Document Detail

Additive interaction between peripheral and central mechanisms involved in the antinociceptive effect of diclofenac in the formalin test in rats.
MedLine Citation:
PMID:  18602417     Owner:  NLM     Status:  MEDLINE    
It has been proposed that the antinociception of systemic diclofenac is the outcome of peripheral and central actions. Hence, our purpose was to examine if systemic diclofenac is able to achieve effective concentrations at local and spinal sites and to characterize the interaction between its local and spinal actions. Pain was produced in the rat using the formalin test. Oral diclofenac (1-10 mg/kg) reduced formalin-induced pain. The antinociceptive effect of oral diclofenac (10 mg/kg) was abolished by local or spinal administration of either L-NAME (1-100 microg and 1-50 microg) or glibenclamide (12.5-100 microg and 25-75 microg). These results suggest that oral diclofenac achieves effective concentrations producing an antinociceptive effect involving participation of the NO-potassium channel pathway at both, the local and spinal levels. In an additional experimental series, diclofenac was administered either locally (25-200 microg) or spinally (12.5-100 microg), yielding an antinociceptive effect by both routes. Then, diclofenac was given simultaneously by these two routes in a fixed-ratio, and antinociception was assayed. Isobolographic analysis revealed an additive interaction between the local and spinal effects of diclofenac. Hence, our results provide evidence that the overall antinociceptive effect induced by systemic diclofenac is the outcome of central and peripheral mechanisms.
Mario I Ortiz; Jair Lozano-Cuenca; Vinicio Granados-Soto; Gilberto Castañeda-Hernández
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Publication Detail:
Type:  Journal Article     Date:  2008-06-18
Journal Detail:
Title:  Pharmacology, biochemistry, and behavior     Volume:  91     ISSN:  0091-3057     ISO Abbreviation:  Pharmacol. Biochem. Behav.     Publication Date:  2008 Nov 
Date Detail:
Created Date:  2008-09-05     Completed Date:  2008-11-06     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0367050     Medline TA:  Pharmacol Biochem Behav     Country:  United States    
Other Details:
Languages:  eng     Pagination:  32-7     Citation Subset:  IM    
Area Académica de Medicina del Instituto de Ciencias de la Salud, Universidad Autónoma del Estado de Hidalgo, Pachuca, Hidalgo, Mexico.
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MeSH Terms
Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
Area Under Curve
Central Nervous System / drug effects*
Diclofenac / pharmacology*
Enzyme Inhibitors / pharmacology
Formaldehyde / diagnostic use*
NG-Nitroarginine Methyl Ester / pharmacology
Nitric Oxide / physiology
Nitric Oxide Synthase / antagonists & inhibitors
Pain Measurement / drug effects*
Peripheral Nervous System / drug effects*
Potassium Channels / physiology
Rats, Wistar
Spinal Cord / drug effects,  physiology
Reg. No./Substance:
0/Anti-Inflammatory Agents, Non-Steroidal; 0/Enzyme Inhibitors; 0/Potassium Channels; 10102-43-9/Nitric Oxide; 15307-86-5/Diclofenac; 50-00-0/Formaldehyde; 50903-99-6/NG-Nitroarginine Methyl Ester; EC Oxide Synthase

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