Male Neuroendocrinology: Chronic Pain/Morphine/Placebo

多份报告表明，阿片类药物用于缓解慢性疼痛的接受和使用正在大幅增加，阿片类药物（特别是高剂量）和慢性疼痛都会扰乱神经内分泌功能，特别是下丘脑-垂体-肾上腺轴和下丘脑-垂体-性腺轴。此外，大量控制良好的镇痛试验证明，安慰剂效应在疼痛治疗中的高频率和重要性。一些研究表明，神经内分泌的改变是安慰剂效应的生物学基础。后一种观察结果在最近的神经影像学研究中更具有煽动性，这些研究表明，安慰剂镇痛与真正的镇痛摄入与皮层类似的解剖成分的激活有关。然而，迄今为止，对于慢性（与急性）疼痛、常规（与高）剂量阿片类药物使用和安慰剂给药对慢性肌肉骨骼疼痛患者的神经内分泌功能、疼痛症状或生活质量的影响，还很少有系统的研究。因此，本研究的目的是评估由于骨关节炎（OA）引起的慢性肌肉骨骼疼痛的中年男性，慢性OA疼痛本身与长期使用阿片类药物对神经内分泌功能（ACTH、皮质醇、LH和睾酮分泌）、疼痛症状、情绪和生活质量的影响，以及安慰剂镇痛是否会对神经内分泌功能、疼痛症状产生类似的影响。阿片类镇痛药引起的情绪和生活质量。

Multiple reports suggest that acceptance and use of opioid medicines for relief of chronic pain are increasing substantially, and that opioidergic medications (especially in high doses) and chronic pain each perturb neuroendocrine functions, particularly those of the hypothalamic-pituitary-adrenal and hypothalamic-pituitary-gonadal axes. In addition, numerous well-controlled analgesic trials attest to the high frequency and importance of the placebo effect in the treatment of pain. Several investigations suggest that neuroendocrine alterations underly the biology of the placebo effect. The latter observation is made more provocative by recent neuroimaging studies suggesting that placebo analgesia is associated with activation of similar anatomic components of the cortex as with bona fide analgesic intake. To date, however, there has been little systematic inquiry comparing the effects of chronic (versus acute) pain, conventional (versus high) dose opioid use and placebo administration on neureoendocrine function, pain symptomatology, or quality of life in a well-defined population of individuals with chronic musculoskeletal pain. Thus, the objectives of the current study are to evaluate, in middle-aged men with chronic musculoskeletal pain due to osetoarthritis (OA), the effects of chronic OA pain per se versus long-term opioid usage on neuroendocrine function (ACTH, cortisol, LH and testosterone secretion), pain symptomatology, mood and quality of life, and whether placebo analgesia results in similar, albeit soemwhat lesser, effects on on neuroendocrine function, pain symptomatology, mood and quality of life as those elicited by an opioid analgesic. To address these questions, we are initiating a 4-part study. In part I, we shall compare 12 men with chronic osteoarthritis (OA) pain on long term opioids, 12 narcotic naive men with chronic OA pain and 12 healthy, age- and BMI-matched men by assessing 12 hour overnight q 20 min blood sampling for measurements of ACTH, cortisol, LH and testosterone, as well as measures of pain symptomatology, mood and QOL. In part II, 36 narcotic naive patients with chronic OA pain, all of whom will have undergone overnight hormone sampling and neuropsychological evaluations in Part I, will be randomized to one of three treatment groups: MS Contin (15-90 mg), placebo or ?standard treatment? with NSAID's. Doses of placebo and MS Contin will be escalated over 4 weeks in a similar fashion with two-week maintenance and 2 week taper. At the end of maintenance at 6 weeks, all patients will return for repeat 12 hour frequent sampling and neuropsychological studies as in Part I. At the end of part II, patients will be invited to go on to an open label treatment period (Part III) with MS Contin (15-120 mg), which will consist of a 6-week dose escalation and 8 weeks of maintenance on opioid medication. At the conclusion of Part III, patients will be seen in outpatient clinic, and undergo AM endocrine testing and repeat neurpopsychologcal assessment. They will then be referred back to their physicians with recommendations for continued treatment with MS Contin, if patients are interested in this option. In Part IV of the study, patients will be followed by telephone for 6 months, after which they will be asked to return for an outpatient assessment like that at the end of Part III. The primary endpoints of this study will be measures of ACTH, cortisol, LH, and testosterone secretion, whereas the secondary endpoints will include selected neurobehavioral indices of pain and bothersomeness symptomatology, and measures of mood and quality of life. It is anticipated that this study will provide novel information regarding the effects of chronic musculoskeletal pain, and treatment with opioids versus placebo, on selected neuroendocrine functions in men.