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Questions and Answers
Nociceptors are specialized nerve cell endings that initiate the sensation of pain.
Nociceptors are specialized nerve cell endings that initiate the sensation of pain.
False (B)
The conduction velocity of Aδ fibers is slower than that of C fibers.
The conduction velocity of Aδ fibers is slower than that of C fibers.
False (B)
Aδ fibers can be classified based on their sensitivity to different types of stimuli.
Aδ fibers can be classified based on their sensitivity to different types of stimuli.
True (A)
C-fiber nociceptors are exclusively responsive to mechanical stimuli.
C-fiber nociceptors are exclusively responsive to mechanical stimuli.
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The pain threshold for perceiving a thermal stimulus as noxious is approximately 43°C.
The pain threshold for perceiving a thermal stimulus as noxious is approximately 43°C.
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The vanilloid receptor (TRPV1) is only found in C fibers.
The vanilloid receptor (TRPV1) is only found in C fibers.
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Type I Aδ fibers have a lower heat threshold compared to Type II Aδ fibers.
Type I Aδ fibers have a lower heat threshold compared to Type II Aδ fibers.
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The sensation of sharp first pain is typically followed by a quick response.
The sensation of sharp first pain is typically followed by a quick response.
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TRP channels share structural characteristics with voltage-gated calcium channels.
TRP channels share structural characteristics with voltage-gated calcium channels.
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Subsets of C-fiber nociceptors can respond preferentially to only chemical stimulation.
Subsets of C-fiber nociceptors can respond preferentially to only chemical stimulation.
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The receptors responsible for the transduction of mechanical and chemical forms of nociceptive stimulation are well understood.
The receptors responsible for the transduction of mechanical and chemical forms of nociceptive stimulation are well understood.
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C fibers terminate exclusively in Rexed’s laminae I and II.
C fibers terminate exclusively in Rexed’s laminae I and II.
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The anterolateral system transmits information only about pain and not temperature.
The anterolateral system transmits information only about pain and not temperature.
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Wide-dynamic-range neurons in the spinal cord only receive inputs from nociceptive afferents.
Wide-dynamic-range neurons in the spinal cord only receive inputs from nociceptive afferents.
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The spinothalamic tract is primarily responsible for the sensory–discriminative aspects of pain.
The spinothalamic tract is primarily responsible for the sensory–discriminative aspects of pain.
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Second-order neurons in the dorsal horn send their axons across the midline of the spinal cord.
Second-order neurons in the dorsal horn send their axons across the midline of the spinal cord.
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Neurons in the anterior cingulate cortex show minimal changes in activity in response to changes in stimulus unpleasantness.
Neurons in the anterior cingulate cortex show minimal changes in activity in response to changes in stimulus unpleasantness.
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First-order neurons for facial pain originate in the trigeminal ganglion.
First-order neurons for facial pain originate in the trigeminal ganglion.
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The term 'pain matrix' refers to a specific area of the brain dedicated solely to processing intense pain.
The term 'pain matrix' refers to a specific area of the brain dedicated solely to processing intense pain.
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The majority of inputs processed by the parabrachial nucleus come from the spinothalamic tract.
The majority of inputs processed by the parabrachial nucleus come from the spinothalamic tract.
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The primary somatosensory cortex is completely inactive when observing another person in pain.
The primary somatosensory cortex is completely inactive when observing another person in pain.
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The anterior insula and the middle cingulate cortex are associated with both self-related pain and empathizing with pain in others.
The anterior insula and the middle cingulate cortex are associated with both self-related pain and empathizing with pain in others.
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The secondary somatosensory cortex (SII) is less active than the primary somatosensory cortex (SI) during the observation of touch.
The secondary somatosensory cortex (SII) is less active than the primary somatosensory cortex (SI) during the observation of touch.
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The discriminative aspects of facial pain are mediated by projections to the contralateral VPM nucleus through the trigeminal tract.
The discriminative aspects of facial pain are mediated by projections to the contralateral VPM nucleus through the trigeminal tract.
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The medial nuclei of the thalamus are primarily responsible for mediating the discriminative aspects of nociception.
The medial nuclei of the thalamus are primarily responsible for mediating the discriminative aspects of nociception.
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Common activation is represented in red, indicating areas activated when experiencing pain in oneself and in others.
Common activation is represented in red, indicating areas activated when experiencing pain in oneself and in others.
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C-tactile fibers are high-threshold mechanoreceptors that encode intense pain stimuli.
C-tactile fibers are high-threshold mechanoreceptors that encode intense pain stimuli.
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The posterior insula is exclusively involved in empathetic pain response.
The posterior insula is exclusively involved in empathetic pain response.
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Bilateral anterior insula and a region at the anterior medial cingulate cortex form a core network for emotional empathy.
Bilateral anterior insula and a region at the anterior medial cingulate cortex form a core network for emotional empathy.
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The anterior cingulate cortex is involved in processing the emotional aspects associated with visual nociceptive information.
The anterior cingulate cortex is involved in processing the emotional aspects associated with visual nociceptive information.
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Hypotheses regarding somatosensory stimulation suggest a significant connection between the brain's response to self-pain and observed pain in others.
Hypotheses regarding somatosensory stimulation suggest a significant connection between the brain's response to self-pain and observed pain in others.
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Descending pain-modulating pathways regulate the transmission of nociceptive information to higher brain centers.
Descending pain-modulating pathways regulate the transmission of nociceptive information to higher brain centers.
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The periaqueductal gray matter is primarily involved in the sensory processing of pain.
The periaqueductal gray matter is primarily involved in the sensory processing of pain.
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The activity registered during actual touch and observed touch shows no anatomical overlap.
The activity registered during actual touch and observed touch shows no anatomical overlap.
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The middle cingulate cortex is only involved in self-related pain responses, not in empathizing with others.
The middle cingulate cortex is only involved in self-related pain responses, not in empathizing with others.
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Animal studies indicate that stimulation of the periaqueductal gray matter results in selective analgesia without affecting other sensory modalities.
Animal studies indicate that stimulation of the periaqueductal gray matter results in selective analgesia without affecting other sensory modalities.
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Green regions in the model represent areas related to empathy for others.
Green regions in the model represent areas related to empathy for others.
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Information from C fibers can inhibit the activity of projection neurons in the spinal cord.
Information from C fibers can inhibit the activity of projection neurons in the spinal cord.
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The insular cortex is exclusively involved in encoding somatosensory information.
The insular cortex is exclusively involved in encoding somatosensory information.
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Social pain is solely processed by the lateral nucleus of the thalamus.
Social pain is solely processed by the lateral nucleus of the thalamus.
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Study Notes
Nociceptors and Pain Pathways
- Nociceptors are nerve cell endings that detect pain. They originate in dorsal root ganglia (or trigeminal ganglion) and have one axon extending to the periphery and another to the spinal cord/brainstem.
- Nociceptors' axons conduct pain signals slowly, either lightly myelinated (Aδ fibers, 5-30 m/s) or unmyelinated (C fibers, <2 m/s).
- Two main types of pain are perceived: sharp first pain (Aδ fibers) and delayed, diffuse second pain (C fibers).
- Type I Aδ fibers respond to intense mechanical/chemical stimuli but have high heat thresholds, while Type II Aδ fibers have low heat thresholds but high mechanical thresholds.
- C fibers are polymodal, responding to thermal, mechanical, and chemical stimuli. Subsets are specialized for heat or chemical stimuli.
- Nociceptive threshold for heat is around 43°C (110°F).
- TRPV1 (vanilloid receptor) is a transient receptor potential channel, sensitive to noxious heat and found in both Aδ and C fibers; activated by sodium and calcium influx triggering action potentials. Mechanoreceptors less understood, but include other TRP family members (TRPV4), Piezo2, ASICs.
Central Pain Pathways
- Pain pathways begin in dorsal root ganglia. Central axons enter the dorsal roots of the spinal cord.
- Nociceptive axons branch into ascending and descending collaterals in Lissauer's tract, then dorsal horn grey matter.
- Axons in the dorsal horn contact second-order neurons in Rexed's laminae I, II, and V.
- Laminae I and V neurons project to brainstem/thalamus.
- C fibers terminate exclusively in laminae I and II, while Aδ fibers terminate in laminae I and V.
- Wide-dynamic-range (WDR) neurons in lamina V receive nociceptive and non-nociceptive input (potential for referred pain).
- Second-order neurons cross the midline (anterolateral/ventrolateral quadrant) to brainstem.
- Anterolateral system conveys pain and temperature info.
Parallel Pain Pathways
- Spinothalamic tract (anterolateral system part) mediates pain's sensory-discriminative aspects: location, intensity, quality.
- Information from laminae I and V-VII relayed to VPL nucleus, and then to primary/secondary somatosensory cortex.
- Spinoreticular and spinomesencephalic tracts convey pain's affective-motivational aspects (unpleasantness, fear, autonomic response).
- These tracts project to the reticular formation, periaqueductal gray, superior colliculus, and parabrachial nucleus.
- Parabrachial nucleus relays second pain to amygdala, hypothalamus, and medial thalamic nuclei.
- Medial thalamic nuclei project to anterior cingulate cortex and insula, which contribute to affective/motivational pain aspects.
- Pain matrix: interconnected areas like somatosensory cortex, insula, amygdala, and anterior cingulate cortex, active during pain experience. Stimulus intensity mainly affects somatosensory cortex, while unpleasantness mainly affects cingulate cortex.
Pain and Temperature Pathways for the Face
- Pain/temperature from the face originates from neurons in the trigeminal ganglion and cranial nerves VII, IX, and X.
- Trigeminal fibers enter the pons, descend to medulla, forming spinal trigeminal tract.
- Fibers terminate in pars interpolaris and pars caudalis of spinal trigeminal nucleus.
- Second-order neurons cross the midline to brainstem/thalamic targets.
- Discriminative aspects of facial pain mediated by contralateral VPM nucleus (trigeminothalamic tract) projections to primary/secondary somatosensory cortex.
- Affective aspects mediated by connections to reticular formation, parabrachial nucleus, and medial thalamic nuclei projecting to cingulate/insular cortex.
Nociception - Thalamic Nuclei and Primary Somatosensory Cortex
- VPL nucleus receives spinothalamic pathway info from body, VPM receives trigeminothalamic pathway info from face.
- Medial thalamic nuclei (central lateral and intralaminar complex) process affective/motivational aspects of nociception.
- Primary somatosensory cortex receives info from lateral nuclear group, but cingulate and insular cortices more active with nociceptive stimuli.
Pain Modulation
- Descending pain-modulating pathways project to dorsal horn, regulating pain signals. Periaqueductal gray (PAG) is a crucial area.
- Cingulate and insular cortices modulate pain via descending pathways to PAG.
- Animal studies show PAG stimulation elicits analgesia without impacting other senses. PAG connections inhibit projection neurons in laminae I and V (spinothalamic pathway) and laminae I, II, and V (other pain pathways), especially in the Locus Coeruleus (noradrenergic) and Nucleus Raphe Magnus (serotonergic) regions.
Peripheral Regulation of Pain Perception (Gate Control Theory)
- Wall and Melzack's gate control theory describes peripheral modulation.
- Projection neuron in spinal cord receives inputs from C fibers (exciting) and inhibitory interneurons.
- A-beta fibers inhibit the interneuron, reducing the projection neuron firing rate.
C-Tactile Afferents
- Recent discovery of a class of C fibers that transmit gentle touch.
- C-tactile fibers are low-threshold mechanoreceptors in hairy skin. Likely associated with positive autonomic responses and project to posterior insula.
- May play a role in pain modulation.
Social Pain
- Cingulate and insular cortices process social pain (visual pain observation).
- Area activation is similar to actual pain experience.
- Anterior cingulate cortex processes emotional state, insular cortex processes internal body state.
Insular Cortex in Pain
- Insular cortex topographically organizes nociceptive information, from posterior (foot) to anterior (face).
- Represents ascending sympathetic and parasympathetic system afferents, integrating nociceptive with arousal/autonomic responses.
Social Touch & Social Pain
- Study by Keysers demonstrates mirroring of somatosensory sensations between people.
- Observing another person feeling touch activates somatosensory areas in observer, similar to actual touch, overlapping in SII/VP.
- Common activation areas in pain and pain observation (anterior insula, middle cingulate cortex).
- Anterior insula and anterior cingulate cortex thought to mediate pain empathy.
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Description
Test your knowledge on nociceptors and their role in pain perception. This quiz covers the types of nociceptors, their functions, and the pain pathways involved. Understand the differences between Aδ and C fibers and the physiological mechanisms of pain detection.
