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Reviews on Recent Clinical Trials

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ISSN (Print): 1574-8871
ISSN (Online): 1876-1038

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Clinical Trial

N-Acetyl Cysteine as an Add-on Therapy is Useful in Treating Acute Lumbar Radiculopathy Caused by Disc Herniation: Results of a Randomized, Controlled Clinical Trial

Author(s): Bijan Heidari, Zeinab-Alsadat Seyedian, Maryam Mehrpooya*, Davoud Ahmadimoghaddam*, Mahtabalsadat Mirjalili and Masood Ghiasian

Volume 18, Issue 4, 2023

Published on: 27 September, 2023

Page: [288 - 299] Pages: 12

DOI: 10.2174/0115748871250545230919055109

Price: $65

Abstract

Background: Available experimental and clinical evidence indicates that N-Acetyl cysteine (NAC) may have an analgesic role in specific pain conditions, particularly neuropathic pain. Thus, we hypothesized that NAC supplementation might be also helpful in decreasing pain and improving pain-related disability in patients with acute radiculopathy. We designed this study to investigate the potential use of NAC-adjunctive treatment to Nonsteroidal Anti- Inflammatory Drugs (NSAIDs) in patients with acute radiculopathy secondary to lumbar intervertebral disc herniation.

Methods: Sixty-two patients diagnosed with acute lumbar radiculopathy associated with disc herniation were randomly allocated to the NAC or the placebo groups. Besides naproxen at a dose of 500 mg twice a day, participants based on their allocation group started with NAC or matched placebo at a dose of 600 mg twice a day for eight weeks. The pain severity, measured by the Visual Analog Scale (VAS), and pain-related disability measured by the Oswestry Disability Index (ODI) were measured at baseline and weeks 2, 4, and 8 of treatment. Global improvement of symptoms rated by Patient and Clinical Global Impressions of Change (PGIC and CGIC) was also recorded at the end of week 8. All analyses were conducted on an Intentionto- Treat (ITT) analysis data set.

Results: A comparison of the VAS and ODI scores at weeks 2 and 4 of the treatment between the two groups did not show a significant difference. In contrast, from week 4 to week 8, we noticed a significantly greater reduction in the mean VAS and ODI scores in the NAC group compared to the placebo group (p-value <0.001 for both variables). In parallel with these results, also, more NAC-treated than placebo-treated patients achieved treatment success defined as ‘‘very much’’ or ‘‘much improved’’ on CGIC and PGIC scales, and these differences reached a significant level (p-value = .011 and p-value = .043).

Conclusions: This study suggested that NAC might be a relevant candidate for adjunct therapy in managing acute lumbar radiculopathy. Additional clinical trials are needed to validate these findings.

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[1]
Tarulli AW, Raynor EM. Lumbosacral radiculopathy. Neurol Clin 2007; 25(2): 387-405.
[http://dx.doi.org/10.1016/j.ncl.2007.01.008] [PMID: 17445735]
[2]
Katz JN. Lumbar disc disorders and low-back pain: Socioeconomic factors and consequences. J Bone Joint Surg Am 2006; 88 (Suppl. 2): 21-4.
[http://dx.doi.org/10.2106/00004623-200604002-00005] [PMID: 16595438]
[3]
Amin RM, Andrade NS, Neuman BJ. Lumbar disc herniation. Curr Rev Musculoskelet Med 2017; 10(4): 507-16.
[http://dx.doi.org/10.1007/s12178-017-9441-4] [PMID: 28980275]
[4]
Berry JA, Elia C, Saini HS, Miulli DE. A review of lumbar radiculopathy, diagnosis, and treatment. Cureus 2019; 11(10): e5934.
[http://dx.doi.org/10.7759/cureus.5934] [PMID: 31788391]
[5]
Lin JH, Chiang Y-H, Chen C-C. Lumbar radiculopathy and its neurobiological basis. World J Anesthesiol 2014; 3(2): 162-73.
[http://dx.doi.org/10.5313/wja.v3.i2.162]
[6]
Cosamalón-Gan I, Cosamalón-Gan T, Mattos-Piaggio G, Villar-Suárez V, García-Cosamalón J, Vega-Álvarez JA. Inflammation in the intervertebral disc herniation. Neurocirugía 2021; 32(1): 21-35.
[http://dx.doi.org/10.1016/j.neucie.2020.04.001] [PMID: 32169419]
[7]
Miyamoto H, Saura R, Harada T, Doita M, Mizuno K. The role of cyclooxygenase-2 and inflammatory cytokines in pain induction of herniated lumbar intervertebral disc. Kobe J Med Sci 2000; 46(1-2): 13-28.
[PMID: 11193500]
[8]
Genevay S, Finckh A, Payer M, et al. Elevated levels of tumor necrosis factor-alpha in periradicular fat tissue in patients with radiculopathy from herniated disc. Spine 2008; 33(19): 2041-6.
[http://dx.doi.org/10.1097/BRS.0b013e318183bb86] [PMID: 18758358]
[9]
Yang H, Zhang Y, Sun G, et al. Correlation of inflammatory cytokines with radicular pain after lumbar intervertebral disc protrusion. Int J Clin Exp Med 2019; 12(8): 10380-6.
[10]
Klyne D, Barbe M, Van Den Hoorn W, Hodges P. Longitudinal analysis of inflammatory, psychological, and sleep-related factors following an acute low back pain episode: A potential factor in tissue effects in low back pain. J Bodyw Mov Ther 2018; 22(4): 866.
[http://dx.doi.org/10.1016/j.jbmt.2018.09.056]
[11]
Bhatia A, Flamer D, Shah PS, Cohen SP. Transforaminal epidural steroid injections for treating lumbosacral radicular pain from herniated intervertebral discs: A systematic review and meta-analysis. Anesth Analg 2016; 122(3): 857-70.
[http://dx.doi.org/10.1213/ANE.0000000000001155] [PMID: 26891397]
[12]
Roncoroni C, Baillet A, Durand M, Gaudin P, Juvin R. Efficacy and tolerance of systemic steroids in sciatica: A systematic review and meta-analysis. Rheumatology 2011; 50(9): 1603-11.
[http://dx.doi.org/10.1093/rheumatology/ker151] [PMID: 21525139]
[13]
Abram SE, O’Connor TC. Complications associated with epidural steroid injections. Reg Anesth 1996; 21(2): 149-62.
[PMID: 8829408]
[14]
Poetker DM, Reh DD. A comprehensive review of the adverse effects of systemic corticosteroids. Otolaryngol Clin North Am 2010; 43(4): 753-68.
[http://dx.doi.org/10.1016/j.otc.2010.04.003] [PMID: 20599080]
[15]
Tardiolo G, Bramanti P, Mazzon E. Overview on the effects of N-acetylcysteine in neurodegenerative diseases. Molecules 2018; 23(12): 3305.
[http://dx.doi.org/10.3390/molecules23123305] [PMID: 30551603]
[16]
Schwalfenberg GK. N-acetylcysteine: A review of clinical usefulness (an Old Drug with New Tricks). J Nutr Metab 2021; 2021: 9949453.
[17]
Aldini G, Altomare A, Baron G, et al. N-Acetylcysteine as an antioxidant and disulphide breaking agent: The reasons why. Free Radic Res 2018; 52(7): 751-62.
[http://dx.doi.org/10.1080/10715762.2018.1468564] [PMID: 29742938]
[18]
Sun SY. N-acetylcysteine, reactive oxygen species and beyond. Cancer Biol Ther 2010; 9(2): 109-10.
[http://dx.doi.org/10.4161/cbt.9.2.10583] [PMID: 19949311]
[19]
Sadowska AM, Manuel-y-Keenoy B, De Backer WA. Antioxidant and anti-inflammatory efficacy of NAC in the treatment of COPD: Discordant in vitro and in vivo dose-effects: A review. Pulm Pharmacol Ther 2007; 20(1): 9-22.
[http://dx.doi.org/10.1016/j.pupt.2005.12.007] [PMID: 16458553]
[20]
Berk M, Malhi GS, Gray LJ, Dean OM. The promise of N-acetylcysteine in neuropsychiatry. Trends Pharmacol Sci 2013; 34(3): 167-77.
[http://dx.doi.org/10.1016/j.tips.2013.01.001] [PMID: 23369637]
[21]
Wuyts WA, Vanaudenaerde BM, Dupont LJ, Demedts MG, Verleden GM. N‐acetylcysteine reduces chemokine release via inhibition of p38 MAPK in human airway smooth muscle cells. Eur Respir J 2003; 22(1): 43-9.
[http://dx.doi.org/10.1183/09031936.03.00064803] [PMID: 12882449]
[22]
Wang X, Jiang M, He X, Zhang B, Peng W, Guo L. N acetyl cysteine inhibits the lipopolysaccharide induced inflammatory response in bone marrow mesenchymal stem cells by suppressing the TXNIP/NLRP3/IL-1β signaling pathway. Mol Med Rep 2020; 22(4): 3299-306.
[http://dx.doi.org/10.3892/mmr.2020.11433] [PMID: 32945495]
[23]
Askari M, Faryabi R, Mozaffari H, Darooghegi Mofrad M. The effects of N-Acetylcysteine on serum level of inflammatory biomarkers in adults. Findings from a systematic review and meta-analysis of randomized clinical trials. Cytokine 2020; 135: 155239.
[http://dx.doi.org/10.1016/j.cyto.2020.155239] [PMID: 32799012]
[24]
Heidari N, Sajedi F, Mohammadi Y, Mirjalili M, Mehrpooya M. Ameliorative effects of N-acetylcysteine as adjunct therapy on symptoms of painful diabetic neuropathy. J Pain Res 2019; 12: 3147-59.
[http://dx.doi.org/10.2147/JPR.S228255] [PMID: 31819599]
[25]
Sabetghadam M, Mazdeh M, Abolfathi P, Mohammadi Y, Mehrpooya M. Evidence for a beneficial effect of oral N-acetylcysteine on functional outcomes and inflammatory biomarkers in patients with acute ischemic stroke. Neuropsychiatr Dis Treat 2020; 16: 1265-78.
[http://dx.doi.org/10.2147/NDT.S241497] [PMID: 32547030]
[26]
Mohiuddin M, Pivetta B, Gilron I, Khan JS. Efficacy and safety of N-acetylcysteine for the management of chronic pain in adults: A systematic review and meta-analysis. Pain Med 2021; 22(12): 2896-907.
[http://dx.doi.org/10.1093/pm/pnab042] [PMID: 33560443]
[27]
Perez MRSG, Zuurmond AWW, Bezemer DP, et al. The treatment of complex regional pain syndrome type I with free radical scavengers: A randomized controlled study. Pain 2003; 102(3): 297-307.
[http://dx.doi.org/10.1016/S0304-3959(02)00414-1] [PMID: 12670672]
[28]
Batooei M, Tahamoli-Roudsari A, Basiri Z, et al. Evaluating the effect of oral N-acetylcysteine as an adjuvant treatment on clinical outcomes of patients with rheumatoid arthritis: A randomized, double blind clinical trial. Rev Recent Clin Trials 2018; 13(2): 132-8.
[http://dx.doi.org/10.2174/1574887113666180307151937] [PMID: 29521247]
[29]
Yaryari Am, Mousavibahar SH, Amirhassani S, Bagheri M, Mohammadi Y, Mehrpooya M. Men suffering from category III chronic prostatitis may benefit from N-acetylcysteine as an adjunct to alpha-blockers. Low Urin Tract Symptoms 2022; 14(3): 199-207.
[http://dx.doi.org/10.1111/luts.12425]
[30]
Fricke JR, Halladay SC, Francisco CA. Efficacy and safety of naproxen sodium and ibuprofen for pain relief after oral surgery. Curr Ther Res Clin Exp 1993; 54(6): 619-27.
[http://dx.doi.org/10.1016/S0011-393X(05)80692-7]
[31]
Cooper SA, Desjardins PJ, Bertoch T, et al. Analgesic efficacy of naproxen sodium versus hydrocodone/acetaminophen in acute postsurgical dental pain: A randomized, double-blind, placebo-controlled trial. Postgrad Med 2022; 134(5): 463-70.
[http://dx.doi.org/10.1080/00325481.2021.2008180] [PMID: 34878953]
[32]
Cooper SA, Desjardins P, Brain P, et al. Longer analgesic effect with naproxen sodium than ibuprofen in post-surgical dental pain: A randomized, double-blind, placebo-controlled, single-dose trial. Curr Med Res Opin 2019; 35(12): 2149-58.
[http://dx.doi.org/10.1080/03007995.2019.1655257] [PMID: 31402718]
[33]
Boonstra AM, Schiphorst Preuper HR, Reneman MF, Posthumus JB, Stewart RE. Reliability and validity of the visual analogue scale for disability in patients with chronic musculoskeletal pain. Int J Rehabil Res 2008; 31(2): 165-9.
[http://dx.doi.org/10.1097/MRR.0b013e3282fc0f93] [PMID: 18467932]
[34]
Fairbank JCT. Why are there different versions of the oswestry disability index? J Neurosurg Spine 2014; 20(1): 83-6.
[http://dx.doi.org/10.3171/2013.9.SPINE13344] [PMID: 24206036]
[35]
Mousavi SJ, Parnianpour M, Mehdian H, Montazeri A, Mobini B. The oswestry disability index, the roland-morris disability questionnaire, and the quebec back pain disability scale: Translation and validation studies of the iranian versions. Spine 2006; 31(14): E454-9.
[http://dx.doi.org/10.1097/01.brs.0000222141.61424.f7] [PMID: 16778675]
[36]
Nakashima H, Kanemura T, Ando K, et al. Is pregabalin effective against acute lumbar radicular pain? Spine Surg Relat Res 2019; 3(1): 61-6.
[http://dx.doi.org/10.22603/ssrr.2018-0003] [PMID: 31435553]
[37]
Molinos M, Almeida CR, Caldeira J, Cunha C, Gonçalves RM, Barbosa MA. Inflammation in intervertebral disc degeneration and regeneration. J R Soc Interface 2015; 12(104): 20141191.
[http://dx.doi.org/10.1098/rsif.2014.1191] [PMID: 25673296]
[38]
Grönblad M, Virri J, Tolonen J, et al. A controlled immunohistochemical study of inflammatory cells in disc herniation tissue. Spine 1994; 19(24): 2744-51.
[http://dx.doi.org/10.1097/00007632-199412150-00002] [PMID: 7899973]
[39]
Habtemariam A, Grönblad M, Virri J, Seitsalo S, Ruuskanen M, Karaharju E. Immunocytochemical localization of immunoglobulins in disc herniations. Spine 1996; 21(16): 1864-9.
[http://dx.doi.org/10.1097/00007632-199608150-00005] [PMID: 8875717]
[40]
Goupille P, Mulleman D, Paintaud G, Watier H, Valat JP. Can sciatica induced by disc herniation be treated with tumor necrosis factor α blockade? Arthritis Rheum 2007; 56(12): 3887-95.
[http://dx.doi.org/10.1002/art.23051] [PMID: 18050220]
[41]
Goupille P, Jayson MI, Valat J-P, Freemont AJ. The role of inflammation in disk herniation-associated radiculopathy. In: Seminars in arthritis and rheumatism: 1998. Elsevier 1998; pp. 60-71.
[http://dx.doi.org/10.1016/S0049-0172(98)80029-2]
[42]
Rasi AM, Mirbolook A, Darestani RT, Sayadi S, Ebadi S. Conservative treatment of low back pain in lumbar disc herniation: Comparison of three therapeutic regimens. Sys Rev Pharma 2020; 11(8): 765-9.
[43]
Roelofs PD, Deyo RA, Koes BW, Scholten RJ, van Tulder MW. Non-steroidal anti-inflammatory drugs for low back pain. Cochrane Database Syst Rev 2008; 2008(1): CD000396.
[http://dx.doi.org/10.1002/14651858.CD000396.pub3]
[44]
Vane JR, Botting RM. Mechanism of action of nonsteroidal anti-inflammatory drugs. Am J Med 1998; 104(A3): 2S-8S.
[http://dx.doi.org/10.1016/S0002-9343(97)00203-9]
[45]
Strom BL, Schinnar R, Bilker WB, Feldman H, Farrar JT, Carson JL. Gastrointestinal tract bleeding associated with naproxen sodium vs ibuprofen. Arch Intern Med 1997; 157(22): 2626-31.
[http://dx.doi.org/10.1001/archinte.1997.00440430108013] [PMID: 9531232]
[46]
Rainsford KD. Ibuprofen: Pharmacology, efficacy and safety. Inflammopharmacology 2009; 17(6): 275-342.
[http://dx.doi.org/10.1007/s10787-009-0016-x] [PMID: 19949916]
[47]
Poddighe D, Brambilla I, Licari A, Marseglia GL. Ibuprofen for pain control in children: New value for an old molecule. Pediatr Emerg Care 2019; 35(6): 448-53.
[PMID: 29912084]
[48]
Li S, Li X, Xie X, et al. N-acetylcysteine attenuates hyperalgesia in rats with diabetic neuropathic pain: role of oxidative stress and inflammatory mediators and CXCR4. J Diabetes Res 2021; 16: 1-10.
[49]
Li J, Xu L, Deng X, et al. N-acetyl-cysteine attenuates neuropathic pain by suppressing matrix metalloproteinases. Pain 2016; 157(8): 1711-23.
[http://dx.doi.org/10.1097/j.pain.0000000000000575] [PMID: 27075430]
[50]
Horst A, Kolberg C, Moraes MS, et al. Effect of N-acetylcysteine on the spinal-cord glutathione system and nitric-oxide metabolites in rats with neuropathic pain. Neurosci Lett 2014; 569: 163-8.
[http://dx.doi.org/10.1016/j.neulet.2014.03.063] [PMID: 24704379]
[51]
Notartomaso S, Scarselli P, Mascio G, et al. N-Acetylcysteine causes analgesia in a mouse model of painful diabetic neuropathy. Mol Pain 2020; 16.
[http://dx.doi.org/10.1177/1744806920904292] [PMID: 32009537]
[52]
Elberry AA, Sharkawi SMZ, Wahba MR. Antinociceptive and anti-inflammatory effects of N-acetylcysteine and verapamil in Wistar rats. Korean J Pain 2019; 32(4): 256-63.
[http://dx.doi.org/10.3344/kjp.2019.32.4.256] [PMID: 31569917]
[53]
Hashemi G, Mirjalili M, Basiri Z, et al. A pilot study to evaluate the effects of oral N-acetyl cysteine on inflammatory and oxidative stress biomarkers in rheumatoid arthritis. Curr Rheumatol Rev 2019; 15(3): 246-53.
[http://dx.doi.org/10.2174/1573403X14666180926100811] [PMID: 30255760]
[54]
Lete I, Mendoza N, de la Viuda E, Carmona F. Effectiveness of an antioxidant preparation with N-acetyl cysteine, alpha lipoic acid and bromelain in the treatment of endometriosis-associated pelvic pain: LEAP study. Eur J Obstet Gynecol Reprod Biol 2018; 228: 221-4.
[http://dx.doi.org/10.1016/j.ejogrb.2018.07.002] [PMID: 30007250]
[55]
Moore TB. The role of N-acetyl-L-cysteine (NAC) as an adjuvant to opioid treatment in patients with inadequately controlled chronic neuropathic pain. Virginia Commonwealth University 2016.
[56]
Gorpynchenko I, Nurimanov K, Poroshina T, Savchenko V, Drannik G, Dubuske L. The clinical and immunologic effects of acetylcysteine in the treatment of chronic abacterial prostatitis. J Allergy Clin Immunol 2020; 145(2): AB30.
[http://dx.doi.org/10.1016/j.jaci.2019.12.821]
[57]
Truini A, Piroso S, Pasquale E, et al. N-acetyl-cysteine, a drug that enhances the endogenous activation of group-II metabotropic glutamate receptors, inhibits nociceptive transmission in humans. Mol Pain 2015; 11: 14.
[http://dx.doi.org/10.1186/s12990-015-0009-2]
[58]
Ozcamdalli M, Misir A, Kizkapan TB, et al. Comparison of intra-articular injection of hyaluronic acid and N-acetyl cysteine in the treatment of knee osteoarthritis: A pilot study. Cartilage 2017; 8(4): 384-90.
[http://dx.doi.org/10.1177/1947603516675915] [PMID: 28934876]
[59]
Yeh YT, Liang CC, Chang CL, Hsu CY, Li PC. Increased risk of knee osteoarthritis in patients using oral N-acetylcysteine: A nationwide cohort study. BMC Musculoskelet Disord 2020; 21(1): 531.
[http://dx.doi.org/10.1186/s12891-020-03562-1] [PMID: 32778089]
[60]
Sins JW, Fijnvandraat K, Rijneveld AW, et al. Effect of N-acetylcysteine on pain in daily life in patients with sickle cell disease: A randomised clinical trial. Br J Haematol 2017; 182(3): 444-8.
[PMID: 28643376]
[61]
Nur E, Brandjes DP, Teerlink T, et al. N-acetylcysteine reduces oxidative stress in sickle cell patients. Ann Hematol 2012; 91(7): 1097-105.
[http://dx.doi.org/10.1007/s00277-011-1404-z] [PMID: 22318468]
[62]
Pace BS, Shartava A, Pack-Mabien A, Mulekar M, Ardia A, Goodman SR. Effects of N-acetylcysteine on dense cell formation in sickle cell disease. Am J Hematol 2003; 73(1): 26-32.
[http://dx.doi.org/10.1002/ajh.10321] [PMID: 12701116]
[63]
Sözbir E, Nazıroğlu M. Diabetes enhances oxidative stress-induced TRPM2 channel activity and its control by N-acetylcysteine in rat dorsal root ganglion and brain. Metab Brain Dis 2016; 31(2): 385-93.
[http://dx.doi.org/10.1007/s11011-015-9769-7] [PMID: 26612073]
[64]
Naik AK, Tandan SK, Dudhgaonkar SP, et al. Role of oxidative stress in pathophysiology of peripheral neuropathy and modulation by N-acetyl-l-cysteine in rats. Eur J Pain 2006; 10(7): 573-9.
[http://dx.doi.org/10.1016/j.ejpain.2005.08.006] [PMID: 16214382]
[65]
Horst A, de Souza J. Effects of N-acetylcysteine on spinal cord oxidative stress biomarkers in rats with neuropathic pain. Braz J Med Biol Res 2017; 50.
[66]
Hoffer E, Baum Y, Nahir AM. N-Acetylcysteine enhances the action of anti-inflammatory drugs as suppressors of prostaglandin production in monocytes. Mediators Inflamm 2002; 11(5): 321-3.
[http://dx.doi.org/10.1080/09629350210000015737] [PMID: 12467525]
[67]
Nakhaee S, Dastjerdi M, Roumi H, Mehrpour O, Farrokhfall K. N-acetylcysteine dose-dependently improves the analgesic effect of acetaminophen on the rat hot plate test. BMC Pharmacol Toxicol 2021; 22(1): 4.
[http://dx.doi.org/10.1186/s40360-020-00469-4] [PMID: 33413696]
[68]
Liu Y, Ni Y, Zhang W, Sun YE, Ma Z, Gu X. N-acetyl-cysteine attenuates remifentanil-induced postoperative hyperalgesia via inhibiting matrix metalloproteinase-9 in dorsal root ganglia. Oncotarget 2017; 8(10): 16988-7001.
[http://dx.doi.org/10.18632/oncotarget.15217] [PMID: 28199982]
[69]
Lakhan SE, Avramut M. Matrix metalloproteinases in neuropathic pain and migraine: Friends, enemies, and therapeutic targets. Pain Res Treat 2012; 2012: 952906.
[http://dx.doi.org/10.1155/2012/952906]
[70]
Amen SL, Piacentine LB, Ahmad ME, et al. Repeated N-acetyl cysteine reduces cocaine seeking in rodents and craving in cocaine-dependent humans. Neuropsychopharmacology 2011; 36(4): 871-8.
[http://dx.doi.org/10.1038/npp.2010.226] [PMID: 21160464]

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