Open access peer-reviewed chapter

Chronic Headache and Neuromodulation

Written By

Vicente Vanaclocha-Vanaclocha, Nieves Sáiz-Sapena, José María Ortiz-Criado and Leyre Vanaclocha

Submitted: 09 July 2017 Reviewed: 02 November 2017 Published: 20 December 2017

DOI: 10.5772/intechopen.72150

From the Edited Volume

Transcranial Magnetic Stimulation in Neuropsychiatry

Edited by Libor Ustohal

Chapter metrics overview

1,064 Chapter Downloads

View Full Metrics


The immense majority of patients with chronic headaches can be controlled with medical treatments. However, there is a subset of them with poor response, and it is for those patients that new therapeutic strategies are being designed. Neuromodulation has been used for chronic pain management in many areas for the past 50 years. The application of these techniques to the treatment of the most refractory chronic headache disorders has offered hope to these patients. There is a large variety of different techniques, each of them particularly suitable to specific types of chronic headaches. The surgically implanted devices are still in use in some particularly recalcitrant cases. Nevertheless, new percutaneous devices allow new treatment strategies. Percutaneous devices do not always show the same effectivity as surgically implanted stimulating devices, but they are user-friendly and have no serious adverse effects. Thus, they are becoming the treatment of choice once the pharmacological means are no longer effective. In case of failure, the surgical procedures would still be available as a last resort.


  • chronic headache
  • chronic migraine
  • cluster headache
  • neuromodulation
  • neurostimulation

1. Introduction

Chronic headache is one of the most frequent pain syndromes, affecting 3% of the population. It can be rather disabling [1, 2], particularly for young people who are most affected by it. The International Classification of Headache subdivides headaches into 300 different entities [3], each of those with a different pathophysiology and involving different anatomical structures. Pain can originate from the central nervous system, the cranium or the cervical area [4]. Primary headaches such as tension headache, migraine (CM), or trigeminal autonomic cephalagias (TACs), show the highest incidence. TACs are particularly incapacitating [5]. Most cases can be controlled with medication and physiotherapy. Abuse of medication is common with these patients, via the dose, the drugs or both [6]. When the pharmacological and conservative treatments fail, surgery may be considered. In the past, ablative surgical techniques have been applied. These techniques have been replaced by neuromodulation techniques. In them, the anatomical structures are not lesioned, but instead the electric impulses block the nervous structures in a reversible fashion [7]. These techniques can be subdivided into two broad categories: non-invasive and invasive [1]. The non-invasive options include transcranial stimulation either electric [810] or magnetic [1113] and transdermal stimulation of occipital [14, 15], supraorbital [9, 1419] or vagus [2023] nerves. Invasive procedures include stimulation of occipital [5, 17, 2435], supraorbital [19, 31, 36], infraorbital [31] or greater auricular [37] nerves as well as sphenopalatine ganglion [3844], cervical spinal cord [4548], or hypothalamus [4, 25, 27, 4952].

Non-invasive neuromodulation techniques are user-friendly, have low costs and few and minor side effects [815, 1923]. Unfortunately, their effectivity is lower than their invasive counterparts. Invasive neuromodulation is reserved for the most refractory cases as they are associated with increased aggressiveness, more severe adverse events (AE) and higher costs [7].

All costs have to be taken into consideration. The full cost of neuromodulation would include the disability grants as well as further possible treatments for AEs [33, 34, 53].

Taking the net expenditure into consideration, some have reported that the reductions in cost are evident at 5 years post-implantation [53]. In any case, invasive neuromodulation must only be used in the most refractory cases and only after all other medical and non-invasive treatments have failed [46]. This is particularly important due to the high incidence of AEs and the possibility of new surgical procedures to solve them [29, 33]. A trial of temporary stimulation is required to evaluate the possible response of a definitive implant [45, 46, 54], to avoid wasting of time and resources.

These techniques present promising new treatment strategies. The available evidence will be analysed, describing the possible future trends.


2. Historical aspects of neuromodulation

Electricity to treat chronic headaches was first used in ancient Rome [55], but it was not until the 1950s that neuromodulation was used in the treatment of chronic pain disorders [56, 57]. Thalamic stimulation to treat chronic headaches was introduced in 1976 [58] and percutaneous peripheral nerve stimulation a year later [59]. At the beginning of the 1990s, hypothalamic deep brain stimulation (hDBS) was applied to the treatment of some chronic headache syndromes and particularly in TACs [60]. The first report of occipital nerve stimulation (ONS) to treat occipital neuralgia was in 1999 [61]. In the year 2000, the hypothalamic stimulation was applied in the treatment of drug-resistant cluster headache (CH) [62]. The first two cases of supraorbital nerve stimulation (SONS) were reported in 2002 [63]. The first cases of hDBS in the treatment of CH were reported in 2003 [62]. In 2004, the ONS was applied in the treatment of CM [64]. The first case reported with cervical spinal stimulation (SCS) in the treatment of CH was in 2008 [65]. The first report on stimulation of the sphenopalatine ganglion was presented in 2009 [38]. Ever since, there has been an explosion of reports on the effectiveness, indications and AEs of all these techniques. Simultaneously, new devices that allow percutaneous stimulation have reached the market, allowing new solutions to old problems.


3. Indications for neuromodulation

The first step is to diagnose the patient and select an appropriate treatment by an experienced team that is familiarised with all available treatments. Neuromodulation techniques are indicated in cases that have failed all other medical treatments available for this specific headache type. It is also recommended that patients receive a psychological assessment.

The next step is to attempt non-invasive neuromodulation techniques particularly useful in this type of chronic headache. Should all fail, a period of temporary trial stimulation is suitable [33]. Patients showing no response are not implanted and are redirected to other forms of treatment. This temporary stimulation also helps to predict the results to be expected if the definitive implant is attempted [32, 46].


4. Classification of the different techniques

4.1. Non-invasive procedures

4.1.1. Transcranial electric stimulation (TES)

This technique involves applying a low amperage continuous electric stimulation directly to the scalp [10]. In most cases, the electric stimulus spreads out of the area covered by the electrodes [10]. AEs have been moderate, such as skin burns due to inadequate electrode skin contact, fatigue or local prickling and burning sensation during the stimulation [8, 10]. Its effectivity and experience are limited [8, 10].

4.1.2. Transcranial magnetic stimulation (TMS)

A magnetic field is applied to the head. In chronic headache related to mild post-traumatic head injury (MTHI-H), it has showed a 57% improvement in the intensity and frequency of the pain [11]. The left prefrontal cortex is stimulated [11]. A continuous application is required for the effects to be persistent, which can be impractical.

4.1.3. Transcutaneous supraorbital-supratrochlear stimulation

This technique involves a special equipment that looks like a pair of glasses, which has to be worn on the forehead. It provides a 50% chronic headache pain reduction, including CM [14, 16, 18]. When used for CM prevention, it reduces the number of attacks, but not their intensity [16, 18]. In the episodic, CM patients induced a 50% headache frequency reduction in 38.2% of the patients [18]. Although not very effective, the only side effects are local discomfort, redness or temporary skin irritation [16].

4.1.4. Transcutaneous vagus nerve stimulation (VNS)

The first reports entailed electrodes implanted surgically around the vagal nerve in the neck [66]. However, it never gained acceptance because the procedure was invasive and the results limited. In 2013, a percutaneous VNS device was introduced, showing promising results in the treatment of chronic CM (CM) [20, 23]. Its best advantage is that it is applied directly to the neck by the patient him/herself [21, 23]. Its main drawback is its low effectiveness (22%) [22, 23, 67]. It is well tolerated with minor side effects like neck twitching, raspy voice or redness at the application site [22, 23, 68].

In CH, it is helpful in the episodic but not in the chronic type [67, 68]. In the episodic type, it induces a positive response in 26.7% of the cases [67]. Some have used it in the acute treatment of the chronic variant of this disease with a higher than 50% pain reduction in 40% of the patients [68]. In CM, it provides a 50% or more pain reduction in 22–56.3% of the patients which is better in the episodic than in chronic variant [20, 22, 69]. It has been helpful in a single case of hemicrania continua (HC) unresponsive to indomethacin [70].

4.2. Invasive procedures

4.2.1. Sphenopalatine ganglion stimulation (SPGS)

The sphenopalatine ganglion has been a target in the treatment of chronic headaches for over a century. Initially, destructive lesions were applied [71], but since 2009, neuromodulation is also available [38]. It is effective in two thirds of episodic CH cases, preventing at least 50% of attacks, showing a decrease in intensity of at least 50%, or both [38, 4143, 72, 73]. SPGS is both preventive and therapeutic in acute phases [72, 74]. About 30% of the patients can stop the medication [72, 74]. A transoral technique has been described with a remote powering system that avoids extension leads and the need to replace the batteries [73], where patients switch-on the stimulation with a handheld remote controller when the pain attack starts [72]. This markedly reduces the incidence of AEs [73]. Some patients use the stimulation continuously to reduce the attack incidence [72]. Bilateral stimulation is more effective than unilateral [39], but it is not so effective in the chronic variant of this disease [72]. AEs are uncommon and mild, including sensory loss in the maxillary region (81%) [74], that may last over 1 year (2–28%), epistaxis (13%), facial numbness (25%) and local pain (4%) [73]. SPGS has also been used successfully in CM [44].

4.2.2. Occipital nerve stimulation (ONS)

ONS is the stimulation of the distal branches of C2 and C3 nerve roots (greater and lesser occipital nerves). The electrodes (one at each side) can be inserted either through a 2-cm midline skin incision at C1 level and tunnelled subcutaneously through a bent Tuohy needle inserted laterally from the mastoid area, or alternatively from a lateral approach with a bilateral mastoid area skin incision and the electrodes inserted from a lateral to medial direction with the Tuohy needle [14, 61, 75]. As ONS only covers 85% of the head leaving the forehead uncovered, some have combined it with SONS [15, 76, 77]. Percutaneous ONS is recommended to foresee the results of a permanent implantation [78]. In any case, a temporary external stimulation must be performed before definitive implantation [35]. Those with no positive response are referred to other treatment modalities.

ONS has been used in chronic CH [5, 2426, 28, 29, 3235, 40], CM [29, 32, 33], TACs [5], hypnic headaches (happening during sleep) [79], SUNCT/SUNA [80, 81] and occipital neuralgia [32]. In chronic CH, it reduces the attack incidence in over 50% in 70% of patients [5, 24, 25, 28, 33, 40]. In CM, its average success rate is 65.4% in 67.9–80% of the cases [29, 82]. In SUNCT/SUNA, bilateral ONS induced a 69% pain improvement in 77% of the patients [80, 81]. In idiopathic intracranial hypertension, it has been used to treat the associated headache and the residual headache, once the intracranial hypertension is resolved, with higher than 75% pain improvement [76]; but it requires bilateral stimulation [76].

AEs plague 33–70% of the cases [24, 25, 29, 33, 83]. Among them are: lead erosion [19, 76], local infection [29, 33], electrode emigration [83, 84], lead breakage [28, 30, 33], hardware-related discomfort [55], hardware/stimulation dysfunction [25] and early battery depletion related to high energy consumption [25, 33]. Some technical modifications have been devised to reduce the chance of lead migration [84], that in some series reaches 24% [85]. These include using silicone glue with silicone anchors [86], 2-point anchoring stimulator leads with a tension-relief loop [26], narrow paddle electrodes [87] and to insert the impulse generator as close as possible to the leads (i.e. supraclavicular area) [83]. Unfortunately, solving the AE entails additional surgical procedures in 26–40.7% of the cases [25, 29].

Simultaneous ONS and SONS in CH provide more than 50% pain reduction in over 70% of patients [14]. This dual stimulation has also been successful in HM [15] and TACs [19]. Although the results are promising, the number of cases is too small to draw any statistically significant conclusions.

4.2.3. Great auricular nerve stimulation (GANS)

Pain relief was reported using this technique in a single case of persistent MTHI-Ha 90% [37]. Further studies are needed.

4.2.4. Supraorbital nerve stimulation (SONS)

The first case was reported in 2009 in the treatment of CH [36]. In this disorder, SONS produced more than 50% pain reduction in 71% of the patients [19, 36, 77]. In a series of five patients with TACs, it improved the pain in all of them, but the series is too short to draw any conclusions [19]. It can be used alone or associated with ONS [14, 15, 19, 77].

4.2.5. Cervical spinal cord stimulation (SCS)

The electrode is introduced in the epidural space at the upper thoracic level and advanced to the cervical spinal cord until its distal tip is at the C2 level. One or two electrodes are inserted. The leads are connected to a subcutaneous impulse generator inserted at the infra-clavicular area [46].

SCS has been used in CM [46, 47], SUNA [54], CH [45, 65] and MTBI-HA [48], reducing the headache frequency and/or intensity by ≥50% in 71% of the patients [4547]. In CM, it improves the headache by >30% in 50% of the cases [46, 47, 88]. The AEs are frequent (71%) and usually require system explant and replacement in a second surgery [88]. Among these AEs are infections (13%) and lead rupture or migration (17%) [4547, 88].

4.2.6. Hypothalamic deep brain stimulation (hDBS)

hDBS was introduced in 2000 to treat drug-resistant CH [62]. It is useful in many types of chronic headache disorders such as HC, CH, SUNCT/SUNA and in TACs [4, 50]. In chronic CH, it results in reduction of ≥50% of the attacks in 60% of the patients [5, 40, 50, 52].The response rate in HC and SUNA is 82% [49]. In TACSs, the improvement rate is >50% in 69.9% of patients [50].

AEs include incision site pain, subcutaneous dislodgement of the impulse generator, transient gaze disturbance (oscillopsia, diplopia), autonomic disturbances, myosis, dizziness, wound infection, cervical dystonia, intracranial haemorrhage and lead disconnection or rupture [40, 49, 52]. Many of these complications require system explant [49]. hDBS is reserved for those very few cases, in which everything else has failed as death has been reported [50].

The target was initially in the posterior hypothalamus [89, 90], but other areas have also been used like the mesencephalic grey substance, the red nucleus, the fasciculus retroflexus, the dorsal longitudinal fasciculus, the ansa lenticularis, the medial longitudinal fasciculus or the medial thalamus superficialis [90]. In the latest years, the ventral tegmental area is used to decrease the chance of haemorrhages [49, 52].


5. Indications and results for specific chronic headache disorders

5.1. Cluster headache (CH)

CH consists of bouts of unilateral periorbital pain, lasting between 15 min and 3 h, which follow an annual pattern [91]. It is considered the most painful headache type, with a 0.12% prevalence. About 10% of the cases cannot be controlled with medical treatment [34]. CH has two variants: chronic and episodic [92]. In the episodic, headache periods alternate with others of remission and the attacks last between 7 days and 1 year, with a pain-free period lasting at least 1 month [91]. The chronic variant represents 10–15% of the cases [34, 73] and has pain-free periods shorter than 1 month or attacks that are present non-stop through at least 1 year [91].

Percutaneous VNS has been used in the acute treatment of the chronic variant of CH with a higher than 50% pain reduction in 40% of the patients [33, 42, 68, 93]. Although not universally effective, it is minimally invasive and with very minor and reversible AEs.

Both ONS [25, 26, 34] and SPGS [4043, 72] are the first options among the invasive techniques [5, 73]. About 70% of patients respond to these treatments with a 48% of excellent responders [25, 34]. ONS together with SONS has been applied with >50% pain reduction in 71% of the patients [77]. Cervical SCS has also been used with some success [88]. hDBS should be left as the very last resource as its complications are more severe and potentially life threatening [5, 52].

5.2. Hemicrania continua (HC)

It is a continuous and unilateral headache (it only affects one side of the head), associated with autonomic symptoms and episodes of increased headache intensity [91]. Indomethacin is the drug of choice, but some patients do not tolerate it due to side effects such as hypertension, gastrointestinal problems (particularly when combined with aspirin), vascular events or bronchial spasms [70]. In a single case, it was found to respond to non-invasive percutaneous VNS [70]. Others tried repetitive sphenopalatine ganglion block [94]. The data are not statistically significant and no definite conclusions can be drawn.

5.3. Chronic migraine (CM)

CM is described as having migraine headaches 15 or more days in every month [85]. Worldwide, it is the seventh cause of disability [95]. It affects 2–5% of the adult population [3, 91, 96].

The transcranial stimulation has contradictory results, so no recommendations can be offered [9]. The cervical percutaneous VNS shows promising but moderate results, better in the episodic than in chronic variant [20, 97].Transcutaneous SONS reduces the number of attacks but not its intensity [18, 97]. Much more efficient is the ONS via implanted electrodes [5, 24, 29, 46], with a success rate of 65.4% in 67.9–80% of the cases [29, 82]. Unfortunately, 70% of the patients suffer AEs, 40.7% of which require a new surgical procedure [29]. Some have combined the ONS with the SONS with ≥50% pain reduction in >70% of the patients [14]. The SCS has also been applied with 30% pain reduction in 50% of the cases [46].

5.4. Hemiplegic migraine

It is a very severe migraine variant, refractory to most known therapies and that often evolves to a very debilitating state. It has been treated with combined SONS and ONS with a 92% average decrease in the number of attacks [15]. The number of cases is limited, so further studies are needed.

5.5. Trigeminal autonomic cephalalgias (TACs)

TACs are a group of headache disorders characterised by unilateral headache accompanied by cranial autonomic symptoms. Although SONS has been attempted [19], ONS is the first option [27], reserving the hDBS to the most recalcitrant cases [49, 50, 52].

5.6. Short-lasting unilateral neuralgiform headache attacks with autonomic symptoms (SUNA) and short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing (SUNCT)

These consist of primary headache attacks associated with cranial autonomic dysfunction. In refractory cases, bilateral ONS induced a 69% pain improvement in 77% of the patients [80, 81]. Deep brain ventral tegmental area stimulation achieved a 78% headache rate improvement in almost all patients, but with frequent AEs that at times required to explant the system [49].

5.7. Mild traumatic head injury related headache (MTHI-H)

MTHI-H represents about 4% of the chronic headaches [98]. Transcranial magnetic stimulation has shown a 57% improvement in the intensity and frequency in this disorder [1113]. SCS or GANS [37] stimulation has been used, stimulating the left prefrontal cortex [11]. In both cases, there was a 90% headache frequency reduction. Unfortunately, only two case reports exist and no conclusions can be drawn.


6. Availability and usefulness of ambulatory techniques that can be practiced at home

All non-invasive procedures can be safely practiced at home. Their only drawback is low effectiveness, but they induce no harm in those in whom no beneficial results are obtained. Further studies are necessary. The AEs are minor and completely reversible once the device is no longer used. The biggest problem may arise from the economical point of view, as health providers could choose not to pay for treatments that show moderate response.


7. Conclusions

Although the immense majority of chronic headache disorders can be controlled with pharmacological means, there is a subset of patients that are refractory to all of them. A thorough diagnosis of the specific headache subtype is essential to provide an effective treatment. For those few refractory patients to the current available drugs, there are other treatment possibilities. We have now a wide array of non-invasive techniques that can be tried as a first attempt. In case of failure, surgically implanted stimulating systems can be of help. We should choose the more suitable option to the specific headache variant, keeping in mind the effectivity possible incidence of AEs of each treatment. hDBS should be considered the very last resource as it is associated with some serious AEs, and potentially to death.


Appendices and nomenclatures

AEAdverse event
CHCluster headache
CMChronic migraine
GANSGreat auricular nerve stimulation
HCHemicrania continua
hDBSHypothalamic deep brain stimulation
HMHemiplegic migraine
MTHI-HMild traumatic head injury related headache
ONSOccipital nerve stimulation
SCSSpinal cord stimulation
SONSSupra-orbital nerve stimulation
SPGSSphenopalatine ganglion stimulation
SUNAShort-lasting unilateral neuralgiform headache attacks with autonomic symptoms
SUNCTShort-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing
TACsTrigeminal autonomic cephalagias
TMSTranscranial magnetic stimulation
tSNSNon-invasive transcutaneous supraorbital neurostimulation
VNSVagus nerve stimulation


  1. 1. Leone M, Cecchini AP. Central and peripheral neural targets for neurostimulation of chronic headaches. Current Pain and Headache Reports. 2017 Mar;21(3):16
  2. 2. Schuster NM, Rapoport AM. New strategies for the treatment and prevention of primary headache disorders. Nature Reviews. Neurology. 2016 Oct 27;12(11):635-650
  3. 3. Lipton RB. Chronic migraine, classification, differential diagnosis, and epidemiology. Headache. 2011 Aug;51(Suppl 2):77-83
  4. 4. Altinay M, Estemalik E, Malone DA. A comprehensive review of the use of deep brain stimulation (DBS) in treatment of psychiatric and headache disorders. Headache. 2015 Feb;55(2):345-350
  5. 5. Láinez MJ, Guillamón E. Cluster headache and other TACs: Pathophysiology and neurostimulation options. Headache. 2017 Feb;57(2):327-335
  6. 6. Hsu ES. Medication overuse in chronic pain. Current Pain and Headache Reports. 2017 Jan;21(1):2
  7. 7. Puledda F, Goadsby PJ. An update on non-pharmacological neuromodulation for the acute and preventive treatment of migraine. Headache. 2017 Apr;57(4):685-691
  8. 8. Antal A, Alekseichuk I, Bikson M, Brockmöller J, Brunoni AR, Chen R, Cohen LG, Dowthwaite G, Ellrich J, Flöel A, Fregni F, George MS, Hamilton R, Haueisen J, Herrmann CS, Hummel FC, Lefaucheur JP, Liebetanz D, Loo CK, McCaig CD, Miniussi C, Miranda PC, Moliadze V, Nitsche MA, Nowak R, Padberg F, Pascual-Leone A, Poppendieck W, Priori A, Rossi S, Rossini PM, Rothwell J, Rueger MA, Ruffini G, Schellhorn K, Siebner HR, Ugawa Y, Wexler A, Ziemann U, Hallett M, Paulus W. Low intensity transcranial electric stimulation: Safety, ethical, legal regulatory and application guidelines. Clin Neurophysiol. 2017 Sep;128(9):1774-1809
  9. 9. Schoenen J, Roberta B, Magis D, Coppola G. Noninvasive neurostimulation methods for migraine therapy: The available evidence. Cephalalgia. 2016 Oct;36(12):1170-1180
  10. 10. DaSilva AF, Truong DQ, DosSantos MF, Toback RL, Datta A, Bikson M. State-of-art neuroanatomical target analysis of high-definition and conventional tDCS montages used for migraine and pain control. Frontiers in Neuroanatomy. 2015;9:89
  11. 11. Leung A, Metzger-Smith V, He Y, Cordero J, Ehlert B, Song D, Lin L, Shahrokh G, Tsai A, Vaninetti M, Rutledge T, Polston G, Sheu R, Lee R. Left dorsolateral prefrontal cortex rTMS in alleviating MTBI related headaches and depressive symptoms. Neuromodulation. 2017 May 30
  12. 12. Leung A, Fallah A, Shukla S, Lin L, Tsia A, Song D, Polston G, Lee R. rTMS in alleviating mild TBI related headaches—A case series. Pain Physician. 2016 Feb;19(2):E347-E354
  13. 13. Leung A, Shukla S, Fallah A, Song D, Lin L, Golshan S, Tsai A, Jak A, Polston G, Lee R. Repetitive transcranial magnetic stimulation in managing mild traumatic brain injury-related headaches. Neuromodulation Journal—International Neuromodulation Society. 2016 Feb;19(2):133-141
  14. 14. Clark SW, Wu C, Boorman DW, Chalouhi N, Zanaty M, Oshinsky M, Young WB, Silberstein SD, Sharan AD. Long-term pain reduction does not imply improved functional outcome in patients treated with combined supraorbital and occipital nerve stimulation for chronic migraine. Neuromodulation Journal—International Neuromodulation Society. 2016 Jul;19(5):507-514
  15. 15. Reed KL, Will KR, Conidi F, Bulger R. Concordant occipital and supraorbital neurostimulation therapy for hemiplegic migraine; initial experience; a case series. Neuromodulation Journal—International Neuromodulation Society. 2015 Jun;18(4):297-303; discussion 304
  16. 16. Przeklasa-Muszyńska A, Skrzypiec K, Kocot-Kępska M, Dobrogowski J, Wiatr M, Mika J. Non-invasive transcutaneous supraorbital neurostimulation (tSNS) using Cefaly(®) device in prevention of primary headaches. Neurologia i Neurochirurgia Polska. 2017 Apr;51(2):127-134
  17. 17. Robbins MS, Lipton RB. Transcutaneous and percutaneous neurostimulation for headache disorders. Headache. 2017 Apr;57(Suppl 1):4-13
  18. 18. Riederer F, Penning S, Schoenen J. Transcutaneous supraorbital nerve stimulation (t-SNS) with the Cefaly(®) device for migraine prevention: A review of the available data. Pain Ther. 2015 Dec;4(2): 135-147
  19. 19. Vaisman J, Lopez E, Muraoka NK. Supraorbital and supratrochlear stimulation for trigeminal autonomic cephalalgias. Current Pain and Headache Reports. 2014 Apr;18(4):409
  20. 20. Kinfe TM, Pintea B, Muhammad S, Zaremba S, Roeske S, Simon BJ, Vatter H. Cervical non-invasive vagus nerve stimulation (nVNS) for preventive and acute treatment of episodic and chronic migraine and migraine-associated sleep disturbance: A prospective observational cohort study. The Journal of Headache and Pain. 2015;16:101
  21. 21. Yuan H, Silberstein SD. Vagus nerve stimulation and headache. Headache. 2017 Apr;57(Suppl 1):29-33
  22. 22. Barbanti P, Grazzi L, Egeo G, Padovan AM, Liebler E, Bussone G. Non-invasive vagus nerve stimulation for acute treatment of high-frequency and chronic migraine: An open-label study. The Journal of Headache and Pain. 2015;16:61
  23. 23. Goadsby PJ, Grosberg BM, Mauskop A, Cady R, Simmons KA. Effect of noninvasive vagus nerve stimulation on acute migraine: An open-label pilot study. Cephalalgia: An International Journal of Headache. 2014 Oct;34(12):986-993
  24. 24. Mekhail NA, Estemalik E, Azer G, Davis K, Tepper SJ. Safety and efficacy of occipital nerves stimulation for the treatment of chronic migraines: Randomized, double-blind, controlled single-center experience. Pain Pract off J world Inst. Pain. 2017 Jun;17(5):669-677
  25. 25. Fontaine D, Blond S, Lucas C, Regis J, Donnet A, Derrey S, Guegan-Massardier E, Jarraya B, Dang-Vu B, Bourdain F, Valade D, Roos C, Creach C, Chabardes S, Giraud P, Voirin J, Bloch J, Rocca A, Colnat-Coulbois S, Caire F, Roger C, Romettino S, Lanteri-Minet M. Occipital nerve stimulation improves the quality of life in medically-intractable chronic cluster headache: Results of an observational prospective study. Cephalalgia. 2017 Oct;37(12):1173-1179
  26. 26. Pittelkow TP, Pagani-Estevez GL, Landry B, Pingree MJ, Eldrige JS. Occipital neuromodulation: A surgical technique with reduced complications. Pain Physician. 2016 Oct;19(7):E1005-E1012
  27. 27. Lambru G, Giakoumakis E, Al-Kaisy A. Advanced technologies and novel neurostimulation targets in trigeminal autonomic cephalalgias. Neurological Sciences: Official Journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology. 2015 May;36(Suppl 1):125-129
  28. 28. Bermejo PE, Torres CV, Sola RG. Occipital nerve stimulation for refractory chronic migraine. Revista de Neurologia. 2015 Jun 1;60(11):509-516
  29. 29. Dodick DW, Silberstein SD, Reed KL, Deer TR, Slavin KV, Huh B, Sharan AD, Narouze S, Mogilner AY, Trentman TL, Ordia J, Vaisman J, Goldstein J, Mekhail N. Safety and efficacy of peripheral nerve stimulation of the occipital nerves for the management of chronic migraine: Long-term results from a randomized, multicenter, double-blinded, controlled study. Cephalalgia: An International Journal of Headache. 2015 Apr;35(4):344-358
  30. 30. Freeman JA, Trentman TL. Clinical utility of implantable neurostimulation devices in the treatment of chronic migraine. Medical Devices (Auckland, N.Z.). 2013 Nov 20;6:195-201
  31. 31. Verrills P, Rose R, Mitchell B, Vivian D, Barnard A. Peripheral nerve field stimulation for chronic headache: 60 cases and long-term follow-up. Neuromodulation Journal—International Neuromodulation Society. 2014 Jan;17(1):54-59
  32. 32. Palmisani S, Al-Kaisy A, Arcioni R, Smith T, Negro A, Lambru G, Bandikatla V, Carson E, Martelletti P. A six year retrospective review of occipital nerve stimulation practice—Controversies and challenges of an emerging technique for treating refractory headache syndromes. The Journal of Headache and Pain. 2013 Aug 6;14:67
  33. 33. Mueller O, Diener H-C, Dammann P, Rabe K, Hagel V, Sure U, Gaul C. Occipital nerve stimulation for intractable chronic cluster headache or migraine: A critical analysis of direct treatment costs and complications. Cephalalgia: An International Journal of Headache. 2013 Dec;33(16):1283-1291
  34. 34. Wilbrink LA, Teernstra OPM, Haan J, van Zwet EW, Evers SMAA, Spincemaille GH, Veltink PH, Mulleners W, Brand R, Huygen FJPM, Jensen RH, Paemeleire K, Goadsby PJ, Visser-Vandewalle V, Ferrari MD. Occipital nerve stimulation in medically intractable, chronic cluster headache. The ICON study: Rationale and protocol of a randomised trial. Cephalalgia: An International Journal of Headache. 2013 Nov;33(15):1238-1247
  35. 35. Brewer AC, Trentman TL, Ivancic MG, Vargas BB, Rebecca AM, Zimmerman RS, Rosenfeld DM, Dodick DW. Long-term outcome in occipital nerve stimulation patients with medically intractable primary headache disorders. Neuromodulation Journal—International Neuromodulation Society. 2013 Dec;16(6):557-562-564
  36. 36. Narouze SN, Kapural L. Supraorbital nerve electric stimulation for the treatment of intractable chronic cluster headache: A case report. Headache. 2007 Aug;47(7):1100-1102
  37. 37. Elahi F, Reddy C. Neuromodulation of the great auricular nerve for persistent post-traumatic headache. Pain Physician. 2014 Aug;17(4):E531-E536
  38. 38. Tepper SJ, Caparso A. Sphenopalatine ganglion (SPG): Stimulation mechanism, safety, and efficacy. Headache. 2017 Apr;57(Suppl 1):14-28
  39. 39. Meng D-W, Zhang J-G, Zheng Z, Wang X, Luo F, Zhang K. Chronic bilateral sphenopalatine ganglion stimulation for intractable bilateral chronic cluster headache: A case report. Pain Physician. 2016;19(4):E637-E642
  40. 40. Fontaine D, Vandersteen C, Magis D, Lanteri-Minet M. Neuromodulation in cluster headache. Advances and Technical Standards in Neurosurgery. 2015;42:3-21
  41. 41. Narouze S. Neurostimulation at pterygopalatine fossa for cluster headaches and cerebrovascular disorders. Current Pain and Headache Reports. 2014 Jul;18(7):432
  42. 42. Jürgens TP, Schoenen J, Rostgaard J, Hillerup S, Láinez MJA, Assaf AT, May A, Jensen RH. Stimulation of the sphenopalatine ganglion in intractable cluster headache: Expert consensus on patient selection and standards of care. Cephalalgia: An International Journal of Headache. 2014 Nov;34(13):1100-1110
  43. 43. Jürgens TP, Barloese M, May A, Láinez JM, Schoenen J, Gaul C, Goodman AM, Caparso A, Jensen RH. Long-term effectiveness of sphenopalatine ganglion stimulation for cluster headache. Cephalalgia: An International Journal of Headache. 2017 Apr;37(5):423-434
  44. 44. Khan S, Schoenen J, Ashina M. Sphenopalatine ganglion neuromodulation in migraine: What is the rationale? Cephalalgia: An International Journal of Headache. 2014 Apr;34(5):382-391
  45. 45. Lambru G, Trimboli M, Palmisani S, Smith T, Al-Kaisy A. Safety and efficacy of cervical 10 kHz spinal cord stimulation in chronic refractory primary headaches: A retrospective case series. The Journal of Headache and Pain. 2016 Dec;17(1):66
  46. 46. Arcioni R, Palmisani S, Mercieri M, Vano V, Tigano S, Smith T, Fiore MRD, Al-Kaisy A, Martelletti P. Cervical 10 kHz spinal cord stimulation in the management of chronic, medically refractory migraine: A prospective, open-label, exploratory study. European Journal of Pain (London, England). 2016 Jan;20(1):70-78
  47. 47. De Agostino R, Federspiel B, Cesnulis E, Sandor PS. High-cervical spinal cord stimulation for medically intractable chronic migraine. Neuromodulation Journal—International Neuromodulation Society. 2015 Jun;18(4):289-296 discussion 296
  48. 48. Elahi F, Reddy C. High cervical epidural neurostimulation for post-traumatic headache management. Pain Physician. 2014 Aug;17(4):E537-E541
  49. 49. Miller S, Akram H, Lagrata S, Hariz M, Zrinzo L, Matharu M. Ventral tegmental area deep brain stimulation in refractory short-lasting unilateral neuralgiform headache attacks. Brain: A Journal of Neurology. 2016 Oct;139(Pt 10):2631-2640
  50. 50. Leone M, Proietti Cecchini A. Deep brain stimulation in headache. Cephalalgia. 2016 Oct;36(12):1143-1148
  51. 51. Avecillas-Chasin JM, Alonso-Frech F, Parras O, Del Prado N, Barcia JA. Assessment of a method to determine deep brain stimulation targets using deterministic tractography in a navigation system. Neurosurgical Review. 2015 Oct;38(4):739-750 discussion 751
  52. 52. Seijo F, Saiz A, Lozano B, Santamarta E, Alvarez-Vega M, Seijo E, Fernández de León R, Fernández-González F, Pascual J. Neuromodulation of the posterolateral hypothalamus for the treatment of chronic refractory cluster headache: Experience in five patients with a modified anatomical target. Cephalalgia: An International Journal of Headache. 2011 Dec;31(16):1634-1641
  53. 53. Farber SH, Hatef J, Han JL, Marky AH, Xie J, Huang K, Verla T, Lokhnygina Y, Collins TA, Lad SP. Implantable Neurostimulation for headache disorders: Effect on healthcare utilization and expenditures. Neuromodulation Journal—International Neuromodulation Society. 2016 Apr;19(3):319-328
  54. 54. Barolat G, Ketcik B, He J. Long-term outcome of spinal cord stimulation for chronic pain management. Neuromodulation Journal—International Neuromodulation Society. 1998 Jan;1(1):19-29
  55. 55. Magis D, Schoenen J. Advances and challenges in neurostimulation for headaches. Lancet Neurology. 2012 Aug;11(8):708-719
  56. 56. Leone M. Deep brain stimulation in headache. Lancet Neurology. 2006 Oct;5(10):873-877
  57. 57. Schwalb JM, Hamani C. The history and future of deep brain stimulation. Neurotherapeutics. 2008 Jan;5(1):3-13
  58. 58. Mazars G, Pull H. Neurosurgical treatment of headaches. Minerva Medica. 1976 Jun 23;67(31):2020-2022
  59. 59. Picaza JA, Hunter SE, Cannon BW. Pain suppression by peripheral nerve stimulation. Chronic effects of implanted devices. Applied Neurophysiology. 1977-1978;40(2-4):223-234
  60. 60. Wichmann T, Delong MR. Deep brain stimulation for neurologic and neuropsychiatric disorders. Neuron. 2006 Oct 5;52(1):197-204
  61. 61. Weiner RL, Reed KL. Peripheral neurostimulation for control of intractable occipital neuralgia. Neuromodulation Journal—International Neuromodulation Society. 1999 Jul;2(3):217-221
  62. 62. Franzini A, Ferroli P, Leone M, Broggi G. Stimulation of the posterior hypothalamus for treatment of chronic intractable cluster headaches: First reported series. Neurosurgery. 2003 May;52(5):1095-1099 1101
  63. 63. Dunteman E. Peripheral nerve stimulation for unremitting ophthalmic postherpetic neuralgia. Neuromodulation Journal—International Neuromodulation Society. 2002 Jan;5(1):32-37
  64. 64. Matharu MS, Bartsch T, Ward N, Frackowiak RSJ, Weiner R, Goadsby PJ. Central neuromodulation in chronic migraine patients with suboccipital stimulators: A PET study. Brain: A Journal of Neurology. 2004 Jan;127(Pt 1):220-230
  65. 65. Wolter T, Kaube H, Mohadjer M. High cervical epidural neurostimulation for cluster headache: Case report and review of the literature. Cephalalgia: An International Journal of Headache. 2008 Oct;28(10):1091-1094
  66. 66. Sadler RM, Purdy RA, Rahey S. Vagal nerve stimulation aborts migraine in patient with intractable epilepsy. Cephalalgia: An International Journal of Headache. 2002 Jul;22(6):482-484
  67. 67. Silberstein SD, Mechtler LL, Kudrow DB, Calhoun AH, McClure C, Saper JR, Liebler EJ, Rubenstein Engel E, Tepper SJ. ACT1 study group. Non-invasive Vagus nerve stimulation for the ACute treatment of cluster headache: Findings from the randomized, double-blind, sham-controlled ACT1 study. Headache. 2016 Sep;56(8):1317-1332
  68. 68. Gaul C, Diener H-C, Silver N, Magis D, Reuter U, Andersson A, Liebler EJ, Straube A, PREVA Study Group. Non-invasive vagus nerve stimulation for prevention and acute treatment of chronic cluster headache (PREVA): A randomised controlled study. Cephalalgia: An International Journal of Headache. 2016 May;36(6):534-546
  69. 69. Straube A, Ellrich J, Eren O, Blum B, Ruscheweyh R. Treatment of chronic migraine with transcutaneous stimulation of the auricular branch of the vagal nerve (auricular t-VNS): A randomized, monocentric clinical trial. The Journal of Headache and Pain. 2015;16:543
  70. 70. Eren O, Straube A, Schöberl F, Schankin C. Hemicrania continua: Beneficial effect of non-invasive Vagus nerve stimulation in a patient with a contraindication for indomethacin. Headache. 2017 Feb;57(2):298-301
  71. 71. Akbas M, Gunduz E, Sanli S, Yegin A. Sphenopalatine ganglion pulsed radiofrequency treatment in patients suffering from chronic face and head pain. Brazilian Journal of Anesthesiology. 2016 Feb;66(1):50-54
  72. 72. Barloese MCJ, Jürgens TP, May A, Lainez JM, Schoenen J, Gaul C, Goodman AM, Caparso A, Jensen RH. Cluster headache attack remission with sphenopalatine ganglion stimulation: Experiences in chronic cluster headache patients through 24 months. The Journal of Headache and Pain. 2016 Dec;17(1):67
  73. 73. Assaf AT, Hillerup S, Rostgaard J, Puche M, Blessmann M, Kohlmeier C, Pohlenz P, Klatt JC, Heiland M, Caparso A, Papay F. Technical and surgical aspects of the sphenopalatine ganglion (SPG) microstimulator insertion procedure. International Journal of Oral and Maxillofacial Surgery. 2016 Feb;45(2):245-254
  74. 74. Schoenen J, Jensen RH, Lantéri-Minet M, Láinez MJA, Gaul C, Goodman AM, Caparso A, May A. Stimulation of the sphenopalatine ganglion (SPG) for cluster headache treatment. Pathway CH-1: A randomized, sham-controlled study. Cephalalgia: An International Journal of Headache. 2013 Jul;33(10):816-830
  75. 75. Magis D, Allena M, Bolla M, De Pasqua V, Remacle J-M, Schoenen J. Occipital nerve stimulation for drug-resistant chronic cluster headache: A prospective pilot study. Lancet Neurology. 2007 Apr;6(4):314-321
  76. 76. Shaw AB, Sharma M, Shaikhouni A, Marlin ES, Ikeda DS, McGregor JM, Deogaonkar M. Neuromodulation as a last resort option in the treatment of chronic daily headaches in patients with idiopathic intracranial hypertension. Neurology India. 2015 Oct;63(5):707-711
  77. 77. Hann S, Sharan A. Dual occipital and supraorbital nerve stimulation for chronic migraine: A single-center experience, review of literature, and surgical considerations. Neurosurgical Focus. 2013 Sep;35(3):E9
  78. 78. Kinfe TM, Pintea B, Roeske S, Güresir Á, Güresir E, Vatter H. Percutaneous nerve field stimulation (PENS) of the occipital region as a possible predictor for occipital nerve stimulation (ONS) responsiveness in refractory headache disorders? A feasibility study. Cephalalgia: An International Journal of Headache. 2016 Jul;36(8):779-789
  79. 79. Son B-C, Yang S-H, Hong J-T, Lee S-W. Occipital nerve stimulation for medically refractory hypnic headache. Neuromodulation Journal—International Neuromodulation Society. 2012 Jul;15(4):381-386
  80. 80. Lambru G, Shanahan P, Watkins L, Matharu MS. Occipital nerve stimulation in the treatment of medically intractable SUNCT and SUNA. Pain Physician. 2014 Feb;17(1):29-41
  81. 81. Miller S, Watkins L, Matharu M. Long-term follow up of intractable chronic short lasting unilateral neuralgiform headache disorders treated with occipital nerve stimulation. Cephalalgia: An International Journal of Headache. 2017 Jan 1 333102417721716
  82. 82. Tavanaiepour D, Levy RM. Peripheral neuromodulation for treatment of chronic migraine headache. Neurosurgery Clinics of North America. 2014 Jan;25(1):11-14
  83. 83. Sharan A, Huh B, Narouze S, Trentman T, Mogilner A, Vaisman J, Ordia J, Deer T, Venkatesan L, Slavin K. Analysis of adverse events in the management of chronic migraine by peripheral nerve stimulation. Neuromodulation Journal—International Neuromodulation Society. 2015 Jun;18(4):305-312 discussion 312
  84. 84. Zimmerman RS, Rosenfeld DM, Freeman JA, Rebecca AM, Trentman TL. Revision of occipital nerve stimulator leads: Technical note of two techniques. Neuromodulation Journal—International Neuromodulation Society. 2012 Jul;15(4):387-391
  85. 85. Saper JR, Dodick DW, Silberstein SD, McCarville S, Sun M, Goadsby PJ, ONSTIM Investigators. Occipital nerve stimulation for the treatment of intractable chronic migraine headache: ONSTIM feasibility study. Cephalalgia: An International Journal of Headache. 2011 Feb;31(3):271-285
  86. 86. Rogers LL, Swidan S. Stimulation of the occipital nerve for the treatment of migraine: Current state and future prospects. Acta Neurochirurgica. Supplement. 2007;97(Pt 1):121-128
  87. 87. Abhinav K, Park ND, Prakash SK, Love-Jones S, Patel NK. Novel use of narrow paddle electrodes for occipital nerve stimulation—technical note. Neuromodulation Journal—International Neuromodulation Society. 2013 Dec;16(6):607-609
  88. 88. Wolter T, Kiemen A, Kaube H. High cervical spinal cord stimulation for chronic cluster headache. Cephalalgia: An International Journal of Headache. 2011 Aug;31(11):1170-1180
  89. 89. Fontaine D, Lanteri-Minet M, Ouchchane L, Lazorthes Y, Mertens P, Blond S, Geraud G, Fabre N, Navez M, Lucas C, Dubois F, Sol JC, Paquis P, Lemaire JJ. Anatomical location of effective deep brain stimulation electrodes in chronic cluster headache. Brain: A Journal of Neurology. 2010 Apr;133(Pt 4):1214-1223
  90. 90. Matharu MS, Zrinzo L. Deep brain stimulation in cluster headache: Hypothalamus or midbrain tegmentum? Current Pain and Headache Reports. 2010 Apr;14(2):151-159
  91. 91. Headache Classification Committee of the International Headache Society (IHS). The international classification of headache disorders, 3rd edition (beta version). Cephalalgia: An International Journal of Headache. 2013 Jul;33(9):629-808
  92. 92. Fischera M, Marziniak M, Gralow I, Evers S. The incidence and prevalence of cluster headache: A meta-analysis of population-based studies. Cephalalgia: An International Journal of Headache. 2008 Jun;28(6):614-618
  93. 93. Nesbitt AD, Marin JCA, Tompkins E, Ruttledge MH, Goadsby PJ. Initial use of a novel noninvasive vagus nerve stimulator for cluster headache treatment. Neurology. 2015 Mar 24;84(12):1249-1253
  94. 94. Androulakis XM, Krebs KA, Ashkenazi A. Hemicrania continua may respond to repetitive sphenopalatine ganglion block: A case report. Headache. 2016 Mar;56(3):573-579
  95. 95. Vos T, Flaxman AD, Naghavi M, Lozano R, Michaud C, Ezzati M, Shibuya K, Salomon JA, Abdalla S, Aboyans V, Abraham J, Ackerman I, Aggarwal R, Ahn SY, Ali MK, Alvarado M, Anderson HR, Anderson LM, Andrews KG, Atkinson C, Baddour LM, Bahalim AN, Barker-Collo S, Barrero LH, Bartels DH, Basáñez M-G, Baxter A, Bell ML, Benjamin EJ, Bennett D, Bernabé E, Bhalla K, Bhandari B, Bikbov B, Bin Abdulhak A, Birbeck G, Black JA, Blencowe H, Blore JD, Blyth F, Bolliger I, Bonaventure A, Boufous S, Bourne R, Boussinesq M, Braithwaite T, Brayne C, Bridgett L, Brooker S, Brooks P, Brugha TS, Bryan-Hancock C, Bucello C, Buchbinder R, Buckle G, Budke CM, Burch M, Burney P, Burstein R, Calabria B, Campbell B, Canter CE, Carabin H, Carapetis J, Carmona L, Cella C, Charlson F, Chen H, Cheng AT-A, Chou D, Chugh SS, Coffeng LE, Colan SD, Colquhoun S, Colson KE, Condon J, et al. Years lived with disability (YLDs) for 1160 sequelae of 289 diseases and injuries 1990-2010: A systematic analysis for the Global Burden of Disease Study 2010. Lancet (London, England). 2012 Dec 15;380(9859):2163-2196
  96. 96. Irimia P, Palma J-A, Fernandez-Torron R, Martinez-Vila E. Refractory migraine in a headache clinic population. BMC Neurology. 2011 Aug;11(1):94
  97. 97. Magis D. Neuromodulation in migraine: State of the art and perspectives. Expert Review of Medical Devices. 2015 May;12(3):329-339
  98. 98. Seifert TD, Evans RW. Posttraumatic headache: A review. Current Pain and Headache Reports. 2010 Aug;14(4):292-298

Written By

Vicente Vanaclocha-Vanaclocha, Nieves Sáiz-Sapena, José María Ortiz-Criado and Leyre Vanaclocha

Submitted: 09 July 2017 Reviewed: 02 November 2017 Published: 20 December 2017