Watkins L R, Cobelli D A, Mayer D J
Brain Res. 1982 Jul 8;243(1):119-32. doi: 10.1016/0006-8993(82)91125-8.
Opiate and non-opiate footshock induced analgesia (FSIA) has recently been observed to be differentially elicited dependent upon the body region shocked; front paw and hind paw shock produce opiate and non-opiate analgesia, respectively. Previous studies have shown that footshock can also produce classically conditioned analgesia; that is, when shock is delivered to an animal, environmental cues become associated with the noxious stimulus such that these cues become capable, in and of themselves, of producing potent analgesia. The present series of experiments examined analgesia classically conditioned to either front paw or hind paw shock. The non-electrified shock grid served as the conditioned stimulus (CS), 90-s footshock as the unconditioned stimulus (UCS) and tail-flick inhibition as the unconditioned response (UCR). Following CS-UCS pairings, exposure to the non-electrified grid reliably produced prolonged analgesia. This classically conditioned analgesia appears to involve endogenous opioids, regardless of the body region shocked during conditioning trials, since the analgesia is attenuated by systemic naloxone and shows cross-tolerance to morphine. A spinal opioid site is involved since 1 microgram of naloxone delivered directly to the lumbosacral cord antagonizes the analgesia. Like front paw (opiate) FSIA, CCA can be prevented but cannot be reversed by naloxone; naloxone can antagonize classically conditioned analgesia only if it is delivered prior to exposure to the conditioned stimulus. Lastly, a similarity was recognized between classically conditioned analgesia and the analgesia induced by morphine, brain stimulation, front paw shock and hind paw shock in that all are mediated via descending pathways within the dorsolateral funiculus of the spinal cord.
最近观察到，阿片类和非阿片类足部电击诱导的镇痛（FSIA）因电击的身体部位不同而有差异地引发；前爪电击产生阿片类镇痛，后爪电击产生非阿片类镇痛。先前的研究表明，足部电击还可产生经典条件性镇痛；也就是说，当对动物施加电击时，环境线索会与有害刺激相关联，从而这些线索本身就能够产生强效镇痛。本系列实验研究了经典条件化至前爪或后爪电击的镇痛情况。非通电电击网格作为条件刺激（CS），90秒的足部电击作为非条件刺激（UCS），甩尾抑制作为非条件反应（UCR）。在CS-UCS配对后，暴露于非通电网格可可靠地产生延长的镇痛作用。这种经典条件性镇痛似乎涉及内源性阿片类物质，无论在条件试验期间电击的身体部位如何，因为该镇痛作用会被全身性纳洛酮减弱，并显示出对吗啡的交叉耐受性。由于将1微克纳洛酮直接注入腰骶脊髓可拮抗镇痛作用，因此涉及脊髓阿片类位点。与前爪（阿片类）FSIA一样，CCA可被纳洛酮预防但不能被逆转；纳洛酮只有在暴露于条件刺激之前给药才能拮抗经典条件性镇痛。最后，人们认识到经典条件性镇痛与吗啡、脑刺激、前爪电击和后爪电击诱导的镇痛之间存在相似性，即所有这些镇痛均通过脊髓背外侧索内的下行通路介导。
