Myofascial pain syndrome (MPS) is a common pain disorder and a major source of work interruption and disability. It is characterized by focal pain felt in the area of trigger points. Trigger points include tight muscle bands (taut band) with sensitivity to touch both to induce pain (local or referred) and muscle twitch response. Trigger points can be active or latent (inactive). Active trigger points produce spontaneous pain and after being pressed whereas latent TPs may generate pain only when they are pressed upon. Latent TPs can be activated by prolonged exercise, low-load repetitive muscle activity, persistent stress, and prolonged ischemia of the muscle (Celik and Mutlu 2013).

The criteria of Simon’s et al. (1999) for trigger points is generally accepted and used in clinical practice. It consists of: (1) presence of a palpable taut band in a skeletal muscle, (2) presence of a hypersensitive tender spot in the taut band, (3) local twitch response provoked by the snapping palpation of the taut band, and (4) reproduction of the typical referred pain pattern of the trigger point in response to compression. These criteria have shown good inter-examiner reproducibility and reliability (Gerwin et al. 1997).

Myofascial pain syndrome is reported with a variable prevalence of 30–93 %, is common in patients with decreased motor activity, has peak age presentation between ages 30–50 years, and is more common among women (Fricton et al. 1985; Gerwin 2001; Han and Harrison 1997; Simons et al. 1999).

The trigger points in patients with MPS consist of hypersensitive indurated muscle fibers called “taut bands.” Taut bands show an increased number of spontaneous, small-amplitude ongoing end plate potential discharges at rest (end plate potential) indicating a rich acetylcholine content (Simons et al. 2002, 2008). Increased level of acetylcholine in these muscle bands makes them sensitive to touch and elicits the “twitch response” (Ferguson et al. 2004).

Exactly how trigger points develop in the muscles of patients with MPS is unclear. The integral theory of Simons et al. (1999) proposes ischemic/metabolic derangement of the muscle and local failure of energy. Hypo-perfused muscle develops areas of low pH that inhibit acetylcholine esterase and lead to local accumulation of acetylcholine.

Development of trigger points in the muscle causes spontaneous or pressure-induced local muscle pain and referred pain. Pain may be partly related to low pH, increased local accumulation of protons (H+), and acid-sensing channels in the extracellular fluid of trigger points affecting terminal nerve endings.

The mechanism of pain induction in MPS has been investigated by Shah et al. (2005, 2008). These investigators have shown increased levels of pain mediators such as substance P and CGRP and of inflammatory mediators such as cytokines in both active and latent trigger points (less in latent). Local accumulation of pain mediators and inflammatory elements leads to peripheral sensitization of nerve endings and dorsal root ganglia. Continued peripheral sensitization causes central sensitization of spinal cord neurons leading to pain chronicity (Aokie and Francis 2011).

The treatment of myofascial pain syndrome is focused on deactivation of active trigger points. A number of pharmacological and non-pharmacological approaches have been employed. Non-pharmacological approaches include massage, compression, stretching (Travell and Simons 1992; Esenyel et al. 2000), superficial heat (74.5 C), laser therapy (Uemoto et al. 2013), ultrasound with continuous mode 1.25–1.5 w/cm^2j (Blikstad and Gemmell 2008; Srbely et al. 2008), and TENS employing pulse duration of 100–110 uS/frequency—70–80 HZ for 25 min (Santiesteban 1985; Rachlin 1994).

Recently, in a double-blind, placebo-controlled study, Tekin et al. (2013) reported efficacy of dry needling causing both short-term relief of pain and improved performance of daily activities (p < 0.0 %) in patients with MPS. Another open and prospective study found a positive effect of dry needling comparable with physical therapy in deactivation of trigger points (Rayegani et al. 2014). Acupuncture has also been reported to be partially effective in a controlled study (Sun et al. 2010).

The pharmacological approach encompasses a large number of agents used either alone or more often in combination. These include nonsteroidal anti-inflammatory drugs (NSAID), muscle relaxants, antidepressants, and antiepileptic analgesic agents. Trigger point injections with anesthetic agents and steroids are also often used. Despite the availability of a wide range of treatment modalities for deactivation of trigger points in MPS, it is generally believed that current strategies offer only transient pain relief (Desai et al. 2014; Zhou and Wang 2014). Novel therapeutic modalities with acceptable safety profile and infrequent side effects are needed to provide more sustained relief.

With increasing recognition of the analgesic effects of BoNTs in human subjects (Jabbari and Machado 2011), there is a high level of interest among clinicians at academic and nonacademic settings to use this mode of therapy for alleviating muscle pain including the pain associated with MFPS. This interest is reflected in a recent increase in the number of reviews published on this subject (Gerwin 2014; Adelowo et al. 2013; Zhou and Wang 2014; Desai et al. 2014).

Ten studies have investigated the effect of BoNTs in deactivating trigger points and relieving the pain of MPS (Table 8.1):

Twenty years ago (1994), Cheshire and colleagues first suggested the efficacy of onabotulinumtoxinA (onaA) in MPS based on a small double-blind crossover study. Six patients (four women), 35–50 years of age, participated in and completed the 8-week-duration study. Compared to saline, patients who had injections of onaA into trigger points of trapezius and cervical paraspinal muscles showed significant (p < 0.05) reduction of pain (using VAS) and perception of unpleasantness (by patient account) at 2, 4, and 8 weeks. The dose of onaA was 50 units diluted in 4 cc of normal saline and equally divided between two and three sites.

Wheeler et al. (1998) studied 33 patients with myofascial pain syndrome affecting cervical and upper thoracic paravertebral muscles. Patients were randomized into three groups: high-dose (100 units) and low-dose (50 units) onabotulinum toxin and saline. Injections were introduced into a single trigger point identified by palpation-evoked referred pain. If patients had several trigger points, only the one causing the most pain was injected. Patients’ response was measured by pressure algometer, patient’s global assessment of pain, as well as neck and pain disability scale before injection and at weeks 1, 3, 6, 9, 12, and 16 postinjection. A positive response was defined as total absence of pain with all three measures in three consecutive evaluations. No significant difference was found between the three groups. Nonetheless, both onaA and saline improved pain significantly compared to the baseline values. Eleven patients received a second injection of 100 units. Among these patients, those whose first injection also consisted of 100 units of onaA had better pain control (details were not provided).

In another study (Freund and Schwartz 2000), the effect of onabotulinumtoxinA (14 subjects) was compared with that of saline (12 subjects) in myofascial pain syndrome. Five trigger points were injected in each patient. Assessments included VAS, total neck range of motion (ROM), and Vernon-Mior objective function index. All were assessed before injection and at weeks 2 and 4 postinjection. Subjects who received onaA demonstrated significant (p < 0.01) pain relief (assessed by VAS) and improved neck range of motion at 4 weeks posttreatment.

In a more recent study, Wheeler et al. (2001) evaluated 50 patients injected with onabotulinumtoxinA at multiple trigger points at the discretion of the physician. The total number of injected sites (mean and range) is not clear from the publication. Most patients were injected into trapezius (36) and low cervical (12) regions. The mean dose was 231 units with 50 units as 1 standard deviation. Evaluation methods included pain algometer, patient and physician global assessment of pain, neck and pain disability scale, as well as both physical and mental SF36 (weeks 0, 4, 8, 12, 16). Both onaA and saline groups showed significant improvement in all assessments (except SF36), but the difference between the drug and placebo groups was not significant.

Ferrante et al. (2005) conducted a large single-center study on 132 patients with MPS. Subjects were randomized into four groups (three onaA groups and one saline) and studied blindly over 16 weeks. In the toxin groups, investigators injected 10, 25, and 50 units into the trigger points (up to five). Before treatment, all patients were taken off their pain medications and were put on a new tripartite regimen: amitriptyline (10–75 mg), ibuprofen 800 mg every 6 h, and propoxyphene/acetaminophen as a rescue drug. Pain relief and quality of life were assessed by VAS (past 24 h), pain algometry (sensitivity to pressure), and SF36 questionnaires at 1, 2, 4, 6, and 12 weeks. No significant differences were noted between any of the four groups in respect to any of the assessed parameters. In all four groups, including the placebo group, patients demonstrated significant improvement of their pain (assessed by VAS and pain algometer) and used less rescue medication compared to their baseline values before treatment, however (p < 0.001).

In another study (double-blind, crossover), Ojala et al. (2006) assessed the efficacy of onaA in 31 patients with MFPS. Patients had two injections, 4 weeks apart. onaA injections consisted of five units into each trigger point; the total dose injected varied between 15 and 35 units. Pain intensity was assessed by VAS. There was no difference between onaA and saline in respect to pain relief, but both alleviated pain significantly compared to the baseline level (p < 0.001); >60 % of the subjects reported 30–50 % pain reduction over the course of the study.

Qerama et al. (2006) compared injection of 50 units of onaA into a single trigger point with saline in 30 patients. Pain level was measured at baseline and day 3 and day 28 after injection by VAS and trigger point pressure sensitivity. No difference was detected between onaA and saline. Subjects in both groups, however, experienced significant reduction in pain (>30 %) compared to baseline.

In 2006, Gobel et al. conducted a well-designed, double-blind, placebo-controlled, multicenter study in 145 subjects who had moderate to severe pain affecting the neck and shoulder muscles. Injections of saline or aboA (40 units per point) were made into the ten most tender trigger points. The primary outcome was the proportion of patients with mild or no pain at week 5 compared to baseline. At week 5, significantly more patients (51 %) in the aboA group reported mild or no pain compared to the patients in the placebo group (26 %; p = 0.002). During the period between week 5 and the study’s last evaluation, patients in the aboA group experienced significantly more days per week without pain (p = 0.036) and significantly more days per week with no or mild pain (p = 0.023) compared with patients in the placebo group.

In another small blinded study (Lew et al. 2008), 15 subjects with onaA injections were compared with 14 subjects who received saline injection. The dose of onaA was 50 units/trigger point. The maximum dose was 200 units injected into four trigger points, with no more than two trigger points per side. Assessments included VAS for pain, quality of life by SF36, and neck disability index (NDI) performed at week 1 and months 1, 2, 3, 4, and 6. No significant difference was noted between onaA- and saline-treated subjects although all assessed values showed some improvement in the onaA group over the duration of the study. The authors concluded that patients in both groups noted improvement in assessed parameters over baseline, but the details and magnitude of improvements were not reported.