Chapter 1 Anatomy and Physiology of Somatosensory and Pain Processing

Question 1

What is Pain?

Answer 1

Pain is a physiological consequence of tissue injury that serves a vital protective function.

Question 2

The International Association for the Study of Pain
defines pain as…

Answer 2

“An unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage.”

Question 3

What is Somatosensation?

Answer 3

The physiologic process by which neural substrates are activated by physical stimuli resulting in
the perception of what we describe as touch, pressure, and pain.

Question 4

What is Nociception?

Answer 4

The physiologic process of activation of neural pathways by stimuli that are potentially or currently
damaging to tissue.

Question 5

What are the sequence of events by which a stimulus is perceived?

Answer 5

Involves four processes:
(1) transduction, (2) transmission, (3) modulation, and (4) perception

Question 6

What is Transduction?

Answer 6

Transduction occurs in the peripheral terminals of primary afferent neurons where different forms of energy (e.g., mechanical, heat, chemical, or cold) are converted to electrical activity (action potentials)

Question 7

What is Transmission?

Answer 7

Transmission is the process by which electrical activity induced by a stimulus is conducted
through the nervous system

Question 8

What are the three major components
of the transmission system?

Answer 8

1) The peripheral sensory cells in the ~~dorsal root ganglia~~ transmit impulses from the site of transduction at their peripheral terminal to the
spinal cord where the central terminals synapse with second- order neurons.

2) The ~~spinal neurons~~ are the second
component in the transmission network. These cells send projections to the thalamus and various brainstem and diencephalic structures.

3) Neurons of the brainstem and diencephalon form the third component of the transmission network as they project to various cortical sites.

Question 9

What is Modulation?

Answer 9

Modulation is the process whereby neural activity
may be altered along the pain transmission pathway. A major site of modulation occurs within the dorsal horn of the spinal cord.

Question 10

What is Perception?

Answer 10

Perception is the final stage of the pain-signaling process by which neural activity in the somatosensory transmission pathway results in a subjective sensation of pain.
It is presumed that this process results from the concerted activation of primary and secondary somatosensory and limbic cortices.

Question 11

How does somatosensation begins?

Answer 11

Somatosensation begins with activation of primary
afferent fibers. These fibers are part of the peripheral
nervous system with cell bodies located in the dorsal root ganglia.

Question 12

What are the three classes of primary afferent
fibers in skin?

Answer 12

They are categorized based on conduction velocity that may be activated by a given cutaneous stimulus.
The fastest conducting fibers are the large-diameter myelinated A-beta (Ab) fibers. When activated they do not normally transmit the sensation of pain, but rather of light touch, pressure, or hair movement.

The axons of nociceptive neurons are generally unmyelinated C fibers or thinly myelinated A-delta (Ad) fibers. Nociceptors have the capacity to respond to intense heat, cold, mechanical, and
chemical stimuli.

Question 13

What sensations do nociceptive neurons evoke?

Answer 13

C-fiber activity is associated with a prolonged
burning sensation.
In contrast, activation of fasterconducting
(5 to 20 m/s) Ad fibers evokes a sharp, intense,
tingling sensation.

Question 14

What is Dual Pain Sensation?

Answer 14

As Ad fibers convey the rapid-onset first pain sensation, a pricking pain, while C fibers mediate the slower-onset, burning second pain
sensation that follows brief intense heat stimulation to the skin.
Combined, Ad- and C-fiber nociceptors encode and
transmit information to the central nervous system concerning the intensity, location, and duration of noxious stimuli.

Question 15

Where does the first synapse in somatosensory processing of information from the body surface occur?

Answer 15

Occurs at either the spinal dorsal horn or in the dorsal column nuclei at the spinal cord–brainstem junction.

Question 16

Where does the first synapse in somatosensory processing of information from the face occur?

Answer 16

Processed either in the spinal trigeminal nucleus (pain and temperature) or in the chief sensory nucleus of the trigeminal nerve located in the midpons region of the brainstem.

Question 17

(Spinal dorsal horn and spinal trigeminal nucleus ) and (Dorsal column nuclei and the chief sensory nucleus) selectively process inputs from what fibers?

Answer 17

The spinal dorsal horn and spinal trigeminal nucleus process inputs of the nociceptive Ad and C fibers.

The dorsal column nuclei and the chief sensory nucleus can be considered to selectively process inputs from the large myelinated Ab-fiber classes related to light touch.

Question 18

Where do nociceptive primary afferent fibers terminate in the spinal dorsal horn?

Answer 18

The dorsal horn is anatomically organized in the form of layers or laminae.
The unmyelinated C fibers terminate primarily in the most superficial lamina (I and II outer), while
the thinly myelinated Ad fibers end in lamina
I, and in laminae III to V.
Collaterals of the large myelinated fibers (Ab) terminate laminae III to V of the dorsal horn

Question 19

What are the two predominant types of second-order nociceptive spinal and spinal trigeminal projection neurons?

Answer 19

Wide-Dynamic-Range neurons (WDR) and Nociceptive-specific (NS) neurons.

Question 20

Where are Wide-Dynamic-Range neurons (WDR) concentrated? What nociceptive primary afferent fibers do there receive input from?

Answer 20

WDR cells are especially concentrated in the deeper laminae of the dorsal horn (III to V) where they receive input from both low-threshold
Ab and nociceptive Ad and C fibers, and hence are activated by both innocuous and noxious stimuli.
The noxious stimuli evoke a greater response than
non-noxious stimuli.

Question 21

Where are Nociceptive-specific (NS) neurons concentrated?

Answer 21

The majority of NS cells are found in the superficial laminae of the dorsal horn (I and outer II).NS projection cells respond only to noxious stimuli under physiologic conditions.

Question 22

What is the pathway of axons of the WDR and NS second-order neurons?

Answer 22

The axons of both the WDR and NS second-order neurons cross the midline near the level of the cell body, gather into bundles of ascending fibers in the contralateral, anterolateral spinal region, and then ascend toward targets in the brainstem and diencephalon

Question 23

Where are the axons of WDR and NS found in the spinal column?

Answer 23

In the anterolateral spinal column, the NS cell axons are found in the dorsal medial region, while axons of WDR cells are more concentrated in the ventral lateral region

Question 24

What is the Gate Control Theory?

Answer 24

This theory suggested that input along low-threshold (Ab) fibers inhibits the responses of WDR cells to nociceptive input.

Question 25

What is the function of intrinsic spinal neuron?

Answer 25

Release a plethora of neurotransmitters in the spinal cord that play a role in the modulation of nociceptive impulses.

Question 26

What is Central Sensitization?

Answer 26

Special type of spinal modulation.
In this phenomenon, the capacity for transmission
in the nociceptive system is changed or shows neuronal plasticity. The result of this plasticity is that following a noxious stimulus of sufficient intensity and duration, such as a surgical incision, the coding of pain-signaling neurons for a given stimulus may be increased

Question 27

What is Wind- Up Phenomenon?

Answer 27

It is an example of central plasticity.
phenomenon whereby repeated stimulation of C fibers at intervals of 0.5 to 1 Hz results in a progressive increase in the number of discharges
evoked by each volley.

Question 28

What are the Supraspinal structures involved in somatosensory processing?

Answer 28

brainstem, and cortical sites.
(the primary and secondary somatosensory cortices) , insula, anterior cingulate
cortex, prefrontal cortex, and several nuclei of the thalamus

Question 29

Where do the axons of spinal projection neurons terminate?

Answer 29

First, many axons and axon collaterals
of the spinal projection neurons that ascend in the
anterolateral spinal quadrant depart this ascending tract to terminate in a number of nuclei of the brainstem and midbrain.

Question 30

What are the target site of axons of spinal projection neurons?

Answer 30

These target sites include brainstem autonomic
regulatory sites that influence cardiovascular and respiratory functions, while in the midbrain there are multiple inputs to centers from which both descending as well as ascending (e.g., to thalamus) modulation of somatosensory processing is evoked.

Question 31

Where do the axons of anterolateral system fibers terminate?

Answer 31

The remainder of the so-called anterolateral system fibers continues through the brainstem and midbrain to terminate in diencephalic structures, including the hypothalamus and posterior, lateral, and medial regions of the thalamus.

Question 32

What is the second set of somatosensory inputs to the brainstem?

Answer 32

Includes those primary afferent fibers that ascend in the dorsal (posterior) columns of the spinal cord to form their first synapse at the dorsal column nuclei

Question 33

How are the somatosensory inputs to the brainstem organized?

Answer 33

These inputs are organized so that the fibers from the lower extremities synapse most medially in the nucleus gracilis and
inputs from the upper extremities synapse laterally in the nucleus cuneatus.
The trunk is represented in regions of both nuclei

Question 34

Where are the sometosensory input from the face processed?

Answer 34

inputs from the face are processed in the chief sensory nucleus of the trigeminal nerve located at the origin site of cranial nerve five in the midpons
of the brainstem.

Question 35

How do axons of the second-order cells in the dorsal column nuclei travel?

Answer 35

The axons of the second-order cells in the dorsal column nuclei cross the midline and form the medial lemniscus on the contralateral side of the brainstem.
These fibers then ascend through the brainstem and midbrain acquiring the functionally related fibers from the trigeminal nerve as they pass and continue on to provide the second somatosensory input to the diencephalon as they terminate in the ventral posterior lateral (VPL) nucleus (inputs from the body) and ventral posterior medial (VPM) nucleus (inputs from the face) of the thalamus

Question 36

What are the somatosensory inputs to the cortex?

Answer 36

The somatosensory inputs to the cortex include the
third-order projections from thalamic somatosensory
relay neurons of VPL and VPM as well as third- (and higher-) order neurons projecting from brainstem and midbrain relay neurons

Question 37

Where does plasticity and modulation of somatosensory signaling occur?

Answer 37

Brainstem, Midbrain, and Diencephalic levels ( It is made up of four distinct components: the thalamus, the subthalamus, the hypothalamus, and the epithalamus)

Question 38

What are the pathways involved in descending modulation?

Answer 38

the periaqueductal gray (PAG) and
rostral ventromedial medulla (RVM) pathway.

Question 39

PAG and RVM receive descending projections from what sites?

Answer 39

The PAG and RVM receive descending projections from a variety of cortical and limbic sites known to be involved in the affective component of pain processing such as the anterior cingulate cortex, amygdala, and prefrontal cortex.

Activation of these structures results in pro- or anti-nociceptive effects and requires the
PAG and RVM.

PAG has few direct projections to the spinal cord and instead projects to the RVM, which sends either inhibitory or excitatory impulses to nociceptive projection and WDR neurons in the superficial and deep layers of the dorsal horn of the spinal cord.

Question 40

How does RVM facilitate its effect?

Answer 40

It is hypothesized that the RVM is able to facilitate both inhibitory and facilitatory effects on the dorsal horn via different types of neurons termed “ON” and “OFF” cells

Question 41

What are “ON” and “OFF” cells?

Answer 41

OFF cells are tonically active except during nociceptive input and activated by known analgesics such as morphine.
ON cells become more active during nociceptive input and are inhibited by morphine. It is generally accepted that OFF cells are required for descending inhibition.
Activation of ON cells within the RVM induces
hyperalgesia. Descending facilitation via ON cell activation is thought to induce hyperalgesia by upregulating spinal dynorphin, which is linked to the increased release of excitatory neurotransmitters from primary afferent neurons, which can lead to central sensitization and chronic pain.

Question 42

What are the position of “ON” and “OFF” cells in chronic pain?

Answer 42

ON cells are activated, and OFF cells suppressed, in models of chronic pain

Question 43

What are the two main signaling channels of the somatosensory system?

Answer 43

The anterolateral system is the primary pain-signaling channel.
The dorsal column–medial lemniscal system is primarily a highspeed, very discrete signaling channel for innocuous stimuli.