Weaver Shelley A, Diorio Josie, Meaney Michael J
War-Related Illness and Injury Study Center, Department of Veterans Affairs, New Jersey Health Care System, East Orange, New Jersey 07018, USA.
J Pain. 2007 Dec;8(12):962-9. doi: 10.1016/j.jpain.2007.07.001. Epub 2007 Aug 7.
We determined responses to noxious thermal stimuli, before and after morphine, and mu-opioid receptor binding in brain regions involved in nociception in maternally separated (MS), neonatally handled (H) and nonhandled (NH) female rats. Long-Evans dams were randomly assigned to either 180-minute (MS) or 15-minute (H) minute daily separations from their litters or left undisturbed (NH). At 120 days of age, paw lick latency (50 degrees C hot plate) was determined in offspring during diestrous. Rats were then given 1, 2, 5, or 10 mg/kg morphine and paw lick latency was measured. Rats were killed during diestrous and mu-opioid receptor binding was determined in discrete brain regions, using [(3)H]DAMGO autoradiography. MS rats had significantly longer (P < .05) paw lick latencies compared with H rats. The percent maximal possible effect of morphine was significantly (P < .05) lower in MS compared with H rats for the 5 mg/kg dose. Mu-Opioid receptor binding capacity was significantly greater (P < .05) in MS rats compared with H rats in the medial preoptic nucleus. In conclusion, MS and H treatments led to antipodal differences in pain sensitivity in female rats and differential mu-opioid receptor binding in the medial preoptic nucleus.
This article describes the persistent impact of early life adversity on pain sensitivity and the analgesic potency of morphine. Clinically, early life history may play an important role in pain symptoms and responses to opioid analgesics.
我们测定了母鼠分离(MS)、新生期处理(H)和未处理(NH)的雌性大鼠在伤害感受相关脑区中,给予吗啡前后对有害热刺激的反应以及μ-阿片受体结合情况。将Long-Evans品系的母鼠随机分为三组,分别为每天与幼崽分离180分钟(MS组)、15分钟(H组)或不进行分离(NH组)。在子代120日龄时,于动情间期测定其爪舔潜伏期(50摄氏度热板法)。然后给大鼠注射1、2、5或10mg/kg吗啡,并测量爪舔潜伏期。在动情间期将大鼠处死,使用[³H]DAMGO放射自显影法测定离散脑区中的μ-阿片受体结合情况。与H组大鼠相比,MS组大鼠的爪舔潜伏期显著更长(P <.05)。对于5mg/kg剂量的吗啡,MS组大鼠的最大可能效应百分比显著低于H组大鼠(P <.05)。与H组大鼠相比,MS组大鼠在内侧视前核中的μ-阿片受体结合能力显著更强(P <.05)。总之,MS和H处理导致雌性大鼠在疼痛敏感性上出现相反的差异,以及内侧视前核中μ-阿片受体结合的差异。
本文描述了早期生活逆境对疼痛敏感性和吗啡镇痛效力的持续影响。临床上,早期生活史可能在疼痛症状和对阿片类镇痛药的反应中起重要作用。