Cyclooxygenase inhibition in nerve-injury- and TNF-induced hyperalgesia in the rat
Cyclooxygenase inhibition in nerve-injury- and TNF-induced hyperalgesia in the rat
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DOI：
10.1016/j.expneurol.2003.09.015
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发表时间：
2004-01-01
影响因子：
5.3
通讯作者：
Sommer, C
中科院分区：
文献类型：
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作者：
Schäfers, M;Marziniak, M;Sommer, C
神经损伤后，环氧化酶-2 （COX-2）在脊髓和周围神经中表达上调，后者依赖于肿瘤坏死因子- α (TNF)。在这里，我们询问COX抑制剂是否减轻慢性收缩性坐骨神经损伤（CCI）或神经内注射TNF （2.5 pg/ml）引起的疼痛行为。大鼠术前2天、术后12小时、7天分别灌胃0.9%生理盐水、非选择性COX-2抑制剂布洛芬（40 mg/kg）或选择性COX-2抑制剂塞来昔布（10或30 mg/kg），每天2次。CCI引起的机械性异常痛和热痛觉过敏是中度的，但在早期（CCI后第2天或12小时）布洛芬和塞来昔布治疗后（CCI后7天）持续减弱，而不是晚期（CCI后7天）。布洛芬可减轻机械性异常性痛，但神经内TNF诱导的热痛觉过敏没有减轻，注射后5和7天塞来昔布治疗则没有减轻。对术后12 h开始治疗的大鼠坐骨神经、腰椎背根神经节（DRG）和脊髓进行CCI后10天前列腺素E-2 （PGE(2)）水平分析。在受损神经和同侧DRG中，PGE(2)水平升高。布洛芬治疗逆转了受损神经和DRG中的PGE2水平，而塞来昔布仅阻断了神经中PGE2水平的升高。在脊髓中，PGE2水平未见变化。与COX抑制剂明显抑制神经损伤诱导的PGE上调(2)相反，对疼痛行为的影响是温和的。神经损伤和tnf诱导的疼痛相关行为似乎只部分依赖于外周前列腺素。(C) 2003 Elsevier Inc.版权所有。
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 E-2 (PGE(2)) levels 10 days after CCI. In injured nerves and ipsilateral DRG, PGE(2) levels were increased. Ibuprofen treatment reversed PGE2 levels in injured nerves and DRG, whereas celecoxib blocked increased PGE(2) 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 PGE(2) 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. (C) 2003 Elsevier Inc. All rights reserved.