An introduction to pain Flashcards
What is pain?
An unpleasant sensory and emotional experience, associated with actual tissue damage to described in terms of such damage
What are the three forms of pain?
Nocioceptive-adaptive
Inflammatory-adaptive
Patholgical-maladaptive
What is a nociceptor?
Specific peripheral primary sensory afferent neurones normally activated by intense noxious stimuli(mechanical, thermal or chemical)- they relay information to second order neurones in the CNS by chemical synaptic transmission
What is congenital insensitivity to pain (CIP) and what may occur?
A very rare condition due to loss of function mutations in a gene that encoded voltage-activated Na+ channel that is highly expressed in nociceptive neurones
May have lip and joint injury, bruises and cute, multiple scare, bone fractures, joint deformity and premature mortality due to multiple injuries
Subtypes of nociceptor
Aδ- and C-fibres
Aδ- –> mechanical/thermal nocioceptors,thinly myelinated. Medaite first or fast pain
C-fibres –> Unmyelinated, collectively respond to all noxious stimuli. Mediate second or slow pain
First and second pain
First pain- e.g. lancing, stabbing,prickling sensation
Second pain- e.g. burning, throbbing,cramping,aching sensation
Peptidergic C-fibres have both afferent and efferent functions T/F
T
Afferent- transmit nociceptive information to the CNS via release of glutamate and peptides (substance P,neurokinin A) within the dorsal horn
Efferent- release pro-inflammatory mediators e.g. calcitonin gene-related peptide (CGRP),substance P from peripheral terminals. Contributes to neurogenic inflammation
Define hyperalgesia
Heightened sensitivity to noxious stimuli.
Describe the development of neurogenic stimulation
Free nerve ending
Axon of nociceptor (first order neuronese)
Soma within dorsal(posterior) root ganglion
Dorsal (posterior) horn of spinal cord
axon of projection (second order) neurone
Spinothalmic and spinoreticulothalamic tracts
What is inflammatory pain caused by?
Activation of the immune system in injury or infection.
How does inflammatory pain assist with the healing of a damaged body part?
discourages physical contact and movement
(However although adaptive nonetheless required reduction in ongoing inflammation (e.g. rheumatoid arthritis) to alleviate suffering
What are the two types of pathological pain?
neuropathic-neural lesion, pos and neg symptoms
dysfunctional- no neural lesion, no inflammation, positive symptoms
What receptor is particularly activated by noxious heat
TRVP1- greatly sensitised in inflammation to become active at body temperature
What ion channels does H+ activate
acid sensing ion channels (ASIC)
What receptors does ATP activate?
P2X and P2Y
What receptors does bradykinin activate?
B2
In the long term what does noxious stimulation increase
spinal excitability contributing to hyperalgesia and allodynia
Brief outline of neurogenic inflammation
- Peptides (SP and CGRP) released from free nerve ending of peptidergic nociceptor due to tissue damage, or inflammatory mediators
- SP causes vasodilation and extravasation of plasma proteins (promotes formation of bradykinin and prostaglandins), release histamine from mast cells and sensitises surrounding nociceptors
- CRGP induces vasodilation
- Primary and secondary hyperalgesia and allodynia ensue
What is the chain of events in neurotransmission between the primary afferent and second order neurone in the dorsal horn
Action Potential
Opening of voltage-gated Ca2+ channels
Ca2+ influx
Glutamate release
Activation of glutamate receptors
Membrane depolarisation
opening of voltage-gated Na+ channels
Action Potential
What is the primary transmitter in the neurotransmission between the primary afferent and second order neurone in the dorsal horn?
Glutamate - fast e.p.s.p and neuronal excitation
(peptides- substance P and CGRP also participate particularly during high frequency stimulation causing a slow and prolonged e.p.s.p
Where are primary afferent cell bodies located?
Dorsal root ganglia
The axons terminate centrally in the dorsal horn of the spinal cord in various laminae of Rexed
Cells that receive input from only Ab-fibres are ______
Proprioceptive
Wide dynamic range (WDR) neurones receive input from…
all three types of fibre ( C- and Aδ and Aβ) and thus respond to a wide range of stimuli
Second order neurones ascend the spinal cord in the anterolateral system comprising mainly…
- The spinothalamic tract (STT)
- The spinoreticular tract(SRT)
What projection neurones are involved in the STT?
STT
-Fast fibre Aδ pain. Originate lamina I, terminate in posterior nucleus of thalamus
-WDR neurones. Originate lamina V, terminate in posterior and ventroposterior nucleus of the thalamus
Pain perception required simultaneous firing in both pathways
What in involved in the SRT
SRT
- slow C-fibre pain
- makes extensive connections with reticular nuclei in the brainstem
- Involved in autonomic response to pain, arousal, emotional responses, fear of pain
