Skip to main content
SpringerLink
Log in

The leguminous lectin of Lonchocarpus araripensis promotes antinociception via mechanisms that include neuronal inhibition of Na+ currents

  • Original Research Paper
  • Published:
Inflammation Research Aims and scope Submit manuscript

Abstract

Objective and design

Sodium channels are highly expressed in nociceptive sensory neurons during hypernociceptive conditions. Based on the presence of a glycosidic portion in the sodium channel β subunit associated to the antinociceptive effect of leguminous lectins via lectin domain, this study investigated the antinociceptive activity of the lectin isolated from Lonchocarpus araripensis seeds (LAL) in mice behavioral models and in NaV current in the nociceptor of rat dorsal root ganglion (DRG).

Material/methods

LAL antinociceptive activity and the participation of opioid system, lectin domain and sodium channels were evaluated in Swiss mice models of nociception (formalin, capsaicin, hot plate, tail flick, von Frey) and in primary cultures of Wistar rats neurons of DRG (patch clamp).

Results

LAL presented inhibitory effects in the nociception induced by chemical and mechanical, but not by thermal stimuli and reduced total Na+ current. LAL activity was inhibited by the lectin association with its binding sugar N-acethyl-glucosamine.

Conclusion

LAL inhibits peripheral hypernociception by mechanisms that involve the lectin domain, inflammatory mediators and Na+ channels. The innovative inhibitory action of leguminous lectins on NaV current brings new insights for the investigation of sodium channels role in nociception.

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

  1. Millan MJ. The induction of pain: an integrative review. Prog Neurobiol. 1999;57:1–164.

    Article  CAS  PubMed  Google Scholar 

  2. Aley KO, Messing RO, Mochly-Rosen D, Levine JD. Chronic hypersensitivity for inflammatory nociceptor sensitization mediated by the epsilon isozyme of protein kinase C. J Neurosci. 2000;15:4080–5.

    Google Scholar 

  3. Souza AL, Moreira FA, Almeida KR, Bertollo CM, Costa KA, Coelho MM. In vivo evidence for a role of protein kinase C in peripheral nociceptive processing. Br J Pharmacol. 2002;135:239–47.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. England JD, Gamboni F, Ferguson MA, Levinson SR. Sodium channels accumulate at the tips of injured axons. Muscle Nerv. 1994;17:593–8.

    Article  CAS  Google Scholar 

  5. Matzner O, Devor M. Hyperexcitability at sites of nerve injury depends on voltage-sensitive Na+ channels. J Neurophysiol. 1994;72:349–59.

    CAS  PubMed  Google Scholar 

  6. Patton DE, Isom LL, Catterall WA, Goldin AL. The adult rat brain beta 1 subunit modifies activation and inactivation gating of multiple sodium channel alpha subunits. J Biol Chem. 1994;269:17649–55.

    CAS  PubMed  Google Scholar 

  7. Isom LL. Beta subunits: players in neuronal hyperexcitability? Novartis Found Symp. 2002;241:124–38.

    Article  CAS  PubMed  Google Scholar 

  8. Sharon N, Lis H. Lectins–proteins with a sweet tooth: functions in cell recognition. Essays Biochem. 1995;30:59–75.

    CAS  PubMed  Google Scholar 

  9. Holanda FR, Coelho-de-Souza AN, Assreuy AM, Leal-Cardoso JH, Pires AF, Nascimento KS, Cavada BS, Santos CF. Antinociceptive activity of lectins from Diocleinae seeds on acetic acid-induced writhing test in mice. Protein Pept Lett. 2009;16:1088–92.

    Article  CAS  PubMed  Google Scholar 

  10. Pinto NV, Santos CF, Cavada BS, do Nascimento KS, Pereira Junior FN, Pires AF, Assreuy AM. Homologous Canavalia lectins elicit different patterns of antinociceptive responses. Nat Prod Commun. 2013;8:1621–4.

    CAS  PubMed  Google Scholar 

  11. de Freitas Pires A, Assreuy AM, Lopes EA, Celedônio NR, Soares CE, Rodrigues NV, Sousa PL, Benevides RG, Nagano CS, Cavada BS, Leal-Cardoso JH, Coelho-De-Souza AN, Santos CF. Opioid-like antinociceptive effects of oral administration of a lectin purified from the seeds of Canavalia brasiliensis. Fund Clin Pharmacol. 2013;27:201–9.

    Article  Google Scholar 

  12. Napimoga MH, Cavada BS, Alencar NM, Mota ML, Bittencourt FS, Alves-Filho JC, Grespan R, Gonçalves RB, Clemente Napimoga JT, Parada CA, Ferreira SH, Cunha FQ. Lonchocarpus sericeus lectin decreases leukocyte migration and mechanical hypernociception by inhibiting cytokine and chemokines production. Int Immunopharmacol. 2007;7:824–35.

    Article  CAS  PubMed  Google Scholar 

  13. Pires AF, Rodrigues NV, Soares PM, Ribeiro RA, Aragao KS, Marinho MM, Silva MT, Cavada BS, Assreuy AM. A novel N-acetyl-glucosamine lectin of Lonchocarpus araripensis attenuates acute cellular inflammation in mice. Inflamm Res. 2016;65:43–52.

    Article  CAS  PubMed  Google Scholar 

  14. Sakurada T, Katsumata K, Tan-No K, Sakurada S, Kisara K. The capsaicin test in mice for evaluating tachykinin antagonists in the spinal cord. Neuropharmacology. 1992;31:1279–85.

    Article  CAS  PubMed  Google Scholar 

  15. Hunskaar S, Role K. The formalin test in mice: dissociation between inflammatory and non-inflammatory pain. Pain. 1987;30:103–14.

    Article  CAS  PubMed  Google Scholar 

  16. Vaz ZR, Cechinel Filho V, Yunes RA, Calixto JB. Antinociceptive action of 2-(4-bromobenzoyl)-3-methyl-4,6-dimethoxy benzofuran, a novel xanthoxyline derivative on chemical and thermal models of nociception in mice. J Pharmacol Exp Ther. 1996;278:304–12.

    CAS  PubMed  Google Scholar 

  17. Eddy NB, Leimbach D. Synthetic analgesics. II. dithienylbutenyl and dithienylbutylamines. J Pharmacol Exper Ther. 1953;107:385–93.

    CAS  Google Scholar 

  18. D’amour FE, Smith DL. A method for determining loss of pain sensation. J Pharmacol Exp Ther. 1941;72:74–9.

    Google Scholar 

  19. Cunha TM, Verri WA Jr, Vivancos GG, Moreira IF, Reis S, Parada CA, Cunha FQ, Ferreira SH. An electronic pressure-meter nociception paw test for mice. Braz J Med Biol Res. 2004;37:401–7.

    Article  CAS  PubMed  Google Scholar 

  20. Dunham NW, Miya TS. A note on a simple apparatus for detecting neurological deficits in rats and mice. J Am Pharm Assoc Am Pharm Assoc. 1957;19(46):208–9.

    Article  Google Scholar 

  21. Capaz FR, Vasconcellos LE, De Moraes S, Neto JP. The open field: a simple method to show ethanol withdrawal symptoms. Arch Int Pharmacodyn Ther. 1981;251:228–36.

    CAS  PubMed  Google Scholar 

  22. Joca HC, Cruz-Mendes Y, Oliveira-Abreu K, Maia-Joca RP, Barbosa R, Lemos TL, Lacerda Beirão PS, Leal-Cardoso JH. Carvacrol decreases neuronal excitability by inhibition of voltage-gated sodium channels. J Nat Prod. 2012;75:1511–7.

    Article  CAS  PubMed  Google Scholar 

  23. Leal-Cardoso JH, da Silva-Alves KS, Ferreira-da-Silva FW, dos Santos-Nascimento T, Joca HC, de Macedo FH, de Albuquerque-Neto PM, Magalhães PJ, Lahlou S, Cruz JS, Barbosa R. Linalool blocks excitability in peripheral nerves and voltage-dependent Na+ current in dissociated dorsal root ganglia neurons. Eur J Pharmacol. 2010;645:86–93.

    Article  CAS  PubMed  Google Scholar 

  24. Elliott AA, Elliott JR. Characterization of TTX-sensitive and TTX-resistant sodium currents in small cells from adult rat dorsal root ganglia. J Physiol. 1993;463:39–56.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Figueiredo JG, da Silveira Bitencourt F, Beserra IG, Teixeira CS, Luz PB, Bezerra EH, Mota MR, Assreuy AM, De Queiroz Cunha F, Cavada BS, De Alencar NM. Antinociceptive activity and toxicology of the lectin from Canavalia boliviana seeds in mice. N-S Arch Pharmacol. 2009;380:407–14.

    Article  CAS  Google Scholar 

  26. Delatorre P, Rocha BA, Simões RC, Pereira-Júnior FN, Silva HC, Bezerra EH, Bezerra MJ, Marinho ES, Gadelha CA, Santi-Gadelha T, Farias DL, Assreuy AM, Marques-Domingos GF, Nagano CS, Cavada BS. Mass spectrometry and X-ray diffraction analysis of two crystal types of Dioclea virgata lectin: an antinociceptive protein candidate to structure/function analysis. Appl Biochem Biotech. 2011;164:741–54.

    Article  CAS  Google Scholar 

  27. Cunha TM, Verri WA Jr, Silva JS, Poole S, Cunha FQ, Ferreira SH. A cascade of cytokines mediates mechanical inflammatory hypernociception in mice. Proc Natl Acad Sci. 2005;102:1755–60.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Alencar NMN, Teixeira EH, Assreuy AMS, Cavada BS, Flores CA, Ribeiro RA. Leguminous lectins as tools for studying the role of sugar residues in leukocyte recruitment. Mediat Inflamm. 1999;8:107–13.

    Article  CAS  Google Scholar 

  29. Tj∅lsen A, Hole K. Animal models of analgesia. In: Besson MJ, Deckeson A, editors. The pharmacology of pain. Heidelberg: Springer; 1997. p. 21–41.

    Google Scholar 

  30. Rush AM, Cummins TR, Waxman SG. Multiple sodium channels and their roles in electrogenesis within dorsal root ganglion neurons. J Physiol. 2007;579:1–14.

    Article  CAS  PubMed  Google Scholar 

  31. Scroggs RS, Fox AP. Multiple Ca+2 currents elicited by action potential waveforms in acutely isolated adult rat dorsal root ganglion neurons. J Neurosci. 1992;12:1789–801.

    CAS  PubMed  Google Scholar 

  32. dos Santos-Nascimento T, Veras KM, Cruz JS, Leal-Cardoso JH. Inhibitory effect of Terpinen-4-ol on voltage-dependent potassium currents in rat small sensory neurons. J Nat Prod. 2015;78(2):173–80.

    Article  CAS  PubMed  Google Scholar 

  33. Ferreira-da-Silva FW, da Silva-Alves KS, Alves-Fernandes TA, Coelho-de-Souza AN, Leal-Cardoso JH. Effects of 1,8-cineole on Na(+) currents of dissociated superior cervical ganglia neurons. Neurosci Lett. 2015;595:45–9.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

The authors thank Conselho Nacional de Desenvolvimento Científico e Tecnológico-CNPq, Fundação Cearense de Amparo a Pesquisa-FUNCAP and Coordenação de Aperfeiçoamento de Pessoal de Nível Superior-CAPES. Leal-Cardoso JH, Cavada BS and Assreuy AM are senior investigators of CNPq.

Author information

Authors and Affiliations

  1. Instituto Superior de Ciências Biomédicas, Universidade Estadual do Ceará, Av. Dr. Silas Munguba 1700, CEP 60740-000, Fortaleza, CE, Brazil

    Renata Morais Ferreira Amorim, Alana Freitas Pires, Tiago dos Santos-Nascimento, José Henrique Leal-Cardoso, Mário Rogério Lima Mota & Ana Maria S. Assreuy

  2. Laboratório de Moléculas Biologicamente Ativas (BioMol-Lab), Departamento de Bioquímica e Biologia Molecular, Universidade Federal do Ceará, Campus do Pici, s/n; Bloco 907, CEP 60455-970, Fortaleza, CE, Brazil

    Benildo S. Cavada, Kyria Santiago do Nascimento & João Batista Cajazeiras

  3. Centro de Ciências da Saúde, Unidade Via Corpvs, Centro Universitário Estácio do Ceará, Rua Eliseu Uchoa Becco, 600, 60810-270, Fortaleza, CE, Brazil

    Alana Freitas Pires

  4. Departamento de Farmácia, Odontologia e Enfermagem, Universidade Federal do Ceará, Rua Alexandre Baraúna 949, CEP 60430-170, Fortaleza, CE, Brazil

    Mário Rogério Lima Mota

Authors
  1. Renata Morais Ferreira Amorim
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Alana Freitas Pires
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Tiago dos Santos-Nascimento
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Benildo S. Cavada
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Kyria Santiago do Nascimento
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. João Batista Cajazeiras
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. José Henrique Leal-Cardoso
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Mário Rogério Lima Mota
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Ana Maria S. Assreuy
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Ana Maria S. Assreuy.

Additional information

Responsible Editor: Ji Zhang.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Amorim, R.M.F., Pires, A.F., dos Santos-Nascimento, T. et al. The leguminous lectin of Lonchocarpus araripensis promotes antinociception via mechanisms that include neuronal inhibition of Na+ currents. Inflamm. Res. 65, 701–708 (2016). https://doi.org/10.1007/s00011-016-0951-0

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00011-016-0951-0

Keywords

Search

Navigation