The anti-inflammatory effects of venlafaxine in the rat model of carrageenan-induced paw edema

Document Type : Original Article

Authors

1 Department of Pharmacology and Toxicology and Isfahan Pharmaceutical Research Center, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, Iran

2 Department of Pharmacology and Toxicology and Isfahan

3 Pharmaceutical Research Center, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, Iran

4 Physiology Research Center, Kashan University of Medical Sciences, Kashan, Iran

5 Department of Pharmacology, School of Medicine, Kashan University of Medical Sciences, Kashan, Iran

Abstract

Objective(s):Recently anti-inflammatory effects of antidepressants have been demonstrated. Venlafaxine belongs to newer antidepressants with serotonin norepinephrine reuptake inhibition property. The pain alleviating properties of venlafaxine in different pain models such as neurogenic pain, diabetic neuropathy, and fibromyalgia have been demonstrated. Anti-inflammatory effects of venlafaxine and also its underlying mechanisms remain unclear. The present study was designed to evaluate the anti-inflammatory effects of venlafaxine and determine possible underlying mechanisms.
Materials and Methods: We examined the anti-inflammatory effects of intraperitoneal (IP) and intracerebroventricular (ICV) administration of venlafaxine in the rat model of carrageenan-induced paw edema.
Results: Our results showed that both IP (50 and 100 mg/kg) and ICV (50 and 100 μg/rat) injection of venlafaxine inhibited carrageenan-induced paw edema. Also IP and ICV administration of venlafaxine significantly decreased myeloperoxidase (MPO) activity and interleukin (IL)-1β and tumor necrosis factor (TNF)-α production. Finally, we tried to reverse the anti-inflammatory effect of venlafaxine by yohimbine (5 mg/kg, IP), an alpha2-adrenergic antagonist. Our results showed that applied antagonist failed to change the anti-inflammatory effect of venlafaxine.
Conclusion: These results demonstrated that venlafaxine has potent anti-inflammatory effect which is related to the peripheral and central effects of this drug. Also we have shown that anti-inflammatory effect of venlafaxine is mediated mostly through the inhibition of IL-1β and TNF-α production and decreases MPO activity in the site of inflammation.

Keywords

References

1. Gurgel JA, Lima-Júnior RC, Rabelo CO, Pessoa BB, Brito GA, Ribeiro RA. Amitriptyline, clomipramine, and maprotiline attenuate the inflammatory response by inhibiting neutrophil migration and mast cell degranulation. Rev Bras Psiquiatr 2013; 35:387-392.
2. Bohren Y, Tessier LH, Megat S, Petitjean H, Hugel S, Daniel D, et al. Antidepressants suppress neuropathic pain by a peripheral β2-adrenoceptor mediated anti-TNFα mechanism. Neurobiol Dis 2013; 60:39-50
3. Panahi Y, Davoudi SM, Beiraghdar F, Amiri M. Doxepin cream vs betamethasone cream for treatment of chronic skin lesions due to sulfur mustard. Skin Med 2011; 9:152-158.
4. Kostadinov ID, Delev DP, Murdjeva MA, Kostadinova II. Experimental study on the role of 5-HT2 serotonin receptors in the mechanism of anti-inflammatory and antihyperalgesic action of antidepressant fluoxetine. Folia Med (Plovdiv) 2014; 56:43-49.
5. Saito H, Wakai J, Sekiguchi M, Kikuchi S, Konno S. The effect of selective serotonin reuptake inhibitor (SSRI) on pain-related behavior in a rat model of neuropathic pain. Eur Spine J 2014; 23:2401-249.
6. Hochstrasser T, Ehrlich D, Sperner-Unterweger B, Humpel C. Antidepressants and anti-inflammatory drugs differentially reduce the release of NGF and BDNF from rat platelets. Pharmacopsychiatry 2013; 6:29-34.
7. Baldessarini R J. Drugs for the treatment of psychiatric disorders. In: Hardman JG, LE. Limbird LE.  Goodman & Gilman’s The Pharmacological Basis of Therapeutics, 10th eds. McGraw Hill, New York: USA: 2001.p.447–483.
8. Sumpton JE, Moulin DE. Treatment of neuropathic pain with venlafaxine. Ann Pharmacother 2001; 35:557–559.
9. Cegielska-Perun K, Bujalska-Zadrożny M, Tatarkiewicz J, Gąsińska E, Elżbieta H, Nowak M. Venlafaxine and neuropathic pain. Pharmacology 2013; 91:69–76.
10. Dwight MM, Arnold LM, O’Brien H, Metzger R, Morris-Park E, Keck PE. An open clinical trial of venlafaxine treatment of fibromyalgia. Psychosomatics 1998; 39:14–17.
11. Ellingrod VL, Perry PJ.Venlafaxine: a heterocyclic antidepressant. Am J Hosp Pharm 1994; 51:3000-3046.
12. 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 1993; 43:1045–1051.
13. Winter CA, Risely EA, Nuss GW. Carrageenin-induced edema in hind paw of the rat as an assay for anti-inflammatory drugs. Proc Soc Exp Biol Med 1962; 111:544–547.
14. Aricioğlu F, Buldanlioğlu U, Salanturoğlu G, Ozyalçin NS. Evaluation of antinociceptive and anti-inflammatoryeffects of venlafaxine in the rat. Agri 2005; 17:41-46.
15. Hajhashemi V, Banafshe HR, Minaiyan M, Mesdaghinia A, Abed A. Antinociceptive effects of venlafaxine in a rat model of peripheral neuropathy: role of alpha2-adrenergic receptors. Eur J Pharmacol 2014 5; 738:230-236
16. Bradley PP, Priebat DA, Christensen RD, Rothstein G. Measurement ofcutaneous inflammation: estimation of neutrophil content with an enzyme marker. J Invest Dermatol 1982; 78:206–209.
17. Sadeghi H, Hajhashemi V, Minaiyan M, Movahedian A, Talebi A. A study on the mechanismsinvolving the anti-inflammatoryeffect of amitriptyline in carrageenan-inducedpawedema in rats. Eur J Pharmacol 2011; 667:396-401.
18. Gilligan JP, Lovato SJ, Erion MD, Jeng AY. Modulation of carrageenan induced hind paw edema by substance P. Inflammation 1994; 18:285–292.
19. 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; 566:215–221.
20. Nacife VP, Soeiro MN, Gomes RN, D'Avila H, Castro-FariaNeto HC, Meirelles MN. Morphological and biochemical characterization of macrophages activated by carrageenan and lipopolysaccharide in vivo. Cell Struct Funct 2004; 29:27–34.
21. Codarri L, Fontana A, Becher B. Cytokine networks in multiple sclerosis: lost in translation. Curr Opin Neurol 2010; 23:205–211.
22. Feldmann M, Maini SR. Role of cytokines in rheumatoid arthritis: an education in pathophysiology and therapeutics. Immunol Rev 2008; 223:7–19.
23. Ichinose M, Barnes PJ. Cytokine-directed therapy in asthma. Curr Drug Targets Inflamm Allergy 2004; 3:263–269.
24. Papadakis KA, Targan SR. Role of cytokines in the pathogenesis of inflammatory bowel disease. Annu Rev Med 2000; 51:289–298.
25. 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; 30:421–428.
26. Tian L, Rauvala H, Gahmberg CG. Neuronal regulation of immune responses in the central nervous system. Trends Immunol 2009; 30:91–99.
27. Eskandari F, Webster JI, Sternberg EM. Neural immune pathways and their connection to inflammatory diseases. Arthritis Res Ther 2003; 5:251–265.
28. Berrocoso E, Mico JA. In vivo effect of venlafaxine on locus coeruleus neurons: role of opioid, α2-Adrenergic, and 5-Hydroxytryptamine1A receptors. J Pharmacol Exp Ther 2007; 322:101-107.
29. Egan TM, Henderson G, North RA, Williams JT. Noradrenaline-mediated synaptic inhibition in rat locus coeruleusneurones. J Physiol 1983; 345:477–488.
30. Iravani MM, Sadeghian M, Rose S, Jenner P. Loss of locus coeruleus noradrenergic neurons alters the inflammatory response to LPS in substantia nigra but does not affect nigral cell loss. J Neural Transm 2014; 121:1493-1505.
31. Lembeck F, Holzer P. Substance P as neurogenic mediator of antidromic vasodilation and neurogenic plasma extravasation. Naunyn Schmiedebergs Arch Pharmacol 1979; 310:175–183.

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