| The Anatomy of Pain
Pain has always been a mystery, but to try to
understand it, even at a superficial level, requires
some familiarity with the organs and structures in
our bodies that are involved. The principle ones
are:
-
the sensory receptors in the skin and internal
organs
- the nerve fibres that run to and from the spinal
cord
- the structure of the spinal cord itself
- the brain.
For thousands of years, people had no concept of
nerves or a nervous system and had little
understanding of what the brain did. In fact, it was
not until the middle of the seventeenth century that
the French
philosopher and
mathematician,
René Descartes,
suggested that
organs in the skin
were connected ‘by
threads’ to the brain,
and that it was the
brain that interpreted the
signals and generated the
sensation of pain.
Descarte’s brilliant insight
has been confirmed and extended by modern science, so that today we
locate the interface between body and mind and
between sensation and perception in particular
areas within the brain. Pain becomes the
interpretation in the cerebral cortex of signals that
reach it from the site of stimulation of free nerve
endings, through nerves that run into the spinal
cord and then up to the brain – an exact parallel
with the interpretation by the brain of messages
from the eye as visual images. Of course, we do
not ‘feel’ pain in the brain, but at the site at which
the stimulation has occurred – if you stub your toe,
it is not your brain that hurts!
Sensory receptors and their function: Pain
is just one way that the body interacts with its
surroundings and interprets the information it
receives. Other similar interactions mediated
through our senses are sight, hearing, taste, smell,
and touch. The structures involved in these senses
are sometimes clearly concentrated in organs such
as the eye, ear, tongue and nose.
The sense of touch is less obvious, as there is no
visible organ: rather, it is spread all over the body.
Touch structures are there of course, in the form of
special nerves called sensory neurons which have
millions of microscopic nerve endings (corpuscles)
in the skin and internal organs.
The corpuscles are of several different types and
each has a different function specialising in
pressure, deep and light touch, vibration,
temperature, and stretch. These minute organs pick
up contacts with the outside world and feed
information back to the brain which, in turn,
generates an internal picture of a person’s shape
and status and the individual can feel external
stimulation such as a stone in the shoe, or even a
fly crawling on the hairs of the arm.
In addition to the nerves ending in corpuscles,
there are millions of nerves that have so-called
free nerve endings or nociceptors. These are
involved specifically in the sensation of pain.
Several organs do not have pain receptors as
such. For example, the brain lacks them
altogether; headaches arise in the membranes (meninges) covering it, while pains in the intestinal
tract are generated by distended stretch receptors.
Nerve fibres: The sensory receptors and
nociceptors are connected to the spinal cord by
sensory nerves. Most of these originate from
clusters of cells called ganglia that lie close to the
spinal column – there is one set of ganglia for each
spinal vertebra. These nerves can be over a metre
long, for example, those running from the toes to
the spine, or just a few centimetres. The skin is
especially well supplied with sensory nerves, but
not all are the same. On close examination they
are found to be of three main kinds, called Aß
(A-delta), Aß (A-beta), and C. The Aß fibres are
wrapped in a sheath of a fatty material called
myelin – somewhat like the insulation on an electric
wire – and are sensitive to gentle pressure. The Aß
fibres are thinner and are sensitive to heavy pressure and temperature, while the C-fibres
are very thin, lack the myelin coat and are
sensitive to pressure, chemicals and temperature.
The A-fibres conduct at great speed. Once an
event is detected at their tips, the message travels
to the spinal cord at a rate of from three to about
100 metres per second. The C-fibres are slow and
conduct their messages by absorbing chemicals
from the tissue and transporting them back to the
ganglia – a process that may take hours or even
days for the longer nerves.
The spinal cord and ganglia: The spinal cord
is a cylinder of nervous tissue composed of
millions of individual nerves, running inside the
length of the spine and entering the brain at the
base of the skull, where it becomes the brain stem.
Nerves enter the cord and leave it through holes in
each vertebra. In many ways, the cord can be
regarded as a junction box where incoming nerves
make connections (synapses) with many other
nerves which pass up to the brain or out into the
body. In cross section, the spinal cord is roughly
circular with bundles of nerves grouped towards
the outer margin ascending to the brain. Inside
these are bundles of descending nerves bringing
data back down from the brain. In this central region, many small interconnecting nerves
(interneurons) are to be found. Here, sensory
information is collected, analysed and passed
either to the brain or to the motor nerves emerging
from the ventral root. The junctions in the cord
have become an important area for pain research
in recent years, because it is here that many of the
physical changes and functional errors occur in
chronic and neuropathic pain.
The brain stem and brain: The spinal cord
enters the brain through a hole in the base of the
skull. It immediately merges with the medulla and
then enlarges to form the pons. Next to the pons is
the cerebellum. Above this point, the brain stem
forms the mid-brain which terminates in two
structures called the thalamus and the
hypothalamus. The latter is concerned with many
of the automatic functions of the body such as
temperature regulation, hormone release, and so
on. The thalamus passes pain signals to other parts
of the brain, including the limbic system, where
behavioural and emotional reactions are
generated. Wrapped around all these structures is
the large cerebral cortex, where most of the higher
processes, such as thinking, logic and reasoning
go on.
Many of these brain structures are involved in pain
response, and generate messages which are
passed down descending nerve fibres to the spinal
ganglion, where they can modulate the incoming
pain signals; the nature of these will be described
in a later section. If this fails, then pain will be
perpetuated. It is also important to recognise that if
acute pain goes untreated or persists it has the
capacity to evolve into a chronic state which may
be accompanied by changes in the structure and
operation of the nervous system, especially in the
spinal cord.
The wide range of medicines that are used in pain
management act at a variety of sites in these
systems. Some act in the peripheral tissues at the
site of damage. Others act in the spinal cord,
while yet others act in the brain. How and where
they act, how they modify nerve impulses, and
what targets these various sites offer for new
medicines development will be described in a later
section.
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