The effect of aging and sex in nociception

衰老和性别对伤害感受的影响

• 批准号: 7215815
• 负责人: Zenaide Quezado
• 金额: --
• 依托单位: CLINICAL CENTER
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/7215815
• 关键词: C fiber; age difference; electrostimulus; gender difference; laboratory mouse; pain; pain threshold; sensory mechanism; somatic afferent nerve; vocalization

Age-related change in nociception is an area of significant clinical and scientific interest in the study of pain mechanisms and treatment of pain. One reason for such interest is that in the growing elderly population, pain is often associated with chronic illnesses and is one of the most common reasons prompting the need for medical care. It is unclear whether in addition to increased incidence of chronic illness, age-related physiologic changes on nociception contribute to the increased prevalence of pain in the elderly. Another reason to study age-related changes in nociception is that when pain occurs at younger ages it can lead to long-term changes in pain perception, processing, and development. Therefore, a better understanding of age-specific mechanisms of nociception would enable the development and delivery of age-appropriate therapy. Age-related physiologic changes, such as changes in myelin, in biochemistry of sensory neurons, and nerve fiber density are known to occur. While the impact of age-related physiologic changes on transmission, processing, and perception of pain is incompletely understood, these age-related changes could certainly affect nociception. With regard to sex, it is well know that it impacts on the perception of noxious stimuli. Some studies have shown that in humans, analgesic requirement after surgery are greater in females compared to males. Women have lower response threshold to thermal stimulus compared to males. Therefore in order to properly treat pain, we have to further understand the impact of sex on nociception as well. In humans and animals, few studies have evaluated the effect of aging on Aa (pressure sensation), Aa (well-localized sharp pain), and C (diffuse burning pain) sensory nerve fibers and none has followed animals through the aging process. We are investigating the effects of aging on pain thresholds of Aa, Aa, and C fibers in female and male mice. Using our model of nociception we are measuring current vocalization threshold. We developed this novel assay to evaluate pain thresholds using electrical stimulus of increasing intensity at 5 Hz to stimulate C, 250 Hz to stimulate Aa, and 2000 Hz to stimulate Aa nerve fibers. We define vocalization as the pain-avoiding behavior to electrical stimuli, and measured current vocalization threshold in mice starting at an early age and longitudinally through their life span or 104 weeks. We showed that with the aging process, female mice have a U-shaped response to electrical stimulus. Additional studies are being conducted to further define the mechanism of this pattern of response to electrical stimulus.

与年龄相关的伤害感受是对疼痛机制研究和疼痛治疗的重要临床和科学兴趣的领域。引起这种兴趣的原因之一是，在不断增长的老年人群中，疼痛通常与慢性疾病有关，并且是促使需要医疗需求的最常见原因之一。尚不清楚除了增加慢性疾病的发生率是否增加，与年龄相关的伤害感受的生理变化有助于老年人的疼痛患病率增加。研究与年龄相关的伤害性变化的另一个原因是，当年轻时发生疼痛时，它可能会导致疼痛感知，加工和发育的长期变化。因此，对伤害感受的年龄特异性机制有更好的了解将使适合年龄的治疗的发展和交付。已知与年龄相关的生理变化，例如髓磷脂，感觉神经元和神经纤维密度的变化。尽管与年龄相关的生理变化对传播，加工和疼痛感知的影响尚不完全理解，但这些与年龄有关的变化肯定会影响伤害受伤。关于性，众所周知，它会影响有害刺激的感知。一些研究表明，在人类中，与男性相比，女性手术后的镇痛性要求更高。与男性相比，女性对热刺激的反应阈值较低。因此，为了正确治疗疼痛，我们也必须进一步了解性别对伤害感受的影响。 在人类和动物中，很少有研究评估了衰老对AA（压力感觉），AA（位置良好的急性疼痛）和C（弥漫性燃烧疼痛）感觉神经纤维的影响，没有一个人跟随动物进行衰老过程。我们正在研究衰老对雌性和雄性小鼠AA，AA和C纤维疼痛阈值的影响。使用我们的伤害感受模型，我们正在测量电流发声阈值。我们开发了这种新颖的测定法，以使用在5 Hz处增加强度的电刺激来评估疼痛阈值，以刺激C，250 Hz以刺激AA，并刺激2000 Hz以刺激AA神经纤维。我们将发声定义为对电刺激的避免疼痛的行为，并测量了从小就开始在其寿命或104周纵向的小鼠中的当前发声阈值。我们表明，随着衰老过程，雌性小鼠对电刺激有U形反应。正在进行其他研究，以进一步定义这种对电刺激的反应模式的机制。