Pain and analgesia Flashcards
What is the definition of pain?
unpleasant sensory and emotional experience associated with actual or potential tissue damage or described in terms of such damage
What is chronic pain?
pain that persists beyond the normal healing time or pain that persists in conditions where healing has not or will not occur
What is the difference between acute and chronic pain?
acute: obvious cause, relatively short duration, protective mechanism, easier to tx
chronic: multiple causes, persists after healing, non adaptive mechanism, often refractory to tx
What are the 3 types of pain?
nociceptive
inflammatory
maladaptive-pathological
What is nociceptive pain?
noxious stimuli activate neural receptors
What is inflammatory pain?
response of immune system to injury or infection
What is maladaptive-pathological pain?
amplification of pain, peripheral and central hypersensitization
What is the transduction pain pathway?
noxious stimulus is converted to electrical signal at a nociceptor
What is the transmission pain pathway?
transmission of nerve impulse along the nerve fiber to dorsal horn of spinal cord
What is the modulation pain pathway?
modulation of incoming pain at various CNS sites
What are the fiber systems that transmit pain impulses?
myelinated ao fibers: fast sharp well localised pain,fast conduction velocity
unmyelinated c fibers: slow dull poorly localised/visceral pain, slow conduction velocity
What is the gate control theory?
there are thought to be gates at the spinal cord, if these can be closed the pain cant be transmitted to the brain
What is hyperalgesia?
when peripheral sensory nerves impulses are amplified by the spinal cord
get confused and touch can feel like pain
What is part of the pain matrix?
primary and secondary somatosensory cortex, insular, anterior cingulate cortex and prefrontal cortex, thalamus
What is the role of the descending pathways in pain?
inhibitory and facilatory pathways
project to dorsal horn and inhibit pain transmission
What are the 4 tiers of descending inhibition (blocking pain)?
cortex and thalamus
prei-aquductal grey matter in midbrain
nucleus raphe magnus in pons, rostral medulla
medulla oblongata, spinal cord
What are the neurotransmitters involved in the descending pathways for inhibition of pain?
mainly: noradrenaline and serotonin
alose: dopamine, endocannabinouds, GABA, glycine, tonic control
What is central sensitisation?
sensitisation of nerves in the spinal cord and brain
amplification, facilitation of synaptic transfer from the periphery
What is the trigger and key role of central sensitisation?
trigger: intense nociceptor input
key role: nmethyldaspartate NMDA receptors
What is peripheral sensitisation?
injury/inflammation of tissue causing alterations of the chemical environment of the peripheral nerve terminal = activation/sensitisation
What is hyperalgesia?
increased sensitivity to a normally painful stimulus
How does hyperalgesia come about?
occurs at site of injury due to the inflammatory mediators
activation/sensitisation of nociceptors
spreads to surrounding non-injured tissues due to spinal cord events (central sensitisation)
What is allodynia?
painful response to a normally innocuous stimulus
mechanical receptors recruited to relay pain info
What are the ideal characteristics of a pain assessment tool?
discriminate presence or absence of pain
evaluate both the sensory and emotional aspects of the conditiion
evaluate pain in different contexts or at least clearly state the possible limitations
be as simple as possible, requiring minimal training and instrumentation
What are the 3 domains of the psychological state of pain?
sensory-discriminatory: intensity, location, duration of pain
affective motivational: emotional, unpleasantness and aversive aspects
cognitive-evaluative: evaluation upon quality of life
What are physiological and neuroendocrine markers for pain?
HR
RR
BP
circulating stress hormones
What is an algometer?
pressure testing device to determine pain in a quantitative way
What are the subjectives measure of pain?
behavioural assessment!
body posture and activity
locomotor activity
vocalisation
altered facial expression
appetite
response to manipulation
urinary and bowel habits
physiological signs
anxiety
What are the unidimensional pain scales?
simple descriptive scales
numerical rating scale
visual analog scale
Why do we use pre-emptive analgesia?
prevention or minimization of pain by the dministration of analgesics before the production of pain or the induction of noxious stimulus (surgery) if pain already exists
decreased need for follow up meds
What is multimodal analgesia?
administration of multiple drugs that act by different mechanisms of action to produce the desired analgesic effect
What are pharmacological interventions that provide analgesia?
opioids
nsaids
local anaesthesia
alpha 2 adrenergic agonist
ketamine
tramadol
gabapentin
amantadine
tricyclic antidepressants
maropitant
biphosphates
What are non pharmacological modalities that can provide an analgesic effect?
weight optimization
acupuncture
physical rehabilitation
nutrition amanagement
thermal modification
environement modification
chiropractic care
homeopathy
surgical intervention
What are opioids?
general term that refers to any naturally occuring, semi-synthetic and synthetic substance with morphine like activity
What is morphine?
a natural alkaloid from the seeds of the opium poppy
binds to opioid receptors in CNS and periphery
receptor distribution varies among species
What are the classes of opioids?
delta
kappa
mu
epsilon (theoretical receptor for endogenous endorphin)
nociceptin/orphanin fq peptide (NOP) receptor
What are the 4 pure mu agonist opioids?
morphine
pethidine
methadone
fentanyl/alfentanyl/remifentanyl
Wha is the agonist antagonist opioid?
butorphanol
What is the mu anatgonist opioid?
naloxone
What are the characteristics of morphine?
IM SC IV extradurally intraarcticular
cats have poor gluuronyl transferase activity = spread out dose
What are the characteristics of pethidine?
SC IM
no IV due to histamine release
anticholinergic
spasmolytic action
can cause seizures in high doses
NMDA antagonist
What are the characteristics of methadone?
IV IM SC
similar to morphine
doesnt initiate vomiting because crosses BBB
great lipid solubility
NMDA antagonist
What are the characteristics of fentanyl?
very potent analgesic
fast onset and short half life time
potent resp depressant
high fat solubility
What are the characteristics of buprenorphine?
high affinity for mu receptors
doesnt produce max effect, differs in species
analgesia, not as profound as full agonists
appropriate only for mild to moderate pain
What is the partial mu agonist opioid?
buprenorphine
What are the characteristics of butorphanol?
anatgonist at mu: poor analgesic
agonist at kappa: sedation, mild anagesia, antitussive
What are the characteristics of naloxone?
pure antagonist in all opioid receptors
used to anatgonis effect of full and partial agonists
short duration of action, repeated doses needed
Why is tramadol an atypical opioid?
synthetic analogue of codeine
weak mu opioid receptor agonist
NMDA receptor antagonist
serotonin reuptake inhibitor
norepinephrine reuptake inhibitor
How do opioids allow an analgesic effect?
determined by receptor location
spinal cord: inhibit release of pain neurotransmitters
grey matter: stimulate descending pain control system
limbic system: emotional aspect of pain
What type of pain transmission are opioids analgesic effect most effective against?
dull pain C fibers
not as effective for sharp pain
How do opioids affect arousal in dogs, monkey and people?
CNS depression
translated in a sedative effect
= sedative
How do opioids affect arousal in cats, horses and ruminants?
CNS stimulation (excitement, locomotor activity)
euphoria and dysphoria
Why do opioids affect arousal differently in different species?
differences in type and districution of receptors in various regions of the brain
presence or abence of pain
dose and route of administration
specific opioid administeres
What are the unwanted effects of opioids?
nausea and vomitinh
variation in pupil size
catecholamine release in cats
How do opioids cause nausea and vomiting?
direct stimulation of CRTZ antiemetic effects on vomit center
mostly in dogs
morphine ++++, methadone +
rarely occur if pain is already present
How do opioids affect pupil size?
increase firing in oculomotor nucleus neurons
miosis in dogs and humans
How do opioids affect thermoregulation?
dogs: decrease in thermoregulatory point and panting
cats, horses, swine, ruminants: hyperthermia due to increase in muscular activity
How do opioids affect respiratory depression?
mu mediated effect in resp center
due to decrease responsiveness to CO2
especially if coadministeres with sedative
How do opioids affects bradycardia?
vagal stimualtion
responsice yo anicholinergics
What is the schedule 2 legislation of controlled drugs?
pure agonists
must be kept in locked cupboard
records kept of purchase and use
special RX requirements
must be disposed of according to legislation
What is the schedule 3 legislation for controlled drugs?
partial agonists: buprenorphine
should be kept in locked cupboard with schedule 2 drugs
no record of use necessary
Which opioid is currently exempt from controled drug legislation restrictions?
butorphanol
What are the common adverse effects of nsaids?
GI toxicity, ulcers, erosions
nephrotoxicity
idiosyncratic hepatocellular necrosis
platelet effects
What are the pharmacokinetic properties of nsaids?
oral/parenteral administration
highly protein bound (except aspirin)
hepatic metabolism
renal excretion dtermined by plasma protein binding and urine pH
What can decrease effectiveness of NSAIDs in the body?
leakage of plasma protein at the site of inflammation promotes entrapment of nsaids
What is important to know when administering NSAIDs?
animal needs to be eating and drinking
Which NSAID is cox1 selective?
aspirin
What are the different effects of NSAIDs?
antiinflammatory
antipyretic
analgesic
antihyperalgesic
antiendotoxic
antithrombotic
weak antispasmodic effects
some are chondroprotective (meloxicam, carprofen)
What is Grapriprant?
new type of NSAID
analgesic/antiinflammatory drug in priprant class
functions as a selective EP4 PRA
How does grapiprant work?
it functions as a selective EP4 PRA
PGE2 (prostaglandin) is a key inflammatory mediator
it exerts its effects via 4 receptors: EP4 receptor is the primary mediator
drug blocks this receptor and doesn’t interfere with the other prostglandin receptor pathways/functions
How do most NSAIDs work?
inhibiting COX (selective or not vs 1 or 2)
COX is responsible for producing prostagalndins
prostaglandins are and inflammatory mediator among other things
How does ketamine work?
NMDA receptor antagonist
antihyperalgesic and antiallodynic effect with sub anaesthetic constant rate infusion
sympathomimetic effect increases vasc tone, HR and myocardial oxygen demand
direct myocardial depressant effect
What is paracetamol?
NSAID not classic cox-1 inhibitor, may act on central cox3
acts as a prodrug
active substance is an endogenous cannabinoid
How is paracetamol metabolised?
hepatic metabolism by conjugation
once overwhelmed: oxidative metabolism
causing protein damage, red cell lysis, hepatic necrosis
When is paracetamol contraindicated?
in cats! causes anorexia, vomiting, facil swelling, heinz body anaemia, metheglobinaemia
with hepatic dz?
What is the antidote to paracetamol?
n-acetylcysteine
What are Monocolonal antibodies?
produced from single b lymphocyte clones in mice through recombinant engineering
target specific molecules
What is NGF?
cytokine
key regulator involved in both inflammatory and neuropathic pain
major determinant of plasticity in PNS and CNS
What are the types of anti NFG monoclonal antibodies in vet med?
Ranevetmad/bedinvetmab (librela) in clinical trials in dogs
injection improved pain scores
frunevetmab in cats (solencia?)
improvement of lameness, increased activity
What are the characteristics of systemic lidocaine?
anaesthetic sparing effect
beneficial effect in visceral pain and bowel function (prokinetic)
What are the things to be careful with when using lidocaine?
rapid IV administration can cause muscle tremors and collapse in horses
profound negative cardiovascular effect on cats
What is gabapentin?
anticonvulsant with analgesic properties
modulate and inhibit the action of voltage gates calcium channels
What is maropitant?
central antiemetic
inhibits binding of substance P to the neurokinin 1
anaesthetic sparing effect after IV administration
What are SSRIs?
selective serotonin (norepinephrine) reuptake inhibitors
increase serotonin with or without norepinephrine in the synaptic cleft
What is amantadine
pain modifying effect
NMDA antagonist
similar to ketamine
What are biphosphates?
used for hypercalcemia treatment
analgesia for bone cancer, inflammatory bone disorders
