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镇痛药对紧张性疼痛中枢处理的影响:一项交叉安慰剂对照研究。

The effects of analgesics on central processing of tonic pain: A cross-over placebo controlled study.

作者信息

Lelic Dina, Hansen Tine M, Mark Esben B, Olesen Anne E, Drewes Asbjørn M

机构信息

Mech-Sense, Department of Gastroenterology & Hepatology, Aalborg University Hospital, Aalborg, Denmark.

Mech-Sense, Department of Radiology, Aalborg University Hospital, Aalborg, Denmark; Department of Clinical Medicine, Aalborg University, Aalborg, Denmark.

出版信息

Neuropharmacology. 2017 Sep 1;123:455-464. doi: 10.1016/j.neuropharm.2017.06.022. Epub 2017 Jun 22.

Abstract

INTRODUCTION

Opioids and antidepressants that inhibit serotonin and norepinephrine reuptake (SNRI) are recognized as analgesics to treat moderate to severe pain, but the central mechanisms underlying their analgesia remain unclear. This study investigated how brain activity at rest and exposed to tonic pain is modified by oxycodone (opioid) and venlafaxine (SNRI).

METHODS

Twenty healthy males were included in this randomized, cross-over, double-blinded study. 61-channel electroencephalogram (EEG) was recorded before and after five days of treatment with placebo, oxycodone (10 mg extended release b.i.d) or venlafaxine (37.5 mg extended release b.i.d) at rest and during tonic pain (hand immersed in 2 °C water for 80 s). Subjective pain and unpleasantness scores of tonic pain were recorded. Spectral analysis and sLORETA source localization were done in delta (1-4 Hz), theta (4-8 Hz), alpha (8-12 Hz), beta1 (12-18 Hz) and beta2 (18-32 Hz) frequency bands.

RESULTS

Oxycodone decreased pain and unpleasantness scores (P < 0.05), whereas venlafaxine decreased the pain scores (P < 0.05). None of the treatments changed the spectral indices or brain sources underlying resting EEG. Venlafaxine decreased spectral indices in alpha band of the EEG to tonic pain, whereas oxycodone decreased the spectral indices and brain source activity in delta and theta frequency bands (all P < 0.05). The brain source activity predominantly decreased in the insula and inferior frontal gyrus.

CONCLUSION

The decrease of activity within insula and inferior frontal gyrus is likely involved in pain inhibition due to oxycodone treatment, whereas the decrease in alpha activity is likely involved in pain inhibition due to venlafaxine treatment.

摘要

引言

阿片类药物以及抑制5-羟色胺和去甲肾上腺素再摄取(SNRI)的抗抑郁药被公认为是治疗中度至重度疼痛的镇痛药,但其镇痛的中枢机制仍不清楚。本研究调查了羟考酮(阿片类药物)和文拉法辛(SNRI)如何改变静息状态和持续性疼痛状态下的大脑活动。

方法

本随机、交叉、双盲研究纳入了20名健康男性。在使用安慰剂、羟考酮(10毫克缓释剂,每日两次)或文拉法辛(37.5毫克缓释剂,每日两次)治疗五天前后,于静息状态和持续性疼痛状态(手浸入2℃水中80秒)下记录61通道脑电图(EEG)。记录持续性疼痛的主观疼痛和不适感评分。在δ(1-4赫兹)、θ(4-8赫兹)、α(8-12赫兹)、β1(12-18赫兹)和β2(18-32赫兹)频段进行频谱分析和sLORETA源定位。

结果

羟考酮降低了疼痛和不适感评分(P<0.05),而文拉法辛降低了疼痛评分(P<0.05)。所有治疗均未改变静息EEG的频谱指数或脑源。文拉法辛降低了EEG在持续性疼痛时α频段的频谱指数,而羟考酮降低了δ和θ频段的频谱指数及脑源活动(均P<0.05)。脑源活动主要在脑岛和额下回降低。

结论

脑岛和额下回内活动的降低可能与羟考酮治疗引起的疼痛抑制有关,而α活动的降低可能与文拉法辛治疗引起的疼痛抑制有关。

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