Compare the peripheral and central mechanisms

involved in the perception of pain and touch. How

can they be modified?
For both pain and touch, the sensory receptor (of the peripheral nervous system), is a
dorsal root ganglion cell. The sensation of touch involves a number of skin receptors,
each responding to slightly different stimuli. For example, there are the Meissner’s
corpuscles, responding to shear (as occasioned by motion), the Merkel’s discs
responding to (light) contact, the Pacinian corpuscles responding to deep pressure and
the Ruffini endings responding to stretch. These send information to the central
nervous system by various pathways, but the main one is the lemniscal system. The
brain, in particular the cerebral cortex (most importantly the primary somatic sensory
cortex, S-I) is responsible for putting this information together. This allows us to form
judgements about what we are touching, for example providing the feedback for the
fine motor control required to play the piano, or to enable us to establish the shape of
an object that we might be touching, even if it is much bigger than any of the
individual receptive fields of the receptor cells, termed “stereognosis”. For pain, the
stimuli and receptors are more difficult to characterise. The receptors are termed
“nociceptors”, since they respond to “noxious” stimuli. This time, the main pathway
to the brain is the antero-lateral system (which formally divides into the paleo- and
neo- spinothalamic tract) and once again the cerebral cortex is involved with the
processing of the stimuli. Recent research has indicated that the insula has an
important role to play in this, along with the cingulate gyrus, which is a part of the
limbic system. Although pain and touch can be thought of as just two “submodalities”
of a more general “skin sense” (also including proprioception and temperature
perception), there is an emotional, subjective quality to pain1. There is no one “painful
stimulus” which will cause the same degree of pain when applied to everyone. Pain
depends to some extent on the mood of the person, with anecdotal evidence of
soldiers on the battlefield not feeling pain from their injuries until they leave the field,
and sportsmen similarly playing “through the pain barrier”2. Taking opiate drugs has a
well documented analgesic effect, which mimics that of the endogenous enkephalins
and endorphins, and marijuana also increases the level of stimulation needed before
someone feels pain.

Returning to the dorsal root ganglion cells responsible for the initial sensation of both
pain and touch, one useful distinction to be made is that the peripheral terminals of
touch receptors tend to be encapsulated, while those of pain receptors are bare. Also,
the touch receptors have thick myelinated axons (Aβ and even Aα), while those for
pain divide into Aδ and C (smaller myelinated and unmyelinated respectively). This
means that sensation of touch can be transmitted more quickly to the CNS, which is
particularly useful for feedback on fine motor control. As for pain, this represents the
distinction between two types of pain. The Aδ fibres carry sharp pricking pain, for
example which might cause one to withdraw one’s foot from a drawing pin, while the
1
This has at least one important clinical ramification. In the now superseded frontal leucotomy
(lobotomy) operation, performed to relieve certain types of “intractable pain”, the patient can feel the
pain, even being able to distinguish between sharp and burning pain, but are not emotionally affected
by it. In a manner of speaking, they sense it, but cease to “feel” it.
2
On the other hand, merely expecting pain, as when in the dentist’s chair, seems to make people
exquisitely sensitive to it!
C fibres carry a slower, burning pain. Since it is more long term, there is less need for
a very fast transmission. Indeed, while stimulation of the Aδ fibres might be seen as
eliciting “withdrawal”, it has been suggested that stimulation of the C fibres leads to
“immobilisation”3. This has important clinical relevance, as best seen from local
anaesthetics4. These block the smallest nerve fibres, which means that first the C
fibres and then the Aδ fibres are blocked. Thus pain perception is blocked.

As already mentioned, there are at least four types of touch receptors, although the
Krause receptors, of undetermined function, may also have a role to play5. Each of
these touch receptors needs to be deformed in a specific way, by a specific type of
stimulus, for the sensory nerve to be excited. In addition to the different classes of
stimulus, explained above, they can be distinguished from each other in terms of
adaptation, with Meissner’s and Pacinian corpuscles showing complete adaptation
(meaning that they respond to changes in stimulus rather than their absolute values,
for more efficient information coding), while the other two show incomplete
adaptation (meaning that following a change in stimulus the action potential
frequency will settle down to some new, different value, and thus both changes in and
absolute levels of stimulus are signalled). They also differ in terms of location, with
the Meissner’s corpuscle and Merkel’s disc occurring more superficially, and the
other two occurring in deep subcutaneous tissue. A single dorsal root ganglion might
have input from 10-25 superficial receptors (of the same type), while there is a one to
one correspondence between the deep receptors and the sensory neurons.
Functionally, the superficial receptors are more closely packed, each with a tiny
receptive field and can thus resolve fine spatial differences6. The deeper receptors,
meanwhile, resolve only the more coarse detail. Also, the density of packing of the
receptors varies over different parts of the skin, with for example the skin of the
fingers having a greater density than the skin of the trunk. As shall be described later,
this peripheral characteristic is mirrored centrally, in the Penfield maps of
somatosensory cortex.

In contrast to the largely well defined touch receptors, the nociceptors are not so well
understood. I have not even been able to find any information on the relative density
of their distribution in different parts of the body! In general, however, three classes
are recognised. There are the mechanical and thermal nociceptors, respondent to
noxious stimuli in the form of pressure and temperature, and then there are the
polymodal nociceptors, which seem to respond based on how destructive a stimulus is
rather than to its physical properties7 (and so would respond to an irritant chemical,
but not to light pressure). These in general are the receptors that provide the burning
pain (via the C fibres). So for both pain and touch, there are various classes of
receptor providing different stimuli. It is for the central nervous system to integrate
these into an overall picture. In terms of location, there are pain receptors in the
viscera (from which can be derived burning, but also often referred, pain), whereas
there are no touch receptors here.
3
Neurophysiology R.H.S. Carpenter
4
And the application of local anaesthetics, in particular the order in which the various sensations are
lost, provides experimental evidence for the size of the nerve fibres carrying the sensory information.
5
Neurophysiology R. H. S. Carpenter
6
Lateral inhibition at the level of the synapse with the secondary neurons, at the cuneate and gracile
nuclei, will sharpen things up further. Lateral inhibition is in fact common to many different sensations,
not just pain and touch.
7
Principles of Neural Science Kandel and Schwartz
The lemniscal and antero lateral systems, along which occur the “transport” of the
stimuli due to touch and pain, are also sometimes called the epicritic and protopathic
pathways, respectively. These words describe more than just an anatomical structure,
but rather a whole different class of sensation. In each case, the dorsal root ganglion
cells terminate in the dorsal root of the spinal cord. This is divided into six layers,
known as Rexed’s laminae. The smaller, mostly unmyelinated, fibres from the
nociceptors (amongst others) branch to form the tract of Lissauer and enter at levels I
and II. They terminate, and synapse with secondary neurons which cross over to the
other side of the spinal column and ascend in the anterolateral column8. Those in the
paleo-spinothalamic tract pass via the reticular formation and the peri-aqueductal grey
(both very important for the modification of pain), while those in the neo-spino
thalamic tract proceed directly to the ventroposterior nuclei of the thalamus. From
here there are projections to the insular cortex as mentioned above. This is the older
pathway in evolutionary terms, which functions to transmit what might be regarded as
important, specific stimuli requiring responses. These responses, like withdrawing
one’s hand from a hot surface, are often quite difficult to control consciously. In
addition to pain, another example of this type of stimulus is temperature.
Experimentally, electrical stimulation of the spinothalamic tract results in pain,
whereas lesions to one side of the tract result in analgesia on the other side of the
body. Clinically, injury to the spinothalamic tract causes the phenomenon of “central
pain”, whereby patients might experience a spontaneous burning pain, or other
unusual sensations (dyesthaesia) in parts of the body where noxious stimuli do not
normally lead to pain9.

Touch, on the other hand, ascends via the newer (more developed in primates)
lemniscal system. Here, the larger fibres that respond to touch ascend to the cuneate
or gracile nuclei higher up in the spinal column. Here, they synapse, and the
secondary neurons cross over the midline, and ascend to the ventroposterior nuclei of
the thalamus. Once again there are projections to the cortex. The lemniscal system
offers a rapid system for providing feedback to the brain. This epicritic sensation
provides for several functions10: detecting gentle contact of the skin and localization
of the position that is touched (topognosis), discerning vibration and determining its
frequency and amplitude, two point discrimination (resolving fine detail), and
recognizing the shape of objects grasped in the hand (stereognosis, mentioned above).
In the broadest terms, here structure reflects function. The neurons of the protopathic
pathway enter the spinal cord and synapse with other neurons there. Responses may
come directly from the spine, which can then “choose” to inform the brain about it.
But with the epicritic pathway, the neurons hardly enter the dorsal root. Instead,
information goes straight to the thalamus and from there to cerebral cortex.

Having these two different pathways, which cross over from one side of the body to
the other at different levels, has interesting clinical ramifications in the diagnosis of
hemisections of the spinal cord11. In Brown-Sequard syndrome, hemisection of the
cord results in loss of deep pressure and vibration on the same side, and loss of pain,

8
While pain is said to ascend in up to five structures, if the anterolateral system is sectioned there is a
complete peripheral analgesia, and so I will concentrate on this.
9
Principles of Neuroscience, Kandel and Schwartz
10
As listed by Kandel and Schwartz
11
The following explanation is after Neurophysiology R.H.S. Carpenter
temperature and light touch on the other. Deliberate anterolateral chordotomy is
sometimes performed to relieve peripheral, intractable pain.

In addition to this pathway for touch, the large dorsal root ganglion neurons often give
out branches to levels III and IV of the dorsal horn. Here, these branches synapse with
short interneurons, which then synapse with cells in layer II. So in addition to the
comparisons that can be drawn between the pathways for touch and pain, the two
pathways do interact. This has important consequences for the perception of pain.
This was first realised in the 1960’s, and is termed the gate control theory12. The
internuerons in layers I and II of the dorsal horn, mentioned above as receiving
excitatory input from motor neurons, serve to inhibit the nociceptors. Functionally,
the response to a stimulus will depend on the balance between touch and pain
receptors. A clinical application of this is transcutaneous electrical stimulation
(TENS), used to relieve pain. This technique activates a large number of Aβ “touch”
fibres simultaneously, and thus alleviates pain via this gating control mechanism.

As already hinted at, primary somatic cortex S-I is the most important cortical area for
the perception of touch. This area contains Brodmann’s areas 1, 2, 3a and 3b. These
areas were mapped by Vernon Mountcastle for monkeys in the 1950’s. He made the
assumption that perception is directly related to electrical activity in populations of
sensory neurons13, and then used an extracellular electrode to measure the activity of
different areas of cortex when applying stimulation to various areas of the monkeys’
bodies14.

Several interesting results emerged. The first was that the cortex preserves the general
topological relationship between parts of the body, with nearby parts of the body
generally represented by nearby parts of cortex. So in the S-I area, on each side there
is a reasonably accurate map of the other side of the body. But the map, termed a
sensory homunculus15, devotes much greater area to parts of the body such as the lips
and fingers, which have the greatest sensitivity to touch. The homunculus below is
distorted to show the relative areas the cortex devotes to mapping different parts of
the body. There is a lot of flexibility in these areas. If a monkey’s hand is bandaged,
there is a reduction in cortex area devoted to that hand within a few hours16.

17

12
Originally proposed by Melzack and Wall. This can be used to provide a logical (“Western”) basis
for acupuncture.
13
Fundamental Neuroscience Zigmond and Bloom
14
He was later able to show that monkey and human brains are very similar in their responses to touch.
15
Penfield and Rasmussen
16
Neurophysiology, R.H.S Carpenter
17
http://psychlops.psy.uconn.edu/eric/pics/homunc.gif
This alone, however, almost a simple point for point representation, would imply too
great a similarity between the CNS and PNS. The cortex is organised into columns of
cells18, each a few hundred micrometers in diameter. Cells in a particular column will
tend to respond to the same area of skin. The column arrangement allows for
integration of information between the cortical cells. It also allows for easy
connection to other parts of the brain. Layer IV receives sensory input from the
thalamus while layer VI projects back to it; meanwhile layers II and III project to
other cortical regions and layer V projects to subcortical structures. Layers III and VI
also receive input from the cortex. Like the touch receptors themselves, each cell will
be either slowly adapting or rapidly adapting. And when a point on the skin is
touched, and the dorsal root ganglion cell is excited, a specific population of cortical
cells will be excited.

In addition to the S-I area, in primates there is also an S-II area, and there are various
“higher areas” in the cortex for more sophisticated processing such as the posterior
parietal cortex. Very generally, here neurons tend to receive input from both sides of
the body. Cells also start to respond to more esoteric things, such as moving stimuli,
or a combination of modalities19. Indeed, one of these modalities is pain. So while a
lesion in S-I might cause a raised tactile threshold, for example, a lesion in the
posterior parietal cortex might not have any effect on that, but might lead to a loss of
higher functions such as stereognosis.

Pain is also processed in the cerebral cortex, and S-II has a major role to play, in
particular for the Aδ pain. In general, however, the pathways for pain in the cerebral
cortex are not well understood (although as mentioned above in the last five years it
has been recognised that the insula has an important role to play). It is also well
known that the thalamus is important, in particular the lateral nuclear group of the
thalamus, but lesions of the thalamus do not seem to have a predictable effect, these
varying from relief of existing chronic pain to introduction of new, unbearable
spontaneous pain20. Probably this owes to the fact that the sensation of pain is
evolutionarily probably far older, and thus the systems more diffuse, than the
sensation of touch: newer systems have pushed the old pathways out of recognition,
perhaps a bit like how the original Roman roads are scarcely recognisable among
today’s highways.

One feature that distinguishes the central pathways of pain sensation from those of
touch, however, is the various controls that can be exerted on sensation of pain. The
gating control mechanism and the use of TENS was mentioned earlier. Direct
electrical stimulation of the periaqueductal grey in experimental animals also induces
analgesia21. The descending pathways responsible for this have been largely
elucidated. Neurons in this region make excitatory connections to the serotonergic
connections of the nucleus raphe magnus. These neurons inhibit neurons in laminae I,
II and IV of the dorsal horn, which includes the neurons of the spinothalamic tract in
levels I and II. The periaqueductal area itself is probably innervated by nociceptive
18
This is true of the entire cortex, not just the somatosensory areas
19
Very broadly speaking, here there are parallels to visual cortex, where there is a contrast between
cells such as in the retina merely forming an image of what as been seen, and then cells responding, for
example, to faces, or horizontal lines, or bars of a certain orientation etc.
20
Neurophysiology, R.H.S. Carpenter
21
The ensuing discussion is after Kandel and Schwartz
fibres, thus providing a negative feedback system for the transmission of pain. The
noradrenergic locus ceruleus is the origin of another descending inhibitory pathway
for pain.

At the beginning of this essay, the emotional state of the person was mentioned. In
conditions of stress, like the soldier or the sportsman introduced earlier, there is often
analgesia. At least part of the response is opioid mediated: it can be partly blocked by
the opioid antagonist naloxone22. The endogenous endorphins in the brain include the
enkephalins, the dynorphins and β endorphin. In terms of pain, they seem to act on μ
opioid receptors, which are found on the periaqueductal grey, the ventral medulla and
the dorsal horn, all regions that are important in the transmission of pain. Naloxone
injected into periaqueductal grey or raphe magnus removes the analgesic effects of the
opioids and morphine. Clinically, this has enormous use, since morphine, an opioid
receptor agonist, is used to control pain. Mechanistically, stimulation of the opioid
receptor has two effects. There is an increase in K+ conductance postsynaptically,
which hyperpolarises the postsynaptic cell, and presynaptically there is an inhibition
of the release of glutamate, substance P, and other neurotransmitters. These two
effects reduce the transmission of the excitatory signals along the pain pathway.

So in this essay pain and touch have been compared: pain represents an older, more
diffuse system that remains poorly understood. In contrast, much of our knowledge
about the cortex was first discovered from investigating touch. What is particularly
fascinating about the two systems, but in particular pain, is the variety of ways in
which it can be modified. This provides great clinical opportunity, both now and for
the future.

22
Although this does suggest that stress also has analgesic effects that aren’t through opioids.