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Chemical mediators of migraine: preclinical and clinical observations.

ABSTRACT: Migraine is a neurovascular disorder, and although the pathophysiology of migraine has not been fully delineated, much has been learned in the past 50 years. This knowledge has been accompanied by significant advancements in the way migraine is viewed as a disease process and in the development therapeutic options. In this review, we will focus on 4 mediators (nitric oxide, histamine, serotonin, and calcitonin gene-related peptide) which have significantly advanced our understanding of migraine as a disease entity. For each mediator we begin by reviewing the preclinical data linking it to migraine pathophysiology, first focusing on the vascular mechanisms, then the neuronal mechanisms. The preclinical data are then followed by a review of the clinical data which support each mediator's role in migraine and highlights the pharmacological agents which target these mediators for migraine therapy.

SUBMITTER: Gupta S

PROVIDER: S-EPMC3986727 | biostudies-literature | 2011 Jun

REPOSITORIES: biostudies-literature

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Chemical mediators of migraine: preclinical and clinical observations.

Gupta Saurabh S Nahas Stephanie J SJ Peterlin B Lee BL

Headache 20110601 6

Migraine is a neurovascular disorder, and although the pathophysiology of migraine has not been fully delineated, much has been learned in the past 50 years. This knowledge has been accompanied by significant advancements in the way migraine is viewed as a disease process and in the development therapeutic options. In this review, we will focus on 4 mediators (nitric oxide, histamine, serotonin, and calcitonin gene-related peptide) which have significantly advanced our understanding of migraine ...[more]

PMID: 21631491

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Project description:The study objective was to investigate whether sex influences 3'-deoxy-3'-18F-fluorothymidine (18F-FLT) uptake and tissue distribution in mouse models of cancer. Methods:18F-FLT biodistribution was measured in 3 strains of male and female mice (129S6/SvEv, athymic nude, and BALB/c). 18F-FDG biodistribution was measured for comparison. 18F-FLT uptake was also measured in female 129S6/SvEv mice bearing estrogen-dependent SSM3 mouse mammary tumors, male athymic nude mice bearing androgen-dependent CWR22 prostate cancer xenografts, and male and female athymic nude mice bearing estrogen-independent MDA-MB-231 human breast cancer xenografts. Ki-67 expression was assayed by immunohistochemistry. PET/CT imaging was performed to visualize 18F-FLT biodistribution and to determine pharmacokinetics. Results: Greater 18F-FLT activity was observed in blood, liver, muscle, heart, kidney, and bone in female than male mice. Pharmacokinetic analysis demonstrated higher early renal 18F-FLT activity and greater accumulation of 18F-FLT in the urinary bladder in male than female mice. The differential pattern of 18F-FLT biodistribution between the sexes seen with 18F-FLT was not observed with 18F-FDG. Increased tumoral 18F-FLT uptake compared with muscle was observed in both the SSM3 mammary tumors (2.4 ± 0.17 vs. 1.6 ± 0.14 percentage injected dose [%ID]/g at 2 h after injection, P = 0.006) and the CWR22 prostate cancer xenografts (0.34 ± 0.08 vs. 0.098 ± 0.033 %ID/g at 2 h after injection, P = 0.03). However, because of higher nonspecific muscle uptake in female mice, tumor-to-muscle uptake ratios were greater for CWR22 tumors than for SSM3 tumors (4.2 ± 0.78 vs. 1.5 ± 0.049 at 2 h after injection, P = 0.008). Sex-dependent differences in 18F-FLT uptake were also observed for MDA-MB-231 xenografts (tumor-to-muscle ratio, 7.2 ± 0.9 for female vs. 16.9 ± 8.6 for male, P = 0.039). Conversely, greater tumoral Ki-67 staining was observed in female mice (71% ± 3% for female vs. 54% ± 2% for male, P = 0.009), and this finding more closely matched the relative differences in absolute 18F-FLT tumor uptake values (4.5 ± 0.99 %ID/g for female vs. 1.9 ± 0.30 %ID/g for male, P = 0.03). Conclusion: Depending on whether female or male mice are used, differences in biodistribution and nonspecific tissue uptake can adversely affect quantitative measures of 18F-FLT uptake. Thus, sex is a potential variable to consider in defining quantitative imaging metrics using 18F-FLT to assess tumor proliferation.

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Chemical mediators of migraine: preclinical and clinical observations.

Publications

Chemical mediators of migraine: preclinical and clinical observations.

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