Pathophysiology of Pain

Dr.M.S.Biji
Assistant Professor
Department of Cancer Palliative Medicine
MALABAR CANCER CENTRE
Quality care means that pain is measured and
treated ”
American Pain Society
• Pain is the most common symptoms in
patients with cancer and it is certainly the
most feared.
 INCIDENCE
• Pain and advanced cancer are not
synonymous.
- ¾ of patients experience pain.
- ¼ of patients do not experience pain
• Most cancer patients have more than one
type of pain(80%)
 INCIDENCE
• Pain can be completely relieved in 80-90% of
patients through relatively simple means, and
acceptable relief is possible in most of the
remainder.
• However , pain often progresses with cancer
and regular reassessment and modifications
are necessary.
 “Pain is
what the patient says,
hurts.”

Believe the patient

about his/her pain!
 IASP Definition of Pain
“Pain is an unpleasant , sensory and emotional
experience associated with actual or potential
tissue damage or described in terms of such
damage”

(International Association for the study of pain,1979)

 2020 Revised definition of pain

• “ Pain is an unpleasant , sensory and

emotional experience associated with ,or
resembling that associated with, actual or
potential tissue damage”.
• Expanded upon by the addition of six Key
Notes.
 Pain is always a personal experience that is influenced to varying
Keynote 1 degrees by biological, psychological, and social factors.

Pain and nociception are different phenomena. Pain cannot be

Keynote 2 inferred solely from activity in sensory neurons.

Through their life experiences, individuals learn the concept of pain.

Keynote 3
A person's report of an experience as pain should be respected.
Keynote 4
Although pain usually serves an adaptive role, it may have adverse
Keynote 5 effects on function and social and psychological well-being.

Verbal description is only one of several behaviors to express pain;

Keynote 6 inability to communicate does not negate the possibility that a human
or a nonhuman animal experiences pain.
 Bio-psycho-social factors that influence
pain
Aspect that lower pain Aspects that raise the pain
threshold threshold
• Discomfort • Relief of other symptoms
• Insomnia • Sleep
• Fatigue • Rest
• Anxiety • Relaxation
• Fear • Support
• Boredom • Understanding/empathy
• Sadness • Companionship/Listening
• Social isolation • Social inclusion
• Abandonment • Encouragement to express
emotions
 Acute Vs Chronic Pain

• Acute pain :
– Pain of recent onset and limited duration with
identifiable relation with injury or disease.
• Chronic pain :
– Pain which persist a month beyond the usual
course of an acute disease or a reasonable time
for an injury to heal, or
– Is associated with chronic pathological process
which causes continuous pain, or
– Pain which recurs at intervals for months or years
 Difference in Presentation of Acute & Chronic
Pain
Acute Chronic

• Transient & self limiting • Persistent & unremitting

- symptom - disease
• Positive - attention to • Negative- no useful
injury or illness purpose
• Accompanying features • Vegetative
- Pupillary Dilation - Sleep disturbance
- Sweating,↑BP - Anorexia
- No pleasure in life
- Tachypnoea
- Personality change
- Tachycardia
Tendency to disbelieve the patient.
 ?Chronic pain difficult to treat
• The emotional component

• Pharmacological reasons

• Pathophysiological reasons
 When negative emotions are expressed
through physical symptoms like pain, it is
called SOMATISATION.

Somatisation is NOT
the patient’s fault!
 Pharmacological reasons
• Interaction between the individual and the
drug can be variable.
• Differences in absorption, distribution,
metabolism and excretion can occur from
patient to patient.
• Clinical significance: A step-wise approach,
looking for problems in any one of the above
four kinetic events, may help us find a
solution.
 Pathophysiological reasons
• Unrelieved pain can keep worsening for
several reasons.
• Eventually it can even cause permanent
abnormalities in the nervous system,
themselves generating pain.
• A 36 years old gentleman with Carcinoma
pancreas diagnosed 10 months back .
• No definitive treatment taken.
• On irregular pain medications for abdominal
pain. Now c/o pain all over his body.
• Why?
The Pain Pathway
 Pain Pathway

Courtsey: Armando Hasudungan - https://www.youtube.com/watch?v=5c8maFAhqIc

 Pain Pathway

Courtsey: Armando Hasudungan - https://www.youtube.com/watch?v=5c8maFAhqIc

 Pain impulses are relayed……….
• Sensory areas of parietal lobe –localization
and interpretation of pain
• Limbic system -involved in emotional &
autonomic response to pain
• Temporal lobe -Pain memory
• Frontal lobe –pain behavior
 Fast Pain

• Aδ fibers(myelinated)
• Sharp, well localized and pricking sensation
• Felt about 0.1 sec after a pain stimulus is
applied
• Accompaniment of fast pain
- Reflex withdrawal response -
- Sympathetic response i.e. increase BP, HR,
respiration.
 Slow Pain
• C fibres(unmyelinated)
• Poorly localised, dull, throbbing, burning
sensation.
• Usually begins after 1 sec or more
• Accompaniment
 Emotional perception in the form of unpleasantness,
 Long standing cases irritation, frustration and depression.
 Autonomic symptoms-Nausea, vomiting, profuse sweating,
hypotension.

tone
 Pain supression system in CNS
• Two major components

-Spinal Pain suppression system

-Supraspinal pain suppression system

 Gate Control Theory
• Melzack & Wall 1965
• Proposes a mechanism how pain is reduced by
activating a non-painful sensation.
• Pain signals can be interrupted in the
Substantia Gelatinosa of the spinal cord which
acts as a GATE.
 I
II
III
IV
V
VI

A-beta  laminae III, IV, V & VI

A- delta  laminae I & II
C  laminae I & II
 Segmental suppression
• Myelinated Aβ touch
fibres
• Collaterals
• Presynaptic inhibition
• Blocking of calcium
channels
 A
I A
II
III
C
IV
V
VI

Transcutaneous Electrical Nerve

Stimulation (TENS). Stimulation of touch
fibres closes a gate in lamina ll so that
Pain fibres cannot function properly
Transcutaneous Electrical Nerve
Stimulation (TENS).
Supraspinal pain suppression

Descending Inhibitory pathways.

Descending Inhibitory Pathway
 Descending inhibiting pathway
Two important descending inhibitory pathways from
the brainstem to the spinal cord.

First originate[s] at the level of the midbrain in the

periaqueductal gray and it has predominantly
serotonin its major neurotransmitter

Other originates at the level of the locus ceruleus in the

medulla and it has norepinephrine as the major
neurotransmitter.
 Aetiology of pain in palliative care
• Disease related - soft tissue infiltration, nerve
compression, bone spread, muscle spasm,
lymphoedema, raised ICT.
• Treatment related - surgery, chemo, radiation
• Debility related –pressure sore, constipation,
bladder spasm
• Comorbidities related -Low back ache,
arthritis, angina, trauma
• A 36 years old gentleman with Carcinoma
pancreas diagnosed 10 months back .
• No definitive treatment taken.
• On irregular pain medications for abdominal
pain. Now c/o pain all over his body.
• Why?
Peripheral sensitisation
 Peripheral sensitization
• At sites of injury or cancer, pain occurs due to
the stimulation of the sensory nerve ending
(nociceptor).
• One of the mediators, prostaglandin, makes
the nerve-ending more sensitive to other
pain-producing substances.
• Therefore blocking the generation of
prostaglandins with NSAIDS can prevent pain
caused by the other chemicals too.
 Central sensitisation
“wind-up”
NMDA

The nervous system becomes more sensitive in perceiving

pain to a given stimulus.
Woolf CJ, Anesth Analg. 1993;77:362-379.
Recruitment
 Recruitment

Peripheral

Peripheral recruitment :
The silent or sleepy nociceptors get recruited.
Central recruitment :
Newer areas in the central nervous system get recruited so that
more areas start responding to a painful stimulus.
 Reflex responses

Skeletal muscle spasm

Muscles go into spasm generating new pain

 Reflex responses

Vasoconstriction

 Reflex vasoconstriction causes liberation of more chemicals.

 In ischaemic pain, analgesics alone may improve vascularity to
a point
• Sensitisation of nociceptors.
• Sensitisation of dorsal horn cell.
• Recruitment of silent (sleepy) nociceptors.
• Recruitment of adjacent spinal segments
• Skeletal muscle spasm
• Vasoconstriction
Result:
Worsening pain in intensity and extent.
Long-standing Pain Pathological Changes

• Anatomical changes in the nerves, dorsal

horn and the brain

• Even genetic changes!

Clinical relevance?
• The earlier the pain is treated, the less these
perpetuating changes.
• All continuous pain warrant continuous
analgesia.
• Total relief is difficult if permanent changes
have taken place.
 Types of pain

Nociceptive Neuropathic
 Nociceptive & Neuropathic Pain
• Any pain caused primarily by stimulation of
the nociceptor can be said to be nociceptive
pain.
• Pain caused by a lesion or disease of the
somatosensory nervous system is called
neuropathic pain.
 Nociceptive pain
Visceral Somatic
• Visceral membrane, • Bone –periosteum
capsule-stretching
• Soft tissue
• Bowel – spasm, colicky

• Cardiac -ischaemia
 Neuropathic

Nerve compression Nerve injury

Peripheral Central Sympathetically

maintained
 Nerve injury pain
• Peripheral
Peripheral neuropathies
Post Herpetic Neuralgia
Phantom limb pain
• Central
Post stroke
Spinal cord compression
• Sympathetically maintained pain
 Complex regional pain syndrome
• CRPS – I : Reflex sympathetic dystrophy –
“Continuous pain in a portion of extremity
after trauma which may include fracture but
not involved major nerve, associated with
sympathetic over activity”
• CRPS – II : Causalgia – “Burning pain, allodynia,
usually in the hand and foot after partial injury
of a nerve or one of its major branches”
 Neuropathic pain Manifestations

1. Nature of pain (burning, pricking, aching,

shooting, lancinating)
2. Neural / dermatomal distribution
3. Abnormal sensations like allodynia
 Allodynia & Hyperalgesia

• Allodynia : Pain caused by a stimulus

that normally does not provoke pain
• Hyperalgesia : increased response to a
normally painful stimulus
 A
I A
II
III
C
IV
V
VI

Reorganisation may cause “touch”

to be perceived as “pain”!
 Breakthrough pain
• A transitory flare of pain that occurs in the context of
otherwise well-controlled pain

• Treat with a rescue dose (1/6 of the total daily dose) of

an immediate release preparation of morphine

• For morphine, if 3 or more rescue doses needed in one

day, increase baseline medication by 30-50%

• Always add a rescue

 End of dose failure pain
• If pain is experienced before the 4th hourly
dose of (i/r)opioid is due ,it is known as end of
dose failure pain
• Increase the baseline dose of the regular 4
hourly morphine
 Incident pain
• Pain precipitated by a particular activity,
washing, change in position, eating, or
disimpaction
• Can be anticipated
• Supplement regular analgesic regimen with a
rescue dose given 20-30 minutes before the
procedure
 Referred pain
• Pain which originates due to irritation of a
visceral organ and is not felt in the organ but
in some other somatic structure(usually skin)
supplied by the same neural segment.
• The Convergence Projection theory is the
leading theory behind referred pain.
 Convergence Projection Theory
• A dorsal horn neuron has
convergent input from
two different body
regions.
• Skin is topographically
mapped and the viscera
are not, hence the pain is
identified as originating
on the skin and not within
the viscera by the
thalamic neurons
Referred pain
 Total pain

social physical

spiritual emotional
 Total pain
• Physical
-disease
-immobility
-comorbiity
-poor sleep
-advere effects of treatment.
 Total pain
• Psychological
-anger
-delay in diagnosis
-treatment failure
-despair
-anxiety
-depression/sadness
 Total pain
• Social
-loss of job/status
-financial pressure
-worry about family
-isolation
-abandonment.
 Total pain
• Spiritual
-why has this happened to
me?
-what is the meaning of my
life?
-why did God allow this?
-what is the point?
 Conclusion
• Pain is what patient says.
• Not related to tissue damage.
• Bio-psychosocial factors influence pain.
• Pain causes more pain. Prevent/treat pain.
• Assess the type of pain
• Different types of pain require different
treatment plans
“Pain is a more terrible lord of mankind than
even death itself”
Albert Schweitzer(1875-1965)