肌筋膜疼痛激痛点自发性电活动与痛觉增敏的机制研究
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摘要
研究背景
     肌筋膜疼痛综合征(myofascial pain syndrome, MPS)是临床常见的疼痛综合症,指身体局部的肌肉疼痛,同时有激痛点(myofascial trigger point, MTrP)的出现。MTrP的临床特点为:局部疼痛、肌紧张带、局部抽搐反应及牵涉痛。若持续按压MTrP会有牵涉性自主神经现象,包括:肌肉挛缩、血管收缩、流汗增加和发冷等。
     MTrP通过肌电图针可以记录到特征性的自发性电位活动(spontaneous electromyographic activity, SEA),包括两种成分,一种是高频低幅持续性背景电流(<50μV);另一种为低频高幅间断性放电(100-700μV)。1995年Simons在动物激痛点上也记录到了相似的电位,只是波幅相对小:持续的背景电位波幅为10~50uV,间断的高幅电位为80uV。MTrP可分为活性MTrP和潜在MTrP。活性MTrP指不论肌肉处于休息或活动状态都会产生所熟悉的疼痛;潜在MTrP指在身体检查触摸到的时候才会产生疼痛。
     虽然MTrP的临床特征已得到广泛研究和认可,但其病理基础及SEA的来源还未得到证实,各种感觉纤维在MTrP疼痛及SEA中的作用还未阐明。目前关于MTrP的SEA的来源存在很多假说,但都不能完全解释MTrP的复杂临床特征,且存在自相矛盾现象。我们的前期研究结果显示:与非激痛点(non-MTrP)相比,潜在MTrP处H反射增强,阈值降低,MTrP对非伤害性刺激同样具有高敏感性。推测低阈值A类神经纤维可能参与了MTrP的病理性疼痛和自发性电位活动过程。本研究在此基础上通过切断大鼠相应脊神经根前根或后根,河豚毒素(TTX)阻断A类感觉传入纤维,观察大鼠股二头肌潜在MTrP的机械性痛敏和自发性电活动的改变,以明确A类感觉纤维是否参与了MTrP的病理性疼痛和自发性电活动过程。
     目的
     明确A类感觉纤维在激痛点自发性电活动及机械痛敏中的作用。
     方法
     46只雄性Wistar大鼠分为3组。
     第一组12只大鼠,轻度麻醉大鼠后,在大鼠股二头肌上仔细寻找肌紧张带,确定MTrP,并作标记。解剖分离L5脊神经根(预实验证明支配大鼠股二头肌的脊神经是L5),充分暴露其前根、后根和脊神经节。浸有人工脑脊液的湿纱布覆盖。平衡1h后,在标记MTrP处用中空针刺电极缓慢刺入MTrP,出现特征性自发性电位并稳定记录3分钟,此点即为MTrP区。先切断脊神经前根,10min后观察SEA电位变化,再切断后根,10min后观察SEA电位变化。切断前后SEA平均波幅或频率下降50%被认为有明显改变。
     第二组24只Wistar大鼠,随机分为2组,TTX组和等渗生理盐水组。如上实验先麻醉大鼠,寻找MTrP。在同侧股骨中部水平分离坐骨神经,切口周围皮肤及筋膜层提起做成一个浴槽,覆以人工脑脊液。在大鼠股二头肌MTrP处稳定记录到SEA3min后,分别在坐骨神经浴槽中加入1μM TTX或等体积等渗生理盐水,10min后观察SEA的电位变化。SEA平均波幅或频率下降50%被认为有明显改变。
     第三组10只Wistar大鼠,如同上实验先麻醉大鼠达轻麻醉状态,在大鼠股二头肌上仔细寻找肌紧张带和MTrP,进行标记。在对侧股二头肌上对应位置标记non-MTrP。分别在MTrP和non-MTrP区测定引起大鼠后肢扑动反应的机械刺激阈值,再用lml空针向MTrP及non-MTrP缓慢注入0.1mlTTX,于注射后5min、15min及30min分别在MTrP和non-MTrP区进行机械刺激阈值的测定。对照比较MTrP及non-MTrP区各个时刻的机械刺激阈值。
     在本研究中,波幅大于20uV的波被认为是大鼠SEA的高幅波。
     结果
     1.在切断脊神经前根/后根实验中,1只大鼠在切断脊神经前根后,SEA明显变小,余11只无明显变化;7只大鼠在切断脊神经后根后电位明显变小,余5只无明显变化。经Chi-square分析,两组问差异有统计学意义(Chi-square value:6.314,P<0.05)。
     2.在TTX阻断坐骨神经的A类神经纤维实验中,TTX组:7只大鼠在TTX阻断后,SEA明显变小,5只变化不明显;等渗生理盐水组:2只大鼠SEA明显变小,10只变化不明显;经Chi-square分析,两组间差异有统计学意义(Chi-square value:4.444,P<0.05)。
     3.在微量TTX局部注射MTrP和non-MTrP的实验中,MTrP和non-MTrP局部注射TTX后不同时刻的机械刺激阈值不同,两因素间有显著的交互作用(两因素方差分析显示(F=12.141,P<0.01:F=96.128,P<0.01:F=6.913,P<0.01)。TTX注射前MTrP区的机械刺激阈值明显小于non-MTrP(q=12.438,P<0.01);注射TTX 5min、15min和30min后MTrP区的机械刺激阈值明显升高(q=4.476,P<0.01:q=7.504,P<0.01:q=9.313,P<0.01);注射TTX后30minMTrP区的机械刺激阈值明显低于non-MTrP区TTX注射30min后的机械刺激阈值(q=4.255,P<0.01);局部注射TTX5min后non-MTrP区的机械刺激阈值低于注射前(q=3.569,P<0.05);TTX局部注射15min和30min后non-MTrP区的机械刺激阈值和注射前差异无统计学意义(q=1.129,P>0.05:q=0.547,P>0.05)。
     结论
     1.A类感觉纤维或许参与了MTrP的病理性疼痛和自发性电位活动。
     2.脊髓后角的兴奋性和MTrP的自发性电活动有关。
Background
     Myofascial trigger points (MTrPs), defined as hyperirritable nodules of spot tenderness in a muscle taut band, have been suggested to be the common cause of myofascial pain syndromes (MPS) which is one of the most prevalent and disabling pain syndromes in chronic pain patients. A latent MTrP is clinically quiescent with respect to spontaneous pain, but is painful when stimulated manually or with a needle. It does everything else that an active trigger point does, but does not reproduce familiar pain.
     To date, the pathogenesis of myofascial trigger points remains elusive. Snapping palpation and/or dry needling of the myofascial trigger points can evoke local and referred pain in addition to a local twitch response. Spontaneous electromyography activity (SEA), as measured by needle electrodes at myofascial trigger points, is a common characteristic; however the source of the SEA and the relationship between pain and SEA are unknown and the role of sensory afferent fibers and motor units at myofascial trigger points has not been fully clarified.
     An increased H-reflex response induced by intramuscular electrical stimulation at MTrPs has also been reported, indicating the hypersensitive large diameter muscle afferents at MTrPs. Human study found that electrically induced muscle pain was decreased after ischemic compression block (ICB) for 20min when it mainly affects A muscle afferents. The fatigable muscle fiber may increase large diameter myelinated muscle afferents input. Thus, it is possible that large diameter muscle afferents may play a role in the pathophysiology of MTrPs.
     We hypothesize that active myofascial trigger points are a result of hypersensitive A muscle spindle afferents. To validate the hypothesis, we did below experiments
     Aim
     The aim of this present study is to test the hypothesis that myofascial trigger points are a result of hypersensitive A muscle afferents fiber and these hypersensitive A muscle afferents fiber contribute to the pathophysiology of myofascial trigger points.
     Methods
     Forty-six male Wistar rats were used in this study which consisted of three sessions. A specially designed hollow-needle electrode was used for searching MTrP in the biceps femoris muscle of anesthetized rat which SEA will be recorded for 3 min.
     In the first session, in 12 rats, the SEA is recorded before and after dissection of ventral or dorsal roots innervating biceps femoris muscle. The average amplitude and frequency of the intermittent spike activity of SEA were analysised. The average amplitude and frequency of the intermittent spike activity of EMG were considered to be significant change when lower or higher 50% than before.
     In the second session, SEA recorded at myofascial trigger points was compared before and 10min after a sensory nerve block by TTX injection or injection of iso-osmia physiologic saline at sciatic nerve in 24 rats.
     In the third session, the threshold of mechanical stimulation that elicited the ipsilateral hindpaw shaking behavior was assessed by electronic von frey before and 5mn、15min and 30min after a local sensory nerve block by TTX at the region of MTrP and at non-MTrP in 10 rats.
     Results
     The average amplitude and frequency of the intermittent spike activity of SEA were considered to be significant change when lower or higher 50% than before.
     1. In the experiment of dissection of dorsal roots, there were 7 rats in which SEA evoked from MTrP were significantly decreased and 5 rats being no significantly change. In the experiment of dissection of ventral roots, there were only 1 rats in which SEA evoked from MTrP was significantly decreased and 11 rats being no significantly change.Chi-square test revealed a significant difference in the incidence of SEA after dissection of ventral or dorsal roots (Chi-square value:6.314, P< 0.05).
     2. In this experiment, there were 7 rats in which SEA evoked from MTrP were significantly decreased after A sensory nerve block by TTX and 2 rats decreased after injection of iso-osmia physiologic saline at sciatic nerve. Chi-square test revealed a significant difference in the incidence of SEA after A sensory nerve block (Chi-square value:4.444, P< 0.05).
     3. Two-way AN OVA revealed that there were significant difference in mechanical threshold for evoking the hind paw responses between MTrP region and non-MTrP region at the time of before and 5、15、30min after TTX local block with significant interaction between these two factors (F=12.141, P<0.01; F=96.128, P <0.01; F=6.913, P<0.01). Mechanical threshold was significantly lower in MTrP than in non-MTrP at pre-block by TTX (q=12.438, P< 0.01). Mechanical thresholds at 5、15、30min after TTX local block were significantly higher than before at MTrP region (q=4.476, P<0.01; q=7.504, P<0.01; q=9.313, P<0.01). Mechanical threshold at 30min after TTX local block at MTrP region was significantly lower than that of non-MTrP region (q=4.255, P<0.01). There was also significantly lower in Mechanical threshold at 5min after TTX local block at non-MTrP region than before (q=3.569, P<0.05). No significant difference was found at before-.15min and 30min after TTX local block at non-MTrP region(q=1.129, P> 0.05; q=0.547, P > 0.05).
     Conclusion
     1. These results suggest that A muscle afferent fiber play an important role in myofascial pain and in the SEA of MTrP.
     2. The excitability of cornu posterius medullae spinalis may contribute the SEA of MTrP.
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    1. Travell JG, Simons DG Myofascial pain and dysfunction:the trigger point manual, Vol.2. Baltimore (MD):Williams & Wilkins; 1992
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