【編者的話】

這個初步研究不一定準(zhǔn)確，因?yàn)閴浩鹊姆较蚝头绞綄?shí)在難以統(tǒng)一，結(jié)論中與皮質(zhì)和自主神經(jīng)系統(tǒng)的關(guān)聯(lián)也沒有詳實(shí)的證據(jù)。

發(fā)表在這里，是想請各位浮針人多了解相關(guān)方面的知識。他山之石可以攻玉。

符仲華

慢性頸部疼痛的肌筋膜觸發(fā)點(diǎn)的壓迫可以通過前額皮質(zhì)和自主神經(jīng)系統(tǒng)緩解疼痛：一項(xiàng)初步研究

森川慶樹^1?，高本奎^2?，西丸廣史¹，田口徹²，浦川蘇木^2?，坂井重和²，小野武雄²和西野久雄^1*

王娟譯

文摘

肌筋膜觸發(fā)點(diǎn)(MTrPs)的壓迫被稱為“缺血壓迫”，據(jù)報(bào)道可以立即緩解肌肉骨骼疼痛，減少加重慢性疼痛的交感神經(jīng)活動。我們進(jìn)行了初步研究，探討在目前的研究中，肌筋膜觸發(fā)點(diǎn)壓迫緩解疼痛可能與前額皮質(zhì)的參與有關(guān)，并分析了在有或沒有肌筋膜觸發(fā)點(diǎn)壓迫下慢性頸部疼痛患者前額葉血流動力學(xué)活動、自主神經(jīng)系統(tǒng)的活動和主觀疼痛之間的關(guān)系。21名女性慢性頸部疼痛患者被隨機(jī)分為兩組：MTrP壓迫(n = 11)和非MTrP壓迫(n = 10)。進(jìn)行4次壓迫，每次30秒。在實(shí)驗(yàn)中，分別用近紅外光譜(NIRS)和心電圖(ECG)監(jiān)測了前額葉血流動力學(xué)活動(oxy-血紅蛋白(Hb)、Deoxy-Hb和總-Hb濃度的變化)和基于心率變異性(HRV)的自主活動。結(jié)果表明，與非MTrP壓迫組相比，MTrP壓迫組顯著減輕主觀疼痛。HRV的頻譜頻域分析表明，在MTrP壓迫過程中，HRV的一個低頻成分降低，HRV的一個高頻成分增加，而在MTrP壓迫過程中，LF/HF比值降低。此外，與非MTrP壓迫相比，在MTrP壓迫期間，前額血流動力學(xué)活動明顯減少。另外，自主活動的變化與主觀疼痛和前額葉血流動力學(xué)的變化顯著相關(guān)。與先前的研究表明交感神經(jīng)活動在慢性疼痛加劇中起作用一樣，目前的結(jié)果表明，MTrP在頸部區(qū)域的壓迫改變了通過前額皮質(zhì)的自主神經(jīng)系統(tǒng)的活動，以減少主觀疼痛。

介紹

近年來，頸部疼痛在普通人群中的發(fā)病率一直在上升(Hoy et al.，2010)，女性比男性頸部疼痛更頻繁(gueet al.，2002；Cote et al .，2004；Fejer et al .，2006)。據(jù)報(bào)道，肌肉骨骼頸部疼痛是由頸部和肩部肌肉的肌筋膜觸發(fā)點(diǎn)(MTrPs)引起的(Simons etal .，1999)。MTrPs是骨骼肌纖維中可觸及的緊繃帶的敏感部位(Simons etal .，1999)，最近的臨床研究報(bào)道，慢性頸部疼痛的患者在上斜方肌上的MTrPs比健康的受試者多(dez-de- lasl - penas etal .， 2007；Munoz-Munoz et al .，2012)。這些研究表明慢性頸部疼痛與MTrPs有關(guān)。

自主神經(jīng)系統(tǒng)的異常被認(rèn)為與慢性肌肉骨骼疼痛的維持有關(guān)(Passatore and Roatta， 2006；Martinez-Lavin，2007)。慢性疼痛患者如頸肩痛和纖維肌痛癥(Gockel et al.，1995；Furlan et al .，2005；Hallman et al .，2011)的交感神經(jīng)系統(tǒng)過度活躍和副交感神經(jīng)系統(tǒng)活性降低。MTrP區(qū)域的交感神經(jīng)活動與出汗、血管收縮、血管擴(kuò)張和牽張有關(guān)(Simons et al.，1999)。交感神經(jīng)活動興奮被認(rèn)為會加重慢性頸肩痛患者MTrPs的自發(fā)性局部疼痛(Ge et al.，2006)。因此，自主神經(jīng)系統(tǒng)的異常可能與MTrPs相關(guān)的慢性疼痛有關(guān)。

最近的人體神經(jīng)影像學(xué)研究表明，包括前額葉皮層在內(nèi)的幾個大腦區(qū)域參與了疼痛信息的治療和自主調(diào)節(jié)(Hallman and Lyskov， 2012)。在慢性疼痛患者中，內(nèi)側(cè)前額葉皮層(mPFC)出現(xiàn)了解剖和功能異常，所以自發(fā)性疼痛的高評分與慢性疼痛患者的mPFC活動增加有關(guān)(Baliki et al.， 2006)。此外，一項(xiàng)使用功能磁共振成像(fMRI)的研究表明，mPFC參與了自主神經(jīng)系統(tǒng)反應(yīng)的產(chǎn)生(Critchley et al.， 2000)。這些結(jié)果表明，前額葉皮層通過自主神經(jīng)系統(tǒng)的異常激活參與慢性疼痛的產(chǎn)生。

MTrPs的壓迫是一種有效的肌肉骨骼疼痛的按摩技術(shù)，通過副交感神經(jīng)活動增加和交感神經(jīng)活動減少(Delaney etal .， 2002；Takamoto et al .，2009)，可以立即緩解慢性頸部疼痛(Hou etal .， 2002)。MTrP壓迫被認(rèn)為通過外周、脊髓、上棘和自主通路發(fā)揮其治療作用(Bialosky et al.， 2009；高本et al .，2009)。然而，它對前額葉皮層疼痛感知和自主控制的影響尚不清楚。

在本研究中，我們假設(shè)MTrP壓迫可能會影響參與自主調(diào)節(jié)的mPFC，進(jìn)而導(dǎo)致疼痛緩解。為了研究這個假設(shè)，我們對兩組患者均分析了用近紅外光譜(NIRS)測量的前額葉血流動力學(xué)活動、基于心率變異性(HRV)的自主神經(jīng)系統(tǒng)的活動和慢性頸部疼痛患者主觀疼痛之間的關(guān)系。NIRS是一種非侵入性的神經(jīng)成像技術(shù)，可以測量由局部皮層神經(jīng)元活動引起的皮層表面氧血紅蛋白(Oxy-Hb)、脫氧血紅蛋白(deoxy- hb)和總血紅蛋白(total - hb)的變化(Ferrari和Quaresima， 2012)，來調(diào)查可能參與壓迫肌筋膜觸發(fā)點(diǎn)而緩解疼痛的mPFC。值得注意的是，與其他非侵入性的方法，包括fMRI和正電子發(fā)射斷層掃描(PET)相比，NIRS應(yīng)用在有限的空間中對身體和頭部限制較少。因此，NIRS可以在與實(shí)際臨床環(huán)境相似的情況下測量大腦活動。

材料和方法

主題

參與者由頸部疼痛發(fā)作持續(xù)時(shí)間超過3個月的21歲女性患者(20-31歲；23.4±0.9年，平均年齡±標(biāo)準(zhǔn)誤差(SE))組成。所有患者均由一名訓(xùn)練有素并獲得國家針灸醫(yī)師執(zhí)業(yè)執(zhí)照的臨床醫(yī)生診斷為肌筋膜疼痛綜合征。納入標(biāo)準(zhǔn)：(1)上斜方肌上可觸及帶狀或變硬的結(jié)節(jié)，(2)從可觸及帶狀局部區(qū)域散發(fā)出的肌筋膜疼痛。根據(jù)隨機(jī)分配軟件，將患者隨機(jī)分為兩組(MTrP組和非MTrP組)(圖1)。所有患者都嚴(yán)格遵守《赫爾辛基宣言》和《聯(lián)邦保護(hù)人類受試者條例》。實(shí)驗(yàn)是通過對每個受試者的理解和知情的書面同意進(jìn)行的，并經(jīng)富山大學(xué)臨床研究和倫理委員會批準(zhǔn)。

肌肉壓迫

缺血壓迫由拇指持續(xù)的深部壓力構(gòu)成，這種壓力作用于斜方肌的MTrPs或非MTrPs。斜方肌的MTrPs的位置是由一位在MTrPs診斷和治療中有6年以上的經(jīng)驗(yàn)、有國家執(zhí)照、在日本進(jìn)行針灸治療的從業(yè)人員確定的。肌筋膜觸發(fā)點(diǎn)的識別是基于西蒙斯等(1999)和Gerwin等(1997)推薦的最小診斷標(biāo)準(zhǔn)，該標(biāo)準(zhǔn)要求(1)在肌肉緊繃帶存在高度敏感點(diǎn)，(2)當(dāng)該點(diǎn)受壓迫時(shí)，患者能夠“熟悉”識別疼痛，和(3)當(dāng)包括肌筋膜觸發(fā)點(diǎn)在內(nèi)的肌肉拉伸時(shí)誘導(dǎo)疼痛。在對照組中，非MTrPs定義為2厘米外的點(diǎn)和給定MTrP的近端點(diǎn)，在此點(diǎn)上施加壓迫時(shí)未檢測到緊繃帶，也未引起局部疼痛。

壓迫強(qiáng)度設(shè)置在壓力疼痛閾值(PPT)和最大耐受疼痛(MTP)之間的一個點(diǎn)，該點(diǎn)對應(yīng)每個患者“適度疼痛均值”強(qiáng)度(侯等人，2002)。PPTs和MTPs使用數(shù)字痛覺計(jì)(Atkins et al.， 1992；Bendtsen et al .，1994)測量。該裝置由一個電容式壓力傳感器(直徑為6毫米)和與傳感器相連的數(shù)據(jù)采集硬件(SME-101A： Kyowa Dengyou，日本)組成。傳感器被安裝在拇指上。壓力強(qiáng)度在任意單位(AU)表示；550歐相當(dāng)于1公斤。壓力強(qiáng)度用設(shè)備監(jiān)視器監(jiān)測，對觸診醫(yī)生或患者是不可見的。兩個實(shí)驗(yàn)者在數(shù)據(jù)收集過程中一起工作。實(shí)驗(yàn)人員1(觸診醫(yī)生)對監(jiān)控記錄不知情，根據(jù)患者的行為反應(yīng)確定PPT和MTP，實(shí)驗(yàn)者2記錄設(shè)備監(jiān)視器的壓力強(qiáng)度值。實(shí)驗(yàn)人員1使用帶有壓力傳感器的拇指對已識別的MTrPs或非MTrPs施加穩(wěn)定的、逐漸增加的壓力。當(dāng)患者一開始感到疼痛時(shí)，他們被告知按下按鈕，0 = 無疼痛， 4 =疼痛閾值， 10 =劇痛。當(dāng)患者感到劇烈疼痛時(shí)，壓迫停止，實(shí)驗(yàn)者2記錄下壓力強(qiáng)度值。每個刺激點(diǎn)記錄PPT和MTP 3次，之后實(shí)驗(yàn)的壓迫強(qiáng)度設(shè)置在平均PPT和平均MTP之間的中間強(qiáng)度。

協(xié)議

患者在額葉區(qū)域安裝了NIRS頭墊(圖2A)，在胸部安裝了心電圖電極?；颊咂教稍诖采希i椎處于中立位置。要求患者閉上眼睛并盡可能地放松。在NIRS和ECG記錄開始1分鐘后開始施加肌肉壓迫。將MTrPs或非MTrPs壓迫30秒，接下來休息120秒。重復(fù)4次這個過程(4個周期)。通過監(jiān)測，從業(yè)者保持恒定的壓力(即：在PPT和MTP之間的壓力強(qiáng)度)。

心理物理數(shù)據(jù)

為了主觀評價(jià)壓迫治療，受試者被要求報(bào)告實(shí)驗(yàn)前后頸部的疼痛水平，實(shí)驗(yàn)使用100級視覺模擬量表(血管)，單位是毫米。在主觀疼痛評分中，得分0表示“沒有痛苦”，得分100表示“受試者認(rèn)為經(jīng)歷過的最強(qiáng)疼痛”。在實(shí)驗(yàn)結(jié)束時(shí)，受試者還被要求在每個周期內(nèi)以-10到10的分?jǐn)?shù)報(bào)告壓迫的愉快程度，極端值分別代表最不愉快和最愉快的體驗(yàn)(舒適/不舒適分?jǐn)?shù))。4個周期的舒適度/不適評分均取平均值。此外，受試者在每個周期中使用10級量表報(bào)告疼痛強(qiáng)度，0分表示“沒有疼痛”，4分表示“閾值水平的疼痛感覺”，10分表示“最強(qiáng)烈的疼痛”(疼痛強(qiáng)度分?jǐn)?shù))。對4個周期的疼痛強(qiáng)度評分進(jìn)行平均。

自主神經(jīng)系統(tǒng)活動的測量

使用HRV測量系統(tǒng)(Makin AD2)測量自主活動。使用心電圖的V5胸導(dǎo)。采用最大熵法對節(jié)拍間隔進(jìn)行分析計(jì)算HRV譜。用RR間區(qū)計(jì)算了心臟變異性的低頻(LF) (0.04-0.15 Hz)和高頻(HF) (0.15-0.40 Hz)分量。此外，還得到了LF/HF比值。低頻/高頻比率已用作sympatho-vagal平衡指數(shù)，交感神經(jīng)調(diào)制的低頻組件作為一個索引，和高頻組件作為副交感神經(jīng)(迷走神經(jīng))調(diào)制指數(shù)(專責(zé)小組的歐洲心臟病協(xié)會和北美社會的節(jié)奏和電生理學(xué)，1996；帕加尼et al .，1997；金縷梅et al .，2010)。然而，最近的研究表明，這些指標(biāo)的含義更為復(fù)雜(見局限性)(Billman， 2011， 2013)。此外，這些指標(biāo)也被一些非自主神經(jīng)因素調(diào)節(jié)，如呼吸和心率本身(Billman， 2013；Gasior et al .，2016)。因此，呼吸速率是通過使用一個自由軟件的心電圖數(shù)據(jù)的R-R區(qū)間來估計(jì)的(Kubios HRV ver.2.2；http：//www。kubios.com；芬蘭東部大學(xué)，芬蘭，Kuopio；Tarvainen et al .，2014)。

測量前額皮質(zhì)的腦血流動力學(xué)活動

NIRS儀器(光譜分析OEG-16；日本橫濱Spectratech公司）用于測定腦血流動力學(xué)活性。6個光源和6個檢測器(總共有16個記錄通道)固定在正面區(qū)域(圖2A，B)。在10-20腦電圖系統(tǒng)中，探頭的橫線位于Fp1-Fp2線上。光源和探測器被放置在任意2者之間的距離為3厘米處。光源和檢測器之間的中點(diǎn)被稱為“通道”，血流動力學(xué)活動通過光源和檢測器的配對檢測，使用兩個不同的波長(770和840nm)。使用改進(jìn)的Lambert-Beer定律(Seiyama et al.， 1988)估計(jì)基線中血紅蛋白(Hb)濃度(OOxy-Hb)、ODeoxy-Hb和OTotal-Hb (OOxy-Hb + ODeoxy-Hb)的變化(OOxy-Hb)；雷et al .，1988)。錄音結(jié)束后，利用數(shù)字化儀(日本島津公司)，參照腦和雙側(cè)外耳道，測量了NIRS探頭的三維位置。

數(shù)據(jù)分析

提出數(shù)據(jù)的平均值±標(biāo)準(zhǔn)錯誤(SE)。用Shapiro-Wilk檢驗(yàn)評估數(shù)據(jù)分布的正態(tài)性。通過Levene的測試，對所有變量的方差齊性進(jìn)行了評估。采用學(xué)生t檢驗(yàn)(Mann- Whitney U檢驗(yàn))和方差分析(ANOVA)對MTrP組和非MTrP組的分析參數(shù)進(jìn)行比較。當(dāng)壓迫過程中的數(shù)據(jù)與MTrP和非MTrP組進(jìn)行比較時(shí)，在壓迫過程中數(shù)據(jù)(VAS、心率、呼吸速率和HRV參數(shù))都得到了校正。

HF和LF組分被報(bào)告為百分比(HF%， LF%，分別)，并將它們除以所有成分的和(LF + HF)。推薦LF和HF的歸一化，因?yàn)樗鼉A向于將總功率變化對LF和HF分量的影響降到最低(歐洲心臟病學(xué)會和北美起搏和電生理學(xué)學(xué)會，1996年；帕加尼et al .，1997)。此外，利用自然對數(shù)變換(lnLF， lnHF， lnLF/HF)對HF、LF、LF/HF的低值進(jìn)行了歸一化。治療后HRV的變化由壓迫前30-s休止期各參數(shù)的平均值減去壓迫期間30-s期的平均值進(jìn)行評估。所有自主數(shù)據(jù)(人力資源的變化、呼吸速率和HRV參數(shù))平均在4周期，因?yàn)樗凶灾鲄?shù)除了呼吸速率顯示沒有明顯的“循環(huán)”的主要作用(P > 0.05)，重復(fù)測量單向方差分析因素的“循環(huán)”在每個治療組呼吸數(shù)據(jù)顯示“循環(huán)”效果不顯著(P > 0.05)，弗里德曼的測試。學(xué)生的t檢驗(yàn)用于比較MTrP和非MTrP組的自主活動變化。P <>為差異有統(tǒng)計(jì)學(xué)意義。

為了識別每個受試者的NIRS通道的解剖位置，每個受試者的NIRS探頭和通道的3D位置通過NIRS SPM軟件(統(tǒng)計(jì)參數(shù)映射：http：//bisp./NIRS-SPM，第3.1版et al .，2009)在空間上歸一化為一個標(biāo)準(zhǔn)坐標(biāo)系；使用虛擬注冊(Tsuzuki等，2007)將每個NIRS通道的坐標(biāo)規(guī)范化為MNI(蒙特利爾神經(jīng)研究所)空間。然后，我們使用MRIcro軟件(www.mricro.com， 1.4版)識別了與每個受試者的NIRS通道對應(yīng)的Brodmann區(qū)域。我們將通道分為5個區(qū)域：背外側(cè)前額葉皮層(DLPFC)；在圖2中，與Ca (rDLPFC)和Ce (lDLPFC)相對應(yīng)的每個半球的Brodmann區(qū)，分別位于DMPFC (DMPFC)的圖2、3個區(qū)域；圖2中對應(yīng)Cb (rDMPFC)、Cc (cDMPFC)和Cd (lDMPFC)的Brodmann area 10)。在兩個研究對象中，通過立體定位疊加在每個研究對象的三維MRI重建大腦表面來確定NIRS通道的位置。對于三維MRI，薄層三維矢狀T1加權(quán)梯度回波磁共振成像是在1.5 T時(shí)使用專門為重建而定制的協(xié)議(Takeuchi et al.， 2009)。這兩名受試者有以下協(xié)議：在與腦干平行的平面上獲得(TR/TE/NSA) 25/5/1，翻轉(zhuǎn)角10，FOV 87.5 cm，矩陣256 9256，1.0 mm連續(xù)切片。

MTrPs和非MTrPs受壓時(shí)的腦血流動力學(xué)變化轉(zhuǎn)化為效應(yīng)大小。效應(yīng)大小可以根據(jù)不同受試者和不同皮層區(qū)域不同路徑長度因子的影響進(jìn)行調(diào)整(Schroeter et al.， 2003；鈴木et al .，2008)。血流動力學(xué)響應(yīng)的影響大小按以下公式計(jì)算：影響大小=[(壓迫30s時(shí)平均氧- hb水平)

?(平均Oxy-Hb水平在休息期間30年代之前開始

[壓迫][[壓迫開始前30秒內(nèi)氧- hb水平的標(biāo)準(zhǔn)偏差]。對于每個通道，4個周期的影響值被平均。然后對來自大腦各區(qū)域通道的數(shù)據(jù)進(jìn)行平均治療，得出每個患者在每個區(qū)域的平均血流動力學(xué)響應(yīng)。這些在MTrPs和非MTrPs ls上的壓迫數(shù)據(jù)被平均分配給每個病人在每個區(qū)域的平均血流動力學(xué)響應(yīng)。這些數(shù)據(jù)壓迫在肌筋膜觸發(fā)點(diǎn)和非MTrPs比較采用重復(fù)測量雙向方差分析(治療×大腦區(qū)域)。P <>為差異有統(tǒng)計(jì)學(xué)意義。

我們還分析了DMPFC中血流動力學(xué)響應(yīng)的影響大小、可能的自主活動與壓迫(HF%、LF%、LF/HF、lnHF、lnLF/HF)的相關(guān)性，以及使用簡單回歸分析得出的主觀疼痛評分隨壓迫(VAS評分)的變化。

所有的數(shù)據(jù)分析都使用SPSS 19.0 (IBM公司，紐約，美國)進(jìn)行。p <>為差異有統(tǒng)計(jì)學(xué)意義。

樣本大小

使用免費(fèi)樣本大小計(jì)算器(https：//www.stat./~rollin/stats/ssize/n2.html， rollin Brant， University of British Columbia)估計(jì)兩個獨(dú)立樣本(雙尾t檢驗(yàn))的樣本大小為n = 10，基于以下條件；肌筋膜觸發(fā)點(diǎn)組=?35歲的血管改變，非MTrP組=?16的血管變化，標(biāo)準(zhǔn)偏差(SD)= 15日= 0.05水平的意義，統(tǒng)計(jì)力量= 0.8。我們之前的初步數(shù)據(jù)用于這個樣本大小估計(jì)。

結(jié)果

兩組的基線特征和壓迫引起的感覺

表1顯示了患者的基線臨床特征(年齡、頸部疼痛VAS評分、PPT、壓迫強(qiáng)度、心率、呼吸率)。兩組在這些參數(shù)的基線特征上無顯著差異(學(xué)生t檢驗(yàn)，P > 0.05)。此外，兩組間的壓力(疼痛強(qiáng)度評分、舒適度/不適評分)(學(xué)生t檢驗(yàn)，P > 0.05)之間沒有顯著差異。

主觀疼痛評分在頸部的變化

圖3比較了MTrP組和非MTrP組由于壓迫而產(chǎn)生的主觀疼痛評分的變化。與非MTrPs相比，MTrPs的壓迫顯著改善了主觀疼痛評分(學(xué)生t-test， P <>。

心率變異性的變化從治療前的基線。

MTrP組和非MTrP組壓迫治療后的心率變化沒有顯著差異(學(xué)生的t檢驗(yàn)，P > 0.05)(補(bǔ)充圖1A)，在壓迫期間MTrP組和非MTrP組呼吸速率的變化也沒有顯著的差異(Mann - Whitney U檢驗(yàn)，P > 0.05)(補(bǔ)充圖1 b)。圖4比較了MTrP組和非MTrP組之間在壓迫過程中自主神經(jīng)反應(yīng)的變化。高頻組件(高頻%)在MTrP組比非MTrP組(學(xué)生的t檢驗(yàn)，P <>明顯更大，而且低頻組件(如果%)明顯的MTrP組比非MTrP組(學(xué)生的t檢驗(yàn)，P <>大。低頻/高頻比率大大減少，MTrP組相比非MTrP組(學(xué)生的t檢驗(yàn)，P <>。這些結(jié)果表明，壓迫肌筋膜觸發(fā)點(diǎn)抑制交感神經(jīng)活動。

我們還分析了對數(shù)變換后的HRV參數(shù)(補(bǔ)充圖1C-E)。 結(jié)果的趨勢與圖4中的結(jié)果基本一致。變化在lnLF壓迫在肌筋膜觸發(fā)點(diǎn)組相比顯著減少非MTrP組(學(xué)生的t檢驗(yàn)，P <>，盡管沒有明顯的差異變化在lnHF壓迫之間的肌筋膜觸發(fā)點(diǎn)和非MTrPs(學(xué)生的t檢驗(yàn)，P > 0.05)(D)。此外，壓迫期間lnLF /HF變化在MTrP組顯著減少，相比非MTrP組(學(xué)生的t檢驗(yàn)，P <>。

前額葉血流動力學(xué)反應(yīng)

圖5顯示了在非MTrPs組 (A)和MTrPs 組(B)開始壓迫后的Oxy-Hb圖25秒的典型例子。在受試者的大腦3D-MRIs上立體疊加NIRS數(shù)據(jù)，構(gòu)建Oxy-Hb濃度圖。在非MTrPs 組(A)的壓迫過程中，DMPFC中的Oxy-Hb濃度逐漸增加，而在MTrPs 組(B)的壓迫過程中，其濃度降低。

圖6比較了MTrP組和非MTrP組5個前額葉區(qū)血流動力學(xué)響應(yīng)的平均影響大小。使用重復(fù)測量數(shù)據(jù)的統(tǒng)計(jì)分析雙向方差分析與“治療”(肌筋膜觸發(fā)點(diǎn)比非MTrP)和“大腦區(qū)域”因素表明，治療有顯著主效應(yīng)(F(19)= 6.624，P <>，而不是大腦區(qū)域(F(2.697，51.236)= 1.672，P > 0.05)，而沒有顯著的治療和腦區(qū)之間的相互作用(F(2.697，51.236)= 1.179，P > 0.05)。結(jié)果表明，MTrPs的壓迫顯著降低了前額皮質(zhì)的血流動力學(xué)活性。相比之下，MTrP組和非MTrP組脫氧Hb沒有顯著差異，在同一使用重復(fù)測量雙向方差分析的統(tǒng)計(jì)分析中；治療的主要療效不顯著[F(1，19) = 0.019 P > 0.05]，治療與腦區(qū)之間的交互作用不顯著[F(2.8， 53.73) = 0.664， P > 0.05]。

主觀疼痛、自主活動和前額葉血流動力學(xué)反應(yīng)之間的關(guān)系

圖7A-C顯示了自主活動的變化與壓迫和主觀疼痛評分的變化之間的相關(guān)性。HF%變化與主觀疼痛分?jǐn)?shù)的變化呈顯著負(fù)相關(guān)，r2 = 0.272，F(20)= 7.092，P <>。相比之下，LF%變化和主觀疼痛分?jǐn)?shù)的變化呈顯著正相關(guān)，r2 = 0.272，F(20)= 7.092，P <>。另外，LF/HF比率變化明顯與主觀疼痛分?jǐn)?shù)的變化間呈正相關(guān)，r2 = 0.285，F(20)= 7.573，P <>。

圖7 - f顯示了cDMPFC受壓過程中自主神經(jīng)活動與腦血流動力學(xué)反應(yīng)的平均效應(yīng)大小變化之間的相關(guān)性。HF%與DMPFC血流動力學(xué)反應(yīng)變化之間呈明顯的負(fù)相關(guān)，r2 = 0.235，F(20)= 5.830，P <>。相比之下，LF%與DMPFC血流動力學(xué)響應(yīng)的影響大小的變化之間有明顯的正相關(guān)性，r2 = 0.235，F(20)= 5.830，P <>。此外，LF/HF比率有顯著的變化，與DMPFC血流動力學(xué)響應(yīng)的影響大小呈正相關(guān)。然而，主觀疼痛評分與DMPFC血流動力學(xué)反應(yīng)的效應(yīng)大小的改變之間沒有明顯關(guān)系。

我們還分析了對數(shù)變換參數(shù)(lnLF、lnHF和lnLF/HF)(補(bǔ)充圖2)，結(jié)果與圖7基本一致。lnLF的變化與主觀疼痛評分的變化顯著正相關(guān)，r2 = 0.299， F(1，20) = 8.121， P <>。lnLF/HF的變化與主觀疼痛評分的變化具有顯著的正相關(guān)關(guān)系，r2= 0.332， F(1，20) = 9.439， P < 0.05="">，但lnHF的變化與主觀疼痛評分的變化之間沒有顯著的相關(guān)性(數(shù)據(jù)未顯示)。另一方面，lnHF與DMPFC血流動力學(xué)響應(yīng)的影響大小的變化之間呈明顯負(fù)相關(guān)，r2 = 0.205，F(20)= 4.890，P <>。此外，lnLF / HF與DMPFC血流動力學(xué)響應(yīng)的影響大小變化間有明顯的正相關(guān)，r2 = 0.247，F(20)= 6.223，P <>。然而，InLF與DMPFC血流動力學(xué)反應(yīng)的變化之間沒有明顯相關(guān)性。

討論

MTrP壓迫對疼痛感知和自主神經(jīng)系統(tǒng)活動的影響。

在目前的研究中，壓迫MTrPs明顯改善主觀疼痛，對比壓迫非MTrPs(圖3)。它也顯著增加HRV參數(shù)，據(jù)信反映副交感神經(jīng)的活動，和抑制HRV參數(shù)，據(jù)信反映交感神經(jīng)活動(圖4中，補(bǔ)充圖1)。此外，這些變化在自主活動中主觀疼痛分?jǐn)?shù)的變化有顯著相關(guān)性(圖7中，補(bǔ)充圖2).與本研究一致的是，先前的生理學(xué)研究報(bào)道在MTrPs處的壓迫增加副交感神經(jīng)系統(tǒng)的活性并降低交感神經(jīng)活性(Delaney et al.， 2002；高本et al .，2009)。此外，在頸部熱療期間交感神經(jīng)活動的減少與頸部僵硬和疲勞的降低有關(guān)(Yasui et al.， 2010)。

急性或慢性肌肉超負(fù)荷導(dǎo)致神經(jīng)肌肉連接過度激活，導(dǎo)致乙酰膽堿的過度釋放(Gerwin et al.， 2004；出生和Dommerholt，2012)。在運(yùn)動端板上過量的乙酰膽堿會導(dǎo)致肌肉纖維中的節(jié)，其特征是連續(xù)收縮。收縮結(jié)的形成導(dǎo)致局部缺血和缺氧的發(fā)生。收縮肌肉中能量和氧氣供應(yīng)的損失導(dǎo)致敏感物質(zhì)的釋放，導(dǎo)致過敏和疼痛的增加。交感神經(jīng)系統(tǒng)活動的增加可能加劇這些過程并導(dǎo)致MTrP的形成。交感神經(jīng)系統(tǒng)通過附屬分支控制外肌和筋內(nèi)肌纖維(塞爾科維茨，1992；Bombardi et al .，2006)，并從運(yùn)動神經(jīng)終端提高乙酰膽堿的釋放是由α-和β-adrenoceptors運(yùn)動神經(jīng)終端(Gerwin et al .，2004)。

相比之下，MTrP壓迫降低交感神經(jīng)活性可能抑制MTrP過程和相關(guān)疼痛。在上斜方肌的MTrPs處的壓迫已經(jīng)被證明可以改善運(yùn)動末端的疼痛感和減少自發(fā)的電活動(SEA)。MTrPs上的板塊(Kostopoulos et al.， 2008)。SEA被認(rèn)為是由過量的乙酰膽堿釋放引起的(Gerwin et al.， 2004)。疼痛在肌筋膜觸發(fā)點(diǎn)和海洋也減少了注射阻滯交感神經(jīng)的代理商，如α1-adrenergic拮抗劑(哈伯德和露出，1993；McNulty et al .，1994；Hong and Simons， 1998)和放松技術(shù)以減少交感神經(jīng)活動(Banks et al.， 1998)。這些發(fā)現(xiàn)表明MTrP壓迫抑制交感神經(jīng)活動可能會減少乙酰膽堿的釋放并減少肌肉收縮。

此外，梯形肌痛的局部血流減少與疼痛強(qiáng)度相關(guān)(Larsson et al.， 1990)，這可能歸因于交感神經(jīng)活動增加導(dǎo)致血管收縮。MTrPs受壓可引起MTrP區(qū)域反應(yīng)性充血(Simons et al.， 1999)。綜上所述，這些結(jié)果表明，MTrPs的壓迫通過抑制交感神經(jīng)活動來減輕疼痛，(1)可能增加外周血流量，并隨后去除有害物質(zhì)，(2)可能阻止乙酰膽堿的過度釋放。然而，對于產(chǎn)生MTrPs的其他假說，如神經(jīng)源性假說(Srbely， 2010)和神經(jīng)生理學(xué)假說(Partanen et al.， 2010)也被提出。進(jìn)一步的研究需要充分了解交感神經(jīng)活動在肌筋膜疼痛綜合征中的作用。

MTrP壓迫對前額葉血流動力學(xué)的影響

本研究中，與非MTrP組相比，包括DMPFC在內(nèi)的PFC在MTrPs壓迫過程中Oxy-Hb濃度顯著降低，而MTrP組與非MTrP組的Deoxy-Hb無顯著差異。因此，目前的結(jié)果并沒有顯示典型的血流動力學(xué)變化(即。，在本研究中，Oxy-Hb的反應(yīng)模式與Deoxy-Hb濃度的反應(yīng)模式并不相反)。然而，據(jù)報(bào)道，Deoxy-Hb的變化在個體和不同任務(wù)之間并不一致(Hoshi等人，2001；Toichi et al .，2004；Sato et al.， 2005)， Oxy-Hb濃度與fMRI BOLD信號的相關(guān)性強(qiáng)于Deoxy-Hb濃度(Strangman et al.， 2002；山本和加藤，2002)。這些發(fā)現(xiàn)提示Oxy-Hb濃度可能是皮質(zhì)活性最一致的參數(shù)(Okamoto et al.， 2006)。

fMRI信號的減少與神經(jīng)元活動的局部減少有關(guān)(Shmuel et al.， 2006)。抑制神經(jīng)遞質(zhì)GABA的濃度與fMRI信號強(qiáng)度的降低有關(guān)(Northoff et al.， 2007；Muthukumaraswamy et al .，2009)。在NIRS研究中，Oxy-Hb濃度的降低可能對應(yīng)于大腦活動的抑制(Seitz和Roland， 1992；Shmuel et al .，2002；假摔et al .，2004)。因此，Oxy-Hb的減少表明，在MTrPs中，前額活動被壓迫抑制。然而，非mtrps的壓迫增加了前額皮質(zhì)的Oxy-Hb濃度。MTrP和非MTrP壓迫中相反的血流動力學(xué)響應(yīng)不能歸因于MTrP和非MTrP壓迫的心理物理特征的差異；MTrP與非MTrP壓迫在壓迫強(qiáng)度、疼痛強(qiáng)度和舒適度/不適程度上沒有顯著差異。需要進(jìn)一步的研究來確定導(dǎo)致MTrPs和非MTrPs壓迫之間的血流動力學(xué)反應(yīng)差異的生理因素。

此外，DMPFC中Oxy-Hb濃度的變化與HRV參數(shù)的變化顯著相關(guān)(HF%， LF%， LF/HF；lnHF、lnLF、lnLF/HF在壓迫過程中(圖7，補(bǔ)充圖2)。頸部區(qū)域的熱療也有類似的相關(guān)報(bào)道(Yasui et al.， 2010)。以前的神經(jīng)解剖學(xué)的和非嗎?侵入性影像學(xué)研究報(bào)道，包括DMPFC在內(nèi)的PFC與下丘腦和腦干有直接聯(lián)系，它們與疼痛的自主和行為反應(yīng)有關(guān)(Ongur et al.， 1998；Hadjipavlou et al .，2006)。疼痛過程中DMPFC活性的增加與皮膚血流減少和皮膚電導(dǎo)反應(yīng)增加有關(guān)，提示交感神經(jīng)活性增加(Seifert et al.， 2013)。此外，在DMPFC和自主功能中，腦電圖gamma-band振蕩隨著精神壓力的變化而發(fā)生一致的變化，gamma-band振蕩的增加先于自主波動(Umeno et al.， 2003)。慢性疼痛狀態(tài)如慢性腰痛和交感神經(jīng)介導(dǎo)的慢性疼痛被發(fā)現(xiàn)與mPFC(包括DMPFC)的多動相關(guān)(Apkarian et al.， 2001；Baliki et al .，2008)。另一方面，背側(cè)PFC與疼痛感知抑制有關(guān)(Lorenz et al.， 2003；Brighina et al.， 2004)，在MTrP和慢性腰痛慢性頸部疼痛患者中報(bào)告了該腦區(qū)灰質(zhì)萎縮(Fritz et al.， 2016)；Niddam et al .，2017)。這些發(fā)現(xiàn)表明PFC內(nèi)不平衡的活動可能與慢性疼痛有關(guān)。因此，現(xiàn)有的研究結(jié)果表明，包括DMPFC在內(nèi)的mPFC中的高活性可能與慢性疼痛狀態(tài)下自主活動的改變有關(guān)，而MTrPs的壓迫可能通過mPFC抑制交感神經(jīng)活動。

MTrP壓迫的可能的生理機(jī)制的影響

在目前的研究中觀察MTrPs和非MTrPs的不同的腦血流動力學(xué)和自主神經(jīng)系統(tǒng)反應(yīng)。 70% MTrPs的空間位置被報(bào)道與傳統(tǒng)穴位的位置重疊(Melzack et al.，1997)。針刺點(diǎn)和肌筋膜觸發(fā)點(diǎn)的針刺刺激被證明與非肌筋膜觸發(fā)點(diǎn)和非針刺點(diǎn)的針刺刺激相比，具有更強(qiáng)的特異性的感覺，稱為“得氣”(Roth et al.， 1997；高本et al .，2010)。得氣感覺是一種獨(dú)特感覺的合成，描述為疼痛、酸痛、壓力、沉重、脹滿、溫暖、涼爽、麻木、刺痛和鈍痛(Kong et al.， 2007)。穴位壓力刺激也可引起得氣的感覺(葉澤，2004，2006；李et al .，2007)。此外，MTrPs的持續(xù)壓力刺激也引起了類似得氣的感覺，包括刺激點(diǎn)遠(yuǎn)端和近端區(qū)域的疼痛和鈍痛(Simons， 1995；克拉克，2008；Delany，2014)。因此，肌筋膜觸發(fā)點(diǎn)和穴位的刺激都會引起類似的得氣感。MTrPs和針刺點(diǎn)被認(rèn)為是多模型受體敏化發(fā)生的部位(Kawakita和Itoh， 2002)。多模型受體存在于傳導(dǎo)速度低的傳入纖維上(A-delta和c -纖)(Almeida et al.， 2004)，可能參與針刺點(diǎn)針刺刺激誘發(fā)得氣感覺(Lu， 1983；王et al .，1985)。本研究中MTrPs受壓引起的生理效應(yīng)可歸結(jié)為得氣感覺。

針刺穴位引起得氣感覺已被證明能增加局部血流，而非針刺穴位的刺激只能輕微改變局部血流(Kuo et al.， 2004)。此外，在穴位針刺引起的得氣感覺的數(shù)量與交感神經(jīng)活動減少和副交感神經(jīng)活動增加有關(guān)(酒井法子et al .，2007)，特定的針刺感強(qiáng)度和心率反應(yīng)之間觀測到明顯的負(fù)相關(guān)(Beissner et al .，2012)。一項(xiàng)神經(jīng)影像學(xué)研究報(bào)告稱，在針刺點(diǎn)時(shí)，額葉前部皮層活動的減少與得氣感覺強(qiáng)度的增加和心率反應(yīng)的增加有關(guān)(Beissner et al.， 2012)。此外，在針刺點(diǎn)時(shí)，心率反應(yīng)與mPFC的fMRI BOLD信號相關(guān)，mPFC活性的降低與心率的降低有關(guān)(Napadow et al.， 2013)。之前的一項(xiàng)NIRS研究也表明，在MTrPs上的針刺會引起得氣感覺，從而降低DMPFC和輔助運(yùn)動皮層的Oxy-Hb濃度(Takamoto et al.， 2010)。綜上所述，不同的治療方法在MTrPs和/或穴位使用壓迫或針刺，可能通過常見的傳入神經(jīng)纖維來減輕疼痛，從而誘發(fā)得氣感覺。需要進(jìn)一步研究MTrPs的壓迫誘導(dǎo)腦血流動力學(xué)和自主神經(jīng)系統(tǒng)反應(yīng)的生理機(jī)制。

結(jié)論

我們進(jìn)行了一項(xiàng)試點(diǎn)研究，通過NIRS和HRV分析研究慢性頸痛患者頸部MTrPs壓迫對主觀疼痛感知、前額葉血流動力學(xué)活動以及可能的自主神經(jīng)活動的影響。與非MTrPs相比，MTrPs的壓迫顯著改善了主觀疼痛評分。研究認(rèn)為，能反映副交感神經(jīng)活動的HRV參數(shù)在MTrPs處與非mtrp處的壓迫引起的HRV參數(shù)相比顯著增加，認(rèn)為能反映交感神經(jīng)活動的HRV參數(shù)則減少。此外，與非mtrp壓迫相比，MTrPs處的壓迫顯著降低了DMPFC中的Oxy-Hb濃度。認(rèn)為反映交感神經(jīng)活動的HRV參數(shù)的變化與DMPFC中Oxy-Hb濃度的變化呈正相關(guān)，與缺血壓迫期間主觀疼痛評分的變化呈正相關(guān)。目前的研究結(jié)果和之前的研究結(jié)果表明，MTrPs的壓迫效應(yīng)可能通過抑制DMPFC活性來調(diào)節(jié)，這可能有利于治療與交感神經(jīng)系統(tǒng)亢進(jìn)有關(guān)的慢性疼痛。

原文鏈接https://www.ncbi.nlm./pmc/articles/PMC5386976/

Compression at Myofascial Trigger Point on Chronic Neck Pain Provides Pain Relief through the Prefrontal Cortex and Autonomic Nervous System: A Pilot Study

probes was set at 3 cm. The midpoints between a source and a detector were called “channels,” and hemodynamic activity was detected by pairs of source and detector using two different wavelengths (770 and 840 nm). Changes in the hemoglobin (Hb) concentration (OOxy-Hb, ODeoxy-Hb, and OTotal-Hb [OOxy- Hb + ODeoxy-Hb]) from the baseline were estimated using a modified Lambert-Beer law (Seiyama et al., 1988; Wray et al., 1988). After the recording, the 3-D locations of the NIRS probes were measured using a digitizer (Shimadzu Co. Ltd., Japan) with reference to the nasion and bilateral external auditory meatus.

Data Analysis

The data are presented as the mean ± standard error (SE). Normality of the data distribution was assessed by Shapiro-Wilk test. The homogeneity of variance in all variables with normality was  assessed  by  the  Levene’s  test.  Student’s  t-test  (or  Mann- Whitney U test) and ANOVA were used to compare the data in analyzed parameters between the MTrP and Non-MTrP groups. When the data during compression  were  compared  between the MTrP and Non-MTrP groups, the data (VAS, heart rate, respiratory rate, and HRV parameters) during compression were corrected for the baselines.

The HF and LF components were reported as percentages (HF%, LF%, respectively), and normalized by dividing them by the sum of all components (LF + HF). This normalization of LF and HF is recommended since it tends to minimize the effect  on the values of LF and HF components of the changes in total power (Task Force of the European Society of Cardiology and the North American Society of Pacing and Electrophysiology, 1996; Pagani et al., 1997). Furthermore, the low values of HF, LF, and LF/HF were also normalized by natural logarithm transformation (lnLF, lnHF, lnLF/HF, respectively). Changes in HRV after the treatments were assessed by subtracting the mean value of each parameter in the 30-s rest period before the application of compression from the mean value for the 30-s period during compression. All autonomic data (changes in HR, respiratory rate, and HRV parameters) were averaged across 4 cycles, since the all autonomic parameters except respiratory rate showed no significant main effect of “cycle” (P > 0.05) by repeated measures one-way  ANOVAs  with  a  factor  of  “cycle”  in  each  treatment group while respiratory data showed no significant effect of “cycle” (P  > 0.05) by Friedman’s test. Student’s t-test was used to compare changes in autonomic activity between the MTrP and Non-MTrP groups. Findings of P < 0.05="" were="" considered="">

To identity the anatomical locations of NIRS channels in each subject, the 3D locations of the NIRS probes and channels in each subject were spatially normalized to a standard coordinate system using NIRS SPM software (statistical parametric mapping: http://bisp./NIRS-SPM, version 3.1; Ye et al., 2009); the coordinates for each NIRS channel were  normalized  to MNI (Montreal Neurological Institute) space using virtual registration (Tsuzuki et al., 2007). We then identified the Brodmann areas corresponding to the NIRS channels of each subject using MRIcro software (www.mricro.com, version 1.4). We divided the channels into 5 regions: the dorsolateral prefrontal cortex (DLPFC; Brodmann areas 45 and 46) in each hemisphere corresponding to Ca (rDLPFC) and Ce (lDLPFC) in Figures 2, 3 regions in the dorsomedial prefrontal cortex (DMPFC; Brodmann area 10) corresponding to Cb (rDMPFC), Cc (cDMPFC), and Cd (lDMPFC) in Figure 2. In two subjects, the locations of NIRS channels were determined by stereotaxic superimposition on the surface of the 3-D MRI reconstructed brain of each subject. For 3-D MRI, thin-slice 3-D sagittal T1- weighted gradient echo MR images were obtained at 1.5  T using a specific protocol tailored for reconstruction (Takeuchi   et al., 2009). These two subjects had the following protocol: (TR/TE/NSA) 25/5/1, flip angle 10, FOV 87.5 cm, matrix 256 9 256, 1.0 mm contiguous slices, obtained in a plane parallel to the brain stem.

Cerebral hemodynamic changes during compression at MTrPs and Non-MTrPs were converted to effect sizes. Effect sizes can adjust for the influence of different path-length factors among different subjects and cortical regions (Schroeter et al., 2003; Suzuki et al., 2008). The effect sizes of hemodynamic responses were calculated according to the following formula: effect size = [(mean Oxy-Hb levels during compression for 30 s) ? (mean Oxy-Hb levels during the rest period for 30 s before start of compression)]/[standard deviation of Oxy-Hb levels during the rest period of 30 s before the start of compression]. For each channel, the effect sizes from 4 cycles were averaged. The data from the channels in each brain region were then averaged to give the mean hemodynamic responses in each area for each patient. These data for compression at MTrPs and Non-MTrPs ls in each brain region were then averaged to give the mean hemodynamic responses in each area for each patient. These data for compression at MTrPs and Non-MTrPs were compared using a repeated-measures two-way ANOVA (treatment × brain region). Findings of P < 0.05="" were="" considered="">

We also analyzed correlations among the effect sizes of hemodynamic responses in the DMPFC, changes in possible autonomic activity with compression (HF%, LF%, LF/HF, lnHF, lnLF, and lnLF/HF), and changes in subjective pain scores with compression (VAS scores) using simple regression analysis.

All data analyses were performed using SPSS 19.0 (IBM Inc., New York, USA). A p < 0.05="" was="" considered="" statistically="">

Sample Size

Sample size for comparison of two independent samples (two- tailed t-test) was estimated using a free sample size calculator (https://www.stat./~rollin/stats/ssize/n2.html by Dr. Rollin Brant, University of British Columbia) as n = 10 based on the following condition; changes in VAS in the MTrP group =?35, changes in VAS in the Non-MTrP group = ?16, standard deviation (SD) = 15, level of significance = 0.05, statistical power= 0.8. Our previous preliminary data were used for this sample size estimation.

RESULTS

Baseline Characteristics and Sensations Evoked by Compression in the Two Groups

Table 1 shows the baseline clinical characteristics of the patients (age, VAS score for neck pain, PPT, and intensity of compression, heart rate, and respiratory rate). There were no significant differences between the two groups in the baseline characteristics of  these  parameters (Student’s  t-test,  P > 0.05).Furthermore, there were no significant differences in the sensations evoked by compression between the two groups (pain intensity scores, comfort/discomfort scores) (Student’s t-test, P > 0.05).

Changes in Subjective Pain Scores in the Neck

Figure 3 compares the changes in subjective pain scores resulting from compression in the MTrP and Non-MTrP groups. Compression at MTrPs significantly ameliorated subjective pain scores  compared  with  compression  at  Non-MTrPs  (Student’s t-test, P <>

Changes in Heart Rate Variability from the Pre-treatment Baseline

There was no significant difference in changes in heart rates during compression between the MTrP and Non-MTrP groups (Student’s  t-test,  P >  0.05)  (Supplementary  Figure  1A),  nor significant difference in changes in respiratory rates during compression between the MTrP and Non-MTrP groups (Mann- Whitney U test, P > 0.05) (Supplementary Figure 1B). Figure 4 compares changes in autonomic responses during compression between the MTrP and Non-MTrP groups. The HF components (HF%) were significantly greater in the MTrP group compared with the Non-MTrP group (Student’s t-test, P < 0.01)="" (a),="" while="" the="" lf="" components="" (lf%)="" were="" significantly="" greater="" in="" the="" mtrp="" group="" compared="" with="" the="" non-mtrp="" group="" (student’s="" t-test,="">< 0.01)="" (b).="" the="" lf/hf="" ratio="" was="" significantly="" less="" in="" the="" mtrp="" group="" compared="" with="" the="" non-mtrp="" group="" (student’s="" t-test,="">< 0.01)="" (c).="" these="" results="" suggest="" that="" compression="" at="" mtrps="" suppressed="" sympathetic="">

We also analyzed logarithmically transformed HRV parameters (Supplementary Figures 1C–E). The trend of the results was essentially consistent with that in Figure 4. Changes in lnLF during compression were significantly less in the MTrP group compared with the Non-MTrP group (Student’s t-test, P < 0.01)="" (c),="" while="" there="" were="" no="" significant="" differences="" in="" changes="" in="" lnhf="" during="" compression="" between="" the="" mtrps="" and="" non-mtrps="" (student’s="" t-test,="" p=""> 0.05) (D). Furthermore,changes in lnLF/HF during compression were significantly less in the MTrP group compared with the Non-MTrP group (Student’s t-test, P < 0.01)="">

Prefrontal Hemodynamic Responses

Figure 5 shows typical examples of Oxy-Hb maps 25 s after starting compression at Non-MTrPs (A) and MTrPs (B). The NIRS data were stereotaxically superimposed on the 3D-MRIs of the brain of the subject to construct the Oxy-Hb concentration maps. The Oxy-Hb concentration in the DMPFC gradually increased during compression at Non-MTrPs (A), while it decreased during compression at MTrPs (B).

Figure 6 compares the mean effect sizes of hemodynamic responses in the 5 prefrontal regions of the MTrP and Non-MTrP groups. Statistical analysis of the data using a repeated-measures 2-way ANOVA with “treatment” (MTrP vs. Non-MTrP) and“brain region” as factors indicated that there was a significant main effect of treatment [F(1, 19) = 6.624, P < 0.05],="" but="" not="" brain="" region="" [f(2.697,="" 51.236)="1.672," p=""> 0.05], and no significant interaction between treatment and brain region [F(2.697, 51.236) =1.179, P > 0.05]. The results indicate that compression at MTrPs significantly decreased hemodynamic activity in the prefrontal cortex. In contrast, there was no significant differences in DeoxyHb between the MTrP and Non-MTrP group in the same statistical analysis using a repeated measures 2-way ANOVA; 

there was no significant main effect of treatment [F(1, 19) = 0.019 P > 0.05], nor significant interaction between treatment and brain region [F(2.8, 53.73) = 0.664, P > 0.05].

Relationships among Subjective Pain, Autonomic Activity, and Prefrontal Hemodynamic Responses

Figures 7A–C show the correlations between changes in autonomic activity with compression and changes in subjective pain scores. Changes in HF% were significantly and negatively correlated with changes in subjective pain scores, r2 = 0.272, F(1, 20) = 7.092, P < 0.05="" (a).="" in="" contrast,="" changes="" in="" lf%="" were="" significantly="" and="" positively="" correlated="" with="" changes="" in="" subjective="" pain="" scores,="" r2="0.272," f(1,="" 20)="7.092," p="">< 0.05="" (b).furthermore,="" changes="" in="" lf/hf="" were="" significantly="" and="" positively="" correlated="" with="" changes="" in="" subjective="" pain="" scores,="" r2="0.285," f(1,="" 20)="7.573," p="">< 0.05="">

Figures 7D–F show correlations between changes in autonomic activity and the mean effect sizes of cerebral hemodynamic responses in the cDMPFC during compression. Changes in HF% were significantly and negatively correlated with the effect sizes of hemodynamic responses in the DMPFC, r2 = 0.235, F(1, 20) = 5.830, P < 0.05="" (d).="" in="" contrast,="" changes="" in="" the="" lf%="" were="" significantly="" and="" positively="" correlated="" with="" the="" effect="" size="" of="" hemodynamic="" responses="" in="" the="" dmpfc,="" r2="0.235," f(1,="" 20)="5.830," p="">< 0.05="" (e).="" furthermore,="" changes="" in="" the="" lf/hf="" ratio="" were="" significantly="" and="" positively="" correlated="" with="" the="" effect="" size="" of="" hemodynamic="" responses="" in="" the="" dmpfc,="" r2="0.192," f(1,="" 20)="4.514," p="">< 0.05="" (f).="" however,="" there="" was="" no="" significant="" correlation="" between="" changes="" in="" subjective="" pain="" scores="" and="" the="" effect="" size="" of="" hemodynamic="" responses="" in="" the="" dmpfc="" (data="" not="">

We also analyzed logarithmically transformed parameters (lnLF, lnHF, and lnLF/HF) (Supplementary Figure 2). The results were essentially consistent with those in Figure 7. 

Changes in lnLF were significantly and positively correlated with changes in subjective pain scores, r2 = 0.299, F(1, 20) = 8.121, P < 0.05(a).="" furthermore,="" changes="" in="" lnlf/hf="" were="" significantly="" and="" positively="" correlated="" with="" changes="" in="" subjective="" pain="" scores,="" r2="0.332," f(1,="" 20)="9.439," p="">< 0.05="" (b).="" however,="" there="" was="" no="" significant="" correlation="" between="" changes="" in="" lnhf="" and="" changes="" in="" subjective="" pain="" scores="" (data="" not="" shown).="" on="" the="" other="" hand,="" changes="" in="" lnhf="" were="" significantly="" and="" negatively="" correlated="" with="" the="" effect="" size="" of="" hemodynamic="" responses="" in="" the="" dmpfc,="" r2="0.205," f(1,="" 20)="4.890," p="">< 0.05="" (c).="" furthermore,="" changes="" in="" lnlf/hf="" were="" significantly="" and="" positively="" correlated="" with="" the="" effect="" size="" of="" hemodynamic="" responses="" in="" the="" dmpfc,="" r2="0.247," f(1,="" 20)="6.223," p="">< 0.05="" (d).="" however,="" there="" was="" no="" significant="" correlation="" between="" changes="" in="" lnlf="" and="" the="" effect="" size="" of="" hemodynamic="" responses="" in="" the="" dmpfc="" (data="" not="">

DISCUSSION

Effects of MTrP Compression on Pain Perception and the Activity of the Autonomic Nervous System

In the present study, compression at MTrPs significantly ameliorated subjective pain compared with compression at Non-MTrPs (Figure 3). It also significantly increased HRV parameters, which are believed to reflect parasympathetic activity, and inhibited HRV parameters, which are believed to reflect sympathetic activity (Figure 4, Supplementary Figure 1). Furthermore, these changes in autonomic activity were significantly correlated with changes in subjective pain scores (Figure 7, Supplementary Figure 2). Consistent with the present study, previous physiological studies have reported that compression at MTrPs increases the activity of the parasympathetic nervous system and decreases sympathetic activity (Delaney et al., 2002; Takamoto et al., 2009). Furthermore, a reduction of sympathetic activity during thermotherapy for the neck has been associated with decreased neck stiffness and fatigue (Yasui et al., 2010). These findings suggest that altered sympathetic activity might exacerbate neck pain, and that compression at MTrPs might reduce neck pain by suppressing sympathetic activity. 

Acute or chronic muscle overload induces hyperactivation of the neuromuscular junction, which leads to an excessive release of acetylcholine (Gerwin et al., 2004; Bron and Dommerholt, 2012). This excess of acetylcholine at the motor endplates leads to the formation of knots in muscle fibers that are characterized by continuous contraction. Formation of contraction knots then leads to the development of local ischemia and hypoxia. The loss of energy and O2 supply in contracting muscle causes the release of sensitizing noxious substances that lead to increased hypersensitivity and pain. Increased activity of the sympathetic nervous system might exacerbate these processes and cause MTrP formation. The sympathetic nervous system controls extrafusal and intrafusal muscle fibers through collateral branches (Selkowitz, 1992; Bombardi et al., 2006), and enhances the release of acetylcholine from motor nerve terminals that is mediated by α- and β-adrenoceptors on motor nerve terminals (Gerwin et al., 2004).

By contrast, a reduction in sympathetic activity by MTrP compression might suppress MTrP processes and the associated pain. Compression at MTrPs in the upper trapezius muscle has been shown to ameliorate the perception of pain and reduce spontaneous electrical activity (SEA) in motor end?plates at MTrPs (Kostopoulos et al., 2008). SEA is thought to be induced by excessive acetylcholine release (Gerwin et al., 2004). Pain at MTrPs and SEA is also decreased by the injection of sympatholytic agents, such as α1-adrenergic antagonists (Hubbard and Berkoff, 1993; McNulty et al., 1994; Hong and Simons, 1998) and relaxation techniques to reduce sympathetic activity (Banks et al., 1998). These findings suggest that suppression of sympathetic activity by MTrP compression might reduce acetylcholine release and decrease muscle contraction.

Furthermore, reduced local blood flow has been observed in trapezius myalgia and was correlated with pain intensity (Larsson et al., 1990), which might be ascribed to vasoconstriction due to increased sympathetic activity. Compression at MTrPs can induce reactive hyperemia in the MTrP region (Simons et al., 1999). Taken together, these results suggest that compression at MTrPs induces pain relief through inhibition of sympathetic activity, which (1) might increase the peripheral blood flow and subsequent removal of noxious substances, and (2) might block the excessive release of acetylcholine. However, other alternative hypotheses for generation of MTrPs such as the neurogenic hypothesis (Srbely, 2010) and the neurophysiologic hypothesis (Partanen et al., 2010) have been also proposed. Further studies are required to fully understand the role of sympathetic activity in myofascial pain syndrome.

Effects of MTrP Compression on Prefrontal Hemodynamic Responses

In the present study, the Oxy-Hb concentration was significantly decreased in the PFC including the DMPFC during compression at MTrPs compared with Non-MTrPs, while there was no significant difference in Deoxy-Hb between the MTrP and Non-MTrP groups. Thus, the present results did not show typical hemodynamic changes (i.e., the response patterns of Oxy-Hb were not opposite to those of Deoxy-Hb concentration in the present study). However, changes in Deoxy-Hb were reported to be not consistent across individuals and across tasks (Hoshi et al., 2001; Toichi et al., 2004; Sato et al., 2005), while the Oxy-Hb concentration was stronger correlated with fMRI BOLD signals than Deoxy-Hb concentration (Strangman et al., 2002; Yamamoto and Kato, 2002). These findings suggest that Oxy-Hb concentration may be the most consistent parameter for cortical activity (Okamoto et al., 2006).

Decreases in fMRI signals were associated with local decreases in neuronal activity (Shmuel et al., 2006). Concentration of inhibitory neurotransmitter GABA was associated with decreases in signal intensity in fMRI (Northoff et al., 2007; Muthukumaraswamy et al., 2009). In NIRS studies, a decrease in Oxy-Hb concentration might correspond to inhibition of brain activity (Seitz and Roland, 1992; Shmuel et al., 2002; Stefanovic et al., 2004). Thus, the decrease in Oxy-Hb suggests that prefrontal activity was suppressed by compression at MTrPs. However, it is noted that compression at Non-MTrPs increased the Oxy-Hb concentration in the prefrontal cortex. The opposite hemodynamic responses in MTrP and Non-MTrP compression cannot be ascribed to differences in the psychophysical characteristics of compression between MTrPs and Non-MTrPs; there were no significant differences in compression intensity, pain intensity scores, and comfort/discomfort scores between MTrP and Non-MTrP compression. Further studies are required to determine the physiological factors contributing to differences in prefrontal hemodynamic responses between compression at MTrPs and Non-MTrPs.

Furthermore, changes in Oxy-Hb concentration in the DMPFC were significantly correlated with changes in HRV parameters (HF%, LF%, LF/HF; lnHF, lnLF, lnLF/HF) during compression (Figure 7, Supplementary Figure 2). A similar correlation has been reported for thermotherapy on the neck region (Yasui et al., 2010). Previous neuroanatomical and non?invasive imaging studies have reported that the PFC including the DMPFC has direct connections with the hypothalamus and brainstem, which are involved in autonomic and behavioral responses to pain (Ongür et al., 1998; Hadjipavlou et al., 2006). Increased activity in the DMPFC during the experience of pain has been correlated with decreased skin blood flow and increased skin conductance responses, suggesting increased sympathetic activity (Seifert et al., 2013). Furthermore, EEG gamma-band oscillation in the DMPFC and autonomic functions coherently changed in response to mental stress, and an increase in gamma-band oscillation went ahead of the autonomic fluctuation (Umeno et al., 2003). Chronic pain states such as chronic low back pain and sympathetically mediated chronic pain were found to be associated with hyperactivity in the mPFC including the DMPFC (Apkarian et al., 2001; Baliki et al., 2008). On the other hand, the dorsolateral PFC is implicated in inhibition of pain perception (Lorenz et al., 2003; Brighina et al., 2004), and gray matter atrophy in this brain region was reported in patients with chronic neck pain with MTrP and chronic low back pain (Fritz et al., 2016; Niddam et al., 2017). These findings suggest that unbalanced activity within the PFC might be associated with chronic pain. Thus, the available findings suggest that hyperactivity in the mPFC including the DMPFC might be involved in altered autonomic activity in the chronic pain state, and that compression at MTrPs might suppress sympathetic activity via the mPFC.

Possible Physiological Mechanisms for theEffects of MTrP Compression

Different cerebral hemodynamic and autonomic nervous system responses were observed for compression at MTrPs and Non?MTrPs in the present study. The spatial locations of 70% of MTrPs have been reported to overlap with the locations of traditional acupuncture points (Melzack et al., 1997). Needling stimulation at both acupuncture points and MTrPs has been shown to significantly induce a stronger specific sensation known as “deqi” compared with needling stimulation at Non-MTrPs and non-acupuncture points (Roth et al., 1997; Takamoto et al., 2010). Deqi sensation is a composite of unique sensations described as aching, soreness, pressure, heaviness, fullness, warmth, cooling, numbness, tingling, and dull pain (Kong et al., 2007). Deqi sensations have also been induced by pressure stimulation at acupuncture points (Yip and Tse, 2004, 2006; Li et al., 2007). Furthermore, sustained pressure stimulation at MTrPs has also elicited deqi-like sensations including aching and dull pain in the distal or proximal areas from the point of stimulation (Simons, 1995; Clark, 2008; Delany, 2014). Thus, stimulation at both MTrPs and acupoints induces similar deqi sensations. MTrPs and acupuncture points are considered to be locations where the sensitization of polymodal-type receptors occurs (Kawakita and Itoh, 2002). Polymodal-type receptors are present on afferent fibers with low conduction velocity (A-delta and C-fibers) (Almeida et al., 2004), which might be involved in deqi sensations evoked by needling stimulation at acupuncture points (Lu, 1983; Wang et al., 1985). The physiological effects induced by compression at MTrPs in the present study might be attributed to

deqi sensations.

Needling at acupuncture points that induced deqi sensations has been shown to increase local blood flow, whereas the stimulation of non-acupuncture points changes the local blood flow only slightly (Kuo et al., 2004). Furthermore, the number of episodes of deqi sensations induced by needling at acupuncture points was correlated with a decrease in sympathetic activity and an increase in parasympathetic activity (Sakai et al., 2007), and a significant negative correlation was observed between the intensity of the specific acupuncture sensations and heart rate responses (Beissner et al., 2012). A neuroimaging study reported that decreased activity in the prefrontal cortex was associated with both increased intensity of deqi sensation and heart rate responses during needling at acupuncture points (Beissner et al., 2012). Furthermore, heart rate responses were correlated with fMRI BOLD signals in the mPFC during needling at acupuncture points, and a greater decrease in mPFC activity was associated with a greater decrease in heart rates (Napadow et al., 2013). A previous NIRS study also showed that needling at MTrPs, which induced deqi sensations, decreased Oxy-Hb concentrations in the DMPFC and supplementary motor cortex (Takamoto et al., 2010). Taken together, different therapeutic methods employing either compression or needling at MTrPs and/or acupuncture points, might provide pain relief through common afferent nerve fibers that induce deqi sensations. Further studies are required to investigate the physiological mechanisms that induce cerebral hemodynamic and autonomic nervous system responses by compression at MTrPs.

CONCLUSIONS

We conducted a pilot study to investigate the effects of compression at MTrPs in the neck region of patients with chronic neck pain on subjective pain perception, prefrontal hemodynamic activity, and possible autonomic activity using NIRS and HRV analyses. Compression at MTrPs significantly improved subjective pain scores compared with compression at Non-MTrPs. HRV parameters that are believed to reflect parasympathetic activity were significantly increased during compression at MTrPs compared with that induced by compression at Non-MTrP, and HRV parameters that are believed to reflect sympathetic activity were decreased. Furthermore, compression at MTrPs significantly decreased the Oxy-Hb concentration in the DMPFC compared with that induced by Non-MTrP compression. Changes in HRV parameters that are believed to reflect sympathetic activity were positively correlated with changes in Oxy-Hb concentrations in the DMPFC, and were positively correlated with changes in subjective pain scores during ischemic compression. The present results, along with those of previous studies, suggest that the effects of compression at MTrPs might be mediated through inhibitory effects on DMPFC activity, which might be beneficial for treating chronic pain in which hyperactivity of the sympathetic nervous system is involved.