TY - JOUR
T1 - Antiallodynic interaction and motor performance of the pregabalin/thioctic acid and pregabalin/α-tocopherol combinations in neonatal streptozotocin-induced diabetic rats
AU - Cruz-Álvarez, Lidia Elizabeth de la
AU - Zúñiga-Romero, Ángel
AU - Huerta-Cruz, Juan Carlos
AU - Flores-Murrieta, Francisco Javier
AU - Reyes-García, Juan Gerardo
AU - Araiza-Saldaña, Claudia Ivonne
AU - Rocha-González, Héctor Isaac
N1 - Publisher Copyright:
© 2018 Wiley Periodicals, Inc.
PY - 2018/11
Y1 - 2018/11
N2 - Painful peripheral neuropathy can be associated with nerve damage caused by diabetes mellitus. Although pregabalin is the first-line therapy for peripheral neuropathy, it shows substantial discontinuation rates, mainly because of nervous system side effects as motor incoordination. Multimodal therapy may improve the motor side effect profile of pregabalin. The aim of this study was to evaluate the interaction of pregabalin + thioctic acid or pregabalin + α-tocopherol on allodynia and motor performance in neonatal streptozotocin-induced diabetic rats. Efficacy of drugs separately or in combination was tested by tactile allodynia using von Frey filaments. Isobolographic and interaction index analysis were used to determine the antiallodynic interaction between pregabalin and either thioctic acid or α-tocopherol. Motor performance was measured using a rotarod test. Pregabalin, thioctic acid, and α-tocopherol reduced, in a dose-dependent fashion, tactile allodynia. Pregabalin + thioctic acid and pregabalin + α-tocopherol combinations also dose-dependently reduced allodynic behavior in diabetic rats. Isobolographic analysis revealed an additive interaction for both combinations. Consistently, the interaction indices confirmed the additive effect between pregabalin + thioctic acid and pregabalin + α-tocopherol. In addition, the administration of either combination improved motor incoordination induced by pregabalin. Data suggests that thioctic acid or α-tocopherol could positively impact the therapeutic profile of pregabalin, because they might be useful for reducing motor incoordination associated to pregabalin in patients with peripheral neuropathy.
AB - Painful peripheral neuropathy can be associated with nerve damage caused by diabetes mellitus. Although pregabalin is the first-line therapy for peripheral neuropathy, it shows substantial discontinuation rates, mainly because of nervous system side effects as motor incoordination. Multimodal therapy may improve the motor side effect profile of pregabalin. The aim of this study was to evaluate the interaction of pregabalin + thioctic acid or pregabalin + α-tocopherol on allodynia and motor performance in neonatal streptozotocin-induced diabetic rats. Efficacy of drugs separately or in combination was tested by tactile allodynia using von Frey filaments. Isobolographic and interaction index analysis were used to determine the antiallodynic interaction between pregabalin and either thioctic acid or α-tocopherol. Motor performance was measured using a rotarod test. Pregabalin, thioctic acid, and α-tocopherol reduced, in a dose-dependent fashion, tactile allodynia. Pregabalin + thioctic acid and pregabalin + α-tocopherol combinations also dose-dependently reduced allodynic behavior in diabetic rats. Isobolographic analysis revealed an additive interaction for both combinations. Consistently, the interaction indices confirmed the additive effect between pregabalin + thioctic acid and pregabalin + α-tocopherol. In addition, the administration of either combination improved motor incoordination induced by pregabalin. Data suggests that thioctic acid or α-tocopherol could positively impact the therapeutic profile of pregabalin, because they might be useful for reducing motor incoordination associated to pregabalin in patients with peripheral neuropathy.
KW - allodynia, diabetes, isobologram, motor performance, pregabalin, thioctic acid
KW - α-tocopherol
UR - http://www.scopus.com/inward/record.url?scp=85054186366&partnerID=8YFLogxK
U2 - 10.1002/ddr.21473
DO - 10.1002/ddr.21473
M3 - Artículo
C2 - 30276837
SN - 0272-4391
VL - 79
SP - 362
EP - 369
JO - Drug Development Research
JF - Drug Development Research
IS - 7
ER -