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 · Dorsal root ganglia · Spinal cord · Grey matter of the cord · Thalamus · 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.

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.

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See it in 3D

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

In Biochemistry

Eicosanoids: prostaglandins, thromboxanes and leukotrienes

In Pharmacology

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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 (OpenStax (Rice University), 2022); 14.2 Central Processing (OpenStax (Rice University), 2022); Neuroanatomy, Spinal Cord (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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