Physiology and Pharmacology 5 - Pain Flashcards
What is pain?
An unpleasant sensory and emotional experience, associated with actual tissue damage or described in terms of such damage
What are the 3 forms of pain?
Nociceptive pain
Inflammatory pain
Pathological pain
What of the 3 forms of pain are adaptive?
Nociceptive and inflammatory pain = adaptive
Pathological pain = maladaptive
What are nociceptors?
Specific peripheral primary sensory afferent enrolees normally activated preferentially by intense stimuli e.g. thermal, mechanical, chemical, that are noxious
Are nociceptors first or second order neurones?
First order neurones (they relay information to second order neurones in the CNS by chemical synaptic transmission)
What are first order neurones?
Neurones that conduct impulses from receptors of the skin and from proprioceptors, to the spinal cord or brain stem, where they synapse with second order neurones
What is adaptive pain?
Helpful pain that produces behaviour that promotes healing and recovery (compared with maladaptive pain)
Why can nociceptive pain be described as adaptive?
It serves as an early warning system to detect and minimise contact with damaging stimuli (noxious events)
Threshold of nociceptive pain?
High threshold - provoked only by intense stimuli that activate nociceptors
Features of nociceptive pain? (5)
Overrides most other ongoing activities of the nervous system
Initiates a withdrawal reflex
Extremely unpleasant
Engages adverse emotional components
Serves to inscribe memories that allow avoidance of harm in the future
What causes inflammatory pain?
Activation of the immune system in injury, or infection
what does activation of the immune system in injury, or infection, cause in terms of inflammatory pain? (2)
Pain hypersensitivity (heightened sensitivity to noxious stimuli) Allodynia (innocuous stimuli now elicit pain)
How is inflammatory pain protective and adaptive?
Assists in the healing of a damaged body part by:
Discouraging physical contact e.g. a wound
Discouraging movement e.g. an inflamed joint
What causes pathological pain?
Abnormal nervous system function
2 types of pathological pain?
Neuropathic
Dysfunctional
What causes neuropathic pain?
peripheral nerve damage
What causes dysfunctional pain?
No identified cause
What type of fibres are nociceptors either?
Aδ- and C-fibres (not all Aδ- and C-fibres are nociceptors)
What type of nociceptors are Aδ- fibres?
Mechanical/ thermal nociceptors
Myelination of Aδ- fibres?
Thinly myelinated
What type of stimuli do Aδ- fibres respond to?
Noxious mechanical and thermal stimuli
What type of pain do Aδ-fibres mediate?
First/ fast pain
Myelination of C-fibres?
Unmyelinated
What type of stimuli do C-fibres respond to?
All noxious stimuli
What type of pain do C-fibres cause?
Second/ slow pain
4 examples of receptors that pick up chemical stimuli on polymodal nociceptors?
ASIC
P2X
P2
B2 receptors
Example of a thermal receptor that is activated by noxious heat?
What happens to this in inflammation?
Members of the transit receptor potential (TRP) family - particularly TRPV1
Greatly sensitised in inflammation to become active at body temperature
What ion channel (chemical receptor) does H+ activate?
Acid sensing ion channel (ASICs)
What ion channel (chemical receptor) does ATP activate?
P2X and P2Y receptors
What ion channel (chemical receptors) does bradykinin activate?
B2 receptors
What happens when a stimulus (mechanical, thermal or chemical) activates a receptor?
It open ion channels (cation selective) in nerve terminal to elicit a depolarisaiton receptor (or generatory) potnetial
What is amplitude of generator potential proportional to?
Stimulus intensity (it is graded)
What does local current flow (hermann currents) in a sensory neurone terminal trigger?
all or none action potentials at a frequency proportion to the amplitude of the receptor potential
What type of signals do c-polymodal nociceptors pick up?
Thermal, chemical and mechanical stimuli
What temperature stimulates c-polymodal fibres?
43 degrees C
What temperature stimulates type I Aδ-fibres?
53 degrees C
What temperature stimulates type II Aδ-fibres?
43 degrees C
Where does the first order and second order neurone synapse in the nociceptive pathway?
in the dorsal (posterior) horn of the spinal cord
What is the name of the subset of C-fibres that have both afferent and efferent functions?
Peptidergic polymodal nociceptors
How do afferent peptidergic polymodal nociceptors transmit nociceptive information to the CNS?
Via release of glutamate and peptides (substance p, Neurokinin A) within the dorsal horn
What do efferent peptidergic polymodal nociceptors do?
Release pro-inflammatory mediators e.g. substance P, calcitonin gene-related peptide (CGRP) from peripheral terminals - contributes to neurogenic inflammation
What does noxious stimulation of peptidergic polymodal nociceptors do in the long term?
Increases spinal excitability contributing to hyperalgesia and allodynia
What are released from free nerve endings of peptidergic nociceptor due to tissue damage?
Peptides (SP and CGRP) or inflammatory mediators
What does substance P (released from peptidergic nociceptors due to tissue damage) cause?
Vasodilation and extravasation of plasma proteins (promotes formation of bradykinin and prostaglandins)
Release of histamine from mast cells
Sensitised surrounding nociceptors
What does CGRP released from free nerve endings of peptidergic nociceptors cause?
Vasodilation
What does the release of SP and CGRP, or inflammatory mediators, from peptidergic nociceptors due to tissue damage cause? (neurogenic inflammation)
primary and secondary hyperalgesia and allodynia
What happens when the action potential arrives at the terminal of the primary afferent neurone?
Opening of voltage-gated Ca2+ channels occurs
Ca2+ influx
glutamate release
What happens to glutamate released by the primary afferent neurone in the dorsal horn?
It activates glutamate receptors on the projection neurone in the distal horn causing membrane depolarisation
This leads to the opening of voltage-gated Na+ channels and the production of the action potential
Aside from glutamate, what else is involved in neurotransmission between the primary afferent and second order neurone in the dorsal horn?
petides - substance P and CGRP (cause a slow prolonged e.p.s.p. that facilitates activation of NMDA receptors by relieving voltage-dependent block by Mg2+
Where are primary afferent cell bodies located?
What is the exception to this?
Dorsal root ganglia
Apart from the trigeminal syste
Where do primary afferent axons terminate?
Centrally in the dorsal horn of the spinal cord in various laminae of Rexed
What laminae in the spinal cord do nociceptive C and Aδ fibres terminate?
Superficially in laminae I and II (also V for Aδ fibres)
What do nociceptive specific cells only synapse with?
C and Aδ fibres
What type of cells are those that only receive input from Aβ-fibres?
Proprioceptive
What do wide dynamic range neurones receive input from?
All 3 types of fibre - therefore respond to a wide range of stimuli
Second order nociceptive neurones ascend the spinal cord in the anterolateral system comprising mainly of?
Spinothalamic tract (STT) Spinoreticular tract (SRT)
Where do projection neurones originating from lamina I (fast fibre Aδ pain) terminate?
Posterior nucleus of the thalamus
Where do projection neurones originating from lamina V (WDR neurones) terminate?
Posterior and ventroposterior nucleus of the thalamus
What type of pain does the spinoreticular tract largely transmit?
Slow C-fibre pain
