#Pain physiology

#Define pain

Pain is an unpleasant sensory and emotional experience associated with actual or potential tissue damage.

It is not purely sensory, and incorporates perception and emotion.

Pain may be considered a protective mechanism:

• promotes withdrawal from harmful stimuli
• reinforces avoidance

#Describe how pain is detected and modulated in response to a peripheral noxious stimulus

#Pain detection

Pain begins with activation of peripheral nociceptors, followed by transmission through ascending pathways.

Nociceptors are free nerve endings in peripheral tissues that respond to:

• mechanical deformation
• thermal stimuli (hot or cold)
• chemical stimuli

Chemical mediators can be:

1. stimulating
   • H⁺ (acidosis)
   • K⁺
   • bradykinin
   • serotonin
2. or sensitising (lower activation threshold)
   • prostaglandins
   • substance P

Fast/sharp pain is detected and transmitted via a different pathway to slow/dull pain.

Feature	Fast (sharp) pain	Slow (dull) pain
Overview
Function	Immediate, protective	Persistent, affective
Localisation	Good	Poor
Stimulus	Mainly mechanical and acute thermal	Mechanical, thermal, chemical
Behavioural response	Rapid withdrawal from painful stimulus	Prolonged/sophisticated response
First-order neurone
Entry to spinal cord	In both pathways, the first order neurone enters the spinal cord via the dorsal root, with the cell body in the dorsal root ganglion
Synapse location	Lamina I in the dorsal horn	Lamina II–III (aka substantia gelatinosa) in the dorsal horn
Additional processing	—	Interneurons → lamina V
Main neurotransmitter(s)	Glutamate	Substance P + glutamate
Fibre type	Myelinated Aδ fibres	Unmyelinated C fibres
Conduction velocity	~20 m/s	~2 m/s
Second-order neurone
Pathway	In both pathways, the second-order neurone decussates immediately and ascends in the lateral spinothalamic tract
Termination	Mainly thalamus	Mainly brainstem
Key targets	Thalamus ± brainstem	Periaqueductal grey (PAG), tectal area, reticular nuclei
Third-order neurone
Projection	Somatosensory cortex + higher centres	Thalamus → somatosensory cortex
Functional role	Precise localisation	Affective/autonomic processing

#Pain modulation

Pain is not simply transmitted from periphery to cortex — it is continuously modulated, particularly at the level of the spinal cord. The final perception of pain reflects a balance between ascending nociceptive input and descending inhibitory control.

#Central inhibitory modulation

Pain signals ascending from the periphery are not passively transmitted to the brain — they are actively regulated by descending pathways from higher centres. This system allows the brain to turn down (or occasionally amplify) pain depending on context.

At a basic level, this is a top-down control system. Higher centres in the brain send signals to the spinal cord to modify how much pain information is allowed through.

These inhibitory pathways arise from several key regions:

1. Cortex

   • integrates cognitive and emotional context
   • e.g. attention, expectation, stress

2. Periaqueductal grey (PAG)

   • major control centre for pain modulation
   • integrates input from cortex and limbic system

3. Nucleus raphe magnus (in the medulla)

   • key relay station
   • sends inhibitory signals from higher centres to the spinal cord

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At the spinal level, these inhibitory pathways terminate in the dorsal horn of the spinal cord, near incoming nociceptive afferents. These pathways then reduce pain transmission in two main ways:

1. Direct inhibition of second-order neurones

   • reduces their ability to transmit signals up the spinothalamic tract

2. Activation of inhibitory interneurons

   • these interneurons suppress transmission from first → second order neurones
   • effectively 'blocking' the signal at the spinal level

The inhibitory effect is mediated by several key neurotransmitters (SONG):

• serotonin
• opioids (e.g. enkephalins)
• noradrenaline
• GABA

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#Gate control theory

Pain transmission can also be modulated locally within the spinal cord by competing sensory input. Spinal processing acts as a dynamic filter, integrating multiple inputs before transmission to the brain.

Mechanism:

• non-nociceptive stimuli (e.g. touch, pressure) carried by Aβ fibres activate inhibitory interneurons in the substantia gelatinosa

• these interneurons inhibit transmission from nociceptive C fibres to second-order neurones

• → reduced ascending pain signal (“closing the gate”).

This explains why rubbing or applying pressure to an injured area reduces perceived pain .

#Summary

Pain is a modulated sensory signal, not a fixed transmission of tissue injury.

Peripheral noxious stimuli activate nociceptors and are carried via:

• Aδ fibres → fast, sharp, well-localised pain
• C fibres → slow, dull, poorly localised pain

Signals synapse in the dorsal horn and ascend via the spinothalamic tract to the brain for conscious perception.

However, final pain perception is shaped by modulation at multiple levels:

• descending inhibitory pathways dampen transmission in the dorsal horn depending on context
• spinal gating mechanisms modulate input via competing Aβ (touch) fibre activity

The final pain experience reflects a balance between ascending nociceptive input and descending/spinal inhibition.