INDOMETHACIN REDUCES BOTH KROX-24 EXPRESSION IN THE RAT LUMBAR SPINAL-CORD AND INFLAMMATORY SIGNS FOLLOWING INTRAPLANTAR CARRAGEENAN

This study evaluated the 'evoked' expression of Krox-24 protein in the lumbar spinal cord after peripheral carrageenan-induced inflammation and its modification by preadministration of indomethacin, a non-stero idal anti-inflammatory drug, in freely moving rats. Three h after intr aplantar carrageenan (6 mg/150 mu l saline) a maximal 'evoked' Krox-24 expression was observed in L2-L6 segments of the dorsal horn ipsilate ral to carrageenan inflammation. A maximal number of 'evoked' Krox-24 neurons was observed in L4-L5 segments, predominantly in the superfici al laminae (I-II) and to a lesser extent in the medial part of neck (l aminae V-VI) of the dorsal horn. Such an increase was not observed aft er an intraplantar injection of control vehicle saline. Increasing dos es of carrageenan (1, 3 and 6 mg) induced a dose-dependent increase (r (2) = 0.617, P < 0.0001) in the number of 'evoked' Krox-24 neurons obs erved in the superficial dorsal horn 3 h after carrageenan. Systemic p readministration of indomethacin (1, 2.5 and 5 mg/kg) dose-dependently reduced (r(2) = 0.508, P < 0.0001) the total number of carrageenan (6 mg at 3 h)-'evoked' Krox-24 neurons (29 +/- 5, 45 +/- 4 and 57 +/- 2% reduction as compared with control, respectively). Systemic indometha cin dose-dependently reduced the inflamed paw and ankle diameter (16 /- 8, 34 +/- 12, 54 +/- 6% and 48 +/- 14, 75 +/- 16, 90 +/- 7% reducti on as compared with the control carrageenan inflammation, respectively ). There was a positive correlation between the effect of systemic ind omethacin on both 'evoked' Krox-24 expression in superficial laminae a nd the inflammatory signs (r(2) = 0.25, P < 0.01 for the paw diameter; r(2) = 0.22, P < 0.05 for the ankle diameter). In addition, the total number of 'evoked' Krox-24 neurons was significantly reduced (43 +/- 5% reduction as compared with control) by an oral pretreatment of indo methacin (10 + 10 mg/kg). Oral indomethacin totally blocked the ankle diameter and reduced the paw diameter (100 +/- 14 and 30 +/- 6% reduct ion of the control carrageenan inflammation, respectively).