PATHOPHYSIOLOGY OF PAIN

PAIN????• 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”.

PAIN????

• “The fifth vital sign” – American Pain Society 2003

• Identifying pain as the fifth vital sign suggests that the assessment of pain should be as automatic as taking a patient’s BP and pulse

Pain is the most COMMON reason patients seek medical advice

Pain is a protective mechanism or a warning to prevent further injury

THE PATHOPHYSIOLOGY OF PAIN

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) A myelinated nerve fibers b) C unmyelinated nerve fibers

Points A 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

6) Specific stimulus More sensitive to pressure

Chemical agents e.g. LA, Histamine, kinins, PG

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, -endorphins Glutamate Norepinephrine, adrenaline Aspartate GABAATP Glycine

Chemical mediators of pain acting on CNS

Pain threshold and pain tolerance

The pain threshold is the point at which a stimulus is perceivedas painIt does not vary significantly among healthy people or in the same person over time

Perceptual dominance- intense pain at one location may cause an increase in the pain threshold in another location

• The pain tolerance is expressed as duration of time or the intensity of pain that an individual will endure before initiation overt pain responses. It is influenced by - persons cultural prescriptions

- expectations - role behaviours - physical and mental health

• Pain tolerance is generally decreased: - with repeated exposure to pain, - by fatigue, anger, boredom, apprehension, - sleep deprivation

• Tolerance to pain may be increased: - by alcohol consumption, - medication, hypnosis, - warmth, distracting activities, - strong beliefs or faith

Pain tolerance varies greatly among people and in the same person over time

A decrease in pain tolerance is also evident in the elderly, and women appear to be more tolerant to pain than men

Age and perception of pain• Children and the elderly may experience or express pain differently than adults

• Infants in the first 1 to 2 days of life are less sensitive to pain (or they simply lack the ability to verbalise the pain experience).• A full behavioural response to pain is apparent at 3 to 12 month

of life • Older children, between the ages of 15 and 18 years, tend to

have a lower pain threshold than do adults

• Pain threshold tends to increase with ageing • This change is probably caused by peripheral neuropathies and

changes in the thickness of the skin

Neuroanatomy of pain

The portions of the nervous system responsible for the sensation and perception of pain may be divided into three areas:

1. afferent pathways

2. CNS

3. efferent pathways

The afferent portion is composed of:

a) nociceptors (pain receptors)b) afferent nerve fibresc) spinal cord network

· Afferent pathways terminate in the dorsal horn of the spinal cord (1st afferent neuron)

● 2nd afferent neuron creates spinal part of afferent system

· The portion of CNS involved in the interpretation of the pain signals are the limbic system, reticular formation, thalamus, hypothalamus and cortex.

● The efferent pathways, composed of the fibers connecting the reticular formation, midbrain, and substantia gelatinosa, are responsible for modulating pain sensation

The brain first perceives the sensation of pain

• The thalamus, sensitive cortex : perceiving

describing of pain localising

• Parts of thalamus, brainstem and reticular formation: - identify dull longer-lasting, and diffuse pain

• The reticular formation and limbic system: - control the emotional and affective response to pain Because the cortex, thalamus and brainstem areinterconnected with the hypothalamus and autonomic nervous system, the perception of pain is associated with an autonomic response

The role of the afferent and efferent pathways inprocessing of pain information

Nociceptive painNociceptors: Endings of small unmyelinated and lightly myelinated afferent neuronsStimulators: Chemical, mechanical and thermal noxae

Mild stimulation positive, pleasurable sensation (e.g. tickling)

Strong stimulation painThese differences are a result of the frequency

and amplitude of the afferent signal transmitted from the nerve endings to the CNS

Location: In muscles, tendons, epidermis, subcutanous tissue, visceral organs

- they are not evenly distributed in the body (in skin more then in internal structures)

Afferent pathways:

• From nociceptors transmitted by small A-delta fibers and C- fibers to the spinal cord form synapses with neurons in the dorsal horn(DH)

• From DH transmitted to higher parts of the spinal cord and to the rest of the CNS by spinothalamic tracts

*The small unmyelinated C- neurons are responsible for the transmission of diffuse burning or aching sensations

*Transmission through the larger, myelinated A- delta fibers occurs much more quickly. A - fibers carry well-localized, sharp pain sensations

Efferent analgesic system

Its role: - inhibition of afferent pain signals Mechanisms: - pain afferents stimulates the neurons in periaqueductal gray (PAG) - gray matter surrounding the cerebral aqueduct in the midbrain results in activation of efferent (descendent) anti-nociceptive pathways

- from there the impulses are transmitted through the spinal cord to the dorsal horn

- there thay inhibit or block transmission of nociceptive signals at the level of dorsal horn

The role of the spinal cord in pain processing

• Most afferent pain fibers terminate in the dorsal horn of the spinal segment that they enter. Some, however, extend toward the head or the foot for several segments before terminating

• The A- fibers, some large A-delta fibers and small C- fibers terminate in the laminae of dorsal horn and in the substantia gelatinosa • The laminae than transmit specific information (about burned or crushed skin, about gentle pressure) to 2nd afferent neuron

• 2nd afferent neurons transmit the impulse from the substantia gelatinosa (SG) and laminae through the ventral and lateral horn, crossing in the same or adjacent spinal segment, to the other side of the cord. From there the impulse is carried through the spinothalamic tract to the brain. The two divisions of spinothalamic tract are known:

1. the neospinothalamic tract - it carries information to the mid brain, thalamus and post central gyrus (where pain is perceived)

2. the paleospinothalamic tract - it carries information to the reticular formation, pons, limbic system, and mid brain (more synapses to different structures of brain)

Theory of pain production and modulation

• Most rational explanation of painproduction and modulation is based on gate control theory (created by Melzack and Wall)

• According to this theory, nociceptive impulses are transmitted to the spinal cord through large A- delta and small C- fibers

• These fibers create synapses in the SG • The cells in this structure function as a gate, regulating transmission of impulses to CNS

Stimulation of larger nerve fibers (A-alfa, A-beta) causes the cells in SG to "close the gate". • A closed gate decreases stimulation of T-cells (the 2nd afferent neuron), which decreases transmission of impulses, and diminishes pain perception

Stimulation of small fiber input inhibits cells in SG and "open the gate".

• An open gate increases the stimulation of T-cells transmission of impulses enhances pain perception

• In addition to gate control through large and small fibers stimulation, the central nervous system, through efferent pathways, may close, partially close, or open gate. Cognitive functioning may thus modulate pain perception

Action of endorphins(ED)All ED act by attaching to opiate receptors on the plasma membrane of the afferent neuron. The result than is inhibition of releasing of the neurotransmitter, thus blocking the transmission of the painful stimulus

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 catabolismFat metabolism : Increase lypolysis and oxidation

Immunological : Immune dysfunction. Infection Tumour recurrence Coagulations : Deep venous thrombosis and pulmonary embolismPSYCHOLOGICAL 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

2) Signal of organic disease process

2) No such function serve

3) Usually caused by noxious stimulation

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

4) Associated with potent neuroendocrinal response

4) Absent

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 A 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.

b) 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

Acute and chronic pain• Acute pain is a protective mechanism that alerts the • individual to a condition or experience that is immediately • harmful to the body• Sudden onset

Relief - after the chemical mediators that stimulate the nociceptors, are removed• This type of pain mobilises the individual to prompt action to relieve it• Stimulation of autonomic nervous system can be observed during this type of pain (mydriasis, tachycardia, tachypnoe, sweating, vasoconstriction)• Psychological and behavioural response to acute pain- fear - general sense of unpleasantness or unease- anxiety

• Chronic pain is persistent or intermittent usually defined as lasting at least 6 months

• The cause is often unknown, often develops insidiously, very often is associated with a sense of hopelessness and helplessness. Depression often results

Psychological response to chronic painIntermittent pain produces a physiologic response similar to acute pain.Persistent pain allows for adaptation (functions of the body are normal but the pain is not reliefed)

Chronic pain produces significant behavioural and psychological changesThe main changes are:- depression - an attempt to keep pain - related behaviour to a minimum- sleeping disorders- preoccupation with the pain - tendency to deny pain

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