ENHANCED EFFECTS OF CO-ADMINISTERED DEXAMETHASONE AND DICLOFENAC ON INFLAMMATORY PAIN PROCESSING AND ASSOCIATED SPINAL C-FOS EXPRESSION IN THE RAT

This Study determines the effects of dexamethasone versus co-administe red dexamethasone and diclofenac, on carrageenan-evoked spinal c-Fos e xpression and peripheral oedema in the freely moving rat. Drugs were a dministered intravenously 25 min before intraplantar injection of carr ageenan (6 mg/150 mu l of saline). Three hours later the number of spi nal c-Fos-LI neurones and peripheral oedema were assessed. The total n umber of control carrageenan-evoked c-Fos-LI neurones in the lumbar sp inal 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-admi nistered dexamethasone (0.05, 0.10 and 0.50 mg/kg i.v.) dose-dependent ly reduced the total number of c-Fos-LI neurones (30 +/- 4%, 52 +/- 3% and 58 +/- 2% reduction, respectively), with effects of the higher do ses 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 per ipheral oedema were positively correlated. Go-administration of low do ses of dexamethasone and diclofenac (0.025 + 1.5 mg/kg i.v. respective ly), which had negligible effects when administered separately, greatl y reduced both the total number of carrageenan-evoked c-Fos-LI neurone s (61 +/- 5% reduction as compared to control value) and the periphera l oedema (80 +/- 8% and 60 +/- 5% reduction for ankle and paw oedema, respectively). The attenuation by co-administered dexamethasone and di clofenac, of both c-Fos expression and the peripheral oedema, was sign ificantly greater than the effect of dexamethasone alone (P < 0.001 fo r both) and diclofenac alone (P < 0.001 for both). Our study illustrat es enhanced attenuating effects of co-administered dexamethasone and d iclofenac on both inflammatory oedema and the associated spinal expres sion of c-Fos, an indicator of nociceptive transmission at the spinal level. The apparent interactions between the mechanisms of action of N SAIDs and steroids suggest that co-therapy may produce beneficial infl ammatory and pain relief in the absence of excessive side effects.