The use of botulinum neurotoxin type A (Botox) - Journal of the ...

Botulinum neurotoxinpositive results were found when the mean Botox-A dosewas 63.2 units, for a mean total treatment time of 8.6months, during which patients received an average of 3.4treatments. 12In 2005, the Cochrane Collaboration released a reviewon the effects of Botox-A injections on mechanical neckdisorders. It examined studies that were published up to2002 and concluded that there was moderate evidence indicatingno benefit for Botox-A compared to saline intramuscularinjections. The five studies examined in thisreview, however, looked only at the results of one treatmentand the pain outcomes over four to eight weeks posttreatment 13 . Most recently in 2005, the two largest randomlydouble-blind, placebo-controlled trials were publishedby Mathew et al and Silberstein et al. These studiesused 702 and 571 patients respectively and conductedtheir studies over a period of 11 months. Both studies indicateda statistically significant decrease in the numberof headache days per 30 day period when compared to aplacebo group. 10,11 Silberstein et al. looked at variousdosages and concluded that the most benefits comparedto placebo groups were found when the patient received150 Units of Botox-A per treatment. 10 This is significantlymore than the 20 Units used in Schmitt’s 2001 study.Also of note is the fact that both of these studies utilizedmultiple injection sites in multiple muscles, includingmuscles of both the head and neck. 10,11 All studies reportedadverse effects to be transient and mild to moderate inseverity. 9,10,11,12,14 Overall the current research suggeststhat Botox-A treatment may be an effective, well toleratedalternative treatment for the management of chronicheadache disorders.Central sensitization of central trigeminovascular neuronshas been determined to be an integral factor in the development,progression and maintenance of migrainetypeheadaches. Botox has been shown to inhibit this. 5 Althoughthe patient in this case report obtained reliefthrough conservative management of her headaches, itwas only up to two days. Alternatively, when she receivedthe Botox-A treatments the relief lasted up to 4 months.As indicated by its various uses, and as illustrated inthe case report, the most therapeutic use of Botox-A is todecrease pain. This is accomplished through variousmethods. One method is by blocking the neuromusculartransmission. Blocking the release of acetylcholine stopsthe contraction of the muscle spindle, which in turn stopsthe pain-spasm-pain cycle and gives the patient relieffrom a painful posture. 15Another method is based on the evidence that Botox-A’s effect on the SNARE proteins also decreases the releaseof pain mediators including substance P, calciumgene-related peptide (CGRP), and glutamate. 16 This maybe accomplished directly by blocking both substance Pfrom the trigeminal sensory afferent terminals, and therelease of CGRP from autonomic vascular nerve terminals.It may also do this indirectly by inhibiting therelease of glutamate, which stimulates the release ofsubstance P and CGRP. 17,18 These pain mediators are releasedfrom primary sensory afferent terminals in the injuredarea. They produce neurogenic inflammation andsensitized pain receptors, providing a feedback circuit forcontinuing inflammation and muscle pain, hyperalgesiaand allodynia. 17 By blocking their release peripherally ananalgesic effect is created, however glutamate may alsobe blocked centrally.A third method relates to a recent study which foundthat Botox-A may cause an analgesic effect without paralysiswhen it is conjugated with lectin and applied todorsal root ganglion cells. Here it selectively affects thenociceptive sensory afferents, C fibers, and can attenuatenociceptive transmission in vitro and in vivo for at least24 days. 17 Botox-A can thus prevent pain facilitation byalleviating the painful muscle contraction, blocking thepain neurotransmitters and interrupting the nociceptivesensory afferents.When administered for the treatment of headaches,Botox is released intramuscularly into various sites in thehead and neck. The dosage is dependant on the size ofmuscle. Studies have shown effectiveness with as little as25 units. 19 According to one study, the clinical dose formigraine headaches is 25 to 100 units. 6 As there is not yeta standardized methodology for the administration of Botox-A,the total dose administered should be individual,considering various factors such as the type of headache,severity of symptoms and body size. 12 The patient in theabove case report experienced relief with doses of 120units.In disorders such as tension-type headaches, cervicogenicheadaches and migraines it is difficult to determinespecifically the involvement of hyperactive muscles. 6With respect to the occipital and cervical paraspinal regions(trapezius, splenius capitis, seminspinalis capitis),266 J Can Chiropr Assoc 2006; 50(4)

Botulinum neurotoxinFigure 1 Anterior injection sites in procerus andfrontalis muscles.Figure 3 Posterior view displaying splenius capitis andtrapezius muscles.Figure 2 Potential injection sites in temporalis muscle.Some patients received more or less depending upon painlocation.Figure 4 Injection sites in trapezius and splenius capitismuscles. The number of injection sites and doses varyfrom patient to patient depending upon size, painlocation, and palpable muscle spasm.268 J Can Chiropr Assoc 2006; 50(4)

M Oliver, J MacDonald, M Rajwanience any side effects, they can occur. Adverse effects arelocalized to the area of injury and may be related to an excessivedose, or the inadvertent injection to adjacent areas.Adverse effects with respect to facial injections may includetransient ptosis, dry eyes, and bruising. Adverse effectswith respect to neck musculature may includedyspnea, xerostomia, nausea, fatigue, blurry vision andphotophobia. 21 Expected effects of Botox-A injections includelocal muscle weakness, flu-like symptoms, andrash. 23 According to a systematic review on the safety ofBotox-A, the overall rate of adverse events from treatmentwith Botox-A was 25%, of which there were no severe orsystemic events. 21 Long term studies according to the systematicreview indicated that no severe effects occurred.Another randomized double blind study indicated that 7out of 33 participants noted transient symptoms such asarm heaviness, and contralateral pain. One of these participantsnoted a shift of neck pain to the midline which wassuccessfully managed with a chiropractic adjustment. 22According to an 11-month randomized double-blindplacebo-controlled study, Botox was shown to be an effectivetherapy for these types of headaches. 6 Specifically,in the prevention and treatment of headaches, Botoxwas shown to be most effective in patients with recurringmigraines that interfere with their activities of normal lifedespite other treatments, in patients with frequent headaches,and with those who do not tolerate or complypoorly with acute treatment. 20In this case report, the patient had been experiencingchronic headaches and neck pain, and with increasedtime, began experiencing symptoms of anxiety, sleep disturbanceand short-term memory loss, all of which interferedwith her activities of normal life. After attemptingto relieve these symptoms through conservative treatment,it was the Botox-A injections that finally allowedher to resume her daily activities in a pain-free manner.Given these findings, it would be beneficial for chiropractorsto learn more about Botox-A, specifically, whenit should be offered as an alternative treatment. A proposalfor the development of guidelines is suggested, suchthat chiropractors can in the future determine suitablecandidates for Botox-A treatment.SummaryBotox-A is the serotype of a neurotoxin which, whencombined with non-toxic proteins can be utilized fortherapeutic purposes. It is injected into a target tissue andflaccid paralysis occurs, which decreases muscle hyperactivityand ultimately decreases pain within a short timeframe. At the present time, Botox injection for pain managementremains somewhat controversial, and more RCTstudies as well as studies of the long term outcomes andoutcome measures are necessary.A case of a 45-year-old woman who was treated withBotox-A for chronic neck pain and headaches is presented.She was initially treated with conservative care includingmanipulation, acupuncture and trigger point therapy,however, this only provided short-term relief. FollowingBotox-A treatment she experienced pain relief immediatelywhich lasted up to 4 months. She has been receivingBotox-A injections approximately every 4 months for oneyear and has noticed an increase in energy and overallimprovements in her normal daily activities. This caseillustrates the importance of having alternatives to conservativetreatment for chiropractors. Development of aresearch proposal is suggested for the next steps in creatingguidelines that can be utilized by chiropractors andother professionals in determining suitable candidates forthis treatment alternative.AcknowledgementsThe authors would like to thank Dr. Hanif Alibhai of MDCosmetic and Laser Clinic for his guidance and his effortsin providing the resources for this report.Figures 1–4 with kind permission of Springer Scienceand Business Media and Dr. Todd Troost.References1 Setler PE. Therapeutic uses of botulinum toxins:background and history. Clinical J Pain. 2002;18(6):S119–S124.2 Dressler D, Saberi FA. Botulinum toxin: mechanisms ofaction. European Neurology. 2005; 53:3–9.3 Bell MS, Vermeulen LC, Sperling KB. Pharmacotherapywith botulinum toxin: harnessing nature’s most potentneurotoxin. Pharmacotherapy. 2000; 20(9):1079–1091.4 Lowe N. Cosmetic uses of botulinum toxins for loweraspects of the face and neck. Clinics in Dermatology. 2004;22(1):18–22.5 Lew M. Review of the FDA-approved uses of botulinumtoxins, including data suggesting efficacy in pain reduction.Clinical J Pain. 2002; 18(6):S142–S46.J Can Chiropr Assoc 2006; 50(4) 269