Exploring the Role of Testosterone as a Novel Anti-Nociceptive Agent in Women with Chronic Pain and Opioid Use

探索睾酮作为新型抗伤害剂对患有慢性疼痛和阿片类药物使用的女性的作用

基本信息

批准号：
10413965
负责人：
Shehzad Basaria
金额：
$ 22.38万
依托单位：
BRIGHAM AND WOMEN'S HOSPITAL
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-06-01 至 2025-04-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10413965
关键词：
Absence of pain sensation Age Aging Analgesics Androgen Receptor Animal Experimentation Back Pain Brief Pain Inventory Caring Chronic Chronic low back pain Clinical Clinical Trials Data Development Dose Double-Blind Method Exhibits Female Fibromyalgia Foundations Goals Gonadal Steroid Hormones Human Hypogonadism Incidence Injections Intramuscular Intramuscular Injections Measures Menopause Moods Neuraxis Observational Study Opioid Opioid Analgesics Outcome Pain Pain Threshold Pain interference Pathway interactions Patient Care Patients Pharmaceutical Preparations Physical Function Physiological Placebo Control Placebos Play Postmenopause Production Property Public Health Quality of life Questionnaires Randomized Randomized Controlled Trials Reporting Rodent Role SF-36 Sensory Serum Severities Sex Differences Sexual Dysfunction Stimulus Testing Testosterone Uncontrolled Study United States Walking Woman chronic back pain chronic pain chronic pain management clinical pain comparative efficacy disability efficacy evaluation experience hypothalamic pituitary gonadal axis improved male men non-cancer chronic pain novel older women opioid use pain perception pain reduction pain sensitivity prescription opioid response transmission process young woman

项目摘要

PROJECT SUMMARY There is abundant evidence that women and men do not experience pain equally. Compared to men, women are overrepresented in the majority of clinical pain conditions and also exhibit greater sensitivity to experimental pain. Similarly, use of analgesics is twice as common in women, compared to men, for conditions of comparable severities. Women not only have 20-fold lower serum testosterone concentrations compared to men but also experience a reduction in testosterone levels with age. Taken together, these data suggest that testosterone has anti-nociceptive properties which may explain why women have a higher incidence and severity of chronic pain compared to men. Additionally, patients who are prescribed opioid-analgesics for chronic pain experience further reduction in testosterone levels as opioids potently suppress the gonadal axis. Both pre- and postmenopausal women on chronic opioids demonstrate >50% reduction in testosterone levels compared to women not using opioids. In recent years, the use of sustained-action opioids in the management of chronic non-cancer pain has grown with many women taking multiple opioid analgesics. The development of opioid-induced hypogonadism deprives these women of the anti-nociceptive properties of testosterone and leads to a vicious cycle resulting in perpetuation of chronic pain despite being on opioids, subjecting patients to long-term requirement of even higher doses of opiates. Previous trials of testosterone replacement in men with opioid-induced hypogonadism have shown improvement in both clinical and experimental pain, and improvement in quality of life (QOL). However, despite having significantly higher burden of chronic pain, the efficacy of testosterone replacement on pain perception and tolerance has not been studied in women. The overall goal of this proposal is to evaluate the efficacy of physiologic testosterone replacement in improving clinical and experimental pain in a double-blind, randomized-controlled trial in postmenopausal women with chronic back pain who are being treated with opioid-analgesics for at least 6 months and have low testosterone. We will also assess the efficacy of testosterone replacement on QOL, mood and physical function. We propose a 12-week double-blind, randomized-controlled, proof-of-concept trial to determine the efficacy of physiologic testosterone replacement with weekly intramuscular injections versus placebo injections in women age 60 years and older with chronic back pain and testosterone deficiency. The following outcomes will be measured: 1) clinical pain, 2) experimental pain with quantitative sensory testing, and 3) QOL, mood and physical function. Because chronic pain is a major public health problem for which existing therapies are suboptimal and only provide partial relief, if this trial confirms benefits of testosterone therapy, patients will have an inexpensive, relatively safe and easy to administer medication available that has the potential to transform the care of these patients.

项目概要有大量证据表明，女性和男性所经历的疼痛并不相同。与男性相比，女性在大多数临床疼痛病症中所占比例过高，并且对实验性疼痛。同样，由于病情原因，女性使用镇痛药的比例是男性的两倍具有可比的严重性。与男性相比，女性的血清睾酮浓度不仅低 20 倍男性的睾酮水平也会随着年龄的增长而降低。综合起来，这些数据表明睾酮具有抗伤害特性，这可以解释为什么女性的发病率更高与男性相比，慢性疼痛的严重程度。此外，接受阿片类镇痛药治疗的患者由于阿片类药物有效抑制性腺轴，慢性疼痛会导致睾酮水平进一步降低。长期服用阿片类药物的绝经前和绝经后女性的睾酮水平均下降超过 50% 与不使用阿片类药物的女性相比。近年来，持续作用阿片类药物在治疗中的应用随着许多女性服用多种阿片类镇痛药，慢性非癌症疼痛的比例有所增加。的发展阿片类药物引起的性腺功能减退症剥夺了这些女性睾酮的抗伤害特性，导致恶性循环，导致尽管服用阿片类药物但慢性疼痛持续存在，使患者遭受长期需要更高剂量的阿片剂。先前对患有以下疾病的男性进行睾酮替代试验阿片类药物引起的性腺功能减退症已显示出临床和实验疼痛的改善，并且生活质量（QOL）的改善。然而，尽管慢性疼痛的负担明显更高，尚未在女性中研究睾酮替代疗法对疼痛感知和耐受性的功效。该提案的总体目标是评估生理睾酮替代疗法的功效在绝经后双盲、随机对照试验中改善临床和实验疼痛患有慢性背痛的女性，接受阿片类镇痛药治疗至少 6 个月，并且症状较轻睾酮。我们还将评估睾酮替代疗法对生活质量、情绪和身体的功效功能。我们提议进行一项为期 12 周的双盲、随机对照、概念验证试验，以确定每周肌内注射的生理性睾酮替代与安慰剂注射的疗效 60 岁及以上患有慢性背痛和睾酮缺乏的女性。以下结果将测量：1) 临床疼痛，2) 通过定量感觉测试进行的实验疼痛，以及 3) 生活质量、情绪和身体机能。因为慢性疼痛是一个主要的公共卫生问题，现有的治疗方法无法解决次优且仅提供部分缓解，如果该试验证实睾酮治疗的益处，患者将有一种廉价、相对安全且易于管理的药物，有可能改变这些患者的护理方式。