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Flashcards in L12 Analgesia Deck (14)
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Learning outcomes (for general perusal)

Part A:

Analgesia via descending pathways

􏰀 Describe the descending pathway and explain how it’s activation causes analgesia

􏰀Identify circumstances when it may be active

Part B: Analgesics

􏰀 Identify three types of analgesics and explain how they work 


What is the phenomenon known as 'stress analgesia'?

a persons mental and physical state can influence the perception of pain. The body has it’s own pain relieving pathway under extreme circumstances/stress. 


Analgesia via descending pathways

  1. What does this pathway start with?
  2. Explain the pathway until the enkephalin neurons
  3. What mediates neurotransmission between the enkephalin neurons?
  4. What is released in response to the serotonin NT?

1. The activation of the the neurones in the periventricular nucleui (PVN) of the hypothalamus


  •  Signals are relayed from PVN to to the Periaqueductal gray (PAG) of the mesencephalon and upper pons
  • Then on to the raphe magnus nucleus (RMN) of the pons
  • Signals then reach the inhibitory interneurons (enkephalin neurons) in the dorsal horn of the spinal cord

3. Serotonin

4. neurotransmitters GABA and enkephakin (the bodies endogenous opioids) are released by the inhibitory interneurones to prevent signals being carried any further by the 2nd order projection neurones. 


Why does rubbing a damaged area reduce pain?

the connection here between interneurones and Aβ fibres explains why rubbing a damaged area (activating mechanoreceptors) reduces pain. 


What may explain why antidepressants act as analgesics?

the fact that serotonin mediates transmission between neurones from the RMN and inhibitory interneurones


What does the release of enkephalin do?

Inhibits the transmission of pain signals

 Enkephalin activates μ opioid receptors expressed by the membranes of the C and Aδ fibres and also the dorsal horn neurones. Opioid receptor activation prevents neurotransmitter release by C and Aδ fibres (presynaptic inhibition) and prevents action potential generation by the dorsal horn neurones (postsynaptic inhibition), therefore interfering with pain signals before they can reach the brain. 


If enkephalins inhibit action potential generation in the DHN via membrane hyperpolarization, which type of ion channel would they open?



Enkephalins act presynaptically on the C and Aδ fibres by preventing the opening of what kind of channel which would inhibit neurotransmitter release? 

Ca2+ channel



  1. Name 3 opioid medications
  2. How do they act?
  3. What is a worry?
  4. When are they prescribed?
  5. Why are there so many side effects?
  6. Name a desirable side-effect
  7. Name some non-desirable side effects
  8. What is the most dangerous side-effect? What causes it?

  1. morphine, pethidine, codeine
  2. inhibit transmission of pain signals at the level of the spinal cord by activating the same opioid receptors that the endogenous enkephalins do. They can also activate the descending pathway by removing GABA mediated inhibition of PAG activity, so it doesn’t need a signal from the PVN. 

  3. Addiction, so are strictly controlled

  4. Surgical pain, childbirth, or pain that doesn't respond to any other drugs

  5. opioid receptors are located at sites other than dorsal horn neurones

  6. Euphoria/sense of wellbeing (terminal pain, sedative effect)

  7. Constipation (inhibition of parasympathetic activity) Nausea and vomiting (stimulation of the chemoreceptor trigger zone in the medulla oblongata)

  8. respiratory depression - reduction in the sensitivity of the respiratory centre to CO2 (This is the most common cause of death due to an overdose)


Non-steroidal anti-inflammatory drugs (NSAIDs)

  1. Name a NSAID
  2. How do they work?
  3. How do prostaglandins effect nociceptor activity?
  4. What type of a molecule are prostaglandins?
  5. What are they produced from?

  1. Aspirin
  2. NSAIDs inhibit prostaglandin and thromboxane A2 production by inhibiting the action of the enzyme which catalyses the conversion of arachidonic acid, cyclooxygenase (COX), this explains why such drugs are sometimes known as COX inhibitors. Inhibition of prostaglandin production reduces the hyperalgesia associated with inflammation. 

  3. increase it

  4. eicosanoid and their production is increased when tissue is damaged. 

  5. Phospholipid precursors



  1. Describe how and why prostaglandins are produced

  1. When the tissue is damaged, the cytosolic enzyme phospholipase A2 is activated and arachidonic acid is formed. The diagram opposite illustrates how arachidonic acid is converted firstly into cyclic endoperoxides, and then into prostaglandins and thromboxane A2. The prostaglandins produce the characteristic signs of inflammation, vasodilation and allodynia (pain from a non-painful stimulation)/hyperalgesia (increased sensitivity to pain)


What do NSAIDs inhibit?

the action of the enzyme which catalyses the conversion of arachidonic acid, cyclooxygenase (COX) 


Local Anaesthetics

  1. Name two local anaesthetics 
  2. How do they have their effect?
  3. How does the LA gain access to the channel?

  1. lidocaine, benzocaine 
  2. blocking the initiation and propagation of the action potential by pain fibres. The ionised form of the drug does this by physically plugging voltage dependent Na+ channels. 


Use dependent block (Hydrophilic pathway)

They are mainly ionized at physiological pH’s, so are membrane impermeable. The ionized form therefore needs to directly permeate the channel in it’s open state. 

A use dependent channel block means that the depth of block increases with each action potential (repetitive activity of a nerve in the presence of a local anaesthetic reduces the sodium entry (or current) a little further with each action potential. This occurs because channel opening provides a route by which the ionised form has the opportunity to enter an open channel. )

Non-Use Dependent Block (hydrophobic pathway)

The unionised form is membrane permeant and once inside the cell it can gain access to the channel pore indirectly and become ionised to block activity. 


Bacteria produce acidic by products, reducing tissue fluid pH and as a result more LA is in it’s ionised form. What could this do to the effectiveness of the LA? 




What was the first local anaesthetic?

Greater requirement for channel opening to gain access

May reduce effectiveness





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