Physiology of Pain Flashcards
Pain is classified by what three forms?
- Nociceptive pain: maladaptive.
- Inflammatory pain: adaptive.
- Pathological pain: maladaptive.
Describe nociceptive pain.
- Adaptive.
- Immediate protective response.
- Short-lived.
Describe inflammatory pain.
- Adaptive.
- Assists in healing.
- Persists over days, possibly weeks.
Describe pathological pain.
- Maladaptive.
- No physiological purpose.
- Persists over months, years or even a lifetime.
Acute mild pain is often controlled effectively by what?
- NSAIDs +/- paracetamol.
Moderate severe cases of pain may require addition of what to NSAIDs/paracetamol?
Opioids
Chronic pain may sometimes be managed by alternative drug classes such as?
- Anti-depressants.
- Anti-convulsants.
- Local anaesthetics.
How may pain in skin present?
- Well localised.
- Pricking, stabbing, burning.
How may pain of muscle present?
- Poorly localised.
- Aching, soreness/tenderness, cramping/stabbing/burning.
How may pain of viscera present?
- Poorly localised (often referred to a somatic structure).
- Dull, vague, fullness, nausea.
What are nociceptors?
Specific peripheral primary sensory afferent neurones.
What normally activates nociceptors?
Preferentially activated by intense noxious stimuli e.g. thermal, mechanical, chemical.
Describe the relay of nociceptors to the CNS.
- Nociceptors are 1st order neurons relaying information by APs to 2nd order neurons of CNS by chemical synaptic transmission.
Nociceptors innervate what?
They are primary afferent neurons innervating peripheral tissues.
Nociceptors are comprised of what type of fibres?
- Aδ- and C-fibres.
NB not all of these fibres are nociceptors.
Aδ-fibres are what kind of nociceptors?
Mechanical/thermal nociceptors that are thinly myelinated
Aδ-fibres contribute to nociceptors that respond to what?
Noxious mechanical and thermal stimuli.
Aδ-fibres mediate what kind of pain?
- First or fast pain.
C-fibres are what kind of nociceptors?
Unmyelinated.
C-fibres contribute to nociceptors that respond to what?
ALL noxious stimuli - they are polymodal.
C-fibre nociceptors mediate what kind of pain?
“second”/slow pain.
Describe “first”/fast pain of Aδ-fibre nociceptors.
- Lancinating, stabbing, pricking.
Describe “second”/slow pain of C-fibre nociceptors.
- Burning, throbbing, cramping, aching sensations.
Noxious thermal stimuli activate which receptors?
Members of the transient receptor potential (TRP).
- Especially TRPA1, TRPC3, TRPV1.
Which member of the transient receptor potential (TRP) family is greatly sensitised in inflammation to become active at body temperature?
TRPV1.
Chemical stimuli activates what?
- H+: Acid sensing ion channels (ASICs).
- ATP: P2X and P2Y receptors.
- Bradykinin: B2 receptors.
Where do the axons of nociceptor (1st order) synapse with 2nd order neurons?
Dorsal (posterior) horn of spinal cord.
The afferent branch of peptidergic polymodal nociceptors have which function?
To transmit nociceptive info to CNS via release of glutamate and peptides within the dorsal horn.
The efferent branch of peptidergic polymodal nociceptors have which function?
Release pro-inflammatory mediators e.g. CGRP from peripheral terminals (contributes to neurogenic inflammation).
Long term noxious stimulation increases what?
Spinal excitability, contributing to hyperalgesia and allodynia.
In neurogenic inflammation, peptides (SP & CGRP) are released from free nerve endings of peptidergic nociceptors due to what?
Tissue damage or inflammatory mediators.
The peptide SP causes what?
- Vasodilation and extravasation of plasma proteins (promotes formation of bradykinin and prostaglandins).
- Histamine release from mast cells.
- Sensitisation of surrounding nociceptors.
The peptide CGRP induces what?
Vasodilation.
What ultimately results from release of SP and CGRP in neurogenic inflammation?
Primary and secondary hyperalgesia and allodynia.
Primary afferent cell bodies are located in the dorsal root ganglia, apart from which system?
The trigeminal system.
In the neurotransmission between the primary afferent and second order neuron in dorsal horn, what is the primary transmitter?
Glutamate.
- Produces fast e.p.sp. and neuronal excitation.
In the neurotransmission between the primary afferent and second order neuron in dorsal horn, Glutamate produces a fast e.p.s.p. and neuronal excitation by doing what?
Activating primarily postsynaptic AMPA receptors with NMDA receptor participation.
What peptides - except glutamate - also participate in the neurotransmission between the primary afferent and second order neuron in dorsal horn?
Substance P and CGRP, particularly during high frequency stimulation.
Substance P and CGRP in the neurotransmission between the primary afferent and second order neuron in dorsal horn cause what?
Slow and prolonged e.p.s.p. that facilitates activation of NMDA receptors, by relieving voltage-dependent block by Mg2+.
Where do most nociceptive C- and Aδ-fibre nociceptors terminate superficially?
In laminae I and II of the laminae of Rexed.
- Also V for Aδ-fibres.
Nociceptive specific (NS) cells, synapse only with what?
C- and Aδ-fibres.
The central projections of primary afferent axon fibres terminate where>
Dorsal horn of the spinal cord in various laminae of Rexed.
Cells that receive input from only Aβ-fibres are what?
Proprioceptive.
Wide dynamic range (WDR) neurons receive input from what types of fibres?
- C-fibres.
- Aβ-fibres.
- Aδ-fibres.
WDR neurons receive input from: - C-fibres. - Aβ-fibres. - Aδ-fibres. Meaning what?
They respond to a wide range of stimuli.
Visceral pain originates from what structures?
Nociceptors covering tissues (e.g. peritoneum, pleura) or the walls of hollow organs.
Visceral pain originates from what (not structures)?
- Stretching, twisting, inflammation and ischaemia.
But NOT cutting or burning.
Visceral pain tends to be described as?
Poorly localised, dull, aching, throbbing.
Visceral afferents from nociceptors follow what pathways before entering the dorsal horn?
Sympathetic.
Some visceral and skin afferents converved upon what neurons?
Spinothalamic.
Terminals of visceral nociceptors terminate in which laminae?
I and V.
NOT II.
What gives rise to referred pain?
Brain interprets nociceptive information from viscera as arising from an area of skin (may be distant to internal organ).
Visceral referred pain is often associated with which autonomic features?
Nausea, vomiting, sweating, pallor etc.
Area of visceral pain referral is to where?
The segmental dermatome which may show signs of hyperalgesia.
- e.g. heart T1-5, gallbladder C4.
Viscerosomatic pain is described as?
Sharp and well localised.
When does viscerosomatic pain occur?
When inflammatory exudate from a diseased organ contacts a somatic structure.
Pain evoked by activity in:
- C-fibres.
- Aδ-fibres.
may be reduced by simultaneous activity in what?
Low threshold mechanoreceptors i.e. Aβ-fibres.
Projection (P) neurones within substantial gelatinosa project to the spinothalamic tract and thought to be excited by what?
- Large diameter (Aβ) sensory axons.
- Unmyelinated (C/Aδ) nociceptive axons.
Projection neuron inputs are inhibited by what?
An interneuron.
What excites the interneuron inhibiting projection neuron inputs?
- Large diameter (Aβ) sensory axons.
What inhibits the interneuron inhibiting projection neuron inputs?
- Unmyelinated (C/Aδ) nociceptive axons.
Maximal excitation of the projection neuron is due to what?
Activity solely in the unmyelinated (C/Aδ) nociceptive axons.
Maximal excitation of the projection neuron allows what?
Nociceptive signals to arise to the brain.
Second order neurones (of major nociceptive tracts) ascend the spinal cord in the anterolateral system, comprising mainly of what tracts?
- Spinothalamic tract.
- Spinoreticular tract.
Projection neurons of the spinothalamic tract originate from where?
Lamina I.
Lamina V.
Where do projection neurons of the spinothalamic tract originating from lamina I terminate?
Posterior nucleus of thalamus.
Where do projection neurons of the spinothalamic tract originating from lamina V (WDR) terminate?
Posterior and ventroposterior nucleus of thalamus.
The spinoreticular tract largely transmits what type of pain?
Slow C-fibre pain.
The spinoreticular tract makes extensive connections with what in the brainstem?
Reticular nuclei e.g. periaqueductal grey and parabrachial nucleus.
The spinoreticular tract is involved in autonomic responses to what?
Pain, arousal, emotional responses, fear of pain.
Thermoreceptors are neurons specialised to respond to what?
Small changes in temperature.
Why is temperature sensitivity not uniform across the body surface?
- Hot-sensitive and cold-sensitive spots exist.
