Age- and sex-specific nociceptive response to endothelin-1
Age- and sex-specific nociceptive response to endothelin-1
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DOI：
10.1016/j.jpain.2007.04.002
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发表时间：
2007-08-01
期刊：
影响因子：
4
通讯作者：
Sweitzer, Sarah M.
中科院分区：
文献类型：
--
作者：
McKelvy, Alvin D.;Mark, Teresa R. M.;Sweitzer, Sarah M.
内皮素-1（ET-1）是由身体在损伤和疾病部位释放的化学介质。本研究验证了ET-1诱导的伤害性感受随年龄和性别而变化的假设。足底注射ET-1（1.1和3.3nmol）可引起年龄特异性的缩足和舔足（出生后7天> 21天> 60天）。伤害性反应的发作和持续时间取决于年龄。出生后第21天和第60天的大鼠表现出随时间推移而消退的立即行为发作，而P7大鼠具有延迟的行为反应，其在ET-1给药后20分钟发作，并持续超过75分钟的观察期。与雌性相比，P7雄性动物表现出更大的缩爪。除了自发的伤害性行为外，ET-1在所有年龄段均产生机械性异常性疼痛。与自发性伤害性感受一样，ET-1诱导的机械性异常性疼痛在年轻老年大鼠中的持续时间比成年大鼠长。这些研究结果表明，ET-1产生自发的伤害性行为和诱发的机械异常性疼痛，在年轻和成年大鼠，但时间曲线和大小的反应是年龄和性别依赖性的。这些发现是第一次描述的年龄和性别特异性ET-1诱导的伤害性感受。视角：内皮素-1是一种血管活性肽，在应激和冷痛后释放到体循环中，以及在损伤和疾病后局部释放到组织中。这些发现表明，与老年人相比，年轻人对释放内源性内皮素的刺激产生更大的疼痛。这种研究ET-1诱导的疼痛的发展方法进一步说明了理解疼痛机制作为生物体发展的一个功能的必要性，以便更好地治疗整个生命周期的疼痛。(c)2007年，美国疼痛协会。
Endothelin-1 (ET-1) is a chemical mediator released by the body at sites of injury and disease. This study tests the hypothesis that ET-1-induced nociception changes with age and sex. Intraplantar ET-1 (1.1 and 3.3 nmol) produced age-specific paw flinching and licking (postnatal day 7 > 21 > 60). The onset and duration of the nociceptive responses was dependent on age. Postnatal day (P) 21 and 60 rats displayed an immediate onset of behavior that subsided with time, whereas the P7 rats had a delayed behavioral response that onset at 20 minutes after ET-1 administration and continued beyond the 75 minute observation period. P7 males showed greater paw flinching compared with females. In addition to spontaneous nociceptive behaviors, ET-1 produced mechanical allodynia in all ages. As with spontaneous nociception, ET-1-induced mechanical allodynia was of a longer duration in the younger aged rats compared with adult rats. These findings show that ET-1 produces both spontaneous nociceptive behaviors and evoked mechanical allodynia in both young and adult rats but that the temporal profile and the size of the responses are age- and sex-dependent. These findings are the first description of age- and sex-specific ET-1-induced nociception. Perspective: Endothelin-1 is a vasoactive peptide released into the systemic circulation after stress and cold pain as well as locally in tissue after injury and disease. These findings suggest greater pain to stimuli that release endogenous endothelin in younger versus older organisms. This developmental approach to studying ET-1-induced pain further illustrates the need for understanding pain mechanisms as a function of the development of the organism so as to better treat pain across the life span. (c) 2007 by the American Pain Society.