Download - Pain
PAIN SENSATIONPAIN SENSATION PAIN SENSATIONPAIN SENSATION
According to The International Association for the Study of Pain (IASP):
Definition: Pain is an unpleasant sensory and emotional experience
associated with actual or potential tissue damage.
Significance
1) warning signal against tissue damage. Pain is one of the most
prominent symptoms of tissue damage.
2) Initiate protective reflexes which causes the subject to get rid of the
painful stimulus, or at least, to minimize tissue injury or damage
If persistent, physiological pain may progress to a If persistent, physiological pain may progress to a pathological condition pathological condition
itself, often referred to as itself, often referred to as maladaptivemaladaptive pain, in which case pain is pain, in which case pain is
dissociated from the original noxious stimulation or the healing process dissociated from the original noxious stimulation or the healing process
and thus does not represent anymore a symptom of disease but rather and thus does not represent anymore a symptom of disease but rather
abnormal sensory processing due to abnormal sensory processing due to damage to tissuesdamage to tissues (inflammatory (inflammatory
pain) or pain) or the nervous system the nervous system (neuropathic pain), or to (neuropathic pain), or to abnormal function abnormal function
of the nervous system itself (functional pain)of the nervous system itself (functional pain)..
pain resulting from activation of pain receptors may be referred to as pain resulting from activation of pain receptors may be referred to as
adaptiveadaptive or or physiologicalphysiological pain, because it minimizes tissue damage and pain, because it minimizes tissue damage and
promotes healing. promotes healing.
Classification:
Pain is classified into nociceptive, neuropathic and psychogenic; all
can be either acute or chronic. Pain is defined as chronic if persists more than 7 weeks.
1. Nociceptive is pain caused by tissue damage (inflammation) which stimulate
pain receptors (nociceptors).
1. Nociceptive is pain caused by tissue damage (inflammation) which stimulate
pain receptors (nociceptors).
2. Neuropathic: (pain due to injury of nerve pathway)
site of injury: CentralCentral Central pain (thalamic infarct).
MixedMixed Plexus avulsion, Post herpetic neuralgia.
PeripheralPeripheral Neuroma, nerve compression, phantom, neuralgias.
character: burning, tingling, numbness, pressing, squeezing, itching, constant +/-
intermittent shooting, lancinating, electric.
2. Neuropathic: (pain due to injury of nerve pathway)
site of injury: CentralCentral Central pain (thalamic infarct).
MixedMixed Plexus avulsion, Post herpetic neuralgia.
PeripheralPeripheral Neuroma, nerve compression, phantom, neuralgias.
character: burning, tingling, numbness, pressing, squeezing, itching, constant +/-
intermittent shooting, lancinating, electric.
3. Psychogenic: (difficult to differentiate whether secondary to or actual cause
of pain), anxiety, depression (30% of depressives complain of pain on initial
presentation).
3. Psychogenic: (difficult to differentiate whether secondary to or actual cause
of pain), anxiety, depression (30% of depressives complain of pain on initial
presentation).
Pain Receptors (Nociceptors)
Types of Pain Receptors
Free nerve endings which are morphologically similar but functionally
specific. They are classified according to their sensitivity into:
Polymodal Pain Receptors (most pain receptors)
These respond to a combination of mechanical, thermal, and chemical
noxious stimuli.
Mechanical Pain Receptors
respond to strong mechanical forces, such as cutting, crushing, pricking, or
even firm pressure on tissues.
Thermal Pain Receptors
respond to excessive changes in temperature (above 45oC and below 10oC).
Chemical Pain Receptors
respond to noxious chemical stimuli.
Distribution of Pain Receptors
Pain receptors are found in most tissues of the body but varies in their density.
They are abundant and widely spread in the skin and some internal
tissues such as: - the periosteum of the bone,
- arterial walls,
- joint surfaces,
- the dura of the falx and tentorium in the cranial cavity,
- the skeletal muscle,
- the parietal layer of serous membranes.
Many of the other deep tissues and viscera are poorly supplied with pain
receptors. So,
- for pain to occur, painful stimulus must by intense and widespread.
- The deep & visceral pain are poorly localized.
On the other hand, the brain itself and also the parenchymal tissues of the
liver, kidneys, and lungs have no pain receptors. They are called “pain
insensitive structures”
N.B.: Serious diseases in these structures don’t produce pain till they
extend to a pin sensitive structure like arterial wall or serous covering.
Pain Threshold:
Pain threshold is the lowest intensity of stimulus that can cause pain when
the stimulus is applied for sufficient period of time.
Pain threshold can be measured in many ways.
One of the accurate methods to quantify the threshold is heating the skin with
measured amounts of radiant heat from a calibrated electric lamp.
It has been shown that the majority of subjects begin to perceive pain when the
skin temperature reaches 45oC, and almost everyone perceives pain before the
temperature reaches 47oC.
So, it seems that the great majority of people do not show significant
differences in their sensitivity to painful stimuli. However, they differ widely in
their reaction to pain.
Stimulation of Pain Receptors:
noxious stimuli are strong enough
-----> tissue damage ------> release of
chemical agents from destructed cells
into the surrounding interstitial spaces
which are called “pain producing
compounds” (PPCs) ------> stimulate
pain receptors in the affected tissues.
PGE2
IL-1
Both threshold of pain receptors facilitating their
stimulation
The PPCs may be classified into:
1- Direct stimulators1- Direct stimulators
Substances which when reach
specific threshold directly stimulate
pain receptors ----> pain, as:
- K+ ions. - H+ ions
- Serotonin. - Histamine
- Bradykinin
2- Sensitizers2- Sensitizers
Substances which lower the threshold for
stimulation of pain receptors by direct
stimulators ----> facilitate pain
production. They include:
a) Substances released by the injured
tissues as: PGE2 & IL-1
b) Substances released by pain
receptors through antidromic impulses
as: substance P
N.B.: Substance P also stimulate mast
cells to release histamine which is a
direct stimulator.
The surface membrane of pain receptors contain several molecular receptors
which can be activated by various PPCs.
Molecular receptorFunction
Acid sensing receptor (H+)Stimulation
Purinergic receptor (ATP)Stimulation
Transient receptor potential rec. (thermal)
Stimulation
Bradykinin receptorStimulation
& sensitization
Histamine recptorStimulation
& sensitization
Serotonin receptorStimulation
& sensitization
Prostaglandin receptorsensitization
Interleukin-1 receptorsensitization
Substance P receptorsensitization
Cannabinoid receptorInhibition
Opioid receptorInhibition
Pain Tolerance:
It is the maximum intensity of pain can be tolerated by the subject without obvious
complaint.
Pain tolerance is affected by a number of factors:
- Anxiety, depression & fatigue ------> pain tolerance.
- rest, sever exercise & strong emotional excitement ------> pain tolerance.
Non Adaptation of Pain Receptors
Pain receptors do not adapt to continuing noxious stimuli.
Non adaptation to pain serves a protective function to keep the individual
trying to remove the damaging stimulus or to get away from it.
THE CHARACTER (QUALITY) of pain
1) Pricking or Cutting Pain
2) Burning Pain
3) Aching Pain
4) Throbbing Pain
5) Colicky Pain
A sharp and localized pain. It is of cutaneous origin and is caused by pricking or
cutting the skin by a sharp object.
A less well localized pain. It is usually of cutaneous origin and is caused by burns
or inflammations of the skin .
A dull-aching nature. It is more diffuse and felt coming from deeper tissues, e.g.
rheumatic pains.
is characterized by fluctuation of its intensity with arterial pulsations. It results
from localized inflammation in deep tissues, as in abscess formation.
Pain results from spasm of plain muscles in the walls of hollow viscera.
SomaticVisceral
sitesitecutaneous, deep tissuessympathetically innervated organs can be transferredto body surface
charactercharacterconstant, localisedaching, throbbing, gnawing
vague distribution and Quality deep, ache, dragging, squeezingacute: colic, paroxysmal, +/- N/V, sweating, BP and heart rate changes
Acute nociceptive pain:Acute nociceptive pain:
Fast (Immediate) physiological pain
Slow (delayed) pathophysiological pain
onset: during application of the stimulus
Duration: short duration.
Nature: pricking
Localization: well-localized
Afferent: A-delta fibers
Higher center: CC
Neurotransmitter: glutamate
Significance: * determine site & severity.
* Initiate withdrawal reflexes.
Abolished by deep pressure and not
abolished by morphine.
Shortly after application if tissue
damage occurs
Longer duration
Burning
Poorly-localized
C-fibers
Thalamus
Substance-P
* Associated with arousal, autonomic &
emotional reactions
Abolished by local anaethesia &
morphine
Reactions to Pain:
1) Somatic Motor Reactions
2) Autonomic Reactions
3) Emotional and Psychogenic Reactions
4) Hyperalgesia.
1) Somatic Motor Reactions
a) Excess neuromuscular excitability throughout the body.
b) Withdrawal Reflexes.
-initiated by cutaneous pain.
- Aim to withdraw the whole body or a part of it away from a painful
stimulus mainly by contraction of flexor muscles.
- It is a prepotent reflex; inhibit all other reflexes during its occurrence.
Reflex spasm of the nearby skeletal muscles in case of deep pain ---->
minimize mobilization of the pained part -----> stimulation of pain
receptors.
c) Immobilization Reaction.
d) Guarding Reaction.
Reflex spasm of the overlying skeletal muscles in case of visceral pain
----> stimulation of pain receptors in the diseased viscus.
2) Autonomic Reactions
Mild Cutaneous pain ------> a pressor reaction = rise of blood pressure
and heart rate, mediated by sympathetic stimulation.
Sever cutaneous, deep and visceral pain ------> a depressor reaction
associated with hypotension, bradycardia, and nausea, due to parasympathetic
stimulation.
Such pain is often described as sickening pain and may be accompanied
by vomiting.
3) Emotional and Psychogenic Reactions
Anxiety, fear, crying, depression, as well as the feeling of being hurt may
be felt by the pained person.
these reactions vary:
- From person to person on exposure to similar pain stimuli.
- in the same person according to his emotional state:
- Worry about the cause of pain augment the feeling of pain. Thus, Patients
suffer than healthy subject to the same degree of pain.
- Strong emotional excitement & sever physical exertion may block the feeling
of pain. Thus, seriously wounded soldiers in a battlefield suffer little or no pain till the
battle is over.
NEURAL PATHWAYS FOR PAINPain impulses are transmitted to CNS by two separate pathways, which
correspond to the two different types of pain; a fast-acute (pricking) pain, and a
slow-chronic (burning or aching) pain.
Cutaneous HyperalgesiaDefinition: Increased skin sensitivity to pain.
Types: 1- Primary hyperalgesia. 2- Secondary hyperalgesia.
1- Primary hyperalgesia2- Secondary hyperalgesia
- Develop 30-60 min. after injury.
- Lasts for several hours or days.
- In the area of redness.
- Non-painful stimuli (as touch)
becomes painful.
Mechanism:
Decreased pain threshold due to
local axon reflex releasing
substance P
- Develops later.
- Shorter duration than 1ry.
- In healthy skin surrounding red area.
- Pain is felt more sever than normal.
Central sensitization explained by
convergence-facilitation theory.
Referred Pain
Definition: Pain felt away from the original site of the painful stimulus.
Radiating pain: Pain which appear to migrate away from its original site.
Referred pain is a part of radiating pain.
Visceral pain is usually referred.
Deep pain may be referred.
Cutaneous pain is never referred.
Site of referral is determined by dermatomal rule:
The pain from a viscera is referred to a somatic structure (skin or deep structure)
which were developed in the same embryonic segment and supplied by the same
dorsal root ganglia.
Abnormal sites are due to migration of viscera.
Mechanism of referred pain (Convergence-projection theory):
Nerves from viscera and from a somatic structure developed in the same
embryonic segment develops from the same DRG and converge to a great extent
on the same SGR.
Thus, visceral pain afferents usually excite the same spinothalamic tract neurons
and the same neurons in the higher centers that are activated by the pain afferents
from somatic structures to which the visceral pain is referred.
Brain is accustomed to receive pain impulses from somatic structures as the
frequency of somatic pain is much more frequent than the visceral pain.
Thus, the brain would misinterpret the origin of the visceral pain impulses, and the
pain is perceived as if arising from the skin area or deep somatic structures which
are innervated by the same spinal segments that innervate the diseased viscera.
Examples of Referred Pain from Visceral Organs
1.Cardiac Pain
is referred mainly to the base of the neck, over the left shoulder, inner side
of the left arm, and under the sternum (retrosternal).
All these structure developed from embryonic segments which enter the spinal
coed along 2,3,4,5 thorathic nerves.
2. Gall Bladder Pain
is referred to epigastric region, slightly to the right, and if an inflammed gall
bladder irritates the diaphragm, the pain may also be referred to the tip of the right
shoulder & small area at the tip of the right scapula.
3. Renal and Ureteric Pain
is usually felt directly behind the diseased viscera in the back. However, the pain
is occasionally referred to the anterior abdominal wall near the inguinal region,
scrotum & testis (L1).
4. Appendicitis Pain
is initially referred to a remote area around the umbilicus (Th10), but when the
inflammatory process spreads to the overlying parietal peritoneum the pain is also
localized in the right iliac fossa just over the site of irritation.
5. Gastric Pain
is usually referred to the skin of epigastric region in the anterior abdominal
wall between the xyphoid process and the umbilicus.
Relief of pain (analgesia)
This may be done by:
1- Physiological method (edogenous analgesic system).
2- Pharmacological.
3- Surgical by many methods as cutting of the peripheral nerves. Prefrontal
lobectomy may be used in sever cases. It abolishes only the emotional and
psychogenic effect of pain but associated with sever personality changes.
So, this method is used in terminal stages of severly painful conditions as
tumour.
THE PAIN CONTROL SYSTEM
also called the endogenous
analgesic system.
consists of special areas in the
brain and spinal cord, which when
activated can greatly reduce or
even completely abolish pain
sensation.
Location
1-The periaqueductal gray area (PAG area) around the aqueduct of sylvius in
the midbrain and pons.
2-The raphe magnus (NRM) nucleus located in the lower region of the pons and
upper region of the medulla.
3-The nucleus reticularis paragiganto -cellularis in the medulla.
4- Locus ceruleus (NC) in pons
5- A pain inhibitory complex located in the dorsal horn of the spinal cord
(probably in laminae II and III : the substantia gelatinosa of Rolandi).
Opioid Peptides
Endogenous naturally-occurring physiologic peptides which are similar in
structure and function to opium (=morphine).
They can bind to the morphine receptors -----> produce long-lasting analgesic
effect.
The opioid peptides consist of three major groups : The enkephalins, the
endorphins, and the dynorphins.
Opiate Receptors
Three different types of opiate receptors have been characterized : delta (δ),
kappa (k), and muta (μ)
Binding of opioid peptides with opiate receptors at specific sites in the nervous
system functions to stop synaptic transmission of pain impulses through
the central pathways of pain.
Can be blocked by naloxone, which is a morphine antagonist
Activation of the Pain Control System
Clinical (Experimental)Clinical (Experimental) Natural (physiological)Natural (physiological)
1- Electrical stimulation of certain
regions of pain control system
2- Local application of opiates (such
as morphine) at particular regions in
the nervous system.
(pharmacological anesthesia)
Exposure to severe stress,
particularly when associated with
strong emotional excitement.
PAG Midbrain
C.C.
Periventricular area of the hypothalamus
Limbic system
Reticular formation
Asc
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pa
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ath
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++
++ +
---
GABA
--- ++LCLC NRMNRM
GABA
--- ++
---
Serotonin +++
Epinephrine +++
Pons
Spinal Cord
1st order neuron in the pain pathway2nd order neuron in the pain pathway
---
How
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activ
ates
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pai
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?H
ow s
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Enkephalin binds to opiate receptors in:
1- Central terminal of 1st order neuron
-----> opening of Cl channel -----> Cl
influx -----> hyperpolarization ----->
block of Ca influx -----> inhibit release
of chemical transmitter from 1st order
neuron
2- postsynaptic 2nd order neuron in
pain pathway ------> opening of K
channels -----> hyperpolarization ----->
inhibit their response to the pain
chemical transmitter.
PAIN GATE CONTROL
The sites of synapses along the pain
pathway are considered as gates through
which pain transmission can be facilitated (if
the gate is open) or blocked (if the gate is
closed).
The main pain gates are:
1- Spinal gate: at the SGR.
2- Brain stem gate: at the nuclei of reticular
formation.
3- Thalamic gate: At neurons of PVLNT &
intalaminar thalamic nuclei.
3
1
2
At the spinal gate:
Pain transmission is blocked by:
1- Descending inhibitory impulses through the pain control system activating
enkephalin-secreting interneuron (see before)
2- Stimulation of the Large Diameter terminating peripherally in
mechanoreceptors, such as tactile receptors or proprioceptors. This may explain
why simple maneuvers such as rubbing the skin (thus exciting tactile and pressure
receptors), near a painful area is often effective in relieving certain types of pain.
Impulses from
tactile receptors
+
3- Acupuncture
Acupuncture has been practiced in China for more than 4000 years as a method
for pain relief.
Mechanism:Mechanism:
1- needles in appropriate body regions are thought to excite certain sensory neural
pathways which feed into the brain stem centers (such as the PAG) involved
in the pain control system, with release of endogenous opioid peptides.
2- simultaneous suppression of pain transmission at the spinal pain-gate by
acupuncture