Brazilian Journal of Anesthesiology
https://app.periodikos.com.br/journal/rba/article/doi/10.1590/S0034-70942009000300004
Brazilian Journal of Anesthesiology
Scientific Article

Citocinas pró-inflamatórias em pacientes com dor neuropática submetidos a tratamento com Tramadol

Proinflammatory cytokines in patients with neuropathic pain treated with Tramadol

Durval Campos Kraychete; Rioko Kimiko Sakata; Adriana Machado Issy; Olívia Bacellar; Rogério Santos Jesus; Edgar M Carvalho

http://dx.doi.org/10.1590/S0034-70942009000300004 Braz J Anesthesiol, vol.59, n3, p.297-303, 2009
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Resumo

JUSTIFICATIVA E OBJETIVOS: As citocinas pró-inflamatórias têm função importante na fisiopatologia das síndromes dolorosas neuropáticas. O objetivo desse estudo foi avaliar os níveis plasmáticos de citocinas pró-inflamatórias antes e após o tratamento com tramadol em pacientes com hérnia discal e síndrome do túnel do carpo e compará-los com indivíduos normais. MÉTODO: Investigou-se 38 pacientes com dor neuropática por hérnia discal ou síndrome do túnel do carpo. Todos os pacientes foram tratados com tramadol de liberação controlada (100 mg em 12h) durante 10 dias. Realizaram-se coletas de sangue venoso (5 mL), no período matutino, antes do tratamento e no 11º dia e as amostras foram armazenadas até análise (-70ºC). Foram utilizados testes enzimáticos ELISA para dosagem de citocinas plasmáticas (TNF-±, IL-1, IL-6) e receptores sTNF-R1, (R & D Systems). Realizou-se dosagem de citocinas em soro de 10 voluntários sadios. RESULTADOS: A concentração de TNF-± antes (5,8 ± 2,8 pg.mL-1) foi significativamente maior que após o tramadol (4,8 ± 2,1 pg.mL-1; p = 0,04, Teste Mann-Whitney). Não houve diferença significativa de IL-1², IL-6 e sTNF-R1 antes e após o tratamento. As concentrações plasmáticas de TNF-± (sadios: 1,4 ± 0,5; pacientes com dor: 5,8 ± 2,8 pg.mL-1; p = 0.01) e IL-6 (sadios: 1,2 ± 0,8; pacientes com dor: 3,5 ± 2,6 pg.mL-1; p = 0,01) foram significativamente maiores nos pacientes com dor neuropática que nos voluntários, Teste de Mann-Whitney. CONCLUSÕES: Nos pacientes com hérnia discal e síndrome do túnel do carpo as concentrações plasmáticas de TNF-± e IL-6 foram maiores que em voluntários sadios, não havendo diferença das concentrações de sTNF-R e IL-1². Houve redução da concentração plasmática de TNF-± após tratamento com tramadol (100 mg em 12h), mas não de IL-6, sTNF-R e IL-1².

Palavras-chave

ANALGÉSICO, CITOCINAS, CITOCINAS, CITOCINAS, CITOCINAS, DOR, neuropática, DOR, neuropática

Abstract

BACKGROUND AND METHODS: Proinflammatory cytokines play an important role in the pathophysiology of neuropathic pain syndromes. The objective of this study was to evaluate plasma levels of proinflammatory cytokines before and after treatment with tramadol in patients with herniated intervertebral disks and carpal tunnel syndrome, and to compare them with normal individuals. METHODS: Thirty-eight patients with neuropathic pain secondary to herniated intervertebral disks or carpal tunnel syndrome participated in this study. All patients were treated with controlled release tramadol (100 mg every 12 hours) for 10 days. Venous blood (5 mL) was collected in the morning, before treatment and on the 11th day, and stored (-70° C) until analysis. ELISA was used to determine the plasma levels of cytokines (TNF-±, IL-1, IL-6) and receptors sTNF-R1 (R & D Systems). Plasma levels of cytokines of 10 healthy volunteers were also determined. RESULTS: The concentration of TNF-± before (5.8 ± 2.8 pg.mL-¹) was significantly higher than after treatment with tramadol (4.8 ± 2.1 pg.mL-1; p = 0.04, Mann-Whitney test). The levels of IL-1², IL-6, and sTNF-R1 before and after treatment with tramadol showed no significant differences. Plasma levels of TNF-± (healthy individuals: 1.4 ± 0.5; pain patients: 5.8 ± 2.8 pg.mL-1; p = 0.01) and IL-6 (healthy individuals: 1.2 ± 0.8; pain patients: 3.5 ± 2.6 pg.mL-1; p = 0.01) were significantly higher in patients with neuropathic pain, Mann-Whitney Test. CONCLUSIONS: In patients with herniated intervertebral disks and carpal tunnel syndrome, plasma levels of TNF-± and IL-6 were higher than in healthy volunteers, while differences in the concentrations of sTNF-R and IL-1² were not observed. Plasma levels of TNF-±, but not of IL-6, sTNF-R, and IL-1², decreased after treatment with tramadol (100 mg every 12 hours).

Keywords

ANALGESIC, CYTOKINES, CYTOKINES, CYTOKINES, CYTOKINES, PAIN, neuropathic, PAIN, neuropathic

References

Backonja MM, Coe CL, Muller DA. Altered cytokine levels in the blood and cerebrospinal fluid of chronic pain patients. J Neuroimmunol. 2008;195:157-163.

Alexander GM, van Rijn MA, van Hilten JJ. Changes in cerebrospinal fluid levels of pro-inflammatory cytokines in CRPS. Pain. 2005;116:213-219.

Van de Beek WJ, Remarque EJ, Westendorp RGJ. Innate cytokine profile in patients with complex regional pain syndrome is normal. Pain. 2001;91:259-261.

Watkins LR, Wiertelak EP, Goehler LE. Characterization of cytokine-induced hyperalgesia. Brain Res. 1994;654:15- 26.

Woolf CJ, Allchorne A, Safieh-Garabedian B. Cytokines, nerve growth factor and inflammatory hyperalgesia: the contribution of tumour necrosis factor alpha. Br J Pharmacol. 1997;121:417-424.

Junger H, Sorkin LS. Nociceptive and inflammatory effects of subcutaneous TNFalpha. Pain. 2000;85:145-151.

Wagner R, Myers RR. Endoneurial injection of TNF-alpha produces neuropathic pain behaviors. Neuroreport. 1996;7:2897-2901.

Sorkin LS, Xiao WH, Wagner R. Tumour necrosis factor-alpha induces ectopic activity in nociceptive primary afferent fibres. Neuroscience. 1997;81:255-262.

Clatworthy AL, Castro GA, Budelmann BU. Induction of a cellular defense reaction is accompanied by an increase in sensory neuron excitability in aplysia. J Neurosci. 1994;14:3263-3270.

Sommer C, Kress M. Recent findings on how proinflammatory cytokines cause pain: peripheral mechanisms in inflammatory and neuropathic hyperalgesia. Neurosci Lett. 2004;361:184-187.

McDermott MF. TNF and TNFR biology in health and disease. Cell Mol Biol. 2001;47:619-635.

Ferreira SH, Lorenzetti BB, Cunha FQ. Bradykinin release of TNF-alpha plays a key role in the development of inflammatory hyperalgesia. Agents Actions. 1993;38:C7-9.

Cunha FQ, Lorenzetti BB, Poole S. Interleukin-8 as a mediator of sympathetic pain. Br J Pharmacol. 1991;104:765-767.

Schafers M, Geis C, Svensson CI. Selective increase of tumour necrosis factor-alpha in injured and spared myelinated primary afferents after chronic constrictive injury of rat sciatic nerve. Eur J Neurosci. 2003;17:791-804.

Brisby H, Olmarker K, Larsson K. Proinflammatory cytokines in cerebrospinal fluid and serum in patients with disc herniation and sciatica. Eur Spine J. 2002;11:62-66.

Geiss A, Varadi E, Steinbach K. Psychoneuroimmunological correlates of persisting sciatic pain in patients who underwent discectomy. Neurosci Lett. 1997;237:65-68.

Kunz-Ebrecht SR, Mohamed-Ali V, Feldman PJ. Cortisol responses to mild psychological stress are inversely associated with proinflammatory cytokines. Brain Behav Immun. 2003;17:373-383.

Machelska H, Stein C. Immune mechanisms in pain control. Anesth Analg. 2002;95:1002-1008.

Uceyler N, Valenza R, Stock M. Reduced levels of antiinflammatory cytokines in patients with chronic widespread pain. Arthritis Rheum. 2006;54:2656-2664.

Uceyler N, Rogausch JP, Toyka KV. Differential expression of cytokines in painful and painless neuropathies. Neurology. 2007;69:42-49.

Mosmann TR, Coffman RL. TH1 and TH2 cells: Different patterns of lymphokine secretion lead to different functional properties. Annu Rev Immunol. 1989;7:145-173.

Plunkett JA, Yu CG, Easton JM. Effects of interleukin-10 (IL-10) on pain behavior and gene expression following excitotoxic spinal cord injury in the rat. Exp Neurol. 2001;168:144-154.

Heinrich PC, Castell JV, Andus T. Interleukin-6 and the acute phase response. Biochem J. 1990;265:621-636.

Aderka D. The potential biological and clinical significance of the soluble tumor necrosis factor receptors. Cytokine Growth Factor Rev. 1996;7:231-240.

Le Roux PJ, Coetzee JF. Tramadol today. Curr Opin Anaesthesiol. 2000;13:457-461.

Rowbotham MC, Reisner-Keller LA, Fields HL. Both intravenous lidocaine and morphine reduce the pain of postherpetic neuralgia. Neurology. 1991;41:1024-1028.

Sindrup SH, Andersen G, Madsen C. Tramadol relieves pain and allodynia in polyneuropathy: a randomized, double-blind, controlled trial. Pain. 1999;83:85-90.

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