Term
|
Definition
|
|
Term
|
Definition
|
|
Term
| free nerve endings as pain 'receptors' |
|
Definition
|
|
Term
|
Definition
|
|
Term
|
Definition
|
|
Term
|
Definition
| analgesia (job of analgesics) |
|
|
Term
| how do analgesics relieve pain? |
|
Definition
| by altering perception of nociceptive stimuli without loss of consciousness |
|
|
Term
|
Definition
|
|
Term
| lack of perception or loss of sensation |
|
Definition
| anesthesia (job of anesthetics) |
|
|
Term
| what type of experience is pain? |
|
Definition
unpleasant sensory and emotional experience
associated with actual or potential tissue damage |
|
|
Term
| what is the purpose of pain? |
|
Definition
| to signal the organism about tissue damage |
|
|
Term
| where is somatic pain well-localized? |
|
Definition
|
|
Term
| where is somatic pain less well-localized? |
|
Definition
bone
connective tissues
blood vessels
muscles |
|
|
Term
| 3 clinical classifications of pain |
|
Definition
1. somatic pain
2. visceral pain
3. neuropathic pain |
|
|
Term
|
Definition
| incisional pain, bone fractures, bony mets, osteoarthritis and RA, peripheral vascular disease |
|
|
Term
poorly localized, crampy, diffuse, and deep sensation originating from an internal organ or cavity lining
what classification of pain? |
|
Definition
|
|
Term
| examples of visceral pain |
|
Definition
bladder distention and spasms
intestinal distention
inflammatory bowel disease
hiatal hernia
organ mets
pericarditis |
|
|
Term
| what is neuropathic pain? |
|
Definition
poorly localized, electric-shock- like, lancinating, shooting sensation
**originating from injury to a peripheral nerve, the spinal cord, or the brain |
|
|
Term
| examples of neuropathic pain? |
|
Definition
diabetic neuropathy
radiculopathy
post-herpetic neuralgia
phantom limb pain
tumor related nerve compression |
|
|
Term
| how is pain characterized in an H&P exam? |
|
Definition
1. location
2. mode and time of onset
3. associated features (nausea, muscle spasm)
4. quality and time-intensity attributes
5. duration
6. severity (scale 0-10)
7. provoking and relieving factors |
|
|
Term
| specific pain stimuli to the skin |
|
Definition
| pricking, cutting, crushing, burning, freezing |
|
|
Term
| specific pain stimuli to the viscera? |
|
Definition
| inflamed mucosa, distention or spasm of SM, traction on the mesenteric attachment |
|
|
Term
| what pain stimuli are the viscera insensitive to? |
|
Definition
| pricking, cutting, crushing, burning, freezing (those of the skin) |
|
|
Term
| specific pain stimuli to the skeletal and cardiac muscle? |
|
Definition
| ischemia (intermittent claudication/angina), necrosis, hemorrhage, injection of irritation solutions, injuries of CT sheaths |
|
|
Term
| specific pain stimuli to the joints? |
|
Definition
| synovial membrane inflammation, exposure to hypertonic saline |
|
|
Term
| what types of pain stimuli are the joints insensitive to? |
|
Definition
| pricking, cutting, cautery |
|
|
Term
| specific pain stimuli to the ligaments? |
|
Definition
|
|
Term
| specific pain stimuli to the periosteum? |
|
Definition
|
|
Term
| specific pain stimuli to the BV? |
|
Definition
| piercing by a needle, inflammation, distention, traction |
|
|
Term
| specific pain stimuli to the nerves? |
|
Definition
| inflammation, compression of roots and sensory ganglia |
|
|
Term
| what begins pain signaling? |
|
Definition
| depolarization of the axon of a neuron in the periphery |
|
|
Term
| 3 types of sensory receptors? |
|
Definition
neuroepithelial
epithelial
neuronal |
|
|
Term
| what part of the neuroepthelial sensory receptor is the sensor? |
|
Definition
|
|
Term
| fate of the neuroepithelial axon? |
|
Definition
| synapses with 2nd order neuron |
|
|
Term
| example of neuroepithelial receptor? |
|
Definition
| olfactory epithelium neurons |
|
|
Term
| in epithelial sensory receptors, innervation of sensory epithelial cell is by? |
|
Definition
|
|
Term
| examples of epithelial sensory receptors |
|
Definition
epidermal Merkel cells (sustained pressure mechanoreceptors)
taste buds
auditory receptors
retinal photoreceptors |
|
|
Term
| organization of neuronal sensory receptor |
|
Definition
primary sensory neuron with soma in a craniospinal ganglion
peripheral axon with sensory terminal |
|
|
Term
| examples of neuronal sensory receptors |
|
Definition
cutaneous sensors (except Merkel)
proprioceptors |
|
|
Term
| what type of sensory receptors are nociceptors (or pain sensors)? |
|
Definition
| neuronal sensory receptors |
|
|
Term
| nociceptors are terminals of bifurcated axons of _____ ______ in the ______ of the vertebral foramen |
|
Definition
|
|
Term
| which layer of skin contain nociceptors? |
|
Definition
|
|
Term
| what ligands are excitatory in nociception? |
|
Definition
| substance P, CGRP, glutamate, aspartate, histamine, bradykinin, prostaglandins, capsaicin, K, ATP |
|
|
Term
|
Definition
|
|
Term
| receptors for glutamate and aspartate |
|
Definition
|
|
Term
|
Definition
|
|
Term
|
Definition
|
|
Term
|
Definition
|
|
Term
|
Definition
|
|
Term
| how do local anesthetics work to block pain? |
|
Definition
| block peripheral nerve conduction |
|
|
Term
| how many different axonal types of neurons are in a peripheral nerve? what are they? |
|
Definition
three
1. primary sensory afferents
2. motor neurons
3. sympathetic postganglionic neurons |
|
|
Term
| location of cell bodies of primary sensory afferents |
|
Definition
| DRG in the vertebral foramen |
|
|
Term
| what happens to the primary afferent axon as it leaves DRG? |
|
Definition
| bifurcates to send one process into spinal cord and other to innervate tissues |
|
|
Term
| 7 functional groups of primary afferent axons |
|
Definition
1. Aα
2. Aβ
3. Aγ
*4. Aδ
5. B
*6. Cdorsal root
7. Csympathetic |
|
|
Term
|
Definition
somatic motor
proprioception |
|
|
Term
|
Definition
touch and pressure
circumvents dorsal horn by giving off collaterals that ascend in the posterior columns |
|
|
Term
|
Definition
proprioception
motor to muscle spindles |
|
|
Term
|
Definition
pain
cold temp
touch
synapse in Rexed lamina I of dorsal horn |
|
|
Term
|
Definition
|
|
Term
| *Cdorsal root fibers modalities |
|
Definition
pain, temp
mechanoreception
reflex response
synapse in substantia gelatinosa of the dorsal horn |
|
|
Term
| Csympathetic fibers modalities |
|
Definition
| postganglionic sympathetics |
|
|
Term
|
Definition
| in Rexed lamina I of dorsal horn |
|
|
Term
| *Cdorsal root fibers synapse |
|
Definition
| in the substantia gelatinosa of dorsal horn |
|
|
Term
|
Definition
sharp, pricking, electric, fast
occurs in 0.1 sec after stimulus |
|
|
Term
|
Definition
*Aδ - myelinated, thicker (1-5 micrometer diameter)
conduction velocity = 6-30 m/s |
|
|
Term
|
Definition
slow, dull, burning, aching, throbbing pain
begins after >1 sec
progressively increases in intensity |
|
|
Term
|
Definition
*C fibers - unmyelinated, thinner (0.5-2 micrometer diameter)
conduction velocity = 0.5-2 m/s |
|
|
Term
| how does slower pain signal transmission differ from fast pain? |
|
Definition
it has an extra synapse in the brain stem
faster pain - goes only to the thalamus |
|
|
Term
| pain fibers are the axons of what? |
|
Definition
| *unipolar 1st order neurons in DRG |
|
|
Term
| fate of pain fibers after enter dorsal spinal roots |
|
Definition
| divide into thousand or more terminal fibrils |
|
|
Term
| fast Aδ fibers termination |
|
Definition
| *in lamina marginalis neurons of dorsal horn |
|
|
Term
| slow C fibers termination |
|
Definition
| *in substantia gelatinosa neurons of dorsal horns |
|
|
Term
| slow C fibers termination |
|
Definition
| *in substantia gelatinosa neurons of dorsal horns |
|
|
Term
|
Definition
with dendrites or bodies of a pool of 2nd order neurons in dorsal horns*
the signal is then passed on to 3rd order neurons of the dorsal horn |
|
|
Term
| path of axons of 3rd order dorsal horn neurons |
|
Definition
*cross to the opposite side of spinal cord through anterior commissure
continue to brainstem in anterolateral columns* (neo and paleospinothalamic tracts) |
|
|
Term
| transmits fast, acute pain in CNS |
|
Definition
|
|
Term
| neospinaothalamic tract ends in: |
|
Definition
1. ventrobasal complex of thalamus - most fibers
2. reicular nuclei of brain stem
3. posterior nuclear group of thalamus
higher order neurons of thalamus send their axons to neurons in other basal areas and to somatosensory cortex |
|
|
Term
| transmits slow, chronic pain in CNS |
|
Definition
|
|
Term
| paleospinothalamic tract ends in: |
|
Definition
1. reticular nuclei of brain stem
2. tectal area of mesencephalon
3. periaqueductal gray matter
higher order neurons of brain stem project to thalamus, hypothalamus, and other basal regions |
|
|
Term
| 3 aspect of pain integration in the brain |
|
Definition
1. sensory - experienced; intensity, location, modality
2. affective - emotional and empathic; fear, unpleasantness
3. cognitive - attention, memory |
|
|
Term
general rule:
strong analgesics - affect ____
mild analgesics - actions _____ |
|
Definition
CNS structures
at the synapse |
|
|
Term
| characteristics of strong analgesics |
|
Definition
blocks all types of pain
site of action - CNS
tolerance/dependence - yes (1-4 addictions/10,000 opioid treated patients) |
|
|
Term
| examples of strong analgesics |
|
Definition
morphine
merperidine
codeine too - only has 1/2 the effect of morphine; can't be used for intense pain |
|
|
Term
| characteristics of mild analgesics |
|
Definition
blocks mild pains
site of action - CNS, PNS
tolerance/dependence - no |
|
|
Term
| example of mild analgesic |
|
Definition
|
|
Term
what is the most important ligand for nociceptors?
is it generated physiologically? |
|
Definition
prostaglandin
NO - only in pathological conditions |
|
|
Term
| how is arachidonic acid released in prostaglandin synthesis? |
|
Definition
inflammatory processes activate PLA2
PLA2 acts on membrane phospholipids to release AA |
|
|
Term
| what enzyme makes PGH2 from AA? |
|
Definition
|
|
Term
| what are the final products of PGH2? |
|
Definition
TXA2 - platelets, lung
PGE2 - renal collecting tubule
PGI2 - endothelial cells
PGD2 (PGJ2) - brain
PGF2a - uterus |
|
|
Term
| activity of lipoxygenase? |
|
Definition
| takes AA and makes HETEs and leukotrienes |
|
|
Term
| prostaglandin effects in inflammation |
|
Definition
PGE2 - causes redness (rubor), heat (color), *pain (dolor), swelling (tumor)
potentiate effect of bradykinin and histamine on *pain and fever |
|
|
Term
what are the 4 signs of inflammation?
what is the final sign of inflammation? |
|
Definition
rubor (redness), calor (heat), dolor (pain), tumor (swelling)
loss of function is the final sign |
|
|
Term
| is pain a sign or a symptom? |
|
Definition
|
|
Term
| what is the clinical sign of pain elicited in the physical exam? |
|
Definition
|
|
Term
| what defines the type of pain response in a tissue? |
|
Definition
| the type of receptor present |
|
|
Term
| where does perception of pain occur? |
|
Definition
|
|
Term
| site of action of mild analgesics? |
|
Definition
| primarily at level where signals are generated |
|
|
Term
| site of action of local anesthetics? |
|
Definition
| interrupt signal conductions |
|
|
Term
| site of action of strong analgesics? |
|
Definition
| interrupt synaptic transmission in the CNS |
|
|
Term
| site of action of general anesthetics? |
|
Definition
block perception of pain
most have no analgesic properties - can't relieve pain, only shut down conscious perception of it |
|
|
Term
| are nociceptors true receptors? |
|
Definition
| no, they are free nerve endings |
|
|
Term
| what is the importance of PGH2 in prostaglandin synthesis? |
|
Definition
| it is the precursor for all bioactive prostaglandins |
|
|
Term
| what is special about PGH synthase? |
|
Definition
| its a bifunctional enzyme - one protein can catalyze 2 biochemical reactions |
|
|
Term
| what are the 2 components of PGH synthase? |
|
Definition
COX (cyclooxygenase) 1 or 2
hydroperoxidase |
|
|
Term
|
Definition
makes a cyclic oxygen compound (PGG2) from AA
constitutive in most cells |
|
|
Term
which COX is the inducible isoform?
what causes this induction and in what cells? |
|
Definition
COX-2
induced by inflammation in macrophages and synoviocytes |
|
|
Term
| activity of hydroperoxidase? |
|
Definition
degradation of hydrogen peroxide to produce PGH2
catalase is an example |
|
|
Term
| what is the clinical importance of PGF2a? |
|
Definition
causes uterine contractions
used to induce abortions and after delivery to stop uterine bleeding |
|
|
Term
|
Definition
| mediate leukocyte infiltration (histo sign of inflammation) |
|
|
Term
| will leukocyte infiltration be blocked by NSAIDs (aspirin-like drugs) or any mild analgesic? |
|
Definition
| *NO - it is a different enzyme |
|
|
Term
| what 2 outcomes of inflammation are mediated by the lipoxygenase pathway? |
|
Definition
1. leukocyte infiltration
2. anaphylaxis |
|
|
Term
| effect of PGE2 and PGI2 in the vasculature? |
|
Definition
vasodilators
PGI2 (Prostacyclin) - used to treat pulmonary HTN |
|
|
Term
| use of PGE1 (Alprostadil) in the vasculature? |
|
Definition
| maintain patency of ductus arteriosus impotence treatment |
|
|
Term
| effect of TXA2 and leukotrienes in the vasculature? |
|
Definition
|
|
Term
| effect of PGE2 in resp SM? |
|
Definition
relax bronchi
irritation prevents use |
|
|
Term
| effect of TXA2 and leukotrienes in resp SM? |
|
Definition
|
|
Term
| effect of PGE2 and PGF in the GI tract? |
|
Definition
| inhibit acid secretion, increase mucous secretion |
|
|
Term
| what drug can be used to treat drug induced ulcers in the elderly? |
|
Definition
| Misoprotol - PGE2 analog; cytoprotective and prevents ulceration |
|
|
Term
| effect of PGE2 and PGF2a on uterine SM? |
|
Definition
|
|
Term
| what drug can be used to contract the uterus and expel the fetus? |
|
Definition
| Misoprostol - PGE2 analog; used in combo with progesterone receptor blocker (Mifepristone, RU-486) |
|
|
Term
| how does concomitant use of NSAIDs effect loop diuretics? |
|
Definition
reduces effectiveness
2nd mechanism by which loop diuretics increase urine output is via induction of COX-2 that produces PGE2. PGE2 inhibits NaCl reabsorption |
|
|
Term
| what is a side effect of COX inhibitors in the kidney? |
|
Definition
|
|
Term
|
Definition
1. anti-inflammatory - reduce the 5 signs of inflammation
2. analgesic
3. anti-pyretic - fever reduction
4. anti-aggregation |
|
|
Term
| NSAIDs uses as analgesics |
|
Definition
| RA, osteoarthrosis, anklosing spondilytis, gouty athritis, acute tendinitis, bursitis, primary dysmenorrhea |
|
|
Term
| adverse effects of NSAIDs |
|
Definition
1. CNS - tinnitus, dizziness, headache
2. CV - edema, HTN (fluid retention), CHF
3. GI - nausea, ulcers, bleeding
4. heme - neutropenia, thrombocytopenia, anemia
5. liver - hepatic failure
6. pulmonary - asthma
7. renal - insufficiency, hyperkalemia, proteinuria |
|
|
Term
| examples of non selective COX inhibitor NSAIDs |
|
Definition
1. aspirin
2. diclofenac
3. etodolac
4. ibuprofen
5. indomethacin
6. ketoprofen
7. ketorolac
8. naproxen
9. piroxicam
10. sulindac |
|
|
Term
| what is the only parenteral analgesic NSAID? |
|
Definition
*ketorolac
given IM injection |
|
|
Term
| what NSAID is safe for people with ulcers? |
|
Definition
naproxen
less GI bleeding than ibuprofen and well tolerated |
|
|
Term
| what are the benefits of using COX-2 selective inhibitor NSAIDs? |
|
Definition
avoid side effects when used in joint disorders (less GI bleeding, no anti-aggregation)
nephrotoxic, higher thrombotic events |
|
|
Term
| examples of COX-2 selective inhibitor NSAIDs |
|
Definition
|
|
Term
|
Definition
no anti-inflammatory effect - quickly inactivated in inflamed tissue
treat fever and pain |
|
|
Term
|
Definition
willow tree bark and medowsweet contain the alkaloid salicilin
acetylsalicylic acid = aspirin
salicylic acid - irritant and keratolyte; used for warts, corn fungus, eczema
methyl salicylate - oil of wintergreen; external application only |
|
|
Term
| mechanism of action of aspirin |
|
Definition
| irreversibly acetylates serine residue (Ser530) of PGH synthase --> changes the conformation of PGH synthase --> prevents the binding of substrate aof arachidonate |
|
|
Term
| aspirin uses as an analgesic |
|
Definition
1. vascular, inflammatory, headache, dental, arthritis, bursitis, dysmenorrhea, neuralgia, and myalgia type pain
2. prevents sensitization of receptors by prostaglandins and hyperalgesia
3. subcortical level of pain transmission also affected |
|
|
Term
| mechanism of prostaglandins in pain |
|
Definition
| sensitize nociceptors - threshold of activation of normal ligand is lowered (hyperalgesia) |
|
|
Term
|
Definition
system becoming extremely sensitive to stimuli which would not normally evoke pain, but will evoke pain in a person with inflammation
mediated by prostaglandins |
|
|
Term
| aspirin effect in anti-pyresis? |
|
Definition
1. inhibits pyrogen-induced prostaglandin synthesis
2. resets hypothalamic thermostat
3. vasodilation of skin vessels dissipates more heat |
|
|
Term
| aspirin effect as anti-inflammatory agent? |
|
Definition
1. block redness or local vasodilation due to PGE2
2. blocks swelling due to increased vascular permeability by endoperoxides
3. DOES NOT block leukocyte infiltration due to HETEs (a lipoxygenase product) |
|
|
Term
| aspirin effects as anti-thrombotic agents? |
|
Definition
irreversible acetylates PGH synthase --> anucleate platelets are unable to synthesize new PGH
replacement of new platelets occur every 8-10 days. loss of TXA leads to inhibition of platelet aggregation and increases bleeding time.
in other tissues - synthesis of new PGH limits duration of action to 12 hours |
|
|
Term
| oral analgesic or anti-pyretic dose for aspirin |
|
Definition
| 325-650 mg every 4-6 hours |
|
|
Term
| oral anti-inflammatory dose of aspirin for rheumatic fever |
|
Definition
|
|
Term
| aspirin dose for anti-aggregative prophylaxis of coronary artery disease and post-op deep vein thrombosis |
|
Definition
| 81 mg/day to inhibit platelet thromboxane but minimally affect endothelial cell PGI2 |
|
|
Term
| GI adverse effects of aspirin |
|
Definition
epigastric distress
nausea
gastric ulceration, bleeding - due to inhibition of PGE2 synthesis locally |
|
|
Term
| CNS adverse effects of aspirin |
|
Definition
1. salicylinsm - chronic toxicity - tinnitus, decreased hearing, vertigo
2. direct effect on resp center to increase rate and depth of breathing
3. acute salicylate toxicity - medical emergency |
|
|
Term
| what oral dose of aspirin is fatal in adults? |
|
Definition
|
|
Term
| what is the mechanism for ulcer formation with aspirin use? |
|
Definition
PGA2 induced mucous production protects from ulcer formation
by blocking this --> ulcers form |
|
|
Term
|
Definition
chronic toxicity from aspirin use
tinnitus, decreased hearing, vertigo |
|
|
Term
| what drug interaction will enhance salicylate intoxication? |
|
Definition
| acetazolamide - CA inhibitor in the proximal convoluted tubule diuretic |
|
|
Term
| effect of alcohol + aspirin? |
|
Definition
| increases GI bleeding produced by salicylates |
|
|
Term
| how do the effects of acetaminophen differ from aspirin? |
|
Definition
| *no anti-inflammatory effect |
|
|
Term
| why does acetaminophen not have an anti-inflammatory effect? |
|
Definition
| high concentration of peroxides in inflamed tissue blocks its action |
|
|
Term
| does acetaminophen inhibit neutrophil activation? |
|
Definition
|
|
Term
|
Definition
325-1000 mg/dose (<4000 mg/day)
10 mg/kg in children per dose |
|
|
Term
| toxic effect of acetaminophen? |
|
Definition
*hepatic necrosis
with a single dose of 10-15 g; >25 g single dose is fatal |
|
|
Term
| how is acetaminophen overdose treated? |
|
Definition
N-acetylcystein
replenishes GSH in hepatocytes |
|
|
