JD - Pain III Flashcards
Describe the pathway of pain sensation (3)
1) Periphery: Nociceptor Transmission: The pathway starts with nociceptors, which are sensory neurons that detect potential tissue damage. When nociceptors are stimulated by injury or inflammation, they send a signal to the spinal cord.
2) Spinal Cord: The signal from the nociceptor travels to the spinal cord. Here, the signal can be modulated by the action of opioids which can inhibit the transmission of the pain signal.
3) Supraspinal (e.g., Affective Response): The signal then travels to the brainstem and thalamus, which are regions of the brain involved in the perception of pain and the emotional response to pain
What are opioids, and how do they work?
Opioids are natural, synthetic, or endogenous substances that mimic the effects of morphine
- They bind to opioid receptors, mainly in the central nervous system, to reduce pain perception
List some endogenous opioids (3)
- Endorphins
- dynorphins
- enkephalins
How are opioid agonists and antagonists classified?
Opioid agonists activate opioid receptors, mimicking morphine’s effects (e.g., morphine, codeine, heroin).
Opioid antagonists block opioid receptors, reversing opioid effects and used in overdose situations (e.g., nalorphine, naloxone, naltrexone).
What are some common side effects of morphine? (6)
- Respiratory depression
- constipation
- nausea
- vomiting
- drowsiness
- pupillary constriction
Codeine (3) vs Heroin (5)
Codeine
- Most commercial opioid
- Metabolised to morphine
- Pain killer with very little or no euphoria
Heroin / Diamorphine
- Injected directly into blood stream
- Very lipid soluble (BBB)
- Highly potent but short lasting
- Metabolised to morphine
- Classified as a Class A drug
Naloxone vs Naltrexone
Both opioid antagonist (acts on all receptor subtypes)
NALOXONE
- Short acting 2-4 hours
NALTREXONE
- Longer-acting (>2-4 hours ~ 10hrs)
Phenylpiperidine (4) vs Methadone (5) vs Benzomorphan (3) series
Phenylpiperidine series
- Pethidine & Fentanyl
- Fully synthetic
- Less potent and Shorter duration
- Labour and Post-operative pain
Methadone series
- Longer duration of action (24-36 hrs) vs morphine (4-6 hrs)
- Opioid substitution therapy in heroin addiction
- effects are less intense = physical dependence
- Less euphoria than heroin and morphine
- Blocks the effects of heroin and morphine (euphoria)
Benzomorphan series
- Synthetic Opioid
- Mixed agonist-antagonist (depends on receptor subtype)
- Used as an analgesic – can cause dysphoria
What is the relevance of stereoisomers as opioids? (2)
- Levorphan 8x more potent, highly addictive and same side effects
- Dextrophan – no analgesic properties and is non addictive
What are opioid receptors, and how many subtypes are there?
Opioid receptors belong to the G protein-coupled receptor family. There’s evidence for multiple subtypes (mu, delta, kappa) with distinct effects.
- Mu (µ): Primary pain reliever but causes side effects like sedation and dependence.
- Delta (δ): May contribute to pain relief, more important in gut functions.
- Kappa (κ): May contribute to pain relief, can cause sedation and dysphoria (opposite of euphoria), doesn’t cause dependence.
What are the actions of opiods on pre-synaptic neurons? (2)
1) Inhibit the influx of calcium ions (Ca2+) through voltage-gated calcium channels.
- This reduces the release of neurotransmitters from the pre-synaptic neuron.
2) Increase the efflux of potassium ions (K+) through potassium channels.
- This hyperpolarizes the membrane of the post-synaptic neuron, making it less excitable.
What are the actions of opiods on post-synaptic neurons? (1)
Inhibits the activity of adenylyl cyclase (AC) enzyme.
- Reduces the production of cyclic adenosine monophosphate (cAMP), a second messenger molecule.
- Downregulates the activity of cAMP-dependent protein kinases
How do opioids affect nociceptive pathways? (2)
1) PERIPHERAL ACTIONS
- inhibit discharge of nociceptive afferents
- morphine also releases histamine from mast cells
2) IN THE SPINAL CORD
- inhibits neurotransmission in the dorsal horn
- Injection into the spinal cord is very effective
How does morphine reduce pain perception?
It binds to mu (µ) opioid receptors on:
- Mast cells, causing histamine release (degranulation) and vasodilation (potentially leading to hypotension)
- Primary afferent C-fibers, inhibiting voltage-gated calcium channels and reducing substance P release. This reduces pain signal transmission in the spinal cord
How does inhibitng SubP release reduce pain signal transmission in the spinal cord? (2)
- Substance P binds to neurokinin-1 (NK1) receptors on neurons in the dorsal horn.
- Activation of NK1 receptors by substance P excites these neurons, which leads to the perception of pain
