Dionne Raymond A, Gordon Sharon M, Rowan Janet, Kent Allison, Brahim Jaime S
Pain and Naurosensory Mechanisms Branch, National Institute of Dental and Craniofacial Research/NIH, 10 Center Drive, Bethesda, MD 20892-2292, USA.
J Oral Maxillofac Surg. 2003 Sep;61(9):997-1003. doi: 10.1016/s0278-2391(03)00310-0.
The therapeutic effects of glucocorticoids are generally attributed to suppression of multiple signaling pathways involved in the inflammatory response leading to decreased levels of inflammatory mediators at the site of injury. This study evaluated the in vivo relationship between levels of prostanoids at the site of tissue injury and analgesia after dexamethasone administration in a clinical model of tissue injury.
Subjects were administered dexamethasone 4 mg or placebo 12 hours and 1 hour before the removal of 2 mandibular third molars. A microdialysis probe was implanted at each surgical site for measurement of immunoreactive prostaglandin E2 (PGE(2)) or immunoreactive thromboxane B(2) (TxB(2)), and pain was measured concurrently. Subjects received either ketorolac 30 mg intravenously or placebo at pain onset.
PGE(2) was detectable in the first postoperative sample, decreased over the next hour and then increased coincident with the onset of postoperative pain. Administration of dexamethasone suppressed PGE(2) levels in samples collected at pain onset in comparison to placebo and significantly suppressed TxB(2) at the surgical site but without any effect on pain report. Subsequent administration of ketorolac significantly reduced pain while decreasing both PGE(2) and TxB(2) levels at the surgical site.
The lack of an analgesic effect for dexamethasone while reducing both PGE(2) and TxB(2) at the site of injury in comparison to ketorolac analgesia accompanied by greater reductions in levels of these prostanoids suggests that glucocorticoids at this dose do not suppress PGE(2) release sufficiently to attenuate peripheral sensitization of nociceptors after tissue injury.
糖皮质激素的治疗作用通常归因于对多种参与炎症反应的信号通路的抑制，从而导致损伤部位炎症介质水平降低。本研究在组织损伤的临床模型中评估了地塞米松给药后组织损伤部位前列腺素水平与镇痛之间的体内关系。
在拔除2颗下颌第三磨牙前12小时和1小时，受试者分别接受4mg地塞米松或安慰剂。在每个手术部位植入一个微透析探针，用于测量免疫反应性前列腺素E2（PGE₂）或免疫反应性血栓素B₂（TxB₂），并同时测量疼痛程度。疼痛发作时，受试者静脉注射30mg酮咯酸或接受安慰剂。
术后首个样本中可检测到PGE₂，在接下来的1小时内下降，然后随着术后疼痛的发作而升高。与安慰剂相比，地塞米松给药抑制了疼痛发作时采集的样本中的PGE₂水平，并显著抑制了手术部位的TxB₂，但对疼痛报告没有任何影响。随后给予酮咯酸可显著减轻疼痛，同时降低手术部位的PGE₂和TxB₂水平。
与酮咯酸镇痛相比，地塞米松在降低损伤部位PGE₂和TxB₂的同时缺乏镇痛作用，且酮咯酸能更大程度地降低这些前列腺素的水平，这表明该剂量的糖皮质激素不能充分抑制PGE₂的释放以减轻组织损伤后伤害感受器的外周敏化。
