Flashcards in Pain Deck (172):
What is nociception?
The sensory process that provides signals in the nervous system that trigger pain.
What is pain?
The feeling/perception of sensations from a part of the body.
What controls pain sensations?
A specific part of the somatosensory system.
What is congenital analgesia?
Inability to feel pain from birth.
-decreased lifespan as don't learn from pain
-rare: ~32 people
What is the structure of nociceptors found in peripheries?
Free nerve endings.
-Pacinian, Ruffini's, etc
What happens to nociceptive nerve endings in the dermis?
They branch out to unmyelinated endings.
-leads to difficulties localising pain
Where are the cell bodies of normal sensory receptors located?
In the dorsal root ganglion.
What does tissue damage and inflammation trigger?
The release of peripheral chemical mediators.
-e.g. prostaglandins, bradykinin
What effect does substance P have on mast cells?
Substance P stimulates mast cells to release histamine and bradykinin
>> chemical nociceptors.
What is the function of prostaglandins/bradykinin/histamines in pain?
They sensitise chemical nociceptors >> easier for an AP to be generated.
-can induce hyperalgesia
What is hyperalgesia?
Abnormally heightened sensitivity to pain.
What are the main modalities of nociceptors? (3)
-Chemical (e.g. histamine)
Do most nociceptors only respond to one modality?
No, most are polymodal.
-respond to mechanical, thermal and chemical stimuli
Which types of free nerve endings does transduction of nociceptive stimuli occur in? (2)
-Unmyelinated C fibres
-Thinly myelinated A-delta fibres
How do sensory fibres project to the brain?
Travel to dorsal horn, and project to brain via ascending pathways.
What sort of pain do TRPV receptors detect?
Thermal - heat.
(TRPV1 also detects chemical)
What sort of pain does a TRPM8 receptor detect?
Thermal - cold.
What sort of pain do TRPV1, ASIC and DRASIC recptors detect?
What sort of pain do MDEG, DRASIC and TREK-1 receptors detect?
What is microneurography?
An experiment that records transcutaneous nerve signals and is used to discriminate sensory afferents.
What is the difference between detectors that sense warmth and pain from heat?
THERMORECEPTORS sense temperature, but no increase above a certain threshold
NOCICEPTOR transmission increases when temperature becomes painful (45*+)
What sort of fibres are associated with low threshold mechanoreceptors?
Large diameter, rapidly conducting afferents (I/II).
What sort of fibres are associated with nociceptors and thermoreceptors?
Small diameter, slow conducting afferents (III/IV).
What types of nociceptors have A-delta fibres?
Thermal and mechanical nociceptors.
What types of nociceptors have C fibres?
What are the 2 categories of pain perception?
1st and 2nd pain.
What sort of sensation is 1st pain, and which fibres carry it?
-Fast A-delta fibres
What sort of sensation is 2nd pain, and which fibres carry it?
-Slow C fibres
What type of pain is more easily localised; 1st or 2nd?
1st pain is more easily localised.
What type of pain has slow onset; 1st or 2nd?
2nd pain has slow onset.
1st pain has rapid onset.
Which type of pain is more persistent; 1st or 2nd pain?
2nd pain is more persistent.
1st pain has a shorter duration.
What type of receptors produce 1st pain?
What type of receptors produce 2nd pain?
Summarise 1st pain.
-Fast A-delta fibres
-Mechanical and thermal nociceptors
Summarise 2nd pain.
-Slow C fibres
Is it possible to selectively anaethetise A-delta and C fibres?
Yes, but wouldn't do it clinically.
Where are nociceptive fibre cell bodies located?
Within dorsal root ganglion.
Upon entering the dorsal horn, what happens to primary afferents?
-They can ascend/descend on spinal cord level in the ZONE OF LISSAUER (dorsolateral)
-Then synapse within superficial laminae
What effect does the fact that 1* fibres can ascend/descend before synapsing have?
Can lead to pain localisation issues.
What are the principle laminae that nociceptor afferents enter?
Laminae I and II.
(substantia gelatinosa; most dorsal)
Why does referred pain occur between viscera and cutaneous sources?
Nociceptive afferents from internal organs and the skin enter the spinal cord through common routes and synapse with the same 2* neurons.
Where is pain from angina often referred to?
Upper chest wall and left arm.
Where is pain from appendicitis often referred to?
Abdominal wall around the navel.
Where is pain from the oesophagus often referred to?
Where is pain from the bladder often referred to?
Where is pain from the ureter often referred to?
Lower abdomen and back.
Where is pain from the prostate often referred to?
Lower trunk and legs.
What excitatory neurotransmitter do pain afferents release?
What substances do vesicles at synaptic terminals of pain afferent contain?
-e.g. substance P
What is the function of substance P?
Mediator of nociceptive synaptic transmission in the dorsal horn.
-helps to differentiate between different levels of pain
Where is substance P most dense?
In the superficial dorsal horn.
What type of pathway are ascending pain pathways?
Contralateral spinothalamic pathways.
-cross at level of spinal cord entry
What is the process of pain information travelling to the brain?
Stimulus >> 1* neuron >> dorsal horn of spinal cord >> synapses >> 2* neuron >> ascends to thalamus >> synapses >> 3* neuron >> somatosensory cortex (PCG).
What is the overall pathway for conveying pain/temperature called?
What are the 3 components of the anterolateral system?
-Lateral spinothalamic tract
-Anterior spinothalamic tract
What is another name for the spinoreticulothalamic tract?
Where does the anterior spinothalmic tract project to?
-Periaqueductal grey matter
Which sensory afferents follow the same route to the sensory cortex as pain afferents?
Non-nociceptive temperature afferents.
-both spinothalamic pathway
What is dissociated sensory loss (Brown-Sequard syndrome)?
Unilateral spinal cord lesion.
>> sensory loss of touch/proprioception on same side (DORSAL COLUMN PATHWAY)
>> sensory loss of pain on opposite side (SPINOTHALAMIC PATHWAY)
What pathway carries pain and temperature sensations from the face/head?
How do pain and temperature sensations from the face and head travel to the somatosensory cortex?
1* afferents travel in spinal trigeminal tract to brainstem >> synapse in pars caudalis >> 1* neurons >> trigeminothalmic tract >> thalamus >> VPM >> cortex.
How can pain be 'visualised'?
Using a PET scan of regional cerebral blood flow.
Which areas of the brain light up on a PET scan when thermal pain is induced to the hand?
-1* somatosensory cortex
-Limbic cortex (insular and anterior cingulate)
What is 'phantom pain'?
Pain and touch sensations with no sensory inputs.
What proportion of amputees suffer from phantom pain?
How is phantom pain treated?
Highly resistant to treatment.
-various drugs/treatments tried
What is the cause of phantom pain?
Aetiology is unclear.
-may be due to cortical reorganisation (thalamus/cortex)
-may be due to central sensitisation (change in synaptic structure of dorsal horn)
What are opiates?
Analgesic drugs derived from opium.
What are the main opiate receptors in the brain? (3)
Where are mu opiate receptors found in higher concentrations in the brain?
Thalamus and cerebral cortex.
Give 2 examples of commonly-used opiate drugs?
What are endorphins?
Endogenous opioids produced by the CNS and pituitary gland.
-control pain and immune responses
Give examples of endorphins.
-Peptides E and F
Which propeptides are endogenous opioid peptides synthesised from?
What is the endocannabinoid system?
Endogenous cannabinoid receptors located in the brain and throughout the CNS/PNS.
What endogenous ligands respond to cannabis? (2)
How does cannabis affect the body?
Inhibits behavioural responses to noxious stimuli and limits hyperalgesia and neuropathic pain.
-acts at spinal and supraspinal sites
What are the main higher brain centres involved in pain perception? (3)
Where do descending endogenous analgesic pathways project from? (2)
-Periaqueductal grey matter
How do descending endogenous analgesic pathways decrease transmitter release from 1* afferent terminals?
They interact with opioid receptors.
What proportion of the adult population endure chronic pain?
What is hyperalgesia?
Increased pain or touch sensations.
-usually due to inflammation
What is allodynia?
Increased pain sensitisation (touch-evoked pain).
>> increased response
What type of afferents cause hyperalgesia?
What type of afferents cause allodynia?
What are the 3 causes of hyperalgesia?
-Reduced pain threshold
-Increased stimulus intensity
What does the Gate Theory of Pain (Melzack and Wall) explain?
Why pain can be reduced by stimulating mechanoreptors (e.g. rubbing knee after falling over).
How is pain classified?
What are the main features of acute pain? (3)
-Resolves with healing of injury
-Assists wound healing
What are the main features of chronic pain? (2)
-Extends beyond expected healing time
-Ceases to serve protective function
What system regulates nociceptive pain?
Does a distal radius fracture cause acute or chronic pain?
-resolves with healing
Does osteoarthritis cause acute or chronic pain?
What are possible adverse effects of acute pain? (3)
What is the process of pain perception?
>> conduction (receptor)
>> transmission (CNS)
>> perception (pain/withdrawal)
What are the main factors that affect changes in pain perception?
What are the levels of the WHO analgesia ladder? (3)
1. Freedom from cancer pain
2. Pain persisting/increasing
3. Pain persisting/increasing
What pain relief is given for level 1 on the WHO analgesia ladder (freedom from cancer pain)?
What pain relief is given for level 2 on the WHO analgesia ladder (pain persisting/increasing)?
What pain relief is given for level 3 on the WHO analgesia ladder (pain persisting/increasing)?
Which non-opioid analgesics are used to treat acute pain?
What is the mode of action of NSAIDs?
-Decreases prostaglandin synthesis
What are the main side effects of NSAIDs? (4)
-CVS side effects (COX2)
What is the mode of action of paracetamol?
-Analgesic and antipyretic effects
-Inhibit central prostagladin synthesis
What is the main side effect of paracetamol?
Toxic liver damage risk.
Which 2 sites in the spinal cord do opioid analgesics act at?
How do opioid analgesics act pre-synaptically?
Reduce pain signal transmission.
How do opioid analgesics act post-synaptically?
Hyperpolarise membrane >> decrease the probability of AP generation.
What do opioid analgesics mainly act on?
-only partially effective in neuropathic pain
Give 2 examples of weak opioids.
Give 2 examples of strong opioids.
What is the mode of action of opioid analgesics?
-Activate endogenous analgesic system
-Stimulate receptors in limbic system
-Affect descending pathways that modulate pain
-Reduce ascending pain transmission
What are the main side effects of opioid analgesics?
What is a problem with large bolus opioid analgesics?
Large fluctuations between pain/analgesia/side effects.
Why is patient-controlled analgesia beneficial?
Less fluctuations in concentration - stays in analgesic range.
What is the dose for patient-controlled morphine?
1mg bolus, with a 5 minute lockout time.
What is a serious side effect of systemic opioid analgesia?
Respiratory depression and hypoxia.
What is the best early warning sign of respiratory depression?
-not respiratory rate or SpO2
Which opioids should be avoided if a patient is suffering from renal failure?
Morphine and codeine.
What is epidural analgesia?
Drugs administered to epidural space (between dura mater and canal wall).
What is epidural analgesia commonly used for? (3)
What are the main benefits of epidural analgesia?
-High quality pain relief
-Improved pulmonary function
-Reduced cardiac morbidity
Where is a high thoracic (T3-5) epidural analgesic delivered?
Where is a low thoracic (T5-10) epidural analgesic delivered?
Where is a low thoracic/high lumbar (T10-L3) epidural analgesic delivered?
Where is a lumbar (L2-S3) epidural analgesic delivered?
Where is a caudal (S2-5) epidural analgesic delivered?
What proportion of patients with advanced cancer experience pain?
What proportion of cancer pain is treated with opioids?
What is oromorph?
What is MST/MXL?
Sustained release morphine.
Cancer treatment: What is the dose of morphine on day 1?
-10mg oromorph (4 hourly)
TOTAL - 90mg
Cancer treatment: What is the dose of morphine on day 2?
-15mg oromorph (4 hourly)
TOTAL - 120mg
Cancer treatment: What is the dose of morphine on day 3?
-20mg oromorph (4 hourly)
TOTAL - 120mg
Cancer treatment: What is the dose of morphine on day 4?
-60mg MST (12hourly)
-20mg oromorph breakthrough
What type of cancer is the celiac plexus block commonly used for?
-Upper abdominal neoplasia
What nerves does a celiac plexus block affect?
Nerves surrounding the abdominal aorta.
Which part of the spinal cord do spinal opioids act at?
The dorsal horn.
Where does lipophobic spinal morphine go?
Reaches the brainstem.
Where does lipophilic spinal fentanyl go?
Remains segmentally localised.
What proportion of the population suffer from neuropathic pain?
What is neuropathic pain?
Spontaneous pain / hypersensitivity to pain in association with damage to the nervous system.
Give some examples of neuropathic pain.
-Post herpetic neuropathy (shingles)
What is the mechanism of neuropathic pain?
Trauma >> hyperexcitable dorsal horn >> nociceptive signals.
What are supraspinal mechanisms of neuropathic pain?
Melzack's neuromatrix; active generation.
What are the main features of neuropathic pain? (6)
-In absence of tissue damage
-In area of sensory loss
What does paroxysmal mean?
A sudden attack or increase in symptoms.
What is allodynia?
Pain in response to a non-painful stimulus.
What is dysaesthesias?
Unpleasant abnormal sensations.
-e.g. "ants crawling on skin"
What are the main co-morbidities of neuropathic pain? (3)
What does the McGill pain questionnaire measure?
-78 ranked descriptors
What are the advantages of the McGill pain questionnaire? (2)
What are the disadvantages of the McGill pain questionnaire? (2)
-Insensitive to small change
What type of pain medication acts at the brain?
Which types of pain medications act at the dorsal horn synapses? (4)
Which types of pain medications act at peripheral nociceptors? (2)
What drugs are used to treat neuropathic pain? (4)
What is the efficacy of antidepressants? (3)
-Complex regional pain syndrome
What is the mode of action of antidepressants?
Inhibit neuronal reuptake of noradrenaline and serotonin (5-HT).
What are the main side effects of antidepressants?(4)
What type of antidepressants are most effective for neuropathic pain?
Tri-cyclic agents (TCAs).
-serotonin uptake inhibitors relatively ineffective
What is the efficacy of anticonvulsants?
What are the main anticonvulsants used to treat neuropathic pain? (3)
What is the mode of action of gabapentin?
Binds to presynaptic voltage-dependent calcium channels.
What is the mode of action of pregabalin?
Interacts with special N-type calcium channels.
What is the mode of action of carbamazepine?
Blocks sodium and calcium channels.
What are the main side effects of anticonvulsants? (4)
What is ataxia?
The loss of full control of bodily movements.
Which anticonvulsants are GABA agonists? (2)
What sort of pain does gabapentin prevent?
Neuropathic, but not nociceptive.
What are the 4 dimensions of pain conceptualised by Loeser?