The effects of greater occipital nerve block and trigger point injection on brush allodynia and pain in migraine

OBJECTIVE: To evaluate the effect of GONB, with or without trigger point injection (TPI), on dynamic mechanical (brush) allodynia (BA) and on head pain in migraine. Background.-Patients with migraine often have cutaneous allodynia that is related to sensitization of central pain neurons. Greater occipital nerve block (GONB) is an effective treatment for migraine headache; however, its effect on cutaneous allodynia in migraine is unknown. METHODS: We studied patients with migraine and BA who were treated with GONB with or without TPI. Demographic data, migraine history, and headache features were documented. Allodynia was evaluated using a structured questionnaire and by applying a 4 x 4-inch gauze pad to skin areas in the trigeminal and cervical dermatomes. Degree of allodynia (the allodynia score) was measured on a 100-mm visual analog scale (VAS) before treatment and 10 and 20 minutes thereafter. Headache levels were assessed using an 11-point verbal scale. Allodynia scores, as well as headache levels, before and after treatment were compared. RESULTS: Nineteen patients were studied. Mean age was 43.6+/-11.8 years. Twenty minutes after treatment, headache was reduced in 17 patients (89.5%) and did not change in 2 (10.5%). The average headache level was 6.53 before treatment and 3.47, 20 minutes after it. The average allodynia score decreased after 20 minutes in all patients. Average allodynia score per site was reduced by 18.69 mm and 13.74 mm in the trigeminal and cervical areas, respectively. There was a positive correlation between allodynia index, obtained through the questionnaire, and allodynia score, obtained by examination. CONCLUSION: GONB, with or without TPI, reduced both head pain and brush allodynia in this migraine patient group.     

Comparison of dynamic (brush) and static (pressure) mechanical allodynia in migraine

Allodynia has been described in migraine but has not been fully investigated for the different sensory modalities. The aim of this study was to compare the prevalence of dynamic (brush) and static (pressure) mechanical allodynia in migraine patients and to suggest a practical method of testing them in a clinical setting. Patients with International Headache Society-defined episodic migraine (EM) or with transformed migraine (TM) as defined by Silberstein and Lipton were prospectively recruited from the Jefferson Headache Center out-patient clinic. A questionnaire of migraine features and symptoms of allodynia was administered. Brush allodynia (BA) was tested by cutaneous stimulation with a gauze pad and pressure allodynia (PA) was tested using von Frey hairs (VFH). The prevalence of BA and PA in all patients and in the different subgroups was calculated and correlated with migraine features. We recruited 55 migraine patients. Twenty-five had EM and 30 had TM. BA was present in 18 (32.7%) patients and PA in 18-24 (32.7-43.6%). Allodynia to both brush and pressure was found in 13-17 (23.6-30.9%) patients. If a patient had allodynia to one modality only, it was more likely to be PA than BA. Both BA and PA were more common in patients with TM compared with those with EM [BA 46.7% vs. 16.0%; PA (differences significant for the medium and thick VFHs) 50% vs. 20% and 50% vs. 12%, respectively]. Both types of allodynia were also more common in patients with migraine with aura compared with those with migraine without aura (BA 57.1% vs. 17.6%; PA 57.1-61.9% vs. 17.6-32.7%). There was a positive correlation between allodynia score (as obtained by examination) and allodynia index (as obtained by history) for both BA and PA. The incomplete, although considerable, overlap between BA and PA suggests that allodynia to different sensory modalities is associated with sensitization of different neuronal populations. Because PA was more common than BA, it may be a more sensitive indicator of allodynia in migraine. PA can be tested clinically in a practical and systematic manner.     

Identifying cutaneous allodynia in chronic migraine using a practical clinical method

Cutaneous allodynia is common in migraine. In the majority of previous studies on allodynia in migraine, only patients with episodic migraine (EM) were included. Little is known on patterns of allodynia in chronic migraine (CM). Since the presence of allodynia is associated with a poor response to triptans, a clinically practical method to test migraine patients for allodynia would be useful to the clinician. The aim of this study was to assess the prevalence of dynamic mechanical (brush) allodynia (BA) in CM, using a clinically practical method. Eighty-nine CM patients were prospectively recruited. Patients were given a structured questionnaire regarding demographic data and migraine characteristics. Allodynia was tested using a 10 x 10-cm gauze pad to brush various areas of the skin lightly. The prevalence of BA in the entire study population and in different patient subgroups was calculated. BA was present in 42.7% (38/89) of the patients. The presence of allodynia was unrelated to age, disease duration or to the occurrence of an acute headache exacerbation at the time of testing. Allodynia was positively associated with a history of migraine aura. BA was most common in the cephalic area, but was also seen in cervical dermatomes. BA is common in CM and, unlike in EM, is not significantly affected by the occurrence of an acute headache exacerbation. This suggests that central trigeminovascular neurons are chronically sensitized in patients experiencing migraine headache >15 days per month. The testing of BA in the clinical setting is possible using a simple and brief approach. It allows the clinician to determine whether the patient is sensitized, a diagnosis that affects treatment decisions.     

Acute and interictal allodynia in patients with different headache forms: an Italian pilot study

OBJECTIVE: To investigate allodynia in patients with different primary headaches. BACKGROUND: Many migraineurs have allodynia during headache attacks; some may have allodynia outside attacks; allodynia may also be associated with other primary headaches. METHODS: A total of 260 consecutive primary headache patients presenting for the first time at a headache center, and 23 nonheadache controls answered written questions (subsequently repeated verbally) to determine the presence of acute and interictal allodynia. RESULTS: We divided the patients into: episodic migraine (N = 177), subdivided into only migraine without aura (N = 114) and those sometimes or always reporting migraine with aura (N = 63); episodic tension-type headache (N = 28); chronic headaches (headache > or = 15 days/month, N = 52), including chronic migraine, chronic tension-type headache, and medication-overuse headache; and other headache forms (N = 3). Acute allodynia was present in 132 (50.7%), significantly more often in patients sometimes or always suffering migraine with aura, and those with chronic headache forms, compared to patients with migraine without aura and episodic tension-type headache. Interictal allodynia was present in 63 (24.2%) patients, with significantly higher frequency in those having migraine with aura attacks than controls and common migraine patients. CONCLUSIONS: Allodynia is not specific to migraine but is frequent in all headache patients: acute allodynia was reported in half those interviewed and in over a third of patients in each headache category; interictal allodynia was reported by nearly 25%.     

Migrainous corpalgia: body pain and allodynia associated with migraine attacks

Cephalic and extracephalic allodynia are recognized as a common sign of sensory sensitization during migraine episodes. However, the occurrence of body pain in migraine has not been thoroughly explored. Here we report three patients presenting with spontaneous body pain in association with migraine attacks. A 41-year-old woman experienced face and limb pain along with migraine headaches; it started before, during or after headache, was usually ipsilateral to head pain, and could last from minutes to days. A 39-year-old woman had pain in her right limbs, back and neck for 30–60 min prior to right-sided migraine headaches. A 30-year-old woman perceived pain in her left upper limb for 24–48 h prior to left-sided migraine headaches. All patients had allodynia to mechanical stimuli over the painful areas. Spontaneous body pain may be associated with migraine attacks. Together with allodynia, this might be a consequence of central sensitization.     

Decline in attentional inhibition among migraine patients: an event‐related potential study using the Stroop task

BackgroundAs a disorder of brain dysfunction, migraine has been associated with cognitive decline. However, no consistent results with respect to the attention function in migraineurs have been found, and the relationship between attentional inhibition and migraine is also unclear. In this study, the attentional inhibition function was evaluated using event-related potentials (ERPs) while migraine patients and healthy controls were performing the color–word Stroop task.MethodsIn this study, 75 migraine patients and 41 age-, gender-, and education-matched healthy controls were enrolled. The Stroop task was performed, and both behavioral and ERP data were analyzed.ResultsAs to the behavioral data, the migraine group had a longer reaction time compared to the control group, but no difference in Stroop effect was observed. With respect to ERP components, the amplitudes of both early and late medial frontal negativity (MFN) were decreased in the migraine group. Additionally, obvious differences in the early MFN and sustained potential (SP) amplitudes were found between patients with and without allodynia.ConclusionsAt the behavioral level, migraine patients exhibited decreased executive ability but no obvious decline in inhibition. By contrast, a decline in attentional inhibition during the migraine interictal phase was confirmed by the analysis of ERP components, mainly those associated with changes in the conflict-monitoring stage, independent of confounding factors such as age, education, medication and mood disorders. Migraine patients with allodynia exhibited some significant differences in early MFN and SP compared to those without, supporting the hypothesis that migraine chronification aggravates the decline in attentional inhibition.     

Insights from experimental studies into allodynia and its treatment

Migraine is a common disorder that often is accompanied by cutaneous allodynia. Cutaneous allodynia on the head has been linked to sensitization of neurons in the trigeminal nucleus caudalis in animal models of migraine. In addition, migraine with allodynia is refractory to acute treatment with triptans. Understanding the mechanisms of allodynia, preventing its development, and finding effective treatments have become a priority in headache research. This paper reviews recent research on the pathogenesis of headache and the generation of allodynia. We discuss the regions of the nervous system that are involved in generating and maintaining headache pain and allodynia. We also discuss recent advances in the treatment of migraine based on translation research.     

The prevalence of allodynia, osmophobia and red ear syndrome in the juvenile headache: preliminary data

The aim of the study was to determine the frequency of clinical allodynia, osmophobia and red ear syndrome in a young population. Medical records of the children admitted for headache between 1 December 2004 and 31 March 2005 were consecutively studied. A questionnaire was used to find the prevalence of allodynia, osmophobia and red ear syndrome. We visited 96 children with headache. The range of age was 6–18 years. We classified migraine in 57%, other primary headaches in 25% and secondary headaches in about 18%. The presence of ipsilateral clinical allodynia was 14.5% in migraine, osmophobia in 20% of migraine and red ear syndrome in about 24% of migraine cases and they were absent in the other two headache groups. Our study shows that features like osmophobia, allodynia and red ear syndrome are not uncommon in migraine while they are absent in other types of headache.     

2003 Wolff Award: Possible parasympathetic contributions to peripheral and central sensitization during migraine

BACKGROUND: Neurologic signs of increased parasympathetic outflow to the head often accompany migraine attacks. Because increased parasympathetic outflow to the cranial cavity induces vasodilation of cerebral and meningeal blood vessels, it can enhance plasma protein extravasation and the release of proinflammatory mediators that activate perivascular nociceptors. We recently showed that activation of intracranial perivascular nociceptors induces peripheral and central sensitization along the trigeminovascular pathway and proposed that these sensitizations mediate the intracranial hypersensitivity and the cutaneous allodynia of migraine. METHODS: The present study investigates possible parasympathetic contributions to the generation of peripheral and central sensitization during migraine by applying intranasal lidocaine to reduce cranial parasympathetic outflow through the sphenopalatine ganglion. RESULTS: In the absence of migraine, patients were pain-free, and their skin sensitivity was normal. Their mean baseline pain thresholds were less than 15 degrees C for cold, more than 45 degrees C for heat, and more than 100 g for mechanical pressure. Their mean pain score was 7.5 of 10 (standard deviation, 1.4) during untreated migraine and 3.5 of 10 (standard deviation, 2.4) after the nasal lidocaine-induced sphenopalatine ganglion block (P <.0001). Most patients developed cutaneous allodynia during migraine, and their mean pain thresholds changed to more than 25 degrees C for cold, less than 40 degrees C for heat, and less than 10 g for mechanical pressure. Following the nasal lidocaine administration (sphenopalatine ganglion block), this allodynia remained unchanged in spite of the pain relief. CONCLUSION: These findings suggest that cranial parasympathetic outflow contributes to migraine pain by activating or sensitizing (or both) intracranial nociceptors, and that these events induce parasympathetically independent allodynia by sensitizing the central nociceptive neurons in the spinal trigeminal nucleus.     

Exploring Home Allodynia Testing For Future Clinical and Scientific Uses

Allodynia, a painful response to a usually nonpainful stimulus, is common in chronic migraine. The evaluation of allodynia can be important clinically. Dynamic mechanical allodynia (brush) testing has been shown to be both a simple and reliable way to evaluate allodynia. In this study, we show that self-administered brush allodynia testing at home is a feasible means of evaluating and recording allodynia in relationship to chronic migraine.     

Assessment of normalized cerebral blood flow and its connectivity with migraines without aura during interictal periods by arterial spin labeling

BackgroundMigraine constitutes a global health burden, and its pathophysiology is not well-understood; research evaluating cerebral perfusion and altered blood flow between brain areas using non-invasive imaging techniques, such as arterial spin labeling, have been scarce. This study aimed to assess cerebral blood flow (CBF) and its connectivity of migraine.MethodsThis study enrolled 40 patients with episodic migraine without aura (MwoA), as well as 42 healthy patients as control (HC). Two groups of normalized CBF and CBF connectivity were compared, and the relationship between CBF variation and clinical scale assessment was further evaluated.ResultsIn comparison to HC subjects, MwoA patients exhibited higher CBF in the right middle frontal orbital gyrus (ORBmid.R) and the right middle frontal gyrus, while that in Vermis_6 declined. The increased CBF of ORBmid.R was positively correlated with both the Visual Light Sensitivity Questionnaire-8 (VLSQ-8) and the monthly attack frequency score. In MwoA, significantly decreased CBF connectivity was detected between ORBmid.R and the left superior frontal gyrus, the right putamen, the right caudate, as well as the right angular gyrus. In addition, increased CBF connectivity was observed between the left calcarine cortex and ORBmid.R.ConclusionsOur results indicate that migraine patients exhibit abnormalities in regional CBF and feature CBF connection defects at the resting state. The affected areas involve information perception, information integration, and emotional, pain and visual processing. Our findings might provide important clues for the pathophysiology of migraine.     

Clinical Significance of Brush Allodynia in Emergency Patients With Migraine

Background.— Cutaneous brush allodynia may be a practical and readily assessable marker of progression of an acute migraine attack. We determined the relative frequency of this finding in emergency department (ED) patients with acute migraine and tested the hypothesis that the presence of cutaneous brush allodynia prior to initial treatment in the ED could predict poor 2-hour and 24-hour pain intensity outcomes.
Methods.— As part of a multicenter ED-based clinical trial testing the benefit of dexamethasone vs placebo for the adjuvant parenteral treatment of acute migraine, cutaneous brush allodynia was assessed prior to treatment using an established methodology. In addition to dexamethasone or placebo, all patients received intravenous metoclopramide + diphenhydramine as primary treatment for their migraine. Pain intensity outcomes were assessed in the ED 2 hours after medication administration and again by telephone 24 hours after medication administration.
Results.— An assessment of cutaneous brush allodynia was performed in 182 migraineurs from 3 different EDs, of whom 26 (14%, 95% CI: 10-20%) had cutaneous brush allodynia. A pain-free state within 2 hours of medication administration was achieved by 46% of the allodynic patients and by 47% of the nonallodynic patients ( P  = .91). Median headache intensity over the 24 hours after ED discharge, as measured on a pain intensity scale from zero to 10, was 3 in the allodynic patients and 3 in the nonallodynic patients ( P  = .23).
Conclusions.— Cutaneous brush allodynia is an uncommon finding in the ED, occurring in fewer than 1 in 5 migraineurs. It does not seem to have prognostic relevance for the ED-based management of the acute migraine attack.     

Clarification of developing and established clinical allodynia and pain-free outcomes

OBJECTIVE: The aim of this study was to determine whether clinical indicators of cutaneous allodynia predict the success of migraine therapy with sumatriptan using a brief questionnaire. BACKGROUND: Using quantitative sensory testing (QST) recent studies demonstrate that the presence of cutaneous allodynia, a clinical manifestation of central sensitization, can be detrimental to the success of migraine therapy with sumatriptan. QST is costly and requires much time, therefore it is not feasible to use in clinical practice. METHODS: In this prospective study, migraineurs completed a questionnaire about their skin sensitivity during migraine. Each migraineur treated 2 migraine headaches with sumatriptan (100 mg): 1 headache at the earliest sign of migraine pain (mild, within 1 hour of onset) and 1 headache at least 4 hours after the onset of pain while moderate or severe. RESULTS: Thirty-six migraine headaches were evaluated in 18 migraineurs. A total of 44% of the headaches were not associated with allodynia at any time. Irrespective of allodynic status, headaches were more likely to become pain-free with early versus late treatment (2 hours; 78% vs. 33%, respectively). Headaches were equally likely to become pain-free when allodynia was reported before treatment but not 2 and 4 hours after treatment (2 hours; 67 vs. 63%, respectively, 4 hours 80 vs. 81%, respectively). However, no headaches were pain-free when allodynia was reported at 2 and 4 hours after treatment. CONCLUSIONS: Headaches without allodynia were aborted when treated early or late, and headaches with allodynia were aborted only when allodynia was not present after treatment. These findings suggest that different mechanisms account for allodynia before and after treatment; a developing phase in which central sensitization depends on incoming pain signals from the peripheral nociceptors and an established phase in which the sensitization becomes independent of the pain signals that come from the dura.     

Cutaneous allodynia in transformed migraine patients

BACKGROUND: There is growing evidence that central sensitization plays a role in migraine pathogenesis, and that cutaneous allodynia is its clinical correlate. In headache research, allodynia has largely been studied in episodic migraine. The purpose of this investigation was to determine whether cutaneous allodynia occurs in transformed migraine, using individuals without headaches as controls. METHODS: Fifteen patients with a diagnosis of transformed migraine and 15 control subjects with no history of headaches were included. All subjects were females between 18 and 50. Similar to the methods of Burstein et al, Von Frey hairs (VFH) were sequentially applied to territories supplied by divisions of the trigeminal nerve, cervical paraspinal muscles, trapezius muscles, ventral forearm, and lower leg to determine a pain threshold. As a milder stimulus, a cotton swab was stroked in the same locations. Each trial was repeated 3 times on 2 occasions. Group comparisons were made using the Student's t-test. RESULTS: Mean pain thresholds were lower among migraine patients than control subjects across all test areas. The thresholds were statistically significantly lower in migraine patients than in control subjects for the 1st division of the trigeminal nerve (34.0 g versus 115.8 g, P= .035) and for the 2nd division (23.5 g versus 97.6 g, P= .039). Six patients found a cotton swab-stroke painful, compared to zero control subjects. Using a quantitative definition of allodynia, 75% of patients had allodynia to mechanical stimuli. CONCLUSIONS: This study is the first to demonstrate allodynia in transformed migraine patients using a headache-free control population and supports the hypothesis that central sensitization plays a role in the evolution of transformed migraine.     

Dihydroergotamine for early and late treatment of migraine with cutaneous allodynia: an open-label pilot trial

OBJECTIVE: To explore whether dihydroergotamine (D.H.E. 45) is equally effective and safe for migraine with allodynia, when administered either early or late in an attack. BACKGROUND: Central sensitization may account for the extracranial tenderness and cutaneous allodynia that can occur with migraine. Once allodynia is established, triptans are less effective. Dihydroergotamine is often effective for patients whose refractory headaches have failed prior triptan therapy. METHODS: In this single-center, open-label pilot trial, patients with episodic migraine associated with cutaneous allodynia were treated on 2 occasions with dihydroergotamine 1.0 mg intramuscularly. One attack was treated within 2 hours (early) and a second attack at 4 hours (late) after the onset of throbbing pain. Headache pain and any associated symptoms, subjective cutaneous allodynia, and mechanical (brush) allodynia were assessed. All data were analyzed using the Fisher's exact test. RESULTS: Thirteen patients met the entry criteria; however, data from only 9 patients, those who completed treatment for 2 migraine attacks, were used to evaluate the efficacy and safety of dihydroergotamine. Whether they took dihydroergotamine early or late in the attack, most patients (>55%) had headache relief within 2 hours, and at least 44% of patients achieved headache-free status by 8 hours postdose. Subjective cutaneous allodynia started to decline after 30 minutes postdose in the early treated group and after 120 minutes postdose in the late-treated group. Brush allodynia began to decline after 15 minutes postdose in the early treated group and after 90 minutes postdose in the late-treated group. Six of 9 patients (67%) reported at least 1 adverse event. CONCLUSIONS: The results of this pilot trial provide proof of concept for the headache-relief benefit of dihydroergotamine in patients with migraine headache and allodynia. A large, placebo-controlled trial of dihydroergotamine in allodynic patients is warranted.     

慢性偏头痛患者超敏性疼痛的病理生理机制研究

目的:利用血氧水平依赖(BOLD)功能核磁成像探讨慢性偏头痛患者产生皮肤超敏性疼痛(CA)的病理生理机制。方法:采用前瞻性研究方法,将研究对象分为四组。A组(n=29):伴有一侧前臂(颈8支配区)CA和/或同时有V1区和/或C2-C3区CA者;B组(n=31):伴有一侧额区(三叉神经第一支)和/或伴有一侧颈区(C2-C3支配区)CA者;C组(n=30):不伴CA者;D组(n=30):正常对照。采用BOLD功能核磁成像技术研究慢性偏头痛患者诱发CA时三叉神经感觉系统不同级别神经元激活情况。结果:在诱发CA时,A组的三叉神经节、三叉神经脊束核和丘脑的神经元均被激活致敏,B组的三叉神经节、三叉神经脊束核受到激活致敏,C组则只有三叉神经节受到激活致敏,D组则三级神经元均未激活致敏。结论:慢性偏头痛出现的头痛和躯体不同部位的CA与三叉神经感觉系统不同级别神经元受到激活致敏有关。     

General trigeminospinal central sensitization and impaired descending pain inhibitory controls contribute to migraine progression

Migraine is a chronic disease with episodic manifestations. In a subgroup, attack frequency increases over time, leading to chronic migraine. One of the most important risk factors for migraine progression is frequency of headache attacks at baseline. Unfortunately, the actual effects of repeated activation of dural nociceptors are poorly known. We investigated the behavioral, anatomical, and electrophysiological changes induced by repeated low- and high-intensity stimulation of meningeal nociceptor by injecting an inflammatory soup in rats. Single high-intensity, but not low-intensity, stimulation produces a reversible cephalic allodynia. Upon repetition, however, low-intensity stimulation, too, induces a reversible cephalic allodynia, and high-intensity, reversible cephalic and extracephalic allodynia. Moreover, cephalic allodynia becomes, in part, persistent upon repeated high-intensity stimulation. Fos expression reveals that a single high-intensity stimulation already leads to widespread, trigeminal, and spinal central sensitization, and that such general central sensitization potentiates upon repetition. Trigeminovascular nociceptive neurons become persistently sensitized and their diffuse noxious inhibitory controls (DNIC) concomitantly impaired. Thus, compared with single stimulation, repeated dural nociceptor activation specifically leads to: 1) a gradual worsening of cutaneous hypersensitivity and general neuronal hyperexcitability and 2) spreading of cutaneous hypersensitivity superimposed on 3) persistent cephalic cutaneous hypersensitivity and trigeminal central sensitization. Such repetition-induced development of central sensitization and its consequence, cutaneous allodynia, may arise from both the general neuronal hyperexcitability that results from DNIC impairment and hyperexcitability that likely develops in trigeminal nociceptive neurons in response to their repetitive activation. These neuronal changes may in turn elevate the risk for developing chronic migraine.     

Throbbing pain is related to Queckenstedt's test effect in migraine patients

The Queckenstedt's (Q)-test can aggravate headache intensity during migraine attacks (Q-test effect). The objective of this study was to delineate the Q-test effect in patients experiencing migraine attacks. We performed a 30-s Q- and a sham test on 39 patients with acute migraine attacks in both supine and sitting positions. Headache intensities during and 30 s after the Q- or sham tests were recorded on a 0–10 verbal scale. Brushing allodynia (BA) was recorded after using a gauze-brushing test over the patient's face and forearms. The Q- but not the sham test aggravated headache intensity in both sitting and supine positions. The presence of throbbing pain and higher pain intensities was associated with the Q-test effect in the supine position. However, the presence or absence of BA was not correlated. We concluded that the Q-test effect is likely to be related to peripheral sensitization of the meninges but not central sensitization. The Q-test effect may be used as an objective marker for peripheral sensitization.     

Efficacy and safety of MAP0004, orally inhaled DHE in treating migraines with and without allodynia

Background.— Central sensitization develops once migraine attacks become established and can be clinically detected by the development of cutaneous allodynia. The efficacy of triptans for migraine resolution has been shown to be markedly reduced when administered in patients with established cutaneous allodynia. Objective.— The study aimed to evaluate the efficacy and safety of MAP0004, a novel, orally inhaled, form of dihydroergotamine, in patients with and without cutaneous allodynia at the time of treatment. Methods.— This evaluation was a post hoc subanalysis of a randomized, double‐blind, placebo‐controlled, 2‐arm, phase 3, multicenter study. The presence or absence of baseline cutaneous allodynia at the time of drug administration was based on the response to a standard questionnaire. Treatment efficacy at 2 hours posttreatment was compared in patients with and without baseline allodynia. Results.— At the time of treatment, allodynia was present in 216 patients treated with MAP0004 and 202 patients treated with placebo. MAP0004 treatment efficacy was superior to placebo, as measured by 2‐hour pain relief for patients with and without allodynia (P < .0001) and as measured by 2‐hour pain freedom for patients with (P < .0001) and without (P < .0002) allodynia. No significant within‐treatment differences after treatment with MAP0004 in patients with and without allodynia at baseline were observed. Patients were more likely to be allodynia‐free after treatment with MAP0004 compared with placebo (73% vs 66%, P = .0013). Furthermore, treatment with MAP0004 prevented the development of allodynia in patients not experiencing allodynia at baseline (P = .0057). MAP0004 was generally well tolerated. Conclusions.— This post hoc subanalysis shows that MAP0004 was similarly effective in patients whether or not allodynia was present at treatment baseline. Patients were also more likely to be allodynia‐free following treatment of a migraine with MAP0004.     

基于体素的形态学分析偏头痛患者灰质异常:Meta分析

目的 采用激活似然估计（ALE）的Meta分析方法,探讨偏头痛患者基于体素的形态学（VBM）分析所得的脑灰质改变。方法 在中国知网、PubMed和Embase数据库中检索从2000年1月—2015年6月间基于VBM的偏头痛患者灰质变化的文献,然后通过GingerALE软件包对所检索结果进行Meta分析。结果 检索后共纳入包括246例偏头痛患者和245名健康对照者的10项研究。偏头痛患者双侧额下回（BA44区）、右侧中央前回（BA43、44区）、双侧额中回（BA6、9区）、双侧扣带回前部（BA32区）、左侧扣带回（BA24区）、右侧颞上回（BA22区）、左侧岛叶（BA13区）、右侧顶下小叶（BA40区）灰质与健康对照者比较均显著减少（P均<0.05）。结论 偏头痛患者脑灰质结构的改变为进一步研究与疼痛有关的脑神经网络的病理、生理机制提供了形态学依据。