10 Questions
Explain the main difference between the neothalamic and paleothalamic pain pathways.
Neothalamic is new and fast, specific to the local area, using A delta fibers. Paleothalamic is old and slow, generalized throbbing sensation, using C fibers.
What are the primary effects of opioids binding to Mu receptors?
Analgesia, euphoria, respiratory depression, bradycardia, reduced gut motility.
Differentiate between physical dependence and addiction in the context of opioid use.
Physical dependence leads to withdrawal symptoms when stopping the drug, while addiction is compulsive drug use despite harm.
Explain the primary function of morphine in pain management.
Morphine is a Mu receptor agonist used for moderate to severe acute pain, palliative care, and perioperative settings.
What is the main difference between codeine and oxycodone in terms of their classification?
Codeine is a prodrug that gets activated to morphine, while oxycodone is a synthetic opioid acting as a Mu receptor agonist.
How do NSAIDs exert their analgesic effects?
NSAIDs inhibit cyclooxygenase, which blocks the production of prostaglandins responsible for pain and inflammation.
What are the contraindications for using NSAIDs?
Renal failure, uncontrolled hypertension, GI ulcerations.
Explain the difference between the effects of neothalamic and paleothalamic pain pathways.
Neothalamic pathway is fast and specific to the local area, while paleothalamic pathway is slow and generalized.
What are the primary adverse effects associated with opioid use?
Pruritis, nausea and vomiting, constipation, urinary retention, physical dependence, hypotension, sedation, respiratory depression.
Describe the role of kappa receptors in the context of opioids.
Kappa receptors are associated with analgesia, sedation, and depression, primarily found in the limbic system and cortex.
Study Notes
Pain Physiology
- Noxious stimuli sensitizes a sensory neuron, which travels to the spinal cord via the dorsal horn (first-order neuron)
- The first-order neuron synapses with a second-order neuron on the contralateral side, which travels up the spinal cord via the spinothalamic or dorsolateral tract
- The second-order neuron synapses at the thalamus, from which a third-order neuron enters the somatosensory cortex, suggesting pain in a specific area
Pain Pathways
- Neothalamic pathway:
- New and fast
- Uses A delta fibers, which are heavily myelinated and carry the initial pain sensation
- Causes withdrawal of the body part away from the stimulus and to safety
- Specific to the local area of sensation
- Paleothalamic pathway:
- Old and slow
- Uses C fibers, which are unmyelinated
- Goes to the reticular formation of the brain stem and the thalamus
- Not hyper-specific to the area
- Felt as a general, throbbing sensation in the body
Opioids
- Opioid receptors:
- Mu receptors: analgesia, euphoria, respiratory depression, bradycardia, reduced gut motility, etc.
- Brain stem, dorsal horn of spinal cord, PNS, on nociceptive fibers expressed after injury
- Kappa receptors: analgesia, sedation, depression
- Limbic system, cortex
- Delta receptors: analgesia, physical dependence, respiratory depression
- Mu receptors: analgesia, euphoria, respiratory depression, bradycardia, reduced gut motility, etc.
- Adverse effects of opioids:
- Pruritus
- Nausea and vomiting
- Constipation
- Urinary retention
- Physical dependence
- Hypotension
- Sedation
- Respiratory depression
- As doses of opioids increase, side effects also increase, making it risky to prescribe opioids
- Addiction: compulsive use despite harm
- Tolerance: not addiction, need to increase dose to get same analgesic effect
- Physical dependence: withdrawal symptoms, not addiction, wean opioids off slowly
Opioids (cont.)
- Morphine:
- Mu receptor agonist
- Oral or parenteral
- Dosing: start with low dose, increase as patient takes more to feel same effect (tolerance)
- Many metabolites, morphine 6 glucuronide causes analgesic effects
- Used for moderate to severe acute pain, palliative care, and perioperatively
- Consider risk of airway/breathing
- Codeine:
- Prodrug, inactive, gets activated to morphine
- Oxycodone:
- Synthetic opioid, Mu opioid receptor agonist
- Tramadol:
- Weak opioid agonist, better side effects compared to morphine
- Useful in situations where side effects need to be avoided, certain contraindications
- Some have codeine and paracetamol together for analgesic and anti-pyretic effects in severe to high fevers
Non-Opioids
- NSAIDs:
- Inhibit cyclooxygenase, which converts arachidonic acid to prostaglandins
- Prostacyclin:
- Released by vascular endothelium, causes vasodilation and reduces platelet activation
- Prostaglandins:
- Smooth muscle control and hyperalgesia (increased sensitivity to pain)
- Blocking this pathway can have analgesic effect
- Thromboxane:
- Produced by platelets to enhance platelet aggregation
- Contraindications:
- Renal failure: blocking prostaglandins inhibits vasoconstriction, leading to release of HTN, fluid release, and oedema, contributing to renal dysfunction/failure
- Uncontrolled HTN: due to reduction in renin release, kidney can no longer control blood pressure
- GI ulcerations: when COX is inhibited, prostaglandin production is reduced, leading to GI ulcerations
Learn about the pathway of pain signals from the first order neuron to the somatosensory cortex. Understand how noxious stimuli are transmitted and processed in the body.
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