Chili peppers and pain Capsicum peppers n n

Chili peppers and pain

Capsicum peppers n n n Discovery Early history Botany n n n Member of Solanaceae Capsicum annuum Capsicum frutescens Capsaicin Traditional uses

Contemporary uses of capsaicin n Pepper spray Pesticide Creams for localized pain relief

Capsaicin Receptors n Capsaicin and structurally related molecules bind to specific vanilloid receptors (VR 1) located on the sensitive peripheral terminals of nociceptors

Vanilloids

Efficacy of capsaicin n 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

VR 1 Receptors n n n VR 1 expressed by neurons throughout nervous system including brain Are there endogenous vanilloids? Resiniferatoxin development

Ergot and migraine

Migraine Headaches n n n Migraine Statistics Cost Symptoms Cause Triggers

Treatment n n Ergot alkaloids dihydroergotamine and ergotamine frequently drugs of choice Cause blood vessels in the body to constrict Serious side effects Drug mixtures n n Caffeine-ergotamine combinations Belladonna alkaloids-ergotamine combination Administration Sprays

Ergot alkaloids Vindoline Vinblastine (Catharanthus)

Mode of action n Alkaloids are vasoconstrictors that are believed stimulating 5 -HT 1 B and 5 -HT 1 D receptors 5 -HT 1 B receptors are located on the vascular smooth muscle cells, and their stimulation causes vasoconstriction 5 -HT 1 D receptors are located on the endings of the primary nociceptive nerve fibers in the peripheral and central nervous system

5 -HT 1 D receptors n n 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 -HT 1 D receptors inhibits the release of chemicals that cause pain and inflammation, such as substance P and others

5 -HT receptors n Ergotamine and similar drugs affect migraine two ways n n Induce vasoconstriction and inhibit neurogenic inflammation In the CNS, stimulation of 5 -HT 1 D receptors results in inhibition of pain transmission, another mode of action that may be involved in the abortive treatment of migraine

Ergotamine n n n Produced by the ergot (sclerotium) of Claviceps purpurea Fungal disease of rye and other grasses Claviceps purpurea life cycle n n Ascospores Conidia Sclerotia (ergots) Stroma with perithecia

Claviceps purpurea Ergot of rye

Ergotism n n Ergotism “Dancing Mania” and “St. Anthony’s Fire” Many different toxic alkaloids --- cause many different effects – Mycotoxins Ergotism rare today n n n Outbreak in France in 1951 - 4 deaths and 150 hospitalized 1977 in Ethiopia on contaminated barley Salem Witches? ?