Canonical Question
Pain Physiology
Master answer
Pain is an unpleasant sensory and emotional experience, associated with actual or potential tissue damage, or described in terms of such damage
Anatomical and physiological components of the response to pain
- Primary afferent nociceptors
- Pseudo-Unipolar
- Cell body in dorsal root ganglion
- Free nerve endings or specialized terminal structures
- Pacinian corpuscles
- Location
- Skin
- Connective tissue
- Muscle
- Blood vessels
- Viscera
- Responds to simuli
- Mechanical
- Chemical
- Thermal
- Pseudo-Unipolar
Nociception
- Transient Receptor Potential (TRP) Ion Channels
- Capsaicin
- Heat
- Acid
- Inflammation
- Ischaemia
- Acid-Sensing Ion Channel (ASIC)
- 5-HT3 receptors
- On activation of nociceptors
- Na channels open
- Depolarization from < -60mV to -40mV
- Rapid membrane depolarization
- Voltage Dependent Calcium Channels (VDCC) open and increase intracellular Ca
- Substance P and Calcitonin Gene-Related Peptide (CGRP), Neurokinin A released in response to Ca
- Mediate inflammation → macrophages, neutrophils, mast cells activated
- Increase excitability of sensory and sympathetic fibres
- Vasodilation, extravasation of plasma proteins
- Inflammatory cells release substances
- Histamine
- Bradykinin
- Serotonin
- Nitric Oxide
- Peripheral sensitization → Primary hyperalgesia
- to dampen pain response
- Silent nociceptors – Do not respond to external stimulus, however activated by inflammatory mediators
- Voltage-gated Potassium Channels stabilize the membrane potential
Signal Pathway
- Signal transduced via C fibres (0.5~2m/sec) or Aδ fibres (6~30m/sec) to dorsal horn
- Aδ activation → short, pricking pain
- C activation → burning, aching pain
- Primary afferent enters spinal cord at the spinal level, or above or below the spinal level via lissauer tracts and synapse with interneurons
- Via C fibres or Aδ fibres
- Signal relay via spinal interneurons
- Signalling via Glutamate and NMDA or AMPA receptors
- Nociceptor-specific
- Respond only to pain
- Wide Dynamic Range (WDR)
- Respond to nociceptors and other stimulus
- Central sensitization → allodynia
- Inhibitory interneurons and descending pathways modulate pain
- “Gate control theory of pain” → Aβ fibres carrying signals from benign stimuli inhibit noxious interneuron transmission
- Signal transduction to thalamus via anterolateral spinothalamic tract
- Small but significant proportion of signal transduction also occurs ipsilaterally
- Signal distributed to cerebral cortex via thalamus
- Putamen
- Hypothalamus
- Amygdala
- Periaquaductal grey matter
- Hippocampus
- Cerebellum
- Somatosensory cortex
Descending inhibitory pathways
- Noradrenaline
- Serotonin
- Substance P
- CCK
- GABA
Sakurai 2016
Exam appearances
| Exam | Exact wording | Relationship | Success |
|---|---|---|---|
| 2019B Q12 | Define pain. Outline the processes by which pain is detected in response to a peripheral noxious stimulus. | historical_member | — |
| 2013B Q22 | Define pain. (10% of marks) Describe the anatomical and immediate physiological components of the response to pain arising from the insertion of an arterial line. (90% of marks) | historical_member | — |
| 2023A Q09 | Define pain (10% of Marks). Describe how pain is detected and modulated in response to a peripheral noxious stimulus? (90% of Marks) | historical_member | — |
| 2025B Q05 | (a) Define pain (10% of marks). (b) Describe how pain is detected and modulated in response to a peripheral noxious stimulus (90% of marks). | safe_repeat | 56.00% |