朱燦麟運動創傷與慢性筋骨痛症網

非類固醇消炎藥--幫你還是害你？

By Alain Chu 

處理急性軟組織損傷，除了常規的休息(Rest)、冰敷(Ice)、施壓(Compression)、抬高(Elevation)外，也常用非類固醇消炎藥(Non steroidal anti-inflammatory drugs, NSAIDs)來「消炎」，這些做法似乎已成常規定理。(冰敷的迷思在「冰敷熱熨，何者為適？」一章已討論過)使用NSAIDs的原意，就是及早抑制炎症，減輕痛楚及腫脹，使患者可提早作功能鍛鍊，從而防止肌力減弱及關節僵硬。

 過去對NSAIDs的研究，大多以痛楚及腫脹的消退、功能恢復的速度來作成效指標，甚少關注軟組織的生長速度及張力强度(Tensile strength)。但近代的研究發現，使用NSAIDs治療軟組織受傷勞損，往往弊多於利，為何如此？

 前列腺素(Prostaglandins) 是細胞分泌的化學物質，不同的前列腺素負責不同功能，包括：誘發炎症、產生痛楚、支援血小板的凝血功能及保護胃黏膜免受酸液損害。前列腺素是由花生四烯酸(Arachidonic Acid)衍化而成，這過程需要環氧化酶(Cyclo-oxygenase, COX)催化，NSAIDs的作用就是抑制COX的功能，從而阻止前列腺素的產生，即是所謂消炎，所以NSAIDs又稱COX抑制劑(COX Inhibitor)。

 環氧化酶有兩種，分別是COX-1及COX-2，兩者都能產生前列腺素，而COX-1主要產生保護胃黏膜的前列腺素，當使用NSAIDs抑制COX-1及COX-2的功能時，同樣會抑制保護胃黏膜的前列腺素，是故不少人長期服食NSAIDs後患上胃潰瘍(Wolfe, et al., 1999)，這就是要同時服食胃藥的原因。

 新一代的環氧化酶-2抑制劑(COX-2 inhibitor)，只選擇性地抑制COX-2，所以不會影響胃黏膜，但同時又可抑制炎症，這好像是偉大的發明。

 然而，受傷後的炎症階段，其實是身體組織(包括肌肉、筋膜組織、骨骼)癒合過程的開始，是非常重要的環節。在這時期，巨噬細胞會除去壞死的損傷組織，生長因子會加速細胞再生，分泌膠原蛋白的纖維母細胞(Fibroblast)同趨活躍。

 那麽，過份壓抑炎症階段會否影響身體組織的修復？

 非類固醇消炎藥對肌腱及韌帶癒合的影響

 其實，不少學者認為，壓抑炎症反應即是阻礙軟組織的修復過程，甚至長遠影響軟組織的質量及強度(Cohen, et al., 2006; Dahners, et al., 1988; Elder, et al., 2001; Ferry, et al., 2007 ; Hertal, 1997; Magra, and Maffulli, 2006; McGriff-Lee, 2003)。在離體實驗中發現NSAIDs會抑制纖維母細胞及肌腱細胞的生長(Almekinders, et al. 1995; Tsai, et al., 2006)，及阻礙肌腱細胞游移至受損部位進行修復(Tsai, et al., 2007)。

 在動物實驗中又發現，把白鼠的肌腱切斷再接駁，然後餵以NSAIDs四星期，之後發現服食藥物組的肌腱張力强度只及對照組(無服食藥物組)的20% (屈肌肌腱)及30% (伸肌肌腱)(Kulick, 1986)。

 而在三百六十四位足髁扭傷的澳洲軍人身上發現，服用NSAIDs的患者雖然比對照組痛楚較輕及能較快復操，但其足髁穩定性較差及活動幅度較窄(Slatyer, et al., 1997)。很明顯，這些就是關節韌帶癒合不理想的現象，不過Slatyer仍然建議在治療急性足髁扭傷時使用NSAIDs，似乎只著眼於藥物的止痛功效，卻輕視其對關節力學的長遠影響。

 此外，肌腱的新陳代謝過程及隨運動負荷而變粗壯的現象，都需要COX-1及COX-2來控制(Trappe, et al., 2008)，長期服食能抑制COX的NSAIDs，肌腱及其他筋膜組織又怎會變强韌？怎能抵受運動時產生的負荷？

 非類固醇消炎藥對肌肉癒合的影響

 雖然NSAIDs在肌肉受傷的初期，可能有助減少腫脹及痛楚，但研究發現服食NSAIDs後，在急性肌肉拉傷的部位發現不到巨噬細胞，只有少量肌肉可以再生(Greene, et al., 2002)。不要忘記，巨噬細胞除了負責清除壞死組織外，也會分泌生長因子、化學吸引物(Chemoattractants)及前列腺素幫助肌肉再生(Cantini, et al., 1994; Chazaud, et al., 2003; Lu, et al., 2011; Robertson, et al., 1993)，沒有巨噬細胞，肌肉怎樣修復？

 不少學者都指出NSAIDs會阻礙身體清除壞死組織及減慢肌肉再生的速度(Almekinders, and Gilbert, 1986; Almekinder, et al., 1995; Best, and Hunter, 2000; Kellet, 1986; Mishra, et al., 1995; Peterson, et al., 2003; Weiler, 1992)。

近代研究又發現COX-2 對肌肉創傷後的再生極其重要，使用NSAIDs (即COX-2 抑制劑)便會阻礙肌肉再生(Bondesen, et al., 2004; Mendias, et al., 2004; Shen, et al., 2005)。

 更諷刺的是，在嚴重急性肌肉拉傷後，安慰劑減輕痛楚的速度及程度明顯優於NSAIDs(Reynolds, et al., 1995)。Reynolds認為NSAIDs的止痛作用，並不能抵銷因NSAIDs延遲肌肉復原所產生的疼痛。相反，安慰劑雖無治療作用，但卻容許肌肉自然癒合，「治療」效果更理想！

運動圈子中流行預防性地服食非類固醇消炎藥，以期減輕運動後肌肉痠痛及加速復原(Warden, 2009)，但非類固醇消炎藥會抑制運動後的蛋白質合成(Trappe, et al., 2002)，又怎會幫助運動後復原？

 非類固醇消炎藥對骨骼癒合的影響

 NSAIDs也常用於減輕骨折產生的痛楚，骨折的癒合與筋膜組織一樣，需要炎症期產生的生長因子介導(Simon, and O’Connor, 2007)。Dimmen發現非類固醇消炎藥會阻礙骨折癒合，尤其是疲勞性骨折 (Dimmen, et al., 2008)。阻礙骨折癒合的現象，在服用非類固醇消炎藥超過十五天後更為明顯(Simon, and O’Connor, 2007)。類似的報告常見於有關文獻當中(Dahners, et al., 2004; Gerstenfeld, et al., 2007; Harder, and An, 2003; Simon, et al., 2002;)。不止皮質骨(硬骨)的修復受NSAIDs影嚮，軟骨的生長也會受阻，因為NSAIDs會抑制軟骨內蛋白聚糖的合成(McKenzie, et al., 1976; Palmoski, et al., 1980; Rashad, et al., 1989)。

非類固醇消炎藥對抗氧化能力的影響

 NSAIDs除了會阻礙肌肉、筋膜組織、骨骼及軟骨的生長修復外，近年更發現NSAIDs會增加人體的氧化壓力(Oxidative Stress，自由基與抗氧化劑的比值)，換句話說，就是削弱人體的抗氧化能力。 (自由基-Free Radicle是帶有不成對電子的氧分子，是細胞新陳代謝過程中必然產生的物質，自由基極之容易氧化脂肪酸，而細胞膜正是由脂肪酸組成，簡單點說就是破壞細胞) (McAnulty, et al., 2007)。部份退行性疾病如動脈粥樣硬化、帕金遜症、阿玆海默症(Alzheimer’s Disease)等都與氧化壓力增加有關。維他命C、維他命E、礦物質硒等都是中和自由基的物質，故又稱抗氧化劑。相反，NSAIDs則削弱人體的抗氧化能力，更有學者稱之為「抗抗氧化劑」。

 非類固醇消炎藥的取捨

 處理急性軟組織受傷，要考慮的是在短暫快速舒緩痛楚，與長期身體組織修復理想之間取得平衡，沒有炎症，軟組織不會理想地癒合 (Stovitz, and Johnson, 2003)。若患者因服藥後疼痛減輕而誤以為復原，但其實軟組織韌度根本未足以抵受活動的要求，再次受傷的機會便大增(Orchard, and Best, 2002)。可惜當患者在受傷後，往往要求立即止痛，嚷着翌日便要繼續運動、工作，所以消炎止痛藥就是最「見效」的「治療」方法，醫者、患者雙方都皆大歡喜。即時止痛消炎才是大眾的期望，誰理會將來的後果。

 究竟處方NSAIDs治療軟組織創傷的做法是基於其醫療價值，還是商業利益？若不標榜NSAIDs的消炎止痛功能，只强調其對肌肉、筋膜組織、骨骼癒合的抑制作用，是否也可稱為「非類固醇抗修復藥」(Non-steroidal anti-healing drugs, NSAHDs)？只求短暫止痛卻無視深遠害處又是否合理的療法？

 上述研究結果並非國家機密，讀者可隨時在互聯網上查閱，但這些資訊卻永遠不會在電視廣告播出，更絕少有醫者向患者說明。我們日常接收的廣告資訊，大都是精心部署的行銷策略，當中的知識真假夾雜，目的就是所謂開拓市場，提升銷量。

 除了急性軟組織創傷，在慢性筋骨痛症的治療上，使用NSAIDs也十分普遍，基本上已成常規。所持的理據，就是認為這些慢性痛症是發炎引起，只要將炎症消除，便能治好痛症，使用NSAIDs，不單免卻類固醇的副作用，又能達到消炎的目的。這理論似乎言之成理，不少教科書也如是說，但這論據其實存在謬誤。

 以一般認為的退化性關節炎為例，使用NSAIDs治療差不多已成常規定理。患者當中不乏長者，可是長者的肌肉生長及再生能力已經較弱(McGeachie, and Ground, 1995)，NSAIDs又會阻礙肌肉的生長(Mackey, et al., 2007)，長期服用NSAIDs只會損害肌肉的功能，那麼肌肉又如何能控制關節？更何況這些所謂退化性關節炎，疼痛其實大部份源自關節鄰近的慢性筋膜病變(Fasciosis)或瘢痕攣縮(Adhesion)而非發炎，使用NSAIDs的理據何在？更諷刺的是，有研究發現服食NSAIDs六個月後，反而會加速膝及髖關節的軟骨磨蝕程度(Reijman, et al., 2005)。

 當眾醫者都鸚鵡學舌般嚷着「實証醫學」(Evidence Based Medicine)之時，豈不知原來並沒有堅實的理據支持使用NSAIDs治療慢性筋骨痛症，但又為何成為常規療法？實在諷刺！不過在一個講傳統、論輩份的專業王國，對一些根深蒂固的慨念，無論研究結果怎樣否定，醫者也會依然顧我，除非有份量的權威肯出來指正，眾人才會唯唯諾諾的付和，但所謂專家權威又豈會輕易推翻自己以往的主張？

 使用類固醇及非類固醇消炎藥治療軟組織炎症，其實是源自四十年前治療風濕性關節炎的經驗(Leadbetter, 1995)。然而風濕性關節炎與因創傷勞損引起疼痛的病理相異，治療目的也不同。炎症是風濕性關節炎的主要徵狀，主因是免疫系統的異常反應，在未有更佳治療方法時，用上述藥物消炎也許是權宜之計。但對軟組織創傷，炎症是修復過程的首要步驟，軟組織的修復才是重點，把兩者混為一談，用同樣的思路方法治療，實在說不過去。

 不過，非類固醇消炎藥對治療慢性筋骨痛症並非一無是處，對那些不問因由，盲塞愚昧，只求即時止痛又迷信藥物的患者，是最合適的療法。

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