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Questions and Answers
What is pain according to IASP?
What is the characteristic of pain according to Wall?
What are the three main types of pain?
What type of mechanoreceptor are nociceptors usually considered?
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What are the two types of nerve fibers involved in pain transmission?
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What is the characteristic of transmission times in pain transmission?
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What type of pain is associated with A-delta fibres?
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What is the result of retrograde activation of C-fibres?
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What is the effect of plasma extravasation on nociceptors?
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What is the location of A-delta and C-fibres in the spinal cord?
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What is the result of central sensitization?
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What type of receptors are present on nociceptors?
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What is the term for the process by which spinal cord cells become hyperresponsive to painful stimuli?
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What is the term for the perception of previously innocuous stimuli as painful?
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What type of receptors are present in spinal cord cells that can modulate nociception?
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What is the outcome of prolonged activation of spinal neurons by nociceptive input?
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What is the mechanism underlying referred pain in some cases?
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What is the tract formed by fibres that ascend directly to the thalamus?
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What is the nerve responsible for relaying pain from the head?
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What is the destination of the ventroposterior lateral and medial nuclei in the thalamus?
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What is the characteristic of the signals reflected in the somatotopic map?
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What is the result of reflex activation of the sympathetic nervous system?
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Study Notes
Definition of Pain
- Pain is an unpleasant sensory and emotional experience associated with actual or potential tissue damage or described in terms of such damage (IASP)
- Pain is like hunger and thirst, unlike vision and audition (Wall, P. “On the relation of injury to pain”)
Types of Pain
- Acute pain
- Chronic pain
- Nociceptive (Inflammatory)
- Neuropathic
- Nociplastic
- Cutaneous pain
- Deep Somatic pain
- Visceral pain
- Cancer pain
- Non-cancer pain
Nociceptors
- Distinct classes of mechanoreceptors for somatosensation
- Nociceptors are usually considered a sub-type of mechanoreceptor
- Referred to/ described commonly as “free-nerve endings”
- Thermal, Mechanical, Polymodal, and Silent nociceptors
- A-delta and C-fibre types of nerve fibres
Nociceptor Location and Function
- Nociceptors located from superficial to deep tissues
- Thermal and mechanical nociceptors found most superficially
- Polymodal nociceptors found throughout the body
- Silent nociceptors found in muscle, joint, and viscera
Transmission and Conduction Velocities
- A-delta fibre: “first pain”
- C-fibre: “second pain”
- Transmission times (conduction velocities) have perceptual correlates
Lewis' Triple Response
- “Retrograde activation” of C-fibres
- Ø rubor, turgor, and calor (+ dolor) due to release of transmitter from sensory ending
Tissue Damage and Nociceptor Activation
- Tissue damage triggers local release of bradykinin, PGs, and K+
- Activates nociceptor
Sensitisation of Nociceptors
- Retrograde activation of collaterals triggers release of Substance P
- Mast cells degranulate and release histamine
- Increased swelling and sensitized nociceptor
- Retrograde activation of collaterals triggers release of Substance P
- Acts on vessels and causes plasma extravasation, which may sensitise nociceptor
Sensitisation and Hyperalgesia
- Sensitisation of the nociceptors on peripheral fibres results in primary hyperalgesia/allodynia
- By example, a burn results in a region of flare, and beyond that a region of enhanced sensitivity to mechanical stimuli
- Previously innocuous stimuli are now perceived as painful (allodynia)
- Noxious stimuli are perceived as more noxious (hyperalgesia)
Spinal Cord Processing
- A-delta and C-fibres from the body project into spinal cord
- Spinal cord is a laminated structure
- Each lamina has a specific function
- Neurons in laminae 1, 2, 5, and 10 each receive inputs from nociceptors from distinct body tissues
Neurotransmitters and Receptors
- Nociceptors contain neurotransmitters Glutamate and Substance P
- Spinal cord cells contain opioid, adrenergic, GABA, and 5HT receptors
- Via which nociception may be modulated
Central Sensitization
- Prolonged activation of the spinal neurons by nociceptive input can trigger cell death in the spinal cord
- Cells most vulnerable are the inhibitory type, which may lead to overactivity of the spinal cord
- Prolonged activation of the spinal neurons by nociceptive input can trigger long-term changes in their function, via genomic regulation
Referred Pain
- Convergence of primary afferent fibres onto common pools of spinal neurons results in a perceptual "mistake"
- Reflex activation of the sympathetic nervous system can lead to referral
- Reflex activation of the motor outflow can lead to referral
Ascending Pathways
- Fibres from spinal lamina 1,2,5, and 10 cross the midline in the spinal cord and ascend towards higher brain regions
- Fibres travel in anterolateral quadrant = anterolateral tract
- Some fibres ascend directly to the thalamus, forming the spinothalamic tract
Thalamus and Cortex
- Pain from the head is relayed through the trigeminal nerve: ventral trigemino-thalamic tract
- The ventroposterior lateral and medial nuclei send their information to primary somatosensory cortex (S1)
- Signals are represented in a somatotopic map and reflect onset, location, intensity, and "descriptive" quality
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