Osgood P F, Carr D B, Kazianis A, Kemp J W, Atchison N E, Szyfelbein S K
Department of Anesthesia, Massachusetts General Hospital, Harvard Medical School, Shriners Burns Institute, Boston.
Brain Res. 1990 Jan 15;507(1):11-6. doi: 10.1016/0006-8993(90)90514-c.
Rats placed in a cold environment (4 degrees C) for 2 h had a sustained increase in tail flick latency (TFL) as well as an increase in tail pinch latency (TPch) that was often biphasic with an early peak response at 15 min and a later, often higher, peak at 2 h. Plasma beta-endorphin levels after a modest increase at 5 min (24%) declined throughout the remaining time in the cold. The long-acting opioid antagonist naltrexone had no effect on TFL increases but led to greater increases in TPch (P less than 0.04). In morphine-tolerant rats TFL response was the same as in controls but TPch increases were greater (P less than 0.04). Rats exposed to 2 h of cold for 17 or 18 consecutive days generally developed tolerance to the analgesia of cold, i.e. TFL and TPch increases were diminished; however, the response to morphine on day 18 was the same as in rats never exposed to cold. Adrenalectomy and hypophysectomy led to significantly smaller increases in TFL (P less than 0.02 and P less than 0.001, respectively). The TPch response in contrast, was greater in adrenalectomized (P less than 0.001) and the same in hypophysectomized rats compared to sham controls. An opioid kappa receptor antagonist (Mr 1452) given prior to cold reduced both TFL and TPch response during the first hour. Thus the analgesia induced by cold appeared to shift from an early possibly kappa opioid to a later non-opioid form. The TFL effects seemed to be under hormonal influence while the TPch were not.
置于寒冷环境（4摄氏度）2小时的大鼠，其甩尾潜伏期（TFL）持续增加，夹尾潜伏期（TPch）也增加，且通常呈双相变化，15分钟时出现早期峰值反应，2小时时出现后期且往往更高的峰值。血浆β-内啡肽水平在5分钟时适度升高（24%）后，在寒冷环境中的剩余时间里持续下降。长效阿片类拮抗剂纳曲酮对TFL增加无影响，但导致TPch增加幅度更大（P<0.04）。在吗啡耐受的大鼠中，TFL反应与对照组相同，但TPch增加幅度更大（P<0.04）。连续17或18天暴露于寒冷环境2小时的大鼠，通常会对寒冷镇痛产生耐受性，即TFL和TPch的增加幅度减小；然而，第18天对吗啡的反应与从未暴露于寒冷环境的大鼠相同。肾上腺切除术和垂体切除术导致TFL增加幅度显著减小（分别为P<0.02和P<0.001）。相比之下，肾上腺切除大鼠的TPch反应更大（P<0.001），垂体切除大鼠的TPch反应与假手术对照组相同。在寒冷暴露前给予阿片κ受体拮抗剂（分子量1452）可在第一个小时内降低TFL和TPch反应。因此，寒冷诱导的镇痛似乎从早期可能的κ阿片类形式转变为后期的非阿片类形式。TFL效应似乎受激素影响，而TPch效应则不受激素影响。
