Chili peppers and pain

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Chili peppers and pain
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Capsicum peppers

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

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Contemporary uses of capsaicin

• Pepper spray
• Pesticide
• Creams for localized pain relief
• Application 2 to 4 times/day for 2 to 4 weeks
  will provide pain relief
• Continuous application needed
• Joint and muscle pains
• Pain from shingles (post herpes zoster)

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Capsaicin Receptors

• Capsaicin causes burning when ingested or when
  applied to skin
• Recent study located capsaicin receptor on
  neurons
• Capsaicin and structurally related molecules bind
  to specific vanilloid receptors (VR1) located on
  the sensitive peripheral terminals of nociceptors
• Receptor activation triggers Ca influx into the
  neurons and firing of action potentials
• Apparently releasing Substance P

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Vanilloids
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Mode of action of topical capsaicin

• Suggestion that capsaicin causes sensory nerve
  fibers to deplete substance P, and prevents them
  from renewing their diminished supply
• With fewer neurotransmitters available, neurons
  are unable to transmit pain signals effectively,
  and the individual feels less pain

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Other ideas

• Repeated or lengthy application inactivates the
  receptive terminals of nociceptors and they
  degenerate
• Also may desensitizing nerves to VR1 signal
• As a result capsaicin useful in cases in which
  the pain is maintained by anatomically intact
  sensitized primary nociceptors

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Efficacy of capsaicin

• Review of 13 clinical trials - 991 patients -
  double blind study 480 subjects, 511 controls
• Topically applied capsaicin is useful in
  alleviating the pain associated with diabetic
  neuropathy, osteoarthritis, and psoriasis
• Studied not completely blinded

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Disadvantages of capsaicin

• In the first days of its application, it commonly
  produces intolerable burning, so that many
  patients discontinue their use
• In many patients pain relief is unsatisfactory
• Not a permanent cure
• Concentration of capsaicin in commercially
  available preparations may be too low
• Anecdotal evidence that application of capsaicin
  (5) can produce lengthy pain relief in some
  patients with neuropathic pain

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VR1 Receptors

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

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Ergot and migraine
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Migraine Headaches

• Migraine Statistics
• Cost
• Symptoms
• Cause
• Triggers

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Treatment

• Several different treatments but ergot alkaloids
  dihydroergotamine and ergotamine frequently drugs
  of choice
• Used to treat severe, throbbing headaches, such
  as migraine and cluster headaches
• Will not relieve any kind of pain other than
  throbbing headaches

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Ergot alkaloids
Vindoline Vinblastine (Catharanthus)
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Ergotamine and Dihydroergotamine

• Cause blood vessels in the body to constrict
• Can lead to serious side effects that are caused
  by a decrease in the flow of blood to many parts
  of the body
• Because of this, they are usually used for
  patients whose headaches are not relieved by
  acetaminophen, aspirin, or other pain relievers

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Treatment

• Drug mixtures
• Caffeine-ergotamine combinations
• Belladonna alkaloids-ergotamine combination
• Administration
• Sprays

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Mode of action

• 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

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5-HT1D 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-HT1D receptors inhibits the
  release of chemicals that cause pain and
  inflammation, such as substance P and others

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5-HT receptors

• Ergotamine and similar drugs affect migraine two
  ways - they induce vasoconstriction and inhibit
  neurogenic inflammation
• In addition 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

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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

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Claviceps purpurea Ergot of rye
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Ergotism

• Ergot contains a number of toxic alkaloids, if
  harvested with the grain and milled into the
  flower - it can cause a disease called ergotism
• During Middle Ages called Dancing Mania and
  St. Anthonys Fire
• Ergotism can also occur in grazing animals that
  forage on contaminated grain
• Many different toxic alkaloids --- cause many
  different effects - Mycotoxins

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Alkaloids in ergot

• With modern milling techniques, ergotism rare
• Outbreak in France in 1951 - 4 deaths and 150
  hospitalized
• 1977 in Ethiopia on contaminated barley
• Salem Witches may have been ergotism
• Many alkaloids present - several others besides
  ergotamine