Khalil Z, Sanderson K, Modig M, Nyberg F
National Ageing Research Institute, University of Melbourne, Parkville, Victoria, Australia.
Inflamm Res. 1999 Oct;48(10):550-6. doi: 10.1007/s000110050502.
Neurogenic inflammation is mediated via sensory peptides released from the peripheral terminals of sensory nerves and can be modulated by locally released opioid peptides at the site of injury. Endomorphins are recently discovered endogenous opioid peptides with high selectivity and affinity for the mu-opioid receptor. The aim of this study was to examine the ability of endomorphin-1 (EM-1) to modulate the inflammatory response under different injury conditions.
A vacuum-induced blister model in anaesthetised rats (nembutal 60 mg/kg i.p.) was used to examine the effect of EM-1 on the acute inflammatory response induced by; (1) electrical stimulation (ES) of the distal portion of the exposed/cut sciatic nerve at 20 V, 5 Hz, 2 ms for 1 min or; (2) superfusion of substance P (SP) over the blister base. In addition, the effect of EM-1 on the inflammatory response to SP was examined under acute, recurrent (repeated blister induction) and chronic (chronic sciatic nerve lesion) injury conditions.
Prior and concomitant perfusion of EM-1 (100 microM) significantly inhibited the vascular response to ES by 58% compared to controls. EM-1 also inhibited the inflammatory response to SP (both vasodilatation and plasma extravasation) in a dose-dependent manner. Significant inhibition was achieved at 100 microM and 1 mM concentrations of EM-1. Naloxone (1 mg/kg i.v.) reversed the inhibitory effect of EM-1 on the inflammatory response to SP. EM-1 (100 microM) was equally potent in inhibiting the inflammatory response to SP under acute (34% inhibition) recurrent (39%) and chronic (42%) injury conditions.
The current results demonstrate a greater inhibitory effect of EM-1 on the inflammatory response to electrical nerve stimulation (58% inhibition) compared to SP (34% inhibition) suggesting the involvement of both pre- and post-terminal mechanisms in the inhibitory modulatory actions of EM-1. Evidence is provided for the involvement of opioid receptors in this inhibitory effect. The results also suggest that EM-1 is equipotent in inhibiting the inflammatory response under different injury conditions.
神经源性炎症是通过感觉神经外周终末释放的感觉肽介导的，并且可被损伤部位局部释放的阿片肽调节。内吗啡肽是最近发现的对μ-阿片受体具有高选择性和亲和力的内源性阿片肽。本研究的目的是检测内吗啡肽-1（EM-1）在不同损伤条件下调节炎症反应的能力。
采用麻醉大鼠（腹腔注射戊巴比妥60mg/kg）的真空诱导水疱模型，检测EM-1对以下因素诱导的急性炎症反应的影响：（1）以20V、5Hz、2ms的参数对暴露/切断的坐骨神经远端进行1分钟的电刺激（ES）；或（2）在水疱基部灌注P物质（SP）。此外，还检测了EM-1在急性、复发性（重复诱导水疱）和慢性（慢性坐骨神经损伤）损伤条件下对SP炎症反应的影响。
与对照组相比，预先和同时灌注EM-1（100μM）可使对ES的血管反应显著抑制58%。EM-1还以剂量依赖的方式抑制对SP的炎症反应（血管舒张和血浆外渗）。在EM-1浓度为100μM和1mM时可实现显著抑制。纳洛酮（静脉注射1mg/kg）可逆转EM-1对SP炎症反应的抑制作用。EM-1（100μM）在急性（抑制34%）、复发性（抑制39%）和慢性（抑制42%）损伤条件下对SP炎症反应的抑制作用同样有效。
当前结果表明，与SP（抑制34%）相比，EM-1对神经电刺激炎症反应的抑制作用更强（抑制58%），提示EM-1的抑制调节作用涉及终末前和终末后机制。有证据表明阿片受体参与了这种抑制作用。结果还表明，EM-1在不同损伤条件下抑制炎症反应的效力相同。
