398
P A R T 4
Drugs acting on the central and peripheral nervous systems
P
ain
, by definition, is a sensory and emotional experi-
ence associated with actual or potential tissue damage.
The perception of pain is part of the clinical pres-
entation in many disorders and is one of the hardest
sensations for people to cope with during the course
of a disease or dysfunction. The drugs involved in the
management of severe pain, whether acute or chronic,
are discussed in this chapter. These agents all work in
the central nervous system (CNS)—the brain and the
spinal cord—to alter the way that pain impulses arriving
from peripheral nerves are processed. These agents can
change the perception and tolerance of pain. Two major
types of drugs are considered here: the opioids—the
opium derivatives that are used to treat many types of
pain; and the antimigraine drugs, which are reserved
for the treatment of migraine headache, a type of severe
headache. Opioid antagonists, which are used to block
the effects of the opioids in cases of overdose, are also
discussed.
PAIN
Pain is described as an unpleasant sensation and emo-
tional experience. In many ways it is a subjective
experience. The physiological processes that cause
pain are perceived and reacted to in different ways
because of learned experiences, cultural differences and
environmental stimuli. Pain occurs whenever tissues are
damaged. The injury to cells releases many chemicals,
including kinins and prostaglandins, which stimulate
specific sensory nerves. Pain can be acute or chronic.
Acute pain occurs in response to recent tissue damage
or injury. This type of pain makes a person aware of an
injury and should lead to measures to care for the injury
and teaches the person to avoid similar situations that
could cause this pain. Chronic pain is constant or inter-
mittent pain that keeps occurring long past the time the
injured area would be expected to heal. Chronic pain
can cause a stress reaction, interrupt much-needed sleep
and interfere with all of the activities of daily living. Pain
can also be classified by location. “Where does it hurt?”
is a common question in assessing pain. Sometimes
the location of the pain is a direct indicator of where
the tissue damage has occurred. In some cases so-called
referred pain occurs. A person experiencing pain from
damage to the heart muscle may actually feel the pain in
the neck or jaw. The sensation of pain is experienced in
a different area of the body. Referred pain often follows
predictable pathways, which helps healthcare providers
figure out where the injury has occurred. Pain can be
further classified by originating source as nociceptive,
neuropathic or psychogenic. Nociceptive pain is caused
by a direct stimulus to a pain receptor. Neuropathic pain
is caused by nerve injury. Psychogenic pain is pain that is
associated with emotional, psychological or behavioural
stimuli.
Pain impulse transmission and perception
Two small-diameter sensory nerves, called the
A-delta
and C fibres
, respectively, respond to stimulation by gen-
erating nerve impulses that produce pain sensations. The
A-delta fibres are small, myelinated fibres that respond
quickly to acute pain. The C fibres are unmyelinated
and are slow conducting. Pain impulses from the skin,
subcutaneous tissues, muscles and deep visceral struc-
tures are conducted to the dorsal, or posterior, horn of
the spinal cord on these fibres. In the spinal cord, these
nerves form synapses with spinal cord nerves that then
send impulses to the brain (Figure 26.1).
In addition, large-diameter sensory nerves enter the
dorsal horn of the spinal cord. These so-called
A fibres
do not transmit pain impulses; instead, they transmit
sensations associated with touch and temperature. The
A fibres, which are larger and conduct impulses more
rapidly than do the smaller fibres, can actually block
the ability of the smaller fibres to transmit their signals
to the secondary neurons in the spinal cord. The dorsal
horn, therefore, can be both excitatory and inhibitory
with regard to pain impulses that are transmitted from
the periphery.
The impulses reaching the dorsal horn are transmit-
ted upwards towards the brain by a number of specific
ascending nerve pathways. These pathways run from the
spinal cord into the thalamus, where they form synapses
with various nerve cells that transmit the information
to the cerebral cortex, along the
spinothalamic tracts
.
OPIOIDS
Opioid agonists
alfentanil
codeine
dextropropoxyphene
fentanyl
hydromorphone
methadone
morphine
oxycodone
pethidine
remifentanil
tapentadol
tramadol
Opioid agonists–antagonists
buprenorphine
Opioid antagonists
naloxone
naltrexone
ANTIMIGRAINE AGENTS
Ergot derivatives
ergotamine
Triptans
eletriptan
naratriptan
rizatriptan
sumatriptan
zolmitriptan
