Pharmacology of Pain Flashcards
What are the three main types of pain?
- Nociceptive (e.g. acute noxious mechanical,
thermal, electrical stimuli) - Inflammatory (e.g. semi-acute or chronic ischaemia, infection)
- Neuropathic (e.g. chronic maladaptive
plasticity after traumatic injury)
With pain, what happens in the first seconds to minutes?
Activation of nociceptive specific/wide dynamic range neurones proportional to the intensity of the stimulus
With pain, what happens in the first minutes to days?
Sensitisation of terminals at the injury site and delayed central sensitisation
With pain, what happens in the first days to months?
Changes in the supply of trophic factors, sprouting of fibres and abnormal innervation, and trans-synaptic degeneration
What are some of the targets for treating pain? (5)
COX-2 (make prostaglandins) Nitric oxide synthase Glutamate receptors (NMDA and non-NMDA) Neurokinin 1 receptors Opioid receptors (e.g. µ receptors)
How do opioids affect the periaqueductal gray and nucleus reticularis paragigantocellularis? What else do they affect?
They stimulate the periaqueductal gray and nucleus reticularis paragigantocellularis.
This stimulates the nucleus raphe magnus which inhibits dorsal horn (using 5-HT and enkephalins).
They also directly inhibit the dorsal horn and the nociceptive afferent neuron to the periphery.
What structures are activated by nociceptive stimuli? (8)
Spinal cord Thalamus Somatosensory cortex Anterior cingulate cortex Insula Amygdala Prefrontal cortex Hippocampus
What factors influence pain perception? (6)
Cognition – attention/distraction, etc
Context – beliefs, expectations, placebo
Genetics
Injury – peripheral/central sensitisation
Chemical and structural – atrophy/dysfunction
Mood – depression, anxiety, catastrophizing
What influences your risk of developing chronic pain? (3)
Hardware at birth
Environmental influences
Gene x environment interactions
What endogenous opioid peptides are involved in nociception?
Enkephalins (derivied from proenkephalin)
Dynorphins (derived from prodynorphin)
Beta endorphin
(+ Pro-opiomelanocortin)
Why are endogenous opioids rapidly inactivated in the circulation?
They are targets for peptidases.
Give an example of a pro-nociceptive endogenous system.
Cholecystokinin
Why do opioid agonists have a broad spectrum of effects?
Due to the wide distribution of opioid receptors.
List the 4 types of endogenous opioid system receptors.
Mu (1, 2, 3)
Delta (1, 2)
Kappa (1, 2, 3)
Nociceptin/orphain receptor
What is the effect of morphine on conductance and neurotransmitter release?
Activating potassium conductance and decreasing calcium conductance
Decreased excitability and decreased release of neurotransmitter
Give some examples of opiates. (6)
Morphine Methadone Sufentanil Fentanyl Pethidine Pentazocine
Mu receptor effects:
- What type of analgesia/where?
- What are the main side effects? (4)
- Can it be used as a sedative?
- Is it addictive?
Supraspinal (some spinal and peripheral as well)
Respiratory depression, pupillary constriction, reduced GI motility, euphoria
Yes
Yes
Delta receptor effects:
- What type of analgesia/where?
- What are the main side effects? (2)
- Can it be used as a sedative?
- Is it addictive?
Spinal analgesia
Resp depression (less than Mu) and reduced GI motility
No
No
Kappa receptor effects:
- What type of analgesia/where?
- What are the main side effects? (3)
- Can it be used as a sedative?
- Is it addictive?
Peripheral (and some spinal)
Resp depression (but less than delta and mu), reduced GI motility (less than delta and mu), dysphoria
Yes
No
What other effects do opiates have on the GI system? (3)
Urinary urgery
Decreased secretions
Nausea and vomiting
What effect do opiates have on the cardiovascular system? What about on the skin?
Hypotension
Itching
What is naloxone?
Opiate antagonist