Physiology and Pathology of Pain Flashcards
Define pain
Pain is an unpleasant sensory and emotional experience which we primarily associate with tissue damage or describe in terms of such damage
- It is not a stimulus, it is an experience
- Final product of complex-information processing network
Describe the basic transmission of pain sensation
Tissue damage is transduced into electrical signals thalamus higher systems in cortex
What are the four stages in pain transmission?
- Periphery
- Spinal cord
- Brain
- Modulation
What occurs in periphery stage of pain transmission?
- Detection
- Needs to reach certain threshold to become noxious (i.e. to sense pain)
- Transmission to spinal cord via first order neuron
What occurs in the spinal cord stage of pain transmission?
• Processing
• Transmission to brain (thalamus) via second order neuron
(Doesn’t always need to go to brain, immediate withdrawal occurs as immediate reflex)
What occurs in the brain stage of pain transmission?
Perception, learning, response
Pain is learned, so items causing pain are remembered and know not to touch again
What occurs in the modulation stage of pain transmission?
Descending tracts to withdraw limb from painful stimulus
Define nociception
Detection of tissue damage by special transducers which are connected to A-delta and C fibres
Pain is the product/ecperience due to nociception
Describe nociceptors
- Free nerve ending of A-delta and C-fibres
* Respond to thermal, chemical, mechanical noxious stimuli
Describe the primary afferents (1st order neurone)
- Cell body in dorsal root ganglion
- First order neuron which synapses in the spinal cord
- C fibres transmit slow pain as they’re not myelinated, and A-delta fibres transmits fast pain (sharp pain) as myelinated
What are the features of A-alpha and beta fibres?
- Myelinated
- Large diameter
- Proprioception, light touch
What are the features of A-delta fibres?
- Lightly myelinated
- Medium diameter
- Nociception (mechanical, thermal, chemical)
What are the features of C fibres?
- Unmyelinated
- Small diameter
- Slow conducting
- Innocuous temp, nociception (mechanical, thermal, chemical)
Describe type of pain transmitted by A-delta and C fibre
When someone pinches you, you will have a sharp pain to start with which will slowly transform into dull pain
A-delta transmits fast (sharp) pain as they’re myelinated.
The second dull pain is conducted by unmyelinated, slow conducting C fibres
What divides the grey mater into layers?
Reed lamina divides the grey mater into 10 layers - two and five are the regions which receive pain signals
Where in the spinal do the first order neutrons synapse?
In the dorsal horn
What are the three types of neurone the grey which receive the input?
- Nociceptive
- Low threshold mechanoreceptive
- Wide dynamic range
All axons continue as tracts (spinothalamic)
What fibres input into nociceptive neurones?
A-delta and C fibres
What fibres input into low threshold mechanoreceptive neurones?
A-delta and C fibres
What fibres input into wide dynamic range neurones?
Receive input from A-delta but response to both noxious and non-noxious stimuli via interneurons
What are the two spinothalamic tracts?
- Lateral STT - conveys fast and slow pain (pain and temp)
* Anterior STT - conveys sensation of simple touch
What is the spinothalamic tract?
The major tract sending impulses to the thalamus, with their cell bodies located primarily in Rexed lamina 2 and 5.
Where do fibres in the spinothalamic tract travel to?
Ventroposterior thalamic nuclei in the medial thalamus
What is the importance of the thalamus?
- Thalamus is the second relay station
- Medial thalamus is where 3rd order nuclei starts
- Connections: cortex and limbic system
In what part of the brain does pain occur?
In somatosensory cortex, and before this is nociception
Describe the descending pathways
- Descending pathway from brain to dorsal horn
- Start in periaqeductal grey
- Usually decreases pain signal
- Noradrenergic system
How can transduction influenced through neurones be influences?
Molecules binding to receptors at the synapse junction
Describe sensitisation in terms of hyperalgesia
Leftward shift of the stimulus response curve (so less intensity will cause same pain sensation) -> increased perception of pain or even perception of non-noxious stimuli as noxious stimuli (so will cause pain)
When does hyperalgesia occur?
With tissue injury and inflammation. Primary hyperalgesia occurs at the site of injury, and hyperalgesia in the surrounding uninjured tissue is secondary.
What are the changes that occur in nociceptors in allodynia?
Decreased threshold for response
What are the changes that occur in nociceptors in hyperalgesia?
Exaggerated response to normal and supranormal stimuli
What are the changes that occur in nociceptors in spontaneous pain?
Spontaneous activity in nerve fibres
Describe allodynia
Non-painful stimulus causing pain - the changes that occur in nociceptor include decreased threshold for the response.
Electrical threshold of the nerve does not change change but the range at which the stimuli become noxious is changed
What is central sensitisation?
Pain can modify the CNS, so that a person is more sensitive and produce more pain with less stimulus
It is the response of second order neurones in the CNS to normal input both noxious and non-noxious and occurs in the spinal cord
What are the three main components of central sensitisation?
- Wind-up
- Classical
- Long-term potentiation
Describe wind up central sensitisation
- Involves only activated synapses
- Homosynaptic activity dependent progressive increase in response of the neurons – more stimulus with activated synapse and opens more synapses and more APs are generated
- Manifests over the course of stimuli and terminates with stimuli
Describe classical central sensitisation
- Involves opening up of new synapses - silent nociceptors around are activated (basically asks for help)
- Heterosynaptic activity dependent plasticity
- Immediate onset with appropriate stimuli
- Outlast the initial stimuli duration
- Can be maintained even at low levels of ongoing stimuli
Describe long term potentiation central sensitisation
- Involves mainly the activated synapses
* Occurs primarily for very intense stimuli
What are the two categories of pain?
Acute < 1 month and chronic > 3-6 months
What are the features of acute pain (< 1 month)?
- Usually obvious damage
- Increased nervous system activity
- Presence of noxious stimuli
- Pain resolves upon healing
- Serves a protective function
- Usually nociceptive
What are the features of chronic pain (> 3-6 months)?
- Pain beyond expected period of healing
- Usually has no protective function
- Degrade health and function
- Presence of noxious stimuli is not essential
- Nociceptive, neuropathic or mixed
What is nociceptive pain?
A sensory experience that occurs when specific peripheral sensory neurones (nociceptors) respond to noxious stimuli
What are the features of nociceptive pain?
- Painful region is typically localised at site of injury – often describe as throbbing, aching or stiffness
- Usually time limited and resolves when damaged tissue heals (i.e. bone fractures, burns and bruises)
- Can also be chronic (i.e. osteoarthritis)
- Tends to respond to conventional analgesics
What is neuropathic pain?
Pain initiated or caused by a primary lesion or dysfunction in the somato-sensory nervous system (i.e. damage to a nerve)
What are the features of neuropathic pain?
- Painful region may not be the same as the site of injury – pain occurs in the neurological territory of the affected structure (nerve, root, spinal cord, brain)
- Almost always a chronic condition
- Responds poorly to conventional analgesics
Name different management measurements for pain (blocking transduction)
- NSAIDs
- Ice (closes receptor on synapse junction which is opened by heat)
- Rest
- Local anaesthetic blocks – block Na channels and thus transduction which stops pain
Define the Gate Control Theory
Rubbing acting A-beta fibres which causes them to fire and this inhibits C fibres (therefore nociceptors) via inhibitory interneurons.
They activate non-noxious fibres which compete with noxious fibres to send signal to brain, and happens at a spinal cord level.
What can affect the transmission of signals?
- Nerve blocks – at level of spinal cord
- Drugs; opioids and anticonvulsants (influence receptors at synapse and therefore transduction)
- Surgery; dorsal root ganglion entry zone (DREZ) and cordotomy
How can the perception of pain be altered?
- Education
- Cognitive behavioural therapy
- Distraction
- Relaxation
- Graded motor imagery
- Mirror box therapy
How do you modulate descending pathways?
- Placebos
- Drugs; opioids and antidepressants
- Surgery – spinal cord stimulation