Dexamethasone is widely used in the therapy of chronic inflammatory diseases for its pain-modulating effects. The objective of this study was to evaluate the effect of dexamethasone on nociception and local inflammation, and the levels of brain-derived neurotrophic factor (BDNF) in the spinal cord in male rats with chronic inflammation induced by complete Freund’s adjuvant (CFA). Rats were randomly divided into a control group (not manipulated) and 2 CFA-induced chronic inflammation groups (in the 15th post-CFA injection): 1 injected with vehicle (saline solution) and 1 received dexamethasone (0.25 mg/kg) for 8 days. The hot-plate and electronic von Frey tests were performed 24 h after the end of treatment. BDNF spinal cord levels were determined by enzyme-linked immunosorbent assay (ELISA). The level of inflammation in the tibiotarsal joint (the ankle region) was evaluated histologically at the end of treatment. Dexamethasone produced significantly increased latency in the hot-plate test (one-way ANOVA, p < 0.05) and withdrawal threshold in the electronic von Frey test (p < 0.005). The dexamethasone group showed increased spinal cord BDNF levels compared to the other groups (one-way ANOVA p, < 0.05). Histological analysis showed a local inflammatory response only in animals treated with vehicle, which demonstrated that the dexamethasone treatment decreased the inflammatory process. Our findings corroborate the antinociceptive and anti-inflammatory properties of dexamethasone. In addition, we showed that the dexamethasone treatment increased BDNF levels in the spinal cord; its pain- modulating effects can be attributed to this effect.

1.
Stahn C, Buttgereit F: Genomic and nongenomic effects of glucocorticoids. Nat Clin Pract Rheumatol 2008;4:525–533.
2.
Zhang RX, Lao L, Qiao LT, Malsnee K, Ruda MA: Endogenous and exogenous glucocorticoid suppresses up-regulation of preprodynorphin mRNA and hyperalgesia in rats with peripheral inflammation. Neurosci Lett 2004;359:85–88.
3.
Yoshida M, Koyanagi S, Matsuo A, Fujioka T, To H, Higuchi S, Ohdo: Glucocorticoid hormone regulates the circadian coordination of µ-opioid receptor expression in mouse brainstem. J Pharmacol Exp Ther 2005;315:1119–1124.
4.
Patte-Mensah C, Kibaly C, Boudard D, Schaeffer V, Begle A, Saredi S, Meyer L, Mensah-Nyagan AG: Neurogenic pain and steroid synthesis in the spinal cord. J Mol Neurosci 2006;17:28–32.
5.
Gonzalez S, Moses DF, De Nicola AF: Glucocorticoid receptors and enzyme induction in the spinal cord of rats: effects of acute transection. J Neurochem 1990;54:834–840.
6.
Marlier LN, Csikos T, Rebaudengo N, Borboni P, Patacchioli FR, Angelucci L, Privat A, Lauro R: Distribution of glucocorticoid receptor mRNA in the rat spinal cord. Neuroreport 1995;6:2245–2249.
7.
Zhao J, Seereeram A, Nassar MA, Levato A, Pezet S, Hathaway G, Morenilla-Palao C, Stirling C, Fitzgerald M, McMahon SB, Rios M, Wood JN: Nociceptor-derived brain-derived neurotrophic factor regulates acute and inflammatory but not neuropathic pain. Mol Cell Neurosci 2006;31:539–548.
8.
Zhang HN, Ko MC: Seizure activity involved in the up-regulation of BDNF mRNA expression by activation of central mu opioid receptors. Neuroscience 2009;161:301–310.
9.
Merighi A, Salio C, Ghirri A, Lossi L, Ferrini F, Betelli C, Bardoni R: BDNF as a pain modulator. Prog Neurobiol 2008;85:297–317.
10.
Baker-Herman TL, Fuller DD, Bavis RW, Zabka AG, Golder FJ, Doperalski NJ, Johnson RA, Watters JJ, Mitchell GS: BDNF is necessary and sufficient for spinal respiratory plasticity following intermittent hypoxia. Nat Neurosci 2004;7:48–55.
11.
Schinder AF, Berninger B, Poo M: Postsynaptic target specificity of neurotrophin-induced presynaptic potentiation. Neuron 2000;25:151–163.
12.
Turrigiano GG: The self-tuning neuron: synaptic scaling of excitatory synapses. Cell 2008;135:422–435.
13.
Swanwick CC, Murthy NR, Kapur J: Activity-dependent scaling of GABAergic synapse strength is regulated by brain-derived neurotrophic factor. Mol Cell Neurosci 2006;31:481–492.
14.
Caparroz-Assef SM, Bersani-Amado CA, Kelmer-Bracht AM, Bracht A, Ishii-Iwamoto EL: The metabolic changes caused by dexamethasone in the adjuvant-induced arthritic rat. Mol Cell Biochem 2007;302:87–98.
15.
Bernardi A, Zilberstein ACCV, Jäger E, Campos MM, Morrone FB, Calixto JB, Pohlmann AR, Guterres SS, Battastini AM: Effects of indomethacin-loaded nanocapsules in experimental models of inflammation in rats. Br J Pharmacol 2009;158:1104–1111.
16.
Rezazadeh SH, Zaringhalam J, Manakeji H, Kebryaeezadeh A: Anti-inflammatory and anti-hyperalgesic activities of Stachys athorecalyx extracts on CFA-induced inflammation. J Med Plant Res 2009;5:187–191.
17.
Woolfe G, Macdonald AD: The evaluation of the analgesic action of pethidine hydrochloride. J Pharmacol Exp Ther 1944;80:300–307.
18.
Yamamoto T, Nozaki-Taguchi N, Chiba T: Analgesic effect of intrathecally administered orexin-A in the rat formalin test and in the rat hot-plate test. Br J Pharmacol 2002;137:170–176.
19.
Vivancos GG, Verri WA Jr, Cunha TM, Schivo IR, Parada CA, Cunha FQ, Ferreira SH: An electronic pressure-meter nociception paw test for rats. Braz J Med Biol Res 2004;37:391–399.
20.
Kumamaru E, Numakawa T, Adachi N, Yagasaki Y, Izumi A, Niyaz M, Kudo M, Kunugi H: Glucocorticoid prevents brain-derived neurotrophic factormediated maturation of synaptic function in developing hippocampal neurons through reduction in the activity of mitogen-activated protein kinase. Mol Endocrinol 2008;22:546–558.
21.
Bałkowiec-Iskra E, Balkowiec A: Regulation of BDNF expression in trigeminal ganglion neurons by proinflammatory cytokines. Soc Neurosci Abstr 2009;4:7–10.
22.
Coull JA, Beggs S, Boudreau D, Boivin D, Tsuda M, Inoue K, Gravel C, Salter MW, De Koninck Y: BDNF from microglia causes the shift in neuronal anion gradient underlying neuropathic pain. Nature 2005;438:1017–1021.
23.
Lever IJ, Pezet S, McMahon SB, Malcangio M: The signaling components of sensory fiber transmission involved in the activation of ERK MAP kinase in the mouse dorsal horn. Mol Cell Neurosci 2003;24:259–270.
24.
Malcangio M, Lessmann V: A common thread for pain and memory synapses? Brain-derived neurotrophic factor and Trkb receptors. Trends Pharmacol Sci 2003;24:116–121.
25.
Michael GJ, Averill S, Nitkunan A, Rattray M, Bennett DL, Yan Q, Priestley JV: Nerve growth factor treatment increases brain-derived neurotrophic factor selectively in TrkA-expressing dorsal root ganglion cells and in their central terminations within the spinal cord. J Neurosci 1997;17:8476–8490.
26.
Webster NJG, Pirrung MC: Small molecule activators of the Trk receptors for neuroprotection. BMC Neurosci 2008, DOI:10.1186/1471–2202–9-S2-S1.
27.
Fiumelli H, Kiraly M, Ambrus A, Magistretti PJ, Martin JL: Opposite regulation of calbindin and calretinin expression by brainderived neurotrophic factor in cortical neurons. J Neurochem 2000;74:1870–1877.
28.
Zaringhalam J, Manaheji H, Mghsoodi N, Farokhi B, Mirzaiee V: Spinal mu-opioid receptor expression and hyperalgesia with dexamethasone in chronic adjuvant arthritis rats. Clin Exp Pharmacol Physiol 2008;35:1309–1315.
29.
Millan MJ: The induction of pain: an integrative review. Prog Neurobiol 1999;57:1–164.
30.
Lam FF, Nq ES: Substance P and glutamate receptor antagonists improve the anti-arthritic actions of dexamethasone in rats. Br J Pharmacol 2010;159:958–969.
31.
Pinto-Ribeiro F, Moreira V, Pego JM, Leão P, Almeida A, Sousa N: Antinociception induced by chronic glucocorticoid treatment is correlated to local modulation of spinal neurotransmitter content. Molecular Pain 2009, DOI:10.1186/1744–8069–5–41.
32.
da Silva JAP, Bijlsma JWJ: Optimizing glucocorticoid therapy of rheumatoid arthritis. Rheum Dis Clin North Am 2000;26:859–880.
33.
Lavagno L, Gunella G, Bardelli C, Soina S, Fresu LG, Viano I, Brunelleschi S: Anti-inflammatory drugs and tumor necrosis factor-alpha production: role of transcription factor NF-kappa B and implications for rheumatoid arthritis therapy. Eur J Pharmacol 2004;501:199–208.
34.
Oelzner P, Richter-Fleissner S, Bräuer R, Hein G, Wolf G, Neumann T: Combination therapy with dexamethasone and osteoprotegerin protects against arthritis-induced bone alterations is antigen-induced arthritis of the rat. Inflamm Res 2010;59:731–741.
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