TY - JOUR
T1 - Analysis of the opioid-opioid combinations according to the nociceptive stimulus in mice
AU - Romero, Asunción
AU - Miranda, Hugo F.
AU - Puig, Margarita M.
N1 - Funding Information:
We are grateful to Ms. Carolina Zamora for her excellent technical help. Financial support for this study was provided by grants from Instituto de Salud Carlos III, Madrid, Spain (PI 060669), La Marató de TV3 (071110) and the Endowed Chair in Pain Management UAB-IMAS-MENARINI (MMP).
PY - 2010/6
Y1 - 2010/6
N2 - The purpose of the present study was to characterize the antinociceptive effects of tramadol, fentanyl and morphine, when two of them were systemically combined in a 1:1 potency ratio, in the hot plate, the acetic acid writhing, and the formalin tests in mice. Interaction indexes and isobolographic analysis were used to assess the type of interaction. Fentanyl was the most potent drug, followed by morphine and tramadol, with the exception in the phase I of formalin test. Synergistic interactions were obtained when tramadol was combined with fentanyl or with morphine in the writhing and formalin tests. But, in the hot plate only additive interactions were obtained. Changes were induced on the type of interaction depending on the level of effect of opioid-opioid combinations. Moreover, co-administration of fentanyl with morphine showed additivity, regardless of the type of stimulus. Standard rotarod test analysis confirmed intact motor coordination. The present findings suggest that the type of interaction between opioids is not only related to the nature of nociceptive stimulus but also to non-opioid analgesic pathways.
AB - The purpose of the present study was to characterize the antinociceptive effects of tramadol, fentanyl and morphine, when two of them were systemically combined in a 1:1 potency ratio, in the hot plate, the acetic acid writhing, and the formalin tests in mice. Interaction indexes and isobolographic analysis were used to assess the type of interaction. Fentanyl was the most potent drug, followed by morphine and tramadol, with the exception in the phase I of formalin test. Synergistic interactions were obtained when tramadol was combined with fentanyl or with morphine in the writhing and formalin tests. But, in the hot plate only additive interactions were obtained. Changes were induced on the type of interaction depending on the level of effect of opioid-opioid combinations. Moreover, co-administration of fentanyl with morphine showed additivity, regardless of the type of stimulus. Standard rotarod test analysis confirmed intact motor coordination. The present findings suggest that the type of interaction between opioids is not only related to the nature of nociceptive stimulus but also to non-opioid analgesic pathways.
KW - Isobolographic analysis
KW - Nociceptive stimulus
KW - Opioid-opioid interaction
UR - http://www.scopus.com/inward/record.url?scp=77952885754&partnerID=8YFLogxK
U2 - 10.1016/j.phrs.2010.02.011
DO - 10.1016/j.phrs.2010.02.011
M3 - Article
C2 - 20206265
AN - SCOPUS:77952885754
SN - 1043-6618
VL - 61
SP - 511
EP - 518
JO - Pharmacological Research
JF - Pharmacological Research
IS - 6
ER -