Mednotes

L17 Nervous System Pain 1 _ 2

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tagsnervoussystem, lecture, pain, neurophysiology
aliasesNervous System Pain 1 & 2

10 min read

Overview

This lecture builds up the physiology of nociception and pain from the periphery to the brain: what nociception and pain are and how they differ, the case for why pain matters (a child unable to feel pain), the distinction between pain sensitivity and tolerance, the types of nociceptors and pain fibres, how primary afferents enter and are modulated in the spinal cord, where pain is represented in the brain, a clinical framework for classifying pain, and the neural mechanisms that increase or decrease pain — including gate control theory and descending inhibition — finishing with referred and phantom pain.

Nociception and pain: definitions

  • Nociception: an indicator of (potential) tissue damage.
  • Pain: subjective.
  • Pain is further characterised as an affective sensation that is conditional and indispensable, and one that spreads out (distributes) in the brain.

Why pain matters: the case of congenital C-fibre absence

A major function of the pain system is to prevent injury.

A 13-year-old boy born with congenital absence of C fibres had no sensation of pain. Consequences noted: amputated fingers, sores on his knees and elbows, swollen joints, and difficulty standing without assistance. These injuries resulted from his inability to feel pain and so not protect himself from repeated tissue damage.

Pain sensitivity vs pain tolerance

  • Pain sensitivity: the detection threshold; consistent between individuals.
  • Pain tolerance: “what’s bearable”; highly variable between individuals and circumstances.

Nociceptors and peripheral sensitisation

Nociceptor types:

  • Mechanical
  • Thermal
  • Polymodal
  • “Silent” — unresponsive until sensitised

Hyperexcitability: nociceptors become more excitable in response to persistent stimulation (e.g. painful touch after sunburn). Two forms:

  • Peripheral — chemical sensitisation
  • Central — “wind-up”

Peripheral chemical sensitisation mechanism (from a labelled diagram of a primary afferent neuron at a tissue lesion): the primary afferent’s cell body sits in the dorsal root ganglion; its peripheral terminal branches at the skin near the lesion. At the lesion, the terminal is exposed to bradykinin, serotonin, prostaglandin and K+ released from damaged tissue. One branch of the terminal releases substance P onto a nearby mast cell, triggering histamine release from the mast cell; another branch releases substance P onto a blood vessel. This is a neurogenic-inflammation loop: inflammatory mediators sensitise the nerve terminal, while the terminal’s own substance P release acts on mast cells and blood vessels, amplifying the local chemical environment.

Flag: this diagram carries no caption of its own; its content is interpreted from the labelled structures (dorsal root ganglion, mast cell, blood vessel, substance P, histamine, bradykinin, serotonin, prostaglandin, K+, lesion), and its link to "chemical sensitisation" is contextual (based on the preceding slide), not stated on the diagram itself.

Types of pain fibres

Two types of “pain fibres”:

  1. Aδ fibres — small, fast (6–30 m/s), myelinated: sharp, localised, “first pain”; respond to mechanical/thermal stimuli; travel via the neospinothalamic tract; proposed function “?alert”.
  2. C fibres — small, slow (0.5–2 m/s), unmyelinated: dull, aching, diffuse pain; chemical modality; travel via the paleospinothalamic tract; proposed function “?remind”.

Primary afferent neurons and spinal/ascending pathways

Primary afferent neurons (PAN):

  1. Enter the spinal cord via the dorsal horn, where significant modulation of pain occurs.
  2. From there, two routes:
    • Local connections — interneurons / reflex connections.
    • Ascending fibres — anterolateral pathway -> thalamus -> cortex.

Central distribution of pain

Pain is widely distributed in the brainstem (via “slow” C fibres) and cortex (via “fast” Aδ fibres):

  • Somatosensory cortex — awareness / location
  • Limbic system — emotional component
  • Diffusely in cerebrum/brainstem — arousal
  • Hypothalamus — nausea

The brainstem also branches to the reticular formation and the periaqueductal grey matter (PAG).

Clinical classification of pain

Clinically, pain is considered at three levels, plus chronic pain as a separate issue:

  • Nociceptive pain
  • Neuropathic pain
  • Central pain
  • Chronic pain — other issues

Mechanisms that increase pain (aggravators)

  • Nociceptor sensitisation
  • Peptide release
  • Spinal cord “wind-up”
  • Muscle spasm

Mechanisms that reduce pain (alleviators)

  • Activation of large-diameter afferents (“gate theory”)
  • Descending inhibition
  • Opioid peptides
  • Cerebral inputs

Gate control theory

Diagram legend: I = inhibitory interneuron; P = projection neuron; ”–” = inhibition; ”+” = excitation.

  • Small-fibre (nociceptive) input: inhibits I (”–”) and directly excites P (”+”).
  • Large-fibre (non-nociceptive) input: excites both I and P (both ”+”).
  • I makes an inhibitory (”–”) connection onto P.
  • P projects onward (”+”) to the brain, producing “PAIN”.

Net effect: small-fibre input suppresses I (reducing I’s inhibition of P) while directly exciting P — favouring pain transmission. Large-fibre input excites both I and P; I’s inhibition of P then tends to reduce net pain transmission — i.e. large-fibre activity “closes the gate”. Clinically, activation of large-diameter (touch) fibres blocks/inhibits transmission from small (pain) fibres.

Flag: exact placement of some of the diagram's +/– signs is small and dense in the source; transcribed as best read. The overall logic matches standard gate control theory, but individual sign positions should be checked against the original slide if fine detail is needed.

Descending inhibitory pathway

  1. The midbrain periaqueductal grey matter (PAG) receives excitatory (”+”) input from various brain areas.
  2. The PAG sends a descending projection (via an inhibitory interneuron) down to the medulla (raphe nuclei). Neurons at both the PAG and raphe nuclei levels are opioid-peptide-releasing neurons.
  3. The raphe nuclei send a further descending projection, releasing 5-HT (serotonin) and noradrenaline, down to the spinal cord dorsal horn.
  4. At the dorsal horn, this descending pathway makes an inhibitory (”–”) synapse onto a dorsal horn interneuron/projection cell, while the primary afferent neuron (PAN) makes an excitatory (”+”) synapse onto the same cell.
  5. The dorsal horn cell projects onward to the anterolateral pathway.

This is descending inhibitory modulation of incoming nociceptive (PAN) signal at the dorsal horn, via PAG -> raphe nuclei -> spinal cord, using opioid peptides, serotonin and noradrenaline. We inhibit pain fairly immediately on feeling it, via activation of these inhibitory pathways (which opioid/opiate drugs also activate).

Flag: this is a hand-drawn diagram; some labels (e.g. the exact synaptic sign near the medulla-to-cord projection) are small and slightly ambiguous, though the overall descending-inhibition circuit is clear.

Referred and phantom pain

Referred pain: body-map diagrams show “zones of hyperalgesia produced by disease of different viscera” for six conditions — oesophagus, angina (heart), left ureter, urinary bladder, labour pain, and right prostate — each with its own area(s) of referred/hyperalgesic skin.

Proposed spinal mechanism (from a labelled cross-section diagram): a somatic afferent from the “Skin” and a visceral afferent from a “Viscus” converge onto overlapping second-order neurons in the dorsal horn, whose axon ascends as the anterolateral tract axon.

Flag: this convergence diagram carries no text/title of its own; the "referred pain" interpretation is inferred purely from its position immediately after the referred-pain slide, not from any label on the diagram itself.

Phantom pain: introduced as a heading only — not elaborated within this slide range. [slide does not elaborate]

Self-test

  1. Distinguish nociception from pain as defined in the lecture.
  2. Why does the case of the boy with congenital absence of C fibres illustrate the function of the pain system?
  3. Distinguish pain sensitivity from pain tolerance.
  4. List the four categories of nociceptors described.
  5. Describe the mechanism of peripheral chemical sensitisation shown in the lesion diagram, including the roles of substance P, mast cells, and inflammatory mediators.
  6. Distinguish Aδ fibres from C fibres in terms of conduction velocity, myelination, pain quality, modality, spinal tract, and proposed function.
  7. Describe the two routes a primary afferent neuron’s signal can take after entering the spinal cord via the dorsal horn.
  8. List the brain regions/areas involved in pain processing and the function attributed to each.
  9. List the three clinical levels at which pain is considered, plus the additional chronic pain category.
  10. List the neural mechanisms described as increasing pain, and the neural mechanisms described as reducing pain.
  11. Explain, using the gate control theory diagram, why large-fibre (touch) activation reduces pain transmission while small-fibre activation favours it.
  12. Describe the steps of the descending inhibitory pathway from the periaqueductal grey matter to the spinal cord dorsal horn, including the neurotransmitters/peptides involved at each level.
  13. Describe the proposed spinal mechanism for referred pain shown in the convergence diagram.
  14. A patient presents with pain referred to the left shoulder tip region during a cardiac event (angina). Using the concepts from this lecture, what general mechanism explains why visceral disease produces pain felt at a distant skin site?
  15. A patient with a dislocated shoulder tenses their neck muscles and guards the area. Which aggravating mechanism from the “increase pain” list does this illustrate?

Answers

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