PRACTICE | INNOVATIONS CPD

Spinal cord stimulation: a nonopioid alternative for chronic

Aaron Hong MD MSc, Vishal Varshney MD, Gregory M.T. Hare MD PhD, C. David Mazer MD n Cite as: CMAJ 2020 October 19;192:E1264-7. doi: 10.1503/cmaj.200229

hronic pain affects 1 in 5 Canadians and is associated 1 with considerable socioeconomic burden. Although opi- KEY POINTS oids have been the mainstay of treatment, they have lost stimulation masks pain signals through a Cfavourability owing to crises of addiction, abuse, tolerance and • transcutaneous implantable electric pulse generator. dependence.1,2 Consequently, alternatives — including cognitive • Spinal cord stimulation is safe, efficacious and cost-effective in behavioural therapy, physical rehabilitation, non-opiate pharma- chronic pain management of conditions, 1,3 cology and integrative therapies — have been developed. including failed back surgery syndrome, chronic regional pain When conventional therapies produce unacceptable adverse syndrome and chronic peripheral neuropathies. effects or do not provide sufficient pain relief, spinal cord • Newer spinal cord stimulation technologies are expanding stimulation () may offer a rescue option, either clinical indications such as visceral and ischemic pain, with alone or in conjunction with other modalities.3,4 potential for further improved efficacy. Neuromodulation, defined as the alteration of activity • Increased awareness of and access to spinal cord through targeted stimulus delivery, was first introduced in stimulation therapy may allow more Canadians to benefit 2,3,5 from relief of intractable chronic pain and may reduce 1967. It is based on the principle of electrically stimulating the opioid consumption. dorsal column of the spinal cord, to mask pain signals.2 The tech- nology has since advanced, and it was a Canadian neurosurgeon who helped demonstrate both the efficacy and cost-effectiveness of spinal cord stimulation in chronic pain treatment.6,7 last 5–10 years, depending on rechargeability, and are replace- Usage of spinal cord stimulators has increased worldwide, and able. Patients are asked not to twist, bend or stretch excessively according to the United States Food and Drug Administration, an for 6–8 weeks postoperatively. After this period, patients may estimated 50 000 devices are implanted annually in the US resume most physical activities. (150 cases/million population; www.fda.gov/medical-devices/letters​ The generators continuously emit low-frequency electrical -health-care-providers/conduct-trial-stimulation-period-implanting​ pulses (tonic stimulation) that mask pain signals travelling up -spinal-cord-stimulator-scs-letter-health-care-providers). How- the spinal cord and replace them with nonpainful paresthe- ever, uptake in Canada has been substantially lower, with sias.8 Wall and Melzack’s gate control theory is the most 172 implant­ations performed in Ontario in 2018 (12 cases/­ accepted proposed pain relief mechanism, which asserts that million population).3 This difference is likely related, at least in nonpainful inputs close the “nerve-gates” to painful inputs, part, to a lack of awareness about spinal cord stimulation and thereby preventing pain sensations from reaching the brain2,7 high upfront device costs ($20 000–$30 000).3 (Figure 1).

What is spinal cord stimulation? How is treatment delivered?

Spinal cord stimulation consists of leads placed in the epidural Initially, spinal cord stimulators were implanted by spine sur- space alongside the dorsal column and then tunnelled subcuta- geons, necessitating general anesthesia, laminectomy, electrode neously to an implantable pulse generator. These generators placement directly onto dura, and postoperative hospital admis- contain a battery and microprocessor (similar to a pacemaker) sion. Over the last decade, development of percutaneous epi- that are internalized within a subcutaneous pocket either within dural leads inserted under fluoroscopic guidance has enabled the abdominal wall or posteriorly in the flank or gluteal region, specially trained anesthesiologists or other pain specialists to and programmed transcutaneously while allowing remote con- safely implant spinal cord stimulators as outpatient procedures, trol by the physician or patient. Implantable pulse generators using light sedation and local anesthesia (Figure 2).

E1264 CMAJ | OCTOBER 19, 2020 | VOLUME 192 | ISSUE 42 © 2020 Joule Inc. or its licensors PRACTICE 2 2,7 E1265 Only if 50% or Only if 50% or 2 s or Additional expanding pt 2,4 ce 2,4,8 ain re P People with a history of abuse or People with a history of abuse or 2 Dorsal horn olumn Contraindications include active infections, infections, active include Contraindications Spinal cord stimulation is delivered in 2 phases: Spinal cord stimulation referrals can be made immunosuppression and inability to withhold anti- coagulation. a trial phase and a permanent implant phase. phase. implant permanent a and phase trial a 1 week Implantation of a trial system for about helps determine effectiveness. - to most Canadian university–based interven tional pain specialists or spine surgeons. greater improvement from baseline pain is pain is greater improvement from baseline achieved will permanent systems be implanted. Who is eligible? Most chronic neuropathic pain conditions have been reported to respond to spinal cord stimula- tion, including failed back surgery syndrome, chronic and syndrome pain regional complex peripheral neuropathies. trauma, poor social support and substantial cogni- tive deficits tend to have poorer outcomes, and expert mental health assessment is recommended. indications include refractory , diabetic indications include refractory angina, diabetic neuralgia, post-herpetic neuralgia, and visceral or peripheral ischemic pain. ISSUE 42 ISSUE | Dorsal c VOLUME 192 VOLUME | -section rd stimulation rd cross Spinal co Spinal co OCTOBER 19, 2020 OCTOBER | CMAJ C fibres A-Δ fibres tion) thalamic ep al spino r te act (nocic La tr

Radiograph of a spinal cord stimulator device. Note: IPG = implantable pulse Figure 2: Radiograph of a spinal cord stimulator device. Note: IPG = implantable pulse generator. - pain signal transmission via the spinothalamic tract from pain-transmitting fibres (unmyelin Figure 1: Gate theory of pain. This theory postulates that is blocked by stimulating the dorsal column large myelinated fibers and the polysynaptic interneurons ated C fibres and lightly myelinated A-Δ fibres) horn, blocking pain receptors from synapsing. Illustration by Jean Chan. (PSINs). The PSINs then fire back up on the dorsal PRACTICE tonic stimulation(p up, 68.2%preferredburstascompared with23.9%whopreferred . Aftertheinitialcrossover periodand1yearoffollow- ing theburstphase,89%ofpatientsexperiencedreducedto no within eachpatientinoverallimprovement100mmVAS.Dur - found thatburststimulationwassuperiortotonic multicentre, randomized,controlledcrossovernoninferioritytrial (2%) withsolemedicalmanagement. receiving spinalcordstimulationceasedopioids,versus1of44 treatment satisfaction.Furthermore,8of50(16%)patients improved qualityoflifeandfunctionalcapacity,withgreater outcomes, patients receiving spinal cord stimulation experienced who weresolely medicallymanaged(p patients receivingspinalcordstimulationversus7%of scale score(VAS).At12months,thiswasachievedin34%of visualanalogue come was50%orbetterlegpainreliefon10 cm withfailedbacksurgerysyndrome. Theprimaryout- 100 patients ical management,versusmedicalmanagementalonein domized trialcomparingtonicspinalcordstimulationplusmed­ study, conducted in 2007, was an international, multicentre, ran- treatment. of themostinfluentialstudiesconductedonefficacy E1266 supporting spinalcordstimulation. Hofmeister and colleagues found a robust body of evidence In a2020systematicreviewof15randomizedcontrolledtrials, What istheevidence? correctable. failure oftheimplantablepulsegenerator,butallarereadily hardware related,includingelectrodemigrationorfracture,and invasiveness and reversibility. More common complications are Spinal cordstimulationisgenerallysafebecauseofitsminimal What arethepotentialharms? trial comparedburstwithtonicstimulationin100 patients. the tonicgroup(26.4%;p tion, whichwashigherinthehigh-frequencygroup(35.5%)than in outcomes includedreductionoreliminationofopioidconsump - reducing backandlegpain(79%v.51.3%;p high-frequency stimulationprovedsuperiortotonic in without astimulation-relatedneurologicdeficit.At12 months, was 50%orgreaterreductionon10cmVASforbackandlegpain with chronicintractablebackandlegpain.Theprimaryoutcome cord stimulationtotraditionaltonicin198 patients parallel-arm, noninferioritytrialcomparinghigh-frequencyspinal stimulation technology has advanced, with “paresthesia-free” thesia makes blinding infeasible. In the last 3–5 years, spinal cord injuries areuncommon(< 0.3%). plications likeepiduralabscessesorhematomasandneurologic tions (3.4%)andduralpunctureheadaches(0.3%).Seriouscom- seromas at the insertion site of the generator (2.5%), local infec- The Patients with Failed Back Surgery Syndrome (PROCESS) The Success Using Neuromodulation With BURST (SUNBURST) The SuccessUsingNeuromodulationWithBURST(SUNBURST) The Senzastudywasamulticentre,randomized,pragmatic, These trialswereunblindedbecause theexperienceofpares- 9 Biologiccomplicationsarelesscommon,including < 0.001). < 0.05). 8 10 9 4 6 Belowisadescriptionof3 CMAJ =0.005).Forsecondary < 0.001). Secondary 0.001).Secondary < | OCTOBER 19, 2020 7 This This | VOLUME 192 direct andindirectcosts. term, prospectivedatafromrandomizedtrialsthatincludeboth using high-frequency spinalcordstimulation with30 beyond 2years. term studieswouldhelptestefficacyofspinalcordstimulation devices mayallowforblindedstudiesinthefuture,andlonger- recovery phase. emulating neuronalfiringwithstimuliburstsseparatedbya to besuperiortraditionaltonicstimulus. leagues dened withhighupfrontandrecurrentcosts.Hoelschercol- Chronic backandlimbpaintreatmentsarehistoricallybur- Cost-effectiveness 1. References novel technology. and thelatestdevicesmayfurthersupportwideruseofthis year. Datafromrandomizedtrialsevaluatingcost-effectiveness tion butgenerallylimitthenumberofdeviceinsertionseach activity levelsasaresultofreductioninpain. devices may allow parameter tracking, such as any increase in tion mayfacilitatereprogrammingfromhome,andwearable the needforanexternalinductioncharger.Remotecommunica- able pulsegeneratorssmaller,holdagreaterchargeoreliminate tion basedonbodyposition(closed-loopspinalcordstimulator). strengths, combining stimulus types or even allowing stimulus titra- erator. Furtherrefinementhasalsooccurredbytitratingstimulus tomes. Somesystemsnolongerrequireimplantationofapulsegen- cord, whichrequireslessenergyandtreatsmoretargetedderma- for stimulation of the dorsal root ganglion rather than the spinal Recent HealthCanada–approvedneuromodulationdevicesallow What canbeexpectedinthefuture? stimulus development. recovered within2–3 years. cord stimulation treatment suggests that initial costs can be ited mainlytomodellingdirectcostdata,butdurabilityofspinal gained. Informationaboutlong-termcost-effectivenesswaslim- olds ofUS$50 000–US$100 000quality-adjustedlife-years results fellwithinusualthird-party“willingness-to-pay”thresh- studies performedcost-effectivenessanalysesandfoundthat low-amplitude pulses, 3. 2.

Currently, allprovincescoverthecostofspinalcordstimula- Improved batterytechnologyisexpectedtomakeimplant- Health TechnolAssess Ser2020;20:1-109. adults withchronicnoncancerpain:a healthtechnologyassessment.Ont Ontario Health(Quality).10-kHzhigh-frequency spinalcordstimulationfor Neuromodulation 2014;17:515-50,discussion550. emic diseases: the neuromodulation appropriateness consensus committee. cord andperipheral nervous system for thetreatment of chronic pain andisch- Consensus Committee.Theappropriate useofneurostimulationthespinal Deer TR,MekhailN,ProvenzanoD,etal.;NeuromodulationAppropriateness adian PainTaskForce,June2019.Ottawa:HealthCanada;2019. Chronic paininCanada:layingafoundationforaction—reportbytheCan­ 7 reviewedcostdatafrom21retrospectivestudies.Five | ISSUE 42 8 Bothburstandhigh-frequencystimuliappear 10 2 andusingburstspinalcordstimulation Asubperceptionstimulusisproduced 7 Thereremainsaneedforlong- 8,10 Paresthesia-free µ s 10kHz PRACTICE - E1267 ISSUE 42 ISSUE | Aaron Hong reports receiving personal fees fees reports receiving personal interests: Aaron Hong Competing and Laboratories Abbott from grants and Canada Stimwave from inter competing other No work. submitted the outside Medtronic, ests were declared. been peer reviewed. This article has Hare, Mazer), of Anesthesia (Hong, Department Affiliations: of Anesthesiology and Pain MedicineSt. Michael’s Hospital; Department of Toronto, Toronto, Ont.; Department(Hong, Hare, Mazer), University Providence Health Care, Vancouver, BC; of Anesthesia (Varshney), (Hare, Mazer), University of Toronto; KeenanDepartment of Physiology Knowledge Shing Ka Li the in Science Biomedical for Centre Research Michael’s Hospital, Toronto, Ont. Institute (Hare, Mazer), St. Varshney contributed to theContributors: Aaron Hong and Vishal the work and drafted the manuscript. All ofconception and design of to the analysis and interpretation of data. Allthe authors contributed manuscript critically for important intellec- of the authors revised the approval of the version to be published andtual content, gave final for all aspects of the work. agreed to be accountable Correspondence to: Aaron Hong, [email protected] VOLUME 192 VOLUME | - OCTOBER 19, 2020 OCTOBER | CMAJ Deer TR, Mekhail N, Provenzano D, et al.; Neuromodulation Appropriateness D, et al.; Neuromodulation Appropriateness Deer TR, Mekhail N, Provenzano appropriate use of : avoidance Consensus Committee. The of neurostimulation therapies for the treat- and treatment of complications 2014;17:571-97. ment of chronic pain. Neuromodulation M, et al. Novel 10-kHz high-frequency therapy is Kapural L, Cong Y, Doust for the treatment ­superior to traditional low-frequency spinal cord stimulation 2015;123:851-60. of chronic back and leg pain (SENZA-RCT). Anesthesiology Deer T, Slavin KV, Amirdelfan K, et al. Success Using Neuromodulation With K, et al. Success Using Neuromodulation With Deer T, Slavin KV, Amirdelfan results from a prospective, randomized controlled BURST (SUNBURST) study: Neuromodulation 2018;21:56-66. trial using a novel burst waveform. tional medical management for neuropathic pain: a multicentre randomised randomised multicentre a pain: neuropathic for management medical tional with failed back surgery syndrome. Pain 2007;132:​ controlled trial in patients 179-88. cord spinal regarding data Cost-effectiveness al. et C, Wu J, Riley C, Hoelscher Spine 2017;42(Suppl 14):S72-9. stimulation for low back pain. Kumar K, Taylor RS, Jacques L, et al. Spinal cord stimulation versus conven versus stimulation cord Spinal al. et L, Jacques RS, Taylor K, Kumar Hofmeister M, Memedovich A, Brown S, et al. Effectiveness of neurostimulation of neurostimulation S, et al. Effectiveness A, Brown M, Memedovich Hofmeister ­ review. Neuro pain: a systematic management of chronic for the technologies modulation 2020;23:150-7. by stimulation of pain inhibition JB. Electrical Reswick JT, CN, Mortimer Shealy report. Anesth Analg 1967;46:489-91. preliminary clinical of the dorsal columns:

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