Abstract

Calcitonin gene-related peptide (CGRP) is a pivotal messenger in the inflammatory process in migraine. Limited evidence indicates that diet impacts circulating levels of CGRP, suggesting that certain elements in the diet may influence migraine outcomes. Interruption of calcium signaling, a mechanism which can trigger CGRP release, has been suggested as one potential route by which exogenous food substances may impact CGRP secretion. The objective of this study was to investigate the effects of foods and a dietary supplement on two migraine-related mechanisms in vitro: CGRP secretion from neuroendocrine CA77 cells, and calcium uptake by differentiated PC12 cells. Ginger and grape pomace extracts were selected for their anecdotal connections to reducing or promoting migraine. S-petasin was selected as a suspected active constituent of butterbur extract, the migraine prophylactic dietary supplement. Results showed a statistically significant decrease in stimulated CGRP secretion from CA77 cells following treatment with ginger (0.2 mg dry ginger equivalent/mL) and two doses of grape pomace (0.25 and 1.0 mg dry pomace equivalent/mL) extracts. Relative to vehicle control, CGRP secretion decreased by 22%, 43%, and 87%, respectively. S-petasin at 1.0 μM also decreased CGRP secretion by 24%. Meanwhile, S-petasin and ginger extract showed inhibition of calcium influx, whereas grape pomace had no effect on calcium. These results suggest that grape pomace and ginger extracts, and S-petasin may have anti-inflammatory propensity by preventing CGRP release in migraine, although potentially by different mechanisms, which future studies may elucidate further.

Highlights

  • Migraine is a complex primary headache condition that affects 17% of American women and 5.6%of men annually [1]

  • The calcitonin gene-related peptide (CGRP) secretion assay demonstrated that grape pomace extracts, ginger extract, and purified

  • The high and medium dose of purified S‐petasin could inhibit CGRP secretion in CA77 cells at various doses. The high and both grape pomace extracts produced a significant decrease in CGRP secretion by CA77 cells, upon medium dose of both grape pomace extracts produced a significant decrease in CGRP secretion by a 1 h pre-treatment with the extracts

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Summary

Introduction

Migraine is a complex primary headache condition that affects 17% of American women and 5.6%of men annually [1]. Migraine is a complex primary headache condition that affects 17% of American women and 5.6%. Migraine is responsible for half of all neurological disease-induced disability [2]. Suggestions abound regarding the potential connection between food and migraine, but valid scientific evidence on the subject remains limited. The current pathophysiological understanding of migraine entails over-sensitization of the brain, which produces a painful response to otherwise normal stimuli, in combination with an inflammatory response. A key inflammatory mediator in neurogenic inflammation of migraine is calcitonin gene-related peptide (CGRP). The connections of CGRP to migraine are numerous. Fibers originating in the trigeminal ganglion terminate in the dura where they release CGRP, and this connection is thought to be central to the genesis of migraine pain [3].

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