chili peppers and pain. capsicum peppers discovered by columbus and introduced to spain capsicum...
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Capsicum peppers Discovered by
Columbus and introduced to Spain
Capsicum fruits as pungent as the Oriental black pepper
He believed that his voyage west in search of spices had been justified
Early history of Capsicum peppers
Cultivated for thousands of years in tropical America
Exact time of domestication not known Fragments of a 9000 year old chili
pepper were discovered in a Mexican cave
After their introduction to Spain, spread throughout Europe, Asia, and Africa
Botany Fruits of genus Capsicum, several cultivated
species and hundreds of varieties Member of Solanaceae (nightshade family) Fruits are berries - immature fruits green and
mature fruits vary from yellow to purple to red, from long narrow to spherical Capsicum annuum most widely cultivated
sweet bell peppers ---> hot peppers Capsicum frutescens mainly in the tropics -
more fiery taste such as tabasco pepper
Capsaicin Biting taste due to the alkaloid capsaicin Found in the seeds and placental area Capsaicin content is negligible in the
sweet bell peppers and high concentrations in hot chili, jalapeno, or habanero peppers
Capsaicin can be tasted in concentrations as low as one part per million
Traditional medical uses In Andean cultures, chili peppers were
used against severe headaches and strokes
Aztecs, Mayans, and Incas used chili peppers to suppress the desire for alcohol, to treat poor memory, and to serve as an aphrodisiac
Ground chili peppers, added to milk, were applied externally to reduce swellings
Contemporary uses of capsaicin Utilized as a pepper spray Used in creams for localized pain
relief Application 2 to 4 times/day for 2 to 4
weeks will provide pain relief Continuous application needed
Use of capsaicin creams & gels Capsaicin-containing topical creams
and ointments are available as over-the-counter products to ease joint and muscle pains
Also for relieving pain from shingles -post-herpes zoster condition (caused by reactivation in adults of the chicken pox virus experienced in childhood)
Capsaicin Receptors
Capsaicin causes burning when ingested or when applied to skin
Recent study located capsaicin receptor on neurons
Same receptor that senses heat but not all types of pain
Receptors 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
Substance P Main neurotransmitter for relaying pain
signals to the brain Also implicated in a number of diseases
including arthritis, psoriasis, and inflammatory bowel disease
When eating chili peppers capsaicin produces the sensation of heat caused by the irritation of the trigeminal cells that release substance P
Topical capsaicin Capsaicin, applied to the skin, can
disrupt this process 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
Other ideas Repeated or lengthy application
inactivates the receptive terminals of nociceptors, and they may degenerate
Also may desensitizing nerves to the VR1 signal
As a result capsaicin itself can be used as an analgesic in cases in which the pain is maintained by anatomically intact sensitized primary nociceptors
Not permanent cure
Process is reversible. After capsaicin-containing cream
or ointment is no longer applied topically, more substance P may be produced
Pain may return
VR1 Receptors The work is among the first to identify a
molecular basis for a pain response By blocking VR1, researchers might be
able to find more effective treatments for chronic pain due to arthritis, spinal cord injury or nerve damage caused by diabetes
Find better ways was to block VR1 receptors
Efficacy of capsaicin Review of 13 clinical trials - 991
patients - dble 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
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 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
VR1 Receptors VR1 expressed by neurons
throughout nervous system Endogenous compounds must bind
there - vanilloids VR1 also in the brain Endogenous vanilloids have been
suggested to be involved in control of emotions and learning
VR1 in brain The recent finding of vanilloid
receptors in several brain areas suggests that other therapeutic uses may eventually appear
However, the wide distribution of these receptors also suggests that these drugs might cause a broad range of side-effects
Migraine Headaches Migraine headaches affect 28
million Americans, 75 % of whom are women
Migraines can cause significant disability
Costs about $13 billion in missed work or reduced productivity annually in US
Migraines Migraines usually begin between
the ages of 5 and 35 Peak prevalence is between the
ages of 35 and 45 Some people can get as many as
10 migraines a month, but the average is around 1.5 per month
Migraine symptoms Include pain, extreme sensitivity to
light and sound, nausea and vomiting The pain is an intense pulsing or
throbbing pain usually on one side of the head - during 4 to 72 hrs
Some individuals (15% to 20%) can predict the onset of a migraine with tell-tale signs that include visual disturbances (aura)
Cause of migraines For many years, scientists believed that
migraines were linked to the dilation and constriction of blood vessels in the head
Now believe that cause is inherited abnormalities in certain cells in the migraine pain center located in the brainstem
As neurons fire, surrounding blood vessels dilate and become inflamed, causing the characteristic pain of a migraine
Other ideas Recent study found that the meninges,
(membranes surrounding the brain) are inflamed during a migraine attack
Some believe this is the source of migraine pain although they acknowledge that blood flow changes do occur
Exactly how this inflammation occurs is unknown
What triggers migraine? Lack of food or sleep Exposure to light Hormonal irregularities in women Anxiety, stress or relaxation after
stress, and fatigue also triggers
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
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
Drugs are often mixtures The caffeine present in many ergotamine-
containing combinations helps ergotamine work better and faster by causing more of it to be quickly absorbed into the body
Belladonna alkaloids in some combinations help to relieve nausea and vomiting, which often occur together with the headaches and also help the patient relax and even sleep
Administration Migraine drugs often taken on a
regular basis to prevent attacks Other sufferers only take
medication during attack New nasal ergotamine sprays allow
for quicker absorption
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
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
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
Ergotamine Produced by the ergot (sclerotium)
of Claviceps purpurea Fungal disease of rye and other
grasses
Claviceps purpurea Cause of ergot or rye Ascospores are produced in the spring at
about the same time rye is flowering Ascospores land on flower, invades the
ovary and destroys it - produces conidia in a sticky, sweet material that attracts insects - spread spores to other flowers
As season progresses, mycelium in ovary develops into a hard, dark structure called an ergot (technically it is a sclerotium - hardened fungal tissue)
Ergot Overwinters Ergot replaces the grain - it may be
harvested along with the grain or it may fall to the ground and overwinter
In the spring, the ergot produces several stroma each containing perithecia
Ascospores are long and thin and start the infection cycle all over when they are released from the perithecia
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. Anthony’s Fire”
Ergotism can also occur in grazing animals that forage on contaminated grain
Many different alkaloids --- cause many different effects
Alkaloids in Ergot Some of the ergots constrict blood vessels
and impair circulation - in extreme conditions can result in gangrene - limbs may drop off or require amputation
Other toxins affect the CNS resulting in hallucinations and convulsions - loss of mental function
Feelings of burning in calves or intense cold