Hyperexcitability to electrical stimulation and accelerated muscle fatiguability of taut bands in rats

Transcription

1 1 Department of Physical Medicine and Rehabilitation, Qilu Hospital, Medical School of Shandong University, Jinan, People s Republic of China 2 Department of Chemistry and Chemical Engineering, Heze University, Heze, People s Republic of China 3 Department of Health Science and Technology, Laboratory for Experimental Pain Research, Center for Sensory Motor Interaction (SMI), Aalborg University, Aalborg, Denmark Correspondence to Dr Shou-Wei Yue, Department of Physical Medicine and Rehabilitation, Qilu Hospital, Medical School of Shandong University, Jinan , People s Republic of China; wangyonghui0000@sina.com.cn Received 17 August 2013 Revised 20 November 2013 Accepted 21 November 2013 Published Online First 6 December 2013 To cite: Wang Y-H, Yin M-J, Fan Z-Z, et al. Acupunct Med 2014;32: Hyperexcitability to electrical stimulation and accelerated muscle fatiguability of taut bands in rats Yong-Hui Wang, 1 Ming-Jing Yin, 2 Zhen-Zhen Fan, 1 Lars Arendt-Nielsen, 3 Hong-You Ge, 3 Shou-Wei Yue 1 ABSTRACT Objective Myofascial trigger points contribute significantly to musculoskeletal pain and motor dysfunction and may be associated with accelerated muscle fatiguability. The aim of this study was to investigate the electrically induced force and fatigue characteristics of muscle taut bands in rats. Methods Muscle taut bands were dissected out and subjected to trains of electrical stimulation. The electrical threshold intensity for muscle contraction and maximum contraction force (MCF), electrical intensity dependent fatigue and electrical frequency dependent fatigue characteristics were assessed in three different sessions (n=10 each) and compared with non-taut bands in the biceps femoris muscle. Results The threshold intensity for muscle contraction and MCF at the 10th, 15th and 20th intensity dependent fatigue stimuli of taut bands were significantly lower than those of non-taut bands (all p<0.05). The MCF at the 15th and 20th intensity dependent fatigue stimuli of taut bands were significantly lower than those at the 1st and 5th stimuli (all p<0.01). The MCF in the frequency dependent fatigue test was significantly higher and the stimulus frequency that induced MCF was significantly lower for taut bands than for non-taut bands (both p<0.01). Conclusions The present study demonstrates that the muscle taut band itself was more excitable to electrical stimulation and significantly less fatigue resistant than normal muscle fibres. INTRODUCTION Myofascial trigger points (MTPs), defined as hyperirritable nodules of spot tenderness in a taut muscle band, are considered to be a common cause of myofascial pain and also contribute significantly to other musculoskeletal pain conditions. 1 Motor dysfunction, decreased maximal voluntary contraction strength and accelerated fatigue are prevalent in patients with chronic musculoskeletal pain. 2 4 Thus, MTPs may be associated with accelerated muscle fatiguability. Muscle fatigue may arise not only from peripheral changes at the level of the muscle, but also from the central nervous system. 5 Central fatigue is associated with changes in firing rates, recruitment pattern and rotation between motor units. At the peripheral level, limitations in energy supply as well as the intramuscular accumulation of metabolic by-products emerge as key factors responsible for fatigue. 6 These may result in changes in the contractile properties (twitch force) and muscle fibre conduction velocity. 7 In addition, biomechanical changes, such as stiffness, may also result from muscle fatigue. 8 One of the characteristics of MTPs is the taut band in which the muscle fibres are stiffer than the surrounding fibres. 1 8 There is no trigger point, however, without a taut band. Magnetic resonance elastography indicates that the stiffness of the taut band is approximately 50% greater than that of the surrounding muscle tissue. 9 Ultrasound visualisation of taut bands demonstrates that the MTP is a localised and stiff nodule. 10 A taut band can be felt and identified in humans and animals by the examiner during manual palpation. Animal models, including rabbits and rats, have been developed and have proven very useful in studying the pathophysiology of MTPs The constant features of MTPs are pain, restriction of joint motion and muscle weakness. Thus we proposed that muscle taut bands associated with MTPs are associated with accelerated muscle fatiguability, which might activate MTPs and in turn aggravate 172 Wang Y-H, et al. Acupunct Med 2014;32: doi: /acupmed

2 musculoskeletal pain. However, whether taut bands contribute to muscle weakness and fatiguability is unknown and the biomechanical properties of taut bands have not been previously described. Low frequency electrical stimulation has been extensively used as a method for inducing skeletal muscle fatigue Thus, in this study, taut and non-taut bands in rats were surgically separated from their neighbouring muscle fibres and subjected to trains of electrical stimuli. The aims of the study were: (1) to measure electrical threshold intensity for muscle contraction and the maximum contraction force (MCF) of taut versus non-taut bands; and (2) to investigate the muscle fatigue characteristics of taut versus non-taut bands in electrical intensity and frequency dependent fatigue tests. METHODS Animal and surgical procedure The study was approved by the Chinese Institutional Animal Care Committee and all efforts were made to minimise suffering and the number of animals used. All protocols were approved by the Animal Use and Care Committee of Shandong University. Adult male Wistar rats, weighing g, were housed in a controlled environment (12h light/dark cycle, room temperature 23±2 C, 50 60% relative humidity). After initial anaesthesia with sodium pentobarbital (40 mg/ kg, by intraperioneal injection), rats underwent monitoring of heart rate and respiratory rate to avoid overdose of anaesthetics, and were allowed to recover naturally from the anaesthesia. During the recovery period, a level of light anaesthesia was determined by providing a noxious pinch to the tail with a calibrated clip (600 g). 21 The lightly anaesthetised animals typically responded to the noxious tail pinch with an abdominal contraction within about 30 min of the initial anaesthesia. At this point, a taut band was identified manually and marked with a coloured pen (see below), then the rat was fixed on an immobilisation board and placed onto a heating pad to maintain a constant body temperature. The area of skin around the marked position was shaved and cleaned with isopropyl alcohol before surgery. After making an incision in the skin and subcutaneous tissues, the marked taut band within one biceps femoris muscle and a non-taut band in the contralateral biceps muscle were dissected bluntly to about mm size. It was required that both ends of the taut and non-taut bands remained well connected with the muscle. The tissues were covered with a saline-soaked sterile gauze for 1 h. After appropriate physiological stimulation using a BL-420E+ organism function experiment system (BL-420E+ OFES), the muscle contraction curves of the taut and non-taut bands were derived using a transducer and recorder. After the taut bands had been identified, additional doses of anaesthetic were frequently given to keep the rats in the state of regular anaesthesia during the stimulation experiments. Identification of taut band Under light anaesthesia, the biceps femoris muscle of the rat was grasped between the fingers and gently palpated to find a taut band (roughly 2 3 mm or more in diameter) which was much firmer than the surrounding muscle fibres. The location along the taut band where snapping palpation produced a vigorous local twitch response was identified as the MTP. This response was absent in non-taut bands. 22 The taut band was reconfirmed by pincer palpation of the biceps femoris muscle once it had been separated posteriorly from the semimembranous muscle This method of identifying taut bands has been used in our previous studies, in which the taut bands and MTPs were well correlated with the existence of spontaneous electrical activity recorded with a needle electrode. Needling of the muscle fibres was avoided in the present study to avoid negatively impacting their mechanical properties. A taut band in biceps femoris muscle is commonly observed in adult male rats and can be reliably detected In the current study, taut bands were identified and confirmed by two trained examiners. 23 Fifty-six male rats were subjected to taut band examination. Of these, 30 rats with a palpable taut band on one leg were included in the experiments. Experimental protocol The study was performed using a BL-420E+ OFES and FT-100 force transducer (Chengdu Technology & Market Co. LTD, China) at the biomedical research laboratory of Shandong University. The force transducer, about 1mm in diameter, which senses the contraction force of muscles, was clamped to the middle part of the taut or non-taut bands with a clip and connected to BL-420E+ OFES. The muscle fibres of taut or non-taut bands were naturally relaxed. The bipolar chloride silver electrodes (1.5 mm wide) were clamped to the two separate ends of the taut or non-taut band and electrical stimuli were delivered by the electrical stimulator. Thirty male Wistar rats were divided randomly into three groups with 10 rats in each group. In the first session, rats in group A were used to assess the electrical threshold intensity for muscle contraction and MCF of taut and non-taut bands under a train of electrical stimuli (monophase square wave, 1 ms pulse width, 2 s interstimulus interval). The electrical intensity was initially set at 0.5 V, and increased in stepwise increments of 0.05 V until there was no further increase in contraction force with increasing intensity. Threshold intensity for muscle contraction, the MCF and the optimal stimulation intensity for MCF were recorded. Threshold intensity is the minimum electrical intensity which produces visible muscle Wang Y-H, et al. Acupunct Med 2014;32: doi: /acupmed

3 contraction. MCF is the maximum contraction force, beyond which there is no further increase with increasing intensity. The optimal stimulation intensity for MCF is the lowest electrical intensity which produces MCF. In the second session, rats in group B were used to investigate the intensity dependent fatigue characteristics of taut and non-taut bands under 20 intensity stimulus cycles. Trains of electrical stimuli (as above) were delivered across the intensity range 2 10 V, with stepwise increases of 0.4 V for each intensity stimulus cycle up to a total of 20 cycles. The electrically generated forces at each intensity were recorded. In the third session, rats in group C were used to study the frequency dependent fatigue characteristics induced by a train of stimuli (monophase square wave, 1ms pulse width) with the electrical intensity fixed at 2 V. The stimuli were given at different frequencies from 1 to 63 Hz, with a stepwise increase of 2 Hz, stimulus duration of 2 s and interstimulus interval of 4 s. The contraction forces generated by each stimulus were recorded. Statistical analysis Two-way repeated measures analysis of variance (ANOVA) was applied to compare the differences in MCF at the 1st, 5th, 10th, 15th and 20th intensity dependent fatigue stimulus cycles between taut and non-taut bands. The Student Newman-Keuls (SNK) test was used for post hoc comparison. The paired t test was used to compare the differences in threshold intensity, MCF and the optimal stimulus in the first session, and was also used to compare the differences in MCF and stimulus frequency induced MCF in the frequency fatigue test between taut and non-taut bands. The data in the text are expressed as mean ±SEM, and the significance level was set to p<0.05. RESULTS Threshold Intensity and MCF The average threshold intensity for muscle contraction of taut bands was significantly lower than that of non-taut bands (0.82±0.05 V vs 1.20±0.08 V, p<0.001, n=10). The average MCF and the optimal stimulus were not significantly different (both p>0.05) between taut bands (2.21±0.12 g and 2.79 ±0.09 V, respectively) and non-taut bands (2.14 ±0.11 g and 2.72±0.19 V, respectively) (figure 1). Intensity fatigue test Two-way ANOVA revealed a significant difference in MCF between taut and non-taut bands at the 1st, 5th, 10th, 15th and 20th intensity dependent fatigue stimulus cycles (F=9.82, p<0.001; F=15.04, p<0.001, respectively). The MCF at the 15th and 20th intensity dependent fatigue stimulus cycles was significantly lower than the 1st and 5th in taut bands (1.42±0.089 g, 0.93±0.170 g, 1.98±0.098 g, 1.97 ±0.085 g, respectively; p<0.001). MCF at the 10th, 15th and 20th intensity dependent fatigue stimulus cycles of taut bands was significantly lower than that of non-taut bands (1.62±0.092 g vs 2.02±0.077 g; 1.42±0.089 g vs 1.97±0.105 g; and 0.93±0.170 g vs 1.86±0.109 g, respectively; all p<0.001). No significant differences in MCF were found between the 1st, 5th and 10th intensity dependent fatigue stimulus cycles of taut bands. In addition, no significant differences in MCF were found at the 1st and 5th intensity dependent fatigue stimulus cycles between taut bands and non-taut bands (figure 2). Frequency fatigue test In the frequency dependent fatigue test, the average stimulus frequency that induced MCF of taut bands was significantly lower than for non-taut bands (12.40 ±0.67 Hz vs 20.62±1.60 Hz, p= , n=10). The average MCF of taut bands was significantly higher than that of non-taut bands (1.04±0.13 g vs 0.68±0.06 g, p=0.02, n=10) (figure 3A,B). DISCUSSION The main finding of the present study was that the threshold intensity for muscle contraction was lower for taut bands than for non-taut bands. A significantly lower electrical intensity was able to induce MCF of Figure 1 Threshold intensity, the optimal stimulus and maximum contraction force (MCF) of taut bands and non-taut bands (A, B); # Indicates significantly lower threshold intensity of taut bands than that of non-taut bands. 174 Wang Y-H, et al. Acupunct Med 2014;32: doi: /acupmed

4 Figure 2 Maximum contraction force (MCF) of taut bands and non-taut bands during intensity fatigue test; # Indicates significantly lower MCF at the15th and 20th intensity dependent fatigue stimulus cycles of taut bands than those at the 1st and 5th; *indicates significantly lower MCF at the10th, 15th and 20th intensity dependent fatigue stimulus cycles of taut bands than those of non-taut bands. taut bands than non-taut bands. The MCF of taut, but not non-taut bands, decreased significantly in the intensity dependent fatigue test. Significantly lower frequencies induced higher MCF of taut bands than non-taut bands. These findings suggest that muscle taut bands were more excitable and significantly less fatigue resistant than normal muscle fibres in rats. Animal models of MTPs and taut bands For a better understanding of the pathophysiology of taut bands, which are one of the key characteristics of MTPs, various animal models of taut bands associated with MTPs have been developed over the years. When rabbits and rats are lightly anaesthetised or awake, they will respond to finger compression or snapping palpation over a sensitive spot in a taut band Original paper with a strong response suggestive of pain. Taut bands, in which the fibres are much firmer than the surrounding muscles, are roughly 2 3 mm or more in diameter. When a certain sensitive spot in a taut band is stimulated mechanically with a needle or by a blunt metal probe, the local twitch response can be elicited. 24 Electromyographic activities, similar to those of human MTPs, can also can be recorded in rabbits and rats. 12 On the basis of these investigations, it has been suggested that the taut bands associated with MTPs found in rabbits and rats are equivalent to those of humans. Hayashi and Ozaki applied eccentric contraction to the rat gastrocnemius muscle for 2 weeks to develop an animal model relevant to myofascial pain syndrome. 16 A blunt striking injury and eccentric exercise have also been applied to the vastus medialis of rats for 8 weeks, following which new MTPs were identified. 17 While these models are useful to investigate the role of muscle injury in the formation of MTPs, taut bands are also found to naturally occur in wild type rats. Kuan and Hong searched for taut bands and MTPs in wild type rats by slipping a finger and injecting horseradish peroxidase into them to delineate the connections between MTPs and the spinal cord. 15 Hou and Chung assessed the effects of a calcium channel blocker on electrical activity in MTPs of wild type rabbits. 14 Therefore, it is acceptable to choose wild type rats as animal models of MTPs to study the pathophysiology of taut bands. Hyperexcitability to electrical stimulation of taut bands In this study, the two ends of the dissected taut or non-taut bands remained well connected with the muscle. Hence the electrical stimuli by bipolar silver chloride electrodes might have activated nerve endings as well as the cell membrane of the muscle fibres. The results of the current study, namely a low threshold intensity for muscle contraction and induction of MCF at a low level of electrical frequency, Acupunct Med: first published as /acupmed on 6 December Downloaded from Figure 3 Stimulus frequency induced maximum contraction force (MCF) and MCF of taut bands and non-taut bands during frequency fatigue test; # Indicates significantly lower stimulus frequency of MCF of taut bands than that of non-taut bands (A). *Indicates significantly higher MCF of taut bands than that of non-taut bands (B). Wang Y-H, et al. Acupunct Med 2014;32: doi: /acupmed on 21 October 2018 by guest. Protected by copyright.

5 suggest that the muscle contraction force is largely due to the activation of peripheral nerve endings. Compared with non-taut bands, the threshold intensity for muscle contraction was lower, and a significantly lower electrical intensity was capable of inducing MCF in taut bands. These findings suggest that the muscle fibres of taut bands were more excitable and therefore more responsive to electrical stimuli than those of non-taut bands in rats. Thus, the sensitised nerve endings may be involved in hypersensitivity of taut bands to electrical stimulation. These findings are in accordance with the observation of nociceptive and non-nociceptive hypersensitivity at MTPs 25 and the finding of a greater number of small nerve fibres at taut bands in the rabbit. 26 Muscle taut bands associated with MTPs may result from increased motor unit excitability with an increased release of acetylcholine at motor endplates In the present study, the tauts band and MTPs might have been latent as they were found naturally in adult male Wistar rats who had not undergone any extraneous interventions. Thus the current study may show that latent MTPs, rather than active MTPs with spontaneous pain and motor dysfunction, are associated with increased excitability of motor units in rats. However, the detailed mechanisms of the increased excitability of motor units at latent MTPs need to be investigated further. Muscle weakness and accelerated fatigability of taut bands In the first session of the experiment, there were no significant differences in the MCF between taut and non-taut bands. In the second session of the experiment, the MCF at the 1st and 5th intensity dependent fatigue stimulus cycles of taut bands did not differ to that of non-taut bands. However, the MCF at the 10th, 15th and 20th intensity dependent fatigue stimulus cycles of taut bands were significantly lower than those of non-taut bands, and MCF at the 15th and 20th intensity dependent fatigue stimuli of taut bands were significantly lower than those at the 1st and 5th. These findings show that, compared with non-taut bands, the muscle fibres of taut bands were more vulnerable to fatigue. Muscle taut bands may therefore contribute to the development of muscle weakness and accelerated fatiguability. Accelerated muscle fatiguability of taut bands may be related to multiple factors. The energy during muscle contraction derives from ATP, which mainly results from glucose and fatty acid oxidative phosphorylation, and partly from anaerobic metabolism. During this process, the aggregation of calcium ions around myofilament and calcium sensitivity are very important for muscle contraction force. Compared with normal muscle, the sustained activation of taut muscle bands caused by motor unit hyperexcitability has been observed during muscle contraction The sustained activation of taut muscle bands may slow calcium ion re-absorption by the sarcoplasmic reticulum and may thereby result in incomplete calcium ion absorption. Thus, sarcoplasmic reticulum calcium ion concentration is reduced when the muscle contracts repetitively and results in a reduction in the release of calcium ions. The sustained muscle fibre contraction within muscle taut bands can also increase the concentrations of metabolites and algesic substances Excessive muscle metabolites such as hydrogen ions and phosphate accumulation during muscle contraction can decrease myofilament sensitivity to calcium ions and cause muscle excitation-contraction uncoupling Sustained muscle activation also induces muscle ischaemia and muscle oxygenation reduction in turn contributes to skeletal muscle fatigue. Another potential mechanism is the existence of taut bands in a muscle inducing disordered muscle activation patterns in a group of functionally related muscles during a motor task. Increased muscle co-activation has also been observed in local pain conditions and this increased co-activation of antagonist musculature may reflect reorganisation of the motor control strategy in patients, potentially leading to muscle overload and increased nociception. 38 The inefficient muscle recruitment may possibly lead to muscle overuse and premature muscle fatigue. 39 However, the contribution of structural and biomechemical changes at taut bands to the muscle force production and fatiguability needs further investigation. In conclusion, this is the first study to investigate the biomechanical characteristics of taut bands in rats. This present study showed that the muscle fibres of taut bands were highly excitable to electrical stimulation and more vulnerable to fatigue than normal muscle fibres. These biomechanical characteristics of the taut bands may contribute significantly to muscle weakness and accelerated fatiguability in acute and chronic musculoskeletal pain conditions associated with MTPs. Acknowledgements We would like to thank Jianfeng Ma and Hongyan Xu for supplying the FT-100 force transducer and bipolar chloride silver electrodes friendly. Contributors Y-HW designed and managed the study, identified the taut bands, conducted the experimental protocol, analysed the data and wrote the manuscript. M-JY helped with study design and data analysis. Z-ZF identified the taut bands. LA-N helped with writing the manuscript. H-YG contributed to the study design and helped with writing the manuscript. S-WY contributed to the study design and management of the study. Funding This work was supported by the National Natural Science Foundation of China (grant no and no ) and the Natural Science Foundation of Shandong (grant no. ZR2010HQ021). Competing interests None. Provenance and peer review Not commissioned; externally peer reviewed. REFERENCES 1 Simons DG. Review of enigmatic MTPs as a common cause of enigmatic musculoskeletal pain and dysfunction. J Electromyogr Kinesiol 2004;14: Wang Y-H, et al. Acupunct Med 2014;32: doi: /acupmed

6 2 Falla D, Lindstrøm R, Rechter L. Effect of pain on the modulation in discharge rate of sternocleidomastoid motor units with force direction. Clin Neurophysiol 2010;121: Maquet D, Croisier J, Dupont C. Fibromyalgia and related conditions: electromyogram profile during isometric muscle contraction. Joint Bone Spine 2010;77: Ge HY, Nie HL, Graven-Nielsen T, et al. Descending pain modulation and its interaction with peripheral sensitization following sustained isometric muscle contraction in fibromyalgia. Eur J Pain 2012;16: Gandevia SC. Spinal and supraspinal factors in human muscle fatigue. Physiol Rev 2001;81: Girard O, Mendez-Villanueva A, Bishop D. Repeated-sprint ability part I: factors contributing to atigue. Sports Medicine 2011;41: Arendt-Nielsen L, Zwarts M. Measurement of muscle fiber conduction velocity in humans: techniques and applications. J Clin Neurophysio 1989;(l 2): Mademli L, Arampatzis A. Effect of voluntary activation on age-related muscle fatigue resistance. J Biomech 2008;41: Chen Q, Bensamoun S, Basford JR, et al. Identification and quantification of myofascial taut bands with magnetic resonance elastography. Arch Phys Med Rehabil 2007;88: Sikdar S, Shah JP, Gebreab T, et al. Novel applications of ultrasound technology to visualize and characterize myofascial trigger points and surrounding soft tissue. Arch Phys Med Rehabil 2009;90: Simons DG, Stolov WC. Microscopic features and transient contraction of palpable bands in canine muscle. Am J Phys Med 1976;55: Hong C-Z, Torigoe Y, Jen Y. The localized twitch responses in responsive bands of rabbit skeletal muscle fibers are related to the reflexes at spinal cord level. JMusculoskeletPain1995; 3: Kuan TS, Chen JT, Chen SM, et al. Effect of botulinum toxin on endplate noise in myofascial trigger spots of rabbit skeletal muscle. Am J Phys Med Rehabil 2002;81: Hou CR, Chung KC, Chen JT, et al. Effects of a calcium channelblocker on electrical activity in myofascial trigger spots of rabbits. Am J Phys Med Rehabil 2002;81: Kuan TS, Hong CZ, Chen JT, et al. The spinal cord connections of the myofascial trigger spots. Eur J Pain 2007;11: Hayashi K, Ozaki N, Kawakita K, et al. Involvement of NGF in the rat model of persistent muscle pain associated with taut band. J Pain 2011;12: Huang QM, Ye G, Zhao ZY, et al. Myoelectrical activity and muscle morphology in a rat model of myofascial trigger points induced by blunt trauma to the vastus medialis. Acupunct Med 2013;31: Marcil M, Karelis AD, Péronnet F, et al. Glucose infusion attenuates fatigue without sparing glycogen in rat soleus muscle during prolonged electrical stimulation in situ. Eur J Appl Physiol 2005;93: Wawrow PT, Jakobi JM, Cavanaugh JM. Fatigue response of rat medial longissimus muscles induced with electrical stimulation at various work/rest ratios. J Electromyogr Kinesiol 2011;21: Ibrahim MY, Ashour OM. Changes in nitric oxide and free radical levels in rat gastrocnemius muscle during contraction and fatigue. Clin Exp Pharmacol Physiol 2011;38: Ro JY, Capra N, Masri R. Development of a behavioral assessment of craniofacial muscle pain in lightly anesthetized rats. Pain 2003;104: Ge HY, Zhang Y, Boudreau S, et al. Induction of muscle cramps by nociceptive stimulation of latent myofascial trigger points. Exp Brain Res 2008;187: Wang YH, Ding XL, Zhang Y, et al. Ischemic compression block attenuates mechanical hyperalgesia evoked from latent myofascial trigger points. Exp Brain Res 2010;202: Hong CZ. Pathophysiology of myofascialtrigger point. J Formos Med Assoc 1996;95: Li LT, Ge HY, Yue SW, et al. Nociceptive and non-nociceptive hypersensitivity at latent myofascial trigger points. Clin J Pain 2009;25: Hong CZ, Chen JT, Chen SM, et al. Sensitive loci in a myofascial trigger point region are related to sensory nerve fibers. Am J Phys Med Rehabil 1997;76: Gerwin RD, Dommerholt J, Shah JP. An expansion of Simons integrated hypothesis of trigger point formation. Curr Pain Headache Rep 2004;8: Gerwin RD. The taut band and other mysteries of the trigger point: an examination of the mechanisms relevant to the development and maintenance of the trigger point. J Musculoskelet Pain 2008;15: Schwarz PB, Yee N, Mir S, et al. Noradrenaline triggers muscle tone by amplifying glutamate-driven excitation of somatic motoneurones in anaesthetized rats. J Physiol 2008;23: Ge HY, Nie H, Madeleine P. Contribution of the local and referred pain from active myofascial trigger points in fibromyalgia syndrome. Pain 2009;147: Kuan TS. Current studies on myofascial pain syndrome. Curr Pain Headache Rep 2009;13: Gerdle B, Gronlund C, Karlsson S. Altered neuromuscular control mechanisms of the trapezius muscle in fibromyalgia. BMC Musculoskelet Disord 2010;11: Hoyle JA, Marras WS, Sheedy JE, et al. Effects of postural and visual stressors on myofascial trigger point development and motor unit rotation during computer work. J Electromyogr Kinesiol 2011;21: Serrao M, Arendt-Nielsen L, Ge HY, et al. Experimental muscle pain decreases the frequency threshold of electrically elicited muscle cramps. Exp Brain Res 2007;182: Shah JP, Danoff JV, Desai MJ, et al. Biochemicals associated with pain and inflammation are elevated in sites near to and remote from active myofascial trigger points. Arch Phys Med Rehabil 2008;89: Dahlstedt AJ, Katz A, Westerblad H. Role of myoplasmic phosphate in contractile function of skeletal muscle: studies on creatine kinase-defi-cient mice. J Physiol 2001;533: Murthy G, Hargens AR, Lehman S. Ischemia causes muscle fatigue. J Orthop Res 2001;19: Fernandez-de-las-Peñas C, Falla D, Arendt-Nielsen L, et al. Cervical muscle co-activation in isometric contractions is enhanced in chronic tension-type headache patients. Cephalalgia 2008;28: Lucas KR, Rich PA, Polus BI. Muscle activation patterns in the scapular positioning muscles during loaded scapular plane elevation: the effects of latent myofascial trigger points. Clin Biomech 2010;25: Wang Y-H, et al. Acupunct Med 2014;32: doi: /acupmed