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新生儿损伤导致青春期时出现性别依赖性痛觉过敏和社交行为缺陷,但不改变吗啡反应。

Neonatal Injury Results in Sex-Dependent Nociceptive Hypersensitivity and Social Behavioral Deficits During Adolescence, Without Altering Morphine Response.

机构信息

Department of Comparative Biology and Experimental Medicine, Department of Physiology and Pharmacology, Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta, Canada.

Department of Comparative Biology and Experimental Medicine, Department of Physiology and Pharmacology, Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta, Canada.

出版信息

J Pain. 2017 Nov;18(11):1384-1396. doi: 10.1016/j.jpain.2017.07.003. Epub 2017 Jul 12.

Abstract

UNLABELLED

Neonatal injury is associated with persistent changes in sensory function and altered nociceptive thresholds that give rise to aberrant pain sensitivity in later life. Although these changes are well documented in adult rodents, little is known about the consequences of neonatal injury during adolescence. Because adolescence is a critical developmental period during which persistent pain conditions can arise, we examined the effect of neonatal injury on nociception, social behavior, and response to morphine in adolescent Sprague Dawley rats. Male and female rats exposed to plantar incision injury at postnatal day 3 displayed mechanical hypersensitivity that resolved by 24 hours after incision. When these animals reached adolescence (postnatal day 28-40), neonatally-injured male rats showed ipsilaterally restricted mechanical, heat, and cold hypersensitivity, as well as social behavioral deficits. In contrast, these effects were not seen in female rats. Neonatal injury did not alter acute morphine antinociception or the development of analgesic tolerance in either sex. Morphine-induced conditioned place preference, behavioral sensitization, and physical withdrawal were also not affected by neonatal incision. Thus, early-life injury results in sex-dependent pain-related hypersensitivity and social behavior deficits during adolescence, without altering the response to opioids.

PERSPECTIVE

Neonatal surgery has greater effects on adolescent male than female rats, resulting in pain-related hypersensitivity and social behavioral deficits. Neonatal surgery does not alter the antinociceptive effects of morphine or abuse liability.

摘要

未标记

新生儿损伤与感觉功能的持续变化以及伤害感受阈值的改变有关,这些变化导致成年后出现异常的疼痛敏感性。尽管这些变化在成年啮齿动物中已有详细记录,但对于青春期新生儿损伤的后果知之甚少。由于青春期是持续疼痛状况可能出现的关键发育时期,我们研究了新生儿损伤对青春期 Sprague Dawley 大鼠的伤害感受、社会行为和对吗啡反应的影响。在出生后第 3 天接受足底切口损伤的雄性和雌性大鼠表现出机械性超敏反应,这种反应在切口后 24 小时内消失。当这些动物进入青春期(出生后第 28-40 天)时,新生大鼠表现出同侧机械性、热和冷超敏反应以及社会行为缺陷。相比之下,这些影响在雌性大鼠中并未出现。新生儿损伤并未改变两种性别的急性吗啡镇痛作用或镇痛耐受的发展。吗啡诱导的条件位置偏好、行为敏化和躯体戒断也不受新生切口的影响。因此,早期生活中的损伤会导致青春期雄性大鼠而非雌性大鼠出现与疼痛相关的超敏反应和社会行为缺陷,而不会改变对阿片类药物的反应。

观点

新生儿手术对青春期雄性大鼠的影响大于雌性大鼠,导致与疼痛相关的超敏反应和社会行为缺陷。新生儿手术不会改变吗啡的镇痛作用或滥用倾向。

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