Pain Flashcards
Define pain
Unpleasant sensory or emotional experience associated with actual or potential tissue damage, and described in terms of such damage
(Intl. association for study of pain)
What is dysesthesia
decrease or exaggeration of spontaneous or provoked sensitivity
Compare allodynia and hyperalgesia
Allodynia - pain caused by usually non-painful stimuli
Hyperalgesia - heightened pain response to normally painful stimuli
What is hyperpathia
painful syndrome characterized by abnormal pain reaction to a stimulus, especially repeated stimulus
What are the nociceptive nerve fibres that carry information about pain?
A-delta fibres - thinly myelinated
C-fibres - unmyelinated
Describe key characteristics of the A-delta fibres
- Poorly myelinated
- Transmit “quick” pain signals
- Acute, highly localized pain
- Carry signals to the dorsal horn
Describe the key features of the C fibres
- Unmyelinated
- Slow impulse conduction
- “polymodal” pain signals (mechanical, thermal, and chemical)
- “secondary pain” (radiating, shooting, burning, piercing following the acute pain signal)
Which 2 neurotransmitters carry pain signals between peripheral and central nociceptive fibres?
What are their corresponding receptors?
1) substance P (neurokinin receptor)
2) glutamate (AMPA - alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic-acid receptor)
(Activation of NMDA occurs much later, induced by “floods” of glutamate)
3 enzymes for methadone metabolism
cyp 3a4, 2d6, 2b6, 1a2
3 inhibitors of cyp 3a4
antibiotics (cipro, erythro, metronidazole)
antifungal (fluconazole, ketoconazole)
CCB (dilt, verapamil)
benzo (alprazolam, diazepam)
cyp3a4 inducers
antiepileptic - phenytoin, phenobarb, carbamaz
antibiotic - rifampin
steroid - dex high dose over 16mg /d
tca - ami/nortryp
list opioids in phenanthrene class
morphine, oxy, hydro, codeine
list opioid in phenylpiperidine class
fent, sufent, meperidine
what class of opioid (structurally) is methadone?
diphenylheptane
2 types of opioid allergy (immune mediated reactions)
- allergic dermatitis (type IV)
- anaphylaxis / anaphylactoid
define chronic pain
pain that persists beyond usual course of healing
OR
associated with a chronic pathological illness that causes continuous or recurrent pain over months/years
2 neuropathic pain screening tools
leeds assessment
neuropathic pain questionnaire
most common cause of pain in cancer
bone mets
ion channel involved in peripheral sensitization
sodium
ion channel involved in central sensitization
calcium
receptor responsible for wind up
what blocks the receptor under normal activity?
NMDA
magnesium ion
3 key mechanisms of bone pain
- osteoclast activation and acidity increases nociceptor activity
- inflammatory factors (cytokines, IL’s, chemokines etc.)
- structural damage
most common neuropathic pain syndrome in HIV patients (from disease not NRTI’s)
distal polyneuropathy
gabapentin / pregabalin target
alpha-2-delta subunit voltage gated ca-channels
2 ion channels that upregulate after a nerve injury
Na
Ca
proposed mechanism for opioid headache
histamine
describe spinal opioid hyperalgesia syndrome
intrathecal / epidural opioid (HIGH DOSE) complicated by:
- segmental myoclonus
- hyperalgesia
- piloerection
- priapism
- pain (perineal/leg/butt)
cause of spinal injection pain
compression of adjacent nerve root
what are 4 IV chemo infusion pain syndromes?
1) venous spasm
2) chemical phlebitis
3) vesicant extravasation
4) anthracycline related flare - flare with urticaria
most common agents causing chemo mucositis
- 5FU and capecitabine
- doxorubicin
- cytarabine
- etoposide
- methotrexate
- everolimus (mTOR inhib)
most common agents causing chemo induced peripheral neuropathy
- vinka alkaloids (vincristine/vinblastine/vinorelbine)
- platinums (cisplatin/oxaliplatin)
- taxanes (paclitaxel)
1 unique pain syndrome with fluorouracils
anginal chest pain (coronary vasospasm)
unique pain syndrome with vinka alkaloids
neuropathic acute pain (trigeminal and glossopharyngeal nerves common)
agents associated with hand foot syndrome
treatment
5fu, doxorubicin, paclitaxel
some TKI’s (nibs)
MTX
everolimus (mTOR)
pyridoxine treatment
common s/e of g-csf
bone pain and constitutional symptoms
most common symptoms of acute RT brachial plexopathy
paresthesia
pain and weakness less common
most common manifestation / location of RT related subacute myelopathy
L’hermittes sign (cervical cord)
what is the incidence of RT induced bony pain flare
what is the timeline
30-40%
timeline 1-2d, resolves by 3-5days
how does acute herpetic neuralgia manifest in patients with malignancy
more common in areas associated with tumor, and areas previously irradiated
cancers with highest thrombosis risk
bone
brain
pancreas
ovary
what is phegmasia cerulea dolens
tissue ischemia +/- gangrene in context of DVT, without arterial occlusion
cancers most likely to metastasize to bone
lung
prostate
breast
myeloma
most common site of bone mets
vertebra (most commonly thoracic)
list 3 ddx other than bone mets for bony pain in cancer
- OP fracture
- focal osteonecrosis
- ## paraneoplastic osteomalacia
describe malignant piriformis syndrome
buttock / leg pain exacerbated by internal rotation of hip
describe hypertrophic pulmonary osteoarthropathy
- associated with which ca.
- features
- management
NSCLC
clubbing, periostitis of long bones, rheumatoid like polyarthritis
pain, tenderness, swelling in knees, ankles, wrists
cancer therapy
bisphosphonates
which cancers are most likely to cause leptomeningeal disease
hematologic - non-hodgkins, ALL
solid tumor - breast, SCLC
2 key diagnostic tests for leptomeningeal ca., and their pros/cons
MRI (gad enhanced) - sensitive, not as specific
CSF cytology - more specific, sensitive only with numerous samples (55% after one, 90% after three)
describe the pain patterns of cervical plexopathy (direct and referred)
what are 2 associated features?
which nerve roots are involved?
direct pain - periauricular, anterior neck
referred - face and shoulder
associated - horner’s and hemidiaphragmatic paralysis
roots - C1-4
differentiate early vs. late RT brachial plexopathy
1) early onset - transient,
2) delayed onset - progressive (6mo.-20yrs)
weakness and sensory changes dominate
describe paraneoplastic painful sensory neuropathy
features
cause
injury to dorsal root ganglion or peripheral nerve
pain (paresthesia), sensory loss, severe sensory ataxia
SCLC associated
sensorimotor peripheral neuropathy
most common ca. association
hodgkin’s disease and paraproteinemia (5-15% MM patients)
2 causes of aseptic avascular necrosis of femoral head in cancer patients
prolonged steroids
high dose chemo with BMT
diagnosis of avascular necrosis
- presentation
- diagnostic imaging
- pain precedes radiological change by weeks to months
- bone scan and MRI are both sensitive (MRI superior)
common pain s/e of aromatase inhibitors
MSK pain and stiffness (arthralgias, bone pain, joint stiffness)
list symptom 3 s/e of IV bisphosphonates
- flu like (fevers, arthralgias, myalgias)
- osteonecrosis of the jaw
- chronic diffuse pain (unknown etiology, FDA warning 2008)
list risk factors for phantom limb pain after surgery
- tumor-related surgery > trauma-related surgery
- prolonged pain pre-amputation
- post-operative chemotherapy
describe the pathophysiology of stump pain
neuroma development at site of nerve transection
differentiate the presentation of chronic RT myelopathy from plexopathy
myelopathy - sensory symptoms predate motor and autonomic, burning dysesthesia’s typically, brown-sequard pattern
plexopathy - pain is rare and weakness / sensory manifestation predominates
what is the difference b/w efficacy and effectiveness
efficacy - performance of an intervention under controlled circumstances (clinical trials with strict control standards, exclusionary criteria etc.)
effectiveness - performance of an intervention on population level (real-world circumstances)
factors that influence pharmacokinetics
age
organ function (hepatic and renal)
body mass (obesity increases Vd)
hypotension
hypovolemia
hypo/hyperthermia
4 aspects of pharmacokinetics
Absorption
Distribution
Metabolism
Excretion
What is bioavailability
amount of drug that gains unchanged access to systemic circulation
how is bioavailability impacted in liver disease
blood shunting away from liver increases effect of oral medication (in relation to parenteral)
2 phases of metabolism in the liver and the processes:
Phase 1 - oxidation, reduction, hydrolysis (CYP450 enzymes)
Phase 2 - conjugation, glucuronidation
define potency
dose-response relationship
intensity of a specified effect at a specified dose
5 poor prognostic factors for pain
delirium
neuropathic
severe incidental pain
somatization / total pain
chemical coping / substance abuse history
why are opioids considered first line for cancer neuropathic pain management
non cancer neuropathic pain - >60% response to non-opioid
cancer neuropathic pain - <30% response to non-opioid (>60% response to opioid)
outline the cellular mechanism of opioids
- binds to g protein coupled receptors and inhibits adenyl cyclase (decreases cAMP)
- inhibits voltage gated Ca channels
- causes K efflux (hyperpolarization)
- decreases neurotransmitter release (substance p, neurokinin a + b, glutamate)
what is the receptor effect of buprenorphine
mu partial agonist
kappa and delta antagonist
what is the receptor action of nalbuphine
mu agonist (moderate affinity)
kappa agonist (strong affinity)
no affinity for delta
which opioids undergo phase 1 metabolism
codeine
oxycodone
fentanyl
methadone
which opioids undergo phase 2 metabolism
morphine
hydromorphone
oxymorphonne
morphine metabolites and actions
m3g - neuroexcitatory (not a mu agonist)
m6g - analgesic (mu activity)
oxycodone metabolites
oxymorphone - active, analgesic with 6h half life
noroxycodone - weak, inactive
codeine metabolites
phase 1 -> morphine, norcodeine
phase 2 -> codeine6g
HM metabolites
HM3G - neuroexcitatory
3 adverse effects of tramadol
serotonin syndrome
hypoglycemia
seizures
which CYP enzymes play a role in methadone metabolism
cyp2d6
cyp2b6
cyp3a4
cyp1a2
methadone mechanisms of action
mu agonist
nmda antagonist
weak snri effect
weak a2 agonist?
methadone has biphasic distribution and elimination
outline the 2 phases and the clinical relevance
alpha phase - distribution and early elim.
- lasts 6-8h
- correlates with analgesic period
beta phase - elimination
- 15-60h
- prevents withdrawal for this period
- can accumulate and produce toxicity
how to opioids cause constipation
- decr gastric motility
- decr intestinal propulsion
- reduced pancreatic, biliary, intestinal secretions
- incr. anal sphincter tone
- incr. amplitude of non-propulsive segmental contractions
stellate ganglion block
- nerves blocked
- indications
- adverse effects
- nerves blocked - sympathetic nerves to arm or face
- indications - CRPS, sympathetic maintained pain, shingles of head / face (most commonly)
- adverse effects - horner’s syndrome, hoarseness (rec. laryngeal), hemidiaphragm paralysis (phrenic)
gasserian ganglion block
- clinical significance
- indications
- ganglion from which 3 branches of trigeminal originate
- for secondary trigeminal neuralgia
list 3 other nerve blocks of head and neck
- occipital - headaches
- glossopharyngeal - tongue and posterior pharynx
- sphenopalatine ganglion - headaches?
celiac plexus block
- innervation
- location (anatomical)
- indications
- complications
- innervation - sympathetic outflow, and sensory innervation from:
- stomach, liver, spleen, pancreas, intestine (to splenic flexure of colon), kidney
- location (anatomical)
- retroperitoneal, T12-L2 level anterior to aorta
- indications
- pain from abdominal malignancy (most commonly pancreatic)
- complications
- diarrhea
- orthostatic hypotension
- bleeding
- organ injury
- spinal cord injury (artery of adamkiewics)
superior hypogastric plexus block
- innervation
- location (anatomical)
- indications
- innervation
- sensory - pelvic viscera (bladder, prostate, vagina, uterus, rectum)
- sympathetic outflow (descending colon down)
- location (anatomical)
- anterior to L5-S1 - technically challenging
- indications
- lower abdominal and pelvic pain
Ganglion impar block indications
- perineal and rectal pain
- distal 1/3 of vagina, vulvodynia
- proctalgia fugax
- prostatitis
- distal urethra and scrotum
- proctitis
- coccygodynia
difference between kyphoplasty and vertebroplasty
kyphoplasty - balloon expansion, cement injection
vertebroplasty -
which patients are more likely to respond to kypho
- recent fracture (<2mo)
- single/few levels
- pain correlates with edematous / fractured area on MR
- no sclerosis
baclofen mechanism
gaba-b agonist
match the antiepileptic to the mechanism of action
- block na channel
- promote inhibitory GABA transmission
- block ca channels
- inhibit excitatory glutamate
carbamazepine, phenytoin
VPA, topiramate
gaba/pregabalin
lamotrigine
main benefit of pregabalin over gabapentin
quicker time to onset and effect
more rapid ability to titrate
max dose of gabapentin
AND
dose above which effect is questionable
max: 3600mg/d
questionable benefit beyond 2700mg/d
benefit of oxcarbazepine over carbamazepine
- no CYP induction
- less toxicity (no aplastic anemia)
5 categories of risk factors for opioid misuse
health related - complex pain (intense, frequent, generalized)
psychosocial - emotional distress, trauma, limited supports
drug-related - previous or current substance use d/o, cravings
genetic - family history of drug abuse
demographic - male, caucasian
selective COX2 inhibitors protect against which 2 s/e of non-selective COX inhibitors?
- GI ulceration
- Bleeding risk (platelet aggregation)
list all s/e of NSAIDs
- PUD and GIB
- Hypertension
- Edema
- Renal failure
- Bleed risk
what negates the relative GI protection benefit of celecoxib vs. other NSAIDs?
concomitant ASA use
Which NSAID has the lowest CV risk?
Naproxen
What is unique about ASA?
Irreversible COX 1 and 2 blockade
Will inhibit COX enzyme for entire life of platelet
mechanism of:
- bisphosphonate
- denosumab
- osteoclast inhib.
- RANKL inhib.
3 evidence based strategies for behavioural pain management
- pain coping skills training (CBT type interventions)
- mindfulness based stress reduction (MBSR)
- acceptance and commitment therapy (ACT)
other:
- hypnosis
- meaning centred psychotherapy
Evidence for bisphosphonate and denosumab is strongest for bone pain mgmt. and prevention of SRE’s in which cancers?
- prostate (castrate resistant, not castrate sensitive)
- breast
- multiple myeloma
other solid tumors:
- use case by case (not a first line intervention)
4 topical agents that can be used for acute and chronic wound pain
- opioids - morphine and methadone
- ketamine
- lidocaine and prilocaine
- TCA - amitriptyline
which patients might need to be considered for naloxone kit in the home
- MEDD > 100mg/d
- Methadone
- Benzodiazepines in combination with opioids
- History of overdose
- History of substance use disorder
- Chronic renal, hepatic, or pulmonary disease
greatest concern about prescribing naloxone to patient with terminal illness
caregivers may administer when actively dying
list opioids in order of protein binding
least to most
hydromorphone (8%)
morphine (20%)
oxycodone (45%)
methadone (70-80%)
fentanyl (85%)
2 types of cannabinoid receptors and their locations / effects
CB1 - CNS - pain, nausea, appetite, memory
CB2 - immune system
effects of THC and location of action
Psychoactive
CNS (CB1 receptor)
effects of CBD
modulate psychoactive effect of THC
other therapeutic effects (anti-inflammatory)
What is nabilone approved for?
CINV (adjunct)
what is nabiximols?
what is it approved for?
1:1 THC:CBD formulation (?naturally derived)
spasticity - MS
cancer pain
very expensive
optimal route for plant based cannabis?
buccal / sublingual
- predictable absorption / onset
- no smoking risks
Greatest evidence for cannabis use in which 4 illnesses
chronic pain
spasticity in MS
seizures (dravet and lennox-gastaut)
CINV
Which illnesses have moderate evidence for cannabis use
glaucoma
sleep disturbances
key s/e of cannabis
dizziness
fatigue
increased appetite
dry mouth
psychoactive
cyclic vomiting
cognitive impairments
main CBD related concern for those who are on immune therapy
immune suppression with high doses
what is phenazopyridine used for?
how does it work?
dysuria and bladder spasms (irritative component)
local anaesthetic and analgesic effect on bladder
3 receptors mediating opioid induced pruritis
mu-opioid
histamine
5ht3
