Pain

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Definition:
Pain is defined by the International Association for the Study of Pain (IASP) as “an
unpleasant sensory and emotional experience associated with actual or potential
tissue damage, or described in terms of such damage”.

Also known as: a feeling of distress, suffering or agony, caused by stimulation of

specialized nerve endings. Its purpose is chiefly protective; it acts as a warning
that tissues are being damaged and induces the sufferer to remove or withdraw
from the source.

All receptors for pain stimuli are free nerve endings of groups of myelinated or
unmyelinated neural fibers abundantly distributed in the superficial layers of the
skin and in certain deeper tissues such as the periosteum, surfaces of the joints,
arterial walls, and the falx and tentorium of the cranial cavity. The distribution of
pain receptors in the gastrointestinal mucosa apparently is similar to that in the
skin; thus, the mucosa is quite sensitive to irritation and other painful stimuli.
Although the parenchyma of the liver and the alveoli of the lungs are almost
entirely insensitive to pain, the liver as an organ and the bile ducts are extremely
sensitive, as are the bronchi, ureters, parietal pleura and peritoneum.

Some pain receptors are selective in their response to stimuli, but most are
sensitive to more than one of the following types of excitation: (1) mechanical
stress of trauma; (2) extremes of heat and cold; and (3) chemical substances,
such as histamine, potassium ions, acids, prostaglandins, bradykinin and
acetylcholine.
The conscious perception of pain probably takes place in the thalamus and lower
centers; interpretation of the quality of pain is probably the role of the cerebral
cortex.

There are some naturally occurring internal systems in the body that are known to
control pain but none of them has been completely verified. One of the best

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known is the gate control system in which it is thought that pain impulses are
mediated in the substantia gelatinosa of the spinal cord.

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Sources of pain [Types of Pain]:
The experience of physiological pain can be grouped according to the source and
related nociceptors (pain-detecting neurons).

• Cutaneous pain is
caused by injury to the skin or
superficial tissues. Cutaneous
nociceptors terminate just
below the skin, and due to the
high concentration of nerve
endings, produce a well-
defined, localized pain of
short duration. Examples of
injuries that produce
cutaneous pain include paper
cuts, minor cuts, minor (first
degree) burns and
lacerations.

• Somatic pain
originates from ligaments,
tendons, bones, blood vessels, and even nerves themselves. It is detected with
somatic nociceptors. The scarcity of pain receptors in these areas produces a
dull, poorly-localized pain of longer duration than cutaneous pain; examples
include sprains and broken bones. Myofascial pain usually is caused by trigger
points in muscles, tendons and fascia, and may be local or referred.

• Visceral pain originates from body's viscera, or organs. Visceral

nociceptors are located within body organs and internal cavities. The even
greater scarcity of nociceptors in these areas produces pain that is usually
more aching and of a longer duration than somatic pain. Visceral pain is
extremely difficult to localize, and several injuries to visceral tissue exhibit
"referred" pain, where the sensation is localized to an area completely
unrelated to the site of injury. Myocardial ischemia (the loss of blood flow to a
part of the heart muscle tissue) is possibly the best known example of referred
pain; the sensation can occur in the upper chest as a restricted feeling, or as
an ache in the left shoulder, arm or even hand. The popularized term "brain
freeze" is another example of referred pain, in which the vagus nerve is cooled

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 by cold inside the throat. Referred pain can be explained by the findings that
pain receptors in the viscera also excite spinal cord neurons that are excited
by cutaneous tissue. Since the brain normally associates firing of these spinal
cord neurons with stimulation of somatic tissues in skin or muscle, pain signals
arising from the viscera are interpreted by the brain as originating from the
skin. The theory that visceral and somatic pain receptors converge and form
synapses on the same spinal cord pain-transmitting neurons is called "Ruch's
Hypothesis".

• Referred pain
It is a phenomena used to describe pain perceived at a site adjacent to or at a
distance from the site of an injury's origin. One of the best examples of this is
during ischaemia brought on by an angina pectoris, or heart attack. Even
though the heart is directly affected the pain is often felt in the neck,
shoulders and back rather than the chest. The International Association for the
Study of Pain, as of 2001, has not officially defined the term; hence several
authors have defined the term differently. Despite an increasing amount of
literature on the subject there is no definitive answer regarding the
mechanism behind this phenomena. It is interesting to note that physicians
and scientists have known about referred pain since the late 1880s and to this
day there is no definitive evidence to prove conclusively that one of the many
theories proposed is correct. Critics have stated that one reason for this is the
lack of a good referred pain model, or the incomplete understanding of
neuronal organization in the brain.

Mechanism of referred pain:

• The Convergent-Projection Theory
This represents one of the earliest theories on the subject of referred pain.
It is based on the work of W.A. Sturge and J. Ross from 1888 and later TC
Ruch in 1961. This theory proposes that afferent nerve fibers from tissues
converge onto the same spinal neuron. This theory explains why referred
pain is believed to be segmented in much the same way as the spinal cord.
Additionally, experimental evidence shows that when local pain (pain at
the site of stimulation) is intensified the referred pain is intensified as well.
Criticism of this model arises from its inability to explain why there is a
delay between the onset of referred pain after local pain stimulation.
Experimental evidence also shows that referred pain is often unidirectional.

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 For example stimulated local pain in the anterior tibial muscle causes
referred pain in the ventral portion of the ankle; however referred pain
moving in the opposite direction has not been shown experimentally.
Lastly, the threshold for the local pain stimulation and the referred pain
stimulation are different, but according to this model they should both be
the same.

• The Convergence-Facilitation Theory

In 1893 J MacKenzie created an alternate theory based on the ideas of
Sturge and Ross. He believed that the internal organs were insensitive to
stimuli. Furthermore, he believed that non-nociceptive afferent inputs to
the spinal cord created what he termed "an irritable focus". This focus
caused some stimuli to be perceived as referred pain. However, the theory
did not gain widespread acceptance from critics due to its dismissal of
visceral pain. Recently this simple idea has regained some credibility under
as a new term, central sensitization. This theory, therefore, explains why
changes in somatosensory sensibility could be undergoing processes
similar to the dorsal horn and the brainstem. Additionally, the delay in
appearance of referred pain shown in laboratory experiments can be
explained due to the time required to create the central sensitization.

• The Axon-Reflex Theory

This theory suggests that the afferent fiber is bifurcated before connecting
to the dorsal horn. Bifurcated fibers do exist in muscle, skin, and
intervertebral discs. Yet these particular neurons are rare and are not
representative of the whole body. Axon-Reflex also does not explain the
time delay before the appearance of referred pain, threshold differences
for stimulating local and referred pain, and somatosensory sensibility
changes in the area of referred pain.

• The Hyperexcitability Theory

Out of all the theories present on the subject of referred pain this one
appears to be backed by the largest amount of evidence. This theory
hypothesizes that referred pain has no central mechanism. However, it
does say that there is one central characteristic that predominates. This
theory is derived from experiments involving noxious stimuli and
recordings from the dorsal horn of animals. Experiments revealed that

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 referred pain sensations began minutes after muscle stimulation. Pain was
felt in a receptive field that was some distance away from the original
receptive field. According to the theory new receptive fields are created as
a result of the opening of latent convergent afferent fibers in the dorsal
horn. This signal could then be perceived as referred pain. Several
characteristics are in line with this theory of referred pain such as
dependency on stimulus and the time delay in the appearance of referred
pain as compared to local pain. However, the appearance of new receptive
fields, which is interpreted to be referred pain, conflicts with the majority of
experimental evidence from studies including studies of healthy
individuals. Furthermore, referred pain generally appears within seconds in
humans as opposed to minutes in animal models. Some scientists attribute
this to a mechanism or influence downstream in the supraspinal pathways.
Neuroimaging techniques such as PET scans or fMRI may visualize the
underlying neural processing pathways responsible in future testing.

• The Thalamic-Convergence Theory

The last theory suggests that referred pain is perceived as such due to the
summation of neural inputs in the brain, as opposed to the spinal cord,
from the injured area and the referred area. Experimental evidence on this
theory is lacking. However, pain studies performed on monkeys revealed
several pathways converging on both subcortical and cortical neurons.

Examples:
1. Myocardial ischaemia (the loss of blood flow to a part of the heart
muscle tissue) is possibly the best known example of referred pain; the
sensation can occur in the upper chest as a restricted feeling, or as an
ache in the left shoulder, arm or even hand.
2. “Ice cream headache” or “brain freeze” is another example of
referred pain, in which the vagus nerve is cooled by cold inside the
throat.
3. Phantom limb pain, a type of referred pain, is the sensation of pain
from a limb that has been lost or from which a person no longer
receives physical signals.

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 • Phantom limb pain, a type of referred pain, is the sensation of pain
from a limb that has been lost or from which a person no longer receives
physical signals. It is an experience almost universally reported by amputees
and quadriplegics.

• Neuropathic pain can occur as a result of injury or disease to the

nerve tissue itself. This can disrupt the ability of the sensory nerves to
transmit correct information to the thalamus, and hence the brain interprets
painful stimuli even though there is no obvious or known physiologic cause for
the pain. Neuropathic pain is, as stated above, the disease of pain. It is not the
sole definition for chronic pain, but does meet its criteria.

• Psychological pain refers to pain caused by psychological stress and

by emotional trauma, as distinct from that caused by physiological injuries and
syndromes.
Psychological pain is distinct and separate from emotional pain, which is
'heartache' due to a true or perceived loss.

Description:
Pain arises from any number of situations. Injury is a major cause, but pain may
also arise from an illness. It may accompany a psychological condition, such as
depression, or may even occur in the absence of a recognizable trigger.

• Acute pain
Acute pain often results from tissue
damage, such as a skin burn or broken
bone. Acute pain can also be associated
with headaches or muscle cramps. This
type of pain usually goes away as the
injury heals or the cause of the pain
(stimulus) is removed.

To understand acute pain, it is necessary

to understand the nerves that support it.
Nerve cells, or neurons, perform many functions in the body. Although their
general purpose, providing an interface between the brain and the body,

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 remains constant, their capabilities vary widely. Certain types of neurons are
capable of transmitting a pain signal to the brain.

As a group, these pain-sensing neurons are called nociceptors, and virtually

every surface and organ of the body is wired with them. The central part of
these cells is located in the spine, and they send threadlike projections to
every part of the body. Nociceptors are classified according to the stimulus
that prompts them to transmit a pain signal. Thermoreceptive
nociceptors are stimulated by temperatures that are potentially tissue
damaging. Mechanoreceptive nociceptors respond to a pressure stimulus
that may cause injury. Polymodal nociceptors are the most sensitive and
can respond to temperature and pressure. Polymodal nociceptors also
respond to chemicals “chemosensitive nociceptors” released by the cells
in the area from which the pain originates.

Nerve cell endings, or receptors, are at the front end of pain sensation. A
stimulus at this part of the nociceptor unleashes a cascade of
neurotransmitters (chemicals that transmit information within the nervous
system) in the spine. Each neurotransmitter has a purpose. For example,
substance P relays the pain message to nerves leading to the spinal cord
and brain. These neurotransmitters may also stimulate nerves leading back
to the site of the injury. This response prompts cells in the injured area to
release chemicals that not only trigger an immune response, but also
influence the intensity and duration of the pain.

• Chronic and abnormal pain

Chronic pain refers to pain that persists after an injury heals cancer pain,
pain related to a persistent or degenerative disease, and long-term pain from
an unidentifiable cause.
Chronic pain may be caused by the body's response to acute pain. In the
presence of continued stimulation of nociceptors, changes occur within the
nervous system. Changes at the molecular level are dramatic and may
include alterations in genetic transcription of neurotransmitters and
receptors. These changes may also occur in the absence of an identifiable
cause; one of the frustrating aspects of chronic pain is that the stimulus may

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 be unknown. For example, the stimulus cannot be identified in as many as
85% of individuals suffering lower back pain.

Other types of abnormal pain include allodynia, hyperalgesia, and

phantom limb pain. These types of pain often arise from some damage to
the nervous system (neuropathic). Allodynia refers to a feeling of pain in
response to a normally harmless stimulus. For example, some individuals
who have suffered nerve damage as a result of viral infection experience
unbearable pain from just the light weight of their clothing. Hyperalgesia is
somewhat related to allodynia in that the response to a painful stimulus is
extreme. In this case, a mild pain stimulus, such as a pin prick, causes a
maximum pain response. Phantom limb pain occurs after a limb is
amputated; although an individual may be missing the limb, the nervous
system continues to perceive pain originating from the area.

Hypnosis as well as diverse perceptional techniques provoking altered states

of consciousness have proven to be of important help in the management of
all types of pain. Some kinds of physical manipulation or exercise are
showing interesting results as well.

• How the body feels pain?

Nociceptors
All nociceptors are free nerve endings that have their cell bodies outside
the spinal column in the dorsal root ganglion and are named based upon
their appearance at their sensory ends. Nociceptors can detect
mechanical, thermal, and chemical stimuli, and are found in the skin and
on internal surfaces such as the periosteum or joint surfaces. Deep internal
surfaces are only weakly supplied with pain receptors and will propagate
sensations of chronic, aching pain if tissue damage in these areas occurs.

Nociceptors do not adapt to stimulus. In some conditions, excitation of

pain fibers becomes greater as the pain stimulus continues, leading to a
condition called hyperalgesia.

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 Transmission of nociception to the central
nervous system
There are two ways for nociceptive information
to reach the central nervous system, the
neospinothalamic tract for 'fast spontaneous
pain' and the paleospinothalamic tract for 'slow
increasing pain'.

• Neospinothalamic tract
Fast pain travels via type Aδ fibers to
terminate on the dorsal horn of the spinal
cord where they synapse with the dendrites
of the neospinothalamic tract. The axons of
these neurons travel up the spine to the
brain and cross the midline through the anterior white commissure,
passing upwards in the contralateral anterolateral columns. These
fibers terminate on the ventrobasal complex of the thalamus and
synapse with the dendrites of the somatosensory cortex. Fast pain is
felt within a tenth of a second of application of the pain stimulus and
is a sharp, acute, prickling pain felt in response to mechanical and
thermal stimulation. It can be localized easily if Aδ fibers are stimulated
together with tactile receptors.

• Paleospinothalamic tract
Slow pain is transmitted via slower type C fibers to laminae II and III of
the dorsal horns, together known as the substantia gelatinosa.
Impulses are then transmitted to nerve fibers that terminate in lamina
V, also in the dorsal horn, synapsing with neurons that join fibers from
the fast pathway, crossing to the opposite side via the anterior white
commissure, and traveling upwards through the anterolateral pathway.
These neurons terminate throughout in the brain stem, with one tenth
of fibers stopping in the thalamus, and the rest stopping in the
medulla, pons and periaqueductal grey of the midbrain tectum. Slow
pain is stimulated by chemical stimulation, is poorly localized and is
described as an aching, throbbing or burning pain.

Effects in CNS

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 When the nociceptors are stimulated they transmit signals through sensory
neurons in the spinal cord. These neurons release the exicitory
neurotransmitter glutamate at their synapses.

If the signals are sent to the reticular formation and thalamus, the
sensation of pain enters consciousness in a dull poorly localized manner.
From the thalamus, the signal can travel to the somatosensory cortex in
the cerebrum, when the pain is experienced as localized and having more
specific qualities.

Nociception can also cause generalized autonomic responses before or

without reaching consciousness to cause pallor, diaphoresis, bradycardia,
hypotension, lightheadedness, nausea and fainting.

Analgesia
The body possesses an endogenous analgesia system, which can be
supplemented with analgesic drugs to regulate nociception and pain. There
is both an analgesia system in the central nervous system and peripheral
receptors that decreases the grade in which pain reaches the higher brain
areas. The perception of pain can be modified by the body according to
gate control theory of pain.

• Central
The central analgesia system is mediated by 3 major components: the
periaquaductal grey matter, the nucleus raphe magnus and the
nociception inhibitory neurons within the dorsal horns of the spinal
cord, which act to inhibit nociception-transmitting neurons also located
in the spinal dorsal horn.

• Peripheral
The peripheral regulation consists of several different types of opioid
receptors that are activated in response to the binding of the body's
endorphins. These receptors, which exist in a variety of areas in the
body, inhibit firing of neurons that would otherwise be stimulated to do
so by nociceptors.

• Factors

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 The gate control theory of pain, proposed by Patrick Wall and Ron
Melzack, postulates that nociception (pain) is "gated" by non-
nociception stimuli such as vibration. Thus, rubbing a bumped knee
seems to relieve pain by preventing its transmission to the brain. Pain
is also "gated" by signals that descend from the brain to the spinal cord
to suppress (and in other cases enhance) incoming nociception (pain)
information.

In addition to receiving and interpreting pain signals, the brain responds to

pain by activating parts of the nervous system that send additional blood
to the injured part of the body or that release natural pain-relieving
chemicals, including serotonin, endorphins, and enkephalins.

• Factors that affect pain perception

1. Location and Severity of pain
Pain varies in intensity and quality. It may be mild, moderate, or
severe. In terms of quality, it may vary from a dull ache to sharp,
piercing, burning, pulsating, tingling, or throbbing sensations; for
example, the pain from jabbing one's finger on a needle feels different
from the pain of touching a hot iron, even though both injuries involve
the same part of the body. If the pain is severe, the nerve cells in the
dorsal horn transmit the pain message rapidly; if the pain is relatively
mild, the pain signals are transmitted along a different set of nerve
fibers at a slower rate.

The location of the pain often affects a person's emotional and

cognitive response, in that pain related to the head or other vital
organs is usually more disturbing than pain of equal severity in a toe or
finger.

2. Gender
Recent research has shown that sex hormones in mammals affect the
level of tolerance for pain. The male sex hormone, testosterone,
appears to raise the pain threshold in experimental animals, while the
female hormone, estrogen, appears to increase the animal's
recognition of pain. Humans, however, are influenced by their personal

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 histories and cultures as well as by body chemistry. Studies of adult
volunteers indicate that women tend to recover from pain more quickly
than men, cope more effectively with it, and are less likely to allow pain
to control their lives. One explanation of this difference comes from
research with a group of analgesics known as kappa-opioids, which
work better in women than in men. Some researchers think that female
sex hormones may increase the effectiveness of some analgesic
medications, while male sex hormones may make them less effective.
In addition, women appear to be less sensitive to pain when their
estrogen and progesterone levels are high, as happens during
pregnancy and certain phases of the menstrual cycle. It has been
noted, for example, that women with irritable bowel syndrome (IBS)
often experience greater pain from the disorder during their periods.

3. Family
Another factor that influences pain perception in humans is family
upbringing. Some parents comfort children who are hurting, while
others ignore or even punish them for crying or expressing pain. Some
families allow female members to express pain but expect males to
"keep a stiff upper lip." People who suffer from chronic pain as adults
may be helped by recalling their family's spoken and unspoken
"messages" about pain, and working to consciously change those
messages.

4. Culture and Ethnicity

In addition to the nuclear family, a person's cultural or ethnic
background can shape his or her perception of pain. People who have
been exposed through their education to Western explanations of and
treatments for pain may seek mainstream medical treatment more
readily than those who have been taught to regard hospitals as places
to die. On the other hand, Western medicine has been slower than
Eastern and Native American systems of healing to recognize the
importance of emotions and spirituality in treating pain. The recent
upsurge of interest in alternative medicine in the United States is one
reflection of dissatisfaction with a one-dimensional "scientific" approach
to pain.

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 There are also differences among various ethnic groups within Western
societies regarding ways of coping with pain. One study of African
American, Irish, Italian, Jewish, and Puerto Rican patients being treated
for chronic facial pain found differences among the groups in the
intensity of emotional reactions to the pain and the extent to which the
pain was allowed to interfere with daily functioning. However, much
more work on larger patient samples is needed to understand the many
ways in which culture and society affect people's perception of and
responses to pain.

Some possible causes of pain by region:

Visceral pain sensation is often referred by the CNS to a dermatome region which
may be far away from the originating organ. These correlate to the position of the
organ in the embryo. Examples of this include the heart which originates in the
neck, thus producing the classical pain and arm pain experienced during acute
cardiac pain.

• Head and neck

- Jaw  Temporal arthritis (serious), trauma
- Ear  otitis media (very common esp. in children), otitis externa, trauma
- Eye  glaucoma, trauma
- Head  migraine, tension headache, cluster headache, cancer, cerebral
aneurysm, sinusitis, meningitis
- Neck pain  MI (atypical), trauma

• Thorax
- Back  cancer
- Breast  perimenstrual, cancer, and trauma
- Chest  MI (common and sometimes fatal), GERD (very common),
pancreatitis, hiatal hernia, aortic dissection (rare), pulmonary embolism
(more frequently asymptomatic), Costochondritis
- Shoulder  cholecystitis (right side), MSK

• Abdomen

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 - Left and right upper quadrant  peptic ulcer disease, gastroenteritis,
hepatitis, pancreatitis, cholecystitis, MI (atypical), abdominal aortic
aneurysm, gastric cancer (usually asymptomatic)
- Left and right lower quadrant  appendicitis (serious), ectopic pregnancy
(serious/women only), endometriosis (women only), pelvic inflammatory
disease (women only), diverticulitis (common in the elderly), urolithiasis,
pyelonephritis, cancer (colorectal cancer most common)

• Back
- Back  MSK (muscle strain), cancer, spinal disc herniation, degenerative
disc disease, coccyx (coccydynia)

• Limbs
- Arm  myocardial infarction (classically the left arm, sometimes bilateral),
musculoskeletal
- Leg  deep vein thrombosis, peripheral vascular disease (claudication),
musculoskeletal, spinal disc herniation, sciatica

• Joints
- Classically small joints  osteoarthritis (common in the elderly),
rheumatoid arthritis, systemic lupus erythematosis, gout,
pseudogouttarsal/carpal tunnel syndrome
- Classically large joints (hip, knee)  osteoarthritis (common in the elderly),
septic arthritis, hemarthrosis, osteonecrosis, trauma
- Classically back  ankylosing spondylitis, inflammatory bowel disease
- Other  psoriatic arthritis, Reiter's syndrome

Insensitivity to pain:
Inability to experience pain, as in the rare condition congenital insensitivity to pain
or congenital analgesia, is a cause of physical damage due to unawareness.
Insensitivity to pain may also be caused by Hansen's disease or other forms of
nerve damage.

CIP presents in early childhood with a child frequently getting injuries, such as
broken bones and bruises, because they fail to develop the normal avoidance of
pain and so take risks others would not.

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 While such conditions are extremely rare, they may present a picture of child
abuse to the health care provider who frequently reports to child protection, the
police, or other agencies.

Phenomena of Modified Pain Sensation

• Hyperalgesia
Hyperalgesia is an increased sensitivity to pain, which in one form is caused
by damage to nociceptors in the body's soft tissues.

Hyperalgesia can be experienced in focal, discrete areas, or as a more

diffuse, body-wide form. Conditioning studies have established that it is
possible to experience a learned hyperalgesia of the latter, diffuse form. The
focal form is typically associated with injury, and is divided into two
subtypes:
1. Primary hyperalgesia describes pain sensitivity that occurs directly
in the damaged tissues.
2. Secondary hyperalgesia describes pain sensitivity that occurs in
surrounding undamaged tissues.

Hyperalgesia is induced by Platelet Aggregating Factor (PAF) which comes

about in an inflammatory or an allergic response. This seems to occur via
immune cells interacting with the peripheral nervous system and releasing
pain-producing chemicals (cytokines and chemokines)
One unusual cause of focal hyperalgesia is platypus venom.

Long term opioid users (ie. Heroin) and those on opioid medications may
experience hyperalgesia and experience pain out of proportion to physical
findings.

Ikeda, Stark, Fischer, Wagner, Drdla, Jäger, et al. (2006) showed that
stimulation of pain fibres in a pattern consistent with that from inflammation
switched on a form of amplification in the spinal cord, long term potentiation.
This occurred where the pain fibres contacted a pain pathway, the
periaqueductal grey. Ikeda et al. argued that amplification in the spinal cord
is another way of producing hyperalgesia.

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• Hypoalgesia
Hypoalgesia or hypalgesia denotes a decreased sensitivity to painful stimuli.

Hypoalgesia occurs when nociceptive (painful) stimuli are interrupted or

decreased somewhere along the path between the input (nociceptors), and
the places where they are processed and recognized as pain in the conscious
mind. Hypoalgesic effects can be mild, such as massaging a stubbed toe to
make it hurt less or taking aspirin to decrease a headache, or they can be
severe, like being under strong anesthesia. Hypoalgesia can be caused by
exogenous chemicals such as opioids, as well as by chemicals produced by
the body in phenomenon such as fear- and exercise- induced hypoalgesia
,Hypoalgesia can also be associated with diseases, such as CIPA or in less
severe cases with diabetes or other diseases associated with hypertension.
Chemical causes:
1. Analgesics
Analgesics are a class of biochemicals that cause hypoalgesia. Analgesics
can act on both the peripheral and central nervous systems to decrease
pain. Certain analgesics also work to decrease the source of the pain by
working to decrease swelling an inflammation, as in the case of NSAIDs.

2. Opioids
Opioids refers to a specific group of analgesics - including morphine,
codeine, and opium - that act on opioid receptors, which are located
mainly in the central nervous system.

Endogenous opioids are a type of opioid produced by the body

specifically to modulate pain. They include endorphins, enkephalins,
dynorphins and endomorphins. These proteins are especially important
for modulating pain in response to the environment. These can be
released in response to a number of things, including increased blood
pressure, pain and danger. It has been found that endogenous opioids
are at least partially responsible for phenomenon like “Runner’s high”,
hypoalgesia in the fight-or-flight response, and even for the analgesic
effects of acupuncture therapy. In all these cases, there is a certain level
of signal processing that occurs in the CNS which leads to the release of
these chemicals.

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 3. Exercise induced hypoalgesia
There has been a great deal of research examining the link between
exercise and hypoalgesia. Many studies have shown the direct link
between the two by subjecting patients to exercise and rating their pain
responses, but despite the great deal of research, the mechanism of
action is still poorly understood. It has been shown that the triggering
mechanism for the hypoalgesic effects is the increase in blood pressure
that accompanies a good workout. The body senses the increased blood
pressure, and it is hypothesized that in response, endogenous opioids are
released. This hypothesis is well supported in human research, and it has
been verified that it plays a part, but animal research implies that other
mechanisms are also involved.

4. Fear induced hypoalgesia

Fear induced hypoalgesia is another example of a mechanism controlled
by opioids. It is postulated that fear is a defense mechanism that has
evolved over time to provide protection. In the case of hypoalgesia, a
decreased response to pain would be very beneficial in a situation where
an organism’s life was at stake, since feeling pain would be a hindrance
rather than a help. It has been well documented that fear does cause a
decrease in pain response, however much like the exercise induced
hypoalgesia, the exact mechanisms of action are not well understood.
Studies have shown that opioids are definitely involved in the process,
yet opiates alone do not completely explain the analgesic response.
What the other mechanisms of action are is still unknown.

Pain and alternative medicine:

A recent survey by NCCAM (part of the NIH) found pain was the most common
reason that people use alternative medicine. Among American adults who used
CAM in 2002, 16.8% used CAM to treat back pain; 6.6% for neck pain; 4.9% for
arthritis; 4.9% for joint pain; 3.1% for headache; and 2.4% used CAM to treat
recurring pain. (Some survey respondents may have used CAM to treat more than
one of these pain conditions.)

One such alternative, traditional Chinese medicine, views pain as a qi "blockage"

equivalent to electrical resistance, or as "stagnation of blood" – theorized as

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 dehydration inhibiting metabolism. Traditional Chinese treatments such as
acupuncture are said to be more effective for nontraumatic pain than traumatic
pain. Although these claims have not found broad scientific acceptance, research
into both the mechanism and clinical efficacy of acupuncture supports that it can
have a role in pain reduction for both humans and animals. Although the
mechanism is not fully understood, it is likely that acupuncture stimulates the
release of large quantities of endogenous opioids.

An opioid is a chemical substance that has a morphine-like action in the body. The main use is for
pain relief. These agents work by binding to opioid receptors, which are found principally in the
central nervous system and the gastrointestinal tract. The receptors in these two organ systems
mediate both the beneficial effects, and the undesirable side effects. There are a number of broad
classes of narcotics:
• natural opiates, alkaloids contained in the resin of the opium poppy including
morphine, codeine, thebaine, and oripavine;
• semi-synthetic opiates, created from the natural opioids, such as
hydromorphone, hydrocodone, oxycodone, and heroin;
• fully synthetic opioids, such as fentanyl, pethidine, methadone, and
propoxyphene;

• Endogenous opioid peptides, produced naturally in the body, such as

endorphins, enkephalins, dynorphins, and endomorphins.
Examples of opioids:
• Endorphins
• Enkephalins
• Dynorphins
• Endomorphins

Another common alternative treatment for chronic pain is use of nutritional

supplements such as:
• Curcumin, a polyphenol found in turmeric (Curcuma Longa) and said to be
a natural cox-2 inhibitor
• Glucosamine
• Chondroitin
• Bromelain (a digestive enzyme from pineapple core)
• Omega-3 fatty acids.
The efficacy of Glucosamine and Chondroitin, popular supplements for patients
with arthritis, were examinied in the GAIT study, a $12 million trial funded by the
NIH which showed statistical evidence for the treatment's positive effect only
amongst patients with moderate to severe pain, a small subsection of the study.

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Demographics:
Acute pain, particularly in its milder forms, is a commonplace experience in the
general population; most people can think of at least one occasion in the past
week or month when they had a brief tension headache, felt a little muscle
soreness, cut themselves while shaving, or had a similar minor injury. On the
other hand, chronic pain is more widespread than is generally thought; the
American Chronic Pain Association estimates that 86 million people in the United
States suffer from and are partially disabled by chronic pain. Two Canadian
researchers evaluating a set of 13 studies of chronic pain done in North America,
Europe, and Australia reported that the prevalence of severe chronic pain in these
parts of the world is about 8% in children and 11% in adults. In terms of the
economic impact of chronic pain, various productivity audits of the American
workforce have stated that such pain syndromes as arthritis, lower back pain, and
headache cost the United States between $80 and $90 billion every year.

The demographics of chronic pain depend on the specific disorder, including:

• Chronic pelvic pain (CPP) is more common in women than in men; it is thought
to affect about 14% of adult women worldwide. In the United States, CPP is
most common among women of reproductive age, particularly those between
the ages of 26 and 30. It appears to be more common among African
Americans than among Caucasians or Asian Americans. In addition, a history
of sexual abuse before age 15 is a risk factor for CPP in adult life.
• Lower back pain (LBP) is the most common chronic disability in persons
younger than 45. One researcher estimates that 80% of people in the United
States will experience an episode of LBP at some point in life. About 3–4% of
adults are disabled temporarily each year by LBP, with another 1% of the
working-age population disabled completely and permanently. While 95% of
patients with LBP recover within six to 12 weeks, the back pain becomes a
chronic syndrome in the remaining 5%.

• Headaches in general are very common in the adult population in North

America; about 95% of women and 90% of men in the United States and
Canada have had at least one headache in the past twelve months. Most of
these are tension headaches. Migraine headaches are less common than
tension headaches, affecting about 11% of the population in the United States
and 15% in Canada. Migraines occur most frequently in adults between the
ages of 25 and 55; the gender ratio is about 3 F:1 M. Cluster headaches are

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 the least common type of chronic headaches, affecting about 0.4% of adult
males in the United States and 0.08% of adult females. The gender ratio is
7.5–5 M: 1 F.

• Atypical facial pain is a less-common chronic pain syndrome, affecting one or

two persons per 100,000 populations each year. It is almost entirely a disorder
of adults. Atypical facial pain is thought to affect men and women equally, and
to occur with equal frequency in all races and ethnic groups.

Qualification of pain:
Nurses use the PQRST method to qualify the pain
P = provocation / palliation: what were you doing when the
pain started? What caused it? What makes it better? Worse? What seems to
trigger it? Stress? Position? Certain activities? Arguments? Does it seem to be
getting better, or getting worse, or does it remain the same? What relieves it:
changing diet? Changing position? Taking medications? Being active? Resting?
What makes (the problem) worse?

Q = quality / quantity: What does it feel like? Is it sharp? Dull?

Stabbing? Burning? Crushing? Throbbing? Nauseating? Shooting? Twisting?
Stretching? Other? (The person who is suffering the pain should describe the
pain, rather than saying what they think you would like to hear.) How does it
feel, look or sound? How much of it is there?

R = region / radiation: Where is the pain located? Does the pain

radiate (i.e. spread to another location, eg. pain source is from thumb but pain
spreads to elbow)? Where does it radiate? Is it all in one place? Does it go
anywhere else? Did it start elsewhere and now localized to one spot? Does it
feel like it travels/moves around?

S = severity scale: How severe is the pain on a scale of 0 - 10, zero

being no pain at all and 10 being the worst pain ever? Does it interfere with
activities? How bad is it when it's at its worst? Does it force you to sit down, lie
down, and slow down? How long does an episode last?

T = timing: When did the pain start, at what time? How long did it last?
How often does it occur? Is it sudden or gradual? What were you doing when
you first experienced or noticed it? How often do you experience it: hourly?
Daily? Weekly? Monthly? When do you usually experience it: daytime? Night?
In the early morning? Are you ever awakened by it? Does it lead to anything

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 else? Is it accompanied by other signs and symptoms? Does it ever occur
before, during or after meals? Does it occur seasonally?

Other questions to ask when assessing a person in pain: Any medication or

allergies?
Does it hurt on deep inspiration?
Activity at onset?
Any history of pain?
Is it the same?
Different?
Any family history of heart disease, lung problems, diabetes, stroke,
hypertension?
Pupils?
The purposes for these questions are to be as
specific as possible in the description of the pain:
when and where, what it feels like... The more
specific and detailed information, the better it
will be to diagnose the problem/cause and find a
way to alleviate it.

New Medicines for Pain Treatment

Are Cannabinoids an Effective and Safe Treatment Option in the

Management of Pain?
This review of twenty randomized and controlled trials reveals that
cannabinoids are no more effective than codeine in controlling pain.
Furthermore, the depressant effects of cannabinoids on the central nervous
system that limit their use. Before cannabinoids can be considered for treating
spasticity and neuropathic pain, further valid randomised controlled studies
are needed.

Are COX-2 Inhibitors as Effective as Conventional NSAIDs in Acute

Pain?
Rofecoxib (Vioxx) in 50 mg doses seems to be more effective than celecoxib
(Celebrex) 200 mg in acute pain.

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Pre-Incisional Dextromethorphan Reduces Post-operative Pain
Dextromethorphan is an NMDA receptor antagonist. In theory, such a
medication should help block the increased neuronal sensitivity that develops
after a painful stimulus. This study supports this theory. Patients who received
dextromethorphan 120mg intramuscularly, prior to incision, reported less post-
operative pain, and used less post-operative pain medicine.

Lamotrigine for Post-Stroke Central Pain

A small, controlled study, with 30 patients, showed that lamotrigine 200 mg
per day provided relief in 44% of patients with post-stroke central pain. One
patient had to discontinue the study because of a rash. Otherwise the drug
was well tolerated.
Development of the Aerosol AERx (R) Pain Management System is
Underway
New opioid delivery systems are being developed. Aradigm is developing
aerosol-based drug delivery alternatives to injectable therapeutics. Current
development programs focus on diabetes, pain management, cystic fibrosis
and the pulmonary delivery of emerging protein therapeutics.

COX-2 Inhibitors Show Good Pain Relief, Safety Record

Studies on the COX-2 inhibitors (Celebrex and Vioxx) show that their efficacy
mirrors that of non-steroidal anti-inflammatory drugs (NSAIDs) in the
treatment in osteoarthritis, rheumatoid arthritis and wound pain, according to
Gary Williams, MD, who spoke at a symposia given here during Digestive
Disease Week. In fact, the toxicity has been so low and the safety profile so
promising that there is speculation COX-2 inhibitors will all but replace NSAIDs.

Venlafaxine For the Treatment of Painful Diabetic Neuropathy

In the United States, an estimated two to three million diabetic patients have
at least one type of neuropathy as a consequence of their disease, Dr. Kunz
said. Ten percent of patients with diabetic neuropathy experience associated
pain that is often severe and can interfere with their quality of life. By the sixth
week, 56 percent of patients treated with extended-release venlafaxine 150 to
225 mg experienced significantly reduced pain intensity versus 39 percent
who received 75 mg per day and 34 percent who received placebo.

Synvisc for osteoarthritis of the Hip

Synvisc is an injectable, elastoviscous hylan preparation that has similar
elasticity and viscosity to human synovial (joint) fluid, providing shock
absorption and lubrication. This preliminary study indicates that Synvisc
injected into hips with osteoarthritis is safe and effective in providing

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 significant and sustained pain relief in most patients. Based on these positive
findings, the company expects to initiate a large, multi-center pivotal clinical
trial. Synvisc is already approved to treat osteoarthritic knee pain.

Venlafaxine Reduces the Pain of Diabetic Neuropathy

Study results showed that patients who took Effexor XR in doses ranging from
150-225 mg per day had significantly less pain, compared to placebo. This
may help the 6 million sufferers of painful diabetic neuropathy, a condition of
nerve damage caused by diabetes.

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 Examples of Pain Killers
Vicodin™ and other hydrocodone products: Hydrocodone is a
semi-synthetic opioid similar in effects to morphine. Vicodin™ is hydrocodone
mixed with acetaminophen. Hydrocodone products, when abused, can lead to
dependence, tolerance, and addiction. Vicodin™ is one of the most frequently
prescribed medications for pain. Other products include Vicoprophen™,
Tussionex™, and Lortab™ .

OxyContin™ and other oxycodone products: Oxycodone is

used as an analgesic and is formulated into numerous
pharmaceuticals including OxyContin™ (a controlled-release product)
and with aspirin (Percodan™) or with acetaminophen (Percoset™).
These drugs are prescribed for pain relief. They all require a doctor's prescription and
are prescribed for moderate to severe pain.

FENTANYL™ is extensively used for anesthesia and analgesia. Duragesic™

is a fentanyl transdermal patch used in chronic pain management, and Actiq
is a solid formulation of fentanyl citrate on a stick that dissolves slowly in the
mouth for transmucosal absorption. Illicit use of pharmaceutical fentanyl first
appeared in the mid-1970's in the medical community. To date, over 12
different analogues of fentanyl have been produced clandestinely and identified in
the U.S. drug traffic. The biological effects are indistinguishable from those of heroin,
with the exception that the fentanyls may be hundreds of times more potent.
Fentanyls are most commonly used by intravenous administration, but like heroin,
they may also be smoked or snorted.

ULTRAM™(tramadol hydrochloride) and ULTRACET™ (tramadol with

acetaminophen) are prescription medications indicated for the management
of moderate to moderately severe pain. Side effects include: dizziness,
drowsiness, or headache; nervousness, tremor, or anxiety; nausea, vomiting,
constipation, or diarrhea; or itching, dry mouth, or sweating.

Tramadol is habit forming. Physical and/or psychological dependence can occur, and
withdrawal effects are possible if the medication is stopped suddenly after prolonged
or high-dose treatment.

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 References
http://en.wikipedia.org/wiki/Hyperalgesia
http://www.iasp-pain.org//AM/Template.cfm?Section=Home
http://en.wikipedia.org/wiki/Opioids
http://en.wikipedia.org/wiki/Hypoalgesia
http://www.justthinktwice.com/drugfacts/painkillers.cfm
http://en.wikipedia.org/wiki/Pain#Phenotype_and_pain
http://www.painmed.org/
http://en.wikipedia.org/wiki/Psychological_pain
http://www.nlm.nih.gov/medlineplus/pain.html
http://www.aapainmanage.org/
http://www.medicinenet.com/chronic_pain/focus.htm
http://www.nlm.nih.gov/medlineplus/pain.html
http://plato.stanford.edu/entries/pain/
http://www.theacpa.org/
http://www.medicinenet.com/neuropathic_pain/article.htm
http://en.wikipedia.org/wiki/Nociceptor

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