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[Physiology](https://durgical.com/en/physiology/) · [Neurophysiology](https://durgical.com/en/physiology/#s-neuro)

# Pain and temperature: pathways and modulation

- Mechanism
- Exam priority: high

Pain starts at free nerve endings, rides two fibre speeds up the spinal cord, and the body can turn its volume up or down.

Updated 2026-11-01

Also called: Nociception, Descending analgesia

**See it in 3D:** [Skin](https://durgical.com/en/anatomy/skin/) · [Dorsal root ganglia](https://durgical.com/en/anatomy/spinal-ganglion/) · [Spinal cord](https://durgical.com/en/anatomy/spinal-cord/) · [Grey matter of the cord](https://durgical.com/en/anatomy/grey-matter-of-spinal-cord/) · [Thalamus](https://durgical.com/en/anatomy/thalamus/) · [Midbrain](https://durgical.com/en/anatomy/midbrain/)

## Key points

- Aδ fibres (thinly myelinated, ≈6–30 m/s): fast, pricking pain, glutamate. C fibres (unmyelinated, ≈0.5–2 m/s): slow, burning pain, glutamate plus substance P.
- Nociceptors adapt very little and sensitize: prostaglandins and bradykinin lower their threshold (hyperalgesia).
- Descending analgesia: periaqueductal gray → raphe magnus (serotonin) and locus coeruleus (norepinephrine) → dorsal horn enkephalin interneurons that block pain transmission.
- Gate control: Aβ touch fibres excite inhibitory dorsal horn interneurons, which is why rubbing a hurt area helps.
- NSAIDs reduce prostaglandin sensitization; opioids act on μ receptors in dorsal horn, brainstem and cortex; local anesthetics block Na⁺ channels, small fibres first.
- Temperature sensors are TRP channels: TRPV1 (heat, capsaicin) and TRPM8 (cold, menthol).

## What it is

Nociceptors are free nerve endings activated by intense mechanical, thermal or chemical stimuli. Fast Aδ fibres carry sharp, well-localized first pain; slow C fibres carry dull, burning, poorly localized second pain. Signals enter the dorsal horn, cross and ascend in the anterolateral system to the thalamus and cortex. The dorsal horn works as a gate: descending pathways and touch input can close it, while inflammation and repeated firing can open it wider.

## How it works, step by step

- Tissue injury releases K⁺, H⁺, bradykinin, prostaglandins, ATP and histamine around free nerve endings.
- Transducer channels (TRPV1, acid-sensing, mechanosensitive) depolarize the nociceptor; prostaglandins lower its threshold.
- Aδ fibres signal the first, sharp pain; C fibres follow with the second, burning pain.
- In the dorsal horn (laminae I, II, V) they release glutamate and, from C fibres, substance P and CGRP.
- Second-order neurons cross in the anterior white commissure and ascend in the anterolateral tract.
- The neospinothalamic part reaches VPL thalamus and somatosensory cortex: where the pain is and what it feels like.
- The paleospinothalamic part reaches the reticular formation, intralaminar thalamus, insula and cingulate: how unpleasant it is and the arousal.
- Periaqueductal gray and raphe magnus send fibres down that activate enkephalin interneurons and damp the signal.
- Repeated C fibre firing (windup) and NMDA activation cause central sensitization: allodynia and spreading hyperalgesia.

## Reference values

| Parameter | Value | Note |
| --- | --- | --- |
| Aδ fibre conduction velocity | ≈6–30 m/s | |
| C fibre conduction velocity | ≈0.5–2 m/s | |
| Heat pain threshold | ≈43–45 °C | skin; TRPV1 activation |

Approximate values for a healthy adult at rest; each laboratory sets its own ranges.

## Regulation

- *+* **Prostaglandins (PGE₂), bradykinin**: Sensitize nociceptors: lower threshold, hyperalgesia
- *+* **Substance P and NMDA activation in the dorsal horn**: Central sensitization (windup), allodynia
- *−* **Enkephalins and endorphins (μ, δ receptors)**: Reduce presynaptic Ca²⁺ entry and hyperpolarize dorsal horn neurons
- *−* **Descending serotonin and norepinephrine**: Suppress transmission in the dorsal horn
- *−* **Aβ touch input (gate control)**: Activates inhibitory interneurons and reduces pain

## Clinical notes

- Postherpetic neuralgia after herpes zoster is neuropathic pain from damaged sensory neurons plus central sensitization.
- Congenital insensitivity to pain (loss of the Nav1.7 channel) causes painless fractures and burns: pain is protective.
- Diabetic small-fibre neuropathy removes protective pain, so foot ulcers go unnoticed.
- Opioids also act on μ receptors in the brainstem respiratory centres, so they depress breathing; naloxone reverses it by competing for the receptor.

## Memory aid

Aδ is the alarm (sharp, first); C is the one that continues (dull, burning, later).

## Test yourself

Think of the answer, then tap the question to see it.

## Why does a hammer blow to the thumb cause a sharp pain followed a second later by a throbbing ache?

Two fibre types: myelinated Aδ fibres conduct at ≈6–30 m/s and arrive first; unmyelinated C fibres conduct at ≈0.5–2 m/s, so their dull, burning pain arrives later.

## How do NSAIDs and opioids reduce pain at different sites?

NSAIDs block cyclooxygenase, so less prostaglandin sensitizes nociceptors. Opioids bind μ receptors in the dorsal horn, brainstem and cortex, reducing transmitter release and the firing of pain neurons.

## Why do local anesthetics usually remove pain before touch and movement?

Thin fibres (C, Aδ) stop conducting when a shorter length of nerve is blocked, so they fail first; large Aβ and Aα fibres need a longer blocked segment.

## What is allodynia and how does central sensitization explain it?

Pain from a normally harmless stimulus such as light touch. After intense C fibre input, dorsal horn neurons become hyperexcitable (NMDA, windup) and respond to Aβ touch input as if it were pain.

[Add to my cards (4)](https://durgical.app/estudiar/?add=/en/physiology/pain-and-temperature-pathways-and-modulation/)

## See it in 3D

The structures of Durgical's 3D anatomy where it happens.

- [Skin](https://durgical.com/en/anatomy/skin/)
- [Dorsal root ganglia](https://durgical.com/en/anatomy/spinal-ganglion/)
- [Spinal cord](https://durgical.com/en/anatomy/spinal-cord/)
- [Grey matter of the cord](https://durgical.com/en/anatomy/grey-matter-of-spinal-cord/)
- [Thalamus](https://durgical.com/en/anatomy/thalamus/)
- [Midbrain](https://durgical.com/en/anatomy/midbrain/)

## Related topics

- [Somatosensory pathways: dorsal column and anterolateral](https://durgical.com/en/physiology/somatosensory-pathways-dorsal-column-and-anterolateral/)
- [Visceral and referred pain](https://durgical.com/en/physiology/visceral-and-referred-pain/)
- [Headache physiology](https://durgical.com/en/physiology/headache-physiology/)
- [Sensory receptors, coding and neuronal circuits](https://durgical.com/en/physiology/sensory-receptors-coding-and-neuronal-circuits/)
- [The physiology of inflammation](https://durgical.com/en/physiology/the-physiology-of-inflammation/)
- [Types of nerve fibers](https://durgical.com/en/physiology/types-of-nerve-fibers/)

## Related conditions

- [Herpes zoster (shingles)](https://durgical.com/en/conditions/herpes-zoster/)
- [Trigeminal neuralgia](https://durgical.com/en/conditions/trigeminal-neuralgia/)
- [Type 2 diabetes mellitus](https://durgical.com/en/conditions/type-2-diabetes-mellitus/)

## In Biochemistry

- [Eicosanoids: prostaglandins, thromboxanes and leukotrienes](https://durgical.com/en/biochemistry/topics/eicosanoids-prostaglandins-thromboxanes-and-leukotrienes/)

## In Pharmacology

- [Opioids and antagonists](https://durgical.com/en/pharmacology/classes/opioids-and-antagonists/)
- [Morphine](https://durgical.com/en/pharmacology/morphine/)
- [Naloxone](https://durgical.com/en/pharmacology/naloxone/)
- [Nonsteroidal anti-inflammatory drugs (NSAIDs)](https://durgical.com/en/pharmacology/classes/nonsteroidal-anti-inflammatory-drugs/)
- [Local anesthetics](https://durgical.com/en/pharmacology/classes/local-anesthetics/)
- [Lidocaine](https://durgical.com/en/pharmacology/lidocaine/)

[← All of physiology](https://durgical.com/en/physiology/)

Educational physiology content; not a diagnostic or treatment guide and no substitute for a health professional's advice. Values are approximate references. No doses are given.

Sources: [14.1 Sensory Perception](https://openstax.org/books/anatomy-and-physiology-2e/pages/14-1-sensory-perception) (OpenStax (Rice University), 2022); [14.2 Central Processing](https://openstax.org/books/anatomy-and-physiology-2e/pages/14-2-central-processing) (OpenStax (Rice University), 2022); [Neuroanatomy, Spinal Cord](https://www.ncbi.nlm.nih.gov/books/NBK559056/) (StatPearls (NCBI Bookshelf), 2023); Hall JE. Guyton and Hall Textbook of Medical Physiology, 13th ed. (ch. 49). Reference book used to check facts; its text and figures are not reproduced (Elsevier, 2016).

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Representative model, for educational purposes only.

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License: CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/). Cite as: DurgiPedia (durgical.com), https://durgical.com/en/physiology/pain-and-temperature-pathways-and-modulation/