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

• Published in: Pain (Amsterdam) Vol. 64; no. 3; pp. 559 - 568
• Main Authors: Buritova, Jaroslava, Honoré, Prisca, Chapman, Victoria, Besson, Jean-Marie
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 01.03.1996; Elsevier
• Subjects: Analgesics; Animals; Anti-Inflammatory Agents - pharmacology; Anti-Inflammatory Agents - therapeutic use; Anti-Inflammatory Agents, Non-Steroidal - pharmacology; Anti-Inflammatory Agents, Non-Steroidal - therapeutic use; Biological and medical sciences; c-Fos; Carrageenan; Dexamethasone; Dexamethasone - pharmacology; Dexamethasone - therapeutic use; Diclofenac; Diclofenac - pharmacology; Diclofenac - therapeutic use; Dose-Response Relationship, Drug; Drug Synergism; Edema - chemically induced; Edema - drug therapy; Edema - physiopathology; Immunohistochemistry; Inflammation - chemically induced; Inflammation - drug therapy; Inflammation - physiopathology; Inflammatory pain; Male; Medical sciences; Neuropharmacology; Pain - physiopathology; Pharmacology. Drug treatments; Proto-Oncogene Proteins c-fos - biosynthesis; Rat; Rats; Rats, Sprague-Dawley; Spinal cord; Spinal Cord - drug effects; Spinal Cord - metabolism; Synaptic Transmission - drug effects; PBS; Spinal cord; Dexamethasone; Rat; Fisher's PLSD test; c-Fos; COX; Diclofenac; PB; ANOVA; NSAIDs; Carrageenan; c-Fos-LI; Inflammatory pain; Corticosteroid; Drug combination; Rodentia; Inflammation; Gene expression; Non steroidal antiinflammatory agent; Vertebrata; Chemotherapy; Mammalia; Analgesic; Pain; Treatment; Animal; Drug interaction; Immediate early gene
• ISSN: 0304-3959; 1872-6623
• DOI: 10.1016/0304-3959(95)00167-0

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 μ1 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 diclofenace 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.