Sphenopalatine ganglion: block, radiofrequency ablation and ......the past century, it has been a...

REVIEW ARTICLE Open Access

Sphenopalatine ganglion: block,radiofrequency ablation andneurostimulation - a systematic reviewKwo Wei David Ho1*, Rene Przkora2 and Sanjeev Kumar2

Abstract

Background: Sphenopalatine ganglion is the largest collection of neurons in the calvarium outside of the brain. Overthe past century, it has been a target for interventional treatment of head and facial pain due to its ease of access. Block,radiofrequency ablation, and neurostimulation have all been applied to treat a myriad of painful syndromes. Despite theroutine use of these interventions, the literature supporting their use has not been systematically summarized.This systematic review aims to collect and summarize the level of evidence supporting the use of sphenopalatine ganglionblock, radiofrequency ablation and neurostimulation.

Methods: Medline, Google Scholar, and the Cochrane Central Register of Controlled Trials (CENTRAL) databases werereviewed for studies on sphenopalatine ganglion block, radiofrequency ablation and neurostimulation. Studies includedin this review were compiled and analyzed for their treated medical conditions, study design, outcomes and proceduraldetails. Studies were graded using Oxford Center for Evidence-Based Medicine for level of evidence. Based on the levelof evidence, grades of recommendations are provided for each intervention and its associated medical conditions.

Results: Eighty-three publications were included in this review, of which 60 were studies on sphenopalatine ganglionblock, 15 were on radiofrequency ablation, and 8 were on neurostimulation. Of all the studies, 23 have evidence levelabove case series. Of the 23 studies, 19 were on sphenopalatine ganglion block, 1 study on radiofrequency ablation,and 3 studies on neurostimulation. The rest of the available literature was case reports and case series. The strongestevidence lies in using sphenopalatine ganglion block, radiofrequency ablation and neurostimulation for cluster headache.Sphenopalatine ganglion block also has evidence in treating trigeminal neuralgia, migraines, reducing the needs of analgesicsafter endoscopic sinus surgery and reducing pain associated with nasal packing removal after nasal operations.

Conclusions: Overall, sphenopalatine ganglion is a promising target for treating cluster headache using blocks, radiofrequencyablation and neurostimulation. Sphenopalatine ganglion block also has some evidence supporting its use in a few otherconditions. However, most of the controlled studies were small and without replications. Further controlled studies arewarranted to replicate and expand on these previous findings.

Keywords: Sphenopalatine ganglion, Block, Radiofrequency ablation, Neurostimulation, Nerve stimulation,Neuromodulation

* Correspondence: [email protected] of Neurology, University of Florida, PO Box 100236,1149 NewellDrive, Room L3-100, Gainesville, FL 32611, USAFull list of author information is available at the end of the article

The Journal of Headache and Pain

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Ho et al. The Journal of Headache and Pain (2017) 18:118 DOI 10.1186/s10194-017-0826-y

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ReviewThe sphenopalatine ganglion (SPG) is also known as pter-ygopalatine ganglion, nasal ganglion or Meckel’s ganglion.It is the largest and most superior ganglion of sensory,sympathetic and parasympathetic nervous system. It hasthe largest collection of neurons in the calvarium outsideof the brain. It is also the only ganglion having access tothe outside environment through the nasal mucosa. SPGgives rise to greater and lesser palatine nerves, nasopala-tine nerve, superior, inferior and posterior lateral nasalbranches, as well as the pharyngeal branch of the maxil-lary nerve. There are also orbital branches reaching thelacrimal gland.Because of its proximity to multiple important neuro-

anatomic structures in pain perception, SPG has beenpostulated to be involved in facial pain and headachesfor over a century. For headache, SPG is thought to playa central role in the generation of trigeminal autonomiccephalalgia (TAC). TAC is a broad term that encom-passes cluster headache, paroxysmal hemicrania, andshort-lasting unilateral neuralgiform headache attackwith conjunctival injection and tearing (SUNCT). It istypically distributed in the trigeminal distribution withipsilateral cranial autonomic features. TAC is character-ized by parasympathetic (lacrimation, rhinorrhea, nasalcongestion and edema) activation and sympathetic dys-function (ptosis and miosis). These clinical features canbe explained by the activation of the sympathetic andparasympathetic pathways within SPG [1]. The disrup-tion of this pathway by SPG blockade is thought to becentral to relieving the headache produced by TAC. Forface and neck neuralgias, connections of SPG with facialnerve, lesser occipital nerve and cutaneous cervicalnerves are thought to be the mechanism [1]. Irritation ofthe SPG can also cause orbital, periorbital and mandibu-lar symptoms through its connection with the ciliaryand otic ganglions and reflex otalgia by its connectionwith the tympanic plexus. Connections of SPG with thevagus nerve may produce visceral symptoms in dysfunc-tional states [1]. SPG may also play an important role invasodilation to protect the brain against ischemia fromstroke or migraine with aura. This mechanism is thoughtto be through the postganglionic parasympathetic fibers,which are connected to the vascular beds of the cerebralhemisphere [2]. Because the upper cervical roots areconnected to the superior cervical ganglion through thesympathetic trunk, which is connected to the deep pe-trosal nerve then to the SPG, SPG blockade is thoughtto be able to relieve pain from the head, face, neck andupper back [1]. This is the rationale for using SPG blockin treating any head, face, neck pain refractory to con-ventional treatment. Through the inhibition of the sym-pathetic trunk, SPG block was also thought to be usefulin treating generalized muscle pain including

fibromyalgia and low back pain [3]. For postdural punc-ture headache, the pain mechanism is thought to be sec-ondary to cerebrospinal fluid leak that exceeds theproduction rate, causing traction on the meninges andparasympathetic mediated reflex vasodilatation of themeningeal vessels. SPG blockade is thought to workthrough blocking the parasympathetic flow to the cere-bral vasculature, allowing the cerebral vessels to returnto normal diameter, thus relieving the headache [4].Although the mechanism by which pain is produced

from SPG is not well-characterized, SPG has been thetreatment target ranging from cluster headache to lowback pain. Three main types of interventions are cur-rently available: chemical nerve block/lysis, radiofre-quency ablation and neurostimulation. Some of theseinterventions are commonly performed in interventionalpain clinics for treatment of headache resistant to con-servative measures. Despite their use, the level of evi-dence for using SPG interventions varies widely across amyriad of conditions.In this systematic review, we sought to systematically

collect the evidence supporting the use of these SPGinterventions in treating various painful conditions. Wealso summarized the level of evidence for each conditionand intervention.

MethodsProtocolThis systematic review applies the guidelines issued inthe latest Preferred Reporting Items for SystematicReviews and Meta-Analysis (Additional file 1: PRISMA).

Information sourcesThe electronic databases of PubMed (https://www.ncbi.nlm.-nih.gov/pubmed/), Cochrane Central Register of ControlledTrials (CENTRAL, www.cochranelibrary.com), GoogleScholar (https://scholar.google.com/) were searched to iden-tify relevant articles. Additionally, references within eligiblepapers were screened for additional articles.

Literature search strategyThe search was conducted in May 2017. The search strat-egy was based on the Population, Intervention, Compara-tor, Outcome (PICO) framework and was conducted tofind studies on sphenopalatine ganglion block, radiofre-quency ablation and neurostimulation. Population (P) wasdefined as patients suffering from any medical condition;intervention (I) was limited to sphenopalatine ganglionblock, sphenopalatine radiofrequency ablation, and sphe-nopalatine ganglion neurostimulation; patients receivinginterventions were compared (C) to preintervention sta-tus, patients without treatment or healthy controls; theoutcome (O) needed to either qualitatively or quantita-tively measure the reduction in disease severity with

Ho et al. The Journal of Headache and Pain (2017) 18:118 Page 2 of 27

https://www.ncbi.nlm.nih.gov/pubmedhttps://www.ncbi.nlm.nih.gov/pubmedhttp://www.cochranelibrary.comhttps://scholar.google.com/

intervention. The complete entered search strategy inPubMed was: “(sphenopalatine) AND ganglion) ANDblock” for sphenopalatine ganglion block; “(sphenopala-tine) AND ganglion) AND radiofrequency” for radiofre-quency ablation; and (sphenopalatine AND ganglion ANDneurostimulation) OR (sphenopalatine AND ganglionAND neuromodulation).

Eligibility criteria and study selectionTo be included in this review, studies had to meet thefollowing criteria: 1. The study sample was human. 2.Interventions must be SPG block, SPG radiofrequencyablation or SPG neurostimulation. 3. Articles had to bewritten in English. 4. Full-Text articles had to be avail-able. 5. Conference abstracts and reviews were excluded.

Data items and collectionThe following items were compiled in the evidence tablesfor SPG block (Table 2-12): first author, year of publica-tion, medical condition treated, approach, imaging modal-ity, medication used for the procedure, number of cases,study design and outcome. For radiofrequency ablation,the following additional items were collected: radiofre-quency ablation temperature, type of radiofrequency abla-tion, parameter used and how to identify the correctposition of the radiofrequency cannula/probe. For neuro-stimulation, the following additional items were collected:type of stimulator, type of stimulation and how to identifythe correct position.

Risk of bias assessmentThe quality of randomized-controlled studies wasassessed using the 7-item criteria in Review ManagerSoftware version 5.35 provided by the Cochrane Collab-oration [5]. The 7-item criteria contained: (1) randomsequence generation; (2) allocation concealment; (3)blinding of participants and personnel; (4) blinding ofoutcome assessment; (5) incomplete outcome data; (6)selective reporting and (7) other bias.

Analysis of evidence and recommendationsLevel of evidence was graded based on Oxford Center forEvidence-based Medicine (1a: Systematic review ofrandomized-controlled trials. 1b: Individual randomized-controlled trials with narrow confidence interval. 2a: Sys-tematic review of homogenous cohort studies. 2b: Individ-ual cohort studies and low quality randomized-controlledtrial. 3a: Systematic review of homogenous case-controlstudies. 3b: Individual case-control study. 4. Case seriesand poor-quality cohort and case-control studies. 5.Expert opinion. Grade of recommendation: A: Consistentlevel 1 studies. B: Consistent level 2 or 3 studies or extrap-olations from level 1 studies. C: Level 4 studies or extrapo-lations from level 2 or 3 studies. D: Level 5 evidence or

troublingly inconsistent or inconclusive studies of anylevel. Risk of bias in individual studies and across studieswere not systematically assessed as most studies includedin this review were case reports and case series.

ResultsOverall summaryThe result of the search process is provided in Fig. 1. 60 arti-cles were included for SPG block, 15 articles for SPG radio-frequency ablation, and 8 articles for SPG neurostimulation.The evidence levels and grades of recommendation for

SPG block, radiofrequency ablation and neurostimula-tion are summarized in Table 1. Any study with evidencelevel above case series is included in Table 2. Risk of biasof randomized-controlled studies is summarized in Fig. 2.Most randomized-controlled studies included in thisreview have adequate randomization and blinding ofparticipants and personnel.

Fig. 1 Overview of the systematic review process


In the following sections, we will summarize the levelof evidence and grades of recommendations by the typeof SPG interventions and associated medical conditions.

Sphenopalatine ganglion blockSixty articles were included for sphenopalatine ganglionblock. Of the 60 studies, 11 were small randomized-

controlled studies, and 1 was retrospective case-control study. The rest of the literature included casereports and case series. The type of blocking agentvaried across studies, but they could be broadly putinto three categories: cocaine, voltage-gated sodiumchannel blocker (local anesthetics), and a combinationof voltage-gated sodium channel blocker and steroids.

Table 1 Summary of evidence level and grade of recommendation for SPG block, radiofrequency ablation and neurostimulation

Medical condition Application/ Medicationused in controlledstudies

Number ofcontrolledstudies

Highest levelof evidence

Grade ofrecommendation

SPG block

Cluster headache Cotton swab/cocaineor lidocaine

1 2b B

Second-division trigeminal neuralgia Lidocaine spray 1 2b B

Reducing the needs of analgesicsafter endoscopic sinus surgery

Needle injection,transnasal and palatalapproach/lidocaine,bupivacaine, levobupivacaine,tetracaine

6 1b B

Reducing the pain associatedwith nasal packing removalafter nasal operation

Needle injection,infrazygomaticapproach/lidocaine

1 3b B

Migraine Tx360 device/ bupivicane 1 2b B

Postdural puncture headache,sphenopalatine maxillary neuralgia,facial neuralgia, sympathetic neuralgia,post-traumatic atypical facial pain,atypical odontalgia, pain from midlinegranuloma, herpetic keratitis, hemifacialheadache,paroxysmal hemicrania, nasalpain, hemicrania continua, trigeminalneuropathy, cancer pain, seizuresassociated nasal pathology, arthriticpain and muscle spasm, intercostalneuritis, persistent hiccups, ureteralcolic, dysmenorrhea, peripheral painfulvascular spasm, complex regional painsyndrome and hypertension

Various protocols 0 4 C

Myofascial pain Cotton-tipped applicator,nasal spray/lidocaine

2 2b Not recommended

SPG radiofrequency ablation

Cluster headache Infrazygomatic approach/80 °C, 60s ×2

0 (1 cohort study) 2b B

Sluder’s neuralgia, posttraumaticheadache, chronic head and face pain,atypical trigeminal neuralgia, atypicalfacial pain, chronic facial pain secondaryto cavernous sinus meningioma,trigeminal neuralgia, SPG neuralgiadue to herpes zoster

Various protocols 0 4 C

SPG neurostimulation

Cluster headache Customized to each patient,mean frequency120.4 ± 15.5 Hz,pulse width 389.7 ± 75.4 μs,intensity 1.6 ± 0.8 mA

1 1b B

Idiopathic facial pain, migraine Various protocols 0 4 C


Table 2 Studies with evidence level above case series in SPG block, radiofrequency ablation and neurostimulationEvidence level above case series

Author Year Medicalproblems

Approach Imaging Medication Numberof cases

Study design Outcome

SPG Block

Bergeret al. [32]

1986 Low back pain Cotton tipapplicatorand transnasalneedle

None Cocaine orlidocaine

7 cases withcocaine, 7 caseswith lidocaine,7 controls

Case-control No statisticalsignificancebetweencases andcontrols

Slade et al.[51]

1986 Tear secretionwith topicalanesthesia

Needle injection,through thegreater palatineforamen

None 2% lidocaine 10 Case-control(using self ascontrol)

Tear secretionsignificantlyreducedby 73%(p < 0.001)

Hennebergeret al. [36]

1988 Nicotineaddiction

Cotton tippedapplicator,transnasalapproach

None Bupivacaine,cocaine orsaline

6 with bupivacaine,5 with cocaine,6 with saline

Double-blindplacebo-controlled

Significantlyfewer symptomsof discomfort forpatients in theanesthetictreatmentgroupsthan placebogroup

Silvermanet al. [37]

1993 Experimentallyinduced pain(submaximaleffort tourniquettest)

Cotton tippedapplicator

None 20% lidocaineand epinephrine

16 healthyvolunteers

Double-blind,cross-over study

No significantdifferencebetweenexperimentaland placebogroup.

Scudds et al.[3]

1995 Chronic musclepain syndrome


None 4% lidocaine 42 withfibromyalgia,19 with myofascialpain syndrome

Double-blindrandomizedcontrolled

No statisticalsignificancebetween4% lidocaineand placebo

Janzen et al.[30]

1997 Myofascial painsyndrome andfibromyalgia

Nasal spray None 4% lidocaine 42 withfibromyalgia,19 with myofascialpain syndrome

Double-blind,placebo-controlled

No statisticalsignificancebetween 4%lidocaine andplacebo

Ferranteet al. [31]

1998 Myofascial painsyndrome of thehead, neck andshoulders

NA None 4% lidocaine 13 cases,7 controls

Double-blind,placebo-controlled,crossover design

No statisticalsignificance

Costa et al.[6]

2000 Clusterheadache(nitroglycerininduced)


None 10% cocaine or10% lidocaine

6 episodic CH,9 chronic CH

Double-blind,placebo-controlled,

All patientswith inducedpain respondedto cocaine after31.3 min andlidocaine after37 min

Hwang et al.[23]

2003 Removal ofnasal packingafter nasaloperation

Needle injectioninto the greaterpalatine canal

None 1% lidocaine 11 Case-control Injectionside hadsignificantlylower painthan thecontrol side

Kanai et al.[11]

2006 Second divisiontrigeminalneuralgia

Nasal spray None Lidocaine 25 Randomizedcontrol

Significantlydecreased painwith intranasallidocaine spray

Ahmed et al.[18]

2007 Sinonasalsurgeryintraoperativeisofluoraneconsumption,hypotensiveagents used,postoperativepain

Bilateral SPG block,injected betweenthe middle andinferior turbinates

None 0.5% lidocaineand epinephrine.

15 cases, 15controls

Randomized-controlled

Significantlyreducedintraoperativeisofluoraneconsumptionand esmololuse, postoperativetramadol use andpostoperative pain.

Ali et al. [20] 2010 Endoscopictrans-nasalresection ofpituitaryadenoma,anesthetic,vasodilatorand analgesicsparing effect


None 1.5% lidocaineand epinephrine

15 cases and15 controls


Significantlyreduced insevofluraneand nitroglycerineconsumption,emergence time,postoperativepain and needof meperidineanalgesia.


Table 2 Studies with evidence level above case series in SPG block, radiofrequency ablation and neurostimulation (Continued)Evidence level above case series




Cho et al.[17]

2011 Endoscopicsinus surgerypostoperativeanalgesiaefficacy

Transoral, throughthe greaterpalatine foramen

None 0.25%bupivacainewithepinephrine

60 Double-blindrandomized,placebo-controlled

Pain notsignificantlydifferent fromcontrol

Kesimci et al.[22]


Bilateral SPG block,injected betweenthe middle and inferior turbinates

None 0.5%bupivacaineor 0.5%levobupivacaine


Postoperativepain significantlyreduced, alsosignificantlyfew patientsrequiringadditionalanalgesicsin thepostoperative24 h.

Demariaet al. [21]


Bilateral SPG block,palatal approach

None 2% lidocaineand 1%tetracaine


Patients weredischargedsooner thanthe controlgroup. Theblock groupalso requiredless totalfentanyl inthe recoveryroom.

Cady et al.[15]

2015 Chronicmigraine

Tx360 None 0.5%bupivacaine

38 Double blind,placebo control

Significantlydecreasedheadacheat 24 h

Cady et al.[16]


Repetitive block(twice a week)with Tx360

None 0.5%bupivacaine

38 Double blind,placebo control

No statisticaldifference at1 month and6 monthsbetweentreatmentand controlgroups.

Schafferet al. [34]

2015 Acute anterioror globalheadache

Tx360 device None 0.5%bupivacaine

93 Randomizedplacebo-controlled

No statisticallysignificantdifference

Al-Qudahet al. [19]


Applied tothe SPGregion

None 2% lidocaineandepinephrine

60 (30 cases,30 controls)

Double-blind,placebocontrolled

Significantpain reductionin the SPGblock group

Narouzeet al. [38]

2009 Chronic clusterheadache

Infrazygomaticapproach

Fluoroscopy NA 15 Prospectivecohort

Mean attackintensity,mean attackfrequency,pain disabilityindex significantreduced at 1year follow-up(P < 0.0005,P < 0.0003,P < 0.002,respectively)

SPG Neurostimulation

Schoenenet al. [41]

2013 Clusterheadache

ATI SPGstimulatorpositioned on thelateral-posteriormaxilla medialto the zygoma.Customized,mean frequency120.4 Hz, meanpulse width 389.7us, mean intensity1.6 mA

CT – 28 cases,with 3randomizedsettings.

Randomizedcontrolled

Pain reliefachieved in67.1% offull stimulation-treated attackscompared to7.4% of sham-treated attacks.P < 0.0001

Jurgens et al. [42] 2016 Cluster headache Neurostimulator,described inSchoenenet al. [41]

CT – 33 cases Cohort study.Long-termfollow-upfrom [41]

61% ofpatientswere eitheracuteresponder(>50% relief


Voltage-gated sodium channel blocker is the mostcommonly used agent.

Cluster headacheThere were nine articles on chronic cluster headachescollected through our literature search (see Table 3).One was a small double-blind placebo-controlled study(level 2b), six were case series and two were case reports(level 4, see Table 3). Costa et al. [6] reported a double-blind, placebo-controlled study using 15 cases of epi-sodic and chronic cluster headaches. Cluster headachewas induced with nitroglycerin, and SPG was treatedwith 10% solution of cocaine hydrochloride (1 ml, meanamount of application of 40-50 mg), 10% lidocaine(1 ml) or saline using a cotton swab previouslyimmersed in these solutions. The cotton swab wasplaced in the region corresponding to the sphenopala-tine fossa under anterior rhinoscopy. This was done inboth the symptomatic and the non-symptomatic sidesfor 5 min. Patients treated with cocaine and lidocaine re-ported relief in 31.3 min in the cocaine group and37 min for lidocaine group, compared to 59.3 min in thesaline group. The side effect was mainly the unpleasanttaste of lidocaine. This study was limited by its smallnumber of participants, the acutely induced clusterheadache from nitroglycerin, and its measure on onlyshort-term outcome.Other case reports/series using cocaine and local anes-

thetics as blocking agents generally reported good im-mediate outcomes for aborting acute cluster headache.One study using cocaine reported 10 out of 11 patientsreceiving 50-100% relief from spontaneous cluster head-ache [7], another study using lidocaine reported four outof five patients receiving relief from nitrate-inducedcluster headache [8]. Because of the short-term relieffrom cocaine and lidocaine, steroid has been tried to

prolong the relief provided by SPG block. In one caseseries, combination of triamcinolone, bupivacaine, mepi-vacaine and epinephrine helped improve severity andfrequency of cluster headaches in 11 out of 21 patients[9]. The same cocktail helped 55% of the 15 treated pa-tients in another case series [10].In summary, SPG block has moderate evidence in

treating cluster headache. The overall grade of recom-mendation is B for SPG block on cluster headache. Thestrongest evidence lies in aborting nitroglycerin-inducedcluster headache using local application of cocaine orlidocaine with cotton swab through the transnasal ap-proach. The side effect was mainly the unpleasant tasteof lidocaine. Addition of steroid may provide longer re-lief, but the evidence remains weak (Grade Crecommendation).

Trigeminal neuralgiaThere were four articles on SPG block for trigeminalneuralgia through our literature search. One was arandomized-controlled study (level 2b), two were caseseries and one case report (level 4, see Table 4). Kanai etal. performed a randomized-controlled study with 25participants with refractory second-division trigeminalneuralgia [11]. In this study, twenty-five patients withsecond-division trigeminal neuralgia were randomized toreceive two sprays (0.2 ml) of either lidocaine 8% or sa-line placebo in the affected nostril using a metered-dosespray. The paroxysmal pain triggered by touching ormoving face was assessed. Intranasal lidocaine 8% spraysignificantly decreased the paroxysmal pain for an aver-age of 4.3 h. The side effects were limited to local irrita-tion with burning, stinging or numbness of the nose andeye, and bitter taste and numbness of the throat. Onecase series [12] and one case report [13] reported imme-diate pain relief from nerve blocks with lidocaine and

Table 2 Studies with evidence level above case series in SPG block, radiofrequency ablation and neurostimulation (Continued)Evidence level above case series




frommoderateor greaterpain) or frequencyresponder(>50% inattackfrequency)at 24 months

Barloese et al. [43] 2016 Cluster headache Neurostimulator,described inSchoenenet al. [41]

CT – 33 cases Cohort study.Long-termfollow-upfrom [41]

30%experiencedat least 1episode ofcompleteattackremission(attack-freeperiodexceeding1 month)


bupivacaine. One case series used a combination ofdexamethasone and ropivacaine with the Tx360 applica-tor, which resulted in short-term pain relief [14]. Mul-tiple blocks over time seemed to provide longer painrelief but it was restricted to isolated cases.In summary, the overall grade of recommendation is B for

SPG block on trigeminal neuralgia. The strongest evidencelies in treating with 8% lidocaine nasal spray in the affectednostril. The analgesia is effective but temporary (4.3 h). It iswell-tolerated with side effects limited to local irritations.Addition of steroid and use of the Tx360 applicator may beuseful but there has not been a controlled study.

MigraineThere was one small double-blind, placebo-controlledstudy and one long-term follow-up of the same study(level 2b), two case series and one case report (level 4,see Table 5). Cady et al. [15] reported a randomized-controlled study using the Tx360 device and bupivacaineto acutely treat chronic migraines with repetitive SPGblockade. 38 subjects with chronic migraines wereincluded in the final analysis. Participants received aseries of 12 SPG blocks with either 0.3 cm3 of 0.5% bupi-vacaine or saline delivered with the Tx360® through eachnostril, over a 6-week period (2 SPG blocks/week). SPGblock was found to be effective in reducing the severityof migraines up to 24 h. However, repetitive blocks didnot provide any statistically significant relief at 1-monthor 6-month follow-ups [16]. The most common sideeffects were mouth numbness, lacrimation, and badtaste, but there was no statistical difference infrequency of side effects between the bupivacaine andsaline groups.Given the positive randomized-controlled study, grade

of recommendation is B for short term treatment ofchronic migraines using 0.5% bupivacaine with theTx360 device®. It should be noted that the effect is onlypresent for 24 h. and it is not suitable for patients seek-ing relief greater than 24 h.

Postoperative pain of the head and faceThere were six randomized-controlled studies, one case-control study and one case series falling under this cat-egory (Table 6).Six randomized-controlled studies examined the effi-

cacy of SPG blockade in reducing the needs of analgesicsafter endoscopic sinus surgery (level 2b). One study byCho et al. [17] did not show significant difference be-tween SPG block and placebo, but five additionalrandomized-controlled studies showed significant reduc-tion in the need of post-operative analgesics in the grouptreated with SPG block [18–22]. The five positive studiesused 0.5% lidocaine with epinephrine [18], 1.5% lido-caine with epinephrine [22], 0.5% bupivacaine or 0.5%levobupivacaine [22], 2% lidocaine and 1% tetracaine[21]. The SPG block was applied using injections, bilat-erally through the transnasal or palatal approach. Therewas no difference in complications between the treat-ment and placebo group.Hwang et al. [23] reported a case-control study to

assess the efficacy of SPG block in reducing the painassociated with nasal packing removal after nasal oper-ation (level 3b). 1% lidocaine was injected into thegreater palatine canal ipsilaterally using infrazygomaticapproach. Participants reported significantly lower painon the side of the nose that received SPG block com-pared to the control side.

Fig. 2 Risk of bias summary of randomized-controlled studies


Robiony et al. [24] reported one case series (level 4) onthe effectiveness of combined maxillary transcutaneousnerve block and SPG block in reducing postoperativepain for surgical correction of skeletal transverse dis-crepancy of the maxilla.Given five positive double-blind placebo-controlled

studies and one negative study, the grade of recom-mendation is B for SPG block in improving postoper-ative analgesia efficacy after endoscopic sinus surgery.

Each study blocked SPG with injection of differentlocal anesthetics using different approaches. In 5studies, SPG block was consistently found to be ef-fective in reducing the need of analgesics after endo-scopic sinus surgery. A combination with maxillarytranscutaneous nerve block may be also helpful butfurther systematic study is necessary to evaluate itsefficacy. Grade of recommendation is also B for redu-cing pain associated with nasal packing removal after

Table 3 Studies of SPG block for cluster headache

Cluster headache

Author Year Medical problems Approach Imaging Medication Numberof cases

Studydesign

Outcome

Devoghelet al. [52]

1981 Cluster headache Needle injection.Supra-zygomaticapproach

None Pure alcohol 120 Caseseries

85.8% hadcomplete relief

Barre et al.[7]

1982 Cluster headache Cotton swab.Applied tosphenopalatineforamen.Self-applicationif responded totreatment

None 50 mg of cocaineflakes, then 10%and 5% cocainesolution

11 Caseseries

10 out of 11 had50-100% abortionrate in spontaneousheadache

Kittrelleet al. [8]

1985 Cluster headache Lidocaine directlydropped intothe nostrils

None 4% lidocaine 5 Caseseries

4 of 5 patientsobtained reliefof nitrate-inducedcluster headaches

Costa et al.[6]

2000 Cluster headache(nitroglycerininduced)


None 10% cocaine or10% lidocaine

6 episodic CH,9 chronic CH

Double-blind,placebo-controlled,

All patients withinduced painresponded tococaine after31.3 min andlidocaine after37 min

Felisati et al.[9]


Endoscopicneedle injectionthat approachesthe pterygopalatinefossa by way of thelateral nasal wall

None Triamcinoloneacetonide, 1%bupivacaineand 2%mepivacainewith adrenaline

21 Caseseries

11 out of 21 haveimprovement insymptoms

Yang et al.[53]


Transnasal needle Fluoroscopy 0.2% Ropivacaineand triamcinolone

1 Casereport

60% pain relief

Pipolo et al.[10]

2010 Drug-resistantchronic clusterheadache

Needle into theinferior portionof the sphenopalatineforamen (transnasalendoscopictechnique-prasanna 1993

None 40 mgtriamcinoloneacetonide,1% bupivacaine,2% mepivacainewith adrenaline

15 Case series 55% experiencecomplete subsidenceof CH symptoms

Zarembinskiet al. [54]

2014 Drug-resistantchronic clusterheadache,with Jacob’sdisease

Sphenopalatineganglion blockvia mandibularnotch, thenradiofrequencyoblation.

Fluoroscopy,CT

0.25%bupivacaine and10 mg/mldexamethasone

1 Case report Pain significantlyimproved.

Kastler et al.[55]

2014 Cluster headache(14), persistentidiopathic facialpain (10), andother types offacial pain (18)


CT Absolute alcohol 14 Caseseries

76.5% of patientshave 50% painrelief at 1 month


nasal surgery, using lidocaine injection through theinfrazygomatic approach.

Head and neck cancer painThree case reports and series were found (level 4 evi-dence, Table 7). One study was SPG block and two onSPG neurolysis with phenol. The largest case series wasby Varghese et al. [25], who reported 22 cases of suc-cessful treatment with 6% phenol used via nasal endos-copy, as a neurolytic sphenopalatine ganglion block, forpain caused by advanced head and neck cancer. Theoverall grade of recommendation is C for any of thesepainful conditions.

Postherpetic neuralgiaA total of three case reports and series were foundthrough our search process (level 4 evidence, Table 8).All three articles reported successful treatment of post-herpetic neuralgia with SPG block using local anes-thetics. One study reported successful treatment ofpostherpetic neuralgia involving the ophthalmic division

of the trigeminal nerve, by SPG block under directvisualization through nasal endoscopy [26]. Another art-icle reported success in treating sinus arrest in posther-petic neuralgia by SPG block through trans-nasalapproach utilizing cotton tipped applicators [27], andone study reported successful treatment of herpes zosterwithin a heterogeneous case series [28]. The overallgrade of recommendation is C.

Musculoskeletal painThere were two negative randomized-controlled studyon head, neck and shoulder myofascial pain. There werealso a small case-control study on low back pain, a smallrandomized-controlled study on chronic muscle painsyndrome and two large case series in our literaturesearch (Table 9).Successful treatment of lumbosacral pain with SPG

block was initially reported in two large case series inthe 1940s [28, 29]. However, further randomized-controlled studies dismissed these findings. Scudds et al.[3] reported a randomized-controlled study applying

Table 5 Studies of SPG block for migraine

Migraine


Approach Imaging Medication Number ofcases


Amsteret al. [28]

1948 Migraine Cotton tippedapplicator,transnasalapproach

None Nupercaine,pontocaine,monocaine

4 Case series Relief of pain and spasm in90% of cases

Maizelset al. [56]

1999 Migrainewith aura

Self-administeredintranasal 4%lidocaine

None 4% lidocaine 1 Case report Most headaches were successfullyaborted for 15 months

Yarnitskyet al. [57]

2003 Migraine Cotton tipapplicator

None 2% lidocaine 32 Case series Significant reduction in pain scoreduring migraine

Cadyet al. [15]


Tx360 None 0.5% bupivacaine 38 Double blind,placebo control

Significantly decreased headacheat 24 h

Cadyet al. [16]


Tx360 None 0.5% bupivacaine 38 Double blind,placebo control

No statistical difference at 1 monthand 6 months between treatmentand control groups.

Table 4 Studies of SPG block for trigeminal neuralgia

Trigeminal neuralgia

Author Year Medical problems Approach Imaging Medication Number of cases Study design Outcome

Petersonet al. [12]

1995 Trigeminal neuralgia Cotton tipapplicator

None 4% lidocaine 2 Case series Pain free

Manahanet al. [13]

1996 Trigeminal neuralgia NA None Bupivacaine 1 Case report Pain free

Kanaiet al. [11]

2006 Second divisiontrigeminal neuralgia

Nasal spray None Lidocaine 25 Randomizedcontrol

Significantly decreasedpain with intranasallidocaine spray

Candidoet al. [14]

2013 Trigeminal neuralgia,chronic migraineheadache,post-herpeticneuralgia

Tx360 Nasalapplicator,transnasal

None 0.5% ropivacaineand 2 mgdexamethasone

3 Case series Satisfactory


SPG block (cotton-tipped pledgelets with 4% lidocaine)to 42 participants with fibromyalgia and 19 participantswith myofascial pain syndrome. He reported no statis-tical difference between treatment and placebo group inpain intensity, headache frequency, sensitivity to pressure,

anxiety, depression, and sleep quality. Janzen et al. [30]reported a similar randomized-controlled study by apply-ing SPG block with lidocaine spray. Forty-two participantswith fibromyalgia and 19 with myofascial pain syndromewere included in his study. He again found not difference

Table 6 Studies of SPG blocks for operative pain of the head and face

Operative Pain of the head and neck



Robionyet al. [24]

1998 Skeletal transversediscrepancy of themaxilla

Transcutaneous truncalanesthesia of the maxillarynerve in association withtransmucosal anesthesiaof the sphenopalatineganglion

None Prilocainecarbocainecream

12 Case series Total anesthesiaof the maxillaryarea facilitatedthe operationsand appreciablyreduced amountof postoperativepain

Hwanget al. [23]

2003 Removal of nasalpacking after nasaloperation

Needle injection into thegreater palatine canal

None 1% lidocaine 11 Case-control Injection sidehad significantlylower pain thanthe control side

Ahmedet al. [18]

2007 Endoscopic sinonasalsurgery intraoperativeisofluorane consumption,hypotensive agents used,postoperative pain

Bilateral SPG block,injected between themiddle and inferiorturbinates

None 0.5% lidocaineand epinephrine.

15 cases,15 controls


Significantlyreducedintraoperativeisofluoraneconsumptionand esmololuse, postoperativetramadol useand postoperativepain.

Ali et al. [20] 2010 Endoscopic trans-nasalresection of pituitaryadenoma, anesthetic,vasodilator and analgesicsparing effect


None 1.5% lidocaineand epinephrine

15 casesand15 controls


Significantlyreduced insevoflurane andnitroglycerineconsumption,emergence time,postoperativepain and needof meperidineanalgesia.

Kesimciet al. [22]

2012 Endoscopic sinus surgerypostoperative analgesiaefficacy


None 0.5%bupivacaineor 0.5%levobupivacaine


Postoperativepain significantlyreduced, alsosignificantly fewpatients requiringadditionalanalgesics in thepostoperative24 h.

Demariaet al. [21]


Bilateral SPG block,palatal approach

None 2% lidocaineand 1%tetracaine


Patients weredischargedsooner than thecontrol group.The block groupalso required lesstotal fentanyl inthe recoveryroom.

Al-Qudahet al. [19]


Applied to the SPGregion


60 (30cases, 30controls)

Double-blind,placebocontrolled

Significant painreduction in theSPG block group


between the treatment and placebo group. Ferrante et al.[31] reported a randomized-controlled study with 13 casesof head, neck and shoulder myofascial pain and 7 healthycontrols. He also showed no significant effect with SPGblock. On low back pain, Berger et al. [32] reported acase-control study with 21 patients randomized tococaine, lidocaine and saline. He did not find significantdifferences in outcomes. Given the negative randomized-controlled studies, it is not recommended to use SPGblock on musculoskeletal pain.

Postdural puncture headacheThere were two case series and one case report (level 4)reporting successful treatment of postdural punctureheadache (Table 10). No higher-level studies were avail-able. Cohen et al. [33] reported the largest case series of32 cases with postdural puncture headache. In the series,69% of the patients treated with transnasal SPG blockwere saved from epidural blood patch. The overall gradeof recommendation is C for SPG block on postduralpuncture headache.

Other pain syndromes of the head and facePain syndromes involving the head and face not belong-ing to any category mentioned above are summarized inTable 11. There was a negative randomized-controlledstudy using Tx360 device treating acute anterior and

global headache [34]. There were also multiple casereports and series on the effectiveness of SPG in control-ling various types of head and facial pain. Local anes-thetics and steroids have been used for SPG block, whilephenol and alcohol have been used for SPG neurolysis.They have been successfully used in Sluder’s neuralgia,sphenopalatine maxillary neuralgia, facial neuralgia,sympathetic neuralgia, post-traumatic atypical facialpain, atypical odontalgia, pain from midline granuloma,herpetic keratitis, hemifacial headache, paroxysmalhemicrania, nasal pain, hemicrania continua and trigem-inal neuropathy. The largest case series was provided byRodman et al. [35], documenting 147 patients with vari-ous types of nasal pain and headache. He reported that81.3% of the patients had pain relief after receiving SPGblock with a mixture of bupivacaine and triamcinolone.Schaffer et al. [34] reported a randomized placebo-controlled study using Tx360 device to treat acute anter-ior or global headache. A total of 93 participants wererecruited in the study, but the study showed no statis-tical significance between the treatment and controlgroups. Because of the result, we do not recommendSPG block for anterior or global headache. The overallgrade of recommendation is C for other types of headand facial pain, including Sluder’s neuralgia, sphenopala-tine maxillary neuralgia, facial neuralgia, sympatheticneuralgia, post-traumatic atypical facial pain, atypical

Table 7 Studies of SPG block for cancer pain

Head and neck cancer pain

Author Year Medical problems Approach Imaging Medication Number ofcases


Prasannaet al. [58]

1993 Pain from carcinoma of thetongue and floor of the mouth

Nasal sinuscope None 0.25%bupivacaine

10 Case series Immediate pain relief

Vargheseet al. [25]

2001 Pain due to advanced headand neck cancer

Endoscopic needleinjection

None 6% phenol 22 Case series 17 out of 22 patientshad significant painrelief

Vargheseel al. [59]

2002 Pain due to advanced headand neck cancer

Transnasal through thesphenopalatine foramen

None 6% phenol 1 Case report Significant pain relief

Table 8 Studies of SPG block on postherpetic neuralgia

Postherpetic neuralgia


Studydesign

Outcome

Prasannaet al. [26]

1993 Postherpetic neuralgiainvolving the ophthalmicdivision of the trigeminalnerve

Combination of stellateganglion and sphenopalatineganglion block, cottontip applicator

None Lidocaine andbupivacaine

1 Case report Pain free

Saberskiet al. [27]

1999 Sinus arrest inpostherpetic neuralgia

Cotton tipped applicator,transnasal approach

None 20% lidocaine 1 Case report No paroxysmal painor sinus pausesimmediatelyafter block

Amsteret al. [28]

1948 Herpes zoster Cotton tipped applicator,transnasal approach


3 Case series Relief of pain andspasm in 90% ofcases


odontalgia, pain from midline granuloma, herpetic kera-titis, hemifacial headache, paroxysmal hemicrania, nasalpain, hemicrania continua and trigeminal neuropathy.

Other syndromesSPG block has been used for a myriad of other condi-tions not involved in painful syndromes of the head andface. These conditions include seizures associated nasalpathology, arthritic pain and muscle spasm, intercostalneuritis, persistent hiccups, ureteral colic, dysmenorrhea,peripheral painful vascular spasm, complex regional painsyndrome and hypertension (Table 12). Most of thesestudies reported significant improvement, but none ofthem had evidence level above case series. There wasone randomized-controlled study in assessing theefficacy of SPG block in treating nicotine addiction, butthe result was negative [36]. One small double-blindcross-over study examined whether SPG block reduces

experimentally induced pain using submaximal efforttourniquet test, but the SPG block failed to make adifference in pain perception [37].Overall, the grade of recommendation for any of

these syndrome remains at C. SPG block is not rec-ommended for nicotine addiction due to the negativerandomized study.

Summary for SPG blockGrade of recommendation of using SPG block is B forcluster headache, second-division trigeminal neuralgia,migraine, reducing the pain associated with nasal pack-ing removal after nasal operation and for reducing theneeds of analgesics after endoscopic sinus surgery. Outof these conditions, SPG block has the best evidence inreducing the needs of analgesics after endoscopic sinussurgery, as there are six randomized-controlled studies.It should be noted that the recommendation for cluster

Table 9 Studies of SPG block for musculoskeletal pain

Musculoskeletal pain

Author Year Medical problems Approach Imaging Medication Number of cases Study design Outcome

Amsteret al. [28]

1948 Lumbosacral andsacroiliac pain



61 Case series Relief of pain and spasm in90% of cases

Ruskinet al. [29]

1946 Lumbo-sacralspasm

Unknown None Cocaine,novocaineor nupercaine

36 Case series Pain partially or completelyrelieved with SPGB andintramuscular injections ofironyl and calcium ascorbate

Bergeret al. [32]

1986 Low back pain Cotton tipapplicator andtransnasal needle

None Cocaine orlidocaine

7 cases withcocaine, 7 caseswith lidocaine,7 controls

Case-control No statistical significancebetween cases and controls

Scuddset al. [3]

1995 Chronic musclepain syndrome


None 4% lidocaine 42 withfibromyalgia,19 with myofascialpain syndrome

Double-blindrandomizedcontrolled

No statistical significancebetween 4% lidocaine andplacebo

Janzenet al. [30]

1997 Myofascial painsyndrome andfibromyalgia

Nasal spray None 4% lidocaine 42 with fibromyalgia,19 with myofascialpain syndrome

Double-blind,placebo-controlled

No statistical significancebetween 4% lidocaine andplacebo

Ferranteet al. [31]

1998 Myofascial painsyndrome of thehead, neck andshoulders

NA None 4% lidocaine 13 cases,7 controls

Double-blind,placebo-controlled,crossoverdesign

No statistical significance

Table 10 Studies of SPG blocks for postdural puncture headache

Postdural puncture headache


Studydesign

Outcome

Cohen et al. [60] 2014 Postdural punctureheadache

Cotton-tipapplicator

None 5% lidocaine 32 Case series 69% of the patients were savedfrom epidural blood patch

Kent et al. [4] 2015 Postdural punctureheadache


None 2% lidocaine 3 Case series 1 patient had relief, 2 had to getepidural blood patch.

Cardoso et al. [61] 2017 Postdural punctureheadache


None 0.5% Levobupivacaine 1 Case report Symptoms relieved by 5 min.


Table 11 Studies of SPG blocks for other pain syndromes of the head and facePain syndromes of the head and face




Ruskin et al. [62] 1925 SP maxillary neuralgia,SP facial neuralgia,SP sympathetic neuralgia,SPG cell neuralgia

Needle injection. None 20% Cocaine,10% silver nitrate,70% alcohol

7 Case series Improvementsor completerelief

Stechison et al. [63] 1994 Post-traumatic atypicalfacial pain syndrome

Needle injection.Transfacialtranspterygomaxillaryaccess to foramenrotundum SPG andmaxillary nerve

CT First stage: 0.5%bupivacaine,Second stage: 98%ethyl alcohol and0.5% bupivacainein 2:1 ratio

5 Case series 3 had alcoholneurotomyand pain freeat 5, 8 and12 months.2 respondedpoorly to firststage blockadeand did nothave alcoholneurotomy.

Peterson et al. [12] 1995 Atypical odontalgia Cotton tip,self-application

None 4% lidocaine 1 Case report Pain free

Saade et al. [64] 1996 Pain from midlinegranuloma

Self-administeredSPG block

None Lidocaine 1 Case report Significantpain relief

Puig et al. [65] 1998 Sluder’s neuralgia Cotton tipapplicator andtransnasal needle

None 88% phenol 8 Case series 90% decreasein head andface pain for9.5-monthduration

Windsor et al. [66] 2004 Herpetic keratitis Transnasal cottontip applicator

None Tetracaine,adrenalin and10% cocaine]

1 Case report Effect of blocklasts for amonth. Requiresmonths blocks

Obah et al. [67] 2006 Hemifacial and headache Transnasal None 4% lidocaine 1 Case report 80% reductionin painintensity

Cohen et al. [33] 2009 Postdural punctureheadache

Cotton tipapplicator

None Lignocaine 13 Case series 11 out of 13had immediaterelief ofheadache

Morelli et al. [68] 2010 Paroxysmal hemicraniaresistant to multipletherapies

Endoscopic needleinjection into thenasal mucousmembraneimmediatelybehind and overthe inferior portionof the sphenopalatineforamen and intothe fossa

None Triamcinoloneacetonide,1% bupivacaine,2% mepivacainewith adrenalin

1 Case report Reduction infrequencyand intensityof pain

Rodman et al. [35] 2012 Nasal pain or headache Endoscopic needleinjection

None 0.5% bupivacaineand triamcinoloneacetonide

147 Case series 81.3% of patientshave improvement

Grant et al. [69] 2014 Tension headache inpregnant woman

Cotton tipapplicator

None 4% lidocaine 1 Case report BID block fora total of 7blocks, painfree after

Kastler et al. [55] 2014 Cluster headache (14),persistent idiopathicfacial pain (10), andother types of facialpain (18)


CT Absolute alcohol 28 Case series 85.7% ofpatient withpersistentidiopathicfacial painand 40% ofother typesof facial painhad 50%pain reliefat 1 month


headache, second-division trigeminal neuralgia and mi-graine are each based on one small study, and it is onlymeant for acute treatment. There is no positive con-trolled study warranting chronic treatment with SPGblock. For other pain syndromes, grade of recommenda-tions is C due to the lack of positive controlled studies.These syndromes include postdural puncture headache,sphenopalatine maxillary neuralgia, facial neuralgia,sympathetic neuralgia, post-traumatic atypical facialpain, atypical odontalgia, pain from midline granuloma,herpetic keratitis, hemifacial headache, paroxysmalhemicrania, nasal pain, hemicrania continua, trigeminalneuropathy, cancer pain, seizures associated nasal path-ology, arthritic pain and muscle spasm, intercostal neur-itis, persistent hiccups, ureteral colic, dysmenorrhea,peripheral painful vascular spasm, complex regional painsyndrome and hypertension. Use of SPG block for myofas-cial pain, including fibromyalgia and head, neck, shouldermyofascial pain and low back pain, is not recommendeddue to several negative randomized-controlled studies.

Radiofrequency ablationFifteen studies were included on the topic of SPG radio-frequency ablation. One study was a small but positiveprospective cohort study for cluster headaches, while theother 14 studies were case reports and case series. Therewere no controlled studies.

Cluster headacheThere was one prospective cohort study and eight casereports/series on the treatment of cluster headache.Three case reports were on pulsed radiofrequency andsix on continuous radiofrequency ablation (Table 13).Narouze et al. [38] performed a prospective cohort studyof 15 cases of chronic cluster headaches treated withradiofrequency ablation using infrazygomatic approachunder fluoroscopy guidance. A total of 0.5 mL of lido-caine 2% was injected and 2 radiofrequency lesions werecarried out at 80 °C for 60 s each. After the ablation,

0.5 mL of bupivacaine 0.5% and 5 mg of triamcinolonewere injected. He reported statistically improved attackintensity, frequency and pain disability index up to18 months (level 2b). As for side effects: 50% (7/15)reported temporary paresthesias in the upper gums andcheek that lasted for 3-6 weeks with complete reso-lution. In only one patient, a coin-like area of permanentanesthesia over the cheek persisted. Sanders et al. [39]reported the largest case series of 66 cluster headachepatients treated with radiofrequency ablation after 12 to70 months. He reported complete relief in 60.7% ofpatients with episodic cluster headache, and in 30% ofpatients with chronic cluster headache. Of the 66 treatedpatients, eight patients experienced temporary postoper-ative epistaxis and 11 patients exhibited cheek hemato-mas. A partial radiofrequency lesion of the maxillarynerve was inadvertently made in four patients. Ninepatients complained of hypoesthesia of the palate, whichdisappeared in all patients within 3 months.The grade of recommendation is B for treating cluster

headache with radiofrequency ablation because of thepositive cohort study.

Other head and facial painThere were Seven case reports/series on various headand facial pain other than cluster headaches (all level 4,Table 14). These included Sluder’s neuralgia, posttrau-matic headache, chronic head and facial pain, atypicaltrigeminal neuralgia, atypical facial pain, chronic facialpain secondary to cavernous sinus meningioma, trigemi-nal neuralgia and SPG neuralgia due to herpes zoster.Akbas et al. [40] reported a 27-case series with varioustypes of head and facial pain. In 35% of the cases, painwas completely relieved, while 42% had moderate reliefand 23% had no relief with the SPG radiofrequency abla-tion. Because there were only case reports and caseseries available, the grade recommendation is C for anyof these conditions.

Table 11 Studies of SPG blocks for other pain syndromes of the head and face (Continued)Pain syndromes of the head and face




Androulakiset al. [70]

2016 Hemicraniacontinua

Tx360 device None Repetitive 0.5%bupivacaine

1 Case report Significantimprovementin headacheby 14 week

Malec-Milewskaet al. [71]

2015 Trigeminalneuropathy

Zygomaticapproach

Fluoroscopy 65% ethanolwith lidocaine

20 Case series Significantpain relief

Schaffer [34] 2015 Acute anterior or globalheadache

Tx360 device None 0.5% bupivacaine 93 Randomizedplacebo-controlled

No statisticallysignificantdifference

Sussman et al. [72] 2016 Chronic posttraumaticheadache after sport-related concussion

Cotton-tip applicator None 2% lidocaine and0.5% bupivacaine

1 Case report Symptom free at6-month follow-up


Table 12 Studies of SPG blocks for other syndromes

Other syndromes

Author Year Medical problems Approach Imaging Medication Number ofcases

Studydesign

Outcome

Byrd et al. [73] 1930 “Remote dysfunctions” Cotton tippedapplicator,transnasalapproach

None 50% butyn Over 2000cases

Case series Remotedysfunctionswere arrested

Sparer et al. [74] 1935 Recurrent convulsiveseizures associatedwith nasal pathology

Needleinjection

None Mixture ofalcohol andnovocaine

3 Case series Cessation ofseizures

Ruskin et al. [29] 1946 Muscle spasms andarthritic pain

Unknown None cocaine,novocaineor nupercaine

68 Case series Pain partiallyor completelyrelieved withSPGB andintramuscularinjections ofironyl andcalciumascorbate

Amster et al. [28] 1948 4 migraine, 2 acute torticollis,12 painful spastic shoulder,2 intercostal neuritis,3 herpes zosters,4 persistent hiccups,5 ureteral colic,3 dysmenorrhea,7 peripheral painfulvascular spasm,61 lumbosacraland sacroiliac pain



103 Case series Relief of painand spasm in90% of cases

Ruskin et al. [75] 1949 Arthritic pain Unknown None Unknown 30 Case series Pain partiallyor completelyrelieved withSPGB and ironsalt of theadenylicnucleotide

Slade et al. [51] 1986 Tear secretion withtopical anesthesia

Needle injection,through thegreater palatineforamen

None 2% lidocaine 10 Case-control(using selfas control)

Tear secretionsignificantlyreduced by73% (p < 0.001)

Hennebergeret al. [36]

1988 Nicotine addiction Cotton tippedapplicator,transnasalapproach

None Bupivacaine,cocaine orsaline

6 withbupivacaine,5 with cocaine,6 with saline

Double-blindplacebo-controlled

Significantlyfewer symptomsof discomfortfor patients inthe anesthetictreatmentgroups than theplacebo group

Silvermanet al. [37]

1993 Experimentally inducedpain (submaximal efforttourniquet test)

Cotton tippedapplicator


16 healthyvolunteers

Double-blind,cross-overstudy

No significantdifferencebetweenexperimentaland placebogroups

Quevedoet al. [76]

2005 Complex regional painsyndrome involving thelower extremity

Cotton tipapplicator,transnasal

None 4% tetracaine 2 Case series 50% painreduction

Triantafyllidiet al. [77]

2016 Hypertension Cotton tipapplicator,transnasal

None 2% lidocaine 22 Cohort study Systolic bloodpressuresignificantlydecreased by24 hrs and by21-30 days


Table

13Stud

iesof

SPGradiofrequ

ency

ablatio

non

clusterhe

adache

Cluster

headache

Firstauthor

Year

Med

icalprob

lem

App

roach

Imaging

Tempe

rature

(°C)

Type

ofRFA

Parameter

How

toiden

tifyrig

htspot

Stud

yde

sign

Num

ber

ofcases

Outcome

Sand

ers

etal.[39]

1997

Cluster

headache

Infrazygo

matic

approach

Fluo

roscop

y70

Highfre

quen

cy50

Hz,

0.2-1V

Paresthe

sia

inthepalate

Case-on

ly66

60.7%

ofep

isod

iccluster

headache

patientsreceived

completerelief,30%

inchronicclusterhe

adache

patientsachieved

complete

relief

Narou

zeet

al.[38]

2009

Chron

iccluster

headache

Infrazygo

matic

approach

Fluo

roscop

y80

Unkno

wn

50Hzat

<0.5Vto

prod

uce

deep

paresthe

sia

behind

the

root

ofthe

nose

.Prospe

ctive

coho

rt15

Meanattack

intensity,m

ean

attack

frequ

ency,p

ain

disabilityinde

xsign

ificant

redu

cedat

1year

follow-up

(P<0.0005,P

<0.0003,

P<0.002,respectively)

Chu

aet

al.[78]

2011

Cluster

headache

sInfrazygo

matic

approach

Fluo

roscop

y42

Pulsed

50Hz,

0.5-0.7V

Paresthe

sia

attheroot

oftheno

se

Caseseries

3Tw

ohadexcellent

relief,on

ehadpartialreliefby

2mon

ths

Oom

enet

al.[79]

2012

Atypical

facialpain,

clusterhe

adache

,Slud

er’sne

uralgia,

Slud

er’sne

urop

athy

Infrazygo

matic

approach

Fluo

roscop

y80

Unkno

wn

50Hz

Paresthe

sia

intheno

seandno

tin

thearea

ofthemaxillary

nerve

Caseseries

3Ade

quatepain

redu

ction:4/4

inatypicalfacialpain,2/3

inclusterhe

adache

,1/2

inSlud

er’sne

uralgia,2/2in

Slud

er’sne

urop

athy,1/1

inpo

sttraumaticne

urop

athy,0/1

inpo

st-herpe

ticne

uralgia,0/1

inSU

NCT(60%

show

edcon

side

rablepain

reliefaftera

sing

leproced

ure).

Zarembinski

etal.[54]

2014

Drug-resistant

chroniccluster

headache

,with

Jacob’sdisease

Initially

sphe

nopalatin

egang

lionblock,

then

radiofrequ

ency.

Fluo

roscop

y,CT

Unkno

wn

Unkno

wn

Unkno

wn

NA

Case

repo

rt1

Pain

sign

ificantlyim

proved

.

Fang

etal.

[80]

2015

Cluster

headache

Infrazygo

matic

approach

CT

42Pu

lsed

Unkno

wn

0.1-0.3V

toindu

ceparesthe

sia

ofthenasal

root

Caseseries

1611

episod

icand1chronic

clusterhe

adache

patients

hadcompletereliefby

6.3

days.2

episod

icand2chronic

clusterhe

adache

patientshad

norelief.

Bend

ersky

etal.[81]

2015

Cluster

headache

Infrazygo

matic

approach

Fluo

roscop

y42

Pulsed

45V,2Hz,

pulsewidth

20ms

Paresthe

sia

attheroof

oftheno

se

Caseseries

32patientshadno

relief,1had

reliefun

til1mon

th.C

ontin

ueRFAgave

reliefto

allthree

patients.

Dharm

avaram

etal.[82]

2016

Cluster

headache

Lateralapp

roach

Fluo

roscop

y80

Con

tinuo

usUnkno

wn

paresthe

sia

attheroot

Case

repo

rt1

Pain

freefor2mon

ths


Table

13Stud

iesof

SPGradiofrequ

ency

ablatio

non

clusterhe

adache

(Con

tinued)

Cluster

headache

Firstauthor

Year

Med

icalprob

lem

App

roach

Imaging

Tempe

rature

(°C)

Type

ofRFA

Parameter

How

toiden

tifyrig

htspot

Stud

yde

sign

Num

ber

ofcases

Outcome

oftheno

sewas

obtained

at0.3V

Loom

baet

al.[83]

2016

Cluster

headache

Infrazygo

matic

approach

CT

80Con

tinuo

us50

Hz

<0.3Vto

indu

ceparesthe

sia

ofthenasal

root

Case

repo

rt1

Nearcomplete

resolutio

nat

6mon

ths


Table

14Stud

iesof

SPGradiofrequ

ency

ablatio

non

head

andfacialpain

First

author

Year

Med

ical

prob

lem

App

roach

Imaging

Tempe

rature

(°C)

Type

ofRFA

How

toiden

tifythe

right

spot

Stud

yde

sign

Num

ber

ofcases

Outcome

Salar

etal.[50]

1987

Slud

er’s

neuralgia

Lateral

extraoral

approach

Fluo

roscop

y60

and65

Con

tinuo

us0.2-0.3V,

paresthe

siain

thedistrib

ution

ofthemaxillary

nerve

Caseseries

7Disappe

arance

ofthetypical

pain

attacks,lacrim

ationand

nasalsecretio

n,ho

wever,a

slight,d

eep-seated

trou

ble

somesensationpe

rsisted

Shah

etal.[84]

2004

Posttraumatic

headache

Infrazygo

matic

approach

Fluo

roscop

y42

Pulsed

50Hzand

0.5Vprod

uced

tinglingsensation

attheroot

ofthe

nose

Caserepo

rt1

Pain

redu

cedfro

m10/10to

1/10

Bayer

etal.[85]

2005

Chron

iche

adandface

pain

Infrazygo

matic

approach

Fluo

roscop

y42

Pulsed

50Hzup

to1V,

paresthe

siaelicited

attheroof

ofthe

nose,m

otor

stim

ulation

perfo

rmed

at2Hzto

ruleou

ttrigem

inalcontact,

which

results

inrhythm

icmandibu

larcontraction

Caseseries

3021%

hadcompletepain

relief,65%

hadmod

erate

pain

relief,14%

hadno

pain

relief.

Ngu

yen

etal.[86]

2010

Atypicaltrig

eminal

neuralgia

Coron

oid

approach

Fluo

roscop

y42

Pulsed

50Hzwith

1mspu

lse

duratio

n,0.6V

Caserepo

rt1

Symptom

-free

after2yrs.

Oom

enet

al.[79]

2012

Atypicalfacialp

ain,

clusterhe

adache

,Slud

er’sne

uralgia,

Slud

er’sne

urop

athy

Infrazygo

matic

approach

Fluo

roscop

y80

Unkno

wn

50Hz,paresthe

siain

the

nose

andno

tin

thearea

ofthemaxillaryne

rve

Caseseries

4atypicalfacialpain,2

Slud

er’sne

uralgia,

2Slud

er’sne

urop

athy,

1po

st-traum

atic

neurop

athy

ofinfraorbital

nerve,1po

sthe

rpetic

neuralgia,1SU

NCT

Ade

quatepain

redu

ction:

4/4in

atypicalfacialpain,

2/3in

clusterhe

adache

,1/2in

Slud

er’sne

uralgia,

2/2in

Slud

er’sne

urop

athy,

1/1in

posttraumatic

neurop

athy,0/1

inpo

st-herpe

ticne

uralgia,

0/1in

SUNCT(60%

show

edconsiderablepain

relief

afterasing

leproced

ure).

Elahi

etal.[87]

2014

Facialpain

second

ary

tocavernou

ssinu

smen

ingiom

aremoval

Infrazygo

matic

approach

Fluo

roscop

y80

Con

tinuo

us50

Hz,paresthe

siain

the

nasolabialmidlineregion

Caserepo

rt1

Satisfactorypain

reliefat

12mon

ths

Akbas

etal.

[40]

2016

Atypicalfacialp

ain,SPG

neuralgiadu

eto

herpes

zoster,atypical

Trigem

inalne

uralgia

Infrazygo

matic

approach

Fluo

roscop

y42

Con

tinuo

usParesthe

siaat

theroof

oftheno

seat

0.5–0.7V.

Toruleou

ttrigem

inal

contact,motor

stim

ulationat

afre

quen

cyof

2Hz

was

applied

Caseseries

27Pain

reliefno

t

achieved

in23%,

completely

relievedin

35%

andmod

erately

relievedin

42%

ofpatients


Summary for SPG radiofrequency ablationGrade of recommendation is B for applying SPG radio-frequency ablation to intractable cluster headache. Theprotocol used in the cohort study took infrazygomaticapproach under fluoroscopy and two radiofrequencyablations were carried out at 80 °C for 60 s. However,there is not yet a randomized-controlled study to test itsefficacy. Grade of recommendation is C for other headand facial pain, including Sluder’s neuralgia, posttrau-matic headache, atypical trigeminal neuralgia, atypicalfacial pain, chronic facial pain secondary to cavernoussinus meningioma, trigeminal neuralgia and SPG neural-gia due to herpes zoster.

Sphenopalatine ganglion neurostimulationEight studies were included for SPG neurostimulation.There was one randomized-controlled study with twolong-term follow-ups of the same study and five casereport/case series on sphenopalatine ganglion neurosti-mulation (Table 15).

Cluster headacheThere was one randomized-controlled study with twolong-term follow-ups of the same study, and two casereports/series on cluster headache. Schoenen et al. [41]reported a randomized-controlled trial using SPG neuro-stimulator for patients with refractory cluster headaches.Twenty-eight patients underwent SPG stimulatorimplantation and stimulations were applied at the onsetof cluster headache. The study employed a protocol thatrandomly inserted a placebo when treatment was initi-ated by the patient for a cluster headache attack. Threesettings were delivered in a randomized fashion (1:1:1):full stimulation (i.e. customized stimulation parametersestablished during the therapy titration period), sub-perception stimulation, and sham stimulation. A total of566 cluster headaches were treated, and pain relief wasachieved in 67.1% of patients receiving full stimulationcompared to 7.4% receiving sham treatment (P < 0.0001).Pain relief using sub-perception stimulation was not sig-nificantly different from sham stimulation (P = 0.96).Acute rescue medication was used in 31% of cluster head-ache attacks in patients receiving full stimulation, com-pared to 77.4% treated with sham stimulation (P < 0.0001)and 78.4% with sub-perception stimulation (P < 0.0001).In terms of side effect, most patients (81%) experiencedtransient, mild to moderate loss of sensation withindistinct maxillary nerve regions; 65% of events resolvedwithin 3 months. Jurgens et al. [42] reported a cohortstudy from the subjects who volunteered to be followedfor 24 months from the study by Schoenen et al. In thisstudy, 61% of patients were either acute responder (>50%relief from moderate or greater pain) or frequencyresponder (>50% in attack frequency) at 24 months.

Barloese et al. [9] analyzed participants who experiencedremission from the same dataset. 30% of participants werefound to have at least 1 episode of complete attack remis-sion in the 24-month period. Ansarinia et al. [44] reporteda case series of 6 patients. Out of the 18 attacks recorded,there were 11 attacks receiving complete relief from thestimulations, 3 getting partial relief and 4 without relief.With the positive randomized-controlled trial, the

grade of recommendation is B for using SPG neurosti-mulation on cluster headache. Given the positive effectfrom these studies, further trials are encouraged.

Migraine headacheThere was one case series of 11 cases on SPG neurosti-mulation in acutely treating intractable migraine head-aches [45]. In this study, 11 patients with a history ofmigraine headache for a mean of 20 years were studied.Spontaneous and induced migraine headaches wereacutely treated with SPG neurostimulation. Out of the11 treated, two patients were pain-free, three had somepain reduction, while five had no response. Because ofthe largely negative response, there is currently notenough evidence for treating intractable migraine withSPG neurostimulation.

Other head and facial painThere was one case series and one case report on othertypes of head and facial pain. William et al. [46] reporteda case series on idiopathic facial pain, supraorbital neur-opathy, hemicrania continua, facial anesthesia dolorosaand occipital neuropathy. SPG neurostimulation wascombined with trigeminal or peripheral stimulation. 80%of the patients reviewed reported sustained relief infacial pain. It is unclear whether SPG stimulation alonewould provide the same relief in these cases. Elahi et al.[47] reported a single case of SPG neurostimulation foridiopathic facial pain with good success.Given the sparse literature, the grade of recommenda-

tion is C for SPG neurostimulation in idiopathic facialpain and D for SPG stimulation combined with trigemi-nal/peripheral stimulation in supraorbital neuropathy,hemicrania continua, facial anesthesia dolorosa andoccipital neuropathy.

Summary for SPG neurostimulationGrade of recommendation is B for applying SPG neuro-stimulation to cluster headache and C for idiopathicfacial pain. There may be a role of combined SPG andtrigeminal or peripheral neurostimulation in isolatedcases. Due to its invasive nature, SPG neurostimulationwarrants further investigations with more high quality,large-scale studies.


Table

15Stud

iesof

SPGne

urostim

ulation

Neurostim

ulation

First

author

Year

Med

icalprob

lem

Stim

ulator

App

roach

Imaging

Type

sof

stim

ulation

How

toiden

tify

therig

htspot

Stud

yde

sign

Num

ber

ofcases

Outcome

Tepp

eret

al.[45]

2009

Intractablemigraine

Med

tron

icmod

el3625

or3628

Infrazygo

matic

approach

Fluo

roscop

yCustomized

,averageam

plitu

de,

1.2V,pu

lserate

67Hz,

pulsewidth

462μs

Paresthe

siawith

stim

ulationat

the

back

oftheno

seandde

epin

the

back

ofthesoft

palate

Caseon

ly11

2pain-free,3

had

pain

redu

ction,5

hadno

respon

se,1

was

notstim

ulated

Ansarinia

etal.[44]

2010

Cluster

headache

Med

tron

icmod

el3625

Pterygop

alatine

fossa

Fluo

roscop

yCustomized

,average

amplitu

de,1.7V,

frequ

ency

88Hz,

pulsewidth

294μs

paresthe

siawith

stim

ulationin

the

posteriornasoph

arynx

androot

oftheno

se

Caseon

ly6

Total18CH

attacks,complete

resolutio

nwith

SPGstim

ulationin

11attacks,partial

in3,no

reliefin

4.

Scho

enen

etal.[41]

2013

Cluster

headache

ATISPG

stim

ulator

Pterygop

alatine

fossaproxim

ate

tothesphe

nopalatin

egang

lion

CT

Customized

,mean

frequ

ency

120.4Hz,

meanpu

lsewidth

389.7μs,m

ean

intensity

1.6mA

X-ray

Rand

omized

controlled

28cases,

with

3rand

omized

settings.

Pain

reliefachieved

in67.1%

offull

stim

ulation-treated

attackscompared

to7.4%

ofsham

-treatedattacks.

P<0.0001

Elahi

etal.[47]

2015

Idiopathicrig

htfacial

pain

Med

tron

icmod

el3378

Thepterygop

alatine

fossa

Fluo

roscop

y0.5mV,pu

lsewidth

250–450μs,and

40–80

Hz

X-ray

Caserepo

rt1

2/10

pain

on6-mon

thfollow-up

Men

get

al.[88]

2016

Cluster

headache

Med

tron

icmod

el3487A

Pterygop

alatine

fossa

Fluo

roscop

yBilateralstim

ulation,

right

0-,1+,130

Hz,

120μs,0.7V;left8-,

9+,130

Hz,120μs,

0.8V

X-ray

Caserepo

rt1

Headache

frequ

ency

redu

ced

toon

ceaweek,

pain

level1/10at

4mon

ths

William

etal.[46]

2016

Idiopathicfacialpain,

supraorbitaln

europathy,

hemicraniacontinua,

facialanesthesiado

lorosa,

occipitaln

europathy

Med

tron

icSubcom

pact

Octrode

SPG

Fluo

roscop

yUnkno

wn

X-ray

Caseseries

580%

repo

rted

sustaine

dfacial

pain

atmean

follow-upof

9.6mon

ths.

Jurgen

set

al.[42]

2016

Cluster

headache

Neurostim

ulator,

describ

edin

[41]

Pterylop

alatine

fossa

CT

Customized

,app

lied

assoon

asthepatient

feelsclusterhe

adache

attacks

X-ray

Coh

ortstud

y.Long

-term

follow-up

from

[41]

33cases

61%

ofpatients

wereeither

acuterespon

der

(>50%

relief

from

mod

erate

orgreaterpain)

orfre

quen

cyrespon

der

(>50%

inattack

frequ

ency)

at24

mon

ths

2016

Cluster

headache

CT

X-ray

33cases


Table

15Stud

iesof

SPGne

urostim

ulation(Con

tinued)

Neurostim

ulation

First

author

Year

Med

icalprob

lem

Stim

ulator

App

roach

Imaging

Type

sof

stim

ulation

How

toiden

tify

therig

htspot

Stud

yde

sign

Num

ber

ofcases

Outcome

Barlo

ese

etal.[43]

Neurostim

ulator,

describ

edin

[41]

Pterylop

alatine

fossa

Customized

,app

lied

assoon

asthepatient

feelsclusterhe

adache

attacks

Coh

ortstud

y.Long

-term

follow-up

from

[41]

30%

expe

rienced

atleast1ep

isod

eof

completeattack

remission

(attack-

freepe

riod

exceed

ing

1mon

th).


DiscussionSphenopalatine ganglion blockSphenopalatine ganglion block has been used for over acentury. In 1908, Sluder first proposed that inflamma-tion in the posterior ethmoid and sphenoid sinuses maybe involved in unilateral facial pain associated with tear-ing, congestion and rhinorrhea. He also claimed to havesuccessfully treated facial neuralgia, asthma, earache andlower-half headache. Over time, the term Sluder’s neur-algia has varied definitions across the medical literature.Its characteristics mostly resemble cluster headache andit has been suggested that the term Sluder’s neuralgia bediscarded [48]. However, an analysis suggested that clus-ter headache and Sluder’s neuralgia may be two differententities [49]. This review kept Sluder’s neuralgia andcluster headaches as two distinct type of headaches be-cause of the differences. Since Sluder’s first publication,SPG block has been reported to be used successfully intreating multiple pain syndromes, including clusterheadaches, trigeminal neuralgia, migraine, postherpeticneuralgia and atypical facial pain. It was also used fortreating intractable cancer pain of the head and face aswell as facial pain management after endoscopic sinussurgery. However, for most pain syndromes the evidencefor using SPG nerve block remains at case report andcase series level. There were a few small yet positiverandomized-controlled studies in nitroglycerin-inducedcluster headache, second-division trigeminal neuralgia,migraine, reducing the pain associated with nasal pack-ing removal after nasal operation and for reducing theneeds of analgesics after endoscopic sinus surgery. Itshould be emphasized that the evidence for treatingthese conditions with SPG block is based on very fewsmall studies. The exception lies in reducing the needsof analgesics after endoscopic sinus surgery, which isbacked by five randomized-controlled studies. It shouldbe also noted that long-term treatment may not bebeneficial, as demonstrated by the chronic repetitiveblock study in migraine by Cady et al. [16]. When SPGblock is offered as a treatment option, patients should beinformed of such caveats.

Blocking strategiesSeveral techniques exist for SPG blockade. Four types ofapplications exist: cotton-tip applicator, Tx360 device,nasal spray and needle injections. Three main types ofapproaches exist: transnasal, transoral and infrazygo-matic approaches. Cotton-tip applicator, Tx360 deviceand nasal spray can only be applied through the transna-sal approach. Needle injection, on the other hand, canbe performed in any approach. Applied local anestheticsincluded lidocaine, bupivacaine, ropivacaine, levobupiva-cine, mepivacaine, novocaine, nupercaine, pontocaine,monocaine, tetracaine, and prilocaine, with varying

concentrations, but lidocaine and bupivacaine were by farthe most common. Other medications include cocaine,ethanol and phenol. Co-medications included epineph-rine, triamcinolone and dexamethasone. Some studiesused fluoroscopy or CT to guide needle placement.Unfortunately, there are no head-to-head trials comparingthe efficacy among different blocking strategies. The rec-ommendations made in this article are based on strategiesused in the positive controlled studies.

Side effectsSide effects from SPG blockade is typically local. Poten-tial side effects are numbness and stinging at the root ofthe nose and palate, numbness or lacrimation of ipsilat-eral eye, and bitter taste and numbness of the throat.With needle injection techniques, there is also the riskof bleeding, infection and epistaxis.

Sphenopalatine ganglion radiofrequency ablationThe use of radiofrequency on sphenopalatine ganglionwas first reported by Salar et al. [50] for treating Sluder’sneuralgia. Since the first report, there were multiple casereports on using SPG radiofrequency ablation in treatinghead and facial pain. About half of the reports focusedon treating cluster headaches, but it has also been suc-cessfully used on patients with post-traumatic headache,atypical trigeminal neuralgia and anesthesia dolorosaafter cavernous meningioma surgery. However, most ofthe literature today remains at the case report and caseseries level. There was only one small prospective cohortstudy on the effectiveness of SPG radiofrequency abla-tion. Well-controlled studies are yet to be performed toconfirm the validity of this therapeutic modality in treat-ing headache and facial pain.Compared to the short-lived effect of SPG block, SPG

radiofrequency ablation tend to be long lasting. Narouzeet al. [38] reported statistically improved attack intensity,frequency and pain disability index up to 18 months inpatients who underwent SPG radiofrequency ablation.As a comparison, Costa et al. [6] only reported shortercluster headache duration with SPG block, and Cady etal. reported only up to 24 h of relief in chronic migraine[15] while no difference was found at 1 and 6 monthswith repetitive SPG block [16].

Ablation strategiesMost radiofrequency ablation of SPG were carried outwith the infrazygomatic approach. The most commonlyused temperature is 80 °C for thermal ablation, and 42 °C for pulsed ablation. There is unfortunately no head-to-head comparison between the two types of ablations.All studies confirmed the position of RF cannula/probeby applying low voltage sensory stimulation (between0.2-0.1 V) while patients felt paresthesia or tingling


sensation at the root of the nose. The only study withevidence level above case series was a cohort study on pa-tients with chronic cluster headache [38]. In this positivestudy, the authors applied 2 rounds of thermal ablation at80 °C for 60 s each. Pre- and post-ablation medicationswere also given (pre: 0.5 ml of 2% lidocaine; post: 0.5 mlof 0.5% bupivacaine and 5 mg of triamcinolone).

Side effectsBased on the study by Narouze et al. [38], about 50% (7/15) reported temporary paresthesias in the upper gumsand cheek that lasted for 3-6 weeks with complete reso-lution. Rare permanent small zone of hypoesthesia overthe cheek could also happen. In the large case series bySanders et al. [39], of the 66 treated patients, eightpatients experienced temporary postoperative epistaxisand 11 patients exhibited cheek hematomas. A partialradiofrequency lesion of the maxillary nerve was inad-vertently made in four patients. Nine patients com-plained of hypoesthesia of the palate, which disappearedin all patients within 3 months.

Sphenopalatine ganglion neurostimulationNeurostimulation has emerged in recent years as apotential therapeutic modality for headaches and facialpain. Even though number of studies on SPG neurosti-mulation has not been abundant, the overall quality ofthe studies has been high. The study by Shoenen et al.[41] was the only randomized-controlled study in usingSPG neurostimulation to treat chronic cluster headache.Despite the small number of participants, the effective-ness is demonstrated by the large effect size and highlysignificant P value. The two long-term follow-up articlescontinued to support the effectiveness of such interven-tion [42, 43]. These three studies combined is the stron-gest piece evidence to date, suggesting that SPGneurostimulation is effec

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