Physiology and Pathophysiology of Pain Flashcards
What is pain?
Pain is an unpleasant sensory and emotional experience which we primarily associate with tissue damage or describe in terms of such damage or both
It is not a stimulus
Final product of complex-information processing network
When nociceptive information reaches the thalamus where does it go?
Cingulate cortex
Somatosensory cortex
Limbic system
Describe the process of pain transmission
Step 1: Periphery
- Nociception (detection)
- Transmission to spinal cord (1st order neurons)
Step 2: Spinal cord
- Processing
- Transmission to brain (Thalamus) (Secondary order neurons)
Step 3: Brain
-Perception, Learning, Response
Step 4: Modulation
-Descending tracts
What processing of painful sensory information occurs in the spinal cord?
Assessed for need to send to brain
Descision made if there is any reflex response needed (to pull away from stimulus)
What is nociception?
The detection of tissue damage by specialised transducers connected to A-delta and C fibres
What are nociceptors?
Free nerve endings of A-delta and C fibres
Respond to thermal, chemical, machanical and noxious stimuli
Where does the Primary afferents/ 1st order neurons cell body lie?
Dorsal root ganglion
Describe A-alpha and A-beta fibres
Myelinated
Large diameter
Proprioception, light touch
Describe A-delta fibres
Lightly myelinated
Medium diameter
Nociception
(mechanical, thermal, chemical)
Fast pain (sharp pain)
Describe C fibres
Unmeylinated
Small diameter
Innocuous temperature, itch
Nociception
(mechanical, thermal, chemical)
Slow pain (Dull pain)
How is the grey matter of the spinal cord divided?
Based on location:
-ventral, lateral and dorsal horns
Based on cytoarchitecture:
-10 Laminae of rexed
What are the 3 types of neuron predominantly in the grey matter?
- Low threshold mechanoreceptive neurons
- Nociceptive specific neurons
- Wide dynamic range neurons
In addition there are interneurons which influence both the projection neurons and afferent input
What are low threshold mechanoreceptive neurons?
Loacted primarily in layer 3 + 4 (middle of dorsal horn)
Recieve input from A-beta fibres
What are Nociceptive specific neurons?
Located primarily in layer 1 + 2 (the most posterior, right at the back of the dorsal horn)
Recieving input from C and A- delta fibres
What are wide dynamic range neurons?
Located in layer 5 (anterior of dorsal horn near lateral horn)
Recieves painly input from A-beta but responds to both noxious and non-noxious stimuli via interneurons
Where do the nociceptive 1st order neurons we are concerned with synapse in the dorsal horn?
Substantia gelatinosa
(Laminae II)
also info in laminae V
Waht does the lateral spinothalamic tract convey?
Fast and slow pain
pain and temperature sensations
What does the anterior spinothalamic tract convey?
Simple touch
What is the spinothalamic tract?
The major tract sending impulses to the thalamus.
Cell bodies located primarily in Rexed lamina 1, 2 and 5.
There are 2 types of STT: Lateral and ventral (or neo and paleo)
Where does the lateral spinothalamic tract terminate?
Ventroposterior thalamic nuclei.
This nuclei primarily feeds to somatosensory cortex to facilitate spatial, temporal and intensity discrimination of painful stimuli.
Where does the ventral spinothalamic tract terminate?
Medial thalamic nuclei
This projects to cortical regions such as anterior cingulate and insular cortex as well as other parts of the limbic system.
How is the limbic syste related to pain?
Limbic system is closely connected with behaviours, thus behavioural state influence the firing in medial thalamus.
The anterior cingulated cortex may contribute to the affective component of pain experience and modulate the autonomic and motor components of pain.
Where does pain perception occur?
Somatosensory cortex
What parts of the brain feed back and forward with brainstem centres for the affective and emotional component as well as descending control of pain?
Prefrontal cortex Amygdala Hippocamus Cingulate cortex Insula PAG of Brainstem
Describe the periaqueductal grey of the descending pathways of pain
Periaqueductal grey (PAG)
- On cells or off cells
- Off cells inhibit pain
- Usually decreases pain signal
Noradrenergic system
What is sensitisation?
Injury sensitises nociceptors
After sensitisation -> hyperalgesia (= increased sensitivity to pain)
What is hyperalgesia?
Increased perception of pain or even perception of non-noxious stimuli as noxious stimuli.
It happens whenever there is tissue injury and inflammation.
Hyperalgesia can be divided into Primary and Secondary Hyperalgesia.
What is the difference between the two?
Primary hyperalgesia is hyperalgesia at the site of injury while hyperalgesia in the surrounding uninjured tissue is termed secondary hyperalgesia. It can be for any stimuli – thermal, mechanical
What is allodynia?
Refers to central pain sensitization (increased response of neurons) following painful, often repetitive, stimulation.
Allodynia can lead to the triggering of a pain response from stimuli which do not normally provoke pain.
Temperature or physical stimuli can provoke allodynia, which may feel like a burning sensation, and it often occurs after injury to a site.
Allodynia is different from hyperalgesia, an extreme, exaggerated reaction to a stimulus which is normally painful.
What is central sensitisation?
Response of second order neurons in the CNS to normal input both noxious and non-noxious.
Very similar to peripheral sensitisation but happens at level of spinal cord
What are the 3 main components of central sensitisation?
Wind up
Classical
Long term potentiation
What is wind up in central sensitisation?
Literally winding up the response to the input so the wind up happens only in neurons taking part in the synapses with primary afferent input.
It is actively dependent; progressively increases the response of the neutrons.
It manifests only over a course of a stimulus and terminates with stimulus.
What is the mechanism of wind up in central sensitisation?
The mechanism has been identified and is mainly mediated by the neurotransmitters: Substance-P and CGRP
What is classical central sensitisation?
Involves opening up of new synapses in the dorsal horn.
So the new synapses, which were silent before will start to recieve input and record the nociception.
How is classical central sensitisation activated?
It does occur with all stimuli but the intensity has to be strong to elicit this response.
If intesnity is strong enough, it occurs immediately with the stimuli and can OUTLAST THE INITAL STIMULI DURATION
NDMA receptor activation by glutamate triggers
What is the clinical result of classical central sensitisation?
Secondary hyperalgesia, where the area surrounding the injury site is also painful and hwere touch also becomes painful.
Once activated it can be MAINTAINED EVEN AT LOW LEVELS OF ONGOING STIMULI
What is long term potentiation?
Involves mainly the activated synapses
Occurs primarily for very intense stimuli
Involves mainly activated synapses and occurs primarily for very intense stimuli
The mechanism involves both AMPA and NMDA receptor activation by glutamate
What is acute pain?
What is chronic pain?
> /= 3-6 months
- Pain for 3-6 months or more
- Pain beyond expected period of healing
- Usually has no protective function
- Degrades health and function
Describe Acute pain vs Chronic pain
Acute pain is physiological while chronic pain is pathological
Acute pain has the presence of noxious stimuli while in chronic pain this is not essentail
Acute pain serves a protective function while chronic pain has no purpose
Chronic pain can be nociceptive , neuropathic or mixed while acute pain is only nociceptive
What is nociceptive pain?
A sensory experience that occurs when specific peripheral sensory neurones (nociceptors) respond to noxious stimuli
Describe nocicpetive pain
Painful region is typically located at site of injury - often described as throbbing, aching or stiffness
Usually time limited and resolves when damaged tissue heals
Can also be chronic (osteoarthritis)
How does nociceptive pain respond to conventrial analgesics?
Tends to respond
What is neuropathic pain?
Pain initiated or caused by a primary lesion or dysfunction in the tomato-sensory nervous system
Describe neuropathic pain
Painful region may not necessarily be the same as the site of injury- pain occurs in the neurological territory of the affected structure (nerve, root, SC, brain)
Almost always a chronic condition (posttherpetic neuralgia, poststroke pain)
How does neuropathic pain respond to convential analgesics?
Responds poorly
What is postherpetic pain?
Postherpetic neuralgia (PHN) is a nerve pain (neuralgia) that persists after a shingles rash has cleared. If the pain goes, but then returns at a later date, this too is called PHN.
What analgesia works for transduction?
NSAIDs
ICE
Rest
LA blocks
What analgesia works for transmission?
Nerve blocks
Drugs
- Opiates
- Anticonvulsants
Surgery
-DREZ
Cordotomy
What analgesia works for perception?
Education
Cognitive behavioural therapy
Distraction
Relaxation
Graded minor imagery
Mirror box therapy
What analgesia works for Descending modulation?
Placebos
Drugs
- Opioids
- Antidepressants
Surgery
-Spinal cord stimulation
