We use cookies to improve your experience. By continuing to browse this site, you accept our cookie policy.×
Skip main navigation
Aging Health
Bioelectronics in Medicine
Biomarkers in Medicine
Breast Cancer Management
CNS Oncology
Colorectal Cancer
Concussion
Epigenomics
Future Cardiology
Future Medicine AI
Future Microbiology
Future Neurology
Future Oncology
Future Rare Diseases
Future Virology
Hepatic Oncology
HIV Therapy
Immunotherapy
International Journal of Endocrine Oncology
International Journal of Hematologic Oncology
Journal of 3D Printing in Medicine
Lung Cancer Management
Melanoma Management
Nanomedicine
Neurodegenerative Disease Management
Pain Management
Pediatric Health
Personalized Medicine
Pharmacogenomics
Regenerative Medicine

Effect of the combination of uridine nucleotides, folic acid and vitamin B12 on the clinical expression of peripheral neuropathies

    Luis Negrão

    *Author for correspondence:

    E-mail Address: luisnegraoster@gmail.com

    Service of Neurology. Hospital Universitario. Ladeira da Porteladinha, No. 46, 3030-203 Coimbra, Portugal

    ,
    Pedro Almeida

    USF São Jõao Junqueira. Vila do Conde, Portugal

    ,
    Sérgio Alcino

    Service of Reumathology. Hospital of Ponte de Lima. Ponte de Lima, Portugal

    ,
    Helena Duro

    Clinica Fisiatrica Antas. Porto, Portugal

    , ,
    Ulisses Melo Silva

    Service of Orthopedics. Hospital São Teutónio. Viseu, Portugal

    ,
    Ricardo Figueira

    Service of Reumathology. Hospital Nélio Mendonça. Funcha, Portugal

    , &
    Published Online:https://doi.org/10.2217/pmt.14.10

    SUMMARY: 

    Aims: Peripheral neuropathy (PN) is a common condition whose incidence is approximately 8% in elderly persons. Neuropathic pain (NeP) has a significant incidence in the general population and affects more than half of all patients with PN. The pathophysiology of PN is characterized by lesions of myelin-producing Schwann cells in peripheral nerves. Regeneration/protection of the myelin sheath after a nerve lesion is a fundamental element of repair in PN. Nucleotides such as uridine monophosphate (UMP) have proven to be efficacious in treating the cause of the myelin sheath lesion in several experimental and clinical models. Our objective was to evaluate clinical improvement in patients with PN and NeP treated with a combination of UMP+folic acid+vitamin B12 (Keltican®). Patients and Methods: We performed an exploratory, open-label, multicenter, study of 212 patients followed for 2 months. Pain was assessed using the painDETECT questionnaire (PDQ). Results: The intensity of the NeP assessed at the time of the consultation progressed favorably and decreased significantly (p<0.001) in all the types of PN included. The global score for pain assessed using PDQ decreased from 17.5 points to 8.8 points at the final evaluation (p<0.001). Nonsteroidal anti-inflammatory drugs were decreased/withdrawn in 77.4% of patients. Conclusions: The combination of UMP+folic acid+vitamin B12 is effective against NeP associated with PN. It leads to statistically significant reductions not only in the total PDQ score but also in the intensity of pain, number of areas affected, and pain radiation. Furthermore, it makes it possible to reduce the dosage of concomitant medication.

    References

    • 1 Hughes RA. Peripheral neuropathy. BMJ 324(7335), 466–469 (2002). 
    • 2 Martyn CN, Hughes RA. Epidemiology of peripheral neuropathy. J. Neurol. Neurosurg. Psychiatr. 62(4), 310–318 (1997).
    • 3 Peripheral Neuropathy (3rd Edition). Dick PJ, Thomas PK, Griffin JW, Low PA, Poduslo JF (Eds). WB Saunders, Philadelphia, PA, USA, 747–775 (1993). 
    • 4 Dyck PJ, Kratz KM, Karnes JL et al. The prevalence by staged severity of various types of diabetic neuropathy, retinopathy and neuropathy in a population-based cohort: the Rochester Diabetic Neuropathy Study. Neurology 43(4), 817–824 (1993). 
    • 5 Berger A, Dukes EM, Oster G. Clinical characteristics and economics costs of patients with painful neuropathic disorders. J. Pain 5(3), 143–149 (2004). 
    • 6 Turk DC. Clinical effectiveness and cost-effectiveness of treatments for patients with chronic pain. Clin. J. Pain 18(6), 355–365 (2002). 
    • 7 Dick PJ, Oviatt KF, Lambert EH. Intensive evaluation of referred unclassified neuropathies yields improved diagnosis. Ann. Neurol. 10(3), 222–226 (1981). 
    • 8 Toth C, Au S. A prospective identification of neuropathic pain in specific polyneuropathy syndromes and response to pharmacological therapy. Pain 138(3), 657–666 (2008). 
    • 9 McDermott AM, Toelle TR, Rowbotham DJ, Schaefer CP, Dukes EM. The burden of neuropathic pain: results from a cross-sectional survey. Eur. J. Pain 10(2), 127–135 (2006). 
    • 10 Ide C. Peripheral nerve regeneration. Neurosci. Res. 25(2), 101–121 (1996). 
    • 11 Navarro X, Vivó M, Valero-Cabré A. Neural plasticity after peripheral nerve injury and regeneration. Prog. Neurobiol. 82(4), 163–201 (2007). 
    • 12 Wattig B, Schalow G, Heydenreich F, Warzok R, Cervós-Navarro J. Enhancement of nerve fibre regeneration by nucleotides after peripheral nerve crush damage. Electrophysiologic and morphometric investigations. Arzneimittelforschung 42, 1075–1078 (1992). 
    • 13 Wattig B, Schalow G, Madauss M, Heydenreich F, Warzok R, Cervós-Navarro J. Acceleration of nerve and muscle regeneration by administration of nucleotides – electroneurophysiological and morphometrical investigations. Acta Histochem. Suppl. 42, 333–339 (1992).. 
    • 14 Okada M, Nakagawa T, Minami M, Satoh M. Analgesic effects of intrathecal administration of P2Y nucleotide receptor agonists UTP and UDP in normal and neuropathic pain model in rats. J. Pharmacol. Exp. Ther. 303(1), 66–73 (2002).. 
    • 15 Andó RD, Méhész B, Gyires K, Illes P, Sperlágh B. A comparative analysis of the activity of ligands acting at P2X and P2Y receptor subtypes in models of neuropathic, acute and inflammatory pain. Br. J. Pharmacol. 159(5), 1106–1117 (2010). 
    • 16 Martiañez T, Carrascal M, Lamarca A et al. UTP affects the Schwannoma cell line proteome through P2Y receptors leading to cytoskeletal reorganisation. Proteomics 12(1), 145–156 (2012). 
    • 17 Müller D. Treatment of neuropathic pain syndrome: results of an open study on the efficacy of a pyrimidine nucleotide preparation. Fortschr. Med. Orig. 120(4), 131–133 (2002). 
    • 18 Gallai V, Mazzotta G, Montesi S, Sarchielli P, Del Gatto F. Effects of uridine in the treatment of diabetic neuropathy: an electrophysiological study. Acta Neurol. Scand. 86(1), 3–7 (1992). 
    • 19 Cartier L, Castillo JL, Verdugo R. Effect of the Nucleus CMP forte in 46 patients with progressive spastic paraparesis. Randomized and blind study. Rev. Med. Chil. 124(5), 583–587 (1996). 
    • 20 Larm G, Ruckert U. [Neurotropic nutrients promote recovery after intervertebral disc operations]. Extracta Ortho. 2, 44–45 (2008). 
    • 21 Peres-Serra J, Grau-Veciana JM, Barraquer-Bordás L. Therapeutic results of an association of CMP, UTP and vitamin B12 in 50 cases of peripheral neuropathy. N. Engl. J. Med. 6(64), (1972). 
    • 22 Keltican®. Prescribing information in Portugal.
    • 23 Freynhagen R, Baron R, Gockel U, Tölle TR. painDETECT: a new screening questionnaire to identify neuropathic components in patients with back pain. Curr. Med. Res. Opin. 22(10), 1911–1920 (2006).. 
    • 24 Perucca E, Berlowitz D, Birnbaum A et al. Pharmacological and clinical aspects of antiepileptic drug use in the elderly. Epilepsy Res. 68S, S49–S63 (2006).. 
    • 25 Blanco Tarrio E, Gálvez Mateos R, Zamorano Bayarri E, López Gómez V, Pérez Páramo M. Effectiveness of pregabalin as monotherapy or combination therapy for neuropathic pain in patients unresponsive to previous treatments in a Spanish primary care setting. Clin. Drug Investig. 33(9), 633–645 (2013).