Skip to main content
Log in

Central and peripheral anti-inflammatory effects of maprotiline on carrageenan-induced paw edema in rats

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

Abstract

Objective

To explore the site of action of maprotiline, as an atypical antidepressant, on carrageenan-induced paw edema.

Subjects

Male Wistar rats were used.

Methods

Firstly, the anti-inflammatory effect of systemic maprotiline (12.5, 25 and 50 mg kg−1) was assessed using a paw edema model. Secondly, different doses of maprotiline were administrated intracerebroventricularly, intrathecally and locally before carrageenan challenge. Finally, we tried to reverse the anti-inflammatory effect of maprotiline by propranolol (10 mg kg−1), prazosin (4 mg kg−1), yohimbine (10 mg kg−1), naloxone (4 mg kg−1) and mifepristone (5 mg kg−1).

Results

Systemic, intracerebroventricular and subplantar application of maprotiline significantly inhibited peripheral edema, but intrathecal maprotiline did not alter the degree of paw swelling. The applied antagonists failed to change the anti-inflammatory activity of maprotiline.

Conclusion

These results demonstrate that maprotiline has a potent anti-inflammatory effect and this effect is linked to the peripheral and supraspinal actions of the drug.

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

Access this article

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

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7

Similar content being viewed by others

References

  1. Egbunike IG, Chaffee BJ. Antidepressants in the management of chronic pain syndromes. Pharmacotherapy. 1990;10:262–70.

    CAS  PubMed  Google Scholar 

  2. Hauser W, Bernardy K, Uceyler N, Sommer C. Treatment of fibromyalgia syndrome with antidepressants: a meta-analysis. JAMA. 2009;301:198–209.

    Article  PubMed  Google Scholar 

  3. Wong MC, Chung JW, Wong TK. Effects of treatments for symptoms of painful diabetic neuropathy: systematic review. BMJ. 2007;335:87.

    Article  CAS  PubMed  Google Scholar 

  4. Abdel-Salam OM, Baiuomy AR, Arbid MS. Studies on the anti-inflammatory effect of fluoxetine in the rat. Pharmacol Res. 2004;49:119–31.

    Article  CAS  PubMed  Google Scholar 

  5. Roumestan C, Michel A, Bichon F, Portet K, Detoc M, Henriquet C, et al. Anti-inflammatory properties of desipramine and fluoxetine. Respir Res. 2007;8:35.

    Article  PubMed  Google Scholar 

  6. Bianchi M, Sacerdote P, Panerai AE. Chlomipramine differently affects inflammatory edema and pain in the rat. Pharmacol Biochem Behav. 1994;48:1037–40.

    Article  CAS  PubMed  Google Scholar 

  7. Abdel-Salam OM, Nofal SM, El Shenawy SM. Evaluation of the anti-inflammatory and anti-nociceptive effects of different antidepressants in the rat. Pharmacol Res. 2003;48:157–65.

    Article  CAS  PubMed  Google Scholar 

  8. Siegert RJ, Abernethy DA. Depression in multiple sclerosis: a review. J Neurol Neurosurg Psychiatry. 2005;76:469–75.

    Article  CAS  PubMed  Google Scholar 

  9. Dickens C, McGowan L, Clark-Carter D, Creed F. Depression in rheumatoid arthritis: a systematic review of the literature with meta-analysis. Psychosom Med. 2002;64:52–60.

    PubMed  Google Scholar 

  10. Zautra AJ, Yocum DC, Villanueva I, Smith B, Davis MC, Attrep J, et al. Immune activation and depression in women with rheumatoid arthritis. J Rheumatol. 2004;31:457–63.

    CAS  PubMed  Google Scholar 

  11. Castanon N, Leonard BE, Neveu PJ, Yirmiya R. Effects of antidepressants on cytokine production and actions. Brain Behav Immun. 2002;16:569–74.

    Article  CAS  PubMed  Google Scholar 

  12. Raison CL, Capuron L, Miller AH. Cytokines sing the blues: inflammation and the pathogenesis of depression. Trends Immunol. 2006;27:24–31.

    Article  CAS  PubMed  Google Scholar 

  13. Schiepers OJ, Wichers MC, Maes M. Cytokines and major depression. Prog Neuropsychopharmacol Biol Psychiatry. 2005;29:201–17.

    Article  CAS  PubMed  Google Scholar 

  14. Ahles S, Gwirtsman H, Halaris A, Shah P, Schwarcz G, Hill MA. Comparative cardiac effects of maprotiline and doxepin in elderly depressed patients. J Clin Psychiatry. 1984;45:460–5.

    CAS  PubMed  Google Scholar 

  15. Gruter W, Poldinger W. Maprotiline. Mod Probl Pharmacopsychiatry. 1982;18:17–48.

    CAS  PubMed  Google Scholar 

  16. Fukunishi I, Kitaoka T, Shirai T, Watanabe S. Cardiac arrest caused by maprotiline in an elderly hemodialysis patient. Nephron. 1998;78:225.

    Article  CAS  PubMed  Google Scholar 

  17. Gareri P, Falconi U, De Fazio P, De Sarro G. Conventional and new antidepressant drugs in the elderly. Prog Neurobiol. 2000;61:353–96.

    Article  CAS  PubMed  Google Scholar 

  18. Humble M. Noradrenaline and serotonin reuptake inhibition as clinical principles: a review of antidepressant efficacy. Acta Psychiatr Scand. 2000;402:S28–36.

    Article  Google Scholar 

  19. Lucchelli A, Santagostino-Barbone MG, D’Agostino G, Masoero E, Tonini M. The interaction of antidepressant drugs with enteric 5-HT7 receptors. Naunyn Schmiedebergs Arch Pharmacol. 2000;362:284–9.

    Article  CAS  PubMed  Google Scholar 

  20. Korzeniewska-Rybicka I, Plaznik A. Supraspinally mediated analgesic effect of antidepressant drugs. Pol J Pharmacol. 2000;52:93–9.

    CAS  PubMed  Google Scholar 

  21. Vrethem M, Boivie J, Arnqvist H, Holmgren H, Lindstrom T, Thorell LH. A comparison of amitriptyline and maprotiline in the treatment of painful polyneuropathy in diabetics and nondiabetics. Clin J Pain. 1997;13:313–23.

    Article  CAS  PubMed  Google Scholar 

  22. Hajhashemi V, Minaiyan M, Efthekhari M. Anti-Inflammatory activity of a selection of antidepressant drugs. Int J Plant Sci. 2008;4:225–30.

    Google Scholar 

  23. Budantsev AI, Kisliuk OS, Shul’govskii VV, Rykunov DS, Iarkov AV. The brain in stereotaxic coordinates (a textbook for colleges). Zh Vyssh Nerv Deiat Im I P Pavlova. 1993;43:1045–51.

    PubMed  Google Scholar 

  24. Mestre C, Pelissier T, Fialip J, Wilcox G, Eschalier A. A method to perform direct transcutaneous intrathecal injection in rats. J Pharmacol Toxicol Methods. 1994;32:197–200.

    Article  CAS  PubMed  Google Scholar 

  25. Winter CA, Risley EA, Nuss GW. Carrageenan-induced edema in hind paw of the rat as an assay for anti-inflammatory drugs. Proc Soc Exp Biol Med. 1962;111:544–7.

    CAS  PubMed  Google Scholar 

  26. Suleyman H, Halici Z, Cadirci E, Hacimuftuoglu A, Bilen H. Indirect role of beta2-adrenergic receptors in the mechanism of anti-inflammatory action of NSAIDS. J Physiol Pharmacol. 2008;59:661–72.

    CAS  PubMed  Google Scholar 

  27. Watanabe S, Yamakami J, Tsuchiya M, Terajima T, Kizu J, Hori S. Anti-inflammatory effect of theophylline in rats and its involvement of the glucocorticoid receptor system. J Pharmacol Sci. 2008;106:566–70.

    Article  CAS  PubMed  Google Scholar 

  28. Kovaru H, Pav M, Kovaru F, Raboch J, Fiserova A. Cell signaling in CNS and immune system in depression and during antidepressant treatment: focus on glial and natural killer cells. Neuro Endocrinol Lett. 2009;30:421–8.

    CAS  PubMed  Google Scholar 

  29. Tian L, Rauvala H, Gahmberg CG. Neuronal regulation of immune responses in the central nervous system. Trends Immunol. 2009;30:91–9.

    Article  CAS  PubMed  Google Scholar 

  30. Eskandari F, Webster JI, Sternberg EM. Neural immune pathways and their connection to inflammatory diseases. Arthritis Res Ther. 2003;5:251–65.

    Article  CAS  PubMed  Google Scholar 

  31. Frazer A. Pharmacology of antidepressants. J Clin Psychopharmacol. 1997;17:S2–18.

    Article  Google Scholar 

  32. Fuller RW. Uptake inhibitors increase extracellular serotonin concentration measured by brain microdialysis. Life Sci. 1994;55:163–7.

    Article  CAS  PubMed  Google Scholar 

  33. Feighner JP. Mechanism of action of antidepressant medications. J Clin Psychiatry. 1999;60:S4–11.

    Article  Google Scholar 

  34. Elenkov IJ, Wilder RL, Chrousos GP, Vizi ES. The sympathetic nerve–an integrative interface between two supersystems: the brain and the immune system. Pharmacol Rev. 2000;52:595–638.

    CAS  PubMed  Google Scholar 

  35. Brain SD, Cambridge H. Calcitonin gene-related peptide: vasoactive effects and potential therapeutic role. Gen Pharmacol. 1996;27:607–11.

    CAS  PubMed  Google Scholar 

  36. Lembeck F, Holzer P. Substance P as neurogenic mediator of antidromic vasodilation and neurogenic plasma extravasation. Naunyn Schmiedebergs Arch Pharmacol. 1979;310:175–83.

    Article  CAS  PubMed  Google Scholar 

  37. Brock SC, Tonussi CR. Intrathecally injected morphine inhibits inflammatory paw edema: the involvement of nitric oxide and cyclic-guanosine monophosphate. Anesth Analg. 2008;106:965–71.

    Article  CAS  PubMed  Google Scholar 

  38. Daher JB, Tonussi CR. A spinal mechanism for the peripheral anti-inflammatory action of indomethacin. Brain Res. 2003;962:207–12.

    Article  CAS  PubMed  Google Scholar 

  39. Daher JB, de Melo MD, Tonussi CR. Evidence for a spinal serotonergic control of the peripheral inflammation in the rat. Life Sci. 2005;76:2349–59.

    Article  CAS  PubMed  Google Scholar 

  40. Bianchi M, Rossoni G, Sacerdote P, Panerai AE, Berti F. Effects of clomipramine and fluoxetine on subcutaneous carrageenan-induced inflammation in the rat. Inflamm Res. 1995;44:466–9.

    Article  CAS  PubMed  Google Scholar 

  41. Biegon A, Samuel D. Interaction of tricyclic antidepressants with opiate receptors. Biochem Pharmacol. 1980;29:460–2.

    Article  CAS  PubMed  Google Scholar 

  42. Wahlstrom A, Lenhammar L, Ask B, Rane A. Tricyclic antidepressants inhibit opioid receptor binding in human brain and hepatic morphine glucuronidation. Pharmacol Toxicol. 1994;75:23–7.

    Article  CAS  PubMed  Google Scholar 

  43. Di Rosa M, Giroud JP, Willoughby DA. Studies on the mediators of the acute inflammatory response induced in rats in different sites by carrageenan and turpentine. J Pathol. 1971;104:15–29.

    Article  CAS  PubMed  Google Scholar 

  44. Gilligan JP, Lovato SJ, Erion MD, Jeng AY. Modulation of carrageenan-induced hind paw edema by substance P. Inflammation. 1994;18:285–92.

    Article  CAS  PubMed  Google Scholar 

  45. Halici Z, Dengiz GO, Odabasoglu F, Suleyman H, Cadirci E, Halici M. Amiodarone has anti-inflammatory and anti-oxidative properties: an experimental study in rats with carrageenan-induced paw edema. Eur J Pharmacol. 2007;566:215–21.

    Article  CAS  PubMed  Google Scholar 

  46. Redrobe JP, MacSweeney CP, Bourin M. The role of 5-HT1A and 5-HT1B receptors in antidepressant drug actions in the mouse forced swimming test. Eur J Pharmacol. 1996;318:213–20.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This research was supported by research council of the Isfahan University of Medical Sciences, Isfahan, Iran.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to H. Sadeghi.

Additional information

Responsible Editor: Gerd Geisslinger.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Hajhashemi, V., Sadeghi, H., Minaiyan, M. et al. Central and peripheral anti-inflammatory effects of maprotiline on carrageenan-induced paw edema in rats. Inflamm. Res. 59, 1053–1059 (2010). https://doi.org/10.1007/s00011-010-0225-1

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00011-010-0225-1

Keywords

Navigation