title: Cyclooxygenase inhibition in nerve-injury- and TNF-induced hyperalgesia in the rat.
abstract: After nerve injury, cyclooxygenase-2 (COX-2) is upregulated in spinal cord and peripheral nerve, the latter being dependent on tumor necrosis factor-alpha (TNF). Here we asked whether COX inhibitors attenuate pain behavior induced by chronic constrictive sciatic nerve injury (CCI) or intraneural injection of TNF (2.5 pg/ml). Rats received either 0.9% saline, the nonselective COX inhibitor ibuprofen (40 mg/kg) or the selective COX-2 inhibitor celecoxib (10 or 30 mg/kg) twice daily by gavage started 2 days before, 12 h or 7 days after surgery. Mechanical allodynia and thermal hyperalgesia induced by CCI was moderately, but consistently attenuated by early (day -2 or 12 h after CCI), but not late (7 days after CCI) ibuprofen and celecoxib treatment. Mechanical allodynia, but not thermal hyperalgesia induced by intraneural TNF, was reduced by ibuprofen, but not by celecoxib treatment 5 and 7 days after injection. Sciatic nerves, lumbar dorsal root ganglia (DRG) and spinal cords from rats with treatment started 12 h after surgery were analyzed for prostaglandin E2 (PGE2) levels 10 days after CCI. In injured nerves and ipsilateral DRG, PGE2 levels were increased. Ibuprofen treatment reversed PGE2 levels in injured nerves and DRG, whereas celecoxib blocked increased PGE2 levels only in nerves. In spinal cord, no change in PGE2 levels was observed. In contrast to the marked inhibition of nerve-injury-induced upregulation of PGE2 by COX inhibitors, the effect on pain behavior was modest. Nerve-injury- and TNF-induced pain-related behavior seem to be only partly dependent on peripheral prostaglandins.
authors.affiliation: Department of Neurology, University of Würzburg, 97080 Würzburg, Germany. schaefers_m@klinik.uni-wuerzburg.de
authors.forename: Maria
authors.initials: M
authors.lastname: Schäfers
authors.forename: Martin
authors.initials: M
authors.lastname: Marziniak
authors.forename: Linda S
authors.initials: LS
authors.lastname: Sorkin
authors.forename: Tony L
authors.initials: TL
authors.lastname: Yaksh
authors.forename: Claudia
authors.initials: C
authors.lastname: Sommer
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D000068579:Celecoxib; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000627:therapeutic use*; D015232:Dinoprostone / Q000378:metabolism; D004195:Disease Models, Animal; D005727:Ganglia, Spinal / Q000378:metabolism; D006930:Hyperalgesia / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology; D007052:Ibuprofen / Q000627:therapeutic use*; D007527:Isoenzymes / Q000037:antagonists & inhibitors; D010147:Pain Measurement / Q000187:drug effects; D011451:Prostaglandin-Endoperoxide Synthases; D011720:Pyrazoles; D051381:Rats; D017207:Rats, Sprague-Dawley; D020426:Sciatic Neuropathy / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology; D013116:Spinal Cord / Q000378:metabolism; D013449:Sulfonamides / Q000627:therapeutic use*; D014409:Tumor Necrosis Factor-alpha
chemical_list: D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007527:Isoenzymes; D011720:Pyrazoles; D013449:Sulfonamides; D014409:Tumor Necrosis Factor-alpha; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; D000068579:Celecoxib; D015232:Dinoprostone; D007052:Ibuprofen