1. Chili peppers and pain

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

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

5. Capsaicin Receptors Capsaicin and structurally related molecules bind to specific vanilloid receptors (VR1) located on the sensitive peripheral terminals of nociceptors

6. Vanilloids

7. Efficacy of capsaicin 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

8. VR1 Receptors VR1 expressed by neurons throughout nervous system including brain Are there endogenous vanilloids? Resiniferatoxin development

9. Ergot and migraine

10. Migraine Headaches Migraine Statistics Cost Symptoms Cause Triggers

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

12. Ergot alkaloids Vindoline Vinblastine (Catharanthus)

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

14. 5-HT 1D receptors 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 1D receptors inhibits the release of chemicals that cause pain and inflammation, such as substance P and others

15. 5-HT receptors Ergotamine and similar drugs affect migraine two ways Induce vasoconstriction and inhibit neurogenic inflammation In the CNS, stimulation of 5-HT 1D receptors results in inhibition of pain transmission, another mode of action that may be involved in the abortive treatment of migraine

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

17. Claviceps purpurea Ergot of rye

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