Pain Medicine Flashcards
Where do A-β fibers terminate in the spinal cord?
Dorsal horn laminae III-V
Where do C fibers terminate in the spinal cord?
dorsal horn laminae I and II
Where do A-δ terminate in the spinal cord?
dorsal horn laminae I, III-V
What are the second-order neurons in the pain signaling pathway?
Wide dynamic range (WDR) neurons: located mostly in laminae III-V, receive input from low threshold A-β, nociceptive A-δ, and C fibers. Responses from WDR are graded - reflecting the type of stimulus fiber
Nociceptive-specific (NS) neurons; I and II only respond to noxious stimuli
What is gate control theory (Melzack and Wall, 1965)?
Input along low-threshold A-β fibers inhibit responses of nociceptive input to WDR (wide dynamic range) neurons
What is the size, velocity, myelination status, function of A-β fibers?
A-β: myelinated, 12-14 microns, 30-60m/s velocity
Function: touch, pressure, vibration, proprioception
What is the size, velocity, myelination status, function of A-δ fibers?
A-δ fibers: myelinated, 6-8 microns, 10-15 m/s velocity
Function: sharp pain, light touch, temperature
What is the size, velocity, myelination status, and function of C-fibers?
C fibers: unmyelinated, < 1 microns, < 1.5 m/s velocity
Function: dull, achy, burning pain, temperature
Opioid receptor types and function?
- *Mu1**: analgesia
- *Mu2**: respiratory depression, sedation, vomiting, euphoria, anorexia, physical dependence, pruritus
Delta: analgesia, spinal analgesia
Kappa: analgesia, sedation, psychotomimetic effects, dyspnea, respiratory depression, euphoria, dysphoria
What is pKa in relation to opioid pharmacology?
pH at which 50% of the drug is ionized. The non-ionized form crosses lipid membranes easily → The lower the pKa, the faster the onset of the drug
What does the octanol/water partition coefficient indicate?
Indicates lipid solubility (the higher the number, the more lipophilic the drug) - lipid-soluble drugs, such as fentanyl, exert most of their effect at the localized area where they are administered (less spreading of medication)
Oxycodone pKa, Octanol/H2O partition coefficient, mechanism of action?
Oxycodone
- pKa: 8.5 (lower pKa signifies faster onset of drug effect)
- Octanol/H2O partition coefficient: 0.7 (higher the number = more lipophilic)
- Mechanism: Mu agnoist (metabolites = oxymorphone, noroxycodone)
Oxymorphone pKa, Octanol/H2O partition coefficient, mechanism of action?
Oxymorphone
- pKa 9.3 (lower = faster onset)
- Octanol/H2O partition coefficient: 0.98 (higher = more lipophilic)
- Mechanism: opioid agonist (metabolites = 6-hydroxy-oxymorphone)
Hydromorphone pKa, Octanol/H2O partition coefficient, mechanism of action?
Hydromorphone (Dilaudid)
- pKa = 8.1 (lower = faster onset)
- Octanol/H2O partition coefficient: 1.28 (higher = more lipophilic)
- mechanism: Mu agonsit
- Metabolites = hydromorphone-3-glucuronide
Tramadol pKa, Octanol/H2O partition coefficient, mechanism of action?
Tramadol
- pKa: 9.4
- Octanol/H20 coefficient: 1.35
- Mechanism: weak mu agonist, weak NE/5HT re-uptake inhibitor
- Metabolite: O-desmethyltramadol
- **Contraindicated with MAOi or SSRI (increased risk of seratonin syndrome)
Morphine pKa, Octanol/H2O partition coefficient, mechanism of action?
Morphine
- pKa = 8.0 (lower = faster onset)
- Octanol/H2O partition coefficient = 1.4 (higher = more lipophilic)
- Mechanism: Mu agonist
- Metabolites: morphine-3-glucuronide, morphine-6-glucuronide, hydromorphone
- Do not use in renal failure
Talpentadol pKa, Octanol/H2O partition coefficient, mechanism of action?
Talpentadol
- pKa = 9.34-10.45 (lower = faster onset)
- Octanol/H2O partition coefficient: 2.87 (higher = more lipophilic)
- Mechanism: Mu agonist and NE reuptake inhibitor
- Metabolites: tapentadol-O-glucouronide
- **Do not use in severe hepatic dysfunction
Meperidine pKa, Octanol/H2O partition coefficient, mechanism of action?
Meperidine
- pKa: 8.5 (lower = faster onset)
- Octanol/H2O partition coefficient: 39 (higher = lipophilic)
- Mechanism: weak mu agonist
- Metabolite: normeperidine
- **contraindicated with MAOi
Codeine pKa, Octanol/H2O partition coefficient, mechanism of action?
Codeine
- pKa: 8.2 (lower = faster onset)
- Octanol/H2O partition coefficient: N/A
- Mechanism: weak mu and delta agonist
- Metabolites: morphine, hydrocdone, codeine-6-glucuronide
- **Antitussive, anti-diarrhea, metabolized to morphine for analgesia
Hydrocodone pKa, Octanol/H2O partition coefficient, mechanism of action?
Hydrocodone
- pKa: 8.9 (lower = faster onset)
- Octanol/H2O partition coefficient: N/A
- Mechanism: Mu and kappa agonist
- Metabolites: Dihydrocodeine, hydromorphone
Methadone pKa, Octanol/H2O partition coefficient, mechanism of action?
Methadone
- pKa: 9.3 (lower = faster onset)
- Octanol/H2O partition coefficient: 116 (higher = more lipophilic)
- Mechanism: Mu and delta agonist, NE and 5HT re-uptake inhibitor, NMDA antagonist
- Metabolites: EDDP (inactive)
- **May cause QT prolongation
Fentanyl pKa, Octanol/H2O partition coefficient, mechanism of action?
Fentanyl
- pKa: 8.4 (lower = faster onset)
- Octanol/H2O partition coefficient: 860 (higher = more lipophilic)
- Mechanism: Mu agonist
- Metabolite: norfentanyl
Buprenorphine mechanism of action?
partial mu and kappa agonist, delta antagonist
suboxone contains buprenorphine + naloxone [receptor antagonist]
Mechanism of action of pentazocine (talwin); butorphanol (stadol); nalbuphine (nubain)?
kappa agonist, mu antagonist
Side effects of opioids?
- Respiratory suppression (act on brainstem to reduce sensitivity of respiratory center to PCO2)
- Suppresses cough reflex (effect on brainstem nuclei in cough reflex pathway) - common use for codeine
- Constipation (maintained contraction of smooth muscles in the gut)
- Sexual Dysfunction (erectile dysfunction, decreased libido); correlated to hypogonadism and low testosterone levels
NSAID mechanism of action?
inhibit COX-1 and COX-2 enzymes, which produce prostaglandins involved in promoting inflammatory responses after tissue injury
NSAIDs with more COX-2 selectivity?
Meloxicam > Celecoxib >> diclofenac > sulindac (*most common to cause liver failure)
NSAIDs w/ less COX-2 selectivity?
Ibuprofen, naproxen, salicylate >> indomethacin, ketorolac
Concerning side effect of SSRIs/SNRIs?
serotonin syndrome (especially when used in conjunction with TCAs, monoamine oxidase inhibitors (MAOIs), triptans, tramadol, or some antiemetics may result in serotonin syndrome
Gabapentin mechanism of action?
not entirely known, interacts with alpha-2-delta subunits of L-type calcium channels in CNS
Used to treat pain from diabetic neuropathy, postherpetic neuralgia, HIV-associated neuropathy, GBS, phantom limb pain, spinal cord injury pain, cancer-associated neuropathic pain
Main side effects of gabapentin?
somnolence, dizziness, edema
main pregabalin side effects?
somnolence, dizziness, dry mouth, edema
Mechanism of action of carisoprodol?
blocks interneuronal activity in descending reticular formation and dorsal horn of spinal cord to depress polysynaptic reflexes
Uses: acute MSK pain
Side Effects: drowsiness, dizziness, HA, hepatotoxicity, ataxia, N/V
**Use w/ caution - increasingly abused due to metabolite meprobamate (controlled substance)
Nociceptive/Somatic Pain is mediated by what part of the nervous system?
Somatic nervous system
Description:
- deep somatic pain: dull/aching
- superficial somatic pain: sharp, pricking
- burning, localized, reproducible
Caused by noxious perception from tissue damage can originate from the skin, muscle, bone, or fascia
Visceral pain is mediated by which part of the nervous system?
Autonomic nervous system
Description: crampy, dull, vague in location
Caused by internal structures of solid/hollow organs
Neuropathic Pain/Central pain caused by?
primary lesion or dysfunction of the pain-sensing nervous system (CNS or PNS)
Description: burning, tingling, shooting, stabbing, electric-like; may be associated with numbness/tingling
Treatment options for Myofascial Pain?
- Physical therapeutics
- Modalities (heat/ice, ultrasound, transcutaneous electrical nerve stimulation [TENS])
- Cooling analgesic spray
- Stretch, massage, postural alignment, acupressure
- Trigger point injection w/ or w/o injectants (dry needling)
- Botulinum toxin has been used in significant refractory cases (postprocedural stretching is important)
Migraine headache presentation
unilateral > bilateral, pulsing/throbbing, stabbing, frontal, or temporal pain
Can occur with or without aura
Can be associated w/ N/V, photophobia, phonophobia, vertigo, diarrhea, diaphoresis
Typically lasts for 30 min to 1 day, can be intractable and last up to 1 week (status migrainosus)
Two main migraine subtypes
- Migraine without aura (common)
- Migraine with aura (classic): focal neurological symptoms preceding or accompanying headache
- visual disturbances (bright spots, dark spots, tunnel vision), tremor, pallor, vertigo, unilateral numbness or weakness, transient aphasia, or thick speech
- Premonitory and resolution symptoms: hyperactivity, hypoactivity, depression, craving for particular foods, repetitive yawning, other less typical symptoms
Migraine cortical spreading depression (CSD) theory
wave of neuronal depolarization in cortical grey matter followed by neuronal activity suppression, resulting in blood flow changes (hyperemia, then oligemia)
Migraine neurovascular theory?
Trigeminovascular system: plexus of unmyelinated fibers from trigemical ganglion innervating cerebral and pial arteries, venous sinuses, and dura mater -→ stimulation by cortical spreading depression causes antidromic activation of trigeminovascular system, resulting in release of peptide neurotransmitters (substance P, neurokinin A, and calcitonin gene-related peptide)
Effect of peptide neurotransmitters on vasculature in setting of migraine?
Peptide neurotransmitters (substance P, neurokinin A, calcitonin gene-related peptide - CGRP) vasodilate nearby blood vessels, which causes extravasation of plasma or “sterile neurogenic inflammation” -→ stimulates the trigeminal nerve endings, causing nociceptive orthodromic activation to the trigeminal ganglion, resulting in pain
Migraine HA vascular theory?
Intracranial vasoconstriction results in ischemia, which then causes the aura that precedes migraines. Subsequent rebound vasodilation and activation of perivascular nociceptors results in the migraine HA
Stratified care approach to migraine headaches?
Migraine Disability Assessment (MIDAS) scores to choose treatment based on severity and degree of disability
Abortive Migraine medications
- Acetaminophen
- NSAIDs (ASA, ibuprofen, naproxen, ketorolac)
- Opioids (butalbital, meperidine)
- Adjunctive medications (prochlorperazine and metoclopramide)
- Ergotamines (FDA pregnancy category X)
- Triptans (5-HT 1B and 1D agonists)
Migraine HA preventative medications?
- Beta-blockers (propranolol, timolol)
- NSAIDs
- TCAs (e.g. amitryptyline)
- SSRIs (e.g. fluoxetine)
- Anti-epileptics (valproic acid, carbamazepine, gabapentin)
- Magnesium
- Botulinum toxin injections
Most common HA type?
Tension headaches (bilateral, usually lasts 30min to several days or weeks), responds to OTC analgesics (NSAIDs, acetaminophen)
Postmastectomy pain syndrome typically affects which thoracic levels?
Intercostobrachial neuralgia (T1-T2) - chronic neuropathic pain that develops shortly after, or several months postsurgery. Prevalence is higher after lumpectomy than mastectomy and especially when axillary lymph node dissection has been performed. Pain is localized to the axilla, shoulder, arm, and/or chest wall.
Hypertrophic pulmonary osteoarthropathy is associated with what malignancy?
Lung cancer - clubbing and periosteal proliferation of the tubular bones → causing symmetricla painful arthropathy affecting the ankles, knees, wrists, and elbows. Pain improves if tumor is resected. In advanced lung cancer, NSAIDs/bisphosphonates are treatment mainstays
World Health Organization Analgesic Ladder for Cancer Pain relief?
- Mild to moderate pain: nonopioid analgesics +/- adjuvant
- Moderate pain: short-acting opioids +/- nonopioid analgesics +/- adjuvant
- Moderate to severe pain: short- and long-acting opioids +/- nonopioid analgesics +/- adjuvant
When is a dorsal root entry zone (DREZ) lesioning indicated?
Selective destruction of neurons in the posterolateral spinal cord used to treat medically refractory chronic pain syndromes associated w/ neurons that develop paroxysmal hyperactivity following deafferention (e.g. brachial plexus avulsion)
When is a cordotomy indicated?
surgical procedure that ablates the spinothalamic tract, providing selective loss of pain and temperature perception several segments below and contralateral to where the lesion is placed.
- Used for severe pain secondary to cancer (especially for pleural and peritoneal mesothelioma) where treatment to level 3 of the WHO pain ladder is ineffective
- B/l cordotomies may be required for visceral or bilateral pain (effect usually temporary)
Etiology of Complex Regional Pain Syndrome
thought to be caused by dysfunction of the central and peripheral nervous systems, resulting in allodynia, edema, changes in skin blood flow, and/or abbnormal sudomotor activity
What is the distinction b/t CRPS type I and type II?
CRPS 1: diagnosed if previous symptoms
