Thalamus – Integration of Sensation & Pain

Question 1

The thalamus is a complex structure with multiple, complex sensory, motor, and modulatory functions. For the purposes of this presentation we will focus on the sensory functions (that is exclusive of hearing and vision).

Answer 1

Accordingly, recognize that the ventral posterior lateral (VPL), the ventral posterior medial (VPM), the dorsal medial (DPM), and the intralaminar centromedian (CM) and parafascicular (PF) nuclei are important for peripheral sensory function.

Question 2

The ascending anterior lateral spinothalamic tract can be functionally divided into what?

Answer 2

an older paleo-spinothalamic pathway and an evolutionary newer neo-spinothalamic pathway.

Question 3

What does the neo-spinothalamic pathway do?

Answer 3

Encodes for the intensity, location, and quality of pain. It mediates “fast pain” that is sharp, well-localized and relayed rapidly to somatosensory cortex.

Question 4

In contrast, the paleo-spinothalamic tract encodes for:

Answer 4

the emotional and visceral responses to pain and also influences the descending pathways from the brain stem that modulate pain. Pain responses carried by the paleo-spinothalamic pathway are characterized as dull, throbbing, and poorly localized pain.

Question 5

The VPL receives both protopathic (that is 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 where?

Answer 5

the ‘neo-spinothalamic tract that is relayed on to the Lateral Pain System.

Question 6

The DPM, CM and PF nuclei receive pain information from where:

Answer 6

the paleo-spinothalamic tract and relay this information on to the Medial Pain System.

Question 7

Question 8

What are the main pain sensors of the body?

Answer 8

free nerve endings

ü Temp. - via Transient Receptor Potential Channels (TRP)

• TRPV1 sensitive to >43 C & Capsaicin
• TRPM8 sensitive to <25

ü Mechanical

ü Chemical

Question 9

What afferent fibers relay pain?

Answer 9

Adelta and C fibers

Question 10

Describe Adelta fibers

Answer 10

üthinly myelinated, transmit temp & mechanical pain, discrete location, fast, sharp pain

Question 11

Describe C fibers

Answer 11

üunmyelinated, transmit temp, mechanical, and chemical pain (polymodal), diffuse, slow pain

Question 12

Aδ & C Fiber’s cell bodies lie where?

Answer 12

In the dorsal root ganglian and use glutamate, substance P, and calcitonin-gene related peptide (CGRP) as neurotransmitters.

NOTE – these transmitters may be released at both the central (dorsal horn) and peripheral (skin, other organs) terminals

Question 13

This figure graphically summarizes the Peripheral Pain Receptor Sensitization process. Describe the initial steps of this process.

Answer 13

1) Tissue injury triggers release of several substances including hydrogen ion, 5-HT, bradykinin, ATP and prostaglandins, that activate nociceptive receptors.
2) These receptors consist of free nerve endings that are stimulated to fire an action potential back to the dorsal horn neuron.

Question 14

Activation of the nociceptive receptors also causes the local release of what?

Answer 14

substance P and calcitonin gene-related peptide or CGRP from the free nerve endings at the site of injury.

Question 15

What do Substance P and CGRP in turn trigger?

Answer 15

a release of histamine from mast cells and vasodilation of nearby blood vessels. The release of the above substances in the site of injury combined with 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.

Finally, the inflammatory chemical milieu activates previously silent nociceptive receptors on free nerve endings thus further sensitizing the area to painful stimuli.

Question 16

What are nociceptive specific neurons or SPNs?

Answer 16

Neurons that lie in the laminae I & II of the dorsal horn that respond only to Aδ or C fiber action potentials and encode only pain.

Question 17

What are wide dynamic range neurons (WDRNs)?

Answer 17

Neurons in laminae V of the dorsal horn that respond to a variety of synaptic input that encode pain and non-pain stimuli.

The WDRNs fire action potentials in a graded fashion depending upon stimulus intensity, the latter being proportional to stimulus frequency. Thus the greater the C-fiber action potential frequency, the greater the action potential response in the WDRNs.

Question 18

T or F. It is the WDRNs that are responsible for Wind Up, that is the Signal Amplification of pain

Answer 18

T.

Question 19

The Signal Amplification of pain activity, or so-called Wind Up is an important component of spinal cord processing. What causes it?

Answer 19

1) Repetitive action potentials from C-fibers trigger Wind Up by releasing glutamate that in turn activate WDRN AMPA receptors and CGRP activation of WDRN CGRP receptors.

Question 20

Activation of WDRN receptors leads to what?

Answer 20

WDRN depolarization and release of the Mg++ block of the NMDA channel.

The enhanced Ca ++ influx through the NMDA channel causes insertion of more Na+ channels and blockade of K+ channels in the WDRNs. In addition substance P activation of NK1 receptors contributes to the process by prolonging WDRN depolarization. It is the combined activation from these neurotransmitters, meaning glutamate, substance P and CGRP, that reduces the threshold of the WDRNs and increases the insertion of more receptors in WDRNs, leading to a lowered threshold for firing action potentials.

Question 21

What are the main functional consequences of Wind Up?

Answer 21

Relatively brief C-fiber stimulation can lead to long lasting facilitation of the pain pathway stimulated. This is a partial explanation of why and how patients experience hyperalgesia and is partially an explanation for long lasting or chronic pain.

Question 22

The central modulation of pain involves at least three separate mechanisms, namely:

Answer 22

1) gate control mechanisms,
2) descending pathways and
3) the endogenous opioid systems.

Question 23

Describe gate control mechanisms

Answer 23

Action potentials traveling through Aβ fibers activate dorsal column interneurons that inhibit WDRN neurons, thus blunting activation of the latter neurons’ response to Aδ and C-fiber activity.

Question 24

Describe descending pathways

Answer 24

Descending pathways from cortex, amygdala, hypothalamus, all impinge upon the 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

Question 25

Describe endogneous opiod mediated central modulation of pain

Answer 25

Activation of endogenous opioid receptors:

1) block presynaptic voltage-gated Ca++ channels to decrease neurotransmitter release and
2) open postsynaptic K+ channels to hyperpolarize the postsynaptic neuron.

Both mechanisms reduce action potentials in the postsynaptic neuron thereby blunting pain.

Question 26

How does the concept of referred pain work?

Answer 26

Nociceptive receptors lying in the viscera of the intrathoracic, abdominal and pelvic organs send axons that synapse on dorsal horn neurons primarily devoted to surface (that is dermatomal) receptors. Even though the viscera are sparsely populated with the nociceptive receptors, 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 as shown in the above figure. Heart muscle pain is sometimes referred into the neck region as well but that is not shown in the figure.

Question 27

Describe the initial route of the newly discovered visceral pain pathway

Answer 27

Consists of the the same visceral nociceptive receptors, but some of these receptors send afferent fibers that bypass the secondary dorsal horn neurons (those associated with the anterior-lateral spinothalamic tract) and instead synapse on neurons lying in the intermediate gray zone near the central canal.

Question 28

What is the next step of the visceral pain pathway?

Answer 28

These secondary neurons send their fibers upward and travel with the dorsal column pathway. The fibers of this visceral pain pathway may be distinguished by the fact that they travel very close to the midline in the dorsal column.

These secondary visceral pain fibers synapse, as expected, in the ventral posterior lateral nucleus of the thalamus or VPL and the tertiary fibers are distributed to somatosensory cortex and other pain matrix centers.

Question 29

What is the clinical consequences of the visceral pain pathway?

Answer 29

Small midline lesions of the dorsal column at the lower thoracic cord alleviates chronic visceral pain, such as intractable cancer pain.