Gescuk B D, Lang S, Kornetsky C
Laboratory of Behavioral Pharmacology, Boston University School of Medicine, MA 02118, USA.
Brain Res. 1995 Dec 1;701(1-2):279-87. doi: 10.1016/0006-8993(95)01009-2.
The 2-deoxy-D-[14C]glucose (2-DG) method was used to examine the effects of morphine sulfate (MS) on local cerebral metabolic rates for glucose (LCMRglu) in male F-344 rats required to turn a wheel manipulandum in order to escape from nociceptive footshock. This nociceptive stimulus was identical with that utilized in a previous 2-DG study from this laboratory [15] except that animals were exposed to 15 daily 30 min sessions of footshock prior to the 2-DG testing day rather than a single footshock exposure. This allows a direct comparison of the effects of morphine in chronic and acute pain. Unlike the acute footshock study, morphine in chronic footshock rats did not have a significant effect compared with chronic footshock alone in any of the 73 measured brain structures, including limbic and midline thalamic structures previously shown to be important in morphine-induced analgesia during acute pain [15]. Whereas 93% of measured cerebral structures showed decreases in LCMRglu following morphine administration in the acute footshock rats, morphine given to chronic footshock rats caused decreases in only 56% of the structures as compared with chronic footshock plus saline. It is hypothesized that these differential effects of morphine are due in part to a habituation to the chronic stressor such that chronic footshock rats are less stressed than acute footshock rats. Additionally, it is suggested that chronic exposure to pain produces a constant elevation of opioid peptides leading to opioid receptor downregulation and consequently morphine tolerance. These results demonstrate that, even in the presence of the same nociceptive stimulus, morphine can have widely disparate effects on brain metabolism if there are differences in the pain history of the animal.
采用2-脱氧-D-[14C]葡萄糖（2-DG）法，研究硫酸吗啡（MS）对雄性F-344大鼠局部脑葡萄糖代谢率（LCMRglu）的影响。这些大鼠需要转动操纵轮以逃避伤害性足部电击。这种伤害性刺激与本实验室先前一项2-DG研究中使用的刺激相同[15]，只是在2-DG测试日前，动物每天接受15次、每次30分钟的足部电击，而不是单次足部电击暴露。这使得能够直接比较吗啡在慢性疼痛和急性疼痛中的作用。与急性足部电击研究不同，在慢性足部电击大鼠中，与单独的慢性足部电击相比，吗啡对所测量的73个脑结构中的任何一个都没有显著影响，这些结构包括先前在急性疼痛期间吗啡诱导的镇痛中显示重要作用的边缘和中线丘脑结构[15]。在急性足部电击大鼠中，给予吗啡后，93%的测量脑结构显示LCMRglu下降，而给予慢性足部电击大鼠的吗啡与慢性足部电击加生理盐水相比，仅使56%的结构LCMRglu下降。据推测，吗啡的这些不同作用部分归因于对慢性应激源的适应，使得慢性足部电击大鼠比急性足部电击大鼠受到的压力更小。此外，有人认为长期暴露于疼痛会导致阿片肽持续升高，从而导致阿片受体下调，进而产生吗啡耐受性。这些结果表明，即使存在相同的伤害性刺激，如果动物的疼痛史不同，吗啡对脑代谢的影响也可能有很大差异。
