In one breath
Pain climbs in the lateral spinothalamic tract of the anterolateral system, as two parallel pathways. The neospinothalamic pathway carries fast pain on Aδ fibers from laminae I and V to the specific (VPL) thalamic nuclei and on to the postcentral gyrus, so it tells you where the pain is and how bad. The older paleospinothalamic pathway carries slow pain on C fibers from lamina II, sheds collaterals into the reticular formation, midbrain and hypothalamus, and relays in the non-specific (intralaminar and midline) nuclei, so it supplies arousal, emotion and autonomic reactions. Damaged tissue releases the chemicals that excite nociceptors, and substance P from the C-fiber ending sensitizes them further.
Builds on: Pain: concepts, receptors and fibers · Ascending tracts: dorsal column and anterolateral system · Leads to: Visceral and referred pain · Endogenous pain control and gate control theory · Thalamus: nuclei, functions and thalamic syndrome · Somatosensory cortex
The two pain pathways
- All pain reaches the brain through the lateral spinothalamic tract, one limb of the anterolateral system (Ascending tracts: dorsal column and anterolateral system).
- Inside that tract run two pathways of different age and different job:
| Paleospinothalamic | Neospinothalamic | |
|---|---|---|
| Age | phylogenetically oldest | best developed in primates |
| Carries | slow pain | fast pain |
| Fibers | mostly C | mostly Aδ |
| Dorsal horn | lamina II | laminae I and V |
| Position in tract | more medial | more lateral |
| Thalamus | non-specific nuclei | specific (VPL) nuclei |
| Cortex | wide areas, limbic included | postcentral gyrus |
| Gives | arousal, emotion, autonomic | localization, quality, intensity |
Paleospinothalamic pathway
A slow-conducting, multineuron chain. It carries the pain that is hard to place, from deep somatic structures and from viscera.
First order neurons
- Enter the cord and end mainly in lamina II of the dorsal horn.
Second order neurons
- Decussate, then ascend in the spinothalamic pathway of the opposite side.
- They lie more medially within the spinothalamic tract.
- Climbing through the brainstem they shed collaterals into three nuclear groups, making three named subsystems:
| Subsystem | Target |
|---|---|
| Spinoreticulothalamic | reticular formation of the medulla (a heavy projection) |
| Spinomesencephalic | midbrain reticular formation, parabrachial nuclei, periaqueductal gray |
| Spinohypothalamic | hypothalamus |
Third order neurons
- The fibers end mainly in the medial nuclear group of the thalamus: the midline and intralaminar nuclei, also called the non-specific nuclei (Thalamus: nuclei, functions and thalamic syndrome).
- From there the third-order neurons fan out to many cortical areas, limbic cortex included.
Special features
- The projection is non-specific, which is exactly why slow pain is poorly localized.
- The large projection to the reticular formation keeps the person awake — a toothache will not let you sleep.
- The limbic connection supplies the emotional experience of pain; the hypothalamic connection supplies the autonomic responses.
- Together these make the motivational-affective component of pain.
So arousal, feeling and autonomic reaction all come from this pathway.
Neospinothalamic pathway
First order neurons
- End mainly in laminae I and V of the dorsal horn.
- Transmitters released by these primary nociceptive afferents: glutamate, plus neuropeptides, of which substance P matters most (Neurotransmitters).
Second order neurons
- Cross to the opposite side in the same spinal segment, then ascend in the lateral spinothalamic tract.
- The tract is arranged topographically:
| Body region | Position in the tract |
|---|---|
| Sacral | most lateral, outermost |
| Lumbar, then thoracic | progressively inward |
| Cervical | most medial, innermost |
- In short: lower body outside, upper body inside.
- They end in the lateral nuclear group of the thalamus: the ventrobasal and posterior nuclear complexes, also called the VPL or specific nuclei.
- On the way up they also give a sparse projection to the midbrain reticular formation, periaqueductal gray and hypothalamus.
Two tracts, opposite rules
In the spinothalamic tract the sacral fibers are the most lateral. In the dorsal column the sacral fibers are the most medial, in the gracile fasciculus, because every new segment adds itself on the outside (Ascending tracts: dorsal column and anterolateral system). So a tumour pressing on the cord from outside takes pain from the legs first, while a lesion growing in the centre of the cord spares the legs longest.
Third order neurons
- Cell bodies in the specific thalamic nuclei; their axons end in the postcentral gyrus, that is the sensory cortex (Somatosensory cortex).
Special features
- The map stays concrete all the way: thalamic and cortical fibers keep their topography, and the cortical neurons sit in modality-specific columns. That is why fast pain is well localized.
- Because it ends in specific, discrete thalamic and cortical territory, this pathway serves the sensory-discriminative side of pain: where the pain is, what kind it is, and how strong.
Draw it: the pain pathways
- Draw a tall outline with three levels marked across it: spinal cord, brainstem (medulla and midbrain), and thalamus with the cortex above.
- First order neuron: from the skin, through the dorsal root ganglion, into the dorsal horn. Label an Aδ fiber ending in laminae I and V and a C fiber ending in lamina II.
- Second order neurons: cross the midline and turn up the opposite lateral spinothalamic tract. Put the neospinothalamic fibers laterally and the paleospinothalamic fibers medially.
- From the paleo fibers draw three sets of collaterals: to the medullary reticular formation, to the midbrain reticular formation, parabrachial nuclei and periaqueductal gray, and to the hypothalamus. Name the three subsystems beside them.
- Thalamus: paleo fibers into the intralaminar and midline (non-specific) nuclei, neo fibers into the VPL (specific) nuclei.
- Third order neurons: from the non-specific nuclei, arrows spraying over wide cortex and limbic areas; from VPL, one tidy arrow to the postcentral gyrus.
- Mark the neo route fast pain and the paleo route slow pain, and add a small inset of the cord cross-section with sacral fibers outermost.
Deep pain
Pain from nociceptors in the deeper somatic structures: muscle, tendon, bone, periosteum, internal ligaments.
- Its character is dull, aching and poorly localized, unlike superficial pain. Two reasons: deep tissues are short of Aδ fibers, and they hold relatively few receptors.
- Like visceral pain it often comes with autonomic symptoms, because autonomic fibers travel alongside the neurons from these deep structures.
- It usually sets off contraction of the surrounding skeletal muscle. Held long enough, that contraction makes the muscle ischemic, and the ischemia worsens the pain — a vicious circle.
Applied: muscle pain and the P factor
A muscle held contracted for a long time hurts because it turns ischemic, and the pain settles once blood flow returns. Your book credits a build-up of the Lewis factor, also called the P factor; its exact chemistry is unknown, though accumulated K⁺ is the likeliest candidate. Two everyday examples: angina pectoris, brought on by exertion and relieved by rest, and intermittent claudication of the calf in occlusive vascular disease, which appears on walking and goes with rest.
Worth knowing, though not in your pages: your book prints “caudication”; the word is claudication, from the Latin for limping.
Mechanism of pain recognition
- A noxious stimulus damages tissue, and the damaged tissue releases proteolytic enzymes.
- Those enzymes work on local proteins and cells, freeing the substances that then excite nociceptors:
| Group | Mediators |
|---|---|
| Amines | histamine, serotonin |
| Lipid mediators | prostaglandins, leukotrienes |
| Peptides | kinins and other polypeptides |
| Ions | K⁺ leaking from broken cells |
- Once a nociceptor is firing, the primary afferent fiber itself releases a polypeptide mediator that sensitizes the nociceptor — positive feedback at the ending.
- That mediator is substance P. The C-fiber endings in the skin put it out themselves. It heightens pain perception, and it drives the other features of inflammation as well (the triple response).
- Worth knowing, though not in your pages: this is how aspirin and the other NSAIDs relieve pain peripherally — they block prostaglandin synthesis, so the nociceptor is never sensitized.
Modulation of pain perception
- The threshold for feeling pain is much the same in everyone, but inflammation lowers it.
- What raises the threshold: local anesthetics, many centrally acting analgesics, and placebos.
- Distraction, which pulls attention away from the painful part, reduces awareness of pain.
- Strong emotion reduces pain perception too, probably by driving the descending adrenergic system (Endogenous pain control and gate control theory). How far it does so differs from person to person.
- Conscious awareness of pain appears only when the impulse reaches the thalamocortical level:
| Level | What it does |
|---|---|
| Thalamus | recognizes that the stimulus is noxious |
| Sensory cortex | judges intensity, localizes, discriminates quality |
Recognition is thalamic, appreciation is cortical
Lose the cortex and pain is still recognized, because the thalamus does that part. What is lost is the fine work: where the pain is, how strong it is, what sort it is. This split is a favourite viva question.
Exam-answer skeleton: "Trace the pathways of pain with a labelled diagram and describe the physiology of pain" (long essay)
- Define pain (IASP) and nociception; say that pain is protective.
- Nociceptors and their fibers: Aδ mechanical and polymodal C, with diameters and speeds; fast versus slow pain (Pain: concepts, receptors and fibers).
- Dorsal horn: Aδ to laminae I and V, C to lamina II; Lissauer’s tract. Draw it.
- The pathways, with the full labelled diagram: neospinothalamic (first, second and third order neurons, VPL, postcentral gyrus) and paleospinothalamic (lamina II, the three brainstem subsystems, non-specific nuclei, limbic cortex).
- Topographic organization in the spinothalamic tract, sacral fibers outermost.
- What each pathway contributes: sensory-discriminative versus motivational-affective.
- Mechanism of pain recognition: proteolytic enzymes, the mediators, substance P.
- Modulation: threshold and inflammation, analgesics and placebo, distraction, emotion; thalamus recognizes and cortex appreciates.
- Close with a line on the endogenous analgesia systems (Endogenous pain control and gate control theory).
Asked in exams
- Pain pathways: Jul 2013, 10 marks · Apr 2021, 5 marks · Apr 2021, 4 marks · May 2022, 15 marks · Jan 2023, MCQ