Browsing by Subject "Migraine"

Now showing 1 - 6 of 6
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    Complementary and integrative medicine perspectives among veteran patients and VHA healthcare providers for the treatment of headache disorders: a qualitative study
    (Springer, 2022-01-25) Kuruvilla, Deena E.; Lindsey, Hayley; Grinberg, Amy S.; Goldman, Roberta E.; Riley, Samantha; Baird, Sean; Fenton, Brenda T.; Sico, Jason J.; Damush , Teresa M.; Medicine, School of Medicine
    Objective To evaluate veteran patient and provider perceptions and preferences on complementary and integrative medicine (CIM) for headache management. Background The Veterans Health Administration (VHA) has spearheaded a Whole Health system of care focusing on CIM-based care for veteran patients. Less is known about patients’ and providers’ CIM perceptions and preferences for chronic headache management. Methods We conducted semi-structured interviews with 20 veteran patients diagnosed with headache and 43 clinical providers, across 12 VHA Headache Centers of Excellence (HCoE), from January 2019 to March 2020. We conducted thematic and case comparative analyses. Results Veteran patients and VHA clinical providers viewed CIM favorably for the treatment of chronic headache. Specific barriers to CIM approaches included: (1) A lack of personnel specialized in specific CIM approaches for timely access, and (2) variation in patient perceptions and responses to CIM treatment efficacy for headache management. Conclusion Veteran patients and VHA clinical providers in this study viewed CIM favorably as a safe addition to mainstream headache treatments. Advantages to CIM include favorable adverse effect profiles and patient autonomy over the treatment. By adding more CIM providers and resources throughout the VHA, CIM modalities may be recommended more routinely in the management of veterans with headache.
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    Environmental Toxin Acrolein Alters Levels of Endogenous Lipids, Including TRP Agonists: A Potential Mechanism for Headache Driven by TRPA1 Activation
    (Elsevier, 2017-01) Leishman, Emma; Kunkler, Phillip E.; Manchanda, Meera; Sangani, Kishan; Stuart, Jordyn M.; Oxford, Gerry S.; Hurley, Joyce H.; Bradshaw, Heather B.; Medicine, School of Medicine
    Exposure to airborne toxins can trigger headaches, but the mechanisms are not well understood. Some environmental toxins, such as acrolein, activate transient receptor potential ankyrin 1 (TRPA1), a receptor involved in pain sensation that is highly expressed in the trigeminovascular system. It has been shown in rat models that repeated exposure to acrolein induces trigeminovascular sensitization to both TRPA1 and TRP vanilloid 1 (TRPV1) agonists, a phenomenon linked to headache. In this study, we test the hypothesis that the sensitization of trigeminovascular responses in rats after acrolein exposure via inhalation is associated with changes in levels of endogenous lipids, including TRPV1 agonists, in the trigeminal ganglia, trigeminal nucleus, and cerebellum. Lipidomics analysis of 80 lipids was performed on each tissue after acute acrolein, chronic acrolein, or room air control. Both acute and chronic acrolein exposure drove widespread alterations in lipid levels. After chronic acrolein exposure, levels of all 6 N-acyl ethanolamines in the screening library, including the endogenous cannabinoid and TRPV1 agonist, N-arachidonoyl ethanolamine, were elevated in trigeminal tissue and in the cerebellum. This increase in TRPV1 ligands by acrolein exposure may indicate further downstream signaling, in that we also show here that a combination of these TRPV1 endogenous agonists increases the potency of the individual ligands in TRPV1-HEK cells. In addition to these TRPV1 agonists, 3 TRPV3 antagonists, 4 TRPV4 agonists, and 25 orphan lipids were up and down regulated after acrolein exposure. These data support the hypothesis that lipid signaling may represent a mechanism by which repeated exposure to the TRPA1 agonist and environmental toxin, acrolein, drives trigeminovascular sensitization.
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    Impact of migraine on health care utilization and expenses in obese adults: A U.S. population-based study
    (Dove Press, 2018-12) Wu, Jun; Davis-Ajami, Mary L.; Lu, Zhiqiang K.
    Purpose: Migraine prevalence increases in people with obesity, and obesity may contribute to migraine chronicity. Yet, few studies examine the effect of comorbid migraine on health care utilization and expenses in obese US adults. This study aimed to identify risk factors for migraine and compare the use of health care services and expenses between migraineurs and non-migraineurs in obese US adults. Subjects and methods: This 7-year retrospective study used longitudinal panel data from 2006 to 2013 from the Household Component of the Medical Expenditure Panel Survey to identify obese adults reporting migraines. Outcomes compared in migraineurs vs non-migraineurs were as follows: annualized per-person medical care, prescription drug, and total health expenses. Results: In 23,596 obese adults, 4.7% reported migraine (n=1,025) approximating 3 million civilian noninstitutionalized US individuals. Logistic regression showed that the following sociodemographic characteristics increased migraine risk: age (18-45 years), females, White race, poor perceived health status, and greater Charlson comorbidity index. Migraineurs showed US$1,401 (P=0.007), US$813 (P<0.001), and US$2,213 (P=0.001) greater annual medical, prescription drug, and total health expenses than non-migraineurs, respectively. After adjustment, total health expenses increased by 31.6% in migraineurs vs non-migraineurs. Conclusion: In this US adult obese population, migraineurs showed greater total health care utilization and expenses than non-migraineurs. Treatment plans that address risk factors associated with migraine and comorbidities may help reduce the utilization of health care services and costs.
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    Improvement in Function after Lasmiditan Treatment: Post Hoc Analysis of Data from Phase 3 Studies
    (Springer, 2020-12) Smith, Timothy; Krege, John H.; Rathmann, Suchitrita S.; Dowsett, Sherie A.; Hake, Ann; Nery, Emel S. M.; Matthews, Brandy R.; Doty, Erin G.; Neurology, School of Medicine
    Introduction: Migraine is associated with substantial functional impairment and affects many aspects of daily life. Methods: Using data from SAMURAI and SPARTAN (double-blind, placebo-controlled, phase 3 studies) and GLADIATOR (an open-label, phase 3 study enrolling patients who had completed SAMURAI or SPARTAN), we assessed the effects of lasmiditan on migraine-related functional disability at multiple time points from 0.5 to 48 h post dose by asking patients to rate how much the migraine was interfering with normal activities. Pooled data from SAMURAI and SPARTAN (SAMURAI + SPARTAN) and data from GLADIATOR were analyzed using the intention-to-treat populations. Results: For SPARTAN + SAMURAI, significantly more patients who received lasmiditan at any dose versus placebo reported freedom from migraine-related functional disability at every timepoint from 2 h post dose, and this difference persisted to 48 h (p < 0.05). Significant differences from placebo in freedom from migraine-related functional disability commenced at 1 h post dose for lasmiditan 200 mg, 1.5 h for lasmiditan 100 mg, and 2 h for lasmiditan 50 mg. Findings from GLADIATOR supported those from SAMURAI + SPARTAN. Conclusion: All doses of lasmiditan resulted in an improvement in migraine-related functional disability that persisted to 48 h. In SAMURAI + SPARTAN, a significant difference from placebo was observed as early as 1 h post dose. TRIAL REGISTRATION AT CLINICALTRIALS.GOV: SAMURAI (NCT02439320), SPARTAN (NCT02605174), and GLADIATOR (NCT02565186).
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    Lasmiditan mechanism of action – review of a selective 5-HT1F agonist
    (Springer, 2020-06-10) Clemow, David B.; Johnson, Kirk W.; Hochstetler, Helen M.; Ossipov, Michael H.; Hake, Ann M.; Blumenfeld, Andrew M.; Neurology, School of Medicine
    Migraine is a leading cause of disability worldwide, but it is still underdiagnosed and undertreated. Research on the pathophysiology of this neurological disease led to the discovery that calcitonin gene-related peptide (CGRP) is a key neuropeptide involved in pain signaling during a migraine attack. CGRP-mediated neuronal sensitization and glutamate-based second- and third-order neuronal signaling may be an important component involved in migraine pain. The activation of several serotonergic receptor subtypes can block the release of CGRP, other neuropeptides, and neurotransmitters, and can relieve the symptoms of migraine. Triptans were the first therapeutics developed for the treatment of migraine, working through serotonin 5-HT1B/1D receptors. The discovery that the serotonin 1F (5-HT1F) receptor was expressed in the human trigeminal ganglion suggested that this receptor subtype may have a role in the treatment of migraine. The 5-HT1F receptor is found on terminals and cell bodies of trigeminal ganglion neurons and can modulate the release of CGRP from these nerves. Unlike 5-HT1B receptors, the activation of 5-HT1F receptors does not cause vasoconstriction. The potency of different serotonergic agonists towards 5-HT1F was correlated in an animal model of migraine (dural plasma protein extravasation model) leading to the development of lasmiditan. Lasmiditan is a newly approved acute treatment for migraine in the United States and is a lipophilic, highly selective 5-HT1F agonist that can cross the blood-brain barrier and act at peripheral nervous system (PNS) and central nervous system (CNS) sites. Lasmiditan activation of CNS-located 5-HT1F receptors (e.g., in the trigeminal nucleus caudalis) could potentially block the release of CGRP and the neurotransmitter glutamate, thus preventing and possibly reversing the development of central sensitization. Activation of 5-HT1F receptors in the thalamus can block secondary central sensitization of this region, which is associated with progression of migraine and extracephalic cutaneous allodynia. The 5-HT1F receptors are also elements of descending pain modulation, presenting another site where lasmiditan may alleviate migraine. There is emerging evidence that mitochondrial dysfunction might be implicated in the pathophysiology of migraine, and that 5-HT1F receptors can promote mitochondrial biogenesis. While the exact mechanism is unknown, evidence suggests that lasmiditan can alleviate migraine through 5-HT1F agonist activity that leads to inhibition of neuropeptide and neurotransmitter release and inhibition of PNS trigeminovascular and CNS pain signaling pathways.
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    Role of intraganglionic transmission in the trigeminovascular pathway
    (Sage, 2019) Zhang, LuJuan; Kunkler, Phillip Edward; Knopp, Kelly L.; Oxford, Gerry Stephen; Hurley, Joyce Harts; Biochemistry and Molecular Biology, School of Medicine
    Migraine is triggered by poor air quality and odors through unknown mechanisms. Activation of the trigeminovascular pathway by environmental irritants may occur via activation of transient receptor potential ankyrin 1 (TRPA1) receptors on nasal trigeminal neurons, but how that results in peripheral and central sensitization is unclear. The anatomy of the trigeminal ganglion suggests that noxious nasal stimuli are not being transduced to the meninges by axon reflex but likely through intraganglionic transmission. Consistent with this concept, we injected calcitonin gene-related peptide, adenosine triphosphate, or glutamate receptor antagonists or a gap junction channel blocker directly and exclusively into the trigeminal ganglion and blocked meningeal blood flow changes in response to acute nasal TRP agonists. Previously, we observed chronic sensitization of the trigeminovascular pathway after acrolein exposure, a known TRPA1 receptor agonist. To explore the mechanism of this sensitization, we utilized laser dissection microscopy to separately harvest nasal and meningeal trigeminal neuron populations in the absence or presence of acrolein exposure. mRNA levels of neurotransmitters important in migraine were then determined by reverse transcription polymerase chain reaction. TRPA1 message levels were significantly increased in meningeal cell populations following acrolein exposure compared to room air exposure. This was specific to TRPA1 message in meningeal cell populations as changes were not observed in either nasal trigeminal cell populations or dorsal root ganglion populations. Taken together, these data suggest an important role for intraganglionic transmission in acute activation of the trigeminovascular pathway. It also supports a role for upregulation of TRPA1 receptors in peripheral sensitization and a possible mechanism for chronification of migraine after environmental irritant exposure.