Antinociceptive synergy between dexamethasone and the B vitamin complex in a neuropathic pain model in the rat.
The combination of dexamethasone and B-vitamins is widely used in Mexico to treat neuropathic pain in human beings. However, so far there is no evidence in preclinical models about the efficacy of this combination. The purpose of this study was to assess the possible synergistic interaction between dexamethasone and the B-vitamin complex in a neuropathic pain model in the rat. Neuropathic pain was induced by ligation of the left L5 and L6 spinal nerves in female Wistar rats. Tactile allodynia was determined by measuring paw withdrawal in response to probing with a series of calibrated von Frey filaments. Dexamethasone (4-32 mg/kg), B-vitamins (75-600 mg/kg), or a combination of dexamethasone and B-vitamins (100:100:1 of vitamin B1, B6 and B12, respectively) was administered subcutaneously and the antiallodynic effect was determined. Isobolographic analyses were used to define the nature of the functional interactions between dexamethasone and B-vitamins (0.5:0.5). Dexamethasone (ED30 5.4+/-1.2 mg/kg), B-vitamins (ED30 181.1+/-2.6 mg/kg), and fixed-dose ratio dexamethasone-B-vitamins combinations dose-dependently reduced tactile allodynia in the rat. Theoretical ED30 value for the combination estimated from the isobologram was 128.2+/-5.8 mg/kg. This value was significantly higher than experimental ED30 value which was 21.8+/-2.3 mg/kg. Results indicate that subcutaneous administration of dexamethasone and B-vitamins interacted synergistically to reduce tactile allodynia in the rat and suggest the use of this combination to reduce neuropathic pain in humans.
Caram-Salas
Nadia L
NL
Departamento de Farmacobiología, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, México, DF, Mexico.
Medina-Santillán
Roberto
R
Reyes-García
Gerardo
G
Granados-Soto
Vinicio
V
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000494:pharmacology*; D003907:Dexamethasone / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D005260:Female; D007279:Injections, Subcutaneous; D008026:Ligation; D010147:Pain Measurement / Q000187:drug effects*; D010523:Peripheral Nervous System Diseases / Q000150:complications*; D010812:Physical Stimulation; D051381:Rats; D017208:Rats, Wistar; D013127:Spinal Nerves / Q000473:pathology / Q000502:physiology; D014803:Vitamin B Complex / Q000494:pharmacology*
D000893:Anti-Inflammatory Agents; D014803:Vitamin B Complex; D003907:Dexamethasone