SAQPhysiologyNeurophysiology2016 · Pain and the cardiovascular response

Question bank · 2016 · Physiology

The anaesthetised patient cannot say it hurts.
The heart rate and blood pressure can, and part (c) is why.

Show the model answerAttempt it first — that is what makes it stick

Define pain

What earns the marks

The whole definitionBoth qualities (sensory and emotional) and both kinds of damage (actual or potential)
The distinctionPain is an experience; nociception is a neural process
DefinitionOccurs without the other
NociceptionThe neural process of encoding noxious stimuli.Yes: it continues in an anaesthetised patient who feels nothing
PainThe conscious experienceYes: phantom limb pain, with no nociceptors to activate

(b) The pain pathway

What earns the marks

Receptor and transductionFree nerve endings; mediators open transducer channels; action potentials generated
FibresAδ first pain, C second pain
First-order neuroneCell body in the dorsal root ganglion; synapse in the dorsal horn
Second-order neuroneCrosses within one or two segments; contralateral spinothalamic tract
Third-order neuroneThalamus to somatosensory cortex, and medially to cingulate and insula
A diagramThe fastest way to earn the structure marks

Read the question: “Pain pathway” is the ascending pathway from receptor to cortex. Modulation is a sentence here at most, and part (c) is where the reflex response belongs.

Pathway

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.

CortexS1, S2, insula, anterior cingulateThalamusVPL (lateral) and intralaminar (medial)BrainstemReticular formation, periaqueductal greySpinal cordDorsal horn, laminae I, II and VPeripheryFree nerve endings of nociceptorsmidlineDorsal root ganglionfirst-order cell bodyDorsal horncrosses hereReticular formationand PAGVPLIntralaminarS1: locationCingulate, insula: affect123NeospinothalamicPaleospinothalamic
StepStructureDetail
TransductionNociceptor: free nerve endings in skin, muscle, joints and visceraTissue damage releases K⁺, H⁺, ATP, bradykinin, serotonin, histamine and prostaglandins; TRPV1, ASIC and P2X3 open; the generator potential fires action potentials through voltage-gated Na⁺ channels
FibresAδ and CAδ: thinly myelinated, 12 to 30 m/s, sharp and localised first pain. C: unmyelinated, 0.5 to 2 m/s, dull, diffuse second pain
First-order neuroneCell body in the dorsal root ganglionEnters the dorsal root, divides in Lissauer's tract over 2 to 3 segments, synapses in the dorsal horn: Aδ in laminae I and V, C in lamina II. Glutamate and substance P
Second-order neuroneCell body in the dorsal hornNociceptive-specific or wide dynamic range. Crosses in the anterior white commissure within one or two segments; ascends in the contralateral anterolateral quadrant as the spinothalamic tract
Third-order neuroneCell body in the thalamusLateral route: ventral posterolateral nucleus to primary and secondary somatosensory cortex (location, intensity). Medial route: via reticular formation and periaqueductal grey to intralaminar nuclei, anterior cingulate and insula (unpleasantness, arousal, autonomic response)

The medial stream matters for part (c): its targets in the reticular formation sit beside the regions that control blood pressure, and the insula carries the pain-related autonomic response. That is where the cardiovascular response starts.

(c) The cardiovascular response to pain

What earns the marks

AfferentNociceptive input via the spinoreticular, spinolimbic and paleospinothalamic routes
IntegrationMedullary cardiovascular centres and hypothalamus; defence and alerting responses
EfferentSympathetic outflow and adrenal catecholamines up; vagal tone down
EffectsHeart rate, contractility, cardiac output, vascular resistance and blood pressure up
ConsequencesMyocardial oxygen demand up while supply may fall; salt and water retention; hypercoagulability
The exceptionSevere visceral pain: hypotension and bradycardia

Read the question: “Discuss” asks for mechanism and consequence. A list of “tachycardia, hypertension” without the pathway that produces them and what they cost the heart is a description, not a discussion.

From nociceptive input to the cardiovascular response

Afferent
Nociceptive input ascends in the spinoreticular and spinolimbic tracts and the medial (paleospinothalamic) stream, reaching the reticular formation, hypothalamus and limbic structures.

Integration

Medulla
Rostral ventrolateral medulla, the vasomotor area, drives sympathetic outflow; the nucleus ambiguus and dorsal vagal nucleus hold the cardiac vagal neurones.
Hypothalamus and limbic system
Pressor defence and alerting responses from the hypothalamus, activated by the amygdala in fear.

Efferent

Sympathetic nerves
Noradrenaline at β1 (heart, kidney) and α1 (arteriolar smooth muscle) adrenoceptors.
Adrenal medulla
Adrenaline and noradrenaline into the circulation.
Vagus
Cardiac vagal tone withdrawn.
Neuroendocrine
Renin, angiotensin II, aldosterone, ADH and cortisol rise.
Tachycardia, increased contractility and cardiac output, vasoconstriction, hypertension, and a raised myocardial oxygen demand.
VariableChangeMechanismWhy it matters
Heart rateRisesβ1 stimulation of the sinoatrial node; vagal withdrawalShortens diastole, the time for coronary flow to the left ventricle
ContractilityRisesβ1 stimulation; circulating adrenalineMore myocardial work
Cardiac outputRisesRate and contractility together
Systemic vascular resistanceRisesα1 arteriolar vasoconstriction; angiotensin IIRaises afterload
Arterial pressureRisesCardiac output and resistance both upUnder anaesthesia, hypertension and tachycardia are the usual signs of nociception
Myocardial oxygen balanceDemand up; supply may fallRate, contractility and afterload raise demand; sympathetic coronary vasoconstriction and a blunted metabolic vasodilatation reduce supplyMyocardial ischaemia and infarction in a patient with coronary disease
Circulating volumeExpandsRenin, angiotensin II, aldosterone and ADH: sodium and water retentionMore preload
CoagulationHypercoagulableFewer natural anticoagulants, more procoagulants, inhibited fibrinolysis, more reactive platelets, higher viscosityDeep venous thrombosis, vascular graft failure, myocardial ischaemia
  • The size of the neuroendocrine and sympathetic response is proportional to the degree of surgical trauma, and is reduced by reducing the nociceptive input.
  • That is the cardiovascular argument for effective analgesia, regional block and multimodal regimens: less input, less sympathetic outflow, less myocardial oxygen demand.
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