Week 1 - Pain Flashcards
What are the characteristics of acute pain?
Tissue injury
Varying severity
Intensity relates to injury severity
Predictable time course
Successful treatment
What are the characteristics of chronic pain?
Pain > 3 months
Lasts after normal healing
Sometimes non-identifiable cause
No obvious pathological process
Unpredictable time course
Difficult to treat
What are the mechanisms of nocioceptive pain?
Good pain
Sensation associated with detection of damaging stimuli
Protective mechanism
What are the mechanisms of inflammatory pain?
Obvious tissue injury
Infiltration of immune cells promoting repair, causing pain until healed
Protective
Sharp/dull ache/throb
Well localised
What are the mechanisms of pathological pain?
Maladaptive
Results from abnormal NS function
Disease states caused by damage to NS (neuropathic pain) or abnormal function (nociplastic pain)
What are the mechanisms of neuropathic pain?
Cause by lesion or disease of SNS
Tissue injury not obvious
No protective function
Burning, shooting, pins and needles, numbness
Well localised
What are the mechanisms of nociplastic pain?
Substatial pain but no noxious stimuli or peripheral inflammatory pathology
No neuronal damage
Fibromyalgia, IBS, tension headache, interstitial cystitis
How to take a pain history?
PQRST
Precipitating factors
Quality of pain
Radiation
Severity
Timing
How to assess pain in dementia patients?
Assess via observation
What are the goals for pain reduction with analgesics?
>50% reduction
No worse than mild pain
Relief from related problems
No side effects
What are the properties of the dopamine pathway?
Reward
Pleasure
Motor function
Compulsion
Preservation
What are the properties of the serotinin pathway?
Mood
Memory processing
Sleep
Cognition
What are the properties of the brain reward pathway?
Meso-limbic dopamine pathway
+ drugs of abuse increase dopamine release
Some enhance serotinin 5HT function
Some block NMDA antagonists
What happens during opiate dependence liability and what are the chronic effects?
Agonist at G protein-coupled opioid receptors
Low neurotransmitter release in brain
Analgesia, euphoria, respiratory depression, dysphoria, sedation
Chronic effects = anhedonia, constipation, depression, insomnia
What happens in cocain dependence liability and what happens with a high dose?
Euphoria, excitement, + capacity to work
+ catecholamine neurotransmitter fucntion by preventing re-uptake
Sedative effects
High dose = overactivity of SNS = hypertension, tachycardia, hyperpyrexia, dilated pupil, palpitations
What happens in amphetamine drug dependence liability and what happens with high dose?
Produce wakefulness and concentration
Performance enhancing
Release monoamines from neuronal storage vesciles, blocking reuptake transporters
+ synaptic DA, NA, 5HT
Euphoria, + libido, energy, self-esteem, aggression, + power, obession, paranoia
High dose = psychosis
+Cv tone, + bp, + HR
WHat happens in cannabis dependence liability?
THC = active agent
Inhibits neurotransmitter release in brain via GI protein -coupled cannabinoid receptors
Mild euphoria
Dysphoria in high doses
+ appetite stimulation through actions on feeding centers in hypothalamus and gut, analgesic
Treatment for drug dependence?
Agonist substitution
Partial receptor agonist
Antagonist treatment
Anti-craving medicine
What is inflamed in meningitis?
What is inflamed in encephalitis?
Meninges
Brain
What is inflamed in myelitis?
What is inflamed in neuritis?
SPinal cord
Peripheral nerves
What are the main routes of infection?
Blood-borne
Parameningeal supparation
Spread through dura defect
Soread through cribiform plate
What are the symptoms of meningitis?
Meningism = headache, stiff neck and back, nausea/vomiting, photophobia
Fever
Rash
Infants = flaccid, bluging frontalle, fever, vomiting, strange cry, convulsions
How do you investigate meningitis?
Lumbar puncture (distinguish between bact. and vir.)
CSF analysis (if >5 white cells = meningitis)
Gram stain
Zn
PCR
Antigen agglutination tests
How do you manage meningitis?
Antibiotics
+ oxygenation
Prevent hypoglycaemia and hyponatraemia
Antoconvulsants
Decrease intracranial hypertension
Steroids prior to antibiotics
What are the causes of viral meningitis?
Predisposition (immunosuppression, alcohol, diabetes, hyposplenism, myeloma)
Pneumonia
Impaired conscioussness
Immunocompromised, neonate, > 50
What are the symptoms of encephalitis?
Cerebral irritation (irritated, altered personality, drowsiness, ataxia, brisk tendon reflexes, sluggish pupils)
Fever
Seizures
CSF pleocytosis
Abnormal neuroimaging
What causes encephalitis?
Herpes simplex virus
Arboviruses and rabies
Mosquitos, ticks, sandlfies
What are the clinical features of myelitis?
Vasculitis of anterior spinal artery
Primary = TB, syphilis
Post-infection = MMR
Ascending flaccid paralysis and sensory loss
What are the clinical features of encephalomyelitis?
Mix of 2
Viral and non-viral
PAthogenesis = direct invasion, vasculitis, immune infection response
Entry to CNS = respiratory, GI, subcutaneous, mucosa
What si the function of the somatosensory system?
Receives info from body parts
Detects + stimuli
Nociception (neural process activating C-fibres)
What is the function of the sensory system?
Receptive fields on sensory receptors
Single neuron in CNS can receive + inputs = convergence
Converts natural stimulus into action potentials
What happens during transduction?
Sensory nerve:
- Deformation of membrane
- Opening of Na+ and K+ channels
- Receptor potential
- Local depolarisation of receptive membrane
- Action potential propagated to CNS
What happens during transmission of tactile messages?
Central touch fibre branches ascend in dorsal columns
Synapse in dorsal column nuclei
Thalamus = synapse on cells
Sends projections to primary somatosensory cortex
What are the properties of alpha-beta fibres?
Myelinated fibres
Fast conduction velocity
Terminate in intermediate lamina of dorsal horn
Responses sensitive to glutamate receptor and peptide receptor antagonists
What are the properties of C-fibres?
Unmyelinated fibres
Slower conduction velocity
Terminate in superficial lamina or dorsal horn
Responses sensitive to glutamate receptor and peptide receptor antagonists
What is the process of spinal processing in pain?
- Dorsal horn of spinal cord receives innocuous and noxious messages
- Signals from nociceptor afferents activates second order neurones in SC
- Projection neurones project to brain
- Pain signals set up withdrawal reflexes
What are the spinal responses to pain?
- Not fixed and proportional to intensity of stimulus
- Enhanced responses for a given noxious stimulus are associated with repeated higher stimulation
What makes up the ascending pain pathway?
- Spinothalamic tract from laminae 1 and 5 to thalamus
- Post-synaptic dorsal column pathway
- Spino-reticular tract
- Spino-mesenphalic pathway
What happens to brainstem when in pain?
- Stimulated through spinoreticular tract and branches of psinothalamic tract
- Changes in bp, respiration, orientation
What is the function of the thalamus in pain?
- VPL = main somatosensory area of thalamus
- Final relay before sensory signals reach cortex
What is the function of the cortex when in pain?
Conscioussness of pain and limbic system for emotional response
What is the function of the hypothalamus whe in pain?
Where repsonses are mediated
Neuroendocrine changes and behaviours
What are causes of migraines?
- Genetic
- Autosomal dominant
- Vascular origin theory
- Hormonal disturbance = abnormal cerebral bloodflow
- Cortical spreading depression theory
- Cause of aura
- Sensory nerve activation theory
- trigeminovascular neuron activity
How do you treat migraines?
- Analgesics
- Anti-emetics
- Triptans
- CGRP receptor antagonists
- Beta-blockers, CC blockers, anti-epileptics, pre-menstrual oestrogen
- Acupuncture
What are the mechanisms behind vomiting?
- Chemoreceptor trigger zone
- Neurokinin = major output transmitter
- Vestibular system = motion sickness
- Intracranial pressure recptors
- Vagal nerve afferents = gag reflex
- Descending inputs = smells etc.
How do you treat emesis?
- 5HT3 antagonists
- Eicosanoid synthesis inhibition (corticosteroids)
- Neurokinin1 antagonists
- Dopamine D2 antagonists
- Muscarinin antagonists
- Antihiastamines
- Histamine H3 antagonist
- Cannabinoid agonists
What 3 agents go into anaestetics?
Hypnotics
Opioids
Neuromuscular blockers
How are eicosanoids involved in inflammation and what are examples of some?
- Main source = arachidonic acid
- Sythensis is driven by + stimuli, such as cell damage
Examples = prostaglandins, thromboxanes, leukotrienes
What are the roles of COX1 and COX2?
COX1 = enzyme in most tissues and blood platelets, tissue homeostasis
COX2 = induced in activated inflammatory cells, responsible for prostaglandin mediators of inflammation production
What are mediators from COX and their functions?
- Cyclic endoperoxides
- PGI2 - hyperalgesic, vasodilator, - platelet aggregation
- PGE2 - hyperalgesic, vasodilator
- PGD2 - vasodilator, - platelet aggregation
- TXA2 - thrombotic vasoconstrictor
How do prostanoids generate prostaglandins?
- Inflammatory response = prostanoid produced
- PGD2 released by mast cells
- Synergise with histamine and bradykinin
- Redness and + bloodflow
- Prostaglandins potentiate actions of bradykinin and histamine on blood vessels and peripheral nerves
How does bradykinin generate prostaglandins?
- Synthesised during tissue injury
- Activated by enzymes
- Activates nociceptors by B1 and B2 receptor
- PG production
How do NSAIDs reduce pain?
- Reduce inflammation
- Inflammation causes pain
- Decrease in pain
How do NSAIDs act as antipyretics?
- Reset thermostat and hypothalamus actions
- Inhibition of PG production in hypothalamus
- Temperature regulated, so decrease in temperature
What are NSAIDs mechanism of action?
- Inhibit cyclooxygenase enzyme
- Reduce eicosanoid generation
- Less PGs and inflammation
What are the opioid receptor mechanisms?
What are the effects of morphine?
- Act via u-receptor
- Analgesia
- Euphoria and dysphoria
- Anti-tussive (prevent cough)
What are the sites of action of opioids?
- Increase descending control from brain to SC via excitation
- Bind to GABAergic neuron
- Blocks transmission of neurotransmitter from glutamate
- Increases excitation at neurone
