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U N I T 1 0
Nervous System
through the inhibition of the cyclooxygenase (COX)
enzymes, which mediate the biosynthesis of prosta-
glandins. Prostaglandins (particularly prostaglandin
E
2
) exert their effect through peripheral sensitization of
nociceptors to chemical mediators such as bradykinin
and histamine.
27
The NSAIDs also decrease the sensitiv-
ity of blood vessels to bradykinin and histamine, affect
cytokine production by T lymphocytes, inhibit vasodila-
tion, and decrease the release of inflammatory mediators
from granulocytes and mast cells. Acetaminophen is an
alternative to the NSAIDs. Although usually considered
equivalent to aspirin as an analgesic and antipyretic
agent, it lacks anti-inflammatory properties.
Opioid Analgesics.
The term
opioid
or
narcotic
is used
to refer to a group of medications, natural or synthetic,
with morphinelike actions. The opioids (e.g., morphine,
codeine, and many other semisynthetic congeners of
morphine) exert their action through opioid receptors.
There are three major categories of opioid receptors in
the CNS, designated as mu (
μ
, for “morphine”), delta
(
δ
), and kappa (
κ
).
27
Analgesia, as well as respiratory
depression, miosis (constriction of the pupil), reduced
gastrointestinal motility (causing constipation), feelings
of well-being or euphoria, and physical dependence,
principally result from morphine and morphinelike opi-
oid analgesics that act at the mu receptors. Part of the
pain-relieving properties of exogenous opioids such as
morphine involve the release of endogenous opioids.
27
Opioids are used in the management of acute and
chronic pain. When given for temporary relief of severe
pain, such as that occurring after surgery, there is much
evidence that opioids given routinely before the pain
starts or becomes extreme are far more effective than
those administered in a sporadic manner. Persons who
are treated in this manner usually require fewer doses
and are able to resume regular activities sooner. Opioids
also are used for persons with chronic pain such as that
caused by cancer. Morphine remains the most useful
strong opioid, and the WHO has recommended that
oral morphine be part of the essential medication list
and be made available throughout the world as the med-
ication of choice for cancer pain.
24,27
Adjuvant Analgesics.
Adjuvant analgesics include
medications such as tricyclic antidepressants, antisei-
zure medications, and neuroleptic anxiolytic agents.
28
Serotonin has been shown to play an important role in
producing analgesia. In recent years the use of medi-
cations classified as serotonin norepinephrine reup-
take inhibitors (SNRIs) have been shown to help with
the treatment of chronic pain. The Food and Drug
Administration (FDA) has approved two drugs in this
class, duloxetine and milnacipran, for the treatment of
chronic pain associated with fibromyalgia.
29
The use
of these drugs has also shown potential benefit for the
treatment of postherpetic neuralgia and painful diabetic
neuropathy.
30
The tricyclic antidepressant medications
that block the removal of serotonin from the synaptic
cleft have been shown to produce pain relief in some
persons. These medications are particularly useful in
some chronic painful conditions, such as postherpetic
neuralgia. Antiseizure medications that suppress spon-
taneous neuronal firing are particularly useful in the
management of pain that occurs after nerve injury
(neuropathic pain), including diabetic neuropathy and
chronic regional pain syndrome. Other agents, such as
the corticosteroids, may be used to decrease inflamma-
tion and the nociceptive stimuli responsible for pain.
Surgical Interventions
If surgery removes the problem causing the pain, such as a
tumor pressing on a nerve or an inflamed appendix, it can
be curative. In other situations, surgery is used for symp-
tom management rather than for cure. However, with
rare exceptions, noninvasive analgesic approaches for
pain relief should precede invasive surgical approaches.
16
Surgery for severe, intractable pain of peripheral or cen-
tral origin has met with some success. It can be used to
remove the cause or block the transmission of intractable
pain from phantom limb pain, severe neuralgia, inoper-
able cancer of certain types, and other disorders.
SUMMARY CONCEPTS
■■
Pain is both a protective and an unpleasant
physically and emotionally disturbing sensation
originating in pain receptors that respond to a
number of stimuli that threaten tissue integrity. It
is a symptom common to many illnesses and is a
highly individualized experience that is shaped by
a person’s culture and previous life experiences.
■■
Nociceptors, which are receptive nerve endings
that respond to noxious or painful stimuli,
transmit impulses to the dorsal horn neurons in
the spinal cord using chemical neurotransmitters.
■■
There are two pathways for pain transmission:
The pathway for fast, sharply discriminated pain
that moves directly from the receptor to the spinal
cord and from the spinal cord to the thalamus
using the neospinothalamic tract; and the pathway
for slow, continuously conducted pain that is
transmitted to the spinal cord and from the spinal
cord to the thalamus using the more circuitous
and slower-conducting paleospinothalamic tract.
■■
The central processing of pain information
includes transmission to the somatosensory
cortex, where pain information is perceived
and interpreted; the limbic system, where the
emotional components of pain are experienced;
and the brain stem centers, where autonomic
nervous system responses are recruited.
