Algesia, from the Greek word algesis, is the sensitivity to pain.

The term is sometimes

used to refer to hyperalgesia (an extreme sensitivity).

Analgesics, most commonly known as painkillers, are used to reduce the feeling of pain

Two of the most commonly used terms in the pain research and medicine world are
hyperalgesia and allodynia. The word hyperalgesia means an increased response to a
painful stimulus. The word allodynia means a painful response to a normally innocuous
stimulus.

Here is an example of hyperalgesia: if your arm was pricked by a pin and you said that it
gave you 3 out of 10 pain this would be your baseline response. If an experimenter then
gave you some injection (let’s say capsaicin — the pungent ingredient in hot peppers)
and then 30 minutes later pricked you with the pin again and you reported 6 out of 10
pain this would be hyperalgesia. For hyperalgesia to occur it is important for the stimulus
to be painful to begin with. Remember that hyperalgesia is always an increased pain
response to a noxious stimulus.

Here is an example of allodynia: if an experimenter brushed your arm with a cotton bud
(like a q-tip) you would almost certainly say that the stimulus was not painful — 0 out of
10. If the experimenter then injected your arm with capsaicin and brushed your arm again
30 minutes later you would likely report that it was painful — let’s say 4 out of 10 pain.
This is an allodynia, a painful response to an innocuous stimulus. In order for allodynia to
occur the stimulus MUST NOT normally be painful.

So now that we know what these word mean it is time to understand why they occur.
First of all, there are a variety of pain conditions where one of these conditions is present
but not the other. This is because they are mechanistically different. Sensory neurons that
innervate your skin and visceral organs roughly fall into three categories: 1) Rapidly
adapting mechanotransducers. These are neurons that respond to touch and non-noxious
temperatures, they conduct action potentials (or nerve impulses) rapidly and they make a
subset of nerve fibers called A-beta fibers. 2) Proprioceptive neurons. These are neurons
that tell you about the position of your muscles, they also conduct action potentials
rapidly and they comprise the other subset of nerve fibers called A-beta fibers. 3)
Nociceptors. These are pain sensing neurons that respond to painful mechanical or
thermal stimulation. They also comprise the class of neurons that respond to chemical
irritants (like capsaicin). They are lightly or unmyelinated so they conduct action
potentials more slowly than A-beta fibers. They also generally fail to adapt to stimulation
so they keep firing until the stimulus is removed or escaped from. These neurons fall into
two classes, A-delta (the lightly myelinated ones) or C-fibers (the unmyelinated ones).
Neurons of all of these classes send a projection into the dorsal horn of the spinal cord
where processing of incoming sensory information first occurs (all you neuroscientists
forget about A-betas and the dorsal funiculus, they send a projection to lamina III as well
where they synapse on interneurons that send projections back into lamina I/II). This
processing center in the dorsal horn of the spinal cord is commonly referred to as “the
gate” — a term that was spawned from Melzack and Wall’s famous gate theory of pain
control. These signals are then sent onto the brain where sensory perception occurs.

The physiological basis of hyperalgesia and allodynia lies in the distinction between the
type of fibers that carry the information evoked by the stimulus in the periphery.

HYPERALGESIA:
Remember that hyperalgesia always involves a noxious stimulus, it just becomes more
painful when hyperalgesia is present. The noxious stimulus activates nociceptors in the
periphery that then send the signal onto the spinal cord. Hyperalgesia involves an
amplification of the pain signal. This amplification can occur in the periphery (e.g. the
nociceptor is sensitized by an irritant, by inflammation or by disease) or in the spinal cord
(via an amplification of synaptic transmission between the nociceptor and the dorsal horn
neuron that sends the signal to the brain) or in both locations. There are some cases where
the amplification is thought to occur in higher brain centers as well. This can happen, for
instance, after a stroke. We will talk more about mechanisms of amplification and there
promise for therapy in a later post.

ALLODYNIA:
Allodynia involves a noxious response to an innocuous stimulus (think putting on a shirt
with a severe sunburn). Because the stimulus is innocuous, and generally of the
mechanical variety, it could be carried by rapidly adapting mechanotransducers or by
sensitized nociceptors. These two possibilities have been the focus of decades of research
both in humans and in animals. While there is evidence that the information can be
carried by sensitized nociceptors this is quite controversial. Our current understanding of
allodynia suggests that nociceptor mechanical thresholds do not change enough for them
to carry information concerning light touch, brush or gentle vibration in conditions where
allodynia is present. Rather, it appears that rapidly adapting mechanotransducers (or A-
beta fibers) continue to be the sole carrier of this information in conditions where
allodynia is present. The change that causes allodynia occurs in the spinal cord. Through
an unknown process, A-beta-fibers gain access to the nociceptive channel. In normal
conditions A-beta-fibers cannot activate dorsal horn neurons that respond only to painful
stimulation. In allodynic conditons, these same neurons begin to receive input from A-
beta-fibers. This allows for A-beta-mediated information to gain access to the nociceptive
channel thereby stimulating the perception of pain in the brain. Because allodynia can
occur rapidly it is unlikely that this change is mediated by a physical change in the
connections of neurons in the dorsal horn (although this may occur over the longer term).
Rather, it appears that there are changes in the neurochemistry of the “gate” such that
inhibitory neurotransmission can switch to excitation. Because GABA (the primary
inhibitory neurotransmitter in the brain) can switch from inhibition to excitation (or vice-
a-versa) in certain conditions (like epilepsy and during early neural development) much
current focus is on the role of GABA in allodynia.

In chronic pain conditions both allodynia and hyperalgesia are major problems for these
patients. Small movements, putting on or wearing clothes and even sitting or laying down
can become very painful due to allodynia. Patients are often able to avoid hyperalgesia
but hyperalgesia can be so intense that it causes an aversion to even the most mundane of
activities for fear of triggering an attack. In the chronic pain patient both of these
conditions are extremely difficult to treat. Allodynia is notoriously resistant to opiate and
NSAID analgesics especially in conditions involving a peripheral neuropathy caused by
injury or disease (like diabetes).

To wrap up:
Hyperalgesia is an increased response to a noxious stimulus. It is caused by sensitization
of peripheral nociceptors and/or by sensitization of central neurons that carry nociceptive
information.
Allodynia is a painful response to a non-painful stimuli. It is caused by a change in the
dorsal horn of the spinal cord that gives non-noxious sensory information access to the
nociceptive system causing innocuous stimuli to be perceived as painful.

Halaman 325

Halaman 325 selectively preserved are often associated with a qualitative

change in pain by which its disagreeable character is heightened-the
phenomenon of hyperapatia