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Nancy
Johnson, a Philadelphia housewife, received a
patent
for the hand crank ice cream freezer in 1843. She sold
the
patent for 200 dollars because she couldn’t afford
the
manufacturing cost. She received the patent on Sept. 9,
which makes me think the idea sprung from a 4th of July
problem of
ice availability. It took her two months or so to
solve the
problem.
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But all is not happiness and light in ice cream land ---
ever had “brain freeze?” The typical ice cream headache is sensed as a pain in
your head. Pain sensing neurons are
located throughout your body, except
for your brain – so……..
Question of the Day: If
your brain doesn’t have pain receptors, why does brain freeze hurt?
Nociception (from
Latin noxa = pain) is the input of
stimuli from the environment that will be sensed as pain, but how can ice cream
be a noxious stimulus? Not much research has been done in this area, especially
given the number of names for the phenomenon – brain freeze, ice cream
headache, cold stimulus headache, even sphenopalatine ganglion cephalgia (ceph = head, and algia = pain).
The incidence of cold-stimulus headache has only been looked
at in three populations. Some Danes (15%) and Taiwanese teenagers (41%) have ice
cream headaches, but a more complete 2012 study has been published from Brazil. These
researchers indicate that 37% of over 400 people did experience cold headache,
with migraine sufferers more susceptible (50%). Apparently, cold weather people
don’t experience ice cream headache as much, maybe because they eat less ice
cream.
Let me describe the typical ice cream headache for those of
you who haven’t had the pleasure. The pain, usually in the forehead (60%) or
sides of head (48%), begins just a few seconds after a big mouthful of ice cream, typically lasts about
20-60 seconds, and then subsides over a short period of time. The faster the
cold is applied, ie. the faster you gobble down your dessert, the more likely
the headache. This is an important point, as we will see later.
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Neurons
that sense thermal stimuli, both hot and cold, have
receptors
on the sensory endings. Nociceptors for pain the
shallow
skin do not have receptors, they are merely free
nerve
endings. The mechanical nociceptors respond to
deformation
pressure, but also to incision wounds. Chemical
nociceptors
responds through TRP channels, much like for hot.
This is why capsaicin pepper spray hurts, it is like being burned. |
Specific channels found only in nociceptive nerve endings
allow for the flow of sodium ions to start en electrical impulse. There are
different versions of the Na+ channel that respond to cold, the more active Nav1.7
and the much less active Nav1.8. It wasn’t until 2007 that scientists even found a reason for the 1.8 receptor.
There is a desensitization of neural endings as they fire
over and over. It is harder for the neurons to keep rebuilding their electrical
potential after repeated impulses; like when you stop feeling your backside
against the chair after you’ve been sitting for a while.
The researchers found that if the 1.7 receptors keep
receiving a cold input, they stop firing and you will not be aware of the
continued cold. But this is where the 1.8 receptors come in. Nav1.8’s
are harder to stimulate, but they will react to the continued signal even when the
1.7 receptors have been desensitized. This is why you feel the intense cold as
pain.
The scientists in the 2007 study were able to inactivate the
1.8 channels in mice. They then desensitized the 1.7 receptors with a cold
stimulus and the mice would run around on dry ice without feeling any pain at
all. They would stay there until they froze solid if the researchers didn’t
pick them up.
The desensitization of the normal receptors is what is
behind cold analgesia (a = without, algen = to feel pain). On the other hand, the Nav1.8
receptors are responsible for cold hyperalgesia
(hyper = more or beyond). So, is this
why the ice cream hurts your head?
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Hyperalgesia
is an amplified pain response. Things that should
hurt
a little end up hurting a lot. The chart shows that sensitivity
to
pain is not changed, it takes the same amount of stimulus to
cause
pain. Neither is the maximum amount of pain felt changed.
The
hyperalgesia is in the middle, a stimulus causes more pain
than
it should. In a weird twist, long-term use of painkillers
(opioids) can actually result in hyperalgesia – too bad for addicts. |
First is the vascular
theory of headache, related to the body’s desire to retain heat. A loss of
heat is potentially dangerous, especially in the brain. When cold food is
passed over the palate (the roof of the mouth), the cold stimulus is passed
through the bones of the palate and to the blood vessels that enter the brain
from the sinuses.
The brain doesn’t want to allow this cold stimulus to cool
the blood going to the brain, so the nerve (trigeminal nerve, cranial nerve V)
for much of the head and neck will cause the vessels to constrict. Problem
solved, right? No, the brain also needs oxygen, so vasoconstriction isn’t the
best idea. Constriction means less blood; less blood means less oxygen.
Therefore, the nerve causes the vessels to undergo a rebound vasodilation,
also called the trigeminoparasympathetic
reflex. This is similar to when the blood vessels of the face and other
skin are exposed to cold, and then your skin appears reddened from the
vasodilation. Of course, the reddened skin (dilation of skin capillaries)
doesn’t hurt until the Nav1.7 cold receptors start to desensitize
and the Nav1.8 receptors kick in. In the case of ice cream on your
palate, the faster you stuff it in your mouth, the larger the constriction, and
the larger the rebound vasodilation.
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The
trigeminal nerve is divided into three divisions, the
ophthalmic
nerve (V1), the maxillary nerve (V2), and the
mandibular
nerve (V3). V1 and V2 carry only sensory
(afferent)
information, but V3 carries both sensory and
motor
signals. The entire nerve is above the level of the
spinal
column, so it is called a cranial nerve (there are 10).
The
pain signals from the palatal region or most often
referred to the ophthalmic region. |
Arguing against this theory is the fact that things other
than ice cream can stimulate an ice cream headache. Some folks get the same
headache when they have a cold breeze pass across their head, or when they
scuba dive. In these cases, we need a different reason for the pain in the
forehead.
A second hypothesis is available and has to do with
something called referred pain.
Heart attacks are famous for referred pain. It is common during myocardial
infarction (heart attack) to have pain in the left arm or the jaw or neck. Sometimes this is
the only pain that is felt, while in other heart attacks there is no referred
pain at all.
Referred pain occurs when there is a noxious stimulus in a
deep tissue, from a place that there is normally little pain stimulation.
There are fewer nociceptive receptors in organs and vessels as compared to
the skin and other shallow structures that get hurt more often. In referred pain, the discomfort is sensed in some
other location, not where the stimulation occurred.
How does this error in localization happen? The brain sends
nerves out to the body (efferent
neurons), and there are also nerves that carry information from the peripheral
body to the brain (afferent
neurons). In the majority of cases, these afferent and efferent signals travel
a distance in the spinal column and then exit to the brain on one end and to
the peripheral body on the other.
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On
the left is a close up cartoon showing spinal nerves leaving the
vertebral
column. At each level, a spinal nerve leaves the column on
each side. A cartilage disc separates
each of the vertebrae and
ensures
that there is sufficient space for the spinal nerve to exit the
column
without being impinged. When the cartilage degrades, you
can
end up with a herniated disc and a pinched nerve. On the right,
you
see that spinal nerves leave the column at all levels, from the neck
to
the sacrum. Those that exit together at the coccygeal end are called
the cauda equina (horse’s tail). |
The brain isn’t used to having a pain stimulus come from a
vessel or an organ, so it sometimes gets confused, and tries to sort "present"
information in the context of "past" experience. The sensory information gets
switched as to its apparent source. Therefore, the brain may assign the pain to
superficial area innervated by the afferent neurons that enter the spinal
column at that same level.
In a heart attack, afferent neurons that would sense damage
to be interpreted as pain enter the spinal column at T1-T4 levels (from between
the first and fourth thoracic vertebrae). These also happen to be the levels
that collect sensory information from the left arm, left side of chest, neck,
parts of the jaw, and the upper back. When the signals are confused by the
brain, the signals interpreted as pain are assigned to one or more of the areas
with common spinal level innervation. Hence, your heart attack may hurt in your
left arm, jaw, neck, chest, or back.
For a cold stimulus headache, the idea is the same, but the
anatomy is just a little different. Nerves that innervate the head don’t
necessarily enter or leave the spinal column. They sense things and send
signals to areas above the level where the spinal cord begins. The trigeminal nerve
(cranial nerve V) carries afferents from all the cranial vessels but also from
parts of the face and forehead and sends efferents to the head and face.
 |
The
marine plankton organism Gambierdiscus
toxicus
(150
µm dia.) lives in saltwater and is the food item
for
several species of marine organism. It produces
several
different types of ciguatera toxins, which can
work
their way up the food chain as bigger
things
eat littler things. When we eat the fish that is
contaminated
with the toxin, we have a trip much like on LSD.
The
toxins can also produce a severe cold allodynia in the
mouth
and all over the body.
|
The theory says that when the nociceptive receptors are triggered because of the cold stimulus on the palate, either directly or via the rebound dilation of the cranial blood vessels, the pain is wrongly assigned by the brain as coming from the forehead. Your ice cream headache is a mistake your body makes. Just be glad you don’t have cold allodynia (allo = other, and dynia = pain), a condition where any cool or cold sensation is sensed as pain. A 2011 dental study indicates that cold allodynia is not only in response to subtle stimuli, but the pain also lasts much longer than in the control population.
Worse would be a cold allodynia induced by fish. Seem
impossible? Well several kinds of fish can carry ciguatoxins, which can induce hallucinations (ichythosarcotoxism) and a potent cold allodynia. I worry for many
of the judges on Iron Chef America when a chef decides to make fish ice cream. Now
that I know about a “hallucinogenic fish toxin-induced pain from anything cool”
– well, I’ll have to pass on the fish ice cream.
Being considering the animals you think are the toughest. Next week I will give you my contender, an animal you've probably never heard of.
Being considering the animals you think are the toughest. Next week I will give you my contender, an animal you've probably never heard of.
