Citations

Female selective nociceptor sensitization and opioid-induced hyperalgesia result from an imbalance of prolactin receptor isoforms.

Background and Objectives Migraine with aura (MwA) is associated with increased brain hyper‐responsiveness to visual stimuli and increased visual network connectivity relative to migraine without aura (MwoA). Despite this, prior studies have provided conflicting results regarding whether MwA is associated with higher photophobia symptom scores compared to MwoA. The relationships between MwA and other types of sensory hypersensitivity, such as phonophobia and cutaneous allodynia (CA), have not been previously investigated. The purpose of this cross‐sectional observational study was to investigate whether MwA is associated with greater symptoms of photophobia, phonophobia, and CA compared to MwoA. Methods This analysis included 321 migraine patients (146 MwA; 175 MwoA) who had been enrolled into the American Registry for Migraine Research. The diagnosis of either MwoA or MwA was determined by headache specialists using ICHD diagnostic criteria. Patients completed the Photosensitivity Assessment Questionnaire, the Hyperacusis Questionnaire, and the Allodynia Symptom Checklist. Mean or median values were compared between groups. Regression models were created to analyze the relationship between MwA with photophobia scores, hyperacusis scores, and the presence of interictal CA. Results Those with MwA had higher mean photophobia scores than those with MwoA (4.1 vs 3.0, P = .0003). MwA was positively associated with photophobia symptom severity ( B = 0.50 [SE = 0.14], P = .0003), after controlling for age, patient sex, and headache frequency. Aura was not associated with hyperacusis symptom severity ( B = 0.07 [SE = 0.08], P = .346) or the presence of interictal CA (OR 1.33 [95% CI 0.70‐2.53], P = .381). Conclusion MwA is associated with higher photophobia symptom scores compared to MwoA. Aura is not associated with greater hyperacusis or interictal allodynia scores. These findings complement prior imaging and neurophysiologic studies that demonstrated MwA to be associated with hyper‐responsiveness of brain visual processing regions. The findings suggest that MwA is associated specifically with visual hypersensitivity, as opposed to being associated with a general hypersensitivity to multiple types of sensory stimuli.

Objectives: The Ice Hockey Summit III provided updated scientific evidence on concussions in hockey to inform these 5 objectives: (1) describe sport related concussion (SRC) epidemiology; (2) classify prevention strategies; (3) define objective, diagnostic tests; (4) identify treatment; and (5) integrate science and clinical care into prioritized action plans and policy. Methods: Our action plan evolved from 40 scientific presentations. The 155 attendees (physicians, athletic trainers, physical therapists, nurses, neuropsychologists, scientists, engineers, coaches, and officials) voted to prioritize these action items in the final Summit session. Results: To (1) establish a national and international hockey database for SRCs at all levels; (2) eliminate body checking in Bantam youth hockey games; (3) expand a behavior modification program (Fair Play) to all youth hockey levels; (4) enforce game ejection penalties for fighting in Junior A and professional hockey leagues; (5) establish objective tests to diagnose concussion at point of care; and (6) mandate baseline testing to improve concussion diagnosis for all age groups. Conclusions: Expedient implementation of the Summit III prioritized action items is necessary to reduce the risk, severity, and consequences of concussion in the sport of ice hockey.

Objectives The objectives of this study were to determine the rates of nausea, phonophobia, and photophobia reported overall and as the most bothersome symptom (MBS) in individuals with migraine and to identify individual characteristics associated with each of the 3 candidate MBSs. Background The MBS has emerged as an important coprimary efficacy endpoint in clinical trials of acute treatments for migraine, as recommended by the Food and Drug Administration. The current understanding of how persons with migraine designate an associated symptom as the most bothersome has been assessed primarily in the context of randomized trials. Methods Respondents (n = 95,821) in the cross‐sectional, observational Migraine in America Symptoms and Treatment (MAST) study were adults (aged ≥18 years) recruited from a US nationwide online research panel. A validated diagnostic screener identified 15,133 individuals who met modified International Classification of Headache Disorders (ICHD)‐3 beta criteria for migraine and reported at least 1 monthly headache day (MHD) over the previous 3 months. The survey ascertained sociodemographic variables, headache‐related disability, MHDs, cutaneous allodynia, medication overuse, a migraine symptom severity score, pain interference, noncephalic pain, anxiety and depression symptoms, visual aura over the previous year, and acute treatment optimization. The current analysis is based on respondents who also completed a 6‐month follow‐up assessment that included questions about their most bothersome headache symptom. Results A total of 7518 respondents completed the 6‐month follow‐up, and 6045 met inclusion criteria and were included in the analysis. The mean age of respondents was 47 (SD 13.4) years, 76.0% (4596/6045) were women, and 84.8% (5103/6017) were white. Among all respondents, 64.9% reported all 3 migraine symptoms. The MBS was photophobia in 49.1% (2967/6045), nausea in 28.1% (1697/6045), and phonophobia in 22.8% (1381/6045). Respondents reporting photophobia as the MBS were more likely to be men, to be obese, and to report visual aura. Those reporting nausea as the MBS were more likely to be women, to have lower incomes, and to report lower levels of treatment optimization. Respondents reporting phonophobia as the MBS were more likely to have cutaneous allodynia and less likely to have visual aura. Conclusion Most people with migraine in the MAST observational study reported all 3 cardinal symptoms of nausea, photophobia, and phonophobia. As in clinical trials, the most common MBS was photophobia. Patient profiles differed among the groups defined by their MBS.

Background The American Registry for Migraine Research (ARMR) is a multicenter, prospective, longitudinal patient registry, biorepository, and neuroimaging repository that collects clinical data, electronic health record (EHR) data, blood samples, and brain imaging data from individuals with migraine or other headache types. In this manuscript, we outline ARMR research methods and report baseline data describing an initial cohort of ARMR participants. Methods Adults with any International Classification of Headache Disorders (ICHD) diagnosis were prospectively enrolled from one of the 8 participating headache specialty centers. At baseline, ARMR participants complete web‐based questionnaires, clinicians enter the participant’s ICHD diagnoses, an optional blood specimen is collected, and neuroimaging data are uploaded to the ARMR neuroimaging repository. Participants maintain the ARMR daily headache diary longitudinally and follow‐up questionnaires are completed by participants every 3 months. EHR data are integrated into the ARMR database from a subset of ARMR sites. Herein, we describe the ARMR methodology and report the summary data from ARMR participants who had, from February 2016 to May 2019, completed at least 1 baseline questionnaire from which data are reported in this manuscript. Descriptive statistics are used to provide an overview of patient’s sociodemographics, headache diagnoses, headache characteristics, most bothersome symptoms other than headache, headache‐related disability, comorbidities, and treatments. Results Data were available from 996 ARMR participants, enrolled from Mayo Clinic Arizona, Dartmouth‐Hitchcock Medical Center, University of Utah, University of Colorado, Thomas Jefferson University, University of Texas Health Science Center at Houston, Georgetown University Medical Center, and DENT Neurological Institute. Among ARMR participants, 86.7% (n = 864) were female and the mean age at the time of enrollment was 48.6 years (±13.9; range 18‐84). The most common provider‐reported diagnosis was chronic migraine (n = 622), followed by migraine without aura (n = 327), migraine with aura (n = 196), and medication overuse headache (n = 65). Average headache frequency was 19.1 ± 9.2 days per month (n = 751), with 68% reporting at least 15 headache days per month. Sensitivity to light was the most frequent (n = 222) most bothersome symptom overall, other than headache, but when present, cognitive dysfunction was most frequently (n = 157) the most bothersome symptom other than headache. Average migraine disability assessment (MIDAS) score was 52 ± 49 (n = 760), (very severe headache‐related disability); however, 17% of the ARMR population had MIDAS scores suggesting “no” or “mild” disability. The most common non‐headache health issues were allergies (n = 364), back pain (n = 296), neck pain (n = 296), depression (n = 292), and anxiety (n = 278). Nearly 85% (n = 695) of patients were using preventive medications and 24.7% were using non‐medication preventive therapy (eg, vitamins and neuromodulation). The most common preventive medication classes were neurotoxins, anticonvulsants, antidepressants, vitamins/supplements, and anticalcitonin gene‐related peptide ligand or receptor‐targeted monoclonal antibodies. Nearly 90% (n = 734) of ARMR participants was taking medications to treat migraine attacks, with the most common classes being triptans, non‐steroidal anti‐inflammatory drugs, antiemetics, acetaminophen, and combination analgesics. Conclusions ARMR is a source of real‐world patient data, biospecimens, and brain neuroimaging data that provides comprehensive insight into patients with migraine and other headache types being seen in headache specialty clinics in the United States. ARMR data will allow for longitudinal and advanced analytics that are expected to lead to a better characterization of patient heterogeneity, healthcare resource utilization, identification of endophenotypes, factors that predict treatment outcomes and clinical course, and ultimately advance the field toward precision headache medicine.

Objective To evaluate onset of effect of galcanezumab in patients with episodic migraine. Background Galcanezumab is a monoclonal antibody that binds to calcitonin gene‐related peptide and is indicated for preventive treatment of migraine. Design/Methods Data on the primary outcome measure were analyzed from 2 previously published double‐blind, Phase 3 studies (EVOLVE‐1 [N = 858] and EVOLVE‐2 [N = 915]) wherein adult patients with episodic migraine were randomized to receive monthly subcutaneous injections of galcanezumab 120 mg (with 240‐mg loading dose) or 240 mg or placebo for up to 6 months. Monthly onset of effect was defined as the earliest month at which galcanezumab achieved and subsequently maintained statistical superiority to placebo on the mean change from baseline in the number of monthly migraine headache days (MHDs). If onset occurred in Month 1, weekly onset was evaluated and defined as the earliest week at which galcanezumab statistically separated from placebo and maintained statistical separation for remaining weeks in that month. Day of onset of effect was also analyzed, as were monthly and weekly onset, for occurrence of ≥50% reduction from baseline in number of MHDs. Results For both studies, change from baseline in monthly MHDs showed a statistically significant separation of galcanezumab from placebo at Month 1 and each subsequent month (each P < .001). Analysis of the first month for both studies indicated onset of effect in the first week, with galcanezumab‐treated patients having significantly higher odds of having fewer MHDs in the first week (odds ratio [95% confidence interval] for EVOLVE‐1, 2.71 [2.00, 3.66], and for EVOLVE‐2, 2.88 [2.16, 3.86]; both P < .001) and each subsequent week compared with placebo‐treated patients ( P ≤ .004). Daily analysis showed onset of effect at Day 1 (first day after injection day). Galcanezumab also demonstrated superiority to placebo on occurrence of ≥50% reduction in MHDs starting at Week 1 (percentage of patients with 50% response in galcanezumab group vs placebo group for EVOLVE‐1, 54.3% vs 32.4% [ P < .001], and for EVOLVE‐2, 59.4% vs 38.0% [ P < .001]). Conclusion Rapid onset of preventive effect on the first day after injection of galcanezumab was confirmed in both studies of episodic migraine.

Objective The objective of this study was to evaluate the efficacy, tolerability, and safety of 120 mg DFN‐15 vs placebo for the acute treatment of migraine. Background Certain nonsteroidal anti‐inflammatory drugs (NSAIDs) are guideline‐recommended therapies for the acute treatment of migraine, but patients who use them may have issues with gastrointestinal tolerability. Celecoxib, a selective inhibitor of cyclooxygenase‐2, produces analgesia similar to nonselective NSAIDs. DFN‐15 is an oral, ready‐made liquid solution of celecoxib being investigated for the acute treatment of migraine. Methods A randomized, double‐blind, placebo‐controlled, efficacy, tolerability, and safety study in adults with migraine was conducted. Subjects treated a single migraine attack with 120 mg DFN‐15 or placebo as soon as possible after the onset of pain of moderate to severe intensity. The 2 independent coprimary efficacy endpoints were the proportion of subjects with freedom from pain and the absence of the most bothersome symptom (MBS) at 2 hours postdose. A second double‐blind treatment period followed the first, but did not contribute to the primary outcomes and will be reported elsewhere. Results There were 622 subjects randomized (1:1) to double‐blind treatment with either 120 mg DFN‐15 or placebo, and 567 (91.2%) treated a migraine with study drug (n = 285 DFN‐15; n = 282 placebo). Groups were balanced in demographic characteristics; the mean age was 40, and most subjects were female (87% [494/567]). At 2 hours postdose, DFN‐15 was significantly superior to placebo for pain freedom (35.6% [98/275] vs 21.7% [57/263], P < .001), with an odds ratio (95% CI) of 2.00 (1.36, 2.94) and for freedom from the MBS (57.8% [134/232] vs 44.8% [104/232], P = .007), with an odds ratio (95% CI) of 1.68 (1.17, 2.43). A total of 13.3% (38/285) of DFN‐15‐treated subjects and 8.9% (25/282) of placebo‐treated subjects reported a treatment‐emergent adverse event (TEAE). Study drug‐related TEAEs were reported by 9.1% (26/285) of DFN‐15 subjects and 6.0% (17/282) of placebo subjects, the most common of which were dysgeusia (4.2% [12/285] vs 1.4% [4/282]) and nausea (3.2% [9/285] vs 1.8% [5/282]). No subjects treated with DFN‐15 reported TEAEs that were severe or led to withdrawal, and no serious TEAEs or deaths were reported in the study. Conclusions DFN‐15 was significantly more effective than placebo for the acute treatment of migraine, with a generally favorable tolerability and safety profile.