Pain Flashcards
What is pain?
Unpleasant sensory and emotional experience associated with actual/potential tissue damage
What are some physiological stimuli for nociceptive pain?
Mechanical
Termal
Chemical injury
What are some clinically relevant stimuli for nociceptive pain?
Abnormal mechanical forces - Osteoarthritis Organ injury - Angina - 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?
High threshold
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?
Electrical signal
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?
Sensory
Emotional
What does the sensory part of pain perception do?
Identifies discriminative aspects
- Location
- Intensity
- Quality
What two ganglia contain primary afferent sensory neuron cell bodies?
Trigeminal ganglia
Dorsal root ganglia
What nociceptors do the trigeminal ganglia contain?
Those projecting to head
- Migraine
- Tooth and jaw pain
What nociceptors do the dorsal root ganglia contain?
Those projecting to body - most
- Somatic
- Visceral
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?
C fibre
A delta fibre
Describe C fibres
Thin
Unmyelinated
Slow
Describe A delta fibres
Thin
Myelinated
Medium-fast
Compared to touch receptors, are nociceptive receptors fast or slow?
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?
Anterolateral tract
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?
Sharp
What type of pain do C fibres elicit?
Slow, burning
What type of behaviours are A delta fibres more likely to elicit?
Withdrawal reflex
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?
Sensory amplification
Where can amplification happen?
Peripherally
Centrally
What are clinically relevant stimuli for peripheral amplification?
Tissue trauma
Surgery
Joint inflammation; eg: rheumatoid arthritis
What is one type transducer protein that’s found on nociceptors?
TRPV1
What is TRPV1 activated by?
Capsaicin
Heat
Acid
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?
Polymodal nociceptors
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?
In airways Responds to - Nicotine - Formalin - Others
What does TRPM8 respond to?
Menthol
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
Define hyperalgesia
Increased response to normally painful stimulus
Define allodynia
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?
Stroke
Spinal cord injury
MS
What causes central amplification in neuropathic pain?
Neuroimmune interactions in periphery and CNS
What causes peripheral amplification in neuropathic pain?
Nerve trauma
Toxic and metabolic neuropathies
Herpes zoster
AIDS
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
- Sensory
- Motor
- Autonomic
- 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?
CRPS
Migraines
Myalgia
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
Transition phase
Define recurrent pain
Occurs on cyclical basis
- Migraine
- Pelvic pain
Define chronic pain
Lasts beyond time expected for healing
What area in the brain does pain activate?
No single area
Activates network
What roles do the periaqueductal grey and rostral ventral medulla in the brainstem play in pain?
Form chain projecting back down to spinal cord
Modulate pain
What are some major classes of centrally acting analgesic drugs?
Opioids NSAIDs Anticonvulsants Tricyclic antidepressants (TCAs) Serotonin-noradrenaline reuptake inhibitors (SNRIs) Alpha 2-adrenergic agonists Cannabinoids
What is an example of an opioid?
Morphine
What are two examples of anticonvulsants?
Gabapentin
Pregabalin
What is an example of an alpha 2-adrenergic agonist?
Clonidine
What is an example of a cannabinoid?
Marijuana
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?
Hypoalgesia
What cortical areas are involved in the modulation of pain?
Anterior cingulate
Prefrontal
Insula
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?
Hyperalgesia
What are the factors in the psychobiological model of pain perception?
A delta and C nociceptive input Injury - Peripheral and central sensitisation Chemical and structure - Neurodegeneration - Metabolic - Maladaptie plasticity Cognitive set - Hypervigilance - Attention - Distraction - Catastrophising Mood - Depression - Catastrophising - Anxiety Context - Pain beliefs - Expectation - Placebo
