the use of botulinum toxins for the management of chronic pain and headache: making the most of an...

The Use of Botulinum Toxins for theManagement of Chronic Pain and Headache:Making the Most of an Evidence-BasedMedicine Approach for These RapidlyEvolving Treatmentspme_1268 1581..1582

Charles E. Argoff, MD

Comprehensive Pain Center, Albany Medical Center,Albany, New York, USA

As noted by Hayes et al., evidence-based medicine hasfocused primarily on identifying the best research evi-dence regarding a clinical problem and using that evi-dence to address it. These same authors point out thatthe evidence-based medicine approach can be con-trasted with earlier approaches to clinical decision making,which has relied more on the physiological rationale of atreatment as well as one’s clinical experience. Currentviews of evidence-based decision making now recognizethat published research evidence alone is not sufficient onits own to provide optimal clinical care. Clinicians insteadmust integrate both their own expertise as well as currentpublished research-based evidence when evaluating andtreating patients, including the recognition of patient treat-ment preferences as well as individualized treatmentresponses [1]. This dynamic is epitomized in general whenconsidering the evolution of the use of botulinum toxins forchronic pain and headache and specifically in two articlesin this issue of Pain Medicine.

Göbel et al. report in this issue the results of their study ofthe use of botulinum toxin type A (BoNT-A) for the relief ofupper back myofascial pain syndrome. The title of thearticle, “Botulinum Type A Toxin Complex for the Relief ofUpper Back Myofascial Pain Syndrome: How Do FixedLocation Injections Compare with Trigger Point-FocusedInjections” itself needs to be commented upon. While thereader may expect to review results of a comparativestudy in which two treatment approaches were activelycompared, in fact, in the currently published study byGöbel et al. the intervention involves the injection of eitherBoNT-A or saline into 10 predetermined fixed injectionsites in the head, neck and shoulder [2]. (Göbel et al. this

edition of Pain Medicine) The trigger point focused botu-linum toxin injection approach mentioned in the title actu-ally refers to a study previously published in a differentjournal 5 years ago by Göbel and a different group ofinvestigators at different institutions [3]. In this previouslypublished study, when compared with placebo, Dysport(abobotulinum toxin A) injections (400 units) resulted in asignificantly greater change from baseline in pain intensityduring weeks 5–8 (P < 0.05), and significantly fewer daysper week without pain between weeks 5 and 12(P = 0.036). In the present study published in this issue,there was no significant improvement in the treatmentgroup (abobotulinum toxin A 400 units) compared to theplacebo group until week 8 [2]. The reader must realizethat this does not reflect a true comparison of treatmentapproaches within the same group of patients evaluatedand treated consistently by the same providers. This in myopinion makes any true meaningful comparative analysisof the treatment approaches as suggested by the article’stitle difficult at best.

In addition, in the article by Göbel et al. published in thisissue, the authors describe the use of botulinum type Atoxin complex in a general manner without recognition ofthe various types of type A toxin currently commerciallyavailable. These include those available in the UnitedStates: onabotulinum toxin A (Botox), abobotulinum toxinA (Dysport), and incobotulinum toxin A (Xeomin) as wellas a Chinese preparation, Prosigne [4]. The importanceof this omission cannot be overstated because it hasbeen well established that each of these currently avail-able type A toxins are not interchangeable either withrespect to treatment doses nor with respect to analgesicbenefit. In fact, the authors refer to a study of BoNT-A byCui et al. in which the subcutaneous administration ofbotulinum toxin A into the rat paws reduced formalin-induced pain as evidence of the antinociceptive proper-ties of the toxin—what they did not indicate is that thepreparation used in this study is onabotulinum A(BOTOX) and not the preparation that was used in theirstudy (abobotulinum toxin A) [5]. It has not yet beenestablished what if any differences there may be in theanalgesic properties of the type A toxins currently avail-able. The study by Göbel et al. included in this issue ofPain Medicine adds to the evidence base that has pre-viously been published regarding the use of botulinum

Reprint requests to: Charles E. Argoff, MD,Comprehensive Pain Center, Albany MedicalCenter, 47 New Scotland Avenue, MC70 Albany,NY 12208, USA. Tel: 518-262-5226; Fax: 518-262-6261; E-mail: argoffc@mail.amc.edu.

Pain Medicine 2011; 12: 1581–1582Wiley Periodicals, Inc.

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toxin in this clinical area; however, it does not add suf-ficient clarity with respect to clinical guidance.

Jabbari and Machado’s evidence-based review of thetreatment of refractory pain with botulinum toxins, alsopublished in this month’s issue, provides the reader with acomprehensive, thorough, and current evidence-basedreview of this subject [4]. The literature used to developthis review is rated by the authors using a published andrigorous rating system developed by the AmericanAcademy of Neurology (AAN) and one that is used by theAAN when developing practice parameters for variousneurological disorders [6]. Based upon these ratings, thereview is organized in such a manner that the reader canclearly learn for which painful conditions there is the stron-gest evidence for treatment with botulinum toxins and forwhich there may not be as robust evidence for their use.For example, those conditions with level A evidence, e.g.,those where the efficacy is established and the treatmentrecommended based upon the presence of two or moreclass I studies, include: neck pain associated with cervicaldystonia, chronic migraine, and chronic lateral epicondyli-tis. At the other end of the ratings is level U, so designatedwhen the evidence to support or refute efficacy is insuffi-cient due to contradictory results. It is within this recom-mendaton that myofascial pain syndrome lies. Otherconditions, including post-herpetic neuralgia (level B),plantar fasciitis (level B), low-back pain (level C), and dia-betic neuropathy (level C), among others reported, have alevel of evidence to support their use that is between levelA and level U. Each section is associated with a clinicalcomment that greatly adds to the clinical relevance of thisreview.

The emerging use of botulinum toxins for the manage-ment of chronic pain and headache disorders is exempli-fied by this month’s issue of Pain Medicine as well asanother recent issue in which the role of botulinum toxinfor the treatment of post-herpetic neuralgia and otherneuropathic pain conditions was discussed [7,8]. It is safeto say that the development process for many medicaltreatments is often associated with various “bumps in theroad.” Initial studies may have less than robust response(s)for many reasons, including trial design, treatment para-digm, and definition of treatment population as well ofcourse that the treatment itself is ineffective. With respectto the use of botulinum toxin for chronic headache, onecan see in the review by Jabbari and Machado in thismonth’s issue that the evidence for the use of botulinumtoxin for different headache disorders varies greatly

depending upon the headache type. For myofascial paindisorders the current evidence level is uncertain; however,the study by Göbel et al. in this issue suggests that resultsmay at least in part vary based upon treatment regimen.Other factors, including standard diagnostic methods aswell as further subclassification of patient groups (whichappears to have been useful for headache disorders), mayhelp to provide us with more consistent expectationsregarding the use of botulinum toxins for myofascial paindisorders.

References1 Hayes RB, Devereaux PJ, Guyatt GH. Clinical expertise

in the era of evidence-based medicine and patientchoice. Evid Based Med 2002;7:36–8.

2 Benecke R, Heinze A, Reichel G, Hefter H, Göbel H onbehalf of the Dysport Myofascial Pain Study Group.Botulinum type A toxin complex for the relief of upperback myofascial pain syndrome: How do fixed-locationinjections compare with trigger point-focused injec-tions? Pain Med 2011;12:1607–14.

3 Göbel H, Heinze A, Reichel G, Hefter H, Benecke R.Efficacy and safety of a single botulinum type a toxincomplex treatment (Dysport) for the relief of upper backmyofascial pain syndrome: Results from a randomizeddouble-blind placebo controlled multicentre study. Pain2006;125:82–8.

4 Jabbari B, Machado D. Treatment of refractory painwith botulinum toxins—An evidence-based review. PainMed 2011;12:1594–606.

5 Cui M, Khanijou S, Rubino J, Aoki KR. Subcutaneousadministration of botulinum toxin A reduces formalin-induced pain. Pain 2004;107:125–33.

6 Gronseth G, French J. Practice parameters and tech-nology assessments: what they are, what they are not,and why you should care. Neurology 2008;71:1639–43.

7 Xiao L, Mackey S, Hui H, et al. Subcutaneous injectionof botulinum toxin A is beneficial in postherpetic neu-ralgia. Pain Med 2010;11(12):1827–33.

8 Argoff CE. The emerging uses of botulinum toxins forthe treatment of neuropathic pain. Pain Med2010;11(12):1750–2.

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