Flashcards in Pain Deck (83):
What is pain?
Unpleasant sensory and emotional experience associated with actual/potential tissue damage
What are some physiological stimuli for nociceptive pain?
What are some clinically relevant stimuli for nociceptive pain?
Abnormal mechanical forces
- Ischaemic claudication
What is pain proportional to?
Strength of stimulus
Describe the nociceptive pathway in general
Nociceptor encodes info
Relayed to spinal cord/brainstem
Travels via ascending pathways
Much of info goes through thalamus
Up to areas of cortex
Converted into pain perception
Is nociception different to somatosensation?
No, it's a subclass
What is the threshold for nociceptors?
What do nociceptors transduce and encode, in general?
Noxious stimuli; eg:
- Strong mechanical forces damaging tissue
- Extremes in temperature
- Chemical stimuli that damage skin like acid
What is a noxious stimulus encoded into by the nociceptor terminal?
What is a noxious stimulus?
Stimulus that's damaging/threatens damage to normal tissues
What are the three steps in transmission of nociception?
1) Action potential transfers electrical signal from periphery to spinal cord
2) Spinal cord nociceptive neurons integrate and transfer info to brains/other parts of spinal cord - 2nd neuron
3) Thalamic/brainstem nociceptive neurons integrate and transfer information to cortical and other brain regions
What are the two components of pain perception?
What does the sensory part of pain perception do?
Identifies discriminative aspects
What two ganglia contain primary afferent sensory neuron cell bodies?
Dorsal root ganglia
What nociceptors do the trigeminal ganglia contain?
Those projecting to head
- Tooth and jaw pain
What nociceptors do the dorsal root ganglia contain?
Those projecting to body - most
How many axons does a nociceptive fibre have?
1 axon with 2 parts
- Peripheral axon projecting via peripheral nerves to endings in somatic/visceral targets
- Central axon projecting to dorsal horn of spinal cord
What are the types of nociceptive fibres?
A delta fibre
Describe C fibres
Describe A delta fibres
Compared to touch receptors, are nociceptive receptors fast or slow?
Describe the terminal of the peripheral axon of a nociceptive fibre
Free nerve endings
Not encapsulated in specialised cell like touch receptors
In which layers of the spinal cord do the central axons of nociceptors terminate?
Superficial layers - usually laminae 1 and 3
What is the nociceptive pathway in the spinal cord?
Those in dorsal horn project to brain via spinothalamic tract on opposite side of spinal cord
Where is the point of decussation in the nociceptive pathway?
Dorsal horn - via synapse
What white matter tract do nociceptors travel up in the spinal cord?
Does all nociceptive information go up to the brain?
No, some only goes to spinal cord > forms reflex circuit
What happens when a noxious mechanical stimulus is detected by a nociceptor in the knee region?
Elicits complex withdrawal reflex in both legs without any input from brain
What happens to nociceptive information when the spinal cord is anaesthetised?
Perception of pain blocked because ascending pathway blocked
Spinal cord reflexes aren't blocked
What type of pain do A delta fibres elicit?
What type of pain do C fibres elicit?
What type of behaviours are A delta fibres more likely to elicit?
What type of behaviours are C fibres more likely to elicit?
Behaviours that remove stimulus
Why can you feel a first and second pain?
When both A delta and C fibres are activated, they transmit signals at different speeds, so pain from A delta fibres is felt first, and quickly. Pain from C fibres follows and remains for a longer time
What is inflammatory pain?
Pain felt during active inflammation
How is inflammatory pain detected?
Properties of nociceptors altered by chemicals released by damaged tissues/immune system in context of disease
What is spontaneous pain?
Pain felt when there is no external stimulus/pain with innocuous stimulus
Why do we get spontaneous pain?
Where can amplification happen?
What are clinically relevant stimuli for peripheral amplification?
Joint inflammation; eg: rheumatoid arthritis
What is one type transducer protein that's found on nociceptors?
What is TRPV1 activated by?
Certain lipids - endogenous equivalents of cannabinoids
Where is TRPV1 found?
Most membrane terminals of nociceptors?
What type of receptor is TRPV1?
Gated ion channel for Na and Ca
Do all nociceptors express the same transducer proteins?
No, different functional classes express different types
What type of nociceptors is TRPV1 found on?
Heat specialised nociceptors
Do all members of the TRP respond to the same stimuli?
No, different members respond to different stimuli
Where is TRPA1 found, and to what does it respond?
What does TRPM8 respond to?
How does the "inflammatory soup" affect nociceptor activity?
Chemical signals released by tissue damage/disease
Detected by different receptors on nociceptor terminals
Downstream cell signalling causes sensitisation
How does downstream signalling affect nociceptor sensitisation?
Changes properties of terminal and lowers threshold
Increased response to normally painful stimulus
Painful response to normally innocuous stimulus
How can allodynia be clinically detected?
Stroke skin softly with paintbrush/cue tip > intensely painful to patient
What can central sensitisation result from?
Increased nociceptor activity after peripheral sensitisation
Describe secondary hyperalgesia
If you have localised painful stimulus, get localised pain induced by stimulus
Over time, hyperalgesia extends into areas that aren't damaged because initial signal activates regions of spinal cord, including across segments
Amplifies info coming in from adjacent nociceptive and non-nociceptive afferent fibres
What is neuropathic pain?
Nervous system lesion or disease/ marked neuroimmune response causing pain
What are examples of a CNS problem causing neuropathic pain?
Spinal cord injury
What causes central amplification in neuropathic pain?
Neuroimmune interactions in periphery and CNS
What causes peripheral amplification in neuropathic pain?
Toxic and metabolic neuropathies
What does it mean for neuropathic pain to be maladaptive and persistent?
Abnormal amplification maintained independent of lesion/disease
How can peripheral neuropatic pain occur?
Damage to peripheral nerves > develop inappropriate branches
Pain perception altered
How can a cut terminal continue to produce spontaneous electrical activity?
Cell damage > nerve loses input > central part of axon continues to generate electrical activity
What are complex regional pain syndromes (CRPS)?
Multifactorial pain disorder
- Pain and other clinical abnormalities
- Signs and symptoms spread distally glove- or stocking-like in affected limbs
- Sudden change for pain after fracture/surgery to persistent burning pain
What is the cause of CRPS?
No identifiable pathology
What are examples of functional pain syndromes?
Define acute pain
Lasts for short time
Occurs after surgery/trauma/other condition
Warning to body to seek help
Define sub-acute pain
Progressing to chronic pain
Can be prevented
Define recurrent pain
Occurs on cyclical basis
- Pelvic pain
Define chronic pain
Lasts beyond time expected for healing
What area in the brain does pain activate?
No single area
What roles do the periaqueductal grey and rostral ventral medulla in the brainstem play in pain?
Form chain projecting back down to spinal cord
What are some major classes of centrally acting analgesic drugs?
Tricyclic antidepressants (TCAs)
Serotonin-noradrenaline reuptake inhibitors (SNRIs)
Alpha 2-adrenergic agonists
What is an example of an opioid?
What are two examples of anticonvulsants?
What is an example of an alpha 2-adrenergic agonist?
What is an example of a cannabinoid?
How can pain experience be modulated?
Feedback pathway to spinal cord that can inhibit/amplify info brought by nociceptors
What effect does fear have on the perception of pain?
What cortical areas are involved in the modulation of pain?
By giving a person a placebo and telling them that it reduces pain, what effect does this have in the brain?
Produces genuine analgesia via endogenous pain modulation
Placebo analgesia reduced/prevented by opioid antagonists
What effect on the brain does it have by giving a patient a nocebo?