Anatomy and Physiology of Pain Flashcards
What is pain? What type of information is it usually associated with?
An unpleasant sensory and emotional experience associated with actual or potential tissue damage. A cerebral construct - a perception usually associated with tissue-damaging stimuli.
Nociceptive information
What are the physiological mechanisms of pain?
Transduction
Transmission
Perception
Modulation
What is transduction?
Noxious stimuli translated into electrical activity at sensory nerve endings.
What is transmission?
Propagation of impulses along pain pathways
What is perception?
Discrimination/affect
What is modulation?
Positive and negative modulation occurs. Transduction, transmission and perception are modified.
What is another name for acute pain?
Normal or nociceptive
What is a nociceptor?
A sensory neuron transducing potentially harmful stimuli. Normal pain results from activity of these.
What are the two main nociceptors involved?
C fibres
A delta fibres
What do the membranes of nociceptors contain that allow response to noxious stimuli?
Receptor proteins
What are the following receptor proteins for?
TRPV1
TRPM8
ASIC
Hot stimuli
Acid
Cold stimuli
Diabetes causes peripheral neuropathy. What does this result in the lack of?
Pain fibres
What are the A delta fibres for?
Sharp pricking fast pain (thermal and mechanical)
Precise localisation of stimulus
Reflex withdrawal
What are the two broad classes of C fibres?
Peptidergic
Peptide-poor
What are C fibres for in general?
Slow burning pain
What do peptidergic C fibres release peripherally? What does this promote?
Peptides e.g. substance P and CGRP
Inflammatory responses and healing
What is special about peptide-poor C fibres?
They have distinct receptors and projections e.g. P2X3 ATP receptors
What type of nociception for peptidergic fibres? What type for peptide-poor fibres?
Thermal
Mechanical
What are the main two lamina that A delta and C nociceptors connect to?
Which horn is this?
I and II
Dorsal horn
What is NaV1.7?
What does loss of it cause?
A sodium channel sub-unit
Congenital indifference to pain
What does loss of mutation of NGF receptor trkA cause?
Congenital insensitivity to pain with anhydrosis (CIPA) due to loss of C fibres.
Where does the lateral spinothalamic tract end? (3) What for? Where does it not end?
Limbic system - subjective sensations of pain and pleasure
Reticular formation - pain-induced arousal and descending control of nociceptor input
Intralaminar (reticular) nuclei of thalamus - alerting cerebral cortex and focus of attention on pain
NOT the VPL (ventral posterolateral nucleus of the thalamus)
The unpleasant character of pain is mediated via projections to what system?
Limbic
What lamina do C fibres innervate? (3)
I and inter-neurons in lamina II (they also innervate lamina V through these inter-neurons)
What lamina do A delta fibres innervate?
Lamina I and V projection neurons
From where do projection neurons in lamina V receive input?
A beta fibres (touch) - direct input
C fibres - indirect input via inter-neurons
A delta fibres
Where do axons of projection neurons decussate close to? Where do the axons travel after decussating?
Where the nociceptors enter the spinal cord
In the anterior spinothalamic tract (lamina V) and lateral spinothalamic tract (lamina I)
What do projection neurons carry and to where?
Pain message onward from the primary afferent
What is the anterior spinothalamic tract also known as?
‘Neo’spinothalamic tract
What does the anterior spinothalamic tract subserve?
First, discriminative aspects of pain – e.g. move arm!
Anterior spinothalamic tract - where is the main projection to? What nuclei does it come from? What type of information does this give about the noxious stimulus?
Primary somatosensory cortex
Ventral posterior lateral (VPL) nucleus and ventral posterior medial (VPM) nucleus
Localisation & physical intensity
What other two projections are there from the anterior spinothalamic tract? Where do they provide input to?
Ventral posterior inferior (VPI) nucleus - input to secondary somatosensory cortex
Central lateral (CL) nucleus (reticular and limbic associated areas) - input to sites for cognitive function (prefrontal cortex and striatum) AND sites for emotion (anterior cingulate cortex)
What is the lateral spinothalamic tract also known as?
‘Paleo’ spinothalamic tract
What does the lateral spinothalamic tract subserve?
Second, punishing aspects of pain e.g. ouch, that hurts!
What fibres innervate projection neurons in lamina I?
C fibres
A delta fibres
Lateral spinothalamic tract - what nuclei are involved? (3)
Where do they project to?
Mediodorsal nucleus –> anterior cingulate cortex
Posterior nucleus –> anterior/rostral insula
Ventral medial nucleus –> anterior/rostral insula
What collateral projections does the lateral spinothalamic tract have? (4)
Spinal circuitry (for reflexes)
Reticular formation
Periaqueductal gray
Parabrachial nucleus
What does the lateral spinothalamic tract project to the reticular formation for?
Arousal and alerting cortex
What does the lateral spinothalamic tract project to the periaqueductal gray for?
Descending pain modulation
Where is the parabrachial nucleus?
Where does it project to?
Pons
Amygdala
What is the role of the amygdala? (2)
Limbic activation (memory) Autonomic integration and response (w/ insular cortex)
What is the role of the insula? (3)
Interoception (detects internal regulation responses e.g. hunger)
Homeostatic adjustment
Emotion
What are the four cardinal signs of inflammation?
Calor
Rubor
Dolor
Tumor
What does normal acute pain result from?
Nociceptor activity
Define acute pain.
Acute pain is of sudden onset, usually the result of a clearly defined cause. It resolves with the healing of its underlying cause. It enables protection and facilitates healing.
What is fast pain?
What is slow pain?
Fast - sharp pain conveyed by A delta fibres, elicits a reflexive withdrawal
Slow - burning, lingering, emotionally charged pain
What is peripheral sensitisation?
Increased sensitivity to afferent nerve stimuli. It can occur as a result of inflammation. It can cause hyperalgesia, allodynia and spontaneous pain.
Define hyperalgesia.
Abnormally heightened sensitivity to pain
Define allodynia.
Pain following non-noxious stimuli
In peripheral sensitisation, due to effects of inflammatory mediators, nociceptors show reduction in ____ and increase in _____. Some nociceptors become tonically _____.
Activation threshold
Responsiveness
Active
Prostaglandins play an key role in what type of pain?
Inflammatory
What enzymes do NSAIDs target?
COX-1 and COX-2
What do COX-1 and 2 use as a substrate for prostaglandin synthesis?
What releases this substrate? What type of drugs target this?
Arachidonic acid
Phospholipase A2
Steroids
COX-1 is present in tissue at ___ levels
COX-2 is induced during _____
Low
Inflammation
How do prostaglanadins sensitise C fibres? (2)
Increasing numbers of other receptors
Increasing the number of open sodium channels
Prolonged nociceptor input produces an increase in excitability of…
This causes modified responsiveness.
Dorsal horn projection
Describe central sensitisation.
There are enhanced responses and even low level inputs produce responses.
It causes pain - allodynia, secondary hyperalgesia and spontaneous pain.
It differs from peripheral sensitisation as it extends outside the region of flare.
What is flare due to?
Release of peptides by C-fibres and other local inflammatory mediators
How many weeks does pain have to last for it to be classified as chronic?
12 weeks
What does maladaptive mean in terms of pain?
It continues past the healing phase following an injury
Chronic pain is normally associated with an underlying condition/arises from nociceptive pain? - True or False
True
Maladaptive pain is due to…?
Abnormal activity in the neural system
Are normal analgesics effect for maladaptive pain?
No
How is maladaptive pain treated? Does it respond well to treatment?
Anticonvulsants
Anti-depressants
No - often resistant to treatment
What is neuropathic pain due to?
Injury/dysfunction in PNS or CNS
What is dysfunctional pain due to?
What is it characterised by?
No known lesion or inflammation
Hyperalgesia, allodynia, spontaneous pain
Where does pain modulation occur? (4)
Cortex
From the brain/brainstem
Spinal cord (central sensitisation)
Periphery (inflammation)
Where does endogenous modulation occur?
At the spinal cord level
Superior parietal cortex – insula – amygdala path is for…?
Cognitive/attention control/intensity of pain
Anterior cingulate cortex – pre-frontal cortex – periaqueductal gray path is for…?
What drug is it sensitive to?
Emotion/unpleasantness
Naloxone
What fibres does acupuncture activate?
What pathway does it work through?
Aδ fibres
Periaqueductal gray mediated control
What is the basis of the TENS (transcutaneous electrical nerve stimulation) machine?
Stimulation of non-noxious afferents (or mildly noxious afferents) - these stimulate lamina II inter-neurons.
