There are two types of nociceptors corresponding to

different pain sensations. Myelinated pain fibers conduct

at speeds of 12 to 30 m/sec and produce the sensation of
fast (first) paina feeling of sharp, localized, stabbing
pain perceived at the time of injury. Unmyelinated pain
fibers conduct at speeds of 0.5 to 2.0 m/sec and produce
the slow (second) pain that followsa longer-lasting, dull,
diffuse feeling. Pain from the skin, muscles, and joints is
called somatic pain, while pain from the viscera is called
visceral pain. The latter often results from stretch, chemical
irritants, or ischemia (poor blood flow), and it is often
accompanied by nausea. 590
Saladin: Anatomy &
Physiology: The Unity of
Form and Function, Third
Edition The McGrawHill
Companies, 2003

Cutaneous and Deep Somatic Pain

Cutaneous pain arises from superficial structures, such as
the skin and subcutaneous tissues. A paper cut on the finger
is an example of easily localized superficial, or cutaneous,
pain. It is a sharp, bright pain with a burning quality
and may be abrupt or slow in onset. It can be localized accurately
and may be distributed along the dermatomes. Because
there is an overlap of nerve fiber distribution between
the dermatomes, the boundaries of pain frequently are not
as clearcut as the dermatomal diagrams indicate.
Deep somatic pain originates in deep body structures,
such as the periosteum, muscles, tendons, joints, and blood
vessels. This pain is more diffuse than cutaneous pain.
Various stimuli, such as strong pressure exerted on bone,
ischemia to a muscle, and tissue damage, can produce
deep somatic pain. This is the type of pain a person experiences
from a sprained ankle. Radiation of pain from the
original site of injury can occur. For example, damage to a
nerve root can cause a person to experience pain radiating
along its fiber distribution.

Skin Pain and Deep Sensibility As indicated earlier, the nerve

endings in each tissue are activated by different mechanisms, and
the pain that results is characterized by its quality, locale, and temporal
attributes. Skin pain is of two types: a pricking pain, evoked
immediately on penetration of the skin by a needle point, and a
stinging or burning pain, which follows in a second or two. Together
they constitute the double responseof Lewis. Both types
of dermal pain can be localized with precision. Compression of
nerve by the application of a tourniquet to a limb abolishes pricking
pain before burning pain. Like the sensation of a limb falling
asleep,this is not due to ischemia as commonly thought. The first
(fast) pain is thought to be transmitted by the larger (A-_) fibers
and the second (slow) pain, which is somewhat more diffuse and
longer-lasting, by the thinner, unmyelinated C fibers.
Deep pain from visceral and skeletomuscular structures is basically
aching in quality; if intense, it may be sharp and penetrating
(knife-like). Occasionally there is a burning type of pain, as in the
heartburnof esophageal irritation and rarely in angina pectoris.

The pain is felt as being deep to the body surface. It is diffuse and
poorly localized, and the margins of the painful zone are not well
delineated, presumably because of the relative paucity of nerve
endings in viscera. Visceral pain produces two additional sensations.
First, there is tenderness at remote superficial sites (referred
hyperaglesia) and, second, an enhanced pain sensitivity in the
same and in neaerby organs (visceral hyperalgesia). This is a
restatement of Heads early observations, discussed above, and
MacKenzies mapping of the referred Head zones,where somatic
and visceral sensibility overlap as discussed below. The concept of
visceral hyperalgesia has received considerable attention in a number
of pain syndromes in reference to the transition from acute to
chronic pain, particularly in headache. It has been speculated that
the central mechanism of these syndromes involves glutamate. 119

Endogenous Pain-Control Mechanisms

In recent years, the most important contribution to our understanding
of pain has been the discovery of a neuronal analgesia system
which can be activated by the administration of opiates or by naturally
occurring brain substances that share the properties of opiates.
This endogenous system was first demonstrated by Reynolds,
who found that stimulation of the ventrolateral periaqueductal gray
matter in the rat produced a profound analgesia without altering
behavior or motor activity. Subsequently, stimulation of other discrete
sites in the medial and caudal regions of the diencephalon
and rostral bulbar nuclei (notably raphe magnus and paragigantocellularis)
were shown to have the same effect. Under the influence
of such electrical stimulation, the animal could be operated upon
without anesthesia and move around in an undisturbed manner despite
the administration of noxious stimuli. Investigation disclosed
that the effect of stimulation-produced analgesia (SPA) is to inhibit
the neurons of laminae I, II, and V of the dorsal horn, i.e., the
neurons that are activated by noxious stimuli. In human subjects,
stimulation of the midbrain periaqueductal gray matter through
stereotactically implanted electrodes has also produced a state of
analgesia, though not consistently. Other sites in which electrical
stimulation is effective in suppressing nociceptive responses are
the rostroventral medulla (nucleus raphe magnus and adjacent reticular
formation) and the dorsolateral pontine tegmentum. These
effects are relayed to the dorsal horn gray matter via a pathway in
the dorsolateral funiculus of the spinal cord. Ascending pathways
from the dorsal horn, conveying noxious somatic impulses, are also
important in activating the modulatory network.
As indicated earlier, opiates also act pre- and postsynaptically
on the neurons of laminae I and V of the dorsal horn, suppressing
afferent pain impulses from both the A-_ and C fibers. Furthermore,
these effects can be reversed by the narcotic antagonist naloxone.
Interestingly, naloxone can reduce some forms of stimulationproduced
analgesia. Levine and colleagues have demonstrated that
not only does naloxone enhance clinical pain but it also interferes
with the pain relief produced by placebos. These observations suggest
that the heretofore mysterious beneficial effects of placebos
(and perhaps of acupuncture) may be due to activation of an endogenous
system that shuts off pain through the release of painrelieving
endogenous opioids, or endorphins (see below). Prolonged
pain and fear are the most powerful activators of this
endogenous opioid-mediated modulating system. The same system
is probably operative under a variety of other stressful conditions;
for example, some soldiers, wounded in battle, require little or no

analgesic medication (stress-induced analgesia). The opiates also

act at several loci in the brainstem, at sites corresponding with those
producing analgesia when stimulated electrically and generally
conforming to areas in which neurons with endorphin receptors are
localized.
Soon after the discovery of specific opiate receptors in the
central nervous system (CNS), several naturally occurring peptides,
which proved to have a potent analgesic effect and to bind specifically
to opiate receptors, were identified (see Hughes et al for a
summary of these substances). These endogenous, morphine-like
compounds are generically referred to as endorphins, meaning the
morphines within. The most widely studied are _-endorphin, a
peptide sequence of the pituitary hormone _-lipotropin, and two
other peptides, enkephalin and dynorphin. They are found in greatest
concentration in relation to opiate receptors in the midbrain. At
the level of the spinal cord, exclusively enkephalin receptors are
found. A theoretical construct of the roles of enkephalin (and substance
P) at the point of entry of pain fibers into the spinal cord is
illustrated in Fig. 8-4. A subgroup of dorsal horn interneurons also
contains enkephalin; they are in contact with spinothalamic tract
neurons.
Thus it would appear that the central effects of a painful condition
are determined by many ascending and descending systems
utilizing a variety of transmitters. A deficiency in a particular region
would explain persistent or excessive pain. Some aspects of
opiate addiction and also the discomfort that follows withdrawal
of the drug might conceivably be accounted for in this way. Indeed,
it is known that some of these peptides not only relieve pain but
suppress withdrawal symptoms.
Finally it should be noted that the descending pain-control
systems contain noradrenergic and serotonergic as well as opiate
links. A descending norepinephrine-containing pathway, as mentioned,
has been traced from the dorsolateral pons to the spinal
cord, and its activation blocks spinal nociceptive neurons. The rostroventral
medulla contains a large number of serotonergic neurons.
Descending fibers from the latter site inhibit dorsal horn cells concerned
with pain transmission, perhaps providing a
rationale for the use of certain antidepression medications
that are serotonin agonists in patients with
chronic pain.

ADAMS AND VICTORS

PRINCIPLES OF
NEUROLOGY
Eighth Edition
Allan H.Ropper, M.D.

McGraw-Hill
MEDICAL PUBLISHING DIVISION 2005,

Managing pain
Considering the different causes and types of pain,
as well as its nature and intensity, management can

require an interdisciplinary approach. The elements of

this approach include treating the underlying cause of
pain, pharmacological and nonpharmacological therapies,
and some invasive (surgical) procedures.
Treating the cause of pain underpins the idea of
managing it. Injuries are repaired, diseases are diagnosed,
and certain encounters with pain can be anticipated
and treated prophylactically (by prevention). However,
there are no guarantees of immediate relief from pain.
Recovery can be impeded by pain and quality of life can
be damaged. Therefore, pharmacological and other therapies
have developed over time to address these aspects
of disease and injury.
PHARMACOLOGICAL OPTIONS. Pain-relieving drugs,
otherwise called analgesics, include nonsteroidal antiinflammatory
drugs (NSAIDs), acetaminophen, narcotics,
antidepressants, anticonvulsants, and others.
NSAIDs and acetaminophen are available as over-thecounter
and prescription medications, and are frequently
the initial pharmacological treatment for pain. These drugs
can also be used as adjuncts to the other drug therapies,
which might require a doctors prescription.
NSAIDs include aspirin, ibuprofen (Motrin, Advil,
Nuprin), naproxen sodium (Aleve), and ketoprofen
(Orudis KT). These drugs are used to treat pain from
inflammation and work by blocking production of painenhancing
neurotransmitters, such as prostaglandins.
Acetaminophen is also effective against pain, but its ability
to reduce inflammation is limited.
NSAIDs and acetaminophen are effective for most
forms of acute (sharp, but of a short course) pain, but
moderate and severe pain may require stronger medication.
Narcotics handle intense pain effectively, and are
used for cancer pain and acute pain that does not respond
to NSAIDs and acetaminophen. Narcotics are classified
as either opiates or opioids, and are available only with adoctors prescription. Opiates
include morphine and
codeine, which are derived from opium, a substance naturally
found in some poppy species. Opioids are synthetic
drugs based on the structure of opium. This drug class
includes drugs such as oxycodon, methadone, and
meperidine (Demerol).
Narcotics may be ineffective against some forms of
chronic pain, especially since changes in the spinal cord
may alter the usual pain signaling pathways. Furthermore,
narcotics are usually not recommended for longterm
use because the body develops a tolerance to narcotics,
reducing their effectiveness over time. In such situations,
pain can be managed with antidepressants and
anticonvulsants, which are also only available with a
doctors prescription.
Although antidepressant drugs were developed to
treat depression, it has been discovered that they are also
effective in combating chronic headaches, cancer pain,
and pain associated with nerve damage. Antidepressants

that have been shown to have analgesic (pain reducing)

properties include amitriptyline (Elavil), trazodone
(Desyrel), and imipramine (Tofranil). Anticonvulsant
drugs share a similar background with antidepressants.
Developed to treat epilepsy, anticonvulsants were found
to relieve pain as well. Drugs such as phenytoin (Dilantin)
and carbamazepine (Tegretol) are prescribed to treat
the pain associated with nerve damage.
Other prescription drugs are used to treat specific
types of pain or specific pain syndromes. For example,
corticosteroids are very effective against pain caused by
inflammation and swelling, and sumatriptan (Imitrex)
was developed to treat migraine headaches.
Drug administration depends on the drug type and
the required dose. Some drugs are not absorbed very well
from the stomach and must be injected or administered
intravenously. Injections and intravenous administration
may also be used when high doses are needed or if an
individual is nauseous. Following surgery and other medical
procedures, patients may have the option of controlling
the pain medication themselves. By pressing a button,
they can release a set dose of medication into an
intravenous solution. This procedure has also been
employed in other situations requiring pain management.
Another mode of administration involves implanted
catheters that deliver pain medication directly to the
spinal cord. Delivering drugs in this way can reduce side
effects and increase the effectiveness of the drug.
NONPHARMACOLOGICAL OPTIONS. Pain treatment
options that do not use drugs are often used as adjuncts
to, rather than replacements for, drug therapy. One of the
benefits of non-drug therapies is that an individual can
take a more active stance against pain. Relaxation techniques,
such as yoga and meditation, are used to
decrease muscle tension and reduce stress. Tension and
stress can also be reduced through biofeedback, in
which an individual consciously attempts to modify skin
temperature, muscle tension, blood pressure, and heart
rate.
Participating in normal activities and exercising can
also help control pain levels. Through physical therapy,
an individual learns beneficial exercises for reducing
stress, strengthening muscles, and staying fit. Regular
exercise has been linked to production of endorphins, the
bodys natural pain killers.
Acupuncture involves the insertion of small needles
into the skin at key points. Acupressure uses these same
key points, but involves applying pressure rather than
inserting needles. Both of these methods may work by
prompting the body to release endorphins. Applying heat
or being massaged are very relaxing and help reduce
stress. Transcutaneous electrical nerve stimulation
(TENS) applies a small electric current to certain parts of
nerves, potentially interrupting pain signals and inducing
release of endorphins. To be effective, use of TENS

should be medically supervised.

INVASIVE PROCEDURES. There are three types of
invasive procedures that may be used to manage or treat
pain: anatomic, augmentative, and ablative. These procedures
involve surgery, and certain guidelines should be
followed before carrying out a procedure with permanent
effects. First, the cause of the pain must be clearly identified.
Next, surgery should be done only if noninvasive
procedures are ineffective. Third, any psychological
issues should be addressed. Finally, there should be a
reasonable expectation of success.
Anatomic procedures involve correcting the injury
or removing the cause of pain. Relatively common
anatomic procedures are decompression surgeries, such
as repairing a herniated disk in the lower back or relieving
the nerve compression related to carpal tunnel syndrome.
Another anatomic procedure is neurolysis, also
called a nerve block, which involves destroying a portion
of a peripheral nerve.
Augmentative procedures include electrical stimulation
or direct application of drugs to the nerves that are
transmitting the pain signals. Electrical stimulation
works on the same principle as TENS. In this procedure,
instead of applying the current across the skin, electrodes
are implanted to stimulate peripheral nerves or nerves in
the spinal cord. Augmentative procedures also include
implanted drug-delivery systems. In these systems,
catheters are implanted in the spine to allow direct delivery
of drugs to the CNSand diagnostic tests to determine underlying causes.
Some evaluations require assessments from several viewpoints,
including neurology, psychiatry and psychology,
and physical therapy. If pain is due to a medical procedure,
management consists of anticipating the type and
intensity of associated pain and managing it preemptively
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