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Symptomatic Improvement in an Acute, Non-Traumatic Spine Pain Model with a Combination of Uridine Triphosphate, Cytidine Monophosphate, and Hydroxocobalamin

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Symptomatic Improvement in an Acute, Non-Traumatic Spine Pain Model with a Combination of Uridine Triphosphate, Cytidine Monophosphate, and Hydroxocobalamin Vol.2, No.1, 6-10 (2014) Pain Studies and Treatment http://dx.doi.org/10.4236/pst.2014.21002 Symptomatic improvement in an acute, non-traumatic spine pain model with a combination of uridine triphosphate, cytidine monophosphate, and hydroxocobalamin Marco Antonio Mibielli, Carlos Pereira Nunes, Ari Boulanger Scussel Jr., Mendel Suchmacher Neto, Lisa Oliveira, Mauro Geller* Teresópolis Medical School-UNIFESO, Rio de Janeiro, Brazil; *Corresponding Author: [email protected] Received 11 November 2013; revised 18 December 2013; accepted 8 January 2014 Copyright © 2014 Marco Antonio Mibielli et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. In accordance of the Creative Commons Attribution License all Copyrights © 2014 are reserved for SCIRP and the owner of the intellectual property Marco Antonio Mibielli et al. All Copyright © 2014 are guarded by law and by SCIRP as a guardian. ABSTRACT 1. INTRODUCTION Rationale: In a previously published trial on spi- In a previously published clinical trial by Mibielli et nal acute non-traumatic pain, peripheral neuro- al., on spinal acute non-traumatic pain [1], carried out in regenerative combination of UTP, CMP and hy- a double-blind comparative manner, the authors rando- droxocobalamin presented unexpected analgesic mized a sample of patients with non-traumatic lower properties. Objective: To corroborate analgesic back, hip, and neck pain into two groups: 1) group DN effects of UTP, CMP and hydroxocobalamin com- (nND = 40)—a combination of diclofenac-cholestyramine bination in a self-paired evolutionary model. Me- (equivalent to 70 mg of diclofenac) once daily + two thods: Mean VAS scores from pretreatment, V2 capsules with uridine triphosphate (UTP) 1.5 mg, cyti- (5th treatment day) and V3 (10th treatment day) dine monophosphate (CMP) 2.5 mg, and hydroxocoba- were plotted and statistically analyzed (ANOVA) lamin 1000 mcg, thrice daily, and 2) group NB (nNB = for differences. PFQ scores from pretreatment, 41)—two capsules with UTP 1.5 mg, CMP 2.5 mg, and V2, and V3 were analyzed using the chi-square hydroxocobalamin 1000 mcg, thrice daily. Their primary test. Results: The difference between V3 and objective was to evaluate the superiority of group DN pretreatment mean VAS scores was statistically over group NB, regarding pain visual analog scale (VAS), significant (p < 0.0001). The improvement in PFQ patient functionality questionnaire (PFQ), and overall scores throughout the study was found to be efficacy evaluation by the investigating physician. Group DN showed statistically significant better results in all statistically significant (p < 0.0001). Conclusion: three evaluated endpoints. The combination of UTP, CMP and hydroxoco- The original study reported on the results of a double- balamin seems to have analgesic properties in blind, randomized comparative trial comparing the ef- medium-term use. The complex peripheral neu- fects of treatment with the combination of diclofenac + roregenerative pharmacodynamics of this com- CMP + UTP + vitamin B12 versus the combination of bination provides a plausible basis for this only CMP + UTP + vitamin B12. Efficacy measures in- finding. Further randomized studies are needed cluded a 100 mm visual analog pain scale, in which each to explore this combination for the indication of subject placed a vertical mark along a 100 mm line from neuropathic pain due to spinal structure involve- 0 mm on the left side, corresponding to “no pain” to 100 ment. mm on the right side, corresponding to “most severe pain”. The scores were recorded as the distance from the KEYWORDS left side of the line (0 mm) to the subject’s mark. The Uridine Triphosphate; Cytidine Monophosphate; Patient Functionality Questionnaire was also used as an Hydroxocobalamin; Analgesia efficacy measure, in which one point was awarded to Copyright © 2014 SciRes. OPEN ACCESS M. A. Mibielli et al. / Pain Studies and Treatment 2 (2014) 6-10 7 each “Yes” answer to the following questions: Table 1. Demographic data. 1. Due to the pain in my (lower back/hips/neck): Demographic data Group NB 2. I do not sleep well 3. I have to lie down more often Gender 4. It is difficult for me to get up from my bed or a chair Female 17 5. I can stand only for a short while Male 24 6. I can walk up stairs only slowly 7. It is difficult for me to wash or dry off my whole Ethnicity body Asian 0 8. It is difficult for me to put on my clothes 9. I can only walk short distances Black 16 10.I try to avoid picking things up from the floor Caucasian 8 11. I have to change my posture more often 12. I cannot carry heavy things Mulatto 17 13. I have to ask other people for assistance Age (years) 46.29 (±0.908) The authors noticed an unexpected favorable perfor- mance of group NB, regarding mean pain VAS endpoint, Height (cm) 170.2 (±1.261) after publishing their paper. Seemingly, mean VAS score Weight (kg) 74.95 (±1.715) decreased at visit V2 (5th treatment day) in relation to Blood pressure (mmHg) pretreatment levels, and from V3 (10th treatment day) in relation to V2 and to pretreatment levels, in a self-paired Systolic 123.2 (±0.99) fashion. This finding sounded interesting, given that the Diastolic 79.9 (±1.294) combination of UTP, CMP and hydroxocobalamin was pharmacologicaly classified as peripheral neuroregenera- Heart rate (bpm) 70.27 (±0.849) tive, and no analgesic properties were attributed to it in Pain location medical literature. A new investigational process was Knee 9 then derived, in order to assess the clinical efficacy res- ponses obtained among the subjects of group NB. Hip 5 Lower back 27 2. METHODS We performed an analysis of previously unpublished deviation (SD). data from investigators’ files pertaining to the pain VAS Mean VAS scores at pretreatment in the NB patient and PFQ scores of the patient group treated with the group were 59.44 mm (±12.43). At Visit 2, mean VAS combination of UTP, CMP, and hydroxocobalamin scores decreased to 42.41 mm (±17.66), a reduction of (Group NB). The data was tabulated and statistical eval- 17.03 mm in mean total score in relation to pretreatment. uation was performed using GraphPad Prism software At Visit 3, mean VAS scores were 30.35 mm (±17.51), version 5.04. The VAS score results from Pretreatment, representing a further mean reduction of 12.06 mm in V2 (after 5 days of treatment), and V3 (after 10 days of relation to Visit 2, and a 28.29 mm reduction in relation treatment) were compared using the one-way repeated to pretreatment values. The difference in mean VAS measures analysis of variance (ANOVA). PFQ scores scores from pretreatment to V3 was statistically signifi- from Pretreatment, V2, and V3 were analyzed using the cant (p < 0.0001) (Figure 1). chi-square test. At Pretreatment, PFQ score median was 7 points, We also performed an updated literature review based while at Visit 2, score median decreased to 6 points and on a search of PubMed and SciElo using the search terms at Visit 3, score median was 4 points, indicating an im- “uridine + cytidine + hydroxocobalamin + analgesia”, provement in functionality during the treatment period. “uridine + analgesia”, “cytidine + analgesia”, “uridine + The improvement in PFQ scores throughout the study cytidine + analgesia” “nucleotides + analgesia”, “hy- was found to be statistically significant (χ2 = 60.74; DF = droxocobalamin + analgesia”, and “vitamin B12 + anal- 24; p < 0.0001) (Figure 2). gesia”. 4. DISCUSSION 3. RESULTS Pyrimidinic nucleotides UTP and CMP, plus hydrox- Briefly, the demographic data of the NB group is ocobalamin, are available as a peripheral neuroregene- summarized in Table 1, reported as n or mean ± standard rating combination. Pharmacological properties attri- Copyright © 2014 SciRes. OPEN ACCESS 8 M. A. Mibielli et al. / Pain Studies and Treatment 2 (2014) 6-10 becomes a plausible proposition. One can find a corres- pondence for this assumption in a study published by Goldberg et al. [21]. Actually, the present study partially reproduces the results from this former trial. In this comparative, double blinded study, the authors rando- mized a sample of patients with spinal and hip structural bone changes complicated with neural compression and neuropathic pain, into two groups: 1) group A-two cap- sules with UTP 1.5 mg, CMP 2.5 mg, and hydroxocoba- lamin 1000 mcg, thrice daily, and 2) group B- two cap- sules of hydroxocobalamin 1000 mcg, thrice daily. Re- sults from group A mean VAS scores and SD progression from pretreatment, V2, and V3, are detailed in a self- paired box-plot graph (Figure 3). The difference be- tween V3 (15) and pretreatment (58) VAS means was statistically significant (p < 0.0001). In a clinical assessment of patients presenting with al- coholic polyneuropathy, the combination of UTP, CMP Figure 1. Self-paired evolutionary performance of mean VAS and hydroxocobalamin was found to reduce pain, pares- scores in NB group (pretreatment, V2, and V3). thesia, altered motor coordination and altered vibration Distribution of PFQ Scores at each Study Visit perception among 120 subjects treated with a 6-day 15 intramuscular injection of: cytidine monophosphate Pretreatment Visit 2 (CMP) 5.0 mg; uridine triphosphate (UTP) 3.0 mg; hy- 10 Visit 3 droxocobalamin 2.0 mg; and lidocaine 20 mg (for local pain relief), followed by a 30-day treatment period of 5 thrice daily oral ingestion of: cytidine monophosphate (CMP) 2.5 mg; uridine triphosphate (UTP) 1.5 mg; hy- Number of PatientsNumber of 0 droxocobalamin 1.0 mg [22]. 0 1 2 3 4 5 6 7 8 9 10 11 12 Regarding analgesic capacity itself, pharmacological PFQ Score properties of two pyrimidinic nucleotides were experi- Figure 2.
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