallarida RJ (2000) Drug synergism and dose-effect data analysis. Chapman and Hall/CRC, Boca Raton, pp 26–131

    Book  Google Scholar 

  • Tallarida RJ (2001) Drug synergism: its detection and applications. Pharmacol Exp Ther 298:865–872

    CAS  Google 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 38:124–130

    Article  CAS  PubMed  Google Scholar 

  • Veves A, Backonja M, Malik RA (2008) Painful diabetic neuropathy: epidemiology, natural history, early diagnosis, and treatment options. Pain Med 9:660–674

    Article  PubMed  Google Scholar 

  • Wodarski R, Clark AK, Grist J, Marchand F, Malcangio M (2009) Gabapentin reverses microglial activation in the spinal cord of streptozotocin-induced diabetic rats. Eur J Pain 13:807–811

    Article  CAS  PubMed  Google 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 8:181–188

    CAS  Google Scholar 

Download references

Acknowledgements

This work was partially supported by project from Andres Bello University.

Author information

Authors and Affiliations

  1. Faculty of Medicine, School of Pharmacy, Andres Bello University, República 590, Santiago, Chile

    H. F. Miranda, V. Jorquera, P. Poblete, J. C. Prieto & V. Noriega

  2. Pharmacology Program, ICBM, Faculty of Medicine, University of Chile, Independencia 1027, Santiago, Chile

    H. F. Miranda & F. Sierralta

  3. Faculty of Odontology, Finis Terrae University, Pedro de Valdivia 1509, Providencia, Chile

    F. Sierralta

  4. Cardiovascular Department, Clinic Hospital, University of Chile, Santos Dumont 999, Santiago, Chile

    J. C. Prieto & V. Noriega

Authors
  1. H. F. Miranda
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. F. Sierralta
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. V. Jorquera
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. P. Poblete
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. J. C. Prieto
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. V. Noriega
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to H. F. Miranda.

Ethics declarations

Conflict of interest

The authors declare no conflicts of interest in this manuscript.

Additional information

An erratum to this article is available at http://dx.doi.org/10.1007/s10787-017-0368-6.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Miranda, H.F., Sierralta, F., Jorquera, V. et al. Antinociceptive interaction of gabapentin with minocycline in murine diabetic neuropathy. Inflammopharmacol 25, 91–97 (2017). https://doi.org/10.1007/s10787-017-0308-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10787-017-0308-5

Keywords

Search

Navigation