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-steroidal anti-inflammatory drug, in freely moving rats. Three h after intraplantar carrageenan (6 mg/150 microliters saline) a maximal 'evoked' Krox-24 expression was observed in L2-L6 segments of the dorsal horn ipsilateral to carrageenan inflammation. A maximal number of 'evoked' Krox-24 neurons was observed in L4-L5 segments, predominantly in the superficial laminae (I-II) and to a lesser extent in the medial part of neck (laminae V-VI) of the dorsal horn. Such an increase was not observed after an intraplantar injection of control vehicle saline. increase doses of carrageenan (1, 3 and 6 mg) induced a dose-dependent increase (r2 = 0.617, P < 0.0001) in the number of evoked' Krox-24 neurons observed in the superficial dorsal horn 3 h after carrageenan. Systemic preadministration of indomethacin (1, 2.5 and 5 mg/kg) dose-dependently reduced (r2 = 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 indomethacin dose-dependently reduced the inflamed paw and ankle diameter (16 +/- 8, 34 +/- 12, 54 +/- 6% and 48 +/- 14,. 75 + 16, 90 +/- 7% reduction as compared with the control carrageenan inflammation, respectively). There was a positive correlation between the effect of systemic indomethacin on both 'evoked' Krox-24 expression in superficial laminae and the inflammatory signs (r2 = 0.25, P < 0.01 for the paw diameter; r2 = 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 indomethacin (10 + 10 mg/kg). Oral indomethacin totally blocked the ankle diameter and reduced the paw diameter (100 + 14 and 30 +/- 6% reduction of the control carrageenan inflammation, respectively).
Buritova
J
J
Physiopharmacologie du Système Nerveux, INSERM U161, Paris, France.
Honoré
P
P
Besson
J M
JM
D000818:Animals; D002351:Carrageenan; D004268:DNA-Binding Proteins / Q000096:biosynthesis*; D003864:Depression, Chemical; D051766:Early Growth Response Protein 1; D005528:Foot / Q000473:pathology; D017874:Immediate-Early Proteins; D007150:Immunohistochemistry; D007213:Indomethacin / Q000494:pharmacology*; D007249:Inflammation / Q000378:metabolism* / Q000473:pathology / Q000517:prevention & control; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D014157:Transcription Factors / Q000096:biosynthesis*; D016335:Zinc Fingers
D004268:DNA-Binding Proteins; D051766:Early Growth Response Protein 1; C486110:Egr1 protein, rat; D017874:Immediate-Early Proteins; D014157:Transcription Factors; D002351:Carrageenan; D007213:Indomethacin