Myofascial pain research
Uncovering the biochemical milieu of myofascial trigger points using in vivo microdialysis: An application of muscle pain concepts to myofascial pain syndrome

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Summary

This article discusses muscle pain concepts in the context of myofascial pain syndrome (MPS) and summarizes microdialysis studies that have surveyed the biochemical basis of this musculoskeletal pain condition. Though MPS is a common type of non-articular pain, its pathophysiology is only beginning to be understood due to its enormous complexity. MPS is characterized by the presence of myofascial trigger points (MTrPs), which are defined as hyperirritable nodules located within a taut band of skeletal muscle. MTrPs may be active (spontaneously painful and symptomatic) or latent (non-spontaneously painful). Painful MTrPs activate muscle nociceptors that, upon sustained noxious stimulation, initiate motor and sensory changes in the peripheral and central nervous systems. This process is called sensitization. In order to investigate the peripheral factors that influence the sensitization process, a microdialysis technique was developed to quantitatively measure the biochemical milieu of skeletal muscle. Biochemical differences were found between active and latent MTrPs, as well as in comparison with healthy muscle tissue. In this paper we relate the findings of elevated levels of sensitizing substances within painful muscle to the current theoretical framework of muscle pain and MTrP development.

Introduction

Myofascial pain syndrome (MPS) is a major progenitor of non-articular local musculoskeletal pain and tenderness that affects every age group, and is commonly recognized as “muscle knots” (Kao et al., 2007). MPS has been associated with numerous pain conditions including radiculopathies, joint dysfunction, disk pathology, tendonitis, craniomandibular dysfunction, migraines, tension-type headaches, carpal tunnel syndrome, computer-related disorders, whiplash-associated disorders, spinal dysfunction, and pelvic pain and other urologic syndromes, post-herpetic neuralgia, and complex regional pain syndrome (Borg-Stein and Simons, 2002).

Characterized by a physical finding and symptom cluster, MPS lacked demonstrable pathology and attracted little research attention until recently. Although the specific pathophysiological basis of MTrP development and symptomatology is unknown, several promising lines of scientific study (i.e. histological, neurophysiological, biochemical, and somatosensory) have revealed objective abnormalities (Reitinger et al., 1996; Windisch et al., 1999; Mense, 2003; Shah et al., 2005, Shah et al., 2008; Kuan et al., 2007; Niddam et al., 2007). These findings suggest that myofascial pain is a complex form of neuromuscular dysfunction consisting of motor and sensory abnormalities involving both the peripheral and central nervous systems. MPS is not to be confused with fibromyalgia syndrome, which is ascribed to a collection of complaints including chronic widespread pain, accompanied by tactile allodynia, fatigue, sleep disturbance, and psychological distress (Wolfe et al., 1990).

Section snippets

Historical terminology

Since muscle pain and particularly MPS is described as diffuse and can often refer to deep somatic tissue, terminology regarding muscle pain has been controversial. The first descriptions of “muscular rheumatism” were made by a French physician, de Baillou, in the 16th century (Stockman, 1904). Later observations by the British physician Balfour in 1816 described nodular tumors and thickenings (Stockman, 1904). In the early 20th century, literature on muscle pain used several terms that

Myofascial trigger point diagnostic criteria

Myofascial pain is identified by palpating skeletal muscle for myofascial trigger points (MTrPs). A MTrP is classically defined by Simons and Travell as “a hyperirritable spot in skeletal muscle that is associated with a hypersensitive palpable nodule in a taut band” (Simons et al., 1999). Figure 1 illustrates the trigger point complex. MTrPs are sensitive to pressure and are stiffer than surrounding tissue. Palpation of a MTrP produces local pain and sensitivity, as well as diffuse and

Electrophysiology

The pathophysiology of MTrPs is incompletely understood. MTrPs are hypothesized to be a result of physiological dysfunction within the neuromuscular junction and the surrounding connective tissue. There is evidence that motor endplates of neurons terminating at the muscle fibers of a MTrP have abnormal activity. Electromyographic studies have revealed spontaneous electrical activity (SEA) generated at MTrP loci that was not seen in surrounding tissue (Hubbard and Berkoff, 1993). Originally

Nociceptor properties

Sensory processing and pain perception are key aspects in the description of MPS, along with the abnormal motor findings mentioned above. Transduction of local pain sensation often begins with the sensitization and activation of nociceptive sensory receptors. Nociceptors are located at free nerve endings in muscle, joint, skin, viscera, and blood vessels. Furthermore, muscle nociceptors may make up 50% of the composition of muscle nerves (Willard, 2008). The abundance of these nociceptors may

Uncovering the biochemical milieu of myofascial trigger points

We developed a microanalytical system to sample the unique biochemical milieu of substances related to pain and inflammation in muscle tissue with and without MTrPs (Shah et al., 2005). This system employed a minimally invasive 30-gauge needle capable of in vivo collection of small volumes (∼0.5 μl) at sub nanogram levels (<75 kDa). The needle (Figure 4) has the same size and shape as an acupuncture needle and allows simultaneous sampling of skeletal muscle tissue when an LTR is elicited by

pH

Acidic pH levels within muscle have been shown to be associated with pain and lowered nociceptor threshold sensitivity (Issberner et al., 1996). This association is supported by the microdialysis studies above, which found acidic pH levels in muscles containing active (painful) MTrPs. In a study of mouse model hyperalgesia, Sluka et al. (2001) showed that unilateral injections of acidic saline into the gastrocnemius resulted in long-lasting bilateral mechanical hyperalgesia. Contralateral

Conclusion

Myofascial trigger points are a very common and complex component of non-articular musculoskeletal pain and dysfunction. However, they are also regularly found in asymptomatic individuals. Therefore, our studies sought to determine if there are biochemical aspects that differentiate active MTrPs from latent MTrPs, and muscle without MTrPs. Our microanalytical technique permits direct sampling of the biochemical milieu of MTrPs, including bioactive substances (e.g., inflammatory mediators,

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