Spivey J R, Jorgensen R A, Gores G J, Lindor K D
Department of Internal Medicine, Mayo Medical School, Rochester, Minnesota.
Am J Gastroenterol. 1994 Nov;89(11):2028-32.
Opiate antagonist agents ameliorate pruritus in some patients with cholestatic liver disease, suggesting that endogenous opioids may mediate pruritus in cholestasis. However, the endogenous opioids potentially responsible for pruritus remain unknown. Methionine-enkephalin is an endogenous opioid synthesized in numerous tissues including the gastrointestinal tract, and released into the portal circulation. Serum methionine-enkephalin concentrations are elevated in patients with chronic liver disease, making this opioid a candidate for opioid-mediated pruritus in cholestatic liver disease. The aim of our study was to determine whether elevated circulating methionine-enkephalin concentrations are associated with pruritus.
Serum concentrations of methionine-enkephalin were measured in 54 consecutive, untreated patients with primary biliary cirrhosis and 20 healthy controls. There was a direct correlation between methionine-enkephalin concentrations and total serum bilirubin (r = 0.42, p < 0.05) and the Mayo risk score (r = 0.5, p < 0.005). Methionine-enkephalin concentrations were significantly higher in histological stages 3 and 4 (48 +/- 4 pg/ml, n = 44), compared with stages 1 and 2 (29 +/- 12 pg/ml, n = 10, p < 0.05). Methionine-enkephalin concentrations in both histological groups were significantly higher than those in 20 healthy controls (16 +/- 4 pg/ml, p < 0.005).
There was no significant correlation between methionine-enkephalin concentrations and the presence of pruritus (46 +/- 25 pg/ml with pruritus vs. 40 +/- 22 pg/ml without pruritus, n = 20).
Increased serum methionine-enkephalin concentrations in patients with primary biliary cirrhosis were not associated with pruritus.
阿片类拮抗剂可改善部分胆汁淤积性肝病患者的瘙痒症状，这表明内源性阿片类物质可能介导胆汁淤积性瘙痒。然而，潜在导致瘙痒的内源性阿片类物质仍不明确。甲硫氨酸脑啡肽是一种在包括胃肠道在内的多种组织中合成并释放进入门静脉循环的内源性阿片类物质。慢性肝病患者血清甲硫氨酸脑啡肽浓度升高，使得这种阿片类物质成为胆汁淤积性肝病中阿片类介导瘙痒的候选物质。我们研究的目的是确定循环中甲硫氨酸脑啡肽浓度升高是否与瘙痒相关。
对54例未经治疗的原发性胆汁性肝硬化患者和20名健康对照者测定血清甲硫氨酸脑啡肽浓度。甲硫氨酸脑啡肽浓度与血清总胆红素（r = 0.42，p < 0.05）和梅奥风险评分（r = 0.5，p < 0.005）之间存在直接相关性。与组织学1期和2期（29±12 pg/ml，n = 10）相比，组织学3期和4期（48±4 pg/ml，n = 44）的甲硫氨酸脑啡肽浓度显著更高（p < 0.05）。两个组织学组的甲硫氨酸脑啡肽浓度均显著高于20名健康对照者（16±4 pg/ml，p < 0.005）。
甲硫氨酸脑啡肽浓度与瘙痒的存在之间无显著相关性（有瘙痒者为46±25 pg/ml，无瘙痒者为40±22 pg/ml，n = 20）。
原发性胆汁性肝硬化患者血清甲硫氨酸脑啡肽浓度升高与瘙痒无关。
