Lowback Pain Management with a Combination of Uridine Triphosphate, Cytidine Monophosphate, and Hydroxocobalamin: A Systematic Review and Meta-Analysis

Abstract

Low back pain is a common complaint. This syndrome comprehends different underlying mechanisms, which are difficult to differentiate in a timely manner only through semiotic, laboratory, and imaging resources available in an emergency setting. Such circumstances make practitioners prone to an initial symptomatic approach in the form of medications (non-steroid anti-inflammatory drugs, analgesics, muscle relaxants) or local procedures (local heat, massage). Peripheral neurotrophic substances, such as pyrimidine nucleotides (uridine triphosphate and cytidine monophosphate) combined with vitamin B12 (hydroxocobalamin), have been used as anabolic precursors able to provide spinal nerve roots with triggering elements useful for nerve and glial cells regeneration, once a likely spinal compression mechanism is contained. The authors performed a systematic review and meta-analysis with the above combination with the aim of better determining its role in low back pain management.

Resumo

A dor lombar é uma queixa comum. Essa síndrome tem diferentes mecanismos subjacentes, difíceis de diferenciar em tempo hábil apenas por meio dos recursos semióticos, laboratoriais e de imagem disponíveis no atendimento de emergência. Isso faz com que os profissionais tendam a uma abordagem sintomática inicial composta por medicamentos (anti-inflamatórios não esteroidais, analgésicos, relaxantes musculares) ou procedimentos locais (calor local, massagem). Substâncias neurotróficas periféricas, como nucleotídeos de pirimidina (trifosfato de uridina e monofosfato de citidina) combinados com vitamina B12 (hidroxicobalamina), têm sido usadas como precursores anabólicos capazes de fornecer às raízes nervosas espinhais elementos desencadeadores úteis para a regeneração de neurônios e células da glia, uma vez que um provável mecanismo de compressão espinhal seja contido. Os autores realizaram uma revisão sistemática e meta-análise com a combinação acima com o objetivo de determinar melhor seu papel no tratamento da dor lombar.

Keywords

cytidine monophosphate - hydroxocobalamin - low back pain - spinal nerve roots - uridine triphosphate

Palavras-chave

dor lombar - hidroxocobalamina - monofosfato de citidina - raízes nervosas espinhais - uridina trifosfato

Publikationsverlauf

Eingereicht: 06. September 2024

Angenommen: 25. Oktober 2024

Artikel online veröffentlicht:
10. Juli 2025

• References

• 1 Prather H, van Dillen L. Links between the hip and the lumbar spine (hip spine syndrome) as they relate to clinical decision making for patients with lumbopelvic pain. PM R 2019; 11 (Suppl. 01) S64-S72
• 2 Casser HR, Seddigh S, Rauschmann M. Acute lumbar back pain. Dtsch Arztebl Int 2016; 113 (13) 223-234
• 3 Fleury G, Nissen MJ, Genevay S. Conservative treatments for lumbar radicular pain. Curr Pain Headache Rep 2014; 18 (10) 452
• 4 Moher D, Liberati A, Tetzlaff J, Altman DG. PRISMA Group. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. BMJ 2009; 339: b2535
• 5 RStudio Team. RStudio: Integrated Development for R (Version 4.2.1) [Software]. RStudio, PBC. Available from: http://www.rstudio.com/ . [accessed Aug 2023]
• 6 Brisby H. Nerve root injuries in patients with chronic low back pain. Orthop Clin North Am 2003; 34 (02) 221-230
• 7 Garfin SR, Rydevik B, Lind B, Massie J. Spinal nerve root compression. Spine 1995; 20 (16) 1810-1820
• 8 Davis G, Curtin CM. Management of pain in complex nerve injuries. Hand Clin 2016; 32 (02) 257-262
• 9 Houdek MT, Shin AY. Management and complications of traumatic peripheral nerve injuries. Hand Clin 2015; 31 (02) 151-163
• 10 Barnes SL, Miller TA, Simon NG. Traumatic peripheral nerve injuries: diagnosis and management. Curr Opin Neurol 2022; 35 (06) 718-727
• 11 Gunning PW, Kaye PL, Austin L. In vivo RNA synthesis within the rat nodose ganglia. J Neurochem 1977; 28 (06) 1237-1240
• 12 Neary JT, Rathbone MP, Cattabeni F, Abbracchio MP, Burnstock G. Trophic actions of extracellular nucleotides and nucleosides on glial and neuronal cells. Trends Neurosci 1996; 19 (01) 13-18
• 13 Oderfold-Nowak B, Niemierko S. Synthesis of nucleic acids in the Schwann cells as the early cellular response to nerve injury. J Neurochem 1969; 16 (02) 235-248
• 14 Pooler AM, Guez DH, Benedictus R, Wurtman RJ. Uridine enhances neurite outgrowth in nerve growth factor-differentiated PC12 [corrected]. [corrected] [published correction appears in Neuroscience 2005;135(2):657] Neuroscience 2005; 134 (01) 207-214
• 15 Canales TM. Estudio del fármaco CMP Forte y del nucleótido UTP en células de Schwann. Tesis Doctorales. Universitat Internacional de Catalunya. Departament de Medicina; 2011
• 16 Connolly GP, Duley JA. Uridine and its nucleotides: biological actions, therapeutic potentials. Trends Pharmacol Sci 1999; 20 (05) 218-225
• 17 Cansev M. Uridine and cytidine in the brain: their transport and utilization. Brain Res Brain Res Rev 2006; 52 (02) 389-397
• 18 G-Coviella IL, Wurtman RJ. Enhancement by cytidine of membrane phospholipid synthesis. J Neurochem 1992; 59 (01) 338-343
• 19 Pizzorno G, Cao D, Leffert JJ, Russell RL, Zhang D, Handschumacher RE. Homeostatic control of uridine and the role of uridine phosphorylase: a biological and clinical update. Biochim Biophys Acta 2002; 1587 (2-3): 133-144
• 20 Richardson UI, Watkins CJ, Pierre C, Ulus IH, Wurtman RJ. Stimulation of CDP-choline synthesis by uridine or cytidine in PC12 rat pheochromocytoma cells. Brain Res 2003; 971 (02) 161-167
• 21 Trovarelli G, Palmerini CA, Floridi A, Piccinin GL, Porcellati G. The transport of cytidine into rat brain in vivo, and its conversion into cytidine metabolites. Neurochem Res 1982; 7 (10) 1199-1207
• 22 Vecchini A, Binaglia L, Palmerini CA, Floridi A, Porcellati G. Cytidine uptake and utilization in primary culture from the rat brain. Ital J Biochem 1981; 30 (05) 367-374
• 23 Wang L, Albrecht MA, Wurtman RJ. Dietary supplementation with uridine-5′-monophosphate (UMP), a membrane phosphatide precursor, increases acetylcholine level and release in striatum of aged rat. Brain Res 2007; 1133 (01) 42-48
• 24 Goracci G, Francescangeli E, Horrocks LA, Porcellati G. The reverse reaction of cholinephosphotransferase in rat brain microsomes. A new pathway for degradation of phosphatidylcholine. Biochim Biophys Acta 1981; 664 (02) 373-379
• 25 Goracci G, Francescangeli E, Horrocks LA, Porcellati G. The effect of CMP on the release of free fatty acids of rat brain in vitro. Neurochem Res 1983; 8 (08) 971-981
• 26 Mibielli MA, Nunes CP, Cohen JC. et al. Treatment of acute, non-traumatic pain using a combination of diclofenac-cholestyramine, uridine triphosphate, cytidine monophosphate, and hydroxycobalamin. Proc West Pharmacol Soc 2010; 53: 5-12
• 27 Tanaka H. [Old or new medicine? Vitamin B12 and peripheral nerve neuropathy]. Brain Nerve 2013; 65 (09) 1077-1082
• 28 Voet D, Voet JG, Pratt CW. Fundamentos de Bioquímica. Porto Alegre: Artmed Editora; 2002
• 29 Goldberg H, Scussel Jr AB, Cohen JC. et al. Neural compression-induced neuralgias: clinical evaluation of the effect of nucleotides associated with vitamin B12. Rev Bras Med 2009; 66 (11) 380-385
• 30 Goldberg H, Mibielli MA, Nunes CP. et al. A double-blind, randomized, comparative study of the use of a combination of uridine triphosphate trisodium, cytidine monophosphate disodium, and hydroxocobalamin, versus isolated treatment with hydroxocobalamin, in patients presenting with compressive neuralgias. J Pain Res 2017; 10: 397-404
• 31 Mibielli MAN, Nunes CP, Goldberg H. et al. Nucleotides cytidine and uridine associated with vitamin B12 vs B-Complex vitamins in the treatment of lowback pain: The NUBES Study. J Pain Res 2020; 13: 2531-2541
• 32 Mibielli MA, Nunes CP, Scussel Júnior AB. et al. Symptomatic improvement in an acute, non-traumatic spine pain model with a combination of uridine triphosphate, cytidine monophosphate, and hydroxocobalamin. Pain Studies and Treatment 2014; 2 (01) 6-10