Janas Aleksandra, Folwarczna Joanna
Department of Pharmacology, School of Pharmacy with the Division of Laboratory Medicine in Sosnowiec, Medical University of Silesia, Katowice, Poland.
Naunyn Schmiedebergs Arch Pharmacol. 2017 Feb;390(2):175-185. doi: 10.1007/s00210-016-1295-6. Epub 2016 Nov 28.
The results of epidemiological, clinical, and in vivo and in vitro experimental studies on the effect of opioid analgesics on bone are inconsistent. The aim of the present study was to investigate the effect of morphine (an agonist of opioid receptors), buprenorphine (a partial μ opioid receptor agonist and κ opioid receptor antagonist), and naloxone (an antagonist of opioid receptors) on the skeletal system of female rats in vivo. The experiments were carried out on 3-month-old Wistar rats, divided into two groups: nonovariectomized (intact; NOVX) rats and ovariectomized (OVX) rats. The bilateral ovariectomy was performed 7 days before the start of drug administration. Morphine hydrochloride (20 mg/kg/day s.c.), buprenorphine (0.05 mg/kg/day s.c.), or naloxone hydrochloride dihydrate (2 mg/kg/day s.c.) were administered for 4 weeks to NOVX and OVX rats. In OVX rats, the use of morphine and buprenorphine counteracted the development of osteoporotic changes in the skeletal system induced by estrogen deficiency. Morphine and buprenorphine beneficially affected also the skeletal system of NOVX rats, but the effects were much weaker than those in OVX rats. Naloxone generally did not affect the rat skeletal system. The results confirmed the role of opioid receptors in the regulation of bone remodeling processes and demonstrated, in experimental conditions, that the use of opioid analgesics at moderate doses may exert beneficial effects on the skeletal system, especially in estrogen deficiency.
关于阿片类镇痛药对骨骼影响的流行病学、临床以及体内和体外实验研究结果并不一致。本研究的目的是在体内研究吗啡（阿片受体激动剂）、丁丙诺啡（μ阿片受体部分激动剂和κ阿片受体拮抗剂）和纳洛酮（阿片受体拮抗剂）对雌性大鼠骨骼系统的影响。实验在3月龄的Wistar大鼠上进行，分为两组：未去卵巢（完整；NOVX）大鼠和去卵巢（OVX）大鼠。在开始给药前7天进行双侧卵巢切除术。将盐酸吗啡（20mg/kg/天，皮下注射）、丁丙诺啡（0.05mg/kg/天，皮下注射）或二水合盐酸纳洛酮（2mg/kg/天，皮下注射）给予NOVX和OVX大鼠4周。在OVX大鼠中，使用吗啡和丁丙诺啡可抵消雌激素缺乏引起的骨骼系统骨质疏松变化的发展。吗啡和丁丙诺啡对NOVX大鼠的骨骼系统也有有益影响，但作用比OVX大鼠弱得多。纳洛酮一般不影响大鼠骨骼系统。结果证实了阿片受体在骨重塑过程调节中的作用，并在实验条件下表明，中等剂量使用阿片类镇痛药可能对骨骼系统产生有益影响，尤其是在雌激素缺乏的情况下。
