Azarov A V, Szabó G, Telegdy G
Department of Pathophysiology, Albert Szent-Györgyi Medical University, Szeged, Hungary.
Pharmacol Biochem Behav. 1992 Sep;43(1):193-7. doi: 10.1016/0091-3057(92)90657-2.
Atrial natriuretic peptide (ANP) is known to participate in different vegetative functions. The aim of the present study was to investigate the influence of ANP on nociception itself, pain sensitivity to morphine, and the development of acute and chronic tolerance to morphine. Morphine withdrawal signs were also evaluated by injecting naloxone. In adult, male NMRI mice, ANP administered SC or ICV did not affect pain sensitivity itself in a heat-radiant tail-flick test. Peptide treatment, however, depressed the acute nociceptive effect of a single dose of morphine (4 mg/kg, SC) after both SC (20-200 ng/animal) and ICV (5, 10, 20, or 200 ng/animal) ANP administration. ANP given SC and ICV attenuated the development of acute morphine tolerance. Acute morphine tolerance was assessed by giving a bolus injection of morphine (60 mg/kg) 24 h before the pain sensitivity to a challenge dose of morphine (4 mg/kg) was measured. ICV treatment with ANP also blocked the development of chronic morphine tolerance, but did not affect the appearance of naloxone-precipitated withdrawal syndromes. ANP seems to act differently on the development of tolerance to and dependence upon morphine.
已知心房利钠肽(ANP)参与多种自主功能。本研究的目的是探讨ANP对痛觉本身、对吗啡的痛觉敏感性以及对吗啡急性和慢性耐受性形成的影响。还通过注射纳洛酮评估吗啡戒断症状。在成年雄性NMRI小鼠中,皮下或脑室内注射ANP在热辐射甩尾试验中不影响痛觉敏感性本身。然而,在皮下(20 - 200 ng/动物)和脑室内(5、10、20或200 ng/动物)注射ANP后,肽治疗均抑制了单剂量吗啡(4 mg/kg,皮下注射)的急性伤害性作用。皮下和脑室内给予ANP减弱了急性吗啡耐受性的形成。急性吗啡耐受性通过在测量对挑战剂量吗啡(4 mg/kg)的痛觉敏感性前24小时给予大剂量吗啡(60 mg/kg)进行评估。脑室内注射ANP治疗也阻断了慢性吗啡耐受性的形成,但不影响纳洛酮诱发的戒断综合征的出现。ANP似乎对吗啡耐受性形成和依赖性的作用不同。