Enhanced effects of co-administered dexamethasone and diclofenac on inflammatory pain processing and associated spinal c-Fos expression in the rat

Abstract

This study determines the effects of dexamethasone versus co-administered dexamethasone and diclofenac, on carrageenan-evoked spinal c-Fos expression and peripheral oedema in the freely moving rat. Drugs were administered intravenously 25 min before intraplantar injection of carrageenan (6 mg/150 microliters of saline). Three hours later the number of spinal c-Fos-LI neurones and peripheral oedema were assessed. The total number of control carrageenan-evoked c-Fos-LI neurones in the lumbar spinal cord was 121 +/- 5 labelled neurones per section, segments L4-L5, which were predominantly located in the superficial and deep laminae (41 +/- 3% and 40 +/- 2% of the total number of c-Fos-LI neurones per section, respectively) of the dorsal horn of the spinal cord. Pre-administered dexamethasone (0.05, 0.10 and 0.50 mg/kg i.v.) dose-dependently reduced the total number of c-Fos-LI neurones (30 +/- 4%, 52 +/- 3% and 58 +/- 2% reduction, respectively), with effects of the higher doses being strongest on the deep laminae c-Fos-LI neurones. The effects of dexamethasone on the total number of c-Fos-LI neurones and the peripheral oedema were positively correlated. Co-administration of low doses of dexamethasone and diclofenac (0.025 + 1.5 mg/kg i.v. respectively), which had negligible effects when administered separately, greatly reduced both the total number of carrageenan-evoked c-Fos-LI neurones (61 +/- 5% reduction as compared to control value) and the peripheral oedema (80 +/- 8% and 60 +/- 5% reduction for ankle and paw oedema, respectively). The attenuation by co-administered dexamethasone and diclofenac, of both c-Fos expression and the peripheral oedema, was significantly greater than the effect of dexamethasone alone (P < 0.001 for both) and diclofenac alone (P < 0.001 for both). Our study illustrates enhanced attenuating effects of co-administered dexamethasone and diclofenac on both inflammatory oedema and the associated spinal expression of c-Fos, an indicator of nociceptive transmission at the spinal level. The apparent interactions between the mechanisms of action of NSAIDs and steroids suggest that co-therapy may produce beneficial inflammatory and pain relief in the absence of excessive side effects.

Evaluation of fatty acid amides in the carrageenan-induced paw edema model

“…DIC was injected 30 min before carrageenan and DEX was injected 1 h before carrageenan. These doses and administration times were based on previous reports (Amann and Schuligoi, 2000;Buritova et al, 1996) and pilot studies in our laboratory in which these doses and time points maximally decreased edema in the carrageenan model. Next, the effects of AEA (50 mg/kg), PEA (50 mg/kg), OEA (50 mg/kg), THC (50 mg/kg), DEX (10 mg/kg), and DIC (5 mg/kg) were tested in FAAH (-/-) mice to determine if they would augment the anti-edema phenotype.…”

Assessment of the drug loading, in vitro and in vivo release behavior of novel pH-sensitive hydrogel

“…For example, it could achieve good results in the treatment of ulcerative colitis (Fedorak et al, 1995;Buritova et al, 1996;Van Meeteren et al, 2000;Keely et al, 2009;Webber et al, 2012). However, due to the hydrophobicity, its in vivo release behavior and function were limited.…”

Antinociceptive Effect of Amygdalin Isolated from <i>Prunus armeniaca</i> on Formalin-Induced Pain in Rats

“…14) Formalin injection into the plantar surface of the hind paw dramatically increases spinal Fos expression, while the intracerebroventricular injection of morphine dose-dependently reduces it. 41) Analgesic drugs such as dexamethasone 42) and aspirin 43) also lower spinal Fos expression induced by nociceptive stimuli. In Fos expression in the spinal cord, the superficial dorsal horn, which is involved in nociceptive signaling, is the most important area in the formalin-induced pain behavior.…”