Steinman J L, Faris P L, Mann P E, Olney J W, Komisaruk B R, Willis W D, Bodnar R J
Institute of Animal Behavior, Rutgers, State University.
Neurosci Biobehav Rev. 1990 Spring;14(1):1-7. doi: 10.1016/s0149-7634(05)80155-1.
The demonstrated existence of opioid and nonopioid forms of pain control has raised questions as to how they interact. Previous indirect evidence suggests that activation of one system inhibited the activation of the other. The present study assessed this directly using morphine as an opiate form of analgesia and continuous cold-water swims (CCWS, 4 degrees C, 2 min) as the nonopioid form. A significant reduction in morphine (8 mg/kg, SC) analgesia on the tail-flick test was observed if rats were acutely exposed to CCWS immediately prior to morphine administration. The inability of naloxone (10 mg/kg, SC) to reduce CCWS analgesia verified its nonopioid nature. The antagonism of morphine (3 mg/kg, SC) analgesia was greater following preexposure to 2 min of CCWS than 1 min of CCWS. CCWS was also more effective in antagonizing analgesia induced by the 3 mg/kg than the 8 mg/kg dose of morphine. The antagonism of morphine analgesia by CCWS was dependent upon the temporal patterning of stimulus presentation: exposure to CCWS 20 or 60 min prior to morphine failed to alter subsequent morphine analgesia. A significant reduction in analgesia induced by intraperitoneal administration of morphine (10 mg/kg) was also observed when CCWS was presented immediately prior to injection, suggesting that pharmacokinetic factors such as altered drug absorbance by CCWS-induced vasoconstriction do not appear to explain these effects. These data provide direct support for the existence of collateral inhibitory mechanisms activated by CCWS and morphine, and suggests that these opioid and nonopioid forms of analgesia do not function synergistically, but instead involve some form of hierarchical order.
阿片类和非阿片类疼痛控制形式的已证实存在引发了它们如何相互作用的问题。先前的间接证据表明，一个系统的激活会抑制另一个系统的激活。本研究使用吗啡作为阿片类镇痛形式，连续冷水游泳（CCWS，4摄氏度，2分钟）作为非阿片类形式，直接评估了这一点。如果大鼠在给予吗啡之前立即急性暴露于CCWS，则在甩尾试验中观察到吗啡（8毫克/千克，皮下注射）镇痛作用显著降低。纳洛酮（10毫克/千克，皮下注射）不能降低CCWS镇痛作用，证实了其非阿片类性质。在预先暴露于2分钟CCWS后，吗啡（3毫克/千克，皮下注射）镇痛作用的拮抗作用比暴露于1分钟CCWS后更大。CCWS在拮抗3毫克/千克剂量吗啡诱导的镇痛作用方面也比8毫克/千克剂量更有效。CCWS对吗啡镇痛作用的拮抗作用取决于刺激呈现的时间模式：在吗啡之前20或60分钟暴露于CCWS未能改变随后的吗啡镇痛作用。当在注射吗啡（10毫克/千克，腹腔注射）之前立即进行CCWS时，也观察到镇痛作用显著降低，这表明诸如CCWS诱导的血管收缩导致药物吸收改变等药代动力学因素似乎无法解释这些效应。这些数据为CCWS和吗啡激活的并行抑制机制的存在提供了直接支持，并表明这些阿片类和非阿片类镇痛形式并非协同发挥作用，而是涉及某种形式的等级顺序。
