pain management

Question 1

Describe the classification schemes of pain relating to duration, intensity, and origin of the pain.

Answer 1

acute: short duration, resolves, Pain is directly related to the resolution or healing of tissue damage. Acute pain is primarily nociceptive - somatic more common than visceral. Chronic: longer duration, persists beyond normal healing time (neuropathic), related to chronic dz, wihtout identifiable cause or associated with cancer

Question 2

severity intensity of pain

Answer 2

0 No pain,Relaxed, calm expression
1-2 Least pain, Stressed, tense, expression
3-4 Mild pain, Guarded movement, grimacing
5-6 Moderate pain, Moaning, restless
7-8 Severe pain, Crying out
9-10 Excruciating pain, Increased intensity of above0 No pain,Relaxed, calm expression
1-2 Least pain, Stressed, tense, expression
3-4 Mild pain, Guarded movement, grimacing
5-6 Moderate pain, Moaning, restless
7-8 Severe pain, Crying out
9-10 Excruciating pain, Increased intensity of above0 No pain,Relaxed, calm expression
1-2 Least pain, Stressed, tense, expression
3-4 Mild pain, Guarded movement, grimacing
5-6 Moderate pain, Moaning, restless
7-8 Severe pain, Crying out
9-10 Excruciating pain, Increased intensity of above

Question 3

Compare and contrast the components of nociceptive pain vs neuropathic pain emphasizing those aspects that are most relevant to targeting pharmacotherapy.

Answer 3

Nociceptive: “Normal” pain resulting from activation of nociceptive nerve fibers. Can be somatic (skin, bone, joint, CT, muscle) or visceral. Neuropathic: persists and has become disengaged from noxious stimuli or the healing process. Result of nerve damage and abnormal operation of nervous system.
Nociceptive: “Normal” pain resulting from activation of nociceptive nerve fibers. Can be somatic (skin, bone, joint, CT, muscle) or visceral. Neuropathic: persists and has become disengaged from noxious stimuli or the healing process. Result of nerve damage and abnormal operation of nervous system.
Nociceptive: “Normal” pain resulting from activation of nociceptive nerve fibers. Can be somatic (skin, bone, joint, CT, muscle) or visceral. Neuropathic: persists and has become disengaged from noxious stimuli or the healing process. Result of nerve damage and abnormal operation of nervous system.

Question 4

nociceptive pain is described as…

Answer 4

throbbing and well localized (somatic) or referred/ well localized (visceral)

Question 5

neuropathic pain is described as…

Answer 5

burning, tingling, shock-like or shooting, with an exaggerated response to normal painful stimuli (hyperalgesia) and/or a painful response to normally nonnoxious stimuli (allodynia)

Question 6

nociceptive pain is carried by what fibers

Answer 6

Ad and C fibers > DRG > synapsing at dorsal horn projection neurons > spinothalamic tract or spinobulbar tract > somatosensory cortex (location and intensity) or limbic system (emotional and motivational aspects) respectively

Question 7

Peripheral sensitization

Answer 7

Tissue inflammation may change chemical environment at terminals of nociceptor. Damaged cells release-synthesize proinflammatory mediators that can directly activate the terminal and produce pain or render the terminal hypersensitive to subsequent stimuli.

Question 8

central sensitization

Answer 8

NMDA receptor is central to the amplification of synaptic transfer from terminal to dorsal horn neurons. Initial sensitization is activity dependent, then later sustained by transcriptional changes (via COX-2, BDNF, substance P, NK1).

Question 9

ectopic activity

Answer 9

Increased excitability of injured sensory neurons can generate pacemaker-like ectopic discharges that result in sensory inflow that is independent of any peripheral stimuli.

Question 10

Principle of chronic pain management

Answer 10

mainly neuropathic pain: Non-opioid and adjuvant medications are emphasized. Long acting opiods may be required in some, and short acting opioids may be required for breakthrough pain

Question 11

General mechanisms for managing chronic pain

Answer 11

Enhancement of Descending Inhibitory pathway, Decrease in Central Sensitization and Decrease in Peripheral Sensitization

Question 12

Drugs used for Enhancement of Descending Inhibitory pathway in chronic pain

Answer 12

Activation of opioid receptors: opioid analgesics, tramadol. Block of NE-5HT reuptake: antidepressants-TCAD-SNRI-SSRI

Question 13

Drugs used for Decrease in Central Sensitization in chronic pain

Answer 13

Block of VSCC: decrease excess NT release: anticonvulsants- gabapentin, pregabalin (a2d ligands). Block of NMDA-Glu receptors: ketamine. Block of Cyclooxygenase-2: NSAID, celecoxib, acetaminophen

Question 14

drugs used to Decrease Peripheral Sensitization in chronic pain

Answer 14

Block of Voltage sensitive sodium channel: inhibit excess neurotransmission: local anesthetics- lidoacaine, anticonvulsants- carbamazepine, oxcarbazepine.

Question 15

Common syndromes causing neuropathic pain

Answer 15

Diabetic nephropathy, Postherpetic neuralgia, Trigeminal neuralgia, Low back pain, Fibromyalgia, Irritable bowel syndrome

Question 16

List adjuvant medications for chronic pain and syndromes they are used for

Answer 16

• TCADs (nortriptyline, desipramine): Diabetic neuropathy, migraine, low back pain, postherpetic neuralgia • SNRIs (duloxetine, venlafaxine, milnacipran): Fibromyalgia • Anticonvulsants (pregabalin): Spinal cord injury, trigeminal neuralgia, diabetic neuropathy • Local Anesthetic (topical): Post herpetic neuralgia, allodynia if pain localized

Question 17

List non-opiod analgesics for chronic pain and syndromes they are used for

Answer 17

traditional NSAIDs, acetaminophen, COX-2 selective. Indicated for mild to moderate pain, particularly of somatic origin (soft tissue injury, strains, sprains, headaches, osteoarthritis, arthritis). For pain localized to specific joints, can try topical NSAIDs

Question 18

Use of opioids in chronic pain

Answer 18

may be used for patients with acute neuropathic pain, neuropathic cancer pain, or episodic exacerbations of severe pain

Question 19

management of mild (1-3) acute pain

Answer 19

Non-opioid (e.g., NSAID or acetaminophen) ± Adjuvant analgesics (useful, not classified as analgesics)

Question 20

management of moderate (4-6) acute pain

Answer 20

Immediate-release, short-acting opioids with slow titration + Non-opioid (NSAIDs more effective) ± adjuvant analgesics

Question 21

management of severe (7-10) acute pain

Answer 21

Immediate-release, short-acting opioids with rapid titration + Non-opioid ± adjuvant analgesics (most commonly LAs) Commonly managed with multimodal analgesia approach

Question 22

Describe the mechanistic approach to multimodal management of acute pain.

Answer 22

Use of different classes of analgesics that act through different pathways. Opioid monotherapy is useful in postoperative pain and side effects limit practical efficacy. Benefits of combinding opioids with other agents: Greater analgesic efficacy from synergistic actions of agents with different mechanisms and Synergism between agents allows use of lower doses (“opioid-sparing”) limiting dose-related side effects

Question 23

What are the available targets in multimodal analgesia

Answer 23

transduction: local anesthetics, anticonvulsants,
NSAIDs-COX-2 inhibitors. Transmission: local anesthetics, opioids. enhance descnding Modulation: opioids, NMDA antagonists, a2-agonists. Perception reaction: : opioids acetaminophen-NSAIDs-COX-2 inhibitors, anticonvulsants, α2-agonists, NMDA antagonists,transduction: local anesthetics, anticonvulsants,
NSAIDs-COX-2 inhibitors. Transmission: local anesthetics, opioids. enhance descnding Modulation: opioids, NMDA antagonists, a2-agonists. Perception reaction: : opioids acetaminophen-NSAIDs-COX-2 inhibitors, anticonvulsants, α2-agonists, NMDA antagonists,

Question 24

Opioids -use in acute pain

Answer 24

Agonists at m-opioid receptors - modulate both transmission of pain (dorsal horn) and the perception - reaction to pain (cortex -limbic system). Opioids ar mainstay for moderate to severe acute pain

Question 25

Opioids route of administration

Answer 25

For any given route, the more lipid-soluble opioids will have the more rapid onset of analgesia. IV is fastest, > neuraxial > transmucosal > IM > oral > transdermal

Question 26

opioids onset/duration

Answer 26

Immediate release: most last 2-4hrs. Fentanyl – 0.5-1 hrs. Methadone – 6-8 hrs. Sustained release: Morphine (MS Contin®) to 8-24 hrs and oxycodone (OxyContin®) to 12 hours. Transdermal: Fentanyl (Duragesic®) to 48-72 hrs

Question 27

Opioids nausea management

Answer 27

Nausea/vomiting- managed with antagonists( 5HT3: ondansetron, D2: metoclopramide-prochlorperazine, Muscarinic: scopolamine, decreased PG: dexamethasone, GABA: propofol)

Question 28

Most serious acute side effect of opioids and management

Answer 28

respiratory dpression (Mu)- decrease in sensitivity of respiratory centers to CO2 that leads to a fall in the respiratory rate. Sedation precedes significant depression. Reverse with naloxone

Question 29

sedation scale

Answer 29

5 = Wide awake, 4 = Drowsy, 3 = Sleeping but arousable, 2 = Difficult to arouse, 1 = Not able to arouse

Question 30

opioid induced constipation management

Answer 30

Managed with stool softeners (docusate), stimulant laxatives (bisacodyl, senna), osmotic laxatives (Miralax®, milk of magnesia)

Question 31

opioid induced pruritis management

Answer 31

Mast cells release histamine-H1 receptors. Managed with antihistamines (diphenhydramine) for systemic admin, or opioid partial agonist (nalbuphine) for neuraxial admin.
Mast cells release histamine-H1 receptors. Managed with antihistamines (diphenhydramine) for systemic admin, or opioid partial agonist (nalbuphine) for neuraxial admin.

Question 32

How do local anesthetics work

Answer 32

Block voltage-sensitive sodium channels (VSSC) to interfere with nociceptive transmission

Question 33

local anesthetic benefits, routes and side effects

Answer 33

Intense, prolonged analgesia: opioid sparing action with reduced potential for opioid-related side effects. Allows earlier ambulation:decreased potential for DVTs. Mobilizes secretions: better cough. Earlier return of bowel function. Routes: Neuraxial (epidural or spinal) infusion or peripheral nerve block. Side effects: Neurotoxicity, hypotension, dizziness, drowsiness

Question 34

Differential nerve block- which fibers are affected first

Answer 34

Small fibers affected before larger fibers, If same size (diameter), myelinated fibers affected before unmyelinated. Sensory pain and postganglionic sympathetic neurons smallest. The faster the neuronal firing rate, greater the blocking effect (use dependent)

Question 35

Describe which nerve functions are lost first to last with differential nerve block

Answer 35

Autonomic (SNS postganglionic [C fiber] to vessels)
Pain [C fiber > Aδ]
Note: Any dose of LA that causes loss of pain will cause loss of SNS vasoconstriction  vasodilation
Cold > warmth > touch
Pressure > vibration > proprioception > motor. recovery happens in revers order

Question 36

ketamine- action, benefits, routes, side effects

Answer 36

Block glutamate binding at NMDA receptors in the ascending pain pathway. Ketamine administration can reduce the development of tolerance to long-term opioid use. Routes: Administered as IV infusion and intranasal spray. Side effects: Suboptimal tolerability profile limits usefulness. Side effects include hypertension, diplopia, dizziness, arrhythmias, nausea-vomiting, psychotomimetic reactions

Question 37

memantine- MOA

Answer 37

low-affinity non-competitive antagonist at Mg++ site in open NMDA channel and can block effects of tonic excessive glutamate in Alzheimer’s disease. However, a phasic burst of glutamate and depolarization will remove the low-affinity memantine and allow normal neurotransmission

Question 38

alpha2- adrenergic agonists- MOA, examples, route, side effects

Answer 38

Action at postsynaptic α2 adrenergic receptors on dorsal horn neurons and in LC cells to modulate pain transmission. May decrease opioid requirements - generally reserved for severe intractable pain as adjunct to neuraxial opioids. Route: Epidural infusion
Side effects: Analgesic efficacy limited by potential for:
Hypotension, Bradycardia, Excessive sedation, Rebound hypertension upon withdrawal

Question 39

NSAIDs and acetaminophen MOA in acute pain

Answer 39

COX-2 blockers

Question 40

NSAIDs and acetaminophen side effects

Answer 40

NSAIDS: GI upset, bleeding, decreased renal function, decreased labor. Acetaminophen: hepatotoxicity only main concer, b/c it doesn’t act at COX-2 in periphery

Question 41

caution with acetaminophen in opoiod combo

Answer 41

tolerance develops to analgesic effect but not to hepatotoxicity