脊髓損傷后疼痛的臨床研究證據(jù)

王玉明，唐麗，李建軍

脊髓損傷后疼痛的臨床研究證據(jù)

王玉明1，唐麗2，李建軍1

疼痛是脊髓損傷后常見并發(fā)癥。有關(guān)臨床研究涉及疼痛機(jī)制、分類及治療等。由于脊髓損傷后疼痛需要綜合性治療，其中每一種干預(yù)措施可能都只產(chǎn)生很小的療效。本文通過文獻(xiàn)復(fù)習(xí)脊髓損傷后疼痛方面臨床研究，審慎地應(yīng)用最佳證據(jù)做出臨床決策。

脊髓損傷；疼痛；康復(fù)；綜述

[本文著錄格式]王玉明，唐麗，李建軍.脊髓損傷后疼痛的臨床研究證據(jù)[J].中國(guó)康復(fù)理論與實(shí)踐,2014,20(10):945-949.

最近幾十年，脊髓損傷后膀胱、皮膚、心血管和呼吸系統(tǒng)護(hù)理等方面取得顯著成效，但是脊髓損傷后疼痛仍然缺乏有效的治療措施。目前脊髓損傷疼痛機(jī)制眾說紛紜，而且缺乏標(biāo)準(zhǔn)的分類方法，這都將影響脊髓損傷后疼痛的治療效果[1]。

1 發(fā)病率、性質(zhì)及分類

疼痛是脊髓損傷常見并發(fā)癥之一。各種文獻(xiàn)所報(bào)道的脊髓損傷后疼痛發(fā)生率差異較大，為11%～94%[2]，最近報(bào)道多為60%～80%的脊髓損傷患者需要經(jīng)歷疼痛煎熬[3-4]。估計(jì)30%～40%的脊髓損傷患者患有嚴(yán)重的致殘性疼痛[4-5]。四肢癱患者、胸脊髓損傷患者與馬尾神經(jīng)病變者的重度疼痛發(fā)生率分別為10%～15%、25%和42%～51%[6]。Bonica研究發(fā)現(xiàn)疼痛在脊髓損傷患者中普遍存在，但異質(zhì)性明顯[5]。脊髓損傷后疼痛國(guó)際協(xié)會(huì)專家組最新提出了一種分類標(biāo)準(zhǔn)，將疼痛分為感受傷害(肌肉骨骼性和內(nèi)臟性疼痛)和神經(jīng)性疼痛(損傷水平以上、之中和以下的疼痛)[7]。Finnerup等研究發(fā)現(xiàn)神經(jīng)痛隨著時(shí)間逐漸加重，而肌肉骨骼性疼痛則相反，且損傷后1個(gè)月內(nèi)出現(xiàn)感覺過敏預(yù)示著損傷平面以下疼痛的發(fā)展[8]。

2 心理因素

大多數(shù)慢性脊髓損傷疼痛研究主要集中在醫(yī)學(xué)原因和臨床表現(xiàn)。Woollaars問卷調(diào)查后發(fā)現(xiàn)脊髓損傷后疼痛發(fā)生率高達(dá)77%。與輕度疼痛相關(guān)的因素有疼痛控制和應(yīng)對(duì)、淡然對(duì)待、高損傷水平和非外傷性脊髓損傷原因。高抑郁水平與脊髓損傷后無助感、“災(zāi)難化”和憤怒相關(guān)。令人驚訝的是疼痛強(qiáng)度與健康、幸福感、抑郁沒有獨(dú)立關(guān)系[9]。使用藥物、手術(shù)治療脊髓損傷后疼痛之前，應(yīng)充分了解患者的心理社會(huì)環(huán)境[10-12]。Giardino指出根據(jù)“共同應(yīng)對(duì)災(zāi)難化”模型，疼痛患者可向社會(huì)獲得支持[13]。

3 脊髓損傷后疼痛的非藥物管理

3.1 按摩

按摩主要用于治療肌肉骨骼疼痛。Budh等對(duì)脊髓損傷3年病史的患者進(jìn)行調(diào)查，發(fā)現(xiàn)按摩和熱療是最好的非藥物治療[14]。Heutink等通過問卷調(diào)查發(fā)現(xiàn)脊髓損傷患者常用按摩緩解疼痛并認(rèn)為治療效果較好[15]。Norrbrink等研究中發(fā)現(xiàn)針灸與按摩皆能緩解脊髓損傷后疼痛[16]。研究證實(shí)按摩可一定程度緩解脊髓損傷后疼痛。

3.2 整骨療法

整骨療法經(jīng)證實(shí)對(duì)患者骨關(guān)節(jié)炎和炎癥條件的慢性疼痛有效。整骨療法緩解疼痛與它影響β-內(nèi)啡肽釋放和減少5-羥色胺相關(guān)[17]。Arienti等研究證實(shí)單獨(dú)整骨療法緩解脊髓損傷后疼痛效果有限[18]。

3.3 針刺療法

針灸是中醫(yī)的重要組成部分，可激活Ⅱ型和Ⅲ型肌肉傳入神經(jīng)纖維或A-δ纖維，通過刺激大感覺神經(jīng)元以及釋放內(nèi)源性阿片類藥物、神經(jīng)遞質(zhì)和神經(jīng)激素阻斷疼痛閘門[19-20]。Lee等最近報(bào)道針灸通過抑制星形膠質(zhì)細(xì)胞jun-氨基末端激酶激活緩解脊髓損傷后神經(jīng)痛[21]。Dyson-Hudson等證實(shí)針刺及Trager治療對(duì)減輕脊髓損傷患者功能活動(dòng)性肩痛均有效[20,22]。Nayak等發(fā)現(xiàn)42%中樞性疼痛患者和80%肌肉骨骼疼痛患者疼痛得到了明顯緩解[23]。Rapson等試驗(yàn)報(bào)道，67%患者疼痛改善，特別是雙側(cè)對(duì)稱恒定的燒灼痛[24]。樊留博等發(fā)現(xiàn)針灸緩解脊髓損傷后疼痛效果顯著[25]。因此，有證據(jù)證明針灸可緩解脊髓損傷后傷害性肌肉骨骼肩部疼痛及神經(jīng)性疼痛。

3.4 運(yùn)動(dòng)療法

運(yùn)動(dòng)可以改善慢性疾病，增強(qiáng)個(gè)人主觀幸福感。Ditor證實(shí)肩胛骨訓(xùn)練特異地拉伸肩胛骨并加強(qiáng)肩袖肌肉，對(duì)減輕肩關(guān)節(jié)疼痛和改善功能都有效果[26]。Nash等報(bào)道中年截癱患者經(jīng)過4個(gè)月循環(huán)抗阻訓(xùn)練(CRT)后的肌力、耐力、無氧功率明顯增強(qiáng)，而肩疼痛評(píng)分也明顯降低(P=0.008)[27]。Finley等研究顯示特殊輪椅(MAGICwheels)減少肩部疼痛[28]。

3.5 行為管理

3.5.1 催眠暗示

催眠用于治療脊髓損傷后疼痛機(jī)制不明。催眠是非藥物性、有潛力的治療，鑒于催眠反應(yīng)的可變性，目前對(duì)它的使用存在爭(zhēng)議。Jensen等研究發(fā)現(xiàn)81%的脊髓損傷患者在損傷1年后仍使用催眠，但只有23%的患者疼痛強(qiáng)度緩解[29]，這些數(shù)據(jù)說明催眠也許不是直接緩解疼痛強(qiáng)度，而是減輕患者的疼痛體驗(yàn)。

3.5.2 認(rèn)知行為療法

認(rèn)知行為療法(CBT)是一種對(duì)慢性疼痛常用的心理干預(yù)，是全面疼痛管理計(jì)劃的一部分。Norrbrink Budh等治療脊髓損傷后疼痛患者的疼痛管理計(jì)劃包括教育、行為療法、放松療法、運(yùn)動(dòng)和主體意識(shí)培養(yǎng)，研究發(fā)現(xiàn)這種管理計(jì)劃并沒有明顯改變疼痛強(qiáng)度[30]。Perry等將脊髓損傷慢性疼痛患者置于多學(xué)科疼痛認(rèn)知行為管理計(jì)劃中，治療組中出現(xiàn)改善疼痛強(qiáng)度和醫(yī)院焦慮抑郁量表(HADS)評(píng)分下降的趨勢(shì)。然而，9個(gè)月隨訪時(shí)分?jǐn)?shù)恢復(fù)到治療前[31]。有研究者認(rèn)為行為認(rèn)知療法可能是通過控制脊髓損傷疼痛相關(guān)的心理癥狀幫助患者應(yīng)對(duì)疼痛。

3.5.3 視覺意象

視覺意象療法使用引導(dǎo)圖像改變感知和行為，促進(jìn)皮質(zhì)重組從而緩解疼痛[32]，已在各種研究中應(yīng)用[33-34]。Soler等發(fā)現(xiàn)視覺意象結(jié)合經(jīng)顱直流電刺激(TDCS)可減少疼痛感知、緩解疼痛、改善工作能力和睡眠(P＜0.05)。結(jié)合組30%參與者疼痛強(qiáng)度改善30%以上。視覺意象組報(bào)道疼痛強(qiáng)度顯著改善(P= 0.02)，然而效果維持不到12周[35]。視覺意象療法對(duì)馬尾神經(jīng)損傷患者效果顯著，因此應(yīng)用視覺意象療法時(shí)應(yīng)考慮脊髓損傷類型[36]。

3.6 經(jīng)顱電刺激

經(jīng)顱電刺激(TCES)在頭皮上應(yīng)用電極施加電流，是脊髓損傷后疼痛一種相對(duì)較新的治療方法。3個(gè)隨機(jī)對(duì)照試驗(yàn)(Soler[35]、Tan[37]、Fregni[38])都表明它可能緩解脊髓損傷相關(guān)的慢性疼痛。但治療參數(shù)，如刺激時(shí)間、治療周期等未達(dá)成一致。

3.7 經(jīng)顱磁刺激

經(jīng)顱磁刺激(TMS)是一種非侵入性、相對(duì)安全的技術(shù)，線圈電磁流產(chǎn)生的脈沖磁場(chǎng)穿過顱骨誘導(dǎo)神經(jīng)元去極化[39]。Defrin等[39]和Kang等[40]的兩個(gè)隨機(jī)試驗(yàn)提供1級(jí)證據(jù)：經(jīng)顱磁刺激可降低痛閾，但不減輕疼痛強(qiáng)度。今后的研究應(yīng)致力于參數(shù)研究，如刺激時(shí)間與強(qiáng)度。

3.8 經(jīng)皮神經(jīng)電刺激

經(jīng)皮神經(jīng)電刺激(TENS)常用于緩解疼痛，已被證明對(duì)慢性肌肉骨骼疼痛治療有效[41]。TENS優(yōu)先刺激大α感覺神經(jīng)，在脊髓背角突觸水平通過傷害性抑制來減少疼痛[42]。Norrbrink Budh等的交叉研究提供1級(jí)證據(jù)：TENS降低疼痛強(qiáng)度、重度疼痛強(qiáng)度、疼痛不適感。但高頻率或低頻率TENS在改善神經(jīng)性疼痛方面沒有顯著差別[30]。

3.9 靜態(tài)磁場(chǎng)

Panagos等應(yīng)用靜態(tài)磁場(chǎng)(SMF)治療脊髓損傷后疼痛，發(fā)現(xiàn)0.05 T的靜磁場(chǎng)磁體可緩解刺痛、銳痛、觸疼痛(P＜0.05)；然而視覺模擬評(píng)分(VAS)沒有顯著變化[43]。此試驗(yàn)未設(shè)置對(duì)照組且樣本量相對(duì)較少，僅提供有限的4級(jí)證據(jù)。

4 藥物治療

藥物治療脊髓損傷后疼痛是標(biāo)準(zhǔn)治療。非藥物治療效果有局限，重度致殘性疼痛往往需要增加藥物干預(yù)處理。

4.1 抗驚厥藥

抗癲癇藥物用于治療脊髓損傷后神經(jīng)性疼痛或部分去傳入性疼痛。加巴噴丁和普瑞巴林是神經(jīng)性疼痛的一線用藥[44]。2007年加拿大疼痛協(xié)會(huì)指南僅推薦卡馬西平治療原發(fā)性三叉神經(jīng)痛有效，不推薦用于治療其他神經(jīng)病理性疼痛。Finnerup等報(bào)道拉莫三嗪對(duì)不完全脊髓損傷患者疼痛有治療效果(2級(jí)證據(jù))[45]。Finnerup等進(jìn)行了隨機(jī)雙盲交叉試驗(yàn)，發(fā)現(xiàn)左乙拉西坦和安慰劑對(duì)改善疼痛強(qiáng)度無顯著性差異(P=0.46)(1級(jí)證據(jù))[46]。

4.2 三環(huán)類抗抑郁藥

三環(huán)類抗抑郁藥(TCA)通過在中樞神經(jīng)系統(tǒng)中制造更多的血清素治療抑郁來調(diào)節(jié)疼痛。Vranken等發(fā)現(xiàn)度洛西汀可顯著改善疼痛[47]。對(duì)患有抑郁癥的脊髓損傷患者，阿米替林優(yōu)于苯海拉明(1級(jí)證據(jù))[48]。

4.3 麻醉藥物

Finnerup等報(bào)道多卡因靜脈注射后短期減少疼痛(1級(jí)證據(jù))[49]。Kvarnstrom等發(fā)現(xiàn)氯胺酮能成功減少脊髓損傷后神經(jīng)性疼痛(1級(jí)證據(jù))[50]。而慢心利不能改善脊髓損傷感覺觸物感性疼痛(1級(jí)證據(jù))[51]。

4.4 抗痙攣的藥物

已證實(shí)巴氯芬可抑制觸刺激誘發(fā)痛。Uchikawa等對(duì)7例有痙攣性肩關(guān)節(jié)疼痛的脊髓損傷患者進(jìn)行運(yùn)動(dòng)點(diǎn)苯酚石碳酸阻滯注射，隨訪時(shí)明顯有肩痛視覺模擬評(píng)分(VAS)改善(P＜0.05)[52]。Marciniak等應(yīng)用A型肉毒毒素注射治療29例患者的局灶性肌痙攣，疼痛改善83.3%[53]。

4.5 阿片類藥物

由于存在藥物成癮及濫用，阿片類鎮(zhèn)痛藥治療脊髓損傷后疼痛的研究相對(duì)較少。Barrera等發(fā)現(xiàn)結(jié)合抗驚厥治療時(shí)，羥考酮明顯降低脊髓損傷后疼痛強(qiáng)度并改善睡眠(4級(jí)證據(jù))[54]。

4.6 大麻素

Wade等與Hagenbach等對(duì)減少脊髓損傷后痙攣性疼痛提供的證據(jù)相互矛盾[55-56]，可能是一種新的治療，但需要進(jìn)一步研究。Rintala等研究鎮(zhèn)吐藥屈大麻酚與苯海拉明對(duì)脊髓損傷后疼痛的治療效果，發(fā)現(xiàn)兩治療組間疼痛強(qiáng)度差異不顯著(1級(jí)證據(jù))[57]。

4.7 可樂定

可樂定是一種α2腎上腺素能受體興奮劑，通過激活在脊髓背角的α2腎上腺素能受體來抑制傷害感受沖動(dòng)。Ackerman指出那些對(duì)阿片類藥物無反應(yīng)的患者可使用可樂定緩解疼痛[58]。

4.8 局部辣椒素

辣椒素是辣椒中的活性生物堿。它已成功地用于減少帶狀皰疹后神經(jīng)痛、糖尿病神經(jīng)病變神經(jīng)痛與術(shù)后疼痛綜合征[59]。作為P物質(zhì)抑制劑，局部辣椒素可用來治療脊髓損傷后1～2周的神經(jīng)根性疼痛，且有長(zhǎng)期效果(4級(jí)證據(jù))[59]。

5 手術(shù)干預(yù)

5.1 脊髓電刺激

脊髓電刺激已被用來嘗試治療頑固性疼痛[60]，可用于改善脊髓損傷后疼痛。

5.2 背側(cè)縱T形脊髓切開術(shù)

Livshits等發(fā)現(xiàn)Pourpre手術(shù)似乎比Bischof II緩解疼痛效果更明顯[61]。

5.3 脊神經(jīng)后根切斷術(shù)

當(dāng)患者下肢輕癱且是單根局限疼痛，可考慮一個(gè)或兩個(gè)水平脊神經(jīng)后根切斷術(shù)[62]。既往研究缺乏對(duì)照組及遠(yuǎn)期效果的監(jiān)測(cè)，仍需進(jìn)一步研究。

5.4 交感神經(jīng)切除術(shù)

對(duì)脊髓損傷后疼痛患者不推薦交感神經(jīng)切除術(shù)[63]。

5.5 全脊髓損毀術(shù)

賴光輝等對(duì)14例脊髓損傷后神經(jīng)痛患者經(jīng)過磁共振檢查和體格檢查確定損傷平面，在其上1～2個(gè)節(jié)段，應(yīng)用CT引導(dǎo)定位經(jīng)椎板穿刺至脊髓進(jìn)行持續(xù)射頻熱凝治療所有患者均毀損成功，除1例在治療后3年疼痛復(fù)發(fā)進(jìn)行二次脊髓毀損治療后疼痛消失外，其余患者均無疼痛發(fā)生，其有效率為92.9%[64]。

6 總結(jié)

脊髓損傷后疼痛治療方法多樣，但療效欠佳。有效聯(lián)合應(yīng)用以上治療方法不僅能緩解脊髓損傷后疼痛，同時(shí)還能提高患者日常生活活動(dòng)能力，減輕家庭和社會(huì)負(fù)擔(dān)。

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Clinical Research Evidences for Pain after Spinal Cord Injury(review)

WANG Yu-ming,TANG Li,LI Jian-jun.Capital Medical University School of Rehabilitation Medicine,Department of General Surgery,Beijing Bo'ai Hospital,China Rehabilitation Research Center, Beijing 100068,China

Pain is a common complication after spinal cord injury.Clinical studies involve pain mechanisms,classifications and treatments,etc.Pain after spinal cord injury needs comprehensive treatment.However,each of these interventions may produce only small curative effect,so this article aims to emphasize the best evidences and provide clear,wise and prudent evidences for clinical decision by reviewing clinical researches about pain after spinal cord injury.

spinal cord injury;pain;rehabilitation;review

10.3969/j.issn.1006-9771.2014.10.012

R651.2

A

1006-9771(2014)10-0945-05

2014-05-29

2014-06-30)

1.中國(guó)康復(fù)研究中心北京博愛醫(yī)院脊柱脊髓功能重建科，北京市100068；2.首都醫(yī)科大學(xué)康復(fù)醫(yī)學(xué)院，北京市100068。作者簡(jiǎn)介：王玉明(1965-)，男，內(nèi)蒙古包頭市人，碩士，副主任醫(yī)師，主要研究方向：骨科、脊柱脊髓損傷。