445
CHAPTER TWELVE
Nervous System III
T
oo many people are in pain. Several stud-
ies estimate that at any given time, one in
four individuals worldwide is in moderate
to severe chronic pain. A quarter of them may be
undertreated.
Most pain remedies are nonsteroidal anti-
inF
ammatory drugs (NSAIDs) such as aspirin, ibu-
profen, and COX-2 inhibitors (±
g. 12A), or opiates
g. 12B). Many recently approved painkillers are
variations on these traditional themes, with mol-
ecules tweaked or formulations changed, such
as from injectable to oral delivery. The topselling
painkiller is acetaminophen, sold under the brand
name Tylenol. It has an interesting history.
Acetaminophen was first described in the
chemical literature in 1878. In 1886, its analgesic
and fever-lowering effects were noted, by acci-
dent, but not recognized. Two doctors in ²rance
were treating a patient with intestinal parasites
with the chemical naphthalene. One day a phar-
macist gave them the compound acetanilide in
error. The mistake was fortuitous—fever dropped
and pain faded. In 1899, a chemist discovered that
acetanilide is metabolized to acetaminophen. By
1909, the compound had been further studied
and produced as a drug, used ±
rst in England. It
became available by prescription in the United
States in 1953 and over-the-counter in 1960. The
success of acetaminophen is attributed to its lack
of side e³
ects seen with the NSAIDs. It does not
irritate the gastrointestinal lining, and does not
thin the blood.
In 2005 a new painkiller became available.
Ziconotide is a synthetic version of a peptide that
the marine cone snail
Conus magus
releases to
paralyze its ±
sh prey (±
g. 12C). When researchers
noticed that the natural peptide binds to a type
of calcium receptor on spinal cord neurons that
receive pain impulses, the effort began to turn
the snail’s weapon into a pain reliever. Ziconotide
is delivered by catheter to the a³
ected body part
and is prescribed to relieve intractable chronic
pain. Similar drugs are in development.
The types of patients in greatest need of pain
relief are people with cancer or chronic pain syn-
dromes. More than half of people nearing the end
of their battle against cancer su³
er pain that can
be treated, or at least dulled, but is not. The fear is
unfounded that giving opiate drugs to ease their
su³
ering will lead to addiction. Narcotics are much
more likely to be addicting when they are abused
to induce euphoria than when they are taken to
relieve severe pain. Cancer patients take NSAIDs,
weak narcotics such as hydrocodone, strong nar-
cotics such as morphine, and opiates delivered
directly to the spine via an implanted reservoir.
Patients may use devices to control the delivery
of pain medications. Anti-anxiety medications can
ease the perception of pain.
Chronic pain is of three types: lower back
pain, migraine, and myofascial syndrome (inF
am-
mation of muscles and their fascia). Treatment
approaches include NSAIDs, stretching exercises,
injection of local anesthetic drugs into cramp-
ing muscles, and antidepressants to raise sero-
tonin levels in the CNS. Chronic pain may also
be treated with electrodes implanted near the
spinal cord (a dorsal column stimulator); trans-
cutaneous electrical nerve stimulation (TENS),
which also places electrodes on pain-conducting
nerves; and an invasive nerve block, which inter-
rupts a pain signal by freezing or introducing an
anesthetic drug.
12.1
CLINICAL APPLICATION
Treating Pain
a refl ex with an effect opposite that of a stretch refl ex. The
Golgi tendon refl ex also helps maintain posture, and it pro-
tects muscle attachments from being pulled away from their
insertions by excessive tension.
Table 12.2
summarizes some
of the receptors of the general senses and their functions.
cle F bers and is innervated by a sensory neuron (F g. 12.4
b
).
These receptors have high thresholds and are stimulated
by increased tension. Sensory impulses from them produce
a refl
ex that inhibits contraction of the muscle whose ten-
don they occupy. Thus, the Golgi tendon organs stimulate
FIGURE 12C
A newer analgesic for
extreme and unrelenting chronic pain is
based on a peptide from the marine cone
snail
Conus magus.
FIGURE 12A
Painkillers come from
nature. Aspirin derives from bark of the
willow tree.
FIGURE 12B
Poppies are the source of
opiate drugs.
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