Myofascial Pain Syndrome in the Craniomandibular Region

Jan Dommerholt, PT, MPS*

Craniomandibular disorders (CMD) are characterized by a combination of symptoms that may include pain, tenderness and dysfunction of the temporomandibular joint, the mouth and the occlusal contacts, the cervical spine, and the muscles of mastication. Patients may present with local dentoalveolar pain; muscle pain; head, facial and neck pain; sounds during condylar movements; deviations and limitations of mandibular movements; altered occlusal relations; parafunctions and poor oral habits; and functional limitations of mastication. Craniofacial pain conditions have special emotional and psychological meaning. The face, the mouth, speech, and other oral functions are essential for nearly all human interactions; craniofacial pain conditions interfere with such functions and with the ability to communicate. Approximately 10% of the general population experience craniomandibular pain (1). The prevalence is estimated to range from 0% to 10% for males and from 2% to 18% for females. The prevalence in children and adolescents is estimated to range between 2% to 6% (2). Pain complaints range from acute and transient conditions such as toothaches to chronic ailments, such as trigeminal neuralgia and temporomandibular disorders. While in the majority of pain patients, pain decreases over time with or without treatment, for a small percentage the pain complaint persists. Similarly to other musculoskeletal pain problems, between 5% and 15% of all CMD patients become chronic pain patients (3-5). Patients with persistent craniomandibular pain without objective clinical or radiographic findings are especially challenging not only to the general dentist, but also to orthodontists, oral surgeons, TMJ specialists, and other clinicians. Some patients may be considered good candidates for splint therapy. Others are referred to oral surgeons when common dental procedures fail to offer relief. Some frustrated pain patients may even request surgical treatment in an effort to eliminate chronic craniomandibular pain (6). It is generally accepted that CMD have a multifactorial etiology (7). Although many diseases, such as dental disease, infections and tumors, can be associated with pain, most chronic pain problems are thought to be musculoskeletal in nature. Different perspectives of the primary source of pain have passed the revue. Some researchers and clinicians have emphasized joint dysfunction (8, 9); others have focused more on muscular problems (10-12). The relation between occlusion and CMD has been the subject of several investigations (13-16). Multiple studies have considered the impact of stress on CMD and in particular the impact of stress on pain and tenderness of the masticatory muscles (17-19). With the advancement of the pain sciences, more and more emphasis is placed on peripheral and central nervous system sensitization (20-23).

# Previously published as Dommerholt, J: El sindrome de dolor miofasical en la region craneomandibular. In: Padrs Serrat, E. (ed) Bases diagnosticas, terapeuticas y posturales del functionalismo craniofacial. Madrid, Ripano, 2006: 564-581 * Bethesda Physiocare / Myopain Seminars, 7830 Old Georgetown Road, Suite C-15, Bethesda, MD 20814 2440, USA; +301.656.5613 (phone); +301.654.0333 (fax); dommerholt@bethesdaphysiocare.com

Functional relations with spine dysfunction need to be considered in the management of patients with craniomandibular pain syndromes (24, 25). Rocabado has developed a pragmatic approach incorporating the intricate relationships between the cervical spine and mandible and temporomandibular function. He has demonstrated that centric position can only be achieved when there is a balance between the position and movement patterns of the subcranial region, the mid and lower cervical spine, the hyoid, and the mandible (26, 27). A detailed biomechanical assessment is important. Rocabados pain map is an excellent tool to determine which joint structures cause or may contribute to the pain complaint (see Rocabados chapter in this book for a more detailed description of his approach). In addition to a biomechanical joint assessment, clinicians need to include a detailed evaluation of the muscles in the cervical and craniomandibular region. Numerous studies of craniomandibular muscle pain and dysfunction have incorporated the research diagnostic criteria for temporomandibular disorders by Dworkin and LeResche, which include a section on muscle dysfunction (28). The research criteria were developed to classify and quantify both the physical and psychosocial components of temporomandibular dysfunction. Although the criteria are widely used in dental research, they are remarkable simplistic where it involves muscle dysfunction. The section Axis I, Group I, Muscle Disorders of the criteria includes only two options to describe muscle dysfunction: tender muscles with or without limited mouth opening. The inclusion of the word diagnostic in the title of Dworkin and LeResches classification criteria may be interpreted that the criteria can be used in clinical practice. However, research criteria do not necessarily provide a mechanism for clinical diagnosis. For example, MTrPs, myositis, and other less common conditions affecting muscles, such as myoadenylate deaminase deficiency or fascioliasis can not be diagnosed using the research criteria. Therefore, Dworkin and LeResches criteria do not provide any starting points to treat patients with craniomandibular muscular dysfunction in clinical settings, even though they have been validated for research purposes (29-32). Myofascial Pain Syndrome In the dental literature, muscle pain with or without limits in mouth opening is commonly referred to as myofascial pain dysfunction syndrome, a somewhat unfortunate term, as it is often confused and used interchangeably with the more practical and better

defined concept of myofascial pain syndrome (MPS) described by Simons, Travell and Simons (33). MPS is the main subject of this chapter and can be described as the sensory, motor, and autonomic symptoms caused by myofascial trigger points. A myofascial trigger point (MTrP) is clinically defined as a hyperirritable spot in skeletal muscle that is associated with a hypersensitive palpable nodule in a taut band. The spot is painful on compression and can give rise to characteristic referred pain, referred tenderness, motor dysfunction, and autonomic phenomena (33). Although there are many peer-reviewed studies and reports in the international medical literature supporting the importance of MTrPs in clinical practice, many of these reports are not included in major medical library indices. Fortunately, several prominent researchers are now investigating MTrPs and the results of many of these studies support the theoretical foundations and clinical applications. Nevertheless, there is a substantial lack of basic scientific studies; in general, MTrPs are underexplored by research investigators (34). A better understanding and working knowledge of MTrPs and MPS will provide dentists, orthodontists, oral surgeons, and other clinicians with an effective approach to relieve human suffering, and contribute significantly to their patients quality of life. If MTrPs are not considered in the differential diagnosis, a common cause of patients pain complaints will be overlooked (34, 35). MPS should be considered with any pain syndrome in the head, neck, face, and TMJ area (12, 33, 36). Dentists need to be aware that apparent dental or TMJ pain does not necessarily have a dental or joint origin (37). Myofascial pain tends to be dull, poorly localized, and deep, in contrast to the precise location of dental pain and cutaneous pain. Muscles can refer pain to other deep somatic structures, such as fascia, joints, viscera, and other muscles (38). Clinically, referred pain is confusing to many clinicians, as frequently, patients complain more of pain in the referred pain zone and not necessarily of pain in the immediate area of a MTrP. Signs and symptoms suggestive of non-odontogenic pain include an inadequate local dental cause for the pain; a recurrence of pain in spite of reasonable dental therapy of the tooth or TMJ; poor lasting pain relief after local anesthetic blocking; positive findings with Rocabados pain map; postural abnormalities such as forward head posture; and other pain problems, such as chronic and recurrent headaches and widespread chronic pain conditions. Patients with MPS usually have a history of acute or chronic muscle overload. In dental practice, MPS is commonly seen in patients with a history of

bruxism or clenching (12, 39-41). A common iatrogenic cause of MPS occurs when patients are required to keep their mouths open for prolonged periods of time during dental procedures (42). Patients with MPS in the head-neck region often are unable to relax their muscles in between contractions, i.e., the masseter, sternocleidomastoid and trapezius muscles. The muscles are in continuous contracture, which can result in muscle ischemia, fatigue and pain (23, 43, 44). Historical Overview of Myofascial Pain Syndrome MTrPs are the principal characteristic of MPS. During the past nearly 200 years, numerous authors have described MTrPs in the English, German, Dutch, and French medical literature, illustrating that musculoskeletal pain due to MTrPs is very common (45, 46). Already in 1816, British physician Balfour described MTrPs as nodular tumours and thickenings which were painful to the touch, and from which pains shot to neighbouring parts. Balfour speculated that the nodules were due to inflammation of the fibrous connective tissue in muscle (47). Historically, multiple terms have been used to describe muscle pain syndromes, many of which would have been diagnosed as MPS using the current definition, including fibrositis, myofasciitis, muscular rheumatism, rheumatic myositis, muscle hardening, myogelosis, myalgia, myofascial pain, and even fibromyalgia (45). In 1938, British rheumatologist Kellgren published a seminal paper describing specific referred pain patterns of many muscles and spinal ligaments following injections of hypertonic saline. In 1952, Travell wrote the first of many articles introducing the myofascial genesis of pain illustrated by specific referred pain patterns of over 30 muscles (48). Travell (1901 - 1997) has been referred to as the pioneer in the treatment of musculoskeletal pain through the recognition of MTrPs. She coined the term myofascial pain syndrome to describe pain as a result of trigger points in muscle, tendon, skin, fascia, and ligaments (the term trigger point was introduced by Steindler in 1940 (49)). Several of Travells subsequent papers included referred pain patterns relevant for head, neck, facial, and craniomandibular pain (50-52). Travell and Simons authored the classic two-volume text Myofascial Pain and Dysfunction The Trigger Point Manual. The first volume was published in 1983 for the upper half of the body followed by the second volume in 1992 for the lower half (53, 54). The second edition of the first volume, authored by Simons, Travell and Simons, was released in 1999 and includes contributions by experts in the growing field of myofascial pain and dysfunction (33).

The second edition summarizes significant progress in the understanding of the pathophysiological basis of the clinical presentations associated with MTrPs. The manuals have been translated into six different languages, including Spanish. Several other MTrP manuals have been published in Switzerland, the United States and the UK (46, 55, 56). Several assessment and treatment approaches have emerged independently of each other both in Europe and in the United States, including myofascial trigger point therapy (USA), neuromuscular technique or NMT (UK), neuromuscular therapy, also abbreviated as NMT (USA), and manual trigger point therapy (Switzerland). It is not a coincidence that these approaches share many similarities and have common goals and objectives (57). Recent insights in the nature, etiology and neurophysiology of MTrPs and their associated symptoms have propelled the interest in the diagnosis and treatment of persons with MPS worldwide (58). Diagnostic Criteria A diagnosis of MPS can be made only by palpation. There are no laboratory tests, imaging studies, or standardized diagnostic criteria to make an initial diagnosis of MPS. While this may suggest, that a diagnosis of MPS can not be established, clinical evidence combined with multiple scientific studies and case reports support the practice of evaluating patients for the presence of MTrPs. In a survey of physician members of the American Pain Society, 85% of 493 medical pain specialists, representing fourteen medical specialties, agreed that MPS is a distinct syndrome (59). MPS may actually be the most overlooked diagnosis in chronic pain patients (60). The diagnosis depends on the clinicians skills, training and experience in taking a patients history, performing a comprehensive examination, and assessing patients for MTrPs. Clinicians should not assume knowing how to identify MTrPs without specific training (61, 62). Unfortunately, few medical, dental and allied health school curricula include education and training in the assessment and treatment of MTrPs. Most clinicians trained in the diagnosis and treatment of MTrPs have been trained through post-graduate continuing education programs, such as the Interessengemeinschaft f!r Myofasziale Triggerpunkttherapie (Society for Myofascial Trigger Point Therapy) in Switzerland (www.imtt.ch) and the Janet G. Travell, MD Seminar Seriessm in the US (www.painpoints.com). The International Myopain Society has established a multidisciplinary international committee to design a study model for validation of diagnostic criteria. The

committee aims to establish reliable methods for diagnosis of MPS, determine the interrater reliability of MTrP examination, and determine the sensitivity and specificity with which classification criteria can distinguish patients with MPS from healthy control subjects (63). Simons, Travell and Simons defined a MTrP as a localized spot of tenderness in a nodule of a palpable taut band of contractured muscle fibers (33). Taut bands are examined by gently palpating a muscle perpendicular to the direction of the muscle fibers. Taut bands need to be differentiated from more generalized muscle spasms, that can be defined as electromyographic activity as a result of increased neuromuscular tone of the entire muscle (64, 65). A taut band feels like a rope or string of contractured fibers, that may extend from one end of the muscle to the other end. There are two basic palpation techniques for the proper identification of MTrPs. A flat palpation technique is used for example with palpation of the temporalis and masseter muscles (Figure 1). A pincher palpation technique is used for example with palpation of the sternocleidomastoid and the upper trapezius muscles (Figure 2).

Figure 1 c. Intra-oral palpation of the masseter muscle

Figure 2 a. Pincher palpation of the sternocleidomastoid muscle

Figure 1 a. Flat palpation of the temporalis muscle

Figure 2 b. Pincher palpation of the trapezius muscle Two recent studies have established excellent overall interrater reliability of the clinical examination used to establish the presence of MTrPs (62, 66). To make a diagnosis of MPS, the minimum essential features that need to be present are a taut band, an exquisitely tender spot or nodule in the taut band, and

Figure 1 b Flat palpation of the masseter muscle

the patients recognition of the pain complaint with pressure on the tender nodule (62). Simons, Travell and Simons add a painful limit to stretch range of motion as the fourth essential criterion (33). Taut bands and MTrPs are found in asymptomatic individuals and are only considered clinically relevant when the patient recognizes the elicited pain or when the functional limitations imposed by the taut band contribute to mechanical dysfunction secondary to muscle shortening (61, 67). The presence of a local twitch response, referred pain, and the electromyographic demonstration of endplate noise increase the certainty and specificity of the diagnosis. Local Twitch Response A local twitch response (LTR) is elicited by either strong digital palpation or needling/injection of a taut band or MTrP, that results in an involuntary brief burst of motor action potentials propagated only by fibers of that taut band or by fibers of a taut band from another muscle (68-70). A LTR is a spinal cord reflex, mediated through the spinal cord without supraspinal influences (69). During the physical examination, a LTR confirms the presence of a MTrP. Although the LTR can occur during physical examination of MTrPs, eliciting a LTR is not essential for making a diagnosis of MPS. Eliciting a LTR manually or with needling can be difficult and rather painful for patients, which suggests that a LTR perhaps originates from stimulation of sensitized nociceptors in the MTrP region rather than exclusively from mechanical stimulation (38). Eliciting a LTR during needling procedures is critical for the successful treatment of a MTrP (61, 71). Close proximity to the MTrP is essential (68). Gerwin and Duranleau were able to objectively visualize the LTR using diagnostic sonography, following stimulation of a MTrP by insertion of a hypodermic needle (72). High resolution sonography was however, not sensitive enough to visualize the actual MTrP (73). Referred Pain Since Kellgrens early studies on referred pain from muscle, multiple clinical reports have been published on referred pain from MTrPs (74). Referred pain is challenging for clinicians, as the patients perception of localization of pain can be very different from the original source of pain (75). To better appreciate the clinical implications of referred pain from MTrPs, a more extended review is included in this chapter. Although Asina and colleagues did not

specifically mention MTrPs, they described many of the symptoms commonly associated with MTrPs, such as increased myofascial tenderness, hardness, referred pain causing headaches, and central sensitization as a result of persistent nociceptive input from pericranial and extracranial muscles (76). Many case reports describe that MTrPs can cause or contribute to persistent headaches, facial pain, and temporomandibular pain (50, 77-80). Carlson demonstrated the clinical significance of referred pain by eliminating pain of the masseter muscle by treating MTrPs in the trapezius muscle (81). Many scientific studies and review articles have focused on muscle referred pain (12, 23, 44, 8293). Referred pain is not specific to MTrPs, but it is more common and much easier to elicit over MTrPs than over other structures (85). Hong found that all subjects reported referred pain with pressure directly over active MTrPs, but less than 50% of subjects reported referred pain with pressure over latent MTrPs (85). Compared to active MTrPs, latent MTrPs do not produce spontaneous pain; they require more pressure to elicit localized and referred pain (33). Normal muscle tissue and other body tissues, including skin, zygopophyseal joints, and internal organs may also refer pain to distant regions with prolonged and sufficient mechanical pressure (67, 89, 94-99). In the orofacial region, it is relevant that the teeth can also refer pain to other areas, including the TMJ and the sinuses (75). By mechanically stimulating an active MTrP, patients often report the development of referred pain in fairly consistent patterns, either immediately or after a brief 10-15 second delay. Mechanical stimulation may consist of manual pressure, needling of the MTrP, movement of the involved body region, or even prolonged postural strains, such as forward head posture or prolonged mouth opening. Usually, pain in reference zones is described as deep tissue pain of a dull and aching nature. However, some patients report burning or tingling sensations or other paresthesia (89, 100). In that sense, the term referred sensation reflects the clinical condition sometimes more accurately than the established term referred pain. Common referred pain patterns for nearly all skeletal muscles are documented by Travell and Simons (33, 53, 54). Dejung and colleagues have modified several referred pain patterns in their recent publication on MTrPs (55).

Neurobiology of Referred Pain In recent years, much new information has become available about the neurobiology of muscle referred pain (23, 38). Although the majority of data has been obtained from animal experiments, it is probably applicable to patients. Mense and colleagues have demonstrated that skeletal muscles have different types of nociceptors (101-103). Under normal conditions, skeletal muscle nociceptors require high intensities of nociceptive stimulation involving highthreshold mechanosensitive neurons, that do not respond to moderate local pressure, contractions or muscle stretches (65). Muscle nociceptors are activated by endogenous pain-producing substances such as bradykinin or serotonin. At least one of the muscle nociceptors is specifically sensitive to ischemic conditions (104). Local ischemia is associated with MTrPs. Looking at MTrPs from a biomechanical perspective, it is conceivable that at the cytoskeletal level, myosin filaments literally get stuck in the Z band of the sarcomere. During sarcomere contractions, titin filaments are folded into a gel-like structure at the Z band. In MTrPs, gel-like titin appears to prevent the myosin filaments from detaching. The myosin filaments may actually damage the regular motor assembly and prevent the sarcomere from restoring its resting length (105). The contracted sarcomeres are thought to reduce the local circulation by compressing the capillary blood supply and thus cause a significant lack of local oxygen. One study has shown that the oxygen saturation in the center of a MTrP is less than 5% of normal (106). Histological studies also suggest that MTrPs are ischemic: ragged-red and moth-eaten fibers have been identified in myogeloses and MTrPs (107-110). Moth-eaten fibers indicate a change in the distribution of mitochondria or the sarcotubular system, while ragged-red fibers reflect an accumulation of mitochondria (111). Both are usually associated with muscle ischemia, denervation, or strenuous exercise (112). Simons suggested that myogeloses and MTrPs may represent the same phenomenon (113). Local hypoxia is associated with the release of endogenous inflammatory substances, such as prostaglandin, bradykinin, serotonin, capsaicin, histamine, and interleukins. Activation and sensitization of muscle nociceptors leads to inflammatory hyperalgesia, an activation of high threshold nociceptors associated with C fibers, and an increased production of bradykinin. Furthermore, bradykinin stimulates the release of tumor necrosis factor (TNF-"), which in turn activates the production

of the interleukins IL-1#, IL-6 and IL-8. Especially IL8 can cause hyperalgesia that is independent from prostaglandin mechanisms. Via a positive feedback loop, IL-1 beta can also induce the further release of bradykinin (114). Bradykinin triggers the release of calcitonin gene related peptide (CGRP), which reduces the effectiveness of acetylcholinesterase (115-117). The combination of endogenous substances reinforces the observed hyperalgesia. Injections of bradykinin and serotonin into the temporal muscle of healthy volunteers caused more severe pain than either bradykinin or serotonin by itself (118). Following muscle trauma multiple substances are released simultaneously, which appears to occur in MTrPs as well. In their studies of the neurochemical milieu of MTrPs, Shah and colleagues at the U.S. National Institute of Health have confirmed increased concentrations of bradykinin, substance P, TNF-", interleukins, CGRP, and norepinephrine in active MTrPs when compared with latent MTrPs and healthy control subjects (119). In addition, the pH of the MTrP site was significantly lower in the active MTrP group. The endogenous substances bind to specific receptor molecules in the membrane of nociceptive nerve endings, including the so-called purinergic and vanilloid (VR-1) receptors. Purinergic receptors bind adenosine triphosphate and stimulate nociceptors accordingly. VR-1 receptors are especially sensitive under conditions of lowered tissue pH and muscle ischemia. Mense suggested that pain during tooth clenching, bruxism, and tension-type headaches is mediated by the VR-1 receptor molecule (44). Bradykinin, serotonin and prostaglandin interact at many levels at the vanilloid receptors (120). Referred pain is generated by central mechanisms dependent on peripheral input from the referred pain area. MTrPs are a source of ongoing peripheral nociceptive input. Long-term nociceptive input into the spinal cord or brain stem causes changes in function and connectivity of sensory dorsal horn neurons or neurons in the trigeminal nucleus caudalis respectively (21, 44, 121, 122). The ongoing afferent barrage into the dorsal horn and the trigeminal nucleus results in central sensitization, the unmasking of sleeping receptors in the dorsal horn, referred pain, and hyperexcitability (121, 123-125). There is considerable evidence that both neurokinin and N-methyl-Daspartate (NMDA) receptors are involved in triggering hyperalgesia and the MTrP-induced hyperexcitability of dorsal horn cells and brainstem nociceptive neurons (21, 44, 126).

In MTrPs, low-threshold mechanosensitive neurons may also get activated (127). Strong or longlasting nociceptive input from damaged muscle tissue or from MTrPs results in spatial summation in the dorsal horn or brain stem and the appearance of new receptive fields, which means that input from previously ineffective regions can now stimulate the neurons. In other words, the population of dorsal horn sensory neurons responding to the MTrP afferent input grows larger. As interneurons are located over various segments, the expansion may reach sensory neurons that supply peripheral areas outside the initial MTrP area. The expansion of pain areas is commonly seen in patients with headaches, whiplash, and other diagnoses (128, 129). There is no nociceptor activity in the referred pain area (44). Masseter MTrPs can trigger maxillary and mandibular tooth pain, TMJ pain, facial pain, including pain commonly associated with sinusitis, deep ear pain, tinnitus, and frontal and temporal headaches (Figure 3).

Figure 3 b. Referred pain pattern of the superficial masseter muscle Temporalis MTrPs can induce maxillary tooth pain and temporal headaches (Figure 4).

Figure 3 a. Referred pain pattern of the deep masseter muscle Figure 4 Referred pain pattern of the temporalis muscle Medial pterygoid MTrPs result in pain in the mouth, tongue, pharynx, hard palate, and behind the temporomandibular joint (Figure 5).

Figure 5 Referred pain pattern of the medial pterygoid muscle Lateral pterygoid MTrPs cause TMJ pain and pain in the maxillary sinus (Figure 6).

Figure 7 Referred pain pattern of the digastric muscle MTrPs in the platysma muscle cause referred pain sensations over the lateral surface of the mandible. Most cervical muscle MTrPs have referred pain patterns into the head and face regions (Figure 8) (33). Simons, Travell and Simons described the formation of so-called satellite MTrPs in referred pain areas (33).

Figure 6 Referred pain pattern of the lateral pterygoid muscle MTrPs in the posterior belly of the digastric muscle refer pain to the upper part of the sternocleidomastoid muscle, the front of the throat, and sometimes into the occiput. MTrPs in the anterior belly of the digastric muscle refer pain to the mandibular incisors, the alveolar ridge, and the tongue (Figure 7).

Figure 8 a. Referred pain pattern of the sternocleidomastoid muscle, sternal portion

Figure 8 b. Referred pain pattern of the sternocleidomastoid muscle, clavicular portion

Figure 8 c. Referred pain pattern of the trapezius muscle

Electromyographic Findings Hubbard and Berkhoff recorded both lowamplitude continuous action potentials (10-50 microvolts), which they labeled spontaneous electrical activity, and intermittent spikes (100-600 microvolts) from active MTrPs (130). The electrical activity was only present in sites of active MTrPs and was absent in adjacent non-tender muscle tissue. Subsequent studies indicated that the low-amplitude noise-like potentials represented grossly abnormal endplate activity (EPN) as compared to the normal miniature endplate potentials (MEPP) commonly reported by electromyographers (131-134). In the EMG literature, abnormal EPN is assumed to be associated with normal motor endplates and normal disease-free muscles (135). However, the physiology literature indicates that EPN represents an abnormal concentration of acetylcholine up to three times normal levels (132, 134, 136, 137). Recent studies by Shah and colleagues confirmed high concentrations of acetylcholine at MTrP sites (119, 138). EPN is not exclusive to MTrPs. Already in 1956, Liley reported that a normal endplate could exhibit abnormal noise-like discharge patterns by mechanically stressing the endplate (139). Simons suggested that Lileys observation may help to account for the activation of MTrPs by mechanical overload or mechanical trauma (34). In 1997, Maselli confirmed that damage to the endplate caused by the tip of the advancing EMG needle could convert normal miniature endplate potentials (MEPP) to EPN, because of a massive release of acetylcholine (140). Brown and Varkey suggested that the spikes, that Hubbard and Berkhof had observed in MTrPs, could also arise from mechanical stimulation of the endplate, however, Wiederholt had already provided evidence that the spikes indeed originated in the neuromuscular junction (130, 135, 141). In Masellis words, the origin of the spikes corresponds to single muscle fiber action potentials postsynaptically activated by suprathreshold end-plate noise (140). By using a very slow insertional technique as described by Simons and colleagues, EPN from MTrP can be reliably observed (132, 134).

Integrated Trigger Point Hypothesis Combining all available supporting evidence of the existence of MTrPs, Simons has recently proposed a new integrated trigger point hypothesis (33). The integrated trigger point hypothesis has evolved through several steps of progress since its first introduction as the energy crisis hypothesis in 1981 (142). The hypothesis builds on the finding that excessive amounts of acetylcholine from the motor nerve terminal cause miniature motor endplates potentials that produce the endplate noise observed with needle EMG of MTrPs. The excessive acetylcholine maintains a sustained depolarization of the postjunctional membrane, which in turn results in an excessive release of calcium from the sarcoplasmic reticulum and sustained sarcomeric contractions. Shenoi and Nagler suggested that an impaired re-uptake of calcium into the sarcoplasmic reticulum induced by calcium channel blockers may cause MTrPs (143). According to the integrated trigger point hypothesis, the sarcomeric contractions cause local hypoxia, reducing the available energy supply. The combined decreased energy supply and increased metabolic demand possibly may explain the common finding of abnormal mitochondria in the nerve terminal, referred to as ragged red fibers (Henriksson et al. 1993; Henriksson 1999). The local energy crisis would also impair the calcium pump, which would provide another mechanism of the sustained contractures. The calcium pump is responsible for returning intracellular calcium into the sarcoplasmic reticulum against a concentration gradient, which requires a functional energy supply. As reviewed, hypoxia also stimulates the release of endogenous substances, resulting in hyperalgesia, central sensitization, and stimulation of the autonomic nervous system, which has been shown to increase endplate potentials. For example, an increase in psychological arousal resulted in an immediate increase of endplate spike rates (144, 145). Autogenic relaxation and the administration of the sympathetic blocking agents phentolamine and phenoxybenzamine inhibited the autonomic activation (146-148). Induced autonomic nerve activity would explain autonomic phenomena commonly seen with MPS, and further contribute to the abnormal release of acetylcholine, possibly by increasing the permeability of calcium channels in the cell membrane of the nerve terminal (149, 150). A recent study examined the effects of MTrP massage therapy on the cardiac autonomic tone in healthy subjects. The researchers observed that following MTrP therapy, there was a

significant decrease in heart rate, and systolic and diastolic blood pressure, indicating a significant increase in parasympathetic activity (151). The integrated trigger point hypothesis is summarized in figure 9. The hypothesis is a work in progress that is beginning to be subjected to rigorous scientific review and verification.

Figure 9 Integrated trigger point hypothesis It is likely that new studies will demonstrate that there are many other factors to consider. For example, preliminary data from current studies by Shah and colleagues provide already new insights in the basic pathophysiology of MTrPs (119). The finding of increased levels of several endogenous substances in the neurochemical milieu of MTrPs, including bradykinin, serotonin, prostaglandin, and CGRP, combined with the finding of a lowered pH may alter the current understanding of motor endplate dysfunction in relation to MTrPs. Both CGRP and a lowered pH can effectively reduce the function of acetylcholinesterase, which could cause an overall increase of available acetylcholine (115-117). At the same time, a lowered pH can activate peripheral nociceptors and trigger capsaicin- sensitive afferents, which in turn can release several of the endogenous

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substances from their peripheral endings, including CGRP (152-154). A pH of 6.1 resulted in a threefold increase of the basal CGRP release, which was entirely dependent on the presence of extracellular calcium (155). Bradykinin caused a 50% increase of the basal CGRP release which was also dependent on the presence of extra-cellular calcium (155). Endogenous substances such as bradykinin, serotonin and prostaglandin, clearly interact at multiple levels, including at the vanilloid receptors (120). Although the relevance of these interactions has not been studied specifically in relationship to MTrPs, it is likely that future studies will reveal new aspects of their pathophysiology. Interestingly, Shah and colleagues established an immediate drop in the concentrations of several substances with dry needling of a MTrP (119). If the integrated trigger point hypothesis is basically correct, MTrPs are primarily a muscle disease with secondary but important sensory, motor and autonomic phenomena (156). Clinical Applications MPS and MTrPs should be considered in the differential diagnosis of craniomandibular pain and temporomandibular joint dysfunction, migraines, tension headaches, radiculopathies, complex regional pain syndrome, whiplash injuries, and most other pain syndromes. To diagnose and manage MPS, clinicians must become well-trained in the identification of MTrPs. Through inactivation of MTrPs, clinicians can facilitate return to function and elimination of pain in both acute and chronic pain patients. Together with the patient, ultimate functional goals need to be discussed. For some patients, eating solid foods may be the final goal. For others, it may be restoring sleep, regaining sexual activity, or returning to work. Treating MTrPs is merely an effective tool to assist patients in regaining lost function (157). There are many different manual techniques, including myofascial release techniques, compression, trigger point compression combined with active contractions of the involved muscle, muscle energy or post-isometric relaxation, connective tissue stretches, and general massage therapy. Needling techniques include superficial and deep dry needling, and trigger point injections (61, 158). For persistent cases, botulinum toxin can be used as it blocks the release of acetylcholine (159, 160). Throughout the treatment process, patients must be educated regarding the etiology, perpetuating factors, and selfmanagement. Patients must learn to modify their behaviors and avoid overloading the muscles without resorting to total inactivity (161).

A sudden onset or a clear remembrance of the onset of pain may indicate an acute activation of MTrPs due to mechanical stress, but it may also indicate a sudden change in the patients environment or habits. The mechanical stress may be the result of sudden or abrupt movements, motor vehicle accidents, falls, fractures, joint sprains or dislocations, a direct blow to a muscle, joint, or mandible, excessive exercise or activity, or performing new or unusual activities. A slow insidious onset is usually the result of chronic overloading of tissue, such as habitual chewing gum or tobacco, postural imbalances, poor body mechanics, repetitive movements, and tension as a consequence of psychological or emotional stress (57). Clinicians should consider both the sensory and mechanical aspects of MTrPs. The physical examination must include a thorough evaluation of MTrPs relevant to the patients current pain presentation. The patients current area(s) of pain can be visualized through patient pain drawings. While patients communicate their pain patterns, the clinician can begin identifying those muscles and active MTrPs most likely involved in the pain problem. For example, in a patient with complaints of temporal headaches, the pain complaint may direct the clinician to the sternocleidomastoid, trapezius, temporalis and inferior oblique capitis muscles. The patients head posture in slight side bending and rotation may implicate the scalene muscles, although the referred pain pattern from MTrPs in the scalene muscles does not include the head region. If the patient in addition presents with a paradoxical breathing pattern, it will be necessary to examine and treat the accessory breathing muscles as well, including the pectoralis minor, scalenes, sternocleidomastoid and upper trapezius musculature that may be overloaded due to increased demands. Teaching the patient a normal diaphragmatic breathing pattern and fostering awareness of relaxation techniques for the upper chest and neck region will aid in the long term management of the headaches. Dentists should limit their direct treatment to muscles cranially from the clavicles to stay within the scope of dental practice. Habitual postural patterns need to be assessed (162-164). Does the patient have a forward head posture? Are there certain work postures or habits that maintain the head in an antero-position? Forward head posture is associated with multiple static and dynamic changes in total body alignment. Patients with forward head posture present with posterior cervical rotation of the upper cervical and subcranial motion segments, a posteriorly displaced mandible, altered occlusion, as

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well as shoulder girdle protraction, internally rotated humeri, increased thoracic kyphosis, a loss of lumbar lordosis, and an increase in posterior pelvic rotation. Dentists need to be familiar with the consequences of forward head posture. For example, if a patient with forward head posture receives a splint, the dentist may have to adjust the splint after the patients head posture has been corrected by a physical therapist. Close working relationships between dentists and physical therapists are very important and benefit patients. Simons, Travell and Simons advocated the spray and stretch technique, which combines use of a vapocoolant spray with passive stretching of the muscle (33). Application of vapocoolant spray stimulates thermal and tactile A-beta skin receptors, thereby inhibiting C-fiber and A-delta fiber afferent nociceptive pathways and muscle spasms, MTrPs, and pain when stretching. Prior to applying the spray and stretch method, the patient is positioned comfortably. The muscle involved is sprayed with a few sweeps of a vapocoolant spray, after which the muscle is stretched passively. With the muscle in the stretched position, the spray is applied again over the skin overlying the entire muscle, starting at the trigger zone and proceeding in the direction of and including the referred pain zone. Following the stretch and spray, the area is heated with a moist heat pack for 5-10 minutes. The patient is encouraged to move the body part several times through the full range of motion. The spray and stretch technique can be used in physical therapy as a separate modality or following myofascial trigger point injections. Muscle stretching can be combined with muscle energy techniques or post isometric relaxation, during which the muscle is stretched after a brief submaximal isometric contraction. All techniques are used diagnostically and therapeutically (61, 158). Some patients can learn to use spray and stretch techniques at home. Self treatment programs can be very effective (165). Inactivation of MTrPs by injection or dry needling appears to be the result of the mechanical action of the needle, since it can be successfully accomplished without the use of local anesthetics or other materials. In 1979, Lewit confirmed that the effects of needling were primarily due to mechanical stimulation of a MTrP with the needle. Dry needling of a MTrP using an acupuncture needle caused immediate analgesia in nearly 87% of needle sites. In over 31% of cases, the analgesia was permanent. Twenty percent had several months of pain relief, 22% several weeks, and 11% several days. Fourteen percent had no relief at all (166).

When using injection needles, the use of a local anesthetic is more comfortable for many patients and results in a longer lasting reduction in MTrP pain (167). The use of solid acupuncture needles versus injection needles has not been examined at this time. After identifying and manually stabilizing the tender area in the taut band with the fingers, the needle is quickly passed through the skin and then into the trigger zone. A LTR or a report of referred pain indicates that the trigger zone has been entered. A small amount, usually 0.1 or 0.2 ml, of local anesthetic may be injected into the trigger zone. There is no benefit to adding steroids. The needle is withdrawn to just below the skin, the angle of the needle changed, and the needle is again passed through the muscle to another trigger zone. A conical volume of muscle can thus be examined for active trigger points without withdrawing the needle through the skin. The trigger zone is explored in this manner until no further LTRs are obtained. Dry needling a MTrP is most effective, when LTRs are elicited (71, 138). A LTR has been shown to inhibit abnormal endplate noise. Current (unpublished) research strongly suggests that a LTR is essential in altering the neurochemical milieu of a MTrP (Shah, 2003, personal communication). Patients commonly describe an immediate reduction or elimination of the pain complaint after eliciting LTRs. Once the pain is reduced, patients can start active stretching and strengthening programs. Eliciting a LTR with dry needling is usually a rather painful procedure. Postneedling soreness may last for one to two days, but can easily be distinguished from the original pain complaint. At this point, the taut band is usually gone, and the spontaneous pain of the trigger point has subsided. Patients who have previously undergone treatment can tell when MTrPs remain, and when they have been sufficiently inactivated. A knowledgeable patient will urge the clinician to continue in an area until a key MTrP is inactivated, at which time there will be a noticeable decrease in pain. The process is repeated until the symptomatic MTrPs are treated throughout the functional muscle unit (61). There is no limit to the number of MTrP that can be needled. Common sense and patient comfort dictate restraint. Nevertheless, when treating a regional MPS, a sufficient number of muscles in the region must be treated to resolve the problem and allow effective post-needling stretching. All the muscles in a functional muscle unit must be released and returned to full length, if possible, either by needling or by MTrP compression and stretching. Inadequate treatment that leaves critical MTrPs within a functional muscle unit

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usually results in the recurrence of trigger points throughout the muscles of the functional unit. Five to ten different MTrP sites can readily be treated per session, and some physicians and physical therapists skilled in MPS management will treat considerably more in one session. Repeat injections or dry needling into the same area are best done after an interval of one week to allow the muscle to recover. Muscles of the affected functional unit must always be stretched, to their full length if possible, after MTrP needling. Moist heat is applied to the muscle to improve the local circulation and to reduce post-injection soreness. Otherwise, MTrPs will recur because of residual muscle dysfunction. Local anesthetic patches can be applied to reduce the superficial or cutaneous soreness from needling. Trigger point injections or dry needling are a highly effective way to reduce the local pain and contraction of the taut band. This does not, however, constitute the whole treatment of MPS and MTrPs. The causes that led to the condition must be corrected, when possible. Mechanical, medical, and psychological perpetuating factors must also be eliminated or alleviated in order to reduce the chance of recurrence. Inadequate attention to these aspects of treatment leads to failure to relieve pain and restore function (61, 168). Summary Myofascial pain syndrome as defined by Simons, Travell and Simons offers clinicians an excellent entry point into patients acute and chronic pain problems. Myofascial trigger points are a common source or contributing factor to many musculoskeletal disorders. In the craniomandibular region, myofascial trigger points are frequently responsible for local and referred pain patterns, causing headaches, TMJ pain and dysfunction, tooth aches, and facial pains. Clinicians should routinely incorporate myofascial trigger points in their examinations and differential diagnoses. The results of many scientific studies are beginning to validate several aspects of the integrated trigger point hypothesis and refine others. A better understanding and working knowledge of MTrPs and MPS offers an effective approach to relieve pain, restore function, and contribute significantly to patients quality of life.

References
1. LeResche L. Epidemiology of temporomandibular disorders: implications for the investigation of etiologic factors. Crit Rev Oral Biol Med 1997;8:291-305. 2. Drangsholt M, LeResche L. Temporomandibular disorder pain. In: Crombie IK, Croft PR, Linton SJ, LeResche L, Von Korff M, editors. Epidemiology of pain. Seattle: IASP Press; 1999. p. 203233. 3. Elliott AM, Smith BH, Penny KI, Smith WC, Chambers WA. The epidemiology of chronic pain in the community. Lancet 1999;354(9186):1248-52. 4. Buskila D, Abramov G, Biton A, Neumann L. The prevalence of pain complaints in a general population in Israel and its implications for utilization of health services. J Rheumatol 2000;27(6):1521-5. 5. Zondervan K, Barlow DH. Epidemiology of chronic pelvic pain. Baillieres Best Pract Res Clin Obstet Gynaecol 2000;14(3):403-14. 6. Israel HA, Ward JD, Horrell B, Scrivani SJ. Oral and maxillofacial surgery in patients with chronic orofacial pain. J Oral Maxillofac Surg 2003;61(6):662-7. 7. Curtis AW. Myofascial pain-dysfunction syndrome: the role of nonmasticatory muscles in 91 patients. Otolaryngol Head Neck Surg 1980;88(4):361-7. 8. Kryshtalskyj B. The role of diagnostic arthroscopy in the management of temporomandibular joint dysfunction. J Otolaryngol 1991;20(5):325-8. 9. Widmark G. On surgical intervention in the temporomandibular joint. Swed Dent J Suppl 1997;123:1-87. 10. Velly AM, Gornitsky M, Philippe P. Contributing factors to chronic myofascial pain: a case-control study. Pain 2003;104(3):491-9. 11. Laskin DM. The clinical diagnosis of temporomandibular disorders in the orthodontic patient. Semin Orthod 1995;1(4):197206. 12. Fricton JR. Etiology and management of masticatory myofascial pain. J Musculoskeletal Pain 1999;7(1/2):143-160. 13. Clarke NG. Occlusion and myofascial pain dysfunction: is there a relationship? J Am Dent Assoc 1982;104(4):443-6. 14. Ito H, Okimoto K, Mizumori T, Terada Y, Maruyama T. A clinical study of the relationship between occlusal curvature and craniomandibular disorders. Int J Prosthodont 1997;10(1):78-82. 15. Denbo JA. Malocclusion. Dent Clin North Am 1990;34(1):103-9. 16. Kerstein RB. Treatment of myofascial pain dysfunction syndrome with occlusal therapy to reduce lengthy disclusion time--a recall evaluation. Cranio 1995;13(2):105-15. 17. Flor H, Birbaumer N, Schulte W, Roos R. Stress-related electromyographic responses in patients with chronic temporomandibular pain. Pain 1991;46(2):145-52. 18. Sieber M, Grubenmann E, Ruggia GM, Palla S. Relation between stress and symptoms of craniomandibular disorders in adolescents. Schweiz Monatschr Zahnmed 2003;113(6):648-654. 19. Moss RA, Garrett JC. Temporomandibular joint disfunction syndrome and myofascial pain dysfunction syndrome: a critical review. J Oral Rehabil 1984;11(1):3-28. 20. Ro JY. Contribution of peripheral NMDA receptors in craniofacial muscle nociception and edema formation. Brain Res 2003;979:78-84. 21. Sessle BJ, Hu JW, Cairns BE. Brainstem mechanisms underlying temporomandibular joint and masticatory muscle pain. J Musculoskeletal Pain 1999;7(1/2):161-169.

13

22. Sessle BJ, Hu JW, Amano N, Zhong G. Convergence of cutaneous, tooth pulp, visceral, neck and muscle afferents onto nociceptive and non-nociceptive neurones in trigeminal subnucleus caudalis (medullary dorsal horn) and its implication for referred pain. Pain 1986;27:219-235. 23. Graven-Nielsen T, Mense S. The peripheral apparatus of muscle pain: evidence from animal and human studies. Clin J Pain 2001;17(1):2-10. 24. Kraus SL. Cervical spine influences on the management of TMD. In: Kraus SL, editor. Temporomandibular disorders. New York: Churchill Livingstone; 1994. p. 325-412. 25. Fink M, Whling K, Stiesch-Scholz M, Tschernitschek H. The functional relationship between the craniomandibular system, cervical spine, and sacroiliac joint: a preliminary investigation. J Craniomandib Pract 2003;21(3):202-208. 26. Rocabado M, Tapia V. Radiographic study of the craniocervical relation in patients under orthodontic treatment and the incidence of skeletal symptoms. J Craniomand Practice 1987;5(1):36. 27. Rocabado M. Biomechanical relationship of the cranial, cervical and hyoid regions. J Craniomandibular Pract 1983;3:62-66. 28. Dworkin SF, LeResche L. Research diagnostic criteria for temporomandibular disorders: review, criteria, examinations and specifications, critique. J Craniomandib Disord Facial Oral Pain 1992;6:301-355. 29. Rammelsberg P, LeResche L, Dworkin S, Mancl L. Longitudinal outcome of temporomandibular disorders: a 5-year epidemiologic study of muscle disorders defined by research diagnostic criteria for temporomandibular disorders. J Orofac Pain 2003;17(1):9-20. 30. Dworkin SF, Turner JA, Mancl L, Wilson L, Massoth D, Huggins KH, et al. A randomized clinical trial of a tailored comprehensive care treatment program for temporomandibular disorders. J Orofac Pain 2002;16(4):259-76. 31. Dworkin SF, Sherman J, Mancl L, Ohrbach R, LeResche L, Truelove E. Reliability, validity, and clinical utility of the research diagnostic criteria for Temporomandibular Disorders Axis II Scales: depression, non-specific physical symptoms, and graded chronic pain. J Orofac Pain 2002;16(3):207-20. 32. Dworkin SF, Huggins KH, Wilson L, Mancl L, Turner J, Massoth D, et al. A randomized clinical trial using research diagnostic criteria for temporomandibular disorders-axis II to target clinic cases for a tailored self-care TMD treatment program. J Orofac Pain 2002;16(1):48-63. 33. Simons DG, Travell JG, Simons LS. Travell and Simons' myofascial pain and dysfunction; the trigger point manual. 2 ed. Baltimore: Williams & Wilkins; 1999. 34. Simons DG. Review of enigmatic MTrPs as a common cause of enigmatic musculoskeletal pain and dysfunction. J Electromyogr Kinesiol 2004;in press. 35. Padamsee M, Mehta N, White GE. Trigger point injection: a neglected modality in the treatment of TMJ dysfunction. J Pedod 1987;12(1):72-92. 36. Domnitz JM, Swintak EF, Schriver WR, Shereff RH. Myofascial pain syndrome masquerading as temporomandibular joint pain. Oral Surg Oral Med Oral Pathol 1977;43(1):11-7. 37. Svensson P, Graven-Nielsen T, Arendt-Nielsen L. Mechanical hyperesthesia of human facial skin induced by tonic painful stimulation of jaw muscles. Pain 1998;74(1):93-100. 38. Mense S, Simons DG. Muscle pain; understanding its nature, diagnosis, and treatment. Philadephia: Lippincott Williams & Wilkins; 2001. 39. Ayer WA, Machen JB, Getter L. Survey of myofascial pain-dysfunction syndrome and pathologic bruxing habits among dentists. J Am Dent Assoc 1977;94(4):730-2. 40. Kawazoe Y, Kotani H, Hamada T, Yamada S. Effect of occlusal splints on the electromyographic activities of masseter

muscles during maximum clenching in patients with myofascial paindysfunction syndrome. J Prosthet Dent 1980;43(5):578-80. 41. Arima T, Svensson P, Arendt-Nielsen L. Experimental grinding in healthy subjects: a model for postexercise jaw muscle soreness? J Orofac Pain 1999;13(2):104-14. 42. Abdel-Fattah RA. Preventing temporomandibular joint (TMJ) and odontostomatognatic (OSGS) injuries in dental practice. Boca Raton: CRC Press; 1993. 43. Svensson P, Burgaard A, Schlosser S. Fatigue and pain in human jaw muscles during a sustained, low-intensity clenching task. Arch Oral Biol 2001;46(8):773-7. 44. Mense S. The pathogenesis of muscle pain. Current Pain and Headache Reports 2003;7(6):419-425. 45. Simons DG. Muscle pain syndromes - part 1. Am J Phys Med 1975;54:289-311. 46. Baldry PE. Myofascial pain and fibromyalgia syndromes. Edinburgh: Churchill Livingstone; 2001. 47. Stockman R. The causes, pathology, and treatment of chronic rheumatism. Edinburgh Med J 1904;15:107-116. 48. Travell JG, Rinzler SH. The myofascial genesis of pain. Postgrad Med 1952;11:452-434. 49. Steindler A. The interpretation of sciatic radiation and the syndrome of low-back pain. J Bone Joint Surg Am 1940;22:28-34. 50. Travell J. Identification of myofascial trigger point syndromes: a case of atypical facial neuralgia. Arch Phys Med Rehabil 1981;62(3):100-106. 51. Travell J. Temporomandibular joint pain referred from muscles of the head and neck. J Prosthet Dent 1960;10:745-763. 52. Travell J. Mechanical headache. Headache 1967;7:23-29. 53. Travell JG, Simons DG. Myofascial pain and dysfunction; the trigger point manual. Baltimore: Williams & Wilkins; 1983. 54. Travell JG, Simons DG. Myofascial pain and dysfunction: the trigger point manual. Baltimore: Williams & Wilkins; 1992. 55. Dejung B, Grbli C, Colla F, Weissmann R. Triggerpunkttherapie. Bern: Hans Huber; 2003. 56. Rachlin ES, Rachlin IS. Myofascial pain and fibromyalgia, trigger point management. St. Louis: Mosby; 2002. 57. Dommerholt J, Issa T. Differential diagnosis: myofascial pain. In: Chaitow L, editor. Fibromyalgia; a practitioner's guide to treatment. Edinburgh: Churchill Livingstone; 2003. p. 149-177. 58. Bennett RM. The clinical neurobiology of fibromyalgia and myofascial pain: therapeutic implication. Binghamton: Haworth Press; 2002. 59. Harden RN, Bruehl SP, Gass S, Niemiec C, Barbick B. Signs and symptoms of the myofascial pain syndrome: a national survey of pain management providers. Clin J Pain 2000;16(1):64-72. 60. Hendler NH, Kozikowski JG. Overlooked physical diagnoses in chronic pain patients involved in litigation. Psychosomatics 1993;34(6):494-501. 61. Gerwin RD, Dommerholt J. Treatment of myofascial pain syndromes. In: Weiner R, editor. Pain management; a practical guide for clinicians. Boca Raton: CRC Press; 2002. p. 235-249. 62. Gerwin RD, Shannon S, Hong CZ, Hubbard D, Gevirtz R. Interrater reliability in myofascial trigger point examination. Pain 1997;69(1-2):65-73. 63. Russell IJ. Reliability of clinical assessment measures for the classification of myofascial pain syndrome. J Musculoskeletal Pain 1999;7(1/2):309-324. 64. Janda V. Muscle spasm: a proposed procedure for differential diagnosis. J Manual Med 1991;6:136-139. 65. Mense S. Pathophysiologic basis of muscle pain syndromes. In: Fischer AA, editor. Myofascial pain; update in diagnosis and treatment. Philadelphia: W.B. Saunders Company; 1997. p. 23-53.

14

66. Sciotti VM, Mittak VL, DiMarco L, Ford LM, Plezbert J, Santipadri E, et al. Clinical precision of myofascial trigger point location in the trapezius muscle. Pain 2001;93(3):259-66. 67. Scudds RA, Landry M, Birmingham T, Buchan J, Griffin K. The frequency of referred signs from muscle pressure in normal healthy subjects (abstract). J Musculoskeletal Pain 1995;3 (Suppl 1):99. 68. Hong C-Z, Torigoe Y. Electrophysiological characteristics of localized twitch responses in responsive taut bands of rabbit skeletal muscle. J Musculoskeletal Pain 1994;2::17-43. 69. Hong C-Z, Yu J. Spontaneous electrical activity of rabbit trigger spot after transection of spinal cord and peripheral nerve. J Musculoskeletal Pain 1998;6(4):45-58. 70. Wang F, Audette J. Electrophysiological characteristics of the local twitch response with active myofascial pain of neck compared with a control group with latent trigger points. Am J Phys Med Rehabil 2000;79(2):203. 71. Hong CZ. Lidocaine injection versus dry needling to myofascial trigger point. The importance of the local twitch response. Am J Phys Med Rehabil 1994;73(4):256-63. 72. Gerwin RD, Duranleau D. Ultrasound identification of the myofascial trigger point. Muscle Nerve 1997;20(6):767-768. 73. Lewis J, Tehan P. A blinded pilot study investigating the use of diagnostic ultrasound for detecting active myofascial trigger points. Pain 1999;79(1):39-44. 74. Kellgren JH. Observations on referred pain arising from muscle. Clin Sci 1938;3:175-190. 75. Svensson P. Orofacial musculoskeletal pain. In: Giamberardino MA, editor. Pain 2002 - An updated review: refresher course syllabus. Seattle: IASP Press; 2002. p. 447-458. 76. Ashina S, Jensen R, Bendtsen L. Pain sensitivity in pericranial and extracranial regions. Cephalalgia 2003;23(6):456-62. 77. Gupta MK, el-Sheikh MH, Sherif AM, el-Sharani F. Temporomandibular joint (TMJ) myofascial pain dysfunction syndrome (MPDS) non-surgical management. J Pierre Fauchard Acad 1993;7(3):101-6. 78. Mascia P, Brown BR, Friedman S. Toothache of nonodontogenic origin: a case report. J Endod 2003;29(9):608-610. 79. Kleier DJ. Referred pain from a myofascial trigger point mimicking pain of endodontic origin. J Endod 1985;11(9):408-11. 80. Dunteman E, Turner MS, Swarm R. Pseudo-spinal headache. Reg Anesth 1996;21(4):358-60. 81. Carlson CR, Okeson JP, Falace DA, Nitz AJ, Lindroth JE. Reduction of pain and EMG activity in the masseter region by trapezius trigger point injection. Pain 1993;55(3):397-400. 82. Fricton JR, Kroening R, Haley D, Siegert R. Myofascial pain syndrome of the head and neck: a review of clinical characteristics of 164 patients. Oral Surg Oral Med Oral Pathol 1985;60(6):615-623. 83. Fricton JR. Management of masticatory myofascial pain. Semin Orthod 1995;1(4):229-43. 84. Arendt-Nielsen L, Graven-Nielsen T, Svensson P, Jensen TS. Temporal summation in muscles and referred pain areas: an experimental human study. Muscle Nerve 1997;20(10):1311-3. 85. Hong C-Z, Chen Y-N, Twehous D, Hong DH. Pressure threshold for referred pain by compression on the trigger point and adjacent areas. J Musculoskeletal Pain 1996;4(3):61-79. 86. Hong CZ, Kuan TS, Chen JT, Chen SM. Referred pain elicited by palpation and by needling of myofascial trigger points: a comparison. Arch Phys Med Rehabil 1997;78(9):957-60. 87. Jaeger B. Myofascial referred pain patterns: the role of trigger points. Cda J 1985;13(3):27-32. 88. Svensson P, Arendt-Nielson L. Clinical and experimental aspects of temporomandibular disorders. Curr Rev Pain 2000;4(2):158-65.

89. Vecchiet L, Giamberardino MA. Referred pain: clinical significance, pathophysiology and treatment. In: Fischer AA, editor. Myofascial pain: update in diagnosis and treatment. Philadelphia: W.B. Saunders Company; 1997. p. 119-136. 90. Mense S, Hoheisel U. New developments in the understanding of the pathophysiology of muscle pain. J Musculoskeletal Pain 1999;7(1/2):13-24. 91. Simons DG. Referred phenomena of myofascial trigger points. In: Vecchiet L, Albe-Fessard D, Lindblom U, Giamberardino MA, editors. New trends in referred pain and hyperalgesia. Amsterdam: Elsevier Science Publishers; 1993. p. 341-357. 92. Arendt-Nielsen L, Svensson P. Referred muscle pain: basic and clinical findings. Clin J Pain 2001;17(1):11-9. 93. Wright EF. Referred craniofacial pain patterns in patients with temporomandibular disorder. JADA 2000;131:1307-1315. 94. Fukui S, Ohseto K, Shiotani M, Ohno K, Karasawa H, Naganuma Y, et al. Referred pain distribution of the cervical zygopophyseal joints and cervical dorsal rami. Pain 1996;68:79-83. 95. Hong CZ, Simons DG. Pathophysiologic and electrophysiologic mechanisms of myofascial trigger points. Arch Phys Med Rehabil 1998;79(7):863-872. 96. Torebjrk HE, Ochoa JL, Schady W. Referred pain from intraneural stimulation of muscle fascicles in the median nerve. Pain 1984;18:145-156. 97. Dwyer A, Aprill C, Bogduk N. Cervical zygapophyseal joint pain patterns. I: A study in normal volunteers. Spine 1990;15(6):453-457. 98. Neumann M. Trunk Pain. In: Raj PP, editor. Practical management of pain. St. Louis: Mosby Year Book; 1992. p. 258-271. 99. Bellew JW. Lumbar facets: an anatomic framework for low back pain. The Journal of Manual & Manipulative Therapy 1996;4(4):149-156. 100. Mense S. Nociception from skeletal muscle in relation to clinical muscle pain. Pain 1993;54:241-289. 101. Mense S. Muscular nociceptors. J Physiol (Paris) 1977;73(3):233-40. 102. Diehl B, Hoheisel U, Mense S. The influence of mechanical stimuli and of acetylsalicylic acid on the discharges of slowly conducting afferent units from normal and inflamed muscle in the rat. Exp Brain Res 1993;92(3):431-40. 103. Mense S, Meyer H. Different types of slowly conducting afferent units in cat skeletal muscle and tendon. J Physiol 1985(363):403-417. 104. Mense S, Stahnke M. Responses in muscle afferent fibres of slow conduction velocity to contractions and ischaemia in the cat. J Physiol 1983;342:383-97. 105. Wang K, Yu L. Emerging concepts of muscle contraction and clinical implications for myofascial pain syndrome (abstract). In: Gerwin RD, editor. Focus on Pain; 2000; Mesa, AZ: Janet G. Travell, MD Seminar Seriessm; 2000. 106. Brckle W, Sckfull M, Fleckenstein W, Weiss C, Mller W. Gewebe-pO2-Messung in der verspannten Rckenmuskulatur (m. erector spinae). Z. Rheumatol. 1990;49:208-216. 107. Henriksson KG, Bengtsson A, Larsson J, Lindstrom F, Thornell LE. Muscle biopsy findings of possible diagnostic importance in primary fibromyalgia (fibrositis, myofascial syndrome). Lancet 1982;2(8312):1395. 108. Bengtsson A, Henriksson KG, Larsson J. Muscle biopsy in primary fibromyalgia. Light-microscopical and histochemical findings. Scand J Rheumatol 1986;15(1):1-6. 109. Windisch A, Reitinger A, Traxler H, Radner H, Neumayer C, Feigl W, et al. Morphology and histochemistry of myogelosis. Clin Anat 1999;12(4):266-271. 110. Reitinger A, Radner H, Tilscher H, Hanna M, Windisch A, Feigl W. Morphologische Untersuchung an Triggerpunkten. Manuelle Medizin 1996;34:256-262.

15

111. Henriksson KG, Bengtsson A, Lindman R, Thornell LE. Morphological changes in muscle in fibromyalgia and chronic shoulder myalgia. In: Vry H, Merskey H, editors. Progress in fibromyalgia and myofascial pain. Amsterdam: Elsevier; 1993. p. 6173. 112. Heffner RR, Barron SA. The early effects of ischemia upon skeletal muscle mitochondria. J Neurol Sci 1978;38(3):295-315. 113. Simons DG. Triggerpunkte und Myogelose. Manuelle Medizin 1997;35:290-294. 114. Poole S, de Queiroz Cunha F, Ferreira SH. Hyperalgesia from subcutaneous cytokines. In: Watkins LR, Maier SF, editors. Cytokines and pain. Basel: Birkhaueser; 1999. p. 59-87. 115. Kimura I, Okazaki M, Nojima H. Mutual dependence of calcitonin -gene related peptide and acetylcholine release in neuromuscular preparations. Eur J Pharmacol 1997;330:123128. 116. Fernandez HL, Rossa GS, Nadelhaft I. Neurogenic calcitonin gene-related peptide: a neurotrophic factor in the maintenance of acetylcholinesterase molecular forms in adult skeletal muscles. Brain Research 1999;844:8397. 117. Fernandez HL, Chen M, Nadelhaft I, Durr JA. Calcitonin gene-related peptides: their binding sites and receptor accessory proteins in adult mammalian skeletal muscles. Neuroscience 2003;119:335345. 118. Jensen K, Tuxen C, Pedersen-Bjergaard U, Jansen I, Edvinsson L, Olesen J. Pain and tenderness in human temporal muscle induced by bradykinin and 5-hydroxytryptamine. Peptides 1990;11(6):1127-32. 119. Shah J. The use of a microdialysis/acupuncture needle to assess the neurochemical milieu in active and latent myofascial trigger points in the upper trapezius muscle. In: Focus on Pain 2003; 2003; Orlando: Janet G. Travell, MD Seminar Series; 2003. 120. Vyklicky L, Knotkova Urbancova H, Vitaskova Z, Vlachova V, Kress M, Reeh PW. Inflammatory mediators at acid pH activate capsaicin receptors in cultured sensory neurons from newborn rats. J Neurophysiol 1998;79:670676. 121. Sessle BJ. Acute and chronic craniofacial pain: brainstem mechanisms of nociceptive transmission and neuroplasticity, and their clinical correlates. Crit Rev Oral Biol Med 2000;11(1):57-91. 122. Ellrich J, Andersen OK, Messlinger K, Arendt-Nielsen L. Convergence of meningeal and facial afferents onto trigeminal brainstem neurons: an electrophysiological study in rat and man. Pain 1999;82(3):229-37. 123. Marchettini P, Simone DA, Caputi G, Ochoa JL. Pain from excitation of identified muscle nociceptors in humans. Brain Res 1996;740(1-2):109-116. 124. Hoheisel U, Mense S, Simons D, Yu X-M. Appearance of new receptive fields in rat dorsal horn neurons following noxious stimulation of skeletal muscle: a model for referral of muscle pain? Neurosci Lett 1993;153:9-12. 125. Arendt-Nielsen L, Graven-Nielsen T. Deep tissue hyperalgesia. J Musculoskeletal Pain 2002;10(1/2):97-119. 126. Hu JW, Sessle BJ, Raboisson P, Dallel R, Woda A. Stimulation of craniofacial muscle afferents induces prolonged facilitatory effects in trigeminal nociceptive brainstem neurons. Pain 1992;48:53-60. 127. Bendtsen L, Jensen R, Olesen J. Qualitatively altered nociception in chronic myofascial pain. Pain 1996;65:259-264. 128. Airaksinen O, Pontinen PJ. Effects of the electrical stimulation of myofascial trigger points with tension headache. Acupunct Electrother Res 1992;17(4):285-90. 129. Koelbaek Johansen M, Graven-Nielsen T, Schou Olesen A, Arendt-Nielsen L. Generalised muscular hyperalgesia in chronic whiplash syndrome. Pain 1999;83(2):229-34. 130. Hubbard DR, Berkoff GM. Myofascial trigger points show spontaneous needle EMG activity. Spine 1993;18:1803-1807.

131. Simons DG, Hong C-Z, Simons L. Prevalence of spontaneous electrical activity at trigger spots and control sites in rabbit muscle. J Musculoskeletal Pain 1995;3:35-48. 132. Simons DG. Do endplate noise and spikes arise from normal motor endplates? Am J Phys Med Rehabil 2001;80:134-140. 133. Coupp C, Midttun A, Hilden J, Jrgensen U, Oxholm P, Fuglsang-Frederiksen A. Spontaneous needle electromyographic activity in myofascial trigger points in the infraspinatus muscle: A blinded assessment. J Musculoskeletal Pain 2001;9(3):7-17. 134. Simons DG, Hong C-Z, Simons LS. Endplate potentials are common to midfiber myofascial trigger points. Am J Phys Med Rehabil 2002;81(3):212-222. 135. Wiederholt WC. "End-plate noise" in electromyography. Neurology 1970;20(3):214-24. 136. Ito Y, Miledi R, Vincent A. Transmitter release induced by a 'factor' in rabbit serum. Proc R Soc Lond B Biol Sci 1974;187:235-241. 137. Heuser J, Miledi R. Effects of lanthanum ions on function and structure of frog neuromuscular junctions. Proc R Soc Lond B Biol Sci 1971;179(56):247-60. 138. Shah J, Phillips T, Danoff JV, Gerber LH. A novel microanalytical technique for assaying soft tissue demonstrates significant quantitative biomechanical differences in 3 clinically distinct groups: normal, latient and active. Arch Phys Med Rehabil 2003;84:A4. 139. Liley AW. An investigation of spontaneous activity at the neuromuscular junction. J Physiol 1956;132:650-666. 140. Maselli RA. End-plate electromyography: use of spectral analysis of end-plate noise. Muscle Nerve 1997;20(1):52-8. 141. Brown WF, Varkey GP. The origin of spontaneous electrical activity at the end-plate zone. Ann Neurol 1981;10(6):55760. 142. Simons DG, Travell J. Myofascial trigger points, a possible explanation. Pain 1981;10(1):106-9. 143. Shenoi R, Nagler W. Trigger points related to calcium channel blockers (letter). Muscle Nerve 1996;19(2):256. 144. Lewis C, Gevirtz R, Hubbard D, Berkoff G. Needle trigger point and surface frontal EMG measurements of psychophysiological responses in tension-type headache patients. Biofeedback & Self-Regulation 1994;3:274-275. 145. McNulty WH, Gevirtz RN, Hubbard DR, Berkoff GM. Needle electromyographic evaluation of trigger point response to a psychological stressor. Psychophysiology 1994;31(3):313-316. 146. Banks SL, Jacobs DW, Gevirtz R, Hubbard DR. Effects of autogenic relaxation training on electromyographic activity in active myofascial trigger points. J Musculoskeletal Pain 1998;6(4):23-32. 147. Chen JT, Chen SM, Kuan TS, Chung KC, Hong CZ. Phentolamine effect on the spontaneous electrical activity of active loci in a myofascial trigger spot of rabbit skeletal muscle. Arch Phys Med Rehabil 1998;79(7):790-794. 148. Hubbard DR. Chronic and recurrent muscle pain: pathophysiology and treatment, and review of pharmacologic studies. J Musculoskeletal Pain 1996;4:123-143. 149. Chen JT, Chen SM, Kuan TS, Hong C-Z. Inhibitory effect of calcium channel blocker on the spontaneous electrical activity of myofascial trigger point. J Musculoskeletal Pain 1998;6(Suppl. 2):24. 150. Hou CR, Chung KC, Chen JT, Hong CZ. Effects of a calcium channel blocker on electrical activity in myofascial trigger spots of rabbits. Am J Phys Med Rehabil 2002;81(5):342-9. 151. Delaney J, Leong KS, Watkins A, Brodie D. The shortterm effects of myofascial trigger point massage therapy on cardiac autonomic tone in healthy subjects. J Adv Nurs 2002;37(4):364-371. 152. Geppetti P, Del Bianco E, Patacchini R, Santicioli P, Maggi CA, Tramontana M. Low pH-induced release of calcitonin gene-related peptide from capsaicin-sensitive sensory nerves:

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mechanism of action and biological response. Neuroscience 1991;41(1):295-301. 153. Santicioli P, Del Bianco E, Geppetti P, Maggi CA. Release of calcitonin gene-related peptide-like (CGRP-LI) immunoreactivity from rat isolated soleus muscle by low pH, capsaicin and potassium. Neuroscience Letters 1992;143:19-22. 154. Steen KH, Steen AE, Reeh PW. A dominant role of acid pH in inflammatory excitation and sensitization of nociceptors in rat skin, in vitro. J Neurosci 1995;15:39823989. 155. Averbeck B, Izydorczyk I, Kress M. Inflammatory mediators release calcitonin gene-related peptide from dorsal root ganglion neurons of the rat. Neuroscience 2000;98(1):135140. 156. Borg-Stein J, Simons DG. Focused review: myofascial pain. Arch Phys Med Rehabil 2002;83(3 Suppl 1):S40-7, S48-9. 157. Gerwin RD. Management of persons with chronic pain. In: Ozer MN, editor. Management of persons with chronic neurologic illness. Boston: Butterworth-Heinemann; 2000. p. 265-290. 158. Grbli C, Dommerholt J. Myofasziale Triggerpunkte; Pathologie und Behandlungsmglichkeiten. Manuelle Medizin 1997;35:295-303. 159. de Paiva A, Meunier FA, Molgo J, Aoki KR, Dolly JO. Functional repair of motor endplates after botulinum neurotoxin type A poisoning: biphasic switch of synaptic activity between nerve sprouts and their parent terminals. Proc Natl Acad Sci U S A 1999;96(6):3200-3205. 160. Freund B, Schwartz M, Symington M. Botulinum toxin: new treatment for temporomandibular disorders. Br J Oral Maxillofacial Surg 2000;38:466-471.

161. Simons DG, Simons LS. Chronic Myofascial Pain Syndrome. In: Tollison CD, Satterthwaite JR, Tollison JW, editors. Handbook of Pain Management. Baltimore: Williams & Wilkins; 1994. p. 556-577. 162. Passero PL, Wyman BS, Bell JW, Hirschey SA, Schlosser WS. Temporomandibular joint dysfunction syndrome. A clinical report. Phys Ther 1985;65(8):1203-7. 163. Mannheimer JS. Prevention and Restoration of Abnormal Upper Quarter Posture. In: Gelb H, editor. New Concepts in Craniomandibular and Chronic Pain Management. London: MosbyWolfe; 1994. p. 93-161. 164. Paris SV. Cervical symptoms of forward head posture. Top Geriatr Rehabil 1990;5(4):11-19. 165. Hanten WP, Olsen SL, Butts NL, Nowicki AL. Effectiveness of a home program of ischemic pressure followed by sustained stretch for treatment of myofascial trigger points. Phys Ther 2000;80(10):997-1003. 166. Lewit K. The needle effect in the relief of myofascial pain. Pain 1979;6:83-90. 167. Hong C-Z. Considerations and recommendations regarding myofascial trigger point injection. J Musculoskeletal Pain 1994;2:29-59. 168. Dommerholt J. Muscle pain syndromes. In: Cantu RI, Grodin AJ, editors. Myofascial Manipulation. Gaithersburg: Aspen; 2001. p. 93-140.

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