Ossipov M H, Kovelowski C J, Porreca F
Department of Pharmacology, University of Arizona Health Sciences Center, Tucson 85724, USA.
Neurosci Lett. 1995 Jan 30;184(3):173-6. doi: 10.1016/0304-3940(94)11199-s.
Carrageenan-induced inflammation of the rat hindpaw has been used as a model for persistent pain of inflammatory origin. The induction of inflammation resulting from carrageenan injection in the rat hindpaw has been shown to elicit an increase in the antinociceptive potency of morphine, an effect postulated to be related to reduced levels of spinal cholecystokinin (CCK). Recent findings have related the anti-opioid effect of CCK to a decrease in activation of delta-opioid receptors. For this reason, we have examined the effects of the delta-opioid antagonist naltrindole (NTI) on the modulation of morphine antinociceptive potency resulting from carrageenan-induced inflammation. Rats with carrageenan-induced hindpaw inflammation received several doses of morphine in the absence or presence of NTI and were tested in the hot plate (HP) and tail flick (TF) tests. These results were compared to those of non-carrageenan injected rats. Morphine was significantly more potent in inflamed, than in control, rats in both tests. While NTI did not affect morphine antinociceptive potency in control rats in either test, this opioid delta antagonist blocked the increase in morphine potency resulting from carrageenan inflammation in nearly every case. The blockade of the enhancement of morphine potency was such that the effect of a given dose of morphine was similar in control rats and carrageenan-injected rats with NTI. We suggest that carrageenan-induced inflammation may alter endogenous enkephalin levels, perhaps by a decrease in CCK availability. The enhancement of morphine antinociceptive potency may result from the well-established synergism seen following the activation of opioid delta receptors by enkephalins.
角叉菜胶诱导的大鼠后爪炎症已被用作炎症性起源的持续性疼痛模型。已证明在大鼠后爪注射角叉菜胶所诱导的炎症会引发吗啡抗伤害感受效力的增加，据推测这种效应与脊髓胆囊收缩素（CCK）水平降低有关。最近的研究结果将CCK的抗阿片样物质作用与δ-阿片样物质受体激活的减少联系起来。出于这个原因，我们研究了δ-阿片样物质拮抗剂纳曲吲哚（NTI）对角叉菜胶诱导的炎症所导致的吗啡抗伤害感受效力调节的影响。患有角叉菜胶诱导的后爪炎症的大鼠在不存在或存在NTI的情况下接受了几剂吗啡，并在热板（HP）和甩尾（TF）试验中进行了测试。这些结果与未注射角叉菜胶的大鼠的结果进行了比较。在两项试验中，吗啡在发炎的大鼠中比在对照大鼠中效力显著更高。虽然在任何一项试验中NTI都不影响对照大鼠中吗啡的抗伤害感受效力，但这种阿片样物质δ拮抗剂在几乎所有情况下都阻断了角叉菜胶炎症导致的吗啡效力增加。对吗啡效力增强的阻断使得给定剂量吗啡在对照大鼠和注射了角叉菜胶并使用NTI的大鼠中的效果相似。我们认为角叉菜胶诱导的炎症可能会改变内源性脑啡肽水平，可能是通过减少CCK的可利用性。吗啡抗伤害感受效力的增强可能是由于脑啡肽激活δ-阿片样物质受体后所产生的已确立的协同作用。
