Pain and Thermosensation Flashcards
What is pain?
Unpleasant sensory and emotional experience associated with actual tissue damage or described in terms of such damage
What are the three forms of pain?
Nociceptive = adaptive, short lived, protective Inflammatory = adaptive, helps healing, lasts days Pathological = maladaptive, lasts months, no physiological purpose
How can acute mild pain be controlled?
NSAIDs, paracetamol and opioids in moderate/severe cases
What are some agents used to control chronic pain?
Antidepressants, anticonvulsants and local anaesthetics
What are nociceptors?
Specific peripheral primary sensory afferent neurons = normally activated preferentially by intense noxious stimuli
What order neuron are nociceptors?
First order neurons = relay info to second order neurons in the CNS by chemical synaptic transmission
What are the subtypes of nociceptors?
Comprise of C and Adelta fibres
Where does transduction of nociceptors begin?
In free nerve endings = mediated by numerous receptors and channels
What are some features of Adelta fibres?
Mechanical/thermal nociceptors
Thinly myelinated
Mediate fast pain
What are some features of C fibres?
Unmyelinated nociceptors
Respond to cell noxious stimuli
Mediate slow pain
What are some features of mechanical stimuli?
Receptors and channels remain uncertain despite intense investigation
What are some features of thermal stimuli?
Member of TRP family = TRPA1, TRPC3, TRPV1
Activated by noxious heat
What are some features of chemical stimuli?
H+ activates acid sensing ion channels
ATP activates P2X and P2Y receptors
Bradykinin activates B2 receptors
What are some features of afferent peptidergic polymodal nociceptors?
Transmit nociceptive info to the CNS via release of glutamate and peptides within the dorsal horn
What are some features of efferent peptidergic polymodal nociceptors?
Release pro-inflammatory from peripheral terminals
Contributes to neurogenic inflammation
What does long term noxious stimulation cause?
Increases spinal excitability contributing to hyperalgesia and allodynia
What peptides are released during neurogenic inflammation?
SP and CGRP are released from free nerve ending of peptidergic nociceptor due to tissue damage or inflammatory mediators
What effects does SP have?
Vasodilation and extravasation of plasma proteins
Release of histamine from mast cells
Sensitises surrounding nociceptors
What effect does CGRP have?
Induces vasodilation
What does neurogenic inflammation lead to?
Primary and secondary hyperalgesia and allodynia
Where does neurotransmission between primary afferent and the second order neuron occur?
Occurs in dorsal horn = AP opens voltage gated Ca2+ channels
What causes glutamate release from neurotransmitters?
Ca2+ influx = causes membrane depolarisation and opening of voltage gated Na+ channels which generates AP
How does glutamate produce a fast epsp and neuronal excitation?
Activates primary postsynaptic AMPA receptors with NMDA receptor participation
What causes a slow and prolonged epsp?
Substance P and CGRP = facilitates activation of NMDA receptors by relieving voltage dependent voltage block by Mg2+
Where are primary afferent cell bodies located?
In the dorsal root ganglia (except those from trigeminal system)
Where do axons terminate?
Terminate centrally in the dorsal horn of the spinal cord in various laminae of Rexed
Where do nociceptive C and Adelta fibres terminate?
Mostly superficially in laminae I and II
Also V for Adelta fibres
What are the only fibres that nociceptive specific cells synapse with?
C and Adelta fibres
What property do cells that receive only Abeta fibres have?
Proprioceptive
What input do wide dynamic range neurons receive?
All three types of fibre (C, Abeta and Adelta) = respond to wide range of stimuli
Where does visceral pain originate from?
Nociceptors covering tissues or walls of hollow organs = due to stretching, twisting, inflammation and ischaemia
What are the characteristics of visceral pain?
Poorly localised, dull, aching, throbbing
What do visceral afferent from nociceptors follow before they enter the dorsal horn?
Sympathetic pathways
Can visceral and skin afferents converge upon the same spinothalamic neurons?
Yes
When does referred pain occur?
When the brain interprets the nociceptive info arising from the viscera as originating from an area of skin
What are some features of referred pain?
Often associated with autonomic features
Area of referral is to single segmental dermatome which may show signs of hyperalgesia
Consistent enough to be of diagnostic value
What is the character is viscerosomatic pain?
Sharp and well localised
What causes viscerosomatic pain?
Occurs when inflammatory exudate from a diseased organ contacts a somatic structure
Are pain and nociception identical?
No = pain is awareness of suffering but nociception may occur in the abscence of pain
How is perception of pain variable?
For the same degree of nociceptor activity, depending on the level of concurrent non-painful sensory input and behavioural context, more or less pain may be felt
How can pain evoked by activity in nociceptors be reduced?
By simultaneous activity in low threshold mechanoreceptors
What is the gate control theory?
Nerve impulses evoked by injury are influenced in the spinal cord by other nerve cells that act like gates = either let them through or stop them entering
How do innocuous and nociceptive signals conduct to the spinal cord?
Via Abeta and C/Adelta fibres respectively = are in part processed by neuronal circuits of the substantia gelatinosa
What happens when Abeta fibre activity exceeds that of C/Adelta fibres?
Spinal gate is closed and synaptic transmission of nociceptive signals to the ascending tract is suppressed = pain isn’t perceived
When happens when C/Adelta fibre activity exceeds that of Abeta fibres?
Spinal gate is open and synaptic transmission of nociceptive signals to the ascending tract is facilitated = pain is perceived
What neurons within the substantia gelatinosa project to the spinothalamic tract?
P neurons = postulated to be excited by both large diameter sensory axons and unmyelinated nociceptive axons
What are projection neurons inhibited by?
Interneurons = interneuron is excited by large sensory axons and inhibited by nociceptive axons
What is the basis of nociceptive signals arising in the brain?
The activity of the nociceptive axon alone maximally exciting the projection neuron
How do second order neurons ascend the spinal cord?
In the anterolateral system = comprising mainly the spinothalamic and spinoreticular tracts
What is required in the spinothalamic tract for pain to be perceived?
Simultaneous firing in both pathways
Where do projection neurons of the spinothalamic tract arising in laminae I terminate?
The posterior nucleus of the thalamus
Where do projection neurons of the spinothalamic tract arising in laminae V terminate?
The posterior and ventroposterior nucleus of the thalamus
What does the spinoreticular tract largely transmit?
Slow C fibre pain
What does the spinoreticular tract make extensive connections with?
The reticular nuclei of the brainstem
What is the spinoreticular tract involved in?
Autonomic responses to pain, arousal, emotional responses and fear of pain
What are thermoreceptors?
Neurons that are specialised to respond to small changes in temperature
Is temperature sensitivity uniform across the body?
No = hot sensitive and cold sensitive spots exist
Why does thermosensation require separate neurons and their associated receptors/channels?
To encode between hot and cold
