Subcutaneous Botulinum Toxin for Chronic Post‐Thoracotomy Pain

Objective: Botulinum toxin is a neurotoxin that has been widely used in chronic pain for the treatment of multiple conditions with a component of localized muscle spasm. Recent studies suggest that botulinum toxin is effective in the treatment of neuropathic pain syndromes such as post‐herpetic neuralgia. Case Report: We report the case of a 67‐year‐old man who underwent atypical segmentectomy of a right lower lobe lung nodule. The patient was referred to our pain management department with a of 2‐year history persistent pain along the thoracotomy scar having a predominantly neuropathic component, refractory to standard treatments. He was successfully treated with subcutaneous botulinum toxin type A. Discussion: On the basics of our own experience and on the analysis of the reports published in the literature, fractioned subcutaneous injections of botulinum toxin may be useful for the treatment of various chronic localized pain conditions including chronic post‐thoracotomy pain.     

Headache and Facial Pain Responsive to Botulinum Toxin: An Unusual Presentation of Blepharospasm

The diagnosis of blepharospasm is rarely considered in patients complaining of face pain or headache. This patient illustrates the importance of looking for blepharospasm in patients who present with headache or face pain, as her pain and blepharospasm were successfully treated with botulinum toxin type A injections.     

Botulinum Toxin Treatment of Myofascial Pain: A Critical Review of the Literature

This is a review of literature relevant to the treatment of myofascial pain syndrome by botulinum injections. The objective is to critically review the studies to see if they are appropriately designed, conducted, and interpreted to provide guidance in the management of myofascial pain. The intent is to better understand the mixed results that these studies have provided. A search was made utilizing PubMed for literature relevant to the use of botulinum toxin in the treatment of myofascial pain. All identifiable series were reviewed, including open label, single-blinded and double-blinded studies, randomized and controlled, or not. In general, small case series of only a few patients were not included unless they made a relevant point and there were no available randomized studies or larger studies. Single case reports were not included. This is not a meta-analysis. The studies were evaluated according to their design and the selection of outcome measurements, and the interpretation of results. The studies were individually critiqued, and an overall assessment and commentary was made of the studies in the field as a whole. Problems that were common to the studies were robust placebo responders, incomplete treatment of a regional myofascial pain syndrome, inappropriate or confounding control populations or treatments, and inappropriate time periods for assessment of outcomes, or misinterpretation of the time-frame of action of botulinum toxin. The studies of the effect of botulinum toxin treatment of myofascial trigger points have had mixed results. However, few studies have been designed to avoid many of the pitfalls associated with a trial of botulinum toxin treatment of trigger points. Better-designed studies may give results that can be used to guide practice based on reliable evidence. At the present time, one must conclude that the available evidence is insufficient to guide clinical practice.     

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.     

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.     

A型肉毒毒素治疗脑卒中后瘫痪肌痉挛的临床疗效

目的：探讨A型肉毒毒素治疗脑卒中后瘫痪肌痉挛的临床疗效与安全性。方法：44例脑卒中后瘫痪肢体肌痉挛患者分为2组，其中采用BTX-A治疗的21例为研究组；采用力奥来素治疗的23例为对照组。分别观察2组治疗2、4周后肢体肌力、肌张力及功能改变。结果：肌张力按改良Ashworth评分与治疗前比较。2组均降低（P〈0．01）；治疗2周时研究组低于对照组（P〈0．01）；4周时2组差异无显著性意义（P〉o．05）。研究组在4周后步速、步长、Barthel指数评分与治疗前比较均明显提高（P〈0．01、P〈0．05、P〈0．01），并优于对照组（P〈0．05）。结论：BTX-A治疗瘫痪肌痉挛安全、简便、起效迅速，副作用小，值得在临床推广应用。     

Tension Headache: Botulinum Toxin Paralysis of Temporal Muscles

SYNOPSIS
The pathogenetic mechanism of tension headache (TH) is still unknown. The role of pericranial muscle tension in TH is also enigmatic. To evaluate this factor in chronic TH, pericranial muscles were paralysed in 6 chronic TH patients, using botulinum toxin. All patients fulfilled the IHS criteria of chronic TH associated with involvement of the pericranial muscles, but not the current criteria for cervicogenic headache. The patients were followed-up regularly with evaluation of the paralysis, changes in pain intensity, and pressure pain threshold measurements. We primarily only injected the temporal muscle on the one side, using the other side as a control. Contralateral muscles were in some cases injected at a later stage. In our study, we did not find any significant reduction in pain intensity, as measured by the visual analogue scale, nor any changes in pressure pain threshold, as measured by an algometer. On the basis of our observations, we conclude that muscle tension in these muscles possibly plays a minor role in the genesis of chronic TH. In our study, however, we have only treated a limited number of patients, and only one pericranial muscle has been injected systematically. Further studies of various neck/posterior head muscles ought to be performed in order to further evaluate a possible effect of tension in the pericranial musculature in producing this type of pain.     

肉毒毒素在痉挛型脑瘫治疗中的应用及研究进展

本文介绍了肉毒毒素由毒素到药物的演变过程以及其作用机理，综述了其在痉挛型脑瘫治疗中的应用剂量、治疗效果及副作用等方面的研究进展。     

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. ▪     

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.

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.     

Botulinum Toxin Dilution and Endplate Targeting in Spasticity: A Double-Blind Controlled Study

Gracies J-M, Lugassy M, Weisz DJ, Vecchio M, Flanagan S, Simpson DM. Botulinum toxin dilution and endplate targeting in spasticity: a double-blind controlled study.

Objective

To determine the effects of botulinum neurotoxin type A (BTX-A) dilution and endplate-targeting in spastic elbow flexors.

Design

Double blind randomized controlled trial; 4-month follow-up after a 160-unit injection of BTX-A into spastic biceps brachii (4 sites). Randomization into: group 1: 100 mouse units (MU)/mL dilution, 0.4cc/site, 4-quadrant injection; group 2: 100MU/mL dilution, 0.4cc/site, 4 sites along endplate band; group 3: 20MU/mL dilution, 2cc/site, 4-quadrant injection (n=7 per group).

Setting

Institutional tertiary care ambulatory clinic.

Participants

Referred sample of 21 adults with spastic hemiparesis. No participant withdrew due to adverse effects.

Intervention

A 160-unit injection of BTX-A of different dilutions and locations into biceps brachii.

Main Outcome Measures

Primary: agonist and antagonist (cocontraction) mean rectified voltage (MRV) of elbow flexors/extensors during maximal isometric flexion/extension; secondary: maximal voluntary power of elbow flexion/extension; spasticity angle and grade in elbow flexors/extensors (Tardieu Scale); active range of elbow extension/flexion.

Results

BTX-A injection overall reduced agonist flexor MRV (-47.5%, P<0.0001), antagonist flexor MRV (-12%, P=.037), antagonist extensor MRV (-19%, P<.01), flexion maximal voluntary power (-33%, P<.001), elbow flexor spasticity angle (-30%, P<.001) and grade (-17%, P=.03), and increased extension maximal voluntary power (24%, P=.037) and active range of elbow extension (5.5%, 8°, P=.002). Agonist and antagonist flexor MRV reductions in group 3 (-81% and -31%) were greater than in groups 1 and 2, whereas increase in active range of elbow extension was greater in group 2 (10%) than in groups 1 and 3 (P<.05, analysis of covariance [ANCOVA]). Elbow flexor spasticity was significantly reduced in groups 2 and 3 only (P<.05, ANCOVA).

Conclusions

In spastic biceps, high-volume or endplate-targeted BTX-A injections achieve greater neuromuscular blockade, cocontraction and spasticity reduction, and active range of elbow extension improvement, than low volume, nontargeted injections.     

A型肉毒毒素在泌尿外科领域的应用

A型肉毒毒素注射在大多数泌尿外科情况似乎都有积极的治疗作用,包括：逼尿肌-括约肌协同失调、排尿功能障碍、盆底疼痛、膀胱过度活动症、尿频-尿急综合征、间质性膀胱炎、良性前列腺增生,对于泌尿外科领域中许多下尿路功能障碍性疾病是一种新型、有前途的治疗方法。但是,仍需要进行深入的随机、双盲、安慰剂对照的研究,评价其临床有效性。