A Critical Appraisal of the Evidence for Botulinum Toxin Type A in the Treatment for Cervico‐Thoracic Myofascial Pain Syndrome

Myofascial pain syndrome (MPS) is a musculoskeletal condition characterized by regional pain and muscle tenderness associated with the presence of myofascial trigger points (MTrPs). The last decade has seen an exponential increase in the use of botulinum toxin (BTX) to treat MPS. To understand the medical evidence substantiating the role of therapeutic BTX injections and to provide useful information for the medical practitioner, we applied the principles of evidence‐based medicine to the treatment for cervico‐thoracic MPS. A search was conducted through MEDLINE (PubMed, OVID, MDConsult), EMBASE, SCOPUS and the Cochrane database for the period 1966 to 2012 using the following keywords: myofascial pain, muscle pain, botulinum toxin, trigger points, and injections. A total of 7 trials satisfied our inclusion criteria and were evaluated in this review. Although the majority of studies found negative results, our analysis identified Gobel et al.'s as the highest quality study among these prospectively randomized investigations. This was due to appropriate identification of diagnostic criteria, excellent study design and objective endpoints. The 6 other identified studies had significant failings due to deficiencies in 1 or more major criteria. We conclude that higher quality, rigorously standardized studies are needed to more appropriately investigate this promising treatment modality.     

Effectiveness of Botulinum Toxin A in Treatment of Hemiplegic Shoulder Pain: A Systematic Review and Meta-analysis

ObjectiveTo evaluate the effectiveness of botulinum toxin A (BTX-A) in the treatment of hemiplegic shoulder pain.Data SourcesPubMed, EMBASE, Elsevier, Springer, Cochrane Library, Physiotherapy Evidence Database, CNKI, and VIP were researched from the earliest records to September 1, 2020.Study SelectionRandomized controlled trials that compared shoulder BTX-A injections vs a control intervention in patients with a history of hemiplegic shoulder pain after stroke were selected. Among the 620 records screened, 9 trials with 301 eligible patients were included.Data ExtractionOutcome data were pooled according to follow-up intervals (1, 2, 4, and 12 wk). The primary evaluation indices were pain reduction (visual analog scale [VAS] score) and range of motion (ROM) improvement. The second evaluation indices were upper limb functional improvement, spasticity improvement, and incidence of adverse events. Cochrane risk-of-bias was used to assess the methodological quality of studies independently by 2 evaluators.Data SynthesisMeta-analysis revealed a statistically significant decrease in the VAS score in the BTX group vs the control group at 1, 4, and 12 weeks postinjection (wk 1: standardized mean difference [SMD], 0.91; 95% confidence interval [CI], 0.27 to 1.54; wk 4: SMD, 1.63; 95% CI, 0.76 to 2.51; wk 12: SMD, 1.96; 95% CI, 1.44 to 2.47). Furthermore, the meta-analysis demonstrated a statistically significant increase in abduction at 1, 4, and 12 weeks postinjection (wk 1: SMD, 3.71; 95% CI, 0 to 7.41; wk 4: SMD, 8.8; 95% CI, 2.22 to 15.37; wk 12: SMD, 19.59; 95% CI, 9.05 to 30.13) and external rotation at 1, 2, 4 weeks postinjection (wk 1: SMD, 5.67; 95% CI, 0.88 to 10.47; wk 2: SMD, 9.62; 95% CI, 5.57 to 13; wk 4: SMD, 6.89; 95% CI, 2.45 to 11.33) in the BTX group.ConclusionsBTX-A injection provided greater analgesic effects and increased shoulder abduction and external rotation ROM compared with steroid or placebo injection for the treatment of HSP.     

Evidence for the Use of Botulinum Toxin in the Chronic Pain Setting—A Review of the Literature

▪ Abstract:   A significant proportion of chronic pain is of musculoskeletal origin. Botulinum toxin (BTX) has been successfully used in the treatment of spasmodic torticollis, limb dystonia, and spasticity. Investigators have, thus, become interested in its potential use in treating many chronic pain conditions. Practitioners have used BTX, outside the product license, in the treatment of refractory myofascial pain syndrome and neck and low back pain (LBP). This article reviews the current evidence relating to chronic pain practice. There is evidence supporting the use of both BTX type A and type B in the treatment of cervical dystonias. The weight of evidence is in favor of BTX type A as a treatment in: pelvic pain, plantar fasciitis, temporomandibular joint dysfunction associated facial pain, chronic LBP, carpal tunnel syndrome, joint pain, and in complex regional pain syndrome and selected neuropathic pain syndromes. The weight of evidence is also in favor of BTX type A and type B in piriformis syndrome. There is conflicting evidence relating to the use of BTX in the treatment whiplash, myofascial pain, and myogenous jaw pain. It does appear that BTX is useful in selected patients, and its duration of action may exceed that of conventional treatments. This seems a promising treatment that must be further evaluated. ▪     

Analgesic Effect of Botulinum Toxin A in Myofascial Pain Syndrome Patients Previously Treated with Local Infiltration of Anesthetic and Steroids

The purpose of this study was to evaluate the analgesic effect of botulinum toxin A (BoNTA) injections in patients with myofascial pain syndrome (MPS) who were previously treated with the local infiltration of anesthetic and steroids (LIAS). The study included a retrospective phase and a longitudinal open-label prospective phase, which were conducted on consecutive patients with MPS previously treated with the local infiltration of anesthetic (levobupivacaíne 0.25%) and steroids (triamcinolone 40 mg). Eligible patients were treated with a single intramuscular injection of BoNTA (Botox; Allergan, Inc., Irvine, CA). The treatment efficacy was determined according to the degree of pain relief obtained. Eighty-two patients met the inclusion/exclusion criteria and were included in the study. Successful results were obtained for 32 (39.0%) and 30 (36.6%) patients, during treatment with BoNTA and LIAS, respectively. The mean (standard deviation) length of the analgesic effect was significantly longer with BoNTA (29.6 [SD = 17.7] weeks) than with LIAS (8.5 [SD = 6.4] weeks), P <.0001. As regards the side effects, 19 (23.2%) patients reported transient soreness at the injection site for 2 to 3 days with BoNTA. The MPS patients previously treated with a local infiltration of anesthetic and steroids who then received a single injection of BoNTA experienced significantly reduced pain for a relatively long time.     

Myofascial Low Back Pain Treatment

Pseudotumor cerebri syndrome (PTCS) refers to the primary and secondary disorders that cause elevated intracranial pressure without an intracranial mass lesion, ventriculomegaly, or central nervous system infection or malignancy. Headache is the most frequent symptom of PTCS, but there is considerable overlap between the headache features of raised intracranial pressure and the headache features of primary headache disorders. We review headache subtypes that occur in PTCS, non-headache features that help distinguish PTCS from other headache types, changes to the diagnostic criteria for PTCS with and without papilledema, and headache treatment strategies as they apply to PTCS.     

Botulinum Toxin A in the Treatment of Chronic Tension-Type Headache With Cervical Myofascial Trigger Points: A Randomized, Double-Blind, Placebo-Controlled Pilot Study

Objective.— To evaluate the efficacy of botulinum toxin A (BT-A) as a prophylactic treatment for chronic tension-type headache (CTTH) with myofascial trigger points (MTPs) producing referred head pain. Background.— Although BT-A has received mixed support for the treatment of TTH, deliberate injection directly into the cervical MTPs very often found in this population has not been formally evaluated. Methods.— Patients with CTTH and specific MTPs producing referred head pain were assigned randomly to receive intramuscular injections of BT-A or isotonic saline (placebo) in a double-blind design. Daily headache diaries, pill counts, trigger point pressure algometry, range of motion assessment, and responses to standardized pain and psychological questionnaires were used as outcome measures; patients returned for follow-up assessment at 2 weeks, 1 month, 2 months, and 3 months post injection. After 3 months, all patients were offered participation in an open-label extension of the study. Effect sizes were calculated to index treatment effects among the intent-to-treat population; individual time series models were computed for average pain intensity. Results.— The 23 participants reported experiencing headache on a near-daily basis (average of 27 days/month). Compared with placebo, patients in the BT-A group reported greater reductions in headache frequency during the first part of the study (P = .013), but these effects dissipated by week 12. Reductions in headache intensity over time did not differ significantly between groups (P = .80; maximum d = 0.13), although a larger proportion of BT-A patients showed evidence of statistically significant improvements in headache intensity in the time series analyses (62.5% for BT-A vs 30% for placebo). There were no differences between the groups on any of the secondary outcome measures. Conclusions.— The evidence for BT-A in headache is mixed, and even more so in CTTH. However, the putative technique of injecting BT-A directly into the ubiquitous MTPs in CTTH is partially supported in this pilot study. Definitive trials with larger samples are needed to test this hypothesis further.     

A型肉毒毒素治疗三叉神经痛

目的:观察A型肉毒毒素治疗三叉神经痛(TN)的临床疗效。方法:选取57例TN患者,随机分为A、B 2组。A组28例患者口服卡马西平片治疗;B组29例在疼痛部位及板机点周围皮下注射肉毒素治疗。治疗后1,3及6个月时随访,行简式McGill疼痛问卷表(SF-MPQ)及生活质量评价量表(SF-36)评分,并观察不良反应。结果:治疗中脱失7例,A组3例,B组4例。与治疗前3个月SF-MPQ及SF-36平均分作为基础水平比较,治疗1,3及6个月后2组SF-MPQ评分明显下降,SF-36明显上升(P<0.01),B组表明更明显(P<0.05,P<0.01)。治疗过程中,A组出现不适患者多于B组。结论:A型肉毒毒素疼痛点皮下注射治疗TN发作作用高峰1～3个月,维持时间6个月,且临床疗效显著,不良反应轻微。     

Prolotherapy in the Treatment of Chronic Low Back Pain: A Literature Review

Abstract

Exercise programs are advocated for the treatment of chronic low back pain, but the client often lacks the appropriate ligamentous support that is optimal for an exercise program to be effective. Once injured, ligaments have a limited capacity for recovery and recovery can be related to the degree of ligament injury. Clients that fail to progress adequately with stabilization programs may require further intervention before exercise therapy can achieve optimal results. Prolotherapy is an example of one intervention that may prove beneficial. Prolotherapy is the injection of a proliferant solution into the osseoligamentous junction of the incompetent ligaments in order to induce a healing response that will help strengthen the ligaments and provide more passive support to the joints. A review of the literature is presented that outlines the benefits of prolotherapy in low back pain.     

Effectiveness of Botulinum Toxin A for Persistent Upper Limb Pain After Breast Cancer Treatment: A Double-Blinded Randomized Controlled Trial

Objective

To investigate the effect of a single botulinum toxin A (BTX-A) infiltration in the pectoralis major muscle in addition to a standard physical therapy program for treatment of persistent upper limb pain in breast cancer survivors.

Evidence for Antinociceptive Activity of Botulinum Toxin Type A in Pain Management

The neurotoxin, botulinum toxin type A, has been used successfully, in some patients, as an analgesic for myofascial pain syndromes, migraine, and other headache types. The toxin inhibits the release of the neurotransmitter, acetylcholine, at the neuromuscular junction thereby inhibiting striated muscle contractions. In the majority of pain syndromes where botulinum toxin type A is effective, inhibiting muscle spasms is an important component of its activity. Even so, the reduction of pain often occurs before the decrease in muscle contractions suggesting that botulinum toxin type A has a more complex mechanism of action than initially hypothesized. Current data points to an antinociceptive effect of botulinum toxin type A that is separate from its neuromuscular activity. The common biochemical mechanism, however, remains the same between botulinum toxin type A's effect on the motor nerve or the sensory nerve: enzymatic blockade of neurotransmitter release. The antinociceptive effect of the toxin was reported to block substance P release using in vitro culture systems. ¹
The current investigation evaluated the in vivo mechanism of action for the antinociceptive action of botulinum toxin type A. In these studies, botulinum toxin type A was found to block the release of glutamate. Furthermore, Fos, a product of the immediate early gene, c- fos , expressed with neuronal stimuli was prevented upon peripheral exposure to the toxin.
These findings suggest that botulinum toxin type A blocks peripheral sensitization and, indirectly, reduces central sensitization. The recent hypothesis that migraine involves both peripheral and central sensitization may help explain how botulinum toxin type A inhibits migraine pain by acting on these two pathways. Further research is needed to determine whether the antinociceptive mechanism mediated by botulinum toxin type A affects the neuronal signaling pathways that are activated during migraine.     

Pharmacological Treatment of Neuropathic Cancer Pain: A Comprehensive Review of the Current Literature

Abstract: Neuropathic cancer pain (NCP), commonly encountered in clinical practice, may be cancer‐related, namely resulting from nervous system tumor invasion, surgical nerve damage during tumor removal, radiation‐induced nerve damage and chemotherapy‐related neuropathy, or may be of benign origin, unrelated to cancer. A neuropathic component is evident in about 1/3 of cancer pain cases. Although from a pathophysiological perspective NCP may differ from chronic neuropathic pain (NP), such as noncancer‐related pain, clinical practice, and limited publications have shown that these two pain entities may share some treatment modalities. For example, co‐analgesics have been well integrated into cancer pain‐management strategies and are often used as First‐Line options for the treatment of NCP. These drugs, including antidepressants and anticonvulsants, are recommended by evidence‐based guidelines, whereas, others such as lidocaine patch 5%, are supported by randomized, controlled, clinical data and are included in guidelines for restricted conditions treatment. The vast majority of these drugs have already been proven useful in the management of benign NP syndromes. Treatment decisions for patients with NP can be difficult. The intrinsic difficulties in performing randomized controlled trials in cancer pain have traditionally justified the acceptance of drugs already known to be effective in benign NP for the management of malignant NP, despite the lack of relevant high quality data. Interest in NCP mechanisms and pharmacotherapy has increased, resulting in significant mechanism‐based treatment advances for the future. In this comprehensive review, we present the latest knowledge regarding NCP pharmacological management.