Serum cytokine levels in patients with chronic low back pain due to herniated disc
analytical cross-sectional study
Keywords:
Cytokines, Low back pain, Tumor necrosis factor-alpha, Interleukins, Interleukin-6Abstract
CONTEXT AND OBJECTIVE: The role of immune response and proinflammatory cytokines in the pathogenesis of chronic pain has been of growing interest. In order to evaluate whether there is any association between disc herniation and elevated cytokine levels, we measured cytokine levels in patients with chronic low back pain and in healthy subjects. DESIGN AND SETTING: Analytical cross-sectional study at the Pain Clinic of Universidade Federal da Bahia (UFBA). METHODS: Cytokine levels were measured using the enzyme-linked immunosorbent assay (ELISA) technique on 23 patients with low back pain (G1) and on 10 healthy subjects (G2). RESULTS: The levels of tumor necrosis factor-alpha [TNF-alpha] (G1 = 5.6 ± 2.3 pg/ml; G2 = 1.6 ± 0.5 pg/ml; P = 0.01) and interleukin-6 [IL-6] (G1 = 4.1 ± 3.0 pg/ml; G2 = 0.9 ± 0.4 pg/ml; P = 0.01) were higher in G1. There were no statistically significant differences in relation to interleukin-1 [IL-1] (G1 = 0.5 ± 0.3 pg/ml; G2 = 0.5 ± 0.1 pg/ml; P = 1) or soluble tumor necrosis factor receptor [sTNF-R] (G1 = 572 pg/ml ± 36; G2 = 581 ± 50 pg/ml; P = 0.87). CONCLUSION: The patients with chronic low back pain due to disc herniation presented higher levels of TNF-alpha and IL-6, but not of IL-1 or sTNF-R.
Downloads
References
Waddell G. Low back pain: a twentieth century health care enigma. Spine (Phila Pa 1976). 1996;21(24):2820-5.
Frymoyer JW, Cats-Baril WL. An overview of the incidences and costs of low back pain. Orthop Clin North Am. 1991;22(2):263-71.
Frymoyer JW. Lumbar disk disease: epidemiology. Instr Course Lect. 1992;41:217-23.
Long DM. Decision making in lumbar disc disease. Clin Neurosurg. 1992;39:36-51.
Heliövaara M, Impivaara O, Sievers K, et al. Lumbar disc syndrome in Finland. J Epidemiol Community Health 1987;41(3):251-8.
Hicks GS, Duddleston DN, Russell LD, et al. Low back pain. Am J Med Sci. 2002;324(4):207- 11.
Deyo RA, Rainville J, Kent DL. What can the history and physical examination tell us about low back pain? JAMA. 1992;268(6):760-5.
Kelsey JL, White AA 3rd. Epidemiology and impact of low-back pain. Spine (Phila Pa 1976). 1980;5(2):133-42.
Younes M, Béjia I, Aguir Z, et al. Prevalence and risk factors of disk-related sciatica in an urban population in Tunisia. Joint Bone Spine. 2006;73(5):538-42.
Balagué F, Nordin M, Sheikhzadeh A, et al. Recovery of severe sciatica. Spine (Phila Pa 1976). 1999;24(23):2516-24.
Homma Y, Brull SJ, Zhang JM. A comparison of chronic pain behavior following local appli- cation of tumor necrosis factor alpha to the normal and mechanically compressed lumbar ganglia in the rat. Pain. 2002;95(3):239-46.
Omarker K, Myers RR. Pathogenesis of sciatic pain: role of herniated nucleus pulposus and deformation of spinal nerve root and dorsal root ganglion. Pain. 1998;78(2):99-105.
Schäfers M, Geis C, Svensson CI, Luo ZD, Sommer C. 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(4):791-804.
Shafer DM, Assael L, White LB, Rossomando EF. Tumor necrosis factor-alpha as a biochemi- cal marker of pain and outcome in temporomandibular joints with internal derangements. J Oral Maxillofac Surg. 1994;52(8):786-91; discussion 791-2.
Geiss A, Varadi E, Steinbach K, Bauer HW, Anton F. Psychoneuroimmunological correlates of persisting sciatic pain in patients who underwent discectomy. Neurosci Lett. 1997;237(2- 3):65-8.
Brisby H, Olmarker K, Larsson K, Nutu M, Rydevik B. Proinflammatory cytokines in cere- brospinal fluid and serum in patients with disc herniation and sciatica. Eur Spine J. 2002;11(1):62-6.
Koch A, Zacharowski K, Boehm O, et al. Nitric oxide and pro-inflammatory cytokines correla- te with pain intensity in chronic pain patients. Inflamm Res. 2007;56(1):32-7.
Backonja MM, Coe CL, Muller DA, Schell K. Altered cytokine levels in the blood and cere- brospinal fluid of chronic pain patients. J Neuroimmunol. 2008;195(1-2):157-63.
Alexander GM, van Rijn MA, van Hilten JJ, Perreault MJ, Schwartzman RJ. Changes in cere- brospinal fluid levels of pro-inflammatory cytokines in CRPS. Pain. 2005;116(3):213-9.
van de Beek WJ, Remarque EJ, Westendorp RG, van Hilten JJ. Innate cytokine profile in patients with complex regional pain syndrome is normal. Pain. 2001;91(3):259-61.
Winkelstein BA, Rutkowski MD, Weinstein JN, DeLeo JA. Quantification of neural tissue injury in a rat radiculopathy model: comparison of local deformation, behavioral outcomes, and spinal cytokine mRNA for two surgeons. J Neurosci Methods. 2001;111(1):49-57.
Burke JG, Watson RW, McCormack D, et al. Intervertebral discs which cause low back pain secrete high levels of proinflammatory mediators. J Bone Joint Surg Br. 2002;84(2):196- 201.
Specchia N, Pagnotta A, Toesca A, Greco F. Cytokines and growth factors in the protruded intervertebral disc of the lumbar spine. Eur Spine J. 2002;11(2):145-51.
Watkins LR, Maier SF, Goehler LE. Immune activation: the role of pro-inflammatory cytokines in inflammation, illness responses and pathological pain states. Pain. 1995;63(3):289-302.
Junger H, Sorkin LS. Nociceptive and inflammatory effects of subcutaneous TNFalpha. Pain. 2000;85(1-2):145-51.
Brydon L, Edwards S, Mohamed-Ali V, Steptoe A. Socioeconomic status and stress-induced increases in interleukin-6. Brain Behav Immun. 2004;18(3):281-90.
Cunha FQ, Poole S, Lorenzetti BB, Ferreira SH. The pivotal role of tumour necrosis factor alpha in the development of inflammatory hyperalgesia. Br J Pharmacol. 1992;107(3):660-4.
Solari R, Smithers N, Kennard N, Ray K, Grenfell S. Receptor mediated endocytosis and intracellular fate of interleukin 1. Biochem Pharmacol. 1994;47(1):93-101.
Spangelo BL, Judd AM, Isakson PC, MacLeod RM. Interleukin-6 stimulates anterior pituitary hormone release in vitro. Endocrinology. 1989;125(1):575-7.
Nygaard OP, Mellgren SI, Osterud B. The inflammatory properties of contained and noncon- tained lumbar disc herniation. Spine (Phila Pa 1976). 1997;22(21):2484-8.
Yoshida M, Nakamura T, Sei A, et al. Intervertebral disc cells produce tumor necrosis fac- tor alpha, interleukin-1beta and monocyte chemoattractant protein-1 immediately after herniation: an experimental study using a new hernia model. Spine (Phila Pa 1976). 2005;30(1):55-61.
Aderka D, Wysenbeek A, Engelmann H, et al. Correlation between serum levels of soluble tu- mor necrosis factor receptor and disease activity in systemic lupus erythematosus. Arthritis Rheum. 1993;36(8):1111-20.
Kalinkovitch A, Engelmann H, Harpaz N, et al. Elevated serum levels of soluble tumour necrosis factor receptors (sTNF-R) in patients with HIV infection. Clin Exp Immunol. 1992;89(3):351-5.
Huygen FJ, Niehof S, Zijlstra FJ, van Hagen PM, van Daele PL. Successful treatment of CRPS 1 with anti-TNF. J Pain Symptom Manage. 2004;27(2):101-3.
