Modulation of remifentanil-induced postinfusion hyperalgesia by the beta-blocker propranolol in humans

作者：Chu Larry F^*; Cun Tony; Ngai Lynn K; Kim Julie E; Zamora Abigail K; Young Chelsea A; Angst Martin S; Clark David J

来源：Pain, 2012, 153(5): 974-981.

DOI：10.1016/j.pain.2012.01.014

• Antagonist
• beta(2)-Adrenergic receptor
• Hyperalgesia
• Mechanical stimulation
• Propranolol
• Remifentanil-induced postinfusion hyperalgesia
• Thermal stimulation

Acute and chronic exposure to opioids has been associated with hyperalgesia in both animals and humans. A genetic analysis of opioid-induced hyperalgesia in mice linked the beta(2)-adrenergic receptor to mechanical sensitization after opioid exposure. In humans, expansion of the area of mechanical hyperalgesia surrounding an experimentally induced lesion after the cessation of remifentanil infusion is a commonly used model of opioid hyperalgesia (remifentanil-induced postinfusion hyperalgesia, RPH). The purpose of our translational study was to test the hypothesis that the beta-adrenergic receptor antagonist propranolol modulates the expression of RPH in humans. This double-blinded, randomized, placebo-controlled, crossover study was performed in 10 healthy human volunteers. During test sessions, intracutaneous electrical stimulation was used to generate areas of secondary mechanical hyperalgesia. The area of this sensitization was measured before, during, and after remifentanil infusion. Heat pain sensitivity was also followed. During one test session, subjects received propranolol infusion. We observed an average increase in the areas of secondary mechanical hyperalgesia to 141% of the baseline in subjects infused with remifentanil and placebo (P = 0.00040). However, when remifentanil infusion was combined with propranolol, the area of secondary hyperalgesia after terminating remifentanil was not significantly different than the area before beginning the opioid infusion (P = 0.13). Thermal hyperalgesia was not observed after remifentanil infusion. Propranolol infusion at the selected dose had minor hemodynamic effects. Concomitant infusion of propranolol with remifentanil prevented the expression of RPH. beta-adrenergic receptor blockade may be a useful pharmacological strategy for preventing hyperalgesia in patients exposed to opioids.

• 出版日期2012-5