Pain and its management Flashcards
What is pain?
Unpleasant sensory and emotional experience associated with actual or potential tissue damage, caused by cytokines
Effects of pain
- Danger alert - withdrawal
- Protection - rest injury
- Prevention - learning to avoid injury again
- Suffering
- Impaired function (motor, respiratory, CVS)
Pain pathway
- Pain recognition
- Peripheral conduction
- Spinal processing
- Ascending transmission
- Relay to cortex
- Motor homunculus
- Sensory homunculus detects where pain occurs
What are nociceptors?
- Nociceptors are bare nerve endings, most in skin but some are dormant or in deeper tissues (which are activated by injury)
- Respond to several stimuli (e.g. mechanical/thermal/chemical)
- Sensitized by inflammatory mediators (bradykinin, histamine, prostaglandins)
- Limiting prostaglandins limits pain
What are the two responses to pain?
Fast and slow
Characteristics of fast response to pain
A delta fibres
Large and myelinated
Up to 10m/sec
Sharp, stabbing pain
Characteristics of slow response to pain
C fibres
Small, unmyelinated
1.2 m/sec
Aching, burning
Is the spinal transmission of pain contralateral or ipsilateral?
Contralateral
Is a withdrawal reflex contralateral or ipsilateral?
Ipsilateral
Pathway of visceral pain
Autonomic nerves
What is referred pain?
Pain in one area of the body is felt in another
What is neuropathic pain?
Results from nerve damage e.g. trauma/infection (e.g. Herpes zoster virus)
Difficult to treat
Often becomes chronic
Where is local anaesthetic administered?
Site of injury
What are local anaesthetics?
Bases - proton acceptors
Is lidocaine short or long lasting?
Short
Is bupivacaine short or long lasting?
Long
Characteristics of local anaesthetics
- Ammonium group picks up proton
- Information sent down nerve - sodium enters cell - channel blocks and causes depolarization - depolarization travels along nerve
- Administered extracellularly in ionized from containing proton, it loses the protons and transfers across the membrane where it picks up the proton again
- This ‘blocks up’ the sodium channel which prevents depolarization and transmission of brain signal
What is a spinal block?
- Epidural goes outside of dura
- Action potential blocked at that level
- Paralysis/block of cauda equina
- Moves down by gravity - if moves up could affect intercostals and breathing
What does PGE2 do?
Pain sensitization, renal arteriole dilation, ductus arteriosus patency
What does PGF2-alpha do?
Broncoconstriction, uterine contraction
What does PGI2 do?
Inhibition of platelet aggregation, vasodilation
What does TXA2 do?
Activates platelet aggregation, vasoconstriction
What do steroids do?
Limit the transfer of phospholipids to arachidonic acids
What do NSAIDs do?
Inhibit cycle-oxygenase
Characteristics of prostaglandins
- Part of eicosanoid system - used for local cell signaling, derived from eicosanoic acid
- Short lives - synthesized and released almost instantly
- Involved in mainly actions including peripheral pain sensitization - PGE2
- Phospholipid is beginning substrate
What effect does COX1 have?
Gastric protection
Platelet aggregation
Renal protection
What effect does COX2 have?
Inflammation
Hyperalgesia
Desired effects
Which COX does aspirin effect?
Binds to 1 and 2, irreversible acetylation of COX (1>2), very effective anti-platelet action
Which COX does ibuprofen effect?
Reversible, mainly binds to 1
Characteristics of diclofenac
Reversible but highly potent
Characteristics of paracetamol
Weaker anti-inflammatory - COX-3 inhibition mainly in CNS
Characteristics of opioids?
- Centrally acting - affect how brain perceives pain
- Opioids in epidural injection makes it more effective
- Limits pain receptors in site of injury
- Sites: brain, spinal cord, GI tract, peripherally in response to injury
- G-protein linked (Gi sub-type) - cellular hyper-polarization
Effects of opioids
- Analgesia
- Constipation
- Sedation
- Respiratory depression
- Mood alteration
- Main unwanted effects are nausea and vomiting
What are opiates?
Naturally occurring opioids
2 opiates
Morphine
Codein
Example opioids
Pethidine Fentanyl Tramadol Dihydrocodeine Diamorphine Naloxone
Characteristics of opioids
- Antagonists binds to receptors and reverses all effects
- Naloxone digested quickly - repeated dose
- Diamorphone and codeine are prodrugs - metabolized by the body into active drugs
- Morphine 6-glucoronide mainly binds to mu receptor
- Inhibitor or inducer of CYP2D6 decreases/increases amount of morphine produced
Characteristics of fentanyl
- Highly lipid-soluble
- Highly potent - 10x morphine
- Widely used in anaesthesia
- Transdermal route available - not oral because high 1st pass extraction
- Relatively easy to synthesize
- But major abuse problem
What are endogenous opioids?
- Body’s own analgesics
- Endorphins/enkephalins
- Peptides produced in pituitary and hypothalamus
- Released locally (CNS) or systemically
Spinal processing of pain
- A delta/C fibers enter posterior horn, forms synapse
- Takes information across contralateral side and up to thalamus
- Modulators of pathway - endorphins create negative control (they gate the flow of pain message)
- If endorphins in system, they inhibit pain at this level
- Mechanoreceptors act on inter neurons which activates neurons to release endorphins and inhibit pathway
- Gating is emphasized by descending fibers from peri-aqueductal grey matter which act through 5HT/NA on inter neuron to stimulate the release of endorphins which have a negative effect on the pain pathway
- Effect of endorphins mimicked by spinal administration of opioids
- SSRIs have some control (have effect on mood)
What is the analgesic ladder?
More potent analgesics added as pain progresses to the next level
What is PCA?
Patient controlled analgesic
Allows patient to regulate analgesic
Dosage time and lockout interval set to ensure time allowed for dose to work
