Jacewicz/Sweatman - Pain Pathways and Mgmt Flashcards Preview

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Flashcards in Jacewicz/Sweatman - Pain Pathways and Mgmt Deck (89)
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1

What are the 2 functional divisions of the anterior lateral spinothalamic tract? Associated nuclei?

- NEO-SPINOTHALAMIC: intensity, location, quality of pain; fast pain that is sharp, well localized, and relayed rapidly to somatosensory cortex -> relayed to lateral pain system

1. Ventral posterior lateral (VPL) 

2. Ventral posterior medial (VPM) 

- PALEO-SPINOTHALAMIC: emo, visceral responses to pain, & influences descending pathway from brainstem that modulate pain; dull, throbbing, poorly localized pain; relayed to medial pain system 

1. Dorsal medial (DPM) 

2. Intralaminar centromedian (CM) 

3. Parafascicular (PF) 

2

What are the peripheral pain sensors?

- Free nerve endings: 

1. TEMP via transient receptor potential channels (TRP) -> TRPV1 sensitive to >43o C and Capsaicin, and TRPM8 sensitive to <25C

2. MECHANICAL 

3. CHEMICAL 

3

How is peripheral pain transduced (key fibers and NT's)?

- A-delta fibers (III): thinly myelinated, transmit temp and mechanical pain, discrete location, fast, sharp pain

- C fibers (IV): unmyelinated, transmit temp, mech, and chemical pain (polymodal), diffuse, slow pain

- A-delta and C-fiber cell bodies are in DRG, and use glutamate, substance P, and calcitonin-gene related peptide (CGRP) as NT's 

1. These NT's may be released at both central (dorsal horn) and peripheral (skin, other organs) terminals

4

How does peripheral pain receptor sensitization work?

̧- Stimulation (tissue injury)of nociceptive receptors triggers release of several substances (H+ ion, 5-HT, ATP, bradykinin, prostaglandins) that activate free nerve endings to fire AP back to spinal cord dorsal horn

̧- Activation of nociceptive receptors causes the local (peripheral) release of substance P and CGRP from free N endings at site of injury -> cause release of histamine from mast cells and vasodilation of local blood vessels 

- Combo of local tissue injury (inflam) + release of above substances + SP and CGRP sensitizes free nerve ending receptors so threshold for activation is lowered

̧- Inflam chem milieu activates previously silent nociceptive receptors on free N endings, INC temporal and spatial summation of AP's traveling to dorsal horn

5

What 2 types of neurons are critical for spinal cord pain processing?

- Nociceptive-specific neurons (SPN's): neurons in laminae I and II of dorsal horn that only respond to A-delta or C fiber AP's, and encode only pain 

Wide dynamic range neurons (WDRN's): neurons in laminae V of dorsal horn that respond to variety of synaptic inputs encoding pain AND non-pain stimuli 

1. Fire AP's in graded fashion, depending on stimulus intensity (proportional to stimulus freq)

2. > C-fiber AP frequency = > WDRN Ap response

6

What is wind up (central sensitization)?

- SIGNAL AMPLIFICATION -> repetitive AP's from C-fibers trigger wind up by: 

1. Glutamate activation of WDRN AMPA receptors and CGRP activation of WDRN CGRP receptors lead to WDRN depolarization, and release of Mg2+ block of NMDA channel 

2. Enhanced Ca2+ influx through NMDA channel causes insertion of more Nachannels and blockade of Kchannels in WDRN's 

- Substance P activation of NK1 receptors contributes to process by prolonging WDRN depolarization 

- Combined activation from these NT's reduces threshold and INC insertion of receptors in WDRN's, leading to lowered threshold for firing AP's

7

What is the functional consequence of wind up?

- A relatively brief C-fiber stimulation can lead to long-lasting facilitation of the pain pathway stimulated 

- This is a partial explanation of why and how patients experience hyperalgesia, and long-lasting, chronic pain 

8

What are three endogenous pain modulation methods?

- GATE CONTROL MECHS: A-beta fibers (Ib, II) activate dorsal column interneurons that INH WDR neurons, blunting activation of the latter neurons in response to A-delta and C-fiber activity  

- DESCENDING PATHWAYS: cortex, amygdala, and hypothalamus all impinge on PAG and reticular formation neurons that send descending fibers to modulate lamina II neurons in dorsal horn -> may INH or facilitate pain

- ENDOGENOUS OPIOID: activation of opioid receptors blocks presynaptic voltage-gated Ca2+ channels, and/or opens postsynaptic Kchannels, hyperpolarizing postsynaptic neuron and reducing AP's

9

How might the pain pathways result in referred pain? Provide an example.

- Nociceptive receptors in viscera (intrathoracic, pelvic, abdominal organs) synapse on dorsal horn neurons primarily devoted to surface (dermatomal) receptors 

- Viscera are sparsely populated by these receptors 

- Significant sharing of visceral nociceptive activity with dermatomal system -> REFERRED PAIN

- EXAMPLE: poorly localized nociceptive receptors in heart muscle may generate pain localized to midline L chest, C8-T1 dermatome and neck region

- EXCEPTION: some visceral pain neurons bypass this pathway, and synapse in the intermediate gray zone neurons lying near the central canal

10

Describe the "newly discovered" visceral pain pathway, and its clinical consequences.

- Some visceral nociceptive receptors send afferent fibers that bypass 2o dorsal horn neurons associated with anterior-lateral spinothalamic tract to synapse on intermediate gray zone neurons near central canal 

- These 2o neurons send fibers upward, traveling with dorsal column pathway; distinguished by the fact that they travel very close to midline in dorsal column 

- Synapse in VPL of thalamus; 3o fibers redistributed to somatosensory cortex and other pain matrix centers 

- Clinical consequences of this pathway = small midline lesions of the dorsal column at the lower thoracic cord alleviates chronic visceral pain, such as cancer pain 

11

What are the 3 families of endogenous opioid peptides in the human body (that we need to know)? What are their precursors, and where are they located?

- Enkephalins, endorphins, dynorphins: regulate CNS activity, incl. pain, thermoregulation, appetitie, reward 

- Precursor proteins: preproopio-melanocortin (POMC), preproenkephalin, prepro-dynorphin (multiple peptides from trypsin-like enzyme activity)

- POMC-producing cells: hypothalamic arcuate nucleus and nucleus tractus solitarius -> project to brainstem, limbic system, and spinal cord (ACTH, alpha-MSH)

1. Expression also in ant/int lobes of pituitary (beta-endorphin), and pancreatic islet cells 

- Proenkephalin peptides: in areas of CNS involved in processing of pain info (spinal cord, trigeminal nucleus, PAG), affective beh (amygdala, hippocampus, frontral cerebral cortex), motor control (caudate, globus pallidus), modulation of autonomic control (medulla oblongata), and NE function (median eminence)

1. Circulating proenkephalins from adrenal medulla and exocrine glands of the stomach and intestine 

- Dynorphins: widely distributed in the CNS; freq co-expressed with other opioid peptides

12

What are 4 anatomic sites for therapeutic intervention in the pain pathways?

- Interruption of initiating signal in peripheral tissues: NSAIDs modulate signal transduction 

- Ascending nerve block with local anesthetics: Nachannel blockers block signal conduction in nociceptive fibers

- Modulation of transmission at the spinal cord: opioids, anti-depressants, NSAID's, anti-convulsants, alpha-2 adrenergic agonists modulate transmission of pain sensation in spinal cord by DEC signal relayed from peripheral to central pathways 

- Modulation of perception at the cortical level: opioids also modulate central perception of painful stimuli 

13

26-y/o M in MVA. Weakness of R leg, loss of vibratory sensation up to iliac crest, and loss of pin sensation up to umbilicus on opposite side. Up to where do you image to look for a lesion? Where do you suspect the lesion is?

- Thoracic spine -> hemi-section of the spinal cord (aka, Brown-Sequard) 

- Lesion suspected at: T10 on the right 
 

14

What is the site of action of the opioids? 

Spinal cord and CNS
 

15

What is the MOA of Ketamine?

NMDA antagonist

16

What is the MOA of the local anesthetics?

- Act at voltage-gated Na+ channels

17

Name a highly potent opiate often administered via transdermal patch.

- Fentanyl

- Crucial thing with this patch is that it takes time to accumulate a sufficient concentration

- Have to provide analgesia until this thing begins to reach steady-state concentration

 

18

Action at which opiate receptor produces respiratory depression?

Mu, OP-3
 

19

Which opioids would most likely produce psychotic symptoms that would dissuade abuse?

- Drugs that act on kappa receptor, i.e., Butorphanol 

 

20

Which opioids are commonly used in combo with acetaminophen? Why?

- Hydrocodone

- Oxycodone

- This diversifies MOA 

21

Death from opiate intoxication is the result of?

 


9. Death from opiate intoxication is the result of: respiratory depression. 
10. Which of the following is not an AE of pain mgmt with opiate analgesics? Tachycardia. Why might you see tachycardia in a pt to whom you administer opiate? They are still in pain. 
11. Which of the following is NOT part of the triad of symptoms of opiate overdose? Diarrhea. Pinpoint pupils: opiate overdose, or pontine hemorrhage.
12. Which of the following AE’s to opiate therapy would be least likely to disappear as pt becomes drug tolerant? Constipation. 
13. Which of the following would be most appropriate tx for pt who has become progressively obtunded since last opiate dose? Naloxone; titrate dose.
14. Which of the following opioid antagonists can be used to mitigate peripheral AE’s w/o compromising analgesia? Methylnaltrexone —> does not cross BBB due to methyl.
15. Which antagonist would be most appropriately used in tx of addiction? Naltrexone b/c good oral bioavailability. 
16. The mild pain relief from codeine is: due to conversion to morphine. Pt who is ultra-rapid metabolizer of CYP2D6 can have trouble; neonatal deaths from mom taking codeine and breastfeeding. 
17. Case of man with gastric cancer and admin of crushed tablets. What can you not give? Sustained release oxycodone PGT because crushing would alter the pharmacokinetics of this drug. 
18. Pt with renal problems. Which med? Hydromorphone tablets bc not metabolized to any pharmacologically active metabolite. Oxycodone is the other opiate most suitable for use in pts with renal insufficiency. 

Respiratory depression

22

Why might you see tachycardia in a pt to whom you administer an opiate?

- Because they are still in pain 

- REMEMBER: tachycardia is NOT an AE of pain mgmt with opiate analgesics

 

 

23

What 2 things should you be concerned about in a pt that presents with pinpoint pupils?

- Opiate overdose 

- Pontine hemorrhage 
 

24

What would be the most appropriate tx for a pt who has become progressively obtunded since their last opiate dose?

- Naloxone -> titrate dose 

 

25

What opioid antagonist can be used to mitigate peripheral AE's w/o compromising analgesia?

- Methylnaltrexone -> does NOT cross BBB due to methyl group

 

 

26

Which antagonist would be most appropriately used in tx of addiction?

- Naltrexone -> good oral bioavailability 

 

27

The mild pain relief from codeine is due to...?

15. Which antagonist would be most appropriately used in tx of addiction? Naltrexone b/c good oral bioavailability. 
16. The mild pain relief from codeine is: due to conversion to morphine. Pt who is ultra-rapid metabolizer of CYP2D6 can have trouble; neonatal deaths from mom taking codeine and breastfeeding. 
17. Case of man with gastric cancer and admin of crushed tablets. What can you not give? Sustained release oxycodone PGT because crushing would alter the pharmacokinetics of this drug. 
18. Pt with renal problems. Which med? Hydromorphone tablets bc not metabolized to any pharmacologically active metabolite. Oxycodone is the other opiate most suitable for use in pts with renal insufficiency. 

28

Man with gastric cancer and admin of crushed tablets via EG tube. What can you NOT give?

- Sustained release oxycodone PGT because crushing would alter the pharmacokinetics (how the body affects the drug) of the drug 

 

29

Pt with renal problems who needs analgesia. What can you give?

- Hydromorphone tablets bc not metabolized to any pharmacologically active metabolite

- Oxycodone is the other opiate most suitable for use in pts with renal insufficiency 

30

Why is methadone used in short-term tx of pts experiencing opiate withdrawal symptoms?

- It has a long half-life, so you can space out dosing, and this allows body to become re-acquainted with drug-free state