Case 10
LG1: How is pain defined?
PAIN – DEFINITIONS & TYPES
Pain is an unpleasant sensory & emotional experience associated with actual or potential tissue damage or
described in terms of such damage.
There are two subcategories of pain sensation:
1. Nociceptive pain - Pain that arises from actual or threatening damage to non-neural tissue & is due to
the activation of nociceptors
- Nociceptor: nocere = damage & receptore = receiver damage-receiver
- Nociception is caused by (extensive) triggering of nociceptors more than one nociceptor needs to
be triggered to feel actual pain
- Often well localized – knows where the pain comes from
- Recognizable for the patient based on earlier experiences
- usually aching or throbbing and well-localized
- usually time-limited (resolves when damaged tissue heals) but can become chronic
- generally, responds conventional analgesics (paracetamol, ibuprofen, …)
2. Neuropathic pain – Pain that arises from damage to neural tissue
- pain often described as tingling, shock-like, and burning – commonly associated with numbness
- almost always a chronic condition
- responds poorly to conventional analgesics
- central sensitization is mostly linked to neuropathic pain a lot of new receptors, gene expression,
increase in synapses & strengthening of synapses
- definition: pain caused by a lesion or disease of the somatosensory nervous system
- causes: peripheral nerve injury, spinal cord injury, diabetes, stroke, auto-immune disorders, …
- mechanism: central sensitization, ectopic firing or unknown
very difficult to treat
LG2 & 4: Different types of pain and their pain receptors
Allodynia
Allodynia is a condition where pain is caused by a stimulus that does not normally elicit pain. For example, bad
sunburn can cause temporary allodynia, and touching sunburned skin, or running cold or warm water over
sunburned skin can be very painful. Individuals with allodynia, however, feel pain when something is ordinarily
painless.
Hyperalgesia
is an abnormally increased sensitivity to pain, which may be caused by damage to nociceptors or peripheral
nerves and can cause hypersensitivity to stimulus. Although there are many potential causes associated with
hyperalgesia, the condition is thought to be the result of changes to nerve pathways, which cause a person’s
nerves to have an overactive response to pain. Hyperalgesia is considered a form of neuropathic pain. The chief
symptom of hyperalgesia is an increasingly extreme reaction to painful stimuli without any new injuries or
worsening of a medical condition. In hyperalgesia, a person has experienced a painful stimulus, such as cancer
pain or pain following surgery, but their response to the pain is greater than the expected level of pain.
Analgesia
Analgesia is the insensibility to pain without the loss of consciousness. To stop the sensation of pain analgesic
, Nociceptors are activated by mechanical, chemical or thermal stimuli. The ion channels on the membrane can be
opened by these stimuli, causing depolarization which generates AP’s. Besides this mechanism, damaged cells
at the site injury can release several substances that can cause ion channels on nociceptor membranes to open:
- ATP – causes nociceptors to depolarize by binding directly to ATP-gated ion channels on the
nociceptive membrane
- Potassium – directly depolarizes neuronal membrane
- Proteases (enzyme that digests proteins) – the proteases break down kininogen (an abundant
extracellular peptide) into another peptide called bradykinin.
- Bradykinin – can bind to specific receptor molecules that activate ionic conductance in nociceptors.
Simultaneously, it stimulates long-lasting intracellular changes that make heat-activated ion channels
more sensitive. It directly activates the Aδ-fibers & C-fibers by depolarization and increases the
synthesis and releases of prostaglandins.
- Prostaglandins – chemicals created when the lipid membrane is enzymatically broken down. They
increase the sensitivity of nociceptors to other stimuli (causes hyperalgesia)
- Substance P – a peptide that is synthesized by nociceptors. When one branch of nociceptor is
activated, substance P can be secreted by other branches of that axon in the neighbouring skin. It is the
cause for secondary hyperalgesia and causes vasodilation and the release of histamine by mast cells.
- Histamine – a substance released by mast cells. It activates polymodal nociceptors
LG3: Pathways for pain and the anatomy of the nociceptive system
PATHWAY OF NOCICEPTIVE PAIN
1. It starts with Tissue Damage
LG1: How is pain defined?
PAIN – DEFINITIONS & TYPES
Pain is an unpleasant sensory & emotional experience associated with actual or potential tissue damage or
described in terms of such damage.
There are two subcategories of pain sensation:
1. Nociceptive pain - Pain that arises from actual or threatening damage to non-neural tissue & is due to
the activation of nociceptors
- Nociceptor: nocere = damage & receptore = receiver damage-receiver
- Nociception is caused by (extensive) triggering of nociceptors more than one nociceptor needs to
be triggered to feel actual pain
- Often well localized – knows where the pain comes from
- Recognizable for the patient based on earlier experiences
- usually aching or throbbing and well-localized
- usually time-limited (resolves when damaged tissue heals) but can become chronic
- generally, responds conventional analgesics (paracetamol, ibuprofen, …)
2. Neuropathic pain – Pain that arises from damage to neural tissue
- pain often described as tingling, shock-like, and burning – commonly associated with numbness
- almost always a chronic condition
- responds poorly to conventional analgesics
- central sensitization is mostly linked to neuropathic pain a lot of new receptors, gene expression,
increase in synapses & strengthening of synapses
- definition: pain caused by a lesion or disease of the somatosensory nervous system
- causes: peripheral nerve injury, spinal cord injury, diabetes, stroke, auto-immune disorders, …
- mechanism: central sensitization, ectopic firing or unknown
very difficult to treat
LG2 & 4: Different types of pain and their pain receptors
Allodynia
Allodynia is a condition where pain is caused by a stimulus that does not normally elicit pain. For example, bad
sunburn can cause temporary allodynia, and touching sunburned skin, or running cold or warm water over
sunburned skin can be very painful. Individuals with allodynia, however, feel pain when something is ordinarily
painless.
Hyperalgesia
is an abnormally increased sensitivity to pain, which may be caused by damage to nociceptors or peripheral
nerves and can cause hypersensitivity to stimulus. Although there are many potential causes associated with
hyperalgesia, the condition is thought to be the result of changes to nerve pathways, which cause a person’s
nerves to have an overactive response to pain. Hyperalgesia is considered a form of neuropathic pain. The chief
symptom of hyperalgesia is an increasingly extreme reaction to painful stimuli without any new injuries or
worsening of a medical condition. In hyperalgesia, a person has experienced a painful stimulus, such as cancer
pain or pain following surgery, but their response to the pain is greater than the expected level of pain.
Analgesia
Analgesia is the insensibility to pain without the loss of consciousness. To stop the sensation of pain analgesic
, Nociceptors are activated by mechanical, chemical or thermal stimuli. The ion channels on the membrane can be
opened by these stimuli, causing depolarization which generates AP’s. Besides this mechanism, damaged cells
at the site injury can release several substances that can cause ion channels on nociceptor membranes to open:
- ATP – causes nociceptors to depolarize by binding directly to ATP-gated ion channels on the
nociceptive membrane
- Potassium – directly depolarizes neuronal membrane
- Proteases (enzyme that digests proteins) – the proteases break down kininogen (an abundant
extracellular peptide) into another peptide called bradykinin.
- Bradykinin – can bind to specific receptor molecules that activate ionic conductance in nociceptors.
Simultaneously, it stimulates long-lasting intracellular changes that make heat-activated ion channels
more sensitive. It directly activates the Aδ-fibers & C-fibers by depolarization and increases the
synthesis and releases of prostaglandins.
- Prostaglandins – chemicals created when the lipid membrane is enzymatically broken down. They
increase the sensitivity of nociceptors to other stimuli (causes hyperalgesia)
- Substance P – a peptide that is synthesized by nociceptors. When one branch of nociceptor is
activated, substance P can be secreted by other branches of that axon in the neighbouring skin. It is the
cause for secondary hyperalgesia and causes vasodilation and the release of histamine by mast cells.
- Histamine – a substance released by mast cells. It activates polymodal nociceptors
LG3: Pathways for pain and the anatomy of the nociceptive system
PATHWAY OF NOCICEPTIVE PAIN
1. It starts with Tissue Damage
