Changes in formalin-evoked spinal Fos expression and nociceptive behaviour after oral administration of Bufferin A (aspirin) and L-5409709 (ibuprofen+caffeine+paracetamol)

This study compares the effects of two non-steroidal anti-inflammatory drugs, Bufferin A (BA) and L-5409709 (L-54), on nociceptive behaviour and spinal Fos expression induced by subcutaneous formalin in the rat. BA contains aspirin. L-54 contains ibuprofen, caffeine and paracetamol. Doses based on the human posology were administered orally 30 or 40 min before subcutaneous intraplantar injection of formalin (1.5%, 50 microl) in the right hindpaw. Low doses (BA, 24 mg/kg; L-54, 21.5 mg/kg) did not significantly affect the behavioural pain response. High doses (BA, 480 mg/kg; L-54, 430 mg/kg) reduced the late phase of the response by 42% and 62% respectively, but did not affect the early phase of the response. No sedative side-effects were observed. The two drugs had different effects on the number of spinal Fos-like immunoreactive neurones 2 h after the formalin injection. Fos expression was reduced after BA treatment, and this reduction was correlated to and matched the reduction of the pain response. In contrast, Fos expression after L-54 treatment was not reduced and was not correlated to the reduction in the pain response. The Fos results reveal clear differences in the way that BA (aspirin) and L-54 (ibuprofen + caffeine + paracetamol) affected transmission of the noxious signal. They suggest that BA did not act beyond the spinal cord and that L-54 had more central sites of action than BA.