乙醯胺酚也可以緩解心理性疼痛

作者：Janis C. Kelly  
出處：WebMD醫學新聞

　　December 30, 2009 —一直以來的認知，鴉片類藥物和其他強效止痛藥對心理性和生理性疼痛都有效，但是新證據認為，即使是乙醯胺酚這種弱效的成藥，也可以緩解心理性不適，例如社會排斥的壓力。
　　
　　肯塔基大學藝術與科學院心理系C. Nathan DeWall博士領導的研究團隊，探討神經系統和心理性疼痛之間的交集，他們將健康志願者隨機分派接受3週的治療，每天服用乙醯胺酚或安慰劑，之後比較關於社會疼痛(social pain)的自我報告。
　　
　　另一篇研究中，研究者試圖藉由使用功能性磁振造影，來找出腦部中有關社會排斥和社會疼痛之區域的活性變化。
　　
　　DeWall博士表示，根據我們對於社會和生理疼痛系統之交集的瞭解，緩解生理疼痛的藥物應可減少社會排斥之疼痛的觀念看似簡單易懂，令我意外的是，我發現沒有人對此觀念做過研究。
　　
　　他形容「社會疼痛」是「對於來自於社會的威脅而產生的疼痛反應，社會排斥是社會疼痛事件中的一種」。
　　
　　這項研究將登載於下一期的Psychological Science。
　　
　　【測量疼痛感覺】
　　第一個實驗包括了62名健康志願者，隨機分派接受每天1000 mg的乙醯胺酚或安慰劑。每天傍晚，研究對象使用疼痛感覺量表報告他們當天經歷的社會疼痛程度。
　　
　　研究者報告指出，一如預期，服用乙醯胺酚者的疼痛感覺隨著時間顯著降低(P < .05)，而安慰劑組則沒有改變。
　　
　　DeWall博士向Medscape Psychiatry表示，這些資料首次提供減少生理疼痛可以降低社會排斥疼痛的證據，增加了我們對於表面上看似不同的疼痛經驗是由相同的神經生物系統處理的瞭解。
　　
　　第二個實驗中，乙醯胺酚劑量加倍到每天2000 mg，以補足研究樣本較少的統計強度(10名參與者被隨機分派接受乙醯胺酚，15名參與者被隨機分派使用安慰劑)。
　　
　　服藥後3週，研究對象參加一種會產生社會排斥感覺的電腦遊戲。
　　
　　功能性磁振造影顯示，在遊戲期間，腦部與社會疼痛壓力和生理疼痛感覺有關的區域(背側前扣帶皮質和前腦島)中，乙醯胺酚組的神經活性顯著低於安慰劑組。
　　
　　不過，研究者報告指出，乙醯胺酚組和對照組對於排斥情節(exclusion episode)的社會壓力反應程度相當。
　　
　　【可能可以降低暴力行為？】
　　DeWall博士表示，儘管此藥物缺乏對於社會壓力經驗的影響，研究者結論認為，乙醯胺酚可以在神經層次減少社會排斥疼痛。
　　
　　資料顯示，使用這個一般用於緩解生理疼痛的成藥，至少可以暫時緩和壓力相關的社會疼痛。
　　
　　研究者進一步指出，乙醯胺酚或許可以預防暴力行為，許多研究顯示，被排擠會導致侵犯性與反社會行為，造成社會生活上的併發症。如果乙醯胺酚可以減少排斥壓力，或許也可以減少因排斥而產生的反社會行為。
　　
　　DeWall博士表示，此研究將改變科學家和一般人對於生理和社會疼痛的瞭解。社會疼痛，如長期孤單，對健康的傷害與抽菸及肥胖一樣，我們希望，我們的研究發現可以點出讓研究者找到減緩社會排斥疼痛的方法。
　　
　　【名聲】
　　Bruce G. Charlton醫師應Medscape Psychiatry之邀對該研究發表評論時，推崇研究者的努力。
　　
　　他表示，研究這個古老、便宜的無專利成藥，很難獲得研究資助，所以我對於完成此研究的作者們表達衷心的祝賀。
　　
　　Charlton醫師是Medical Hypotheses 的主編，也是英國Buckingham大學的理論醫學教授，他同意各種的疼痛是相關的，所以有充分理由假設乙醯胺酚或paracetamol對於各種不適感覺引起的疼痛都有幫助，包括壓力引起者。
　　
　　不過，他指出，同樣的效果應可運用到阿斯匹靈、非類固醇抗發炎藥物與鴉片類藥物，他表示，這些有更多證據。
　　
　　【其他解釋】
　　北挪威大學醫院臨床研究部的Magne Arve Flaten醫師也為Medscape Psychiatry發表評論，Flaten醫師最近發表一篇有關安慰劑止痛的認知與情感因素的研究，他認為該研究的資料可以有其他的解釋。
　　
　　Flaten醫師表示，作者們似乎認為排擠會引起「社會疼痛」，但這只是可能，就我的觀點，更精確的說法應該是，疼痛與社會排斥都與不愉快和其他負面情感有關。
　　
　　社會疼痛不是我們一般認知的疼痛，但是它和疼痛有類似的情感，其他負面情感也是。
　　
　　他指出，研究者的第一個實驗顯示，乙醯胺酚降低了「傷害感覺」，但是，這個影響看似顯著，實際並不大。他認為，研究者無法在第二個實驗重現心理效果，因為樣本少導致強度不足。
　　
　　Flaten醫師表示，我不認為這個研究提到有關疼痛的任何事務，無法用這些實驗研究疼痛這個感覺詞彙。該研究告訴我們，乙醯胺酚可以減少社會排斥引起的一些負面情感，是很有趣的論點。
　　
　　國家心智健康研究中心與Gulf Atlantic Group Incorporated公司資助該研究。DeWall醫師、Flaten醫師與 Charlton醫師皆宣告沒有相關財務關係。
　　
　　Psychol Sci (付印中)。  


Acetaminophen May Also Relieve Psychological Pain

By Janis C. Kelly
Medscape Medical News

December 30, 2009 — Opiates and other strong analgesics have long beenknown to numb psychological as well as physical pain, but newevidence suggests that even mild over-the-counter drugs likeacetaminophen may relieve psychological discomfort, such as the stressof social rejection.

A research team led by psychologist C. Nathan DeWall, PhD, from the University of Kentucky College of Arts and Sciences, Departmentof Psychology, Lexington, examined the overlap between neural andpsychological pain by randomly assigning healthy volunteers to 3 weeksof either daily acetaminophen or placebo, then comparing self-reportsof social pain.

In a second study, the researchers used functional magnetic resonanceimaging in an attempt to correlate changes in brain activity in regionsbelieved to be associated with responses to social rejection withsubjects' experiences of social pain.

"Theidea that a drug designed to alleviate physical pain should reduce thepain of social rejection seemed simple and straightforward based onwhat we know about neural overlap between social and physical painsystems. To my surprise, I couldn't find anyone who had ever testedthis idea," Dr. DeWall said.

He described "social pain" as "a painful affective response to aperceived threat to social belonging. Social rejection is one example of a socially painful event."

The research is due to be published in an upcoming edition of Psychological Science.

Hurt Feelings Measured

The first experiment included 62 healthy volunteers randomly assignedto 1000 mg/day of either acetaminophen or placebo. Each evening,participants used a version of the Hurt Feelings Scale to report howmuch social pain they experienced that day.

As expected, hurt feelings decreased significantly over time amongparticipants who took acetaminophen (P < .05), but they wereunchanged in the placebo group, the researchers report.

"These data provide some of the first evidence that reducing physicalpain can reduce the pain of social rejection. They add to ourunderstanding of how seemingly different types of painful experiencesare processed through the same neurobiological systems," Dr. DeWalltold Medscape Psychiatry.

In the second experiment, the acetaminophen dose was doubled to 2000mg/day in an attempt to compensate for the lower statistical powerassociated with the smaller groups (10 participants randomly assignedto acetaminophen, 15 participants randomly assigned to placebo).

After 3 weeks of taking the pills, the subjects participated in a computer game rigged to create feelings of social rejection.

Functional magnetic resonance imaging findings showed that theacetaminophen group had significantly less neural activity than theplacebo group during the game in brain regions associated with thedistress of social pain and with the affective component of physicalpain (the dorsal anterior cingulate cortex and anterior insula).

However, the acetaminophen and control groups "reported equal levels ofsocial distress in response to the exclusion episode," the researchersreport.

Potential to Reduce Violent Behavior?

Dr. DeWall said that despite the drug's lack of effect on theexperience of social distress, the researchers concluded thatacetaminophen reduced the pain of social rejection at the neural level.

The data "suggest that at least temporary mitigation of socialpain–related distress may be achieved by means of an over-the-counterpainkiller that is normally used for physical aches and pains."

The investigators further suggest that acetaminophen may preventviolent behavior, as "many studies have shown that being rejected cantrigger aggressive and antisocial behavior, which could lead to furthercomplications in social life.... If acetaminophen reduces the distressof rejection, the antisocial behavioral consequences of rejection maybe reduced as well."

"This research has the potential to change how scientists andlaypersons understand physical and social pain. Social pain, such aschronic loneliness, damages health as much as smoking and obesity. Wehope our findings can pave the way for interventions designed to reducethe pain of social rejection," said Dr. DeWall.

Kudos

Asked by Medscape Psychiatry to comment on the study, Bruce G. Charlton, MD, applauded the investigators' research efforts.

"It is particularly difficult to get research funding to study old,cheap, unpatented, over-the-counter drugs, so I congratulate theauthors on doing this," he said.

Dr. Charlton, who is editor-in-chief of Medical Hypotheses andprofessor of theoretical medicine at the University of Buckingham,United Kingdom, agreed that different sorts of pain are often related,so there is good reason to assume that acetaminophen or paracetamol maybenefit those who suffer any type of pain of unpleasant feelings,including some types of depression.

However, he noted that the same effect would likely apply to aspirin,nonsteroidal anti-inflammatory drugs, and opiates, "about which thereis more evidence," he said.

Alternative Interpretation

Magne Arve Flaten, MD, from the department of clinical research atUniversity Hospital of North Norway, Tromso, also commented on thestudy for Medscape Psychiatry. Dr. Flaten, who recently published astudy of cognitive and emotional factors in placebo analgesia, saidthat alternative interpretations of the data are possible.

"The authors seem to think that rejection induces 'social pain,' but itwould probably, in my view, be more correct to say that both pain andsocial rejection are associated with unpleasantness and other negativeemotions.

"Social pain is not pain as we ordinarily think of it, but it sharessome of the emotional aspects that pain has, and aspects that probablyother negative emotions also have," said Dr. Flaten.

He noted that the investigators' first experiment showed thatacetaminophen reduced "hurt feelings," but that the effects, althoughsignificant, "seem small." He suspects that the researchers' inabilityto replicate the psychological effect in the second experiment may havebeen a result of lack of power because of the small sample size.

"I do not think this research tells us anything about pain, since pain,in a normal sense of the word, was not investigated in theseexperiments. The research tells us that acetaminophen could reduce someof the negative emotional consequences of social rejection, which isvery interesting," Dr. Flaten said.

The study was funded by the National Institute of Mental Health and theGulf Atlantic Group Incorporated. Dr. DeWall, Dr. Flaten, and Dr.Charlton have disclosed no relevant financial relationships.

Psychol Sci (in press).