L11 Pain: Peripheral Mechanisms + Central Pathways Flashcards Preview

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Flashcards in L11 Pain: Peripheral Mechanisms + Central Pathways Deck (30):

Learning Outcomes (for general perusal) 

  1. Explain the importance of pain to the physician
  2. Define pain and explain how it differs from nociception
  3. Describe the structure of the nociceptor and how it is distributed throughout the body
  4. Explain the difference between fast and slow pain
  5. Describe how chemical, mechanical and thermal stimuli can evoke pain
  6. Identify chemical, mechanical and thermal mediators of pain
  7. Describe the pathways nociceptive signals take to reach the appropriate parts of the brain
  8. Describe how the somatosensory cortex, hypothalamus and limbic system contribute to the sensation of pain
  9. Describe the phenomenon of referred pain and explain why it is thought to occur
  10. Describe the autonomic responses that may accompany pain and explain why knowledge of these are important
  11. Explain the difference between acute and chronic pain
  12. Explain why pain is useful
  13. Describe the characteristics and underlying causes of neuropathic pain
  14. Understand that pain and state of mind are inextricably linked 


Summarise the two components of pain

The unconscious detection of harmful stimuli using sensory receptors, referred to as nociception, and the strong emotional and subjective response to it. 


What type of sense is pain?

A somatic sense


What is the International Association for the Study of Pain's definition of pain?

Pain is an “An unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage


Nociception + Subjective Response


  1. What is the receptor type associated with pain?
  2. Where are these receptors found?
  3. What are the two types of fibres associated with nociceptors?

  1. Nociceptor (simple free nerve ending)
  2. Skin, arterial walls, joint surfaces and deeper tissues of the body. The brain itself very rarely generates the sensation of pain, but there are nociceptors in the walls of brain blood vessels and the meninges
  3. Myelinated Nerve Fibres (Ad fibres) and Unmyelinated Fibres (C fibres)


Give the properties of 

Myelinated Nerve Fibres



Unmyelinated Nerve Fibres

Myelinated Nerve Fibres (Aδ fibres)

Rapid conduction velocity (6 to 30 m/s)

Fast pain


Seems immediate

Highly localised

Superficial tissue

mechanical or thermal stimuli

Unmyelinated Fibres (C Fibres)

Slow conduction velocity (0.5 to 2 m/s)

Slow pain


Delay (tends to linger)

Hard to locate

Superficial and deep tissue

mechanical, thermal or chemical stimuli


The two types are often experienced TOGETHER


Name the chemical mediators of pain which activate nociceptors

1. K+ - released from damaged cells

Histamine and Bradykinin - responsible for changes during inflammation, released from mast cells and basophils when IgE coated antigens attach to their surface (this can occur at the initial appearance of a foreign antigen so pain can preempt tissue damage as a warning signal)

H- released during high-intensity exercise (working muscle has an increasing reliance on anaerobic metabolism and as a result lactic acid production increases) (similar mechanism in distention - constipation and trapped wind - and the ischaemia involved)

5-HT (serotonin) - released from activated platelets when they aggregate at a site of blood vessel damage

Temperature Extremes (<15oC, >45oC) 

Strong Pressure (mechanical stimulus)




What increases the SENSITIVITY of nociceptors without actually activating them?


Production is stimulated by tissue damage

thought to account for the allodynia associated with tissue damage, i.e when a non-noxious stimuli evokes a pain response, such as gentle stroking of a cut.


What is Allodynia?

 the experience of pain from a non-painful stimulation of the skin, such as light touch.


Why are most nociceptors referred to as polymodal?

Most respond to more than one type of stimuli


Nociceptive Pathways

  1. What happens straight after a nociceptor in the torso or limbs is activated?
  2. What is the final destination of these signals?

  1. the associated pain fibres (C or Aδ) carry signals from the affected tissue to the dorsal horn of the spinal cord
  2. The somatosensory cortex on the opposite side of the brain. 


  1. Outline what happens when a pain fibre is activated to DHNs being activated.
  2. Which neurotransmitter mediates synaptic transmission between Aδ fibres and DHNs?
  3. Which NTs mediate synaptic transmission between C fibres and DHNs?

  1. pain fibres are also referred to as 1st order neurones.  They carry the pain signal from the affected tissue to the dorsal horn of the spinal cord, synapsing here with 2nd order neurones referred to simply as dorsal horn neurones (DHNs).  It is the DHNs which carry signals up the spinal cord.
  2. glutamate
  3. both glutamate and substance P 


What are the two main pathways taken by the DHNs (dorsal horn neurones)?

Spinothalamic Tract

Most of the signals are carried via the spinothalamic tract, initially to the thalamus of the brain and finally, via 3rd order neurones to the somatosensory cortex (alternate name = somesthetic cortex)

Spinoreticular Tract

The spinoreticular tract also carries signals to the cortex but via the reticular formation and branches of it innervate the hypothalamus and limbic system.


What carries signals up the spinal cord?


(Dorsal Horn Neurons)


Why would it be advantageous to inform the hypothalamus of injury when a person is in a potentially harmful situation?


The hypothalamus is part of the limbic system, a part of the brain which is associated with emotion, does this area therefore contribute to nociception or pain perception?

 fight or flight, descending analgesic pathway




pain perception


What is the gracile fasciculus?

Another tract only recently been recognized as carrying visceral pain signals, like that associated with stomach ache and kidney stones.  This pathway carries signals, firstly to the gracile nucleus in the medulla oblongata and then to the thalamus and the cortex.


How do pain signals from the head travel?

Pain signals from the head travel primarily via the trigeminal nerve, through the pons, to the medulla.  2nd order neurones  bring the signals through the thalamus and to the cortex


What is referred pain?

When pain from a visceral organ is felt in a superficial area of the body

pain originating in a particular area is not always perceived as coming from that body part


Why does referred pain occur?

because the visceral pain fibres synapse in the spinal cord at the same point and with some of the same neurones that pain fibres from the skin synapse with.  The origin of the pain is interpreted as coming from the skin as opposed to the visceral organ because there are many more receptors in the skin and therefore it is more likely to have originated here. 


eg. pain of angina being referred to the left shoulder and arm is used to illustrate this concept in the diagram opposite.


What are the autonomic responses to pain?

pupillary dilation, pallor, urination, sweating, and nausea.  Cardiovascular responses are usually bradycardia and hypotension.  Obviously, if a patient is in severe pain it is important to consider whether the signs or symptoms could be associated with a response to pain rather than the underlying cause of it.


What is physiologic/acute pain?

is pain which has a sudden onset in response to a discrete

event such as a bone fracture or skin trauma, it doesn’t last very long and recedes during healing


What is pathologic/chronic pain?

persists long after recovery (more than three months), although it is often difficult to tie to a specific event. 

It is also often unresponsive to analgesics like aspirin or morphine.  This type of pain can result from nerve injury and have profound psychological consequences.


  1. What is Congenital insensitivity to pain?
  2. What are the difficulties for affected persons?
  3. Where else can insensitivity to pain arise (other examples)

  1. a very rare genetic condition which results from an abnormally low expression of nociceptors
  2. Affected individuals will often seriously injure themselves
  3. Pressure sores on patients who are confined to bed and taking pain medication

They are unaware of the ischaemic pain that occurs at the points of the body which are under the most weight.  Normally, we shift unconsciously to relieve pressure at those points, these patients don’t do this and if the ischaemia were allowed to persist necrosis and bed sores occur. 


Neuropathic pain

  1. What brings it about?
  2. What is the presentation of neuropathic pain
  3. What is it caused by?

  1. as a result of a lesion or disease in the peripheral or central nervous systems (such as diabetic neuropathy, multiple sclerosis or spinal cord injury)
  2. variable, it may feel like the pain normally felt in the skin, muscles, and joints but it can also have an unusual quality like burning or tingling.  It can also be associated with allodynia or hyperalgesia (an exaggerated response to a noxious stimulus).
  3. It is believed to be caused by sensitization of the peripheral and central neurones involved in nociception.  


How could the increased expression of Na+ channels cause an increase in nociceptor sensitivity?

Increased likelihood that the threshold potential will be reached


Neuropathic Pain

  1. What will an increase of nociceptive signals from C and Ad fibres result in (as a consquence of sensitization)?
  2. When does it occur?
  3. What happens as a result of increased expression of the NMDA subtype receptor?

  1. Central Sensitization = Secondary changes in the at the spinal cord
  2. when the more frequent release of glutamate from 1st order pain fibres bombards the DHNs and increases expression of the associated receptor, the NMDA subtype
  3. This receptor is ionotropic and permeable to Na+ and Ca2+, increased expression of them means that the threshold potential of the DHN is more likely to be reached, and a weaker stimulus than normal will result in a response. 


Neuropathic Pain

Explain primary sensitization

 Peripheral C and Aδ fibres are normally only active when stimulated, after an insult they can show spontaneous activity or respond to much weaker stimuli, a characteristic linked to increased expression of voltage dependent Na+ channels. 


Neuropathic Pain

  1. Explain what happens as a result of the sprouting of Aβ (mechanoreceptor) fibres which occurs when the fibres are damaged after secondary sensitization?

  1. this allowing them to make connections to 2o order pain fibres in the spinal cord (see diagrams below).  This means that stimuli normally perceived as innocuous mechanical activity is now perceived as pain

new connections between Aβ fibres and DHNs are created


  1. What is phantom limb pain?
  2. Why does it occur?

  1. a type of neuropathic pain, which is experienced by a high percentage of amputees (50 to 80%).
  2. The insult to neurones originating in the amputated limb leads to central sensitization, but there also seems to be rearrangement of cortical circuits so that pain is actually perceived as coming from the amputated limb.  This rearrangement results in the cortical region for the missing limb receiving afferents from the skin at the stump 


Psychological Aspects of Pain


  • Pain perception is influenced by psychological factors

  • Chronic pain and depression are linked (both ways) (The analgesic effects of antidepressants lend further support to this link)

  • the same stimulus can be perceived differently by different people

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