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Neural Mechanisms of Muscle Cramp

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DOI: 10.1007/978-4-431-55315-1_8

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Chapter 8
Neural Mechanisms of Muscle Cramp

Kento Nakagawa, Naokazu Miyamoto, and Kazuyuki Kanosue

Abstract Although muscle cramps are a common problem for many athletes, the
underlying mechanisms are still poorly understood. In this chapter, we review
the proposed causes of muscle cramps. Dehydration and electrolyte disturbance
are generally considered to be causes of muscle cramps, but this is unlikely.
Alternatively, either neural activity in the spinal cord or in the peripheral could
be the cause of cramps. Definitive evidence is scarce and controversy abounds.

Keywords Central nervous system • Peripheral • Dehydration • Electrolyte

disturbance • Muscle fatigue

8.1 Introduction

A muscle cramp is defined as a sudden, involuntary, spasmodic and painful

contraction of skeletal muscle (Schwellnus et al. 1997; Minetto et al. 2013). It
often occurs during or after various sports (e.g. triathlon (Sulzer et al. 2005) and
marathons (Schwellnus 2007)), and it is a well known clinical problem that athletes
try hard to avoid. However, the mechanisms underlying muscle cramps are still
poorly understood. Therefore, there is no evidence-based way to efficiently prevent
muscle cramps although it is widely known that stretching a “cramping” muscle can
effectively stop the cramp (Norris et al. 1957; Bertolasi et al. 1993). In this chapter
we evaluate evidence for the various theories that purport to explain the cause of
muscle cramps. We concentrate on mechanisms involving dehydration and elec-
trolyte disturbances as well as neural factors.

K. Nakagawa (*)
Faculty of Sport Sciences, Waseda University, Saitama, Japan
Japan Society for the Promotion of Science, Tokyo, Japan
e-mail: nakagawa@aoni.waseda.jp
N. Miyamoto
National Institute of Fitness and Sports in Kanoya, Kagoshima, Japan
K. Kanosue
Faculty of Sport Sciences, Waseda University, Saitama, Japan

© Springer Japan 2015 79

K. Kanosue et al. (eds.), Sports Performance, DOI 10.1007/978-4-431-55315-1_8
80 K. Nakagawa et al.

8.2 How to Induce Muscle Cramps?

A major problem in the research of muscle cramps is that it is difficult to induce

muscle cramps experimentally, because they normally occur unpredictably and
spontaneously. Anecdotal studies have compared people who got cramps with
those who did not in sports events such as long distance races (Maughan 1986;
Schwellnus 2007) and triathlons (Sulzer et al. 2005). Although the merit of this
method would be the availability of a large number of subjects, it is almost
impossible to control the occurrence, the intensity of the cramps and the chemical
or fatigue state of the cramping muscle.
In the laboratory, researchers have predominantly utilized two methods to
induce muscle cramps: (1) strong voluntary contraction of target muscles, and
(2) electric/magnetic stimulation of nerves or muscles. The former is the classical
approach and is widely available since it does not required a special apparatus to
induce cramps (Khan and Burne 2007; Nakagawa et al. 2013; Norris et al. 1957;
Roeleveld et al. 2000; Ross and Thomas 1995; Ohno and Nosaka 2004; Goodman
and Zwetsloot 2013). Although maximal contraction is required of subjects in most
studies, the target muscle differs across studies. The electrical stimulation approach
has also been utilized widely. The site of stimulation varies depending on the study.
High-frequency electrical stimulation of the tibial nerve innervating calf muscles or
of intrinsic muscles of foot has often been used to induce muscle cramps (Bertolasi
et al. 1993; Lambert 1968; Obi et al. 1993). This method enables the investigator to
quantify the stimulation threshold for the induction of muscle cramps as “threshold
frequency” with high reliability (Miller and Knight 2007; Stone et al. 2003), which
is defined as the minimum frequency of simulation that can provoke muscle cramps
(Miller and Knight 2007, 2009; Stone et al. 2003, 2010). The stimulation intensity
in these studies is generally very high (e.g. 30 % higher intensity than that needed to
evoke a maximal M response at the frequencies of about 10 Hz (Bertolasi
et al. 1993)). In addition, since it has been shown that the threshold frequency
correlates with the incidence of muscle cramps (Miller and Knight 2009), it has
been proposed that the index can be used to evaluate individuals’ risk of cramp.
However, although applying electrical stimulation to a peripheral nerve is a useful
way to maintain constant conditions, it is generally accompanied by strong pain.
Therefore, electrical stimulation is often applied directly to the muscle motor point.
This produces less pain, and has been developed as an alternative to peripheral
nerve stimulation and has been utilized (Minetto and Botter 2009; Minetto
et al. 2008, 2009a, b, 2011). A study with the motor point stimulation demonstrated
that the threshold frequency and pain in intrinsic foot muscle were lower than those
in leg muscle. The authors concluded that the intrinsic foot muscle is the most
suitable for the study of muscle cramps (Minetto and Botter 2009). It has been
found that the high frequency magnetic stimulation to peripheral nerve can provoke
muscle cramps, which are less painful than those produced by electrical stimulation
(Caress et al. 2000). Moreover, other methods based on activating the afferent
nerves have been performed. For example, applying tapping/vibration to the tendon
8 Neural Mechanisms of Muscle Cramp 81

with an electromagnetic hammer, electrical stimulation to the Ia afferent

(Baldissera et al. 1994), or nociceptive stimulation to myofascial trigger points
(Ge et al. 2008) also evoke muscle cramps.

8.3 Do Dehydration and Electrolyte Disturbance Cause

Muscle Cramps?

Dehydration and electrolyte disturbances are popularly thought to cause muscle

cramps, and a large number of studies have evaluated this hypothesis. There is an
early anecdotal observation that cramps often occur in workers toiling in hot and
humid conditions (Talbott and Michelsen 1933). It is typically held that depletion of
sodium with significant dehydration by sweating induces the contraction of the
extracellular fluid compartment which results in a disruption of ion balance. A loss
of interstitial volume can cause a mechanical deformation of nerve endings, and
increase the surrounding neurotransmitter concentration (Bergeron 2003, 2008;
Schwellnus 2009), which could produce muscle cramps. However, there is no
scientific evidence to support these explanations. Studies supporting the above
hypothesis relied heavily on anecdotal reports and involved few properly controlled
experiments (Ohno and Nosaka 2004). Furthermore, the hypothesis cannot explain
why muscle cramps also often occur under cool conditions (Miller et al. 2010;
Armstrong et al. 2007).
Indeed, many studies show no association between muscle cramps and dehy-
dration or electrolyte disturbance. Maughan (1986) investigated biochemical indi-
ces of runners with and without cramps in a full marathon race. Serum electrolyte
concentrations such as sodium and potassium were not different between the two
groups after the race. A similar study on runners in an ultra-marathon race (56 km)
produced the same results (Schwellnus et al. 2004). Other studies also found no
association between serum electrolytes and muscle cramp in a triathlon race (Sulzer
et al. 2005; Schwellnus et al. 2011). That is, there was no significant difference in
serum electrolyte concentrations and hemoglobin concentration between cramping
and non-cramping groups after the race. In addition to these studies in competition
races, a laboratory experiment indicated that muscle cramp occurred both with and
without dehydration and electrolyte loss with fatiguing exercise (Jung et al. 2005).
Braulick et al. (2013) indicated that the threshold frequency for inducing a muscle
cramp with the high frequency electrical stimulation to peripheral nerve did not
differ significantly between the euhydrated and hypohydrated conditions. Addition-
ally, it is also unlikely that magnesium is effective for the treatment of muscle
cramp (Garrison et al. 2012). The above evidence makes it abundantly clear that
muscle cramps are not, or are only very minimally, associated with dehydration and
electrolyte disturbance.
82 K. Nakagawa et al.

8.4 Muscle Fatigue and Cramps

Alternatively, the theory that “muscle fatigue” can cause muscle cramps has been
raised (Schwellnus 2009; Schwellnus et al. 1997). Muscle cramps often occur in
events, such as long distance races that would be expected to induce muscle fatigue
(Maughan 1986; Schwellnus et al. 2004; Sulzer et al. 2005). Thus, it is likely that
the cause of muscle cramp is not dehydration or electrolyte disturbance but muscle
fatigue. Indeed, Jung et al. (2005) demonstrated that supplementation of carbohy-
drate hindered the occurrence of muscle cramps during fatiguing exercise, perhaps
owing to energy from the carbohydrate that delayed the occurrence of muscle
fatigue. One view holds that neuromuscular control is altered by muscle fatigue.
This could lead to an increase in the activity of muscle spindles and a decrease in
the activity of Golgi tendon organs, which together would result in sustained motor
neuron activity, and subsequently muscle cramps (Schwellnus 2009). However, the
causal relationship has never been validated. Additionally, it has been reported that
the threshold frequency for inducing cramps is higher under fatigue than under
non-fatigue conditions (Stone et al. 2010). This seems to contradict the above
proposed fatigue theory. Moreover, the fact that cramps can occur without fatigue
in most laboratory experiments also suggest that muscle fatigue is not a necessary
condition for the occurrence of cramps. Most importantly, studies proposing a
muscle fatigue mechanism have not quantified “muscle fatigue”. The consensus
has now shifted, and it is generally considered that “altered neuromuscular control”
triggered by muscle fatigue is an important cause of muscle cramps rather than
simply muscle fatigue itself (Armstrong and Cross 2013; Schwellnus 2009;
Schwellnus et al. 1997). In succeeding sections, we review investigations the neural
mechanisms involved with muscle cramps.

8.5 Neural Mechanisms of Muscle Cramp

There have been many debates on the nature of the neural origins of muscle cramps
(Miller and Layzer 2005; Minetto et al. 2013; Layzer 1994; Jansen et al. 1990).
There are mainly two theories (Fig. 8.1). The first theory is the “central origin”
theory, which holds that muscle cramps originate from the central nervous system
(CNS), particularly the spinal cord. The second theory is the “peripheral origin”
theory, which holds that muscle cramps are the result of events in the peripheral
level, such as motor nerve fibers, nerve branch terminals or muscle fibers.
8 Neural Mechanisms of Muscle Cramp 83

spinal cord
Ib afferent neuron

Ia afferent neuron

muscle
α-motor neuron

peripheral origin central origin

Fig. 8.1 Scheme depicting the two major mechanisms purported to underlie the development of
muscle cramps

8.5.1 Central Origin Theory

Norris et al. (1957) proposed the central origin theory after performing experiments
involving electromyography (EMG). Their study showed that synchronized dis-
charges between different motor units were observed in cramping muscle. More-
over, voluntary contraction of the homologous muscle in the contralateral limb
increased cramp discharge, while voluntary contraction of the ipsilateral antagonist
muscle reduced cramp discharge. The authors concluded that the neural activity
during muscle cramp originates from the spinal cord. Although this observation was
anecdotal, the following studies have observed similar phenomenon in laboratory
experiments.
Several studies have recorded motor unit activities during cramps (Minetto
et al. 2009b, 2011; Norris et al. 1957; Ross and Thomas 1995). Shapes of the
motor unit potentials (Ross and Thomas 1995; Minetto et al. 2011), and firing rates
(Minetto et al. 2009b) during muscle cramps resemble those seen in normal
voluntary contractions. However, the variability of motor unit firing rates was
larger during cramp than during voluntary contractions (Minetto et al. 2009b,
2011; Ross and Thomas 1995). The high variability of motor unit discharge is
speculated to be caused because the afferent inputs to the motor neurons generate
synaptic noise (Merletti et al. 2011; Minetto et al. 2009b). However, since vari-
ability of motor unit discharge during cramp without afferent contribution by
peripheral nerve block is greater than that during normal cramps (Minetto
et al. 2011), the above mentioned explanation seems precarious. Thus more sub-
stantial evidence is required to implicate spinal involvement in cramp production.
Other studies have produced more direct evidence for spinal involvement in
cramp production by investigating the spinal reflex (e.g. Mills et al. 1982;
84 K. Nakagawa et al.

Baldissera et al. 1994; Khan and Burne 2007). In a case report Mills et al. (1982)
noted that transcutaneous nerve stimulation over the calf muscle (by which afferent
signals affect spinal neural activity) could abort cramps in a patient who suffered
from severe muscle cramps. From this result they inferred that the mechanism of
muscle cramps must involve the spinal cord. However, since only one patient was
involved, the results cannot be generalized. Alternatively, recent studies report that
nociceptive stimulation by a bolus injection of glutamate into latent myofacial
trigger points induces cramps (Ge et al. 2008). In addition, increased nociceptive
muscle afferent activity induced by injection of hypertonic saline decreased the
threshold frequency of electrically elicited muscle cramps (Serrao et al. 2007).
However, since these techniques may affect not only afferent activity but also the
muscle itself, it does not conclusively indicate CNS involvement. Other studies
have clarified the relationship between the kinesthetic afferent input and muscle
cramps. Baldissera et al. (1994) showed that electrical stimulation to the Ia afferent
nerve with low intensity triggered a cramp in the soleus muscle in three subjects
who suffered from muscle cramps. In addition, the finding that taps and continuous
vibration to the Achilles tendon also could induce the cramp (Baldissera et al. 1994)
indicates that the afferent signals may also influence cramps. Moreover, Khan and
Burne (2007) observed that EMG activity during cramp of calf muscle was
inhibited by the electrical stimulation applied to the Achilles tendon. The intensity
and timing of the disappearance of the EMG activity were similar to those of
voluntary contractions seen in the same muscle at similar background EMG levels.
Thus the authors suggested that the same reflex pathway was involved in the
inhibition of both voluntary contractions and muscle cramps. Additionally, Ross
and Thomas (1995) indicated that the tonic vibration reflex was depressed or absent
after muscle cramps, while it never changed after voluntary contractions. This
suggests that muscle cramps may inhibit the function of the spinal reflex. In
contrast, prolonged enhancement of the H-reflex after cramping was observed,
but it was not observed after voluntary contractions (Ross 1976). Because the
H-reflex reflects the excitability of the motor neuron pool in the spinal cord, these
two studies seems to be in conflict; one suggests inhibition and the other suggests
the enhancement of the spinal neural activity. However, the fact that a muscle
cramp has prolonged overall effects on neural excitability of the spinal cord is very
likely.
Although many studies have proposed a central origin theory, the proposed
mechanisms purporting to explain muscle cramps are different. Ideas put forth
includes hyperexcitability of motor neurons with presynaptic inputs produced by a
positive feedback loop between afferent nerves and motor neurons (Ross and
Thomas 1995), bistability of the motor neuron membrane (Baldissera et al. 1994),
and dysfunction of interneurons via GABA (Obi et al. 1993). When looked at
closely, these ideas must be considered suppositions, since they are not supported
by concrete evidences.
8 Neural Mechanisms of Muscle Cramp 85

8.5.2 Peripheral Origin Theory

The first study that supported the peripheral origin theory utilized anesthesia to
produce a peripheral nerve block (Lambert 1968). The nerve block shut off the
contribution of supraspinal neural activity. Thus, efferent signals from the motor
neuron pool could not reach the muscles, and afferent signals from sensory recep-
tors were also unable to reach the spinal cord. It was thus possible to investigate the
role of the nerves distal to the blocked point. Lambert (1968) observed that, in
healthy subjects, repetitive electrical stimulation of the peripheral nerve distal to the
block could induce a muscle cramp. This result strongly suggested that muscle
cramps could occur without a supraspinal contribution, and cramps likely originate
in the periphery, probably in the intramuscular nerve terminal. In later work,
Bertolasi et al. (1993) replicated the induction of muscle cramps during a peripheral
nerve block. In addition, they indicated that no muscle cramp was induced without a
shortening of the muscle even when electrical stimulation was delivered, and also
found that stretching to the muscle could interrupt cramps even after the nerve
block in normal subjects. These data suggest that muscle length strongly influences
muscle cramps, and that muscle cramps probably originate from the periphery, in
particular intramuscular branches, rather than from the CNS. It seems that the
peripheral origin theory was mainly based on the two above-mentioned studies.
Although the two studies (Bertolasi et al. 1993; Lambert 1968) appear to provide
concrete evidences, other some studies have provided differing results. In 1993 Obi
et al. showed that high-frequency electrical stimulation to the peripheral nerve
distal to the blocked portion did not induce a muscle cramp. They additionally
indicated that diazepam or baclofen, a GABA receptor agonist, prevented the
induction of cramps by electrical stimulation. They speculated that abnormal
activity of GABAergic interneurons in the spinal cord were involved in the mech-
anisms underlying cramps. However, this was an anecdotal report. There were no
controls, and the study involved only two patients, both of whom had a motor
neuron disease. A more convincing study was performed by Minetto et al. (2011),
who provided evidence against the peripheral origin theory with experiments
utilizing peripheral nerve block. They studied eight normal subjects, and were
able to induce muscle cramps by electrically stimulating the muscle motor point
with or without nerve block. They investigated the difference in characteristics of
surface EMGs and motor unit potentials between cramps electrically induced under
the two conditions. The results indicated that the threshold frequency of electrical
stimulation for eliciting cramps was greater in the blocked condition than in the
non-blocked condition. In addition, the duration and EMG amplitude of muscle
cramps in the blocked condition were noticeably smaller. Cramps in the blocked
condition showed a higher rate of motor unit discharge as well as irregular dis-
charge patterns. The authors concluded that the CNS is involved in both the origin
and sustenance of muscle cramps, rather than peripheral mechanisms.
In addition, Roeleveld et al. (2000) examined the detailed characteristics of
muscle activity by multi-channel surface EMG recordings on the triceps surae
86 K. Nakagawa et al.

during muscle cramps. They observed that involuntary EMG activity (i.e., muscle
cramps) induced by maximal voluntary contraction (MVC) initially occurred over a
small area and gradually spread over a larger region. Moreover, the strongly-
activated area moved from one area to another, and then the intensity and area of
the cramp decreased and disappeared. The results from these local EMG recordings
indicate that muscle cramp might originate from close to, or even at, the level of the
muscle fiber.
Recently, we investigated the involvement of peripheral mechanisms in muscle
cramps in nine healthy subjects who were able to volitionally evoke muscle cramps
of the abductor halluces (AH) by voluntary contraction (Nakagawa et al. 2013).
High-intensity electrical stimulation to the tibial nerve, which induced a maximal
M-wave (Mmax), was applied during the muscle cramp as well as during voluntary
contraction of the abductor halluces. This was done to evaluate peripheral involve-
ment, since the amplitude of Mmax is not affected by spinal activity. Subjects first
voluntarily elicited a maximal voluntary contraction (MVC) of the target muscle in
order to induce a cramp. Once the cramp occurred, the subjects were instructed to
cease the volitional input and remained relaxed until the cramp diminished natu-
rally. Throughout the trial, electrical stimulation to the tibial nerve was applied
every 3 s, and the evoked EMG activity recorded. The onset of the cramp was
defined as the moment when the subjects declared “I’m cramping” and the offset as
the moment when the EMG burst stopped. The results indicated that the amplitude
of Mmax decreased or disappeared during a muscle cramp, but not during voluntary
contraction task (Fig. 8.2). We suspect that the decrease of Mmax during MVC that
was seen before the occurrence of the cramp (as defined), happened during the time
when the cramp had actually begun but before conscious awareness of this occur-
rence was attained by the subject. A significant negative correlation between Mmax
amplitude and intensity of background EMG was observed during the muscle
cramp task. The larger the background EMG, the greater the decrease in the
amplitude of Mmax, although Mmax did not change during the voluntary contrac-
tion period (Fig. 8.3). Notably, the amplitude of Mmax in the soleus obtained
simultaneously with the M-wave in the AH was not changed during the AH muscle
cramp (Fig. 8.2). Overall, the results strongly suggest that the abnormal discharge
seen during the muscle cramp occurred distal to the site of stimulation. However,
this result does not directly exclude the possibility of spinal reflex involvement.

Problems and Foresight

As we noted, the origin of muscle cramps has been largely seen as either in the
spinal cord or the periphery. However, higher brain activity may also be involved in
the genesis of muscle cramps. For example, muscle cramps occur on occasion in top
ranking athletes even before the start of competition. Since such maladies often
happen in big matches with a large media attendance, it is generally held that in
these cases, mental stress triggers the muscle cramps. This makes good sense, and
thus brain activity must be included as an important influence on the induction of
8 Neural Mechanisms of Muscle Cramp 87

Fig. 8.2 (a) Modulation of maximal M-waves during muscle cramp and (b) voluntary contrac-
tion. The abductor hallucis (AH) is the cramping muscle, and the soleus is the control muscle that
is not cramping. The onset of the cramp was defined as the moment when the subjects declared “I
am cramping” and the offset as the moment when the EMG burst stopped

muscle cramps, either directly or indirectly. There is little doubt that it would be
difficult indeed to explain such phenomena as emanating via with spinal or periph-
eral mechanisms. However, while logically possible, at the current time it would be
88 K. Nakagawa et al.

AH
Amplitude of Mmax (% control)
100 Voluntary contraction
Muscle cramp
80

60
y = -0.71x + 82.49
40
r2 = 0.34
20 p < 0.01

0
0 20 40 60 80 100
Background EMG (% MVC)
Fig. 8.3 Relationship between the amplitude of maximal M-waves (Mmax) and intensity of the
background electromyographic (EMG) activity during muscle cramps (red circles) and voluntary
contraction (blue diamonds) of the abductor hallucis (AH). A significant negative correlation was
found during muscle cramping

extremely difficult to establish the mechanism by which the brain contributes to

stress induced cramps.
The current difficulty of separating the contribution of CNS and peripheral
mechanisms may be due to the fact that both the CNS and the periphery play
roles in the initiation and prolongation of muscle cramps (Minetto et al. 2009a;
Merletti et al. 2011). Very likely, the locus responsible for the generation and
prolongation of muscle cramps will be found to differ in dissimilar situations.
Indeed, involuntary discharge can occur without a spinal contribution, whereas
discharge duration and intensity becomes larger with spinal involvement (Minetto
et al. 2011). That may indicate that peripheral mechanisms produce cramps while
spinal or higher brain mechanisms play a role in cramp prolongation. Future
research will be needed if we are to clarify the detailed mechanisms that produce
muscle cramps. Such an understanding will be critical for developing a strategy to
prevent or minimize the occurrence of muscle cramps and will be a very welcome,
overdue advancement for those who suffer from frequent muscle cramps.

References

Armstrong S, Cross T (2013) Exercise-associated muscle cramps. Med Today 14:62–65

Armstrong LE, Casa DJ, Millard-Stafford M, Moran DS, Pyne SW, Roberts WO (2007) Exertional
heat illness during training and competition. Med Sci Sports Exerc 39:556–572
Baldissera F, Cavallari P, Dworzak F (1994) Motor neuron ‘bistability’ a pathogenetic mechanism
for cramps and myokymia. Brain 117:929–939
8 Neural Mechanisms of Muscle Cramp 89

Bergeron MF (2003) Heat cramps: fluid and electrolyte challenges during tennis in the heat. J Sci
Med Sport 6:19–27
Bergeron MF (2008) Muscle cramps during exercise-is it fatigue or electrolyte deficit? Curr Sports
Med Rep 7:S50–S55
Bertolasi L, de Grandis D, Bongiovanni LG, Zanette GP, Gasperini M (1993) The influence of
muscular lengthening on cramps. Ann Neurol 33:176–180
Braulick KW, Miller KC, Albrecht JM, Tucker JM, Deal JE (2013) Significant and serious
dehydration does not affect skeletal muscle cramp threshold frequency. Br J Sports Med
47:710–714
Caress JB, Bastings EP, Hammond GL, Walker FO (2000) A novel method of inducing muscle
cramps using repetitive magnetic stimulation. Muscle Nerve 23:126–128
Garrison SR, Allan GM, Sekhon RK, Musini VM, Khan KM (2012) Magnesium for skeletal
muscle cramps. Cochrane Database Syst Rev 9, CD009402
Ge HY, Zhang Y, Boudreau S, Yue SW, Arendt-Nielsen L (2008) Induction of muscle cramps by
nociceptive stimulation of latent myofascial trigger points. Exp Brain Res 187:623–629
Goodman A, Zwetsloot KA (2013) Voluntary inducement of triceps surae muscle cramping. Int J
Athlet Ther Train 18:40–43
Jansen PH, Joosten EM, Vingerhoets HM (1990) Muscle cramp: main theories as to aetiology. Eur
Arch Psychiatry Neurol Sci 239:337–342
Jung AP, Bishop PA, Al-Nawwas A, Dale RB (2005) Influence of hydration and electrolyte
supplementation on incidence and time to onset of exercise-associated muscle cramps. J Athl
Train 40:71–75
Khan SI, Burne JA (2007) Reflex inhibition of normal cramp following electrical stimulation of
the muscle tendon. J Neurophysiol 98:1102–1107
Lambert EH (1968) Electromyography in amyotrophic lateral sclerosis. In: Motor neuron diseases
on amyotrophic lateral sclerosis and related disorders. Grune and Stratton, New York, pp
135–153
Layzer RB (1994) The origin of muscle fasciculations and cramps. Muscle Nerve 17:1243–1249
Maughan RJ (1986) Exercise-induced muscle cramp: a prospective biochemical study in marathon
runners. J Sports Sci 4:31–34
Merletti R, Botter A, Lanfranco F, Minetto MA (2011) Spinal involvement and muscle cramps in
electrically elicited muscle contractions. Artif Organs 35:221–225
Miller KC, Knight KL (2007) Pain and soreness associated with a percutaneous electrical
stimulation muscle cramping protocol. Muscle Nerve 36:711–714
Miller KC, Knight KL (2009) Electrical stimulation cramp threshold frequency correlates well
with the occurrence of skeletal muscle cramps. Muscle Nerve 39:364–368
Miller TM, Layzer RB (2005) Muscle cramps. Muscle Nerve 32:431–442
Miller KC, Stone MS, Huxel KC, Edwards JE (2010) Exercise-associated muscle cramps: causes,
treatment, and prevention. Sports Health 2:279–283
Mills KR, Newham DJ, Edwads RH (1982) Severe muscle cramps relieved by transcutaneous
nerve stimulation: a case report. J Neurol Neurosur Psychiatry 45:539–542
Minetto MA, Botter A (2009) Elicitability of muscle cramps in different leg and foot muscles.
Muscle Nerve 40:535–544
Minetto MA, Botter A, Ravenni R, Merletti R, de Grandis D (2008) Reliability of a novel
neurostimulation method to study involuntary muscle phenomena. Muscle Nerve 37:90–100
Minetto MA, Botter A, de Grandis D, Merletti R (2009a) Time and frequency domain analysis of
surface myoelectric signals during electrically-elicited cramps. Neurophysiol Clin 39:15–25
Minetto MA, Holobar A, Botter A, Farina D (2009b) Discharge properties of motor units of the
abductor hallucis muscle during cramp contractions. J Neurophysiol 102:1890–1901
Minetto MA, Holobar A, Botter A, Ravenni R, Farina D (2011) Mechanisms of cramp contrac-
tions: peripheral or central generation? J Physiol 589:5759–5773
Minetto MA, Holobar A, Botter A, Farina D (2013) Origin and development of muscle cramps.
Exerc Sport Sci Rev 41:3–10
 90 K. Nakagawa et al.

Nakagawa K, Miyamoto N, Murakami Y, Kanosue K (2013) Decrease in amplitude of M-wave

during muscle cramp. Tokyo J Phys Educ 4:11–16 (in Japanese)
Norris FH Jr, Gasteiger EL, Chatfield PO (1957) An electromyographic study of induced and
spontaneous muscle cramps. Electroencephalogr Clin Neurophysiol 9:139–147
Obi T, Mizoguchi K, Matsuoka H, Takatsu M, Nishimura Y (1993) Muscle cramp as the result of
impaired GABA function–an electrophysiological and pharmacological observation. Muscle
Nerve 16:1228–1231
Ohno M, Nosaka K (2004) Effect of muscle fatigue and dehydration on exercise induced muscle
cramp (EIMC). Jpn J Phys Fitness Sports Med 53:131–140 (in Japanese)
Roeleveld K, van Engelen BG, Stegeman DF (2000) Possible mechanisms of muscle cramp from
temporal and spatial surface EMG characteristics. J Appl Physiol 88:1698–1706
Ross BH (1976) Muscle cramp and the Hoffmann reflex. In: Proceedings of the 20th world
congress sports medicine, Carlton, pp 67–70
Ross BH, Thomas CK (1995) Human motor unit activity during induced muscle cramp. Brain
113:983–993
Schwellnus MP (2007) Muscle cramping in the marathon: aetiology and risk factors. Sports Med
37:364–367
Schwellnus MP (2009) Cause of exercise associated muscle cramps (EAMC)–altered neuromus-
cular control, dehydration or electrolyte depletion? Br J Sports Med 43:401–408
Schwellnus MP, Derman EW, Noakes TD (1997) Aetiology of skeletal muscle ‘cramps’ during
exercise: a novel hypothesis. J Sports Sci 15:277–285
Schwellnus MP, Nicol J, Laubscher R, Noakes TD (2004) Serum electrolyte concentrations and
hydration status are not associated with exercise associated muscle cramping (EAMC) in
distance runners. Br J Sports Med 38:488–492
Schwellnus MP, Drew N, Collins M (2011) Increased running speed and previous cramps rather
than dehydration or serum sodium changes predict exercise-associated muscle cramping: a
prospective cohort study in 210 Ironman triathletes. Br J Sports Med 45:650–656
Serrao M, Arendt-Nielsen L, Ge HY, Pierelli F, Sandrini G, Farina D (2007) Experimental muscle
pain decreases the frequency threshold of electrically elicited muscle cramps. Exp Brain Res
182:301–308
Stone MB, Edwards JE, Babington JP, Ingersoll CD, Palmieri RM (2003) Reliability of an
electrical method to induce muscle cramp. Muscle Nerve 27:122–123
Stone MB, Edwards JE, Huxel KC, Cordova ML, Ingersoll CD, Babington JP (2010) Threshold
frequency of an electrically induced cramp increases following a repeated, localized fatiguing
exercise. J Sports Sci 28:399–405
Sulzer NU, Schwellnus MP, Noakes TD (2005) Serum electrolytes in Ironman triathletes with
exercise-associated muscle cramping. Med Sci Sports Exerc 37:1081–1085
Talbott JH, Michelsen J (1933) Heat cramps. A clinical and chemical study. J Clin Invest
12:533–549

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