The blood-brain barrier (BBB) is a highly regulated dynamic interface that separates the peripheral circulating blood supply from the central nervous system. Many acute and chronic neurodegenerative diseases show regional degenerative changes and modified BBB integrity. Migraine is a common and potentially debilitating neurological disorder characterized by a paroxysmal unilateral throbbing pain and is often associated with aura, nausea, vomiting, and photophobia. Triptans (serotonin IB/ID receptor agonists) are often used migraine therapy and are thought to relieve headache pain, in part, by inhibiting the release of pronociceptive transmitters through actions on 5HT1B/1D receptors on trigeminal afferent neurons. However, frequent use of triptans over an extended period increased the frequency of migraines in migraineurs, a condition termed medication overuse headache (MOH). Since migraineurs are the most susceptible to develop MOH, some common neuronal mechanisms between migraine and MOH may be expected. The mechanisms that underlie medication overuse headache are not fully understood. Evidence suggests that changes in BBB integrity may play a key role in several clinical situations in which migraine headache is a major feature. We suggest that prolonged exposure to triptans or medication withdrawal results in BBB dysfunction, increasing the potential for the induction of headache. To test this hypothesis, we will use neurochemical, and pharmacological strategies in a rat model of triptan-induced latent sensitization to determine potential structural and functional changes in BBB integrity in two pain pathway brain regions. Medication withdrawal will be precipitated with 5-HT1B/1D antagonist (GRI27935). Behavioral cutaneous allyodyna responses will be assessed and correlated to changes in BBB integrity. Establishing the mechanisms that underlie the pathobiology of MOH will assist in the development of new therapeutic strategies for the treatment of migraine and MOH.
Approximately 22 million Americans suffer from migraine headaches. Frequent and extended use of migraine medication induces medication overuse headache (MOH) in 1-2% of the population. We propose a better understanding of the role of the blood-brain barrier is fundamental to understanding how migraine and MOH may occur and represents a novel pharmacological target in the development of novel therapeutics.
|Deal, Alex L; Erickson, Kristen J; Shiers, Stephanie I et al. (2016) Limbic system development underlies the emergence of classical fear conditioning during the third and fourth weeks of life in the rat. Behav Neurosci 130:212-30|
|Malon, Jennifer T; Cao, Ling (2016) Preparation of Primary Mixed Glial Cultures from Adult Mouse Spinal Cord Tissue. J Vis Exp :|
|Zhang, Yan; Williams, Dwight A; Zaidi, Saheem A et al. (2016) 17-Cyclopropylmethyl-3,14Î²-dihydroxy-4,5Î±-epoxy-6Î²-(4'-pyridylcarboxamido)morphinan (NAP) Modulating the Mu Opioid Receptor in a Biased Fashion. ACS Chem Neurosci 7:297-304|
|Havelin, Joshua; Imbert, Ian; Cormier, Jennifer et al. (2016) Central Sensitization and Neuropathic Features of Ongoing Pain inÂ a Rat Model of Advanced Osteoarthritis. J Pain 17:374-82|
|Malon, Jennifer T; Cao, Ling (2016) Calcitonin gene-related peptide contributes to peripheral nerve injury-induced mechanical hypersensitivity through CCL5 and p38 pathways. J Neuroimmunol 297:68-75|
|Harasawa, Ichiro; Johansen, Joshua P; Fields, Howard L et al. (2016) Alterations in the rostral ventromedial medulla after the selective ablation of Î¼-opioid receptor expressing neurons. Pain 157:166-73|
|Camire, Ryan B; Beaulac, Holly J; Willis, Colin L (2015) Transitory loss of glia and the subsequent modulation in inflammatory cytokines/chemokines regulate paracellular claudin-5 expression in endothelial cells. J Neuroimmunol 284:57-66|
|McParland, Aidan L; Follansbee, Taylor L; Vesenka, Gwendolyn D et al. (2015) Steroid Receptor Isoform Expression in Drosophila Nociceptor Neurons Is Required for Normal Dendritic Arbor and Sensitivity. PLoS One 10:e0140785|
|Remeniuk, Bethany; Sukhtankar, Devki; Okun, Alec et al. (2015) Behavioral and neurochemical analysis of ongoing bone cancer pain in rats. Pain 156:1864-73|
|Warner, Emily; Krivitsky, Rebecca; Cone, Katherine et al. (2015) Evaluation of a Postoperative Pain-Like State on Motivated Behavior in Rats: Effects of Plantar Incision on Progressive-Ratio Food-Maintained Responding. Drug Dev Res 76:432-41|
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