There are few randomized, controlled studies of the use of BoNT in neck and upper back pain. Göbel et al. [16] found that BoNT-A (Dysport^®) significantly reduced or eliminated upper back myofascial pain compared to saline (51 vs. 26 %, p  =  0.002) 5 weeks after injection. However, another study of BoNT-A treatment of pain emanating from cervicothoracic myofascial TrPs showed that low dose (50 units total), higher dose (100 units total), and saline all resulted in a decline in pain and disability scores, with no benefit of BoNT over placebo, but those in the subgroup of subjects who received a second injection of BoNT-A experienced such a high incidence of becoming asymptomatic that the authors concluded that further studies were warranted. In contrast, a RCT, double-blinded study of the effect of BoNT-A in the treatment of refractory neck pain, in which 33 of 47 subjects had neck injury (72 %), resulted in a significant number of subjects classified as excellent responders who had a ≥50 % decrease in VAS for pain, ≥30 % reduction in pain days, and 2 grades or more improvement in the Modified Oswestry Pain Questionnaire (6/23 in the BoNT-A group vs.1/21 in the control group). Pain intensity was greater in the BoNT-A group at baseline, but was significantly decreased at 2 months compared to the saline control group (p  <  0.0018). Injections were made in the trapezius, splenius, and rhomboid muscles as clinically indicated, using 20 units per injection site and ranged in total from 150 to 300 units. No information was given about the criteria for selection of specific injection sites, but it appears that the injection sites were selected to give a general distribution of BoNT-A in the muscles treated, as opposed to injecting in myofascial trigger points. This well-designed and executed study clearly shows efficacy of BoNT-A treatment for chronic neck pain.

Pain in myofascial pain syndrome (MPS) is generated by a tender, taut band that is the fundamental feature of the myofascial trigger point (MTrP). It is thought that relaxation of the taut band through inhibition of acetylcholine release from the motor nerve terminal at the neuromuscular generation and inhibition of the release of neurotransmitters at the sensory nerve will result in decreased pain from MTrPs. However, the few studies that have looked at this have not supported this concept. Often-quoted studies include those of Ferrante et al. [17], Graboski et al. [18], Kamanli et al. [19], and Ojala et al. [20]. Ferrante et al. [17] stopped all pain medication prior to the trial injections, then gave all subjects amitriptyline, ibuprofen 800 mg qid, and prn propoxyphene/apap. In this RCT, subjects were given either BoNT-A (10, 25, or 50 units/trigger point) or saline in up to 5 trigger points. Patients were excluded if they had more than 5 trigger points or more than 2 trigger points in on trapezius muscle, or more than one trigger point in any other single surface muscle. There was no difference in rescue medication, or in pressure pain threshold between saline injected groups and those injected with BoNT-A. Both the lowest dose and highest dose BoNT-A outperformed saline, but not to a significant degree. Some of the possibilities include the fact that all subjects were treated with adjuvant pain medication and that saline is not an inactive control. Finally, the standard deviation of the sum of pain intensity differences, a reflection of the primary outcome measure, was so great that differences between the saline group and the BoNT-A were not significant. For these reasons, the results of this study cannot be seen as conclusive. Graboski et al. [18] compared BoNT-A to bupivicaine. A maximum of 8 trigger points were injected with either 25 units of BoNT-A or saline in this RCT. The end point was a return to 75 % of pre-injection pain. At that time, subjects were injected with the other substance (a crossover study). There was no statistically significant difference between the two treatments. Bupivicaine was considered cheaper. Outcome measures were changed in pain scores and duration of relief. Although there was no significant difference between groups, there was a definite trend toward greater decrease in pain and greater duration of effect with BoNT-A. Possible issues were the low number of subjects completing the trial (17 subjects in all) and the limited number of trigger points injected. Kamanli et al. [19] compared BoNT-A, lidocaine, and dry needling. Pain scores were lower in the subjects treated with BoNT-A and dry needling, and visual analogue scale significantly decreased in the lidocaine and BoNT-A groups at the single follow-up visit of 4 weeks. A single trigger point was treated. BoNT-A was not inferior to lidocaine or dry needling. However, in this study, as well as in the other two studies, no attempt was made to provide a comprehensive treatment to clear all relevant trigger points. In clinical practice, one would treat all of the trigger points deemed to be relevant in producing a pain syndrome. In this regard, inactive trigger points that are known to cause dysfunction [21] also need to be treated. In partial treatments, trigger points tend to recur more quickly. Studies that use pressure pain thresholds as a measure have not shown that this measurement reliably reflects inactivation of trigger points.

Ojala et al. [20] did a single-blind, RCT, crossover design, injecting either saline or BoNT-A in up to six neck and shoulder muscles bilaterally and then injecting the trigger points with the other substance 1 month later. There was no difference between groups 1 month after the second injection when subjects had received both saline and BoNT-A 1 month apart. However, after the first month, before the saline group received BoNT-A, subjects treated with BoNT-A had a significantly greater decrease in pain than those treated with saline. BoNT-A has a peak motor effect at about 6 weeks, and effectiveness is maintained from 10 to 14 weeks in most subjects. Hence, one would expect a difference 1 month after the first injection and no difference 1 month after the crossover injection.

There are a number of other studies that address this issue. Pain in patients with temporomandibular joint disorders was treated with BoNT-A injected into the masseter and temporalis muscles in a randomized, controlled study [22]. The result was a decrease in pain and an improvement in psychological status. Both the studies of Göbel et al. [16] and Wheeler et al. [23] were suggestive of a benefit for BoNT at a certain time and under certain circumstances.

It helps to be very clear in defining the desired outcome using BoNT. All studies show that BoNT treatment of myofascial trigger points can respond well to BoNT, but the placebo effect has also been striking. It is essentially like giving a lidocaine trigger point injection that lasts between 10 and 14 weeks in duration. The local twitch response that marks a successful trigger point injection with lidocaine is generally lost after BoNT injection. The number of lidocaine trigger point injections needed to treat an MPS is usually reduced and sometimes eliminated altogether for the duration of action of the toxin. The effectiveness of the toxin in MPS seems to depend on the care with which the trigger point zone is injected and the comprehensive clearing of TrPs in a functional muscle unit. Treatment of trigger points in only one muscle instead of a functional muscle unit may be a reason why spontaneous pain was not reduced 28 days after BoNT-A was injected in an infraspinatus muscle trigger point [24].