Mechanism of Pain and Pain Management: Questions ANSWERS and Rationale References

MSU-COLLEGE OF MEDICINE
LEVEL 1 LOCOMOTOR MODULE

MECHANISM OF PAIN AND MANAGEMENT
MECHANISM OF PAIN QUESTIONS ................................................... 15

ANSWERS and rationale .............................. 20
AND PAIN MANAGEMENT REFERENCES.................................................. 23
AILEEN ANNE ACOSTA-GERONA, M.D. DPBA
MARCH 5, 2021 (1:00 – 3:00 PM)
TABLE OF CONTENTS PAIN

 Pain (the fifth vital sign) is a vital function of
PAIN................................................................ 1 the nervous system in providing the body
PAIN RECEPTORS AND THEIR STIMULATION ..... 2 with a warning of potential or actual injury.
o It is both a sensory and emotional
RATE OF TISSUE DAMAGE AS A STIMULUS FOR experience, affected by
PAIN ..................................................................... 2 psychological factors such as past
experiences, beliefs about pain, fear
DUAL PATHWAYS FOR TRANSMISSION OF PAIN or anxiety.
SIGNALS INTO THE CENTRAL NERVOUS SYSTEM  Pain occurs whenever tissues are being
............................................................................. 3 damaged and causes the individual to
DUAL PAIN PATHWAYS IN THE CORD AND react to remove the pain stimulus
BRAIN STEM—THE NEOSPINOTHALAMIC TRACT
 Pain is a distressing feeling often caused by
AND THE PALEOSPINOTHALAMIC TRACT ......... 4
intense or damaging stimuli.
PAIN SUPPRESSION (ANALGESIA) SYSTEM IN
THE BRAIN AND SPINAL CORD .......................... 7 Pain is typically classified as either acute or chronic:
THE BRAIN’S OPIATE SYSTEM—ENDORPHINS  Acute Pain - defined as the normal,
AND ENKEPHALINS ............................................. 7 predicted, physiologic response to an
REFERRED PAIN ................................................... 8 adverse chemical, thermal or mechanical
stimulus
VISCERAL PAIN ................................................... 8 o Generally, acute pain resolves within
1 month
―PARIETAL PAIN‖ CAUSED BY VISCERAL
o Poorly managed acute pain that
DISEASE ............................................................... 9 might occur following surgery can
LOCALIZATION OF VISCERAL PAIN— produce pathophysiologic processes
―VISCERAL‖ AND ―PARIETAL‖ PAIN in both the peripheral and central
TRANSMISSION PATHWAYS ............................... 9 nervous systems that have the
potential to produce chronicity.
NEUROPATHIC PAIN ......................................... 10  Chronic Pain - persists for weeks or months
and is usually associated with an underlying
THE SURGICAL STRESS RESPONSE.................... 10
condition, such as arthritis.
Consequences of poorly managed acute o The severity of chronic pain can be
pain ................................................................... 10 mild, moderate, or severe.
PAIN PROCESSING ........................................... 11 Pain can also be classified as slow and fast pain:
SENSTITIZATION ................................................. 11
 Fast pain is felt within about 0.1 second after
Inhibition of pain transmission ....................... 12 a pain stimulus is applied.
o It describes by many alternative
STRATEGIES FOR ACUTE PAIN MANAGEMENT12 names such as sharp pain, pricking
OPIODS ............................................................. 14 pain, acute pain and electric pain
o Fast-sharp pain is not felt in most
NON STEROIDAL ANTI-INFLAMMATORY DRUGS deep tissues of the body.
(NSAIDs) ............................................................ 15 o Described by many alternative
names, such as:
Badelles. But-oy. Gayloa. Lucman. Macabanding.
Macataman. Mendoza. Simihag | Page 1 of 23
 sharp pain signals, which are then conducted to

 pricking pain the central nervous system. They are the
 acute pain free nerve endings of primary afferent
 electric pain
Aδ and C fibres. Distributed throughout
 Slow pain begins only after 1 second or
more and then increases slowly over many the body (skin, viscera, muscles, joints,
seconds and sometimes even minutes. meninges) they can be stimulated by
o This type of pain is usually associated mechanical, thermal or chemical stimuli
with tissue destruction
o It can occur both in the skin and in Three Types of Stimuli Excite Pain Receptors—
almost any deep tissue or organ. Mechanical, Thermal, and Chemical
o Also goes by many names, such as:
 slow burning pain, aching  Fast pain - elicited by the mechanical and
pain thermal types of stimulI
 throbbing pain  Slow pain – elicited by all three types.
 nauseous pain
•Bradykinin, serotonin, histamine, potassium ions,
acids, acetylcholine, and proteolytic enzymes-
chemicals that excite the chemical type of pain.
 Important in stimulating the slow,

suffering type of pain that occurs
after tissue injury.
•Prostaglandins and substance P - enhance the

sensitivity of pain endings but do not directly excite
them.
Nonadapting Nature of Pain Receptors
 chronic pain  Pain receptors adapt very little and

sometimes not at all.
PAIN RECEPTORS AND THEIR STIMULATION
 Excitation of pain fibers becomes
The pain receptors in the skin and other tissues are progressively greater, especially for
all free nerve endings. slow-aching-nauseous pain, as the
pain stimulus continues.
 They are widespread in the superficial  This increase in sensitivity of the pain
layers of the skin, as well as in certain receptors is called hyperalgesia.
internal tissues, such as the periosteum,
the arterial walls, the joint surfaces, and
RATE OF TISSUE DAM AGE AS A STIMULUS FOR
the falx and tentorium in the cranial
PAIN
vault.
 Most other deep tissues are only sparsely
supplied with pain endings; nevertheless,
any widespread tissue damage can
summate to cause the slow-chronic-
aching type of pain in most of these
areas
 Nociceptors are the specialised sensory
receptors responsible for the detection
of noxious (unpleasant) stimuli,
transforming the stimuli into electrical

 Bradykinin and proteolytic enzymes – also

stimulate the pain nerve endings; product of
cells destruction
Muscle Spasm as a Cause of Pain

 Muscle spasm is also a common cause of
pain and is the basis of many clinical pain
syndromes.
o Results partially from the direct effect
of muscle spasm in stimulating
mechanosensitive pain receptors.
o Also result from the indirect effect of
 The average person begins to perceive pain muscle spasm to compress the
when the skin is heated above 45°C blood vessels and cause ischemia.
 This is also the temperature at which the  The spasm also increases the rate of
tissues begin to be damaged by heat; metabolism in the muscle tissue, thus making
indeed, the tissues are eventually destroyed the relative ischemia even greater, creating
if the temperature remains above this level ideal conditions for the release of chemical
indefinitely. pain-inducing substances
 Therefore, it is immediately apparent that Some of the chemicals that excite the chemical
pain resulting from heat is closely correlated type of pain:
with the rate at which damage to the tissues  Bradykinin
is occurring and not with the total damage  Serotonin
that has already occurred.  Histamine
 The intensity of pain is also closely correlated  Potassium ions
with the rate of tissue damage from causes  Acids e.g. Lactic acid
other than heat, such as bacterial infection,  Acetylcholine
tissue ischemia, tissue contusion, and so  Proteolytic enzymes
forth.
Special Importance of Chemical Pain Stimuli During DUAL PATHWAYS FOR TRANSMISSION OF PAIN
Tissue Damage SIGNALS INTO THE CENTRAL NERV OUS SYSTEM
 Bradykinin - agent most responsible for
The two pathways mainly correspond to the two
causing pain after tissue damage
types of pain— a fast-sharp pain pathway and a
 The intensity of the pain felt correlates with
slow-chronic pain pathway.
the local increase in potassium ion
concentration or the increase in proteolytic
enzymes that directly attack the nerve
endings and excite pain by making the
nerve membranes more permeable to ions.
Tissue Ischemia as a Cause of Pain

 When blood flow to a tissue is blocked, the
tissue often becomes very painful within a
few minutes.
 The greater the rate of metabolism of the
tissue, the more rapidly the pain appears..
 Accumulation of large amounts of lactic -
suggested causes of pain during ischemia,
formed as a consequence of anaerobic
metabolism
 The fast type Aδ pain fibers transmit mainly
mechanical and acute thermal pain.

 They terminate mainly in lamina I (lamina
marginalis) of the dorsal horns, and there
 The fast-sharp pain signals are elicited by they excite second-order neurons of the
either mechanical or thermal pain stimuli. neospinothalamic tract
o Transmitted via small type Aδ fibers  The fast-sharp type of pain can be localized
at velocities between 6 and 30 much more exactly in the different parts of
m/sec. the body than can slow-chronic pain.
 The slow-chronic type of pain is elicited  Glutamate - is the neurotransmitter
mostly by chemical types of pain stimuli but
substance secreted in the in the spinal cord
sometimes by persisting mechanical or
at the type Aδ pain nerve fiber endings
thermal stimuli.
o duration of action lasting for only a
o Transmitted via type C fibers at
velocities between 0.5 and 2 m/sec. few milliseconds
 Double system of pain innervation -
Termination of the Neospinothalamic Tract in the
―double‖ pain sensation: a fast-sharp pain
Brain Stem and Thalamus
that is transmitted to the brain by the Aδ
fiber pathway, followed a second or so
 A few fibers of the neospinothalamic tract
later by a slow pain that is transmitted by
terminate in the reticular areas of the brain
the C fiber pathway.
stem, but most pass all the way to the
o Sharp pain – makes the person
thalamus without interruption, terminating in
react immediately to remove him or
the ventrobasal complex along with the
herself from the stimulus.
dorsal column–medial lemniscal tract for
o Slow pain - produces intolerable
tactile sensations
pain and makes the person keep
 A few fibers also terminate in the posterior
trying to relieve the cause of the
nuclear group of the thalamus. From these
pain.
thalamic areas, the signals are transmitted
DUAL PAIN PATHWAYS I N THE CORD AND to other basal areas of the brain, as well as
BRAIN STEM—THE NEOSPINOTHALAMIC TRA CT to the somatosensory cortex
AND THE PALEOSPINOTHALAMIC TRACT
Capability of the Nervous System to Localize Fast
Upon entering the spinal cord, the pain signals take Pain in the Body
two pathways to the brain, through (1) the
neospinothalamic tract and (2) the
paleospinothalamic tract
NEOSPINOTHALAMIC TRACT FOR FAST PAIN
 The fast-sharp type of pain can be localized  Substance P – probable slow-chronic

much more exactly in the different parts of neurotransmitter of type C nerve endings
the body than can slow-chronic pain. o Research suggests that type C pain
o When only pain receptors are fiber terminals entering the spinal
stimulated, without the simultaneous cord release both glutamate
stimulation of tactile receptors, even transmitter and substance P
fast pain may be poorly localized, transmitter.
often only within 10 centimeters o Glutamate transmitter - acts
or so of the stimulated area. instantaneously and lasts for only a
o When tactile receptors that excite few milliseconds
the dorsal column–medial lemniscal
o Substance P is released much more
system are simultaneously
slowly, building up in concentration
stimulated, the localization can be
over a period of seconds or even
nearly exact.
minutes.
 The ―double‖ pain sensation one feels after
PALAEOSPINOTHALAMIC PATHWAY FOR TRANSMITTING
a pinprick might result partly from the fact
SLOW- CHRONIC PAIN
that the glutamate transmitter gives a faster
pain sensation, whereas the substance P
transmitter gives a more lagging sensation.
Projection of the Paleospinothalamic Pathway

(Slow-Chronic Pain Signals) into the Brain Stem and
Thalamus
 T
h
e
paleospinothalamic pathway - much older

system and transmits pain mainly from the
peripheral slow-chronic type C pain fibers,
although it does transmit some signals from
type Aδ fibers as well.
o the peripheral fibers terminate in the
spinal cord almost entirely in laminae
II and III of the dorsal horns, which
together are called the substantia
gelatinosa
 Most of the signals then pass through one or
more additional short fiber neurons within
the dorsal horns themselves before entering
mainly lamina V, also in the dorsal horn.  The slow-chronic paleospinothalamic
Here the last neurons in the series give rise to pathway - terminates widely in the brain
long axons that mostly join the fibers from stem, in the large shaded area shown in
the fast pain pathway, passing first through Figure 49-3. Only one tenth to one fourth of
the anterior commissure to the opposite side the fibers pass all the way to the thalamus.
of the cord, then upward to the brain in the  Most terminate in one of three areas:
anterolateral pathway.
o (1) the reticular nuclei of the

medulla, pons, and mesencephalon;  Electrical stimulation in the reticular areas of
o (2) the tectal area of the the brain stem and in the intralaminar nuclei
mesencephalon deep to the of the thalamus - has a strong arousal effect
superior and inferior colliculi; or on nervous activity throughout the entire
brain.
o (3) the periaqueductal gray region
o constitute part of the brain‘s
surrounding the aqueduct of Sylvius.
principal ―arousal system,‖. This
 These lower regions of the brain appear to
explains why it is almost impossible
be important for feeling the suffering types for a person to sleep when he or she
of pain is in severe pain.
 From the brain stem pain areas, multiple
short-fiber neurons relay the pain signals Surgical Interruption of Pain Pathways
upward into the intralaminar and
ventrolateral nuclei of the thalamus and into
certain portions of the hypothalamus and
other basal regions of the brain.
Poor Capability of the Nervous System to Localize

Precisely the Source of Pain Transmitted in the Slow-
Chronic Pathway
 Localization of pain transmitted by way of

the paleospinothalamic pathway is
imprecise. For instance, slow-chronic pain
can usually be localized only to a major part
of the body, such as to one arm or leg but
not to a specific point on the arm or leg.
 This phenomenon is in keeping with the
multisynaptic, diffuse connectivity of this
pathway. It explains why patients often
have serious difficulty in localizing the source
of some chronic types of pain.  Pain nervous pathways can be cut at any of
several points to relieve a person from a
Function of the Reticular Formation, Thalamus, and severe and intractable pain (rapidly
Cerebral Cortex in the Appreciation of Pain spreading cancer).
 Complete removal of the somatic sensory  Cordotomy - in the thoracic region of the
areas of the cerebral cortex does not spinal cord often relieves the pain for a few
prevent pain perception. weeks to a few months, if the pain is in the
 Thalamus, and other lower brain centers - lower part of the body
cause conscious perception of pain. o Spinal cord on the side opposite to
 Electrical stimulation of cortical the pain is partially cut in its
somatosensory areas does cause a human anterolateral quadrant to interrupt
being to perceive mild pain from about 3 the antero-lateral sensory pathway.
percent of the points stimulated. o Not always successful. First, many
 Cortex - plays an especially important role in pain fibers from the upper part of the
interpreting pain quality, even though pain body do not cross to the opposite
perception might be principally the function
side of the spinal cord until they
of lower centers
have reached the brain, and the
cordotomy does not transect these
Special Capability of Pain Signals to Arouse Overall
Brain Excitability fibers. Second, pain frequently

returns several months later, partly as third and fourth ventricles. Neurons from these areas
a result of sensitization of other send signals to
pathways that normally are too
(2) the raphe magnus nucleus, a thin midline
weak to be effectual (e.g., sparse nucleus located in the lower pons and upper
pathways in the dorsolateral cord). medulla, and the nucleus reticularis
 Another experimental operative procedure paragigantocellularis, located laterally in the
to relieve pain has been to cauterize medulla. From these nuclei, second-order signals
specific pain areas in the intralaminar nuclei are transmitted down the dorsolateral columns in
in the thalamus, which often relieves the spinal cord to
suffering types of pain while leaving intact
(3) a pain inhibitory complex located in the dorsal
one‘s appreciation of ―acute‖ pain, an
horns of the spinal cord. At this point, the analgesia
important protective mechanism.
signals can block the pain before it is relayed to the
brain. At this point, the analgesia signals can block
PAIN SUPPRESSION (AN ALGESIA) SYSTEM IN the pain before it is relayed to the brain.
THE BRAIN AND SPINAL CORD  Electrical stimulation either in the
periaqueductal gray area or in the raphe
magnus nucleus can suppress many strong
pain signals entering by way of the dorsal
spinal roots.
 Stimulation of areas at still higher levels of
the brain that excite the periaqueductal
gray area can also suppress pain.
o (1)periventricular nuclei in the
hypothalamus, lying adjacent to the
third ventricle, and
o (2) medial forebrain bundle, also in
the hypothalamus
 Enkephalin and serotonin – neurotransmitters
involved in the analgesia system
o Enkephalins - derived from the
periventricular nuclei and from the
periaqueductal gray area
 cause both presynaptic and
postsynaptic inhibition of
incoming type C and type
Aδ pain fibers where they
synapse in the dorsal horns
o Serotonin - causes local cord
neurons to secrete encephalin
THE BRAIN‘S OPIATE SYSTEM—ENDORPHINS

 An analgesia system is the capability of the AND ENKEPHALINS
brain itself to suppress input of pain signals to
the nervous system by activating a pain Several transmitter substances are involved in the
control system. analgesia system; especially involved are
Consists of three major components:
(1) The periaqueductal gray and periventricular

areas of the mesencephalon and upper pons
surround the aqueduct of Sylvius and portions of the

enkephalin and serotonin
 When a person feels a pain in a part that is

fairly remote from the tissue causing the
pain.
 Knowledge of the different types of referred
pain is important in clinical diagnosis
because in many visceral ailments the only
clinical sign is referred pain.
Mechanism of Referred pain
 The enkephalin is believed to cause both

presynaptic and postsynaptic inhibition of
incoming type C and type Aδ pain fibers
where they synapse in the dorsal horns.
 Morphine-like agents, mainly the opiates,
have been found to act at many other  In the figure, branches of visceral pain fibers
points in the analgesia system. are shown to synapse in the spinal cord on
the same second-order neurons (1 and 2)
 About a dozen such opiate-like substances
that receive pain signals from the skin.
have now been found at different points of
 When the visceral pain fibers are stimulated,
the nervous system. Among the more
pain signals from the viscera are conducted
important of these opiate-like sub-stances through at least some of the same neurons
are β-endorphin, met-enkephalin, leu- that conduct pain signals from the skin, and
enkephalin, and dynorphin the person has the feeling that the
 The two enkephalins are found in the brain sensations originate in the skin.
stem and spinal cord, in the portions of the
analgesia system described earlier, and β-
VISCERAL PAIN
endorphin is present in both the
hypothalamus and the pituitary gland.  Pain from the different viscera of the
Dysmorphin is found mainly in the same abdomen and chest is one of the few
areas as the enkephalins, but in much lower criteria that can be used for diagnosing
quantities. visceral inflammation, visceral infectious
 Thus, activation of the analgesia system by disease, and other visceral ailments
nervous signals entering the periaqueductal  The viscera have sensory receptors for no
gray and periventricular areas, or other modalities of sensation besides pain
inactivation of pain pathways by morphine-  Difference between surface pain and
like drugs, can almost totally suppress many visceral pain:
pain signals entering through the peripheral o Highly localized types of damage to
nerves. the viscera seldom cause severe
pain.
REFERRED PAIN

o Conversely, any stimulus that causes  Conversely, parietal sensations are con-
diffuse stimulation of pain nerve ducted directly into local spinal nerves from
endings throughout a viscus causes the parietal peritoneum, pleura, or
pain that can be severe. For pericardium, and these sensations are
instance, ischemia caused by usually localized directly over the painful
occluding the blood supply to a area.
large area of gut stimulates many
diffuse pain fibers at the same time
and can result in extreme pain. Localization of Referred Pain Transmitted via
―PARIETAL PAIN‖ CAUSED BY VISCERAL Visceral Pathway
DISEASE
 When visceral pain is referred to the surface
•When a disease affects a viscus, the disease of the body, the person generally localizes it
process often spreads to the parietal peritoneum, in the dermatomal segment from which the
visceral organ originated in the embryo, not
pleura, or pericardium. These parietal surfaces, like
necessarily where the visceral organ now
the skin, are supplied with extensive pain
lies.
innervation from the peripheral spinal nerves.
•Pain from the parietal wall overlying a viscus is

frequently sharp.
 An example can emphasize the difference

between this pain and true visceral pain: a
knife incision through the parietal
peritoneum is very painful, whereas a similar
cut through the visceral peritoneum or
through a gut wall is not very painful, if it is
painful at all.
LOCALIZATION OF VISCERAL PAIN—

―VISCERAL‖ AND ―PARIETAL ‖ PAIN
TRANSMISSION PATHWAY S
Pain from the different viscera is frequently difficult  The heart originated in the neck and upper
to localize, for several reasons thorax, so the heart’s visceral pain fibers
pass upward along the sympathetic sensory
 First, the patient‘s brain does not know from
nerves and enter the spinal cord between
firsthand experience that the different
segments C3 and T5.
internal organs exist; therefore, any pain
 As shown in Figure 49-6, pain from the heart is
that originates internally can be localized
referred to the side of the neck, over the
only generally.
shoulder, over the pectoral muscles, down
 Second, sensations from the abdomen and
the arm, and into the substernal area of the
thorax are transmitted through two
upper chest. These are the areas of the
pathways to the central nervous system: the
body surface that send their own
true visceral pathway and the parietal
somatosensory nerve fibers into the C3 to T5
pathway.
cord segments.
 True visceral pain is transmitted via pain
 The stomach originated approximately from
sensory fibers within the autonomic nerve
the seventh to ninth thoracic segments of
bundles, and the sensations are referred to
the embryo. Therefore, stomach pain is
surface areas of the body often far from the
referred to the anterior epigastrium above
painful organ.
the umbilicus, which is the surface area of

the body subserved by the seventh through  Pain is more likely to be spontaneous and is
ninth thoracic segments. described as burning or ‗like an electric
shock‘.
 Pain may be experienced in response to a
stimulus that does not usually cause pain
(allodynia), or there may be a heightened
response to a stimulus that is usually painful
(hyperalgesia)
Parietal Pathway for Transmission of Abdominal and
Thoracic Pain
 Pain from the viscera is frequently localized THE SURGICAL STRESS RESPONSE
to two surface areas of the body at the
same time because of the dual transmission  Surgical stress causes release of cytokines
of pain through the referred visceral (e.g. interleukins-1. interleukin – 6 and tumor
pathway and the direct parietal pathway. necrosis factor alpha) and precipitates
adverse neuroendocrine and
 Figure 49-7 shows dual transmission from an sympathoadrenal response, resulting in

inflamed appendix. detrimental physiologic responses,
1. Pain impulses pass first from the appendix particularly in high-risk patients.
through visceral pain fibers located within  Increased secretion of the catabolic
sympathetic nerve bundles, and then into hormones such as GH, cortisol, glucagon
the spinal cord at about T10 or T11; this pain
and catecholamines and the decreased
is referred to an area around the umbilicus
secretion of anabolic hormones such as
and is of the aching, cramping type.
insulin and testosterone characterize the
2. Pain impulses also often originate in the
parietal peritoneum where the inflamed neuroendocrine response.
appendix touches or is adherent to the  The end result of this is hyperglycemia and
abdominal wall. These impulses cause pain negative nitrogen balance, the
of the sharp type directly over the irritated consequences of which is POOR WOUND
peritoneum in the right lower quadrant of HEALING, MUSCLE WASTING, FATIGUE AND
the abdomen. IMPAIRED IMMUNOCOMPETENCY
CONSEQUENCES OF POOR LY M ANAGED

NEUROPATHIC PAIN
ACUTE PAIN
Neuropathic pain has some different characteristics
to nociceptive pain.

signals can be either inhibited or facilitated by

neural pathways. This capacity to modulate
signaling may account, in part, for wide variations
in pain perception between different individuals
who sustain the same injury
1. Transduction – event whereby noxious

thermal, chemical, or mechanical stimuli are
converted into an action potential
2. Transmission – occurs when the action
potential is conducted through the nervous
system via the first order, second and third
order neurons, which have cell bodies
located in the dorsal root ganglion, dorsal
NOTE: Consequences of poorly managed acute horn and thalamus respectively.
pain 3. Modulation - involves altering afferent neural
transmission along pain pathway.
 Cardiovascular:
a. Dorsal horn of the spinal cord - most
o Increased heart rate
common site for modulation of the
o Hypertension
pain pathway, and modulation can
o Increase in cardiac workload
involve either inhibition or
 Pulmonary:
augmentation of the pain signals
o Difficulty of expanding the lungs
b. Examples of Inhibitory spinal
o Respiratiory Muscle spasm or
modulation include:
squinting
i. Release of inhibitory
o Hypoxia
neurotransmitters such as
Increased Risk of pulmonary infection (that‘s why GABA and glycine by intrinsic
there is increased risk of pneumonia after surgery) spinal neurons
ii. Activation of descending
 If patient doesn‘t want to move around efferent neuronal pathways
because it is painful, there is a post- from the motor cortex,
operative ileus. Patients don‘t want to hypothalamus,
ambulate because they‘d rather lie down in preaqueductal gray matter,
bed since it is too painful to move around. and the nucleus raphe
There is increased risk of: magnus which results in the
o oliguria release of NE, SE and
o urinary infection endorphins in the dorsal horn
o post-operative ileus. 4. Perception – final common pathway which
o limited circulation in the periphery, results from the integration of the painful
esp. to extremities input into the somatosensory and limbic
o increased risk of thromboemboli cortices
o impaired immune function. a. Traditional analgesic therapies have
only targeted pain perception
PAIN PROCESSING  A multimodal approach to pain therapy
should target all four elements of the pain
The neurophysiologic underpinnings of pain can be
processing pathway
divided into four stages: transduction, transmission,
pain modulation, and perception. At every point in
SENSTITIZATION
the process, the intensity and propagation of pain

 Process that occurs after neurogenic spinal cord level

inflammation when neurons become more
responsive to both nociceptive and non-
nociceptive stimuli.
o NOTES: (examples given by doc)
Peripheral – Pinch on the skin
Central - Toothache
o decreased in thresholds of response,
increase in magnitude of response,
expansion of receptive field, and
emergence of spontaneous activity.
o sensitization processes occur in
primary afferent neurons (peripheral
sensitization) and in TNC and higher-
order neurons (central sensitization).
o Sensitization play a role in a. It helps to explain why when we
transformation of episodic to chronic bang our head, it feels better when
migraine and in each migraine we rub it. By activating Aβ fibres with
attack tactile, non-noxious stimuli inhibitory
interneurones in the dorsal horn are
activated leading to inhibition of
pain signals transmitted via C fibres
2. Descending inhibition pathway
a. The periaqueductal grey (PAG) in
the midbrain and the rostral
ventromedial medulla (RVM) -
important areas of the brain involved
in descending inhibitory modulation
i. contain high concentrations
of opioid receptors and
endogenous opioids, which
helps explain why opioids are
analgesic.
b. Descending pathways project to the
 Hyperalgesia - defined as an exaggerated dorsal horn and inhibit pain
pain response to a normally painful stimulus transmission. These pathways are
 Allodynia - defined as a painful response to monoaminergic, utilising
a typically non-painful stimulus. noradrenaline and serotonin as
neurotransmitters.
INHIBITION OF PAIN T RANSMISSION
STRATEGIES FOR ACUTE PAIN M ANAGEMENT
1. Gate control theory of pain- proposed by
Melzack and Wall in 1965 to describe a 1. Differentiate types of Pain:
process of inhibitory pain modulation at the a. Nociceptive/Somatic
b. Visceral
c. Neuropathic
2. Sex of Patient
NOTES:According to studies, women have
higher threshold of pain because we are the
ones who are able to deliver baby. Men have c. The Verbal Rating Score (VRS)
low threshold of pain. So chances are, if i. List of adjectives that
your patient is a male, they are more likely describe pain intensity,
including no pain, mild,
to ask for pain reliever compared to a
moderate, severe, and very
female.
severe o Used with adults to
explain levels of pain intensity
d. The Wong Baker FACES Pain Scale
3. Assessment of Acute Pain
a. The Numeric Rating Score (NRS)

i. Simplest scale to use, no
equipment needed i. Six gender neutral faces,
ii. Ask the person to rate their ranging from no pain to worst
pain intensity on a scale of 0- pain
10, with 0 being ‗no pain‘ ii. Scored from 0-10
and 10 being ‗the worst pain iii. Can be used for children 4-
ever experienced‘ 18 to illicit information on
iii. Applicable for anyone over pain intensity
the age of 8 with adequate
cognitive abilities NOTES:After assessing pain we now go to managing
b. The Visual Analogue Scale (VAS) the pain. In the body we have opioid receptors.
Women have more opioid receptors compared to
men thus women are more capable of tolerating
pain.
CLINICAL CORRELATES:
1.ACUTE PAIN - Analgesic medications are a first line

of treatment in these cases
2.CHRONIC PAIN - The pain-generating mechanism

is often difficult or impossible to determine with
certainty
i. Use of a 10cm ruler with ‗no
pain‘ written at the 0cm mark -psychological evaluation and behaviorally
and ‗worst pain ever‘ written based treatment paradigms are frequently helpful
at the 10cm mark
ii. Ask the person to place a - Arthritis, cancer, chronic daily headaches,
mark on the scale to fibromyalgia, and diabetic neuropathy are
represent the severity of their examples of this
pain

- depression is the most common emotional

disturbance in patients with chronic pain
OPIODS
 Opium- among the oldest drugs in the 1. Mu

world. 2. Kappa
 Fossilized opium poppies have been found 3. Delta
in Neanderthal excavation sites dating back
to 30,000 B.C. Located in 3 sites:
 Sumerians, Egyptians, Greeks, Romans and
1. Periphery – following inflammation
Chinese 4000 B.C.
2. Spinal cord Dorsal Horn
 Friedrich Serturner – isolated Morphine (after
3. Supraspinally in the brainstem, thalamus and
the Greek god of dreams, Morpheus)
cortex
 Morphine was 10-fold more potent than
NOTE: That is why we can give opioids
opium and soon replaced it not only for the
treatment of severe pain but also for myriad through spinal anaesthesia because there are
of other purposes such as cough and receptors located there.
diarrhea.
1. MORPHINE
a. prototype opioid (Gold standard for
analgesics)
b. Plasma half-life: 2 hours
c. Duration of action: 4-5 hours
d. Hepatic glucoronidationmorphine 6
glucoronide and Morphine 3
glucoronide
e. Cleared by kidneys
3 OPIOID RECEPTORS: 2. FENTANYL - synthetic opioid chemically
related to phenylpiperidines
a. relatively selective mu receptor
agonist
b. 80 times the potency of morphine IV
admin
c. metabolized in liver; excreted in
kidneys
3. MEPERIDINE – a phenylpiperidine

a. synthetic mu opioid receptor agonist 2, which converts arachidonic acid to

with a short half-life prostaglandin H2 (PGH2).
b. biotransformed by liver to  The COX enzyme consists of 2 active sites:
normeperidine – neurotoxic o Cyclooxygenase
c. repetitive dosing can cause o Peroxidase
accumulation of normeperidine which
may lead to seizures  COX-1 produces prostaglandins, which are
important for general ―housekeeping‖
(mosly used by OB) it is known by demerol for
epidural management in laboring women. Drug of o functions as gastric protection and
choice for patients in labor administered through hemostasis
epidural.
 COX-2 is the inducible form of the enzyme
4. NALBUPHINE -a mixed agonist/antagonist that produces prostaglandins that mediate
opioid modulator. pain, inflammation, fever and
a. Specifically, it acts as a moderate- carcinogenesis.
efficacy partial agonist agonist or
 PGE2 – key mediator of both peripheral and
antagonist of the μ-opioid receptor
central pain sensitization
and as a high-efficacy partial agonist
of the κ-opioid receptor. Different Types of NSAIDS
NOTES FROM DOC:  Mefenamic Acid

 Ibuprofen
It acts on moderate efficacy partial agonist. Partial
 Ketorolac
agonist and antagonist means it can act on mu
receptor as an opioid and it can also antagonize *These are Non-Selective meaning it acts on both
opioid on kappa opioid receptor. So it acts on two cyclooxygenase and peroxidase
opioid receptors.
 Celecoxib
If you are going to give morphine to a patient who  Parecoxib
was already given nalbuphine, it will antagonize the
analgesic effect of nalbuphine. The morphine will *Both works on cyclooxygenase (COX-2)
now no longer be effective.
Paracetamol(Acetaminophen)–analgesic,
However, if you have morphine overdose, there is antipyretic. It treats pain mainly by blocking COX-2
too much analgesic that could result to nausea mostly in the central nervous system, but not much
and vomiting from morphine, you can give in the rest of the body.
nalbuhpine to counteract the effects of your
morphine. Or if morphine caused rashes, you give QUESTIONS
nalbuphine to counteract the rashes. So it is an
1. A second-order neuron carrying nociceptive
antagonist to other opioids.
information from the right leg has been badly
damaged. Which structure will not receive input
NON STEROIDAL ANTI -INFLAMM ATORY DRUGS
from this neuron?
(NSAIDS)
a. Right ventral posterolateral nucleus of the
 most commonly used drugs in the world
because of their anti-inflammatory, thalamus
analgesic and antipyretic effects. b. Left ventral posterolateral nucleus of the
 mediated through the inhibition of
thalamus
cyclooxygenase (COX) enzymes
(prostaglandin H2 synthetases), types 1 and c. Left primary somatosensory cortex
d. Right anterior white commissure of the spinal c. An increase in number of NMDA receptors, as
cord well as increased sensitivity of NMDA receptors to
glutamate.
2. What evolutionary changes would increase the
sensitivity of mouse forepaws? d. An increase in number of voltage-gated sodium
channels.
a. Increasing the size of the receptive fields and
receptor density in the forepaws; with the 5. How does morphine works at the level of the
corresponding increase in the forepaw primary spinal cord?
somatosensory cortex.
a. It reduces neurotransmitter release from the
b. Increasing the size of the receptive fields but first-order neuron and induces the hyperpolarisation
reducing the receptor density in the forepaws; with of the second-order neuron via binding to
the corresponding reduction in the forepaw primary glutamate receptors.
b. It reduces neurotransmitter release from the
c. Reducing the size of the receptive fields but first-order neuron and induces the hyperpolarisation
increasing the receptor density in the forepaws; of the second-order neuron via binding to opioid
with the corresponding increase in the forepaw receptors.
primary somatosensory cortex.
c. It reduces neurotransmitter release from the
d. Reducing the size of the receptive fields but second-order neuron and induces the
reducing the receptor density in the forepaws; with hyperpolarisation of the first-order neuron via
the corresponding increase in the forepaw primary binding to opioid receptors.
d. It reduces neurotransmitter release from the
3. Pain sensations have usually two discernible first-order neuron and induces depolarisation of the
components: the first sharp brief pain; followed by a second-order neuron via binding to opioid
deep, dull, longer-lasting ache. Which nociceptors receptors.
are responsible for these components?
6 .Many nerve fibers derived from the
a. Sharp pain: C fibres; dull long-lasting ache: Aδ periventricular nuclei and from the periaqueductal
fibres gray area secrete what transmitter substance at
their endings?
b. Both components are transmitted by Aδ fibres
a. Serotonin
c. Sharp pain: Aδ fibres; dull long-lasting ache: C
fibres b. Enkephalin
d. Sharp pain: AB fibres; dull long-lasting ache: C c. Glutamate

fibres
d. Dopamine
4. What is the mechanism of central sensitisation of
the spinal cord? e. Norepinephrine
a. An increase in number of opioid mu receptors, as 7. Choose the three major components in analgesia
well as increased sensitivity of opioid mu receptors system:
to Β-endorphins
a. Raphe magnus nucleus and nucleus
b. Tissue-mediated release of 5-HT and arachidonic reticularis paragigantocellularis
acid
b. Intralaminar nuclei of the thalamus

c. Reticular nuclei of the brain stem D. None of the above
d. Periaqueductal gray and periventricular 12. Pain intensity d/t heat is directly correlated to?
areas
A. Person being a lil bitch
e. Periventricular nuclei in the hypothalamus
B. Rate of tissue damage
f. Dorsal horns of the spinal cord
C. Total tissue damage
8. Which of the following might be the agent most
responsible for causing pain after tissue damage? 13.What aggravates pain during tissue ischemia?
a. Bradykinin A. Low oxygen level
b. Serotonin B. Person being a lil bitch, ese
c. Histamine C. High metabolic rate
d. Potassium ions D. Blood flow
e. Acetylcholine
9. This type of pain is felt when a needle is stuck into 14. Which is not an alternative name for fast pain?
the skin, when the skin is cut with a knife, or when
A. Sharp pain
the skin actually burned.
B. Throbbing pain
a. slow burning pain
C. Acute pain
b. nauseous pain
D. Electric pain
c. aching pain
OPIOIDS
d. sharp pain
Questions 1 and 2. A 63-year-old man is undergoing
e. throbbing pain
radiation treatment as an outpatient for metastatic
10. It is much older system and transmits pain bone cancer. His pain has been treated with a
mainly from the peripheral slow- chronic type C fixed combination of oxycodone plus
pain fibers, although it does transmit some signals acetaminophen taken orally. Despite increasing
from type Aδ fibers as well. doses of the analgesic combination, the pain is
getting worse.
a. Neospinothalamic tract
1. The most appropriate oral medication for his
b. Paleospinothalamic pathway increasing pain is
a. Buprenorphine
c. Anterolateral pathway b. Codeine plus aspirin
c. Hydromorphone
11.Which of the following pain sitmuli does not d. Pentazocine
cause fast pain? e. Tramadol
2. It is possible that this patient will have to
A. Mechanical
increase the dose of the analgesic as his
condition progresses as a result of
B. Thermal
developing tolerance. However, tolerance
C. Chemical

will not develop to a significant extent with vomiting. His symptoms include hyperventilation
respect to and hyperthermia. The attending physician notes
a. Biliary smooth muscle that his pupil size is larger than normal.
b. Emesis
c. Pupillary constriction 6. What is the most likely cause of these signs
d. Sedation and symptoms?
e. Urinary retention a. The patient had injected
3. You are on your way to take an dextroamphetamine
examination and you suddenly get an b. The patient has hepatitis B
attack of diarrhea. If you stop at a nearby c. The patient has overdosed with an
drugstore for an over-the-counter opioid opioid
with antidiarrheal action, you will be asking d. The signs and symptoms are those of
for the opioid abstinence syndrome
a. Codeine e. These are early signs of toxicity due
b. Dextromethorphan to contaminants in ―street heroin‖
c. Diphenoxylate 7. Which drug will be most effective in
d. Loperamide alleviating the symptoms experienced by
e. Nalbuphine this patient?
4. An emergency department patient with a. Buprenorphine
severe pain thought to be of gastrointestinal b. Codeine
origin received 80 mg of meperidine. He c. Methadone
subsequently developed a severe reaction d. Naltrexone
characterized by tachycardia, e. Tramadol
hypertension, hyperpyrexia, and seizures. 8. Which statement about nalbuphine is
Questioning revealed that the patient had accurate?
been taking a drug for a psychiatric a. Activates μ receptors
condition. Which drug is most likely to be b. Does not cause respiratory
responsible for this untoward interaction with depression
meperidine? c. Is a nonsedating opioid
a. Alprazolam d. Pain-relieving action is not superior to
b. Bupropion that of codeine
c. Lithium e. Response to naloxone in overdose
d. Phenelzine may be unreliable
e. Mirtazapine 9. Which drug does not activate opioid
5. Genetic polymorphisms in certain hepatic receptors, has been proposed as a
enzymes involved in drug metabolism are maintenance drug in treatment programs
established to be responsible for variations in for opioid addicts, and with a single oral
analgesic response to dose, will block the effects of injected heroin
a. Buprenorphine for up to 48 h?
b. Codeine a. Fentanyl
c. Fentanyl b. Nalbuphine
d. Methadone c. Naloxone
e. Tramadol d. Naltrexone
e. Propoxyphene
10. Which drug is a full agonist at opioid
receptors with analgesic activity equivalent
Questions 6 and 7. A young male patient is brought
to morphine, a longer duration of action,
to the emergency department in an anxious and
and fewer withdrawal signs on abrupt
agitated state. He informs the attending physician
discontinuance than morphine?
that he uses ―street drugs‖ and that he gave himself a. Fentanyl
an intravenous ―fix‖ approximately 12 h ago. He b. Hydromorphone
now has chills and muscle aches and has also been c. Methadone
d. Nalbuphine 5. The main advantage of ketorolac over aspirin is

e. Oxycodone that ketorolac
(A) Can be combined more safely with an opioid
such ascodeine
(B) Can be obtained as an over-the-counter agent
(C) Does not prolong the bleeding time
NSAIDS
(D) Is available in a parenteral formulation that can
1. Among NSAIDs, aspirin is unique because it beinjected intramuscularly or intravenously
(A) Irreversibly inhibits its target enzyme (E) Is less likely to cause acute renal failure in
patients withsome preexisting degree of renal
(B) Prevents episodes of gouty arthritis with long-
impairment
term use
6. An 18-month-old boy dies from an accidental
(C) Reduces fever
overdose of acetaminophen. Which of the
(D) Reduces the risk of colon cancer following is the most likely cause of this patient‘s
(E) Selectively inhibits the COX-2 enzyme death?
2. Which of the following is an analgesic and (A) Arrhythmia

antipyretic drug that lacks an anti-inflammatory (B) Hemorrhagic stroke
action?
(C) Liver failure
(A) Acetaminophen
(D) Noncardiogenic pulmonary edema
(B) Celecoxib
(E) Ventilatory failure
(C) Colchicine
(D) Indomethacin
Questions 7 and 8. A 52-year-old woman presented
(E) Probenecid with intense pain, warmth, and redness in the first
3. A 16-year-old girl comes to the emergency toe on her left foot. Examination of fluid withdrawn
department suffering from the effects of an aspirin from the inflamed joint revealed crystals of uric
overdose. Which of the following syndromes is this acid.
patient most likely to exhibit as a result of this drug
overdose?
(A) Bone marrow suppression and possibly aplastic
7. In the treatment of this woman‘s acute attack of
anemia
gout, a high dose of colchicine will reduce the pain
(B) Fever, hepatic dysfunction, and and inflammation. However, many physicians
encephalopathy prefer to treat acute gout with a corticosteroid or
(C) Hyperthermia, metabolic acidosis, and coma indomethacin because high doses of colchicine
are likely to cause
(D) Rapid, fulminant hepatic failure
(A) Behavioral changes that include psychosis
(E) Rash, interstitial nephritis, and acute renal failure
(B) High blood pressure
4. Which of the following drugs is most likely to
increase serum concentrations of conventional (C) Rash
doses of methotrexate, a weak acid that is primarily (D) Severe diarrhea
cleared in the urine?
(E) Sudden gastrointestinal bleeding
(A) Acetaminophen
8. Over the next 7 mo, the patient had 2 more
(B) Allopurinol attacks of acute gout. Her serum concentration of
(C) Colchicine uric acid was elevated. The decision was made to
put her on chronic drug therapy to try to prevent
(D) Hydroxychloroquine subsequent attacks. Which of the following drugs
(E) Probenecid could be used to decrease this woman‘s rate of
production of uric acid?

(A) Allopurinol 6. B Rationale: Several transmitter substances

(B) Aspirin are involved in the analgesia system;
especially involved are enkephalin and
(C) Colchicine
serotonin. Many nerve fibers derived from the
(D) Hydroxychloroquine periventricular nuclei and from the
(E) Probenecid periaqueductal gray area secrete enkephalin
at their endings. Thus, the endings of many
Questions 9 and 10. A 54-year-old woman fibers in the raphe magnus nucleus release
presented with signs and symptoms consistent with enkephalin when stimulated.
an early stage of rheumatoid arthritis. The decision 7. A D F Rationale: The analgesia system
was made to initiate NSAID therapy. consists of three major components: (1) The
9. Which of the following patient characteristics is periaqueductal gray and periventricular
the most compelling reason for avoiding celecoxib areas of the mesencephalon and upper pons
in the treatment of her arthritis? surround the aqueduct of Sylvius and portions
(A) History of alcohol abuse of the third and fourth ventricles. Neurons from
these areas send signals to (2) the raphe
(B) History of gout
magnus nucleus, a thin midline nucleus
(C) History of myocardial infarction
located in the lower pons and upper medulla,
(D) History of osteoporosis and the nucleus reticularis paragiganto
(E) History of peptic ulcer disease cellularis, located laterally in the medulla.
10. Although the patient‘s disease was adequately From these nuclei, second-order signals are
controlled with an NSAID and methotrexate for transmitted down the dorsolateral columns in
some time, her symptoms began to worsen and the spinal cord to (3) a pain inhibitory
radiologic studies of her hands indicated complex located in the dorsal horns of the
progressive destruction in the joints of several spinal cord.
fingers. Treatment with another second-line agent
8. A Rationale: One chemical that seems to be
for rheumatoid
more painful than others is bradykinin.
arthritis was considered. Which of the following is a Researchers have suggested that bradykinin
parenterally administered DMARD whose
might be the agent most responsible for
mechanism of anti-inflammatory action is
antagonism of tumor necrosis factor? causing pain after tissue damage. Also, the
intensity of the pain felt correlates with the
(A) Cyclosporine
local increase in potassium ion concentration
(B) Etanercept or the increase in proteolytic enzymes that
(C) Penicillamine directly attack the nerve endings and excite
(D) Phenylbutazone pain by making the nerve membranes more
permeable to ions.
(E) Sulfasalazine
9. D Rationale: Fast pain is also described by
many alternative names, such as sharp pain,
pricking pain, acute pain, and electric pain.
This type of pain is felt when a needle is stuck
into the skin, when the skin is cut with a knife,
ANSWERS AND RATIONALE or when the skin is acutely burned. It is also felt
when the skin is subjected to electric shock.
1. B
Fast-sharp pain is not felt in most deep tissues
2. C
of the body.
3. C
10. B Rationale: The paleospinothalamic pathway
4. C
is a much older system and transmits pain
5. B
mainly from the peripheral slow-chronic type

C pain fibers, although it does transmit some 3. The answer is D Codeine and nalbuphine could
signals from type Aδ fibers as well. In this decrease gastrointestinal peristalsis, but not without
pathway, the peripheral fibers terminate in marked side effects (and a prescription).
the spinal cord almost entirely in laminae II Dextromethorphan is a cough suppressant. The
and III of the dorsal horns, which together are other 2 drugs listed are opioids with antidiarrheal
called the substantia gelatinosa, as shown by actions. Diphenoxylate is not available over the
the lateral most dorsal root type C fiber. counter because it is a constituent of a proprietary
11. C Rationale: chemical released during tissue combination that includes atropine sulfate
damage (bradykinin, serotonin, etc) involved (Lomotil)..
in slow chronic pain
12. B Rationale: at 45 degree, tissue damage 4. The answer is D Concomitant administration of
begins. If tissue continued to be exposed to meperidine and monoamine oxidase inhibitors such
this temp, tissue continues to be destroyed as isocarboxazid or phenelzine has resulted in life-
13. C Rationale: high metabolic rate tissue has threatening hyperpyrexic reactions that may
more rapid progression of pain probably d/t culminate in seizures or coma. Such reactions have
lactic acid, bradykinin, proteolytic enzymes occurred even when the MAO inhibitor was
faster release administered more than a week after a patient had
14. B Rationale: throbbing pain is a slow-chronic been treated with meperidine. Note that
pain concomitant use of selective serotonin reuptake
inhibitors and meperidine has resulted in the
serotonin syndrome, another life-threatening drug
interaction.
RATIONALE FOR OPIOIDS
5. The answer is B Codeine, hydrocodone, and
1. The answer is C.In most situations, pain oxycodone are metabolized by the cytochrome
associated with metastatic carcinoma ultimately P450 isoform CYP2D6, and variations in analgesic
necessitates the use of an opioid analgesic that is response to these drugs have been attributed to
equivalent in strength to morphine, so genotypic polymorphisms in this isozyme. In the
hydromorphone, oxymorphone, or levorphanol case of codeine, this may be especially important
would be indicated. Pentazocine or the since the drug is demethylated by CYP2D6 to form
combination of codeine plus salicylate would not the active metabolite, morphine.
be as effective as the original drug combination.
Propoxyphene is even less active than codeine 6. The answer is D The signs and symptoms are those
alone. Buprenorphine, a mixed agonist-antagonist, of withdrawal in a patient physically dependent on
is not usually recommended for cancer-associated an opioid agonist. They usually start within 6–10 h
pain because it has a limited maximum analgesic after the last dose; their intensity depends on the
effect (―ceiling‖) and because of possible degree of physical dependence, and peak effects
dysphoric and psy-chotomimetic effects. usually occur at 36–48 h. Mydriasis is a prominent
feature of the abstinence syndrome; other
2. The answer is C.Chronic use of strong opioid symptoms include rhinorrhea, lacrimation,
analgesics leads to the development of tolerance piloerection, muscle jerks, and yawning.
to their analgesic, euphoric, and sedative actions.
Tolerance also develops to their emetic effects and 7. The answer is C Prevention of signs and symptoms
to effects on some smooth muscle, including the of withdrawal after chronic use of a strong opiate
biliary and the urethral sphincter muscles. However, like heroin requires replacement with another strong
tolerance does not develop significantly to the opioid analgesic drug. Methadone is most
constipating effects or the miotic actions of the commonly used, but other strong μ-receptor
opioid analgesics. agonists would also be effective. Acetaminophen
and codeine will not be effective. Beneficial effects
of diazepam are restricted to relief of anxiety and
agitation. The antagonist drug naltrexone may anti-inflammatory effects. Colchicine is a drug used
exacerbate withdrawal symptoms. for gout that also has an anti-inflammatory action.
Probenecid is a uricosuric drug that promotes the
excretion of uric acid.
3. The answer is C. Salicylate intoxication is
associated with metabolic acidosis, dehydration,
and hyperthermia. If these problems are
8. The answer is E Nalbuphine and butorphanol are notcorrected, coma and death ensue.
κ agonists, with weak μ-receptor antagonist activity.
4. The answer is E Like other weak acids,
They have analgesic efficacy superior to that of
methotrexate depends on active tubular excretion
codeine, but it is not equivalent to that of strong in the proximal tubule for efficient elimination.
opioid receptor agonists. Although these mixed Probenecid competes with methotrexate for
agonist-antagonist drugs are less likely to cause binding to the proximal tubule transporter and
respiratory depression than strong μ activators, if thereby decreases the rate of clearance of
depression does occur, reversal with opioid methotrexate.
antagonists such as naloxone is unpredictable. 5. The answer is D. Ketorolac exerts typical NSAID
Sedation is common. effects. It prolongs the bleeding time and can
impair renal function, especially in a patient with
9. The answer is D.The opioid antagonist naltrexone preexisting renal disease. Its primary use is as a
has a much longer half-life than naloxone, and its parenteral agent for pain management, especially
for treatment of postoperative patients.
effects may last 2 days. A high degree of client
compliance would be required for naltrexone to be 6. The answer is C. In overdose, acetaminophen
of value in opioid dependence treatment causes fulminant liver failure as a result of its
conversion by hepatic cytochrome P450 enzymes
programs. The same reservation is applicable to the
to a highly reactive metabolite.
use of naltrexone in alcoholism.
7. The answer is D. At doses needed to treat acute
10. The answer is C Fentanyl, hydromorphone, and gout, colchicine frequently causes significant
methadone are full agonists with analgesic efficacy diarrhea. Such gastrointestinal effects are less likely
with the lower doses used in chronic gout.
similar to that of morphine. When given
intravenously, fentanyl has a duration of action of 8. The answer is A Allopurinol is the only drug listed
just 60–90 min. Hydromorphone has poor oral that decreases production of uric acid. Probenecid
increases uric acid excretion. Colchicine and
bioavailability. Methadone has the greatest
hydroxychloroquine do not affect uric acid
bioavailability of the drugs used orally, and its metabolism. Aspirin actually slows renal secretion of
effects are more prolonged. Tolerance and uric acid and raises uric acid blood levels. It should
physical dependence develop, and dissipate, not be used in gout..
more slowly with methadone than with morphine. 9. The answer is C. Celecoxib is a COX-2-selective
These properties underlie the use of methadone for inhibitor. Although the COX-2 nhibitors have the
detoxification and maintenance programs. advantage over nonselective NSAIDs of reduced
gastrointestinal toxicity, clinical data suggest that
they are more likely to cause arterial thrombotic
events. A history of myocardial infarction would be
a compelling reason to avoid a COX-2 inhibitor.
10. The answer is B. Etanercept is a recombinant
RATIONALE FOR NSAIDS
protein that binds to tumor necrosis factor and
prevents its inflammatory effects.
1. The answer is A Aspirin differs from other NSAIDs
by irreversibly inhibiting cyclooxygenase..
2. The answer is A.Acetaminophen is the only drug
that fits this description. Indomethacin is a
nonselective COX inhibitor and celecoxib is a COX-
2 inhibitor; both have analgesic, antipyretic, and

REFERENCES
Jameson, J. L. MD, PhD, Kasper, D. L. MD, Longo, D.
L. MD, Fauci, A. S. MD, Hauser, S. L. MD,
Loscalzo, J. MD, PhD (2018). Part II. Section 1.
Chapter 10: Pain: Pathophysiology and
Management. Harrison‘s Principles of
Internal Medicine (20th ed., pp. 65-68).
United States. The McGraw-Hill Inc.
Hall, J. E., PhD, Hall, M. E., MD, MS, & Guyton, A.C
, A. C. (2016). Chapter 49: Somatic
Sensations: Pain, Headache, and
Thermal Sensations. In Guyton and
Hall Textbook of Medical Physiology (13th
ed., pp. 621-625).
Opioid Analgesics & Antagonists. (2015). In A. J.
Trevor PhD, B. G. Katzung PhD, & M.
Kruidering-Hall PhD (Eds.), Katzung and
Trevor's Pharmacology Examination & Board
Review (11th ed., pp. 257-258). New York
City, New York: McGraw Hill.
NSAIDS, Acetaminophen, & Drugs Used in
Rheumatoid Arthritis & Gout. (2015). In A. J.
Trevor PhD, B. G. Katzung PhD, & M.
Kruidering-Hall PhD (Eds.), Katzung and
Trevor's Pharmacology Examination & Board
Review (11th ed., pp. 302-303). New York
City, New York: McGraw Hill.


Mechanism of Pain and Pain Management: Questions ANSWERS and Rationale References

Uploaded by

Document Information

Original Description:

Original Title

Copyright

Available Formats

Share this document

Share or Embed Document

Sharing Options

Did you find this document useful?

Is this content inappropriate?

Copyright:

Available Formats

Mechanism of Pain and Pain Management: Questions ANSWERS and Rationale References

Uploaded by

Copyright:

Available Formats

MSU-COLLEGE OF MEDICINE

LEVEL 1 LOCOMOTOR MODULE

MECHANISM OF PAIN QUESTIONS ................................................... 15

TABLE OF CONTENTS PAIN

 sharp pain signals, which are then conducted to

 Important in stimulating the slow,

•Prostaglandins and substance P - enhance the

Nonadapting Nature of Pain Receptors

 chronic pain  Pain receptors adapt very little and

Badelles. But-oy. Gayloa. Lucman. Macabanding.

 Bradykinin and proteolytic enzymes – also

Muscle Spasm as a Cause of Pain

Tissue Ischemia as a Cause of Pain

 The fast type Aδ pain fibers transmit mainly

mechanical and acute thermal pain.

 The fast-sharp type of pain can be localized  Substance P – probable slow-chronic

Projection of the Paleospinothalamic Pathway

paleospinothalamic pathway - much older

o (1) the reticular nuclei of the

Poor Capability of the Nervous System to Localize

 Localization of pain transmitted by way of

Badelles. But-oy. Gayloa. Lucman. Macabanding.

THE BRAIN‘S OPIATE SYSTEM—ENDORPHINS

Consists of three major components:

(1) The periaqueductal gray and periventricular

Badelles. But-oy. Gayloa. Lucman. Macabanding.

enkephalin and serotonin

 When a person feels a pain in a part that is

 The enkephalin is believed to cause both

Badelles. But-oy. Gayloa. Lucman. Macabanding.

•Pain from the parietal wall overlying a viscus is

 An example can emphasize the difference

LOCALIZATION OF VISCERAL PAIN—

Badelles. But-oy. Gayloa. Lucman. Macabanding.

 Figure 49-7 shows dual transmission from an sympathoadrenal response, resulting in

CONSEQUENCES OF POOR LY M ANAGED

Badelles. But-oy. Gayloa. Lucman. Macabanding.

signals can be either inhibited or facilitated by

1. Transduction – event whereby noxious

Badelles. But-oy. Gayloa. Lucman. Macabanding.

 Process that occurs after neurogenic spinal cord level

3. Assessment of Acute Pain

a. The Numeric Rating Score (NRS)

1.ACUTE PAIN - Analgesic medications are a first line

2.CHRONIC PAIN - The pain-generating mechanism

Badelles. But-oy. Gayloa. Lucman. Macabanding.

- depression is the most common emotional

 Opium- among the oldest drugs in the 1. Mu

Badelles. But-oy. Gayloa. Lucman. Macabanding.

a. synthetic mu opioid receptor agonist 2, which converts arachidonic acid to

NOTES FROM DOC:  Mefenamic Acid

d. Sharp pain: AB fibres; dull long-lasting ache: C c. Glutamate

Badelles. But-oy. Gayloa. Lucman. Macabanding.

c. Reticular nuclei of the brain stem D. None of the above

a. Bradykinin A. Low oxygen level

b. Serotonin B. Person being a lil bitch, ese

c. Histamine C. High metabolic rate

d. Potassium ions D. Blood flow

Badelles. But-oy. Gayloa. Lucman. Macabanding.

d. Nalbuphine 5. The main advantage of ketorolac over aspirin is

2. Which of the following is an analgesic and (A) Arrhythmia

Badelles. But-oy. Gayloa. Lucman. Macabanding.