SEMINAR

PATHOPHYSIOLOGY OF PAIN

INTRODUCTION

PATHOPHYSIOLOGY OF PAIN

PERCEPTION

PHYSIOLOGICAL EFFECTS OF PAIN

CLASSIFICATION OF PAIN

ASSESSMENT OF PAIN

INTRODUCTION

Latin word ‘Poena’ - Penalty or punishment.

Definition : IASP - “An unpleasant and emotional experience

associated with actual or potential tissue damage or described in

terms of such damage”.

Sherrington – “The psychical (pertaining to mind) adjunct (joint to)

of an imperative (urgent) protective reflex”.

Subjective experience.

Awareness of harmful agent.

Reflex withdrawal response.

Pain sensation has a protective function.

Why pain should be treated ?

To releive suffering

Reflex muscle spasm

• Respiratory embarrassment

• Itself can be major cause of severe pain

Untreated pain will keep getting worse

Anatomical and genetic changes

PATHOPHYSIOLOGY OF PAIN PERCEPTION

Two major classes

Normal or nociceptive

Abnormal or pathophysiologic

Nociception : “Complex series of physiologic events that occurs between the initiation of tissue damage and perception of pain”

Four processes

• Transduction :

• Transmission :

• Modulation :

• Perception :

PAIN RECEPTORS The receptors which mediate pain is called nociceptorsNociceptors - Two types of nerve fibers. a) Aδ myelinated nerve fibers b) C unmyelinated nerve fibers

Points Aδ Fibre nociceptor C fibre nociceptor

1) Number Less More

2) Myelination Myelinated Unmyelinated

3) Diameter 2 – 5 micron 0.4 – 1.2 micron

4) Conduction velocity

12 – 30 m/sec 0.5 – 2 m/sec

5) Neurotransmitter Glutamic acid Substance P

7) Impulse conduction

Noxious stimulus Fast component

Thermal & mechanical stimulus, Slow component

9) Sensitivity to electrical stimulus

More Less

Pain receptors are activated by three noxious stimuli

• Mechanical, • Thermal, • Chemical

Mechanical :

• Excessive pressure or tension on nerve

• E.g. blow on the head, pulling of hair, pain of child birth.

Thermal :

• Raising skin temperature above 450C or exposure to cold (00) is painful.

Chemical :

• Endogenous – Histamine, Kinins, prostaglandin released from damaged tissue.

• Exogenous – H2SO4, HCl, H2O2

Chemical mediators of pain acting on nociceptors

Potassium, ATP, ADP

Bradykinines

Leukotrines

Serotonin

Histamines

Prostaglandins

Excitatory Inhibitory

Substance P Somatostatin, acetyl choline

Calcitonine gene related peptides Enkephalins, β-endorphins

Glutamate Norepinephrine, adrenaline

Aspartate GABA

ATP Glycine

Chemical mediators of pain acting on CNS

NEURAL PATHWAYS FOR PAIN

Three neuron pathways

1. First order neurons :

Dorsal root ganglion

2. Second order neurons :

Spinal cord and arranged as 10 laminae of rexed.

Cross to the opposite side and form the spino thalamic tract.

Two types of nociceptive spinal projection of second order neurons are

• Wide dynamic range – Aδ, C, Aβ fibers

Both noxious Non noxious stimulus.

• Neuron specific - Aδ, C fibers

Noxious stimulus.

3. Third order neurons :

Thalamus somato sensory area i.e I & II.

PATHWAYS FOR THE FAST PAIN

In peripheral nerves :

Aδ

velocities between 6 and 30 m/sec

DRG spinal cord

In the spinal cord :

Tract of Lissauer

Lamina I.

Opposite side

Neospinothalamic tract.

In the brain stem : Reticular formation thalamus.

In the thalamus : Ventral posterolateral nucleus Primary sensory cortex.

PATHWAYS FOR SLOW PAINIn peripheral nerves : Unmyelinated C fibres Velocities ranging from 0.5 to 2

m/sec DRG Spinal cordIn the spinal cord : Laminae II and III Substantia gelatinosa Crosses the midline Paleospinothalamic tractIn the brain stem : Reticular formation, and also in

superior colliculus, and periaqueductal grey region.

Intralaminar nuclei and posterior nuclei of thalamus

Hypothalamus Brain

PAIN SUPPRESSION SYSTEMS IN CNS

Two major components:

Spinal pain suppression system, and

Supraspinal pain suppression system.

Spinal pain suppression system

Gate control hypothesis

Metzak and Wall in 1965.

Dorsal grey horn

• Segmental suppression

• Supraspinal suppression

A. Segmental Suppression :

Myelinated (Aβ) touch fibres

Collateral

Presynaptic inhibition

Blocking calcium channels

Clinical application

Local application of warmth and cold

Rubbing or massage or pressure in the vicinity of painful area

Local application of counter irritants

Acupuncture

Transcutaneous electric nerve stimulation

Supraspinal pain suppression system :

Descending serotonergic and opiod inhibitory

system

Descending purinergic inhibitory system and

Descending adrenergic inhibitory system

Descending serotonergic and opioid inhibitory system :

Components

Raphe Magnus Nucleus (RMN) :

Lower pons and upper medulla.

Periaqueductal Grey (PAG) reticular formation, hypothalamus, and frontal cortex.

Serotonin and substance P.

Project down the dorsolateral column

postsynaptic inhibition.

Periaqueductal grey (PAG) area

in the midbrain

Raphe Magnus Nucleus

(RMN)

Opioid receptors

Four types of opioid

receptors µ,κ,δ and σ.

Stimulation

Pain suppression circuitry

Reduced pain perception.

Primary afferent pain carrying fibres

Substantia gelatinosa of dorsal horn.

Substance P as neurotransmitter.

endorphin and enkephalin Decrease the release of

substance P Presynaptic inhibition. Stimulate both i.e. PAG

as well as RMN.

OPIOID RECEPTORS

Hypothalamus and frontal cortex Stimulate – PAG as well as RMN

Descending purinergic inhibitory system :

Adenosine.

Pre and postsynaptic

Excitatory amino acid release.

Descending noradrenergic inhibitory system :

Locus coeruleus and medullary reticular formation

Dorsolateral fasciculus.

Stress

Pain perception in children –

26th week of gestation

It has larger receptor field

High concentration of receptors sites for substance P

Less developed descending inhibitory pathway.

PHYSIOLOGICAL AND PSYCHOLOGICAL EFFECTS OF PAIN

Respiratory system

Reduction in lung volume (TV, VC, FRC)

Regional lung collapse (atelectasis)

Decrease alveolar ventilation leads to hypoxemia and hyper capnia.

Cough is decreased

Secretions are retained

Chances of chest infections are more

Increase O2 consumption

Increase metabolic substrate formation.

Cardiovascular system :

Increase in HR, BP, CO, Systemic and coronary vascular resistance.

Increase in cardiac work and myocardial oxygen consumption

Decrease myocardial oxygen delivery

Risk of ischaemia, infarction and deep venous thrombosis increases.

Gastrointestinal and genitourinary system :

Increases intestinal secretion

Increases smooth muscle sphincter tone

Decreases gastrointestinal motility (stasis & ileus)

Increase bladder sphincter tone – retention of urine.

Neuroendocrine and metabolic effects :

↑ Catabolic hormones e.g. ACTH, ADH, GH, Cortisol, Catecholamines, renin, angiotensin II, aldosteron, glucagon.

↓ Anabolic hormones e.g. insulin and testosterone.

Ebb phase Flow phase Catabolism.

Net resulting negative nitrogen balance.

Carbohydrates metabolism :

Hyperglycemia, glucose intolerance, insulin resistance.

Protein metabolism :

Muscle protein catabolism

Fat metabolism :

Increase lypolysis and oxidation

Immunological :

Immune dysfunction.

Infection

Tumour recurrence

Coagulations :

Deep venous thrombosis and pulmonary embolism

PSYCHOLOGICAL RESPONSE :

Behaviour :

Self absorption and concern, withdrawal from inter personal contact, increase sensitivity to external stimuli, grimacing, postering, reduced activity and seeking help and attention.

Affect :

Fear and anxiety

Feeling of helplessness, loss of control, depression and insomnia.

CLASSIFICATION OF PAIN

A) Physiological pain

Brief noxious stimulus

Activates receptors

Impulse modification

Normal neural processing

Allerting mechanism

Good correlation

B) Clinical pain

Prolonged noxious stimulus

Activates receptors

Peripheral and central sensitization

Two types – Nociceptive and Neuropathic

I) Nociceptive pain –

Stimulation of nociceptor.

Primary and secondary hyperalgesia and allodynia.

Hyperalgesia – An increased response to a stimulus which is normally painful.

• Primary hyperalgesia – excessive sensitivity of pain receptors itself e.g. sunburned skin.

• Secondary hyperalgesia – means facilitation of sensory transmission.

Allodynia – Pain due to a stimulus which does not normally provoke pain.

Protective function

Poor correlation

II) Neuropathic pain –

“Pain associated with injury, disease or surgical section of the peripheral and central nervous system”

Three types : Neural injury pain – e.g. Nerve compression pain – e.g. Complex regional pain syndrome

CRPS – I : Reflex symphathetic dystrophy – “Continuous pain in a portion of extremity after trauma which may include fracture but not involved major nerve, associated with symphathetic 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”

No correlation between injury and pain perception

Acute pain Chronic pain

1) Pain of recent onset and limited duration with identifiable relation with injury of disease

1) Pain which persist a month beyond the usual course of an acute disease or a reasonable time for an injury to heal

3) Usually caused by noxious stimulation

3) Cause is often unclear. Psychological and environmental factors play major role

5) Disappear with t/t of cause 5) Often unresponsive to many form of treatment

6) Opioids typically effective and indicated

6) Poorly effective

7) Most commonly – acute medical illness, MI, pancrititis, renal colic

7) Commonly in chronic backache and cancer pain.

CLASSIFICATION ACCORDING TO DURATION OF PAIN

Fast Pain

Aδ fibers

Sharp, well localized and pricking sensation

Within 0.1 msec

Accompanient of fast pain

• Reflex withdrawal response

• Sympathetic response i.e. increase BP, HR,

respiration.

Not radiate.

Slow pain :

C fibres

Poorly localised, dull, throbbing, burning sensation

After 1 sec

Accompanient

• Unpleasantness, irritation, frustration and depression.

• Nausea, vomiting, sweating, bradycardia, hypotension.

• Generalized reduction of skeletal muscle tone

CLINICAL TYPES OF PAIN Somatic pain and visceral pain Referred pain and radiating pain Somatic pain : Arises from the tissue of the body other than the viscera.a) Superficial somatic pain

• Skin and subcutaneous tissue.• Similar to the fast pain.

a) Deep somatic pain • Muscle, joints, bones and fascia. • Similar to slow pain.

Clinical condition • Injuries• Tissue ischaemia • Inflammation of tissues• Muscle spasm

Visceral pain :

Poorly localized

Unpleasant

Nausea, vomiting, decrease BP & HR profuse sweating.

GUARDING

Radiates or referred to other site

C fibres.

Common causes :

Inflammation of viscera

Over distension of hollow viscus.

Spasm of hollow viscus.

Chemical stimuli

Ischaemia

Referred pain :

Pain which originates due to irritation of visceral organ and

is felt not in the organ but in some another somatic

structure. (skin) supplied by same neural segment.

DERMATOMAL RULE.

e.g.

Myocardial infarction

Stone in ureter

Inflammation of diaphragm

THEORIES OF REFERRED PAIN Convergence theory Facilitation theory Convergence theory : First order neuron Somatic area and a visceral organ Second order neuron Source of pain Somatic pain is more commonFacilitation theory : The visceral irritation Facilitates pain fiber Even minor somatic irritation PainRadiating pain :• Pain seems to spread from local area to the distant site is

called radiating pain. • E.g. in appendicitis, pain starts in right iliac fossa and

radiates towards centre of abdomen.

ASSESSMENT OF PAIN

Evaluation of pain in children and adults Verbal rating scale

0 – No pain 1 – Mild pain 2 – Moderate pain 3 – Severe pain

Verbal Numerical rating scale 0 – 10 0 – No pain 10 – Worst pain

Visual analog scale 10 cm horizontal line No pain at one end Worst possible pain on other end Describe intensity not the quality

McGill’s pain questionnaire

20 aspects

1 – 10 – Sensory aspects

11 – 15 – Affective aspects

16 – evaluative aspects or

17 – 20 – Other miscellaneous aspect

Evaluation of pain in preschool children

Physiological and behavioural

Self report

Methods

Happy sad face scale, the oucher scale, colour analog scale, poker chip tool, ladder scale, linear analog scale.

Evaluation of pain in neonate and children

Physiological and behavioural response

Physiological changes - ↑ HR, RR, BP, palmer, sweating

Behavioural changes

Eyebrow bulge, eye squeeze, nasolabial furrow, open

lips, vertical or horizontal stretching of mouth, lip purse.

Diffuse body movement

Type of cry