Transcript pain-3 - Thblack.com

Chili peppers and pain
Capsicum peppers
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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
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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
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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
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sweet bell peppers ---> hot peppers
Capsicum frutescens mainly in the tropics more fiery taste such as tabasco pepper
Capsaicin
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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
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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
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Utilized as a pepper spray
Used in creams for localized pain relief
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Application 2 to 4 times/day for 2 to 4
weeks will provide pain relief
Continuous application needed
Use of capsaicin creams & gels
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Capsaicin-containing topical creams and
ointments are available as over-thecounter 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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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
Ergot and migraine
Migraine Headaches
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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
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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
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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 telltale signs that include visual
disturbances (aura)
Cause of migraines
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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
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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?
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Lack of food or sleep
Exposure to light
Hormonal irregularities in women
Anxiety, stress or relaxation after stress,
and fatigue also triggers
Treatment
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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
Ergot alkaloids
Vindoline
Vinblastine (Catharanthus)
Ergotamine and Dihydroergotamine
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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
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The caffeine present in many ergotaminecontaining 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
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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
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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 - 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
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Produced by the ergot (sclerotium) of
Claviceps purpurea
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Fungal disease of rye and other grasses
Claviceps purpurea
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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
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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
Claviceps purpurea
Ergot of rye
Ergotism
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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
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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
Alkaloids in ergot
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With modern milling techniques, ergotism
rare
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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