Potent anti-inflammatory/analgesic effects of lornoxicam in comparison to other nsaids: a c-fos study in the rat.
This study evaluates the anti-inflammatory/analgesic effects of lornoxicam, a new non-steroidal anti-inflammatory drug, using the method of c-Fos protein immunoreactivity in the carrageenan model of inflammatory nociception in the rat. The immunohistochemical revelation of inflammatory/nociceptive stimulation evoked c-Fos expression in spinal neurons was used as an indirect marker of neurons involved in spinal nociceptive transmission. Lornoxicam (0.1, 0.3, 1, 3 and 9 mg/kg; n=10 rats for each group) was preadministered intravenously 25 min before an intraplantar injection of carrageenan (6 mg/150 ml of saline). Three hours after carrageenan, the peripheral oedema (paw and ankle diameters) and the number of c-Fos-protein-like immunoreactive (c-Fos-LI) neurons in the lumbar spinal cord, were assessed. Preadministered lornoxicam dose relatedly reduced the total number of c-Fos-LI neurons (regression coefficient r=0.79; p<0.001) with the strongest effect corresponding to the 75+/-2% reduction (p<0.001) for the highest dose of 9 mg/kg, and the 45+/-3% reduction (p<0.001) for the low dose of 0.3 mg/kg. Lornoxicam (0.1, 0.3, 1, 3 and 9 mg/kg iv) significantly reduced the number of c-Fos-LI neurons in both superficial (24+/-6, 33+/-5, 53+/-4, 54+/-4, and 63+/-4% reduction, respectively, p<0.001 for all doses) and deep (28+/-4, 48+/-4, 62+/-2, 69+/-3 and 79+/-2% reduction, respectively, p<0.001 for all doses) laminae of the dorsal horn of the spinal cord. These reducing effects were dose related in both superficial and deep laminae (regression coefficient r=0.66 and r=0.08, respectively; p<0.001 for both). The lowes dose of lornoxicam (0.1 mg/kg iv) had a similar effect in both superficial and deep laminae, whereas the four higher doses (0.3, 1, 3 and 9 mg/kg iv) had a significantly stronger effect on the number of c-Fos-LI neurons in deep laminae as compared to that in superficial laminae. Lornoxicam (0.1, 0.3, 1, 3 and 9 mg/kg iv) dose relatedly reduced the carrageenan induced oedema at both the paw and ankle levels (regression coefficient r=0.63 and r=0.53, respectively, p<0.001 for both), with a stronger effect on the ankle diameter (34+/-8, 61+/-9, 66+/-8, 80+/-6 and 83+/-5% reduction, respectively p<0.001 for all doses). Furthermore reductions of the carrageenan evoked peripheral oedema and spinal c-Fos expression were positively correlated (correlation coefficient r=0.74 and r=0.57 for the paw and ankle diameter respectively, p<0.001 for both). These correlations suggest a predominant peripheral site, without excluding central site of action of lornoxicam in the carrageenan-induced inflammation. Our results provide clear evidence for a potent anti-inflammatory/analgesic effects of low doses of lornoxicam which have a reduced risk of side effects. Taken together, the results of the present study revealed the effects of lornoxicam in the same range as those of other previously studied NSAIDs, more precisely, closely comparable to the effects of ketoprofen.
Unité de Recherche de Physiopharmacologie du Système Nerveux, INSERM U-161, 2 rue d'Alésia, F-75014, Paris, France.
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Buritova
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Besson