Thalamus (Integration Of Sensation And Pain)

Front 1

Which nuclei in the thalamus are important for peripheral sensory function?

Back 1

VPL, VPM, DPM (dorsal medial), CM (intralaminar centromedian), PF (parafascicular)

Front 2

What can the ascending anterior lateral spinothalamic tract be functionally divided into?

What does each encode?

Back 2

Paleo-spinothalamic pathway (emotional and visceral responses to pain, medial affective-motivation, influences descending pathways from brain stem that modulate pain)

Neo-spinothalamic pathway (intensity, location, and quality of pain, lateral sensory-discriminative, sharp, well-localized, relayed rapidly to somatosensory cortex)

Front 3

The VPL receives both protopathic (nociceptive) and epicritic sensory information from the _____ and _____ while the VPM receives similar sensory information from the _____. Regarding pain, VPL and VPM receive pain fibers from the ‘___-spinothalamic tract that is relayed on to the Lateral Pain System. The DPM, CM and PF nuclei receive pain information from the _____-spinothalamic tract and relay this on to the Medial Pain System.

Back 3

The VPL receives both protopathic (nociceptive) and epicritic sensory information from the limbs and body while the VPM receives similar sensory information from the face. Regarding pain, VPL and VPM receive pain fibers from the ‘neo-spinothalamic tract that is relayed on to the Lateral Pain System. The DPM, CM and PF nuclei receive pain information from the paleo-spinothalamic tract and relay this on to the Medial Pain System.

Front 4

What are the components of the lateral pain system?

Medial pain system?

Back 4

Primary and secondary somatosensory cortex

Anterior cingulate, ínsula, amygdala, hypothalamus

Front 5

What three stimuli do free nerve endings detect?

Back 5

Temperature

Mechanical

Chemical

Front 6

What temperature receptor potential channels (TRP) are sensitive to >43 degrees and capsaicin?

Which sensitive to <25 degrees?

Back 6

TRPV1

TRPM8

Front 7

What two fiber types conduct pain?

Back 7

A-delta

C-fibers

Front 8

Which fibers are thinly myelinated and carry temperature, mechanical pain, discrete location, fast, and sharp pain sensory information?

Back 8

A-delta fibers

Front 9

Which fibers are unmyelinated, transmit temperature, mechanical, and chemical pain (polymodal), diffuse, and slow pain?

Back 9

C-fibers

Front 10

Where do the cell bodies of A-delta and C fibers lie? What three neurotransmitters are used?

Back 10

Dorsal root ganglia

Glutamate, substance P, CGRP

Front 11

1. Peripheral Pain Receptor Sensitization

̧Stimulation (tissue injury) of nociceptive receptors triggers release of several substances (H+ ion, 5-HT, ATP, _____, _____) that activate free nerve endings to fire an action potential (AP) back to the spinal cord dorsal horn

̧2. Activation of the nociceptive receptors also causes the local (peripheral) release of substance __ and _____ from the free nerve endings at the site of injury. Substance P and CGRP in turn cause release of ____ from mast cells and vasodilation of local blood vessels.

̧3. The combination of local tissue injury (inflammation) with release of the above substances and the release of substance P and CGRP from the free nerve endings sensitizes the free nerve ending receptors such that their threshold for activation is ______

̧4. Finally, the inflammatory chemical milieu activates previously _____ nociceptive receptors on free nerve endings to become active thereby increasing the temporal and spatial _____ of APs traveling to the dorsal horn

Back 11

1. Peripheral Pain Receptor Sensitization

̧Stimulation (tissue injury) of nociceptive receptors triggers release of several substances (H+ ion, 5-HT, ATP, bradykinin, prostaglandins) that activate free nerve endings to fire an action potential (AP) back to the spinal cord dorsal horn

̧2. Activation of the nociceptive receptors also causes the local (peripheral) release of substance P and CGRP from the free nerve endings at the site of injury. Substance P and CGRP in turn cause release of histamine from mast cells and vasodilation of local blood vessels.

̧3. The combination of local tissue injury (inflammation) with release of the above substances and the release of substance P and CGRP from the free nerve endings sensitizes the free nerve ending receptors such that their threshold for activation is lowered

̧4. Finally, the inflammatory chemical milieu activates previously silent nociceptive receptors on free nerve endings to become active thereby increasing the temporal and spatial summation of APs traveling to the dorsal horn

Front 12

Review of peripheral pain sensitization

Back 12

Front 13

What are neurons in the laminae I and II of the dorsal horn that respond only to A-delta or C fiber APs and encode only pain?

Back 13

Nociceptive specific neurons (SPNs)

Front 14

What are neurons in laminae V of the dorsal horn that respond to a variety of synaptic input encode pain and non-pain stimuli?

How do they fire APs? In other words, the greater the C-fiber AP frequency, the greater the AP response in the _________.

What are WDRNs responsible for?

Back 14

Front 15

Describe the process of WIND UP (signal amplification). => How do repetitive APs from C-fibers trigger wind up?

Back 15

Glutamate activation of WDRN AMPA receptors and CGRP activation of WDRN CGRP receptors => WDRN depolarization => Mg2+ block of NMDA channel removed => insertion of more Na+ channels and blockade of K+ channels in WDRNs

Front 16

How does substance P contribute to the process of WIND UP (signal amplification)?

What does the combined action of these neurotransmitters lead to a lower threshold for firing APs?

Back 16

Activates NK1 receptors => prolonging of WDRN depolarization

Combined activation => reduces WDRN threshold => increase insertion of more receptors in WDRN => lower threshold for firing APs

Front 17

What is the functional consequence of WIND UP?

Back 17

Brief c-fiber stimulation => long lasting facilitation of the pain pathway stimulated => hyperalgesia and chronic pain

Front 18

Define gate-control mechanisms:

Back 18

A-beta fibers => dorsal column interneurons => inhibit WDR neurons => blunts activation of WDR neurons in response to A-delta and C-fiber activity.

Front 19

Descending pathways:

Cortex, amygdala, hypothalamus all impinge upon periaqueductal _____ and reticular formation neurons that in turn send descending fibers to modulate lamina II neurons in the ______ horn. These descending systems may either inhibit or facilitate pain.

Back 19

Cortex, amygdala, hypothalamus all impinge upon periaqueductal gray and reticular formation neurons that in turn send descending fibers to modulate lamina II neurons in the dorsal horn. These descending systems may either inhibit or facilitate pain.

Front 20

Endogenous opioid:

Describe it!

Back 20

Opioid receptor activation => block pre-synaptic voltage gated Ca2+ channel and/or opening or K+ channels => hyper polarizing postsynaptic neuron => reduce APs

Front 21

Identify the sites of referred pain:

Liver, SI, appendix, right ureter, heart, stomach, gallbladder, ovary, colon, kidney, bladder

Back 21

Front 22

The CNS pathways responsible for conducting visceral pain have recently been modified to account for a newly discovered pathway. Nociceptive receptors lying in the visceral (intrathoracic, abdominal, pelvic organs) until recently were thought to synapse on dorsal horn neurons primarily devoted to surface (dermatomal) receptors and that viscera were sparsely populated by these receptors. The latter statement remains correct and there is significant sharing of visceral nociceptive activity with the dermatomal system. In fact, this biological arrangement is thought to be the basis of referred pain. For example, poorly localized nociceptive receptors in heart muscle may generate pain localized not only to the midline-left chest but also to the C8-T1 dermatome (see above figure). Heart muscle pain may also be referred into the neck region (not shown in above figure).

Back 22

The CNS pathways responsible for conducting visceral pain have recently been modified to account for a newly discovered pathway. Nociceptive receptors lying in the visceral (intrathoracic, abdominal, pelvic organs) until recently were thought to synapse on dorsal horn neurons primarily devoted to surface (dermatomal) receptors and that viscera were sparsely populated by these receptors. The latter statement remains correct and there is significant sharing of visceral nociceptive activity with the dermatomal system. In fact, this biological arrangement is thought to be the basis of referred pain. For example, poorly localized nociceptive receptors in heart muscle may generate pain localized not only to the midline-left chest but also to the C8-T1 dermatome (see above figure). Heart muscle pain may also be referred into the neck region (not shown in above figure).

Front 23

Draw out the visceral pain pathway.

Back 23