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

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++ +

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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

---

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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