Show the model answerAttempt it first — that is what makes it stick
(a) Define pain 1 mark
Commonly lost: The commonest error was omitting “potential” tissue damage, the word that accommodates pain with no demonstrable injury. Dropping “emotional” reduces pain to nociception.
| Term | Definition | Can occur without the other |
|---|---|---|
| Nociception | The neural process of encoding a noxious stimulus | Yes: it occurs under anaesthesia with no pain |
| Pain | The conscious experience | Yes: central and neuropathic pain occur without nociception |
(b) The afferent pain pathway 5 marks
What earns the marks5 marks
| A diagram | Required, not optional: some answers omitted it |
|---|---|
| Transduction | Nociceptors: free nerve endings; inflammatory mediators lower threshold |
| The two fibres | Aδ = first, fast, sharp; C = second, slow, dull |
| First order neuron | Cell body in the dorsal root ganglion → synapse in the dorsal horn |
| Second order neuron | Dorsal horn → decussates → contralateral spinothalamic tract → thalamus |
| Third order neuron | Thalamus → internal capsule → somatosensory cortex and limbic areas |
Commonly lost: The question said “describe and illustrate”. A diagram was required and some answers omitted it entirely.
The ascending pathway, in three neurons
Read it from the bottom. The first-order neuron has its cell body in the dorsal root ganglion, outside the cord, and synapses in the dorsal horn. The second-order neuron starts in the dorsal horn, crosses in the cord and ascends on the opposite side. At the brainstem the projection divides: the lateral, neospinothalamic route relays in the ventral posterolateral nucleus (VPL) and reaches the primary somatosensory cortex, which is where and how intense; the medial, paleospinothalamic route passes through the reticular formation and periaqueductal grey to the intralaminar nuclei and on to the cingulate and insula, which is how unpleasant. The third-order neuron runs from thalamus to cortex. From the face the plan is the same, with the first-order cell body in the trigeminal ganglion, the second in the spinal trigeminal nucleus and the third in the ventral posteromedial nucleus.
1 · Transduction: the receptor
- Nociceptors are free (bare) nerve endings in skin, muscle, joint, periosteum and viscera.
- Activated by mechanical, thermal or chemical stimuli of intensity sufficient to threaten tissue.
- Threshold lowered by inflammatory mediators: bradykinin, prostaglandins, histamine, serotonin, K⁺, H⁺, substance P.
2 · The two fibre types
| Aδ | C | |
|---|---|---|
| Myelination | Thinly myelinated | Unmyelinated |
| Diameter | 2-5 µm | 0.4-1.2 µm |
| Conduction velocity | ~12-30 m/s | ~0.5-2 m/s |
| Modality | Mechanical and thermal nociception | Polymodal |
| Pain carried | First (fast) pain | Second (slow) pain |
| Character | Sharp, pricking, well localised, rapid onset and offset | Dull, burning, aching, poorly localised, persistent |
| Dorsal horn lamina | I, and more deeply V | II (substantia gelatinosa) |
3 · The three orders of neuron
| Order | Cell body | Course | Terminates |
|---|---|---|---|
| First | Dorsal root ganglion | Pseudounipolar: peripheral process to the nociceptor, central process entering via the lateral division of the dorsal root, branching in the tract of Lissauer over 2-3 segments | Dorsal horn, laminae I, II and V. Transmitters glutamate and substance P |
| Second | Dorsal horn | Decussates in the anterior white commissure within one or two segments; ascends contralaterally in the anterolateral quadrant as the spinothalamic tract | Thalamus: VPL (lateral division) and intralaminar/medial nuclei (medial division) |
| Third | Thalamus | Through the posterior limb of the internal capsule | S1 and S2 in the postcentral gyrus (from VPL); insula and anterior cingulate (from medial nuclei) |
Commonly lost: The dorsal root ganglion (outside the cord, holding the first order cell body) was confused with the dorsal horn (grey matter inside the cord, where that neuron synapses).
4 · The two divisions of the tract
| Lateral (neospinothalamic) | Medial (paleospinothalamic) | |
|---|---|---|
| Thalamic relay | Ventral posterolateral (VPL) nucleus | Intralaminar and medial nuclei |
| Cortical target | Primary and secondary somatosensory cortex | Insula, anterior cingulate, limbic structures |
| Carries | Where and how much: location, intensity, quality | How unpleasant: affect, arousal, autonomic response |
| Collaterals | Few | Reticular formation, periaqueductal grey |
| Corresponds to | The sensory half of the definition in (a) | The emotional half of the definition in (a) |
Because the fibres cross close to their level of entry, cord hemisection gives loss of pain and temperature contralateral to the lesion with loss of proprioception ipsilateral, the dissociation that identifies the tract.
(c) How the perception of pain may be modified 4 marks
What earns the marks4 marks
| Gate control theory | Melzack and Wall; required to pass |
|---|---|
| Large and small fibres | Their opposite effects on the inhibitory interneuron |
| Descending inhibition | PAG → RVM/raphe and locus coeruleus → dorsal horn. Also required to pass |
| Mediators | Serotonin, noradrenaline, endogenous opioids; additional marks |
| Other | Psychological, peripheral and pharmacological modification |
Commonly lost: Both gate control and the descending inhibitory pathway were needed to pass. One without the other did not.
1 · Gate control theory (Melzack and Wall, 1965)
The gate, drawn as a circuit
Solid lines excite (+); dashed lines inhibit (−). Both afferents excite the projection neuron directly. The difference is what each does to the inhibitory interneuron in the substantia gelatinosa: the large Aβ fibre excites it, so touch closes the gate; the small C fibre inhibits it, so a noxious input removes the brake and opens the gate twice over. Descending fibres close it from above, by exciting the interneuron and by inhibiting the projection neuron directly.
Transmission from first to second order neuron in the substantia gelatinosa is not obligatory: an inhibitory interneuron, when active, closes the gate to the projection neuron.
| Input | Effect on the inhibitory interneuron | The gate | Transmission |
|---|---|---|---|
| Large myelinated Aβ (touch, vibration, pressure) | Excites it | Closes | Falls: non-noxious input reduces pain |
| Small Aδ and C (nociceptive) | Inhibits it | Opens | Proceeds |
| Descending fibres from higher centres | Modulate it | Either | How attention, mood and expectation reach the cord |
- Explains why rubbing an injury relieves it.
- The mechanism of transcutaneous electrical nerve stimulation, which selectively stimulates Aβ fibres.
Commonly lost: Many supplementary gate diagrams were drawn inaccurately. Aβ is excitatory to the inhibitory interneuron; C is inhibitory to it. No interneuron means it is not gate control.
2 · The descending inhibitory pathway
| Level | Structure | Mediator | Action |
|---|---|---|---|
| Midbrain | Periaqueductal grey | Endogenous opioids | Activated by cortical, hypothalamic and ascending spinoreticular input; rich in opioid receptors |
| Medulla | Rostral ventromedial medulla, incl. nucleus raphe magnus | Serotonin | Relays the descending signal to the cord |
| Pons | Locus coeruleus | Noradrenaline (α2) | The clonidine and dexmedetomidine target; part of the tricyclic antidepressant mechanism |
| Cord | Dorsal horn, via the dorsolateral funiculus | GABA, glycine, enkephalins | Presynaptic inhibition of transmitter release, postsynaptic hyperpolarisation, and excitation of inhibitory interneurons |
Commonly lost: Naming the mediators, noradrenaline and serotonin in particular, carried additional marks beyond describing the anatomy.
3 · Other modifiers
| Category | Examples | Direction |
|---|---|---|
| Psychological and cognitive | Attention and distraction, anxiety, depression, expectation, previous experience, cultural context. Placebo analgesia acts on the same brain regions as an opioid, presumably by releasing endogenous opioids | Either |
| Peripheral | Sensitisation lowers nociceptor threshold and raises perceived intensity | Increases pain: modification is not only inhibitory |
| Pharmacological | Local anaesthetics (conduction block), NSAIDs (prostaglandin-mediated sensitisation), opioids (all three levels), ketamine (NMDA/wind-up), α2 agonists (descending noradrenergic) | Reduces pain |