Tissue Stimulus Activates the Nociceptor Ending
Free nerve endings in skin sense damage-signaling stimuli.
- Free: Nociceptor endings (unmyelinated terminal branches)
- 3: Stimulus modalities (mechanical, thermal, chemical)
- ~200/cm²: Skin nociceptor density (in human skin)
- Noxious: Activation threshold (only strong stimuli trigger)
What a nociceptor is
A bare sensory ending that detects tissue-damaging stimuli.
Three stimulus types
Pressure, heat or cold, and irritant chemicals all qualify.
Why endings stay bare
No myelin at the tip keeps receptor proteins exposed.
Stimulus-Gated Channels Build a Generator Potential
Ion channels convert stimulus energy into an electrical signal.
- TRPV1: Key channels (heat and capsaicin sensor)
- Piezo2: Mechano channel (pressure-gated pore)
- Graded: Potential type (not all-or-none)
- Na⁺ / Ca²⁺: Ion carrying current (cation influx)
Transduction channels
TRPV1 senses heat; Piezo2 senses stretch and pressure.
Graded depolarization
Channel opening scales smoothly with stimulus strength.
Local, not propagating
The generator potential decays with distance from the source.
Summation matters
Repeated or stronger stimuli sum toward threshold.
Depolarization Crosses Threshold at the First Node
Voltage-gated sodium channels wait near the spike-initiation zone.
- ≈ -55 mV: Threshold voltage (typical axon threshold)
- ≈ -70 mV: Resting potential (before stimulus)
- Nav1.7: Key channel (sets nociceptor excitability)
- No spike: Below-threshold outcome (signal simply fades)
All-or-none decision
Below threshold nothing propagates; above it, a spike fires.
Nav1.7 and Nav1.8
These channel subtypes set nociceptor firing threshold.
Clinical relevance
Nav1.7 mutations cause rare pain-insensitivity syndromes.
Sodium Influx Fires the Action Potential
Voltage-gated sodium channels snap open in a self-reinforcing cascade.
- ≈ +30 mV: Peak voltage (depolarization overshoot)
- <1 ms: Channel kinetics (activation then inactivation)
- K⁺ efflux: Repolarization (restores resting state)
- All-or-none: Signal type (fixed amplitude spike)
Regenerative sodium influx
Open channels depolarize the membrane, opening more channels.
Fast inactivation
Sodium channels close automatically within a millisecond.
Potassium repolarizes
Delayed potassium efflux resets the membrane voltage.
The Signal Travels the Axon to the Spinal Cord
Fiber type sets how fast the pain message reaches the cord.
- 5-30 m/s: A-delta speed (myelinated, sharp fast pain)
- 0.5-2 m/s: C-fiber speed (unmyelinated, dull slow pain)
- Saltatory: A-delta conduction (jumps between nodes)
- Continuous: C-fiber conduction (wave creeps along membrane)
Saltatory conduction
Myelin forces current to jump node to node, speeding transit.
Unmyelinated conduction
C-fibers regenerate the spike continuously along the membrane.
Two pain sensations
Fast A-delta signals sharp pain; slow C-fibers signal dull ache.
Arrival at the cord
The spike reaches synapses in the spinal dorsal horn.