Physiology of pain

Prof. Vajira Weerasinghe

Professor in Physiology, Faculty of Medicine

University of Peradeniya & Consultant Neurophysiologist, Teaching Hospital, Peradeniya

Topics covered in the lecture

1. What is pain (International definition of pain)

2. Dual nature of pain: fast pain and slow pain

3. What causes pain : pain stimuli

4. Nerve pathways carrying pain signals to the brain

5. Brain areas involved in pain perception

6. Pain modulatory pathways

7. Neurochemicals involved in pain pathways

8. Gate control theory of pain

What is pain?• Pain is a difficult word to define

• Patients use different words to describe pain

• eg.• Aching, Pins and needles, Annoying, Pricking, Biting, Hurting,

Radiating, Blunt, Intermittent, Burning, Sore, Miserable, Splitting, Cutting, Nagging, Stabbing, Crawling, Stinging, Crushing, Tender, Dragging, Numbness, Throbbing, Dull, Overwhelming, Tingling, Electric-shock like, Penetrating, Tiring, Excruciating, Piercing, Unbearable

• Different words in Sinhala or in Tamil

What is pain?• There is an International definition of pain

formulated by the IASP (International Association for the study of pain)

• Pain is an unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage

IASP – International Association for the Study of Pain 2009

What is pain?• Pain is

– subjective – protective – and it is modified by developmental, behavioural,

personality and cultural factors

• It is a symptom

• Associated signs are crying, sweating, increased heart rate, blood pressure, behavioural changes etc

Dual nature of pain

• Fast pain

– acute– pricking type– well localised– short duration

– Thin myelinated nerve fibres are involved (A delta)

• Slow pain

– chronic– throbbing type– poorly localised– long duration

– Unmyelinated nerve fibres are involved (c fibres)

• No stimuli, but pain is felt– phantom limb pain

• eg. in amputated limb

• Stimuli present, but no pain felt• eg. soldier in battle field, sportsman in

arena

• Pain due to a stimulus which does not normally provoke pain

• Allodynia

• Pain initiated or caused by a primary lesion or dysfunction in the nervous system

• Neuropathic pain

Different situations

Pain

• Pain as a sensation– physiologically (nociception)

• Pain as an emotional experience– psychologically

Stimuli • Physical

– pressure etc

• Electrical

• Thermal– cold, hot

• Chemical– H+, lactic acid, K+, histamine, bradykinin, acetylcholine, proteolytic

enzymes

– Prostaglandins• these increase the sensitivity (decrease the threshold) for other nociceptive

stimuli

Receptors

• There are no specialised receptors

• Free nerve endings are sensitive to pain stimuli

• Free nerve endings are distributed everywhere (both somatic and visceral tissues)

• Slow adapting type of receptors

Nerve pathways carrying pain signals to the brain

• Pain signals enter the spinal cord

• First synapse is present in the dorsal horn of the spinal cord

• Then the second order neuron travels through the lateral spinothalamic tracts

afferent fibres

• two types– A (thin myelinated)– C (unmyelinated)

central connections• afferent fibre enters the spinal cord

• synapses in laminae ii,iii– substantia gelatinosa

substantiagelatinosa

Neurotransmitter at the first synapse of the pain pathway is substance P

Pain

lateralspinothalamic tract

C fibre

substantiagelatinosa

• crosses the midline

• ascends up as the lateral spinothalamic tract

ascending pathway

lateralspinothalamic tract

thalamus

sensory cortex

C fibre

thalamocorticaltracts

Pain perception

• This occurs at different levels– thalamus is an important centre of

pain perception• lesions of thalamus produces severe

type of pain known as ‘thalamic pain’

– Sensory cortex is necessary for the localisation of pain

– Other areas are also important• reticular formation, limbic areas,

hypothalamus and other subcortical areas

Descending pain modulatory system

• several lines of experimental evidence show the presence of descending pain modulatory system

– discovery of morphine receptors– they were known to be present in the brain

stem areas

– discovery of endogenous opioid peptides

• eg. Endorphines, enkephalins, dynorphin

midbrain

pons

medulla

spinal cord

periaqueductal

grey nucleus

nucleus raphe

magnus

substantia gelatinosa

opioid peptides

• short peptides originally known to be secreted in CNS and later found to be present in GIT etc

opioid peptides endorphin

• earliest to discover, large peptide, present in the pituitary

• encephalins - met & leu• widely distributed

• dynorphin

• Endomorphine 1 & 2

• Pronociceptins

receptors

• delta

• mu

• kappa

• More recently discovered: ORL1 receptor

sensory cortex

C fibre

Final pain perception depends on activity of the

Ascending pain impulse transmitting tracts

Descending pain modulatory (inhibitory) tracts

Gate control theory

• This explains how pain can be relieved very quickly by a neural mechanism

• First described by P.D. Wall & Melzack (1965)

• “There is an interaction between pain fibres and touch fibre input at the spinal cord level in the form of a ‘gating mechanism’

Gate control theory

When pain fibre is stimulated, gate will be opened & pain is felt

pain

pain is felt

+gate is opened

Gate control theory

When pain and touch fibres are stimulated together, gate will be closed & pain is not felt

pain is

not felt

touch

pain

+ -

gate is closed

Gate control theory

• This theory provided basis for various methods of pain relief– Massaging a painful area – Applying irritable substances to a

painful area (counter-irritation)– Transcutaneous Electrical Nerve

Stimulation (TENS)– Acupuncture ?

Summary

• Pain is not just a sensation but is a more complex phenomenon

• Pain can be blocked at many places

• Chemicals play an important role in causing pain as well as in reducing pain

• Neural mechanisms also play a role in pain interaction

• This complex nature of pain perception makes it a very difficult entity to control

“Pain is a more terrible lord of mankind than even death itself”

Dr. Albert Schweitzer (1875-1965)