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纤维肌痛和长期使用阿片类药物患者的热痛敏与时间总和强度之间的相互作用

Interplay between noxious heat sensitivity and temporal summation magnitude in patients with fibromyalgia and long-term opioid use.

作者信息

Bao Jason D, Rosser Morgan A, Park Su Hyoun, Baker Anne K, Martucci Katherine T

机构信息

Human Affect and Pain Neuroscience Laboratory, Department of Anesthesiology, Duke University Medical Center, Durham, NC, United States.

Center for Translational Pain Medicine, Duke University Medical Center, Durham, NC, United States.

出版信息

Front Neurosci. 2023 Oct 12;17:1275921. doi: 10.3389/fnins.2023.1275921. eCollection 2023.

Abstract

INTRODUCTION

In chronic pain conditions such as fibromyalgia (FM), pain amplification within the central nervous system, or "central sensitization," may contribute to the development and maintenance of chronic pain. Chronic pain treatments include opioid therapy, and opioid therapy may maladaptively increase central sensitization, particularly in patients who take opioids long-term. However, it has remained unknown how central sensitization is impacted in patients who use opioids long-term.

METHODS

To investigate how long-term opioid therapy affects central sensitization, we used the validated measure of temporal summation. The temporal summation measurement consists of applying a series of noxious stimuli to a patient's skin and then calculating changes in the patient's pain rating to each stimulus. Using this measurement, we evaluated temporal summation in study participants with fibromyalgia who take opioids long-term (i.e., greater than 90 days duration; = 24, opioid-FM). We compared opioid-FM responses to 2 control groups: participants with fibromyalgia who do not take opioids ( = 33, non-opioid FM), and healthy controls ( = 31). For the temporal summation measurement, we applied a series of 10 noxious heat stimuli (sensitivity-adjusted temperatures) to the ventral forearm (2s duration of each stimulus, applied once every 3 s). Additionally, we collected responses to standard pain and cognitive-affective questionnaires to assess pain severity and other factors.

RESULTS AND DISCUSSION

Group differences in sensitivity-adjusted stimulus temperatures were observed, with only the non-opioid FM group requiring significantly lower stimulus temperatures (The opioid-FM group also required lower temperatures, but not significantly different from the control group). However, all 3 groups exhibited similar magnitudes of temporal summation. Across combined FM groups, temporal summation negatively correlated with pain severity ( = -0.31, = 0.021). Within the opioid-FM group, higher pain sensitivity to heat (i.e., lower sensitivity-adjusted temperatures) showed a trend relationship with higher opioid dosage ( = -0.45, = 0.036), potentially reflective of opioid-related hyperalgesia. Our findings also indicated that heightened pain severity may skew sensitivity-adjusted temporal summation, thereby limiting its utility for measuring central sensitization. Overall, in participants taking opioids, temporal summation may be influenced by hypersensitivity to heat pain, which appeared to vary with opioid dosage.

摘要

引言

在纤维肌痛(FM)等慢性疼痛病症中,中枢神经系统内的疼痛放大,即“中枢敏化”,可能会促使慢性疼痛的产生和维持。慢性疼痛治疗方法包括阿片类药物治疗,而阿片类药物治疗可能会适得其反地加剧中枢敏化,尤其是在长期服用阿片类药物的患者中。然而,长期使用阿片类药物的患者的中枢敏化受到何种影响仍不清楚。

方法

为了研究长期阿片类药物治疗如何影响中枢敏化,我们使用了经过验证的时间总和测量方法。时间总和测量包括向患者皮肤施加一系列有害刺激,然后计算患者对每个刺激的疼痛评分变化。利用这种测量方法,我们评估了长期服用阿片类药物(即持续时间超过90天;n = 24,阿片类药物 - FM组)的纤维肌痛研究参与者的时间总和。我们将阿片类药物 - FM组的反应与2个对照组进行比较:未服用阿片类药物的纤维肌痛参与者(n = 33,非阿片类药物FM组)和健康对照组(n = 31)。对于时间总和测量,我们在前臂腹侧施加一系列10次有害热刺激(根据敏感度调整温度)(每次刺激持续2秒,每隔3秒施加一次)。此外,我们收集了对标准疼痛和认知 - 情感问卷的反应,以评估疼痛严重程度和其他因素。

结果与讨论

观察到在敏感度调整后的刺激温度方面存在组间差异,只有非阿片类药物FM组需要显著更低的刺激温度(阿片类药物 - FM组也需要更低的温度,但与对照组无显著差异)。然而,所有3组的时间总和幅度相似。在合并的FM组中,时间总和与疼痛严重程度呈负相关(r = -0.31,p = 0.021)。在阿片类药物 - FM组中,对热的更高疼痛敏感性(即更低的敏感度调整温度)与更高的阿片类药物剂量呈趋势关系(r = -0.45,p = 0.036),这可能反映了阿片类药物相关的痛觉过敏。我们的研究结果还表明,更高的疼痛严重程度可能会使敏感度调整后的时间总和产生偏差,从而限制其用于测量中枢敏化的效用。总体而言,在服用阿片类药物的参与者中,时间总和可能会受到对热痛超敏反应的影响,而这种超敏反应似乎随阿片类药物剂量而变化。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/08fd/10600517/8bf97f462519/fnins-17-1275921-g001.jpg

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