- sensory: perception of pain characteristics - affective: negative emotion - cognitive: interpretaiton of pain

Lecture 13: Pain & Non-opioids Flashcards by Avery H

cause & examples of nociceptive pain

painful stimuli
- burns, cuts

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cause & examples of neuropathic pain

neuronal damage
- herpes zoster, pDPN

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cause & examples of inflammatory pain

inflammation
- rheumatoid arthritis, psoriatic arthritis

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causes & examples of central pain amplification

abnormal pain processing by CNS
- fibro myalgia

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definition of pain

unpleasant sensory & emotional experience associated w/ actual or potential tissue damage

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pain as perception

pain is highly individual & a subjective interpretation by the cortex of the noxious stimuli, making it difficult to treat & define
- intensity & unpleasantness of pain is affected by surroundings

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types of pain scales

numerical pain scale, visual analog scale, Wong-Baker faces scale

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acute (nociceptive) pain

known cause, typically caused by a specific injury or illness, & resolves when the underlying cause is treated
- well-characterized duration & responsive to treatment

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chronic pain

cause is sometimes unknown, persists beyond the expected healing time, long duration (>3 months), difficult to treat, where the goal is management

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neuropathic pain examples

trauma
surgery
diabetic neuropathy
spinal cord injury
stroke
shingles
chemotherapy
MS

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inflammatory pain examples

rheumatoid arthritis
crohn’s disease
lupus

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idiopathic pain examples

migraine
fibromyalgia
low back pain

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what is the most common chronic pain

musculoskeletal origin

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components of pain

sensory: perception of pain characteristics
affective: negative emotion
cognitive: interpretaiton of pain

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peripheral targets for pain treatment

ion channels, TRPV1, NaV channels

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ion channel function in pain

critical in the generation & propagation of APs in nociceptors

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TRPV1 activating compounds

heat, acid, capsaicin, and endocannabinoids in the brain

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what is a dangerous side effect of TRPV1 antagonists

hypothermia

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which NaV channels are enriched in nociceptors

Nav1.7, Nav1.8, Nav1.9

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what do mutations in NaV1.7 cause

pain disorders

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what antagonists for sodium channels are FDA approved

NaV1.8 sodium channel blocker, Suzetrigine

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lidocaine use

in dentistry & minor surgery - effective local anaesthetic

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lidocaine mechanism

inhibits Na+ channels

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why is the issue of ionization critical for local anesthetics

cationic form is most active at the receptor

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what is the receptor site for local anesthetics

inner vestibule of the Na+ channel

what ionic form of local anesthetics has intracellular access

the uncharged form; charged cations penetrates lipid membranes poorly

what do clinicians sometimes add to local anesthetics

bicarbonate, to raise the effective concentration of the nonionized form

what are the characteristics of more lipid-soluble local anesthetics

- more potent - longer duration of action - longer to achieve clinical effect

what affects absorption of local anesthetics

dose, injection site, drug-tissue binding, local tissue blood flow, use of vasoconstrictor, & physiochemical properties of the drug

what is the metabolism of amide local anesthetics (lidocaine, bupivacaine)

metabolized in the liver via CYP450 enzymes

should patients with hepatic disease take amide-type local anesthetics (lidocaine)

ester local anesthetics metabolism

converted to more water soluble metabolites in the plasma

what is an epidural block

local anesthetic injected extradurally

what is perineural block

injections around peripheral nerves

what is spinal block

injection into CSF in the subarachnoid space

cocaine use as a LA

anesthesia of the ear, nose, & throat procedures - intense vasoconstriction reduces bleeding

Bupivacaine use as a LA

- avoided for high volumes of anesthesia such as epidural & peripheral nerve blocks - used for prolonged peripheral anesthesia & analgesia post op

why is pH important for the effectiveness of LAs?

pH determines ionization state of the LA, which determines its ability to penetrate cell membranes

what is the target of nonselective NSAIDs

both COX1 & COX2 enzymes

examples of nonselective NSAIDs

ibuprofen, naproxen, aspirin

target of selective COX2 inhibitors

COX2 enzymes

selective COX2 inhibitor function

reduce inflammation while minimizing GI side effects associated w/ COX1 inhibition

example of selective COX2 inhibitors

celecoxib

what is an important acetaminophen metabolite

AM404

AM404 function

activates endocannabinoid & transient receptor potential vanilloid-1 (TRPV1)

where is COX1 expressed

in many tissues

what is COX1 involved in

maintaining normal physiological functions like protecting the stomach lining, regulating blood clotting & kidney function

when is COX2 induced

in response to inflammation

COX2 function

production of prostaglandins that mediate pain & inflammation

how does inflammation affect receptors

increases PGE2 synthesis, reduces threshold of activation of transducer receptors (eg TRPV-1), causes influx of Na+ channels

NSAID pharmacological effects

analgesia, anti-inflammatory, antipyretic, antiplatelet

analgesic effect of NSAID

reduce pain by inhibiting prostalandin production

anti-inflammatory function of NSAIDs

reduce inflammation by inhibiting prostaglandin & other inflammatory mediator production

antipyretic function of NSAIDs

reduce fever by inhibiting prostaglandin production in the hypothalamus

antiplatelet effects of NSAIDs

inhibiting COX1-derived thromboxane A2

why do nonselective NSAIDs cause GI issues

COX1 inhibition causes stomach ulcers, bleeding

adverse effects of NSAIDs

- GI - cardiovascular - nephrotoxicity

aspirin real name

acetylsalicylic acid

pharmacological effects of aspirin

- analgesia - antipyretic - antiinflammatory - antiplateley

how is aspirin diff from other NSAIDs

aspirin's ability to suppress production of prostaglandins & thromboxanes is due to the irreversible inactivation of COX1 enzyme

uses for aspirin

anti-thrombotic property = useful for reducing incidence of heart attacks in people who have had a heart attack, unstable angina, ischemic stroke, or transient ischemic attack

adverse effects of aspirin

- reye's syndrome - bleeding risk - preeclampsia during pregnancy

what is reye's syndrome

metabolic disorder that causes swelling in brain & liver

why does aspirin increase risk of bleeding

irreversible inhibition of COX1

what can aspirin do in the third trimester

cause premature closure of ductus arteriosus (blood vessel in fetus that bypasses lungs)

what does early closure of ductus arteriosus cause

fetal pulmonary hypertension & heart failure

role of prostaglandins in labor

- initiate labor

acetaminophen pharmacological effects

- analgesia via inhibition of prostaglandin production - antipyretic - NOT anti-inflammatory, not NSAID

adverse effects of acetaminophen

- liver toxicity - combination products - alcohol interaction

which brain region correlates w/ intensity of pain

S1 somatosensory cortex

which brain region does unpleasantness of pain correlate w/

activation of anterior cingulate cortex

S1 (primary sensory center) function

discriminative component of pain

secondary sensory cortex (SII) function

affective/emotional component of pain

anterior part of insula function

affective/emotional component of pain

cingulate gyrus function

affective/emotional component of pain

prefrontal cortex function in pain

cognitive - evaluation

Lecture 13: Pain & Non-opioids Flashcards

(79 cards)