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Transcript
Chili peppers and pain
Capsicum peppers
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Discovery
Early history
Botany
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Member of Solanaceae
Capsicum annuum
Capsicum frutescens
Capsaicin
Traditional uses
Contemporary uses of capsaicin
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Pepper spray
Pesticide
Creams for localized pain relief
Capsaicin Receptors
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Capsaicin and structurally related
molecules bind to specific vanilloid
receptors (VR1) located on the
sensitive peripheral terminals of
nociceptors
Vanilloids
Efficacy of capsaicin
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Review of 13 clinical trials - 991
patients - double blind study 480
subjects, 511 controls
Capsaicin is useful in alleviating the
pain associated with diabetic
neuropathy, osteoarthritis, and psoriasis
Studied not completely blinded
VR1 Receptors
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VR1 expressed by neurons throughout
nervous system including brain
Are there endogenous vanilloids?
Resiniferatoxin development
Ergot and migraine
Migraine Headaches
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Migraine Statistics
Cost
Symptoms
Cause
Triggers
Treatment
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Ergot alkaloids dihydroergotamine and
ergotamine frequently drugs of choice
Cause blood vessels in the body to constrict
Serious side effects
Drug mixtures
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Caffeine-ergotamine combinations
Belladonna alkaloids-ergotamine combination
Administration
Sprays
Ergot alkaloids
Vindoline
Vinblastine (Catharanthus)
Mode of action
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Alkaloids are vasoconstrictors that are
believed stimulating 5-HT1B and 5-HT1D
receptors
5-HT1B receptors are located on the vascular
smooth muscle cells, and their stimulation
causes vasoconstriction
5-HT1D receptors are located on the endings
of the primary nociceptive nerve fibers in the
peripheral and central nervous system
5-HT1D receptors
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In peripheral nervous system
nociceptive nerve endings coil around
the cranial blood vessels and are
activated when the blood vessels dilate
Stimulation of the 5-HT1D receptors
inhibits the release of chemicals that
cause pain and inflammation, such as
substance P and others
5-HT receptors
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Ergotamine and similar drugs affect
migraine two ways
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Induce vasoconstriction and inhibit
neurogenic inflammation
In the CNS, stimulation of 5-HT1D
receptors results in inhibition of pain
transmission, another mode of action that
may be involved in the abortive treatment
of migraine
Ergotamine
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Produced by the ergot (sclerotium) of
Claviceps purpurea
Fungal disease of rye and other grasses
Claviceps purpurea life cycle
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Ascospores
Conidia
Sclerotia (ergots)
Stroma with perithecia
Claviceps purpurea
Ergot of rye
Ergotism
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Ergotism
“Dancing Mania” and “St. Anthony’s Fire”
Many different toxic alkaloids --- cause many
different effects – Mycotoxins
Ergotism rare today
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Outbreak in France in 1951 - 4 deaths and 150
hospitalized
1977 in Ethiopia on contaminated barley
Salem Witches??