Drug Res (Stuttg) 2013; 63(06): 289-292
DOI: 10.1055/s-0033-1334963
Original Article
© Georg Thieme Verlag KG Stuttgart · New York

B-vitamin Mixture Improves the Analgesic Effect of Diclofenac in Patients with Osteoarthritis: A Double Blind Study

M. C. Magaña-Villa
1   Hospital de Ortopedia Magdalena de las Salinas, Instituto Mexicano del Seguro Social, Mexico City, Mexico
,
H. I. Rocha-González
2   Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina, Instituto Politécnico Nacional, Mexico City, Mexico
,
C. Fernández del Valle-Laisequilla
2   Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina, Instituto Politécnico Nacional, Mexico City, Mexico
,
V. Granados-Soto
3   Departamento de Farmacobiología, Cinvestav, Sede Sur, Mexico City, Mexico
,
J. Rodríguez-Silverio
2   Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina, Instituto Politécnico Nacional, Mexico City, Mexico
,
F. J. Flores-Murrieta
2   Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina, Instituto Politécnico Nacional, Mexico City, Mexico
4   Instituto Nacional de Enfermedades Respiratorias, Secretaría de Salud, Mexico City, Mexico
,
M. C. Carrasco-Portugal
4   Instituto Nacional de Enfermedades Respiratorias, Secretaría de Salud, Mexico City, Mexico
,
J. G. Reyes-García
2   Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina, Instituto Politécnico Nacional, Mexico City, Mexico
› Author Affiliations
Further Information

Publication History

received 28 October 2012

accepted 08 February 2013

Publication Date:
22 March 2013 (online)

Abstract

According to the high consumption of the mixture of B vitamins and diclofenac in several countries, this combination has constituted a frequently used option in pain therapy from inflammatory origin. Although the evidence obtained from inflammatory pain animal models has shown the existence of analgesic synergy between diclofenac and the B vitamins mixture, the corresponding clinical evidence is scarce. A double-blind, randomized clinical trial study was designed to characterize the analgesic effect and safety of diclofenac and B vitamins against diclofenac alone in patients with severe osteoarthritis. Forty eight patients programmed to total knee arthroplasty with a pain level ≥7 in a 1–10 cm visual analogue scale were allocated to receive a single intramuscular injection of sodium diclofenac (75 mg) alone or combined with thiamine (100 mg), pyridoxine (100 mg) and cyanocobalamin (5 mg), and the pain level was evaluated during 12 h post-injection. Diclofenac+B vitamins mixture showed a superior analgesic effect during the assessed period and also a better assessment of the pain relief perception by patients than diclofenac alone. This study constitutes a clinical support on the improvement of the analgesic effect of diclofenac by B vitamins in patients with osteoarthritis programmed to total knee arthroplasty, as a clinical model of inflammatory pain.

 
  • References

  • 1 Menassé R, Hedwall PR, Kraetz J et al. Pharmacological properties of diclofenac sodium and its metabolites. Scand J Rheumatol Suppl 1978; 22: 5-16
  • 2 Skoutakis VA, Carter CA, Mickle TR et al. Review of diclofenac and evaluation of its place in therapy as a nonsteroidal antiinflammatory agent. Drug Intell Clin Pharm 1988; 22: 850-859
  • 3 Roth SH, Bennett RE, Caldron PH et al. Endoscopic evaluation of the long term effects of diclofenac sodium and naproxen in elderly patients with arthritis. Clin Drug Invest 1995; 9: 171-179
  • 4 Marcus R, Coulston AM. The vitamin B complex and ascorbic acid. In: Hardman JG, Limbird LE, Molinoff PB, Ruddon RW, Gilman AG. (eds.). Goodman & Gilman’s the pharmacological basis of therapeutics, Water-soluble vitamins. New York: McGraw-Hill; 1996. p 1555-1572
  • 5 Reyes-García G, Medina-Santillán R, Flores-Murrieta FJ et al. Analgesic effects of B vitamins: a review. Curr Top Pharmacol 2006; 10: 1-31
  • 6 Reyes-García G, Medina-Santillán R, Terán-Rosales F et al. Characterization of the potentiation of the antinociceptive effect of diclofenac by vitamin B complex in the rat. J Pharmacol Toxicol Methods 1999; 42: 73-77
  • 7 Reyes-García G, Medina-Santillán R, Terán-Rosales F et al. Analgesic effect of B vitamins in formalin-induced inflammatory pain. Proc West Pharmacol Soc 2001; 44: 139-140
  • 8 França DS, Souza AL, Almeida KR et al. B vitamins induce an antinociceptive effect in the acetic acid and formaldehyde models of nociception in mice. Eur J Pharmacol 2001; 421: 157-164
  • 9 Reyes-García G, Medina-Santillán R, Terán-Rosales F et al. B vitamins increase the anti-hyperalgesic effect of diclofenac in the rat. Proc West Pharmacol Soc 2002; 45: 147-149
  • 10 Medina-Santillán R, Pérez-Flores E, Mateos-García E et al. A B-vitamin mixture reduces the requirements of diclofenac after tonsillectomy: a double-blind study. Drug Dev Res 2006; 66: 36-39
  • 11 Vetter G, Brüggemann G, Lettko M et al. Shortening diclofenac therapy by B vitamins. Results of a randomized double-blind study, diclofenac 50 mg versus diclofenac 50 mg plus B vitamins, in painful spinal diseases with degenerative changes. Z Rheumatol 1988; 47: 351-362
  • 12 Kuhlwein A, Meyer HJ, Koehler CO. Reduced diclofenac administration by B vitamins: results of a randomized double-blind study with reduced daily doses of diclofenac (75 mg diclofenac versus 75 mg diclofenac plus B vitamins) in acute lumbar vertebral syndromes. Klin Wochenschr 1990; 68: 107-115
  • 13 Bromm K, Herrmann WM, Schulz H. Do the B-vitamins exhibit antinociceptive efficacy in men? Results of a placebo-controlled repeated-measures double-blind study. Neuropsychobiology 1995; 31: 156-165
  • 14 Mibielli MA, Geller M, Cohen JC et al. Diclofenac plus B vitamins versus diclofenac monotherapy in lumbago: the DOLOR study. Curr Med Res Opin 2009; 25: 2589-2599
  • 15 Ponce-Monter HA, Ortiz MI, Garza-Hernández AF et al. Effect of diclofenac with B vitamins on the treatment of acute pain originated by lower-limb fracture and surgery. Pain Res Treat 2012; 1: 1-5
  • 16 Archibeck MJ, Berber RA, Garvin KL et al. Knee reconstruction. In: Koval KJ. (eds.). Orthopaedic Knowledge Update 7. Am Acad Orthop Surg. 2002. 513-520
  • 17 Melzer D, Guralnik JM, Brock D. Prevalence and distribution of hip and knee joint replacements and hip implants in older Americans by the end of life. Aging Clin Exp Res 2003; 15: 60-66
  • 18 World Medical Association Inc. Declaration of Helsinki – Ethical principles for medical research involving human subjects. Available from http://www.wma.net/en/30publications/10policies/b3/. Accessed: February 2, 2012
  • 19 Medina-Santillán R, Reyes-García G, Rocha-González HI et al. B vitamins increase the analgesic effect of ketorolac in the formalin test in the rat. Proc West Pharmacol Soc 2004; 47: 95-99
  • 20 Caram-Salas NL, Reyes-García G, Medina-Santillán R et al. Thiamine and cyanocobalamin relieve neuropathic pain in rats: synergy with dexamethasone. Pharmacology 2006; 77: 53-62
  • 21 Hosseinzadeh H, Moallem SA, Moshiri M et al. Anti-nociceptive and anti-inflammatory effects of cyanocobalamin (vitamin B12) against acute and chronic pain and inflammation in mice. Arzneimittelforschung 2012; 62: 324-329
  • 22 Altman R. International experiences with diclofenac in osteoarthritis. Am J Med 1986; 80: 48-52
  • 23 Ward JR. Efficacy of diclofenac in osteoarthritis. Experience in the United States. Am J Med 1986; 80: 53-57
  • 24 Euchenhofer C, Maihófner C, Brune K et al. Differential effect of selective cyclooxygenase-2 (COX-2) inhibitor NS 398 and diclofenac on formalin-induced nociception in the rat. Neurosci Lett 1998; 248: 25-28
  • 25 Ortiz MI, Torres-López JE, Castañeda-Hernández G et al. Pharmacological evidence for the activation of K+ channels by diclofenac. Eur J Pharmacol 2002; 438: 85-91
  • 26 Ortiz MI, Castañeda-Hernández G, Granados-Soto V. Possible involvement of potassium channels in peripheral antinociception induced by metamizol: lack of participation of ATP-sensitive K+ channels. Pharmacol Biochem Behav 2003; 74: 465-470
  • 27 Gan TJ. Diclofenac: an update on its mechanism of action and safety profile. Curr Med Res Opin 2010; 26: 1715-1731
  • 28 Zimmerman M, Bartoszyk GD, Bonke D et al. Antinociceptive properties of pyridoxine. Neurophysiological and behavioral findings. Ann N Y Acad Sci 1990; 585: 219-230
  • 29 Reyes-García G, Castillo-Henkel C, Medina-Santillán R et al. Mechanisms of analgesic action of B vitamins in formalin-induced inflammatory pain. Proc West Pharmacol Soc 2002; 45: 144-146