Acute Treatment of Intractable Migraine With Sphenopalatine Ganglion Electrical Stimulation

Background.— We report preliminary results of a novel acute treatment for intractable migraine. The sphenopalatine ganglion (SPG) has sensorimotor and autonomic components and is involved in migraine pathophysiology.
Methods.— In 11 patients with medically refractory migraine, the sphenopalatine fossa was accessed with a 20-gauge needle using the standard infrazygomatic transcoronoid approach under fluoroscopy. Patients underwent temporary unilateral electric stimulation of the SPG with a Medtronic 3057 test stimulation lead after induction of full-blown migraine. Both sham and active stimulations with different settings were carried out for ≤60 minutes, and then the lead was removed.
Results.— In 11 evaluations, 2 patients were pain-free within 3 minutes of stimulation. Three had pain reduction; 5 had no response; 1 was not stimulated. Five patients had no pain relief. Stimulation settings: mean amplitude of 1.2V, mean pulse rate of 67 Hz, mean pulse width of 462 µs. Lack of headache relief appeared linked to suboptimal lead placement, poor physiologic sensory response to localization stimulation, and diagnosis of medication overuse headache.
Conclusion.— This study suggests a possible role for SPG stimulation in the treatment of refractory migraine headaches.     

Sphenopalatine Ganglion Block in the Management of Chronic Headaches

Purpose of Review

Sphenopalatine ganglion (SPG) block has been used by clinicians in the treatment of a variety of headache disorders, facial pain syndromes, and other facial neuralgias. The sensory and autonomic fibers that travel through the SPG provided the scientific rationale for symptoms associated with these head and neck syndromes. Yet, despite the elucidation of this pathogenic target, the optimal method to block its pain-producing properties has not been determined. Clinicians have developed various invasive and non-invasive techniques, each of which has shown variable rates of success. We examined the available studies of sphenopalatine ganglion blockade and its efficacy in the treatment of cluster headaches, migraines, and other trigeminal autonomic cephalalgias.

Recent Findings

Studies have demonstrated that SPG blockade and neurostimulation can provide pain relief in patients with cluster headaches, migraines, and other trigeminal autonomic cephalalgias. Patients with these conditions showed varying levels and duration of pain relief from SPG blockade. The efficacy of SPG blockade could be related to the different techniques targeting the SPG and choice of therapeutic agents.

Summary

Based on current studies, SPG blockade is a safe and effective treatment for chronic headaches such as cluster headaches, migraines, and other trigeminal autonomic cephalalgias. Future studies are warranted to define the optimal image-guided technique and choice of pharmacologic agents for SPG blockade as an effective treatment for chronic headaches related to activation of the sphenopalatine ganglion.

     

The Sphenopalatine Ganglion: Anatomy,Pathophysiology, and Therapeutic Targeting in Headache

The sphenopalatine ganglion (SPG) has attracted the interest of practitioners treating head and face pain for over a century because of its anatomical connections and role in the trigemino‐autonomic reflex. In this review, we discuss the anatomy of the SPG, as well as what is known about its role in the pathophysiology of headache disorders, including cluster headache and migraine. We then address various therapies that target the SPG, including intranasal medication delivery, new SPG blocking catheter devices, neurostimulation, chemical neurolysis, and ablation procedures.     

Unsuccessful Pulsed Radiofrequency of the Sphenopalatine Ganglion in Patients with Chronic Cluster Headache and Subsequent Successful Thermocoagulation

We present the results of pulsed and continuous radiofrequency (CRF) of the sphenopalatine ganglion in a case series of 3 patients with chronic cluster headache (CCH). Three patients were referred to our neurosurgical department because of CCH, which was refractory to pharmacological treatment. They underwent pulsed radiofrequency of the sphenopalatine ganglion (PRF‐SPG), and the procedure was performed through an infrazygomatic approach. In the PRF procedures, we applied 2 cycles of PRF at 42°C and 45 V for 120 seconds, with a pulse frequency of 2 Hz and a pulse width of 20 ms. In those procedures where thermocoagulation was carried out, 2 CRF lesions at 80°C for 90 seconds each were performed. Following corticosteroid and local anesthetic (40 mg of methylprednisolone and 1 mL of 1% lidocaine) injection, 2 patients had no pain relief at all, whereas the third one experienced a partial response, which lasted only 1 month and his pain then returned to its baseline level. Thus, this outcome was assessed as a nonsustained partial response. Therefore, all of them underwent a CRF lesioning of the SPG, and after this procedure, they achieved complete pain relief until the end of the follow‐up period. Furthermore, the associated autonomic manifestations disappeared. The 3 patients presented in this case series failed to achieve adequate pain relief after PRF‐SPG. However, these same patients subsequently underwent a successful CRF of the SPG.     

Results of a patient survey for an implantable neurostimulator to treat migraine headaches

Migraine attacks are believed to involve activation of the trigeminovascular system and trigeminal-parasympathetic reflex, which is mediated through the sphenopalatine ganglion (SPG). An implantable SPG neurostimulator has been developed to apply on-demand SPG stimulation for the treatment of severe primary headache. The neurostimulator is implanted via an oral incision and placed along the maxilla, with the lead placed at the SPG. The neurostimulator contains no battery and is powered and controlled via a handheld remote controller. The potential interest of patients with high-frequency, high-disability migraine in having a SPG neurostimulator implanted to treat migraine is unknown. We aimed to evaluate patient interest to undergo such an implantation procedure and to participate in a clinical investigation of on-demand SPG stimulation for migraine by conducting a survey at the Ghent University Hospital in 41 migraineurs. Seventy-seven percent (77%) of subjects expressed an interest in participating in a clinical investigation requiring implantation of a SPG neurostimulator when headache frequency and severity were considered and 69% when pain relief experienced with current migraine treatment was considered. Preventive and acute medications were used in 64 and 95% of the subjects, respectively, and provided a reported reduction of headache frequency, duration and pain. However, acute medications were frequently associated with headache recurrence and bothersome side effects. Results indicate that a majority of high-frequency, high-disability migraineurs, many of whom achieve pain relief with their current medications, have an interest in participating in a clinical investigation of an implantable SPG neurostimulator for the treatment of migraine headache.     

Sphenopalatine ganglion radiofrequency ablation for the management of chronic cluster headache

Objectives.— Chronic cluster headache patients are often resistant to pharmacological management. Percutaneous radiofrequency ablation (RFA) of the sphenopalatine ganglion (SPG) was shown before to improve episodic cluster headache but not chronic cluster headache. We were interested to examine the effect of such intervention in patients with intractable chronic cluster headache who failed pharmacological management.
Methods.— Fifteen patients with chronic cluster headache, who experienced temporary pain relief following SPG block, underwent percutaneous RFA via the infrazygomatic approach under fluoroscopic guidance. Collected data include demographic variables, onset and duration of the headache, mean attack intensity (MAI), mean attack frequency (MAF), and pain disability index (PDI) before and up to 18 months after procedure.
Results.— At 1-, 3-, 6-, 12-, 18-month follow-up, the MAI was 2.6, 3.2, 3.2, 3.4, 4.2, respectively ( P  < .0001, P  < .0001, P  < .0001, P  < .0005, P  < .003, respectively). The PDI improved from 55 (baseline) to 17.2 and 25.6 at 6 and 12 months respectively ( P  < .001). The MAF improved from 17 attacks/week to 5.4, 6.4, 7.8, 8.6, 8.3 at 1-, 3-, 6-, 12-, 18-month follow-up visits ( P  < .0001, P  < .0001, P  < .0001, P  < .002, P  < .004, respectively).
Conclusion.— Our data showed that percutaneous RFA of the SPG is an effective modality of treatment for patients with intractable chronic cluster headaches. Precise needle placement with the use of real-time fluoroscopy and electrical stimulation prior to attempting radiofrequency lesioning may reduce the incidence of adverse events.     

Paroxysmal Hemicrania: An Update

Paroxysmal hemicrania (PH) is an underreported and underdiagnosed primary headache disorder. It usually begins in the third or fourth decade of life. The recent observations indicate that it is equally prevalent in both males and females. PH is characterized by severe, strictly unilateral head pain attacks that occur in association with ipsilateral autonomic features. The attacks in PH are shorter and more frequent compared with cluster headache (CH) but otherwise PH and CH have similar clinical features. The hallmark of PH is the absolute cessation of the headache with indomethacin. However, a range of drugs may show partial to complete relief in certain groups of patients. Neuromodulatory procedures, such as greater occipital nerve blockade, blockade of sphenopalatine ganglion and neurostimulation of the posterior hypothalamus, are reserved for refractory PH.     

Long-term relief of posttraumatic headache by sphenopalatine ganglion pulsed radiofrequency lesioning: a case report

Posttraumatic headache is a common and disabling pain syndrome in patients who sustain a head injury. Unfortunately, conventional treatments may fail or cause intolerable side effects. Because chronic headache may be mediated by central and peripheral neural processes, these structures may be therapeutic targets. One target, the sphenopalatine ganglion (SPG), is implicated in several headache disorders and has been lesioned for headache relief. Because of the risks of neurolytic procedures, nonablative procedures that provide pain relief would be useful. We present a case wherein a man in his late twenties with posttraumatic headache obtained more than 17 months of relief with SPG pulsed-mode radiofrequency lesioning. SPG pulsed-mode radiofrequency is a nonablative, neural lesioning method that may be useful in the treatment of posttraumatic headache.     

Role of Sphenopalatine Ganglion Neuroablation in the Management of Cluster Headache

Cluster headache is a primary neurovascular headache. It is a strictly unilateral head pain that is associated with cranial autonomic symptoms and usually follows circadian and circannual patterns. Chronic cluster headache, which accounts for about 10% to 15% of patients with cluster headache, lacks the circadian pattern and is often resistant to pharmacological management. The sphenopalatine ganglion (SPG), located in the pterygopalatine fossa, is involved in the pathophysiology of cluster headache and has been a target for blocks and other surgical approaches. Percutaneous radiofrequency ablation of the SPG was shown to have encouraging results in those patients with intractable cluster headaches.     

Cluster Headache: Potential Options for Medically Refractory Patients (When All Else Fails)

The most evidence exists for mixed anesthetic/steroid occipital nerve blocks (which are also useful in non‐refractory patients), deep brain stimulation, sphenopalatine ganglion (SPG) blocks, SPG radiofrequency ablation, and SPG stimulation with the Autonomic Technologies, Inc (ATI) SPG Neurostimulator, the latter approved in the European Union and reimbursed in several countries.     

Sphenopalatine ganglion volumetry in episodic cluster headache: from symptom laterality to cranial autonomic symptoms

BackgroundSphenopalatine ganglion (SPG) is a peripheral structure that plays an important role in cluster headache (CH). Hence, a reliable method to measure the volume of SPG is crucial for studying the peripheral mechanism of CH. Additionally, the association between the clinical profiles and the morphology of the SPG in CH remains undetermined. This study aims to use the manual measurement of SPG volume to investigate its associations with CH, including headache laterality, cranial autonomic symptoms (CASs), presence of restlessness or agitation, and other clinical profiles.MethodsWe prospectively recruited consecutive CH patients at a tertiary medical center between April 2020 and April 2022. A total of eighty side-locked, in-bout, episodic CH patients and 40 non-headache healthy controls received 1.5 T brain MRI focusing on structural neuroimaging of the SPG. The manual measurement process for SPG was under axial and sagittal FIESTA imaging, with reference T2 weight images (sagittal and axial) for localization. The inter-observer agreement of the SPG volume (both sides of the SPG from CH patients and controls) between the two observers was calculated. In CH patients, clinical profiles and the number of CASs (range 0–5) were recorded to analyze their association with SPG volume.ResultsThe inter-observer agreement between the two raters was excellent for the new SPG volumetry method at 0.88 (95% CI: 0.84–0.90, p < 0.001). The mean [SD] SPG volume was larger in CH patients than in non-headache controls (35.89 [12.94] vs. 26.13 [8.62] μL, p < 0.001). In CH patients, the SPG volume was larger on the pain side than on the non-pain side (38.87 [14.71] vs. 32.91 [12.70] μL, p < 0.001). The number of CASs was positively moderately correlated with the pain-side SPG volume (Pearson r = 0.320, p = 0.004) but not the non-pain side SPG volume (Pearson r = 0.207, p = 0.066).ConclusionsThis proof-of-concept study successfully measured the SPG volume and demonstrated its associations with symptomatology in patients with episodic CH. The direct measurement of SPG provide insights into studies on peripheral mechanism of CH.     

A History of Cigarette Smoking Is Associated With the Development of Cranial Autonomic Symptoms With Migraine Headaches

(Headache 2011;51:85‐91) Objective.— To look at the smoking history of migraine patients and to determine if a history of cigarette smoking is associated with the development of cranial autonomic symptoms with migraine headaches. Background.— It has recently been noted that a significant number of migraine patients may develop autonomic symptoms during their attacks of headache. Why some headache patients activate the trigeminal autonomic reflex and develop cranial autonomic symptoms while others do not is unknown. Cluster headache occurs more often in patients with a history of cigarette smoking, suggesting a link between tobacco exposure and cluster headache pathogenesis. Could cigarette smoking in some manner lead to activation of the trigeminal‐autonomic reflex in headache patients? If cigarette smoking does lower the threshold for activation of the trigeminal autonomic reflex then do migraine patients who have a history of cigarette smoking more often develop cranial autonomic symptoms than migraineurs who have never smoked? Methods.— Consecutive patients diagnosed with migraine (episodic or chronic) who were seen over a 7‐month time period at a newly established headache center were asked about the presence of cranial autonomic symptoms during an attack of head pain. Patients were deemed to have positive autonomic symptoms along with headache if they experienced at least one of the following symptoms: eyelid ptosis or droop, eyelid or orbital swelling, conjunctival injection, lacrimation, or nasal congestion/rhinorrhea. A smoking history was determined for each patient including was the patient a current smoker, past smoker, or had never smoked. Patients were deemed to have a positive history of cigarette smoking if they had smoked continuously during their lifetime for at least at 1 year. Results.— A total of 117 migraine patients were included in the analysis (96 female, 21 male). Forty‐six patients had a positive smoking history, while 71 patients had no smoking history. Some 70% (32/46) of migraineurs with a positive history of cigarette smoking had cranial autonomic symptoms along with their headaches, while only 42% (30/71) of the nonsmoking patients experienced at least 1 autonomic symptom along with headaches and this was a statistically significant difference (P < .005). In total, 74% of current smokers had autonomic symptoms with their headaches compared with 61% of past smokers and this was not a statistically significant difference. There was a statistically significant difference between the number of current smokers who had autonomic symptoms with their headaches compared with the number of patients who never smoked and had autonomic symptoms (P < .05). Overall, 52% of the studied migraineurs had autonomic symptoms. There was a statistically significant difference between autonomic symptom occurrence in male and female smokers vs male and female nonsmokers. Each subtype of cranial autonomic symptoms was all more frequent in smokers. Conclusion.— A history of cigarette smoking appears to be associated with the development of cranial autonomic symptoms with migraine headaches.     

Invasive and Non-invasive Electrical Pericranial Nerve Stimulation for the Treatment of Chronic Primary Headaches

Chronic primary headaches are widespread disorders which cause significant quality of life and socioprofessional impairment. Available pharmacological treatments have often a limited efficacy and/or can generate unbearable side effects. Electrical nerve stimulation is a well-known non-destructive method of pain modulation which has been recently applied to headache management. In this review, we summarise recent advances in invasive and non-invasive neurostimulation techniques targeting pericranial structures for the treatment of chronic primary headaches, chiefly migraine and cluster headache: occipital nerve, supraorbital nerve, vagus nerve, and sphenopalatine ganglion stimulations. Invasive neurostimulation therapies have offered a new hope to drug-refractory headache sufferers but are not riskless and should be proposed only to chronic patients who failed to respond to most existing preventives. Non-invasive neurostimulation devices are user-friendly, safe and well tolerated and are thus taking an increasing place in the multidisciplinary therapeutical armamentarium of primary headaches.     

Cluster headache--acute and prophylactic therapy

Cluster headache (CH) pain is the most severe of the primary headache syndromes. It is characterized by periodic attacks of strictly unilateral pain associated with ipsilateral cranial autonomic symptoms. The majority of patients have episodic CH, with cluster periods that typically occur in a circannual rhythm, while 10% suffer from the chronic form, with no significant remissions between cluster periods. Sumatriptan injection or oxygen inhalation is the first-line therapy for acute CH attacks, with the majority of patients responding to either treatment. The calcium channel blocker verapamil is the drug of choice for CH prevention. Other drugs that may be used for this purpose include lithium carbonate, topiramate, valproic acid, gabapentin, and baclofen. Transitional prophylaxis, most commonly using corticosteroids, helps to control the attacks at the beginning of a cluster period. Peripheral neural blockade is effective for short-term pain control. Recently, the therapeutic options for refractory CH patients have expanded with the emergence of both peripheral (mostly occipital nerve) and central (hypothalamic) neurostimulation. With the emergence of these novel treatments, the role of ablative surgery in CH has declined.     

Gamma Knife Stereotactic Radiosurgery in the Management of Cluster Headache

Gamma knife stereotactic radiosurgery (SRS) has proven to be an effective management approach for trigeminal neuralgia and as a minimally invasive alternative management option for cluster headache (CH). In CH, patients undergo single-session focused irradiation of the trigeminal nerve root (TN), sometimes coupled with irradiation of the sphenopalatine ganglion (SPG) as well. SRS provides early pain relief in most patients, but is associated with trigeminal sensory dysfunction in some patients. In the future, a prospective trial that compares a single target of TN to dual targets of both the TN and SPG may provide further understanding of the value of SRS for CH.     

The Primary Headaches as a Reflection of Genetic Darwinian Adaptive Behavioral Responses

(Headache 2010;50:273‐289) Objective.— The objective of this study is to present a view of the primary headaches as genetically determined behavioral responses consistent with sickness behavior and defense reaction, respectively. Background and Design.— A review of the literature bearing on the behavioral, humoral, and functional imaging aspects of the primary headaches shows that migraine and cluster headache (CH) are pain conditions characterized by different behaviors during the attacks. Here it is postulated that the behavioral responses to migraine and CH are evolutionary conserved reactions consistent with sickness behavior and defense reaction. Results.— The sickness behavior observed during migraine attacks is a pan‐mammalian adaptive response to internal and external stressors, characterized by withdrawal and motor quiescence, sympatho‐inhibition and lethargy, in which visceral pain signals a homeostatic imbalance of the body and/or brain. In contrast, the defense reaction in CH consists of a fight‐or‐flight reaction, with motor restlessness and agitation, in which pain is exteroceptive in kind. Conclusion.— These different behavioral responses are thus specific to different kinds of pain, distinguished by the behavioral significance of the pain (visceral pain in migraine vs exteroceptive pain in CH), and imply brain matrices involving different networks in the brainstem, hypothalamus, and forebrain regions that engender evolutionarily conserved adaptive genetic responses. Cytokines play an important role in their development. Predictions and limitations of the hypothesis are discussed together with implications for genetic studies on headaches.     

Vasomotor rhinitis and sphenopalatineganglion block

The effectiveness of the sphenopalatine ganglion (SPG) block for the relief of symptoms inchronic vasomotor rhinitis was assessed in 30 patients of both genders. The number of blocks required for complete relief was three (range from two to four) at weekly intervals in 66.7% of volunteers. There was no recurrence of symptoms during a follow-up period of 12–20 months in 29 patients, and one patient was symptom free for 8 months. The technique is simple and can be performed as an outpatient procedure without side effects.     

The pterygopalatine ganglion and its role in various pain syndromes: from anatomy to clinical practice

Abstract The postsynaptic fibers of the pterygopalatine or sphenopalatine ganglion (PPG or SPG) supply the lacrimal and nasal glands. The PPG appears to play an important role in various pain syndromes including headaches, trigeminal and sphenopalatine neuralgia, atypical facial pain, muscle pain, vasomotor rhinitis, eye disorders, and herpes infection. Clinical trials have shown that these pain disorders can be managed effectively with sphenopalatine ganglion blockade (SPGB). In addition, regional anesthesia of the distribution area of the SPG sensory fibers for nasal and dental surgery can be provided by SPGB via a transnasal, transoral, or lateral infratemporal approach. To arouse the interest of the modern‐day clinicians in the use of the SPGB, the advantages, disadvantages, and modifications of the available methods for blockade are discussed.?     

Oxygen Inhibits Neuronal Activation in the Trigeminocervical Complex After Stimulation of Trigeminal Autonomic Reflex, But Not During Direct Dural Activation of Trigeminal Afferents

Objective.— To understand the mechanism of action of oxygen treatment in cluster headache. Background.— Trigeminal autonomic cephalalgias, including cluster headache, are characterized by unilateral head pain in association with ipsilateral cranial autonomic features. They are believed to involve activation of the trigeminovascular system and the parasympathetic outflow to the cranial vasculature from the superior salivatory nucleus (SuS) projections through the sphenopalatine ganglion, via the greater petrosal nerve of the VIIth (facial) cranial nerve. Cluster headache is remarkably responsive to treatment with oxygen, and yet our understanding of its mode of action is unknown. Methods.— Combining models of trigeminovascular nociception and a novel approach that activates the trigeminal‐autonomic reflex, using SuS/facial nerve stimulation, we explored the effect of oxygen on trigeminal nerve activation as well as on autonomic responses through blood flow observations of the lacrimal duct/sac. Results.— Meningeal vasodilation and neuronal firing in the trigeminocervical complex (TCC), in response to dural electrical stimulation, was unaffected by treatment with 100% oxygen. Stimulation of the SuS via the facial nerve caused only marginal changes in dural blood vessel diameter, but did result in evoked firing in the TCC. Two populations of neurons were characterized, those responsive to 100% oxygen treatment, with a maximal inhibition of 33%, 20 minutes after the start of oxygen treatment (t₁₅ = 4.4, P < .0001). A second population of neurons were not inhibited by oxygen and tended to have shorter latency. Oxygen also inhibited evoked blood flow changes in the lacrimal sac/duct caused by SuS stimulation. Conclusions.— The data provide the first systematic, experimental evidence for a mechanism of action of oxygen in cluster headache. The data show oxygen has no direct effect on trigeminal afferents, acting specifically on the parasympathetic/facial nerve projections to the cranial vasculature to inhibit both evoked trigeminovascular activation and activation of the autonomic pathway during cluster headache attacks. Moreover, the studies begin to characterize a novel laboratory model for the most painful primary headache syndrome known – cluster headache.     

Meta‐Analysis of the Efficacy and Safety of Naproxen Sodium in the Acute Treatment of Migraine

(Headache 2010;50:808‐818) Objective.— To assess the efficacy and safety of naproxen sodium in the treatment of acute migraine attacks. Background.— Non‐steroidal anti‐inflammatory drugs including naproxen sodium have been used in treating migraine attack. A number of clinical trials of naproxen sodium in migraine have been reported. However, it remains to be established whether naproxen sodium unequivocally offers clinical benefits taken into account the desired outcomes in acute migraine therapy as recommended by the International Headache Society. Methods.— Clinical trials were identified through electronic searches (MEDLINE, EMBASE, EBM review, and the Cochrane Library) up to June 2009 and historical searches of relevant articles. Studies were included in the meta‐analysis if they were (1) double‐blind, randomized, placebo‐controlled trials that evaluated naproxen sodium tablet in moderate or severe migraine attacks in adult patients, and (2) reporting the efficacy in terms of headache relief, pain‐free, relief of migraine‐associated symptoms, sustained headache relief, sustained pain‐free, or headache recurrence. Data extraction and study quality assessment were performed independently by 2 investigators. Disagreements were resolved by a third investigator. Treatment effects and adverse effects were expressed as risk ratio. A random effects model was used when significant heterogeneity existed, otherwise the fixed effects model was performed. Results.— We identified 16 published randomized controlled trials of naproxen in the treatment of migraine. Four trials met the inclusion criteria and were included in the meta‐analysis. Naproxen sodium was more effective than placebo in reducing pain intensity and providing pain‐free within 2 hours in adults with moderate or severe migraine attacks. The pooled risk ratios were 1.58 (95% confidence interval [CI] 1.41‐1.77, P < .00001), and 2.22 (95% CI 1.46‐3.37, P = .0002), respectively, for headache relief at 2 hours and pain‐free at 2 hours. It was also effective in achieving headache relief at 4 hours, relief of migraine‐associated symptoms, sustained headache relief, and sustained pain‐free responses. There was no significant difference in headache recurrence rate between naproxen sodium and placebo. The risk of any adverse event was greater with naproxen sodium than with placebo (pooled risk ratio 1.29, 95% CI 1.04‐1.60, P = .02). The adverse events commonly associated with naproxen sodium were nausea, dizziness, dyspepsia, and abdominal pain. Conclusions.— The available evidence suggests that naproxen sodium is more effective but may cause more adverse events than placebo in the acute treatment of moderate to severe migraine. It is effective in reducing headache intensity, rendering pain‐free at 2 hours and improving migraine‐associated symptoms. However, its effectiveness relative to other active comparators needs to be better defined by appropriate head‐to‐head clinical trials.