How It Started

Humphrey, PPA

doi:10.1046/0333102401021s0102

Cited by 19 publications

(1 citation statement)

References 9 publications

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“…The decision to work on 5‐HT receptors was accepted and excitingly evidence for a previously unidentified receptor in the vasculature emerged and was presented to the British Pharmacological Society at a meeting in Manchester in 1977 . Although the importance of this observation was not appreciated by most at the time, a team of chemists was assigned to the project at Ware and under the leadership of one of us (PPAH) finally produced a drug (the 5‐HT 1B/D receptor agonist, sumatriptan) that was marketed in 1991 and has provided profound benefit to millions of migraine sufferers right up to the present day . Although there were many difficulties and hurdles presented throughout the project life, David was always supportive providing that one could identify likely ways of circumvention that could be readily tested.…”

mentioning

confidence: 99%

Sir David Jack: an extraordinary drug discoverer and developer

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Humphrey

2013

Brit J Clinical Pharma

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mentioning

confidence: 99%

Sir David Jack: an extraordinary drug discoverer and developer

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Humphrey

2013

Brit J Clinical Pharma

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Central generators of migraine and autonomic cephalalgias as targets for personalized pain management: Translational links

Noseda

Villanueva

2023

European Journal of Pain

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Background and ObjectiveMigraine oscillates between different states in association with internal homeostatic functions and biological rhythms that become more easily dysregulated in genetically susceptible individuals. Clinical and pre‐clinical data on migraine pathophysiology support a primary role of the central nervous system (CNS) through ‘dysexcitability’ of certain brain networks, and a critical contribution of the peripheral sensory and autonomic signalling from the intracranial meningeal innervation. This review focuses on the most relevant back and forward translational studies devoted to the assessment of CNS dysfunctions involved in primary headaches and discusses the role they play in rendering the brain susceptible to headache states.Methods and ResultsWe collected a body of scientific literature from human and animal investigations that provide a compelling perspective on the anatomical and functional underpinnings of the CNS in migraine and trigeminal autonomic cephalalgias. We focus on medullary, hypothalamic and corticofugal modulation mechanisms that represent strategic neural substrates for elucidating the links between trigeminovascular maladaptive states, migraine triggering and the temporal phenotype of the disease.ConclusionIt is argued that a better understanding of homeostatic dysfunctional states appears fundamental and may benefit the development of personalized therapeutic approaches for improving clinical outcomes in primary headache disorders.SignificanceThis review focuses on the most relevant back and forward translational studies showing the crucial role of top‐down brain modulation in triggering and maintaining primary headache states and how these central dysfunctions may interact with personalized pain management strategies.

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Migraine

et al. 2009

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Migraine is a neurovascular disorder which affects one fifth of the general population. Disability due to migraine is severe and involves patients from infancy through senescence and it is aggravated by the fact there is no complete cure. However, various drugs for the symptomatic or prophylactic treatment of the disease are available. Recently, better knowledge of the neurobiological and pharmacological aspects of a subset of trigeminal primary sensory neurons has provided key information for the development of effective molecules that specifically target the activation of the trigeminovascular system and may represent a significant advancement in the treatment of the disease. These novel antagonists block the receptor for the sensory neuropeptide calcitonin gene-related peptide (CGRP), which upon release from peripheral terminals of trigeminal perivascular neurons dilates cranial arterial vessels. Whether neurogenic vasodilatation is the major contributing factor to generate the pain and the associated symptoms of the migraine attack or whether other sites of action of CGRP receptor antagonists are responsible for the antimigraine effect of these compounds is the subject of current and intense research.

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How It Started

Cited by 19 publications

References 9 publications

Sir David Jack: an extraordinary drug discoverer and developer

Sir David Jack: an extraordinary drug discoverer and developer

Central generators of migraine and autonomic cephalalgias as targets for personalized pain management: Translational links

Migraine

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