康 杰（美），張 鵬（譯）

運動相關(guān)性肌肉痙攣的最新研究進展

康 杰（美）1，張 鵬（譯）2

運動相關(guān)性肌肉痙攣（EAMC）是休閑運動和競技運動中的常見病癥，通常需要在運動中或運動后即刻就醫(yī)。盡管EAMC發(fā)病率高，但對EAMC的病因仍然知之甚少，并且缺乏高水平的證據(jù)來指導(dǎo)這種病癥的處理。先前關(guān)于EAMC如何產(chǎn)生的報告受到最新證據(jù)的挑戰(zhàn)，這些證據(jù)表明了一種新的發(fā)生機制。本文旨在檢驗?zāi)壳爸С諩AMC病因的各種觀點的科學(xué)證據(jù)，著重分析有關(guān)這一復(fù)雜病癥的最新觀點。此外，還討論了用于治療和預(yù)防EAMC的各種策略，雖然其中大多數(shù)仍是觀察報告，尚未通過研究實驗證實。

運動相關(guān)性肌肉痙攣；機制；風(fēng)險因素；治療；預(yù)防

0 前言

運動相關(guān)性肌肉痙攣（Exercise-associated muscle cramping，EAMC）是在體育賽事中需要就醫(yī)的常見病癥，常見于參加長距離耐力賽的運動員中，如鐵人三項、馬拉松和超馬拉松賽[1,2]。在其他許多運動中也有報道，包括籃球、足球、美式橄欖球、英式橄欖球、網(wǎng)球和自行車[2]。據(jù)報道，鐵人三項選手的 EAMC發(fā)病率為 67%、馬拉松運動員為30%～50%、橄欖球運動員為52%和自行車運動員為60%[1,2]。盡管EAMC具有高發(fā)病率，但研究人員對其風(fēng)險因素和潛在原因尚未完全了解。肌肉痙攣可以作為各種醫(yī)學(xué)病癥的癥狀發(fā)生，包括遺傳性疾病、肌肉疾病、內(nèi)分泌代謝疾病、水電解質(zhì)紊亂以及藥物中毒等[3]。本文關(guān)注的是運動誘發(fā)的骨骼肌痙攣，不包括平滑肌痙攣或休息時發(fā)生的肌肉痙攣，以及與任何潛在疾病或藥物相關(guān)的痙攣。

0 Introduction

Exercise-associated muscle cramping(EAMC)is a common condition that requires medical attention during sporting events.It is common among athletes who participate in long-distance endurance events,such as triathlon,marathon, and ultra-marathon[1，2].It is also documented in many other sports,including basketball,soccer,American football,rugby, tennis,and cycling[2].The prevalence of EAMC has been re ported for triathletes(67%),marathon runners(30%-50%),rug by players(52%)and cyclists(60%)[1，2].Despite the high prevalence of EAMC,its risk factors and underlying causes are not completely understood.Muscle cramping can occur as a symptom for a variety of medical conditions.These include genetic disorders,muscular diseases,endocrine and metabolic diseases,hydroelectrolyte disorders,and toxic and pharmacological agents[3].This review focuses on cramps that are exercise induced and excludes muscle cramping that occur in smooth muscle or at rest and cramping that is associated with any und erlying disease or drugs.

1 EAMC概述

1.1 EAMC的定義

EAMC被定義為在體育運動期間或運動后立即發(fā)生的、不自主的疼痛性骨骼肌痙攣綜合征[4]。它表現(xiàn)為局部肌肉斷續(xù)性痙攣，可發(fā)生在不同的肌肉群，通常在小腿、腘繩肌或股四頭肌，其中發(fā)在生在小腿后群肌肉是最常見的[4]。

1.2 EAMC的癥狀

EAMC的臨床癥狀為急性疼痛、僵硬、明顯的肌肉突起，以及可能可持續(xù)幾天的疼痛[5，6]。它可能沒有任何預(yù)兆便突然發(fā)生，受影響的肌肉通常是隨機的，當(dāng)一束肌纖維松弛時，相鄰束收縮，給人一種痙攣游走的印象[7，8]，例如，抽搐首先可能出現(xiàn)在股四頭肌中，隨后出現(xiàn)在另一個肌肉群中[7]。大多數(shù)EAMC持續(xù)1～3 min，但運動員常訴說在運動后8 h仍然會發(fā)生EAMC癥狀[9]。這種運動后對EAMC易感性增加的時期被稱為易痙攣狀態(tài)[10]。EAMC可以使肌力下降[11，12]，雖然在某些情況下EAMC似乎不影響運動成績[13，14]。

1.3 風(fēng)險因素

EAMC似乎在長時間、高強度賽事中發(fā)生得更為頻繁。事實上，某些運動賽事的安排可能更易導(dǎo)致EAMC發(fā)生。在網(wǎng)球排名賽的多日比賽中，參賽選手通常每天不僅僅打一場比賽，而且每場比賽之間只有1 h的休息時間。這種競賽模式易引起的肌肉疲勞，不利于每場比賽之間水和電解質(zhì)的補充，并經(jīng)常導(dǎo)致肌肉痙攣，從而影響運動比賽[15]。在對1 300名馬拉松賽選手進行有關(guān)EAMC相關(guān)的風(fēng)險因素的橫向調(diào)查中發(fā)現(xiàn)，與EAMC相關(guān)的特定條件包括高強度跑步、長距離跑（＞30 km）、主觀肌肉疲勞，這些都反映高強度、疲勞性的體力輸出。這項調(diào)查中發(fā)現(xiàn)的其他危險因素包括年齡較大、跑步年限較長、體重指數(shù)較高、日常拉伸運動時間較短、不良的拉伸習(xí)慣，以及痙攣的陽性家族史[16]。在一項對鐵人三項運動員的前瞻性研究中，EAMC唯一的獨立風(fēng)險因素是在高強度比賽中發(fā)生痙攣的既往史[17]。一篇關(guān)于馬拉松賽事中肌肉痙攣的綜述也表明，EAMC易發(fā)生于有該病史的跑步者，并導(dǎo)致這些運動員過早出現(xiàn)肌肉疲勞[18]。

1 Overview of Exercise Associated Muscle Cramps (EAMC)

1.1 Defining exercise associated muscle cramps(EAMC)

EAMC is defined as a syndrome of involuntary painful skeletal muscle spasms that occur during or immediately after physical exercise[4].It presents as localized muscle cramping that happens spasmodically in different exercising muscle groups,usually the calf,hamstring or quadriceps muscles. The calf muscles are the most commonly affected[4].

1.2 Symptoms of EAMC

Clinically,EAMC may be recognized by acute pain, stiffness,visible bulging or knotting of the muscle,and possi ble soreness that can last for several days[5，6].It can occur suddenly with no warning.The affected muscles often appear to be randomly involved,and as one bundle of muscle fibers relax,an adjacent bundle contracts,giving the impression that the spasms wander[7，8].For example,twitches first may appear in the quadriceps and subsequently in another muscle group[7].Most EAMC incidents last 1-3 min,but athletes often complain of EAMC symptoms up to 8 hours after exercise[9]. This post-exercise period of increased susceptibility to EAMC has been termed as the cramp prone state[10].EAMC can be completely debilitating[11，12],although in some cases EAMC do not appear to affect athletic performance[13，14].

1.3 Risk factors

EAMC seems to be more frequent in long-duration, high-intensity events.Indeed,the competitive schedule of certain athletic events may predispose to EAMC.In multiday tennis tournaments,competitors often play more than one match a day,with only an hour between matches.This competition format induces muscle fatigue,impedes fluid and electrolyte replacement between matches,and often results in debilitating muscle cramps[15].Risk factors associated with EAMC in running have also been examined in a cross-sectional survey of 1 300 marathon runners.In this survey,thespecific conditions found to be associatedwith EAMC included high-intensity running,long distance running (＞30 km),subjective muscle fatigue,all of which are intense and exhaustive physical efforts.Other risk factors identified in this survey were older age,a longer history of running,higher body mass index,shorter daily stretching time,irregular stretching habits, and a positive family history of cramping[16].In a prospective study of Ironman triathletes,the only independent risk factors for EAMC were a history of the condition and competing at a higherthan usualexercise intensity[17].A review on muscle cramping in marathonalso suggests that EAMC is associated with running conditions that can lead to premature muscle fatigue in runners who have a history of the condition[18].

2 EAMC的歷史和病因?qū)W

2.1 肌肉痙攣的早期報告

最早有關(guān)肌肉痙攣的報告來自100年前，當(dāng)時工人在礦山和造船廠濕熱的條件下患有痙攣疾病[19，20]。經(jīng)進一步分析發(fā)現(xiàn)建筑工汗液中具有較高的氯化物水平。在這些報告中，發(fā)現(xiàn)肌肉痙攣不僅發(fā)生在高溫條件下，而且痙攣時伴隨大量出汗[20]。最近，通過監(jiān)測美國橄欖球運動員的中暑疾病，Cooper等觀察到95%的痙攣事件發(fā)生在高溫月份，此時中暑疾病的風(fēng)險被評定為“高”或“極高”[21]。 正是由于這些早期觀察結(jié)果，“電解質(zhì)紊亂和脫水”學(xué)說被確認(rèn)為EAMC的基本病因。基本上，該學(xué)說表明過度出汗和由此產(chǎn)生的電解質(zhì)丟失可以影響肌肉和神經(jīng)功能障礙，從而產(chǎn)生肌肉痙攣。因此，目前已普遍認(rèn)為EAMC發(fā)生是因為運動員在熱環(huán)境中運動，電解質(zhì)隨汗液丟失，導(dǎo)致電解質(zhì)紊亂和脫水，并伴隨體溫升高[22，23]。

2.2 電解質(zhì)紊亂和脫水學(xué)說

電解質(zhì)紊亂和脫水學(xué)說表明EAMC與出汗過多或過度消耗水分造成的血清電解質(zhì)濃度降低有關(guān)，特別是鈉和氯[4，8，24]。 的確，在單次訓(xùn)練比賽或重復(fù)運動后，當(dāng)汗液氯化鈉丟失明顯超過鹽攝入量時，總是產(chǎn)生全身可交換鈉明顯減少的現(xiàn)象[25，26]。據(jù)估計由出汗引起的鈉離子池?fù)p失達到約 20%～30%便可導(dǎo)致嚴(yán)重的肌肉痙攣[15，27]。當(dāng)疑似出現(xiàn)所謂的鈉離子池不足時，汗液中其他較低程度的電解質(zhì)損失，即鈣、鎂和鉀也被認(rèn)為與運動中或運動后肌肉痙攣有關(guān)[28-31]。電解質(zhì)紊亂學(xué)說的主要前提是假定汗液鈉濃度增高或“咸汗”導(dǎo)致鈉消耗，從而引起EAMC[25，32]。然而，這一學(xué)說的病理生理學(xué)基礎(chǔ)仍不明確。

由于汗液鈉濃度總是低滲的[33，34]，因此只有伴隨著體液的大量丟失，才能通過汗液發(fā)生明顯的鈉丟失。這意味著運動員發(fā)生 EAMC時同時會出現(xiàn)脫水和明顯的鈉丟失。過度脫水會減少血容量，為補償損失的血容量，組織液中的水將轉(zhuǎn)移到血管內(nèi)以維持中心血容量[35-37]。 隨著繼續(xù)出汗，組織間隙越來越收縮[35]，由于運動后繼續(xù)出汗，這一過程甚至可以在運動后持續(xù)進行，直至體溫恢復(fù)到運動前水平[36]。由于組織間隙收縮，某些神經(jīng)肌肉接點（尤其先發(fā)生在股四頭肌或腘繩?。┛赡苡捎跈C械變形而過度興奮。所產(chǎn)生的機械壓力變化可以誘發(fā)運動神經(jīng)元自發(fā)性放電，從而導(dǎo)致痙攣[38，39]。圖 1說明了出汗引起的脫水如何逐步觸發(fā)EAMC的過程。

痙攣發(fā)作也可歸因于以下事實：運動神經(jīng)元軸突的末端分支，特別是無髓鞘的神經(jīng)末梢，接觸到水平增加的興奮性細胞外物質(zhì)，例如乙酰膽堿或電解質(zhì)（即鈉和鉀）[40-42]。隨著更多的水從組織間隙轉(zhuǎn)移到血管內(nèi)，毗鄰的神經(jīng)末梢和其它神經(jīng)末梢及突觸后膜同樣受到影響。這可以解釋為什么經(jīng)常觀察到痙攣游走現(xiàn)象，也就是痙攣在不同的肌肉纖維和肌肉束中交替發(fā)生[43]。

2.3 EAMC起始病因的反面證據(jù)

如上所述，對電解質(zhì)紊亂和脫水學(xué)說的支持主要來自基于病例報告或觀察的研究，并沒有記錄水合狀態(tài)的實際測量。礦工出現(xiàn)痙攣是因為他們在濕熱環(huán)境工作，出汗較多[20，39]。最近，對美式橄欖球運動員的研究表明，大多數(shù)痙攣發(fā)生在炎熱的月份，運動員在該環(huán)境中發(fā)生中暑的風(fēng)險很高[21]。這個學(xué)說的其他證據(jù)來自案例研究和觀察工作，這些研究中運動員有大量出汗的情況[15，25，26]。

電解質(zhì)紊亂和脫水學(xué)說似乎與許多最新的證據(jù)相矛盾。4項前瞻性隊列研究顯示在馬拉松或鐵人三項運動員中，血清電解質(zhì)異常和 EAMC之間并不相關(guān)[6，13，14，44]。研究結(jié)果表明EAMC機制是汗液濃度增加（“咸汗”）導(dǎo)致鈉消耗，而不是血清電解質(zhì)濃度的變化[45，46]。然而，鈉損耗如何導(dǎo)致EAMC仍沒有生理學(xué)解釋。由嚴(yán)重鈉丟失引起的低鈉血癥與休息時的全身肌肉痙攣有關(guān)[47]?？墒牵缟纤?，在患有EAMC的大多數(shù)運動員中，痙攣發(fā)生在運動期間重復(fù)收縮的局部肌群。對于電解質(zhì)系統(tǒng)不平衡如何導(dǎo)致局部肌肉痙攣尚沒有合理的生理學(xué)解釋。

至于脫水，有人認(rèn)為過度出汗是導(dǎo)致EAMC的主要原因[4]。然而在上述 4個前瞻性隊列研究中，將計算出的體重變化、血容量或血漿容量用作身體水合狀態(tài)的指標(biāo)，發(fā)現(xiàn)當(dāng)時發(fā)生痙攣的運動員脫水情況并不比未發(fā)生痙攣的運動員脫水情況嚴(yán)重。因而，脫水和肌肉痙攣之間的直接關(guān)系假設(shè)不被支持[6，13，14，44]。

圖1 EAMC的電解質(zhì)紊亂和脫水學(xué)說的示意圖Figure 1 Schematic Illustration of the Electrolyte Imbalance and Dehydration TheoryofExerciseAssociated Muscle Cramps(EAMC)

若運動員在涼爽和溫度控制環(huán)境中運動時發(fā)生EMAC，使用電解質(zhì)不平衡和脫水學(xué)說對其進行解釋也不成立[13，48]。例如，Maughan報告稱，即使環(huán)境溫度為10～12℃，一些馬拉松運動員（約18%）仍然產(chǎn)生EAMC[13]。因此，盡管EAMC可能在高溫環(huán)境下更為頻繁地發(fā)生，但是，濕熱環(huán)境并不是發(fā)生EAMC的必要條件[21]。該研究還顯示，在患有和未患EAMC的跑步者之間，血容量和體重的減少沒有顯著差異。

總的來說，電解質(zhì)紊亂和脫水學(xué)說具有局限性。支持性證據(jù)來自于無法提供任何因果結(jié)論的病例報告或調(diào)查。雖然EAMC可能在運動期間存在顯著電解質(zhì)和/或液體丟失的情況下出現(xiàn)，但也可以歸因于其它因素，例如代謝物的積累、能量不足、肌肉損傷，以及訓(xùn)練水平和/或環(huán)境適應(yīng)能力欠缺。

2.4 熱痙攣——用詞不當(dāng)

病例報告和觀察記錄經(jīng)常將痙攣產(chǎn)生與在濕熱環(huán)境下進行體力活動相關(guān)聯(lián)，這導(dǎo)致了“熱痙攣”或“運動性熱痙攣”的名稱的普遍使用。這些術(shù)語通常與EAMC同義使用[2，15，43，45，49]。 支持使用這一術(shù)語的更多實質(zhì)性數(shù)據(jù)來自于一項流行病學(xué)研究，文中美國橄欖球運動員在熱指數(shù)為“高”或“極高”環(huán)境中訓(xùn)練相比“低”或“中等”的環(huán)境中訓(xùn)練時，“熱痙攣”的發(fā)生更加常見[21]。必須注意的是，這些炎熱和潮濕的天氣條件也發(fā)生在賽季訓(xùn)練的前2～3周，此時運動員很可能不能妥善調(diào)整狀態(tài)和/或適應(yīng)炎熱的天氣條件而容易導(dǎo)致疲勞。在適宜溫度至涼爽溫度下運動的人員也會發(fā)生 EAMC[13，48]，在游泳運動員中發(fā)現(xiàn)極端寒冷的條件也與EAMC相關(guān)[50]。還有報道稱，EAMC的發(fā)生與核心體溫的升高沒有直接關(guān)系[13]。顯然，熱本身不是運動中肌肉痙攣產(chǎn)生的直接原因。因此，術(shù)語“熱痙攣”是不準(zhǔn)確的，應(yīng)當(dāng)避免使用。

2 History and Original Etiology of EAMC

2.1 Early reports of muscle cramps

The earliest reports of muscle cramps come from 100 years ago,when labors in hot and humid conditions of the mines and shipyards suffered from cramps[19，20].Upon further analysis,it was noticed that the builders had a high chloride level in their sweat.In these reports,it was noted not only that muscle cramping occurred in the heat,but also that cramps were accompanied by profuse sweating[20].More re cently,by monitoring external heat illness among American football players,Cooper et al.observed that 95% of the cramping incidents occurred in hot months when the risk of developing heat illness was “high”or “extreme”[21].It was because of theseearly observations that the“electrolyte imbalance and dehydration”theory was developed as an underlying cause for EAMC.In principle,this theory suggests that overly sweating and thus loss of electrolytes can cause muscles and nerves that innovate them to malfunction,thereby producing muscle cramps.It is now a common belief that EAMC happens because athletes exercise in the heat,lose electrolytes in their sweat,and the resultingelectrolyte imbalance and dehydration combines with high body temperature[22，23].

2.2 The electrolyte imbalance and dehydration theory

The electrolyte imbalance and dehydration theorysuggests that EAMC is related to the decreased concentration of serum electrolytes,particularlysodium and chloride,resulting from excessive sweating or overconsumption of water[4，8，24].Indeed, a sizeable whole-body exchangeable sodium deficit always develops following a single long race,match,game,or training session or repeated exercisebouts when sweat sodium and chloride lossessignificantly exceed salt intake[25，26].An estimated sweat-induced loss of 20%-30%of the sodiumpool has been linked to severe muscle cramping[15，27].Other electrolytes lost in sweatto a much lesser degree,namelycalcium,magnesium,and potassium,have also been implicatedas the cause of muscle cramping during or afterexercise when purported deficiencies are suspected[28-31].The chiefpremise behind the electrolyte imbalance theory is to suggest that the mechanism for EAMC is increased sweat sodium concentrationor"salty sweating",resulting in sodium depletion,which then causes EAMC[25，32].However,the pathophysiologicalbasis for this hypothesis remains poorly defined.

Because sweat sodium concentration is always hypotonic[33，34],a significant loss of sodium through sweat can therefore only occur if there is an accompanying large loss of bodi ly fluid.This would mean that dehydration would accompanyany significant sodium loss in athletes experiencing with EAMC.Overly dehydration will reduce plasma volume.To compensate for the loss in plasma volume,water fromthe interstitial fluid compartment shifts to the intravascularspace to maintain central blood volume[35-37].As sweating continues,the interstitialfluid compartment becomes increasingly contracted[35].This can persist even after exercise as sweating continuesand body temperature returns to a pre-exercise level[36].Consequent to a contracted interstitial compartment,certain neuromuscular junctions (especially first in the quadriceps or hamstring muscles)could become hyper-excitable by mechanical deformation.The resulting change in mechanical pressure can induce spontaneous discharges of the affected motor neurons, thereby causing cramps[38，39].Figure 1 illustrates a step-by-step processofhow sweat-induced dehydration may trigger EAMC.

Cramp discharges may also be attributed to the fact that terminal branches of motor axons,especially those that are unmyelinated,are exposed to increased levels of excitatory extracellular substances such as acetylcholine or electrolytes(i. e.,sodium and potassium)[40-42].As more water is shifted away from the interstitial compartment to the intravascular space, adjacent and other nerve terminals and post-synaptic membranes could be similarly affected.This may explain why cramping is often observed in various muscle fibers and bundles alternately contracting and relaxing[43].

2.3 Evidence against the original etiology of EAMC

As mentioned earlier,support for the electrolyte imbalance and dehydration theory comes mainly from research based on case report or observations with no actual measures of hydration status reported.Miners develop cramps because of their sweat losses while working in hot and humid conditions[20，39].More recently,research on American football re vealed that most crampingincidents occurred in hot months when football players trained in an environment where the risk of developing heat illness was high[21].Other evidence for this theory comes from case studies and observational work in which large sweat losses occurred in exercising athletes[15，25，26].

The electrolyte imbalance and dehydration theory seems to contradict many recent evidences.Four prospective cohort studies have shown no relationship between serum electrolyte abnormalities and EAMC in marathon runners or triathletes[6，13，14，44].The findings have led to the suggestion that increased sweat concentration (‘salty sweating’)resulting in sodium depletion,rather than changes in serum electrolyte concentrations,is the mechanism for EAMC[45，46].However,the physiologicalexplanation for how sodium depletion may cause EAMC remains unavailable.Hyponatremia resulting from a significant loss of sodium has been associated with general-ized muscle cramping at rest[47].However,as mentioned earlier,in most athletes experiencing EAMC,cramping occurs in the localized muscle groups involved in repetitive contractions during exercise.There is no plausible physiological explanation of how a systemic imbalance of electrolytes could result in localized muscle cramps.

As for dehydration,it has been argued that excessive sweating is the primary cause of EAMC[4].However,in the four prospective cohort studies mentioned above in which calculated body weight changes and volume of blood or plasma were used as indicators of hydration status,it was found that cramping athletes at the time of were not more dehydrated than non-cramping athletes.Thus.the hypothesis of a direct relationship between dehydration and muscle cramping was not supported[13，6，14，44].

The electrolyte imbalance and dehydration theory also does not stand when it is usedto explain EAMC that occurs in athletes exercising in cool and temperature-controlled environ ments[13，48].Forexample,Maughan[13]reported that somemarathoners (～18%)still developed EAMC even though the ambient temperature was 10 to 12℃.Thus,it is unlikely that a hot and humid environment is required for the development of EAMC,although EAMC may occur more frequently under conditions of elevated ambient temperatures[21].This same study also revealed no significant differences inlosses of plasma volume and body weight between runners with and without EAMC.

Overall,the dehydration-electrolyte imbalance theory has limitations.Supporting evidence wasbased on case report or surveys that could not provide any cause-effect conclusions. Although EAMC may appear in the presence of significant electrolyte and/or fluid losses during exercise,it can also be attributedto other factors such as accumulation of metabolites, fuel deficiency,muscle damage,and a lack of conditioning and/or acclimatization.

2.4 “Heat cramps”-a misnomer

Case reports and anecdotal observationsoften related the development of cramping to physical activity performed in hot and humid conditions,and this has led to the use of"heat cramps"or"exertional heat cramps".These terms areoften used synonymously with EAMC[2，15，43，45，49].More substantive data to support the use of this terminology came from an epidemiological study in which the term"heat cramps"was reported to be more common when American football players trained in an environment where the heat index was"high"or "extreme"compared with"low"or"moderate"[21].Itmust be noted that these hot and humid weather conditionsalso occurred during the first 2-3 weeks of training in a season when players were also most likely less well-conditioned and/or acclimatized to the heat.EAMC is also known to occur in individu-als exercising in moderate to cool temperatures[13，48]and exposure to extreme cold has also been associated with EAMC in swimmers[50].It has also been reported that the development of EAMC is not directly related to an increased core temperature[13].Clearly,heat alone is not a direct cause of muscle cramping during exercise.As such,the term"heat cramps"is inaccurate and its use should be discouraged.

3 有關(guān)EAMC的最新發(fā)現(xiàn)

3.1 異常神經(jīng)肌肉控制學(xué)說

在體育競賽和訓(xùn)練或其他各種劇烈的體力活動中，所涉及的肌肉受到長期反復(fù)的負(fù)荷，可導(dǎo)致肌肉或肌腱勞損和局部疲勞。異常神經(jīng)肌肉控制學(xué)說表明，肌肉疲勞破壞了外周肌肉感受器的正常功能，因此導(dǎo)致肌梭的興奮性傳入活動的增加，而高爾基腱器官的抑制性傳入活動降低，兩者共同導(dǎo)致α運動神經(jīng)元向肌肉纖維放電的增加，從而產(chǎn)生局部肌肉痙攣[4]。這一學(xué)說可以通過動物研究予以支持， 此研究在離體的貓腓腸肌上使用了肌電圖記錄[51，52]。在這些研究中，通過電刺激使肌肉產(chǎn)生疲勞，發(fā)現(xiàn)隨著肌肉疲勞的發(fā)展，肌梭的 Ia和 II型傳入纖維沖動發(fā)放增加，并且來自高爾基腱器官的Ib型傳入纖維沖動發(fā)放減少[51，52]。換句話說，肌肉痙攣可以被視為持續(xù)的α運動神經(jīng)元放電的結(jié)果，這種現(xiàn)象發(fā)生時，肌梭的興奮性活動增強觸發(fā)了非自主肌肉收縮，且不能被抑制這種肌肉反應(yīng)的高爾基腱器官所拮抗。圖2基于異常神經(jīng)肌肉控制學(xué)說對肌肉痙攣的產(chǎn)生做出了更詳細的解釋。

值得注意的是，當(dāng)肌肉在已經(jīng)收縮的狀態(tài)繼續(xù)縮短時，更容易發(fā)生局部痙攣[4，41]。這是因為當(dāng)肌肉處于縮短狀態(tài)時，高爾基腱器官的抑制活動將比正常情況減少更多，從而導(dǎo)致α運動神經(jīng)元的抑制和興奮之間更大的不平衡[53]。這也許可以解釋為什么小腿肌肉痙攣在游泳運動員中如此普遍。這是因為在大多數(shù)游泳比賽中，游泳運動員的踝關(guān)節(jié)必須跖屈，而這需要小腿肌肉保持適度收縮。 至于過度負(fù)荷和疲勞所引起的肌肉痙攣，其潛在風(fēng)險因素包括年齡較大、拉伸習(xí)慣差、調(diào)節(jié)功能不足、痙攣既往史、過度的運動強度、過長的持續(xù)時間以及相關(guān)的代謝紊亂（即，肌糖原耗竭）[18，54]。

圖2 EAMC異常神經(jīng)肌肉控制學(xué)說的示意圖Figure 2 Schematic Illustration of the Altered Neuromuscular Control Theory of Exercise Associated Muscle Cramps(EAMC)

3.2 支持異常神經(jīng)肌肉控制學(xué)說的證據(jù)

這一學(xué)說首先于 20世紀(jì) 90年代初通過觀察性研究提出，研究中1 383名馬拉松運動員對關(guān)于EAMC的問卷做出了回答[16]。在這些跑步者中，536名（26%）報告了EAMC病史，其中大多數(shù)（60%）表示肌肉疲勞與EAMC的發(fā)病相關(guān)。這一發(fā)現(xiàn)與Maughan的研究一致，他也發(fā)現(xiàn)EAMC的發(fā)生在馬拉松賽的后期更為常見[13]。關(guān)于運動強度增加和EAMC相關(guān)的更具說服力的證據(jù)來自對鐵人三項運動員進行的前瞻性隊列研究[17]。在這項研究中，參加鐵人三項比賽的 210名鐵人三項運動員為受試者，對所有受試者的訓(xùn)練歷史、個人最好成績，以及比賽之前的痙攣病史進行了調(diào)查。結(jié)果表明，與沒有發(fā)生EAMC的運動員相比，發(fā)生EAMC（N=44）的運動員在比賽期間的運動強度更高，并且比賽用時較少，盡管他們的準(zhǔn)備過程和歷史成績近似。這些結(jié)果表明，痙攣組中更少的比賽用時（或運動強度增加）是這些鐵人三項運動員發(fā)生EAMC的獨立危險因素。在一項使用專門設(shè)計的用于引起小腿肌肉疲勞的運動方案的研究中，記錄了運動期間肌肉痙攣的高發(fā)生率[55]。 這項研究還表明，與無液體補充相比，口服補充碳水化合物和電解質(zhì)在使用小腿疲勞方案后導(dǎo)致EAMC的發(fā)作延遲?？磥頌檫\動員提供更多的碳水化合物可以減輕EAMC。

肌電圖（EMG）的使用使研究人員更確信EAMC是由異常神經(jīng)肌肉控制介導(dǎo)這一觀點。 在上述討論的研究[51，52]中，肌電圖用于在EAMC發(fā)生時客觀地跟蹤疲勞肌肉中α運動神經(jīng)元的放電。例如，在肌電圖中觀察到，EAMC發(fā)生之前，肌肉抽搐情況增加。然而，隨著疲勞運動繼續(xù)，肌電圖中出現(xiàn)一個更大的變化并且與肌肉完全痙攣同時發(fā)生。通過使用肌電圖來比較發(fā)生和沒有發(fā)生EAMC的鐵人三項運動員，Sulzer等人發(fā)現(xiàn)，患有EAMC的鐵人三項運動員的肌電圖基線活動在痙攣肌中明顯高于非痙攣肌[44]。有趣的是，在這些受試者中，EAMC與電解質(zhì)消耗或脫水并不相關(guān)。

被動拉伸是最常見和有效的緩解急性肌肉痙攣的療法[53，56-58]。 支持電解質(zhì)紊亂和脫水學(xué)說的那些人也認(rèn)為它是有效的治療方法[43，59]。 被動拉伸增加肌肉的張力，從而增加高爾基腱器官對 α運動神經(jīng)元的抑制性控制[52，53]。這一機制對異常神經(jīng)肌肉控制介導(dǎo)EAMC的假說提供了進一步支持。

3.3 EAMC中的其他病因?qū)W因素

已推測出在脊髓水平改變神經(jīng)肌肉控制的其他促進EAMC發(fā)展的因素。首先是由疲勞運動引起的肌肉損傷，導(dǎo)致反射性“痙攣”，從而引起持續(xù)的非自主收縮。第二種可能性是來自其它外周感受器 （例如肌肉內(nèi)化學(xué)感受器、壓力感受器或疼痛感受器）的信號改變，可引起來自中樞神經(jīng)系統(tǒng)的反應(yīng)，從而改變神經(jīng)肌肉控制[53]。在一項涉及鐵人三項運動員的前瞻性隊列研究中，與EAMC相關(guān)的一個獨立危險因素是具有EAMC既往史[17]。此外，如前所述，一項橫向研究調(diào)查了 1 383名馬拉松跑步者[16]，痙攣陽性家族史也被報告為EAMC的風(fēng)險因素。在這種情況下，不能排除EAMC的遺傳傾向。其他提出EAMC病因?qū)W的理論是碳水化合物攝入量不足、糖原耗盡、生物力學(xué)或跑姿不正確、丘陵地帶或凹凸不平的地形，以及在比賽前和比賽中缺乏足夠的按摩[4]。

3 Recent Discoveries on EAMC

3.1 The altered neuromuscular control theory

During sports competition and training or a variety of other intense physical activities,repeated or extended loading on selected muscles can lead to muscle or tendon strain and localized fatigue.The altered neuromuscular control theory suggests that muscle fatigue disrupts the normal functioning of peripheral muscle receptors and thus causes an increase in excitatory afferent activity within the muscle spindle and a decrease in inhibitory afferent activity within the Golgi tendon organ,both of which then lead toan increase in alpha motor neuron discharge to the muscle fibers,producing a localized muscle cramp[4].This theory can be supported by animal studies that used isolated gastrocnemius muscles derived from cats and electromyographic recordings[51，52].In these studies, muscle fatigue was introduced via electric stimulation.It was found that as muscle fatigue developed,there was an in creased firing rate of the muscle spindle’s type Ia and II afferents concomitant with a decrease in the type Ib afferent activity from the Golgi tendon organ[51，52].In other words,muscle cramps can be viewed as a consequence of a sustainedalpha motor neuron discharge that occurs when the enhanced excitatory activity of the muscle spindle that triggers an involuntary muscle contraction is unopposed by Golgi tendon organsdesigned to inhibit such a muscular response.Figure 2 ill ustrates more detailed explanations of how muscle cramps may come about based on the altered neuromuscular control theory.

It is worth noting that these localized cramps are more likely to occur when the muscle is contracting in an already-shortened position[4，41].This is because when muscle is in a shortened position,the inhibitory active of the Golgi tendon organ will reduce even more than normal,causing a greater imbalance between inhibitory and excitatory drives to the alpha motor neuron[53].This may explain why calf muscle cramps are so prevalent in swimmers.This is because in most swimming races swimmer must swim with the ankles being planter flexed,which requires calf muscles to remain modestly contracted.The potential risk factors associated with overload and fatigue-related muscle cramping also include older age,poor stretching habits,insufficient conditioning,cramping history,excessive exercise intensity and duration,and related metabolic disturbances (i.e.,muscle glycogen depletion)[54，18].

3.2 Evidence supporting the altered neuromuscular control theory

The theory may be first brought up in the early 1990s by an observational study in which 1383 marathon runners responded to a questionnaire on EAMC[16].Of these runners, 536(26%)reported a history of EAMC and a majority(60%) of them indicated that muscle fatigue was associatedwith the onset of EAMC.This finding concurs with those ofMaughan[13]who also discovered that development of EAMC was more common in the latter stages of a marathon race.Stronger evidence linking increased exercise intensity and EAMC comes from a prospective cohortstudy in Ironman triathletes[17].In this study,210 triathletescompeting in an Ironman triathlon acted as subjects and all the subjects were surveyed for their training history,personal best performances,and cramping history prior to the race.Results of this study showed that those who developed EAMC(n=44)exercised at a higher intensity during the race and had faster overall race time despite similarpreparation and performance histories as compared to those who did not develop EAMC[17].These findings indicate that the faster racing time(or increased exercise intensity)inthe cramp group was an independent risk factor for thedevelopment of EAMC in these triathletes.In a study using an exercise protocol specifically designed to cause fatigue of thecalf muscles,a high incidence of muscle cramping during exercise was documented[55].This study also reveal that supplementingcarbohydrate and electrolytes orally,compared with no fluid administration,resulted in a delay inthe onset of EAMC following a calf fatiguing protocol.It appears that providing athletes with more carbohydrate can alleviate EAMC.

The use of electromyography (EMG)has allowed researchers to be more convincing of the argument that EAMC is mediated by an altered neuromuscular control.In the stud ies discussed earlier[51，52],EMG was used to objectively trace the discharge of alpha motor neurons in fatigued muscles as EAMC developed.For example,a modest increasein EMG was noticed as muscle twitches prior to EAMC.However,as fatiguing exercise continues,there was a much greater change in EMG that coincided witha full-blown muscle cramp.By using EMG to compare ironman triathletes with and without EAMC,Sulzer et al.found that baseline EMG activity in triathletes who suffered from EAMC was significantly higher in a cramping thana non-cramping muscle[44].Interestingly,in these subjects,EAMC was not associated with electrolyte depletion or dehydration.

Passive stretching is the mostcommon and effective therapy to relieve acute muscle cramping[53，56-58].It is also regarded as effective treatment by thosewho support the electrolyte depletion and dehydrationtheory[43，59].Passive stretchingincreas es the tension in a muscle,thereby increasing the Golgi tendon organ’s inhibitory input to the alpha motor neuron[52，53]. This mechanismoffers further support for the hypothesis that abnormalneuromuscular control mediates EAMC.

3.3 Other etiological factors in EAMC

Other factorshave been speculated to alterneuromuscular control at the spinal cord level,thereby contributing to the development of EAMC.The first of theseis the possibility that muscle injury or damage,resultingfrom fatiguing exercise, could cause a reflex"spasm",andthus lead to a sustained involuntary contraction.Thesecond possibility is that changing signals fromother peripheral receptors,such as chemically sensitive intramuscularafferents,pressure receptors,or pain receptors,couldelicit a response from the central nervous system, which mayalterneuromuscular control of the muscles[53].In a prospective cohort study involving triathletes,one independent risk factorassociated with EAMC was a previous history of EAMC[17].In addition,in a cross-sectional study that surveyed 1383 marathon runners as mentioned earlier[16],a positive family history of cramping has also been reported as a risk factor for EAMC.In this context,a genetic predisposition to EAMC cannot be ruled out.Among other theories that have been proposed for the etiology of EAMC arean inadequate intake of carbohydrate,glycogen depletion,poor biomechanics or running gait,hilly terrain,and lack of adequate massage be-fore and during a game[4].

4 治療和預(yù)防

4.1 治療

既然關(guān)于EAMC病因存在多種解說，所以很難為治療或預(yù)防策略提供唯一答案。因此，有許多干預(yù)措施可用于治療肌肉痙攣。這些治療包括拉伸痙攣肌肉，降低運動強度，按摩，溫?zé)岑煼?，冷凍療法，補充運動飲料、鹽和電解質(zhì)、pickle juice（腌黃瓜汁）運動飲料，靜脈輸注和經(jīng)皮神經(jīng)電刺激。這些治療選擇方案很多是觀察記錄，或缺乏實驗研究支持。EAMC可以被視為多種病理過程的結(jié)局，并且可能不同的運動員導(dǎo)致相似 EAMC表現(xiàn)的機制不同。因此，對一名運動員有效的治療，不一定對其他運動員也有效。下面對一些常用的治療方法進行討論。

電解質(zhì)紊亂和脫水學(xué)說表明，攝取含有電解質(zhì)的液體有助于使組織間隙或細胞外容量正常化， 從而減輕EAMC。然而，由于許多運動飲料中的電解質(zhì)較少，即使運動員正常出汗和丟失汗鈉含量，也可能難以充分替代運動期間損失的電解質(zhì)含量。請注意，液體和電解質(zhì)在喝下后不能立即被吸收，也就是說，即使低滲液體，也需要至少13 min被吸收到循環(huán)系統(tǒng)中[60]?；诿撍娊赓|(zhì)紊亂和EAMC之間存在關(guān)系這一假設(shè)，美國國家體育醫(yī)務(wù)管理員協(xié)會建議，在有傾向發(fā)生肌肉痙攣的運動員的飲料中添加0.3～0.7 g/L的鹽，以避免肌肉痙攣[61]。其他運動員建議根據(jù)EAMC[49]的發(fā)生頻率，在運動飲料中添加更多的鈉（約3～6 g/L）。一旦發(fā)現(xiàn)有肌肉抽搐或輕度痙攣的跡象，立即口服高鹽溶液（例如，一次口服或在5～10 min內(nèi)分次服用添加3 g鹽的0.5 L碳水化合物—電解質(zhì)飲料），被證明能夠有效緩解痙攣或防止肌肉震顫發(fā)展成為完全的EAMC[15]。服用高鹽溶液后，通常運動員可立即恢復(fù)訓(xùn)練或比賽，并且在一個小時或更長時間內(nèi)不再發(fā)生肌肉痙攣或抽搐癥狀[15]，盡管仍然需要每隔一定時間服用額外的低鈉液體。

其它經(jīng)常選擇用于緩解EAMC的物質(zhì)包括pickle juice（腌黃瓜汁）運動飲料、奎寧和電解質(zhì)，例如鎂、鉀和鈣。 一項病例報告顯示，使用 pickle juice（腌黃瓜汁）運動飲料來治療EAMC，當(dāng)攝入少量高濃度酸性鹽水后（30～60 mL），可以在 35 s內(nèi)緩解痙攣[48]。 然而， 這種效果被認(rèn)為是由于pickle juice（腌黃瓜汁）運動飲料含有乙酸，可以在口咽部引發(fā)神經(jīng)反射，從而在痙攣的肌肉中增加抑制性神經(jīng)遞質(zhì)的活性[62]。奎寧是一種用于治療由蚊子叮咬引起的瘧疾的藥物，但也常用于治療各種原因引起的痙攣。一項對23項臨床試驗進行的Cochrane綜述發(fā)現(xiàn)，與安慰劑相比，奎寧可以降低痙攣的頻率、強度和天數(shù)，但不能降低持續(xù)時長，不過與安慰劑相比，使用奎寧導(dǎo)致血小板減少癥的風(fēng)險顯著增加[63]。雖然據(jù)報道鎂補充是用于預(yù)防復(fù)發(fā)性痙攣的最有效療法[64]，但大多數(shù)使用者報告這種方法作用很小或者沒有幫助。此外，富鉀補充劑或食物以及其他礦物質(zhì)補充劑，如鈣補劑，尚未被證明能有效緩解熱痙攣的癥狀[15，32]。

如果運動員沒有潛在疾病，那么EAMC最常見的治療是拉伸[41]。事實上，適當(dāng)?shù)睦煲驯蛔C明對所有類型的肌肉痙攣都有效， 包括那些與熱相關(guān)的肌肉痙攣[5，7，10，65]。因此，推薦使用適當(dāng)拉伸以緩解痙攣。被動拉伸增加了肌肉的張力，從而增加高爾基腱器官對α運動神經(jīng)元的抑制性神經(jīng)傳入[52，53]，這將減少 α運動神經(jīng)元的活動，減少EAMC發(fā)生的可能性。其他減少運動神經(jīng)元活動從而減輕EAMC的相關(guān)方法包括按摩、拮抗肌群的主動收縮和局部冰敷。當(dāng)然，降低整體運動強度和改變受累肌肉的負(fù)荷也是有效的[38]。

最近，已致力于評價使用諸如辣椒、姜、芥菜和肉桂等食物的提取物來解決EAMC的方法。此類食物提取物可以激活瞬時感受器電位通道（TRP通道），此通道能夠中斷過度興奮的運動神經(jīng)元活動[66]。TRP通道是位于口、食道和胃中的一組離子通道，可調(diào)節(jié)離子（即帶電粒子如鈉離子和鉀離子）穿過細胞膜的流動。最近有證據(jù)表明，口服TRP通道激動劑，如肉桂、胡椒或芥末，可以通過抑制 α運動神經(jīng)元的興奮性，減弱肌肉痙攣的強度和 /或持續(xù)時間[67，68]。 在這些研究中肌肉痙攣是通過電刺激產(chǎn)生的，因此這種預(yù)防方法尚未在更自然的運動性肌痙攣的臨床試驗中得到驗證。

4.2 預(yù)防

EAMC的病理生理學(xué)機制極有可能是多因素和復(fù)雜的，因此預(yù)防 EAMC也需要多種方法。熱環(huán)境發(fā)生的EAMC似乎能夠通過保持水電解質(zhì)平衡得到預(yù)防。監(jiān)測運動員的體重是一種確保充分補充液體的簡單方法。美國國家體育醫(yī)務(wù)管理員協(xié)會和美國運動醫(yī)學(xué)院都建議，在訓(xùn)練或競賽中體液丟失不能超過體重的 2%[43，61]。運動員在比賽前至少1 h，攝取1 L水或低滲運動飲料，可以確保大部分液體、電解質(zhì)和營養(yǎng)物質(zhì)得到吸收，并且在競賽開始時能夠為身體所用。此外，在運動和競賽期間，應(yīng)提供運動員容易獲得并易于吸收的飲料。出汗和鈉丟失多的運動員，或者有EAMC既往史的運動員，在持續(xù)時間較長的運動中，需要額外補充鈉以保持鹽平衡[7]，在出汗量較大時，可能需要將每日膳食鹽量增加至 5～10 g/d[43]，這在訓(xùn)練中的熱適應(yīng)階段特別重要。在一項案例報告中，Bergeron證明，通過計算汗液鈉丟失量并在運動期間和之后進行補充，兩名先前有EAMC病史的網(wǎng)球運動員，能夠在熱環(huán)境下圓滿完成比賽[15]。

如上所述，EAMC的主要病因是肌肉疲勞。因此，預(yù)防策略也應(yīng)該關(guān)注運動員的適當(dāng)恢復(fù)調(diào)節(jié)。要真正模擬競賽或比賽狀況，高強度的耐力訓(xùn)練是必需的。隨著耐力的增加，肌肉在既定水平的強度下不容易發(fā)生痙攣。耐力訓(xùn)練可擴大血容量和細胞外液體積并延遲神經(jīng)肌肉疲勞[69，70]，也可以作為預(yù)防EAMC的一種有效手段。運動員受傷后恢復(fù)比賽時特別容易發(fā)生EAMC，因為他們很可能提前發(fā)生肌肉疲勞，排汗量減少，對高溫環(huán)境的適應(yīng)能力下降[71]。適當(dāng)?shù)目祻?fù)進程能夠預(yù)防運動員過度應(yīng)激，同時確保在重返競賽前充分恢復(fù)專項體能。

還應(yīng)實施針對肌梭和高爾基肌腱器官的預(yù)防訓(xùn)練，以延遲神經(jīng)肌肉疲勞的發(fā)生，并因此減少EAMC的發(fā)作。增強式訓(xùn)練是值得考慮的一種練習(xí)方法。這種爆發(fā)力練習(xí)可以訓(xùn)練運動單位，以便隨著運動強度的增加而更有效地工作。據(jù)報道，增強式訓(xùn)練可以借助肌梭和高爾基腱器官的訓(xùn)練提高神經(jīng)肌肉控制的效率，從而使肌肉更耐疲勞[72，73]。

已采取的其他預(yù)防措施包括：（1）糾正技術(shù)錯誤、肌肉不平衡和 /或姿勢；（2）常規(guī)拉伸肌肉；（3）進行充分的熱身；（4）在比賽之前和期間使用按摩療法；（5）穿著彈力褲襪；（6）適應(yīng)熱環(huán)境；（7）使用矯形鞋襪和 /或矯形鞋墊。雖然，這些預(yù)防措施尚缺乏實驗證據(jù)。

鑒于上述討論，可以遵循以下建議，以預(yù)防EAMC的發(fā)生。

（1）參照比賽強度進行訓(xùn)練，或者相反，根據(jù)訓(xùn)練中獲得的能力水平進行比賽。

（2）了解您的訓(xùn)練和比賽環(huán)境因素包括濕度、溫度、室內(nèi)與室外、海拔高度和地理環(huán)境，以及它們與通常的訓(xùn)練環(huán)境有何不同。

（3）如果你過去已發(fā)生過痙攣，考慮所有可能引起痙攣的因素，即強度、訓(xùn)練量、高度、地理環(huán)境的劇烈變化，以便相應(yīng)地規(guī)劃你的訓(xùn)練和比賽。

（4）學(xué)習(xí)識別EAMC的早期預(yù)兆，并采取相應(yīng)措施。

（5）最易發(fā)生痙攣的肌肉是那些在小幅度活動范圍內(nèi)重復(fù)使用的肌肉，因此在訓(xùn)練時注重訓(xùn)練方式，避免急性“制動”，并嘗試采用適當(dāng)?shù)捏y關(guān)節(jié)和膝關(guān)節(jié)屈伸動作來增加步幅。

（6）如果你是一個“大量出汗的人”，一定要增加飲食中的鹽攝入量，并攝取含有較高鈉含量的液體，尤其是在較熱、較潮濕的月份。

（7）鹽片或鹽丸是一種簡單的方法，但需要在訓(xùn)練中學(xué)會如何使用，因為一些人可能會出現(xiàn)胃部不適。

（8）攝入足夠的營養(yǎng)，特別是碳水化合物，以防止運動過程中過早的肌肉疲勞。

（9）考慮對關(guān)鍵肌肉群進行增強式訓(xùn)練。

（10）常規(guī)拉伸的同時，考慮配合動作，如主動屈曲拮抗肌并按摩痙攣或易痙攣肌肉。

4 Treatment and Prevention

4.1 Treatment

With multiple theories about the cause of EAMC,it is difficult to provide a single answer for a cure or prevention strategy.Consequently,there are many interventions available for the treatment of muscle cramps.These treatment options include stretching of the affected muscle,decreasing exercise intensity,massage,thermotherapy,cryotherapy,sports drinks, salt and electrolytes,pickle juice,intravenous infusion,and transcutaneous electric nerve stimulation.Many of these treatment options are anecdotal or not supported by experimental research.EAMC can be viewed as the endpoint of a variety of pathways and different athletes may have different mechanisms leading to very similar-appearing EAMC.Therefore,a treatment that works for one athlete may not be effective one for others.Some of the commonly used treatment options are discussed as follows.

The electrolyte disturbance-dehydration theory suggests that ingesting fluids containing electrolytes helps normalize the interstitial or extracellular volume,thereby alleviating EAMC.However,owing to a small quantity of electrolytes in many sports drinks,it may be difficult to sufficiently replace the volume of electrolytes lost during exercise even if the athlete has modest sweat losses and sweat sodium content.Note that fluids and electrolytes are not absorbed immediately after ingestion;that is,even hypotonic fluids require at least 13 minutes to be absorbed into the circulatory system[60].Based on the assumption that a relationship between dehydration-electrolyte imbalance and EAMC exists,the National Athletic Trainers’Association recommends that athletes prone to muscle cramping add 0.3 to 0.7 g/L of salt to their drinks to a vert muscle cramps[61].Others have recommended adding higher amounts of sodium (about 3 to 6 g/L)to sports drinks based on the frequency of EAMC[49].At the first sign of muscle twitches or mild cramps,a prompt oral bolus of a high-salt solution (e.g.,0.5 L of a carbohydrate-electrolyte drink with 3 g of salt added consumed all at once or over 5-10 min)has been proven effective in relieving cramping or preventing muscle fasciculationsfrom developing into a full-blown EAMC[15].After such a high-salt solution bolus,athletes can often promptly resume training or competition effectively without muscle cramping or twitching symptoms for an hour or more[15],although additional lower-sodium fluid should be consumed at regular intervals.

Other substances often chosen to relieve EAMC are pick le juice,quinine,and electrolytes such as magnesium,potassium,and calcium.A case report for using pickle juice to treat EAMC revealed that ingesting of a small volume of highlysalty and acidic brine(30 to 60 mL)could relieve cramp with in 35 s[48].This effect was,however,attributed to the fact that pickle juice contains acetic acid that can trigger a re flex, probably in the oropharyngeal region,that acts to increase inhibitory neurotransmitter activity in cramping muscles[62].Quinine is a medication used to treat malaria caused by mosquito bites,but also often prescribed to treat cramps of all causes. A Cochrane review of 23 clinical trials has concluded that quinine reduces cramp frequency,intensity,and days,but not duration,compared with placebo,and that there is a significantly greater risk of thrombocytopenia for quinine compared with placebo[63].Though magnesium supplementation has beenreported to be the most treatment used to prevent recurrent cramping[64],most users report this method to be of little or no help.Additionally,potassium-rich supplements or foods or other mineral supplements such as calcium have not been proven effective in relievingsymptoms associated with heat-related cramps[15，32].

If the athlete has no underlying illness,then the most common treatment for EAMC is stretching[41].In fact,moderate stretching of the affected muscle has proven to be effective for muscle cramps of all types including those that are heat related[5，7，10，65].Therefore,moderate stretching of the affected muscle to alleviate the cramp is recommended.Passive stretching increases the tension in a muscle,thereby increasing the Golgi tendon organ’s inhibitory input to the alpha motor neuron[52，53].This will then reduce the activity of alpha motor neurons,making EAMC less likely to occur.Other methods that have been implicated for reducing motor neuron activity,thereby alleviating EAMC include massage,active contraction of the antagonist muscle group,and icing of the affected muscles.Certainly,lowering overall exercise intensity and altering the load on the distressed muscles can be effective as well[38].

Recently,an effort has been devoted to evaluate a method of using food extracts like peppers,ginger,mustard, and cinnamon to resolve EAMC.Such food extracts can activate transient receptor potential channels(TRP channels)that are capable of disrupting hyperexcited motor neurons[66].TRP channels are a group of ion channels located in the mouth, esophagus and stomach that regulate the flow of ions,i.e., charged particles like sodium and potassium,across cell membranes.Recent evidence suggests that oral ingestion of TRP channel agonists like cinnamon,peppers,or mustard may attenuate the intensity and/or duration of muscle cramps,presumably by dampening alpha motor neuron excitability[67，68]. These studies produced muscle cramps by electrical stimulation.Therefore,this preventive approach has yet to be examined in clinical trials where cramps can be more naturally induced by physical exercise.

4.2 Prevention

The pathophysiology causing EAMC is most likely multifactorial and complex.As such,prevention of EAMC will need a multifactorial approach.EAMC that occur in hot conditions seemsto be prevented by maintaining fluid and salt balance.Monitoring an athlete’s body weight is an easy method of ensuring adequate fluid replacement.Both the National Athletic Trainers’Association and the American College of Sports Medicine recommend a volume of fluid that allows for less than a 2%body weight reduction from training or competition[43，61].An athlete who ingests a liter of water or hypotonic sports drink at least 1 hour before competition can be confident that the majority of the fluid,electrolytes,and nutrients would be absorbed and become available in the body when the competition begins. Additionally,fluids should be available and easily accessible throughout practices and competitions.Athletes with high sweat rates and sodium loss or who have a history of EAMC may need to consume supplemental sodium during prolonged activities to maintain salt balance[7]and may need to increase dailydietary salt to 5-10 g·day-1when sweat losses are large[43].This is especially important during the heatacclimatization phase of training.In a case report,Bergeron[15]demonstrated that by calculating sweat sodium losses and replacing them during and after activity,two athletes with previously debilitating EAMC were able tocompete successfully in hot conditions.

As mentioned earlier,an important etiology for EAMC is muscle fatigue.As such,prevention strategy should also focus on proper conditioning of an athlete.To truly simulate race or game conditions,intense endurance training is necessary.As endurance capacity increases,muscle would be less prone to cramp at a given level of intensity.Endurance training may also serve as an effective means of preventing EAMC by expanding plasma volume and the extracellular flu id compartment and delaying neuromuscular fatigue[69，70]. Athletes who are returning to competition after injury are particularly susceptible to EAMC as they are likely to experience early muscle fatigue,to be less acclimatized to a hot environment,and to have diminished sweating capacity[71].Proper progression during rehabilitation will prevent overstressing the athlete while ensuring adequate sport specific conditioning before the return to competition.

Prevention exercises that target muscle spindle and Golgi tendon organs should also be implemented to delay the onset of neuromuscular fatigue and,hence,EAMC.Plyometrics may be such exercise to be considered.The explosive nature of this exercise can train neuromuscular units to operate more effectively with increasing levels of intensity.It has been reported that plyometric training can improve the efficiency ofneuromuscular control by muscle spindles and Golgi tendon organs,thereby making them more resistant to fatigue[72，73].

Other preventive measures that have been taken include 1)correctingtechnique errors,muscle imbalance,and/or posture,2)stretching muscle regularly,3)having adequate warm up,4)applying massage therapy before and during competition,5)wearingcompression garments,5)becoming heat acclimatized,and 6)optimizing footwear and/or orthotics.These preventive measures,however,are not evidence-based.

Considering the above discussion,here are some recommendations that can be followed to prevent the occurrence of EAMC:

*Train at race-intensity or,conversely,race according to the level of ability that was attained in training.

*Know your training and competition conditions andfactor in humidity,temperature,indoor versus outdoor,altitude and terrain,and how they might be different than your usual training conditions.

*If you've cramped in the past,think about all factors that could have played a role,i.e.,drastic change in intensity, volume,altitude,terrain,so you can plan your training and competition accordingly.

*Learn to recognize early warning signs of EAMC and respond accordingly.

*Muscles most affected by cramping are those repetitively used and confined to a small arc of motion,so focus on form in training to avoid heavy"braking"and try to stretch out the stride with adequate hip and knee flexion and extension.

*If you’re a“salty sweater,”be sure to increase salt intake in your diet and take in fluids higher in sodium content, especially in the hotter,more humid months.

*Salt tabs or pills are an easy method,but practice using them in training as they can cause upset stomach in some individuals.

*Have adequate nutritional intake,particularly carbohydrates,to prevent premature muscle fatigue during exercise.

*Consider plyometric training of key muscle groups.

*Along with regular stretching,consider corollary activities like flexing opposing muscles and massaging cramped or cramp-prone muscles.

5 總結(jié)

盡管EAMC具有高發(fā)病率，但是關(guān)于其原因、治療和預(yù)防的實驗數(shù)據(jù)很少。EAMC長期以來的解釋是依靠電解質(zhì)紊亂和脫水學(xué)說。然而，其支持性證據(jù)主要來自觀察記錄和病例報告。此外，該學(xué)說沒有闡明合理的病理生理機制，并且據(jù)報道，EAMC可以在沒有電解質(zhì)耗竭或脫水的情況下發(fā)生。最新的證據(jù)表明，EAMC可能由于肌肉疲勞使神經(jīng)肌肉控制改變而產(chǎn)生。支持這種“異常神經(jīng)肌肉控制學(xué)說”的證據(jù)源于實驗室研究，這些研究使用了肌電圖來監(jiān)測對肌肉疲勞和痙攣進行應(yīng)答的脊髓反射活動。雖然有待于進一步證實，但肌肉疲勞和神經(jīng)肌肉控制的改變似乎對關(guān)于這一復(fù)雜病癥的原因、治療和預(yù)防中未知問題提供更加合理的解釋。EAMC的治療和預(yù)防存在許多策略，但其中大多數(shù)是觀察記錄或不受實驗研究支持。未來需要能夠提供高水平證據(jù)的研究來證實EAMC的病因?qū)W、治療方案和預(yù)防策略。

5 Overall Summary

Despite the high prevalence of EAMC,few experimental data exist on their cause,treatment,and prevention.EAMC has long been explained by the electrolyte imbalance and dehydration theory.However,its supporting evidence comes mainly from anecdotal observations and casereports.In addition,the theory does not offer plausible pathophysiological mechanisms and it has been reported that EAMC can occur without electrolyte depletion or dehydration.More recent evidence suggests that EAMC may be mediated by muscle fatigue that altered neuromuscular control.The evidence thatsupport this “altered neuromuscular control”theory stems from the laboratory-based experiments that used EMG to monitor spinal reflex activities in response to muscle fatigue and cramping.Although a definitive proof is still needed, muscle fatigue and altered neuromuscular control seem more plausible in explaining many of the unanswered questions with regard to cause,treatment and prevention of this complex condition.There are numerous strategies existed for the treatment and prevention of EAMC.However,most of them are anecdotal and unsupported by experimental research.Research that provide high levels of evidence is needed to substantiate the etiology,treatment options,and prevention strategies of EAMC.

[1]Kantarowski P.G.,Hiller W.D.,Garrett W.E.Cramping studies in 2600 endurance athletes[J].Med.Sci.Sports Exerc.,1990, 22(2):s104.

[2]Schwellnus M.P.,Drew N.,Collins M.Muscle cramping in athletes-risk factors,clinical assessment and management[J].Clin. Sports Med.,2008(1):183-194.

[3]Parisi L.,Pierelli F.,Amabile G.,et al.Muscular cramps:proposals for a new classification[J].Acta.Neurol Scand.2003, 107:176-186.

[4]Schwellnus M.P.,Derman E.W.,Noakes T.D.Aetiology of skeletal muscle“cramps”during exercise:a novel hypothesis[J]. Sports Sci.,1997,15:277-285.

[5]Maquirriain J.,Merello M.The athlete with muscular cramps: clinical approach[J].Am.Acad.Orthop.Surg.,2007,15:425-431.

[6]Miller T.,Layzer R.B.Muscle cramps[J].Muscle Nerve,2005, 32:431-442.

[7]Bergeron M.Exertional heat cramps.In:Exertional heat illnesses[J].Human Kinstics,2003:91-102.

[8]Ladell W.S.S.Heat cramps[J].Lancet,1949,2:836-839.

[9]Dickhuth H.,Rocker K.,Niess A.,et al.Exercise induced,persistent and generalized muscle cramps[J].Sports Med.Phys.Fitness,2002,42:92-94.

[10]Schwellnus M.Cause of exercise associated muscle cramps(eamc) -altered neuromuscular control,dehydration or electrolyte depletion[J].Br.J.Sports Med.,2009,43:401-408.

[11]Brubaker D.,Whitesel J.,Barth B.Quinine sulfate:a treatment for recurrent muscle spasms[J].Athl.Train(Greenville,NC), 1985,20:121-123.

[12]Moss K.Some effects of high air temperatures and muscular exertion upon colliers[J].Proc.R.Soc.Lond.Biol.Sci,1923, 95:181-200.

[13]Maughan R.J.Exercise induced muscle cramp:a prospective biochemical study in marathon runners[J].Sports Sci.,1986,4: 31-34.

[14]Schwellnus M.,Nicol J.,Laubscher R.,et al.Serum electrolyte concentrations and hydration status are not associated with exercise associated muscle cramping(EAMC)in distance runners [J].Br.J.Sports Med.,2004,38:488-492.

[15]Bergeron M.F.Heat cramps during tennis:a case report[J].Int. J.Sport Nutr.,1996,6:62-68.

[16]Manjra S.I.,Schwellnus M.P.,Noakes T.D.Risk factors for exercise associated muscle cramping(EAMC)in marathon runners[J].Med.Sci.Sports Exerc.,1996,28(5):S167.

[17]Drew N.Exercise-associated muscle cramping(EAMC)in Ironman triathletes[D].Cape Town:University of Cape Town,2006. [18]Schwellnus M.P.Muscle cramping in the marathon:etiology and risk factors[J].Sports Med.,2007,37:364-367.

[19]Edsall D.L.New disorder from heat:A disorder due to exposure to intense heat[J].Journal of the American Medical Association,1908,11:1969-1971.

[20]Swanik C.,Lephart S.,Stone D.,et al.The effects of shoulder plyometric training on proprioception and muscle performance characteristics[J].Shoulder Elbow Surg.,2002,11:579-586.

[21]Cooper E.,Ferrara M.,Broglio S.Exertional heat illness and environmental conditions during a single football season in the Southeast[J].Athl.Train,2006,41:332-336.

[22]Galloway S.Dehydration,rehydration,and exercise in the heat: rehydration strategies for athletic competition[J].Can.J.Appl. Physiol.,1999,24:188-200.

[23]Rehrer N.,Smets A.,Reynaert H.,et al.Effect of exercise on portal vein blood flow in man[J].Med.Sci.Sports Exerc.,2001, 31:701-715.

[24]Armstrong L.E.,Maresh C.M.The exertional heat illness:a risk of athletic participation[J].Med.Exerc.Nutr.Health,1993, 2:125-134.

[25]Bergeron M.Heat cramps:fluid and electrolyte challenges during tennis in the heat[J].Sci.Med.Sport,2003,6:19-27.

[26]Stofan J.,Zachwieja J.,Horswill C.,et al.Sweat and sodium losses in NCAA football players:a precursor to heat cramps[J]. Int.J.Sport Nutr.Exerc.Metab.,2005,15:641-652.

[27]McCance R.A.Proceedings of the Royal Society of London. Series B-Biological Sciences,Volume 119,1935-1936:Experimental sodium chloride deficiency in man[J].Nutr.Rev.,1990, 48:145-147.

[28]Levin S.Investigating the cause of muscle cramps[J].Phys. Sportsmed,1993,21:111-113.

[29]Liu L.,Borowski G.,Rose L.I.Hypomagnesemia in a tennis player[J].Phys.Sportsmed,1983,11:79-80.

[30]Miles M.P.,Clarkson P.M.Exercise-induced muscle pain, soreness,and cramps.[J].Sports Med.Phys.Fitness,1994,34: 203-216.

[31]StamfordB.Musclecramps:untyingtheknots[J].Phys.Sportsmed, 1993,21:115-116.

[32]Eichner E.R.The role of sodium in“heat cramping”[J].Sports Med.,2007,37:368-370.

[33]Inoue Y.,Havenith G.,Kenney W.L.,et al.Exercise-and methylcholine-induced sweating responses in older and younger men: effect of heat acclimation and aerobic fitness[J].Int.J.Biometeorol.,1999,42:210-216.

[34]Shirreffs S.M.,Maughan R.J.Volume repletion after exerciseinduced volume depletion in humans:replacement of water and sodium losses[J].Am.J.Physiol.,1998,274:F868-F875.

[35]Costill D.L.,Cote R.,Fink W.Muscle water and electrolytes following varied levels of dehydration in man[J].Appl.Physiol.,1976,40:6-11.

[36]Nose H.,Mack G.W.,Shi X.R.,et al.Shift in body fluid compartments after dehydration in humans[J].Appl.Physiol.,1988; 65:318-324.

[37]Sanders B.,Noakes T.D.,Dennis S.C.Water and electrolyte shifts with partial fluid replacement during exercise[J].Eur.J. Appl.Physiol.,1999,80:318-323.

[38]Bergeron M.Muscle cramps during exercise:is it fatigue or electrolyte deficit[J].Curr.Sports Med.Rep.,2008,7:S50-S55.

[39]Minetto M.A.,Holobar A.,Botter A.,et al.Origin and development of muscle cramps[J].Exerc.Sport Sci.Rev.,2013,41: 3-10.

[40]Layzer R.B.The origin of muscle fasciculations and cramps[J]. Muscle Nerve,1994,17:1243-1249.

[41]Ruff R.L.Effects of length changes on Na+current amplitude and excitability near and far from the end-plate[J].Muscle Nerve, 1996,19:1084-1092.

[42]Sjogaard G.,Adams R.P.,Saltin B.Water and ion shifts in skeletal muscle of humans with intense dynamic knee extension [J].Am.J.Physiol.,1985,248:R190-R196.

[43]Armstrong L.E.,Casa D.J.,Millard-Stafford M.,et al.Exertional Heat Illness during Training and Competition[J].Med. Sci.Sports Exerc.,2007,39:556-572.

[44]Stone M.,Edwards J.,Stemmans C.,et al.Certified athletic trainers’perceptions of exercise associated muscle cramps[J]. Sport Rehabil.,2003,12:333-342.

[45]Eichner E.Heat cramps:salt is simplest,most effective antidote [J].Sports Med.Dig.,1999,21:88.

[46]Eichner E.R.Treatment of suspected heat illness[J].Int.J.Sports Med.,1998,19:S150-S153.

[47]Meira F.S.,Poli de Figueiredo C.E.,Figueiredo A.E.Influence of sodium profile in preventing complications during hemodialysis[J].Hemodial Int.,2007,3:S29-S32.

[48]Jones B.H.,Rock P.B.,Smith L.S.,et al.Medical complaints after a marathon run in cool weather[J].Phys Sportsmed.,1985, 13:103-110.

[49]Bergeron M.Exertional heat cramps:recovery and return to play [J].Sport Rehabil.,2007,16:190-196.

[50]Laird R.H.Medical care at ultra-endurance triathlons[J].Med. Sci.Sports Exerc.,1989,21:S222-S225.

[51]Hutton R.S.,Nelson L.D.Stretch sensitivity of Golgi tendon organs in fatigued gastrocnemius muscle[J].Med.Sci.Sports Exerc.,1986,18:69-74.

[52]Nelson L.D.,Hutton R.S.Dynamic and static stretch response in muscle spindle receptors in fatigued muscle[J].Med.Sci. Sports Exerc.,1985,17:445-450.

[53]Khan S.,Burne J.Reflex inhibition of normal cramp following electrical stimulation of the muscle tendon[J].Neurophysiol., 2007,98:1102-1107.

[54]Bentley S.Exercise-induced muscle cramp.Proposed mechanisms and management[J].Sports Med.,1996,21:409-420.

[55]Jung A.P.,Bishop P.A.,Al-Nawwas A.,et al.Influence of Hydration and Electrolyte Supplementation on Incidence and Time to Onset of Exercise-Associated Muscle Cramps[J].Athl.Train, 2005,40:71-75.

[56]Eaton J.M.Is this really a muscle cramp[J].Postgrad Med., 1989,86:227-232.

[57]Helin P.Physiotherapy and electromyography in muscle cramp [J].Br.J.Sports Med.,1985,19:230-231.

[58]Sontag S.J.,Wanner J.N.The cause of leg cramps and knee pains:a hypothesis and effective treatment[J].Med.Hypotheses, 1988,25:35-41.

[59]Howe A.S.,Boden B.P.Heat-related illness in athletes[J].Am. J.Sports Med.,2007,35:1384-1395.

[60]Talbot H.T.Heat cramps[J].Medicine,1935,14:323-376.

[61]Binkley H.,Beckett J.,Casa D.,et al.National Athletic Trainers’Association position statement:exertional heat illnesses[J]. Athl.Train,2002,37:329-343.

[62]Vriens,Joris,Bernd N.,et al.Herbal Compounds and Toxins Modulating TRP Channels[J].Cur.Neuropharmacology,2008, 6:79-96.

[63]El-Tawil S.,Musa A.,Valli H.,et al.Quinine for muscle cramps [J].Cochrane Database Syst.Rev.,2010,8:CD005044.

[64]Blyton F.,Chuter V.,Burns J.Unknotting night-time muscle cramp:a survey of patient experience,help-seeking behaviour and perceived treatment effectiveness[J].Foot Ankle Res.,2012, 5:7.

[65]Daniel H.Simple cure for nocturnal leg cramps[J].N.Eng.J. Med.,1979,301:216.

[66]Vist G.,Maughan R.The effect of osmolality and carbohydrate content on the rate of gastric emptying of liquids in man[J].J. Physiol.,1995,486:523-531.

[67]Craighead D.H.,Shank S.W.,Alexander L.M.,et al.Orally ingested transient receptor potential(trp)channel activators attenuatetheintensity-durationofvoluntarilyinducedmusclecramps in humans[J].The FASEB Journal,2016,30:lb706.

[68]Short G.F.,Hegarty B.W.,Westphal C.H.,et al.Orally-administered TRPV1 and TRPA1 activators inhibit electrically-induced muscle cramps in normal healthy volunteers[J].Neurology 2015,84(14):S17.003.

[69]Convertino V.Blood volume:its adaptation to endurance training[J].Med.Sci.Sports Exerc.,1991,23:1338-1348.

[70]Hakkinen K.,Komi P.Fatigability in voluntary and reflex contraction after conditioning of human skeletal muscle[J].Electromyogr Clin.Neurophysiol,1985,25:319-330.

[71]Jung A.P.Exercise-associated muscle cramps and functional return to sport[J].Athl.Ther.Today,2006,11:48-50.

[72]Chimera N.,Swanik K.,Swanik C.,et al.Effects of plyometric training on muscle activation strategies and performance in female athletes[J].Athl.Train,2004,39:24-31.

[73]Sulzer N.U.,Schwellnus M.P.,Noakes T.D.Serum electrolytes in Ironman triathletes with exercise-associated muscle cramping [J].Med.Sci.Sports Exerc.,2005,37:1081-1085.

（責(zé)任編輯：何聰）

Exercise Associated Muscle Cramps-A Current Perspective

KANG Jie1,ZHANG Peng2
(1.Human Performance Laboratory,Department of Health and Exercise Science,The College of New Jersey, USA;2.Shanghai Research Institute of Sports Science,Shanghai 200030,China)

Exercise-associated muscle cramps (EAMC)are a common condition experienced by recreational and competitive athletes and often require medical attention during or immediately after sports events.Despite the high prevalence of this condition,the etiology of EAMC remains poorly understood and there is a lack of high levels of evidence to guide the management of this condition.The previous claim as to how EAMC come about is being challenged by more recent evidence suggesting a distinctive mechanism.The purpose of this article is to examine the existing scientific evidence in support of various views on the etiology of EAMC and to highlight the most current understanding of this complex condition.Various strategies adopted to treat and prevent EAMC are also discussed even though most of them remain anecdotal and have yet to be substantiated by research experimentation.

EAMC；mechanism；risk factors；treatment；prevention

G804.5

A

1006-1207（2017）01-0001-13

2017-02-11

康杰，博士，美國運動醫(yī)學(xué)院院士。主要研究方向：運動人體科學(xué)。E-mail：kang@tcnj.edu。

1.美國新澤西尤英新澤西學(xué)院，健康和運動科學(xué)系；2.上海體育科學(xué)研究所，上海 200030。