,Problem 1 & Lecture 1
Definition and neurobiological basis of pain
Wieser: Neuroscience of Pain and Emotion
Pain: unpleasant sensory and emotional experience associated with actual or potential tissue damage.
Conscious experience of nociception, emerging from cognitive and emotional evaluation of the info gathered
through the nociceptive system.
- Function: warning, supports healing process
- Chronic pain = > 6 months, lost warning function, occurs in absence of noxious stimuli, occurs even
after successive healing (mostly in back/knee). Affects sleeping, exercising, etc.
- sensory/affective component = intensity/quality/valence/distressing
- Multiple response levels = brain/reflexes/facial expressions/VNS/reporting
- Always psychological
- Pain is subjective
Nociception: detection and processing of noxious stimuli that’s triggered by (threat of) tissue damage. Pain
can be felt without nociception
Nociceptors: respond and detect noxious stimuli (skin, joints, walls of organs)
- Stimulation-specific
- Polymodal (most)
→ activity induced in the nociceptor and nociceptive pathways by a noxious stimulus is not pain Pain-
emotion interaction: former alerts body to pain source, latter detects motivationally-relevant stimuli
that may trigger avoidance/approach. Survival is goal
ASCENDING PATHWAYS: afferent nociceptive information enters brain
1. spinothalamic pathway = info from thalamus projects to: INS, ACC, S1, & S2
2. spinoamygdaloid pathway = info from amygdala is projected via the PFC to the Basal Ganglia Video in
Lecture
1. Transduction: convert noxious stimuli to electrical current
2. Conduction: current conducted to nociceptor cell bodies in dorsal root ganglion in spinal cord,
then to the central terminals in the dorsal horn
3. Transmission: electrical impulses initiate NT release from Nociceptor terminals, relaying the signal
across synapses to the dorsal horn neurons
4. Perception: signal relayed via ascending nociceptive pathways to higher centers in the brain
5. Modulation: ascending nociceptive transmissions modulated by inhibitory (provides analgesia in
times of danger, so pain doesn’t compromise function) or facilitatory (provides warning of tissue
injury, fight/flight to protect self) control systems in the dorsal horn of the spinal cord
● Thinly myelinated A-delta neurons = fast conduction; transmits acute and localized pain
● Unmyelinated C-fibers = slower conduction; transmits widespread pain
Wieser
1. Peripheral A-delta & C-fibers terminate in the dorsal horn of the spinal cord
,2. 2nd order neurons are activated and the axons cross the midline of the spinal cord ventral to the
surface of the spinal cord
3. Ascending pain signals are sent to the brain via the spinothalamic tract, which project to the
intralaminar & ventroposterior nuclei of the thalamus
4. Signals reach 2 supraspinal neuronal systems that differentiates the nociceptive info
- Lateral system: encodes sensory discriminative components of pain (lateral nuclei of
thalamus, S1, S2)
- Medial system: encodes affective motivational components of the resulting pain percept
(medial nuclei of thalamus, ACC, PFC)
● Acute pain = Activation of Insula, ACC, Thalamus, Basal Ganglia. Brain stem and descending
modulatory system also play role
● Clinical chronic pain = increased activation of prefrontal cortex (distorts cog and emotional
perception and processing of experiences
● Dual pathway for pain = A-delta mediates pricking first pain & C-fibers mediate dull second pain
, DESCENDING PATHWAY
● Starts in the brain
● Modulates (enhances/inhibits) the ascending pathway signals by altering transmission of
nociceptive inputs at the dorsal horn
● Periaqueductal grey (PAG) & Rostroventral medulla (RVM) helps control pain via PAG-RVM- dorsal
horn pathway
● Descending pain modulatory neurons in RVM Inhibit of nociceptive transmission =
1. direct inhibition of projection neurons
2. Inhibition of transmitter release from primary afferents
3. Excitation of inhibitory interneurons
4. Inhibition of excitatory interneurons
● These can exert bidirectional control of pain in response of higher-order factors e.g. fear,
attention, expectation
● Release of opioids produces an analgesic, reducing transmitter release from the dorsal horn
terminal of primary afferent nociceptors. Also inhibit postsynaptic transmission that’re activated by
noxious stimulation. Also inhibit neuropeptide release from primary afferents.
Descending pathways =
1. Descending input = ACC to PFC to PAG
2. Descending input = from amygdala to insula to PAG
3. Descending pathway from the PAG to the RVM to the dorsal horn (influences nociceptive
afferent transmission)
Definition and neurobiological basis of pain
Wieser: Neuroscience of Pain and Emotion
Pain: unpleasant sensory and emotional experience associated with actual or potential tissue damage.
Conscious experience of nociception, emerging from cognitive and emotional evaluation of the info gathered
through the nociceptive system.
- Function: warning, supports healing process
- Chronic pain = > 6 months, lost warning function, occurs in absence of noxious stimuli, occurs even
after successive healing (mostly in back/knee). Affects sleeping, exercising, etc.
- sensory/affective component = intensity/quality/valence/distressing
- Multiple response levels = brain/reflexes/facial expressions/VNS/reporting
- Always psychological
- Pain is subjective
Nociception: detection and processing of noxious stimuli that’s triggered by (threat of) tissue damage. Pain
can be felt without nociception
Nociceptors: respond and detect noxious stimuli (skin, joints, walls of organs)
- Stimulation-specific
- Polymodal (most)
→ activity induced in the nociceptor and nociceptive pathways by a noxious stimulus is not pain Pain-
emotion interaction: former alerts body to pain source, latter detects motivationally-relevant stimuli
that may trigger avoidance/approach. Survival is goal
ASCENDING PATHWAYS: afferent nociceptive information enters brain
1. spinothalamic pathway = info from thalamus projects to: INS, ACC, S1, & S2
2. spinoamygdaloid pathway = info from amygdala is projected via the PFC to the Basal Ganglia Video in
Lecture
1. Transduction: convert noxious stimuli to electrical current
2. Conduction: current conducted to nociceptor cell bodies in dorsal root ganglion in spinal cord,
then to the central terminals in the dorsal horn
3. Transmission: electrical impulses initiate NT release from Nociceptor terminals, relaying the signal
across synapses to the dorsal horn neurons
4. Perception: signal relayed via ascending nociceptive pathways to higher centers in the brain
5. Modulation: ascending nociceptive transmissions modulated by inhibitory (provides analgesia in
times of danger, so pain doesn’t compromise function) or facilitatory (provides warning of tissue
injury, fight/flight to protect self) control systems in the dorsal horn of the spinal cord
● Thinly myelinated A-delta neurons = fast conduction; transmits acute and localized pain
● Unmyelinated C-fibers = slower conduction; transmits widespread pain
Wieser
1. Peripheral A-delta & C-fibers terminate in the dorsal horn of the spinal cord
,2. 2nd order neurons are activated and the axons cross the midline of the spinal cord ventral to the
surface of the spinal cord
3. Ascending pain signals are sent to the brain via the spinothalamic tract, which project to the
intralaminar & ventroposterior nuclei of the thalamus
4. Signals reach 2 supraspinal neuronal systems that differentiates the nociceptive info
- Lateral system: encodes sensory discriminative components of pain (lateral nuclei of
thalamus, S1, S2)
- Medial system: encodes affective motivational components of the resulting pain percept
(medial nuclei of thalamus, ACC, PFC)
● Acute pain = Activation of Insula, ACC, Thalamus, Basal Ganglia. Brain stem and descending
modulatory system also play role
● Clinical chronic pain = increased activation of prefrontal cortex (distorts cog and emotional
perception and processing of experiences
● Dual pathway for pain = A-delta mediates pricking first pain & C-fibers mediate dull second pain
, DESCENDING PATHWAY
● Starts in the brain
● Modulates (enhances/inhibits) the ascending pathway signals by altering transmission of
nociceptive inputs at the dorsal horn
● Periaqueductal grey (PAG) & Rostroventral medulla (RVM) helps control pain via PAG-RVM- dorsal
horn pathway
● Descending pain modulatory neurons in RVM Inhibit of nociceptive transmission =
1. direct inhibition of projection neurons
2. Inhibition of transmitter release from primary afferents
3. Excitation of inhibitory interneurons
4. Inhibition of excitatory interneurons
● These can exert bidirectional control of pain in response of higher-order factors e.g. fear,
attention, expectation
● Release of opioids produces an analgesic, reducing transmitter release from the dorsal horn
terminal of primary afferent nociceptors. Also inhibit postsynaptic transmission that’re activated by
noxious stimulation. Also inhibit neuropeptide release from primary afferents.
Descending pathways =
1. Descending input = ACC to PFC to PAG
2. Descending input = from amygdala to insula to PAG
3. Descending pathway from the PAG to the RVM to the dorsal horn (influences nociceptive
afferent transmission)
