Pain Flashcards
Definition of pain (from 2019 IASP definition):
An unpleasant sensory and emotional experience associated with, or resembling that associated with, actual or potential tissue damage.
Or described in terms of such damage
Allodynia:
Pain resulting from a stimulus that would not normally be painful
Hyperaesthesia
Increased sensitivity to stimulation
Hypoaesthesia
Decreased sensitivity to stimulation
Hyperalgesia
Increased or exaggerated response to a normally painful stimulus
Hyperpathia
Abnormal pain response to stimulus applied to an area of decreased sensitivity
Repeated stimulus causes pain (think Chinese water torture)
What are the cellular mechanisms of actions of the opioids?
Receptor: Gi protein coupled
Intracellular pathway: inhibit production of cAMP causing closure of Ca channels. This results in hyperpolarisation of cell and decreased firing
Where in the spinal column are opioid receptors located?
Peri-acqueductal grey matter (PAG)
Rostral ventral medulla (RVM)
How do opioid receptors act in the spinal column?
Increase serotonin and noradrenaline levels in the spinal column (5-HT>NA)
Activate descending inhibitory control pathway
Where is most pain modulation done?
Laminae I & II
List some side effects of IT opioids:
Itch Sedation N&V Urinary retention Constipation Sweating Delirium/confusion Respiratory depression
What factors will increase the risk of post operative respiratory depression following administration of IT opioids?
Choice of IT agent: low dose lipophilic agent (fentanyl) will cause early depressoin, whereas hydrophilic agent may cause early or late resp depression Increasing age Positive pressure ventilation Long acting sedatives concurrently given Opioids via another route Pre-existing respiratory disease
Define chronic pain
Pain that persists longer than expected time of tissue healing
Usually longer than 3 months
Serves no purpose
Requires input from MDT
What systems are involved in pain modulation?
Segmental inhibition
Endogenous opioid system- endorphins, enkephalins
Descending inhibitory system
List symptoms of NEUROPATHIC pain
Hyperalgesia Burning Shooting Stabbing Hyperpathia
How does amitriptyline work in treating neuropathic pain?
Serotonin and noradrenaline reuptake inhibitor
Metabolised to nortriptyline which is more selective NA reuptake inhibitor
Enhances descending inhibition
Enhances opioid effectiveness
(Possibly affects Na channels and NMDA receptors)
Define CRPS
Severe continuous pain
Accompanied by sensory, vasomotor, sudomotor, motor/trophic changes
Pain is restricted to a region - not anatomical or dermatomal
Pain is disproportionate to inciting event
What are the criteria required for diagnosis of CRPS?
Budapest criteria
Continuing pain disproportionate to the inciting event
Other diagnoses excluded
One symptom in 3 of 4 categories
One sign in >2 categories at the time of examination
List risk factors for development of Complex Regional Pain Syndrome
Female sex
Period of prolonged immobilisation
Younger age (although not children so much)
Traumatic insult
Perhaps more common in upper limb compared to lower limb
What features may you find on examination for CRPS?
BUDAPEST CRITERIA:
Pain disproportionate to inciting event
1. Sensory - allodynia; hyperalgesia
2. Vasomotor - temperature asymmetry, skin colour changes, skin colour asymmetry
3. Sudomotor/oedema - oedema, sweating changes or asymmetry
4. Motor/trophic - decreased range of motion, motor dysfunction/weakness/tremor; hair loss/nail changes
No other diagnosis to explain symptoms/signs
What drug treatments are there for CRPS?
Regular analgesia Anti-neuropathic drugs - gabapentin, pregabalin, amitriptyline, duloxetine IV ketamine Corticosteroids Capsaicin (with caution)
What NON-drug treatments are there for CRPS?
TENS Spinal cord stimulator Sympathetic block Somatic nerve block Trigger point injection CBT Neuromodulatory techniques
Define persistent postoperative pain
Pain >2 months or longer than would be expected
Pain despite complete tissue healing
Other causes excluded
Pre-existing conditions excluded
List some common surgical procedures that are associated with persistent postoperative pain
Amputation Thoracotomy Mastectomy LSCS CABG Hip and knee arthroplasty Vasectomy
List some risk factors for development of persistent postoperative pain
Female sex
Increasing age (?maybe younger age as well?!?)
Repeat surgery
Radiation therapy to area/chemotherapy
Pre-operative pain/anxiety
Psychological disposition - anxiety/catastrophising/hypervigilance
What pathological changes occur at spinal cord level during the transition from acute to persistent postoperative pain?
Persistence of nociceptive input to dorsal horn
Central sensitisation via:
-‘Wind up’- temporal summation at the second order neurones due to NMDA receptor activity
-Firing of wide dynamic range neutrons in response to non-nociceptive stimulus
-Increased ion channel expression
-Decreased threshold to fire
-Greater influx of Na with action potentials
Decreased dorsal horn inhibitory neurotransmitters
How is Mg thought to work in the management of pain?
Mg used to keep NMDA receptors blocked and thereby hopefully stops wind up
Ketamine also does similar role as NMDA receptor antagonist
(When NMDA receptors open, large increase in pain transmission)
Define phantom limb pain
Perception of pain or discomfort in a limb that is no longer there
Episodic, in short bouts
Unchanged cortical representation of amputated limb (the brain thinks it is still there)
Incidence of 60-80%
May begin within 24 hours; usually within 1 week
Higher risk if severe pain pre-operatively in the limb
List some of the non-pharmacological management of CRPS
Patient education/support Desensitisation Exercises/strengthening Goal setting Relaxation techniques Facilitating self management of condition
List some risk factors for developing Phantom Limb Pain
Severe pain in limb pre-operatively Increasing age Bilateral amputation Stump pain Repeated limb surgeries
What pharmacological options are there to treat Phantom Limb pain?
Regular analgesia etc
Anti-depressants - duloxetine
Anti-convulsants
NMDA receptor angagonists
What non-pharmacological interventions are available for Phantom Limb Pain?
TENS
Mirror therapy
Nerve block
Salmon calcineurin (although that is a drug)
Describe the pathophysiology in post herpetic neuralgia
Degeneration of affected primary afferent neurones
Atrophy of spinal dorsal horn; scarring of dorsal root ganglion
Spontaneous discharge in deafferented central neurones
Intrinsic changes in CNS
Central sensitisation from sprouting alpha/beta fibres and loss of C fibre input
Sensitisation of C fibres
How do you treat post-herpetic neuralgia?
Multimodal/biopsychosocial approach Gabapentin/Pregabalin TCA - amitriptyline/nortriptyline Duloxetine Topical lidocaine patches (5%) Non pharmacological - TENS, acupuncture More invasive - nerve blocks
Briefly describe 4 principles of management of CRPS
Early referral to MDT
Early bisphosphonate infusion (rarely done early enough)
Patient education
Pain physiotherapy: graded exercise/mirror therapy/desensitisation
Pharmacological:
Psychological intervention: acceptance and commitment therapy (ACT)
Spinal cord stimulator in lower limb (?)
Describe the pain pathway associated with labour pain
Primary afferent via the sympathetic chain
Enter at T10-L1
Synapse in dorsal horn
Decussate and ascend to brain via spinothalamic tract
Reach thalamus and higher brain centres
Name areas of the brain involved in perception of pain
Thalamus Primary and secondary somatosensory cortex Amygdala Prefrontal cortex Hippocampus Insula Anterior cingulate gurus
List important variables in determining perception of pain
Memory Past experience Mood Cognition Beliefs Gender Emotions
Why is a higher dermatomal level needed for C-section?
T4 to cover peritoneum (from embryological development)
List 3 aetiologies of mechanical back pain?
Discogenic pain - 40% of back pain
Sacroiliac joint pain - 20% of back pain; usually below L5 process
Lumbar facet joint pain - 10-15% of back pain in young; pain worse on rotation and extension, radiation into leg, tenderness over joints and paravertebral muscle spasm
What are the ‘yellow flags’ in back pain?
“Yellow flags” - indicate likelihood of chronicity/disability
A belief that back pain is harmful or disabling
Fear avoidance behaviour
Reduced activity levels
Expectation that passive treatment will be beneficial (rather than active)
Tendency to depression/low morale/social withdrawal
Social or financial problems
Name the virus that causes shingles
Varicella Zoster Virus
List risk factors for the development of post-herpetic neuralgia
Age >60 Female More intense initial pain More severe rash Prodrome of dermatomal pain before rash Fever
List 6 clinical features of post-herpetic neuralgia
Prodromal pain in single dermatome prior to onset of rash
Continuous or intermittent throbbing/burning pain
Allodynia
Sensory loss
Motor weakness
Autonomic disturbance - abnormal skin temperature/colour/sweating
Depression/anxiety
Poor sleep/chronic fatigue
Weight loss
State a drug that prevents Post Herpetic Neuralgia
VZV booster
Aciclovir/valaciclovir
How much of CRPS is Type I vs Type II?
90% is Type 1
What are the recovery statistics for CRPS?
74% recover after a year
State the peripheral mechanisms for Phantom Limb Pain
Spontaneous discharge of afferent neurons
Spontaneous discharge in dorsal root ganglia
Upregulation of sodium channels
Coupling to nervous system
Neuromas
State the spinal cord mechanisms of development of Phantom Limb Pain
Re-organisation of c-fibres at lamina
Sensitisation of dorsal horn
State the central mechanism of the development of Phantom Limb Pain
Cortical re-organisation
List some questionnaires used to assess CHRONIC pain
Brief Pain Inventory McGill Pain Questionnaire LANSS - Leeds Assessment Neuropathic symptoms and signs HADS - Hospital Anxiety/Depression Score Edmonton Symptom Assessment
List methods of assessing acute pain
Observations/physiological parameters Visual Analogue Score Numerical Rating Score Verbal Rating Score Faces Pain Score
What are the problems of assessment tools in pain?
Snapshot in time Unidimensional Pain at rest or on movement may be different Subjective measure Pain memory not always accurate
What is peripheral sensitisation?
Chemical and inflammatory factors sensitise the peripheral nociceptors to lower their threshold
Peripheral nociceptors that are sensitised only need a reduced stimulus to still fire
How does peripheral sensitisation occur?
- Direct activation from synthesis of bradykinin and prostaglandins which lower the threshold for nociception
- Secondary activation - stimulated release of Substance P causes vasodilatation, further release of bradykinin, histamine and serotonin
—Histamine/serotonin levels increase and sensitise nearby nociceptors
What are the peripheral action of opioids?
Increased opioid receptor production in dorsal root ganglion
These are passed peripherally and acted on by endogenous opioids released by inflammatory cells
What changes occur following a nerve injury?
Damage of a nerve causes ectopic firing at the site of injury
Sympathetic nerve fibres sprout around dorsal root ganglion: causing allodynia/hyperalgesia/burning pain/atrophic changes
Large diameter afferent nerves grow into dorsal horn
Describe central sensitisation
Occurs in dorsal horn following injury
Wind up of spinal cord activity
Dependent on NMDA receptor
Increase in magnitude and duration of response to above-threshold stimuli
Reduced nerve threshold
What are the key mechanisms that occur in the Dorsal Root Ganglion to activate the post-synaptic cell?
Neurotransmitters released from primary afferent nerve: Glutamate & Substance P (as well as Neurokinin)
Act at NMDA/AMPA/NK-1 receptors
Cause Na+ influx & Secondary messenger activation
Mg plug removed from NMDA
Na+ & Ca2+ influx into NMDA receptor
Activation of NMDA receptor increases nociceptive response
Sustained activation of NMDA receptor is associated with chronic pain. Increase in Na+ channels causing wind up
What is central sensitisation and how does it occur?
Normal physiological phenomenon that is responsible for hyperalgesia/allodynia/secondary hyperalgesia.
- Peripheral sensitisation - changes to local environment around peripheral nociceptors (usually due to release of inflammatory mediators)
- Central sensitisation (spinal cord) - changes to receptor expression and activity at spinal cord level
Upregulation of sodium and calcium channels
Increased NMDA receptor activity - Central sensitisation (cortical level) - changes to cortical matrix that controls pain
Increased excitatory or decreased inhibitory
Should normally last for minutes but can be sustained by ongoing peripheral nerve stimulation - nociceptors or A-beta.
In chronic pain - may be all or combination of these mechanisms causing pain
How do epidural opioids exert their effects?
Cross the dura
Bind to opioid receptors in spinal cord white matter/dorsal horns/substantia gelatinosa
—closes calcium channels resulting in K efflux and reduced cAMP production, causing reduced neuronal excitability
Systemic absorption from epidural veins
Cephalic spread and brainstem action
List indications for spinal cord stimulator insertion
CRPS
Failed back surgery syndrome
Neuropathic pain secondary to peripheral nerve damage
Ischaemic pain from PVD
What are the contraindications to spinal cord stimulator insertion?
Psychological unsuitability Uncontrolled bleeding Sepsis Implanted cardiac devices: PPM/ICD Immunosuppression
What are the components of a spinal cord stimulator?
Stimulator leads: 4-8 electrodes
Pulse generator: external or implanted
What are the site of action of intrathecal opioids?
MOP/DOP/KOP receptors
In Laminae I + II of dorsal horn
Found pre-synaptically on primary afferent C and Ad fibres
(A few found post-synaptically)
What are the intra and extra cellular mechanisms of analgesia effect within the spinal cord of IT opioids?
Presynaptic stimulation causes hyperpolarisation of cell and reduced release of excitatory glutamate and substance P
Post-synaptic stimulation causes increased activation of descending inhibitory pathways
IT opioids are pumped caudally and have central effects too:
- Stimulate receptors in NUCLEUS RAPHE MAGNUS and PERIAQUEDUCTAL GREY MATTER
- increases the descending inhibitory pathways
What factors increase the risk of post op respiratory depression following administration of IT opioids?
Hydrophilic opioid use - stay in CSF for longer, cause delay in peak plasma concentration Increasing age Use of sedatives Respiratory disease PPV
Describe the nociceptive pathway
Stimulus -> nociceptor -> dorsal root ganglion -> dorsal horn -> ascending tracts -> thalamus -> cortex
Where are COX enzymes found?
COX 1 - most cells
COX 2 - macrophages and cells of inflammation; catalyses formation of inflammatory mediators
COX 3 - thought to be site of action of paracetamol (maybe)
Describe how NSAIDs exert their effects
Block the conversion of arachidonic acid to prostanoids (thromboxane, prostacyclin and prostaglandin)
Arachidonic acid converted to leukotrienes instead
What are the actions of prostacyclin, thromboxane and prostaglandin?
Prostacyclin:
—vasodilator
—prevents formation of platelet plug
Thromboxane:
—produced by platelets
—vasoconstrictor
—platelet aggregator
Prostaglandin:
—variety of different receptors mean lots of different effects:
—PGE2 - decreased gastric acid secretion, increased gastric mucous secretion
—PGI2 - vasodilatation, platelet aggregation
—PGF2 - uterine contraction, bronchoconstriction
How does TENS work?
Decreases sensitisation in CNS
Decreases nociceptive cell activity
Enhances descending inhibitory pathways in PAG
